High-mobility group box 1 and its related receptors: potential therapeutic targets for contrast-induced acute kidney injury.

Percutaneous coronary intervention (PCI) is a crucial diagnostic and therapeutic approach for coronary heart disease. Contrast agents' exposure during PCI is associated with a risk of contrast-induced acute kidney injury (CI-AKI). CI-AKI is characterized by a sudden decline in renal function occurring as a result of exposure to intravascular contrast agents, which is associated with an increased risk of poor prognosis. The pathophysiological mechanisms underlying CI-AKI involve renal medullary hypoxia, direct cytotoxic effects, endoplasmic reticulum stress, inflammation, oxidative stress, and apoptosis. To date, there is no effective therapy for CI-AKI. High-mobility group box 1 (HMGB1), as a damage-associated molecular pattern molecule, is released extracellularly by damaged cells or activated immune cells and binds to related receptors, including toll-like receptors and receptor for advanced glycation end product. In renal injury, HMGB1 is expressed in renal tubular epithelial cells, macrophages, endothelial cells, and glomerular cells, involved in the pathogenesis of various kidney diseases by activating its receptors. Therefore, this review provides a theoretical basis for HMGB1 as a therapeutic intervention target for CI-AKI.

MiR-126-HMGB1-HIF-1 Axis Regulates Endothelial Cell Inflammation during Exposure to Hypoxia-Acidosis.

Crosstalk between molecular regulators miR-126, hypoxia-inducible factor 1-alpha (HIF-1-α), and high-mobility group box-1 (HMGB1) contributes to the regulation of inflammation and angiogenesis in multiple physiological and pathophysiological settings. Here, we present evidence of an overriding role for miR-126 in the regulation of HMGB1 and its downstream proinflammatory effectors in endothelial cells subjected to hypoxia with concurrent acidosis (H/A). Methods. Primary mouse endothelial cells (PMEC) were exposed to hypoxia or H/A to simulate short or chronic low-flow ischemia, respectively. RT-qPCR quantified mRNA transcripts, and proteins were measured by western blot. ROS were quantified by fluorogenic ELISA and luciferase reporter assays employed to confirm an active miR-126 target in the HMGB1 3'UTR. Results. Enhanced expression of miR-126 in PMECs cultured under neutral hypoxia was suppressed under H/A, whereas the HMGB1 expression increased sequentially under both conditions. Enhanced expression of HMGB1 and downstream inflammation markers was blocked by the premiR-126 overexpression and optimized by antagomiR. Compared with neutral hypoxia, H/A suppressed the HIF-1α expression independently of miR-126. The results show that HMGB1 and downstream effectors are optimally induced by H/A relative to neutral hypoxia via crosstalk between hypoxia signaling, miR-126, and HIF-1α, whereas B-cell lymphoma 2(Bcl2), a HIF-1α, and miR-126 regulated gene expressed optimally under neutral hypoxia. Conclusion. Inflammatory responses of ECs to H/A are dynamically regulated by the combined actions of hypoxia, miR-126, and HIF-1α on the master regulator HMGB1. The findings may be relevant to vascular diseases including atherosclerotic occlusion and interiors of plaque where coexisting hypoxia and acidosis promote inflammation as a defining etiology.

Prognostic Role of Neutrophil to Lymphocyte Ratio in Ovarian Cancer: A Meta-Analysis.

OBJECTIVE: The aim of the study was to investigate the prognostic role of neutrophil to lymphocyte ratio in ovarian cancer. Growing number of articles reported the relationship between neutrophil to lymphocyte ratio and prognosis in ovarian cancer, but the results remains inconclusive. The meta-analysis was conducted to analyze the association of pretreatment neutrophil to lymphocyte ratio with overall survival and progression-free survival. METHODS: We performed a systematic literature research of PubMed, EMBASE, Medline, and Cochrane library for relevant studies up to October 8, 2017. The quality of included studies was assessed by the Newcastle-Ottawa Quality Assessment Scale. The hazard ratio and corresponding 95% confidence intervals were calculated. We checked the heterogeneity by the Q test and Higgins I-squared statistic. Begg funnel plot and Egger linear regression test were also applied for ascertain publication bias. All of the statistical analyses were performed using STATA version 12.0. RESULTS: A total of 12 studies with 4046 patients were included in our study. The results indicated that depressed neutrophil to lymphocyte ratio was significantly correlated with higher overall survival (hazard ratio = 1.409, 95% confidence intervals = 1.112-1.786, P = .005) and progression-free survival (hazard ratio = 1.523, 95% confidence intervals = 1.187-1.955, P = .001) in ovarian cancer. Subgroup analysis by ethnicity of overall survival and progression-free survival showed that the prognostic effect of neutrophil to lymphocyte ratio was found both in Asians and Caucasians. CONCLUSION: Patients with depressed neutrophil to lymphocyte ratio had a higher overall survival and progression-free survival in ovarian cancer. This meta-analysis provided neutrophil to lymphocyte ratio as an available predictor of overall survival and progression-free survival for patients with ovarian cancer.