ALBERT

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Rebecca K. Donegan, Courtney M. Moore, David A. Hanna, Amit R. Reddi〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Heme is an essential cofactor and signaling molecule required for virtually all aerobic life. However, excess heme is cytotoxic. Therefore, heme must be safely transported and trafficked from the site of synthesis in the mitochondria or uptake at the cell surface, to hemoproteins in most subcellular compartments. While heme synthesis and degradation are relatively well characterized, little is known about how heme is trafficked and transported throughout the cell. Herein, we review eukaryotic heme transport, trafficking, and mobilization, with a focus on factors that regulate bioavailable heme. We also highlight the role of gasotransmitters and small molecules in heme mobilization and bioavailability, and heme trafficking at the host-pathogen interface.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918313273-fx1.jpg" width="301" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Tohru Fujiwara, Hideo Harigae〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Sideroblastic anemia is a heterogeneous congenital and acquired disorder characterized by anemia and the presence of ring sideroblasts in the bone marrow. Congenital sideroblastic anemia (CSA) is a rare disease caused by mutations in genes involved in the heme biosynthesis, iron–sulfur [Fe–S] cluster biosynthesis, and mitochondrial protein synthesis. The most prevalent form of CSA is X-linked sideroblastic anemia, caused by mutations in the erythroid-specific δ-aminolevulinate synthase (〈em〉ALAS2〈/em〉), which is the first enzyme of the heme biosynthesis pathway in erythroid cells. To date, a remarkable number of genetically undefined CSA cases remain, but a recent application of the next-generation sequencing technology has recognized novel causative genes for CSA. However, in most instances, the detailed molecular mechanisms of how defects of each gene result in the abnormal mitochondrial iron accumulation remain unclear. This review aims to cover the current understanding of the molecular pathophysiology of CSA.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918313558-fx1.jpg" width="247" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 29 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology〈/p〉 〈p〉Author(s): Sarithaa Sellaththurai, Thanthrige Thiunuwan Priyathilaka, Jehee Lee〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Organisms possess a cellular antioxidant defense system inclusive of ROS scavengers to maintain the homeostasis of antioxidant levels. Catalase is a major ROS scavenger enzyme that plays a significant role in the antioxidant defense mechanism of organisms by reducing toxic hydrogen peroxide molecules into a nontoxic form of oxygen and water with a high turnover rate. In the present study, we performed molecular and functional characterization of the catalase homolog from 〈em〉Hippocampus abdominalis〈/em〉 (HaCat). The 〈em〉HaCat〈/em〉 cDNA sequence was identified as a 1578 bp ORF (open reading frame) that encodes a polypeptide of 526 amino acids with 59.33 kDa molecular weight. Its estimated pI value is 7.7, and it does not have any signal sequences. HaCat shared a conserved domain arrangement including the catalase proximal active site signature and heme ligand signature domain with the previously identified catalase counterparts. Phylogenetic analysis displayed close evolutionary relationships between HaCat and catalases from other teleost fish. According to our qPCR results, ubiquitous expression of 〈em〉HaCat〈/em〉 transcripts were observed in all the tested tissues with high expression in the kidney followed by liver. Significant modulations of 〈em〉HaCat〈/em〉 transcription were observed in blood, liver, and kidney tissues post-challenge with 〈em〉Streptococcus iniae〈/em〉, 〈em〉Edwardsiella tarda〈/em〉, poly I:C, and LPS. Peroxidase activity of recombinant HaCat (rHaCat) was evaluated using an ABTS assay and the ROS removal effect was further confirmed by oxidative DNA damage protection and cell viability assays. The rHaCat showed more than 97% activity over a temperature and pH range of 10 °C–40 °C and 5 to 6, respectively. The above results suggest that HaCat plays an indispensable role in the oxidative homeostasis of the seahorse during pathogenic attack.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 30 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology〈/p〉 〈p〉Author(s): Chunyan Zhao, Guangpeng Jiang, Shun Zhou, Guodong Wang, Zhenxia Sha, Yongjun Sun, Yunji Xiu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Lysin motif (LysM) is involved in chitin, peptidoglycan and other structurally-related oligosaccharides recognition and binding, and it is important for the biological processes of responsing to bacterial and viral infections and pathogen defense. LysM is also a widely spread protein, ranging from prokaryotes to eukaryotes, including bacteria, plants and mammals. However, research of LysM in teleosts especially in marine fish was rarely scarce. In the present study, four novel LysM domain-containing proteins in turbot (〈em〉Scophthalmus maximus〈/em〉), named as 〈em〉SmLysMd1〈/em〉, 〈em〉SmLysMd2〈/em〉, 〈em〉SmLysMd3〈/em〉, and 〈em〉SmLysMd4〈/em〉, were cloned and identified firstly. The full-length cDNA of 〈em〉SmLysMd1〈/em〉 was 1235 bp with a 678 bp ORF, capable of encoding a peptide of 225 amino acids. The complete cDNA sequence of 〈em〉SmLysMd2〈/em〉 was 1273 bp, and contained a 675 bp ORF, encoding a predicted protein of 224 amino acids. The full-length of 〈em〉SmLysMd3〈/em〉 cDNA was 2132 bp, containing a ORF of 987 bp, with a ORF of encoding 328 amino acids. The full-length 〈em〉SmLysMd4〈/em〉 cDNA was 1115 bp contained a 888 bp ORF, encoding 295 amino acids. And all the four predicated proteins contained a specific LYSM domain. Moreover, 〈em〉SmLysMd1〈/em〉 and 〈em〉SmLysMd2〈/em〉 belong to the intracellular non-secretory types, and 〈em〉SmLysMd3〈/em〉 and 〈em〉SmLysMd4〈/em〉 belong to the anchored transmembrane types. In addition, the four 〈em〉SmLysMd〈/em〉 were ubiquitously expressed in all the examined tissues. Moreover, the 〈em〉SmLysMds〈/em〉 levels were up-regulated in muscle and liver, and had a reduce tendency immediately in different degree following 〈em〉Vibrio vulnificus〈/em〉 challenge, indicating that the turbot LysM could be participant in the immune responses to bacterial infections. The present result of LysM in turbot for the first time in a marine fish will provide foundation knowledge for the functions studies of LysM in immune responses. Further studies should be carried out to better understand their immune mechanism in turbot and other teleosts.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: May 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 88〈/p〉 〈p〉Author(s): 〈/p〉

Description: 〈p〉Publication date: Available online 29 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology〈/p〉 〈p〉Author(s): Muhammad Nadeem Abbas, Saima Kausar, Hongjuan Cui〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Peroxiredoxins (Prxs) are a widespread and greatly transcribed family of antioxidant proteins, which rapidly detoxify peroxynitrite, hydrogen peroxide and organic hydroperoxides. The Prxs family members also modulate various physiological functions, including cell growth, differentiation, embryonic development, immune response, apoptosis, lipid metabolism, and cellular homeostasis. In mammals, the physiological functions of Prxs have extensively been studied; however, the knowledge is scanty in their counterpart, aquatic invertebrates. In recent years, substantial progress has been made in our knowledge of Prxs physiological functions in aquatic invertebrates, which has raised interest in defining the contribution of immune responses and removal of reactive oxygen species. In this review, we describe the recent knowledge on the Prxs physiological function in immune responses and DNA protection activity in aquatic invertebrates.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1050464819302116-fx1.jpg" width="500" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 28 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology〈/p〉 〈p〉Author(s): Ping Wang, Zhanying Zhang, Zhongtian Xu, Baoying Guo, Zhi Liao, Pengzhi Qi〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Toll-like receptors (TLRs) are a category of most well recognized pattern recognition molecules that act on an vital role in both innate and adaptive immunity. In the present study, a novel toll-like receptor (〈em〉Mc〈/em〉TLRw) was identified and characterized in thick shell mussel 〈em〉Mytilus coruscus. Mc〈/em〉TLRw possesses one intracellular Toll/interleukin-1 (IL-1) receptor (TIR) domain, one transmembrane region (TM), one leucine rich repeat N-terminal domain (LRR_NT) and a few of leucine-rich repeats (LRRs), which all are common in typical TLRs. 〈em〉Mc〈/em〉TLRw transcripts were constitutively expressed in all examined tissues with higher expression levels in immune related tissues, and were significantly induced in haemocytes with the challenges of live 〈em〉Vibrio alginolyticus〈/em〉, lipopolysaccharide (LPS), peptidoglycans (PGN) and β-glucan (GLU), but not induced by polyinosinic-polycytidylic acid (poly I:C). rMcTLRw exhibited affinity to LPS, PGN and GLU while no affinity to poly I:C. Further, the downstream of TLR signaling pathway myeloid differentiation factor 88a (MyD88a), interleukin-1 receptor-associated kinase-4 (IRAK4) and tumor necrosis factor receptor-associated factor 6 (TRAF6) were significantly repressed in 〈em〉Mc〈/em〉TLRw silenced mussels while challenged with LPS. These results collectively indicated that 〈em〉Mc〈/em〉TLRw is one member of TLR family and involved in immune response to against invaders by taking participate in TLR mediated signaling pathway.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 29 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology〈/p〉 〈p〉Author(s): Xiaorui Song, Ying Song, Miren Dong, Zhaoqun Liu, Weilin Wang, Lingling Wang, Linsheng Song〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The Runx family is a kind of heteromeric transcription factors, which is defined by the presence of a runt domain. As transcriptional regulator during development and cell fate specification, Runx is best known for its critical roles in hematopoiesis. In the present study, a Runx transcription factor (designed as 〈em〉Cg〈/em〉Runx) was identified and characterized from the oyster 〈em〉Crassostrea gigas〈/em〉. The complete coding sequence of 〈em〉Cg〈/em〉Runx was of 1638 bp encoding a predicted polypeptide of 545 amino acids with one conserved runt domain, which shared high similarity with other reported Runx proteins. 〈em〉Cg〈/em〉Runx was highly expressed in hemocytes, gill and mantle both at the protein and nucleic acid levels. 〈em〉Cg〈/em〉Runx protein was localized specifically in the cell nuclei of hemocytes, and distributed at the tubule lumen of gill filament. During the larval developmental stages, the mRNA transcripts of 〈em〉Cg〈/em〉Runx gradually increased after fertilization, reached to a relative high level at the 8 cell embryos and the blastula stage of 2–4 hpf (hours post fertilization) (about 40-fold), and peaked at early trochophore larvae (10 hpf) (about 60-fold). Whole-mount immunofluorescence assay further revealed that the abundant immunofluorescence signals of 〈em〉Cg〈/em〉Runx distributed through the whole embryo at blastula stage (5 hpf), and progressively reduced with the development to a ring structure around the dorsal region in trochophore larvae (10 hpf). Scattered positive immunoreactivity signals finally appeared in the velum region of D-veliger larvae. After LPS and 〈em〉Vibrio splendidus〈/em〉 stimulations, the expression levels of 〈em〉CgRunx〈/em〉 mRNA in hemocytes were up-regulated significantly compared with that in the control (0 h), which were 2.98- and 2.46-fold (〈em〉p〈/em〉 〈 0.05), 2.67- and 1.5-fold (〈em〉p〈/em〉 〈 0.05), 2.36- and 1.38-fold (〈em〉p〈/em〉 〈 0.05) at 3 h, 6 h and 12 h, respectively. These results collectively suggested that 〈em〉Cg〈/em〉Runx involved in immune response and might participate in larvae hematopoiesis in oyster.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 29 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Rochelle M. Soo, James Hemp, Philip Hugenholtz〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉For well over a hundred years, members of the bacterial phylum Cyanobacteria have been considered strictly photosynthetic microorganisms, reflected in their classification as “blue-green algae” in the botanical code. Recently, genomes recovered from environmental sequencing surveys representing two major uncultured basal lineages (classes) of Cyanobacteria have been found to completely lack photosynthetic and CO〈sub〉2〈/sub〉 fixation genes. The most likely explanation for this finding is that oxygenic photosynthesis was not an ancestral feature of the Cyanobacteria, and rather originated following divergence of the primary lines of descent. Here we describe recent findings on the evolution of aerobic respiration in the non-photosynthetic cyanobacterial classes, and how this has been interpreted by researchers interested in the evolution of oxygenic photosynthesis.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918323001-fx1.jpg" width="357" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 27 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Chaolu Chen, Yong Zhou, Changchang Hu, Yinfeng Wang, Zhuqing Yan, Zhi Li, Ruijin Wu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Endometriosis is associated with inflammatory reaction, and reactive oxidative species (ROS) are highly pro-inflammatory factors. Mitochondria are responsible for the production of ROS and energy. However, little is known about how mitochondria regulate ROS generation and energy metabolism in endometriosis. In our study, we investigated mitochondrial structure and function of ectopic endometrial stromal cells (ESCs) in ovarian endometriosis. We found mitochondria in ectopic ESCs generated more ROS and energy than controlled groups. Mitochondrial superoxide dismutase (SOD2), as an antioxidant enzyme, was found highly expressed in ectopic endometrium compared with normal endometrium. Due to its antioxidant role, SOD2 promoted the development of endometriosis by maintaining functional mitochondria to support high energetic metabolism of ectopic ESCs. We also showed that SOD2 promoted cell proliferation and migration in ovarian endometriosis. Inhibiting SOD2 expression reduced proliferation and migration of ectopic ESCS, and increased cell apoptosis. Therefore, understanding the role of mitochondrial dysfunction and SOD2 in ovarian endometriosis may provide new strategies to treat this disease.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919302643-fx1.jpg" width="335" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 26 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Masaru Yamaguchi, Tokuhisa Hirouchi, Haruhiko Yoshioka, Jun Watanabe, Ikuo Kashiwakura〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In cases of radiological accidents, especially victims exposed to high-dose ionizing radiation, the administration of appropriate approved pharmaceutical drugs is the most rapid medical treatment. However, currently, there are no suitable candidates. The thrombopoietin receptor (TPOR) agonist romiplostim (RP) is a therapeutic agent for immune thrombocytopenia and has potential to respond to such victims. Here, we show that RP administration in mice exposed to lethal-dose radiation leads not only to the promotion of haematopoiesis in multiple organs, including the lungs but also a reduction in damage to organs and cells. RP also causes a rapid increase in the number of mesenchymal stem cells in the spleen. In addition, RP suppresses the expression of several miRNAs involved in radiation-induced leukemogenesis, suggesting the presence of targets other than TPOR. Among the currently approved pharmaceutical drugs, RP is the most suitable candidate for victims exposed to high-dose ionizing radiation.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919302485-fx1.jpg" width="236" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 26 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Blazej Rubis, Michal W. Luczak, Casey Krawic, Anatoly Zhitkovich〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Bleomycin is a redox-active drug with anticancer and other clinical applications. It is also frequently used as a tool in fundamental research on cellular responses to DNA double-strand breaks (DSBs). A conversion of bleomycin into its DNA-breaking form requires Fe, one-electron donors and O〈sub〉2〈/sub〉. Here, we examined how a major biological antioxidant ascorbate (reduced vitamin C), which is practically absent in standard cell culture, impacts cellular responses to bleomycin. We found that restoration of physiological levels of vitamin C in human cancer cells increased their killing by bleomycin in 2D cultures and 3D tumor spheroids. Higher cytotoxicity of bleomycin occurred in cells with normal and shRNA-depleted p53. Cellular vitamin C enhanced the ability of bleomycin by produce DSBs, which was established by direct measurements of these lesions in three cell lines. Vitamin C-restored cancer cells also showed a higher sensitivity to killing by low-dose bleomycin in combination with inhibitors of DSB repair-activating ATM or DNA-PK kinases. The presence of ascorbate in bleomycin-treated cells suppressed a DSB-independent activation of the ATM-CHK2 axis by blocking superoxide radical. 〈em〉In vitro〈/em〉 studies detected a greatly superior ability of ascorbate over other cellular reducers to catalyze DSB formation by bleomycin. Ascorbate was faster than other antioxidants in promoting two steps in activation of bleomycin. Our results demonstrate strong activation effects of vitamin C on bleomycin, shifting its toxicity further toward DNA damage and making it more sensitive to manipulations of DNA repair.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919301613-fx1.jpg" width="328" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 25 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Irene Wood, Andrés Trostchansky, Yi Xu, Steven Qian, Rafael Radi, Homero Rubbo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Prostaglandin endoperoxide H synthase (PGHS) is a heme-enzyme responsible for the conversion of arachidonic acid (AA) to prostaglandin H〈sub〉2〈/sub〉 (PGH〈sub〉2〈/sub〉). PGHS have both oxygenase (COX) and peroxidase (POX) activities and is present in two isoforms (PGHS-1 and -2) expressed in different tissues and cell conditions. It has been reported that PGHS activity is inhibited by the nitrated form of AA, nitro-arachidonic acid (NO〈sub〉2〈/sub〉AA), which in turn could be synthesized by PGHS under nitro-oxidative conditions. Specifically, NO〈sub〉2〈/sub〉AA inhibits COX in PGHS-1 as well as POX in both PGHS-1 and -2, in a dose and time-dependent manner. NO〈sub〉2〈/sub〉AA inhibition involves lowering the binding stability and displacing the heme group from the active site. However, the complete mechanism remains to be understood. This review describes the interactions of PGHS with NO〈sub〉2〈/sub〉AA, focusing on mechanisms of inhibition and nitration. In addition, using a novel approach combining EPR-spin trapping and mass spectrometry, we described possible intermediates formed during PGHS-2 catalysis and inhibition. This literature revision as well as the results presented here strongly suggest a free radical-dependent inhibitory mechanism of PGHS-2 by NO〈sub〉2〈/sub〉AA. This is of relevance towards understanding the underlying mechanism of inhibition of PGHS by NO〈sub〉2〈/sub〉AA and its anti-inflammatory potential.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919302308-fx1.jpg" width="358" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Tasuku Hirayama〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Iron (Fe) is the most abundant redox-active metal ion in the human body, and its redox-active inter-convertible multiple oxidation states contributes to numerous essential biological processes. Moreover, iron overload can potentially cause cellular damage and death, as wel as numerous diseases through the aberrant production of highly reactive oxidative species (hROS). Protein-free or weakly-protein-bound Fe ions play a pivotal role as catalytic reactants of the Fenton reaction. In this reaction, hROS, such as hydroxyl radicals and high valent-iron-oxo species, are generated by a reaction between hydrogen peroxide and Fe(II), which is re-generated through reduction using abundant intracellular reductants, such as glutathione. This results in the catalytic evolution of hROS. Thus, selective detection of the catalytic Fe(II) in the living systems can explain both of the pathological and physiological functions of Fe(II). Written from the perspective of their modes of actions, this paper presents recent advances in the development of fluorescent and bioluminescent probes that can selectively detect catalytic Fe(II) together with their biological applications.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S089158491831195X-fx1.jpg" width="498" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Mitchell D. Knutson〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Most cells in the body acquire iron via receptor-mediated endocytosis of transferrin, the circulating iron transport protein. When cellular iron levels are sufficient, the uptake of transferrin decreases to limit further iron assimilation and prevent excessive iron accumulation. In iron overload conditions, such as hereditary hemochromatosis and thalassemia major, unregulated iron entry into the plasma overwhelms the carrying capacity of transferrin, resulting in non-transferrin-bound iron (NTBI), a redox-active, potentially toxic form of iron. Plasma NTBI is rapidly cleared from the circulation primarily by the liver and other organs (e.g., pancreas, heart, and pituitary) where it contributes significantly to tissue iron overload and related pathology. While NTBI is usually not detectable in the plasma of healthy individuals, it does appear to be a normal constituent of brain interstitial fluid and therefore likely serves as an important source of iron for most cell types in the CNS. A growing body of literature indicates that NTBI uptake is mediated by non-transferrin-bound iron transporters such as ZIP14, L-type and T-type calcium channels, DMT1, ZIP8, and TRPC6. This review provides an overview of NTBI uptake by various tissues and cells and summarizes the evidence for and against the roles of individual transporters in this process.