ALBERT

Description: Damage to the corticospinal tract is widely studied following unilateral subcortical stroke, whereas less is known about changes to other sensorimotor pathways. This may be due to the fact that many studies investigated morphological changes in the brain, where the majority of descending and ascending brain pathways are overlapping, and did not investigate the brainstem where they separate. Moreover, these pathways continue passing through separate regions in the spinal cord. Here, using a high-resolution structural MRI of both the brainstem and the cervical spinal cord, we were able to identify a number of microstructurally altered pathways, in addition to the corticospinal tract, post stroke. Moreover, decreases in ipsi-lesional corticospinal tract integrity and increases in contra-lesional medial reticulospinal tract integrity were correlated with motor impairment severity in individuals with stroke.

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Yanjie Hou, Tian Gong, Jiangtao Zhang, Xi Yang, Yurong Guo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The thinned-young apple polysaccharides from three varieties were obtained by hot water extraction at 88 ̊C for 120 min. The compositional monosaccharides of the three polysaccharides were shown to be the same (xylose, mannose, galactose and glucose) and the molecular weights of the polysaccharides were in the range of 200–300 kDa. Compared with “Qinyang” and “Pinklady”, the polysaccharide from “Jinshiji” had the highest emulsifying capacity. Moreover, the variations in pH and cation ion concentrations had also a significant effect on the emulsifying properties of the extracted polysaccharides. At pH 2.0–4.0, the prepared emulsion had smaller droplet sizes than at higher pH values. Although the emulsion was stable at low concentrations of Na〈sup〉+〈/sup〉 and Ca〈sup〉2+〈/sup〉 ions, high concentrations of Na〈sup〉+〈/sup〉 and Ca〈sup〉2+〈/sup〉 led to significant destabilization of the emulsion. Conclusively, our results demonstrated the potential application of thinned-young apple polysaccharide as a natural polysaccharide emulsifying agent.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Shuangdong Chen, Yixiao Gu, Qinxue Dai, Yanshu He, Junlu Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Sirtuin1 (SIRT1), which is regulated by microRNA-34a (miR-34a), can modulate pathophysiology processes, including nonalcoholic fatty liver disease and intestinal ischemia/reperfusion injury. We previously reported that SIRT1, an NAD〈sup〉+〈/sup〉-dependent deacetylase, plays a vital role in the development of neuropathic pain. However, the role of miR-34a/SIRT1 in complete Freund's adjuvant (CFA)-induced inflammatory pain remains unclear. In the present study, we examined miR-34a and SIRT1 in CFA mice. MiR-34a levels increased, while SIRT1 decreased in the spinal cord. Inhibiting miR-34a by intrathecal injection of miR-34a antagomir attenuated CFA-induced pain behavior. Moreover, miR-34a antagomir inhibited the CFA-induced SIRT1 decrease in the spinal cord. Furthermore, the analgesic effect of miR-34a antagomir was abrogated by the SIRT1 inhibitor EX-527. Our data provide support that the underlying mechanisms of miR-34a in promoting inflammatory pain may involve negative regulation of SIRT1.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Lifang Cui, He Zhao, Yujun Yin, Chao Liang, Xiaolong Mao, Yingzheng Liu, Qilin Yu, Mingchun Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Candida albicans〈/em〉 is an important opportunistic pathogenic fungus in the human body. It is a common microbe inhabiting on the mucosa surfaces of healthy individuals, but may cause infections when the host immune system is weak. Autophagy is a “self-eating” process in eukaryotes, which can recover and utilize damaged organelles and misfolded proteins. Here we investigated the role of the autophagy-related protein Atg11 in 〈em〉C. albicans〈/em〉. Deletion of 〈em〉ATG11〈/em〉 led to the defect in growth under the nitrogen starvation condition. Western blotting and GFP localization further revealed that the transport and degradation of Atg8 was blocked in the 〈em〉atg11〈/em〉Δ/Δ mutant under both the nitrogen starvation and hypha-inducing conditions. Moreover, degradation of both Lap41 (the indicator of the cytoplasm-to-vacuole pathway) and Csp37 (the indicator of mitophagy) was also thoroughly suppressed in this mutant under nitrogen starvation. These results indicated that Atg11 plays an essential role in both non-selective and selective autophagy in 〈em〉C. albicans〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Yi-meng Cao, Meng-yu Liu, Zhuo-wei Xue, Yu Qiu, Jie Li, Yang Wang, Qing-kai Wu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Promotion of wound healing is one of the most important fields in clinical medical research. This study aimed to evaluate the potential use of a new surface-structured bacterial cellulose(S-BC) biomaterial with human urine-derived stem cells (hUSCs) for wound healing. In vitro, EA.hy926 were inoculated on structured/non-structured bacterial cellulose, and the growth of EA.hy926 on bacterial cellulose in medium with/without conditioned medium of the hUSCs were observed to explore the effect of bacterial cellulose's surface structure and hUSCs-CM on vascular endothelial cell growth. In vivo, we covered wound surface with various BC materials and/or injected the hUSCs into the wound site on group BC, group S-BC, group hUSCs, group BC + hUSCs, group S-BC + hUSCs to evaluate the effect of S-BC and hUSCs on wound healing in rat full-thickness skin defect model. In vitro study, surface structure of S-BC could promote the growth and survival of EA.hy926, and the hUSCs-CM could further promote the proliferation of EA.hy926 on S-BC. In vivo study, wound healing rate of the group BC, group S-BC, group hUSCs was significantly accelerated, accompanied by faster re-epithelialization, collagen production and neovascularization than control group. It is note worthy that the effect of S-BC on wound healing was better than BC, the effect of S-BC + hUSCs on wound healing was better than BC + hUSCs. Moreover, the effect of S-BC combined with hUSCs on wound is better than treated with S-BC or hUSCs alone. All the findings suggest that the combination of S-BC and hUSCs could facilitate skin wound healing by promoting angiogenesis. This combination of the role of stem cells and biomaterial surface structures may provide a new way to address clinical wound healing problems.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Naohiro Katagiri, Satoru Nagatoishi, Kouhei Tsumoto, Hideya Endo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Methionine aminopeptidase 2 (MetAP2) is one of the effector proteins of S100A4, a metastasis-associated calcium-binding protein. This interaction is involved in angiogenesis. The region of MetAP2 that interacts with S100A4 includes amino acids 170 to 208. A peptide corresponding to this region, named as NBD, has potent anti-angiogenic activity and suppresses tumor growth in a xenograft cancer model. However, the binding mode of NBD to S100A4 was totally unknown. Here we describe our analysis of the relationship between the inhibitory activity and the structure of NBD, which adopts a characteristic helix-turn-helix structure as shown by X-ray crystallographic analysis, and peptide fragments of NBD. We conducted physicochemical analyses of the interaction between S100A4 and the peptides, including surface plasmon resonance, microscale thermophoresis, and circular dichroism, and performed docking/molecular dynamics simulations. Active peptides had stable secondary structures, whereas inactive peptides had a little secondary structure. A computational analysis of the interaction mechanism led to the design of a peptide smaller than NBD, NBD-ΔN10, that possessed inhibitory activity. Our study provides a strategy for design for a specific peptide inhibitor against S100A4 that can be applied to the discovery of inhibitors of other protein-protein interactions.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Xue Mei Li, Soo Jung Kim, Dong-Kyun Hong, Kyoung Eun Jung, Chong Won Choi, Young-Joon Seo, Jeung-Hoon Lee, Young Lee, Chang-Deok Kim〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Kruppel-like factor 4 (KLF4) is a zinc-finger transcription factor that plays a role in terminal differentiation of epidermal keratinocytes. There are conflicting reports regarding the role of KLF4 in tumor development, with both the tumor suppressive and/or oncogenic properties depending on different conditions and cell types. In this study, we investigated the functional importance of KLF4 in cutaneous squamous cell carcinoma (SCC). Immunohistochemistry showed that KLF4 expression was relatively low in SCC lesion compared to normal epidermis. To examine the effects of KFL4, we transduced SCC lines (SCC12 and SCC13 cells) with the KLF4-expressing recombinant adenovirus. Overexpression of KLF4 significantly decreased cell proliferation and colony forming activity. In addition, overexpression of KLF4 markedly reduced invasive potential, along with the downregulation of epithelial-mesenchymal transition (EMT)-related molecules. In a mechanistic study, KLF4 inhibited SOX2, of which expression is critical for tumor initiation and growth of SCC. Further investigations indicated that SOX2 expression is induced by TGF-β/SMAD signaling, and that overexpression of KLF4 inhibited SMAD signaling via upregulation of SMAD7, an important inhibitory SMAD molecule. Based on these data, KLF4 plays a tumor suppressive role in cutaneous SCC cells.