BackgroundMicroglia play key roles in innate immunity, homeostasis, and neurotropic support in the central nervous system. Similar to macrophages, microglia adopt two different activation phenotypes, the classical and alternative activation. Resolvin D1 (RvD1) is considered to display potent anti-inflammatory and pro-resolving actions in inflammatory models. In this present study, we investigate the effect of RvD1 on IL-4-induced alternative activation in murine BV-2 microglial cells.MethodsBV-2 cells were incubated with RvD1 alone, IL-4 alone, or the combination of RvD1 and IL-4. Western blot and immunofluorescence were performed to detect protein levels of alternative activation markers arginase 1 (Arg1), chitinase 3-like 3 (Ym1). Moreover, we investigated the effects of RvD1 on IL-4-induced activation of signal transducer and activators of transcription 6 (STAT6) and peroxisome proliferator-activated receptor gamma (PPARγ).ResultsRvD1 promoted IL-4-induced microglia alternative activation by increasing the expression of Arg1 and Ym1. RvD1 also enhanced phosphorylation of STAT6, nuclear translocation of PPARγ and the DNA binding activity of STAT6 and PPARγ. These effects were reversed by butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (a formyl peptide receptor 2 antagonist). Further, the effects of RvD1 and IL-4 on Arg1 and Ym1 were blocked by the application of leflunomide (a STAT6 inhibitor) or GW9662 (a PPARγ antagonist).ConclusionsOur studies demonstrate that RvD1 promotes IL-4-induced alternative activation via STAT6 and PPARγ signaling pathways in microglia. These findings suggest that RvD1 may have therapeutic potential for neuroinflammatory diseases.

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ObjectiveTo assess the clinical and haemodynamic effects of carvedilol for patients with cirrhosis and portal hypertension.DesignA systematic review and meta-analysis.Data sourcesWe searched PubMed, Cochrane library databases, EMBASE and the Science Citation Index Expanded through December 2015. Only randomised controlled trials (RCTs) were included.Outcome measureWe calculated clinical outcomes (all-cause mortality, bleeding-related mortality, upper gastrointestinal bleeding) as well as haemodynamic outcomes (hepatic venous pressure (HVPG) reduction, haemodynamic response rate, post-treatment arterial blood pressure (mean arterial pressure; MAP) and adverse events).Results12 RCTs were included. In 7 trials that looked at haemodynamic outcomes compared carvedilol versus propranolol, showing that carvedilol was associated with a greater reduction (%) of HVPG within 6 months (mean difference −8.49, 95% CI −12.36 to −4.63) without a greater reduction in MAP than propranolol. In 3 trials investigating differences in clinical outcomes between carvedilol versus endoscopic variceal band ligation (EVL), no significant differences in mortality or variceal bleeding were demonstrated. 1 trial compared clinical outcomes between carvedilol versus nadolol plus isosorbide-5-mononitrate (ISMN), and showed that no significant difference in mortality or bleeding had been found. 1 trial comparing carvedilol versus nebivolol showed a greater reduction in HVPG after 14 days follow-up in the carvedilol group.ConclusionsCarvedilol may be more effective in decreasing HVPG than propranolol or nebivolol and it may be as effective as EVL or nadolol plus ISMN in preventing variceal bleeding. However, the overall quality of evidence is low. Further large-scale randomised studies are required before we can make firm conclusions.Trial registration numberCRD42015020542.

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Hypoxia-inducible gene domain family member 1A (Higd1a) has recently been reported to protect cells from hypoxia by helping to maintain normal mitochondrial function. The potential induction of Higd1a under high-fat exposure and whether it could protect cells from oxidative stress attracted our attention. Initially, 0.4 mM oleic acid and 0.2 mM palmitate were added to the growth media of HepG2 and LO2 cells for 72 hours. We discovered increased Higd1a expression, and knocking down Higd1a impaired mitochondrial transmembrane potential and induced cell apoptosis. We then identified that elevated reactive oxygen species (ROS) is responsible for increased Higd1a expression. Furthermore, we found that ROS promoted Higd1a expression by upregulating HIF-1a and PGC-1a expressions, and these two proteins could exert synergistic effects in inducing Higd1a expression. Taken together, these data suggest that Higd1a plays positive roles in protecting cells from oxidative stress, and ROS could induce Higd1a expression by upregulating PGC-1a and HIF-1a expressions.

Increasing evidence has demonstrated that regulatory T cells (Tregs) suppress innate immunity, as well as protect the kidneys from ischemia-reperfusion injury (IRI) and offer a potentially effective strategy to prevent or alleviate renal IRI. The present study explored whether C-X-C motif chemokine receptor 3 (CXCR3) alleviated renal IRI by increasing Tregs. Male C57BL/6J mice were divided into sham-surgery, IRI, CXCR3 overexpression (OE-CXCR3)+IRI, PC61+IRI and OE-CXCR3+PC61+IRI groups. Histopathological examination of the kidney was carried out using hematoxylin-eosin and Masson staining. The levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Blood and kidney levels of IL-6, TNF-α, C-C motif chemokine ligand (CCL)-2 and IL-10 were detected by ELISA and western blotting. The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in kidney tissues were also measured to assess oxidative stress. The population of Tregs in the kidney was assessed using flow cytometry. The results demonstrated that administration of OE-CXCR3 to IRI mice significantly decreased the levels of Scr, BUN, IL-6, TNF-α, CCL-2 and MDA, increased the levels of IL-10, SOD and GSH-Px, and mitigated the morphologic injury and fibrosis induced by IR compared with the IRI group. In addition, administration of OE-CXCR3 induced significant reductions in the expression levels of fibrosis-related markers, including fibronectin and type IV collagen, and increased the number of Tregs. These roles of OE-CXCR3 were significantly neutralized following deletion of Tregs with PC61 (anti-CD25 antibody). Together, the present study demonstrated that injection of OE-CXCR3 lentiviral vectors into animal models can alleviate renal IRI by increasing the number of Tregs. The results may be a promising approach for the treatment of renal IRI.