ALBERT

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): 〈/p〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): M.A. Baqué, V.V. Gioria, G.A. Micheloud, N.M.C. Casado, J.D. Claus, A.M. Gennaro〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Different spin labels were incorporated to the membranes of cultured insect UFL-AG-286 cells in order to characterize their physical properties by Electron Paramagnetic Resonance spectroscopy (EPR). The spectrum of the spin label 12-SASL incorporated to cell membranes was similar as those obtained in membrane model systems composed of eggPC/cholesterol. However, the spectrum of the spin label CSL, chemically related to cholesterol, was drastically different in the two systems. Interestingly, when cell cholesterol content was reduced using methyl beta cyclodextrin, an EPR spectrum similar to those of model membranes was obtained. The analysis of these experiments suggests the existence of cholesterol rich regions in UFL-AG-286 cell membranes.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Beijun Wu, Chunxia Li, Huimeng Lei〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉SAP90/PSD95-associated proteins (SAPAPs) are one type of scaffold protein in the postsynaptic density (PSD). Scaffold proteins play an important role in synaptic function. Recently, many studies have shown that mutations associated with scaffold proteins cause dysfunction in neuronal circuitry and in behavior. SAPAP4, as a protein in the SAPAP family, may have an impact on synaptic functions and on behaviors. To test this hypothesis, mice with a genetic deletion of SAPAP4 were used in our study. SAPAP4−/− mice displayed decreased cocaine sensitivity behavior after an acute injection of 20 mg/kg cocaine. We also found that the spine density of medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell was reduced in SAPAP4−/− mice. Furthermore, SAPAP4−/− mice displayed altered synaptic transmission and a decreased frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) in the NAc. Our findings demonstrate that SAPAP4 plays a critical role in cocaine-related behavior and in the synaptic function of the NAc.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Shengkai Luo, Hua Huang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉In vivo〈/em〉 growth study indicates that 〈em〉Mycobacterium smegmatis〈/em〉 could utilize D-ribonate as sole carbon source under an unknown pathway. To clarify this pathway, we start with the statistical analysis of genome neighborhood networks(GNNs) of erythrulose kinase which has been approved to participate in several sugars’ degradation. In 〈em〉M. smegmatis〈/em〉, two novel dehydrogenases (3HCDH & ADH_short) and one unknown isomerase (AP_endonuc) are targeted and characterized, for the catabolism of D-ribonate in this organism, this acid sugar is firstly oxidized into 2-keto-D-ribonate by a dehydrogenase, and then sequentially isomerized to 3-keto D-ribonate by an AP_endonuc isomerase; afterward, through decarboxylation, this 3-keto sugar acid is degraded into D-erythrulose which enters a known pathway through erythrulose kinase. Additionally, several other acid sugars (L-ribonate, D/L-lyxonate, L-threonate and D-erythronate) have been proved to be catalyzed by same enzymes and proceed with a similar catabolic pathway.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Chen Lei, Han Xueming, Duan Ruihang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Diabetes mellitus is known as a main cause to induce osteoporosis. However, the pathogenesis of osteoporosis induced by diabetes has not been fully understood. MLN64 is highly homologous to the steroidogenic acute regulatory (STAR) protein, sharing the highly conserved START domain and exhibiting various biological activities. In the study, we attempted to explore the role of MLN64 in osteoporosis progression through the in vitro and in vivo studies. At first, the in vitro study suggested that MLN64 was over-expressed during the osteoclast differentiation induced by receptor activator of NF-kB ligand (RANKL). MLN64-knockdown markedly reduced the number of TRAP-positive multinucleated cells induced by RANKL, along with the down-regulation of specific genes related to osteoclastogenesis, including tartrate-resistant acid phosphatase (TRAP), nuclear factor of activated T cells (NFATc1), cathepsin K (CTSK), tartrate resistant (ACP5) and c-FOS and up-regulation of transcriptional receptor runt related transcription factor 2 (Runx2) and osteopontin (OPN). In contrast, over-expressing MLN64 significantly promoted the production of TRAP-positive multinucleated cells triggered by RANKL. Moreover, RANKL exposure led to remarkable increase in inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and MMP-1, which was attenuated by the knockdown of MLN64. Additionally, the expression of phosphorylated (p)〈img src="https://sdfestaticassets-eu-west-1.sciencedirectassets.com/shared-assets/16/entities/sbnd"〉IKKα, 〈em〉p〈/em〉-IκBα and p-nuclear factor (NF)-κB stimulated by RANKL was clearly alleviated by MLN64 silence. However, RANKL-induced inflammation was accelerated by MLN64 over-expression. Further, the in vivo study suggested that streptozotocin (STZ)-caused reduction in body weight of mice was improved by the loss of MLN64. STZ-induced diabetic mice exhibited higher levels of blood alkaline phosphatase (ALP) and TRAP, while being down-regulated in MLN64-knockout mice. MLN64 deletion reversed STZ-induced trabecular deleterious effects and stimulated bone remodeling. What's more, MLN64 knockout inhibited the expression levels of TRAP, RANKL and RANK in femoral heads of STZ mice, accompanied with the repression of inflammatory response. In conclusion, the results in our study suggested that MLN64 played a critical role in the meditation of osteoclastic differentiation, and its suppression alleviated diabetic osteoporosis in STZ-induced mice. Thus, MLN64 could be served as an essential target for developing effective therapeutic strategy to prevent diabetic osteoporosis.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Yulia Zhitnyuk, Peter Gee, Mandy S.Y. Lung, Noriko Sasakawa, Huaigeng Xu, Hirohide Saito, Akitsu Hotta〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The delivery of mRNA is advantageous over DNA delivery as it is transient and does not carry the risk of genomic DNA integration. However, there are currently few efficient mRNA delivery options available, especially for hard-to-transfect cell types, and thus new delivery methods are needed. To this end, we have established a novel mRNA delivery system utilizing chimeric virus-like particles (VLPs). We generated a novel VLP by fusing protein G of Vesicular stomatitis virus (VSV-G) with a ribosomal protein L7Ae of 〈em〉Archeoglobus fulgidus〈/em〉. This system allowed the efficient delivery of EGFP mRNA which was independent from the presence of BoxC/D motif in the mRNA sequence. Our VSVG-L7Ae VLP system demonstrated high transduction efficacy in hard-to-transfect cell lines, such as human induced pluripotent stem cells (iPS cells) and monocytes. In summary, this platform may serve as an efficient and transient transgene delivery tool for an mRNA of interest.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Tania Yareli Gutiérrez-López, Lennis Beatríz Orduña-Castillo, Magda Nohemí Hernández-Vásquez, José Vázquez-Prado, Guadalupe Reyes-Cruz〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Calcium sensing receptor (CaSR) activates the NLRP3 inflammasome with consequences on homeostatic responses. However, little is known about how this process is orchestrated. Since proteolysis of critical regulators of NLRP3 inflammasome contribute to its activation, we aimed to understand how CaSR stimulates proteolytic pathways to activate the NLRP3 inflammasome. We found that proteasome and lysosome-dependent mechanisms are activated by CaSR to promote the degradation of important regulators of NLRP inflammasome. The pathway involves Gαq/PLC/PKC and Gβγ/PI3K signaling cascades and IRAK1 ubiquitination. In addition, CaSR stimulates Hsp70 expression activating a chaperone-assisted protein degradation that dictates the fate of ASC, NLRP3 (NOD-like receptor family protein 3), IRAK1 and TRAF6 proteins, turning on the NLRP3 inflammasome. In response to CaSR signaling, these proteins are degraded through the combination of CUPS (chaperone-assisted ubiquitin proteasome pathway) and CAEMI (chaperone-assisted endosomal microautophagy) systems being integrated by autophagosomes (chaperone-assisted macroautophagy, CAMA), as indicated by LC3-II, a classical marker for autophagy, that is induced in the process. Furthermore, CaSR triggers the proteolytic cleavage of pro-IL-1β (IL-1β, 31 kDa) into mature IL-1β (IL-1β, 17 kDa), via the proteasome. Taken together, our results indicate that CaSR promotes NLRP3 inflammasome activation and proteolytic maturation of IL-1β by inducing CUPS and CAEMI, chaperone-assisted degradation pathways. Overall, these results support the inclusion of CaSR as an activator of homeostasis-altering molecular processes.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Keita Sonoda, Teppei Matsui, Haruhiko Bito, Kenichi Ohki〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Astrocytes are known to contact with a great number of synapses and may integrate sensory inputs. In the ferret primary visual cortex, astrocytes respond to a visual stimulus with a delay of several seconds with respect to the surrounding neurons. However, in the mouse visual cortex, it remains unclear whether astrocytes respond to visual stimulations. In this study, using dual-color simultaneous 〈em〉in vivo〈/em〉 two-photon calcium imaging of neurons and astrocytes in the awake mouse visual cortex, we examined the visual response of astrocytes and their precise response timing relative to the surrounding neurons. Neurons reliably responded to visual stimulations, whereas astrocytes often showed neuromodulator-mediated global activities, which largely masked small visual responses. Administration of the selective α1-adrenergic receptor antagonist prazosin substantially reduced such global astrocytic activities without affecting the neuronal visual responses. In the presence of prazosin, astrocytes showed weak but consistent visual responses mostly at their somata. Cross-correlation analysis estimated that the astrocytic visual responses were delayed by approximately 5 seconds relative to the surrounding neuronal responses. In conclusion, our research demonstrated that astrocytes in the primary visual cortex of awake mice responded to visual stimuli with a delay of several seconds relative to the surrounding neurons, which may indicate the existence of a common mechanism of neuron–astrocyte communication across species.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Jinxia Wang, Haizhen Li, Xiaoning Wang, Tao Shen, Shuqi Wang, Dongmei Ren〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Alisol B-23-acetate (AB23A), a tetracyclic triterpenoid isolated from the rhizome of 〈em〉Alisma orientale〈/em〉, has been reported to exert anti-proliferative activities in human colon, ovarian and gastric cancer cells. However, the anti-cancer effect of this compound on human lung cancer cells has not yet been thoroughly elucidated. In the present study, we investigated the effects of AB23A on the cell viability and apoptosis in human lung cancer A549 and NCI-H292 cells. The results indicated that AB23A inhibited the growth of A549 and NCI-H292 cells in dose- and time-dependent manner, however, there was only weak cytotoxicity on normal bronchial epithelial cells. The induction of apoptosis by AB23A was demonstrated by DAPI and annexin-V-FITC/PI staining. Further investigation revealed that AB23A decreased mitochondrial membrane potential (MMP) and up regulated reactive oxygen species (ROS) level. Meanwhile, the increased Bax/Bcl-2 ratio, activated caspase-3, caspase-9 and PARP were observed. In addition, AB23A increased the release of cytochrome 〈em〉c〈/em〉 from mitochondria and the translocation of apoptotic inducing factor (AIF) into nuclei. Taken together, these results indicated that AB23A induced apoptosis by activating the intrinsic pathway, and suggested that AB23A can be used as a potential modulating agent in lung cancer.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X18321648-fx1.jpg" width="500" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Shuo Qiu, Yachao Jia, Jin Tang, Xuanzhe Liu, Hai Hu, Tianyi Wu, Yimin Chai〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Enthesis is the region where a tendon attaches to a bone. It is a relatively vulnerable position, and in most cases surgical treatment is required upon rupture. The reconstructed enthesis is usually weaker compared to the original, and is prone to rupture again. Hypoxia-inducible factor-1 α (HIF-1α) is known to be involved in extensive activities in cells. It is inhibited under normoxic conditions, and undergoes two essential processes, hydroxylation and ubiquitination, the latter of which has been largely unexplored. Herein, we measured the levels of HIF-1α and hydroxy-HIF-1α in VH298-treated rat tendon-derived stem cells (TDSCs) by immunoblotting. We also detected the proliferation of TDSCs using CCK-8 assay and the mRNA levels of related genes by quantitative RT-PCR. The TDSCs were observed to be induced and the chondrogenic differentiation related genes were found to be enhanced. We also simulated in-vitro wounding in a scratch test and reconstructed the enthesis in a rat model of Achilles tendon by classical surgery followed by administration of phosphate buffer saline (PBS) injection or VH298 injection. We observed that HIF-1α and hydroxy-HIF-1α levels were increased in VH298-treated TDSCs in a dose- and time-dependent manner. Thirty micromolar VH298 could significantly increase cell proliferation, migration, and expression of collagen-1α, collagen-3α, decorin, tenomodulin, tenascin C genes, and chondrogenic differentiation-related genes, collagen-2α, SRY-box9, aggrecan. VH298-treated enthesis could tolerate more load-to-failure, had a better healing pattern, and activation of HIF signaling pathway. VH298 can thus enhance the functional activities of TDSCs, enhance their chondrogenic differentiation potential, and accelerate enthesis healing by inhibiting the ubiquitination of hydroxy-HIF-1α.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Qian Meng, Jing Gao, Hongwen Zhu, Han He, Zhi Lu, Minhua Hong, Hu Zhou〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Dermal fibroblast is one of the major constitutive cells of skin and plays a central role in skin senescence. The replicative senescence of fibroblasts may cause skin aging, bad wound healing, skin diseases and even cancer. In this study, a label-free quantitative proteomic approach was employed to analyzing the serial passaged human skin fibroblast (CCD-1079Sk) cells, resulting in 3371 proteins identified. Of which, 280 proteins were significantly changed in early passage (6 passages, P6), middle passage (12 passages, P12) and late passage (21 passages, P21), with a time-dependent decrease or increase tendency. Bioinformatic analysis demonstrated that the chromosome condensin complex, including structural maintenance of chromosomes protein 2 (SMC2) and structural maintenance of chromosomes protein 4 (SMC4), were down-regulated in the serially passaged fibroblast cells. The qRT-PCR and Western Blot experiments confirmed that the expression of these two proteins were significantly down-regulated in a time-dependent manner in the subculture of human skin fibroblasts (HSFb cells). In summary, we used serially passaged human skin fibroblast cells coupled with quantitative proteomic approach to profile the protein expression pattern in the temporal progress of replicative senescence in HSFb cells and revealed that the down-regulation of the chromosome condensin complex subunits, such as SMC2 and SMC4, may play an important role in the fibroblast senescence.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Hee-Jung Lee, Yeondong Cho, Hyeon Jeong Kang, Hanul Choi, Kang Rok Han, Chom Kyu Chong, Young Bong Kim〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Zika virus (ZIKV), a mosquito-borne flavivirus that has recently emerged globally, poses a major threat to public health. To control this emerging disease, accurate diagnostics are required for monitoring current ZIKV outbreaks. Owing to the high nucleotide sequence similarity and cross-reactivity of ZIKV with other members of the Flaviviridae family, discrimination from other flavivirus infections is often difficult in endemic areas. ZIKV NS1 induces major virus-specific antibodies and is therefore utilized as a serological marker for ZIKV diagnosis. To identify ZIKV specific epitopes for clinical application, 33 NS1 peptides that are 15–30 amino acid in length covering whole NS1 were synthesized and analyzed linear B-cell epitopes with 38 human serum samples (20 ZIKV-positive and 18 ZIKV-negative). As a result of screening, eight epitope regions were identified. In particular, the Z8 and Z14 peptides located in the β-ladder surface region showed higher levels of binding activity in ZIKV-positive sera without cross-reactivity to other flaviviruses. These identified sensitive and specific epitopes provide a tool for design of diagnostics and structure-based vaccine antigens for ZIKV infection.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Emily J. Onufer, Shirli Tay, Lauren K. Barron, Cathleen M. Courtney, Brad W. Warner, Jun Guo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mammalian target of rapamycin complex 1 (mTORC1) is a major regulator of cell growth and proliferation through fuel sensing. Systemic inhibition of mTOR as well as manipulation of its downstream products prevent diet-induced obesity. The purpose of this study was to determine the consequences of intestine-targeted mTORC1 inhibition. To attenuate intestinal mTORC1 activity, 〈em〉Villin-Cre〈/em〉〈sup〉〈em〉ER〈/em〉〈/sup〉 mice were crossed with 〈em〉Raptor〈/em〉〈sup〉〈em〉flox/flox〈/em〉〈/sup〉 mice, creating an intestinal-specific Raptor null line (〈em〉i-Raptor −/−〈/em〉). Mice were fed a high fat diet (HFD) and compositional changes as well as food intake levels were assessed. Over a five-week time course, i-Raptor −/− mice consistently gained less body weight on a HFD compared to wildtype (WT) mice secondary to significantly reduced food intake. Importantly, the i-Raptor −/− mice did not appear to be malnourished, demonstrated by their preservation of lean body mass. i-Raptor −/− mice also maintained a normal metabolic profile without significant changes in triglyceride or fasting glucose levels. Further investigation revealed that GDF-15 mRNA expression was significantly enhanced in i-Raptor −/− enterocytes when refed with HFD after overnight starvation. In summary, our study establishes that loss of intestinal specific-mTORC1 is protective of the development of diet-induced obesity by reducing food intake without altering the metabolic profile.