ALBERT

Description: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 141〈/p〉 〈p〉Author(s): Chao Wang, Yuan Yuan, Jie Wu, Yuanlin Zhao, Xing Gao, Yihua Chen, Chao Sun, Liming Xiao, Pengfei Zheng, Peizhen Hu, Zengshan Li, Zhe Wang, Jing Ye, Lijun Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉While cardiac hypertrophy and heart failure are accompanied by significant alterations in energy metabolism, more than 50–70% of energy is obtained from fatty acid β-oxidation (FAO) in adult hearts under physiological conditions. Plin5 is involved in the metabolism of lipid droplets (LDs) and is highly abundant in oxidative tissues including heart, liver and skeletal muscle. Plin5 protects the storage of triglyceride (TG) in LDs by inhibiting lipolysis, thereby suppressing excess FAO and preventing excessive oxidative stress in the heart. In this study, we investigated the roles of Plin5 in cardiac hypertrophy and heart failure in mice treated with transverse aortic constriction (TAC). The results indicated that Plin5 deficiency aggravated myocardial hypertrophy in the TAC-treated mice and exacerbated the TAC-induced heart failure. We also found that Plin5 deficiency reduced the cardiac lipid accumulation and upregulated the levels of PPARα and PGC-1α, which stimulate mitochondrial proliferation. Moreover, Plin5 deficiency aggravated the TAC-induced oxidative stress. We consistently found that Plin5 knockdown disrupted TG storage and elevated FAO and lipolysis in H9C2 rat cardiomyocytes. In addition, Plin5 knockdown also provoked mitochondrial proliferation and lipotoxic injury in H9C2 cells. In conclusion, Plin5 deficiency increases myocardial lipolysis, elevates FAO and oxidative burden, and thereby exacerbates cardiac hypertrophy and heart failure in TAC-treated mice.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S089158491930471X-fx1.jpg" width="336" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 92〈/p〉 〈p〉Author(s): Yang Hu, Wei-Chao Chen, Yu-Feng Shen, Bin Zhu, Gao-Xue Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Viral diseases in aquaculture were challenging because there are few preventative measures and/or treatments. Our previous study indicated that imidazole arctigenin derivatives possessed antiviral activities against infectious hematopoietic necrosis virus (IHNV). Based on the structure-activity relationship in that study, a new imidazole arctigenin derivative, 4-(8-(2-ethylimidazole)octyloxy)-arctigenin (EOA), was designed, synthesized and its anti-IHNV activity was evaluated. By comparing inhibitory concentration at half-maximal activity (IC〈sub〉50〈/sub〉), we found that EOA (IC〈sub〉50〈/sub〉 = 0.56 mg/L) possessed a higher antiviral activity than those imidazole arctigenin derivatives in our previous study. Besides, EOA could significantly decrease cytopathic effect (CPE) and viral titer induced by IHNV in epithelioma papulosum cyprinid (EPC) cells. In addition, EOA significantly inhibited apoptosis induced by IHNV in EPC cells. Further data verified that EOA inhibited IHNV replication in rainbow trout, with reducing 32.0% mortality of IHNV-infected fish. The results suggested that EOA was more stable with a prolonged inhibitory half-life in the early stage of virus infection (1–4 days). Consistent with above results, EOA repressed IHNV glycoprotein gene expression in virus sensitive tissues (kidney and spleen) in the early stage of virus infection. Moreover, histopathological evaluation showed that tissues from the spleen and kidney of fish infected with IHNV exhibited pathological changes. But there were no lesions in any of the tissues from the control group and EOA-treaten group. In accordance with the histopathological assay, EOA could elicited anti-inflammation response in non-viral infected rainbow trout by down-regulating the expression of cytokine genes (〈em〉IL-8〈/em〉, 〈em〉IL-12p40〈/em〉, and 〈em〉TNF-α〈/em〉). Altogether, EOA was expected to be a therapeutic agent against IHNV infection in the field of aquaculture.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 92〈/p〉 〈p〉Author(s): Junjun He, Haiying Liang, Jiaping Zhu, Xiaochen Fang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Antibacterial peptides (AMPs) constitute an important part of the body's innate immune system and are responsible for a wide range of inhibitory effects against pathogens such as bacteria, fungi, and viruses. In this study, multi-step high performance liquid chromatography (HPLC), combined with Mass Spectrometry (MS), was used to isolate and identify proteins with antibacterial activity from the serum of 〈em〉Pinctada fucata martensii〈/em〉 (〈em〉P.f. Martensii〈/em〉) and obtain a component named 〈em〉P.f. Martensii〈/em〉 antimicrobial peptide-1 (PmAMP-1). 〈em〉PmAMP-1〈/em〉 cDNA was cloned and sequenced by rapid amplification of cDNA ends (RACE) and mRNA expression of was analyzed by quantitative real-time PCR (qRT-PCR). From the results of this study, full-length 〈em〉PmAMP-1 c〈/em〉DNA was shown to be 700 base pairs (bp) long with an open reading frame (ORF) of 294 bp, encoding 97 amino acids with a predicted structure that is mostly α-helices. 〈em〉PmAMP-〈/em〉1 mRNA was constitutively expressed in all tested tissues including the adductor muscle, mantle, hepatopancreas, gill, gonads and hemocytes. The highest level of 〈em〉PmAMP-〈/em〉1 transcription was observed at 8 h and 2 h after bacterial challenge in hemocytes and adductor muscle (p 〈 0.01), respectively. Furthermore, PmAMP-1 caused significant morphological alterations in 〈em〉E. coli,〈/em〉 as shown by transmission electron microscopy (TEM). The results from this study provide a valuable base for further exploration of molluscan innate immunity and immune response.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 141〈/p〉 〈p〉Author(s): Ningning Wang, Yanan Ma, Zhuoqun Liu, Lei Liu, Keming Yang, Yaguang Wei, Yang Liu, Xin Chen, Xiance Sun, Deliang Wen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Exposure to fine particular matter (≤2.5 μM, PM〈sub〉2.5〈/sub〉) contributes to increased risk of obesity and type 2 diabetes. Hydroxytyrosol (HT), a simple polyphenol found in virgin olive oil, is considered to be beneficial for cardiovascular and metabolic disorders. The current study determined whether HT could improve PM〈sub〉2.5〈/sub〉-induced adiposity and insulin resistance (IR), and explored the underlying mechanisms. Fifteen adult female C57BL/6j mice on a chow diet were randomly divided into three groups receiving (1) sterile PBS, (2) PM〈sub〉2.5〈/sub〉 suspended in sterile PBS (1 mg/mL) and (3) PM〈sub〉2.5〈/sub〉+HT (50 mg/kg/day). PM〈sub〉2.5〈/sub〉/PBS exposure was administered by oropharynx instillation every other day and HT supplementation was achieved by gavage every day. Four-week PM〈sub〉2.5〈/sub〉 exposure did not affect body weight, but significantly increased visceral fat mass. The abdominal adiposity coincided with adipocyte hypertrophy and proliferation in visceral white adipose tissue (WAT), as well as decreased metabolic activity in brown adipose tissue and subcutaneous WAT. PM〈sub〉2.5〈/sub〉 enhanced the oxidative stress by diminishing antioxidant enzyme activities in liver and serum, whereas contents of 4-hydroxynonenal (4-HNE), malondialdehyde (MDA) levels in liver and serum were elevated. These changes were accompanied by macrophage infiltration and activation of NF-κB pathway in the liver. Moreover, PM〈sub〉2.5〈/sub〉 exposure led to glucose intolerance and insulin insensitivity, impaired hepatic glycogenesis, and decreased insulin-stimulated Akt phosphorylation in peripheral tissues. Importantly, HT treatment prevented PM〈sub〉2.5〈/sub〉-induced visceral adipogenesis, oxidative stress, hepatic inflammation and NF-κB activation, systemic and peripheral IR. In vitro, after HepG2 cells were incubated with PM〈sub〉2.5〈/sub〉 (0, 5, 25, 50, 100 and 200 μg/mL), reduced glutathione depletion and 4-HNE, 8-hydroxy-2'-deoxyguanosine, MDA increment in a dose-dependent manner were observed; likewise, insulin-stimulated glucose uptake decreased in a dose-dependent manner. Further, with antioxidant NAC and NF-κB inhibitor PDTC, we confirmed that HT attenuated PM〈sub〉2.5〈/sub〉-induced IR through restraining NF-κB activation evoked by oxidative stress. In addition, HT could expand gut microbiota richness, reduce pathogenic bacteria and accommodate the microbial architecture in PM〈sub〉2.5〈/sub〉-exposed mice, which were correlated with parameters of adiposity, oxidative stress and glycometabolism. HT could effectively correct imbalanced oxidative stress triggered by PM〈sub〉2.5〈/sub〉, in turn ameliorated NF-κB pathway and insulin signaling. Gut microbiota may mediate the actions of HT.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉A schematic illustration of how HT interfered with PM〈sub〉2.5〈/sub〉-induced oxidative stress and metabolic disorders in vivo and in vitro. vWAT, visceral white adipose tissue; scWAT, subcutaneous WAT; BAT, brown adipose tissue; PPARγ, peroxisome proliferator-activated receptor gamma; C/EBPα, CCAAT/enhancer-binding protein alpha; UCP1, uncoupling protein 1; COX2, cyclooxygenase 2; IL-1β, interleukin 1beta; TNFα, tumor necrosis factor alpha; GSK3β, glycogen synthase kinase 3β; GS, glycogen synthase; ↑indicates increase, ↓indicates decrease.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919301856-fx1.jpg" width="281" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 92〈/p〉 〈p〉Author(s): Bin Zhong, Zeyin Jiang, Zhenhuang Chen, Kazue Ishihara, Huilin Mao, Shanghong Wang, Gang Lin, Chengyu Hu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Recently, studies have shown that IκB kinase β (IKKβ), a critical kinase in the nucleus factor kappa-B (NF-κB) pathway, participates in inflammatory responses associated with unfolded protein response (UPR) and plays an important role in ER stress-induced cell death. The unfolded protein response (UPR), which is a regulatory system to restore cellular homeostasis in the endoplasmic reticulum (ER), such as oxidative stress, bacterial infection, and virus invasion. The UPR pathways have been reported to be involved in immune responses in mammals, including the classical NF-κB pathway. However, the molecular mechanism of their crosstalk remains to be elucidated. Previously, we demonstrated that IKKβ also has some conserved functions between fish and human, as grass carp (〈em〉Ctenopharyngodon idella〈/em〉) IKKβ (CiIKKβ) can activate NF-κB pathway. In this study, we found that CiIKKβ level in nucleus was elevated under ER stress and CiIKKβ can interact with grass carp X-box-binding protein 1 (CiXBP1S), a key transcription factor in UPR. Consistently, fluorescent histochemical analysis of grass carp kidney (CIK) cells indicated that CiIKKβ and CiXBP1S colocalized under ER stress. Furthermore, overexpression of CiIKKβ in CIK cells enhanced ER stress tolerance by regulating UPR signaling and resulted in the significant increase of cell viability.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 92〈/p〉 〈p〉Author(s): Lu-Yun Ni, Qing Han, Hong-Ping Chen, Xiao-Chun Luo, An-Xing Li, Xue-Ming Dan, Yan-Wei Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Macrophage expressed gene 1 (Mpeg1) is a molecule that can form pores and destroy the cell membrane of invading pathogens. In this study, we identified two Mpeg1 isoforms from the orange-spotted grouper (〈em〉Epinephelus coioides〈/em〉) and named them EcMpeg1a and EcMpeg1b. Predicted proteins of the two EcMpeg1s contained a signal peptide, a conserved membrane attack complex/perforin (MACPF) domain, a transmembrane segment, and an intracellular region. Sequence alignment demonstrated that two EcMpeg1 proteins share a high sequence identity with that of other teleosts. Tissue distribution analysis showed that EcMpeg1s were expressed in all tissues tested in healthy grouper, with the highest expression in the head kidney and spleen. After infection with the ciliate parasite 〈em〉Cryptocaryon irritans〈/em〉, expression of the two EcMpeg1s was significantly upregulated in the spleen and gills. Furthermore, the recombinant EcMpeg1a showed antiparasitic and antibacterial activity against Gram-negative and -positive bacteria, whereas EcMpeg1b had an inhibitory effect only against Gram-positive bacteria. These results indicated that EcMpeg1s play an important role in the host response against invading pathogens.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 123〈/p〉 〈p〉Author(s): Alicja E. Grzegorzewska, Monika K. Świderska, Hanna Winnicka, Leszek Niepolski, Maciej Bura, Małgorzata Łagiedo-Żelazowska, Paweł P. Jagodziński〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Responsiveness to the hepatitis B virus (HBV) vaccination in hemodialysis (HD) patients who had been exposed to the hepatitis E virus (HEV) and persistently generate antibodies against HEV remains unknown. Interferon (IFN)-λ3 positively correlates with the surface HBV antibodies (anti-HBs) in both healthy and HD subjects. We aimed to show whether HD patients differ in circulating IFN-λ3 and vaccine-induced anti-HBs titers concerning natural HEV immunization. HBV/HCV negative HD patients (31 HEV IgG positive, 45 HEV negative), HBV vaccinated and receiving booster doses as needed, had been tested for anti-HBs titers (CMIA) and IFN-λ3 concentrations (ELISA) in the blood collected before a dialysis session. There were no differences in circulating IFN-λ3 and anti-HBs titers between both groups. In responders to the HBV vaccine, there was a positive correlation between plasma IFN-λ3 levels and anti-HBs titers (r = 0.505, adjusted P = 0.01 in HEV exposed subjects; r = 0.523, adjusted P = 0.001 in controls). HEV past infection does not attenuate post-vaccination anti-HBs generation and does not influence a correlation between circulating IFN-λ3 levels and anti-HBs titers.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 123〈/p〉 〈p〉Author(s): Alan Valaperti, Pascal Bezel, Maya Vonow-Eisenring, Daniel Franzen, Urs C. Steiner〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉Measurement of cytokines in peripheral blood and bronchoalveolar lavage fluid (BALF) is a useful method to assess human immune responses in a large range of pulmonary diseases. One of the major pre-analytical challenges of cytokine analysis is the quality and stability of cytokines in the timeframe between sample collection and the separation of supernatant from cells.〈/p〉 〈p〉To evaluate if the method of storage may affect cytokine quantification, whole blood and BALF were collected, aliquoted, and left at room temperature (RT) to be processed at different time points. In addition, sera and BALF were left either at RT or at 4 °C for 24 h after cell separation to test cytokine variations in the absence of cells. Samples were analysed by a multiple array containing ten cytokines.〈/p〉 〈p〉Most of the cytokines analysed (interleukin (IL)-4, IL-5, IL-6, IL-12p70, IL-13, IL-17A, IL-23, interferon (IFN)-γ, and tumour necrosis factor (TNF)-α) did not show significant variations in whole blood and BALF. Levels of IL-8 however, increased after storage of whole blood and BALF for 24 h at RT. 〈em〉Ex vivo〈/em〉 IL-8 production seems to correlate with higher numbers of macrophages in collected BALF.〈/p〉 〈p〉These data demonstrate that many cytokines are stable for a brief time after sample collection. For IL-8, freshly collected whole blood and BALF should be quickly processed and frozen to avoid false positive results.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 92〈/p〉 〈p〉Author(s): Pengfei Chu, Libo He, Cheng Yang, Wencheng Zeng, Rong Huang, Lanjie Liao, Yongming Li, Zuoyan Zhu, Yaping Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Autophagy is an essential and conserved process that plays an important role in physiological homeostasis, adaptive response to stress and the immune response. Autophagy-related proteins (ATGs) are key components of the autophagic machinery. In the study, grass carp (〈em〉Ctenopharyngodon idella〈/em〉) autophagy-related gene 5 (〈em〉ATG5〈/em〉) and 12 (〈em〉ATG12〈/em〉) were identified. In the gill and intestine, 〈em〉ATG5〈/em〉 and 〈em〉ATG12〈/em〉 were highly expressed, but after grass carp reovirus (GCRV) infection, they were decreased significantly. In 〈em〉Ctenopharyngodon idella〈/em〉 kidney (CIK) cells, the sharp variation of 〈em〉ATG5〈/em〉 and 〈em〉ATG12〈/em〉 expression was observed after poly(I:C) infection. Subcellular localisation showed that ATG5 and ATG12 were evenly distributed in the cytoplasm and nucleus. However, the interaction between ATG5 and ATG12 was only found in cytoplasm in both 293T cells and CIK cells. In addition, the overexpression of ATG5 or ATG12 in 293T cells showed enhanced autophagy, and autophagic process was facilitated when ATG5 and ATG12 were simultaneously overexpressed. Dual-luciferase activity assay indicated that both ATG5 and ATG12 remarkably suppressed the promoter activity of 〈em〉IRF3〈/em〉, 〈em〉IRF7〈/em〉, and 〈em〉IFN-I〈/em〉. Further, ATG5 and ATG12 conjugate showed far stronger inhibitory affection on the expression of 〈em〉IFN-I〈/em〉 than either ATG5 or ATG12 in response to poly(I:C) or GCRV infection. Taken together, the results demonstrate that grass carp ATG5 and ATG12 play an important role in innate immunity and autophagy.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 92〈/p〉 〈p〉Author(s): Chao Xu, Wen-Bin Liu, Sofie Charlotte Remø, Bing-Ke Wang, Hua-Juan Shi, Li Zhang, Jia-Dai Liu, Xiang-Fei Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This study investigated the effects of restricted feeding on the growth performance, oxidative stress and inflammation of 〈em〉Megalobrama amblycephala〈/em〉 fed high-carbohydrate (HC) diets. Fish (46.94 ± 0.04 g) were randomly assigned to four groups containing the satiation of a control diet (30% carbohydrate) and three satiate levels (100% (HC1), 80% (HC2) and 60% (HC3)) of the HC diets (43% carbohydrate) for 8 weeks. Results showed that HC1 diet remarkably decreased final weight (FW), weight gain rate (WGR), specific growth rate (SGR), feed conversion ratio (FCR), hepatic activities of total anti-oxidation capacity (T-AOC), superoxide dismutase (SOD) and catalase (CAT), the AMP/ATP ratio, the p-AMPKα/t-AMPKα ratio, sirtuin-1 (SIRT1) protein expression and hepatic transcriptions of AMPKα2, SIRT1, nuclear factor erythroid 2-related factor 2 (Nrf2), catalase (CAT), manganese superoxide dismutase (Mn-SOD), glutathione peroxidase 1 (GPx1) and interleukin10 (IL 10) compared to the control group, whereas the opposite was true for protein efficiency ratio (PER), nitrogen retention efficiency (NRE), energy retention efficiency (ERE), plasma glucose levels, alanine transaminase (AST) and aspartate aminotransferase (ALT) activities, hepatic contents of malondialdehyde (MDA), tumour necrosis factor α (TNF α) and interleukin 1β (IL 1β), ATP and AMP contents and hepatic transcriptions of kelch-like ECH associating protein 1 (Keap1), IkB kinase α (IKK α), nuclear factor kappa B (NF-κB), TNF α, IL 1β, interleukin 6 (IL 6) and transforming growth factor β (TGF β). As for the HC groups, fish fed the HC2 diet obtained relatively high values of SGR, PER, NRE, ERE, hepatic activities of T-AOC, SOD and CAT, the AMP/ATP ratio, the p-AMPKα/t-AMPKα ratio, SIRT1 protein expression and hepatic transcriptions of AMPKα2, Nrf2, CAT, copper/zinc superoxide dismutase (Cu/Zn-SOD), Mn-SOD, GPx1, glutathione S-transferase (GST) and interleukin10 (IL 10), while the opposite was true for hepatic content of IL 6 and transcription of IKK α. Overall, an 80% satiation improved the growth performance and alleviated the oxidative stress and inflammation of blunt snout bream fed HC diets via the activation of the AMPK-SIRT1 pathway and the up-regulation of the activities and transcriptions of Nrf2-modulated antioxidant enzymes coupled with the depression of the levels and transcriptions of the NF-κB-mediated pro-inflammatory cytokines.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 92〈/p〉 〈p〉Author(s): Jiangfan Zhang, Chuanju Dong, Junchang Feng, Junpeng Li, Shengjie Li, Jianxin Feng, Xiaodi Duan, Gaigai Sun, Peng Xu, Xuejun Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉HIFs〈/em〉 (Hypoxia inducible factors) are the main regulators of the expression change of oxygen-dependent genes, in addition, they also play important roles in immune regulation. 〈em〉HIFs〈/em〉 participate in infectious diseases and inflammatory responses, providing us a new therapeutic target for the treatment of diseases. In this study, 16 〈em〉HIFs〈/em〉 were identified in common carp genome database. Comparative genomics analysis showed large expansion of 〈em〉HIF〈/em〉 gene family and approved the four round whole genome duplication (WGD) event in common carp. To further understand the function of 〈em〉HIFs〈/em〉, the domain architectures were predicted. All HIF proteins had the conserved HLH-PAS domain, which were essential for them to form dimer and bind to the downstream targets. The differences in domain of HIFα and HIFβ might result in their different functions. Phylogenetic analysis revealed that all 〈em〉HIFs〈/em〉 were divided into two subfamilies and the 〈em〉HIFs〈/em〉 in common carp were clustered with their teleost counterparts indicating they are highly conservative during evolution. In addition, the tissue distribution was examined by RT-PCR showed that most of 〈em〉HIF〈/em〉 genes had a wide range of tissue distribution but exhibited tissue-specific expression patterns. The expression divergences were observed between the copy genes, for example, 〈em〉HIF1A-1〈/em〉, 〈em〉HIF2A-1〈/em〉, 〈em〉ARNT-〈/em〉2 had wide tissue distribution while their copies had limited tissue distribution, proving the function divergence of copies post the WGD event. In order to find an effective activation of 〈em〉HIFs〈/em〉 and apply to treatment of aquatic diseases, we investigate the dietary supplementation effects of different strains of 〈em〉Lactococcus lactis〈/em〉 on the expression of 〈em〉HIFα〈/em〉 subfamily members in kidney of common carp infected with 〈em〉A. hydrophila〈/em〉. In addition, all of the 〈em〉HIF〈/em〉 genes have a high expression in the early stages of infection, and decreased in the treatment time point of 48 h in common carp. This phenomenon confirms that as a switch, the main function of 〈em〉HIFs〈/em〉 is to regulate the production of immune response factors in early infection. So activation of the switch may be an effective method for infectious disease treatment. As expected, the treatment groups improved the expression of 〈em〉HIFs〈/em〉 compared with the control group, and the effects of the three strains are different. The strain1 of 〈em〉L. lactis〈/em〉 had a stronger induction on 〈em〉HIF〈/em〉 genes than strain2 and strain3, and it might be applied as a potential activation of 〈em〉HIF〈/em〉 genes for disease treatment. So, adding befitting 〈em〉L. lactis〈/em〉 maybe a well method to activate the 〈em〉HIF〈/em〉 genes to protect them from mycobacterial infection.