Neuroinflammation of microglia polarization in intracerebral hemorrhage and its potential targets for intervention.

Microglia are the resident immune cells of the central nervous system (CNS) and play a key role in neurological diseases, including intracerebral hemorrhage (ICH). Microglia are activated to acquire either pro-inflammatory or anti-inflammatory phenotypes. After the onset of ICH, pro-inflammatory mediators produced by microglia at the early stages serve as a crucial character in neuroinflammation. Conversely, switching the microglial shift to an anti-inflammatory phenotype could alleviate inflammatory response and incite recovery. This review will elucidate the dynamic profiles of microglia phenotypes and their available shift following ICH. This study can facilitate an understanding of the self-regulatory functions of the immune system involving the shift of microglia phenotypes in ICH. Moreover, suggestions for future preclinical and clinical research and potential intervention strategies are discussed.

Efficacy evaluation of Buyang Huanwu Decoction in the treatment of ischemic stroke in the recovery period: A systematic review of randomized controlled trials.

Background and purpose: Buyang Huanwu decoction (BYHWD) is widely used in the treatment of ischemic stroke in the recovery period, and many clinical trials have been reported, but its clinical efficacy and safety have not been fully evaluated. In this study, we conducted a systematic review and meta-analysis to evaluate the clinical efficacy and safety of BYHWD in the recovery period. Materials and methods: Eight databases, including CNKI, Wanfang Database, VIP Database, China Biomedical Literature Database, PubMed, Cochrane Library, EMBASE, and Web of Science, were searched from the establishment of the database to 13 April 2022. We selected all eligible randomized controlled trials of BYHWD in the treatment of ischemic stroke during the recovery period. Systematic review and meta-analysis were conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. The National Institutes of Health Stroke Score (NIHSS) was the primary outcome, and the Chinese Stroke Scale (CSS), activities of daily living (ADL), and adverse drug reaction (ADR) were the secondary outcomes. Results: A total of 39 randomized controlled trials were included, and 3,683 patients in the recovery period of ischemic stroke were recruited. Compared with conventional treatment alone, BYHWD combined with conventional treatment significantly decreased the NIHSS score (MD = -1.44, 95% CI: 1.75, -1.12, p < 0.00001), the CSS score (MD = -1.18, 95% CI: 2.02, -0.34, p = 0.006), improved the ADL (MD = 4.33, 95% CI: 3.06, 5.61, p < 0.00001), and did not increase the adverse reactions of patients (OR = 0.88, 95% CI: 0.48, 1.61, p = 0.67). Conclusion: BYHWD is an effective and safe therapy for the recovery of ischemic stroke. To further determine the efficacy and safety of BYHWD in the treatment of ischemic stroke in the recovery period, more high-quality, multicenter, and prospective RCTs are needed.

Ornithine aminotransferase and carbamoyl phosphate synthetase 1 involved in ammonia metabolism serve as novel targets for early stages of gastric cancer.

OBJECTIVE: The sensitivity and specificity of current biomarkers for gastric cancer were insufficient. The aim of the present study was to screen novel biomarkers and determine the diagnostic values of ornithine aminotransferase (OAT) and carbamoyl phosphate synthetase 1 (CPS1) for detecting gastric cancer. METHODS: With stable isotope tags, we labelled an initial discovery group of four paired gastric cancer tissue samples and identified with LC-ESI-MS/MS. A validation group of 159 gastric cancer samples and 30 healthy controls were used to validate the candidate targets. GSEA was used to explore the pathways activated in gastric cancer. RESULTS: Four hundred and thirty one proteins were found differentially expressed in gastric cancer tissues. Of these proteins, OAT and CPS1 were found over-expressed in gastric cancer patients, with sensitivity of 70.4% (95% CI: 63.3%-77.6%) and specificity of 80.5% (95% CI: 74.3%-86.7%) for ornithine aminotransferase, and with sensitivity of 68.6% (95% CI: 61.3%-75.8%) and specificity of 73% (95% CI: 66%-79.9%) for carbamoyl phosphate synthetase 1. The co-expression of OAT and CPS1 in gastric cancer tissues has a sensitivity of 81% (95% CI: 73.2%-88.8%) and specificity of 89% (95% CI: 83%-95%). Furthermore, both OAT and CPS1 were overexpressed in patients with local invasion T3 and T4 stages than those in patients with T1 and T2 stages. The co-expression of OAT and CPS1 was strongly correlated with histological grade I 68% (95% CI: 58.7%-77.3%) and TNM stage I/II 52% (95% CI: 42%-62%). The areas under ROC curves were up to 0.758 for the co-expression of OAT and CPS1 in gastric cancer. GSEA results showed that two gene sets and 30 gene sets were activated in OAT high- and CPS1 high-expression patients with gastric cancer, respectively. CONCLUSIONS: The present findings indicated a tight correlation between the co-expression of OAT and CPS1 and the histological grade, local invasion, and TNM stages of gastric cancer. Therefore, OAT and CPS1 might be predictors for gastric cancer invasion and potential targets for anticancer drug design for gastric cancer.

DEPDC1 drives hepatocellular carcinoma cell proliferation, invasion and angiogenesis by regulating the CCL20/CCR6 signaling pathway.

DEP domain containing 1 (DEPDC1) functions as an oncogene in hepatocellular carcinoma (HCC). However, the underlying mechanism of DEPDC1 remains largely unknown. The present study revealed that DEPDC1 knockdown inhibited HCC cell proliferation, colony formation and invasion in vitro and suppressed the growth of HCC xenografts in vivo. Furthermore, DEPDC1 overexpression promoted HCC cell proliferation, colony formation and invasion. DNA microarray, reverse transcription­quantitative­PCR and western blotting results demonstrated that DEPDC1 knockdown in Huh­7 significantly inhibited the expression of chemokine (C­C motif) ligand 20 (CCL20) and chemokine (C­C motif) receptor 6 (CCR6). In addition, the expression of CCL20 and CCR6 were upregulated in HCC tissues and cell lines, and were positively correlated with DEPDC1 expression. CCL20 or CCR6 knockdown via small interfering RNA reversed the effects of DEPDC1 overexpression in HCC cells. Furthermore, it was revealed that conditioned medium from DEPDC1 upregulated Li­7 and Hep3B cells led to angiogenesis in vitro, whereas CCL20 knockdown in Li­7 and Hep3B cells or CCR6 knockdown in human umbilical vein endothelial cells reversed the angiogenic effect of DEPDC1 overexpression. In conclusion, DEPDC1 facilitated cell proliferation, invasion and angiogenesis via the CCL20/CCR6 pathway in HCC.