Mcguirekane6836

hat disease severity in SLE may be determined by HLA-DRB1 alleles. The risk of HLA-DRB1*04 allele with LN was supported by the demonstration of an intense inflammatory response in Malay SLE patients in Malaysia. More studies inclusive of a larger and multiple SLE cohorts in the future are warranted to validate these findings.Autophagy is a highly conserved process by which superfluous or harmful components in eukaryotic cells are degraded by autophagosomes. This cytoprotective mechanism is strongly related to various human diseases, such as cancer, autoimmune diseases, and diabetes. DEAH-box helicase 15 (DHX15), a member of the DEAH box family, is mainly involved in RNA splicing and ribosome maturation. Recently, DHX15 was identified as a tumor-related factor. Although both autophagy and DHX15 are involved in cellular metabolism and cancer progression, their exact relationship and mechanism remain elusive. In this study, we discovered a non-classic function of DHX15 and identified DHX15 as a suppressive protein in autophagy for the first time. We further found that mTORC1 is involved in DHX15-mediated regulation of autophagy and that DHX15 inhibits proliferation of hepatocellular carcinoma (HCC) cells by suppressing autophagy. In conclusion, our study demonstrates a non-classical function of DHX15 as a negative regulator of autophagy related to the mTORC1 pathway and reveals that DHX15-related autophagy dysfunction promotes HCC cell proliferation, indicating that DHX15 may be a target for liver cancer treatment.Background One in every four patients with a first episode of non-gallstone-related acute pancreatitis (AP) develops recurrent disease. Recurrent episodes of AP or acute flares of chronic pancreatitis (CP) are associated with decreased quality of life and progression of the disease. Besides removing the etiology of pancreatitis (which sometimes is not possible), there are no effective measures to prevent recurrence. Meta-analyses of randomized controlled trials, as well as epidemiological and cohort studies, suggest that statins may be protective against the development of index AP. Methods The SIMBA study is a triple-blind randomized placebo-controlled, parallel-group multicenter trial. Patients with recurrent AP or with acute flares of CP (at least two episodes in the last 12 months) will be randomized to receive simvastatin 40 mg daily or placebo. During a 3-year study period, 144 patients (72 per arm of treatment) from 26 centers will be enrolled. The patients will receive the study treatment for 1 year. The primary aim is to compare the recurrence of AP or acute flares in CP. Secondary endpoints include the incidence of new-onset diabetes mellitus, new-onset exocrine pancreatic insufficiency (EPI), new-onset imaging signs of CP, frequency of all-cause hospital admissions, severity of AP, adherence to treatment, and frequency of adverse events. Discussion The SIMBA trial will ascertain whether simvastatin, a safe, widely used and inexpensive drug, can change the natural course of recurrent pancreatitis. Trial Registration ClinicalTrials.gov Identifier NCT04021498.[This corrects the article DOI 10.3389/fcell.2020.00484.].[This corrects the article DOI 10.3389/fcell.2020.00794.].Oocyte-specific competence remains one of the major targets of current research in the field of reproduction. Several mechanisms are involved in meiotic maturation and the molecular signature of an oocyte is considered to reflect its quality and to predict its subsequent developmental and functional capabilities. In the present minireview, we focus on the possible role of mechanotransduction and mechanosensor signaling pathways, namely the Hippo and the RhoGTPase, in the maturing oocyte. Due to the limited access to female gametes, we propose the use of cells isolated from parthenogenetic embryos as a promising model to characterize and dissect the oocyte distinctive molecular signatures, given their exclusive maternal origin. The brief overview here reported suggests a role of the mechanosensing related pathways in oocyte quality and developmental competence and supports the use of uniparental cells as a useful tool for oocyte molecular signature characterization.Toll-like receptor-9 (TLR-9) is a potent proinflammatory receptor that mediates renal injury. However, the reported effects of TLR-9 are contradictory. Here, using a traditional mouse AKI→CKD transition model, the roles of TLR-9 during the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) were further explored. Using a TLR-9-/- mouse, the effects and mechanisms of TLR-9 were investigated. Loss of TLR-9 elicited no obvious effects as regards renal function or histology during AKI in the early phases (24-48 h), while TLR-9 KO attenuated renal fibrosis (as shown using fibronectin and collagen III) and epithelial-to-mesenchymal transition (EMT) [E-cadherin (E-Cad) and α-smooth muscle actin (α-SMA)] on the long-term after AKI through the inhibition of macrophages infiltration, especially M2 macrophages. The roles of TLR-9 on macrophages were also explored using Raw264.7 macrophage cell line, and results indicated that the inhibition of TLR-9 on Raw 264.7 macrophages decreased the induction of M2 type macrophage in a dose-dependent manner. The roles of TLR-9 on renal tubular epithelial (RTE) cells were also explored. Conversely, TLR-9 depletion did not contribute to the improvement of fibrosis and EMT in vitro. Therefore, TLR-9 plays a critical role in the AKI→CKD transition. Attenuation of CKD post-AKI in the TLR-9 KO group mainly relies on the effects of TLR-9 on macrophages. These results also suggest that TLR-9 could be a therapeutic target for CKD.Extracellular vesicles (EVs), which are cell released double layered membrane particles, have been found in every circulating body fluid, and provide a tool for conveying diverse information between cells, influencing both physiological and pathological conditions. Viruses can hijack the EVs secretory pathway to exit infected cells and use EVs endocytic routes to enter uninfected cells, suggesting that EVs and viruses can share common cell entry and biogenesis mechanisms. SARS-CoV-2 is responsible of the coronavirus disease 2019 (Covid-19), which may be accompanied by severe multi-organ manifestations. selleck chemical EVs may contribute to virus spreading via transfer of virus docking receptors such as CD9 and ACE2. Covid-19 is known to affect the renin angiotensin system (RAS), and could promote secretion of harmful EVs. In this scenario EVs might be linked to cardiovascular manifestations of the Covid-19 disease through unbalance in RAS. In contrast EVs derived from mesenchymal stem cells or cardiosphere derived cells, may promote cardiovascular function due to their beneficial effect on angiogenesis, fibrosis, contractility and immuno-modulation.