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 92〈/p〉 〈p〉Author(s): K.A.S.N. Shanaka, M.D. Neranjan Tharuka, Thanthrige Thiunuwan Priyathilaka, Jehee Lee〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Viperin, also known as RSAD2 (Radical S-adenosyl methionine domain containing 2), is an interferon-induced endoplasmic reticulum-associated antiviral protein. Previous studies have shown that viperin levels are elevated in the presence of viral RNA, but it has rarely been characterized in marine organisms. This study was designed to functionally characterize rockfish viperin (〈em〉SsVip〈/em〉), to examine the effects of different immune stimulants on its expression, and to determine its subcellular localization. SsVip is a 349 amino acid protein with a predicted molecular mass of 40.24 kDa. It contains an S-adenosyl 〈span〉l〈/span〉-methionine binding conserved domain with a CNYKCGFC sequence. Unchallenged tissue expression analysis using quantitative real time PCR (qPCR) revealed 〈em〉SsVip〈/em〉 expression to be the highest in the blood, followed by the spleen. When challenged with poly I:C, 〈em〉SsVip〈/em〉 was upregulated by approximately 60-fold in the blood after 24 h, and approximately 50-fold in the spleen after 12 h. Notable upregulation was detected throughout the poly I:C challenge experiment in both tissues. Significant expression of 〈em〉SsVip〈/em〉 was detected in the blood following 〈em〉Streptococcus iniae〈/em〉 and lipopolysaccharide challenge, and viral hemorrhagic septicemia virus (VHSV) gene transcription was significantly downregulated during SsVip overexpression. Furthermore, cell viability assay and virus titer quantification with the presence of SsVip revealed a significant reduction in virus replication. As with previously identified viperin counterparts, SsVip was localized in the endoplasmic reticulum. Our findings show that SsVip is an antiviral protein crucial to innate immune defense.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell, Volume 50, Issue 1〈/p〉 〈p〉Author(s): Amir J. Bidhendi, Anja Geitmann〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Morphogenesis of wavy epidermal pavement cells in plants has fascinated researchers for decades. A mechanical mechanism had been proposed in which the anticlinal cell walls, forming the in-plane cell borders, feature contiguous stiff and soft zones that generate waves upon stretching. We replicated this model as designed and also expanded on it to test its validity for three-dimensional (3D) cell geometry. Our results suggest that both the assumptions going into and the predictions arising from this hypothesis do not stand closer scrutiny and may misguide experimentalists. Unlike what the published data seem to suggest, we observed that only waves of negligible magnitude can be formed by this anticlinal stretch model and that these are virtually eliminated when full 3D geometry of the cell is considered. Further, the model produces cell wall stresses that do not match the experimental evidence.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1534580719303727-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 1 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell, Volume 50, Issue 1〈/p〉 〈p〉Author(s): Avinash Thakur, Pamela A. Hoodless〈/p〉 〈div〉〈p〉To date, how epigenetic changes are regulated during liver regeneration remains unclear. In this issue of 〈em〉Developmental Cell〈/em〉, Wang and colleagues (2019) employed transcriptomic and epigenomic profiling to explore how 〈em〉Uhrf1〈/em〉, an epigenetic regulator of DNA methylation, functions in liver regeneration using a mouse model of partial hepatectomy.〈/p〉〈/div〉

Description: 〈p〉Publication date: 1 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell, Volume 50, Issue 1〈/p〉 〈p〉Author(s): Dongjie Zhou, Toru Suzuki, Maki Asami, Anthony C.F. Perry〈/p〉

Description: 〈p〉Publication date: 1 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell, Volume 50, Issue 1〈/p〉 〈p〉Author(s): Siti Nur Sarah Morris, James A. Olzmann〈/p〉 〈div〉〈p〉In this issue of 〈em〉Developmental Cell〈/em〉, Chorlay et al. (2019) provide evidence that asymmetric membrane surface tension determines the directionality of lipid droplet (LD) emergence. Furthermore, phospholipid synthesis “refills” the outer leaflet of the endoplasmic reticulum (ER) membrane to maintain cytosolic LD emergence and prevent disruptions to ER homeostasis.〈/p〉〈/div〉

Description: 〈p〉Publication date: 1 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell, Volume 50, Issue 1〈/p〉 〈p〉Author(s): Colin C. Conine, Fengyun Sun, Lina Song, Jaime A. Rivera-Pérez, Oliver J. Rando〈/p〉

Description: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 141〈/p〉 〈p〉Author(s): Li-Min Zhang, Dong-Xue Zhang, Lan Fu, Yan Li, Xu-Peng Wang, Man-Man Qi, Chen-Chen Li, Pan-Pan Song, Xiao-Dong Wang, Xiang-Jun Kong〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Objective〈/h6〉 〈p〉Carbon monoxide (CO) releasing molecule (CORM)-3, a water-soluble CORM, has protective effects against inflammatory and ischemia/reperfusion injury. We determined the effect of CORM-3 against neuronal pyroptosis in a model of hemorrhagic shock and resuscitation (HSR) in rats via mitochondrial regulation.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉Rats were treated with CORM-3 (4 mg/kg) in vitro after HSR. We measured cortical CO content 3–24 h after HSR; assessed neuronal pyroptosis, mitochondrial morphology, ROS production, and mitochondrial membrane potential at 12 h after HSR; and evaluated brain magnetic resonance imaging at 24 h after HSR and learning ability 30 days after HSR. We also measured soluble guanylate-cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway activity using a blocker of sGC, NS2028, and 〈sup〉125〈/sup〉I-cGMP assay.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Among rats that underwent HSR, CORM-3-treated rats had more CO in the cortical tissue than sham- and iCORM-3-treated rats. CORM-3-treated rats had significantly less neuronal pyroptosis in the cortical tissue; higher sGC activity and cGMP content; lower ROS production; better mitochondrial morphology, function, and membrane potential; and enhanced learning/memory ability than HSR-treated rats. However, these neuroprotective effects of CORM-3 were partially inhibited by NS2028.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉CORM-3 may alleviate neuronal pyroptosis and improve neurological recovery in HSR through mitochondrial regulation mediated by the sGC–cGMP pathway. Thus, CO administration could be a promising therapeutic strategy for hemorrhagic shock.〈/p〉 〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉A proposed diagram tying together the observations involved in CORM-3-induced neuroprotection against HSR. HSR increased neuronal pyroptosis, which might be associated with up-regulation of ROS. CORM-3 not only significantly reduced these neuronal pyroptosis, but also improved long-term learning ability and T2-weighted MRI, which might be associated with inhibition of mitochondrial dysfunction through regulating activity in sGC-cGMP signal pathway, whereas NS2028, a blocker of sGC, could partially inhibit these neuroprotective effects.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S089158491930855X-fx1.jpg" width="441" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 125〈/p〉 〈p〉Author(s): Domenico Galati, Serena Zanotta, Angelo Canora, Giorgio E. Polistina, Carmine Nicoletta, Giacomo Ghinassi, Emanuele Ciasullo, Marialuisa Bocchino〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Recent evidence suggests that alterations of the immune responses are associated with the inflammatory nature of obstructive sleep apnea (OSA) and of its related co-morbidities. In this scenario, we asked whether circulating dendritic cell (DC) subsets may be possible players as their role has not yet been detailed. The frequency distribution of peripheral blood myeloid (mDC1 and mDC2) and plasmacytoid (p) DCs was investigated by mean of multi-parametric flow cytometry in 45 OSA patients (mean age: 53 yrs; M = 29) at the time of the first diagnosis and compared to 30 age- and sex-matched healthy controls. Oxidative burst (OB) and serum levels of tumor necrosis factor (TNF)-α, (interleukin) (IL)-6, interferon (INF)-γ, IL-2, IL-4, IL-10 and vascular endothelial growth factor (VEGF) were also analyzed. All subsets of circulating DCs were significantly depleted in OSA patients as compared to healthy subjects (p 〈 0.01, in all instances), with mDC2 and pDC subtypes being more severely compromised. These findings were co-existing with higher levels of OB along with an increased expression of IL-6, IL-10, TNF-α, IFN-γ, and VEGF (p 〈 0.005 in all instances). In particular, IL6 levels were significantly higher (p = 0.013) in severe OSA patients (apnea/hypopnea index 〉30) and were inversely correlated with both mDC2 (r = −0.802, p 〈 0.007) and pDC (r = −0.317, p = 0.04) subsets. We first provide evidence for a constitutive reduction of all circulating DC subsets in OSA patients. Perturbation of DCs coexists with an inflammatory milieu and is negatively correlated with the expression of IL-6, which is actually recognized as a pivotal inhibitor of DC maturation. Future studies exploring the contribution of DCs in the pathogenesis of OSA and of its complications should be encouraged.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 141〈/p〉 〈p〉Author(s): 〈/p〉

Description: 〈p〉Publication date: Available online 29 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Namrata Rastogi, Rishi Kumar Gara, Rachana Trivedi, Akanksha Singh, Preety Dixit, Rakesh Maurya, Shivali Duggal, M.L.B. Bhatt, Sarika Singh, Durga Prasad Mishra〈/p〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 143〈/p〉 〈p〉Author(s): Gangduo Wang, Maki Wakamiya, Jianling Wang, G.A. Shakeel Ansari, M. Firoze Khan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Reactive trichloroethene (TCE) metabolites and oxidative stress are involved in TCE-mediated autoimmunity, as evident from our earlier studies in MRL+/+ mice. However, molecular mechanisms underlying the autoimmunity remain largely unknown. Cytochrome P450 2E1 (CYP2E1), the major enzyme responsible for TCE metabolism, could contribute to TCE-induced toxic response through free radical generation. The current study was, therefore, aimed to further evaluate the significance of TCE metabolism leading to oxidative stress and autoimmune response by using MRL+/+ mice that lack CYP2E1. The 〈em〉Cyp2e1〈/em〉-null MRL+/+ mice were generated by backcrossing 〈em〉Cyp2e1〈/em〉-null mice (B6N; 129S4-〈em〉Cyp2e1〈/em〉) to MRL +/+ mice. Female MRL+/+ and 〈em〉Cyp2e1〈/em〉-null MRL+/+ mice were given TCE (10 mmol/kg, i.p., every 4th day) for 6 weeks; their respective controls received corn oil only. TCE treatment in MRL+/+ mice induced oxidative stress, evident from significantly increased serum malondiadelhyde (MDA)-protein adducts, their antibodies and reduced liver GSH levels. TCE treatment also modulated Nrf2 pathway with decreased Nrf2 and HO-1, and elevated NF-κB (p65) expression in the liver. TCE exposure also led to increases in serum antinuclear antibodies (ANA) and anti-double stranded DNA antibodies (anti-dsDNA). Although TCE treatment in 〈em〉Cyp2e1〈/em〉-null MRL+/+ mice also led to increases in serum MDA-protein adducts and their antibodies, changes in liver GSH, Nrf2, HO-1 and NF-κB along with increases in serum ANA, anti-dsDNA, the alterations in the oxidative stress and autoimmunity markers in these mice were less pronounced compared to those in MRL+/+ mice. These findings support the contribution of CYP2E1-mediated TCE metabolism in autoimmune response and an important role of Nrf2 pathway in TCE-mediated autoimmunity.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919311682-fx1.jpg" width="155" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Jing Li, Zhi-Bin Wu, Zhao Zhang, Ji-Wei Zha, Shen-Ye Qu, Xiao-Zhou Qi, Gao-Xue Wang, Fei Ling〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Nowadays, there is no suitable treatment for vibriosis in groupers. So an eco-efficient and environmentally friendly treatment is necessary for the grouper industry. Probiotic-feeding has been a promising strategy to control the bacterial pathogens in aquaculture. A new 〈em〉Bacillus velezensis〈/em〉 strain named K2 was isolated from the intestinal tract of healthy grouper, and exhibited wide antimicrobial spectrum of against fish pathogens, including 〈em〉Vibrio harveyi〈/em〉, 〈em〉Vibrio alginolyticus〈/em〉, 〈em〉Aeromonas hydrophila〈/em〉, 〈em〉Aeromonas veronii〈/em〉, 〈em〉Aeromonas caviae〈/em〉, 〈em〉Enterococcus casseliflavus〈/em〉 and 〈em〉Lactococcus garvieae〈/em〉. Moreover, results of the safety of 〈em〉B. velezensis〈/em〉 K2 showed that intraperitoneal injection of K2 in healthy grouper did not cause any pathological abnormality or death, indicating this bacteria could be considered as a candidate probiotic in aquaculture. Groupers were fed with the diets containing 1 × 10〈sup〉7〈/sup〉 cfu/g of 〈em〉B. velezensis〈/em〉 K2 for 4 weeks. Various immune parameters were examined at 1, 2, 3, and 4 weeks of post-feeding. Results showed that diets supplemented with K2 significantly increased serum acid phosphatase (ACP) activity (〈em〉P〈/em〉 〈 0.05). Results of the mRNA expression of immune-related genes in the head kidney of hybrid grouper showed that the expression of lysozyme gene was significantly upregulated after 1 and 2 weeks of feeding (〈em〉P〈/em〉 〈 0.05). A significant up-regulation of the expression of piscidin, IgM and MyD88 were detected at day 21, whereas the TLR3 and TLR5 showed lower expression compared to the controls during 21 days, and a significant decrease of TLR3 gene was found at day 28 (〈em〉P〈/em〉 〈 0.05). After challenge with 〈em〉V. harveyi〈/em〉, the survival rate of fish administrated with the strain K2 for 28 days was signifiacantly higher than the controls without this strain (〈em〉P〈/em〉 〈 0.05). These results collectively suggest that 〈em〉B. velezensis〈/em〉 K2 is a potential probiotic species to improve health status and disease resistance and can be developed as a probiotic agent in grouper industry.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Phennapa Promthale, Pattira Pongtippatee, Boonsirm Withyachumnarnkul, Kanokpan Wongprasert〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Fishmeal is the main source of protein in the shrimp feed industry and is normally derived from trash fish. As such, the production of fishmeal has an adverse effect on the marine environment by taking away small and juvenile fish, leading to depletion of marine species. There is a need for alternative sources of protein which will substitute fishmeal in the aquaculture industry. This study evaluated the components and nutritional efficacy of bioflocs, which were used to substitute fishmeal protein. The effect of bioflocs diets on growth performance, survival rate, and immune response in shrimp compared to normal fishmeal feed were determined. Bioflocs were harvested from the shrimp ponds (C:N ratio 〉12:1) at Shrimp Village, Chaiya district, Surat Thani, Thailand. The total protein in bioflocs was about 48% and the total lipid was about 5% (dried weight) and the percentages of essential amino acids (EAA) and fatty acids (EFA) in bioflocs were similar to those of fishmeal feed. Shrimp fed with the different dietary bioflocs feed regimens [% to replace fishmeal; 0% (B0), 25% (B25), 50% (B50), 75% (B75), and 100% (B100)] for 42 days revealed that all growth parameters were almost similar to those of the control shrimp (shrimp fed with normal fishmeal, B0) including final body weight, weight gain, specific growth rate, and feed conversion ratio. Remarkably, the survival rates, the levels of immune parameters, and expression of immune genes (proPO-I, PEN-4 and dicer) were significantly higher in bioflocs fed shrimp, especially in B25 and B50 shrimp. Moreover, B25 and B50 bioflocs fed shrimp showed notably increased survival rates following 〈em〉Vibrio parahaemolyticus (V. parahaemolyticus)〈/em〉 infection. In conclusion, the present study demonstrates that shrimp survival and immunity are enhanced by biofiocs substituted fishmeal. Significantly, the bioflocs diets activated the immune response to prevent 〈em〉V. parahaemolyticus〈/em〉 infection.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Sarah J. Poynter, Shanee Herrington-Krause, Stephanie J. DeWitte-Orr〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In mammals, the multifunctional DExH/D-box helicases, DDX3 and DHX9, are nucleic acid sensors with a role in antiviral immunity; their role in innate immunity in fish is not yet understood. In the present study, full-length DDX3 and DHX9 coding sequences were identified in rainbow trout (〈em〉Oncorhynchus mykiss)〈/em〉. Bioinformatic analysis demonstrated both deduced proteins were similar to those of other species, with ~80% identity to other fish species and ~70–75% identity to mammals, and both protein sequences had conserved domains found amongst all species. Phylogenetic analysis revealed clustering of DDX3 and DHX9 with corresponding proteins from other fish. Cellular localization of overexpressed DDX3 and DHX9 was performed using GFP-tagged proteins, and endogenous DDX3 localization was measured using immunocytochemistry. In the rainbow trout gonadal cell line, RTG-2, DHX9 localized mostly to the nucleus, while DDX3 was found mainly in the cytoplasm. Tissue distribution from healthy juvenile rainbow trout revealed ubiquitous constitutive expression, highest levels of DDX3 expression were seen in the liver and DHX9 levels were fairly consistent among all tissues tested. Stimulation of RTG-2 cells revealed that DDX3 and DHX9 transcripts were both significantly upregulated by treatment with the dsRNA molecule, poly I:C. A pull-down assay suggested both proteins were able to bind dsRNA. In addition to their roles in RNA metabolism, the conserved common domains found between the rainbow trout proteins and other species having defined antiviral roles, combined with the ability for the proteins to bind to dsRNA, suggest these proteins may play an important role in fish innate antiviral immunity. Future studies on both DDX3 and DHX9 function will contribute to a better understanding of teleost immunity.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Ke-Cheng Zhu, Hua-Yang Guo, Nan Zhang, Bao-Suo Liu, Liang Guo, Shi-Gui Jiang, Dian-Chang Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Interferon regulatory factor 8 (IRF8) increases type I IFN transcription levels by binding to IFN promoters, thereby playing a role in innate immunity. Nevertheless, the detailed mechanism through which IRF8 regulates type II IFN in fish remains ambiguous. In the present study, two genes from the golden pompano (〈em〉Trachinotus ovatus〈/em〉), 〈em〉IRF8〈/em〉 (〈em〉ToIRF8〈/em〉) and 〈em〉IFN gamma〈/em〉 (〈em〉ToIFNγ〈/em〉), were identified in the IFN/IRF-based signalling pathway. The full-length 〈em〉ToIRF8〈/em〉 cDNA was composed of 2,141 bp and encoded a 421 amino acid polypeptide; the genomic DNA was 2,917 bp in length and consisted of 8 exons and 7 introns. The putative protein showed the highest sequence identity (90–92%) with fish IRF8 and possessed a DNA-binding domain (DBD), an IRF-association domain (IAD) and a nuclear localization signal (NLS) motif consistent with those of IRF8 in other vertebrates. Furthermore, the 〈em〉ToIRF8〈/em〉 transcripts were expressed in all examined tissues of healthy fish, with higher levels observed in the central nervous and immune relevant tissues. They were upregulated by polyinosinic acid: polycytidylic acid [poly (I: C)], lipopolysaccharide (LPS) and flagellin treatments in the blood, liver, intestine and kidney. The results from assays of subcellular localization showed that 〈em〉ToIRF8〈/em〉 was localized to the cytoplasm. Moreover, to investigate whether ToIRF8 was a regulator of 〈em〉ToIFNγ〈/em〉, a promoter analysis was performed using progressive deletion mutations of 〈em〉ToIFNγ〈/em〉. The results indicated that the region from −601 bp to −468 bp includes the core promoter. Mutation analyses indicated that the activity of the 〈em〉ToIFNγ〈/em〉 promoter significantly decreased after the targeted mutation of the M1-M3 binding sites. Additionally, overexpressed 〈em〉ToIRF8〈/em〉 in vitro notably increased the expression of several IFN/IRF-based signalling pathway genes. These results suggest that 〈em〉IRF8〈/em〉 is vital in the defence of 〈em〉T. ovatus〈/em〉 against bacterial infection and contributes to a better understanding of the transcriptional mechanisms of ToIRF8 on type II IFN in fish.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): You-Cheng Hseu, Hsin-Ju Cho, Yugandhar Vudhya Gowrisankar, Varadharajan Thiyagarajan, Xuan-Zao Chen, Kai-Yuan Lin, Hui-Chi Huang, Hsin-Ling Yang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Kalantuboside B (KB), a natural bufadienolide derivative extracted from the succulent plant 〈em〉Kalanchoe tubiflora〈/em〉, is well-known for its cardiotonic, immunomodulatory, and anti-inflammatory properties. In this study, we tested 〈em〉in vitro〈/em〉 and 〈em〉in vivo〈/em〉 anti-cancer efficacy with low concentrations of KB (5–30 ng/mL; 8.7–52.2 nM) on A2058 melanoma cells; and for the molecular mechanisms that underlie them. KB significantly inhibited the cell viability and colony formation via arresting the cell cycle at G2/M phase. There was an association with a decrease in Cyclin A/B1, Cdc25C, and Cdc2 expressions. Further, this treatment indicated the induction of apoptosis, DNA fragmentation, cytochrome 〈em〉c〈/em〉 release, and caspase-3, -8, -9, and -12 activation, and PARP cleavage, which shows that mitochondrial, death-receptor, and ER-stress signaling pathways are involved. KB-induced autophagy was apparent from enhanced LC3-II accumulation, GFP-LC3 puncta, and AVO formation. Surprisingly, KB-mediated cell death was potentiated by 3-MA and CQ to suggest the role of autophagy as a cytoprotective mechanism. Moreover, KB-treated A2058 cells enhanced intracellular ROS generation and antioxidant NAC prevented apoptosis and reversed cytoprotective autophagy. Interestingly, KB-induced apoptosis (PARP cleavage) and cytoprotective autophagy (LC3-II accumulation) were mediated by the up-regulation of the ERK signaling pathway. It was also shown that KB promoted cytoprotective autophagy by a calcium dependent-p53 downregulation pathway. 