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Chinmayi R. Kaundinya, Handanahal S. Savithri, K.Krishnamurthy Rao, Petety V. Balaji〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Bacillus subtilis〈/em〉 168 EpsM (UniProt id P71063) has been electronically annotated as putative acetyltransferase in the UniProt database. The gene 〈em〉epsM〈/em〉 was cloned and overexpressed in 〈em〉E. coli〈/em〉 with an N-terminal GST tag. The purified fusion protein was shown by absorption spectroscopy, autoradiography and reverse phase HPLC to catalyse the conversion of UDP-2,4,6-trideoxy-2-acetamido-4-amino glucose to UDP-2,4,6-trideoxy-2,4-diacetamido glucose, commonly known as N,N′-diacetylbacillosamine, using acetyl coenzyme A as the donor substrate. His146 was shown by site-directed mutagenesis to be essential for acetyltransferase activity. It is hypothesized that EpsC (NAD〈sup〉+〈/sup〉 dependent UDP GlcNAc 4,6-dehydratase), EpsN (PLP dependent aminotransferase) and EpsM, all of which are part of the 〈em〉eps〈/em〉 operon, are involved in the biosynthesis of N,N′-diacetylbacillosamine.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Dahu Li, Houjiu Wu, Huating Dou, Li Guo, Wei Huang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Obesity is associated with the changes in gut microbiota. The aim of present study was to investigate the effects of sweet orange essential oil (SOEO) microcapsules on body weight and gut microbiota in obese rats induced by high-fat diet. By analyzing the body weight, fat rate and the sequence of cloned microbial small-subunit ribosomal RNA genes (16S rDNA) in rats fecal samples, we found that SOEO microcapsules decreased the body weight and increased the relative abundance of 〈em〉Bifidobacterium〈/em〉 (genus-level) in gut microbiota. The analysis of endotoxin content proved that SOEO microcapsules protected gut barrier and decreased gut endotoxin levels by increasing the content of 〈em〉Bifidobacterium〈/em〉, then ameliorated low-grade inflammation, achieving the goal of losing weight. This might be the mechanism of SOEO microcapsules to lose body weight and provided a novel anti-obesity dietary supplement.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉In this study, we investigated the effects of sweet orange essential oil (SOEO) microcapsules on body weight and gut microbiota in obese rats induced by high-fat diet. We found that SOEO microcapsules reduced the body weight and increased the relative abundance of 〈em〉Bifidobacterium〈/em〉 (genus-level) in gut microbiota. The analysis of endotoxin content proved that SOEO microcapsules protected gut barrier and decreased gut endotoxin levels by increasing the content of 〈em〉Bifidobacteria〈/em〉, then ameliorated low-grade inflammation, achieving the goal of losing weight. This indicates that changing gut microbiota provides a novel way to lose weight.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X18321818-fx1.jpg" width="289" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 17 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 1〈/p〉 〈p〉Author(s): Wenfeng Shangguan, Xue Liang, Wen Shi, Tong Liu, Manman Wang, Guangping Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Circular RNAs (circRNAs) have emerged as novel molecules of interest in gene regulation as other noncoding RNAs, and participating in the process of many diseases. However, the expression and functions of circRNAs in Rapid atrial pacing (RAP) dog atrial tissue still unknown. 12 canines were randomly assigned to control and pacing group. RAP at 500 beats per minute was maintained 14 days in the pacing group. The expression characterization of circRNAs were revealed by high-throughput sequencing. We totally predicted 15,990 circRNAs in dog atrial tissues. Moreover, we found 146 differentially expressed circRNAs between control and RAP dogs. Five circRNAs were selected for subsequent RT-PCR validation, and four circRNAs confirmed with the high throughput sequencing analysis. GO analysis showed that the differentially expressed circRNAs might involve in the process of “structural constituent of cytoskeleton, ion channel activity”. We explored the circRNA-miRNA interaction network, and found extensive interaction among differentially expressed circRNAs and AF related miRNAs and mRNAs. Our work firstly identified the characterization of circRNAs in the dog atrial, and revealed the differentially expressed circRNAs in the RAP dog, this might lay a solid foundation on the function of circRNA in the mechanisms of AF.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Jian-Zhong Zhang, Dan Chen, Li-Quan Lv, Zheng Xu, Yi-Ming Li, Jun-Yu Wang, Kai-Wei Han, Ming-Kun Yu, Cheng-Guang Huang, Li-Jun Hou〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉microRNAs (miRNAs) control several processes known to be involved in progression of aneurysm. Here, intracranial aneurysms (IAs) were surgically induced in Sprague–Dawley rats, and we found that miR-448-3p was downregulated and KLF5 was upregulated in IA rats. We identified 〈em〉Klf5〈/em〉 as a direct target of miR-448-3p in smooth muscle cells (SMCs). In addition, aneurysms size and the lumen area of the aneurysms were smaller 4 weeks after IA induction in the miR-448-3p–treated group. miR-448-3p treatment protected the wall thickness ratio and suppressed macrophage infiltration after IA induction. IAs caused a significant increase in KLF5 expression and were alleviated by miR-448-3p. Moreover, the anti-inflammatory effect of miR-448-3p was verified in lipopolysaccharide -stimulated RAW 264.7 macrophage cells. The expression levels of KLF5, MMP2, and MMP9 levels were elevated by LPS, and were attenuated by miR-448-3p. These data suggest that miR-448-3p plays the inhibitory role in IA progression, indicating that miR-448-3p overexpression is crucial for preventing the development of IA through downregulation of macrophage-mediated inflammation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Shannon L. Nowotarski, Robert P. Feehan, Christopher Presloid, Lisa M. Shantz〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Non-melanoma skin cancer (NMSC) is the most commonly diagnosed cancer in the United States. Ultraviolet-B (UVB) irradiation is the primary carcinogen responsible for stimulating NMSC development. Ornithine Decarboxylase (ODC), the first rate-limiting enzyme in the synthesis of polyamines, is upregulated in response to a variety of proliferation stimuli, including UVB exposure. Our previous studies have demonstrated regulation of ODC synthesis by the mammalian target of rapamycin complex 1 (mTORC1) in cells transformed by oncogenic Ras. The goal of these studies was to better understand the link between mTORC1 and ODC in nontransformed cells treated with UVB. We show that the ablation of mTORC1 activity by conditional knockout of its essential component Raptor led to decreased levels of ODC protein both before and after exposure to 10 mJ/cm〈sup〉2〈/sup〉 UVB. Moreover, ODC mRNA was destabilized in the absence of Raptor, suggesting post-transcriptional regulation. We have previously shown that the ODC transcript is stabilized by the RNA binding protein (RBP) human antigen R (HuR), and the intracellular localization of HuR responds to changes in mTORC1 activity. To expand these studies, we investigated whether HuR functions to regulate ODC mRNA stability after UVB exposure. Our results show an increased localization of HuR to the cytoplasm after UVB exposure in wild-type cells compared to Raptor knockout cells, and this is accompanied by greater association of HuR with the ODC transcript. These data suggest that the localization of HuR in response to UVB is influenced, at least in part, by mTORC1 and that HuR can bind to and stabilize ODC mRNA after UVB exposure in an mTORC1-dependent manner.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Tomohiro Yoshimura, Kanae Saitoh, Luchuanyang Sun, Yao Wang, Shigeto Taniyama, Kenichi Yamaguchi, Takayuki Uchida, Tsutomu Ohkubo, Atsushi Higashitani, Takeshi Nikawa, Katsuyasu Tachibana, Katsuya Hirasaka〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Cachexia, observed in most cancer patients, is a syndrome that includes wasting of bodily energy reserves and is characterized by muscle atrophy and fat loss. We have previously demonstrated that isoflavones, such as genistein and daidzein, prevent muscle wasting in tumor-bearing mice. In this study, we examined the effect of morin, a flavonoid, on cachexia. The wet weight and myofiber size of muscles in Lewis lung carcinoma (LLC) cell-bearing mice fed a normal diet were decreased, compared with those in control mice fed a normal diet. In contrast, intake of morin prevented the reduction of muscle wet weight and myofiber size. Moreover, the tumor weight in mice fed the morin diet was lower than that in mice fed the normal diet. Both cell viability and protein synthetic ability of LLC cells were reduced by treatment with morin, but C2C12 myotubes were not affected. Binding assay using morin-conjugated magnetic beads identified ribosomal protein S10 (RPS10) as a target protein of morin. Consistent with the result of morin treatment, knockdown of RPS10 suppressed LLC cell viability. These results suggest that morin indirectly prevents muscle wasting induced by cancer cachexia by suppressing cancer growth via binding to RPS10.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Hua Yu, Jingjing Liu, Yizhi Dong, Min Xu, Le Xu, Huaqin Guan, Xiaoru Xia, Liangxing Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background〈/h6〉 〈p〉Previous studies have found that dihydroartemisinin (DHA) has multiple functions such as anti-inflammatory, anti-tumor in addition to anti-malarial effects. Effect of DHA on monocrotaline-induced pulmonary hypertension in rats has been reported, while the specific mechanism is not known.〈/p〉 〈/div〉 〈div〉 〈h6〉Method〈/h6〉 〈p〉A hypoxic model was established with human pulmonary arterial endothelial cells (HPAECs) to investigate the possible mechanism of DHA. Effects of DHA on proliferation of HPAECs were evaluated by CCK-8 and EdU assay. Effects of DHA on cell oxidative stress, cell migration, angiogenesis, cell cycle and autophagy, as well as the possible underlying mechanism were also detected by using the established normoxia/hypoxia cell models.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉DHA significantly inhibited hypoxia induced increase of HPAECs proliferation in a dose dependent manner, migratory ability and angiogenic ability. DHA also significantly reversed hypoxia induced oxidative stress as a reduction of ROS and NO, and an increase of SOD. Autophagosomes, LC3B protein and apoptotic proteins were significantly increased in DHA treated hypoxic HPAECs. Autophagy inhibitor 3-Methyladenine diminishes the anti-hypoxia effects of DHA on cell proliferation, migration, and autophagy and apoptosis protein expression in HPAECs.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉DHA effectively inhibits hypoxia induced increase of cell proliferation, migration, and oxidative stress in HPAECs, and autophagy may be the underlying mechanism of DHA.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Peilong Dong, Song Gu, Yiqiu Jiang, Wangxiang Yao, Kaibin Zhang, Tianqi Tao, Yang Li, Wang Li, Jianchao Gui〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Lateral ankle sprains are one of the most common injuries in sports. Recently, arthroscopic lateral ligament reconstruction has been recently advocated, however no biomechanical studies and clinical application of this technique are available. In this biomechanical study, eighteen fresh-frozen cadaveric ankles were randomized into three groups: (1) intact anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL), (2) arthroscopic anatomic reconstruction of ATFL and CFL, and (3) all arthroscopic remnant-preserving reconstruction of ATFL and CFL. The specimens were then tested for stiffness and load to ultimate failure using a customized jig. In biomechanical test, the all arthroscopic remnant-preserving reconstruction of ATFL and CFL produced a reconstruction that could withstand loads to failure and stiffness similar to the arthroscopic anatomic reconstruction. However, both two reconstruction groups were much weaker than the intact, uninjured ATFL and CFL. Moreover, we used the technique of all arthroscopic remnant-preserving reconstruction of ATFL and CFL on 20 patients from September 2016 to September 2017. American Orthopaedic Foot and Ankle Society (AOFAS) scores and Anterior Talar Translation (ATT) were applied for statistical collection at preoperative and postoperative 12 months to evaluate clinical efficacy. The differences of the preoperative and postoperative 12 months AOFAS scores and ATT of patients were both statistical significant (〈em〉P〈/em〉 〈 0.01). We confirmed that all arthroscopic remnant-preserving reconstruction of ATFL and CFL exhibited positive effect, thus promoting the recovery of ankle function and had good short-term clinical effect.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Hanjun Kim, Young-Jin Choi, Young-Sun Lee, Suk Young Park, Ji-Eun Baek, Ho-Kyoung Kim, Beom-Jun Kim, Seung Hun Lee, Jung-Min Koh〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Previously, we noted that SLIT3, slit guidance ligand 3, had an osteoprotective role with bone formation stimulation and bone resorption suppression. Additionally, we found that global 〈em〉Slit3〈/em〉 KO mice had smaller long bone. Skeletal staining showed short mineralized length in the newborn KO mice and wide hypertrophic chondrocyte area in the embryo KO mice, suggesting delayed chondrocyte maturation. The recombinant SLIT3 did not cause any change in proliferation of ATDC5 cells, but stimulated expressions of chondrocyte differentiation markers, such as COL2A1, SOX9, COL10A1, VEGF, and MMP13 in the cells. SLIT3 suppressed β-catenin activity in the cells, and activation of Wnt/β-catenin signaling by lithium chloride attenuated the SLIT3-stimulated differentiation markers. ATDC5 cells expressed only ROBO2 among their 4 isotypes, and the 〈em〉Robo2〈/em〉 knock-down with its siRNA reversed the SLIT3-stimulated differentiated markers in chondrocytes. Taken together, these indicate that SLIT3/ROBO2 promotes chondrocyte maturation via the inhibition of β-catenin signaling.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): John T. Gamble, Yuriyah Reed-Harris, Carrie L. Barton, Jane La Du, Robert Tanguay, Juliet A. Greenwood〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Glioblastoma (GBM) is a deadly disease due to its ability to quickly invade and destroy brain tissue. Slowing or stopping GBM cell progression is crucial to help those inflicted with the disease. Our lab created an embryo-larval zebrafish xenograft model as a tool to study human GBM progression in an observable brain environment. The zebrafish brain is a dynamic and complex environment providing an optimal setting for studying GBM cell progression. Here we demonstrate the ability of our model to quantitate GBM proliferation, dispersal, blood vessel association, microtumor formation, and individual cell invasion by evaluating the importance of an extracellular matrix protein, laminin alpha 5 (lama5), on U251MG cell progression. Lama5 has been implicated in cancer cell survival, proliferation and invasion and is a known adhesion site for GBM cells. While lama5 is highly expressed in endothelial cells in the brain, it is unknown how lama5 affects GBM behavior. Using a lama5 morpholino, we discovered that lama5 decreased U251MG dispersal by 23% and doubles the formation of blood vessel dependent microtumors. Despite lama5 being a known attachment site for GBM, lama5 expression had no effect on U251MG association with blood vessels. Analysis of individual U251MG cells revealed lama5 significantly lowered invasion as mobile U251MG cells traveled 32.5  μm less, invaded 5.0 μm/hr slower and initiated invasion 60% few times per cell.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Yoon-Jin Lee, Jeong-Eun Oh, Sang-Han Lee〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Extracellular acidity in the tumor microenvironment contributes to chemoresistance of malignant tumors. The objective of this study was to determine anticancer effects of arctigenin, a novel anti-inflammatory lignan extracted from seeds of 〈em〉Arctium lappa〈/em〉, on acidity-tolerant prostate cancer PC-3AcT cells. The PC-3AcT cells manifested increased tolerance to low-pH media with enhanced percent cell viability and increased resistance to docetaxel compared to their parental PC-3 cells. Arctigenin alone or in combination with docetaxel induced potent cytotoxicity. Preferential sensitization of PC-3AcT cells to arctigenin was accompanied by increased cell fractions with sub-G〈sub〉0〈/sub〉/G〈sub〉1〈/sub〉 peak and annexin V-PE(+), increased ROS levels, decreased mitochondrial membrane potential and cellular ATP content, and inhibition of PI3K/Akt/mTOR pathway. A series of changes caused by arctigenin were efficiently reversed through reducing ROS levels by radical scavenger N-acetylcysteine, thus placing ROS upstream of arctigenin-driven cytotoxicity. Collectively, these results demonstrate that arctigenin can increase oxidative stress-mediated mitochondrial damage of acidity-tolerant PC-3AcT cells, suggesting that arctigenin might be a potential therapeutic candidate to overcome acidic-microenvironment-associated chemotherapeutic resistance in prostate cancer.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Shengting Wang, Qian Li, Yufang Wang, Xiaoming Li, Rui Wang, Yuhua Kang, Xukai Xue, Rui Meng, Qi Wei, Xinghua Feng〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Recently, a large number of studies have shown that circular RNA (circRNA) is involved in the development and progression of human cancer. However, its role in triple-negative breast cancer (TNBC) remains largely unknown. In this study, a novel circRNA, circ-UBAP2 (hsa_circ_0001846), was shown to be markedly upregulated in TNBC. Moreover, high circ-UBAP2 expression was closely associated with larger tumour size (〈em〉p〈/em〉 = 0.003), advanced TNM stage (〈em〉p〈/em〉 = 0.005), lymph node metastasis (〈em〉p〈/em〉 = 0.002), and unfavourable prognosis (〈em〉p〈/em〉 = 0.0256). Functionally, lentivirus-mediated stable knockdown of circ-UBAP2 dramatically weakened the ability of TNBC cells to proliferate and migrate and induced apoptosis 〈em〉in vitro〈/em〉 and 〈em〉in vivo〈/em〉. Regarding the mechanism, we found that circ-UBAP2 was mainly observed in the cytoplasm and was capable of sponging miRNA-661 to increase the expression of the oncogene MTA1. Additionally, silencing of miRNA-661 or overexpression of MTA1 could partially rescue the attenuated malignant phenotype caused by circ-UBAP2 knockdown. Taken together, our data reveal that circ-UBAP2 plays a vital regulatory role in TNBC via the miR-661/MTA1 axis and may serve as a promising therapeutic target for TNBC patients.