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918321762-fx1.jpg" width="301" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): W.H. Koppenol, R.H. Hider〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉A major form of toxicity arises from the ability of iron to redox cycle, that is, to accept an electron from a reducing compound and to pass it on to H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 (the Fenton reaction). In order to do so, iron must be suitably complexed to avoid formation of Fe〈sub〉2〈/sub〉O〈sub〉3〈/sub〉. The ligands determine the electrode potential; this information should be known before experiments are carried out. Only one-electron transfer reactions are likely to be significant; thus two-electron potentials should not be used to determine whether an iron(III) complex can be reduced or oxidized. Ascorbate is the relevant reducing agent in blood serum, which means that iron toxicity in this compartment arises from the ascorbate-driven Fenton reaction. In the cytosol, an iron(II)-glutathione complex is likely to be the low-molecular weight iron complex involved in toxicity. When physiologically relevant concentrations are used the window of redox opportunity ranges from +0.1 V to +0.9 V. The electrode potential for non-transferrin-bound iron in the form of iron citrate is close to 0 V and the reduction of iron(III) citrate by ascorbate is slow. The clinically utilised chelators desferrioxamine, deferiprone and deferasirox in each case render iron complexes with large negative electrode potentials, thus being effective in preventing iron redox cycling and the associated toxicity resulting from such activity. There is still uncertainty about the product of the Fenton reaction, HO〈sup〉•〈/sup〉 or FeO〈sup〉2+〈/sup〉.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918316071-fx1.jpg" width="301" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): William Z. Zhang, James J. Butler, Suzanne M. Cloonan〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Iron is one of the most abundant transition elements and is indispensable for almost all organisms. While the ability of iron to participate in redox chemistry is an essential requirement for participation in a range of vital enzymatic reactions, this same feature of iron also makes it dangerous in the generation of hydroxyl radicals and superoxide anions. Given the high local oxygen tensions in the lung, the regulation of iron acquisition, utilization, and storage therefore becomes vitally important, perhaps more so than in any other biological system. Iron plays a critical role in the biology of essentially every cell type in the lung, and in particular, changes in iron levels have important ramifications on immune function and the local lung microenvironment. There is substantial evidence that cigarette smoke causes iron dysregulation, with the implication that iron may be the link between smoking and smoking-related lung diseases. A better understanding of the connection between cigarette smoke, iron, and respiratory diseases will help to elucidate pathogenic mechanisms and aid in the identification of novel therapeutic targets.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918313054-fx1.jpg" width="282" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Samira Lakhal-Littleton〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Heart disease is a common manifestation in conditions of iron imbalance. Normal heart function requires coupling of iron supply for oxidative phosphorylation and redox signalling with tight control of intracellular iron to below levels at which excessive ROS are generated. Iron supply to the heart is dependent on systemic iron availability which is controlled by the systemic hepcidin/ferroportin axis. Intracellular iron in cardiomyocytes is controlled in part by the iron regulatory proteins IRP1/2. This mini-review summarises current understanding of how cardiac cells regulate intracellular iron levels, and of the mechanisms linking cardiac dysfunction with iron imbalance. It also highlights a newly-recognised mechanism of intracellular iron homeostasis in cardiomyocytes, based on a cell-autonomous cardiac hepcidin/ferroportin axis. This new understanding raises pertinent questions on the interplay between systemic and local iron control in the context of heart disease, and the effects on heart function of therapies targeting the systemic hepcidin/ferroportin axis.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918313868-fx1.jpg" width="495" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Tobias M. Seibt, Bettina Proneth, Marcus Conrad〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation and metabolic constraints. Dependence on NADPH/H〈sup〉+〈/sup〉, polyunsaturated fatty acid metabolism, and the mevalonate and glutaminolysis metabolic pathways have been implicated in this novel form of regulated necrotic cell death. Genetic studies performed in cells and mice established the selenoenzyme glutathione peroxidase (GPX4) as the key regulator of this form of cell death. Besides these genetic models, the identification of a series of small molecule ferroptosis-specific inhibitors and inducers have not only helped in the delineation of the molecular underpinnings of ferroptosis but they might also prove highly beneficial when tipping the balance between cell death inhibition and induction in the context of degenerative diseases and cancer, respectively. In the latter, the recent recognition that a subset of cancer cell lines including certain triple negative breast cancer cells and those of therapy-resistant high-mesenchymal cell state present a high dependence on this lipid make-up offers unprecedented opportunities to eradicate difficult to treat cancers. Due to the rapidly growing interest in this form of cell death, we provide an overview herein what we know about this field today and its future translational impact.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918315934-fx1.jpg" width="301" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Caroline C. Philpott, Shyamalagauri Jadhav〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mammalian cells contain thousands of metalloproteins and have evolved sophisticated systems for ensuring that metal cofactors are correctly assembled and delivered to their proper destinations. Equally critical in this process are the strategies to avoid the insertion of the wrong metal cofactor into apo-proteins and to avoid the damage that redox-active metals can catalyze in the cellular milieu. Iron and zinc are the most abundant metal cofactors in cells and iron cofactors include heme, iron-sulfur clusters, and mono- and dinuclear iron centers. Systems for the intracellular trafficking of iron cofactors are being characterized. This review focuses on the trafficking of ferrous iron cofactors in the cytosol of mammalian cells, a process that involves specialized iron-binding proteins, termed iron chaperones, of the poly rC-binding protein family.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918321671-fx1.jpg" width="301" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 February 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 132〈/p〉 〈p〉Author(s): Jesalyn A. Bolduc, John A. Collins, Richard F. Loeser〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Chondrocytes are responsible for the maintenance of the articular cartilage. A loss of homeostasis in cartilage contributes to the development of osteoarthritis (OA) when the synthetic capacity of chondrocytes is overwhelmed by processes that promote matrix degradation. There is evidence for an age-related imbalance in reactive oxygen species (ROS) production relative to the anti-oxidant capacity of chondrocytes that plays a role in cartilage degradation as well as chondrocyte cell death. The ROS produced by chondrocytes that have received the most attention include superoxide, hydrogen peroxide, the reactive nitrogen species nitric oxide, and the nitric oxide derived product peroxynitrite. Excess levels of these ROS not only cause oxidative-damage but, perhaps more importantly, cause a disruption in cell signaling pathways that are redox-regulated, including Akt and MAP kinase signaling. Age-related mitochondrial dysfunction and reduced activity of the mitochondrial superoxide dismutase (SOD2) are associated with an increase in mitochondrial-derived ROS and are in part responsible for the increase in chondrocyte ROS with age. Peroxiredoxins (Prxs) are a key family of peroxidases responsible for removal of H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉, as well as for regulating redox-signaling events. Prxs are inactivated by hyperoxidation. An age-related increase in chondrocyte Prx hyperoxidation and an increase in OA cartilage has been noted. The finding in mice that deletion of SOD2 or the anti-oxidant gene transcriptional regulator nuclear factor-erythroid 2- related factor (Nrf2) result in more severe OA, while overexpression or treatment with mitochondrial targeted anti-oxidants reduces OA, further support a role for excessive ROS in the pathogenesis of OA. Therefore, new therapeutic strategies targeting specific anti-oxidant systems including mitochondrial ROS may be of value in reducing the progression of age-related OA.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918315004-fx1.jpg" width="208" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Tal Hirschhorn, Brent R. Stockwell〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The term ferroptosis was coined in 2012 to describe an iron-dependent regulated form of cell death caused by the accumulation of lipid-based reactive oxygen species; this type of cell death was found to have molecular characteristics distinct from other forms of regulated cell death. Features of ferroptosis have been observed periodically over the last several decades, but these molecular features were not recognized as evidence of a distinct form of cell death until recently. Here, we describe the history of observations consistent with the current definition of ferroptosis, as well as the advances that contributed to the emergence of the concept of ferroptosis. We also discuss recent implications and applications of manipulations of the ferroptotic death pathway.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918317283-fx1.jpg" width="500" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Stefania Recalcati, Elena Gammella, Gaetano Cairo〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉Cancer stem cells (CSCs) are a distinct subpopulation of tumor cells endowed with stem-like properties. Importantly, CSCs can survive current standard therapies, resulting in metastatic disease and tumor recurrence. Here we describe the alterations of iron homeostasis occurring in CSCs, which in general are characterized by high intracellular iron content. Importantly, abnormalities of iron metabolism correlate with faster tumor growth and adverse prognosis in cancer patients.〈/p〉 〈p〉In line with the dependence of cancer on iron, we also discuss iron-dependent mechanisms as druggable pathways, as iron chelators have been considered for tumor therapy and new molecules currently proposed and studied as antineoplastic drugs may impinge on iron and its capacity to promote oxidative stress to have therapeutic value in cancer.〈/p〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918312590-fx1.jpg" width="301" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Charles Badu-Boateng, Richard J. Naftalin〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉This review discusses the chemical mechanisms of ascorbate-dependent reduction and solubilization of ferritin's ferric iron core and subsequent release of ferrous iron. The process is accelerated by low concentrations of Fe(II) that increase ferritin's intrinsic ascorbate oxidase activity, hence increasing the rate of ascorbate radical formation. These increased rates of ascorbate oxidation provide reducing equivalents (electrons) to ferritin's core and speed the core reduction rates with subsequent solubilization and release of Fe(II).〈/p〉 〈p〉Ascorbate-dependent solubilization of ferritin's iron core has consequences relating to the interpretation of 〈sup〉59〈/sup〉Fe uptake sourced from 〈sup〉59〈/sup〉Fe-lebelled holotransferrin into ferritin. Ascorbate-dependent reduction of the ferritin core iron solubility increases the size of ferritin's iron exchangeable pool and hence the rate and amount of exchange uptake of 〈sup〉59〈/sup〉Fe into ferritin, whilst simultaneously increasing net iron release rate from ferritin. This may rationalize the inconsistency that ascorbate apparently stabilizes 〈sup〉59〈/sup〉Fe ferritin and retards lysosomal ferritinolysis and whole cell 〈sup〉59〈/sup〉Fe release, whilst paradoxically increasing the rate of net iron release from ferritin.〈/p〉 〈p〉This capacity of ascorbate and iron to synergise ferritin iron release has pathological significance, as it lowers the concentration at which ascorbate activates ferritin's iron release to within the physiological range (50–250 μM). These effects have relevance to inflammatory pathology and to the pro-oxidant effects of ascorbate in cancer therapy and cell death by ferroptosis.〈/p〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918317180-fx1.jpg" width="421" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Keisuke Hino, Sohij Nishina, Kyo Sasaki, Yuichi Hara〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Hepatitis C virus (HCV) infection often leads to chronic hepatitis that can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Although HCV infection is expected to decrease due to the high rate of HCV eradication via the rapid dissemination and use of directly acting antivirals, HCV infection remains a leading cause of HCC. Although the mechanisms underlying the HCC development are not fully understood, oxidative stress is present to a greater degree in HCV infection than in other inflammatory liver diseases and has been proposed as a major mechanism of liver injury in patients with chronic hepatitis C. Hepatocellular mitochondrial alterations and iron accumulation are well-known characteristics in patients with chronic hepatitis C and are closely related to oxidative stress, since the mitochondria are the main site of reactive oxygen species generation, and iron produces hydroxy radicals via the Fenton reaction. In addition, phlebotomy is an iron reduction approach that aims to lower serum transaminase levels in patients with chronic hepatitis C. Here, we review and discuss the mechanisms by which HCV induces mitochondrial damage and iron accumulation in the liver and offer new insights concerning how mitochondrial damage and iron accumulation are linked to the development of HCC.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918317295-fx1.jpg" width="301" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 February 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 132〈/p〉 〈p〉Author(s): Panagiotis Lepetsos, Kostas A. Papavassiliou, Athanasios G. Papavassiliou〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Human cells have to deal with the constant production of reactive oxygen species (ROS). Although ROS overproduction might be harmful to cell biology, there are plenty of data showing that moderate levels of ROS control gene expression by maintaining redox signaling. Osteoarthritis (OA) is the most common joint disorder with a multi-factorial etiology including overproduction of ROS. ROS overproduction in OA modifies intracellular signaling, chondrocyte life cycle, metabolism of cartilage matrix and contributes to synovial inflammation and dysfunction of the subchondral bone. In arthritic tissues, the NF-κB signaling pathway can be activated by pro-inflammatory cytokines, mechanical stress, and extracellular matrix degradation products. This activation results in regulation of expression of many cytokines, inflammatory mediators, transcription factors, and several matrix-degrading enzymes. Overall, NF-κB signaling affects cartilage matrix remodeling, chondrocyte apoptosis, synovial inflammation, and has indirect stimulatory effects on downstream regulators of terminal chondrocyte differentiation. Interaction between redox signaling and NF-κB transcription factors seems to play a distinctive role in OA pathogenesis.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918316162-fx1.jpg" width="236" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Alessandro F. Gualtieri, Giovanni B. Andreozzi, Maura Tomatis, Francesco Turci〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Iron and its role as soul of life on Earth is addressed in this review as iron is one of the most abundant elements of our universe, forms the core of our planet and that of telluric (i.e., Earth-like) planets, is a major element of the Earth's crust and is hosted in an endless number of mineral phases, both crystalline and amorphous. To study iron at an atomic level inside the bulk of mineral phases or at its surface, where it is more reactive, both spectroscopy and diffraction experimental methods can be used, taking advantage of nearly the whole spectrum of electromagnetic waves. These methods can be successfully combined to microscopy to simultaneously provide chemical (e.g. iron mapping) and morphological information on mineral particles, and shed light on the interaction of mineral surfaces with organic matter. This review describes the crystal chemistry of iron-bearing minerals of importance for the environment and human health, with special attention to iron in toxic minerals, and the experimental methods used for their study. Special attention is devoted to the Fenton-like chain reaction involving Fe〈sup〉2+〈/sup〉 in the formation of highly reactive hydroxyl radicals. The final part of this review deals with release and adsorption of iron in biological fluids, coordinative and oxidative state of iron and in vitro reactivity. To disclose the very mechanisms of carcinogenesis induced by iron-bearing toxic mineral particles, crystal chemistry and surface chemistry are fundamental for a multidisciplinary approach which should involve geo-bio-scientists, toxicologists and medical doctors.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918312991-fx1.jpg" width="411" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 29 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology〈/p〉 〈p〉Author(s): Cuihong You, Baojia Chen, Meng Wang, Shuqi Wang, Mei Zhang, Zhijie Sun, Aweya Jude Juventus, Hongyu Ma, Yuanyou Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Replacement of fish oil (FO) with vegetable oils (VO) in diets is economically desirable for the sustainable development of the aquaculture industry. However, inflammation provoked by FO replacement limited its widely application in fish industry. In order to understand the mechanism of VO-induced inflammation, this study investigated the impact of different dietary vegetable oils on the intestinal health and microbiome in carnivorous marine fish golden pompano (〈em〉Trachinotus ovatus〈/em〉). Three diets supplemented with fish oil (FO, rich in long-chain polyunsaturated fatty acids), soybean oil (SO, rich in 18:2n-6) and linseed oil (LO, rich in 18:3n-3), respectively, were fed on juvenile golden pompano for 8 weeks, and the intestinal histology, digestive enzymes activities, immunity and antioxidant indices as well as intestinal microbiome were determined. The results showed that dietary SO significantly impaired intestinal health, and decreased the number and height of intestinal folds, and muscle thickness, as well as the zonula occludens-1 (〈em〉zo-1〈/em〉) mRNA expression in intestine. Moreover, the two dietary VO significantly decreased the amylase and lipase activities in intestine, and reduced the trypsin activity in the dietary SO group. Furthermore, the two VO diets increased intestinal acid phosphatase (ACP) activity, while intestinal lysozyme (LZM) activity and serum diamine oxidase (DAO) activity in the SO group were also significantly increased (〈em〉P〈/em〉 〈 0.05). Analysis of the intestinal microbiota showed that the two VO diets significantly increased the abundance of intestinal potentially pathogenic bacteria (〈em〉Mycoplasma〈/em〉 and 〈em〉Vibrio〈/em〉) and decreased proportions of intestinal probiotics (〈em〉Bacillus and Lactococcus〈/em〉), especially in the dietary SO group. These results indicate that complete replacement of FO with VO in diets would induce intestinal inflammation and impair intestinal function, which might be due to changes in intestinal microbiota profiles, and that dietary SO would have a more negative effect compared to dietary LO on intestinal health in 〈em〉T. ovatus〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 29 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology〈/p〉 〈p〉Author(s): Hengwei Deng, Xiaopeng Xu, Lei Hu, Jingjing Li, Dandan Zhou, Shanshan Liu, Panpan Luo, Jianguo He, Shaoping Weng〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉JAK/STAT signaling pathways are associated with the innate immune system and play important roles in mediating immune responses to virus infection. In this study, a Janus kinase gene from 〈em〉Scylla paramamosain〈/em〉 (〈em〉Sp〈/em〉JAK) was cloned and characterized. The full length of 〈em〉Sp〈/em〉JAK mRNA contains a 5′ untranslated region (UTR) of 304 bp, an open reading frame of 3300 bp and a 3′ UTR of 302 bp. The 〈em〉Sp〈/em〉JAK protein contains seven characteristic JAK homology domains (JH1 to JH7) and showed 60% identity (78% similarity), 20% identity (35% similarity), and 21% identity (37% similarity) to the 〈em〉Litopenaeus vannamei〈/em〉 JAK (〈em〉Lv〈/em〉JAK) protein, the 〈em〉Drosophila melanogaster〈/em〉 hopscotch protein, and the 〈em〉Homo sapiens〈/em〉 JAK2 protein, respectively. The mRNA of 〈em〉Sp〈/em〉JAK showed high expression in the brain and nerve but low expression in the hemocyte and muscle. Moreover, the expression of 〈em〉Sp〈/em〉JAK was significantly upregulated by stimulation with mud crab reovirus (MCRV), poly(I:C), and 〈em〉Vibrio parahaemolyticus〈/em〉. 