〈em〉In vivo〈/em〉 data showed that KB suppressed tumor growth significantly in A2058-xenografted nude mice. A Western blot indicated cell-cycle inhibition (cyclin A reduction), apoptosis induction (PARP cleavage and Bcl-2 inhibition), and cytoprotective autophagy (LC3-II upregulation and p53 downregulation) in KB-treated A2058-xenografted mice. Our findings suggested that KB-induced ROS pathway plays a role in mediating the apoptosis and cytoprotective autophagy in human melanoma cells. Thus, KB is considered to be a putative anti-tumor agent.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S089158491931278X-fx1.jpg" width="152" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 143〈/p〉 〈p〉Author(s): Lu Sun, Yan-Li Liu, Fang Ye, Jing-Wen Xie, Jia-Wei Zeng, Li Qin, Jing Xue, Yi-Ting Wang, Kai-Min Guo, Ming-Ming Ma, Yong-Bo Tang, Xiao-Yan Li, Min Gao〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Transient Receptor Potential Melastatin-2 (TRPM2) is a nonselective cation channel mediating Ca〈sup〉2+〈/sup〉 influx in response to oxidative stress. Given that insulin resistance-related endothelial dysfunction in obesity attributes to fatty-acid-induced reactive oxygen species (ROS) overproduction, in this study, we addressed the possible role of TRPM2 in obesity-related endothelial insulin resistance and the underlying mechanisms. Whole-cell patch clamp technique, intracellular Ca〈sup〉2+〈/sup〉 concentration measurement, western blot, vasorelaxation assay, and high-fat diet (HFD)-induced obese model were employed to assess the relationship between TRPM2 and endothelial insulin response. We found that both the expression and activity of TRPM2 were higher in endothelial cells of obese mice. Palmitate rose a cationic current in endothelial cells which was inhibited or enlarged by TRPM2 knockdown or overexpression. Silencing of TRPM2 remarkably improved insulin-induced endothelial Akt activation, nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production, while TRPM2 overexpression resulted in the opposite effects. Furthermore, TRPM2-mediated Ca〈sup〉2+〈/sup〉 entry, CaMKII activation and the following activation of PERK/ATF4/TRB3 cascade were involved in the mechanism of obesity or palmitate-induced endothelial insulin resistance. Notably, in vivo study, knockdown of TRPM2 with adeno-associated virus harboring short-hairpin RNA (shRNA) against TRPM2 alleviated endothelial insulin resistance and ameliorated endothelium-dependent vasodilatation in obese mice. Thus, these results suggest that TRPM2-activated Ca〈sup〉2+〈/sup〉 signaling is necessary to induce insulin resistance-related endothelial dysfunction in obesity. Downregulation or pharmacological inhibition of TRPM2 channels may lead to the development of effective drugs for treatment of endothelial dysfunction associated with oxidative stress state.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919308330-fx1.jpg" width="243" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 21 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Lindsey Y.K. Suh, Dinesh Babu, Lusine Tonoyan, Béla Reiz, Randy Whittal, S. Amirhossein Tabatabaei-Dakhili, Andrew G. Morgan, Carlos A. Velázquez-Martínez, Arno G. Siraki〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Edaravone is a highly potent antioxidant drug known to scavenge free radical species and prevent free radical-induced lipid peroxidation. In this study, we investigated the effect of edaravone on the myeloperoxidase (MPO) activity, an enzyme responsible for the production of an array of neutrophil-derived oxidants that can cause cellular damage. The addition of edaravone to the reaction of MPO and H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 significantly enhanced the reduction of MPO Compound II back to native MPO. Interestingly, the MPO-mediated production of toxic hypochlorous acid exhibited a concentration-dependent biphasic effect, with the apparent optimal edaravone concentration at 10 μM. Oxidation of edaravone by MPO was examined by various analytical methods. An MPO-catalyzed product(s) of edaravone was identified at 350 nm by kinetic analysis of UV–Vis spectroscopy. Several MPO-catalyzed metabolites of edaravone were proposed from the LC-MS analyses, including oxidized dimers from edaravone radicals. Electron spin resonance (ESR) spin trapping detected a carbon-centred radical metabolite of edaravone. NMR studies revealed that there are two exchangeable hydrogens, one of which is on the α-carbon, justifying the carbon-centred edaravone radical produced from MPO. Despite the formation of an edaravone carbon-radical metabolite, it did not appear to effectively oxidize GSH (in comparison with phenoxyl radicals). A viability (ATP) and cytotoxicity (LDH release) assay showed a concentration-dependent effect of edaravone in on HL-60 cells treated with either a bolus concentration of 30 μM H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 or a flux of H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 generated by 5 mM glucose and 10 mU/mL glucose oxidase. The H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉-induced toxicity was ameliorated at high edaravone concentration (100–200 μM). In contrast, low concentrations of edaravone (1–10 μM) exacerbated the H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉-induced toxicity. However, the effect of edaravone at low concentration (0–10 μM) appeared more prominent with the LDH assay. The cellular findings correlated with the biochemical studies with respect to hypochlorous acid formation. These findings provide interesting perspectives regarding the duality of edaravone as an antioxidant drug.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919303715-fx1.jpg" width="500" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 125〈/p〉 〈p〉Author(s): André Rolim Belisário, Érica Leandro Marciano Vieira, Jéssica Alves de Almeida, Fabíola Gomes Mendes, Aline Silva Miranda, Paulo Val Rezende, Marcos Borato Viana, Ana Cristina Simões e Silva〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Sickle cell anemia (SCA) is an important cause of chronic kidney disease, but its pathophysiology is not completely understood. The aim of this study was to compare inflammatory biomarkers in urine samples of SCA children with and without albuminuria, and to explore correlations with renin-angiotensin system (RAS) molecules. A cross-sectional study of 213 children selected from the Minas Gerais state cohort were assigned to two groups: Group 1–89 children with SCA who had albuminuria; Group 2–124 children with SCA and normal albuminuria matched by age and sex with group 1. A subset of 89 children was prospectively followed for a median time of 1.1 year. Inflammatory biomarkers (chemokines and cytokines) in urine were measured using cytometric beads array, and RAS molecules were measured by ELISA. Children with albuminuria had significantly higher urinary levels of IP-10/CXCL10, MCP-1/CCL2, MIG/CXCL9, IL-8/CXCL8, IL-12p70, TNF, IL-10, and IL-6 than patients with normal albuminuria. In the correlation analysis, albumin/creatinine ratio was significantly and positively correlated with IP-10/CXCL10, MCP-1/CCL2, MIG/CXCL9, IL-8/CXCL8, TNF, IL-10, and IL-6. Significant correlations were found between inflammatory and RAS molecules. In the prospective analysis, cumulative risk of persistent albuminuria was higher for children with urinary levels of IP-10/CXCL10 or IL-6 above the 50th percentile. Our data showed that inflammatory markers and RAS molecules might contribute to the occurrence of albuminuria in children with SCA, suggesting that both pathways interact in sickle cell nephropathy.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Tetsuro Ikuta, Akihiro Tame, Masaki Saito, Yui Aoki, Yukiko Nagai, Makoto Sugimura, Koji Inoue, Katsunori Fujikura, Kazue Ohishi, Tadashi Maruyama, Takao Yoshida〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In symbiotic systems in which symbionts are transmitted horizontally, hosts must accept symbionts from the environment while defending themselves against invading pathogenic microorganisms. How they distinguish pathogens from symbionts and how the latter evade host immune defences are not clearly understood. Recognition of foreign materials is one of the most critical steps in stimulating immune responses, and pattern recognition receptors (PRRs) play vital roles in this process. In this study, we focused on a group of highly conserved PRRs, peptidoglycan recognition proteins (PGRPs), in the deep-sea mussel, 〈em〉Bathymodiolus septemdierum〈/em〉, which harbours chemosynthetic bacteria in their gill epithelial cells. We isolated 〈em〉B. septemdierum〈/em〉 PGRP genes 〈em〉BsPGRP-S〈/em〉 and 〈em〉BsPGRP-L〈/em〉, which encode a short- and a long-type PGRP, respectively. The short-type PGRP has a signal peptide and was expressed in the asymbiotic goblet mucous cells in the gill epithelium, whereas the long-type PGRP was predicted to include a transmembrane domain and was expressed in gill bacteriocytes. Based on these findings, we hypothesize that the secreted and transmembrane PGRPs are engaged in host defence against pathogenic bacteria and/or in the regulation of symbiosis via different cellular localizations and mechanisms.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Guilherme Rabelo Coelho, Pedro Prezotto Neto, Fernanda Cortinhas Barbosa, Rafael Silva Dos Santos, Patrícia Brigatte, Patrick Jack Spencer, Sandra Coccuzzo Sampaio, Fernanda D’Amélio, Daniel Carvalho Pimenta, Juliana Mozer Sciani〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Stingrays skin secretions are largely studied due to the human envenoming medical relevance of the sting puncture that evolves to inflammatory events, including necrosis. Such toxic effects can be correlated to the biochemical composition of the sting mucus, according to the literature. Fish skin plays important biological roles, such as the control of the osmotic pressure gradient, protection against mechanical forces and microorganism infections. The mucus, on the other hand, is a rich and complex fluid, acting on swimming, nutrition and the innate immune system. The elasmobranch's epidermis is a tissue composed mainly by mucus secretory cells, and marine stingrays have already been described to present secretory glands spread throughout the body. Little is known about the biochemical composition of the stingray mucus, but recent studies have corroborated the importance of mucus in the envenomation process. Aiming to assess the mucus composition, a new non-invasive mucus collection method was developed that focused on peptides and proteins, and biological assays were performed to analyze the toxic and immune activities of the 〈em〉Hypanus americanus〈/em〉 mucus. Pathophysiological characterization showed the presence of peptidases on the mucus, as well as the induction of edema and leukocyte recruitment in mice. The fractionated mucus improved phagocytosis on macrophages and showed antimicrobial activity against 〈em〉T. rubrumç. neoformans〈/em〉 and 〈em〉C. albicans in vitro〈/em〉. The proteomic analyses showed the presence of immune-related proteins like actin, histones, hemoglobin, and ribosomal proteins. This protein pattern is similar to those reported for other fish mucus and stingray venoms. This is the first report depicting the 〈em〉Hypanus〈/em〉 stingray mucus composition, highlighting its biochemical composition and importance for the stingray immune system and the possible role on the envenomation process.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Mariana Maluli Marinho de Mello, Camila de Fátima Pereira de Faria, Fábio Sabbadin Zanuzzo, Elisabeth Criscuolo Urbinati〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In this study, we show that β-glucan can modulate cortisol release in fish. We simulated a common situation in aquaculture: the transport of fish followed by contact with an opportunistic pathogen and observed what effect glucan had on the immune and stress response in these conditions. Pacu (〈em〉Piaractus mesopotamicus〈/em〉) were fed with a diet containing β-glucan (0.1%) for 15 days prior to transport followed by an injection with heat-killed 〈em〉Aeromonas hydrophila.〈/em〉 We sampled fish before transport, at arrival and at 3 and 24 h after bacterial injection. β-Glucans are used in aquaculture and have a known immunostimulatory effect, which was observed in this study. The results showed that β-glucan modulated the plasma cortisol levels differently by increasing these levels up to 24 h after transport and preventing the increase caused by bacterial inoculum injection. In addition, β-glucan enhanced the activity of the complement system at 24 h and reduced the monocytes and lymphocytes number in peripheral blood at 3 and 24 h after bacterial inoculation. Our results suggest that β-glucan modulated a bidirectional interaction between the stress and the immune responses. The modulation of cortisol levels and the immunostimulation by β-glucan at different moments in our study suggest the compound has a protective effect by avoiding higher levels of the hormone and improving resistance against bacterial infection in pacu. These results add evidence to support the use of β-glucan as an immunomodulator in the aquaculture industry.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Min Sun Kim, Ki Hong Kim〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Although the type I interferon-mediated increase of Mx1 and ISG15 gene expression in Epithelioma papulosum cyprini (EPC) cells has been reported, the antiviral role of Mx1 and ISG15 in EPC cells has not been investigated. In this study, to know the anti-viral hemorrhagic septicemia virus (VHSV) role of Mx1 and ISG15 of EPC cells, either Mx1 or ISG15 gene was knocked-out using a CRISPR/Cas9 system, and the progression of cytopathic effects (CPE) and viral growth were analyzed. Mx1 gene and ISG15 gene knockout EPC cells were successfully produced via CRISPR/Cas9 coupled with a single-cell cloning. Through the sequence analysis, one clone showing two heterozygous indel patterns in Mx1 gene and a clone showing three heterozygous indel patterns in ISG15 gene were selected for further analyses. Mx1 knockout EPC cells did not show any differences in VHSV-mediated CPE progression, even when pre-treated with polyinosinic:polycytidylic acid (poly I:C), compared to control EPC cells. These results suggest that Mx1 in EPC cells may be unfunctional to cytoplasmic RNA viruses. In contrast to Mx1, ISG15 knockout cells showed clearly hampered anti-VHSV activity even when pre-treated with poly I:C, indicating that ISG15 plays an important role in type I interferon-mediated anti-viral activity in EPC cells, which allowed VHSV to replicate more efficiently in ISG15 knockout cells than Mx1 knockout and control cells.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): José Luis Sánchez-Salgado, Mohamed Alí Pereyra, Concepción Agundis, Montserrat Calzada-Ruiz, Erika Kantun-Briceño, Edgar Zenteno〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In crustaceans, it has been suggested that specific protection against pathogens could be triggered by vaccines and biological response modifiers; although the specific mechanisms of this protection have not been clarified yet. In the crayfish 〈em〉Cherax quadricarinatus〈/em〉, a humoral lectin (CqL) binds its own granular hemocytes through a specific receptor (CqLR) and increases the production of reactive oxygen species (ROS). In the present study, we challenged 〈em〉in vivo〈/em〉 crayfishes with immunostimulants, β-glucan (200 μg/kg) or LPS (20 μg/kg), and identified the participation of cellular and humoral mechanisms. The stimulants generated a complex modification in the total hemocytes count (THC), as well as in the proportion of hemocyte subsets. At 2 h after the challenge, the largest value in THC was observed in either challenged crayfishes. Furthermore, at the same time, hyaline hemocytes were the most abundant subset in the hemolymph; after 6 h, granular hemocytes (GH) were the most abundant hemocyte subset. It has been observed that a specific subset of GH possesses a CqLR that has been related to ROS production. After 2 and 6 h of the β-glucan challenge, a significant increase in CqLR expression was observed in the three circulating hemocyte subsets; also, an increased expression of CqL was detected in a granular hemocytes sub-population. After 2 and 6 h of stimulation, the specific activity of the serum lectin challenged with β-glucan was 250% and 160% higher than in the LPS-treated-group, respectively (〈em〉P〈/em〉 〈 0.05). Hemocytes from challenged crayfishes were stimulated 〈em〉ex vivo〈/em〉 with CqL, ROS production was 180% higher in hemocytes treated with β-glucan + CqL than in hemocytes treated with LPS + CqL (〈em〉P〈/em〉 〈 0.05). The results evidence the effectivity of immune stimulators to activate specific crayfish defense mechanisms, the participation of CqL and its receptor (CqLR) could play an important role in the regulation of immune cellular functions, like ROS production, in 〈em〉Cherax quadricarinatus〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Nikolai Mugue, Nadezhda Terekhanova, Sergey Afanasyev, Aleksei Krasnov〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Sturgeons represent a substantial scientific interest due to their high economic value, endangered status and also as the most primitive group of ray-finned fishes. Rapid progress in knowledge of sturgeon immunity was achieved recently with use of RNA sequencing. We report transcriptome sequencing of gill, head kidney, and spleen of bester sturgeon (a hybrid of beluga 〈em〉Huso huso〈/em〉 and sterlet 〈em〉Acipen〈/em〉s〈em〉er ruthenus〈/em〉) injected with synthetic double-stranded RNA (polyI:C). The composition of transcriptome and responses to treatment were examined in the context of comparative genomics with focus on immune genes. Sturgeon transcripts matched to 21.5 k different proteins (blastx). With reference to Atlantic salmon, the functional groups and pathways of the immune system were uniformly represented: at average 36.5 ± 0.8% genes were found. Immune genes comprise a significant fraction of transcriptome. Among twenty genes with highest transcription levels, five are specialized immune genes and two encode heme and iron binding proteins (〈em〉serotransferrin〈/em〉 and 〈em〉hemopexin〈/em〉) also known as acute phase proteins. Challenge induced multiple functional groups including apoptosis, cell cycle and a number of metabolic pathways. Treatment stimulated innate antiviral immunity, which is well conserved between sturgeon and salmon, the most responsive genes were 〈em〉mx, rsad2 (viperin)〈/em〉, 〈em〉interferon induced protein 44〈/em〉 and 〈em〉protein with tetratricopeptide repeats 5〈/em〉, 〈em〉cd87〈/em〉 and 〈em〉receptor transporting protein 3〈/em〉. Results added to knowledge of immune phylogeny. Gain and loss of genes was assessed by comparison with genomes from different phylogenetic groups. Among differentially expressed genes, percentage of acquired and lost genes was much lower in comparison with genes present in all vertebrates. Innate antiviral immunity was subject to the greatest changes in evolution of jawed vertebrates. A significant fraction of genes (15%) was lost in mammals and only half of genes is annotated in public databases as involved in antiviral responses. Change of function may have an important role in evolution of immunity together with gain and loss of genes.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Malene Soleng, Lill-Heidi Johansen, Hanne Johnsen, Gunhild S. Johansson, Mette W. Breiland, Lisbeth Rørmark, Karin Pittman, Lars-Flemming Pedersen, Carlo C. Lazado〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Peracetic acid (PAA), a strong organic peroxide, is considered a relatively sustainable disinfectant in aquaculture because of its broad effectivity against many pathogens at low concentrations and because it degrades spontaneously to harmless residues. The impacts of PAA on fish health must be determined before its use as either a routine disinfectant or chemotherapeutant. Here we investigated the systemic and mucosal stress responses of Atlantic salmon (〈em〉Salmo salar〈/em〉) to PAA. In experiment 1, salmon were exposed to different nominal concentrations (0, 0.6, and 2.4 ppm) of PAA for 5 min, followed by a re-exposure to the same concentrations for 30 min 2 weeks later. Sampling was performed before exposure to PAA and at 2 h, 48 h, and 2 w after exposures. In experiment 2, fish were subjected to crowding stress prior to PAA exposure at 4.8 ppm for 30 min. The fish were sampled before exposure and 1 h, 4 h, and 2 w after. The two trials were performed in a recirculation system. Both systemic (i.e., plasma cortisol, glucose, lactate, total antioxidant capacity) and mucosal (i.e., expression of antioxidant coding genes in the skin and gills) stress indicators were affected by the treatments at varying levels, and it was apparent that the fish were able to mount a robust response to the physiological demands of PAA exposure. The cortisol levels increased in the early hours after exposure and returned to basal level afterwards. Prior exposure history to PAA did not markedly affect the levels of plasma lactate and glucose when fish were re-exposed to PAA. Crowding stress before PAA treatment, however, did alter some of the stress indicators (i.e., lactate, glucose and expression of antioxidant genes in the gills), suggesting that stress history serves as both a confounding and compounding factor on how stress responses to PAA are mobilised. Nonetheless, the changes were not substantial. Gene expression profile analyses revealed that the antioxidant system was more responsive to PAA in the gills than in the skin. The increased antioxidant capacity in the plasma, particularly at 2.4 ppm and higher, indicates that antioxidants were produced to neutralise the internal redox imbalance resulting from PAA exposure. In conclusion, the results show that salmon were able to mount a robust adaptive response to different PAA doses and exposure times, and a combined exposure to stress and PAA. These results underscore the potential of PAA as a chemotherapeutant for salmon at PAA concentrations commonly applied to control parasitic infestations.