Rindomdam3130

Importantly, the MICH matrix suppresses tissue ROS production, reducing the inflammatory response, prompting re-epithelization and neoangiogenesis during wound healing. Meanwhile, the remodeling skin treated with MICH matrix demonstrates low collagen deposition and normal dermal collagen architecture. Overall, the MICH prevents burn wound progression and enhances skin regeneration, which might be a promising biomaterial for burn-wound care and other disease therapy induced by oxidative stress. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Cytosolic double-stranded DNA (dsDNA) is a danger signal that is tightly monitored and sensed by nucleic acid-sensing pattern recognition receptors. We study the inflammatory cascade on dsDNA recognition and investigate the neuroprotective effect of cyclic GMP-AMP (cGAMP) synthase (cGAS) antagonist A151 and its mechanisms of neuroprotection in a mouse model of experimental stroke. Here, we found that cerebral ischemia promoted the release of dsDNA into the cytosol, where it initiated inflammatory responses by activating the cGAS. A151 effectively reduced the expression of cGAS, absent in melanoma 2 (AIM2) inflammasome, and pyroptosis-related molecules, including caspase-1, gasdermin D, IL-1β, and IL-18. Furthermore, mice treated with A151 showed a dampened immune response to stroke, with reduced counts of neutrophils, microglia, and microglial production of IL-6 and TNF-α after MCAO. Moreover, A151 administration significantly reduced infarct volume, attenuated neurodeficits, and diminished cell death. Notably, the protective effect of A151 was blocked in a microglia-specific cGAS knockout mouse. These findings offer unique perspectives on stroke pathogenesis and indicate that inhibition of cGAS could attenuate brain inflammatory burden, representing a potential therapeutic opportunity for stroke. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.Osimertinib, a third-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), provides marked clinical benefit for patients with EGFR-activating mutations. Unfortunately, limited treatments exist for patients who acquire osimertinib resistance. We observed two "special" patients who regained an antitumor response with osimertinib plus aspirin treatment. As previous data indicate that aspirin induces anti-proliferative effects in tumor cells, we designed a preclinical study to explore whether aspirin combined with osimertinib could synergistically sensitize osimertinib-resistant NSCLC cells. The effects of combined treatment with osimertinib and aspirin on osimertinib-resistant non-small-cell lung cancer (NSCLC) cell lines were examined in vitro and in vivo. Fasoracetam clinical trial The combination of osimertinib and aspirin induced strong anti-proliferative and proapoptotic effects in osimertinib-resistant NSCLC cells through inhibition of Akt/FoxO3a signaling component phosphorylation and increased Bim expression. Furthermore, Bim knockdown by siRNA significantly attenuated osimertinib resensitization by aspirin. In vivo, combination of aspirin and osimertinib significantly decreased tumor growth of PC-9GROR cell xenografts. Data of patients with NSCLC who received osimertinib treatment at Daping Hospital between January 2015 and January 2019 were reviewed retrospectively. According to clinical data for 45 patients with NSCLC, retrospective analysis showed that the median progression-free survival (PFS) was significantly longer in the osimertinib plus aspirin group than in the osimertinib group. In summary, aspirin synergistically enhances the antitumor activity of osimertinib in osimertinib-resistant lung cancer cells through promoting Bim-dependent apoptosis. This combination therapy may be effective in overcoming acquired resistance to osimertinib and prolonging survival in patients with NSCLC. This article is protected by copyright. All rights reserved.Pneumococcal cell surface-exposed choline-binding proteins (CBPs) play pivotal roles in multiple infectious processes with pneumococci. Intracellular pneumococci can be recognized at multiple steps during bactericidal autophagy. However, whether CBPs are involved in pneumococci-induced autophagic processes remains unknown. In this study, we demonstrate that CbpC from S. pneumoniae strain TIGR4 activates autophagy through an interaction with Atg14. However, S. pneumoniae also interferes with autophagy by deploying CbpC as a decoy to cause autophagic degradation of Atg14 through an interaction with p62/SQSTM1. Thus, S. pneumoniae suppresses the autophagic degradation of intracellular pneumococci and survives within cells. Domain analysis reveals that the coiled-coil domain of Atg14 and residue Y83 of the dp3 domain in the N-terminal region of CbpC are crucial for both the CbpC-Atg14 interaction and the subsequent autophagic degradation of Atg14. Although homology modeling indicates that CbpC orthologs have similar structures in the dp3 domain, autophagy induction through Atg14 binding is an intrinsic property of CbpC. Our data provide novel insights into the evolutionary hijacking of host-defense systems by intracellular pneumococci. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.BACKGROUND We aimed to investigate the effect of a low-protein intake on all-cause mortality in subjects with an estimated glomerular filtration rate (eGFR) ≧60 mL/min/1.73 m2 with or without albuminuria using data from the National Health and Nutrition Examination Survey (NHANES). METHODS We analysed participants in the NHANES from 2003 to 2010. We excluded participants with an eGFR less than 60 mL/min/1.73 m2 from the analyses. Low-protein intake was defined as a protein intake of less than 0.8 g/kg/day. The Healthy Eating Index 2010 was used to assess diet quality. The vital status of all participants in the NHANES was determined by linking to the National Death Index through the end of 2011. The hazard ratios (HRs) for the association of low-protein intake and mortality were determined using weighted Cox proportional hazards regression models. RESULTS A total of 7730 participants were included in the analyses. After a median follow up of 4.7 years, 462 participants died. A low-protein intake was associated with a higher risk of mortality (HRs 1.