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Yan Shen, Shengnan Chen, Yan Zhao〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Hyperglycemia-induced podocyte injury plays a vital role in the development of diabetic nephropathy. Sulfiredoxin-1 (Srxn1) is emerging as a cytoprotective protein that protects from various insults in a wide range of cell types. However, whether Srxn1 is involved in regulating hyperglycemia-induced podocyte injury and participates in diabetic nephropathy remains unknown. In the present study, we aimed to explore the potential role of Srxn1 in regulating high glucose (HG)-induced apoptosis and oxidative stress of podocytes 〈em〉in vitro〈/em〉. Results demonstrated that Srxn1 was induced in HG-stimulated podocytes. The depletion of Srxn1 by Srxn1 siRNA-mediated gene silencing significantly exacerbated HG-induced apoptosis and the production of reactive oxygen species (ROS), while Srxn1 overexpression attenuated HG-induced apoptosis and ROS production. In-depth molecular mechanism research revealed that Srxn1 overexpression promoted the nuclear expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and reinforced antioxidant response element (ARE)-mediated transcription activity. Moreover, results confirmed that Srxn1 increased the activation of Nrf2/ARE signaling associated with inactivating glycogen synthase kinase (GSK)-3β. Notably, the inhibition of GSK-3β significantly reversed Srxn1 silencing-induced adverse effects in HG-treated cells, while the knockdown of Nrf2 abrogated the Srxn1-mediated protective effect against HG-induced podocyte injury. Taken together, our results demonstrated that Srxn1 protects podocytes from HG-induced injury by promoting the activation of Nrf2/ARE signaling associated with inactivating GSK-3β, indicating a potential role of Srxn1 in diabetic nephropathy. Our study suggests that Srxn1 may serve as a potential target for kidney protection.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X19313178-fx1.jpg" width="398" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Yu-Lun Huang, Gota Kawai, Atsuhiko Hasegawa, Mari Kannagi, Takao Masuda〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Reverse transcription of retroviral RNA is accomplished through a minus-strand strong stop cDNA (-sscDNA) synthesis and subsequent strand-transfer reactions. We have previously reported a critical role of guanosine (G) number at 5′-terminal of HIV-1 RNA for successful strand-transfer of -sscDNA. In this study, role(s) of the cap consisting of 7-methyl guanosine (〈sup〉7m〈/sup〉G), a hallmark of transcripts generated by RNA polymerase II, at the 5′-end G nucleotide (5′-G) of HIV-1 RNA were examined. In parallel, contribution of highly conserved GGG tract located at the U3/R boundary in 3′ terminal region of viral RNA (3′-GGG tract) was also addressed. The in vitro reverse transcription analysis using synthetic HIV-1 RNAs possessing the 5′-G with cap or triphosphate form demonstrated that the 5′-cap significantly increased strand-transfer efficiency of -sscDNA. Meanwhile, effect of the 5′-cap on the strand-transfer was retained in the reaction using mutant HIV-1 RNAs in which two Gs were deleted from the 3′-GGG tract. Lack of apparent contribution of the 3′-GGG tract during strand-transfer events in vitro was reproduced in the context of HIV-1 replication within cells. Instead, we noticed that the 3′-GGG tract might be required for efficient gene expression from proviral DNA. These results indicated that 〈sup〉7m〈/sup〉G of the cap on HIV-1 RNA might not be reverse-transcribed and a possible role of the 3′-GGG tract to accept the non-template nucleotide addition during -sscDNA synthesis might be less likely. The 5′-G modifications of HIV-1 RNAs by the cap- or phosphate-removal enzyme revealed that the cap or monophosphate form of the 5′-G was preferred for the 1st strand-transfer compared to the triphosphate or non-phosphate form. Taken together, a status of the 5′-G determined strand-transfer efficiency of -sscDNA without affecting the non-template nucleotide addition, probably by affecting association of the 5′-G with 3′-end region of viral RNA.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X19312926-fx1.jpg" width="307" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Xiong Wang, Huishou Zhao, Wenjun Yan, Yi Liu, Tao Yin, Shan Wang, Miaomiao Fan, Congye Li, Ling Zhang, Ling Tao〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Atherosclerosis is characterized by the accumulation of excess cholesterol in plaques. Reverse cholesterol transport (RCT) plays a key role in the removal of cholesterol. In the present study, we examined the effect of thioredoxin-1 (Trx-1) on RCT and explored the underlying mechanism. We found that Trx-1 promoted RCT 〈em〉in vivo〈/em〉, as did T0901317, a known liver X receptor (LXR) ligand. T0901317 also inhibited the development of atherosclerotic plaques but promoted liver steatosis. Furthermore, Trx-1 promoted macrophage cholesterol efflux to apoAI 〈em〉in vitro〈/em〉. Mechanistically, Trx-1 promoted nuclear translocation of LXRα and induced the expression of ATP-binding cassette transporter A1 (ABCA1). Apolipoprotein E knockout (apoE−/−) mice fed an atherogenic diet were daily injected intraperitoneally with saline or Trx-1 (0.33 mg/kg). Trx-1 treatment significantly inhibited the development of atherosclerosis and induced the expression of ABCA1 in macrophages retrieved from apoE−/− mice. Moreover, the liver steatosis was attenuated by Trx-1. Overall, we demonstrated that Trx-1 promotes RCT by upregulating ABCA1 expression through induction of nuclear translocation of LXRα, and protects liver from steatosis.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 13 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 1〈/p〉 〈p〉Author(s): 〈/p〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Azuma Kosai, Nanao Horike, Yoshiaki Takei, Akihiro Yamashita, Kaori Fujita, Takashi Kamatani, Noriyuki Tsumaki〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The maturation of chondrocytes is strictly regulated for proper endochondral bone formation. Although recent studies have revealed that intracellular metabolic processes regulate the proliferation and differentiation of cells, little is known about how changes in metabolite levels regulate chondrocyte maturation. To identify the metabolites which regulate chondrocyte maturation, we performed a metabolome analysis on chondrocytes of Sik3 knockout mice, in which chondrocyte maturation is delayed. Among the metabolites, acetyl-CoA was decreased in this model. Immunohistochemical analysis of the Sik3 knockout chondrocytes indicated that the expression levels of phospho-pyruvate dehydrogenase (phospho-Pdh), an inactivated form of Pdh, which is an enzyme that converts pyruvate to acetyl-CoA, and of Pdh kinase 4 (Pdk4), which phosphorylates Pdh, were increased. Inhibition of Pdh by treatment with CPI613 delayed chondrocyte maturation in metatarsal primordial cartilage in organ culture. These results collectively suggest that decreasing the acetyl-CoA level is a cause and not result of the delayed chondrocyte maturation. Sik3 appears to increase the acetyl-CoA level by decreasing the expression level of Pdk4. Blocking ATP synthesis in the TCA cycle by treatment with rotenone also delayed chondrocyte maturation in metatarsal primordial cartilage in organ culture, suggesting the possibility that depriving acetyl-CoA as a substrate for the TCA cycle is responsible for the delayed maturation. Our finding of acetyl-CoA as a regulator of chondrocyte maturation could contribute to understanding the regulatory mechanisms controlling endochondral bone formation by metabolites.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Saujanya Acharya, Shubhankar Dutta, Sucheta Chopra, Kakoli Bose〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Human HtrA3 (High temperature requirement protease A3) is a trimeric PDZ bearing propapoptotic serine protease, which is involved in various diseases including cancer and pre-eclampsia. Proposed to be a tumor suppressor, its role as a potential therapeutic target is strongly advocated. Therefore, it becomes imperative to gain insights into its mechanism of action and regulation. Allostery is a well-known mechanism of catalytic activation for many HtrA3 homologs, which opens up avenues for manipulating enzyme functions for therapeutic intervention. In our study, through 〈em〉in silico〈/em〉 and biochemical approaches, we have reported for the first time that HtrA3 shows allosteric behaviour. We identified a novel selective binding pocket, which triggers conformational reorientations through signal propagation to the distantly situated active-site pocket via the functionally important loop regions. Using molecular docking, simulation studies and biochemical studies we have identified the regulatory movements at and around the active site pocket. Our study is the first one to report a non-classical binding site for HtrA3, which is instrumental for formation of a catalytically efficient orthosteric pocket upon substrate binding.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X19313312-fx1.jpg" width="470" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Farnoush Asghari-Paskiabi, Mohammad Imani, Hashem Rafii-Tabar, Mehdi Razzaghi-Abyaneh〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Selenium sulfide is a well-known bioactive chemical whose biosynthesis as a nanoparticle (NP) is a controversial issue. In the present study, we employed 〈em〉Saccharomyces cerevisiae〈/em〉 to generate a novel synthetic process of selenium sulfide NPs. The addition of selenium/sulfur precursors to 〈em〉S. cerevisiae〈/em〉 culture produced NPs, which we isolated and characterized the physicochemical properties, toxicity, and antifungal activity. Transmission electron microscopy indicated the presence of the NPs inside the cells. Selenium sulfide NPs were successfully synthesized with average size of 6.0 and 153 nm with scanning electron micrographs and 360 and 289 nm in Zeta sizer using different precursors. The presence of sulfur/selenium in the particles was confirmed by energy-dispersive X-ray spectroscopy and elemental mapping. Fourier-transform infrared spectroscopy supported the production of selenium sulfide NPs. X-ray diffractograms showed the presence of characteristic peaks of selenium sulfide NPs which were further confirmed by mass spectrometry. The obtained NPs strongly inhibited the growth of pathogenic fungi that belonged to the genera 〈em〉Aspergillus〈/em〉, 〈em〉Candida〈/em〉, 〈em〉Alternaria〈/em〉 and the dermatophytes, while no cytotoxicity was observed in MTT assay. In conclusion, efficient green synthesis of selenium sulfide NPs with appropriate physicochemical properties is possible in bio-systems like 〈em〉S. cerevisiae〈/em〉.