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Zhiwei Cao, Sijia Liu, Hao Nan, Kaixia Zhao, Xiaodong Xu, Gaoxue Wang, Hong Ji, Hongying Chen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Cyprinid herpesvirus 2 (CyHV-2) is the causative pathogen of herpesviral haematopoietic necrosis disease, which has caused huge economic losses to aquaculture industry in China. In this study, nine truncated CyHV-2 membrane glycoproteins (ORF25, ORF25C, ORF25D, ORF30, ORF124, ORF131, ORF136, ORF142A, ORF146) and a GFP reporter protein were respectively expressed using baculovirus surface displaying system. Western blot showed that the proteins were successfully packaged in the recombinant virus particles. In baculovirus transduced gibel carp kidney cells, the target proteins were expressed and displayed on the fish cell surface. Healthy gibel carp were immunized by immersion with the recombinant baculoviruses and the fish treated with phosphate-buffered saline (PBS) were served as mock group. The expression of 〈em〉interleukin-11〈/em〉 (〈em〉IL-11〈/em〉), 〈em〉interferon α〈/em〉 (〈em〉IFNα〈/em〉) and a complement component gene 〈em〉C3〈/em〉 were significantly up-regulated in most experimental groups, and 〈em〉interferon γ〈/em〉 (〈em〉IFNγ〈/em〉) expression in some groups were also induced after immunization. Subsequently, the immunized gibel carp were challenged by intraperitoneal injection of CyHV-2 virus. All the immunized groups exhibited reduced mortality after CyHV-2 challenge. In the groups immunized with baculoviruses displaying and expressing ORF25, ORF25C and ORF146, the relative percentage survival values reached 83.3%, 87.5% and 70.8%, respectively. Our data suggested that baculovirus-displayed ORF25, ORF25C and ORF146 could be potential vaccine candidates for the prevention of CyHV-2 infection in gibel carp.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Armando Vega-López, Nataraj S. Pagadala, Brenda P. López-Tapia, Ruth L. Madera-Sandoval, Erika Rosales-Cruz, Minerva Nájera-Martínez, Elba Reyes-Maldonado〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The signaling mediated by small non-proteinogenic molecules, which probably have the capacity to serve as a bridge amongst complex systems is one of the most exiting challenges for the study. In the current report, stem cells differentiation of the immune system in Nile tilapia treated with sub-basal doses of GABA evaluated as c-kit〈sup〉+〈/sup〉 and Sca-1〈sup〉+〈/sup〉 cells disappearance on pronephros, thymus, spleen and peripheral blood mononuclear cells by flow cytometry was assessed. Explanation of biological response was performed by molecular docking approach and multiparametric analysis. Stem cell differentiation depends on a delicate balance of negative and positive interactions of this neurotransmitter with receptors and transcription factors involved in this process. This in turn depends on the type of interaction with hematopoietic niche to differentiate into primordial, early or late hematopoiesis as well as from the dose delivery. In fish treated with the low doses of GABA (0.1% over basal value) primordial hematopoiesis is regulated by interaction of glutamate (Glu) with the Ly-6 antigen. Early hematopoiesis was influenced by the bond of GABA near or adjacent to turns of FLTR3-Ig-IV domain. During late hematopoiesis, negative regulation by structural modifications on PU.1/IRF-4 complex, IL-7Rα and GM-CSFR mainly prevails. Results of molecular docking were in agreement with the percentages of the main blood cells lineages estimated in pronephros by flow cytometry. Current study provides the first evidences about the role of inhibitory and excitatory neurotransmitters such as GABA and Glu, respectively with the most transcriptional factors and receptors involved on hematopoiesis in adult Nile tilapia.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1050464819308320-fx1.jpg" width="266" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Xianyun Ren, Yunbin Zhang, Ping Liu, Jian Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This study aimed to use isobaric tags (IBTs) to investigate the immune response of the hepatopancreas of 〈em〉Marsupenaeus japonicas〈/em〉 infected with 〈em〉Vibrio parahaemolyticus〈/em〉 or white spot syndrome virus (WSSV). Liquid chromatography-tandem mass spectrometry and protein sequencing identified 1005 proteins. Among them, 109 proteins were upregulated and 94 were downregulated after 〈em〉V. parahaemolyticus〈/em〉 infection. After WSSV infection, 130 proteins were identified as differentially abundant, including 88 that were upregulated and 42 were downregulated. Fifty-four proteins were identified as differentially abundant after both 〈em〉V. parahaemolyticus〈/em〉 and WSSV infection. A number of proteins related to cytoskeletal processes, including actin and myosin, and apoptosis-related proteins were upregulated in shrimp after 〈em〉V. parahaemolyticus〈/em〉 and WSSV infection, indicating that phagocytosis and apoptosis may be involved in the response to in 〈em〉V. parahaemolyticus〈/em〉 or WSSV infection. Quantitative real-time PCR was carried out to verify the reliability of the proteomic data. These data provide a basis to characterize the immunity-related processes of shrimp in response to infection with WSSV or 〈em〉V. parahaemolyticus〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Jiajia Yu, Hongxia Wang, Xin Yue, Baozhong Liu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Meretrix petechialis〈/em〉 is an important commercial aquaculture species in China. During the clam culture period, mass mortality events often occurred due to the 〈em〉Vibrio〈/em〉 infection. In this paper, 〈em〉M. petechialis〈/em〉 were challenged with 〈em〉Vibrio parahaemolyticus〈/em〉 immersion to simulate a natural infection, and the infection process were divided into four phases including latency, prodrome, onset and recovery phases based on the clam mortality data. Then, the dynamic response of clams to 〈em〉Vibrio〈/em〉 infection at different infection phases were investigated by transcriptome analysis. A total of 38,067 differentially expressed genes (DEGs) were identified at different infection phases. DEG annotations showed that immune-related and metabolism-related signaling pathways were enriched, indicating that immune defense and metabolism process play key roles during bacterial infection. Three kinds of expression pattern were classified by cluster analysis, including U-shape, L-shape and inverted V-shape. Anabolism and cellular growth proliferation related signaling pathways were repressed (long-lasting or transient) during bacterial infection. However, the immune related signaling pathways with different immune functions showed induction expression or repression expression against bacterial infection, which indicated that immune system take different strategies against bacterial infection. Furthermore, some signaling pathways such as PI3K-Akt signaling pathway both involved in immune defense and cell metabolism. This study provides a sight that the dynamic immunity and metabolic responses may be integrated to improve the host survival and shift more energy for immune defense.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Guang-hua Wang, Zhao-xia Li, En-mian Guo, Jing-jing Wang, Min Zhang, Yong-hua Hu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Calreticulin (CRT) is a highly conserved and multi-functional protein with diverse localizations. CRT has lectin-like properties and possesses important immunological activities in mammalian. In teleost, very limited studies on CRT immunologic function have been documented. In the present study, a CRT homologue (SsCRT) was cloned, identified and characterized from black rockfish, 〈em〉Sebastes schlegeli〈/em〉, an important aquaculture species in East Asia. The full length of 〈em〉SsCRT〈/em〉 cDNA is 2180 bp and encoded a polypeptide of 425 amino acids. SsCRT contains a signal peptide, three distinct structural and functional domains (N-, P- and C-domains), and an endoplasmic reticulum (ER) retrieval signal sequence (KDEL). The deduced amino acid sequence of SsCRT shares 89–92% overall sequence identities with the CRT proteins of several fish species. 〈em〉SsCRT〈/em〉 was distributed ubiquitously in all the detected tissues and was highly expressed in the spleen, muscle and liver. After the infection of fish extracellular bacterial pathogen 〈em〉Vibrio anguillarum〈/em〉 and intracellular bacterial pathogen 〈em〉Edwardsiella tarda〈/em〉, the mRNA transcripts of 〈em〉SsCRT〈/em〉 in spleen, liver, and head kidney were significantly up-regulated. The expression patterns were time-dependent and tissue-dependent. Recombinant SsCRT (rSsCRT) exhibited apparent binding activities against different bacteria and PAMPs. 〈em〉In vivo〈/em〉 studies showed that the expressions of multiple immune-related genes such as TNF13B, IL-1β, IL-8, SAA, Hsp70, and ISG15 in head kidney were significantly enhanced when black rockfish were treated with rSsCRT. Furthermore, rSsCRT reduced pathogen dissemination and replication in fish kidney and spleen. These results indicated that SsCRT served as an immune receptor to recognize and eliminate the invading pathogens, which played a vital role in the immune response of 〈em〉Sebastes schlegeli〈/em〉. These findings provide new insights into understanding the roles of CRT proteins in immune response and pathogen infection in teleost.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Ying Wu, Yongcan Zhou, Zhenjie Cao, Yun Sun, Yang Chen, Yajing Xiang, Lu Wang, Shengnan Zhang, Weiliang Guo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Interleukins (ILs) are a subgroup of cytokines, which are molecules involved in the intercellular regulation of the immune system. These cytokines have been extensively studied in mammalian models, but systematic analyses of fish are limited. In the current study, 3 IL genes from golden pompano (〈em〉Trachinotus ovatus〈/em〉) were characterized. The IL-1β protein contains IL-1 family signature motif, and four long helices (αA - αD) in IL-11 and IL-34, which were well conserved. All 3 ILs clustered phylogenetically with their respective IL relatives in mammalian and other teleost species. Under normal physiological conditions, the expression of IL-1β, IL-11, and IL-34 were detected at varied levels in the 11 tissues examined. Most of the 3 ILs examined were highly expressed in liver, spleen, kidney, gill, or skin. Following pathogenic bacterial, viral, or parasitic challenge, IL-1β, IL-11, and IL-34 exhibited distinctly different expression profiles in a time-, tissue-, and pathogen-dependent manner. In general, IL-1β was expressed at higher levels following challenge with all pathogens examined than was observed for IL-11 and IL-34. Furthermore, 〈em〉Streptococcus agalactiae〈/em〉 and 〈em〉Cryptocaryon irritans〈/em〉 caused higher levels of IL-1β and IL-11 expression than 〈em〉Vibrio harveyi〈/em〉 and viral nervous necrosis virus (VNNV). The increased expression of IL-34 caused by VNNV and 〈em〉C. irritans〈/em〉 were higher than that caused by 〈em〉V. harveyi〈/em〉 and 〈em〉S. agalactiae〈/em〉. These results suggest that these 3 ILs in 〈em〉T. ovatus〈/em〉 may play different effect pathogen type specific responses.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Dinglong Yang, Yijing Han, Lizhu Chen, Ruiwen Cao, Qing Wang, Zhijun Dong, Hui Liu, Xiaoli Zhang, Qianqian Zhang, Jianmin Zhao〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Bactericidal permeability-increasing protein (BPI) is an antimicrobial protein with potent endotoxin-neutralising activity and plays a crucial role in innate immunity against bacterial infection. In the present study, a 〈em〉bpi〈/em〉 (designed as 〈em〉rpbpi〈/em〉) was identified and characterized from manila clam 〈em〉Ruditapes philippinarum〈/em〉. Multiple alignments and phylogenetic analysis suggested that 〈em〉rpbpi〈/em〉 was a new member of the 〈em〉bpis〈/em〉 family. In non-stimulated clams, 〈em〉rpbpi〈/em〉 transcripts were ubiquitously expressed in all tested tissues with the highest expression level in hemocytes. After 〈em〉Vibrio anguillarum〈/em〉 challenge, the expression levels of 〈em〉rpbpi〈/em〉 mRNA in hemocytes were up-regulated significantly at 3 h and 48 h compared with that in the control, which were 4.01- and 19.10-fold (〈em〉P〈/em〉 〈 0.05), respectively. The recombinant RpBPI (rRpBPI) showed high antibacterial activities against Gram-negative bacteria 〈em〉Escherichia coli〈/em〉 and 〈em〉V. anguillarum〈/em〉, but not 〈em〉Staphylococcus aureus〈/em〉. Moreover, membrane integrity analysis revealed that rRpBPI increased the membrane permeability of Gram-negative bacteria, and then resulted in cell death. Overall, our results suggested that RpBPI played an important role in the elimination of invaded bacteria through membrane-disruptive activity.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Wenlin Wu, Congjie Dai, Xunwei Duan, Cuifang Wang, Xiaosi Lin, Jiaying Ke, Yixuan Wang, Xiaobo Zhang, Haipeng Liu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉White shrimp 〈em〉Litopenaeus vannamei〈/em〉 are widely cultured in the world and white spot syndrome virus (WSSV) led to huge economic losses in the shrimp industry every year. In the present study, miRNAs involved in the response of shrimp 〈em〉L. vannamei〈/em〉 to WSSV infection were obtained through the Illumina HiSeq 2500 high-throughput next-generation sequencing technique. A total number of 7 known miRNAs and 54 putative novel miRNAs were obtained. Among them, 14 DEMs were identified in the shrimp infected with WSSV. The putative target genes of these DEMs were related to host immune response or signaling pathways, indicating the importance of miRNAs in shrimp against WSSV infection. The results will provide information for further research on shrimp response to virus infection and contribute to the development of new strategies for effective protection against WSSV infections.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Rahul Krishnan, Syed Shariq Nazir Qadiri, Myung-Joo Oh〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Nectin-4/PVRL4 belonging to the family of immunoglobulin-like cell adhesion molecules was identified as a potential cellular receptor for several animal viruses. Here we show that nervous necrosis virus that causes viral nervous necrosis in teleosts uses the same receptor in its life cycle. Transfection of SSN-1 cell lines with an expression vector encoding Nectin-4 rendered them to be more susceptible to NNV. Immunofluorescence microscopy on Nectin-4 expressing cells revealed that the protein interacted with NNV specifically. A virus binding assay indicated that Nectin-4 was a bonafide receptor that supported virus attachment to the host cell whereas siRNA directed against Nectin-4 blocked NNV infections in grouper primary brain cells. Results of the present study will improve our understanding of the pathogenesis of NNV infection and provide a target for the development of novel antiviral interventions in marine finfish aquaculture.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Jun Di, Zhipeng Chu, Shuhuan Zhang, Jun Huang, Hao Du, Qiwei Wei〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In the present study, we aimed to screen the potential probiotic 〈em〉Bacillus subtilis〈/em〉 isolated from the gut of healthy fish using 〈em〉in vitro〈/em〉 assays and to evaluate its effect on Dabry's sturgeon (〈em〉Acipenser dabryanus〈/em〉) using 〈em〉in vivo〈/em〉 feeding experiments. Among the isolates, 〈em〉B. subtilis〈/em〉 BSth-5 and BSth-19 exhibited antimicrobial effect against four sturgeon-pathogenic bacteria, including 〈em〉Aeromonas hydrophila〈/em〉, 〈em〉A. veronii〈/em〉, 〈em〉A. media〈/em〉, and 〈em〉Streptococcus iniae〈/em〉. The cell number of 〈em〉B. subtilis〈/em〉 BSth-5 and BSth-19 changed little after 2 h of exposure to pH 3.0 or fresh Dabry's sturgeon bile at 2.5% and 5.0%. Meanwhile, 〈em〉B. subtilis〈/em〉 BSth-5 and BSth-19 produced extracellular protease, cellulose, and lipase. And it was proved that 〈em〉B. subtilis〈/em〉 BSth-5 and BSth-19 were harmless after injection of Dabry's sturgeon. One group of Dabry's sturgeon was fed a control diet and two groups were fed experimental diets containing 2.0 × 10〈sup〉8〈/sup〉 CFU/g BSth-5 (T1 group) or BSth-19 (T2 group) for 8 weeks. No significant differences in final weight, weight gain rate, and special growth rate were observed in the T1 and T2 groups compared to the control group (〈em〉P〈/em〉 〉 0.05), but a significant improvement in survival rate was detected after 4 and 8 weeks of feeding (〈em〉P〈/em〉 〈 0.05). After 8 weeks, serum total antioxidant capacity, total superoxide dismutase activity, and IgM levels were significantly higher in the T1 and T2 groups compared to the control group (〈em〉P〈/em〉 〈 0.05). Moreover, serum lysozyme activity was significantly higher in the T1 group relative to the control group during the whole experiment period (〈em〉P〈/em〉 〈 0.05); however, the differences were not significant between the T2 and control groups (〈em〉P〈/em〉 〉 0.05). Serum malondialdehyde levels in the T1 and T2 groups were significantly lower than those in the control group after 4 weeks (〈em〉P〈/em〉 〈 0.05). Sturgeons in the T1 and T2 groups showed a higher survival rate after 〈em〉Aeromonas hydrophila〈/em〉 infection. To summarize, dietary supplementation with BSth-5 and BSth-19 could enhance the survival rate, antioxidant activity, serum immunity, and disease resistance in 〈em〉A. dabryanus〈/em〉.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1050464819308204-fx1.jpg" width="388" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Håvard Bjørgen, Oskar Mongstad Løken, Ida Bergva Aas, Per Gunnar Fjelldal, Tom Hansen, Lars Austbø, Erling Olaf Koppang〈/p〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Pan Wu, Weiguang Yang, Yuying Dong, Yanling Wang, Ying Zhang, Xuejun Zou, Hui Ge, Dongxue Hu, Yubo Cui, Zhaobo Chen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Application of traditional bait in aquaculture caused environment pollution and disease frequent occurrence. Residual coconut could be re-utilized to culture Spinibarbus sinensis as dietary supplement. Therefore, a novel integrated system of the improvement of yield, antioxidant and nonspecific immunity of Spinibarbus sinensis by dietary residual coconut was proposed and investigated. Spinibarbus sinensis could grow well in all supplement residual coconut groups. Survival rate, yield, whole fish body composition under 15–45% groups were increased compared with control group (CK). Bioactive substances (polyphenols and vitamin) in residual coconut enhanced AKP, ACP, phagocytic, SOD, CAT activities through up-regulating 〈em〉AKP, ACP, SOD, CAT〈/em〉 genes expression levels. Theoretical analysis showed bioactive substances regulated these genes expressions and enzyme activities as stimulus signal, component, active center. Moreover, residual coconut improved mTOR and NF-kB signaling pathway. Furthermore, residual coconut inhibited 〈em〉Aeromonas hydrophila〈/em〉 that increased resistance to diseases. This technology completed the solid waste recovery and the Spinibarbus sinensis culture simultaneously.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Jianting Lu, Xianyong Bu, Shusheng Xiao, Zhideng Lin, Xinyue Wang, Yongyi Jia, Xiaodan Wang, Jian G. Qin, Liqiao Chen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This study evaluates the effect of dietary supplementation of immunostimulants on the Chinese mitten crab (〈em〉Eriocheir sinensis〈/em〉) with a single administration of mannan oligosaccharide (MOS), or its combination with either β-glucan or with inulin for 8 weeks. Four diets included an untreated control diet (C), MOS alone (3 g kg〈sup〉−1〈/sup〉, M), MOS with β-glucan (3 g kg 〈sup〉−1〈/sup〉 MOS + 1.5 g kg 〈sup〉−1〈/sup〉 β-glucan, MB), and MOS with inulin (3 g kg 〈sup〉−1〈/sup〉 MOS + 10 g kg 〈sup〉−1〈/sup〉 inulin, MI). The weight gain and specific growth rate of the crabs fed M, MB, and MI diets were improved by lowing feed conversion ratio. The growth and feed utilization of the crabs fed the MB diet were improved compared with the other three groups. The crabs fed the M, MB and MI diets showed a higher intestinal trypsin activity than that in the M and control groups. The highest trypsin activity in the hepatopancreas was observed in the MB group. Crabs fed M, MB and MI diets increased antioxidant system-related enzyme activities, but reduced malondialdehyde. The highest activities of alkaline phosphatase, acid phosphatase, lysozyme and phenol oxidase in the gut and the respiratory burst of the crabs were found in the MB group. The MB diet promoted the mRNA expression of 〈em〉E. sinensis〈/em〉 immune genes (ES-PT, ES-Relish, ES-LITAF, p38MAPK and Crustin) compared with the control. After 3 days of infection with 〈em〉Aeromonas hydrophila〈/em〉, the highest survival of crabs was also found in the MB group. This study indicates that the combination of MOS with β-glucan or with inulin can improve growth, antioxidant capacity, non-specific immunity and disease resistance in 〈em〉E. sinensis〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Marco Rozas-Serri, Andrea Peña, Lucerina Maldonado〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Piscirickettsiosis is the most challenging disease present in the Chilean salmon industry. The aim of this study was to describe the expression of genes associated with immune response of Atlantic salmon intraperitoneally infected with LF-89 and EM-90 〈em〉Piscirickettsia salmonis〈/em〉 and vaccinated with inactivated whole-cell bacterin of 〈em〉P. salmonis〈/em〉. The fish infected with PS-LF-89 showed an anti-inflammatory response, whereas this finding was not observed in the PS-EM-90-infected fish and vaccinated fish. Fish infected with both 〈em〉P. salmonis〈/em〉 isolates showed 〈em〉mhc1-mhc2〈/em〉, 〈em〉cd4-cd8b〈/em〉 and 〈em〉igm〈/em〉 overexpression, suggesting that 〈em〉P. salmonis〈/em〉 promotes a T CD4〈sup〉+〈/sup〉 and T CD8〈sup〉+〈/sup〉 cell response and a humoral immune response. The vaccinated-fish exhibited 〈em〉mhc1〈/em〉, 〈em〉mhc2〈/em〉 and 〈em〉cd4〈/em〉 overexpression but a significant downregulation of 〈em〉cd8b〈/em〉 and 〈em〉igm〈/em〉, suggesting that the vaccine supported the CD4〈sup〉+〈/sup〉 T-cell response but did not induce an immune response mediated by CD8〈sup〉+〈/sup〉 T cells or a humoral response. In conclusion, the expression pattern of genes related to the humoral and cell-mediated adaptive immune response showed upregulation in fish infected with 〈em〉P. salmonis〈/em〉 and down-regulation in vaccinated fish. The results of this study contribute to our understanding of the immune response against 〈em〉P. salmonis〈/em〉 and can be used in the optimization of SRS prevention and control measures.