〈em〉Sp〈/em〉JAK significantly activated the STAT of 〈em〉S. paramamosain〈/em〉 (〈em〉Sp〈/em〉STAT) to translocate to the nucleus of 〈em〉Drosophila〈/em〉 Schneider 2 cells. 〈em〉Sp〈/em〉JAK significantly enhanced the activity of the promoter of the WSSV wsv069 gene that was activated significantly by 〈em〉Sp〈/em〉STAT by acting on the STAT-binding DNA motif. These results suggest that 〈em〉Sp〈/em〉JAK activates the JAK/STAT pathway. Furthermore, silencing 〈em〉Sp〈/em〉JAK 〈em〉in vivo〈/em〉 resulted in the high mortality rate of MCRV-infected mud crabs and increased the viral load in tissues. Hence, 〈em〉Sp〈/em〉JAK could play an important role in defense against MCRV in mud crab.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 29 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Jagoda Jabłońska, Dan S. Tawfik〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Oxygen is a major metabolic driving force that enabled the expansion of metabolic networks including new metabolites and new enzymes. It had a dramatic impact on the primary electron transport chain where it serves as terminal electron acceptor, but oxygen is also used by many enzymes as electron acceptor for a variety of reactions. The organismal oxygen phenotype, aerobic vs. anaerobic, should be manifested in its O〈sub〉2〈/sub〉-utilizing enzymes. Traditionally, enzymes involved in primary oxygen metabolism such as cytochrome 〈em〉c〈/em〉, and reactive oxygen species (ROS)-neutralizing enzymes (e.g. catalase), were used as identifiers of oxygen phenotype. However, these enzymes are often found in strict anaerobes. We aimed to identify the O〈sub〉2〈/sub〉-utilizing enzymes that may distinguish between aerobes and anaerobes. To this end, we annotated the O〈sub〉2〈/sub〉-utilizing enzymes across the prokaryotic tree of life. We recovered over 700 enzymes and mapped their presence/absence in 272 representative genomes. As seen before, enzymes mediating primary oxygen metabolism, and ROS neutralizing enzymes, could be found in both aerobes and anaerobes. However, there exists a subset of enzymes, primarily oxidases that catabolyze various substrates, including amino acids and xenobiotics, that are preferentially enriched in aerobes. Overall it appears that the total number of oxygen-utilizing enzymes, and the presence of enzymes involved in ‘peripheral’, secondary oxygen metabolism, can reliably distinguish aerobes from anaerobes based solely on genome sequences. These criteria can also indicate the oxygen phenotype in metagenomic samples.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918324699-fx1.jpg" width="404" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 29 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology〈/p〉 〈p〉Author(s): Wen Yang, Chao Liu, Qingsong Xu, Chen Qu, Jiejie Sun, Shu Huang, Ning Kong, Xiaojing Lv, Zhaoqun Liu, Lingling Wang, Linsheng Song〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Beclin-1, the mammalian ortholog of yeast Atg6, plays essential roles in the regulation of various processes, including autophagy, apoptosis, embryonic development and immune responses in vertebrates. However, the information about Beclin-1 in invertebrates especially crustaceans is still very limited. In the present study, a novel Beclin-1 (designated as 〈em〉Es〈/em〉Beclin-1) was identified from Chinese mitten crab 〈em〉Eriocheir sinensis〈/em〉. The open reading frame of 〈em〉Es〈/em〉Beclin-1 cDNA was of 1275 bp, encoding a typical APG6 domain. The deduced amino acid sequence of 〈em〉Es〈/em〉Beclin-1 shared high similarity ranging from 42.9% to 63.6% with the previously identified Beclins. In the phylogenetic tree, 〈em〉Es〈/em〉Beclin-1 was firstly clustered with 〈em〉Drosophila melanogaster〈/em〉 Atg6 and then assigned into the branch of invertebrate Beclin-1. The mRNA transcripts of 〈em〉Es〈/em〉Beclin-1 were highly expressed in hepatopancreas, hemocytes and gill. After lipopolysaccharide (LPS) and 〈em〉Aeromonas hydrophila〈/em〉 stimulations, the relative mRNA expression of 〈em〉Es〈/em〉Beclin-1 in hemocytes was significantly increased from 3 to 24 h with the peak level of 4.70-fold (〈em〉p〈/em〉 〈 0.01) and 2.91-fold (〈em〉p〈/em〉 〈 0.01) at 6 h, respectively. 〈em〉Es〈/em〉Beclin-1 protein was diffusely distributed in the cytoplasm of crab hemocytes under normal conditions, whereas it displayed predominantly punctuate distribution after LPS stimulation. After 〈em〉Es〈/em〉Beclin-1 was interfered with specific 〈em〉Es〈/em〉Beclin-1-dsRNA, the mRNA transcripts of some antimicrobial peptides, including 〈em〉Es〈/em〉ALF2, 〈em〉Es〈/em〉LYZ, 〈em〉Es〈/em〉Crus and 〈em〉Es〈/em〉Crus2 in crab hemocytes were significantly decreased at 6 h post LPS stimulation. These results implicated that 〈em〉Es〈/em〉Beclin-1 played a role in regulating the antimicrobial peptide expressions in the immune response of 〈em〉E. sinensis〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 28 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology〈/p〉 〈p〉Author(s): Younes Bouallegui〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Bivalves' immunity has received much more attention in the last decade, which resulted to a valuable growth in the availability of its molecular components. Such data availability coupled with the economical importance of these organisms aimed to shift the increase in the number of immunological and stress-related studies. Unfortunately, the crowd of generated data deciphering the involved physiological processes, investigators' differential conceptualization and the aimed objectives, has complicated the 〈em〉sensu stricto〈/em〉 outlining of immune-related mechanisms. Overall, this review tried to compiles a summary about the molecular components of the mussels' immune response, surveying an overview of the mussels’ functional immunity through gathering the most recent-related topics of bivalves' immunity as apoptosis and autophagy which deserves a great attention as stress-related mechanisms, the disseminated neoplasia as outbreak transmissible disease, not only within the same specie but also among different species, the hematopoiesis as topic that still generating interesting debate in the scientific community, the mucosal immunity described as the interface where host-pathogen interactions would occurs and determinate the late immune response, and innate immune memory and transgenerational priming, which described as very recent research topic with extensive applications in shellfish farming industry.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1050464819302062-fx1.jpg" width="422" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 28 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Anthony Estienne, Valério M. Portela, Yohan Choi, Gustavo Zamberlam, Derek Boerboom, Vickie Roussel, Marie-Charlotte Meinsohn, Mats Brännström, Thomas E. Curry, Misung Jo, Christopher A. Price〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The generation of free-radicals such as nitric oxide has been implicated in the regulation of ovarian function, including ovulation. Tissues that generate nitric oxide typically generate another free-radical gas, hydrogen sulfide (H〈sub〉2〈/sub〉S), although little is known about the role of H〈sub〉2〈/sub〉S in ovarian function. The hypothesis of this study was that H〈sub〉2〈/sub〉S regulates ovulation. Treatment with luteinizing hormone (LH) increased the levels of mRNA and protein of the H〈sub〉2〈/sub〉S generating enzyme cystathionine γ-lyase (CTH) in granulosa cells of mice and humans in vivo and in vitro. Pharmacological inhibition of H〈sub〉2〈/sub〉S generating enzymes reduced the number of follicles ovulating in mice in vivo and in vitro, and this inhibitory action was reversed by cotreatment with a H〈sub〉2〈/sub〉S donor. Addition of a H〈sub〉2〈/sub〉S donor to cultured mouse granulosa cells increased basal and LH-dependent abundance of mRNA encoding amphiregulin, betacellulin and tumor necrosis alpha induced protein 6, proteins important for cumulus expansion and follicle rupture. Inhibition of CTH activity reduced abundance of mRNA encoding matrix metalloproteinase-2 and -9 and tissue-type plasminogen activator, and cotreatment with the H〈sub〉2〈/sub〉S donor increased the levels of these mRNA above those stimulated by LH alone. We conclude that the H〈sub〉2〈/sub〉S generating system plays an important role in the propagation of the preovulatory cascade and rupture of the follicle at ovulation.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919300632-fx1.jpg" width="464" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 27 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology〈/p〉 〈p〉Author(s): Shisan Xu, Chichi Liu, Fangjing Xie, Li Tian, Sinai HC. Manno, Francis A.M. Manno, Samane Fallah, Bernd Pelster, Gary Tse, Shuk Han Cheng〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Inflammation plays a crucial role in cardiac regeneration. Numerous advantages, including a robust regenerative ability, make the zebrafish a popular model to study cardiovascular diseases. The zebrafish 〈em〉breakdance〈/em〉 (〈em〉bre〈/em〉) mutant shares several key features with human long QT syndrome that predisposes to ventricular arrhythmias and sudden death. However, how inflammatory response and tissue regeneration following cardiac damage occur in 〈em〉bre〈/em〉 mutant is unknown. Here, we have found that inflammatory response related genes were markedly expressed in the injured heart and excessive leukocyte accumulation occurred in the injured area of the 〈em〉bre〈/em〉 mutant zebrafish. Furthermore, 〈em〉bre〈/em〉 mutant zebrafish exhibited aberrant apoptosis and impaired heart regenerative ability after ventricular cryoinjury. Mild dosages of anti-inflammatory or prokinetic drugs protected regenerative cells from undergoing aberrant apoptosis and promoted heart regeneration in 〈em〉bre〈/em〉 mutant zebrafish. We propose that immune or prokinetic therapy could be a potential therapeutic regimen for patients with genetic long QT syndrome who suffers from myocardial infarction.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: June 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 89〈/p〉 〈p〉Author(s): Chunsheng Liu, Xiucong Hu, Zhenjie Cao, Yun Sun, Xiaojuan Chen, Zhengshi Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Streptococcus iniae〈/em〉 is an important aquaculture pathogen that is associated with disease outbreaks in wild and cultured fish species. Streptolysin S has been identified as an important virulence factor of 〈em〉S. iniae.〈/em〉 With an aim to develop effective vaccines against 〈em〉S. iniae〈/em〉 for Japanese flounder (〈em〉Paralichthys olivaceus〈/em〉), in this study, we constructed a DNA vaccine based on the 〈em〉sagH〈/em〉 gene, which belongs to the streptolysin S-associated gene cluster. In fish vaccinated with pSagH, the transcription of 〈em〉sagH〈/em〉 was detected in tissues and SagH protein was also detected in the muscles of pSagH-vaccinated fish by immunohistochemistry. The immunoprotective effect of SagH showed that fish vaccinated with pSagH at one and two months exhibited a high relative percent survival (RPS) of 92.62% and 90.58% against 〈em〉S. iniae〈/em〉 serotype I, respectively. In addition, SagH conferred strong cross protection against 〈em〉S. iniae〈/em〉 serotype II and resulted in an RPS of 83.01% and 80.65% at one and two months, respectively. Compared to the control group, fish vaccinated with pSagH were able to induce much stronger respiratory burst activity, and higher titer of specific antibodies. The results of quantitative real-time PCR demonstrated that pSagH upregulated the expression of several immune genes that are possibly involved in both innate and adaptive immune responses. These results indicate that pSagH is a candidate DNA vaccine candidate against 〈em〉S. iniae〈/em〉 serotype I and II infection in Japanese flounder in aquaculture.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Kazuhiro Iwai〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Because of essentiality and toxicity of iron in our body, iron metabolism is tightly regulated in cells. In mammalian cells, iron regulatory protein 1 and 2 (IRP1 and IRP2) are the central regulators of cellular iron metabolism. IRPs regulate iron metabolism by interacting with the RNA stem-loop structures, iron-responsive elements (IREs), found on the transcripts encoding proteins involved in iron metabolism only in iron depleted condition. It is also well-known that the ubiquitin system plays central roles in cellular iron regulation because both IRPs having the IRE binding activity are recognized and ubiquitinated by the SCF〈sup〉FBXL5〈/sup〉 ubiquitin ligase in condition of iron-replete. FBXL5, which is a substrate recognition subunit of SCF〈sup〉FBXL5〈/sup〉, senses iron availability via its hemerythrin-like domain. In this small article, current understanding of the roles of SCF〈sup〉FBXL5〈/sup〉-mediated degradation of IRPs played in cellular iron metabolism is discussed.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918315892-fx1.jpg" width="288" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Shashank Masaldan, Ashley I. Bush, David Devos, Anne Sophie Rolland, Caroline Moreau〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Perturbations in iron homeostasis and iron accumulation feature in several neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). Proteins such as 〈em〉α〈/em〉-synuclein, tau and amyloid precursor protein that are pathologically associated with neurodegeneration are involved in molecular crosstalk with iron homeostatic proteins. Quantitative susceptibility mapping, an MRI based non-invasive technique, offers proximal evaluations of iron load in regions of the brain and powerfully predicts cognitive decline. Further, small molecules that target elevated iron have shown promise against PD and AD in preclinical studies and clinical trials. Despite these strong links between altered iron homeostasis and neurodegeneration the molecular biology to describe the association between enhanced iron levels and neuron death, synaptic impairment and cognitive decline is ill defined. In this review we discuss the current understanding of brain iron homeostasis and how it may be perturbed under pathological conditions. Further, we explore the ramifications of a novel cell death pathway called ferroptosis that has provided a fresh impetus to the “metal hypothesis” of neurodegeneration. While lipid peroxidation plays a central role in the execution of this cell death modality the removal of iron through chelation or genetic modifications appears to extinguish the ferroptotic pathway. Conversely, tissues that harbour elevated iron may be predisposed to ferroptotic damage. These emerging findings are of relevance to neurodegeneration where ferroptotic signalling may offer new targets to mitigate cell death and dysfunction.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918316800-fx1.jpg" width="301" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Tetsuro Ishii, Eiji Warabi, Giovanni E. Mann〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Astrocyte-neuron interactions protect neurons from iron-mediated toxicity. As dopamine can be metabolized to reactive quinones, dopaminergic neurons are susceptible to oxidative damage and ferroptosis-like induced cell death. Detoxification enzymes are required to protect neurons. Brain-derived neurotrophic factor (BDNF) plays a key role in the regulation of redox sensitive transcription factor Nrf2 in astrocytes and metabolic cooperation between astrocytes and neurons. This article reviews the importance of BDNF and astrocyte-neuron interactions in the protection of neurons against oxidative damages in rodent brains. We previously proposed that BDNF activates Nrf2 via the truncated TrkB.T1 and p75〈sup〉NTR〈/sup〉 receptor complex in astrocytes. Stimulation by BDNF generates the signaling molecule ceramide, which activates PKCζ leading to induction of the CK2-Nrf2 signaling axis. As a cell clock regulates p75〈sup〉NTR〈/sup〉 expression, we suggested that BDNF effectively activates Nrf2 in astrocytes during the rest phase. In contrast, neurons express both TrkB.FL and TrkB.T1, and TrkB.FL tyrosine kinase activity inhibits p75〈sup〉NTR〈/sup〉-dependent ceramide generation and internalizes p75〈sup〉NTR〈/sup〉. Therefore, BDNF may not effectively activate Nrf2 in neurons. Notably, neurons only weakly activate detoxification and antioxidant enzymes/proteins via the Nrf2-ARE signaling axis. Thus, astrocytes may provide relevant transcripts and/or proteins to neurons via microparticles/exosomes increasing neuronal resistance to oxidative stress. Circadian increases in the levels of circulating glucocorticoids may further facilitate material transfer from astrocytes to neurons via the stimulation of pannexin 1 channels-P2X7R signaling pathway in astrocytes at the beginning of the active phase. Dysregulation of astrocyte-neuron interactions could therefore contribute to the pathogenesis of neurodegenerative diseases including Parkinson’s disease.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918315235-fx1.jpg" width="242" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Izumi Yanatori, Fumio Kishi〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Many past and recent advances in the field of iron metabolism have relied upon the discovery of divalent metal transporter 1, DMT1 in 1997. DMT1 is the major iron transporter and contributes non-heme iron uptake in most types of cell. Each DMT1 isoform exhibits different expression patterns in cell-type specificity and distinct subcellular distribution, which enables cells to uptake both transferrin-bound and non-transferrin-bound irons efficiently. DMT1 expression is regulated by iron through the translational and degradation pathways to ensure iron homeostasis. It is considered that mammalian iron transporters including DMT1 cannot transport ferric iron but ferrous iron. Being reduced to ferrous state is likely to damage cells and tissues through the production of reactive oxygen species. Recently, iron chaperones have been identified, which can provide an answer to how ferrous iron is transported safely in cytosol. We summarize DMT1 expression depending on the types of cell or tissue and the function and mechanism of one of the iron chaperones, PCBP2.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918312838-fx1.jpg" width="175" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Shinya Toyokuni〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Cancer is the primary cause of human mortality in most countries. This tendency has increased as various medical therapeutics have advanced, which suggests that we cannot escape carcinogenesis, although the final outcome may be modified by exposomes and statistics. Cancer is classified by its cellular differentiation. Mesothelial cells are distinct in that they line somatic cavities, facilitating the smooth movement of organs, but are not exposed to the external environment. Malignant mesothelioma, or simply mesothelioma, develops either in the pleural, peritoneal or pericardial cavities, or in the tunica vaginalis testes. Mesothelioma has been a relatively rare cancer but is socially important due to its association with asbestos exposure, caused by modern industrial development. The major pathogenic mechanisms include oxidative stress either via catalytic reactions against the asbestos surface or frustrated phagocytosis of macrophages, and specific adsorption of hemoglobin and histones by asbestos fibers in the presence of phagocytic activity of mesothelial cells. Multiwall carbon nanotubes of ~50 nm-diameter, additionally adsorbing transferrin, are similarly carcinogenic to mesothelial cells in rodents and were thus classified as Group 2B carcinogens. Genetic alterations found in human and rat mesothelioma notably contain changes found in other excess iron-induced carcinogenesis models. Phlebotomy and iron chelation therapies have been successful in the prevention of mesothelioma in rats. Alternatively, loading of oxidative stress by non-thermal plasma to mesothelioma cells causes ferroptosis. Therefore, carcinogenesis by foreign fibrous inorganic materials may overlap the uncovered molecular mechanisms of birth of life and its evolution.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918317532-fx1.jpg" width="222" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 February 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 132〈/p〉 〈p〉Author(s): Alvaro Martinez Guimera, Daryl P. Shanley, Carole J. Proctor〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The decline in the musculoskeletal system with age is driven at the cellular level by random molecular damage. Cells possess mechanisms to repair or remove damage and many of the pathways involved in this response are regulated by redox signals. However, with ageing there is an increase in oxidative stress which can lead to chronic inflammation and disruption of redox signalling pathways. The complexity of the processes involved has led to the use of computational modelling to help increase our understanding of the system, test hypotheses and make testable predictions. This paper will give a brief background of the biological systems that have been modelled, an introduction to computational modelling, a review of models that involve redox-related mechanisms that are applicable to musculoskeletal ageing, and finally a discussion of the future potential for modelling in this field.