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X18321685-fx1.jpg" width="301" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Yahong Han, Zhenbiao Xu, Yanan Liu, Da Wei, Jing Zhang, Le Xue, Xiangmin Zhang, Jie Qin, Hongkuan Deng, Linxia Song〈/p〉 〈div xml:lang="en"〉 〈h5〉Absract〈/h5〉 〈div〉〈p〉Y-box binding protein (YB protein) is an ancient conserved multifunctional DNA/RNA-binding protein. A novel YB protein 〈em〉DjY2〈/em〉 gene from planarian 〈em〉Dugesia japonica〈/em〉 was cloned by RACE method and characterized. This cDNA contains 689 bp with a putative open reading frame of 197 amino acids. It has a predicted molecular mass of 22.14 kDa and an isoelectric point of 9.67. Whole-mount in situ hybridization and relative quantitative real-time PCR were used to study the spatial and temporal expression pattern of 〈em〉DjY2〈/em〉 in the process of planarian regeneration. Results showed that 〈em〉DjY2〈/em〉 was expressed in many parts of the body in intact planarian, but the expression level was low in head and pharynx. The transcripts of 〈em〉DjY2〈/em〉 was significantly increased both at the head parts and the tail parts after amputation, especially at the site of cutting. The spatial expression gradually recovered to the state of intact planarian with the time of regeneration. Our results indicated that 〈em〉DjY2〈/em〉 might participate in the process of regeneration in planarian.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Saeko Kimura, Tomoki Uchida, Yuki Tokuyama, Mayumi Hosokawa, Junya Nakato, Atsushi Kurabayashi, Masaru Sato, Hideyuki Suzuki, Ryuhei Kanamoto, Kousaku Ohinata〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Rubisco, an enzyme for photosynthetic carbon dioxide fixation, is a major green leaf protein and known as the most abundant protein on the Earth. We found that Rubisco digested mimicking gastrointestinal enzymatic conditions exhibited anxiolytic-like effects after oral administration in mice. Based on a comprehensive peptide analysis of the digest using nanoLC-Orbitrap-MS and the structure-activity relationship of known anxiolytic-like peptides, we identified SYLPPLTT, SYLPPLT and YHIEPV [termed Rubisco anxiolytic-like peptide (rALP)-1, rALP-1(1–7) and rALP-2, respectively], which exhibited potent anxiolytic-like effects after oral administration. The anxiolytic-like effects of rALP-1/rALP-1(1–7) were blocked by a serotonin 5-HT〈sub〉1A〈/sub〉 receptor antagonist, whereas rALP-2-induced effects were inhibited by a δ-opioid receptor antagonist. In conclusion, novel Rubisco-derived anxiolytic-like peptides, rALP-1/rALP-1(1–7) and rALP-2, act via independent neural pathways.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X18321363-fx1.jpg" width="359" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Debora Levy, Thatiana Correa de Melo, Bianca Yumi Ohira, Maíra Luísa Fidelis, Jorge L.M. Ruiz, Alessandro Rodrigues, Sergio P. Bydlowski〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Oxysterols are 27-carbon oxidation products of cholesterol metabolism. Oxysterols possess several biological actions, including the promotion of cell death. Here, we examined the ability of several oxysterols to induce short-term death in cancerous (human breast cancer and mouse skin melanoma cells) and non-cancerous (human endothelial cells and lung fibroblasts) cell lines. We determined cell viability, Ki67 expression, cell cycle regulation, and apoptosis after 24-h incubations with oxysterols. We found that different oxysterols had different effects on the studied parameters. Moreover, the effects depended on cell type and oxysterol concentration. Three cytotoxic oxysterols (7-ketocholesterol, cholestane-3β-5α-6β-triol, and 5α-cholestane-3β,6β-diol) inhibited the S phase and stimulated the G0/G1 or G2/M phases. These oxysterols promoted apoptosis, determined with Annexin V and propidium iodide assays. These results showed that different oxysterols have cytotoxic effects depending on the cell line. The findings suggest a potential pharmacological utility of cytotoxic oxysterols.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Keigo Kumagai, Cherilyn A. Elwell, Shuji Ando, Joanne N. Engel, Kentaro Hanada〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Chlamydia trachomatis〈/em〉 is an obligate intracellular bacterium that replicates within a membranous compartment, the inclusion, in host cells. Its intracellular life cycle requires host sphingolipids, which are in part acquired through the ER-Golgi localized ceramide transport protein (CERT). The Chlamydia-encoded inclusion membrane protein IncD is composed of two closely linked long hydrophobic domains with their N- and C-termini exposed to the host cytosol. IncD binds directly to the pleckstrin homology (PH) domain of CERT, likely redirecting ceramide to the inclusion. The precise regions of IncD required for this interaction have not been delineated. Using co-transfection studies together with phylogenetic studies, we demonstrate that both the IncD N- and C-terminal regions are required for binding to the CERT PH domain and define key interaction residues. Native gel electrophoresis analysis demonstrates that the transmembrane region of IncD forms SDS-resistant but dithiothreitol-sensitive homodimers, which in turn can assemble to form higher order oligomers through additional N- and C-terminal domain contacts. IncD oligomerization may facilitate high affinity binding to CERT, allowing 〈em〉C. trachomatis〈/em〉 to efficiently redirect host ceramide to the inclusion.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Yukino Morikiri, Eri Matsuta, Hideki Inoue〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The skin consists mostly of extracellular matrix (ECM) composed mainly of collagen, which provides a protective barrier from the environment. The skin continuously experiences harmful stress and damage. As aging progresses, the expression of various genes declines, and physiological functional deterioration occurs. The reduction of collagen accompanying aging impairs the barrier function of the skin and weakens protection from stressors. In the nematode 〈em〉Caenorhabditis elegans〈/em〉, ECM proteins turn over during aging. Older worms of longevity mutants exhibit increased collagen expression, whereas knockdown of collagen genes shortens lifespan. However, it is unclear whether the progression of aging can be delayed by increasing collagen production via an external stimulus. In this study, we examined the effects of collagen tripeptide (CTP), a collagen-derived compound, on lifespan and aging. Our results showed that CTP upregulated collagen genes via the p38 mitogen-activated protein kinase (MAPK)/SKN-1 pathway. Moreover, CTP extended lifespan and delayed aging through p38 MAPK/SKN-1 pathway. In addition, CTP also induced collagen expression via the p38 MAPK pathway in mammals. Our findings supported that external stimuli such as CTP could promote ECM youthfulness using a conserved signaling pathway, thereby contributing to suppression of aging.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Atsushi Masuyama, Tomoya Mita, Kosuke Azuma, Yusuke Osonoi, Kenichi Nakajima, Hiromasa Goto, Yuya Nishida, Takeshi Miyatsuka, Masako Mitsumata, Hirotaka Watada〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Autophagy is considered as an evolutionarily conserved cellular catabolic process. Defective autophagy has been implicated in various human diseases, including cardiovascular diseases. Recently, we and others demonstrated that defective autophagy in vascular smooth muscle cells (SMCs) promotes the progression of atherosclerosis. In this study, we investigated the role of autophagy in SMCs on plaque instability 〈em〉in vivo〈/em〉. We generated mice with a defect 〈em〉atg7〈/em〉in which is an essential gene for autophagy, in SMCs by crossing 〈em〉Atg7〈/em〉〈sup〉〈em〉f/f〈/em〉〈/sup〉 mice with transgelin (〈em〉Tagln〈/em〉) 〈em〉Cre〈/em〉〈sup〉〈em〉+/0〈/em〉〈/sup〉 mice (〈em〉Atg7cKO〈/em〉). Then, 〈em〉Atg7cKO〈/em〉 and apolipoprotein E (〈em〉apoe〈/em〉)-deficient (〈em〉apoeKO〈/em〉) mice were crossed to generate 〈em〉Atg7cKO:apoeKO〈/em〉 mice. To generate a mouse model of plaque instability, we conducted to form a tandem stenosis in the carotid artery of 〈em〉Atg7cKO:apoeKO〈/em〉 mice and their controls (〈em〉apoeKO〈/em〉 mice) at the age of 10 weeks. At 5 weeks after surgery, the percentage of cross-sectional stenosis area in the operated common carotid artery of 〈em〉Atg7cKO:apoeKO〈/em〉 mice was significantly higher than that in 〈em〉apoeKO〈/em〉 mice. In addition, thrombus, which was not observed in 〈em〉apoeKO〈/em〉 mice, was frequently found in 〈em〉Atg7cKO:apoeKO〈/em〉 mice. Furthermore, the number of Berlin blue staining-positive areas, which indicated intraplaque hemorrhage, was significantly higher in 〈em〉Atg7cKO:apoeKO〈/em〉 mice than in control 〈em〉apoeKO〈/em〉 mice. Taken together, our data suggest that defective autophagy in SMCs enhances plaque instability and the risk of plaque rupture.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Zongtai Feng, Huiting Zhou, Shurong Ma, Xinxian Guan, Lulu Chen, Jie Huang, Huan Gui, Xinxin Miao, Shenglin Yu, Jiang Huai Wang, Jian Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Necrotizing enterocolitis (NEC) remains one of the leading causes of death in neonatal infants and new therapeutic strategies for NEC are urgently required. The immunomodulatory agent FTY720 has been shown to have protective effects in various inflammatory diseases. In this study, we hypothesized that treatment with FTY720 confers protection against experimental NEC. Experimental NEC was induced in five-day-old C57BL/6 neonatal mice by hyperosmolar formula feeding plus hypoxia and lipopolysaccharide (LPS) challenges. Induction of NEC resulted in substantial weight loss and high mortality compared to the control group, whereas FTY720 treatment significantly attenuated weight loss and improved survival in NEC-challenged neonatal mice. FTY720 treatment strongly ameliorated NEC-induced intestinal injury with reduced apoptosis and up-regulation of intestinal barrier proteins in the ileal tissues. Furthermore, FTY720 treatment abrogated NEC-initiated intestinal and systemic inflammation with markedly diminished inflammatory cytokines and chemokines. Moreover, FTY720 treatment suppressed NEC-activated CXCL5/CXCR2 axis with down-regulated expression of CXCL5 and CXCR2 at both mRNA and protein levels. Thus, we demonstrate that FTY720 protects neonatal mice against NEC-associated lethality by ameliorating intestinal injury and attenuating inflammation, possibly via its down-regulation of NEC-induced activation of intestinal CXCL5/CXCR2 axis.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Prince Rajaiah Prabhu, Sakthi Devi Moorthy, Jayaprakasam Madhumathi, Satya Narayan Pradhan, Markus Perbandt, Christian Betzel, Perumal Kaliraj〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The notoriety of parasitic nematode survival is directly related to chronic pathogenicity, which is evident in human lymphatic filariasis. It is a disease of poverty which causes severe disability affecting more than 120 million people worldwide. These nematodes down-regulate host immune system through a myriad of strategies that includes secretion of antioxidant and detoxification enzymes like glutathione-S-transferases (GSTs). Earlier studies have shown 〈em〉Wuchereria bancrofti〈/em〉 GST to be a potential therapeutic target. Parasite GSTs catalyse the conjugation of glutathione to xenobiotic and other endogenous electrophiles and are essential for their long-term survival in lymph tissues. Hence, the crystal structure of WbGST along with its cofactor GSH at 2.3 Å resolution was determined. Structural comparisons against host GST reveal distinct differences in the substrate binding sites. The parasite xenobiotic binding site is more substrate/solvent accessible. The structure also suggests the presence of putative non-catalytic binding sites that may permit sequestration of endogenous and exogenous ligands. The structure of WbGST also provides a case for the role of the π-cation interaction in stabilizing catalytic Tyr compared to stabilization interactions described for other GSTs. Hence, the obtained information regarding crucial differences in the active sites will support future design of parasite specific inhibitors. Further, the study also evaluates the inhibition of 〈em〉Wb〈/em〉GST and its variants by antifilarial diethylcarbamazine through kinetic assays.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): He-Nan Liu, Nan-Jue Cao, Xun Li, Wei Qian, Xiao-Long Chen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Diabetic retinopathy (DR) is a progressive microvascular complication associated with diabetes, and remains the leading cause of preventable blindness worldwide. Recent studies have revealed that microRNAs (miRNAs) were involving in the physiological and pathophysiological processes of diabetes and its microvascular and macrovascular complications. The purpose of the current investigation is to identify the candidate miR-211 as a novel biomarker for occurrence and progression of DR in clinical study and experimental research. Firstly, miR-211 was considered as a candidate miRNA identifying by miRNA microarray analysis, Venn diagram analysis, real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and receiver operating characteristic curve in clinical study. Then, the predicted Sirtuin 1 (SIRT1) may be the target gene of miR-211 searching by TargetScan 7.2. Moreover, miR-211 was significantly up-regulated, while SIRT1 mRNA significantly down-regulated measuring by qRT-PCR, meanwhile, SIRT1 protein was significantly down-regulated in coincidence with SIRT1 mRNA detecting by western blot, and even aggravated associated with diabetes duration in diabetic retinal tissues of vivo experiment. Additionally, miR-211 was directly targeted SIRT1 confirming by dual-luciferase reporter assay. Furthermore, with transfection of antagomiR-211, the apoptosis of HUVECs was significantly suppressed employing by flow cytometry analysis, nevertheless the viability of HUVECs was significantly promoted exploiting by Cell Counting Kit-8 assay. Finally, SIRT1 mRNA and SIRT1 protein were significantly up-regulated testing by qRT-PCR and western blot respectively in hyperglycemic HUVECs transfected with antagomiR-211 of vitro experiment. Consequently, the current clinical study and experimental research imply that serum miR-211 as a novel biomarker with high sensitivity and specificity could be associated with occurrence and progression of DR via targeting SIRT1.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Weiqi Hu, Weimin Xu, Yi Shi, Weijun Dai〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background〈/h6〉 〈p〉Nasopharyngeal carcinoma (NPC) is the most common type of head and neck cancers which is notable for its distinctive pattern of geographical distribution. HOTAIR has been reported to regulate nasopharyngeal carcinoma tumorigenesis and progression. However, the detailed mechanism underlying HOTAIR-promoted nasopharyngeal carcinoma remains not fully understood.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉We used RT-qPCR approach to examine genes expression and mRNA level. MTT assay and soft agar assay were used to detect cell growth rate in culture and under suspended condition, respectively. Besides, we employed wound healing assay and transwell invasion assay to determine migration and invasion ability of nasopharyngeal carcinoma cells. We predicted direct downstream targets of miR-101 by bioinformatic analysis, which was confirmed by dual luciferase reporter assay.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉HOTAIR was upregulated in NPC tissues and cells. miR-101 inhibitor greatly enhanced HOTAIR knockdown-regulated cell proliferation, migration and invasion of CNE1 and CNE2 cells. miR-101 was shown to directly bind 3′-UTR of COX-2 and downregulate COX-2 expression. Finally, COX-2 overexpression was demonstrated to rescue the tumor phenotypes of nasopharyngeal carcinoma cells attenuated by HOTAIR knockdown or miR-101 mimic.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉Here, we highlight the importance of HOTAIR/miR-101/COX-2 axis in progression of nasopharyngeal carcinoma cells. Our findings provide a novel mechanism for explaining HOTAIR-induced nasopharyngeal carcinoma and help developing the therapeutical strategies by targeting HOTAIR.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Michela Zamboni, Donato Civitareale〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In non-small lung cancer, the expression of the transcription factor TTF-1/Nkx2.1 correlates with the presence of EGFR mutations, therefore TTF-1/Nkx2.1 expression is used to optimize an EGFR testing strategy and to guide clinical treatment. We investigate the molecular mechanisms underlying the functional connection between EGFR and TTF-1/Nkx2.1 gene expression in lung adenocarcinoma. Using the H1975 cell line as a non-small cell lung cancer model system and short hairpin RNA, we have selected clones with TTF-1/Nkx2.1 silenced expression. We have found that Leucine-rich immunoglobulin repeats-1 (LRIG1) gene is a direct target of TTF-1/Nkx2.1 and the transcription factor binding to the LRIG1 genomic sequence inhibits its gene expression. In TTF-1/Nkx2.1 depleted clones, we have found high levels of LRIG1 and decreased presence of EGFR protein. Furthermore, in TTF-1/Nkx2.1 depleted clones we detected a reduced β-catenin level and we provide experimental evidence indicating that TTF-1/Nkx2.1 gene expression is regulated by β-catenin. Published studies indicate that LRIG1 triggers EGFR degradation and that mutated EGFR induces β-catenin activity. Hence, with the present study we show that mutated EGFR, enhancing β-catenin, stimulates TTF-1/Nkx2.1 gene expression and, at the same time, TTF-1/Nkx2.1, down-regulating LRIG1, sustains EGFR pathway. Therefore, LRIG1 and β-catenin mediate the functional connection between TTF-1/Nkx2.1 and mutated EGFR.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X18321570-fx1.jpg" width="500" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Cong Zu, Guangyuan Qin, Chunshu Yang, Ning Liu, Anning He, Mingdi Zhang, Xinyu Zheng〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Purpose〈/h6〉 〈p〉The resistance to 5-FU often limits its clinical effectiveness on breast cancer treatment. Combination therapy thus is employed to overcome this treatment resistance. We here report a potent antitumor effect of Emodin at low dose on chemotherapy sensitivity of MCF-7 breast cancer cells.