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Wen-rui Li, Yong-hua Hu, Shuai Jiang, Li Sun〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Japanese flounder (〈em〉Paralichthys olivaceus〈/em〉) is an important economic fish species farmed in China and other countries. It is susceptible to infection by 〈em〉Edwardsiella tarda〈/em〉, a severe fish pathogen with a broad host range. In this study, we employed high-throughput deep sequencing technology to identify, in a global scale, flounder kidney microRNAs (miRNAs) induced by 〈em〉E. tarda〈/em〉 at different stages of infection. Differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) exhibiting significantly altered expression levels before and after 〈em〉E. tarda〈/em〉 infection were examined. A total of 96 DEmiRNAs were identified, for which 2779 target genes were predicted. Eighty-seven miRNA–mRNA pairs, involving 29 DEmiRNAs and 86 DEmRNAs, showed negative correlations in their expression patterns. GO and KEGG enrichment analysis revealed that the putative target genes of the DEmiRNAs were associated with diverse biological processes, cellular components, and molecular functions. One of the DEmiRNAs, pol-miR-182-5p, was demonstrated to regulate sphingosine-1-phosphate receptor 1 (PoS1PR1) negatively in a manner that depended on the specific interaction between the seed sequence of pol-miR-182-5p and the 3'-UTR of PoS1PR1. Overexpression of pol-miR-182-5p in flounder cells promoted apoptosis and inhibited cellular viability. Knockdown of PoS1PR1 in flounder enhanced 〈em〉E. tarda〈/em〉 invasion and dissemination in fish tissues. These results provide new insights into miRNA-mediated anti-bacterial immunity in flounder.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Hongli Xia, Yuan Li, Zhiwen Wang, Wenjie Chen, Jun Cheng, Dapeng Yu, Yishan Lu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Nile tilapia (〈em〉Oreochromis niloticus〈/em〉) is a pivotal economic fish that has been plagued by Streptococcus infections. Tumor necrosis factor receptor-associated factor 5 (TRAF5) is a crucial adaptor molecule, which can trigger downstream signaling cascades involved in immune pathway. In this study, Nile tilapia TRAF5 coding sequence (named OnTRAF5) was obtained, which contained typical functional domains, such as RING, zinc finger, coiled-coil and MATH domain. Different from other TRAF molecules, OnTRAF5 had shown relatively low identify with its homolog, and it was clustered into other teleost TRAF5 proteins. qRT-PCR was used to analysis the expression level of OnTRAF5 in gill, skin, muscle, head kidney, heart, intestine, thymus, liver, spleen and brain, In healthy Nile tilapia, the expression level of OnTRAF5 in intestine, gill and spleen were significantly higher than other tissues. While under 〈em〉Streptococcus agalactiae〈/em〉 infection, the expression level of OnTRAF5 was improved significantly in all detected organs. Additionally, over-expression WT OnTRAF5 activated NF-κB, deletion of RING or zinc finger caused the activity impaired. In conclusion, OnTRAF5 participate in anti-bacteria immune response and is crucial for the signaling transduction.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 125〈/p〉 〈p〉Author(s): Zi-Dan Ding, Jie-Fu Zheng, Cheng-Bo Song, Ya-Jing Fu, Jun-Jie Xu, Yong-Jun Jiang, Hong Shang, Zi-Ning Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background〈/h6〉 〈p〉HIV rapid progressors (RPs) present with a rapid decline of CD4〈sup〉+〈/sup〉 T cells within a few years of infection. Determining the underlying mechanisms throughout this decline is important to identify prognostic biomarkers and intervention strategies. Determining the numbers of CD4〈sup〉+〈/sup〉 and CD8〈sup〉+〈/sup〉 T cells is essential for monitoring the immune status of HIV infected patients. There are additional kinds of cell subtypes in T cells, but their relationship to the rapid progression of HIV disease is not well defined.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉Nineteen RPs and twenty-one chronic progressors (CPs) were enrolled in this study. Based on the intensity of CD4 and CD8 expression, different T cell subtypes were identified, including CD4〈sup〉+〈/sup〉CD8〈sup〉+〈/sup〉T cells, CD4〈sup〉−〈/sup〉CD8〈sup〉−〈/sup〉 T cells, CD4〈sup〉+〈/sup〉CD8〈sup〉low〈/sup〉 T cells and CD4〈sup〉−〈/sup〉CD8〈sup〉low〈/sup〉 T cells. Alterations in these T cell subtypes in early HIV infection (within 120 days of infection) between RPs and CPs were measured, and the relationships between these subtypes and HIV disease progression were investigated. In addition, expression of IFN-γ in T cell subtypes after PMA stimulation was analyzed by flow cytometry.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉We found that during early HIV infection, CD4〈sup〉+〈/sup〉CD8〈sup〉low〈/sup〉 T cells both significantly decreased in numbers and percentages in RPs compared to CPs. Furthermore, baseline CD4〈sup〉+〈/sup〉CD8〈sup〉low〈/sup〉 T cells positively correlated not only with baseline CD4〈sup〉+〈/sup〉T cells but also with CD4〈sup〉+〈/sup〉T cells 12 months after infection. Moreover, survival analysis indicated that low levels of baseline CD4〈sup〉+〈/sup〉CD8low T cells significantly accelerated the decline in CD4〈sup〉+〈/sup〉 T cells as well as increased viral loads. CD4〈sup〉+〈/sup〉CD8〈sup〉low〈/sup〉 T cells secreted significantly more IFN-γ after PMA stimulation compared to CD4〈sup〉+〈/sup〉CD8〈sup〉−〈/sup〉T cells and CD4〈sup〉−〈/sup〉CD8〈sup〉+〈/sup〉T cells, which may be beneficial for the prevention of disease progression.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉Our results identified that in early stage HIV-1 infection, a subtype of T cells, CD4〈sup〉+〈/sup〉CD8〈sup〉low〈/sup〉, are associated with subsequent disease progression.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 125〈/p〉 〈p〉Author(s): Patrícia Maurer, Fernanda Barbisan, Veronica Farina Azzolin, Lyana Feijoo Berro, Renata Montagner, Marta Maria Medeiros Frescura Duarte, Ivana Beatrice Mânica da Cruz, Vanusa Manfredini, Jacqueline da Costa Escobar Piccoli〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Introduction〈/h6〉 〈p〉Nitric oxide is a gaseous radical produced by the nitric oxide endothelial synthase (eNOS) whose most studied physiological action is the vasodilation. However, it also acts in the defense of the organism through the formation of cytotoxic radicals, which can potentiate the inflammatory lesion of the cells. The Glu298Asp is a single nucleotide polymorphism (SNP) in the eNOS gene related to the risk of cardiovascular disease. Blacks present a higher prevalence of hypertension and cardiovascular mortality. Then, we aimed to evaluate the influence of Glu298Asp polymorphism on inflammatory response in vitro and gene expression in blacks.〈/p〉 〈/div〉 〈div〉 〈h6〉Material and methods〈/h6〉 〈p〉Peripheral blood mononuclear cells (PBMC) from blacks with different Glu298Asp genotypes were treated with phytohemagglutinin (PHA), a mitogen and activator of T cells. Oxidative, inflammatory markers, and expression of inflammation genes were evaluated.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉The genotype frequencies were TT 6.7%; TG 29.3% and GG 64.0%. Activation of PBMCs with 125 μg of PHA modulated the expression of inflammatory genes and increased levels of inflammatory cytokines. The T allele showed increased susceptibility to inflammation (higher levels of interleukin 1, interleukin 6 and tumor necrosis factor alpha; p 〈 0.001). The G allele exhibited protection through higher levels of nitric oxide (p 〈 0.001) and fewer inflammatory cytokines.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉Despite methodological limitations related to in vitro assays, the whole of results suggested that Glu298Asp modulates inflammatory genes, the T allele is more susceptible to inflammation and the G allele is protective.〈/p〉 〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1043466619302418-ga1.jpg" width="500" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Tianjian Hu, Ran Chen, Lingzhi Zhang, Zhuang Wang, Dahai Yang, Yuanxing Zhang, Xiaohong Liu, Qin Liu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Edwardsiella piscicida〈/em〉 is an important pathogen that infects a wide range of hosts, from fish to human. Its infection leads to extensive losses in a diverse array of commercially important fish, like Japanese flounder, turbot, and tilapia. During the infection, type III secretion system (T3SS) and type VI secretion system (T6SS) of 〈em〉E. piscicida〈/em〉 play significant roles, but how T3SS and T6SS cooperatively contribute to its virulence is still unknown. In this study, we first examined the roles of T3SS and T6SS in different processes during 〈em〉E. piscicida〈/em〉 infection of host cells, and revealed that T3SS of 〈em〉E. piscicida〈/em〉 is responsible for promoting bacterial invasion, the following intracellular replication and inducing cell death in host cells, while T6SS restrains 〈em〉E. piscicida〈/em〉 intracellular replication and cell death in J774A.1 cells, which suggested that T3SS and T6SS antagonistically concert 〈em〉E. piscicida〈/em〉 infection. Furthermore, we found an significant decrease in transcription level of IL-1β in zebrafish kidney infected with T3SS mutant and an drastically increase in transcription level of TNF- α infected with T6SS mutant when compared with the wild-type. Interestingly, both T3SS and T6SS mutants showed significant attenuated virulence in the zebrafish infection model when compared with the wild-type. Finally, considering the cooperative role of T3SS and T6SS, we generated a mutant strain WEDΔT6SS based on the existing live attenuated vaccine (LAV) WED which showed improved vaccine safety and comparable immune protection. Therefore, WEDΔT6SS could be used as an optimized LAV in the future. Taken together, this work suggested a bilateral role of T3SS and T6SS which respectively act as spear and shield during 〈em〉E. piscicida〈/em〉 infection, together contribute to 〈em〉E. piscicida〈/em〉 virulence.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Yuanxia Cheng〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This study aims to investigate the effects of 〈em〉Rhodiola rosea〈/em〉 polysaccharide (RRP) on the growth performance and nonspecific immunity of red swamp crayfish 〈em〉Procambarus clarkia〈/em〉. RRP was prepared by hot water extraction and partly characterised by high-performance liquid chromatography and sugar composition analyses. Three diets supplemented with three different levels of RRP (0.2, 0.6 and 1 g kg diet〈sup〉−1〈/sup〉) were formulated and tested for growth performance and nonspecific immunity of red swamp crayfish 〈em〉Procambarus clarkii,〈/em〉 while a diet without any RRP supplementation served as control. After 8 weeks of feeding, body weight gain, feed efficiency, survival rate, phenoloxidase activity, superoxide dismutase activity, glutathione peroxidase level, total haemocyte count and number of hyaline cells, semigranular cells and granular cells and resistance to 〈em〉Aeromonas hydrophila〈/em〉 were higher than those of the control. Moreover, based on the efficiency of RRP on the growth performance and nonspecific immunity of crayfish, the optimum dose of RRP was found to be 0.6 g kg diet〈sup〉−1〈/sup〉. Hence, intake of diets containing RRP could enhance the growth performance, immune responses and improve resistance of crayfish to infection by 〈em〉A. hydrophila.〈/em〉〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 28 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Zhen Wang, Shi-peng Wang, Qun Shao, Pei-feng Li, Yue Sun, Lan-zi Luo, Xiu-qing Yan, Zi-yi Fan, Juan Hu, Jing Zhao, Peng-zhou Hang, Zhi-min Du〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway is associated with ischemic heart diseases (IHD). 7,8-dihydroxyflavone (7,8-DHF), BDNF mimetic, is a potent agonist of TrkB. We aimed to investigate the effects and the underlying mechanisms of 7,8-DHF on cardiac ischemia. Myocardial ischemic mouse model was induced by ligation of left anterior descending coronary artery. 7,8-DHF (5 mg/kg) was administered intraperitoneally two days after ischemia for four weeks. Echocardiography, HE staining and transmission electron microscope were used to examine the function, histology and ultrastructure of the heart. H9c2 cells were treated with hydrogen peroxide (H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉), 7,8-DHF or TrkB inhibitor ANA-12. The effects of 7,8-DHF on cell viability, mitochondrial membrane potential (MMP) and mitochondrial superoxide generation were examined. Furthermore, mitochondrial fission and protein expression of mitochondrial dynamics (Mfn2 [mitofusin 2], OPA1 [optic atrophy 1], Drp1 [dynamin-related protein 1] and Fis-1 [fission 1]) was detected by mitotracker green staining and western blot, respectively. 7,8-DHF attenuated cardiac dysfunction and cardiomyocyte abnormality of myocardial ischemic mice. Moverover, 7,8-DHF increased cell viability and reduced cell death accompanied by improving MMP, inhibiting mitochondrial superoxide and preventing excessive mitochondrial fission of H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉-treated H9c2 cells. The cytoprotective effects of 7,8-DHF were antagonized by ANA-12. Mechanistically, 7,8-DHF repressed OMA1-dependent conversion of L-OPA1 into S-OPA1, which was abolished by Akt inhibitor. In conclusion, 7,8-DHF protects against cardiac ischemic injury by inhibiting the proteolytic cleavage of OPA1. These findings provide a novel pharmacological effect of 7,8-DHF on mitochondrial dynamics and a new potential target for IHD.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919311827-fx1.jpg" width="266" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 28 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Avinash Kumar, Gangarao Davuluri, Nicole Welch, Adam Kim, Mahesha Gangadhariah, Allawy Allawy, Anupama Priyadarshini, Megan R. McMullen, Yana Sandlers, Belinda Willard, Charles L. Hoppel, Laura E. Nagy, Srinivasan Dasarathy〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Protein synthesis and autophagy are regulated by cellular ATP content. We tested the hypothesis that mitochondrial dysfunction, including generation of reactive oxygen species (ROS), contributes to impaired protein synthesis and increased proteolysis resulting in tissue atrophy in a comprehensive array of models. In myotubes treated with ethanol, using unbiased approaches, we identified defects in mitochondrial electron transport chain components, endogenous antioxidants, and enzymes regulating the tricarboxylic acid (TCA) cycle. Using high sensitivity respirometry, we observed impaired cellular respiration, decreased function of complexes I, II, and IV, and a reduction in oxidative phosphorylation in ethanol-treated myotubes and muscle from ethanol-fed mice. These perturbations resulted in lower skeletal muscle ATP content and redox ratio (NAD〈sup〉+〈/sup〉/NADH). Ethanol also caused a leak of electrons, primarily from complex III, with generation of mitochondrial ROS and reverse electron transport. Oxidant stress with lipid peroxidation (thiobarbituric acid reactive substances) and protein oxidation (carbonylated proteins) were increased in myotubes and skeletal muscle from mice and humans with alcoholic liver disease. Ethanol also impaired succinate oxidation in the TCA cycle with decreased metabolic intermediates. MitoTEMPO, a mitochondrial specific antioxidant, reversed ethanol-induced mitochondrial perturbations (including reduced oxygen consumption, generation of ROS and oxidative stress), increased TCA cycle intermediates, and reversed impaired protein synthesis and the sarcopenic phenotype. We show that ethanol causes skeletal muscle mitochondrial dysfunction, decreased protein synthesis, and increased autophagy, and that these perturbations are reversed by targeting mitochondrial ROS.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉Overall schema of ethanol-induced mitochondrial function in skeletal muscle. Ethanol impairs ETC function with leak of electrons to generate superoxide (O2〈sup〉-〈/sup〉) that causes oxidative injury to tissue and decreases TCA cycle intermediates.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919312973-fx1.jpg" width="282" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 125〈/p〉 〈p〉Author(s): Hossein Salmani, Mahmoud Hosseini, Yousef Baghcheghi, Reyhaneh Moradi-Marjaneh, Amin Mokhtari-Zaer〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In recent years, the role of angiotensin II (Ang II) and Ang II type 1 receptor (AT1) in the crosstalk between the immune system and the central nervous system has received more attention. The present study aimed to investigate the role of losartan, an AT1 receptor blocker, in the modulation of long-lasting adverse effects of repeated systemic lipopolysaccharide (LPS) injection in the brain function. For this purpose, 110 male BALB/c mice were administrated LPS (250 µg/kg) intraperitoneally (i.p.) for seven consecutive days. Mice were i.p. injected with losartan (1 and 3 mg/kg) three days before and during the LPS injection. To determine the role of PPAR-γ activation in the protective actions of losartan, GW9662, a PPAR-γ antagonist, was also co-administrated with losartan. Then, behavioral tests, including Morris water maze (MWM), novel object recognition test, passive avoidance, forced swim test (FST), elevated plus maze, and marble burying task, were conducted. The results demonstrated that losartan improved learning and memory impairment, attenuated anxiety-like behaviors, modulated brain inflammation and oxidative stress, and decreased amyloid-β accumulation. Losartan was unable to improve hippocampal BDNF and IL-10 levels as well as the retention trial in the MWM task and depressive-like behaviors. In addition, the PPAR-γ antagonist did not significantly influence the beneficial effects of losartan. Our findings suggest that AT1R blockade can protect the brain against most long-lasting hallmark effects of systemic inflammation. Also, based on the results, the beneficial actions of losartan were not mediated through PPAR-γ activation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 125〈/p〉 〈p〉Author(s): Stuart D. Dowall, Victoria A. Graham, Roger Hewson〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Zika virus (ZIKV) is phylogenetically divided into two lineages comprising African (ZIKV〈sup〉AF〈/sup〉) and Asian (ZIKV〈sup〉AS〈/sup〉) genotypes. In the type-I interferon receptor deficient mouse model, ZIKV〈sup〉AF〈/sup〉 causes severe disease with all mice meeting humane endpoints with doses as low as 10 plaque-forming units (pfu) whereas a much milder infection is seen after challenge with ZIKV〈sup〉AS〈/sup〉, including with doses as high as 10〈sup〉6〈/sup〉 pfu. Using this mouse model, the elucidation of cytokine, chemokine, growth factor and acute phase protein responses over the course of infection were studied to determine whether these analytes contributed to the stark difference in clinical outcome. Results demonstrated some significant differences, with the ZIKV〈sup〉AF〈/sup〉 infection being associated with increases in a higher number of biomarkers than ZIKV〈sup〉AS〈/sup〉. When low (10 pfu) and high (10〈sup〉6〈/sup〉 pfu) challenge doses were compared, animals given the lower virus inoculum showed a wider range of responses, indicating a different disease progression compared to those challenged with high doses. These results aid with elucidating the different outcomes with the two lineages of ZIKV and with future work to assess pathogenicity of virus infection.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 143〈/p〉 〈p〉Author(s): Chia-Hui Chen, Jin-Feng Zhao, Chiao-Po Hsu, Yu Ru Kou, Tse-Min Lu, Tzong-Shyuan Lee〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background〈/h6〉 〈p〉Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor and has been proposed to be an independent risk factor for cardiovascular diseases. However, little is known about its role in the regulation of lipid metabolism. In this study, we investigated the effect of ADMA on cholesterol metabolism and its underlying molecular mechanism.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉Oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cells were used as an 〈em〉in vitro〈/em〉 model. Apolipoprotein E-deficient (apoE〈sup〉−/−〈/sup〉) hyperlipidemic mice were used as an 〈em〉in vivo〈/em〉 model. Western blot analysis was used to evaluate protein expression. Luciferase reporter assays were used to assess the activity of promoters and transcription factors. Conventional assay kits were used to measure the levels of ADMA, cholesterol, triglycerides, and cytokines〈strong〉〈em〉.〈/em〉〈/strong〉〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Treatment with oxLDL decreased the protein expression of dimethylarginine dimethylaminohydrolase-2 (DDAH-2) but not DDAH-1. Incubation with ADMA markedly increased oxLDL-induced lipid accumulation in macrophages. ADMA impaired cholesterol efflux following oxLDL challenge and downregulated the expression of ATP-binding cassette transporter A1 (ABCA1) and ABCG1 by interfering with liver X receptor α (LXRα) expression and activity. Additionally, this inhibitory effect of ADMA on cholesterol metabolism was mediated through the activation of the NADPH oxidase/reactive oxygen species pathway. 〈em〉In vivo〈/em〉 experiments revealed that chronic administration of ADMA for 4 weeks exacerbated systemic inflammation, decreased the aortic protein levels of ABCA1 and ABCG1, and impaired the capacity of reverse cholesterol transport, ultimately, leading to the progression of atherosclerosis in apoE〈sup〉−/−〈/sup〉 mice.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉Our findings suggest that the ADMA/DDAH-2 axis plays a crucial role in regulating cholesterol metabolism in macrophage foam cells and atherosclerotic progression.