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918315909-fx1.jpg" width="283" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 February 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 132〈/p〉 〈p〉Author(s): C.M. Nascimento, M. Ingles, A. Salvador-Pascual, M.R. Cominetti, M.C. Gomez-Cabrera, J. Viña〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉Sarcopenia is a major component of the frailty syndrome, both being considered as strong predictors of morbidity, disability, and death in older people.〈/p〉 〈p〉In this review, we explore the definitions of sarcopenia and frailty and summarize the current knowledge on their relationship with oxidative stress and the possible therapeutic interventions to prevent or treat them, including exercise-based interventions and multimodal strategies. We highlight the relevance of the impairment of the nervous system and of the anabolic response (protein synthesis) in muscle aging leading to frailty and sarcopenia. We also discuss the importance of malnutrition and physical inactivity in these geriatric syndromes. Finally, we propose multimodal interventions, including exercise programs and nutritional supplementation, as the strategies to prevent and treat both sarcopenia and frailty.〈/p〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918314990-fx1.jpg" width="375" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 February 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 132〈/p〉 〈p〉Author(s): Katrin Schröder〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Bone is a tissue with constant remodeling, where osteoblasts form and osteoclasts degrade bone. Both cell types are highly specialized in their function and both form from precursors and have to be replaced on a regular basis. This replacement represents one control level of bone homeostasis. The second important level would be the control of the function of osteoblasts and osteoclasts in order to keep the balance of bone -formation and -degradation. Both differentiation and control of cellular function are potentially redox sensitive processes. In fact, reactive oxygen species (ROS) are utilized by a wide range of cells for differentiation and control of cellular signaling and function. A major source of ROS is the family of NADPH oxidases. The sole function of those enzymes is the formation of ROS in a controlled and targeted manner. Importantly the members of the NADPH oxidase family differ in their localization and in the type and amount of ROS produced. Accordingly the impact of the members of the NADPH oxidase family on differentiation and function differs between cell types. This review will highlight the function of different NADPH oxidases in differentiation and function of bone cells and thereby will discuss the role of NADPH oxidases in bone homeostasis and osteoporosis.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918315028-fx1.jpg" width="282" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Koji Miyanishi, Shingo Tanaka, Hiroki Sakamoto, Junji Kato〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Iron is an essential for organisms and the liver plays a major role in its storage. In pathologic conditions, where iron absorption from the intestine or iron uptake into the hepatocytes is increased, excess iron accumulates in the hepatocytes, leading to hepatocyte injury through the production of free radicals. Iron exerts its toxicity by catalyzing the generation of reactive oxygen species (ROS). ROS causes cell injury by inducing damage to the lysosomal, cytoplasmic, nuclear and mitochondrial membranes, apoptosis through activation of the caspase cascade, and hyperoxidation of fatty chains. In this manuscript, we reviewed the articles regarding role of iron in hepatic inflammation and hepatocellular carcinoma.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918312097-fx1.jpg" width="301" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 29 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology〈/p〉 〈p〉Author(s): Weilin Wang, Changhao Gong, Zirong Han, Xiaojing Lv, Shujing Liu, Lingling Wang, Linsheng Song〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Lectins are carbohydrate-binding proteins with lectin domains, which are extensively studied for their numerous roles in biological recognition. However, the lectin domain containing proteins (LDCPs) chimerized with other non-lectin domains have not received sufficient attention. In the present study, a genome-wide survey of LDCPs in oyster 〈em〉Crassostrea gigas〈/em〉 was conducted, and an expansive 640 LDCPs derived from ten lectin domains were identified and functionally explored. In these LDCPs, a total of 282 kinds of domains were predicted, and 90% of the LDCPs contained more than one kind of domain. The lectin domains were frequently fused with non-lectin domains, such as epidermal growth factor domain and peptidase related domains, which supplied LDCPs with more diversity in structures and functions. The C-type lectin domains were the most abundant domains in LDCPs, and they were largely co-existed with non-lectin domains of complement activation-related domains (such as CUB domain and PAN-1 domain) but relative independence with other lectin domains. Furthermore, the C-type lectin domain containing proteins (CTLPs) found to mainly act as pattern immune recognition receptors and were highly expressed in mucosal tissues (digestive gland, male gonad and labial palp) to provide mucosal immune protections. The Concanavalin A-like lectin domains were the second richest domains in LDCPs, and they were mostly constructed into chimeric proteins with epidermal growth factor domain and peptidase related domains. The Concanavalin A-like lectin domain containing proteins (CALPs) were significantly enriched with peptidase activities and mainly expressed in digestive tissues. All the results suggested the mucosal immunity and digestive functions of oyster LDCPs, which provided a fresh idea about the functions of invertebrate lectin family.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 29 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Verena Zimorski, Marek Mentel, Aloysius G.M. Tielens, William F. Martin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Eukaryotes arose about 1.6 billion years ago, at a time when oxygen levels were still very low on Earth, both in the atmosphere and in the ocean. According to newer geochemical data, oxygen rose to approximately its present atmospheric levels very late in evolution, perhaps as late as the origin of land plants (only about 450 million years ago). It is therefore natural that many lineages of eukaryotes harbor, and use, enzymes for oxygen-independent energy metabolism. This paper provides a concise overview of anaerobic energy metabolism in eukaryotes with a focus on anaerobic energy metabolism in mitochondria. We also address the widespread assumption that oxygen improves the overall energetic state of a cell. While it is true that ATP yield from glucose or amino acids is increased in the presence of oxygen, it is also true that the synthesis of biomass costs thirteen times more energy per cell in the presence of oxygen than in anoxic conditions. This is because in the reaction of cellular biomass with O〈sub〉2〈/sub〉, the equilibrium lies very far on the side of CO〈sub〉2〈/sub〉. The absence of oxygen offers energetic benefits of the same magnitude as the presence of oxygen. Anaerobic and low oxygen environments are ancient. During evolution, some eukaryotes have specialized to life in permanently oxic environments (life on land), other eukaryotes have remained specialized to low oxygen habitats. We suggest that the K〈sub〉m〈/sub〉 of mitochondrial cytochrome 〈em〉c〈/em〉 oxidase of 0.1–10 μM for O〈sub〉2〈/sub〉, which corresponds to about 0.04%–4% (avg. 0.4%) of present atmospheric O〈sub〉2〈/sub〉 levels, reflects environmental O〈sub〉2〈/sub〉 concentrations that existed at the time that the eukaryotes arose.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918324006-fx1.jpg" width="388" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 29 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Lisa A. Johnson, Laura A. Hug〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Bacteria are the most diverse and numerous organisms on the planet, inhabiting environments from the deep subsurface to particles in clouds. Across this range of conditions, bacteria have evolved a diverse suite of enzymes to mitigate cellular damage from reactive oxygen species (ROS). Here, we review the diversity and distribution of ROS enzymatic defense mechanisms across the domain Bacteria, using both peer-reviewed literature and publicly available genome databases. We describe the specific strategies used by well-characterized organisms in order to highlight differences in oxidative stress responses between aerobic, facultatively anaerobic, and anaerobic lifestyles. We present evidence from genome minimization experiments to suggest that ROS defenses are obligately required for life. This review clarifies the variability in ROS defenses across Bacteria, including the novel diversity found in currently uncharacterized Candidate Phyla.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918322688-fx1.jpg" width="483" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 28 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Yusuke Izumi, Taku Nakashima, Takeshi Masuda, Sachiko Shioya, Kazuhide Fukuhara, Kakuhiro Yamaguchi, Shinjiro Sakamoto, Yasushi Horimasu, Shintaro Miyamoto, Hiroshi Iwamoto, Kazunori Fujitaka, Hironobu Hamada, Noboru Hattori〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Purpose〈/h6〉 〈p〉Although radiotherapy is important in the treatment of malignant thoracic tumors, it has harmful effects on healthy tissues. We previously showed that suplatast tosilate, an anti-allergic agent, scavenged reactive oxygen species (ROS), including hydroxyl radicals. Because ROS-mediated oxidative stress is involved in radiation-induced lung injury, we hypothesized that suplatast tosilate could reduce radiation-induced lung injury via suppression of oxidative stress.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods and materials〈/h6〉 〈p〉Murine alveolar epithelial cells were irradiated with or without a medium containing suplatast tosilate 〈em〉in vitro〈/em〉 to determine whether the agent had cytoprotective effects against radiation-induced injury. On the other hand, the thoracic region of C57BL/6 mice was exposed to a single irradiation dose of 15 Gy and the effects of suplatast tosilate were determined by a histological evaluation and assessment of the following parameters: cell number and inflammatory cytokine levels in bronchoalveolar lavage fluid, and oxidative stress markers and hydroxyproline content in pulmonary tissues.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Suplatast tosilate protected murine alveolar epithelial cells 〈em〉in vitro〈/em〉 from irradiation-induced inhibition of cell proliferation, which was accompanied by the suppression of intracellular ROS and DNA double-strand breaks induced by irradiation. Oxidative stress markers and the levels of inflammatory and fibrogenic cytokines were upregulated in irradiated murine lungs 〈em〉in vivo〈/em〉. Suplatast tosilate suppressed both oxidative stress markers and the levels of cytokines, which resulted in reduced pulmonary fibrosis and clearly improved the survival rate after irradiation.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉These findings demonstrate that suplatast tosilate could be a useful lung-protective agent that acts via suppression of oxidative stress associated with thoracic radiotherapy.〈/p〉 〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918321981-fx1.jpg" width="315" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 27 March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Keiji Yasukawa, Akinobu Hirago, Kazunori Yamada, Xin Tun, Kenji Ohkuma, Hideo Utsumi〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In ulcerative colitis, an inflammatory bowel disease of unknown cause, diagnosis of the degree and location of colitis at an early stage is required to control the symptoms. Changes in redox status, including the production of reactive oxygen and nitrogen species (RONS), have been associated with ulcerative colitis in humans and dextran sodium sulfate (DSS)-induced colitis in rodents. In this study, the 〈em〉in vivo〈/em〉 redox status of colons of DSS-induced colitis mice were monitored by Overhauser-enhanced magnetic resonance imaging (OMRI), and the relationship between redox status and colitis development was investigated. Colitis was induced by administering 5% DSS in drinking water to male Slc:ICR mice, which are a strain classified as closed colony outbred mice (5-week-old, 25–30 g). On the 3rd day of the DSS challenge, when no symptoms of colitis were displayed, the contrast decays of 〈sup〉15〈/sup〉N-CmP and 〈sup〉14〈/sup〉N-CxP tended to show enhancement in the whole colon and were not altered by DMSO. On the 5th day of the DSS challenge, with histological damage of the rectum being displayed, the contrast decay of 〈sup〉15〈/sup〉N-CmP was significantly enhanced not only in the rectum, but also in the proximal colon, and this was suppressed by DMSO. On the 7th day of the DSS challenge, with the mice displaying severe colitis symptoms, the image contrasts of 〈sup〉15〈/sup〉N-labeled 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (〈sup〉15〈/sup〉N-CmP) and 〈sup〉14〈/sup〉N-labeled 3-carboxyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (〈sup〉14〈/sup〉N-CxP) showed much faster decay than those of healthy mice, while the increased decays of both probes were restored by the membrane-permeable reactive oxygen species (ROS) scavenger dimethyl sulfoxide (DMSO). Image differencing between the decay rate images of 〈sup〉15〈/sup〉N-CmP and 〈sup〉14〈/sup〉N-CxP showed the DSS-induced redox imbalance spreading over the whole colon, and a histogram of the difference image showed a smaller peak and broader distribution with the DSS treatment. These data indicate that ROS are produced intracellularly in the distal and proximal colon in the initiation stage of DSS-induced colitis, and that ROS are produced intracellularly and extracellularly in the advanced stage of DSS-induced colitis.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919300929-fx1.jpg" width="328" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 1 February 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 131〈/p〉 〈p〉Author(s): Natália Cestari Moreno, Camila Carrião Machado Garcia, Veridiana Munford, Clarissa Ribeiro Reily Rocha, Alessandra Luiza Pelegrini, Camila Corradi, Alain Sarasin, Carlos Frederico Martins Menck〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The UVA component of sunlight induces DNA damage, which are basically responsible for skin cancer formation. Xeroderma Pigmentosum Variant (XP-V) patients are defective in the DNA polymerase pol eta that promotes translesion synthesis after sunlight-induced DNA damage, implying in a clinical phenotype of increased frequency of skin cancer. However, the role of UVA-light in the carcinogenesis of these patients is not completely understood. The goal of this work was to characterize UVA-induced DNA damage and the consequences to XP-V cells, compared to complemented cells. DNA damage were induced in both cells by UVA, but lesion removal was particularly affected in XP-V cells, possibly due to the oxidation of DNA repair proteins, as indicated by the increase of carbonylated proteins. Moreover, UVA irradiation promoted replication fork stalling and cell cycle arrest in the S-phase for XP-V cells. Interestingly, when cells were treated with the antioxidant N-acetylcysteine, all these deleterious effects were consistently reverted, revealing the role of oxidative stress in these processes. Together, these results strongly indicate the crucial role of oxidative stress in UVA-induced cytotoxicity and are of interest for the protection of XP-V patients.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918325553-fx1.jpg" width="400" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: April 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 87〈/p〉 〈p〉Author(s): Walissara Jirapongpairoj, Ikuo Hirono, Hidehiro Kondo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Fc receptors (FcRs) are specific to the Fc portion of immunoglobulin (Ig) molecules. Here, four Fc receptor-like proteins, JF-FcR-like protein 1-4, were identified in Japanese flounder. Their open reading frames encoded 358, 255, 519 and 441 amino acid residues, respectively. JF-FcR-like protein mRNAs were mainly detected in kidney and spleen of healthy fish. Injection of formalin-killed cells (FKCs) of 〈em〉Edwardsiella tarda〈/em〉 significantly increased the spleen mRNA levels of JF-FcR-like protein 1 but not the other JF-FcR-like proteins. Injection of FKC of 〈em〉Streptococcus iniae〈/em〉 did not significantly affect any of the JF-FcR-like protein mRNAs. These findings suggest that the FcR-like proteins have different involvements in pathogen responses.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 86〈/p〉 〈p〉Author(s): Jie Xu, Yongyao Yu, Zhenyu Huang, Shuai Dong, Yanzhi Luo, Wei Yu, Yaxing Yin, Huili Li, Yangzhou Liu, Xiaoyun Zhou, Zhen Xu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Teleost fish are the most primitive bony vertebrates that contain immunoglobulin (Ig). Although teleost Ig is known to be important during tetrapod evolution and comparative immunology, little is known about the genomic organization of the immunoglobulin heavy-chain (IgH) locus. Here, three Ig isotype classes, IgM, IgD and IgT, were firstly identified in dojo loach (〈em〉Misgurnus anguillicaudatus〈/em〉), and the IgH locus covering τ, μ and δ genes was also illustrated. Variable (V) gene segments lie upstream of two tandem diversity (D), joining (J) and constant (C) clusters and the genomic organization of the IgH locus presented as V〈sub〉n〈/sub〉-D〈sub〉n〈/sub〉-J〈sub〉n〈/sub〉-C〈sub〉τ〈/sub〉-D〈sub〉n〈/sub〉-J〈sub〉n〈/sub〉-C〈sub〉μ〈/sub〉-C〈sub〉δ〈/sub〉, similar to some other teleost fish. However, unlike some other teleost fish, ten V〈sub〉H〈/sub〉, ten D and nine J genes were observed in this locus, which suggest teleost Igs might be conserved and diverse. Thus, it would be interesting to determine how Igs divide among themselves in immune response to different antigens. To address this hypothesis, we have developed three models by bath infection with parasitic, bacterial and fungal pathogens, respectively. We found that IgM, IgD and IgT were highly upregulated in the head kidney and spleen after infection with 〈em〉Ichthyophthirius multifiliis〈/em〉 (Ich), suggesting that the three Igs might participate in the systemic immune responses to Ich. Moreover, the high expression of IgT in mucosal tissue, such as skin or gills, appeared after being infected with three different pathogens infection, respectively, in which the expression of IgT increased more rapidly in response to Ich infection. Interestingly, the expression of IgD showed a higher increase in spleen and head kidney being challenged with fungi, suggesting that IgD might play an important role in antifungal infection.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: April 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 134〈/p〉 〈p〉Author(s): Jing Liu, Haizhou Zhu, Gurdat Premnauth, Kaylin G. Earnest, Patricia Hahn, George Gray, Jack A. Queenan, Lisa E. Prevette, Safnas F. AbdulSalam, Ana Luisa Kadekaro, Edward J. Merino〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉UV irradiation is a major driver of DNA damage and ultimately skin cancer. UV exposure leads to persistent radicals that generate ROS over prolonged periods of time. Toward the goal of developing long-lasting antioxidants that can penetrate skin, we have designed a ROS-initiated protective (RIP) reagent that, upon reaction with ROS (antioxidant activity), self-cyclizes and then releases the natural product apocynin. Apocynin is a known antioxidant and inhibitor of NOX oxidase enzymes. A key phenol on the compound 〈strong〉1〈/strong〉 controls ROS-initiated cyclization and makes 〈strong〉1〈/strong〉 responsive to ROS with a EC50 comparable to common antioxidants in an ABTS assay. In an 〈em〉in vitro〈/em〉 DNA nicking assay, the RIP reagent prevented DNA strand breaks. In cell-based assays, the reagent was not cytotoxic, apocynin was released only in cells treated with UVR, reduced UVR-induced cell death, and lowered DNA lesion formation. Finally, topical treatment of human skin explants with the RIP reagent reduced UV-induced DNA damage as monitored by quantification of cyclobutane dimer formation and DNA repair signaling 〈em〉via〈/em〉 TP53. The reagent was more effective than administration of a catalase antioxidant on skin explants. This chemistry platform will expand the types of ROS-activated motifs and enable inhibitor release for potential use as a long-acting sunscreen.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918312681-fx1.jpg" width="500" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: April 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 134〈/p〉 〈p〉Author(s): M.G. Sharapov, V.I. Novoselov, N.V. Penkov, E.E. Fesenko, M.V. Vedunova, V.I. Bruskov, S.V. Gudkov〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉A radioprotective effect of exogenous recombinant peroxiredoxin 2 (Prx2) was revealed and characterized using an animal model of whole body X-ray irradiation at sublethal and lethal doses. Prx2 belongs to an evolutionarily ancient family of peroxidases that are involved in enzymatic degradation of a wide variety of organic and inorganic hydroperoxides. Apart from that, the oxidized form of Prx2 also exhibits chaperone activity, thereby preventing protein misfolding and aggregation under oxidative stress. Intravenous administration of Prx2 in animals at a concentration of 20 µg/g 15 min before exposure to ionizing radiation contributes to a significantly higher survival rate, suppresses the development of leucopenia and thrombocytopenia, as well as protects the bone marrow cells from genome DNA damage. Moreover, injection of Prx2 leads to suppression of apoptosis, stimulates cell proliferation and results in a more rapid recovery of the cell redox state. Exogenous Prx2 neutralizes the effect of the priming dose on the second irradiation of the cells. The radioprotective properties of exogenous Prx2 are stipulated by its broad substrate peroxidase activity, chaperone activity in the oxidized state, and are also due to the signal-regulatory function of Prx2 mediated by the regulation of the level of hydroperoxides as well as via interaction with redox-sensitive regulatory proteins.