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X19313361-fx1.jpg" width="285" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Masashi Maekawa, Hiromi Hiyoshi, Jun Nakayama, Kohki Kido, Tatsuya Sawasaki, Kentaro Semba, Eiji Kubota, Takashi Joh, Shigeki Higashiyama〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Eukaryotic translation initiation factor 3 subunit D (EIF3D) binds to the 5′-cap of specific mRNAs, initiating their translation into polypeptides. From a pathological standpoint, EIF3D has been observed to be essential for cell growth in various cancer types, and cancer patients with high EIF3D mRNA levels exhibit poor prognosis, indicating involvement of EIF3D in oncogenesis. In this study, we found, by mass spectrometry, that Cullin-3 (CUL3)/KCTD10 ubiquitin (Ub) ligase forms a complex with EIF3D. We also demonstrated that EIF3D is K27-polyubiquitinated at the lysine 153 and 275 residues in a KCTD10-dependent manner in human hepatocellular carcinoma HepG2 cells. Similar to other cancers, high expression of EIF3D significantly correlated with poor prognosis in hepatocellular carcinoma patients, and depletion of EIF3D drastically suppressed HepG2 cell proliferation. These results indicate that EIF3D is a novel substrate of CUL3/KCTD10 Ub ligase and suggest involvement of K27-polyubiquitinated EIF3D in the development of hepatocellular carcinoma.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Xiaobo Chen, Chun Xu, Hong He〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Sustained antibiotic release is important to prevent the infections after surgical treatments such as guided tissue regeneration (GTR). Electrospinning provides a simple way to fabricate nanofibers for drug delivery. In this study, a simple method to achieve sustained antibiotic release by introducing mesoporous silica nanoparticles (MSNs)with electrospinning is developed. The nanoparticles entrapped nanofibers (MSNs-PCL) were successfully fabricated, and a sustained release of gentamicin was demonstrated. The gentamicin loaded MSNs-PCL showed strong antimicrobial effects against 〈em〉E. coli〈/em〉, indicated the sustained release behavior and the retained bioactivity. The MSNs-PCL synthesized by electrospinning method shows great potential for biomedical applications such as fabricating GTR membranes.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Abhishek Anil Dubey, Vikas Jain〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Mycobacterium smegmatis〈/em〉 possesses (〈em〉N〈/em〉,〈em〉N〈/em〉-dimethyl-4-nitrosoaniline)-dependent (NDMA) methanol dehydrogenase (Mno) to establish methylotrophy by utilizing methanol as the source of both carbon and energy. In this study, we show that Mno forms decamer and has NADPH as the bound cofactor. Interestingly, Mno uses NDMA and not NADP〈sup〉+〈/sup〉 as an electron acceptor in 〈em〉in vitro〈/em〉 reactions. We further show that the operon 〈em〉mftAD〈/em〉 required for the biosynthesis of mycofactocin, a ribosomally-synthesized electron carrier, is indispensable for the growth of 〈em〉M. smegmatis〈/em〉 on methanol. Our data obtained from 2,6-Dichlorophenolindophenol reduction assays also suggest that Mno uses mycofactocin as an 〈em〉in vivo〈/em〉 electron acceptor for the oxidation of methanol to formaldehyde. We thus provide here biochemical evidence for mycofactocin as an electron carrier in mycobacterial physiology.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 3 July 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Rastine Merat, Aurore Bugi-Marteyn, Ludovic J. Wrobel, Céline Py, Youssef Daali, Christoph Schwärzler, Nicolas Liaudet〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Strategies that aim to limit the adaptive response to pathway inhibition in BRAF-mutated melanoma face the inherent limit of signaling redundancy and multiplicity of possible bypass mechanisms. Drug-induced expression of selected RNA-binding proteins, like the ubiquitously expressed HuR, has the potential to differentially stabilize the expression of many genes involved in the compensatory mechanisms of adaptive response. Here, we detect in 〈em〉BRAF〈/em〉-mutated melanoma cell lines having a higher propensity for adaptive response and in non-responding melanoma tumors, a larger proportion of HuR〈sup〉Low〈/sup〉 cells in the expression distribution of HuR. Using knockdown experiments, we demonstrate, through expression profiling and phenotypic assays, that increasing the proportion of HuR〈sup〉Low〈/sup〉 cells favors the adaptive response to BRAF inhibition, provided that the HuR〈sup〉Low〈/sup〉 state stays reversible. The MAPK dependency of melanoma cells appears to be diminished as the proportion of HuR〈sup〉Low〈/sup〉 cells increases. In single-cell assays, we demonstrate that the HuR〈sup〉Low〈/sup〉 cells display plasticity in their growth expression profile. Importantly, the adaptive over-proliferating cells emerge in the subpopulation containing the HuR〈sup〉Low〈/sup〉 cells. Therapeutic concentrations of lithium salts, although they moderately increase the global expression of HuR, are sufficient to suppress the HuR〈sup〉Low〈/sup〉 cells, induce an overall less resistant expression profile and attenuate in a HuR-dependent manner the adaptive response of melanoma cells in 〈em〉ex vivo〈/em〉 assays. The therapeutic effectiveness of this approach is also demonstrated 〈em〉in vivo〈/em〉 in mice xenografts. This study has immediate clinical relevance for melanoma therapy and opens a new avenue of strategies to prevent the adaptive response to targeted cancer therapy.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Akira Nakashima, Hisateru Yamaguchi, Yu Kodani, Yoko S. Kaneko, Miho Kawata, Hiroshi Nagasaki, Toshiharu Nagatsu, Akira Ota〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Tyrosine hydroxylase (TH), which catalyzes the conversion of 〈span〉l〈/span〉-tyrosine to 〈span〉l〈/span〉-DOPA, is the rate-limiting enzyme in the biosynthesis of catecholamines. It is well known that both α-synuclein and 14-3-3 protein family members bind to the TH molecule and regulate phosphorylation of its N-terminus by kinases to control the catalytic activity. In this present study we investigated whether other proteins aside from these 2 proteins might also bind to TH molecules. Nano-LC-MS/MS analysis revealed that 5′-nucleotidase domain-containing protein 2 (NT5DC2), belonging to a family of haloacid dehalogenase-type (HAD) phosphatases, was detected in the immunoprecipitate of PC12D cell lysates that had been reacted with Dynabeads protein G-anti-TH antibody conjugate. Surprisingly, NT5DC2 had already been revealed by Genome-Wide Association Studies (GWAS) as a gene implicated in neuropsychiatric disorders such as schizophrenia, bipolar disorder, which are diseases related to the abnormality of dopamine activity in the brain, although the role that NT5DC2 plays in these diseases remains unknown. Therefore, we investigated the effect of NT5DC2 on the TH molecule. The down-regulation of NT5DC2 by siRNA increased the synthesis of catecholamines (dopamine, noradrenaline, and adrenaline) in PC12D cells. These increases might be attributed to the catalytic activity of TH and not to the intracellular stability of TH, because the intracellular content of TH assessed by Western blotting was not changed by the down-regulation of NT5DC2. Collectively, our results indicate that NT5DC2 inhibited the synthesis of dopamine by decreasing the enzymatic activity of TH.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Meilin Shi, Lina Dong, Shaohui Zheng, Pingfu Hou, Lulu Cai, Mingming Zhao, Xiuli Zhang, Qi Wang, Jingjing Li, Kai Xu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉“Bottom-up” method is a popular approach for the preparation of molybdenum disulfide quantum dots (MoS〈sub〉2〈/sub〉 QDs) benefitting from less time consumption and no high-powered sonication required. But the relatively low fluorescent quantum yield of the obtained MoS〈sub〉2〈/sub〉 QDs and the rare study about their 〈em〉in vivo〈/em〉 behavior stimulate us to do more research in this area. In this paper, we proposed a “bottom-up” hydrothermal method to prepare MoS〈sub〉2〈/sub〉 QDs with a quantum yield (QY) of 34.55% by optimizing a series of reaction conditions. The successful fluorescence imaging of tumor cells 〈em〉in vitro〈/em〉 and 〈em〉in vivo〈/em〉 as well as the systematic 〈em〉in vivo〈/em〉 behavior study such as biocompatibility, biodistribution and metabolism route provided the good basis for their wider biomedical applications.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 3 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 4〈/p〉 〈p〉Author(s): Shan Li, Meilian Yao, Chengqun Niu, Dan Liu, Zhiming Tang, Chunming Gu, Hongyan Zhao, Jing Ke, Shengying Wu, Xiong Wang, Fuyun Wu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Intracellular Ca〈sup〉2+〈/sup〉 signals play many important cellular functions such as migration, proliferation and differentiation. Store-operated Ca〈sup〉2+〈/sup〉 entry (SOCE) is a major route of Ca〈sup〉2+〈/sup〉 entry in nonexcitable cells. The activation of SOCE requires engagement between stromal interaction molecule 1 (STIM1) molecules on the endoplasmic reticulum and Ca〈sup〉2+〈/sup〉 release-activated Ca〈sup〉2+〈/sup〉 (CRAC) channel Orais (Orai1-3) on the plasma membrane. Accumulating evidence indicates that SOCE plays critical roles in cancer cell proliferation, invasion and metastasis. Here, we used the synthetic intracellular peptides derived from the C-termini of Orai channels to treat the breast cancer cells. We have found that Orai3-CT peptide exhibits stronger binding to STIM1 than Orai1-CT, and Orai3-CT peptide acts in a dominant negative fashion, blocking the STIM1-Orai1 interaction and reducing the Ca〈sup〉2+〈/sup〉 entry and proliferation of breast cancer cells.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉Schematic model for Orai peptide inhibiting the proliferation of breast cancer cells. SOAR domain of STIM1 binding to CT and NT of Orai1 leads to the channel opened and calcium entry. The synthetic intracellular peptides derived from Orai channels competitive interact with STIM1, blocking the STIM1-Orai1 interaction and calcium entry, thus reducing the activation of Ca〈sup〉2+〈/sup〉-dependent transcription factors and inhibiting the proliferation of breast cells.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X19313075-fx1.jpg" width="283" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 27 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 3〈/p〉 〈p〉Author(s): Miho Sawada, Hiroyasu Yamamoto, Ayako Ogasahara, Yuya Tanaka, Shinji Kihara〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Backgroud〈/h6〉 〈p〉Among various myocyte-derived bioactive molecules (myokines), β-aminoisobutyric acid (BAIBA) is a unique myokine that attenuates skeletal muscle insulin resistance and inflammation, increases browning of white adipose tissue, and enhances hepatic fatty acid oxidation, resulting in upregulated energy expenditure of the whole body. In the present study, we investigated the effects of BAIBA on the vascular endothelial cell function.