〈/p〉 〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919308184-fx1.jpg" width="348" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Xiujuan Zhou, Jing Xing, Xiaoqian Tang, Xiuzhen Sheng, Wenbin Zhan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Interleukin-2 receptor subunit beta of flounder (〈em〉Paralichthys olivace〈/em〉, fIL-2Rβ) was annotated on the NCBI, its gene was cloned and characterized functionally in this study. And then the amino acids sequences and tertiary structure of fIL-2Rβ were analyzed, respectively. RT-PCR and ImageJ analyzed showed that fIL-2Rβ mRNA were expressed in the gill, spleen, kidney, intestines, liver, blood, muscle and skin, which showed high signals in spleen and blood. And then the recombinant protein of fIL-2Rβ extracellular region and its polyclonal antibodies were produced, native fIL-2Rβ molecules in flounder peripheral blood leukocytes (PBLs) were identified at 60.7 kDa by Mass spectrometry, which were in accordance with the molecular mass of full fIL-2Rβ protein calculated on the predicted protein sequence. Then the IL-2Rβ+ cell in T/B lymphocytes were characterized by Flow cytometry and indirect immunofluorescence assay, respectively. The results showed that the percentages of IL-2Rβ+ leukocytes, IL-2Rβ+/CD4+, IL-2Rβ+/IgM+ lymphocytes were 18.4 ± 2.7%, 4.5 ± 0.8%, 4.3% ± 0.5 in PBLs, and were 13.6 ± 0.9%, 4.6 ± 1.1%, 6.1% ± 0.4 in spleen, similarly, the percentages of IL-2Rβ+ leukocytes, IL-2Rβ+/CD4+, IL-2Rβ+/IgM+ lymphocytes were 9.4 ± 0.3%, 4.0 ± 0.5%, 5.7 ± 0.1% in head kidney, respectively. After KLH injection, compared with control group, the gene expression of IL-2, IL-2Rβ, CD3, TCR, CD79b and IgM in spleen of flounder were up-regulated, respectively (〈em〉p〈/em〉 〈 0.05). And the FCM results showed that the percentages of IL-2Rβ+ leukocytes in PBLs were significantly increased post Keyhole limpet hemocyanin (KLH) injection, which peaked 23.9 ± 0.9% at 9〈sup〉th〈/sup〉 day (〈em〉p〈/em〉 〈 0.05). To our knowledge, those results first reported that the characteristics of IL-2R and IL-2R + molecules were expressed on both B and T lymphocytes in fish. At the same time, this study lays a foundation for further exploring the interaction between IL-2 and IL-2R to promote cell proliferation and carrying out biological functions.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Ebru Yilmaz〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The present study investigated the effects of dietary anthocyanin on the growth performance, haematological, non-specific immune, and spleen gene expression responses of Nile tilapia, 〈em〉Oreochromis niloticus〈/em〉. Five experimental groups of fish with mean weights of 8.24 ± 0.64 g were used in the study; four of these were fed with diets incorporating anthocyanin (20 mg kg -〈sup〉1〈/sup〉, 40 mg kg〈sup〉−1〈/sup〉, 80 mg kg〈sup〉−1〈/sup〉 and 160 mg kg〈sup〉−1〈/sup〉), while the fifth was a control group without dietary anthocyanin. Growth performance and haematological parameters of tilapia were not affected by anthocyanin-supplemented diets (p 〉 0.05). Dietary anthocyanin significantly increased respiratory burst activity, phagocytic activity, phagocytic index, lysozyme activity, myeloperoxidase activity, serum total superoxide dismutase (T.SOD) activity, and serum catalase (CAT) activity (p 〈 0.05). The total immunoglobulin level was highest in the 80 mg kg〈sup〉−1〈/sup〉 group compared with the other groups (p 〈 0.05). In addition, with the anthocyanin-containing diets, the gene levels of interleukin 1, beta (〈em〉IL-1β〈/em〉), interleukin 8 (〈em〉IL-8〈/em〉), tumor necrosis factor (〈em〉TNF-α〈/em〉), heat shock protein 70 (〈em〉HSP70〈/em〉), and interferon gamma (〈em〉IFN-γ〈/em〉) were increased in the fish spleen, and the gene levels of 〈em〉CAT〈/em〉, 〈em〉GPx〈/em〉, and 〈em〉SOD〈/em〉 were also increased in fish liver (p 〈 0.05). At the end of the experiment, the fish were subjected to ammonia stress. The groups fed with 20 and 40 mg kg〈sup〉−1〈/sup〉 anthocyanin exhibited higher survival rates than the other groups. In summary, feeding Nile tilapia with anthocyanin-containing diets caused increases in the innate immune parameters, gene expression responses, and the survival rate of the fish subjected to ammonia stress.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Yan-Lin Guo, Lin Feng, Wei-Dan Jiang, Pei Wu, Yang Liu, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Xiao-Qiu Zhou〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Iron is an important mineral element for fish. In this study, we investigated the influences of dietary iron deficiency on intestinal immune function as well as underlying signaling of on-growing grass carp (〈em〉Ctenopharyngodon idella〈/em〉). Fish were fed with six graded level of dietary iron for sixty days, and a fourteen days’ challenge test under infection of 〈em〉Aeromonas hydrophila〈/em〉 thereafter. Results showed that compared with optimal iron level, iron deficiency increased enteritis morbidity, decreased lysozyme (LZ) and acid phosphatase (ACP) activities, complement 3 (C3), C4 and immunoglobulin M (IgM) concentrations and down-regulated mRNA levels of hepcidin, liver expressed antimicrobial peptide 2A (LEAP-2A), LEAP-2B, Mucin2, β-defensin-1, anti-inflammatory cytokines transforming growth factor β1 (TGF-β1), TGF-β2, interleukin 4/13A (IL-4/13A), IL-4/13B, IL-10, IL-11 and IL-15, inhibitor of κBα (IκBα), target of rapamycin (TOR) and ribosomal protein S6 kinase 1 (S6K1), whereas up-regulated mRNA levels of pro-inflammatory cytokines IL-1β, interferon γ2 (IFN-γ2), IL-8, IL-12p35, IL-12p40 and IL-17D, nuclear factor kappa B (NF-κB) p65, IκB kinases α (IKKα), IKKβ and eIF4E-binding protein (4E-BP) in intestine of on-growing grass carp, indicating that iron deficiency impaired intestinal immune function of fish under infection of 〈em〉A. hydrophila〈/em〉. Besides, iron excess also increased enteritis morbidity and impaired immune function of fish under infection of 〈em〉A. hydrophila〈/em〉. In addition, the effect of ferrous fumarate on intestinal immune function of on-growing grass carp is more efficient than ferrous sulfate. Finally, based on ability against enteritis, LZ activities in mid intestine and distal intestine, we recommended adding 83.37, 86.71 and 85.39 mg iron/kg into diet, respectively.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Luqing Pan, Xin Zhang, Liubing Yang, Shanshan Pan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Hemocyanin, a multifunctional oxygen-carrying protein, has critical effects on immune defense in crustaceans. To explore the role of hemocyanin in anti-pathogen mechanism, effects of 〈em〉Vibrio harveyi〈/em〉 (〈em〉V. harvey〈/em〉) and 〈em〉Staphyloccocus aureus〈/em〉 (〈em〉S. aureus〈/em〉) on hemocyanin synthesis and innate immune responses were investigated in 〈em〉Litopenaeus vannamei〈/em〉 (〈em〉L. vannamei〈/em〉) during infection 〈em〉in vivo〈/em〉. Results showed that 10〈sup〉5〈/sup〉 and 10〈sup〉6〈/sup〉 cells mL〈sup〉−1〈/sup〉 〈em〉V. harveyi〈/em〉 and 10〈sup〉6〈/sup〉 cells mL〈sup〉−1〈/sup〉 〈em〉S. aureus〈/em〉 significantly affected plasma hemocyanin concentration, hepatopancreas hemocyanin mRNA and subunits expressions, plasma phenol oxidase (PO), hemocyanin-derived PO (Hd-PO), antibacterial, and bacteriolytic activities during the experiment under bacterial stress, while these parameters did not change remarkably in control group. The concentration of hemocyanin in plasma fluctuated, with a minimum at 12 h and a maximum at 24 h. Moreover, the expression of hemocyanin mRNA peaked at 12 h, while the level of hemocyanin p75 and p77 subunits reached maximum at 24 h. Besides, plasma PO and Hd-PO activities peaked at 24 h, and antimicrobial and bacteriolytic activities peaked at 12 h and 24 h, respectively. In addition, 10〈sup〉5〈/sup〉 cells mL〈sup〉−1〈/sup〉 〈em〉S. aureus〈/em〉 had no significant effect on the synthesis of hemocyanin and prophenoloxidase activating (pro-PO) system, but significantly increased antimicrobial activity at 12 h and bacteriolytic activity at 24 h. Therefore, these results suggest that the hemocyanin synthesis was initiated after invasion of pathogen, and the newly synthesized hemocyanin, acted as an immune molecule, can exerts PO activity to regulate the immune defense in 〈em〉L. vannamei in vivo〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 15 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell〈/p〉 〈p〉Author(s): Antonio D. Barbosa, Koini Lim, Muriel Mari, James R. Edgar, Lihi Gal, Peter Sterk, Benjamin J. Jenkins, Albert Koulman, David B. Savage, Maya Schuldiner, Fulvio Reggiori, Philip A. Wigge, Symeon Siniossoglou〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Cells dynamically adjust organelle organization in response to growth and environmental cues. This requires regulation of synthesis of phospholipids, the building blocks of organelle membranes, or remodeling of their fatty-acyl (FA) composition. FAs are also the main components of triacyglycerols (TGs), which enable energy storage in lipid droplets. How cells coordinate FA metabolism with organelle biogenesis during cell growth remains unclear. Here, we show that Lro1, an acyltransferase that generates TGs from phospholipid-derived FAs in yeast, relocates from the endoplasmic reticulum to a subdomain of the inner nuclear membrane. Lro1 nuclear targeting is regulated by cell cycle and nutrient starvation signals and is inhibited when the nucleus expands. Lro1 is active at this nuclear subdomain, and its compartmentalization is critical for nuclear integrity. These data suggest that Lro1 nuclear targeting provides a site of TG synthesis, which is coupled with nuclear membrane remodeling.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1534580719305817-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 15 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell〈/p〉 〈p〉Author(s): Nathan M. Krah, Shuba M. Narayanan, Deanne E. Yugawa, Julie A. Straley, Christopher V.E. Wright, Raymond J. MacDonald, L. Charles Murtaugh〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Activating mutations in 〈em〉Kras〈/em〉 are nearly ubiquitous in human pancreatic cancer and initiate precancerous pancreatic intraepithelial neoplasia (PanINs) when induced in mouse acinar cells. PanINs normally take months to form but are accelerated by deletion of acinar cell differentiation factors such as 〈em〉Ptf1a〈/em〉, suggesting that loss of cell identity is rate limiting for pancreatic tumor initiation. Using a genetic mouse model that allows for independent control of oncogenic 〈em〉Kras〈/em〉 and 〈em〉Ptf1a〈/em〉 expression, we demonstrate that sustained 〈em〉Ptf1a〈/em〉 is sufficient to prevent 〈em〉Kras〈/em〉-driven tumorigenesis, even in the presence of tumor-promoting inflammation. Furthermore, reintroducing 〈em〉Ptf1a〈/em〉 into established PanINs reverts them to quiescent acinar cells 〈em〉in vivo〈/em〉. Similarly, 〈em〉Ptf1a〈/em〉 re-expression in human pancreatic cancer cells inhibits their growth and colony-forming ability. Our results suggest that reactivation of an endogenous differentiation program can prevent and reverse oncogene-driven transformation in cells harboring tumor-driving mutations, introducing a potential paradigm for solid tumor prevention and treatment.〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 15 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell〈/p〉 〈p〉Author(s): S. Zachary Swartz, Liliana S. McKay, Kuan-Chung Su, Leah Bury, Abbas Padeganeh, Paul S. Maddox, Kristin A. Knouse, Iain M. Cheeseman〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Centromeres provide a robust model for epigenetic inheritance as they are specified by sequence-independent mechanisms involving the histone H3-variant centromere protein A (CENP-A). Prevailing models indicate that the high intrinsic stability of CENP-A nucleosomes maintains centromere identity indefinitely. Here, we demonstrate that CENP-A is not stable at centromeres but is instead gradually and continuously incorporated in quiescent cells including G0-arrested tissue culture cells and prophase I-arrested oocytes. Quiescent CENP-A incorporation involves the canonical CENP-A deposition machinery but displays distinct requirements from cell cycle-dependent deposition. We demonstrate that Plk1 is required specifically for G1 CENP-A deposition, whereas transcription promotes CENP-A incorporation in quiescent oocytes. Preventing CENP-A deposition during quiescence results in significantly reduced CENP-A levels and perturbs chromosome segregation following the resumption of cell division. In contrast to quiescent cells, terminally differentiated cells fail to maintain CENP-A levels. Our work reveals that quiescent cells actively maintain centromere identity providing an indicator of proliferative potential.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1534580719306227-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 15 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell〈/p〉 〈p〉Author(s): Nicole Ritter, Tamer Ali, Nina Kopitchinski, Peggy Schuster, Arica Beisaw, David A. Hendrix, Marcel H. Schulz, Michaela Müller-McNicoll, Stefanie Dimmeler, Phillip Grote〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Precisely controlled gene regulatory networks are required during embryonic development to give rise to various structures, including those of the cardiovascular system. Long non-coding RNA (lncRNA) loci are known to be important regulators of these genetic programs. We have identified a novel and essential lncRNA locus 〈em〉Handsdown〈/em〉 (〈em〉Hdn〈/em〉), active in early heart cells, and show by genetic inactivation that it is essential for murine development. 〈em〉Hdn〈/em〉 displays haploinsufficiency for cardiac development as 〈em〉Hdn〈/em〉-heterozygous adult mice exhibit hyperplasia in the right ventricular wall. Transcriptional activity of the 〈em〉Hdn〈/em〉 locus, independent of its RNA, suppresses its neighboring gene 〈em〉Hand2〈/em〉. We reveal a switch in a topologically associated domain in differentiation of the cardiac lineage, allowing the 〈em〉Hdn〈/em〉 locus to directly interact with regulatory elements of the 〈em〉Hand2〈/em〉 locus.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1534580719305854-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 143〈/p〉 〈p〉Author(s): Hui Wang, Gangduo Wang, Yuejin Liang, Xiaotang Du, Paul J. Boor, Jiaren Sun, M. Firoze Khan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Trichloroethene (TCE) exposure is associated with the development of various autoimmune diseases (ADs), including autoimmune hepatitis (AIH) and systemic lupus erythematosus (SLE), potentially through the generation of excessive reactive oxygen and nitrogen species (RONS; oxidative stress). However, the mechanisms by which oxidative stress contributes to these TCE-mediated ADs are not fully understood, and are the focus of current investigation. Female MRL+/+ mice were treated with TCE along with or without antioxidant N-acetylcysteine (NAC) for 6 weeks (TCE, 10 mmol/kg, i. p., every 4th day; NAC, 250 mg/kg/day via drinking water). TCE-treated mice had elevated antinuclear antibodies (ANA) and 4-hydroxynonenal (HNE)-specific circulating immune complexes, suggesting the association of TCE-induced oxidative stress with autoimmune response. In addition, TCE exposure led to prominent lobular inflammation with sinusoid dilation, increased sinusoidal cellularity and increased staining for proliferating cell nuclear antigen (PCNA), confirming inflammatory and hepatocellular cell proliferation. Importantly, TCE exposure resulted in the activation of hepatic inflammasome (NLRP3 and caspase-1) and up-regulation of pro-inflammatory cytokine IL-1β, and these changes were attenuated by NAC supplementation. TCE treatment also led to dysregulation of hepatic immune response as evident from markedly increased hepatic lymphocyte infiltration (especially B cells) and imbalance between Tregs (decreased) and Th17 cells (increased). Interestingly, TCE-mediated dysregulation of various hepatic and splenic immune cells was also effectively attenuated by NAC. Taken together, our findings provide evidence for TCE-mediated inflammasome activation, infiltration of various immune cells, and skewed balance of Treg and Th17 cells in the liver. The attenuation of TCE-mediated hepatic inflammasome activation and immune responses by NAC further supports a critical role of oxidative stress in TCE-mediated inflammation and autoimmunity. These novel findings could help in designing therapeutic strategies for such ADs.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 143〈/p〉 〈p〉Author(s): Dan Li, Jingjing Qi, Jiali Wang, Yuchen Pan, Jingman Li, Xiaoyu Xia, Huan Dou, Yayi Hou〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease characterized by multi-organ injury. However, whether myeloid-derived suppressor cells (MDSCs) senescence exists and participates in SLE pathogenesis remains unclear. And whether dihydroartemisinin (DHA) attenuates the symptoms of SLE via relieving MDSCs senescence remains elusive. In the present study, we measured the senescence of MDSCs in SLE using SA-β-gal staining, senescence-associated secretory phenotype (SASP) and Western blot analysis of aging-related protein P21, P53 and P16. We identified that the MDSCs senescence promoted the SLE progress by adaptive transfer MDSCs assays. Meanwhile, we further showed DHA ameliorated the symptoms of pristane-induced lupus by histopathological detection, Western blot analysis, immunofluorescence, QPCR and flow cytometry analysis. DHA reversed MDSCs senescence by detecting SA-β-gal staining, senescence-associated secretory phenotype (SASP) and Western blot analysis of aging-related protein P21, P53 and P16. Furthermore, mechanistic analysis indicated that the inhibitory effect of DHA on MDSCs senescence was blocked by ML385, the specific antagonist of Nrf2, which revealed that the effect of DHA on MDSCs senescence was dependent on the induction of Nrf2/HO-1 pathway. Of note, we revealed that DHA inhibited MDSCs senescence to ameliorate the SLE development by adaptive transfer DHA-treated MDSCs assays. In conclusion, MDSCs senescence played a vital role in the pathogenesis of SLE, and DHA attenuated the symptoms of SLE via relieving MDSCs aging involved in the induction of Nrf2/HO-1 pathway.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S089158491930749X-fx1.jpg" width="266" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 125〈/p〉 〈p〉Author(s): Basim Askar, John Higgins, Paul Barrow, Neil Foster〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉Studies have shown that administration of vasoactive intestinal peptide (VIP) in mice rescues them from lethal endotoxaemia and that this is correlated with decreased concentration of inflammatory cytokines. VIP has, therefore, been proposed as a novel anti-inflammatory which could be used in the treatment of Gram negative sepsis. However, the effect of VIP has not been reported in mice infected with viable Gram negative bacteria.〈/p〉 〈p〉Here, we show that 〈em〉Salmonella enterica〈/em〉 serovar Typhimurium 4/74 significantly increased expression of mRNA of a type 1 receptor (VPAC1) for anti-inflammatory vasoactive intestinal peptide (VIP) in murine ileum and mesenteric lymph nodes at day 6 post-infection (d6 pi) and in the spleen at d3 pi. When VIP (5 nmol/ml) was administered to 〈em〉S〈/em〉. Typhimurium-infected mice, there was a significant increase in the number of 〈em〉S〈/em〉. Typhimurium cultured from murine faeces and ileum at d3 and 6 pi and in MLN and spleen at d3 dpi, compared to faeces and tissues examined from mice infected with 〈em〉S〈/em〉. Typhimurium (without VIP administration). Administration of VIP to 〈em〉S〈/em〉. Typhimurium-infected mice also altered the splenic architecture, resulting in a lack of discernable periarterial lymphoid sheaths or marginal zones at d6 pi but liver histology appeared similar on both d3 and d6 pi. The effects of VIP administration were correlated with a significant decrease in expression of inflammatory cytokine mRNA, associated with systemic inflammatory response syndrome (SIRS) of bacteraemia and acute sepsis.〈/p〉 〈p〉We conclude that VIP inhibits expression of diagnostic/prognostic cytokine biomarkers of sepsis in 〈em〉S〈/em〉. Typhimurium-infected mice. However, this occurred with a concomitant increase in 〈em〉Salmonella〈/em〉 growth in tissues and increased bacterial shedding in faeces. Thus, VIP may have potential as an adjunctive therapy to antibiotics in sepsis.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 8 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell〈/p〉 〈p〉Author(s): Jie Ren, Peidong Han, Xuanyi Ma, Elie N. Farah, Joshua Bloomekatz, Xin-Xin I. Zeng, Ruilin Zhang, Megan M. Swim, Alec D. Witty, Hannah G. Knight, Rima Deshpande, Weizhe Xu, Deborah Yelon, Shaochen Chen, Neil C. Chi〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Pacemaker cardiomyocytes that create the sinoatrial node are essential for the initiation and maintenance of proper heart rhythm. However, illuminating developmental cues that direct their differentiation has remained particularly challenging due to the unclear cellular origins of these specialized cardiomyocytes. By discovering the origins of pacemaker cardiomyocytes, we reveal an evolutionarily conserved Wnt signaling mechanism that coordinates gene regulatory changes directing mesoderm cell fate decisions, which lead to the differentiation of pacemaker cardiomyocytes. We show that in zebrafish, pacemaker cardiomyocytes derive from a subset of Nkx2.5+ mesoderm that responds to canonical Wnt5b signaling to initiate the cardiac pacemaker program, including activation of pacemaker cell differentiation transcription factors Isl1 and Tbx18 and silencing of Nkx2.5. Moreover, applying these developmental findings to human pluripotent stem cells (hPSCs) notably results in the creation of hPSC-pacemaker cardiomyocytes, which successfully pace three-dimensional bioprinted hPSC-cardiomyocytes, thus providing potential strategies for biological cardiac pacemaker therapy.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1534580719305866-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 8 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell〈/p〉 〈p〉Author(s): Anne E. Dodson, Scott Kennedy〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Germ granules are biomolecular condensates that promote germ cell totipotency in animals. In 〈em〉C. elegans〈/em〉, MEG-3 and MEG-4 function redundantly to assemble germ granules in germline blastomeres. Here, we show that 〈em〉meg-3/4〈/em〉 mutant animals exhibit defects in RNA interference (RNAi) that are transgenerationally disconnected from the 〈em〉meg-3/4〈/em〉 genotype. Similar non-Mendelian inheritance is associated with other mutations disrupting germ granule formation, indicating that loss of germ granules is the likely cause of the observed disconnects between genotype and phenotype. 〈em〉meg-3/4〈/em〉 animals produce aberrant siRNAs that are propagated for ≅10 generations in wild-type descendants of 〈em〉meg-3/4〈/em〉 ancestors. Aberrant siRNAs inappropriately and heritably silence germline-expressed genes including the RNAi gene 〈em〉sid-1〈/em〉, suggesting that transgenerational silencing of 〈em〉sid-1〈/em〉 underlies inherited defects in RNAi. We conclude that one function of germ granules is to organize RNA-based epigenetic inheritance pathways and that germ granule loss has consequences that persist for many generations.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1534580719306318-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 8 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell〈/p〉 〈p〉Author(s): John Paul T. Ouyang, Andrew Folkmann, Lauren Bernard, Chih-Yung Lee, Uri Seroussi, Amanda G. Charlesworth, Julie M. Claycomb, Geraldine Seydoux〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉P granules are perinuclear condensates in 〈em〉C. elegans〈/em〉 germ cells proposed to serve as hubs for self/non-self RNA discrimination by Argonautes. We report that a mutant (〈em〉meg-3 meg-4〈/em〉) that does not assemble P granules in primordial germ cells loses competence for RNA-interference over several generations and accumulates silencing small RNAs against hundreds of endogenous genes, including the RNA-interference genes 〈em〉rde-11〈/em〉 and 〈em〉sid-1.〈/em〉 In wild type, 〈em〉rde-11〈/em〉 and 〈em〉sid-1〈/em〉 transcripts are heavily targeted by piRNAs and accumulate in P granules but maintain expression. In the primordial germ cells of 〈em〉meg-3 meg-4〈/em〉 mutants, 〈em〉rde-11〈/em〉 and 〈em〉sid-1〈/em〉 transcripts disperse in the cytoplasm with the small RNA biogenesis machinery, become hyper-targeted by secondary sRNAs, and are eventually silenced. Silencing requires the PIWI-class Argonaute PRG-1 and the nuclear Argonaute HRDE-1 that maintains trans-generational silencing of piRNA targets. These observations support a “safe harbor” model for P granules in protecting germline transcripts from piRNA-initiated silencing.〈/p〉〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 123〈/p〉 〈p〉Author(s): Amanda Proudfoot, Meenu Wadhwa〈/p〉