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918325255-fx1.jpg" width="500" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 86〈/p〉 〈p〉Author(s): Arash Akbarzadeh, Somayeh pakravan, Mohammad Niroomand, Kobra Babanejad Abkenar, Masoumeh Eshagh Nimvari, Kimia Karimi, Azin Ghazvini, Seyed Amir Hossein Jalali〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Current study aimed to examine the effect of dietary date seed meal (DSM) as an alternative carbohydrate ingredient on immune-related genes expression of Pacific white shrimp (〈em〉Penaeus vannamei〈/em〉). A total number of 750 shrimp (4.0 ± 0.1 g) were randomly assigned into five experimental treatments, each with three replicates. Experimental diets contained 0, 50, 100, 150 and 230 g/kg DSM substituted for both wheat and rice flour. Shrimp were fed at a rate of 5% body weight three times daily and the mRNA expression of α2-macroglobulin (α2-M), lipopolysaccharide and beta-1,3-glucan-binding protein (LGBP), integrin β, and peroxinectin (PX) was studied on five shrimp per treatment after 8 weeks feeding trial. The results showed that replacement of DSM up to 100 g/kg in the diet of 〈em〉P. vannamei〈/em〉 caused no significant changes in the expression of α2-M and integrin β, however both of these genes showed lower expression in shrimp fed diets containing 150 and 230 g/kg DSM compared to control group. Moreover, no significant differences were observed in the expression of PX and LGBP between shrimp fed diets containing different amounts of DSM and control group. These findings demonstrated that as an inexpensive source of carbohydrate, DSM could be substituted up to 100 g/kg for wheat and rice flour in the diet of farmed shrimp without suppressive effects on the immune status.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 1 February 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 131〈/p〉 〈p〉Author(s): Huynh Nhu Mai, Lan Thuy Ty Nguyen, Eun-Joo Shin, Dae-Joong Kim, Ji Hoon Jeong, Yoon Hee Chung, Xin Gen Lei, Naveen Sharma, Choon-Gon Jang, Toshitaka Nabeshima, Hyoung-Chun Kim〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Compelling evidence indicates that oxidative stress contributes to cocaine neurotoxicity. The present study was performed to elucidate the role of the glutathione peroxidase-1 (GPx-1) in cocaine-induced kindling (convulsive) behaviors in mice. Cocaine-induced convulsive behaviors significantly increased 〈u〉GPx-1〈/u〉, p-IkB, and p-JAK2/STAT3 expression, and oxidative burdens in the hippocampus of mice. There was no significant difference in cocaine-induced p-IkB expression between non-transgenic (non-TG) and GPx-1 overexpressing transgenic (GPx-1 TG) mice, but significant differences were observed in cocaine-induced p-JAK2/STAT3 expression and oxidative stress between non-TG and GPx-1 TG mice. Cocaine-induced glial fibrillary acidic protein (GFAP)-labeled astrocytic level was significantly higher in the hippocampus of GPx-1 TG mice. Triple-labeling immunocytochemistry indicated that GPx-1-, p-STAT3-, and GFAP-immunoreactivities were co-localized in the same cells. AG490, a JAK2/STAT3 inhibitor, but not pyrrolidone dithiocarbamate, an NFκB inhibitor, significantly counteracted GPx-1-mediated protective potentials (i.e., anticonvulsant-, antioxidant-, antiapoptotic-effects). Genetic overexpression of GPx-1 significantly attenuated proliferation of Iba-1-labeled microglia induced by cocaine in mice. However, AG490 or astrocytic inhibition (by GFAP antisense oligonucleotide and α-aminoadipate) significantly increased Iba-1-labeled microglial activity and M1 phenotype microglial mRNA levels, reflecting that proinflammatory potentials were mediated by AG490 or astrocytic inhibition. This microglial activation was less pronounced in GPx-1 TG than in non-TG mice. Furthermore, either AG490 or astrocytic inhibition significantly counteracted GPx-1-mediated protective potentials. Therefore, our results suggest that astrocytic modulation between GPx-1 and JAK2/STAT3 might be one of the underlying mechanisms for protecting against convulsive neurotoxicity induced by cocaine.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918316538-fx1.jpg" width="475" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: April 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 87〈/p〉 〈p〉Author(s): Xue Du, Guang-hua Wang, Bin Yue, Jing-jing Wang, Qin-qin Gu, Shun Zhou, Min Zhang, Yong-hua Hu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉C1q-domain-containing (C1qDC) proteins, which are involved in a series of immune responses, are important pattern recognition receptors in innate immunity in vertebrates and invertebrates. Functional studies of C1qDC proteins in vertebrates are scarce. In the present study, a C1qDC protein (SsC1qDC) from the teleost black rockfish (〈em〉Sebastes schlegelii〈/em〉) was identified and examined at expression and functional levels. The open reading frame of SsC1qDC is 636 bp, and the predicted amino acid sequence of SsC1qDC shares 62%–69% overall identity with the C1qDC proteins of several fish species. SsC1qDC possesses conserved C1qDC features, including a signal sequence and a C1q domain. SsC1qDC was expressed in different tissues and its expression was up-regulated by bacterial and viral infection. Recombinant SsC1qDC (rSsC1qDC) exhibited apparent binding activities against PAMPs including LPS and PGN. rSsC1qDC had antibacterial activity against 〈em〉Vibrio parahaemolyticus〈/em〉, and was able to enhance the phagocytic activity of macrophages towards 〈em〉Vibrio anguillarum〈/em〉. rSsC1qDC interacted with human heat-aggregated IgG. Furthermore, in the presence of rSsC1qDC, fish exhibited enhanced resistance against bacterial infection. Collectively, these results indicated that SsC1qDC serves as a pattern recognition receptor and plays a vital role in the defense system of black rockfish.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: April 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 134〈/p〉 〈p〉Author(s): Yuzhe Wang, Shiyu Li, Mengge Liu, Jiajia Wang, Zhengbin Fei, Feng Wang, Zhenyou Jiang, Wenhua Huang, Hanxiao Sun〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉It is known that mitochondria are associated with the ageing process, and the eukaryotic sir2 family of genes significantly affects cellular lifespan. The mammalian sir2 family affects mitochondrial function by regulating targets in different pathways, including oxidative stress, oxidative phosphorylation, and mitochondrial biosynthesis. This study reports that 〈em〉Rt-sirtuin2〈/em〉 and 〈em〉Rt-sirtuin4〈/em〉 genes transfections significantly impacted the lifespan of 〈em〉Rhodosporidium toruloides〈/em〉, and they can significantly improve cellular responses to H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 treatment, which induces cell senescence, and restore mitochondrial function. The 〈em〉Rt-sirtuin2〈/em〉 and 〈em〉Rt-sirtuin4〈/em〉 genes increase the expression of the mitochondria-associated proteins Mfn1, Mfn2, and Drp1 and the autophagy-associated proteins LC3-II, LC3-I, Beclin-1 and Parkin and reconstitute mitochondrial networks. Overall, the phenotypic reversal of senescent cells is achieved by regulating mitochondrial viability and mitochondrial autophagy. 〈em〉In vivo〈/em〉 experiments with animals also confirmed the improvement of various ageing indexes by the 〈em〉Rt-sirtuin2〈/em〉 and 〈em〉Rt-sirtuin4〈/em〉 genes. Strategies for remodelling mitochondria and improving mitochondrial quality and function can reverse the state of human cells from an ageing phenotype to an active metabolic phenotype. The 〈em〉R. toruloides〈/em〉 Sir2 genes can be used to prevent and treat diseases of ageing or mitochondrial dysfunction.〈/p〉〈/div〉

Description: 〈p〉Publication date: April 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 134〈/p〉 〈p〉Author(s): Xiaojia Ren, Jeriel T.R. Keeney, Sumitra Miriyala, Teresa Noel, David K. Powell, Luksana Chaiswing, Subbarao Bondada, Daret K. St. Clair, D. Allan Butterfield〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Cancer treatments are developing fast and the number of cancer survivors could arise to 20 million in United State by 2025. However, a large fraction of cancer survivors demonstrate cognitive dysfunction and associated decreased quality of life both shortly, and often long-term, after chemotherapy treatment. The etiologies of chemotherapy induced cognitive impairment (CICI) are complicated, made more so by the fact that many anti-cancer drugs cannot cross the blood-brain barrier (BBB). Multiple related factors and confounders lead to difficulties in determining the underlying mechanisms. Chemotherapy induced, oxidative stress-mediated tumor necrosis factor-alpha (TNF-α) elevation was considered as one of the main candidate mechanisms underlying CICI. Doxorubicin (Dox) is a prototypical reactive oxygen species (ROS)-generating chemotherapeutic agent used to treat solid tumors and lymphomas as part of multi-drug chemotherapeutic regimens. We previously reported that peripheral Dox-administration leads to plasma protein damage and elevation of TNF-α in plasma and brain of mice. In the present study, we used TNF-α null (TNFKO) mice to investigate the role of TNF-α in Dox-induced, oxidative stress-mediated alterations in brain. We report that Dox-induced oxidative stress in brain is ameliorated and brain mitochondrial function assessed by the Seahorse-determined oxygen consumption rate (OCR) is preserved in brains of TNFKO mice. Further, we show that Dox-decreased the level of hippocampal choline-containing compounds and brain phospholipases activity are partially protected in TNFKO group in MRS study. Our results provide strong evidence that Dox-targeted mitochondrial damage and levels of brain choline-containing metabolites, as well as phospholipases changes decreased in the CNS are associated with oxidative stress mediated by TNF-α. These results are consistent with the notion that oxidative stress and elevated TNF-α in brain underlie the damage to mitochondria and other pathological changes that lead to CICI. The results are discussed with reference to our identifying a potential therapeutic target to protect against cognitive problems after chemotherapy.〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 86〈/p〉 〈p〉Author(s): Xian Li, Liqin Ji, Lele Wu, Xiaolong Gao, Xueqin Li, Jun Li, Ying Liu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Land-based recirculating aquaculture systems (RAS) are widely utilized for turbot (〈em〉Scophthalmus maximus〈/em〉) culture. Flow velocity in the tank is essential to maintain water quality, conservation of energy and fish welfare. However, little is known about how turbot respond to different velocities in the long term. In this study, water quality was kept constant, allowing the effect of flow velocity on the feeding intake, growth, plasma biochemical indexes, innate (non-specific) immunity and immune-related stress gene expressions in the skin to be examined in isolation in RAS. Turbot (average body length 20.10 cm) were reared for 60 days in RAS under three velocities, 0.06 m s〈sup〉−1〈/sup〉, 0.18 m s〈sup〉−1〈/sup〉, and 0.36 m s〈sup〉−1〈/sup〉, corresponding to approximately 0.3 body length per second (bl s〈sup〉−1〈/sup〉), 0.9 bl s〈sup〉−1〈/sup〉 and 1.8 bl s〈sup〉−1〈/sup〉, respectively. The results showed that at velocities of 0.36 m s〈sup〉−1〈/sup〉 (1.8 bl s〈sup〉−1〈/sup〉), juvenile turbot were subject to stress accompanied by a reduced growth rate. A velocity of 0.36 m s〈sup〉−1〈/sup〉 was also found to significantly reduce SOD and GSH activity, and the concentration of total protein in plasma, while concentrations of urea nitrogen (BUN) and total bilirubin (TBIL) increased. There was an up-regulation of cathepsin D and lysozyme (LZM) in the skin at the highest velocity, implying the activation of stress and immune responses. At the medium velocity of 0.18 m s〈sup〉−1〈/sup〉 (0.9 bl s〈sup〉−1〈/sup〉), turbot increased their feed intake, obtained an elevated special growth rate (SGR), and exhibited significantly higher AKP and ACP activity in plasma. Overall, the results suggest that excessively high velocities are a stressor for turbot inducing an immune response in the skin, which is sensitive to environmental changes. A velocity of approximately 0.9 bl s〈sup〉−1〈/sup〉 is suggested to promote growth and obtain better innate immunity of cultured turbot.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 86〈/p〉 〈p〉Author(s): Ruiqiang Zhang, Ying Jiang, Lei Zhou, Yueping Chen, Chao Wen, Wenbin Liu, Yanmin Zhou〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This study was conducted to evaluate the effects of dietary supplementation with yeast extract on growth, body composition, non-specific immunity, and antioxidant status of Chinese mitten crab (〈em〉Eriocheir sinensis〈/em〉). A total of 432 crabs (initial average weight, 4.62 ± 0.11 g) were randomly distributed into four treatment groups with six replicates of 18 crabs. The crabs were fed a basal diet or the same diet supplemented with 2.5, 5, and 10 g/kg yeast extract for 8 weeks. The results showed that dietary yeast extract inclusion enhanced the edible viscera index (linear, 〈em〉P〈/em〉 〈 0.001), edible viscera crude protein (CP) content (linear, 〈em〉P〈/em〉 = 0.025) and serum phenoloxidase (ProPO) activity (quadratic, 〈em〉P〈/em〉 = 0.023) at 56 day, increased the total superoxide dismutase (T-SOD) activity at 28 day (quadratic, 〈em〉P〈/em〉 = 0.037) and catelase (CAT) activity at 56 day (quadratic, 〈em〉P〈/em〉 = 0.034) of edible viscera, and muscular T-SOD activity (quadratic, 〈em〉P〈/em〉 = 0.020) at 56 day in Chinese mitten crab. Compared with the control group, the inclusion of 5 g/kg yeast extract in the diet increased the edible viscera index, enhanced the CAT activity of edible viscera at 56 day in Chinese mitten crab (〈em〉P〈/em〉 〈 0.05). Dietary 10 g/kg yeast extract inclusion enhanced the edible viscera index at 56 day in Chinese mitten crab than that of the control group (〈em〉P〈/em〉 〈 0.05). These results implied that dietary yeast extract inclusion improved the edible viscera index and crude protein content of edible viscera, enhanced serum immunity, and increased the antioxidant status of edible viscera and muscle in Chinese mitten crab, especially when it is supplemented at 5 g/kg yeast extract in the diet.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 86〈/p〉 〈p〉Author(s): Graciela P. Martins, Marit Espe, Zhihao Zhang, Igo G. Guimarães, Elisabeth Holen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉In aquaculture production, studies of salmon health and interaction between pathogens and nutrition are of high importance. This study aimed to compare genes and pathways involved in salmon head kidney cells and liver cells, isolated from the same fish, towards polyinosinic acid: polycytidylic acid (poly I:C) and lipopolysaccharide (LPS), with and without addition of surplus arginine. Selected transcriptional responses of genes involved in inflammation, polyamine synthesis, oxidation and apoptosis were elucidated.〈/p〉 〈p〉For the genes related to inflammation, 〈em〉viperin〈/em〉, 〈em〉Mx〈/em〉 and 〈em〉Toll like receptor 3〈/em〉 (〈em〉TLR3),〈/em〉 transcription were significantly upregulated by poly I:C in head kidney cells, while 〈em〉viperin〈/em〉 was upregulated in liver cells. Surplus arginine did not affect poly I:C induced responses with the exception of reducing poly I:C induced 〈em〉Mx〈/em〉 transcription in head kidney cells. Gene transcription of 〈em〉Interleukin 1β〈/em〉 (〈em〉IL-1β〈/em〉), 〈em〉Interleukin-8〈/em〉 (〈em〉IL-8〈/em〉) and 〈em〉cyclooxygenase 2〈/em〉 (〈em〉Cox2〈/em〉) were elevated during LPS treatment in all liver and head kidney cell cultures. In addition, LPS induced significantly, 〈em〉CD83〈/em〉 transcription in liver cells and 〈em〉TNF-α〈/em〉 transcription in head kidney cells. Surplus arginine significantly reduced 〈em〉IL-8, Cox2 and TNF-α〈/em〉 transcription in head kidney cells. LPS upregulated arginase in head kidney cells while poly I:C upregulated 〈em〉S-adenosyl methionine decarboxylase〈/em〉 (〈em〉SAMdc〈/em〉) transcription in liver cells. This suggests that LPS and poly I:C modulates genes involved in polyamine synthesis. In addition, in head kidney cells, surplus arginine, when cultured together with LPS, increased the transcription of 〈em〉ornithine decarboxylase〈/em〉 (〈em〉ODC〈/em〉) the limiting enzyme of polyamine synthesis. The genes involved with oxidation and apoptosis were not affect by any of the treatments in liver cells, while LPS decreased 〈em〉caspase 3〈/em〉 transcription in head kidney cells. In liver cells, protein expression of catalase was reduced by surplus arginine alone and when challenged with poly I:C. Both liver cells and head kidney cells isolated from the same individual fish responded to LPS and poly I:C, depending on the gene analyzed. Additionally, arginine could modulate transcription of pro-inflammatory genes induced by LPS in salmon immune cells, thus affecting salmon immunity.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 86〈/p〉 〈p〉Author(s): Ying-Jun Ning, Si-Ying Chen, Xin-Jiang Lu, Jian-Fei Lu, Jiong Chen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The glucocorticoid receptor (GR) is an important feedback regulator of the hypothalamic-pituitary-interrenal (HPI) axis. However, there are a limited number of studies focused on host-pathogen interactions in which an association between GR and immune response has been evaluated in monocytes/macrophages (MO/MФ) after being challenged with highly pathogenic bacteria. Here, we cloned the cDNA sequence of the glucocorticoid receptor (PaGR) gene from ayu fish. The PaGR transcript was expressed in all tissues, and changes in expression were observed in immune tissues and MO/MФ after live 〈em〉Vibrio anguillarum〈/em〉 infection. Subsequently, PaGR was expressed and purified to prepare anti-PaGR antibodies. We analyzed the subcellular localization of PaGR. PaGR was expressed not only in the intracellular space but also in the plasma membrane. PaGR activation decreased the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines. However, PaGR activation suppressed the phagocytosis activity of 〈em〉V. anguillarum〈/em〉-infected ayu MO/MФ via a non-genomic pathway. Interestingly, PaGR activation could enhance MO/MФ bacterial killing capability and apoptosis. Therefore, PaGR may modulate the immune response in ayu MO/MФ by genomic and non-genomic pathways.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 86〈/p〉 〈p〉Author(s): Xiaoze Guo, Jie Li, Chao Ran, Anran Wang, Mingxu Xie, Yadong Xie, Qianwen Ding, Zhen Zhang, Yalin Yang, Ming Duan, Zhigang Zhou〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In this study, we firstly tested the effects of dietary nucleotides on the disease resistance and innate immunity of zebrafish. Further, we investigated the role of intestinal microbiota in the nucleotides-induced immunostimulatory effect by using a germ-free zebrafish model and microbiota transfer technique. Fish were fed control or nucleotides (NT)-supplemented diets (at 0.05%,0.1%, 0.15% or 0.2%, 〈em〉m〈/em〉/〈em〉m〈/em〉) for 4 weeks, followed by immersion challenge with 〈em〉Aeromonas hydrophila〈/em〉 NJ-1. The results showed that 0.1% NT group enhanced the resistance of zebrafish against 〈em〉A. hydrophila〈/em〉 infection. We further observed that the relative expressions of mucin, claudin16, occlusin1, hepcidin, defensin beta-like, myeloperoxidase (Mpo), and serum amyloid A (Saa) increased in the 0.1% NT group compared with control (〈em〉P〈/em〉 〈 0.05), indicating that dietary nucleotides enhanced the physical barrier and mucosal immunity in the intestine of zebrafish. Moreover, ROS level in the head kidney was significantly increased in NT fed zebrafish versus control (〈em〉P〈/em〉 〈 0.05), indicating enhanced systematic immunity. Furthermore, dietary NT significantly elevated the relative expressions of 〈em〉mpo〈/em〉, 〈em〉saa〈/em〉 and the ROS activity in germ-free zebrafish, while germ-free zebrafish colonized with NT-altered microbiota had no significant difference in the relative expressions of 〈em〉mpo〈/em〉, 〈em〉saa〈/em〉 and the ROS activity compared with the control microbiota-colonized fish, suggesting that the immunostimulatory effect of dietary NT is mediated by direct action of NT and does not involve the microbiota. Consistently, dietary NT can protect germ-free zebrafish from pathogenic infection, whereas germ-free zebrafish colonized with NT microbiota showed no difference in disease resistance compared with control microbiota colonized counterparts. Together, these results indicated that the immunostimulatory and disease protection effect of dietary nucleotides in zebrafish was mediated by direct action of the nucleotides, and does not involve the intestinal microbiota.