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉Cell viability, apoptosis, glutathiones (GSH) concentration and Reactive oxygen species (ROS) activity following Emodin and 5-FU treatment was assessed. Cellular senescence following combined treatment and silence of NRARP was examined by senescence-associated β-galactosidase analysis. Western blot analysis was used to determine changes in the expression of p21, p16, p27, E2F1 and NRARP.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Low dose Emodin potentiates 5-FU-induced apoptosis of breast cancer cells, in association with inhibition of NRARP, resulting in cellular senescence. RNA interference of NRARP induced cellular senescence in MCF-7 breast cancer cells. Furthermore, the cellular senescence induced by Emodin and 5-FU treatment could be reverted by pcDNA–NRARP.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉These findings provide preclinical evidence for repurposing use of Emodin in combination with chemotherapeutic agents to treat breast cancer as an alternative salvage regimen.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Jae Yeon Choi, Hyun Jin Shin, In Hwa Bae〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Cellular senescence, a distinctive type of irreversible growth arrest, develops in response to various stimuli. Bcl-w, an oncogene and member of the Bcl-2 family, has been reported to promote tumorigenicity in various cancer cells. Here, we sought to explore the potential role of Bcl-w in premature senescence, which has received relatively little research attention. Our findings demonstrate that Bcl-w enhances the activity of senescence-associated β-galactosidase (SA-β-gal) and promotes histone H3 tri-methylation at lysine 9 (H3K9me3) and expressions of p53, Notch2, p21, and p16—hallmarks of the senescent phenotype—in human U251 glioblastoma and H460 lung carcinoma cells. It is also known that microRNAs (miRNAs) regulate processes related to tumor development, such as cell proliferation, differentiation, survival, metabolism, inflammation, invasion, angiogenesis, and senescence. In this context, we found that miR-93-5p inhibited premature cellular senescence by directly suppressing Bcl-w and p21 expressions. Collectively, these findings suggest that targeting miR-93-5p–regulated Bcl-w may be a useful strategy for preventing premature senescence.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Jong Hyuk Lee, Yoon Hee Chung, Ho Hyun Kim, Joon Seok Bang, Tae Woo Jung, Taekwang Park, Jinwoo Park, Uiseok Kim, Sung Hoon Lee, Ji Hoon Jeong〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The aim of the present study was to examine the effects of p-coumaric acid on the longitudinal growth of the long bone in adolescent male rats. Teatment with p-coumaric acid significantly increased the tibial length and the height of each growth plate zone and the ratio of 5-bromo-2′-deoxyuridine-positive cells relative to total proliferative cells. Expression of insulin-like growth factor 1 and its receptor in the proliferative and hypertrophic zones, and serum levels of growth hormone and insulin-like growth factor 1 were significantly increased as well in the p-coumaric acid-treated group. Via increasing both the serum level of insulin-like growth factor 1 and its expression, p-coumaric acid could promote cell proliferation in growth plate zones. These results suggest that p-coumaric acid has the potential to increase height and may be a feasible alternative to growth hormone therapy.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 10 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 505, Issue 4〈/p〉 〈p〉Author(s): Xiaoyu Chen, Shan Liu, Wei Zhang, Chunyan Wu, Hanchen Liu, Fang Zhang, Zhongbing Lu, Wenjun Ding〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Recent studies have demonstrated that long-term exposure to fine particulate matter (PM〈sub〉2.5〈/sub〉) increases the risk of central nervous (CNS) diseases. As a basic region-leucine zipper (bZip) transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) is essential for protection against chemically induced oxidative stress to restore cellular redox balance. However, the impact of Nrf2 on the neurotoxic effects of PM〈sub〉2.5〈/sub〉 remains to understand. In this study, we exposed wild-type (WT) and Nrf2 knockout (Nrf2〈sup〉−/−〈/sup〉) mice to 1 mg/kg PM〈sub〉2.5〈/sub〉 or deionized water by intranasal instillation for 28 days. After PM〈sub〉2.5〈/sub〉 exposure, Nrf2〈sup〉−/−〈/sup〉 mice exhibited severe nerve injury in olfactory bulb (OB) of mice. In PM〈sub〉2.5〈/sub〉-treated OBs, Nrf2 deficiency resulted in lower levels of antioxidant enzymes, greater induction of oxidative stress, microglia activation, inflammation and nuclear factor kappa B (NF-κB) activation compared to the OBs of WT mice. In PM〈sub〉2.5〈/sub〉-treated BV2 cells, inhibition of Nrf2 activity significantly decreased cell viability and increased the intracellular reactive oxygen species (ROS) generation and nuclear factor kappa B (NF-κB) phosphorylation. Taken together, our results provide the role Nrf2-reuglated antioxidant and cytoprotective enzymes in protective responses to PM〈sub〉2.5〈/sub〉-induced neurotoxicity. Our findings suggest Nrf2-mediated defenses against oxidative stress will help develop new strategies for the prevention and treatment of diseases associated with airborne pollution.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X18322034-fx1.jpg" width="500" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 9 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 507, Issues 1–4〈/p〉 〈p〉Author(s): Yan Jin, Peng Wu, Wenjing Zhao, Xuejun Wang, Jian Yang, Xinying Huo, Jinfei Chen, Wei De, Fen Yang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Long non-coding RNAs (lncRNAs) are a crucial member of the non-coding RNA family, and increasing evidence demonstrates that lncRNAs participate in the initiation and progression of cancers. Our study aimed to explore the role of the lncRNA LINC00165 in gastric cancer (GC) development. In the present study, our results showed that LINC00165 was upregulated in GC tissues and cell lines and high expression of LINC00165 was correlated with tumor-node-metastasis stage, invasion depth, and overall survival of GC patients. Functional assays showed that LINC00165 knockdown inhibited the proliferation, migration and invasion of GC cells and LINC00165 overexpression stimulated their proliferation, migration and invasion. Online transcription factor binding site prediction analysis showed that there were STAT3 binding sites in the LINC00165 promoter region. Furthermore, luciferase reporter and chromatin immunoprecipitation assays provided evidence that STAT3 could bind directly to the region between −547 bp to −537 bp (ATGTTGGGAAA) of LINC00165 promoter and activate its transcription. Then GC cells were partitioned into nuclear and cytoplasmic fractions and we found that LINC00165 was localized preferentially to the nucleus. Mechanistically, we revealed that LINC00165 functioned as a scaffold for interaction with Polycomb Repressive Complex 2 to promote the epithelial-mesenchymal transition in GC cells. Taken together, our study revealed that LINC00165 was involved in the progression and poor prognosis of GC as an oncogenic role. Therefore, LINC00165 might become a new potential target for GC chemotherapy and further predict prognosis of patients.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Chávez-Martínez Ana Isabel, Jasso-Robles Francisco Ignacio, Rodríguez-Kessler Margarita, Sarvajeet S. Gill, Becerra-Flora Alicia, Jiménez-Bremont Juan Francisco〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Arabidopsis amiR:〈em〉ADC〈/em〉-L2 is a non-lethal line with several developmental defects, it is characterized by a drastic reduction in free polyamine content. Herein, we found that catalase application had growth-promoting effects in amiR:〈em〉ADC〈/em〉-L2 and parental Ws seedlings. Differences in ROS content between amiR:〈em〉ADC〈/em〉-L2 and Ws seedlings were detected. Increased H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 levels were found in the amiR:〈em〉ADC〈/em〉-L2, as well as low 〈em〉AtCAT2〈/em〉 gene expression and reduced catalase activity. Estimation of polyamine oxidase activity in amiR:〈em〉ADC〈/em〉-L2 line indicated that the over-accumulation of H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 is independent of polyamine catabolism. However, increments in NADPH oxidase activity and O〈sub〉2〈/sub〉〈sup〉•−〈/sup〉 content could be associated to the higher H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 levels in the amiR:〈em〉ADC〈/em〉-L2 line. Our data suggest that low polyamine levels in Arabidopsis seedlings are responsible for the accumulation of ROS, by altering the activities of enzymes involved in ROS production and detoxification.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Waleed Amjad Khan, Xilin Hou, Ke Han, Nadeem Khan, Huijie Dong, Muhammad Saqib, Zhishuo Zhang, Emal Naseri, Chunmei Hu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Bok choy is an important 〈em〉Brassica〈/em〉 vegetable which is also known for its wide range of cultivars that differ in their appearance, leaf color, size and shape. For the purpose to investigate the effect of these phenotypic differences on their lipid composition, seven morphotypes of NHCC (Suzhouqing, Aijaohuang, Wutacai, Yellowrose, Ziluolan, Xiangqingcai and Zicaitai) were selected for this study. For this reason, extensive metabolic approach was adopted which was mainly focused on lipidomics. The overall metabolic position of lipids was determined and the isolated lipid compounds were characterized on the basis of their lipid classes. Moreover, discriminative analysis was applied to monitor the distribution pattern of lipid in different cultivars. Aijiaohuang was the leading cultivar which contained highest lipid levels, whereas least proportion was found in Zicaitai. We proposed that leaf color might have an effect on the lipid composition such as purple cultivars were dominated in glycerophopholipids, light green in fatty acids and dark green were rich in glycerolipids. The level of metabolites differed greatly among different genotypes. Lipid-metabolite interactions revealed the positive correlation of lipids with flavonoid and hydroxycinnamoyl derivatives, whereas negative correlation was noticed in case of phenylamines. This is the first comprehensive study based on lipidomics in order to evaluate the substantial impact of various phenotypes on the metabolic composition of NHCC.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Yan Zheng, Landi Luo, Jingjing Wei, Qian Chen, Yongping Yang, Xiangyang Hu, Xiangxiang Kong〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Plant glutamate-like receptors (GLRs), which are homologs of mammalian ionotropic glutamate receptors (iGluRs), are thought to be involved in plant growth, development, and environmental stress responses. In this study, we demonstrated that two members of Arabidopsis glutamate-like receptors, 〈em〉AtGLR1.2〈/em〉 and 〈em〉AtGLR1.3〈/em〉, play positive roles in the plant response to cold stress. Genetic and biochemical experiments revealed that exogenous jasmonate could attenuate the cold sensitivity of 〈em〉glr1.2〈/em〉 and 〈em〉glr1.3〈/em〉 mutants, and the overexpression of 〈em〉GLR1.2〈/em〉 or 〈em〉GLR1.3〈/em〉 enhanced cold tolerance by increasing endogenous jasmonate levels under cold stress. In addition, the expression of genes in the 〈em〉CBF/DREB1〈/em〉 signaling pathway was decreased in the 〈em〉glr1.2〈/em〉 and 〈em〉glr1.3〈/em〉 mutants, but was promoted in 〈em〉GLR1.2-OE〈/em〉 and 〈em〉GLR1.3-OE〈/em〉 transgenic plants compared with the wild-type during cold treatment. Further investigation revealed that 〈em〉AtGLR1.2〈/em〉 and 〈em〉AtGLR1.3〈/em〉 independently drove similar functions without directly interacting. Together, our findings suggest that 〈em〉AtGLR1.2〈/em〉 and 〈em〉1.3〈/em〉 positively enhance cold tolerance in 〈em〉Arabidopsis〈/em〉 by activating endogenous jasmonate accumulation and subsequently promoting the downstream CBF/DREB1 cold response pathway during cold stress.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Jianguo Chen, Xiaoming Xu, Junjun Chen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Ribavirin is an anti-viral drug but has recently gained attention as a potential candidate for cancer treatment. In line with these efforts, our work is the first to demonstrate that ribavirin, at clinically relevant concentration, selectively targets pediatric osteosarcoma and increases chemosensitivity. Using preclinical osteosarcoma cell and xenograft models, we found that ribavirin is active against osteosarcoma bulk and subpopulations with highly proliferative and invasive properties via inhibiting growth, inducing apoptosis and suppressing colony formation. At the same concentrations, ribavirin either did not or affected human normal osteoblastic cell and fibroblast cells in a less extent than osteosarcoma cells. Notably, the combination of ribavirin with doxorubicin resulted in greater efficacy than single drug alone. The combination completely arrested the osteosarcoma growth 〈em〉in vivo〈/em〉 throughout the whole duration of drug treatment. We further showed that ribavirin acted on osteosarcoma largely via targeting eIF4E. In addition to eIF4E, ribavirin also modulated phosphorylation of Erk and expression of EZH2 and Snail without affecting Akt and mTOR. Lastly, we found that eIF4E expression and phosphorylation were elevated in osteosarcoma compared to normal cells, which might explain the selective anti-osteosarcoma activity of ribavirin. eIF4E depletion mimics the inhibitory effects of ribavirin, further confirm that eIF4E is the essential target of ribavirin in osteosarcoma. Our work provides fundamental evidence of repurposing ribavirin for the treatment of osteosarcoma. Our findings also highlight the therapeutic value of inhibiting eIF4E in osteosarcoma.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Takumi Yokokawa, Kohei Kido, Tadashi Suga, Kohei Sase, Tadao Isaka, Tatsuya Hayashi, Satoshi Fujita〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mitochondrial function in skeletal muscle and white adipose tissue (WAT) declines with aging and the progression of type 2 diabetes and insulin resistance. Although exercise increases mitochondrial biogenesis and function in both tissues, the molecular mechanisms are not fully understood. CDGSH iron sulfur domain-containing proteins (CISDs) are a novel family of proteins that regulate mitochondrial activity and biogenesis. However, the relationship between exercise and CISD expression is unclear. We addressed this in the present study by examining changes in the expression of CISDs and mitochondrial proteins in skeletal muscle and WAT of mice subjected to chronic exercise training. Mice were randomly assigned to either the sedentary or exercise group and were housed for 4 weeks in a standard cage without or with a running wheel, respectively. CISD and mitochondrial protein levels in the plantaris and soleus muscles and epididymal WAT were evaluated by western blotting. Chronic exercise increased CISD1 and CISD2 as well as mitochondrial protein expression in plantaris muscle and WAT but not soleus muscle. Moreover, this exercise-induced adaptation was strongly correlated with mitochondrial protein expression. Thus, mitochondrial biogenesis induced by chronic exercise coincides with the expression of CISDs in specific tissues, which may be critical for the maintenance of mitochondrial integrity.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Jingzhao Wang, Yuheng Hong, Shuai Shao, Kun Zhang, Wei Hong〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Evidence indicates that diets enriched in Docosahexaenoic acid (DHA), a 22:6 n-3 polyunsaturated fatty acid, reduces the risk of prostate cancer, but the biochemical mechanisms are unclear. The Hippo pathway has been well established as a tumor suppressor pathway and is involved in many diverse biologic processes including cell growth, cell death, and organ size control in organisms. Here we showed that DHA induces cell growth inhibition and apoptosis of human androgen-independent prostate cancer cells dependent on the Hippo pathway. DHA inactivates YAP by promoting phosphorylation in androgen-independent prostate cancer cell lines, accompanied by increased YAP cytoplasm translocation. We also observed that DHA-induced YAP phosphorylation was reversed by both the LATS1 and MST1 siRNAs. Further experiments showed that the mechanism of DHA-induced YAP phosphorylation associated with FFAR1 and FFAR4. Down-regulation of FFAR1 and FFAR4 resulted in reduced YAP phosphorylation and reversed DHA-induced YAP phosphorylation. In addition, DHA-induced YAP phosphorylation was abolished by dominant negative Gαs and PKA inhibitor H-89. Overall, these findings define a mechanism by which FFAR1-and FFAR4-dependent activation of Hippo pathway mediates DHA-induced apoptosis of androgen-independent prostate cancer cells, thus providing a promising therapeutic target for prostate cancer.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Tomoyuki Nishizaki〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Profilin catalyzes the exchange of actin-bound ADP to ATP. The present study investigated the role of profilin in PKCε activation. Profilin associated with PKCε in differentiated PC-12 cells under the basal conditions, which was inhibited by the PKC inhibitor GF109203X. The selective PKCε activator DCP-LA markedly increased the association, which was clearly prevented by GF109203X. The basal PKC activity in PC-12 cells was attenuated by knocking-down profilin, while the basal activities of PKA and CaMKII were not affected. DCP-LA enhanced the PKC activity to approximately 3.5 folds of the basal levels, and the effect was suppressed by knocking-down profilin. In the cell-free system, PKCε was not activated by profilin alone. DCP-LA activated PKCε in an ATP concentration (2–500 μM)-dependent manner, and addition of profilin shifted the ATP concentration/DCP-LA-induced PKCε activity relation curve to the left (the direction of lower ATP concentrations). Taken together, the results of the present study indicate that profilin binds to activated PKCε and facilitates PKCε activation by accelerating ATP supply to PKCε.