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉The mRNA levels of proinflammatory molecules, antioxidants, and their related transcription regulators were examined by quantitative RT-PCR in BAIBA-treated human aortic or umbilical vein endothelial cells (HAEC or HUVEC, respectively), with or without tumor necrosis factor (TNF)-α stimulation. The protein expression and phosphorylation of AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) were determined by Western blot analysis.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉BAIBA pretreatment significantly suppressed the mRNA levels of the adhesion molecules in the TNF-α-stimulated HAEC and HUVEC. BAIBA treatment significantly increased the mRNA levels of antioxidant molecules, catalase, superoxide dismutases, thioredoxin, and gamma-glutamylcysteine ligases, together with mitochondrial biogenesis-related molecules, nuclear respiratory factor 1, and mitochondrial transcription factor A. In addition, BAIBA treatment significantly increased the transcription factors that regulated these genes [〈em〉i.e.〈/em〉, peroxisome proliferator-activated receptor (PPAR)-δ, PPAR-γ, estrogen-related receptor α (ERRα), and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1β]. Adenovirus-mediated PGC-1β overexpression significantly increased the mRNA levels of all antioxidant molecules. The phosphorylation levels of AMPK and eNOS were unaltered by BAIBA.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉In vascular endothelial cells, BAIBA had antiatherogenic effects through the PGC-1β−ERRα/PPAR-δ and PPAR-γ pathway. This can explain the beneficial effects of exercise on vascular endothelial function.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: 27 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 3〈/p〉 〈p〉Author(s): Yanli Lu, Linlin Wang, Jian Zhang, Jun Li, Guohua Wan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Commensal microbiota modulates the anti-tumor immune response and alters the tumor infiltration of T cells in numerous human malignancies. Moreover, the existence of commensals and microbial metabolites has been directly observed inside numerous epithelial tumors. Their effects on the host immune system, independent of the pre-existing malignancy, are not completely understood. To resolve this issue, we compared immune modulatory roles of the fecal bacteria from healthy individuals and the fecal bacteria from colorectal cancer (CRC) patients. Peripheral blood mononuclear cells that were provided by healthy donors were used as study systems. Overall, fecal bacteria could potently activate the degranulation and cytotoxicity of CD8〈sup〉+〈/sup〉 T cells. Interestingly, fecal bacteria from CRC patients in general induced higher degranulation and higher cytotoxicity than fecal bacteria from healthy individuals. These effects were dependent on the presence of antigen-presenting cells, such as monocytes and B cells, as fecal bacteria added directly to isolated CD8〈sup〉+〈/sup〉 T cells failed to induce high cytotoxicity. Additionally, fecal bacteria from CRC patients induced stronger upregulation of CD80 and NOS2 expression in monocytes than fecal bacteria from healthy individuals. On the other hand, the viability of CD8〈sup〉+〈/sup〉 T cells was significantly reduced with increasing levels of bacterial stimulation. Overall, we demonstrated that fecal bacteria from CRC patients could upregulate degranulation and cytotoxicity of CD8〈sup〉+〈/sup〉 T cells in a manner that was dependent on antigen-presenting cells, and was more proinflammatory than fecal bacteria from healthy individuals.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 27 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 3〈/p〉 〈p〉Author(s): Xin Yan, Jian Wang, Yanting Zhu, Wei Feng, Cui Zhai, Lu Liu, Wenhua Shi, Qingting Wang, Qianqian Zhang, Limin Chai, Manxiang Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The upregulation of osteopontin(OPN) has been found to contribute to the proliferation of pulmonary artery smooth muscle cells(PASMCs), and activation of PPARγ has been shown to suppress OPN expression in THP-1 cells. However, the molecular mechanisms underlying the upregulation of OPN expression and PPARγ agonist modulation of OPN expression in PASMCs remain largely unclear. Here we found that S1P stimulated PASMCs proliferation and up-regulated OPN expression in rat PASMCs, which was accompanied with the activation of phospholipase C(PLC), calcineurin and translocation of NFATc3 to nucleus. Further study showed that inhibition of PLC by U73122, suppression of calcineurin activity by cyclosporine A(CsA) or knockdown of NFATc3 using small interfering RNA suppressed S1P-induced OPN up-regulation. Activation of PPARγ by pioglitazone suppressed S1P-induced activation of calcineurin/NFATc3 signaling pathway and followed OPN up-regulation. Taken together, our study indicates that S1P stimulates OPN expression by activation of PLC/calcineurin/NFATc3 signaling pathway, and activation of PPARγ suppresses calcineurin/NFATc3-mediated OPN expression in PASMCs.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 27 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 3〈/p〉 〈p〉Author(s): Ryan A. Bennick, Alexis A. Nagengast, Justin R. DiAngelo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In Western societies where food is abundant, these excess nutrients are stored as fats mainly in adipose tissue. Fats are stored in structures known as lipid droplets, and a genome-wide screen performed in 〈em〉Drosophila〈/em〉 cells has identified several genes that are important for the formation of these droplets. One group of genes found during this screen included those that regulate mRNA splicing. Previous work from our lab has identified some splicing factors that play a role in regulating fat storage; however, the full complement of splicing proteins that regulate lipid metabolism is still unknown. In this study, the levels of a number of serine-arginine (SR) domain containing splicing factors (RSF1, RBP1, RBP1-like, SF2 and Srp-54) were decreased using RNAi in the adult fat body to assess their role in the control of 〈em〉Drosophila〈/em〉 metabolism. Decreasing SF2 and RBP1 showed increased triglycerides, while inducing RNAi towards RSF1, RBP1-Like and Srp-54 had no effect on triglycerides. Interestingly, the increased triglyceride phenotype in the SF2-RNAi flies was due to an increase in the amount of fat stored per cell while the RBP1-RNAi flies have more fat cells. In addition, the splicing of the β-oxidation enzyme, CPT1, was altered in the SF2-RNAi flies potentially promoting the increased triglycerides in these animals. Together, this study identifies novel splicing factors responsible for the regulation of lipid storage in the 〈em〉Drosophila〈/em〉 fat body and contributes to our understanding of the mechanisms, which influence the regulation of fat storage in adipose-like cells.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 27 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 3〈/p〉 〈p〉Author(s): Malena Landoni, Tamara Piñero, Luciana L. Soprano, Facundo Garcia-Bournissen, Laura Fichera, Monica I. Esteva, Vilma G. Duschak, Alicia S. Couto〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This study shows the effects of tamoxifen, a known estrogen receptor antagonist used in the treatment of breast cancer, on the sphingolipid pathway of 〈em〉Trypanosoma cruzi,〈/em〉 searching for potential chemotherapeutic targets. A dose-dependent epimastigote growth inhibition at increasing concentration of tamoxifen was determined. In blood trypomastigotes, treatment with 10 μM showed 90% lysis, while 86% inhibition of intracellular amastigote development was obtained using 50 μM. Lipid extracts from treated and non-treated metabolically labelled epimastigotes evidenced by thin layer chromatography different levels of sphingolipids and MALDI-TOF mass spectrometry analysis assured the identity of the labelled species. Comparison by HPLC-ESI mass spectrometry of lipids, notably exhibited a dramatic increase in the level of ceramide in tamoxifen-treated parasites and a restrained increase of ceramide-1P and sphingosine, indicating that the drug is acting on the enzymes involved in the final breakdown of ceramide. The ultrastructural analysis of treated parasites revealed characteristic morphology of cells undergoing an apoptotic-like death process. Flow cytometry confirmed cell death by an apoptotic-like machinery indicating that tamoxifen triggers this process by acting on the parasitic sphingolipid pathway.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X19312872-fx1.jpg" width="254" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 27 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 3〈/p〉 〈p〉Author(s): Kaiyue Zhang, Wenwen Yang, Hongbin Yu, Can Fu, Xiaxia Liu, Jian Liu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The TFIIB-related factor (BRF) family plays vital roles in RNA polymerase (Pol) III transcription initiation. However, little is known about the role of BRF in plants. Here, we report BRF1 and BRF2 are involved in Arabidopsis reproduction. In this study, we generated BRF1 and BRF2 double mutant plants. We found that no homozygous double mutants of 〈em〉brf1brf2〈/em〉 were obtained when 〈em〉brf1〈/em〉 and 〈em〉brf2〈/em〉 were crossed, although 〈em〉brf1〈/em〉 and 〈em〉brf2〈/em〉 mutants individually developed and reproduced normally. Further experiments revealed that heterozygous 〈em〉brf1/〈/em〉 + 〈em〉brf2/〈/em〉 + produced abnormal pollen and had no seeds in some placentas of siliques. Genetic data derived from reciprocal crosses showed that BRF2 plays a dominant role in Arabidopsis reproduction. Taken together, a double mutation of BRF1 and BRF2 results in a high degree of aborted macrogametes and microgametes and complete failure in zygote generation, ultimately leading to sterility.