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: April 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 134〈/p〉 〈p〉Author(s): Matthew D. Campbell, Jicheng Duan, Ashton T. Samuelson, Matthew J. Gaffrey, Gennifer E. Merrihew, Jarrett D. Egertson, Lu Wang, Theo K. Bammler, Ronald J. Moore, Collin C. White, Terrance J. Kavanagh, Joachim G. Voss, Hazel H. Szeto, Peter S. Rabinovitch, Michael J. MacCoss, Wei-Jun Qian, David J. Marcinek〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Sarcopenia and exercise intolerance are major contributors to reduced quality of life in the elderly for which there are few effective treatments. We tested whether enhancing mitochondrial function and reducing mitochondrial oxidant production with SS-31 (elamipretide) could restore redox balance and improve skeletal muscle function in aged mice. Young (5 mo) and aged (26 mo) female C57BL/6Nia mice were treated for 8-weeks with 3 mg/kg/day SS-31. Mitochondrial function was assessed 〈em〉in vivo〈/em〉 using 〈sup〉31〈/sup〉P and optical spectroscopy. SS-31 reversed age-related decline in maximum mitochondrial ATP production (ATPmax) and coupling of oxidative phosphorylation (P/O). Despite the increased 〈em〉in vivo〈/em〉 mitochondrial capacity, mitochondrial protein expression was either unchanged or reduced in the treated aged mice and respiration in permeabilized gastrocnemius (GAS) fibers was not different between the aged and aged+SS-31 mice. Treatment with SS-31 also restored redox homeostasis in the aged skeletal muscle. The glutathione redox status was more reduced and thiol redox proteomics indicated a robust reversal of cysteine S-glutathionylation post-translational modifications across the skeletal muscle proteome. The gastrocnemius in the age+SS-31 mice was more fatigue resistant with significantly greater mass compared to aged controls. This contributed to a significant increase in treadmill endurance compared to both pretreatment and untreated control values. These results demonstrate that the shift of redox homeostasis due to mitochondrial oxidant production in aged muscle is a key factor in energetic defects and exercise intolerance. Treatment with SS-31 restores redox homeostasis, improves mitochondrial quality, and increases exercise tolerance without an increase in mitochondrial content. Since elamipretide is currently in clinical trials these results indicate it may have direct translational value for improving exercise tolerance and quality of life in the elderly.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918322561-fx1.jpg" width="138" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: April 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 134〈/p〉 〈p〉Author(s): Chris E. Cooper, Gary G.A. Silkstone, Michelle Simons, Badri Rajagopal, Natalie Syrett, Thoufieq Shaik, Svetlana Gretton, Elizabeth Welbourn, Leif Bülow, Nélida Leiva Eriksson, Luca Ronda, Andrea Mozzarelli, Andras Eke, Domokos Mathe, Brandon J. Reeder〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Hemoglobin (Hb)-based oxygen carriers (HBOC) are modified extracellular proteins, designed to replace or augment the oxygen-carrying capacity of erythrocytes. However, clinical results have generally been disappointing due to adverse side effects, in part linked to the intrinsic oxidative toxicity of Hb. Previously a redox-active tyrosine residue was engineered into the Hb β subunit (βF41Y) to facilitate electron transfer between endogenous antioxidants such as ascorbate and the oxidative ferryl heme species, converting the highly oxidizing ferryl species into the less reactive ferric (met) form. We inserted different single tyrosine mutations into the α and β subunits of Hb to determine if this effect of βF41Y was unique. Every mutation that was inserted within electron transfer range of the protein surface and the heme increased the rate of ferryl reduction. However, surprisingly, three of the mutations (βT84Y, αL91Y and βF85Y) also increased the rate of ascorbate reduction of ferric(met) Hb to ferrous(oxy) Hb. The rate enhancement was most evident at ascorbate concentrations equivalent to that found in plasma (〈 100 μM), suggesting that it might be of benefit in decreasing oxidative stress in vivo. The most promising mutant (βT84Y) was stable with no increase in autoxidation or heme loss. A decrease in membrane damage following Hb addition to HEK cells correlated with the ability of βT84Y to maintain the protein in its oxygenated form. When PEGylated and injected into mice, βT84Y was shown to have an increased vascular half time compared to wild type PEGylated Hb. βT84Y represents a new class of mutations with the ability to enhance reduction of both ferryl and ferric Hb, and thus has potential to decrease adverse side effects as one component of a final HBOC product.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918312978-fx1.jpg" width="367" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 1 February 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 131〈/p〉 〈p〉Author(s): Agnes Keszler, Brian Lindemer, Dorothee Weihrauch, Deron Jones, Neil Hogg, Nicole L. Lohr〈/p〉

Description: 〈p〉Publication date: April 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 134〈/p〉 〈p〉Author(s): Tomohisa Takagi, Takujiro Homma, Junichi Fujii, Nobuyuki Shirasawa, Hiroyuki Yoriki, Yuma Hotta, Yasuki Higashimura, Katsura Mizushima, Yasuko Hirai, Kazuhiro Katada, Kazuhiko Uchiyama, Yuji Naito, Yoshito Itoh〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background and Aims〈/h6〉 〈p〉Peroxiredoxin 4 (PRDX4), a secretory protein that is preferentially retained in the endoplasmic reticulum (ER), is encoded by a gene located on the X chromosome and highly expressed in colonic tissue. In this study, we investigated the role of PRDX4 by means of male PRDX4-knockout (PRDX4〈sup〉-/y〈/sup〉) mice in the development of intestinal inflammation using a dextran sulfate sodium (DSS)-induced colitis model.〈/p〉 〈/div〉 〈div〉 〈h6〉Materials and methods〈/h6〉 〈p〉Acute colitis was induced with DSS (2.5% in drinking water) in wild-type (WT) and PRDX4〈sup〉-/y〈/sup〉 male C57BL/6 mice. Histological and biochemical analyses were performed on the colonic tissues.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉PRDX4 was mainly localized in the colonic epithelial cells in WT mice. The disease activity index (DAI) scores of PRDX4〈sup〉-/y〈/sup〉 mice were significantly higher compared to those of WT mice. Specifically, PRDX4〈sup〉-/y〈/sup〉 mice showed marked body weight loss and shortening of colon length compared to WT mice, whereas the myeloperoxidase levels were increased in PRDX4〈sup〉-/y〈/sup〉 compared to WT mice. In addition, the mRNA expression levels of TNF-α and IFN-γ were significantly higher in the colonic mucosa of PRDX4〈sup〉-/y〈/sup〉 compared to WT mice. Moreover, the levels of CHOP and activated caspase 3 were higher in the colonic tissues of PRDX4〈sup〉-/y〈/sup〉 compared to WT mice following treatment with DSS. The ER also showed greater expansion in PRDX4〈sup〉-/y〈/sup〉 than WT mice, which was consistent with severe ER stress under PRDX4 deficiency.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉Our results demonstrated that the lack of PRDX4 aggravated the colonic mucosal damage induced by DSS. Because PRDX4 functions as an ER thiol oxidase as well as an antioxidant, DSS induced oxidative damage and ER stress to a greater degree in PRDX4〈sup〉-/y〈/sup〉 than WT mice. These findings suggest that PRDX4 may represent a novel therapeutic molecule in intestinal inflammation.〈/p〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918325966-fx1.jpg" width="267" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Hiroaki Kajiyama, Shiro Suzuki, Masato Yoshihara, Satoshi Tamauchi, Nobuhisa Yoshikawa, Kaoru Niimi, Kiyosumi Shibata, Fumitaka Kikkawa〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Endometriosis, characterized by the presence of extra-uterine endometrium, is a common gynecologic disorder in reproductive-age women. Although the detailed molecular mechanism of etiology remains unelucidated, recent studies have gradually revealed both genetic and epigenetic backgrounds of the development of endometriosis. In clinical practice, endometriosis has been recognized as a precursor lesion of several types of malignancies and endometriosis-associated carcinoma. An imbalance between reactive oxygen species and local antioxidants has been reported to contribute to the development of endometriosis-associated carcinoma as well as the pathophysiology of this disease through a systemic inflammatory response in the peritoneal cavity. This review mainly presents an epidemiology, possible etiology of endometriosis, precursor lesions, molecular features, and the association between the microenvironmental accumulations of oxidative stress in endometriosis-associated ovarian cancer progression.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉Illustration of the possible involvement of endometriosis in the development of EAOC. Because of an overgrowth of endometrial tissue and retrograde menstrual flow resulting in high levels of hemoglobin, heme, and iron, increasing levels of oxidative stress may continue iron-related oxidative stress and subsequent peritoneal damage or carcinogenesis of ovarian endometrial lesions.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918325644-fx1.jpg" width="396" alt="fx1" title="fx1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: March 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 133〈/p〉 〈p〉Author(s): Christopher J. Greene, Nitika J. Sharma, Peter N. Fiorica, Emily Forrester, Gary J. Smith, Kenneth W. Gross, Eric C. Kauffman〈/p〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Increasing data implicate iron accumulation in tumorigenesis of the kidney, particularly the clear cell renal cell carcinoma (ccRCC) subtype. The von Hippel Lindau (VHL)/hypoxia inducible factor-α (HIF-α) axis is uniquely dysregulated in ccRCC and is a major regulator and regulatory target of iron metabolism, yet the role of iron in ccRCC tumorigenesis and its potential interplay with VHL inactivation remains unclear. We investigated whether ccRCC iron accumulation occurs due to increased cell dependency on iron for growth and survival as a result of VHL inactivation. Free iron levels were compared between four VHL-mutant ccRCC cell lines (786-0, A704, 769-P, RCC4) and two benign renal tubule epithelial cell lines (RPTEC, HRCEp) using the Phen Green SK fluorescent iron stain. Intracellular iron deprivation was achieved using two clinical iron chelator drugs, deferasirox (DFX) and deferoxamine (DFO), and chelator effects were measured on cell line growth, cell cycle phase, apoptosis, HIF-1α and HIF-2α protein levels and HIF-α transcriptional activity based on expression of target genes 〈em〉CA9〈/em〉, 〈em〉OCT4〈/em〉/〈em〉POU5F1〈/em〉 and 〈em〉PDGFβ/PDGFB〈/em〉. Similar assays were performed in VHL-mutant ccRCC cells with and without ectopic wild-type VHL expression. Baseline free iron levels were significantly higher in ccRCC cell lines than benign renal cell lines. DFX depleted cellular free iron more rapidly than DFO and led to greater growth suppression of ccRCC cell lines (〉90% at ~30–150 µM) than benign renal cell lines (~10–50% at up to 250 µM). Similar growth responses were observed using DFO, with the exception that a prolonged treatment duration was necessary to deplete cellular iron adequately for differential growth suppression of the less susceptible A704 ccRCC cell line relative to benign renal cell lines. Apoptosis and G1-phase cell cycle arrest were identified as potential mechanisms of chelator growth suppression based on their induction in ccRCC cell lines but not benign renal cell lines. Iron chelation in ccRCC cells but not benign renal cells suppressed HIF-1α and HIF-2α protein levels and transcriptional activity, and the degree and timing of HIF-2α suppression correlated with the onset of apoptosis. Restoration of wild-type VHL function in ccRCC cells was sufficient to prevent chelator-induced apoptosis and G1 cell cycle arrest, indicating that ccRCC susceptibility to iron deprivation is VHL inactivation-dependent. In conclusion, ccRCC cells are characterized by high free iron levels and a cancer-specific dependency on iron for HIF-α overexpression, cell cycle progression and apoptotic escape. This iron dependency is introduced by VHL inactivation, revealing a novel interplay between VHL/HIF-α dysregulation and ccRCC iron metabolism. Future study is warranted to determine if iron deprivation using chelator drugs provides an effective therapeutic strategy for targeting HIF-2α and suppressing tumor progression in ccRCC patients.〈/p〉〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584918325577-fx1.jpg" width="265" alt="fx1" title="fx1"〉〈/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): Colin T. Shearn, Blair Fennimore, David J. Orlicky, Yue R. Gao, Laura M. Saba, Kayla D. Battista, Stefanos Aivazidis, Mohammed Assiri, Peter S. Harris, Cole Michel, Gary F. Merrill, Edward E. Schmidt, Sean P. Colgan, Dennis R. Petersen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Cholangiopathies such as primary sclerosing cholangitis (PSC) are chronic liver diseases characterized by increased cholestasis, biliary inflammation and oxidative stress. The objective of this study was to elucidate the impact of cholestatic injury on oxidative stress-related factors. Using hepatic tissue and whole cell liver extracts (LE) isolated from 11-week old C57BL/6J (WT) and Mdr2〈sup〉KO〈/sup〉 mice, inflammation and oxidative stress was assessed. Concurrently, specific targets of carbonylation were assessed in LE prepared from murine groups as well as from normal and human patients with end-stage PSC. Identified carbonylated proteins were further evaluated using bioinformatics analyses. Picrosirius red staining revealed extensive fibrosis in Mdr2〈sup〉KO〈/sup〉 liver, and fibrosis colocalized with increased periportal inflammatory cells and both acrolein and 4-HNE staining. Western blot analysis revealed elevated periportal expression of antioxidant proteins Cbr3, GSTμ, Prdx5, TrxR1 and HO-1 but not GCLC, GSTπ or catalase in the Mdr2〈sup〉KO〈/sup〉 group when compared to WT. From immunohistochemical analysis, increased periportal reactive aldehyde production colocalized with elevated staining of Cbr3, GSTμ and TrxR1 but surprisingly not with Nrf2. Mass spectrometric analysis revealed an increase in carbonylated proteins in the Mdr2〈sup〉KO〈/sup〉 and PSC groups compared to respective controls. Gene ontology and KEGG pathway analysis of carbonylated proteins revealed a propensity for increased carbonylation of proteins broadly involved in metabolic processes as well more specifically in Rab-mediated signal transduction, lysosomes and the large ribosomal subunit in human PSC. Western blot analysis of Rab-GTPase expression revealed no significant differences in Mdr2〈sup〉KO〈/sup〉 mice when compared to WT livers. In contrast, PSC tissue exhibited decreased levels of Rabs 4, 5 and increased abundance of Rabs 6 and 9a protein. Results herein reveal that cholestasis induces stage-dependent increases in periportal oxidative stress responses and protein carbonylation, potentially contributing to pathogenesis in Mdr2〈sup〉KO〈/sup〉. Furthermore, during early stage cholestasis, there is cell-specific upregulation of some but not all, antioxidant proteins.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919301601-fx1.jpg" width="357" 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): Wenting Li, Jinghan Feng, Chong Gao, Meiling Wu, Qiaohui Du, Bun Tsoi, Qi Wang, Dan Yang, Jiangang Shen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Active autophagy/mitophagy could mediate neurodegeneration and motor disabilities in multiple sclerosis (MS). Mitochondrial recruitment of dynamin-related protein 1 (Drp1) is a crucial step to initiate mitophagy. Peroxynitrite (ONOO〈sup〉−〈/sup〉) could be a player in MS pathology but the mechanisms remain unknown. We used animal model of experimental autoimmune encephalomyelitis (EAE) and tested whether ONOO〈sup〉−〈/sup〉 mediates Drp1 assembly in mitochondria for mitophagy and aggravates MS pathology. We found that autophagy/mitophagy activation was coincidently increased with axonal damage, apoptosis and disease progression in active EAE mice, which were remarkably attenuated by mitochondrial division/mitophagy inhibitor Mdivi-1. Importantly, increased ONOO〈sup〉−〈/sup〉 production was companied with Drp1 mitochondrial recruitment, PINK1/Parkin-mediated mitophagy, axonal degeneration and neuronal cell death, which were reversed by peroxynitrite decomposition catalyst (PDC). Furthermore, ONOO〈sup〉−〈/sup〉 production induced Drp1 nitration, promoted Drp1 assembly and mitochondrial recruitment for mitophagy activation, contributing to the EAE pathology. Together, we conclude that ONOO〈sup〉−〈/sup〉 serves as a key mediator in Drp1 nitration modification and assembly for facilitating mitophagy activation. Targeting ONOO〈sup〉−〈/sup〉-mediated Drp1 assembly and mitochondrial recruitment could be an important therapeutic strategy for multiple sclerosis treatment.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919304654-fx1.jpg" width="464" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 26 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Emil List Larsen, Allan Weimann, Henrik Enghusen Poulsen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Oxidative stress is associated with the development and progression of numerous diseases. However, targeting oxidative stress has not been established in the clinical management of any disease. Several methods and markers are available to measure oxidative stress, including direct measurement of free radicals, antioxidants, redox balance, and oxidative modifications of cellular macromolecules. Oxidatively generated nucleic acid modifications have attracted much interest due to the pre-mutagenic oxidative modification of DNA into 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), associated with cancer development. During the last decade, the perception of RNA has changed from that of a ‘silent messenger’ to an ‘active contributor’, and, parallelly oxidatively generated RNA modifications measured as 8-oxo-7,8-dihydro-guanosine (8-oxoGuo), has been demonstrated as a prognostic factor for all-caused and cardiovascular related mortality in patients with type 2 diabetes. Several attempts have been made to modify the amount of oxidative modified nucleic acids. Thus, this review aims to introduce researchers to the measurement of oxidatively generated nucleic acid modifications as well as critically review previous attempts and provide future directions for targeting oxidative nucleic acid modifications.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S089158491931144X-fx1.jpg" width="411" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Taotao Zhang, Mimi Zhang, Ting Xu, Shangwu Chen, Anlong Xu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The lamprey is a primitive jawless vertebrate that occupies a critical phylogenetic position, and its larval stage represents the major portion of its life cycle [1]. Lamprey larvae have been proven to be an important model organism for studying numerous biological problems, such as the immune system, due to their unique biological features [2]. In addition, early-stage larvae have never been obtained from the wild [3]; therefore, it is necessary to establish artificial breeding of lampreys in the laboratory. However, during early development, the larvae exhibit susceptibility to saprolegniasis, and the immune responses of lamprey larvae to this infection remain poorly understood. Here, we established a model of fungal infection in lamprey larvae and then used RNA sequencing to investigate the transcript profiles of lamprey larvae and their immune responses to 〈em〉Saprolegnia ferax〈/em〉. Among the profiled molecules, genes involved in pathogen recognition, inflammation, phagocytosis, lysosomal degradation, soluble humoral effectors, and lymphocyte development were significantly upregulated. The results were validated by analysis of several genes by quantitative real-time PCR and whole-mount 〈em〉in situ〈/em〉 hybridization. Finally, we performed a Western blot for VLRs in infected and uninfected lampreys. This work not only provides an animal model for studying fungal infection but also suggests a molecular basis for developing defensive strategies to manage 〈em〉Saprolegnia ferax〈/em〉 infection.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Ning Wang, Mengting Qin, Xihua Chen, Yang Lu, Xinxin Zhao, Yuhui Wu, Jie Shi, Yitian Li, Rui Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Complement component C3 is well recognized as the central mediator of complement system, whose activation is responsible for the immune surveillance and elimination of non-self-antigens. In this study, C3 gene (HcC3) from a pearl making mussel, 〈em〉Hyriopsis cumingii〈/em〉, was successfully identified. The putative HcC3 possessed the canonical domains and highly conserved functional residues of C3 family members. In phylogenetic analysis, HcC3 was also clustered into C3 subfamily and separated from α2 macroglobulin clade. HcC3 gene was constitutively expressed in a wide range of tissues of pearl mussels, among which the immune-related tissues like hemocytes got highest expression. After allograft surgery of mantle tissues for aquaculture pearl production, the gene expression of HcC3 exhibited a rapid upregulation on day 1, dropped back on day 3, peaked the value on day 7, and restored to the level similar to control samples on day 14 after mantle allograft. The biphasic expression within the two weeks post the surgery suggests the important roles for HcC3 in alloimmune responses and an intricate complement activation mechanism in mollusks during tissue allograft.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Chuangye Yang, Xiaodong Du, Ruijuan Hao, Qingheng Wang, Yuewen Deng, Ruijiao Sun〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Postoperative care is a critical step of pearl culture that ultimately determines culture success. To determine the effect of dietary vitamin D3 (VD3) levels on immunity and antioxidant capacity of pearl oyster 〈em〉Pinctada fucata martensii〈/em〉 during postoperative care and explore the mechanisms behind this phenomenon, five isonitrogenous and isolipidic experimental diets were formulated by adding different levels of dietary VD3 (0, 500, 1000, 3000, and 10000 IU/kg), and the diets were fed to five experimental groups (EG1, EG2, EG3, EG4, and EG5) in turn and cultured indoors. The control group (CG) was cultured in the natural sea. Pearl oysters that were 1.5 years old were subjected to nucleus insertion. After culturing for 30 days, EG3 exhibited significantly higher survival rates than those in CG and EG5 (P 〈 0.05). Moreover, EG3 exhibited the highest activities of alkaline phosphatase, acid phosphatase, catalase, superoxide dismutase, and lysozyme. However, EG5 achieved the highest activities of glutathione peroxidase. Metabolomics-based profiling of pearl oysters fed with high levels of dietary VD3 (EG5) and optimum levels of dietary VD3 (EG3) revealed 76 significantly differential metabolites (SDMs) (VIP 〉 1 and P 〈 0.05). Pathway analysis indicated that SDMs were involved in 21 pathways. Furthermore, integrated key metabolic pathway analysis suggested that pearl oysters in EG5 regulated the pentose phosphate pathway, glutathione metabolism, sphingolipid metabolism, and arachidonic acid metabolism in response to stress generated from excessive VD3. These findings had significant implications on strengthening the future development and application of VD3 in aquaculture of pearl oyster 〈em〉P. f. martensii〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 93〈/p〉 〈p〉Author(s): Hamed Kolangi Miandare, Ali Taheri Mirghaed, Marjan Hosseini, Nastaran Mazloumi, Ashkan Zargar, Sajad Nazari〈/p〉

