Danielshandberg3519

Statin therapy is used ubiquitously to reduce cholesterol levels, and recent studies have revealed statin use may be associated with a reduced risk of inflammatory bowel disease (IBD). A comprehensive assessment of the literature was performed to investigate whether statin use may influence the risk of new-onset IBD. We searched the PubMed/MEDLINE, Cochrane, Web of Science, and Scopus online databases, for articles published up to July 31, 2020. Hazard ratios (HR) with 95% confidence intervals (CI) were used. We identified five retrospective studies, with seven arms, comprising >10 million participants, consisting of 89,324 cases of IBD (statin users 14,494 versus non-users 74,830) detected during a mean follow-up of 8.6 years. Overall, statin use was associated with a reduced risk of new-onset IBD (HR = 0.81; 95% CI, 0.63 to 1.06; P = 0.129, I2 = 81.3%). Pooled results indicated a non-significant reduced risk of new-onset CD (HR = 0.94; 95% CI, 0.72 to 1.25; P = 0.684, I2 = 85.9%) and new-onset UC (HR = 0.89; 95% CI, 0.70 to 1.12; P = 0.306, I2 = 92.5%) with statin use. Statin use may confer a protective effect in reducing the risk of new-onset IBD. Indeed, this study provides novel and intriguing insights into a potential preventive agent for IBD.CTRP6, a newly identified adiponectin analogue, has been shown to be involved in inflammation, diabetes and cardiovascular diseases. Recently, increasing evidence has shown that CTRP6 plays a critical role in fibrotic diseases, such as myocardial fibrosis and skin fibrosis. FAO, an important energy source for kidney proximal tubular cells, also participates in the process of fibrosis. Therefore, our study aimed to investigate the effect of CTRP6 on mediating FAO in kidney fibrosis and the underlying associated mechanism. Firstly, the activity of CTRP6 and the key enzymes of FAO (CPT1A, ACOX1) were tested in vivo and vitro. Next, the regulatory effect of CTRP6/AMPK on FAO was accessed in animal models and in cell lines. Additionally, we explored the effect of exogenous recombinant CTRP6 on renal tubular epithelial cell differentiation. Decreased CTRP6 and p-AMPK were detected in UUO-induced kidney fibrosis and in TGF-β1-treated HK-2 cells. We also observed that defective FAO occurred during kidney fibrosis. Moreover, the human CTRP6 peptide could inhibit the ECM deposition and promote the phosphorylation of AMPK by promoting FAO. However, the inhibitory effects of CTRP6 on TGF-β1-induced ECM deposition and the protective effects of CTRP6 on FAO could be abolished by compound C, a selective inhibitor of AMPK. Compound C also reversed the CTRP6-mediated upregulation of p-AMPK. The mediation of FAO by CTRP6 plays a key role in kidney fibrosis by regulating TGF-β1-induced renal tubular epithelial cell differentiation by promoting FAO, which is mediated via AMPK activation.Coronavirus Disease 2019 named as COVID-19 imposing a huge burden on public health as well as global economies, is caused by a new strain of betacoronavirus named as SARS-CoV-2. The high transmission rate of the virus has resulted in current havoc which highlights the need for a fast and effective approach either to prevent or treat the deadly infection. Development of vaccines can be the most prominent approach to prevent the virus to cause COVID-19 and hence will play a vital role in controlling the spread of the virus and reducing mortality. The virus uses its spike proteins for entering into the host by interacting with a specific receptor called angiotensin converting enzyme-2 (ACE2) present on the surface of alveolar cells in the lungs. Researchers all over the world are targeting the spike protein for the development of potential vaccines. Here, we discuss the immunopathological basis of vaccine designing that can be approached for vaccine development against SARS-CoV-2 infection and different platforms that are being used for vaccine development. We believe this review will increase our understanding of the vaccine designing against SARS-CoV-2 and subsequently contribute to the control of SARS-CoV-2 infections. Also, it gives an insight into the current status of vaccine development and associated outcomes reported at different phases of trial.Glioblastoma multiforme (GBM) is the most aggressive brain tumor with a poor prognosis. The current treatment regimen, including surgical resection, radiation, and temozolomide (TMZ) chemotherapy, is still not curative. Therefore, there is an emerging need to develop a drug to treat GBM or synergistic enhance TMZ effect on GBM cells. Flunarizine (FLN), a drug approved for treating migraine and vertigo, was analyzed for its cytotoxicity and synergistic effect with TMZ on GBM cells in this study. Cell proliferation, clonogenic assay, flow cytometry, and Western blotting were used to determine the effects of FLN on three GBM cells, U-87 MG, LN-229, and U-118 MG cells. We found that FLN induced GBM cell death. FLN also interfered with U-87 MG cell cycle progression. Flow cytometric analysis showed an increase of apoptotic cells after FLN treatment. Caspase 9, caspase 3, and Poly (ADP-ribose) polymerase (PARP) activation were involved in apoptosis induction in U-87 MG and LN-229, suggesting the possible involvement of an intrinsic apoptotic pathway. We found that FLN treatment inhibited Akt pathway activation in U-87 MG cells, and synergistically increased the cytotoxicity of three GBM cells when combined with TMZ treatment. In conclusion, our current data suggested that FLN inhibited cell viability by inducing apoptosis. FLN inhibited Akt activation and enhanced the sensitivity of GBM cells to TMZ. These findings may provide important information regarding the application of FLN in GBM treatment in the future.Cellular stress and inflammation, establishing as disease pathology, have reached great heights in the last few decades. read more Stress conditions such as hyperglycemia, hyperlipidemia and lipoproteins are known to disturb proteostasis resulting in the accumulation of unfolded or misfolded proteins, alteration in calcium homeostasis culminating in unfolded protein response. Protein disulfide isomerase and endoplasmic reticulum oxidase-1 are the key players in protein folding. The protein folding process assisted by endoplasmic reticulum oxidase-1 results in the production of reactive oxygen species in the lumen of the endoplasmic reticulum. Production of reactive oxygen species beyond the quenching capacity of the antioxidant systems perturbs ER homeostasis. Endoplasmic reticulum stress also induces the production of cytokines leading to inflammatory responses. This has been proven to be the major causative factor for various pathophysiological states compared to other cellular triggers in diseases, which further manifests to increased oxidative stress, mitochondrial dysfunction, and altered inflammatory responses, deleterious to cellular physiology and homeostasis.