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 27 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 3〈/p〉 〈p〉Author(s): Hai Yu, Suojun Zhang, Ahmed N. Ibrahim, Jia Wang, Zhong Deng, Maode Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Regulator of chromosome condensation 2 (RCC2) is a regulator of cell-cycle progression linked in multiple cancers to pro-tumorigenic phenomena including promotion of tumor growth, tumor metastases and poorer patient prognoses. However, the role of RCC2 in GBM remains under-investigated. Here, we sought to determine the relevance of RCC2 in GBM, as well as its roles in GBM development, progression and prognosis. Initial clinical evaluation determined significant RCC2 enrichment in GBM when compared to normal brain tissue, and elevated expression was closely associated with a poorer prognosis in glioma patients. Via shRNA inhibition, we determined that RCC2 is essential to tumor proliferation and tumorigenicity 〈em〉in vitro〈/em〉 and 〈em〉in vivo〈/em〉. Additionally, RCC2 was determined to promote radioresistance of GBM tumor cells. Investigation of the underlying mechanisms implicated DNA mismatch repair, JAK-STAT pathway and activated transcription of DNA methyltransferase 1 (DNMT1). For validation, pharmacologic inhibition via administration of a DNMT1 inhibitor demonstrated attenuated GBM tumor growth both 〈em〉in vitro〈/em〉 and 〈em〉in vivo〈/em〉. Collectively, this study determined a novel therapeutic target for GBM in the form of RCC2, which plays a pivotal role in GBM proliferation and radio-resistance via regulation of DNMT1 expression in a p-STAT3 dependent manner.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 27 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 3〈/p〉 〈p〉Author(s): Ke Gong, Zi-Jun Gong, Pin-Xiang Lu, Xiao-ling Ni, Sheng Shen, Han Liu, Ji-Wen Wang, De-Xiang Zhang, Hou-Bao Liu, Tao Suo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Gallbladder carcinoma (GBC) is always diagnosed at an advanced stage, and patients often miss the opportunity for surgery. Gemcitabine (GEM) and platinum-based drugs, including oxaliplatin (OXA), are mainstays of chemotherapy. However, drug resistance causes treatment failure. Hence, salvage mechanisms are critical to improve outcomes. This study revealed the positive correlation between placenta-specific protein 8 (PLAC8) overexpression and PD-L1 overexpression in GBC. Given the roles of PLAC8 and PD-L1 in chemotherapy resistance, GEM-resistant and OXA-resistant cell lines (SGC966GR and SGC966OR, respectively) were established to test whether and how PLAC8 and PD-L1 function in chemotherapy resistance. Drug-insensitive SGC966GR and SGC966OR cells upregulated MRP and MDR1 and had high expression of PLAC8. PLAC8 blockade using siRNA reversed chemotherapy resistance and downregulated MRP and MDR1 in SGC966GR and SGC966OR cells, suggesting that PLAC8 mediates chemotherapy resistance in GBC. Consistent with the increased mRNA levels of PD-L1 after the acquisition of resistance, PLAC8 knockdown reduced PD-L1 mRNA expression in SGC966GR and SGC966OR cells. In conclusion, PLAC8 overexpression in GBC patients positively correlated with PD-L1 expression. PLAC8 conferred resistance to GEM and OXA by upregulating PD-L1 expression, and PLAC8 or PD-L1 blockade may have potential for overcoming chemotherapy resistance, providing therapeutic options for chemotherapy-refractory GBC patients.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 27 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 3〈/p〉 〈p〉Author(s): Yuya Miki, Tomoaki Morioka, Atsushi Shioi, Kenta Fujimoto, Takeshi Sakura, Hideki Uedono, Yoshinori Kakutani, Akinobu Ochi, Katsuhito Mori, Tetsuo Shoji, Masanori Emoto, Masaaki Inaba〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Oncostatin M (OSM) is a cytokine of the interleukin-6 family and plays a role in various disorders such as cancer and inflammatory diseases, which are often accompanied by skeletal muscle atrophy, or sarcopenia. However, the role of OSM in the regulation of skeletal muscle mass remains to be identified. In this study, we investigated the effect of OSM on C2C12 myotube formation 〈em〉in vitro〈/em〉. C2C12 myoblasts were induced to differentiate into myotubes for 3 days and then treated with OSM for 24 or 48 h. The diameter of differentiated C2C12 myotubes were reduced by 18.7% and 23.3% compared to control cells after treatment with OSM for 24 and 48 h, respectively. The expression levels of MyoD and myogenin were decreased, while those of atrogin-1, CCAAT/enhancer binding protein δ, and OSM receptor were increased in C2C12 myotubes treated with OSM for 24 h compared to control cells. Furthermore, the inhibitory effect of OSM on myotube formation was significantly attenuated by pretreatment with an inhibitor of signal transducer and activator of transcription (STAT) 3 or by knockdown of 〈em〉Stat3〈/em〉. Finally, the OSM-induced changes in the expression levels of MyoD, myogenin, and atrogin-1 were reversed by pretreatment with an inhibitor of STAT3 or by 〈em〉Stat3〈/em〉 knockdown in C2C12 myotubes. In conclusion, OSM induces C2C12 myotube atrophy by inhibiting myogenic differentiation and activating muscle degradation in a STAT3-dependent manner.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 27 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 3〈/p〉 〈p〉Author(s): Paola Francini Fávero, Victor Augusto Vieira de Lima, Priscila Helena dos Santos, Ana Paula Marques Andrade, Leonardo Oliveira Mendes, Francis Lopes Pacagnelli, Anthony César de Souza Castilho〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉To assist in evaluating and quantifying tissue changes, fractal dimension (FD) is a useful method for assessing the organization in an image from fractals that describes the amount of space and the self-similarity of the structure, once FD detects subtle morphological changes and performs functional quantitative measures. Here, we hypothesized that fractal analysis may be different in functional and regressing bovine corpus luteum (CL) and may be correlated with differential expression of genes involved in extracellular matrix remodeling. CL presents two developmental stages, the functional and regressing CL, according to progesterone levels and morphology. First, we found a lower FD in functional CL using HE staining and picrosirius red approach. Additionally, we found a great amount of total collagen in regressing CL. Regarding gene expression, we showed an up regulation of 〈em〉COL1A1, COL1A2, MMP2〈/em〉, and 〈em〉MMP14〈/em〉 and a down regulation of 〈em〉TIMP1〈/em〉 and 〈em〉TIMP2〈/em〉 in regressing CL compared to the functional one. Thus, we concluded that differential FD observed during luteal regression is an effective method to evaluate the tissue changes observed during luteal development in cattle and is related to differential quantity of genes involved in extracellular matrix remodeling.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 27 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 3〈/p〉 〈p〉Author(s): Tangliang Zhao, Xiaolong Liang, Junming Chen, Yi Bao, Anbang Wang, Xinxin Gan, Xin Lu, Linhui Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Angiopoietin-like proteins (ANGPTLs) 〈u〉comprise〈/u〉 a group of proteins that are structurally similar to angiopoietins. In our previous studies, we found that ANGPTL3 can inhibit sorafenib resistance in renal cell carcinoma (RCC). According to bioinformatics analysis based on data in the Cancer Genome Atlas (TCGA), we found that expression of ANGPTL3 was significantly lower in RCC tissues than in adjacent tissues and that disease-free survival and overall survival were significantly shorter in patients with lower ANGPTL3 levels than in those with higher ANGPTL3 levels. Consistent with these results, we demonstrated that RCC tissues exhibited lower ANGPTL3 mRNA and protein expression levels than paired adjacent tissues. Moreover, we found that ANGPTL3 upregulation was associated with better clinical outcomes in RCC patients. ANGPTL3 overexpression inhibited the metastatic ability in RCC cells. Mechanistically, ANGPTL3 〈u〉binds〈/u〉 to vasodilator-stimulated phosphoprotein (VASP) and inhibits its phosphorylation at amino acid 157 in RCC cells. Finally, ANGPTL3 expression and VASP-157 phosphorylation 〈u〉may〈/u〉 be combined to predict the prognosis of RCC patients. Overall, our findings describe the role of ANGPTL3 in inhibiting RCC metastasis and thus provide new molecular 〈u〉markers〈/u〉 for RCC treatment and prognosis.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 27 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 516, Issue 3〈/p〉 〈p〉Author(s): Yong Won Choi, Ga Eun Nam, Young Hwa Kim, Jung Eun Yoon, Ji Hee Park, Jang Hee Kim, Seok Yun Kang, Tae Jun Park〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉B-Raf〈sup〉V600E〈/sup〉 oncogene mutation occurs in various cancers and is associated with tumor initiation. However, genetic modification of B-Raf〈sup〉V600E〈/sup〉 in cells induces MAPK activation and results in oncogene-induced senescence. Overcoming the oncogene-induced senescence by B-Raf〈sup〉V600E〈/sup〉 requires activation of another oncogene pathway, such as AKT signaling. In the present study, we explored the factors involved in overcoming the senescence program in cells activated by B-Raf〈sup〉V600E〈/sup〉 and AKT signaling. B-Raf〈sup〉V600E〈/sup〉 activation caused a feedback inhibition of AKT phosphorylation and resulted in downregulation of FoxM1, one of the AKT downstream components. AKT activation by PTEN downregulation induced FoxM1 expression, and co-expression of B-Raf〈sup〉V600E〈/sup〉 and FoxM1 overcame the cellular senescence. These observations suggested that FoxM1 is critical downstream gene of AKT and functions to overcome B-Raf〈sup〉V600E〈/sup〉-induced senescence.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 29 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Jaehak Lee, Ilju Kim, Eunsu Yoo, Seung Joon Baek〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Non-steroidal anti-inflammatory drug activated gene-1 (NAG-1), also known as growth differentiation factor 15 (GDF15), is a TGF-β (transforming growth factor beta) superfamily protein with a distinctive secretion pathway. NAG-1 is associated with multiple diseases including cancer, wherein it plays a role in both pro- and anti-cancer activities. We previously reported that NAG-1 is translocated to different subcellular compartments and its activity depends on its localization. In this paper, we report that the transfection of a novel peptide corresponding to the nuclear localization signal (NLS) of NAG-1 blocks its translocation to the nucleus. Further, accumulation of NAG-1 in the cytoplasm decreased mitochondrial membrane potential, thus implying apoptosis induction as a consequence. Overall, our results indicate that the novel peptide derived from NAG-1 NLS sequence is a promising tool for enhancing the anti-tumorigenic activity of NAG-1.