Description: 〈p〉Publication date: 1 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 143〈/p〉 〈p〉Author(s): Maria Faustova, Elena Nikolskaya, Maria Sokol, Artur Zabolotsky, Murad Mollaev, Olga Zhunina, Margarita Fomicheva, Anton Lobanov, Evgeniy Severin, Nikita Yabbarov〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The mechanisms of binary catalyst therapy (BCT) and photodynamic therapy (PDT) are based on the formation of reactive oxygen species (ROS). This ROS formation results from specific chemical reactions. In BCT, light exposure does not necessarily initiate ROS formation and BCT application is not limited to regions of tissues that are accessible to illumination like photodynamic therapy (PDT). The principle of BCT is electron transition, resulting in the interaction of a transition metal complex (catalyst) and substrate molecule. Mn〈sup〉III〈/sup〉- tetraphenylporphyrin chloride (MnClTPP) in combination with an ascorbic acid (AA) has been proposed as an appropriate candidate for cancer treatment regarding the active agents in BCT. The goal of this study was to determine whether MnClTPP in combination with AA would be a promising agent for BCT. The problem of used MnClTPP's, low solubility in water, was solved by MnClTPP loading into PLGA matrix. H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 produced during AA decomposition oxidized MnClTPP to high-reactive oxo-Mn〈sup〉V〈/sup〉 species. MnClTPP in presence AA leads to the production of excessive ROS levels in vitro. ROS are mainly substrates of catalase and superoxide dismutase (H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 and O〈sub〉2〈/sub〉〈sup〉●-〈/sup〉). SOD1 and catalase were identified as the key players of the MnClTPP ROS-induced cell defense system. The cytotoxicity of MnClTPP-loaded nanoparticles (NPs) was greatly increased in the presence of specific catalase inhibitor (3-amino-1,2,4-triazole (3AT)) and superoxide dismutase 1 (SOD1) inhibitor (diethyldithiocarbamate (DDC)). Cell death resulted from the combined activation of caspase-dependent (caspase 3/9 system) and independent pathways, namely the AIF translocation to nuclei. Preliminary acute toxicity and in vivo anticancer studies have been revealed the safe and potent anticancer effect of PLGA-entrapped MnClTPP in combination with AA. The findings indicate that MnClTPP-loaded PLGA NPs are promising agents for BCT.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919309876-fx1.jpg" width="400" 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): Jian Chen, Hui Li, Kang Yang, Yongzhu Wang, Lifei Yang, Liangbin Hu, Ruixian Liu, Zhiqi Shi〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Melatonin, a phytochemical, can regulate lateral root (LR) formation, but the downstream signaling of melatonin remains elusive. Here we investigated the roles of hydrogen peroxide (H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉) and superoxide radical (O〈sub〉2〈/sub〉〈sup〉•〈/sup〉‾) in melatonin-promoted LR formation in tomato (〈em〉Solanum lycopersicum〈/em〉) roots by using physiological, histochemical, bioinformatic, and biochemical approaches. The increase in endogenous melatonin level stimulated reactive oxygen species (ROS)-dependent development of lateral root primordia (LRP) and LR. Melatonin promoted LRP/LR formation and modulated the expression of cell cycle genes (〈em〉SlCDKA1〈/em〉, 〈em〉SlCYCD3;1〈/em〉, and 〈em〉SlKRP2〈/em〉) by stimulating polyamine oxidase (PAO)-dependent H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 production and respiratory burst oxidase homologue (Rboh)-dependent O〈sub〉2〈/sub〉〈sup〉•〈/sup〉‾ production, respectively. Screening of 〈em〉SlPAOs〈/em〉 and 〈em〉SlRbohs〈/em〉 gene family combined with gene expression analysis suggested that melatonin-promoted LR formation was correlated to the upregulation of 〈em〉SlPAO1〈/em〉, 〈em〉SlRboh3〈/em〉, and 〈em〉SlRboh4〈/em〉 in LR-emerging zone. Transient expression analysis confirmed that 〈em〉SlPAO1〈/em〉 was able to produce H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 while 〈em〉SlRboh3〈/em〉 and 〈em〉SlRboh4〈/em〉 were capable of producing O〈sub〉2〈/sub〉〈sup〉•〈/sup〉‾. Melatonin-ROS signaling cassette was also found in the regulation of LR formation in rice root and lateral hyphal branching in fungi. These results suggested that 〈em〉SlPAO1〈/em〉-H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 and 〈em〉SlRboh3/4〈/em〉-O〈sub〉2〈/sub〉〈sup〉•〈/sup〉‾ acted as downstream of melatonin to regulate the expression of cell cycle genes, resulting in LRP initiation and LR development. Such findings uncover one of the regulatory pathways for melatonin-regulated LR formation, which extends our knowledge for melatonin-regulated plant intrinsic physiology.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919313449-fx1.jpg" width="337" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: December 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 145〈/p〉 〈p〉Author(s): Alexander V. Peskin, Paul E. Pace, Christine C. Winterbourn〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Hydrogen peroxide undergoes an equilibrium reaction with bicarbonate/CO〈sub〉2〈/sub〉 to produce peroxymonocarbonate (HCO〈sub〉4〈/sub〉〈sup〉-〈/sup〉). Peroxymonocarbonate is more reactive with thiols than H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 but it makes up only a small fraction of the H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 in physiological bicarbonate buffers so the increase in rate of oxidation of low molecular weight thiols is modest. However, for some thiol proteins such as protein tyrosine phosphatases, the rate enhancement is very much greater. We have investigated the effect of bicarbonate/CO〈sub〉2〈/sub〉 on the oxidation of peroxiredoxins (Prdxs) 2 and 3. Using an assay in which reduced Prdx2 inhibits oxidation of horseradish peroxidase by H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉, we saw no difference between phosphate and bicarbonate buffers (pH 7.4). However, hyperoxidation of both Prdxs in bicarbonate was considerably enhanced. Hyperoxidation involves the reaction of the sulfenic acid formed at the active site with a second H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉, and prevents its condensation to a disulfide. Using LC/MS analysis, we determined that the presence of 25 mM bicarbonate/CO〈sub〉2〈/sub〉 increased the ratio of hyperoxidation compared with condensation 6-fold for Prdx2 and 11-fold for Prdx3. These results imply that Prdx hyperoxidation will occur more readily under physiological conditions than appreciated from in vitro experiments, which seldom use bicarbonate buffers. They also raise the possibility that variations in bicarbonate concentration could provide a mechanism for regulating the cellular level of active Prdxs.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919310366-fx1.jpg" width="467" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Ahmed N.F. Neamat-Allah, Essam A. Mahmoud, Yasser Abd El Hakim〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉As recently applicable, there are few studies on the impact of using nano-selenium (nano-Se) on varied fish species. Where nothing reachable focused on its impact on tilapias so, the present analysis evaluated the efficacy of using nano-Se in tilapias on immune response, antioxidant defense compared by conventional Se form. 480 〈em〉O. niloticus〈/em〉 fingerlings were haphazardly grouped firstly into three groups with four replicates of each. The control one (CT) was fed on a basal diet. The second and third one supplemented with 0.7 mg/kg〈sup〉−1〈/sup〉 Se and nano-Se respectively for ten weeks. At the start day of the ninth week, two replicates from each group were injected by 〈em〉Streptococcus iniae〈/em〉 where, the remaining replicates stand without challenge. Enhancement of growth performance measurements were noted in nano-Se compared to Se or CT groups. Existed anemia in 〈em〉S. iniae〈/em〉 tilapias became alleviated by using nano-Se that also, improves the alteration of leucogram induced by challenge. Elevation of aminotransferases, alkaline phosphatase, lactate dehydrogenase (ALT, AST, ALP and LDH) and creatinine in Se and CT challenged replicates that seemed nearly normal by using nano-Se. Usage of nano-Se showed more powerful antioxidant activities than Se. There were an expansion of immunoglobulin M, lysozymes, glutathione peroxidase, nitric oxide, superoxide dismutase and catalase (IgM, LYZ, GPx, NO, SOD, CAT) and their related gene expression in nano-Se with contrast in Se or CT challenged groups. Nile tilapias challenged by 〈em〉S. iniae〈/em〉 disclosed substantial expansion in the percentage of mortality in CT challenged fish (93.33%), followed by the group supplemented with Se (73.33%), whereas the lowermost one at fish supplemented by nano-Se (26.66%). The mortalities have been stopped from the 5〈sup〉th〈/sup〉, 12〈sup〉th〈/sup〉 and 14〈sup〉th〈/sup〉 days in, nano-Se, Se and CT respectively. It can be concluded that using of Se 0.7 mg/kg〈sup〉−1〈/sup〉induce immunosuppressive, antioxidant, liver and kidneys negative impact on tilapias where the same dose from nano-Se was more potent immunomodulating and antioxidant. Also it is attend in counteracting the serious impact induced by 〈em〉S. iniae〈/em〉 challenge.〈/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): Hoi-Shan Wong, Pierre-Axel Monternier, Martin D. Brand〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mitochondria are important sources of superoxide and hydrogen peroxide in cell signaling and disease. In particular, superoxide/hydrogen peroxide production during reverse electron transport from ubiquinol to NAD〈sup〉+〈/sup〉 though Complex I is implicated in several physiological and pathological processes. S1QELs are small molecules that suppress superoxide/hydrogen peroxide production at Complex I without affecting forward electron transport. Their mechanism of action is disputed. To test different mechanistic models, we compared the effects of two inhibitors of Complex I electron transport (piericidin A and rotenone) and two S1QELs from different chemical families on superoxide/hydrogen peroxide production and electron transport by Complex I in isolated mitochondria. Piericidin A and rotenone (and S1QEL1.1 at higher concentrations) prevented superoxide/hydrogen peroxide production from sites I〈sub〉Q〈/sub〉 and I〈sub〉F〈/sub〉 in Complex I by inhibiting reverse electron transport into the complex. S1QELs decreased the potency of electron transport inhibition by piericidin A and rotenone, suggesting that S1QELs bind directly to Complex I. S1QEL2.1 (and S1QEL1.1 at lower concentrations) suppressed site I〈sub〉Q〈/sub〉 without affecting reverse electron transport or site I〈sub〉F〈/sub〉, showing that sites I〈sub〉Q〈/sub〉 and I〈sub〉F〈/sub〉 are distinct, and that S1QELs do not work simply by decreasing reverse electron transport to site I〈sub〉F〈/sub〉 (or site I〈sub〉Q〈/sub〉). S1QELs did not affect the reduction of NAD〈sup〉+〈/sup〉 or the rate of site I〈sub〉F〈/sub〉 driven by reverse electron transport, therefore they do not alter the driving forces for reverse electron transport and that is not how they suppress site I〈sub〉Q〈/sub〉. We conclude that S1QELs bind to Complex I to influence the conformation of the piericidin A and rotenone binding sites and directly suppress superoxide/hydrogen peroxide production at site I〈sub〉Q〈/sub〉, which is a separate site from site I〈sub〉F〈/sub〉.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919313486-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): Ping Wang, Zhanying Zhang, Zhongtian Xu, Baoying Guo, Zhi Liao, Pengzhi Qi〈/p〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Lizhu Tao, Xiaoyan Xu, Yuan Fang, Anqi Wang, Fenglin Zhou, Yubang Shen, Jiale Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Grass carp septicemia is a systemic inflammatory response that develops following a bacterial infection. The hyperinflammatory state develops could lead to septic shock and lethality. There is increasing evidence that microRNAs are involved in the regulation of the inflammatory response. In the present study, miR-21 was confirmed to be involved in the inflammatory response following infection with 〈em〉Aeromonas hydrophila〈/em〉 and LPS stimulation. Both 〈em〉jnk〈/em〉 and 〈em〉ccr7〈/em〉 were identified as target gene of miR-21 by overexpression, inhibition, and dual luciferase reporter assays experiments. Meanwhile, miR-21 targets the 〈em〉jnk〈/em〉 and 〈em〉ccr7〈/em〉 to modulate downstream pro-inflammatory factors 〈em〉tnf-α, il-1β, il-6,〈/em〉 and 〈em〉il-12〈/em〉. Our results provide a theoretical basis for exploring the molecular mechanism of grass carp miR-21 regulating inflammation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Yunpeng Cao, Na Jin, Mingli Fan, Caiyun Lv, Xiaojun Song, Ping Jin, Fei Ma〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Transforming growth factor-β activated kinase-1 (TAK1) is an important member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, which plays an important role in animal innate immune response. However, the 〈em〉TAK1〈/em〉 gene has yet not been reported in amphioxus to date. Here, we have identified and characterized a 〈em〉TAK1〈/em〉 gene from amphioxus (〈em〉Branchiostoma belcheri〈/em〉) (named as 〈em〉AmphiTAK1〈/em〉) with the full-length cDNA of 3479 bp, including an ORF sequence of 1905 bp, a 5′ UTR of 394 bp and a 3′ UTR of 1180 bp. Moreover, the predicted AmphiTAK1 protein contains STKc_TAK1 domain, TAB1 and TAB2/3 binding domain which are conserved among chordate, and phylogenetic analysis also shows that the AmphiTAK1 is located at the bottom of the chordate, revealing 〈em〉AmphiTAK1〈/em〉 as a new member of the 〈em〉TAK1〈/em〉 gene family. The further qRT-PCR analysis has shown that 〈em〉AmphiTAK1〈/em〉 is widely expressed in six investigated tissues (gonad, gill, hepatic cecum, intestine, muscle and notochord) of 〈em〉Branchiostoma belcheri〈/em〉, with high expression in notochord and gonad, moderate in gill and hepatic cecum. Notably, the expression level of 〈em〉AmphiTAK1〈/em〉 is significantly up-regulated after LPS stimulation. Specially, we also find that AmphiTAK1 protein can interact with AmphiTAB1 by immunoprecipitation assay. These findings reveal that AmphiTAK1 might interact with AmphiTAB1 to involve in innate immune response of 〈em〉Branchiostoma belcheri〈/em〉. Taken together, our present works provide a new insight into evolution and innate immune response mechanism of 〈em〉AmphiTAK1〈/em〉 gene in 〈em〉Branchiostoma belcheri〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Chao Peng, Dongchang Xie, Chao Zhao, Haidong Xu, Sigang Fan, Lulu Yan, Pengfei Wang, Lihua Qiu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Akirin, which are members of the NF-κB signaling pathway, play critical roles in regulating the expression of antimicrobial peptides. In the present study, the 〈em〉Akirin〈/em〉 gene from 〈em〉Penaeus monodon〈/em〉 was identified from a transcriptome database and designated as 〈em〉PmAkirin〈/em〉. The complete sequence of the 〈em〉PmAkirin〈/em〉 cDNA was 1508 bp, encoding a protein of 213 amino acids, and it showed 99% amino acid identity to the 〈em〉Litopenaeus vannamei〈/em〉 Akirin. Two predicted nuclear localization signals (NLSs) were found, and the amino acid sequence alignments showed that PmAkirin was highly conserved at the N-terminus and C-terminus. 〈em〉PmAkirin〈/em〉 expression was found to be the highest in the hemolymph, followed by the heart, gill, stomach, hepatopancreas, intestine, and muscle. When challenged with 〈em〉Vibrio parahaemolyticus〈/em〉 infection, the 〈em〉PmAkirin〈/em〉 mRNA and three antimicrobial peptides (AMPs: 〈em〉PmALF2, PmALF3,〈/em〉 and 〈em〉PmCrus4〈/em〉) were upregulated. However, another five AMPs (〈em〉PmALF6, PmCrus1, PmPEN3a, PmPEN3b,〈/em〉 and 〈em〉PmPEN5〈/em〉) were downregulated by 〈em〉V. parahaemolyticus〈/em〉 infection. Silencing 〈em〉PmAkirin〈/em〉 by dsRNA significantly decreased the expression of the eight AMPs, which lead to an increase in the blood concentration of 〈em〉V. parahaemolyticus〈/em〉 and higher mortality in the shrimp. In contrast, the overexpression of 〈em〉PmAkirin〈/em〉 significantly increased the expression of the eight AMPs, which led to a reduction in the blood concentration of 〈em〉V. parahaemolyticus〈/em〉 and promoted the survival of the shrimp. Taken together, we concluded that 〈em〉PmAkirin〈/em〉 plays an important role in regulating the expression of AMPs in black tiger shrimp to defend against 〈em〉V. parahaemolyticus〈/em〉 infection.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 2 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology〈/p〉 〈p〉Author(s): Jingyi Cen, Lei Cui, Yafei Duan, Hua Zhang, Yarou Lin, Jiping Zheng, Songhui Lu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Palytoxins (PLTXs) are a group of complex and poisonous marine natural products that are toxic to marine life and even human beings. In the present study, the oxidative stress and immune response in the hepatopancreas and gills of 〈em〉Litopenaeus vannamei〈/em〉 were assessed for 72 h after injection with PLTX extracts. Chemical and physiological parameters, e.g., the respiratory burst (O〈sub〉2〈/sub〉〈sup〉−〈/sup〉), activities of antioxidant enzymes, oxidative damage to lipids, carbonylation of proteins, and immune gene mRNA expression levels, were analysed. The results showed that the PLTX extract was not fatal to the shrimp but could reduce their mobility. The O〈sub〉2〈/sub〉〈sup〉−〈/sup〉 levels in the gills gradually increased after exposure to PLTX extracts and were significantly higher than those in the control from 6 to 72 h. The malondialdehyde content, lipid peroxidation, protein carbonyl levels, and total antioxidant capacity in the gills all peaked at 12 h. At the same time, the gills were loosely connected, there was a clear disintegration of the epithelial tissue, and the stratum corneum disappeared after 12 h. In addition, compared to those in the control group, the PLTX extract treatment increased the O〈sub〉2〈/sub〉〈sup〉−〈/sup〉 content, malondialdehyde content, lipid peroxidation, and protein carbonyl levels from 12 to 72 h, 24–48 h, 12–24 h, and 12–72 h after injection in the hepatopancreas of the shrimp, respectively. Both the 〈em〉Crustin〈/em〉 and 〈em〉Toll〈/em〉 gene expression levels significantly increased in the hepatopancreas compared to those in the control 6–72 h after injection of the toxin. In parallel, the expression levels of the manganese superoxide dismutase gene gradually decreased from 6 to 48 h and returned to normal levels after 72 h. Interestingly, the total antioxidant capacity also significantly increased compared to that in the control from 6 to 72 h. Our results indicate that although PLTX extracts cause lipid peroxidation and carbonylation of proteins in hepatopancreatic cells, leading to their damage, they did not cause a decrease in the total antioxidant capacity of the hepatopancreas.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 2 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology〈/p〉 〈p〉Author(s): Qiu-Ning Liu, Ting-Ting Yang, Cheng Wang, Sen-Hao Jiang, Dai-Zhen Zhang, Bo-Ping Tang, Bao-Ming Ge, Jia-Lian Wang, Dong Wang, Li-Shang Dai〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In this study, we identified a fish-specific Toll-like receptor (TLR) in 〈em〉Pelteobagrus fulvidraco〈/em〉, an economically important freshwater fish in China. This TLR, 〈em〉Pf〈/em〉TLR26, was shown to be encoded by a 3084 bp open reading frame (ORF), producing a polypeptide 1027 amino acids in length. The 〈em〉Pf〈/em〉TLR26 protein contains a signal peptide, eight leucine-rich repeat (LRR) domains, two LRR_TYP domains in the extracellular region, and a Toll/interleukin (IL)-1 receptor (TIR) domain in the cytoplasmic region, consistent with the characteristic TLR domain architecture. This predicted 117.1 kDa protein was highly homologous to those of other fish, with phylogenetic analysis revealing the closest relation to TLR26 of 〈em〉Ictalurus punctatus〈/em〉. Real-time quantitative reverse transcription-PCR (qRT-PCR) analysis showed that the 〈em〉Pf〈/em〉TLR26 gene was expressed in all tissues tested, with the highest expression levels seen in the head kidney and blood, and the lowest seen in muscle. 