Description: 〈p〉Publication date: January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 125〈/p〉 〈p〉Author(s): Weifeng Mao, Xin Yi, Jianbing Qin, Meiling Tian, Guohua Jin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉To investigate the effect of CXCL12 on regeneration of radial glia like cells after traumatic brain injury (TBI). We randomly divided 48 rats into 4 groups: (1) the sham group, rats were performed craniotomy only, (2) the control group, saline were injected into the ipsilateral cortex after TBI, (3) the CXCL12 group, CXCL12 were injected, and (4) the CXCL12 + AMD3100 group, a mixture of CXCL12 and AMD3100 were injected. Seven days after TBI, the brain tissues were subjected to immunofluorescence double-labeled staining of BrdU/Nestin, BLBP/Nestin, BLBP/Vimentin, BLBP/SOX2, BLBP/CXCR4, BLBP/DCX. Western Blot assay was used to measure the levels of Nestin, BLBP, and Vimentin. Compared with the control group, CXCL12 treatment significantly increased the number of cells stained with BrdU/Nestin, BLBP/Nestin, and BLBP/Vimentin around the injured cortex and corpus callosum areas. CXCL12 + AMD3100 treatment significantly decreased the number of these cells compared with the CXCL12 treatment and control group. The protein levels of Nestin, BLBP, and Vimentin had the same change trends as those of the immunofluorescence staining. The BLBP/Vimentin positive cells presented with the astrocyte pattern around the injured cortex area but with the RGCs pattern around the injured corpus callosum area. The BLBP positive cells also expressed CXCR4 and SOX2. Altogether, CXCL12 promotes the proliferation of neural precursor cells after TBI by combing to its receptor, CXCR4. The proliferating neural precursor cells presents radial glial cell like cells. The RGCs-like cells can differentiate into immature neurons and promote the migration of immature neurons.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 125〈/p〉 〈p〉Author(s): Nicole E. Speck, Elisabeth Probst-Müller, Sarah R. Haile, Christian Benden, Malcolm Kohler, Lars C. Huber, Cécile A. Robinson〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉Early diagnosis and treatment of acute cellular rejection (ACR) may improve long-term outcome for lung transplant recipients (LTRs). Cytokines have become valuable diagnostic tools in many medical fields. The role of bronchoalveolar lavage (BAL) cytokines is of unknown value to diagnose ACR and distinguish rejection from infection. We hypothesized that distinct cytokine patterns obtained by surveillance bronchoscopies during the first year after transplantation are associated with ACR and microbiologic findings.〈/p〉 〈p〉We retrospectively analyzed data from 319 patients undergoing lung transplantation at University Hospital Zurich from 1998 to 2016. We compared levels of IL-6, IL-8, IFN-γ and TNF-α in 747 BAL samples with transbronchial biopsies (TBB) and microbiologic results from surveillance bronchoscopies. We aimed to define reference values that would allow distinction between four specific groups “ACR”, “infection”, “combined ACR and infection” and “no pathologic process”. No definitive pattern was identified. Given the overlap between groups, these four cytokines are not suitable diagnostic markers for ACR or infection after lung transplantation.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 125〈/p〉 〈p〉Author(s): Stanislava Stošić-Grujičić, Tamara Saksida, Đorđe Miljković, Ivana Stojanović〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Pro-inflammatory nature of macrophage migration inhibitory factor (MIF) has been generally related to the propagation of inflammatory and autoimmune diseases. But this molecule possesses many other peculiar functions, unrelated to the immune system, among which is its supportive role in the post-translational modifications of insulin. In this way MIF enables proper insulin conformation within the pancreatic beta cell and its full activity. The inherent or acquired changes in MIF expression might therefore lead to different insulin processing and initiation of autoimmunity. The relation between MIF and insulin does not stop at this point; these two molecules continue to interact during pathological states characterized by inflammation and insulin resistance. In this context, MIF indirectly and negatively influences insulin action by boosting inflammatory environment and disabling target cells to respond to insulin. On the other side, insulin might interfere with MIF action as well, acting as an anti-inflammatory mediator. Therefore, the proper interaction between MIF and insulin is crucial for maintaining homeostasis, while anti-inflammatory therapies based on the systemic MIF blockage may disturb this balance. This review covers MIF-insulin relationship in the physiological and pathological conditions and discusses the approaches for MIF inhibition and their net effect specifically considering possible impact on insulin misfolding and the possible misinterpretation of previous results due to the discovery of MIF functional homolog D-dopachrome tautomerase.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Fangyi Chen, Kejian Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mud crabs, 〈em〉Scylla paramamosain〈/em〉, are one of the most economical and nutritious crab species in China and South Asia. Inconsistent with the high development of commercial mud crab aquaculture, effective immunological methods to prevent frequently-occurring diseases have not yet been developed. Thus, high mortalities often occur throughout the different developmental stages of this species resulting in large economic losses. In recent years, numerous attempts have been made to use various advanced biological technologies to understand the innate immunity of 〈em〉S. paramamosain〈/em〉 as well as to characterize specific immune components. This review summarizes these research advances regarding cellular and humoral responses of the mud crab during pathogen infection, highlighting hemocytes and gills defense, pattern recognition, immune-related signaling pathways (Toll, IMD, JAK/STAT, and prophenoloxidase (proPO) cascades), immune effectors (antimicrobial peptides), production of reactive oxygen species and the antioxidant system. Diseases affecting the development of mud crab aquaculture and potential disease control strategies are discussed.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1050464819307867-fx1.jpg" width="354" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Ai-Guo Huang, Xiao-Ping Tan, Shen-Ye Qu, Gao-Xue Wang, Bin Zhu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉White spot syndrome virus (WSSV) is a serious epidemic pathogen of crustaceans and cause severe economic losses to aquaculture. However, no commercial drugs presently available to control WSSV infection. Genipin (GN) is a bioactive compound extracted from the fruit of 〈em〉Gardenia jasminoides〈/em〉 and exhibits potential antiviral activity. In the study, the antiviral activity of GN against WSSV was investigated in crayfish 〈em〉Procambarus clarkii〈/em〉 and in shrimp 〈em〉Litopenaeus vannamei〈/em〉. 〈em〉In vitro〈/em〉 antiviral test showed that GN could inhibit WSSV replication in crayfish and in shrimp, and the highest inhibition on WSSV was over 99% when treatment with 50 mg/kg of GN for 24 h. 〈em〉In vivo〈/em〉 antiviral test proved that GN could be used to treat and prevent WSSV infection. GN could also effectively protect crayfish from WSSV infection by reducing the mortality rate of WSSV-infected crayfish. Moreover, GN attenuated the WSSV-induced oxidative stress and inflammatory by upregulation the expression of antioxidant-related genes and downregulation the expression of inflammatory-related genes, respectively. Mechanically, GN inhibited WSSV replication at least via decreasing 〈em〉STAT〈/em〉 (〈em〉signal transducer and activator of transcription〈/em〉) gene expression to block WSSV immediate-early gene 〈em〉ie1〈/em〉 transcription. Additionally, the inhibition of 〈em〉BI-1〈/em〉 (〈em〉Bax inhibitor-1〈/em〉) gene expression also played an important role in the suppression of WSSV infection. In conclusion, GN represented a potential therapeutic and preventive agent to block WSSV infection.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Zhiying He, Fan Mao, Yue Lin, Jun Li, Xiangyu Zhang, Yuehuan Zhang, Zhiming Xiang, Zohaib Noor, Yang Zhang, Ziniu Yu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Phagocytosis is one of the fundamental cellular immune defense parameter that helps in the elimination of the invading pathogens in both vertebrates and invertebrates, which require plenty of energy for functioning. In the present study, we identified the critical energy regulator AMP-activated protein kinase (AMPK) in 〈em〉Crassostrea hongkongensis〈/em〉 which is composed of three subunits, named 〈em〉Ch〈/em〉AMPK-α, 〈em〉Ch〈/em〉AMPK-β, and 〈em〉Ch〈/em〉AMPK-γ, and then analyzed the function of AMPK in regulating hemocyte phagocytosis. All the three 〈em〉Ch〈/em〉AMPK subunits mRNA were detected to be expressed at various embryological stages, and also constitutively expressed in multiple tissues with high expression in gill and mantle. The phylogenetic tree showed that the three subunits of AMPK were correspondingly clustered with its orthologue branches. Furthermore Western Blot analysis revealed that the AMPK pharmacological inhibitors Compound C could effectively down-regulate the Thr〈sup〉172〈/sup〉 phosphorylation level of AMPK-α, and the hemocyte phagocytosis was inhibited by Compound C (CC), which indicate its existence in the oyster. Our results showed that treatment of AMPK inhibitors significantly attenuated the capacity of hemocytes phagocytosis. Moreover, Compound C could also change the organization of actin cytoskeleton in the oyster hemocytes, demonstrating the crucial role of AMPK signaling in control of phagocytosis.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Jian He, Tao-Lin Xie, Xiao Li, Yang Yu, Zhi-Peng Zhan, Shao-Ping Weng, Chang-Jun Guo, Jian-Guo He〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mandarin fish (〈em〉Siniperca chuatsi〈/em〉) is a universally farmed fish species in China and has a large farming scale and economic value. With the high-density cultural mode in mandarin fish, viral diseases, such as infectious spleen and kidney necrosis virus (ISKNV) and 〈em〉Siniperca chuatsi〈/em〉 rhabdovirus (SCRV), have increased loss, which has seriously restricted the development of aquaculture. Y-Box binding protein 1 (YB-1) is a member of cold shock protein family that regulates multiple cellular processes. The roles of mammalian YB-1 protein in environmental stress and innate immunity have been studied well, but its roles in teleost fishes remain unknown. In the present study, the characteristic of 〈em〉S. chuatsi〈/em〉 YB-1 (〈em〉sc〈/em〉YB-1) and its roles in cold stress and virus infection were investigated. The 〈em〉sc〈/em〉YB-1 obtained an 1541 bp cDNA that contains a 903 bp open reading frame encoding a protein of 300 amino acids. Tissue distribution results showed that the 〈em〉sc〈/em〉YB-1 is a ubiquitously expressed gene found among tissues from mandarin fish. Overexpression of 〈em〉sc〈/em〉YB-1 can increase the expression levels of cold shock-responsive genes, such as 〈em〉scHsc70a〈/em〉, 〈em〉scHsc70b〈/em〉, and 〈em〉scp53〈/em〉. Furthermore, the role of 〈em〉sc〈/em〉YB-1 in innate immunity was also investigated in mandarin fish fry (MFF-1) cells. The expression level of 〈em〉sc〈/em〉YB-1 was significant change in response to poly (I:C), poly (dG:dC), PMA, ISKNV, or SCRV stimulation. The overexpression of 〈em〉sc〈/em〉YB-1 can significantly increase the expression levels of NF-κB-responsive genes, including 〈em〉scIL-8, scTNF-α〈/em〉, and 〈em〉scIFN-h.〈/em〉 The NF-κB-luciferase report assay results showed that the relative expression of luciferin was significantly increased in the cells overexpressed with 〈em〉sc〈/em〉YB-1 compared with those in cells overexpressed with control plasmid. These results indicate that 〈em〉sc〈/em〉YB-1 can induce the NF-κB signaling pathway in MFF-1 cells. Overexpressed 〈em〉sc〈/em〉YB-1 can downregulate the expression of ISKNV viral major capsid protein (〈em〉mcp〈/em〉) gene but upregulates the expression of SCRV 〈em〉mcp〈/em〉 gene. Moreover, knockdown of 〈em〉sc〈/em〉YB-1 using siRNA can upregulate the expression of ISKNV 〈em〉mcp〈/em〉 gene but downregulates the expression of SCRV 〈em〉mcp〈/em〉 gene. These results indicate that 〈em〉sc〈/em〉YB-1 suppresses ISKNV infection while enhancing SCRV infection. The above observations suggest that 〈em〉sc〈/em〉YB-1 is involved in cold stress and virus infection. Our study will provide an insight into the roles of teleost fish YB-1 protein in stress response and innate immunity.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Hien Van Doan, Seyed Hossein Hoseinifar, Korawan Sringarm, Sanchai Jaturasitha, Bundit Yuangsoi, Mahmoud A.O. Dawood, Maria Ángeles Esteban, Einar Ringø, Caterina Faggio〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The present study aimed to assess the possible effects of Assam tea (〈em〉Camellia sinensis〈/em〉) extract (ATE) on growth performances, immune responses, and disease resistance of Nile tilapia, 〈em〉Oreochromis niloticus〈/em〉 against 〈em〉Streptococcus agalactiae〈/em〉. Five levels of ATE were supplemented into the based diet at 0, 1, 2, 4, and 8 g kg〈sup〉−1〈/sup〉 feed of Nile tilapia fingerlings (10.9 ± 0.04 g initial weight) in triplicate. After four and eight weeks of feeding, fish were sampled to determine the effects of the tea supplements upon their growth performance, as well as serum and mucosal immune responses. A disease challenge using 〈em〉S. agalactiae〈/em〉 was conducted at the end of the feeding trial. Fish fed ATE revealed significantly improved serum lysozyme, peroxidase, alternative complement (ACH50), phagocytosis, and respiratory burst activities compared to the basal control fed fish (〈em〉P〈/em〉 〈 0.05). The mucus lysozyme and peroxidase activities were ameliorated through ATE supplementation in the tilapia diets. Supplementation of ATE significantly (〈em〉P〈/em〉 〈 0.05) enhanced final body weight, weight gain, and specific growth rate; while a decreased feed conversion ratio was revealed at 2 g kg〈sup〉−1〈/sup〉 inclusion level, after four and eight weeks. Challenge test showed that the relative percent survival (RSP) of fish in each treatment was 33.33%, 60.00%, 83.33%, 76.68%, and 66.68% in groups fed 0, 1, 2, 4, and 8 g kg〈sup〉−1〈/sup〉, respectively. In summary, diets supplemented with ATE especially at 2 g kg〈sup〉−1〈/sup〉 increased the humoral and mucosal immunity, enhanced growth performance, and offered higher resistance against 〈em〉S. agalactiae〈/em〉 infection in Nile tilapia.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Jiquan Zhang, Yujie Liu, Yongzhao Zhou, Wenzheng Wang, Naike Su, Yuying Sun〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Trehalose, a nonreducing disaccharide, is present in a wide variety of organisms and plays a key role in many organisms under different stress conditions. In the study, the full-length cDNA sequence encoding trehalose-6-phosphate synthase (EcTPS) was obtained from 〈em〉Exopalaemon carinicauda〈/em〉. The complete nucleotide sequence of 〈em〉EcTPS〈/em〉 contained a 2532 bp open reading frame (ORF) encoding a putative protein of 843 amino acids. The domain architecture of the deduced EcTPS contained a glycol_transf_20 domain and a trehalose_PPase domain. 〈em〉EcTPS〈/em〉 mRNA was predominantly expressed in the hepatopancreas. The expression of 〈em〉EcTPS〈/em〉 in the prawns challenged with 〈em〉Vibrio parahaemolyticus〈/em〉 and 〈em〉Aeromonas hydrophila〈/em〉 changed in a time-dependent manner. The function of 〈em〉EcTPS〈/em〉 was also studied by double-strand RNA interference. The results showed that the knock-down of 〈em〉EcTPS〈/em〉 increased the mortality of the 〈em〉Vibrio〈/em〉-challenged group and 〈em〉Aeromonas〈/em〉-challenged group compared with the control group. The present study provides some new insight into the immune function of the trehalose-6-phosphate synthase in prawns.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Rui Jia, Zhengyan Gu, Qin He, Jinliang Du, Liping Cao, Galina Jeney, Pao Xu, Guojun Yin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Radix Bupleuri extract (RBE) is one of the most popular oriental herbal medicines, which has anti-oxidative and anti-inflammatory properties. However, its protective effects and underlying molecular mechanisms on oxidative damage in tilapia are still unclear. The aims of the study were to explore the anti-oxidative, anti-inflammatory and hepatoprotective effects of RBE against oxidative damage, and to elucidate underlying molecular mechanisms in fish. Tilapia received diet containing three doses of RBE (0, 1 and 3 g/kg diet) for 60 days, and then were given an intraperitoneal injection of H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 or saline. Before injection, RBE treatments improved growth performance and partial anti-oxidative capacity in tilapia. After oxidative damage, RBE pretreatments were able to signally reduce the higher serum aminotransferases, alkaline phosphatase (AKP) and liver necrosis. In serum and liver, the abnormal lipid peroxidation level and antioxidant status induced by H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 injection were restored by RBE treatments. Furthermore, RBE treatments activated erythroid 2-related factor 2 (Nrf2) signaling pathway, which promoted the gene expression of heme oxygenase 1 (HO-1), NAD(P) H:quinone oxidoreductase 1 (NQO-1), glutathione-S-transferase (GST) and catalase (CAT). Meanwhile, RBE treatments reduced inflammatory response by inhibiting TLRs-MyD88-NF-κB signaling pathway, accompanied by the lower interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-8 mRNA levels. In addition, RBE treatments upregulated complement (C3) gene expression and downregulated heat shock protein (HSP70) gene expression. In conclusion, the current study suggested that RBE pretreatments protected against H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉-induced oxidative damage in tilapia. The beneficial activity of RBE may be due to the modulation of Nrf2/ARE and TLRs-Myd88-NF-κB signaling pathway.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Ye Zhao, Hui Liu, Qing Wang, Bingjun Li, Hongxia Zhang, Yongrui Pi〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The gut microbiota is essential for health and physiological functions in the host organism. However, the toxicological evaluation of environmental pollutants on the gut microbiota is still insufficient. In the present study, the juvenile sea cucumber 〈em〉Apostichopus japonicus〈/em〉 was exposed for 14 days to Benzo[〈em〉a〈/em〉]pyrene (BaP), which is a model polycyclic aromatic hydrocarbon (PAH), at four different concentrations (0, 0.5, 5, and 25 μg/L). We analyzed the intestinal microbial community of 〈em〉A. japonicas〈/em〉 using 16S rRNA gene amplicon sequencing. Our results demonstrate that BaP exposure caused alterations to the microbiome community composition in sea cucumbers. At the phylum level, 〈em〉Planctomycetes〈/em〉 were significantly more abundant in BaP exposure groups at 14 d compared with the control group, and the abundance of 〈em〉Proteobacteria〈/em〉 and 〈em〉Bacteroidetes〈/em〉 increased while the abundance of 〈em〉Firmicutes〈/em〉 decreased following BaP exposure. At the genus level, multiple beneficial and autochthonous genera declined in the BaP treatment groups compared to the control, including 〈em〉Lactococcus〈/em〉, 〈em〉Bacillus〈/em〉, 〈em〉Lactobacillus〈/em〉, 〈em〉Enterococcus〈/em〉, 〈em〉Leuconostoc〈/em〉 and 〈em〉Weissella〈/em〉; however, a bloom of alkane-degrading bacteria was found in BaP-exposed guts and included 〈em〉Lutibacter〈/em〉, 〈em〉Pseudoalteromonas〈/em〉, 〈em〉Polaribacter〈/em〉, 〈em〉Rhodopirellula〈/em〉 and 〈em〉Blastopirellula〈/em〉. Furthermore, histological morphology, enzymatic activity and gene expression analysis revealed that BaP exposure also negatively impacted gut structure and function and presented as inflammation or atrophy, oxidative stress and immune suppression in sea cucumber intestines. Collectively, these findings provide insights into the toxic effects of BaP exposure on 〈em〉A. japonicas〈/em〉 associated with intestinal microbiota and health.