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X19316134-fx1.jpg" width="350" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 29 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Yanjun Zeng, Qingwu Qin, Keyu Li, Haitao Li, Chao Song, Yi Li, Minhui Dai, Fengyu Lin, Zhi Mao, Qian Li, Yuan Long, Yifei Fan, Pinhua Pan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉To explore the effect of double-stranded RNA-dependent kinase (PKR) in acute lung injury (ALI) and resultant acute respiratory distress syndrome (ARDS). A mouse model of lipopolysaccharide (LPS)-induced ALI was used to evaluate the levels of phosphorylated (p)-PKR and NLRP3 in lung tissue, and the protective effects of a PKR inhibitor on lung injury. And in vitro, macrophages were incubated with LPS, with or without PKR inhibitor pre-treatment. It was observed that the levels of p-PKR protein and NLRP3 protein were significantly increased compared with those in control tissues after LPS administration. Meanwhile, treatment with PKR inhibitor decreased inflammation, injury score, wet/dry weight ratio, bronchoalveolar lavage fluid (BALF) protein levels, neutrophil count in BALF, myeloperoxidase activity and expression of high-mobility group box1(HMGB1) and interleukin(IL)-1β in the lungs of LPS-challenged mice. In vitro, we demonstrated that the levels of p-PKR and NLRP3, and cell mortality rate were increased in macrophages which were incubated with LPS compared with those without LPS administration, and PKR inhibitor significantly suppressed the level of NLRP3, caspase-1, HMGB1 and IL-1β. These results indicate that PKR plays a key role in ALI through NLRP3-pyrotosis pathway and pharmacological inhibition of PKR may have potential therapeutic effects in the treatment of patients with ALI and ARDS.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 29 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Marcelo Gomes Granja, Luis Eduardo Gomes Braga, Raphael Monteiro de Oliveira, Eliezer de Mello Silva, Cassiano Felippe Gonçalves-de-Albuquerque, Adriana Ribeiro Silva, Hugo Caire de Castro-Faria-Neto, Aline Araujo dos Santos, Elizabeth Giestal-de-Araujo〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Trophic factors are involved in different cellular responses. Previously we demonstrated that IL-4 treatment induces an increase in retinal ganglion cell survival (RGCS) and regulates cholinergic differentiation of retinal cells 〈em〉in vitro〈/em〉. Data from literature show that IGF-1 also promotes RGCS, an effect mediated by PI-3K/AKT pathway. The aim of this study was to investigate the role of IGF-1 and IGF-1R on RGCS mediated by IL-4 treatment and the role of M1 acetylcholine receptors in this effect. Here we show that the effect of IL-4 on RGCS depends on IGF-1 and IGF-1R activation, the PI-3K/AKT and NFkB intracellular pathways and depends on M1 mAChRs activation. IGF-1 increases the levels of M1 mAChRs in 15min, 45min, 24 h and 48 h in mixed retinal cells culture, modulates the levels of IL-4, pIGF-1R, IGF-1R. IL-4 modulates IGF-1, pIGF-1R and IGF-1R levels in different time intervals. These results put in evidence a crosstalk between IL-4 and IGF-1 and a role of M1 mAChRs, IGF-1 and IGF-1R in RGCS mediated by IL-4.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 21 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Yunfen Huang, Yuying Li, Yingying Qu, Yue Zheng, Mengting Ouyang, Yunqing Zhang, Wei Lai, Qingfang Xu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Autophagy has been associated with a variety of diseases especially aging. Human dermal fibroblasts (HDFs) can internalize and then degrade elastin, collagen and advanced glycation end products (AGEs) in lysosomes, which plays prominent roles in extracellular matrix homeostasis and AGEs removal in the dermis. Although autophagy has been reported to be decreased in photoaged fibroblasts, the underlying mechanism and its relevance to photoaging remain elusive. Here, we showed that GFP-LC3 puncta per cell, LC3Ⅰ/Ⅱ conversion and p62 expression were significantly increased, whereas beclin1 expression was not altered in UVA-induced photoaged fibroblasts compared with non-photoaged control. Moreover, autophagic flux was not significantly affected by chloroquine treatment, but was remarkably induced by rapamycin treatment in photoaged fibroblasts, suggesting that UVA-induced photoaging might inhibit autophagy at the degradation stage. Further lysosomal function studies demonstrated that degradation of formed autophagosomes, LC3Ⅱprotein and DQ-Green BSA was all dramatically decreased in photoaged fibroblasts. LysoSensor yellow/blue DND 160 staining and flow cytometry assays demonstrated that photoaging obviously attenuated lysosomal acidification. Also, decreased expression of cathepsin B, L and D was found in photoaged fibroblasts. These data suggest that lowered lysosomal acidity and decreased cathepsins expression might contribute to the inhibition of autophagic degradation, which might be crucial in the development of photoaging through impairing intracellular degradation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 21 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Xuanzhong Wang, Shan Lu, Chuan He, Chongcheng Wang, Lei Wang, Meihua Piao, Guangfan Chi, Yinan Luo, Pengfei Ge〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉RSL3 is a type of small molecular compound which can inactivate glutathione peroxidase 4 (GPX4) and induce ferroptosis, but its role in glioma cell death remains unclear. In this study, we found RSL3 inhibited the viabilities of glioma cells and induced glioma cell death in a dose-dependent manner. In vitro studies revealed that RSL3-induced cell death was accompanied with the changes of autophagy-associated protein levels and was alleviated by pretreatment of 3-Methyladenine, bafilomycin A1 and knockdown of ATG5 with siRNA. The ATP and pyruvate content as well as the protein levels of HKII, PFKP, PKM2 were decreased in cells treated by RSL3, indicating that RSL3 induced glycolysis dysfunction in glioma cells. Moreover, supplement of exterior sodium pyruvate, which was a final product of glycolysis, not only inhibited the changes of autophagy-associated protein levels caused by RSL3, but also prevented RSL3-induced cell death. In vivo data suggested that the inhibitory effect of RSL3 on the growth of glioma cells was associated with glycolysis dysfunction and autophagy activation. Taken together, RSL3 induced autophagic cell death in glioma cells via causing glycolysis dysfunction.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 22 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Ning Luo, Dan-dan Chen, Li Liu, Li Li, Zhong-ping Cheng〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The CXCL12/CXCR4 axis is strongly implicated as key determinant of tumor invasion and metastasis in ovarian cancer. However, little is known about the potential downstream signals of the CXCL12/CXCR4 axis that contribute to ovarian cancer cell invasion and metastasis. ARHGAP10, a member of Rho GTPase activating proteins is a potential tumor suppressor gene in ovarian cancer. In this study, a negative correlation between the protein levels of CXCL12, CXCR4, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR2) and ARHGAP10 was uncovered in ovarian cancer tissues and paired adjacent noncancerous tissues. CXCL12 stimulation reduced the expression of ARHGAP10. Furthermore, the pretreatment of CXCR4 inhibitor (AMD3100) or the vascular endothelial growth factor receptor-2 (VEGFR2) inhibitor (SU1498) abrogated the CXCL12-deduced expression of ARHGAP10. Finally, an 〈em〉in vitro〈/em〉 functional assay revealed that CXCL12 did not stimulate ovarian cancer cell invasion when ARHGAP10 was overexpressed or when ovarian cancer cells were pre-treated with AMD3100 or SU1498. Knockdown of ARHGAP10 significantly suppressed the inhibitory effects of SU1498 on ovarian cancer cell invasion and lung metastasis. In summary, these findings suggest that CXCL12/CXCR4 promotes ovarian cancer cell invasion by suppressing ARHGAP10 expression, which is mediated by VEGF/VEGFR2 signaling.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 21 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Yojiro Ishida, Keiko Inouye, Ouyang Ming, Masayori Inouye〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉MazF is a sequence-specific endoribonuclease or mRNA interferase, which cleaves RNA at a specific sequence. Since the expression of a specific gene or a group of specific genes can be regulated by MazF, expanding the repertoire of recognition sequences by MazF mRNA interferases is highly desirable for biotechnological and medical applications. Here, we identified a gene for a MazF homologue (MazFme) from 〈em〉Methanohalobium evestigatum〈/em〉, an extremely halophilic archaeon. In order to suppress the toxicity of MazFme to the 〈em〉E. coli〈/em〉 cells, the C-terminal half of the cognate antitoxin MazEme was fused to the N-terminal end of MazFme. Since the fusion of the C-terminal half of MazEme to MazFme was able to neutralize MazFme toxicity, the MazEme-MazFme fusion protein was expressed in a large amount without any toxic effects. After purification of the MazEme, the free MazFme RNA cleavage specificity was determined by primer extension and synthetic ribonucleotides, revealing that MazFme is a CUGGU/UUGGU-specific endoribonuclease.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 21 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Takujiro Homma, Sho Kobayashi, Junichi Fujii〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Singlet oxygen causes a cytotoxic process in tumor cells in photodynamic therapy (PDT) and skin photoaging. The mechanism responsible for this cytotoxicity is, however, not fully understood. 1-Methylnaphthalene-4-propionate endoperoxide (MNPE) is a cell-permeable endoperoxide that generates pure singlet oxygen. We previously reported that cell death induced by MNPE did not show the typical profile of apoptosis, and the cause of this cell death remains elusive. We report herein on an investigation of the mechanism for MNPE-induced cell death from the view point of ferroptosis. The findings indicate that the MNPE treatment decreased the viabilities of mouse hepatoma Hepa 1-6 cells in vitro, and that this decrease was accompanied by increases in the concentrations of both intracellular ferrous iron and the level of lipid peroxidation, but that the caspase-mediated apoptotic pathway was not activated. The intracellular levels of cysteine and glutathione were not affected by the MNPE treatment. Importantly, an assay of lactate dehydrogenase activity revealed that the cell death caused by MNPE was suppressed by ferrostatin-1, a ferroptosis-specific inhibitor. Collectively, these results strongly indicate that ferroptosis is the main cell death pathway induced by singlet oxygen.