〈em〉Pf〈/em〉TLR26 exhibited significant upregulation in liver, spleen, head kidney, and blood at different time points following challenge with the common TLR agonists lipopolysaccharide (LPS) and polyriboinosinic polyribocytidylic acid (Poly I:C). Taken together, these results suggest that 〈em〉Pf〈/em〉TLR26 may be an important component of the 〈em〉P. fulvidraco〈/em〉 innate immune system, participating in the transduction of TLR signaling under pathogen stimulation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 19 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Ibrahim Dogar, Sarah Dixon, Robert Gill, Adrian Young, Sarah Mallay, Catherine Oldford, Ryan J. Mailloux〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Here, we demonstrate that the upregulation of catalase is required to compensate for the loss of nicotinamide nucleotide transhydrogenase (NNT) to maintain hydrogen peroxide (H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉) steady-state levels in C57BL/6J liver mitochondria. Our investigations using the closely related mouse strains C57BL/6NJ (6NJ; +NNT) and C57BL/6J (6J; -NNT) revealed that NNT is required for the provision of NADPH and that the upregulation of isocitrate dehydrogenase-2 (IDH2) activity is not enough to compensate for the absence of NNT, which is consistent with previous observations. Intriguingly, despite the absence of NNT, 6J mitochondria had rates of H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 production (58.56 ± 3.79 pmol mg〈sup〉−1〈/sup〉 min〈sup〉−1〈/sup〉) that were similar to samples collected from 6NJ mice (72.75 ± 14.26 pmol mg〈sup〉−1〈/sup〉 min〈sup〉−1〈/sup〉) when pyruvate served as the substrate. However, 6NJ mitochondria energized with succinate produced significantly less H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 (59.95 ± 2.13 pmol mg〈sup〉−1〈/sup〉 min〈sup〉−1〈/sup〉) when compared to samples from 6J mice (116.39 ± 20.74 pmol mg〈sup〉−1〈/sup〉 min〈sup〉−1〈/sup〉), an effect that was attributed to the presence of NNT. Further investigations into the H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 eliminating capacities of these mitochondria led to the novel observation that 6J mitochondria compensate for the loss of NNT by upregulating catalase. Indeed, 6NJ and 6J mitochondria energized with pyruvate or succinate displayed similar rates for H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 elimination, quenching ~84% and ~86% of the H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉, respectively, in the surrounding medium within 30 s. However, inclusion of palmitoyl-CoA, an NNT inhibitor, significantly limited H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 degradation by 6NJ mitochondria only (~55% of H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 eliminated in 30 s). Liver mitochondria from 6J mice treated with palmitoyl-CoA still cleared ~80% of the H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 from the surrounding environment. Inhibition of catalase with triazole compromised the capacity of 6J mitochondria to maintain H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 steady-state levels. By contrast, disabling NADPH-dependent antioxidant systems had a limited effect on the H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 clearing capacity of 6J mitochondria. Liver mitochondria collected from 6NJ mice, on the other hand, were more reliant on the GSH and TRX systems to clear exogenously added H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉. However, catalase still played an integral in eliminating H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 in 6NJ liver mitochondria. Immunoblot analyses demonstrated that catalase protein levels were ~7.7-fold higher in 6J mitochondria. Collectively, our findings demonstrate for the first time that 6J liver mitochondria compensate for the loss of NNT by increasing catalase levels for the maintenance of H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 steady-state levels. In general, our observations reveal that catalase is an integral arm of the antioxidant response in liver mitochondria.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919315084-fx1.jpg" width="367" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 19 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Vlada Koliadenko, Tomasz Wilanowski〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Protein moonlighting is a phenomenon in which a single polypeptide chain can perform a number of different unrelated functions. Here we present our analysis of moonlighting in the case of selected DNA repair proteins which include G:T mismatch-specific thymine DNA glycosylase (TDG), methyl-CpG-binding domain protein 4 (MBD4), apurinic/apyrimidinic endonuclease 1 (APE1), AlkB homologs, poly (ADP-ribose) polymerase 1 (PARP-1) and single-strand selective monofunctional uracil DNA glycosylase 1 (SMUG1). Most of their additional functions are not accidental and clear patterns are emerging. Participation in RNA metabolism is not surprising as bases occurring in RNA are the same or very similar to those in DNA. Other common additional function involves regulation of transcription. This is not unexpected as these proteins bind to specific DNA regions for DNA repair, hence they can also be recruited to regulate transcription. Participation in demethylation and replication of DNA appears logical as well. Some of the multifunctional DNA repair proteins play major roles in many diseases, including cancer. However, their moonlighting might prove a major difficulty in the development of new therapies because it will not be trivial to target a single protein function without affecting its other functions that are not related to the disease.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919313255-fx1.jpg" width="294" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Chun-Hua Huang, Dan Xu, Li Qin, Tian-Shu Tang, Guo-Qiang Shan, Lin-Na Xie, Pei-Lin Li, Li Mao, Jie Shao, Ben-Zhan Zhu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉We found recently that benzohydroxamic acid (BHA) could detoxify the chlorinated quinoid carcinogens via an unusual Lossen rearrangement reaction. However, it is not clear what would happen when the nitrogen hydrogen of BHA was substituted with methyl and other alkyl groups. Here we show that 〈em〉N〈/em〉-methyl benzohydroxamic acid (〈em〉N〈/em〉-MeBHA, a simple model compound for the classic iron-chelator deferoxamine, which is a typical 〈em〉N〈/em〉-alkyl trihydroxamic acid) could react with 2,5-dichloro-1,4-benzoquinone (DCBQ) to form a relatively stable initial carbon-oxygen bonding conjugation intermediate CBQ-O-〈em〉N〈/em〉-MeBHA. However, the major final product was identified, unexpectedly, as a carbon-nitrogen bonding conjugate CBQ(OH)–N(CH〈sub〉3〈/sub〉)-COAr, which is the rearranged isomer of CBQ-O-〈em〉N〈/em〉-MeBHA. Interestingly, a new 18-line nitrogen-centered radical and a carbon-centered quinone ketoxy radical were observed by the ESR spin-trapping method, which was further confirmed by HPLC-MS and 〈sup〉15〈/sup〉N-isotope labeling methods. We further found that both new DNA adducts and DNA strand breaks could be produced by the reactive nitrogen-centered radical. Taken together, we propose that the reaction between DCBQ and 〈em〉N〈/em〉-MeBHA was not via the Lossen rearrangement, but rather through a novel radical homolysis and recoupling pathway. Analogous results were observed for other chlorinated quinones and 〈em〉N〈/em〉-alkyl hydroxamic acids including the widely-used trihydroxamate iron-chelating drug deferoxamine. This represents the first report of unexpected radical pathway for the reaction between chlorinated quinones and 〈em〉N〈/em〉-alkyl hydroxamic acids under normal physiological conditions, which may have broad biological and environmental significance for future study of carcinogenic chloroquinones and hydroxamic acid drugs.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919312481-fx1.jpg" width="285" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 15 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine〈/p〉 〈p〉Author(s): Julie Brault, Bénédicte Vigne, Mathieu Meunier, Sylvain Beaumel, Michelle Mollin, Sophie Park, Marie José Stasia〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Reactive oxygen species (ROS) produced in hematopoietic stem cells (HSCs) are involved in the balance between quiescence, self-renewal, proliferation and differentiation processes. However the role of NOX enzymes on the early stages of hematopoietic differentiation is poorly investigated. For that, we used induced pluripotent stem cells (iPSCs) derived from X-linked Chronic Granulomatous Disease (X〈sup〉0〈/sup〉CGD) patients with deficiency in NOX2, and AR22〈sup〉0〈/sup〉CGD patients with deficiency in p22〈sup〉〈em〉phox〈/em〉〈/sup〉 subunit which decreases NOX1, NOX2, NOX3 and NOX4 activity. CD34〈sup〉+〈/sup〉 hematopoietic progenitors were obtained after 7, 10 and 13 days of iPS/OP9 co-culture differentiation system. Neither NOX expression nor activity was found in Wild-type (WT), X〈sup〉0〈/sup〉CGD and AR22〈sup〉0〈/sup〉CGD iPSCs. Although NOX2 and NOX4 mRNA were found in WT, X〈sup〉0〈/sup〉CGD and AR22〈sup〉0〈/sup〉CGD iPSC-derived CD34〈sup〉+〈/sup〉 cells at day 10 and 13 of differentiation, NOX4 protein was the only NOX enzyme expressed in these cells. A NADPH oxidase activity was measured in WT and X〈sup〉0〈/sup〉CGD iPSC-derived CD34〈sup〉+〈/sup〉 cells but not in AR22〈sup〉0〈/sup〉CGD iPSC-derived CD34〈sup〉+〈/sup〉 cells because of the absence of p22〈sup〉〈em〉phox〈/em〉〈/sup〉, which is essential for the NOX4 activity. The absence of NOX4 activity and the poor NOX-independent ROS production in AR22〈sup〉0〈/sup〉CGD iPSC-derived CD34〈sup〉+〈/sup〉 cells favored the CD34〈sup〉+〈/sup〉 cells production but lowered their hematopoietic potential compared to WT and X〈sup〉0〈/sup〉CGD iPSC-derived CD34〈sup〉+〈/sup〉 cells. In addition we found a large production of primitive AR22〈sup〉0〈/sup〉CGD iPSC-derived progenitors at day 7 compared to the WT and X〈sup〉0〈/sup〉CGD cell types. In conclusion NOX4 is the major NOX enzyme involved in the early stages of hematopoietic differentiation from iPSCs and its activity can modulate the production, the hematopoietic potential and the phenotype of iPSC-derived CD34〈sup〉+〈/sup〉.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919315710-fx1.jpg" width="214" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Jing Wang, Jia-Jia Du, Biao Jiang, Run-Zhen He, An-Xing Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Short-term feed deprivation or fasting is commonly experienced by aquaculture fish species and may be caused by seasonal variations, production strategies, or diseases. To assess the effects of fasting on the resistance of Nile tilapia to 〈em〉Streptococcus agalactiae〈/em〉 infection, vaccinated and unvaccinated fish were fasted for zero, one, three, and seven days prior to infection. The cortisol levels of both vaccinated and unvaccinated fish first decreased and then increased significantly as fasting time increased. Liver glycogen, triglycerides, and total cholesterol decreased significantly after seven days of fasting, but glucose content did not vary significantly between fish fasted for three and seven days. Hexokinase (HK) and pyruvate kinase (PK) activity levels were lowest after seven days of fasting, while phosphoenolpyruvate carboxykinase (PEPCK) activity levels varied in opposition to those of HK and PK. Serum superoxide dismutase (SOD) and catalase (CAT) activity levels first increased and then decreased as fasting time increased; SOD activity was highest after three days of fasting. Interleukin-1beta (〈em〉IL-1β〈/em〉) and 〈em〉IL-〈/em〉6 mRNA expression levels first increased and then decreased significantly, peaking after three days of fasting. However, suppressor of cytokine signaling-1 (〈em〉SOCS-1〈/em〉) mRNA expression levels were in opposition to those of 〈em〉IL-1β〈/em〉 and 〈em〉IL-6〈/em〉. Specific antibody levels did not vary significantly among unvaccinated fish fasted for different periods. Although specific antibody level first increased and then decreased in the vaccinated fish as fasting duration increased, there were no significant differences in the survival rates of fasted vaccinated fish after challenge with 〈em〉S. agalactiae〈/em〉. The final survival rates of vaccinated fish fasted for zero, one, three, and seven days were 86.67 ± 5.44%, 80.00 ± 3.14%, 88.89 ± 6.28%, and 84.44 ± 8.32%, respectively. Among the unvaccinated fish, the survival rate was highest (35.56 ± 3.14%) in the fish fasted for three days and lowest (6.67 ± 3.14%) in the fish fasted for seven days. Therefore, our results indicated that short-term fasting (three days) prior to an infection might increase the resistance of unvaccinated Nile tilapia to 〈em〉S. agalactiae〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: December 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 145〈/p〉 〈p〉Author(s): Ho Hang Leung, Alex LK. Ng, Thierry Durand, Ryo Kawasaki, Camille Oger, Laurence Balas, Jean-Marie Galano, Ian YH. Wong, Jetty Chung-Yung Lee〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Appropriate diet is essential for the regulation of age-related macular degeneration (AMD). In particular the type of dietary polyunsaturated fatty acids (PUFA) and poor antioxidant status including carotenoid levels concomitantly contribute to AMD risk. Build-up of oxidative stress in AMD induces PUFA oxidation, and a mix of lipid oxidation products (LOPs) are generated. However, LOPs are not comprehensively evaluated in AMD. LOPs are considered biomarkers of oxidative stress but also contributes to inflammatory response. In this cross-sectional case-control study, plasma omega-6/omega-3 PUFA ratios and antioxidant status (glutathione, superoxide dismutase and catalase), and plasma and urinary LOPs (41 types) were determined to evaluate its odds-ratio in the risk of developing exudative AMD (n = 99) compared to age-gender-matched healthy controls (n = 198) in adults with Chinese diet. The odds ratio of developing exudative AMD increased with LOPs from omega-6 PUFA and decreased from those of omega-3 PUFA. These observations were associated with a high plasma omega-6/omega-3 PUFA ratio and low carotenoid levels. In short, poor PUFA and antioxidant status increased the production of omega-6 PUFA LOPs such as dihomo-isoprostane and dihomo-isofuran, and lowered omega-3 PUFA LOPs such as neuroprostanes due to the high omega-6/omega-3 PUFA ratios; they were also correlated to the risk of AMD development. These findings indicate the generation of specific LOPs is associated with the development of exudative AMD.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919313024-fx1.jpg" width="310" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): A. Miccoli, P.R. Saraceni, G. Scapigliati〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This review describes and summarizes the knowledge on established and experimental vaccines developed against viral and bacterial pathologies affecting the most important farmed marine finfish species present in the Mediterranean area, namely European seabass 〈em〉Dicentrarchus labrax〈/em〉, sea bream 〈em〉Sparus aurata〈/em〉, turbot 〈em〉Psetta maxima〈/em〉 and meagre 〈em〉Argyrosomus regius〈/em〉. The diseases that have been recorded in seabass, sea bream and meagre are caused by bacteria 〈em〉Vibrio anguillarum〈/em〉, 〈em〉Photobacterium damselae〈/em〉, 〈em〉Tenacibaculum maritimum〈/em〉 as well as by viruses such as Viral Encephalopathy and Retinopathy/Viral Nervous Necrosis and Lymphocystic disease. The main pathologies of turbot are instead bacteriosis provoked by 〈em〉Tenacibaculum maritimum〈/em〉, 〈em〉Aeromonas〈/em〉 sp. and 〈em〉Vibrio anguillarum〈/em〉, and virosis by viral hemorrhagic septicaemia virus. Some vaccines have been optimized and are now regularly available for the majority of the above-mentioned pathogens. A measurable immune protection has been conferred principally against 〈em〉Vibrio anguillarum, Photobacterium damselae〈/em〉 sub. 〈em〉piscicida〈/em〉 and VER/VNN.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: December 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 95〈/p〉 〈p〉Author(s): Yue Ma, Yabo Liu, Yanyan Wu, Lei Jia, Xiaohong Liu, Qiyao Wang, Yuanxing Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Surface display can expose foreign antigenic protein on the surface of the vaccine vector, which is promising choice to elicit better immune responses. In this study, we apply this strategy to develop an immunoactivator by using a live attenuated 〈em〉Vibrio harveyi〈/em〉 as an antigenic protein carrier with surface displayed VP28, a major envelope protein of white spot syndrome virus (WSSV), for two major pathogens of 〈em〉Litopenaeus vannamei.〈/em〉 As a result, the immunoactivator showed self-limited growth and attenuation of virulence in shrimp via different inoculation routes either with single-repetitive dose or high dose. Moreover, either intramuscular injection or oral administration of the immunoactivator did not affect growth of shrimp body weight or cause pathologic changes. Additionally, the rapid immunoprotection was induced by the immunoactivator after administration for one week with highly relative percent survival (RPS) more than 90% against both 〈em〉V. harveyi〈/em〉 and WSSV. Until 4 weeks post administration, the immunoactivator still possessed efficient immune effect with no less than 60% RPS for both pathogens. Totally, the attenuated 〈em〉V. harveyi〈/em〉 surface displaying VP28 could be a potential immunoactivator for WSSV and vibriosis control in 〈em〉L. vannamei〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Yu Zhou, Long-Feng Lu, Xiao-Bing Lu, Shun Li, Yong-An Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mammalian cyclic GMP-AMP synthase (cGAS) senses double-stranded (ds) DNA in the cytosol to activate the innate antiviral response. In the present study, a cGAS-like gene, namely cGASL, was cloned from grass carp 〈em〉Ctenopharyngodon idellus〈/em〉, and its role as a negative regulator of the IFN response was revealed. Phylogenetic analysis indicated that cGASL was evolutionarily closest to cGAS, but was not a true ortholog of cGAS. Overexpression of cGASL inhibited poly I:C-stimulated grass carp (gc)IFN1pro and ISRE activities. In addition, MITA-, but not TBK1-mediated activation of gcIFN1pro was impaired by cGASL. Co-immunoprecipitation and Western blot experiments indicated that cGASL interacted with MITA and TBK1, resulting in a reduction in the phosphorylation of MITA. Lastly, overexpression of cGASL reduced the transcriptional levels of several IFN-stimulated genes activated by MITA. Collectively, these data suggest that cGASL is a negative regulator of IFN response by targeting MITA 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): Hongjing Zhao, Yu Wang, Xin Yang, Dongxue Fei, Mengyao Mu, Menghao Guo, Hongxian Yu, Mingwei Xing〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This study was designed to evaluate the effects of zinc on inflammation and tight junction (TJ) in different intestinal regions of common carp under sub-chronic arsenic insult. Fish were exposed to zinc (0, 1 mg/L) and arsenic trioxide (0, 2.83 mg/L) in individual or combination for a month. Inflammatory infiltration and TJ structure changes were displayed by H&E staining and transmission electron microscope. To further explore these changes, biochemical indicator (SOD), gene or protein expressions of inflammatory responses (NF-κB, IL-1β, IL-6 and IL-8) and TJ proteins (Occludin, Claudins and ZOs) were determined. In the anterior intestine, arsenic decreased activity of SOD, mRNA levels of Occludin, Claudins and ZOs, increased mRNA levels of ILs. However, unlike the anterior intestine, arsenic has an upregulation effects of Occludin and Claudin-4 in the mid intestine. These anomalies induced by arsenic, except IL-8, were completely or partially recovered by zinc co-administration. Furthermore, transcription factor (NF-κB) nuclear translocation paralleled with its downstream genes in both intestinal regions. In conclusion, our results unambiguously suggested that under arsenic stress, zinc can partly relieve intestinal inflammation and disruption of tight junction segment-dependently.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1050464819309532-fx1.jpg" width="275" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 94〈/p〉 〈p〉Author(s): Yuan Cui, Kai Yin, Yingzheng Gong, Yingying Qu, Honggui Liu, Hongjin Lin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Atrazine (ATR) causes environmental problems and damages the health of fish and aquatic animals. MicroRNAs (miRNAs) play important roles in immune regulation. However, the immunotoxicity mechanism of ATR in fish lymphocytes and the role of miRNA in this process remain unclear. To further study these mechanisms, spleen lymphocytes were exposed to 20, 40 and 60 μg/ml ATR for 18 h. Fluorescence staining and flow cytometry showed that the number of necrotic lymphocytes increased after ATR exposure. Compared with the control group, the mRNA expression of miR-181–5p was inhibited and the mRNA levels of TNF-α and HK2 were increased after ATR exposure. Additionally, the NF-κB inflammatory pathway and the levels of glycometabolism-related genes were upregulated. These results suggest that ATR induces inflammation and elevates glycometabolism in lymphocytes. We further found that the mRNA levels of receptor-interacting serine-threonine kinase 1 (RIP1), receptor-interacting serine-threonine kinase 3 (RIP3), mixed lineage kinase domain-like pseudokinase (MLKL), cylindromatosis (CYLD) and Fas-Associated protein with Death Domain (FADD) and the protein levels of RIP3 and MLKL in the treatment groups were significantly increased compared to those in control group, suggesting that ATR causes lymphocyte necroptosis. We conclude that miR-181–5p plays a key role in necroptosis in carp lymphocytes exposed to ATR by downregulating the expression of HK and TNF-α, which increases the level of glycometabolism and induces the inflammatory response, respectively.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1050464819309520-fx1.jpg" width="485" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 20 November 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 144〈/p〉 〈p〉Author(s): 〈/p〉