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Mengting Luo, Linwei Yang, Zi-ang Wang, Hongliang Zuo, Shaoping Weng, Jianguo He, Xiaopeng Xu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉C-type lectins (CTLs) are a group of lectins with at least one carbohydrate recognition domain (CRD), the binding of which to carbohydrates requires the presence of calcium ions. CTLs generally function as pattern recognition receptors (PRRs), essentially participating in innate immunity. In the current study, a novel CTL termed LvCTL5 was identified from Pacific white shrimp 〈em〉Litopenaeus vannamei〈/em〉, which shared sequence identities with other crustacean CTLs. LvCTL5 was highly expressed in hepatopancreas and could be activated by infection with bacteria, virus and fungi. The recombinant LvCTL5 protein purified from 〈em〉E. coli〈/em〉 showed microbiostatic and agglutination activities against bacteria and fungi 〈em〉in vitro〈/em〉. Silencing of LvCTL5 〈em〉in vivo〈/em〉 could significantly affect expression of a series of immune effector genes and down-regulate the phagocytic activity of hemocytes. Compared with controls, the LvCTL5-silenced shrimp were highly susceptible to 〈em〉Vibrio parahaemolyticus〈/em〉 and white spot syndrome virus (WSSV) infections. These suggest that LvCTL5 has microbiostatic and immune regulatory activities and is implicated in antiviral and antibacterial responses.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Yi Tang, Yujia Sun, Lingmin Zhao, Xiaojin Xu, Lixing Huang, Yingxue Qin, Yongquan Su, Ganfeng Yi, Qingpi Yan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Large yellow croaker (〈em〉Larimichthys crocea〈/em〉) is an economical important farmed fish in China. “Visceral White Spot Disease” caused by 〈em〉Pseudomonas plecoglossicida〈/em〉 is a disease with a high mortality rate in cage-cultured 〈em〉L. crocea〈/em〉 in recent years and resulted in heavy economy lossess. The dual RNA-seq results of previous study showed that the expression of 〈em〉clpV〈/em〉 gene in 〈em〉P. plecoglossicida〈/em〉 was significantly up-regulated during infection. RNAi significantly reduced the expression of 〈em〉clpV〈/em〉 in 〈em〉P. plecoglossicida〈/em〉 with maximum silencing efficiency of 96.1%. Compared with the wild type strain, infection of 〈em〉clpV〈/em〉-RNAi strain resulted in a delayed onset time and a 25% reduction in mortality of 〈em〉L. crocea〈/em〉, as well as lessening the symptoms of the spleen. The results of dual RNA-seq of 〈em〉L. crocea〈/em〉 infected by 〈em〉clpV〈/em〉-RNAi strain of 〈em〉P. plecoglossicida〈/em〉 changed considerably, compared with the counterpart infected with the wild strain. The KEGG enrichment analysis showed that Cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, C-type lectin receptor signaling pathway and MAPK signaling pathway of 〈em〉L. crocea〈/em〉 were most affected by the silence of 〈em〉clpV〈/em〉 in 〈em〉P. plecoglossicida〈/em〉. RNAi of 〈em〉clpV〈/em〉 resulted in the downregulation of genes in flagella assembly pathway and a weaker immune response of host.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Hao Chen, Minxiao Wang, Huan Zhang, Hao Wang, Zhao Lv, Li Zhou, Zhaoshan Zhong, Chao Lian, Lei Cao, Chaolun Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉As domain species in seep and vent ecosystem, Bathymodioline mussels has been regarded as a model organism in investigating deep sea chemosymbiosis. However, mechanisms underlying their symbiosis with chemosynthetic bacteria, especially how the host recognizes symbionts, have remained largely unsolved. In the present study, a modified pull-down assay was conducted using enriched symbiotic methane-oxidation bacteria as bait and gill proteins of 〈em〉Bathymodiolus platifrons〈/em〉 as a target to isolate pattern recognition receptors involved in the immune recognition of symbionts. As a result, a total of 47 proteins including BpLRR-1 were identified from the pull-down assay. It was found that complete cDNA sequence of BpLRR-1 contained an open reading frame of 1479 bp and could encode a protein of 492 amino acid residues with no signal peptide or transmembrane region but eight LRR motif and two EFh motif. The binding patterns of BpLRR-1 against microbial associated molecular patterns were subsequently investigated by surface plasmon resonance analysis and LPS pull-down assay. Consequently, BpLRR-1 was found with high binding affinity with LPS and suggested as a key molecule in recognizing symbionts. Besides, transcripts of BpLRR-1 were found decreased significantly during symbiont depletion assay yet increased rigorously during symbionts or nonsymbiotic 〈em〉Vibrio alginolyticus〈/em〉 challenge, further demonstrating its participation in the chemosynthetic symbiosis. Collectively, these results suggest that BpLRR-1 could serve as an intracellular recognition receptor for the endosymbionts, providing new hints for understanding the immune recognition in symbiosis of 〈em〉B. platifrons〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Yuan Luo, Yun-Ni Zhang, Han Zhang, Hong-Bo Lv, Mei-Ling Zhang, Li-Qiao Chen, Zhen-Yu Du〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Peroxisome proliferator-activated receptor α (PPARα) plays critical physiological roles in energy metabolism, antioxidation and immunity of mammals, however, these functions have not been fully understood in fish. In the present study, Nile tilapia (〈em〉Oreochromis niloticus〈/em〉) were fed with fenofibrate, an agonist of PPARα, for six weeks, and subsequently challenged with 〈em〉Aeromonas hydrophila〈/em〉. The results showed that PPARα was efficiently activated by fenofibrate through increasing mRNA and protein expressions and protein dephosphorylation. PPARα activation increased significantly mitochondrial fatty acid β-oxidation efficiency, the copy number of mitochondrial DNA and expression of monoamine oxidase (MAO), a marker gene of mitochondria. Meanwhile, PPARα activation also increased significantly the expression of NADH dehydrogenase [ubiquinone] 1α subcomplex subunit 9 (NDUFA9, complex I) and mitochondrial cytochrome 〈em〉c〈/em〉 oxidase 1 (MTCO1, complex IV). The fenofibrate-fed fish had higher survival rate when exposed to 〈em〉A. hydrophila〈/em〉. Moreover, the fenofibrate-fed fish also had higher activities of immune and antioxidative enzymes, and gene expressions of anti-inflammatory cytokines, while had lower expressions of pro-inflammatory cytokine genes. Taken together, PPARα activation improved the ability of Nile tilapia to resist 〈em〉A. hydrophila〈/em〉, mainly through enhancing mitochondrial fatty acids β-oxidation, immune and antioxidant capacities, as well as inhibiting inflammation. This is the first study showing the regulatory effects of PPARα activation on immune functions through increasing mitochondria-mediated energy supply in fish.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Ivon F. Maha, Xiao Xie, Suming Zhou, Youbin Yu, Xiao Liu, Aysha Zahid, Yuhua Lei, Rongrong Ma, Fei Yin, Dong Qian〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉The yellow drum 〈em〉Nibea albiflora〈/em〉 is less susceptible to 〈em〉Cryptocaryon irritans〈/em〉 infection than is the case with other marine fishes such as 〈em〉Larimichthys crocea〈/em〉, 〈em〉Lateolabrax japonicus,〈/em〉 and 〈em〉Pagrus major〈/em〉. To investigate further their resistance mechanism, we infected the 〈em〉N. albiflora〈/em〉 with the 〈em〉C. irritans〈/em〉 at a median lethal concentration of 2050 theronts/g fish. The skins of the infected and the uninfected fishes were sampled at 24 h and 72 h followed by an extensive analysis of metabolism. The study results revealed that there were 2694 potential metabolites. At 24 h post-infection, 12 metabolites were up-regulated and 17 were down-regulated whereas at 72 h post-infection, 22 metabolites were up-regulated and 26 were down-regulated. Pathway enrichment analysis shows that the differential enriched pathways were higher at 24 h with 22 categories and 58 subcategories (49 up, 9 down) than at 72 h whereby the differential enriched pathways were 6 categories and 8 subcategories (4 up, 4 down). In addition, the principal component analysis (PCA) plot shows that at 24 h the metabolites composition of infected group were separately clustered to uninfected group while at 72 h the metabolites composition in infected group were much closer to uninfected group. This indicated that 〈em〉C. irritans〈/em〉 caused strong metabolic stress on the 〈em〉N. albiflora〈/em〉 at 24 h and restoration of the dysregulated metabolic state took place at 72 h of infection. Also, at 72 h post infection a total of 17 compounds were identified as potential biomarkers.〈/p〉 〈p〉Furthermore, out of 2694 primary metabolites detected, 23 metabolites could be clearly identified and semi quantified with a known identification number and assigned into 66 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Most of the enriched KEGG pathways were mainly from metabolic pathway classes, including the metabolic pathway, biosynthesis of secondary metabolites, taurine and hypotaurine metabolism, purine metabolism, linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis. Others were glyoxylate and dicarboxylate metabolism, glutathione metabolism, and alanine, aspartate, and glutamate metabolism. Moreover, out of the identified metabolites, only 6 metabolites were statistically differentially expressed, namely, L -glutamate (up-regulated) at 24 h was important for energy and precursor for other glutathiones and instruments of preventing oxidative injury; 15-hydroxy- eicosatetraenoic acid (15-HETE), (S)-(−)-2-Hydroxyisocaproic acid, and adenine (up-regulated) at 72 h were important for anti-inflammatory and immune responses during infection; others were delta-valerolactam and betaine which were down-regulated compared to uninfected group at 72 h, might be related to immure responses including stimulation of immune system such as production of antibodies.〈/p〉 〈p〉Our results therefore further advance our understanding on the immunological regulation of 〈em〉N. albiflora〈/em〉 during immune response against infections as they indicated a strong relationship between skin metabolome and 〈em〉C. irritans〈/em〉 infection.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: 19 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell, Volume 50, Issue 4〈/p〉 〈p〉Author(s): Antoni G. Wrobel, Zuzana Kadlecova, Jan Kamenicky, Ji-Chun Yang, Torsten Herrmann, Bernard T. Kelly, Airlie J. McCoy, Philip R. Evans, Stephen Martin, Stefan Müller, Filip Sroubek, David Neuhaus, Stefan Honing, David J. Owen〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Clathrin-mediated endocytosis (CME) is key to maintaining the transmembrane protein composition of cells’ limiting membranes. During mammalian CME, a reversible phosphorylation event occurs on Thr156 of the μ2 subunit of the main endocytic clathrin adaptor, AP2. We show that this phosphorylation event starts during clathrin-coated pit (CCP) initiation and increases throughout CCP lifetime. μ2Thr156 phosphorylation favors a new, cargo-bound conformation of AP2 and simultaneously creates a binding platform for the endocytic NECAP proteins but without significantly altering AP2’s cargo affinity 〈em〉in vitro〈/em〉. We describe the structural bases of both. NECAP arrival at CCPs parallels that of clathrin and increases with μ2Thr156 phosphorylation. In turn, NECAP recruits drivers of late stages of CCP formation, including SNX9, via a site distinct from where NECAP binds AP2. Disruption of the different modules of this phosphorylation-based temporal regulatory system results in CCP maturation being delayed and/or stalled, hence impairing global rates of CME.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1534580719306239-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 19 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Developmental Cell, Volume 50, Issue 4〈/p〉 〈p〉Author(s): Ilia A. Droujinine, Norbert Perrimon〈/p〉 〈div〉〈p〉Secreted molecules coordinate organ function. In a recent issue of 〈em〉Cell〈/em〉, Hudry et al. (2019) uncover a 〈em〉Drosophila〈/em〉 testis-midgut interaction via cytokine and citrate signaling that regulates intestinal metabolism, spermatogenesis, and food intake. This impressive study is a striking example of the role of spatial organization in sex-specific interorgan communication.〈/p〉〈/div〉

Description: 〈p〉Publication date: January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 125〈/p〉 〈p〉Author(s): Malte Puchert, Jessica Obst, Christian Koch, Konstanze Zieger, Jürgen Engele〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The chemokine, CXCL11, is highly expressed in different solid tumors and controls tumor growth, metastasis, and lymphocyte infiltration. Although of potential clinical interest, it is presently unknown whether these tumor-promoting activities involve the CXCL11 receptors, CXCR3 and/or CXCR7. This issue is further intrigued by the fact that CXCR3 exists in the two functionally divergent splice variants, CXCR3A and CXCR3B, which exert pro- and anti-tumorigenic influences, respectively. To unravel the role of the various CXCL11 receptors in tumor progression, we have now defined their role in CXCL11-induced chemotaxis of the tumor cell lines, A549, C33-A, DLD-1, MDA-MB-231, and PC-3. CXCL11-induced cell migration was either sensitive to the CXCR3 antagonist, ÀMG487 (DLD-1), the CXCR7 antagonist, CCX771 (C33-A, PC-3), or both (A549, MDA-231). Moreover, in C33-A and PC-3 cells, but not in the other tumor cells, pharmacological activation and inhibition of CXCR3B prevented and potentiated CXCL11-induced cell migration, respectively. Both immunocytochemistry and Western blot analysis finally revealed that the observed cell type specific organization of the CXCL11 system is not the result of differences in expression levels or subcellular location of CXCL11 receptors. Our findings imply that the therapeutic use of CXCR3 antagonists in cancer patients requires exact knowledge of the organization of the CXCR3 system in the respective tumor.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 143〈/p〉 〈p〉Author(s): Kandahalli Venkataranganayaka Abhilasha, Mosale Seetharam Sumanth, Vyala Hanumanthareddy Chaithra, Shancy Petsel Jacob, Anita Thyagarajan, Ravi Prakash Sahu, Rajesh Rajaiah, K. Sandeep Prabhu, Kempaiah Kemparaju, Jeffrey Bryant Travers, Chu-Huang Chen, Gopal Kedihithlu Marathe〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Platelet-activating factor (PAF) is a potent inflammatory agonist. In Swiss albino mice, intraperitoneal injection of PAF causes sudden death with oxidative stress and disseminated intravascular coagulation (DIC), characterized by prolonged prothrombin time, thrombocytopenia, reduced fibrinogen content, and increased levels of fibrinogen degradation products. However, the underlying mechanism(s) is unknown. The PAF-R antagonist WEB-2086 protected mice against PAF-induced death by reducing DIC and oxidative stress. Accordingly, general antioxidants such as ascorbic acid, α-tocopherol, gallic acid, and N-acetylcysteine partially protected mice from PAF-induced death. N-acetylcysteine, a clinically used antioxidant, prevented death in 67% of mice, ameliorated DIC characteristics and histological alterations in the liver, and reduced oxidative stress. WEB-2086 suppressed H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉-mediated oxidative stress in isolated mouse peritoneal macrophages, suggesting that PAF signaling may be a downstream effector of reactive oxygen species generation. PAF stimulated all three (ERK, JNK, and p38) of the MAP-kinases, which were also inhibited by N-acetylcysteine. Furthermore, a JNK inhibitor (SP600125) and ERK inhibitor (SCH772984) partially protected mice against PAF-induced death, whereas a p38 MAP-kinase inhibitor (SB203580) provided complete protection against DIC and death. In human platelets, which have the canonical PAF-R and functional MAP-kinases, JNK and p38 inhibitors abolished PAF-induced platelet aggregation, but the ERK inhibitor was ineffective. Our studies identify p38 MAP-kinase as a critical, but unrecognized component in PAF-induced mortality in mice. These findings suggest an alternative therapeutic strategy to address PAF-mediated pathogenicity, which plays a role in a broad range of inflammatory diseases.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919308494-fx1.jpg" width="500" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Hye-Jin Go, Chan-Hee Kim, Ji Been Park, Tae Young Kim, Tae Kwan Lee, Hye Young Oh, Nam Gyu Park〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Fish skin mucus is considered to act as the first line of defense against waterborne pathogens and to be potential source of novel antimicrobial components. Here we report the purification and characterization of a novel hepcidin type 2-like antimicrobial peptide (〈em〉Tp〈/em〉HAMP2) from the skin mucus of the pufferfish 〈em〉Takifugu pardalis〈/em〉. The purified 〈em〉Tp〈/em〉HAMP2 comprised of 23 amino acids (AAs) with eight Cys residues that form four intramolecular disulfide bonds. The 〈em〉Tp〈/em〉HAMP2 gene shared overall structural characteristics with all known hepcidins, which have a tripartite exon-intron gene organization and three structural signatures in the precursor protein. Phylogenetically, 〈em〉Tp〈/em〉HAMP2 was classified as HAMP2 class in acanthopterygian fish. Interestingly, the AA sequence of 〈em〉Tp〈/em〉HAMP2 did not contain a proprotein cleavage site (RXXR motif) that conserved in most hepcidins and showed a highly positive charged (RKR-) short N-terminus and Val〈sup〉18〈/sup〉 and Gly〈sup〉22〈/sup〉 residues, which are distinctive structures compared to other known active hepcidins. Recombinant 〈em〉Tp〈/em〉HAMP2 identical to the native form exhibited a broad spectrum and potent antimicrobial activity against tested gram-positive and -negative bacteria. Expression of 〈em〉Tp〈/em〉HAMP2 mRNA was predominant in the liver and was upregulated in the liver, the spleen, the intestine, and the skin of 〈em〉T. pardalis〈/em〉 post immune challenge. Thus, our findings suggests that 〈em〉Tp〈/em〉HAMP2 might be of importance in the framework of discovering the fish hepcidins, especially type 2s, and provide noteworthy insight into its gene structure and expression and in the innate immunity as well as the mucosal immunity in regard to hepcidins’ evolutionary history in fish species.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Chen Li, Yepin Yu, Xin Zhang, Jingguang Wei, Qiwei Qin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Autophagy is an evolutionarily conserved, multi-step lysosomal degradation process used to maintain cell survival and homeostasis. A series of autophagy-related genes (Atgs) are involved in the autophagic pathway. In mammals, a growing number of studies have attributed functions to some Atgs that are distinct from their classical role in autophagosome biogenesis, such as resistance to pathogens. However, little is known about the functions of fish Atgs. In this study, we cloned and characterized an 〈em〉atg12〈/em〉 homolog from orange spotted grouper (〈em〉Epinephelus coioides〈/em〉) (〈em〉Ecatg12〈/em〉). 〈em〉Ecatg12〈/em〉 encodes a 117 amino acid protein that shares 94.0% and 76.8% identity with gourami (〈em〉Anabas_testudineus〈/em〉) and humans (〈em〉Homo sapiens〈/em〉), respectively. The transcription level of 〈em〉Ecatg12〈/em〉 was lower in cells infected with Singapore grouper iridovirus (SGIV) than in non-infected cells. Fluorescence microscopy revealed that EcAtg12 localized in the cytoplasm and nucleus in grouper spleen cells. Overexpression of EcAtg12 significantly increased the replication of SGIV, as evidenced by increased severity of the cytopathic effect, transcription levels of viral genes, levels of viral proteins, and progeny virus yield. Further studies showed that EcAtg12 overexpression decreased the expression levels of interferon (IFN) related molecules and pro-inflammatory factors and inhibited the promoter activity of IFN-3, interferon-stimulated response element, and nuclear factor-κB. Together, these results demonstrate that EcAtg12 plays crucial roles in SGIV replication by downregulating antiviral immune responses.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2020〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 125〈/p〉 〈p〉Author(s): Daoyuan Gong, Yunuo Wang, Yong Wang, Xin Chen, ShenYuan Chen, Ruixue Wang, Lian Liu, Chaohui Duan, Shuhong Luo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Prostate cancer (CaP) is a common male malignancy. Using prostate specific antigen (PSA) and prostate cancer antigen 3 (PCA3) in the diagnosis of prostate cancer, sensitivity and specificity still require improvement. Additional targets are urgently needed for the diagnosis, prognosis, and prediction of therapeutic response, leading to better treatments in order to reduce the mortality of CaP. Here, we utilized a solid-phase antibody array, which can simultaneously detect 200 proteins, for the screening of novel blood-based biomarkers. The proteins differentially expressed in the pathogenesis of CaP were further analyzed using bioinformatics methods. The identified targets were further validated by the enzyme-linked immunosorbent assay (ELISA). A total of 38 proteins were identified with significantly differential levels in CaP serum compared to healthy control serum, including 21 up-regulated and 17 down-regulated cytokines. ELISA result showed that validated six ones of these differential cytokines were significantly differential between CaP and control, consistent with the antibody array result. The protein-protein interaction (PPI) analysis for these differentially expressed cytokines showed the top five cytokines interacting with most other cytokines were insulin, SDF-1a, CD40L, IL-18 and NCAM-1, suggesting these five targets are important in the pathogenesis of CaP, and more sensitive for the early diagnosis and prognosis of CaP. Targeting these cytokines may be more effective therapies against CaP. Among these differentially expressed cytokines, it was found that AR, BTC, IL-1 F8, IL-31, Marapsin, b-NGF, EDA-A2, MCP-3, MCP-4, MIP-3a, PIGF, and TECK decreased, while Fas, Flt-3L, and NCAM-1 increased in CaP when compared to the controls. Taken together, those 38 differentially expressed cytokines may service as novel serum biomarkers for CaP, which will be further validated with more clinical samples.〈/p〉〈/div〉 〈/div〉