BACKGROUND In order to modulate microglial phenotypes in vivo, M1 microglia were depleted by administration of gadolinium chloride and the expression of M2 microglia was induced by IL-4 administration in an animal model of sepsis to better characterize the role of microglial phenotypes in sepsis-induced brain dysfunction. METHODS Wistar rats were submitted to sham or cecal ligation and perforation (CLP) and treated with IL-4 or GdCl3. Animals were submitted to behavioral tests 10 days after surgery. In a separated cohort of animals at 24 h, 3 and 10 days after surgery, hippocampus was removed and cytokine levels, M1/M2 markers and CKIP-1 levels were determined. RESULTS Modulation of microglia by IL-4 and GdCl3 was associated with an improvement in long-term cognitive impairment. When treated with IL-4 and GdCl3, the reduction of pro-inflammatory cytokines was apparent in almost all analyzed time points. Additionally, CD11b and iNOS were increased after CLP at all time points, and both IL-4 and GdCl3 treatments were able to reverse this. There was a significant decrease in CD11b gene expression in the CLP+GdCl3 group. IL-4 treatment was able to decrease iNOS expression after sepsis. Furthermore, there was an increase of CKIP-1 in the hippocampus of GdCl3 and IL-4 treated animals 10 days after CLP induction. CONCLUSIONS GdCl3 and IL-4 are able to manipulate microglial phenotype in an animal models of sepsis, by increasing the polarization toward an M2 phenotype IL-4 and GdCl3 treatment was associated with decreased brain inflammation and functional recovery. © 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.Axl, a member of the TAM (Tyro3, AXL, Mer) receptor tyrosine kinase family, plays critical roles in cell growth, proliferation, apoptosis, and migration. In this study, we demonstrated that the anti-cancer activity of bufalin, a major bioactive component of the Chinese traditional medicine Chan Su, is mediated by the downregulation of Axl in non-small-cell lung cancer (NSCLC) cells. We observed the inhibitory effect of bufalin on the proliferation of A549 and H460 NSCLC cells and the clonogenicity of these cells was reduced by bufalin treatment in a dose-dependent manner. Next, we found that the protein level of Axl was decreased in proportion to the concentration of bufalin in both A549 and H460 cells. Moreover, the promoter activity of the Axl gene was decreased by bufalin in a dose- and time-dependent manner, indicating that bufalin downregulates Axl gene expression at the transcriptional level. We further examined if the anti-proliferative property of bufalin is influenced by Axl at the protein level. Axl overexpression attenuated the effect of bufalin in inhibiting cell proliferation and colony formation and inducing apoptosis in H460 cells, while knockdown of Axl gene expression induced the opposite effect. Taken together, our data indicate that the anti-proliferative and pro-apoptotic effects of bufalin were associated with the protein level of Axl, suggesting that Axl is a potent therapeutic target of bufalin in suppressing proliferation and inducing apoptosis in NSCLC cells. Copyright 2020 The Author(s).Bent G. Boving, a remarkable pioneer of research on mechanistic aspects of embryo implantation and specifically of using the rabbit model for this purpose, passed away peacefully on November 15, 2019, not long before he would have been able to celebrate his 100th birthday on February 23, 2020. His work has been very stimulating for other researchers, in part possibly because it elicited controversial discussions. This article attempts to give an overview of his scientific contributions, which still harbour some treasures, including potentially stimulating ideas for future research on implantation.  https://www.selleckchem.com/products/catechin-hydrate.html  © The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction.Severe acute pancreatitis (SAP) is a common and life-threatening clinical acute abdominal disease. C1q/tumor necrosis factor-related protein 3 (CTRP3), a novel paralog of adiponectin, has been identified as a crucial regulator in multiple types of inflammatory disorders. However, the biological role of CTRP3 in SAP remains poorly understood. This study aimed to characterize the role of CTRP3 in SAP and illuminate the potential mechanisms involved. In the current study, SAP mouse models were induced by seven hourly intraperitoneal injection of cerulein (50 μg/kg) and an immediate intraperitoneal injection of lipopolysaccharide (10 mg/kg) after the last cerulein administration. Histological examination and serological analysis demonstrated that SAP mouse models were successfully established. Herein, we found that CTRP3 expression was significantly decreased in the pancreatic tissues of SAP mice compared with normal control mice. Furthermore, we explored the effects of CTRP3 rescue in SAP mice and discovered that CTRP3 over-expression attenuated pathological lesions, inhibited inflammatory mediator release and repressed acinar cell apoptosis. Notably, mechanistic studies revealed that CTRP3 over-expression suppressed NF-κB p65 phosphorylation and p53 acetylation to alleviate cerulein-induced SAP in mouse models through activation of silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent protein deacetylase. Collectively, our data indicate that CTRP3 may exert its protective effects in SAP mice via regulation of SIRT1-mediated NF-κB and p53 signaling pathways, implying a promising therapeutic strategy against SAP. Copyright 2020 The Author(s).Chronic hepatitis B is now controllable when treated with nucleoside reverse transcriptase inhibitors (NRTIs), which inhibit hepatitis B virus (HBV) replication. However, once the NRTIs are discontinued, most patients relapse, necessitating lifelong NRTIs treatment. HBV infection relapse is assumed to be caused by the persistent existence of covalently closed circular DNA in the nuclei of infected hepatocytes. The mechanism by which covalently closed circular DNA-positive hepatocytes escape immune surveillance during NRTIs treatment remains elusive. Entecavir (ETV), a commonly used NRTI, post-transcriptionally upregulates programmed cell death-ligand 1 (PD-L1), an immune checkpoint molecule, on the cell surface of hepatocytes regardless of HBV infection. Upregulation by ETV depends on upregulation of CKLF-like MARVEL transmembrane domain-containing 6, a newly-identified potent regulator of PD-L1 expression on the cell surface. ETV-treated hepatic cells suppressed the activity of primary CD3 T cells and PD-1 overexpressed Jurkat cells.