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 21 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Tian Wang, Xi-Ya Sun, Ai-Ling Li, Ming-Xing Zhou, Yang Han, Jiao-Zhen Zhang, Dong-Mei Ren, Hong-Xiang Lou, Xiao-Ning Wang, Tao Shen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Oxidative stress is one of the main pathogenesis for many human diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays a key role in regulating intracellular antioxidant responses, and thus activation of Nrf2/ARE signaling pathway is a potential chemopreventive or therapeutic strategy to treat diseases caused by oxidative damage. In the present study, we have found that treatment of Beas-2B cells with botrysphins D (BD) attenuated sodium arsenite [As (III)]-induced cell death and apoptosis. Meanwhile, BD was able to upregulate protein levels of Nrf2 and its downstream genes NQO1 and γ-GCS through inducing Nrf2 nuclear translocation, enhancing protein stability, and inhibiting ubiquitination. It was also found that BD-induced activation of the Nrf2/ARE pathway was regulated by PI3K, MEK1/2, PKC, and PERK kinases. Collectively, BD is a novel activator of Nrf2/ARE pathway, and is verified to be a potential preventive agent against oxidative stress-induced damage in human lung tissues.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X19315918-fx1.jpg" width="496" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 21 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): ChuanLing Tang, JiaPing Pan, Hui Li, Bin He, Ling Hong, XiaoMing Teng, DaJin Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Oxidative stress is associated with functional disorder of trophoblast cells. Our previous studies have demonstrated that cyclosporin A (CsA) promotes the activity of normal human trophoblast cells. We further investigated the role and mechanism of CsA on oxidative stress in trophoblast cells. JEG-3 cells were co-cultured with H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 and CsA. Cell viability and morphology were measured by MTT assay and inverted microscope. Reactive oxygen species (ROS) was analyzed by fluorescence microscopy. Cell mitochondrial membrane potential (MMP) was determined by flow cytometric analysis. Malondialdehyde (MDA) production, superoxide dismutase (SOD) and catalase (CAT) activities were examined using colorimetric assays. The expression and phosphorylation of FAK and Src kinase proteins were examined by western blotting. CsA increased JEG-3 cell viability and reduced the morphologic injury induced by H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 treatment. CsA decreased ROS and MDA production, increased SOD and CAT activities, and restored the MMP of H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉 treated JEG-3 cells. CsA administration suppressed H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉-induced reduction of FAK and Src phosphorylation. Blocking the activation of FAK or Src attenuated the protective effect of CsA on JEG-3 cells in H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉-induced oxidative injury. CsA protects JEG-3 cells from H〈sub〉2〈/sub〉O〈sub〉2〈/sub〉-induced oxidative injury, and the FAK/Src signaling pathway plays an important role in this process.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 21 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Yu Zhao, Gautam Mahajan, Chandrasekhar R. Kothapalli, Xue-Long Sun〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Cell surface receptors are the key contributors of macrophage function. Most macrophage cell surface receptors are glycoproteins with sialic acids at the terminal of their glycans. It is well recognized that lipopolysaccharide (LPS) induces cell surface sialylation changes that may in turn contribute to macrophage functions. In addition, cellular mechanics such as elasticity is also a major determinant of macrophage function, which in turn is modulated by LPS. In this report, we characterized the sialylation status of macrophages upon LPS stimulation and assessed the changes in its mechanical properties and function. Specifically, we confirmed that sialylation status is closely related to macrophage biomechanical characteristics (elastic modulus, tether force, tether radius, adhesion force, and membrane tension) and thus directly involved in macrophage function. Further, we modulated macrophage sialylation status by feeding the cell with exogenous free sialic acid (Neu5Ac, Neu5Gc) and sialidase inhibitors, and examined the resulting effects on cellular mechanics and function. A systematic recognition of sialylation status related to cellular mechanics of macrophages will contribute to defining their phenotypes and elucidate macrophage functional diversity.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X19316122-fx1.jpg" width="258" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: 8 October 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 518, Issue 1〈/p〉 〈p〉Author(s): You-Jian Zhang, Jian-Rong Song, Ming-Jun Zhao〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Stroke is reported as a leading cause of mortality and disability in the world. Neuroinflammation is significantly induced responding to ischemic stroke, and this process is accompanied with microglial activation. However, the pathogenesis contributing to ischemic stroke remains unclear. NR4A1 (Nur77) is a nuclear receptor that is expressed in macrophages, playing a significant role in regulating inflammatory response. In the present study, we attempted to explore the effects of NR4A1 on ischemic stroke using 〈em〉in vivo〈/em〉 and 〈em〉in vitro〈/em〉 studies. Results suggested that NR4A1 expression in microglia was markedly increased after cerebral ischemic damage. Then, we found that NR4A1 knockout attenuated ischemia-triggered infarction volume and neuron injury. Also, cognitive impairments were improved in ischemic mice with NR4A1 deficiency, resulting in functional improvements. Moreover, M1 polarization in microglia and neutrophil recruitment was significantly alleviated by NR4A1 deletion, as evidenced by the reduced expression of M1 markers, chemokines, as well as intracellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO) levels. Importantly, we found that NR4A1 could interact with nuclear factor-κB (NF-κB)/p65 based on 〈em〉in vivo〈/em〉 and 〈em〉in vitro〈/em〉 results. Suppressing p65 activation by the use of its inhibitor clearly reduced the NR4A1 expression, M1 polarization and neutrophil recruitments, while rescued the expression of anti-inflammatory factors in microglia treated with oxygen-glucose deprivation (OGD). Therefore, NR4A1 suppression in microglia restrained neuroinflammation through interacting with NF-κB/p65 to attenuate ischemic stroke.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 21 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Deepika Sharma, Monika Choudhary, Jitendraa Vashistt, Rahul Shrivastava, Gopal Singh Bisht〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Acinetobacter baumannii〈/em〉 is one of the clinically important nosocomial pathogen that has become resistant to most of the conventional antimicrobials. Biofilms formed by 〈em〉A. baumannii〈/em〉 are difficult to eradicate, thereby highlighting the need for new therapeutic options to treat biofilm associated infections. Antimicrobial peptides have recently emerged as new alternatives to conventional antibiotics, but peptides often suffer with drawbacks such as poor proteolytic stability and high cost of production. To tackle these limitations, mimetics based on antimicrobial peptides are usually designed and synthesized. In this study we have designed and synthesized a peptoid based on a minimum amphipathic template of a twelve residue cationic peptide. Antimicrobial evaluation of peptide and peptoid was carried out against biofilm producing 〈em〉A. baumannii〈/em〉 strains〈em〉.〈/em〉 Further, proteolytic stability study of these compounds was carried out in human serum and morphological alterations caused by them on 〈em〉A. baumannii〈/em〉 were visualized by SEM analysis. In addition, these compounds were found to be non toxic to human erythrocytes at their minimum inhibitory concentrations against 〈em〉A. baumannii〈/em〉 strains. Overall results obtained in this study suggest that these compounds might be potential antimicrobial agents against biofilm forming 〈em〉A. baumannii〈/em〉 and it may be postulated that their mode of action on 〈em〉A. baumannii〈/em〉 is disruption of bacterial cell membrane.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Shahper N. Khan, Shakir Khan, Lama Misba, Muzammil Sharief, Amiruddin Hashmi, Asad U. Khan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Candida albicans〈/em〉 frequently causes variety of superficial and invasive disseminated infections in HIV infected patients. Further, the emergence of non albicans species causing candidiasis predominantly in patients with advanced immune-suppression and drug resistance brings great apprehension. Hence, in this study we evaluate the capability of eugenol (EUG), a natural compound in combination with less toxic concentrations of amphotericin B (AmpB) for enhanced antifungal effects and reduced toxicity. Antifungal activity and time-kill assay were employed according to Clinical Laboratory Standard Institute (CLSI) guidelines with minor modifications on clinical isolates of 〈em〉Candida albicans〈/em〉. To confirm the synergistic interaction of EUG and AmpB, checkerboard experiments were employed. Interestingly, EUG-Amp B combination shows many fold higher anti-candida activity compared to single component treatment. Furthermore, our results depicts reactive oxygen species (ROS) driven killing and mitochondrial hyperpolarisation on treatment. Our data also suggests inhibition of calcium channel by EUG and predicts longer retainment of AmpB. Pronounced cellular damage was observed with combination treatment than to EUG and AmpB alone. Our finding is helpful for the removal of toxic concentrations of antifungal agents.