Berberine plays a cardioprotective role by inhibiting macrophage Wnt5a/ß-catenin pathway in the myocardium of mice after myocardial infarction.

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/ß-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/ß-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.

Clinical efficacy of intravitreal corticoid as an adjunctive therapy to anti-VEGF treatment of neovascular age-related macular degeneration: a Meta-analysis.

AIM: To evaluate the efficacy and safety of intravitreal corticoid as an adjunctive therapy to anti-vascular endothelial growth factor (VEGF) treatment of neovascular age-related macular degeneration (nvAMD). METHODS: Four databases including PubMed, Embase, Cochrane Library, and the clinicaltrials.gov were comprehensively searched for studies comparing intravitreal corticoid plus anti-VEGF (IVC/IVA) vs anti-VEGF monotherapy (IVA) in patients with nvAMD. GRADE profiler was used to assess the quality of outcomes. Best-corrected visual acuity (BCVA), central macular thickness (CMT) and adverse events including the occurrence of severe elevation of intraocular pressure (IOP) and the progress of cataract were extracted from the eligible studies. Review Manager (RevMan) 5.3 was used to analyze the data. RESULTS: There was no statistic difference of mean change in BCVA at 6 and 12mo between IVC/IVA and IVA group [95% confidence interval (CI): -2.28 to 4.24, P=0.55; 95%CI: -3.01 to 8.70, P=0.34]. No statistic difference was found in the change of CMT between two groups at 6mo time point (95%CI: -17.98 to 16.42, P=0.93) while the CMT reduction in IVC/IVA group was significantly more obvious than IVA group at 12mo time point [mean difference (MD)=-44.08, 95%CI: -80.52 to -7.63, P=0.02]. The risk of occurrence of severe elevation of IOP in the IVC/IVA group was higher than that in the IVA group (95%CI: 1.92 to 9.48; P=0.0004). Cataract progression risk was calculated no statistic difference between two groups (95%CI: 0.74 to 4.66; P=0.18). CONCLUSION: No visual or anatomical benefits are observed in IVC/IVA group at 6mo. At 12mo, the CMT of the IVC/IVA group is significantly lower than that of the IVA group. Risk of severe elevation of IOP is significantly higher when treated by IVC/IVA.

Hub biomarkers for the diagnosis and treatment of glioblastoma based on microarray technology.

BACKGROUND: Glioblastoma (GBM) is the most common clinical intracranial malignancy worldwide, and the most common supratentorial tumor in adults. GBM mainly causes damage to the brain tissue, which can be fatal. This research explored potential gene targets for the diagnosis and treatment of GBM using bioinformatic technology. METHODS: Public data from patients with GBM and controls were downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified by Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus 2R (GEO2R). Construction of the protein-protein interaction network and the identification of a significant module were performed. Subsequently, hub genes were identified, and their expression was examined and compared by real-time quantitative (RT-q)PCR between patients with GBM and controls. RESULTS: GSE122498 (GPL570 platform), GSE104291 (GPL570 platform), GSE78703_DMSO (GPL15207 platform), and GSE78703_LXR (GPL15207 platform) datasets were obtained from the GEO. A total of 130 DEGs and 10 hub genes were identified by GEPIA and GEO2R between patients with GBM and controls. Of these, strong connections were identified in correlation analysis between CCNB1, CDC6, KIF23, and KIF20A. RT-qPCR showed that all 4 of these genes were expressed at significantly higher levels in patients with GBM compared with controls. CONCLUSIONS: The hub genes CCNB1, CDC6, KIF23, and KIF20A are potential biomarkers for the diagnosis and treatment of GBM.

Compound sophorae decoction enhances intestinal barrier function of dextran sodium sulfate induced colitis via regulating notch signaling pathway in mice.

BACKGROUND: Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive. METHODS: In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR. RESULTS: CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2. CONCLUSIONS: These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis.