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X18322769-egi10NCW3LQ8Q0.jpg" width="442" alt="Image" title="Image"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): You Cheng, Zhaoyun Li, Jiaogui Xie, Pan Wang, Jie Zhu, Yueguo Li, Yichao Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background/aims〈/h6〉 〈p〉Autophagy is known as a protective intracellular procedure, which can be regulated by several factors. MiRNA has been suggested as a potential element to mediate autophagy pathway in carcinomas. Our study was aim to investigate the role of autophagy in breast cancer cells and identify the involved molecular mechanism〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉The expression of LC3I/II, SQSTM1 and Smad4 were detected by western blot. The mRNA level were quantified by real-time PCR. MDC staining was used to directly visualize autophagosome formation. Target Scan 7.2 was used to predict biological targets of miR-224-5p〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉MiR-224 -5p expression was upregulated in metastatic breast cancer and non-metastatic breast cancer cells compare with control. Moreover, miR-224-5p inhibition enhanced cellular autophagy levels in breast cancer cells. MiR-224-5p could suppress Smad4 expression in MDA-MB-231 cells, which indicated that Smad4 was identified as a target of miR-224-5p in breast cancer cells with high metastatic potential〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉Our study revealed that miR-224-5p inhibited autophagy by targeting Smad4 in MDA-MB-231 cells. The results indicated that miR-224-5p/Smad4 regulating autophagy might be a novel regulatory network contributing to metastasis of breast cancer. MiR-224-5p and Smad4 is involved in breast tumorigenesis, which is possibly a novel target for breast cancer therapy.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Xi Sun, Ying Yuan, Ye Xiao, Qiong Lu, Li Yang, Chao Chen, Qi Guo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Disordered osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) contributes to bone loss. The underlying mechanisms are complicated and not fully understood. Long non-coding RNAs (lncRNAs) are emerging as an important regulatory factors on bone metabolism. Here, we discovered a novel lncRNA, 〈em〉Bmcob〈/em〉, which modulated osteogenic differentiation of primary mouse BMSCs. Expression levels of 〈em〉Bmcob〈/em〉 were significantly upregulated in early-to-mid stages during osteoblast differentiation. Silencing of 〈em〉Bmcob〈/em〉 suppressed osteoblastic differentiation of BMSCs in vitro, whereas its overexpression protected BMSCs from oxidative stress induced inhibition on osteogenesis. Subsequently, we discovered that selenoprotein P (Sepp1), which is located next to the 〈em〉Bmcob〈/em〉 gene, was partly responsible for the regulatory effects of 〈em〉Bmcob〈/em〉. In addition, a series of selenoproteins were downregulated in BMSCs with 〈em〉Bmcob〈/em〉 knockdown. Mechanistically, we found 〈em〉Bmcob〈/em〉 was associated with selenocysteine insertion sequence binding protein 2 (SBP2), a critical trans-acting factor for selenoprotein synthesis. Finally, we suggest an explanatory hypothesis that through modulating nucleocytoplasmic shuttling of SBP2, 〈em〉Bmcob〈/em〉 regulates a number of selenoproteins expression, including sepp1, and then mediates osteogenesis of BMSCs. Taken together, our results revealed a novel mechanism regulating osteogenesis of BMSCs and may function as a potential target for treating osteoporosis.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Wu Duan, Xuefeng Yu, Dongxia Ma, Bo Yang, Yi Li, Li Huang, Li Liu, Gang Chen, Danmei Xu, Yunchuan Ding〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉We previously demonstrated the protective effect of MSCs in an adaptive transfer mouse model. However, their therapeutic potential in an allogeneic immunocompetent setting mimicking clinical context of islet transplantation remained unknown. The aim of this study was to determine whether MSCs therapy, either by itself, or combined with Rapamycin could benefit the allograft survival of fully MHC-mismatched mouse islet transplant. Combination therapy of MSCs and low-dose Rapamycin significantly prolonged the survival of islet allografts, whereas treatment of MSCs, or Rapamycin alone, had no impact. Interestingly, this protective effect was associated with an induced expansion of regulatory T cells in islet grafts and draining lymph nodes, a skewed T-cell differentiation toward immunotolerance, and a profound suppression of alloreactivity against donor antigen. Our study suggests that a combination therapy of MSCs and low-dose Rapamycin can prolong the survival and preserve the function of islet allograft in the MHC-mismatched mouse model of islet transplantation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Chao-Yuan Yu, Wei-Chiao Chang, Jia-Huei Zheng, Wei-Hung Hung, Er-Chieh Cho〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Colon cancer is one of the most common cancers in the developed countries. The association between transforming growth factor TGFα and human cancer incidence has been suggested, yet, the regulatory roles of TGFα and the molecular mechanisms remain unknown, especially in colon cancer. We aim to investigate the functional regulations of TGFα in colon cancer progression. Two colon cancer cell lines were applied, and plasmid overexpression and siRNA-mediated depletion techniques were used to verify the role of TGFα in colon cancer. Cell proliferation was analyzed by MTS assay and colony formation assay, and western blot assay was used to examine protein expression. Migration, invasion, and reporter assays were also carried out to study the regulations of TGFα in colon cancer. Our results evidenced that expression of TGFα facilitates short-term and long-term proliferations of colon cancer cells. Moreover, TGFα was suggested as a migration-and-invasion promoting factor of colon cancer. Finally, our data indicated that TGFα modulates epithelial-mesenchymal transition (EMT) markers and NFκB signaling pathway in colon cancer cells. We provide the first time evidence of the promoting role TGFα plays in colon cancer tumorigenesis with proposed regulatory mechanisms involving EMT alteration and NFκB signaling pathway.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X18323039-egi105ZBZLGDLJ.jpg" width="245" alt="Image" title="Image"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Lei Lei, Houxiang Hu, Yan Lei, Jie Feng〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Diabetic cardiomyopathy is characterized by the deterioration of the myocardial function. Emerging evidences have indicated that leukocytic toll-like receptor 2 (TLR2) played an important role in the development of diabetic cardiomyopathy. Our study aimed to investigate whether TLR2 knockout (KO) exerted a cardioprotective effect 〈em〉in vivo〈/em〉. The establishment of diabetes model was set up in mice via intraperitoneal injection of streptozotocin (STZ). Results demonstrated that blocking of TLR2 significantly suppressed the enhanced left ventricular end-diastolic dimension (LVEDD), left ventricular end systolic diameter (LVESD) and the reduced the heart rate in diabetic cardiomyopathy mice. The decreased resting cell length, PS, TPS and + dL/dt while increased TR90 and - dL/dt caused by diabetic cardiomyopathy were remarkably inhibited by TLR2 KO. Besides that, the alleviated ΔFFI (360/380), decreased SERCA2a and 〈em〉p〈/em〉-NFATc3 expressions, extended Ca〈sup〉2+〈/sup〉 decay time and elevated Calcineurin A induced by diabetic cardiomyopathy were vastly repressed by TLR2 KO in cardiocytes. Moreover, TLR2 gene silence could ameliorate oxidative stress-induced apoptosis, evidences were the up-regulated superoxide generation and Bax/Bcl-2 expression while restrained GSH/GSSG ratio caused by diabetic cardiomyopathy were tremendously repressed in TLR2 KO mice. Furthermore, blocking of TLR2 remarkably attenuated the augmented fibrosis areas of heart tissues in mice with diabetic cardiomyopathy. The result of the enhanced α-SMA and collagenⅠ caused by diabetic cardiomyopathy were suppressed in heart tissues of TLR2 KO mice further validate it. All in all, our study demonstrated that diabetes-induced cardiac dysfunction could be attenuated by TLR2 KO.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Qunhui Wang, Xuan Chen, Dazhuang Yi, Yu Song, Yu-Hao Zhao, Qi Luo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Intracranial aneurysms (IAs) result from the bulging of arterial walls secondary to several factors such as flow, vessel morphology, and genetics. Subarachnoid hemorrhage occurs when such walls rupture, leading to high disability and mortality. Despite numerous investigations pertaining to the relationship between geometric characteristics and IA rupture, only a few have obtained consistent results. This study aimed to further identify the potential genes associated with the pathogenesis of IAs, which may provide novel molecular biomarkers. We downloaded and reanalyzed six datasets, which were divided into four groups. IA walls and blood samples were screened for differentially expressed genes (DEGs); then, functional and pathway enrichment analyses were conducted. In total, 158 common DEGs were identified from Groups 1–3 and 396 genes (187 upregulated and 209 downregulated genes) were differentially expressed in Group 4. The functional analysis revealed that the DEGs were mainly associated with the major histocompatibility complex class II protein complex and antigen processing and presentation. Finally, we identified nine key genes, both in aneurysm tissue samples and blood samples, of which three were mostly associated with the progression and rupture of IAs. Bioinformatics was used to analyze the datasets of the ruptured IAs and identify potential biomarkers, which may provide information for the early detection and treatment of IAs.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Dieniffer Peixoto-Neves, Hitesh Soni, Adebowale Adebiyi〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Reactive oxygen species (ROS) modulate neuronal function, including plasticity and neurotransmitter biosynthesis and release. The cellular mechanisms that underlie redox modulation of neurotransmission are not fully resolved, but potential pathways include ROS-induced alterations in Ca〈sup〉2+〈/sup〉 signaling in nerve terminals. In this study, we show that cold-sensitive receptor TRPM8 is activated by pro-oxidant 〈em〉tert〈/em〉-butyl hydroperoxide (tBHP). Polymerase chain reaction, Western immunoblotting, and immunofluorescence indicated that TRPM8 channels are expressed in rat pheochromocytoma 12 (PC12) cells, a phenotypic model of sympathetic neurosecretion when differentiated with nerve growth factor. WS-12, a selective TRPM8 channel agonist, and tBHP increased intracellular Ca〈sup〉2+〈/sup〉 concentration in differentiated PC12 cells; an effect attenuated by AMTB, a selective TRPM8 channel blocker, and siRNA-mediated TRPM8 knockdown. Blockade of TRPM8 channels also reduced WS-12- and tBHP-evoked norepinephrine secretion from the cells. These data suggest that TRPM8 channels contribute to oxidant-induced neurotransmission in PC12 cells.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Yuma Hotta, Kazuhiko Uchiyama, Tomohisa Takagi, Saori Kashiwagi, Takahiro Nakano, Rieko Mukai, Yuki Toyokawa, Tomoyo Yasuda, Tomohiro Ueda, Yosuke Suyama, Takaaki Murakami, Makoto Tanaka, Atsushi Majima, Toshifumi Doi, Yasuko Hirai, Katsura Mizushima, Mayuko Morita, Yasuki Higashimura, Ken Inoue, Akifumi Fukui〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Intestinal fibrosis with stricture formation is a severe complication of Crohn's disease (CD). Though new therapeutic targets to enable the prevention or treatment of intestinal fibrosis are needed, markers of this condition and the basic mechanisms responsible have not been established. NADPH oxidase (NOX) 4 has already been reported to play a key role in models of fibrogenesis, including that of the lung. However, its importance in intestinal fibrogenesis remains unclear. In this study, we examined the role of NOX4 in collagen production by intestinal myofibroblasts stimulated with transforming growth factor (TGF)-β1. Using LmcMF cells, an intestinal subepithelial myofibroblast (ISEMF) line, we first examined the induction of collagen production by TGF-β1. Subsequently, we investigated the role of NOX4 in TGF-β1-induced collagen I production in these cells using SB525334 (an SMAD2/3 inhibitor), diphenyleneiodonium (an NOX inhibitor), and 〈em〉Nox4〈/em〉 small interfering RNA (siRNA). Production of collagen was assessed with Sirius red staining, and 〈em〉Nox4〈/em〉 expression was measured by quantitative real-time PCR. Reactive oxygen species (ROS) production was determined using DCFDA and fluorescent microscopy. We observed that TGF-β1 induced collagen production via NOX4 activation and ROS generation in LmcMF cells. 〈em〉Nox4〈/em〉 siRNA and inhibitors of TGF-β1 receptor and NOX significantly reduced TGF-β1-induced ROS and collagen production. Thus, in the present study, we revealed that collagen production in ISEMFs is induced via an NOX4-dependent pathway. This work supports a function for NOX4 in intestinal fibrogenesis and identifies it as a potential therapeutic target in recalcitrant fibrotic disorders of CD patients.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Moe Sato, Toshifumi Asano, Jun Hosomichi, Takashi Ono, Takao Nakata〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Bone remodeling is maintained through the balance between bone formation by osteoblasts and bone resorption by osteoclasts. Previous studies suggested that intracellular Ca〈sup〉2+〈/sup〉 signaling plays an important role in the differentiation of osteoblasts; however, the molecular mechanism of Ca〈sup〉2+〈/sup〉 signaling in the differentiation of osteoblasts remains unclear. To elucidate the effect of Ca〈sup〉2+〈/sup〉 signaling in osteoblasts, we employed an optogenetic tool, blue light-activated Ca〈sup〉2+〈/sup〉 channel switch (BACCS). BACCS was used to spatiotemporally control intracellular Ca〈sup〉2+〈/sup〉 with blue light stimulation. MC3T3-E1 cells, which have been used as a model of differentiation from preosteoblast to osteoblast, were promoted to differentiate by BACCS expression and rhythmical blue light stimulation. The results indicated that intracellular Ca〈sup〉2+〈/sup〉 change from the outside of the cells can regulate signaling for differentiation of MC3T3-E1 cells. Our findings provide evidence that Ca〈sup〉2+〈/sup〉 could cause osteoblast differentiation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Yuhui Hong, Jun Cui, Zhen Liu, Yushi Luan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉WRKY transcription factors have been widely known to play key regulatory roles in plant disease resistance. In our previous study, characteristics of 〈em〉SpWRKY6〈/em〉 and its role in response to biotic and abiotic stress was studied. To further investigate the function of 〈em〉SpWRKY6〈/em〉 in tomato resistance to 〈em〉Phytophthora infestans〈/em〉 (〈em〉P. infestans〈/em〉), we studied the effects of loss and gain of function of 〈em〉SpWRKY6.〈/em〉 Inhibition of 〈em〉SpWRKY6〈/em〉 mRNA accumulation in tomato leaves, using virus-induced gene silencing (VIGS), greatly reduced 〈em〉SpWRKY6〈/em〉 mRNA levels, and compromised tomato resistance to 〈em〉P. infestans.〈/em〉 In contrast, overexpressing- 〈em〉SpWRKY6〈/em〉 tomato plants showed enhanced resistance to 〈em〉P. infestans,〈/em〉 accompanied by decreased number of necrotic cells, lesion sizes and disease index. Furthermore, after 〈em〉P. infestans〈/em〉 infection, the expression levels of pathogenesis related (PR) genes in transgenic tomato plants overexpressed 〈em〉SpWRKY6〈/em〉 were significantly higher than those in wild type plants, while the number of necrotic cells and the reactive oxygen species (ROS) accumulation were fewer and lower. Taken together, these results indicating that 〈em〉SpWRKY6〈/em〉 acts as a positive regulator of tomato resistance to 〈em〉P. infestans〈/em〉 infection through regulating the ROS level and the expression level of 〈em〉PR〈/em〉 genes along with alleviating cell membrane injury.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Huijin Zhao, Lan Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mutations in oncogenes or tumor suppressors can reprogram tumor metabolism by controlling multiple metabolic changes including glycolysis, glutaminolysis, increased autophagy, and macropinocytosis. Somatic mutations are essential for the development and growth of gastric cancer (GC), but the precise roles of these mutations in GC glucose metabolism remain largely unknown. In this study, we examined cancer genomes in 375 GC samples and demonstrated several glycolysis-related mutations in GC. Of note, loss-of-function mutation in 〈em〉MUC16〈/em〉 gene was identified. Mutated 〈em〉MUC16〈/em〉 predicted a better prognosis in GC patients. Gene set enrichment analysis suggested that mutated 〈em〉MUC16〈/em〉 status was associated with down-regulation of PI3K/Akt/mTOR signaling and Myc expression. GC cells with 〈em〉MUC16〈/em〉 mutations had reduced glycolytic capacity. Subsequently, genetic silencing of 〈em〉MUC16〈/em〉 in SNU16 and SNU5 cells led to significant reduction in glucose uptake, lactate production, extracellular acidification rate, and colony formation ability, indicating the critical regulatory roles of MUC16 in GC glycolysis and tumorigenesis. Specifically, western blotting showed that 〈em〉MUC16〈/em〉 knockdown inhibited PI3K/Akt/mTOR signaling, and reduced the protein level of Myc, which acts as a key transcription factor in regulating glycolysis. Taken together, our findings identify the MUC16-PI3K/Akt/mTOR-Myc axis as a critical signaling cascade that couples genomic mutations to metabolic reprogramming in GC.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Yanfang Pei, Yan Geng, Lei Su〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Heat stroke is a serious pathological condition with high mortality. Vascular endothelial cell injury is a key feature in the pathogenesis of heat stroke, but the specific pathophysiological process whereby this occurs is still unclear. Currently, relevant studies are primarily based upon examination of apoptosis. Recently, pyroptosis, a new form of inflammation-related programmed cell death, was also demonstrated to be involved in heat stroke pathophysiology. Herein, we present evidence that vascular endothelial cell pyroptosis can be induced by heat stress in a time- and temperature-dependent manner. Furthermore, this process can be significantly inhibited by GSDMD siRNA. These findings suggest a new therapeutic target for heat stroke.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Norichika Ueda, Makoto Kondo, Kentaro Takezawa, Hiroshi Kiuchi, Yosuke Sekii, Yusuke Inagaki, Tetsuji Soda, Shinichiro Fukuhara, Kazutoshi Fujita, Motohide Uemura, Ryoichi Imamura, Yasushi Miyagawa, Norio Nonomura, Shoichi Shimada〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉ATP in the suburothelial layer is released from the bladder urothelium by mechanical stimuli. ATP directly activates purinergic receptors that are expressed on primary bladder afferent neurons and induces the micturition reflex. Although ATP is also released to the bladder lumen from the bladder urothelium, the role of ATP in the bladder lumen is unknown. Recently, clinical studies have reported that urinary ATP levels are much higher in patients with an overactive bladder than healthy controls. These results suggest that ATP in the bladder lumen is also involved in the micturition reflex. In this study, we performed intravesical ATP instillation in the mouse bladder. We evaluated urinary function with novel reliable methods using improved cystometry and ultrasonography, which we previously established. We found that intravesical ATP instillation induced urinary frequency because of activation of bladder afferent nerves without inflammatory changes in the bladder or an increase in post-void residual urine. These results suggest that not only ATP in the suburothelial layer, but also ATP in the bladder lumen, are involved in enhancement of the micturition reflex.