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Yi Qian, Yaoshu Teng, Yuandong Li, Xiaojiang Lin, Ming Guan, Yong Li, Xiaolin Cao, Yueqiu Gao〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Dysregulated microRNAs (miRNAs) play crucial roles in the occurrence and development of multiple tumours, but their roles in the progression of nasal squamous cell carcinoma (NSCC) remain unknown. The aim of our study was to investigate the potential function and molecular mechanism of miR-143-3p in NSCC. Expression of miRNA and mRNA was detected by quantitative real-time reverse transcription-PCR (qRT-PCR). Forced overexpression of miR-143-3p was established by transfecting mimics into NSCC cell line. Then, we investigated the role of miR-143-3p in human NSCC cell proliferation, apoptosis, cycle and migration by using MTT, flow cytometry and transwell assays. Bioinformatics analysis, qRT-PCR, Western blot and luciferase reporter analysis were performed to validate the relationship between miR-143-3p and its potential targets. We found that miR-143-3p was substantially downregulated in human NSCC tissues and cell line. Forced upregulation of miR-143-3p significantly attenuated cell proliferation and migration. Furthermore, this change could induce apoptosis and G1-phase arrest of NSCC cells. Mechanistically, miR-143-3p directly targeted and significantly suppressed Bcl-2 and IGF1R expression. In summary, miR-143-3p regulation of the proliferation, apoptosis, cell cycle and migration of NSCC probably partly depends on inhibition of Bcl-2 and IGF1R, indicating that miR-143-3p may be a novel molecular therapeutic target for NSCC.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X1931592X-fx1.jpg" width="272" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: Available online 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Emily M. Cross, David Aragão, Kate M. Smith, Karli I. Shaw, Jeffrey D. Nanson, Shane R. Raidal, Jade K. Forwood〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Acinetobacter baumannii〈/em〉 (〈em〉A. baumannii〈/em〉) is a clinically relevant, highly drug-resistant pathogen of global concern. An attractive approach to drug design is to specifically target the type II fatty acid synthesis (FASII) pathway which is critical in Gram negative bacteria and is significantly different to the type I fatty acid synthesis (FASI) pathway found in mammals. Enzymes involved in FASII include members of the short-chain dehydrogenase/reductase (SDR) superfamily. SDRs are capable of performing a diverse range of biochemical reactions against a broad spectrum of substrates whilst maintaining conserved structural features and sequence motifs. Here, we use X-ray crystallography to describe the structure of an SDR from the multi-drug resistant bacteria 〈em〉A. baumannii,〈/em〉 previously annotated as a putative FASII FabG enzyme. The protein was recombinantly expressed, purified, and crystallized. The protein crystals diffracted to 2.0 Å and the structure revealed a FabG-like fold. Functional assays revealed, however, that the protein was not active against the FabG substrate, acetoacetyl-CoA. This study highlights that database annotations may show the necessary structural hallmarks of such proteins, however, they may not be able to cleave substrates that are typical of FabG enzymes. These results are important for the selection of target enzymes in future drug development.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 21 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Taotao Li, Shiyan Yang, Xinke Kang, Wei Lei, Kang Qiao, Dawei Zhang, Honghui Lin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Plant growth, development and interaction with the environment involve the action of transcription factor. bHLH proteins play an essential and often conserved role in the plant kingdom. However, bHLH proteins that participate in the cell division process are less well known. Here, we report that the bHLH transcription factor gene 〈em〉AtUPB1〈/em〉 is involved in mediating cell cycle progression and root development. In yeast cells, 〈em〉AtUPB1〈/em〉 inhibits cells proliferation and the cells had increased numbers of nuclei. 〈em〉UPB1〈/em〉 overexpression decreased the expression of the cell division marker 〈em〉CYCB1-1〈/em〉, and 〈em〉CDKA1〈/em〉 expression could overcome the defect of 〈em〉UPB1〈/em〉 overexpression. Moreover, 〈em〉UPB1〈/em〉 could directly bind to the promoter region of the 〈em〉SIM〈/em〉 and 〈em〉SMR1〈/em〉 genes to regulate cell cycle. These results support a new role for 〈em〉AtUPB1〈/em〉 regulating root meristem development by mediating the expression of 〈em〉SIM/SMR1〈/em〉 genes.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 21 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Takuto Fujii, Siriporn Phutthatiraphap, Takahiro Shimizu, Hiroshi Takeshima, Hideki Sakai〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In the stomach, Sonic Hedgehog (Shh) is highly expressed in gastric parietal cells, and acts as a morphogen in early development of the organ. Here, we found that the cleaved N-terminal fragment of Shh (Shh-N) was abundantly expressed in hog gastric vesicles derived from the apical membrane of parietal cells. Interestingly, Shh-N recombinant significantly decreased K〈sup〉+〈/sup〉-dependent ATP-hydrolyzing activity, which is sensitive to an inhibitor of H〈sup〉+〈/sup〉,K〈sup〉+〈/sup〉-ATPase (SCH28080), in hog gastric tubulovesicles and membrane fractions of the H〈sup〉+〈/sup〉,K〈sup〉+〈/sup〉-ATPase-expressing cells. In the living cells, Shh-N recombinant inhibited the SCH28080-sensitive 〈sup〉86〈/sup〉Rb〈sup〉+〈/sup〉-uptake. Together, Shh-N may directly bind to extracellular side of H〈sup〉+〈/sup〉,K〈sup〉+〈/sup〉-ATPase, and negatively regulates the pump activity. This is the first report to explore non-morphogenic property of Shh on ion transporters.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: 24 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications, Volume 517, Issue 3〈/p〉 〈p〉Author(s): Sakthivel Srinivasan, Takuma Hosokawa, Pablo Vergara, Yoan Chérasse, Toshie Naoi, Takeshi Sakurai, Masanori Sakaguchi〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Simultaneous imaging and manipulation of a genetically defined neuronal population can provide a causal link between its activity and function. Here, we designed a miniaturized microscope (or ‘miniscope’) that allows fluorescence imaging and optogenetic manipulation at the cellular level in freely behaving animals. This miniscope has an integrated optical connector that accepts any combination of external light sources, allowing flexibility in the choice of sensors and manipulators. Moreover, due to its simple structure and use of open source software, the miniscope is easy to build and modify. Using this miniscope, we demonstrate the optogenetic silencing of hippocampal CA1 neurons using two laser light sources—one stimulating a calcium sensor (i.e., jGCaAMP7c) and the other serving as an optogenetic silencer (i.e., Jaws). This new miniscope can contribute to efforts to determine causal relationships between neuronal network dynamics and animal behavior.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 28 September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Li Ren, Qing Song, Yunhuan Liu, Lihua Zhang, Zhiming Hao, Wenke Feng〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Intrahepatic cholestasis of pregnancy (ICP) is gestation-specific liver disease associated with liver injury and increased serum and hepatic bile acids. Although the mechanism of ICP is still not fully understood, the reproductive hormones seem to play an important role. Recent studies show that a progesterone metabolite, epiallopregnanolone sulfate (PM5S), is supraphysiologically elevated in the serum of ICP patients, indicating it may play an etiology role in ICP. Bile acid homeostasis is controlled by multiple mechanisms including farnesoid X receptor (FXR)-mediated bile acid export and synthesis. It is known that cholic acid (CA), a primary bile acid, can activate FXR, which is inhibited by PM5S, an FXR antagonist. Here we employed a mouse model of concurrent exposure of CA and PM5S-induced liver injury and determined the effects of probiotic 〈em〉Lactobacillus rhamnosus〈/em〉 GG (LGG) in the prevention of the bile acid disorders and liver injury. Mice challenged with CA + PM5S had significantly increased levels of serum and hepatic bile acids and bilirubin and liver enzyme. Pretreatment with LGG significantly reduced bile acid and bilirubin levels associated with reduced liver enzyme level and mRNA expression levels of pro-inflammatory cytokines. We also showed that the beneficial effects of LGG is likely mediated by hepatic FXR activation and bile salt export pump (BSEP) upregulation. In conclusion, our results provide a rationale for the application of probiotics in the management of ICP through gut microbiota-mediated FXR activation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 18 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉 〈p〉Author(s): Ashraf Yusuf Rangrez, Lucia Kilian, Katharina Stiebeling, Sven Dittmann, Eric Schulze-Bahr, Norbert Frey, Derk Frank〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉We recently identified a novel, heterozygous, and non-synonymous ACTC1 mutation (p.Gly247Asp or G247D) in a large, multi-generational family, causing atrial-septal defect followed by late-onset dilated cardiomyopathy (DCM). Molecular dynamics studies revealed possible actin polymerization defects as G247D mutation resides at the juncture of side-chain interaction, which was indeed confirmed by 〈em〉in vitro〈/em〉 actin polymerization assays. Since polymerization/de-polymerization is important for the activation of Rho-GTPase-mediated serum response factor (SRF)-signaling, we studied the effect of G247D mutation using luciferase assay. Overexpression of native human ACTC1 in neonatal rat cardiomyocytes (NRVCMs) strongly activated SRF-signaling both in C2C12 cells and NRVCMs, whereas, G247D mutation abolished this activation. Mechanistically, we found reduced GTP-bound Rho-GTPase and increased nuclear localization of globular actin in NRVCMs overexpressing mutant ACTC1 possibly causing inhibition of SRF-signaling activation. In conclusion, our data suggests that human G247D ACTC1 mutation negatively regulates SRF-signaling likely contributing to the late-onset DCM observed in mutation carrier patients.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈strong〉G247D mutant ACTC1 leads to reduced actin polymerization and SRF-signaling resulting in cardiac defects.〈/strong〉 G247D: p. Gly247Asp, G-actin: Globular actin, F-actin: Filamentous actin, RhoA: Ras homolog family member A, GTP: Guanosine-triphosphate, SRF: Serum response factor, MKL1: Megakaryoblastic leukemia 1, ASD: Atrial septal defect, DCM: Dilated cardiomyopathy, RA: Right atrium, RV: Right ventricle, LA: Left atrium, LV: Left ventricle.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0006291X19316043-fx1.jpg" width="154" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