Autotaxin-Lysophosphatidic Acid Axis Blockade Improves Inflammation by Regulating Th17 Cell Differentiation in DSS-Induced Chronic Colitis Mice.

Autotaxin-lysophosphatidic acid (ATX-LPA) axis is closely associated with several inflammation-related diseases. In the colonic mucosa of patients with chronic ulcerative colitis (UC), the expression of ATX and the percentage of Th17 cells are found to increase. However, it is unclear whether ATX-LPA axis affects the differentiation of Th17 cells in chronic UC. To investigate whether ATX-LPA axis contributes to Th17 cell differentiation, a mouse model of chronic UC was established by drinking water with DSS at intervals. ATX inhibitor was used as an intervention. The disease active index (DAI), colonic weight to length ratio, colon length, colon histopathology, and MAdCAM-1 were observed. Additionally, the expression of ATX, LPA receptor, CD34, IL-17A, IL-21, IL-6, ROR-γt, STAT3 in colonic tissue, and the percentage of Th17 cells in spleens and mesenteric lymph nodes (MLNs) were measured using different methods. ATX blockade was able to relieve symptoms and inflammatory response of DSS-induced chronic colitis. The DAI and colonic weight to length ratio were apparently decreased, while the colon length was increased. The pathological damage and colitis severity were lighter in the inhibitor group than that in the DSS group. Inhibiting ATX reduced the expression of ATX, LPA receptor, and CD34 and also decreased the percentages of Th17 cells in spleens and MLNs and the expressions of IL-17A and IL-21, as well as the factors in Th17 cell signaling pathway including IL-6, ROR-γt, and STAT3 in colonic tissue. ATX-LPA axis blockade could alleviate inflammation by suppressing Th17 cell differentiation in chronic UC.

Effect of compound sophorae decoction on dextran sodium sulfate (DSS)-induced colitis in mice by regulating Th17/Treg cell balance.

OBJECTIVE: Compound sophorae decoction, a Chinese medicinal formulae composed of six Chinese herbs, is effective for the clinical treatment of ulcerative colitis (UC). Some of its effective monomers had been proven to have suppressive effect on UC models. The aim of this study is to further explore the mechanism whether compound sophorae decoction ameliorates dextran sodium sulfate (DSS)-induced mice colitis by regulating the balance between T helper (Th) 17 and regulatory T (Treg) cells. METHODS: Experimental model of UC, established by drinking water with DSS, was treated with compound sophorae decoction and mesalazine. The stool, activity, body weight of the mice, colon length and colon histopathology were observed to evaluate severity of colitis. The concentration of cytokines in colonic tissues were detected by ELISA. The expression of phosphorylated nuclear factor-kappaB (NF-κB) p65, STAT3 and phosphorylated STAT3 in colonic tissues were determined by western blotting and immunohistochemistry. The percentage of Th17 and Treg cells in spleen and mesenteric lymph nodes (MLNs) were detected by flow cytometry. The levels of transcription factor ROR-γt and FOXP3 in colon tissues were detected by qRT-PCR and immunohistochemistry. RESULTS: The aqueous extract of compound sophorae decoction was able to improve the symptoms and pathological damage of mice. The body weight of mice were increased and DAI were significantly decreased; ulcers were slighter than DSS group. The administration of compound sophorae decoction reduced the level of inflammatory factors interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and phospho-NF-κB p65, and also decreased the proportions of Th17 cells in spleen and MLNs and the expression of ROR-γt, IL-17A, STAT3, IL-6 in colonic tissues; while the percentage of Treg cells in spleen and MLNs and the expression of FOXP3, transforming growth factor (TGF)-ß1, IL-10 in colonic tissues were upregulated. CONCLUSION: Overall, this study suggested that compound sophorae decoction significantly improves the symptoms and the pathological damage of mice with colitis and influences the immune function by regulating Th17/Treg cell balance in DSS-induced colitis in mice.