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 9 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 507, Issues 1–4〈/p〉 〈p〉Author(s): Masaya Hagiwara, Ikuhiko Nakase〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Lung branching morphogenesis is a complex system involving many molecular interactions to filling the three dimensional spaces; however, the underlying developmental mechanisms are still not fully understood. In this paper, we have investigated the effect of epidermal growth factor (EGF) on normal human bronchial epithelial cells and their three-dimensional (3D) branching pattern formation by using 〈em〉in vitro〈/em〉 experiments and mathematical simulation. The results show that EGF is essential for 3D branch pattern formation and its receptor is highly expressed at the tip of branches to generate the drive force for cells to migrate. Macropinocytosis induced by EGFR expression is firmly contributed to the nutrition uptake at the tip of branches. Our findings for effective branching formation of human lung cells contribute to further understanding molecular mechanisms of organogenesis, and the important mechanisms also possibly participate in related lung disease such as malformation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 9 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 507, Issues 1–4〈/p〉 〈p〉Author(s): Wen-Xin Geng, Rui Zhang, Jin-Ge Dang, Ying Wang, Zheng Li, Li-Wen Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Although many protein fusion tags have been developed for recombinant protein production to improve protein yields or facilitate purification, determining the expression and purification of the fusion protein still remain to be a time-consuming and laborious procedure. In this work, we designed a histidine-rich elastin-like polypeptide (HRELP) fusion tag and found that it could be efficiently expressed in 〈em〉E. coli〈/em〉 cells and specifically stained with Pauly's reagent in a couple of minutes post SDS-PAGE analysis. Moreover, in Pauly's reagent-stained polyacrylamide gels, only the bands of HRELP fusion proteins were yellow and could be clearly visualized with little background. Furthermore, both HRELPs and HRELP20-BMP2 fusion protein could be purified by a method of pH shift-mediated inverse transition cycling (ITC). In our opinion, the HRELP established in this study may be considered as a multifunctional protein tag which could make its fusion proteins being quickly detected by Pauly staining and simply purified by pH-triggered ITC in addition to having the potential to sustained release its fusion proteins.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 9 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 507, Issues 1–4〈/p〉 〈p〉Author(s): Yan Huang, Yajuan Duan, Yajuan Zhang, Panpan Fan, Zhoukun Li, Weidong Liu, Zhongli Cui〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Hydroxyquinol 1,2-dioxygenase is a key enzyme in the hydroxyquinol pathway of 〈em〉p〈/em〉-nitrophenol (PNP) degradation, and catalyzes the ring cleavage of benzenetriol to maleylacetate. Here, we report the first structure of a hydroxyquinol 1,2-dioxygenase from the Gram-negative bacterium 〈em〉Pseudomonas putida〈/em〉 DLL-E4 (PnpC) at the resolution of 2.1 Å. The tertiary structure of PnpC resembles that of the homologous intradiol dioxygenases. The catalytic Fe(III) is pentacoordinated by the conserved Tyr160, Tyr194, His218 and His220, the citrate anion and one water molecule. Among the residues expected to interact with the substrate, structural comparison with the (chloro)catechol dioxygenases suggested that Asp80, Thr81 and Val248 are responsible for the substrate specificity. Moreover, truncation of the N-terminal α-helix of PnpC suggested the N-terminal domain is required for its soluble expression and enzyme catalysis. Our results might provide insights in the substrate recognition and rational design of this enzyme class to be used in bioremediation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 9 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 507, Issues 1–4〈/p〉 〈p〉Author(s): Wenling Du, Zejiao Feng, Qinqin Sun〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Long noncoding RNA (lncRNA) LINC00319 has been reported to promote carcinogenesis of lung cancer and cutaneous squamous cell carcinoma. However, the role and mechanism of LINC00319 in ovarian cancer progression is unclear. In this study, LINC00319 expression was found to be upregulated in ovarian cancer tissues and cell lines. And our evidence showed that LINC00319 could be a potential prognostic biomarker for patients with ovarian cancer. Cell Counting Kit-8 (CCK-8), colony formation and transwell assays indicated that LINC00319 upregulation promoted proliferation, migration and invasion of ovarian cancer cells. Bioinformatics analysis and luciferase reporter assay revealed that LINC00319 worked as the sponge for miR-423-5p. Furthermore, miR-423-5p directly targeted NACC1. qRT-PCR and western blot results demonstrated that LINC00319 upregulates NACC1 expression through inhibiting miR-423-5p in ovarian cancer cells. Moreover, we observed an inverse expression correlation between miR-423-5p and LINC00319 or between miR-423-5p and NACC1 in ovarian cancer tissues. Finally, rescue assay showed that NACC1 restoration rescued the potentials of proliferation, migration and invasion in LINC00319-depleted ovarian cancer cells. In conclusion, our findings demonstrated that LINC00319 promotes ovarian cancer progression through upregulating NACC1 expression by restraining miR-423-5p.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 9 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 507, Issues 1–4〈/p〉 〈p〉Author(s): Feng Wang, Yanwen Zu, Shibin Zhu, Yu Yang, Weiping Huang, Hui Xie, Gonghui Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Bladder cancer (BCa) belongs to a popular urological malignancy and leads to large numbers of deaths worldwide. Recently, emerging evidences indicate that long noncoding RNAs (lncRNAs) are closely related with BC occurrence and progression. However, the function of lncRNA MAGI2-AS3 remains poorly understood in BC. In this present study, we screened out a novel lncRNA MAGI2-AS3 whose expression was downregulated in BCa tissues. We showed that MAGI2-AS3 downregulation in BCa patients indicated a poor prognosis. Functionally, we showed that MAGI2-AS3 overexpression inhibits proliferation, migration and invasion of BCa cells. Moreover, ectopic expression of MAGI2-AS3 suppresses BCa growth 〈em〉in vivo〈/em〉. Bioinformatics analysis revealed that MAGI2-AS3 could serve as a competing endogenous RNA (ceRNA) for miR-15b-5p. In the meantime, miR-15b-5p directly targeted CCDC19, a tumor suppressor in BCa. Rescue assays demonstrated that knockdown of CCDC19 restored the proliferation, migration and invasion of BCa cells suppressed by MAGI2-AS3 overexpression. In conclusion, this study identified a novel mechanism that MAGI2-AS3/miR-15b-5p/CCDC19 signaling pathway regulates BCa progression.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 9 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 507, Issues 1–4〈/p〉 〈p〉Author(s): Lu Han, Yumei Liu, Meili Lu, Hongxing Wang, Futian Tang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The present study was designed to investigate the effect of retinoic acid (RA) on anemia of inflammation (AI) induced by lipopolysaccharide (LPS) and explore the potential mechanisms. BALB/c mice were randomly assigned into four groups: control group; LPS (10 mg/kg) group, LPS + RA (3 mg/kg) and LPS + RA (15 mg/kg) groups. Red blood cell count (RBC), hemoglobulin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin contentration (MCHC), erythropoietin (EPO) and iron content in both serum and liver tissue were measured. The AI model induced by LPS was successfully established represented by the decreases in RBC, Hb, HCT, MCV, MCHC and EPO for anemia indicators and by the increases in TNF-α, IL-18 and IL-1β contents for inflammation indicators. However, supplementation of RA increased the levels of anemia indicators and decreased the content of inflammation indicators. In addition, RA increased the content of iron in serum, while decreased its content in liver tissue. Furthermore, RA down-regulated the protein expression of hepcidin, toll-like receptor 4 (TLR4) and p-p65 in liver tissue, while up-regulated that of ferroportin. RA modulates iron metabolism imbalance in AI induced by LPS via reversely regulating hepcidin and ferroportin expression, which might be mediated by TLT-4/NFκB signaling pathway.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Xiao-Li Liu, Ya-Kun Wang, Shu Ouyang, Yan-Yu Zhu, Wei Li, Xiao-you Hong, Hong-Yan Xu, Xin-Ping Zhu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Serum 〈em〉transferrin (tf)〈/em〉, encoding an iron-binding glycoprotein, has been revealed to play important roles in iron transportation and immune response, and it also has been demonstrated to be valuable for phylogenetic analysis in vertebrates. However, the evolutionary conservation, expression profiles and positive selection of 〈em〉transferrin〈/em〉 genes among freshwater turtle species remain largely unclear. Here, the genomic DNA and coding sequences of 〈em〉transferrin〈/em〉 genes were cloned and characterized in seven freshwater turtles including 〈em〉Mauremys mutica〈/em〉, 〈em〉Mauremys sinensis〈/em〉, 〈em〉Cyclemys dentate〈/em〉, 〈em〉Mauremyssi reevesi〈/em〉, 〈em〉Heosemys grandis〈/em〉, 〈em〉Trachemys scripta〈/em〉 and 〈em〉Chrysemys picta〈/em〉. The isolated coding sequences of turtles' 〈em〉tf〈/em〉 genes were 2118 bp or 2121 bp, encoding 706 or 707 amino acids. The predicted Tf proteins of turtles share high identities with 〈em〉M. mutica〈/em〉 Tf, up to 91%–98% and the 〈em〉M. mutica〈/em〉 Tf has the highest identity (91%) in amino acid with the 〈em〉Chelomia mydas〈/em〉 Tf, the moderate with other reptiles' Tfs (65%–59%), chicken (58%), and Human Tf (∼55%), and the lowest with zebrafish Tf (41%). Additionally, 〈em〉tf〈/em〉 genes were consistently composed of 17 exons and 16 introns with the same splicing sites in introns in all the turtles examined. Moreover, 12 positive selected sites were detected in these turtles’ Tf and mainly distributed on the surface of transferrin protein. Importantly, it was found that 〈em〉transferrin〈/em〉 genes in all turtles examined were predominantly expressed in adult liver via real-time quantitative PCR. The molecular characterizations and expression profiles of 〈em〉transferrin〈/em〉 would shed new insights into understanding the conversations and divergences of 〈em〉transferrin〈/em〉 genes in turtles, even in vertebrates.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X18323520-fx1.jpg" width="284" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 9 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 507, Issues 1–4〈/p〉 〈p〉Author(s): Rongjiong Zheng, Wenjie Mao, Zhennan Du, Jun Zhang, Mingming Wang, Meiling Hu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Owing to the poor prognosis, novel biomarkers for lung adenocarcinoma (LACA) are needed nowadays. The aim of the study was to identify the differential miRNAs expression between lung cancer and normal tissues and evaluate the prognostic values of the miRNAs. Multidimensional data of 528 samples were retrieved from The Cancer Genome Atlas archive. Data analysis was based on a computational approach to detect survival-associated molecular signatures. A total of 191 differentially expressed miRNAs were identified between LACA tissues and normal tissues, including 88 up-regulated and 103 down-regulated miRNAs. The Kaplan-Meier survival method revealed the prognostic function of the three miRNAs (miR-1293, miR-873 and miR-1914). Cox regression analysis showed that the three-miRNA signature was an independent prognostic factor in LACA. The functional enrichment analysis suggested that the target genes of three miRNAs may be involved in various pathways related to the cancer. This study demonstrated that the three-miRNA signature (miR-1293, miR-873 and miR-1914) could be used as a prognostic marker in LACA.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 9 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 507, Issues 1–4〈/p〉 〈p〉Author(s): Alejandro González-Torres, Evelyn Gabriela Bañuelos-Villegas, Natalia Martínez-Acuña, Eric Sulpice, Xavier Gidrol, Luis Marat Alvarez-Salas〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The miR-143/145 cluster is down-regulated in cervical tumor cells suggesting a role in tumorigenesis including cytoskeleton remodeling, a key event for tumor progression. The aim of the present work was to determine the role of miR-143/145 in the modulation of the myosin regulator phospho-myosin light chain (pMLC). HeLa monolayer and tridimensional cultures were transfected with miR-143 or miR-145 mimics inhibiting cell viability, proliferation, migration and invasion, mainly through miR-145. MiR-145 transfection increased pMLC levels by targeting the MYPT1 subunit of the regulatory myosin phosphatase. MYPT1 knockdown by siRNAs reproduced miR-145 effects suggesting miR-145 as a tumor suppressor through MYPT1 targeting, leading to a subsequent increase of pMLC levels with implications for cervical cell viability, migration and invasion.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X18324458-fx1.jpg" width="126" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 9 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 507, Issues 1–4〈/p〉 〈p〉Author(s): Siwei Feng, Qingyuan Huang, Chao Ye, Rui Wu, Guihua Lei, Jiali Jiang, Tingting Chen, Yuanyi Peng, Rendong Fang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Streptococcus pneumoniae〈/em〉 is a pathogen of significant clinical importance worldwide that can cause severe invasive diseases, such as pneumonia, otitis media and meningitis. Inflammsomes has been reported to participate in host defense against 〈em〉S. pneumoniae〈/em〉 infection. 〈em〉S. pneumoniae〈/em〉 could induce the assembly of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)/absent in melanoma 2 (AIM2) inflammasome, which mediates the activation of caspase-1 and the subsequent maturation of Interleukin-1β (IL-1β). However, the precise signals that activate inflammasomes during pneumococcal infection remain to be fully elucidated. In the present study, primary mouse macrophages were selected as a cell model, and the effects of kinases on inflammasome activity induced by 〈em〉S. pneumoniae〈/em〉 infection were examined by ELISA and western blotting after pretreatment with a kinase inhibitor. Here, we show that Syk and JNK signaling are required for 〈em〉S. pneumoniae〈/em〉-induced activation of the inflammasome. Inhibitors of Syk and JNK almost abolished the oligomerization of apoptosis-associated speck-like protein containing a caspase-activating and recruitment domain (ASC) and subsequent caspase-1 activation and IL-1β secretion. Moreover, pneumolysin (PLY) participated in this process and was critical for Syk/JNK activation. These results suggested that the Syk/JNK signaling pathway may play a vital role in the inflammasome activation and modulate host immune responses against 〈em〉S. pneumoniae〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 9 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 507, Issues 1–4〈/p〉 〈p〉Author(s): Jung-Gyu Lee, Kyoung Ryoung Park, Jun Yop An, Jung Youn Kang, Haihong Shen, Jimin Wang, Soo Hyun Eom〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The eukaryotic primase/polymerase complex synthesizes approximately 10〈sup〉7〈/sup〉 primers, one per Okazaki fragment, during the replication of mammalian chromosomes, which contain 10〈sup〉9〈/sup〉 base pairs. Primase catalyzes the synthesis of a short RNA segment to a single-stranded DNA template. Primase is important in DNA replication because no known replicative DNA polymerases can initiate the synthesis of a DNA strand without an initial RNA primer. The primase subcomplex is composed of a small catalytic subunit (p49), and a large accessory subunit (p58). Priming mechanisms remain poorly understood, although large numbers of structures of archaeal and eukaryotic p49 and/or p58 as well as structures of bacterial enzymes have been determined. In this study, we determined the structure of human p49 at 2.2 Å resolution with citrate in its inactive forms. Dibasic citrate was bound at the nucleotide triphosphate (NTP) β, γ-phosphate binding site through nine hydrogen bonds. We also measured the dissociation constant of citrate and NTPs. We further demonstrated that the p49 activity is regulated by pH and citrate, which was not previously recognized as a key regulator of DNA replication. We propose that the citrate inhibits the primase and regulates DNA replication at the replication fork.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 9 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 507, Issues 1–4〈/p〉 〈p〉Author(s): Xi Zhang, Jian Wu, Congcong Wu, Wenjun Chen, Ruifang Lin, Yingying Zhou, Xuanzhang Huang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Clear cell renal cell carcinoma (ccRCC), the most common type of kidney malignancy, is an incurable disease characterized by multiple metabolic abnormalities, especially lipid accumulation and desaturation. Though great progresses have been made in understanding the mechanisms of ccRCC, metabolic abnormalities remain largely unclear. Here, we found lncRNA LINC01138 is highly expressed in ccRCC and is associated with poor patient survival. LINC01138 regulates ccRCC growth through sterol regulatory element-binding protein 1 (SREBP1)-mediated lipid desaturation. Mechanistically, we demonstrated that LINC01138 interacts with PRMT5 to increase arginine methylation and protein stability of SREBP1, promoting lipid desaturation and cell proliferation in ccRCC. Our study identified LINC01138 as a novel regulator of metabolic abnormalities in ccRCC, providing a potential therapeutic target for metabolic therapy.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Miyake, Masuyo Miyaki, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Takashi Higuchi, Arun S. Singh, Bartosz Chmielowski, Scott D. Nelson, Tara A. Russell, Mark A. Eckardt, Sarah M. Dry, Yunfeng Li, Shree Ram Singh, Sant P. Chawla, Fritz C. Eilber〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Liposarcoma is the most common type of soft tissue sarcoma. Among the subtypes of liposarcoma, dedifferentiated liposarcoma (DDLPS) is recalcitrant and has the lowest survival rate. The aim of the present study is to determine the efficacy of metabolic targeting with recombinant methioninase (rMETase) combined with palbociclib (PAL) against a doxorubicin (DOX)-resistant DDLPS in a patient-derived orthotopic xenograft (PDOX) model. A resected tumor from a patient with recurrent high-grade DDLPS in the right retroperitoneum was grown orthotopically in the right retroperitoneum of nude mice to establish a PDOX model. The PDOX models were randomized into the following groups when tumor volume reached 100 mm〈sup〉3〈/sup〉: G1, control without treatment; G2, DOX; G3, PAL; G4, recombinant methioninase (rMETase); G5, PAL combined with rMETase. Tumor length and width were measured both pre- and post-treatment. On day 14 after initiation, all treatments significantly inhibited tumor growth compared to the untreated control except DOX. PAL combined with rMETase was significantly more effective than both DOX, rMETase alone, and PAL alone. Combining PAL and rMETase significantly regressed tumor volume on day 14 after initiation of treatment and was the only treatment to do so. The relative body weight on day 14 compared with day 0 did not significantly differ between each treatment group. The results of the present study indicate the powerful combination of rMETase and PAL should be tested clinically against DDLPS in the near future.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Takafumi Numata, Takamichi Yoshizaki, Sachiko Yamaguchi, Eri Shimura, Yoichiro Iwakura, Kazutoshi Harada, Katsuko Sudo, Ryoji Tsuboi, Susumu Nakae〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Levels of IL36α are known to be increased in specimens from patients with atopic dermatitis and psoriasis. In addition, it has been reported that IL-36α is crucial for development of imiquimod-induced psoriatic dermatitis in mice. On the other hand, the role of IL-36α in induction of allergic contact dermatitis/contact hypersensitivity (ACD/CHS) is poorly understood. We found that IL-36α was produced in keratinocytes of mice during imiquimod-induced psoriatic dermatitis, but it was hardly detectable in the skin of mice during either fluorescein isothiocyanate (FITC)- or 1-fluoro-2, 4-dinitrobenzene (DNFB)-induced CHS. Although IL-36α can enhance activation of dendritic cells (DCs) and T cells, in CHS, IL-36α was not essential for DC migration from the skin to draining LNs, but it was required for induction or activation of hapten-specific T cells such as Th/Tc1 or Th17 cells. However, local inflammation, assessed by measurement of ear skin thickness, was comparable between wild-type and IL-36α-deficient mice during both FITC- and DNFB-induced CHS. These observations indicate that IL-36α is involved in induction and/or activation of hapten-specific T-cell subsets in the sensitization phase of CHS, but not essential for induction of local inflammation in the elicitation phase.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Jinjin Feng, Yan Chen, Shaohua Yan, Lu Wen, Xi Guo, Yibo Wen, Jian Guo Wen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Objectives〈/h6〉 〈p〉Aquaporin-2 (AQP2) is an important water channel protein that is expressed in the renal collecting duct and plays a key role in urine concentration and body water homeostasis. It has been demonstrated that the urinary excretion of AQP2 correlates strongly with its expression in the kidney in adult humans and rats. However, there have been no studies on the urinary excretion of AQP2 in human fetuses during development. Fetal urine is the main source of the amniotic fluid; we speculate that the level of AQP2 in the amniotic fluid could reflect the expression level of the AQP2 protein in the fetal kidney. The purpose of the present study was to explore the relationship between AQP2 in the amniotic fluid and that in the fetal kidney.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉In the present study, the concentration of the AQP2 protein in human amniotic fluid was measured by Enzyme-linked immunosorbent assay (ELISA) and its expression level in human fetal kidneys were examined by wastern blot and immunohistochemistry.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Both the expression level of AQP2 in the fetal kidney (F = 195.9, P 〈 0.001) and the concentration of AQP2 in the amniotic fluid increased with gestational age (F = 1098, P 〈 0.001). Moreover, the concentration of AQP2 in the amniotic fluid was positively correlated with its expression level in the fetal kidney (r = 0.872, P 〈 0.0001).〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉Our research indicates that AQP2 levels in the amniotic fluid may be used as a marker for AQP2 expression in the fetal kidney.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Sukwon Lee, Jeongyeon Kim, Sukwoo Choi〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Amyloid beta (Aβ) is known to be one of the strong candidate molecules for initiating Alzheimer's disease and has been extensively studied in the light of disease pathophysiology. However, it is still elusive what roles Aβ play in the normal brain. In this study, we report that Aβ is required for memory forgetting in the normal brain. We monitored object recognition memory, and in order to quench soluble Aβ, we microinjected anti-Aβ antibody (4G8) into the ventricles after memory acquisition. Microinjection of anti-Aβ antibody prolonged the maintenance of object recognition memory. This effect appeared not to be due to modulation of memory consolidation since antibody injection after memory consolidation still had a similar effect on memory maintenance. Furthermore, the maintenance of object recognition memory was prolonged in 〈em〉Fcgr2b〈/em〉 KO mice, which lacks IgG Fcγ receptor II-b (FcγRIIb), a receptor for soluble Aβ oligomers. Taken together, these findings suggest that endogenous Aβ is involved in memory forgetting in the normal brain.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Yufeng Zou, Qianwen Ouyang, Wensong Wei, Shixin Yang, Yan Zhang, Wenlong Yang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉FAT10, an ubiquitin-like protein, functions as a potential tumor promoter in several caners. However, the function and clinical significance of FAT10 in breast cancer (BC) remains unclear. Here, we found that high FAT10 expression was detected frequently in primary BC tissues, and was closely associated with malignant phenotype and shorter survival among the BC patients. Multivariate analyses also revealed that FAT10 overexpression was independent prognostic factors for poor outcome of patients with BC. Function assay demonstrated that FAT10 knockdown significantly inhibited the metastasis abilities and the epithelial-mesenchymal transition (EMT) of breast cancer cell. Further investigation revealed that FAT10 directly bound ZEB2 and decreased its ubiquitination to enhance the protein stability of ZEB2 in BC cells. Moreover, our data shown that the pro-metastasis effect of FAT10 in BC is partially dependent on ZEB2 enhancement. Collectively, our data suggest that FAT10 plays a crucial oncogenic role in BC metastasis, and we provide a novel evidence that FAT10 may be serve as a prognostic and therapeutic target for BC patients.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Hanqing Yu, Yu Chen, Ping Jiang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The current study tested the expression and potential functions of 〈em〉circular RNA HIPK3〈/em〉 (〈em〉circHIPK3〈/em〉) in human lung cancer. Our results show that 〈em〉circHIPK3〈/em〉 expression is upregulated in established (A549 line) and primary human lung cancer cells, when compared to its low level in the lung epithelial cells. siRNA-mediated silencing of 〈em〉circHIPK3〈/em〉 potently inhibited survival and proliferation of lung cancer cells, but inducing significant apoptosis activation. Contrarily, forced overexpression of 〈em〉circHIPK3〈/em〉 by a lentiviral construct promoted lung cancer cell survival and proliferation. 〈em〉CircHIPK3〈/em〉 acted as a 〈em〉microRNA-124〈/em〉 (〈em〉miR-124〈/em〉) sponger and regulated the expression of 〈em〉miR-〈/em〉124 mRNA targets, including 〈em〉SphK1〈/em〉, 〈em〉CDK4〈/em〉 and 〈em〉STAT3〈/em〉, in lung cancer cells. Transfection of 〈em〉miR-124〈/em〉 inhibitor significantly inhibited 〈em〉circHIPK3〈/em〉 siRNA-induced lung cancer cell death and apoptosis. At last, we show that 〈em〉circHIPK3〈/em〉 levels are upregulated in human lung cancer tissues, correlated with 〈em〉miR-124〈/em〉 downregulation. The 〈em〉miR-124〈/em〉 targets (〈em〉SphK1〈/em〉, 〈em〉STAT3〈/em〉 and 〈em〉CDK4〈/em〉) are upregulated in lung cancer tissues. Together, we propose that 〈em〉circHIPK3〈/em〉 promotes lung cancer cell progression possibly by sponging 〈em〉miR-124〈/em〉. These observations indicate a possible novel therapeutic strategy involving 〈em〉circHIPK3〈/em〉-〈em〉miR-124〈/em〉 pathway against lung cancer.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Valérie Gouyer, Bastien Demouveaux, Guillaume Lacroix, Hélène Valque, Frédéric Gottrand, Jean-Luc Desseyn〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The CYS domain occurs in multiple copies in many gel-forming mucins. It is believed that CYS domains can interact with each other in a reversible manner, suggesting a key role of the domain in gel formation. This domain always contains in its amino-terminal sequence the 〈em〉C〈/em〉-mannosylation motif WXXW, but whether the CYS domain is 〈em〉C〈/em〉-mannosylated is debated, and the putative role of 〈em〉C〈/em〉-mannosylation of the domain is unclear. We prepared recombinant CYS domains of the human mucin MUC5B with (WXXW→AXXW) and without a single amino acid mutation and mini-5B mucins made of a large Ser/Thr/Pro region flanked by two CYS domains with the WXXW motif or with the mutated AXXW motif on the first, second or both CYS domains. We found that the single CYS domain and the two CYS domains of mini-5B mucin must be 〈em〉C〈/em〉-mannosylable for the efficient maturation and secretion of the recombinant molecules; otherwise, they are retained in the cell and co-localized with a resident enzyme of the endoplasmic reticulum.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X18323040-fx1.jpg" width="368" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Sissel E. Dyrstad, Deusdedit Tusubira, Stian Knappskog, Karl J. Tronstad, Gro V. Røsland〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉We show that the quantitative PCR reaction volume can be reduced significantly compared to the standard procedures, without compromising data quality. By analyzing dilution series (10〈sup〉0〈/sup〉–10〈sup〉−7〈/sup〉) we found that measurement in 1 μl reaction volume indeed gave valid results comparable to 10 μL, when using a routine pipetting robot. This may enable a significant cost reduction through cutback of both biological material as well as chemical reagents.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Jiong Ren, Zhibin Niu, Xiaoqin Li, Jie Yang, Meijiao Gao, Xudong Li, Tao Zhang, Lei Fang, Boyang Zhang, Junping Wang, Yongping Su, Fengchao Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉As compared with 2D cell line cultures, 3D intestinal organoids are better at maximally recapitulating the physiological features of stem cells 〈em〉in vivo〈/em〉. However, the complex 3D structure is an obstacle which must be objectively and automatically evaluated to assess colony growth and regeneration. Meanwhile, no internal standard currently exists for evaluating the size of heterogeneities in organoids or defining those regenerating colonies. Herein, we developed a simple morphometry system to image MTT-stained organoids. The growth curve of organoids can be automatically generated based upon analyzing the integrated optical density using software. Referencing the definition standards of 〈em〉in vivo〈/em〉 regenerating crypts, the perimeters of crypts cultured 24 h after seeding were selected as an “Organoid Unit” to further evaluate colony survival rate and colony size heterogeneities after exposure to varying doses of irradiation. Moreover, the morphometry-based quantification data collected confirmed other findings associated with radiation sensitizing effects of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related protein (ATR) inhibitor and the radiation protective effect of IL-22. In summary, the novel organoid morphometry system combined with a new internal reference is a practical means for standardizing assessment of growth, survival and regeneration of intestinal organoid colonies. This method has promise to facilitate drug screens in intestinal and other organoid systems.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Meaghan Van Alstyne, Francesco Lotti, Andrea Dal Mas, Estela Area-Gomez, Livio Pellizzoni〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Stasimon (also known as Tmem41b) is an evolutionarily conserved transmembrane protein first identified for its contribution to motor system dysfunction in animal models of the childhood neurodegenerative disease spinal muscular atrophy (SMA). Stasimon was shown to be required for normal neurotransmission in the motor circuit of 〈em〉Drosophila〈/em〉 larvae and proper development of motor axons in zebrafish embryos as well as to suppress analogous neuronal phenotypes in SMA models of these organisms. However, the subcellular localization and molecular functions of Stasimon are poorly understood. Here, we combined immunoprecipitation with mass spectrometry to characterize the Stasimon interactome in mammalian cells, which reveals association with components of the endoplasmic reticulum (ER), mitochondria, and the COPI vesicle trafficking machinery. Expanding on the interaction results, we used subcellular fractionation studies and super-resolution microscopy to identify Stasimon as an ER-resident protein that localizes at mitochondria-associated ER membranes (MAM), functionally specialized contact sites between ER and mitochondria membranes. Lastly, through characterization of novel knockout mice, we show that Stasimon is an essential gene for mouse embryonic development. Together, these findings identify Stasimon as a novel transmembrane protein component of the MAM with an essential requirement for mammalian development.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Geng Chen, Tong Zhou, Ying Liu, Zhenxiang Yu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In addition to the involvement in white matter lesion, tripartite-motif protein family member 65 (TRIM65) has also been implicated in tumorigenesis as a potential oncogene. However, the underlining mechanisms of TRIM65 functions and its clinical implication still remain to be further elucidated. In the present study, we found that TRIM65 binds to the N-terminus of p53 tumor suppressor and thus competes with MDM2 for p53 binding. Intriguingly, analysis of the Cancer Genome Atlas (TCGA) gene alteration database revealed that elevated expression of TRIM65 is mutually exclusive to MDM2 up-regulation in human lung adenocarcinoma patients, indicating potential compensatory effect of one over the other. Indeed, overexpression of TRIM65 renders lung cancer cell line resistance to Nutlin-3a, an effective MDM2 inhibitor, as determined by p53 activation and cell proliferation assays. Furthermore, depletion of TRIM65 using siRNA in combination with Nutlin-3a treatment demonstrates enhanced anti-tumor effects on lung cancer cell line. Collectively, our findings provide the rationale for developing strategies to target TRIM65 for lung cancer intervention, potentially in combination with MDM2 inhibition.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Tianshu Yu, Ling Liang, Xuyang Zhao, Yuxin Yin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA). MPZL1 is upregulated in hepatocellular carcinoma (HCC) and accelerates migration of HCC cells. However, function of MPZL1 as a receptor of ConA and its role in HCC development are largely unknown. To elucidate the functional basis, we have determined the crystal structure of the extracellular domain of MPZL1 at 2.7 Å resolution. Overall, it folds like a typical immunoglobulin variable-like domain that is much like MPZ. Unexpectedly, we found Asn50 is a unique glycosylation site and the glycosylation mediates its interaction with ConA. Furthermore, we also found that MPZL1 exists as a homodimer in the crystal, in which hydrogen bonds between Ser86 and Val145 play an important role. Our results demonstrate that glycosylation of Asn50 is essential for its function as a receptor of ConA. We propose that dimerization of MPZL1 participates in control of its signal transmission in cell adhesion.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Ruizhao Li, Wei Dong, Shu Zhang, Huan Yang, Li Zhang, Zhiming Ye, Xingchen Zhao, Hong Zhang, Zhilian Li, Lixia Xu, Shuangxin Liu, Wei Shi, Xinling Liang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Podocyte depletion is a central pathological mechanism of diabetic nephropathy (DN). Hyperglycemia induced podocyte apoptosis, resulting in podocyte depletion. However, the crucial mechanism of hyperglycemia-induced podocyte apoptosis remains poorly understood. In this study, we evaluated the expression of septin 7, a GTP-binding protein, in glomerular podocytes of patients and mice with DN, and investigated the pro-apoptotic effect of septin 7 on high glucose (HG) induced podocyte apoptosis in vitro. We found septin 7 expression was markedly increased not only in glomerular podocytes of patients and db/db mice with DN but also in cultured podocytes with HG stimulation. Knocking down septin 7 with siRNA could attenuate HG induced podocytes apoptosis and excessive intracellular Ca〈sup〉2+〈/sup〉 concentration. This study revealed septin7 may potentially play a proapoptotic role in podocyte under diabetic conditions and may provide a potential target for preventing podocyte apoptosis in DN.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Yu-Qiong He, Qi Zhang, Yi Shen, Ting Han, Quan-Long Zhang, Jian-Hua Zhang, Bing Lin, Hong-Tao Song, Hsien-Yeh Hsu, Lu-Ping Qin, Hai-Liang Xin, Qiao-Yan Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Rubiadin-1-methyl ether (RBM) is a natural anthraquinone compound isolated from the root of 〈em〉Morinda officinalis〈/em〉 How. In our previous study, RBM was found to have inhibitory effects on the TRAP activity of osteoclasts, which means that RBM may be a candidate for therapy of bone diseases characterized by enhanced bone resorption. However, the further effect of RBM on osteoclasts and the underlying mechanism remain unclear. In the present study, we investigated the effects of RBM isolated from 〈em〉Morinda officinalis〈/em〉 How. on osteoclasts derived from bone marrow macrophages (BMMs) and the underlying mechanism in vitro. RBM at the dose that did not affect the viability of cells significantly inhibited RANKL-induced osteoclastogenesis and actin ring formation of osteoclast, while RBM performed a stronger effect at the early stage. In addition, RBM downregulated the expression of osteoclast-related proteins, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene Fos (c-Fos), matrix metallopeptidase 9 (MMP-9) and cathepsin K (CtsK) as shown by Western blot. Furthermore, RBM inhibited the phosphorylation of NF-κB p65 and the degradation of IκBα as well as decreased the nuclear translocation of p65. Collectively, the results suggest that RBM inhibit osteoclastic bone resorption through blocking NF-κB pathway and may be a promising agent for the prevention and treatment of bone diseases characterized by excessive bone resorption.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Jiamin Xie, Yuqing Xu, Liuxia Wan, Peng Wang, Miaomiao Wang, Minyue Dong〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Introduction〈/h6〉 〈p〉Preeclampsia is a main cause of maternal and perinatal mortality and morbidity. The expression of follistatin-like 3 (FSTL3) is enhanced in maternal serum and placenta of preeclamptic women. However, whether FSTL3 is involved in the pathophysiologic of preeclampsia has not been clarified yet.〈/p〉 〈/div〉 〈div〉 〈h6〉Method〈/h6〉 〈p〉Trophoblast cell lines Swan71 and JAR cells were cultured and siRNA was used to silence FSTL3. The expression of FSTL3 was determined by Western blotting. The matrigel-coated transwell and wound healing assays were used to assess invasion and migration, cell proliferation and apoptosis were detected by CCK-8 and flow cytometric analysis, respectively. Oil red O staining was used to detect the lipid storage in trophoblast.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Hypoxia culture significantly enhanced the expression of FSTL3 by trophoblast. Down-regulation of FSTL3 significantly suppressed the proliferation, migration, invasion and lipid storage but increased apoptosis of trophoblast.〈/p〉 〈/div〉 〈div〉 〈h6〉Discussion〈/h6〉 〈p〉Aberrant expression of FSTL3 in preeclampsia led to the dysfunction of trophoblast, indicating its involvement in the pathogenesis of preeclampsia.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Shuang Chang, Yaning Li, Fang Yuan, Meijie Qu, Yaying Song, Zhijun Zhang, Guo-Yuan Yang, Yongting Wang〈/p〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Xixi Wang, Jing Wu, Yingtong Wu, Hongjun Chen, Shoufeng Zhang, Jinxiang Li, Ting Xin, Hong Jia, Shaohua Hou, Yitong Jiang, Hongfei Zhu, Xiaoyu Guo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉African swine fever virus (ASFV) is a highly pathogenic large DNA virus that causes African swine fever (ASF) in domestic pigs and European wild boars with mortality rate up to 100%. The DP96R gene of ASFV encodes one of the viral virulence factors, yet its action mechanism remains unknown. In this study, we report that DP96R of ASFV China 2018/1 strain subverts type I IFN production in cGAS sensing pathway. DP96R inhibited the cGAS/STING, and TBK1 but not IRF3-5D mediated IFN-β and ISRE promoters activation. Furthermore, DP96R selectively blocked the activation of NF-κB promoter induced by cGAS/STING, TBK1, and IKKβ, but not by overexpression of p65. Moreover, DP96R inhibited phosphorylation of TBK1 stimulated by cGAS/STING activation, and TBK1-induced antiviral response. Finally, truncated mutation analysis demonstrated that the region spanning amino acids 30 to 96 of DP96R was responsible for the inhibitory activity. To our knowledge, this is for the first time that DP96R of ASFV China 2018/1 is reported to negatively regulate type I IFN expression and NF-κB signaling by inhibiting both TBK1 and IKKβ, which plays an important role in virus immune evasion.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Tomohiro Omura, Hiroki Matsuda, Luna Nomura, Satoshi Imai, Masaya Denda, Shunsaku Nakagawa, Atsushi Yonezawa, Takayuki Nakagawa, Ikuko Yano, Kazuo Matsubara〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Endoplasmic reticulum (ER) stress may play a role in the etiology of Parkinson's disease (PD). We have previously reported that ubiquitin ligase 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase degradation 1 (HRD1) involved in ER stress degrades unfolded protein that accumulates in the ER due to loss of function of Parkin, which is a causative factor in familial PD. We have also demonstrated that cell death is suppressed by the degradation of unfolded proteins. These findings indicate that HRD1 may serve as a compensatory mechanism for the loss of function of Parkin in familial PD patients. However, the role of HRD1 in sporadic PD has not yet been identified. This study aimed to reveal the roles of HRD1 and associated molecules in a cellular model of PD. We demonstrated that expressions of HRD1 and Suppressor/Enhancer Lin12 1-like (SEL1L: a HRD1 stabilizer) increased in SH-SY5Y human neuroblastoma cells upon exposure to 6-hydroxydopamine (6-OHDA). The 6-OHDA-induced cell death was suppressed in cells overexpressing wt-HRD1, whereas cell death was enhanced in cells with knockdown of HRD1 expression. These results suggest that HRD1 is a key molecule involved in 6-OHDA-induced cell death. By contrast, suppression of SEL1L expression decreased the amount of HRD1 protein. As a result, 6-OHDA-induced cell death was enhanced in cells suppressing SEL1L expression, and this cell death was much more evident than that in cells with suppression of HRD1 expression. These findings strongly indicate that SEL1L is necessary for maintaining and stabilizing the amount of HRD1 protein, and stabilizing the amount of HRD1 protein through SEL1L may serve to protect against 6-OHDA-induced cell death. Furthermore, the expression of Parkin was reinforced when 〈em〉HRD1〈/em〉 mRNA had been suppressed in cells, but was not observed when 〈em〉SEL1L〈/em〉 mRNA had been restrained. It is possible that Parkin expression is induced as a compensatory mechanism when 〈em〉HRD1〈/em〉 mRNA decreases. This intracellular transduction may suppress the enhancement of 6-OHDA-induced cell death caused by the loss of HRD1. Taken together with these results, it is suggested that HRD1 and its stabilizer (SEL1L) are key molecules for elucidating the pathogenesis and treatment of PD.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Yuan Zhang, Xiangfan Chen, Li Yuan, Yide Zhang, Jianhua Wu, Naifeng Guo, Xu Chen, Jing Liu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes mellitus and often results in chronic renal failure. Here, we found that Interleukin 1 receptor associated kinases (IRAK1) was up-regulated in kidney in both DN patients and high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice. In vivo, down regulation of IRAK1 ameliorated renal injury and function, with lower podocyte apoptosis, increased expression of Nephrin, attenuated thickness of the glomerular basement membrane and podocyte footprocess effacement. Furthermore, 〈em〉in vitro〈/em〉, down regulation of IRAK1 in podocytes treated with high glucose (HG), podocyte apoptosis and inflammatory cytokines were significantly decreased, but Nephrin increased. Meanwhile, apoptosis-related genes caspase-3/-9 were inhibited and phosphorylation levels of PI3K/Akt were dramatically down regulated. Thus, IRAK1 is one of the critical components involved in podocyte apoptosis in DN.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Kumiko Shiozawa, Yusuke Yoshioka, Zhiwei Qiao, Ji Shuting, Takahiro Ochiya, Tadashi Kondo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Secreted proteins enclosed in extracellular vesicles can act as intercellular messengers. The objective of this study was to elucidate the role of proteins secreted from synovial sarcoma cells in the regulatory network underlying pazopanib response. We performed a comprehensive analysis of expression of proteins secreted from four synovial sarcoma cell lines (SYO-1, HS-SYII, 1273/99, and YaFuSS) using mass spectroscopy. Comparison of up-regulated proteins in cells, extracellular vesicles-free conditioned media, and extracellular vesicles revealed significantly up-regulated Wnt in synovial sarcoma vesicles. Furthermore, we compared protein signatures of cells, conditioned media, and extracellular vesicles before and after pazopanib treatment. Interestingly, protein signatures of extracellular vesicles showed robust changes in Wnt signaling pathways in response to pazopanib. Our findings provide insight into the potential role of Wnt, a protein secreted from the extracellular vesicles of synovial sarcoma cells, making it a potential candidate for use in sarcoma diagnosis.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Yazeed Jamalat, Yaser Gamallat, Pires Sanches Jaceline Gislaine, Abdo Meyiah, Abdullah Shopit, Hailong Li, Bashir Ahmed, Peng Chu, Hongyang Wang, Xiaodong Li, Jinyong Peng, Xiaodong Ma, Zeyao Tang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Diabetes mellitus (DM) associated liver damage is a major health burden. Hepatocellular-damage in DM characterized with elevated endoplasmic reticulum stress (ER) and may enhanced insulin-resistance. Phosphocreatine (PCr) a rapidly high-energy-reserve molecule of phosphates naturally occurs in liver, brain and skeletal muscle. This study aimed to investigate the protective effect of PCr on the liver-injury-associated with DM and to report the mechanism involved. Wistar rat's diabetes model was induced using streptozotocin (STZ), and the animals were treated with 20 mg/kg, or 50 mg/kg PCr injection. Blood glucose level, and body wt were recorded. Liver tissues homogenate were analyzed for liver damage markers alanine transaminase (ALT), aspartate transaminase (AST). Liver tissues proteins further evaluated for apoptosis, endoplasmic reticulum stress (ER), and insulin resistance biomarkers using western blotting. Our results revealed that PCr reduced blood glucose level, improved body wt, ameliorates liver function enzymes. Furthermore, PCr upregulates anti-apoptotic Bcl2 proteins expression, and down-regulates significantly pro-apoptotic casp3 and Bax proteins expression in vivo and invitro. Moreover, ER stress CHOP, GRP78 and ATF4 biomarkers level were significantly attenuated in PCr treated animals comparing to STZ diabetes associated liver-damage model with significant improving in insulin-resistance Akt and IRS-1. Our results revealed that treating with PCr in diabetes-associated liver injury models decreased blood glucose level and possess protective effect in-vitro and in-vivo, which could be suggested as potential therapeutic strategy for diabetes associated liver injury patients.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X18322848-fx1.jpg" width="307" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 2 December 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 4〈/p〉 〈p〉Author(s): Leinan Yu, Qun Xu, Weixin Yu, Jianchun Duan, Guofang Dai〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Emerging literature have illustrated the vital regulatory roles of long noncoding RNAs (lncRNAs) on the breast cancer tumorigenesis. Although series of researches have been proceeded on the pathogenesis, there are still much of unsolved mysteries worth investigating. This study uncovered that CASC15 expression level was aberrantly high-expressed in breast cancer tissue specimens and cells. Functionally, the loss-of-functional experiments showed that knockdown of CASC15 suppressed the malignant behaviors of breast cancer cells, such as proliferation, invasion and tumor growth in vitro and vivo. Mechanically, we confirmed that CASC15 functioned as a competing endogenous RNA (ceRNA) of miR-153–3p, besides, miR-153–3p targeted the 3‘-UTR of KLF5 mRNA utilizing the bioinformatics online tools, luciferase reporter assay and RNA immunoprecipitation. Interestingly, we confirmed that the transcription factor KLF5 binds with the promoter region of CASC15 and activates the transcription. In conclusion, we validated the positive feedback loop of KLF5/CASC15/miR-153–3p/KLF5 in the acceleration of breast cancer malignant behaviors and tumorigenesis, suggesting the important biologic roles of CASC15 on the breast cancer tumorigenesis.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Ran Sun, Lin Ye, Min Zhang, Zhu Qiu, Tingxiu Xiang, Jun Tang, Xiangyu Wang, Lili Li, Jie Luo, Dongsheng Zhang, Guosheng Ren〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background〈/h6〉 〈p〉Aberrant expression of interferon regulatory factor 4 (IRF4) has been reported in several hematologic malignancies. However, the prognostic significance of IRF4 expression in esophageal squamous cell carcinoma (ESCC) remains unknown.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉IRF4 protein expression in ESCC tumor specimens was determined immunohistochemically. The correlation of IRF4 expression with clinico-pathological features was assessed from a cohort of 100 patients with primary ESCC. Kaplan-Meier and Cox proportional regression analyses were used to evaluate the association between IRF4 expression and patient survival.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉A Kaplan-Meier analysis indicated that patients with high IRF4 expression had a significantly longer overall survival rate than those with low IRF4 expression (〈em〉p〈/em〉 = 0.0006). Furthermore, multi-variate analyses revealed that IRF4 protein expression is an independent prognostic indicator for ESCC patients.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉Our results suggest that increased IRF4 protein expression correlates with improved outcome in ESCC. IRF4 may therefore represent a promising prognostic biomarker and potential immuno-therapeutic target for patients with ESCC.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Saori Nonaka, Koichiro Kawamura, Aki Hori, Emil Salim, Kazuki Fukushima, Yoshinobu Nakanishi, Takayuki Kuraishi〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The 〈em〉Drosophila〈/em〉 Toll-1 receptor is involved in embryonic development, innate immunity, and tissue homeostasis. Currently, as a ligand for the Toll-1 receptor, only Spätzle (Spz) has been identified and characterized. We previously reported that 〈em〉Drosophila〈/em〉 larva-derived tissue extract contains ligand activity for the Toll-1 receptor, which differs from Spz based on the observation that larval extract prepared from 〈em〉spz〈/em〉 mutants possessed full ligand activity. Here, we demonstrate that Spz5, a member of the Spz family of proteins, functions as a ligand for the Toll-1 receptor. Processing of Spz5 by Furin protease, which is known to be important for ligand activity of Spz5 to Toll-6, is not required for its function to the Toll-1 receptor. By generating a 〈em〉spz5〈/em〉 null mutant, we further showed that the Toll-1 ligand activity of larva-derived extract is mainly derived from Spz5. Finally, we found a genetic interaction between 〈em〉spz〈/em〉 and 〈em〉spz5〈/em〉 in terms of developmental processes. This study identified a novel ligand for the 〈em〉Drosophila〈/em〉 Toll-1 receptor, providing evidence that Toll-1 is a multi-ligand receptor, similar to the mammalian Toll-like receptor.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Ha Na Jang, Yongchao Liu, Namjeong Choi, Jagyeong Oh, Jiyeon Ha, Xuexiu Zheng, Haihong Shen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Alternative splicing of exon 6 in Fas pre-mRNA generates a membrane bound pro-apoptotic isoform or soluble anti-apoptotic isoform. SRSF4 is a member of Arginine-Serine rich (SR) protein family. Here we demonstrate that increased SRSF4 expression stimulates exon 6 inclusion, and that reduced SRSF4 expression promotes exon 6 exclusion. We also show that weaker but not stronger 5’ splice-site strength of exon 6 abolishes the SRSF4 effects on exon 6 splicing. Furthermore, we identified a novel enhancer on exon 6, on which SRSF4 interacts functionally and physically. Our results illustrate a novel regulatory mechanism of Fas pre-mRNA splicing.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Su Yeon Park, Won jin Kim, Jae hwan Byun, Jae Jun Lee, Dooil Jeoung, Sung Taek Park, Youngmi Kim〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Cancer/Testis antigen DDX53 shows high expression level in various tumors and is involved in anti-cancer drug resistance. However, the functional study of DDX53 in cervix cancer remains unknown. In this study, the role of DDX53 in taxol-resistance of cervix cancer cells was investigated. In taxol-resistant Hela〈sup〉TR〈/sup〉 cells, DDX53 was significantly increased as compared to the parental HeLa cells. Hela〈sup〉TR〈/sup〉 cells also showed upregulation of multidrug resistant gene MDR1, invasive characteristics and decreased apoptosis. In addition, increased autophagy level was observed in Hela〈sup〉TR〈/sup〉 cells. Overexpression of DDX53 in HeLa and SiHa markedly led to greater resistance to taxol and cisplatin, whereas knockdown of DDX53 in Hela〈sup〉TR〈/sup〉 cells restored sensitivity, demonstrating that DDX53 regulated taxol resistance in cervix cancer cells. DDX53 overexpression in HeLa and SiHa cells enhanced invasion, migration and anchorage independent growth, DDX53 knockdown showed inverse effects in HeLa〈sup〉TR〈/sup〉 cells. When DDX53 expression was suppressed by siRNA, autophagic flux and drug resistance of Hela〈sup〉TR〈/sup〉 cells were decreased. In addition, DDX53 was upregulated in cervix cancer tissues from patient with a glassy cell carcinoma of cervix. Taken together, these results suggest that DDX53 plays a critical role in taxol-resistance by activating autophagy and a potential therapeutic target for the treatment of taxol-resistant cervix cancer.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 30 November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 506, Issue 3〈/p〉 〈p〉Author(s): Bo Jin, Yanbing Gong, Haixia Li, Lili Jiao, Dianqi Xin, Yanqing Gong, Zhisong He, Liqun Zhou, Yaqiong Jin, Xiujuan Wang, Zheng Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Urothelial Carcinoma Antigen 1 (UCA1) is a cell and tissue specific long non-coding RNA (lncRNA) associated with the tumorigenesis and invasion of bladder cancer. However, the mechanism driving the over-transcription of UCA1 in bladder cancer cells remains unclear. It has been reported that C/EBPβ has a significant role of regulation in tumorigenesis. Here we report that the expression of UCA1 was dramatically inhibited in 5637 cells with C/EBPβ down-regulation. Additionally, the function tests indicated that C/EBPβ could promote 5637 cells growth and colony formation by inducing the expression level of UCA1. These data suggest that C/EBPβ was involved in transcriptional regulation of UCA1 and contributed substantially to its high expression and proliferation promoting in bladder cancer cells.〈/p〉〈/div〉 〈/div〉