Increasing evidences have demonstrated that inflammation is involved in the mechanisms of acute ischemic stroke (AIS). As an important and easy-to-measure inflammatory marker, neutrophil-to-lymphocyte ratio (NLR) shows a high association with mortality in patients with stroke in recent studies. In this study, we evaluated the prognostic role of NLR in patients with AIS. One hundred forty-three patients with AIS were enrolled. Clinical data were collected and the NLR was calculated from the admission blood work. The patients were followed up for 3 months after stroke onset. The occurrence of death and the major disability at 3 months after onset were end points in this study. Modified Rankin Scale score ≥3 was considered as poor outcome. In this study, 75 patients (52%) had poor outcome. We used binary logistic regression model to evaluate risk factor for poor outcome of AIS and found that the NLR was independently associated with the poor outcome of 3 months (P < 0.001). The optimal cutoff value for NLR as a predictor for 3-month outcome was 2.995. Therefore, in our study, high NLRs inversely predicted 3-month outcome in patients with AIS.

The elevated plasma cholesterol level, in particular, LDL cholesterol is regarded as an important risk factor for the development of atherosclerosis and coronary artery disease. A number of studies provide the evidence that taurine has the efficient action to reduce plasma and liver cholesterol concentrations, especially to decrease VLDL and LDL cholesterol in hypercholesterolemia animal induced by high cholesterol diet. Cholesterol lowering effect of taurine is actually involved in the regulatory mechanism of cholesterol and bile acid homeostasis that mediated by CYP7A1, which has become a biomarker for cholesterol metabolism and itself is also regulated by several factors and nuclear receptors. This review summarizes the change of cholesterol concentration in metabolism observed in feeding studies of hypercholesterolemia animal dealing with taurine, and then, addresses the possible metabolic and molecular mechanisms of cholesterol lowering effect by taurine in three aspects, cholesterol clearance from blood circulation, bioconversion of cholesterol to bile acid in liver, and excretion of cholesterol and bile acid from intestine.

Liver ischemia/reperfusion (IR) injury is a severe complication of liver surgery. Moreover, nonalcoholic fatty liver disease (NAFLD) patients are particularly vulnerable to IR injury, with higher rates of postoperative morbidity and mortality after liver surgeries. Our previous study found that renalase (RNLS) was highly sensitive and responsive to oxidative stress, which may be a promising biomarker for the evaluation of the severity of liver IR injury. However, the role of RNLS in liver IR injury remains unclear. In the present study, we intensively explored the role and mechanism of RNLS in fatty liver IR injury in vivo and in vitro. C57BL/6 mice were divided into 2 groups feeding with high-fat diet (HFD) and control diet (CD), respectively. After 20 weeks’ feeding, they were suffered from portal triad blockage and reflow to induce liver IR injury. Additionally, oleic acid (OA) and tert-butyl hydroperoxide (t-BHP) were used in vitro to induce steatotic hepatocytes and to simulate ROS burst and mimic cellular oxidative stress following portal triad blockage and reflow, respectively. Our data showed that RNLS was downregulated in fatty livers, and RNLS administration effectively attenuated IR injury by reducing ROS production and improving mitochondrial function through activating SIRT1. Additionally, the downregulation of RNLS in the fatty liver was mediated by a decrease of signal transduction and activator of transcription 3 (STAT3) expression under HFD conditions. These findings make RNLS a promising therapeutic strategy for the attenuation of liver IR injury.

Increasing evidence has revealed a significant association between microorganisms and oral squamous cell carcinoma (OSCC). Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, is considered an important potential etiologic agent of OSCC, but the underlying immune mechanisms through which P. gingivalis mediates tumor progression of the oral cancer remain poorly understood. Our cohort study showed that the localization of P. gingivalis in tumor tissues was related to poor survival of patients with OSCC. Moreover, P. gingivalis infection increased oral lesion multiplicity and size and promoted tumor progression in a 4-nitroquinoline-1 oxide (4NQO)–induced carcinogenesis mouse model by invading the oral lesions. In addition, CD11b+ myeloid cells and myeloid-derived suppressor cells (MDSCs) showed increased infiltration of oral lesions. Furthermore, in vitro observations showed that MDSCs accumulated when human-derived dysplastic oral keratinocytes (DOKs) were exposed to P. gingivalis, and CXCL2, CCL2, interleukin (IL)–6, and IL-8 may be potential candidate genes that facilitate the recruitment of MDSCs. Taken together, our findings suggest that P. gingivalis promotes tumor progression by generating a cancer-promoting microenvironment, indicating a close relationship among P. gingivalis, tumor progression of the oral cancer, and immune responses.

Metabolic syndrome, a cluster of risk factors for diabetes and cardiovascular disease, has become a very serious public health concern. A number of studies have provided evidence that taurine has an efficient action against metabolic syndrome, which includes reducing triglycerides to prevent obesity, improving insulin resistance to regulate glucose metabolism, lowering cholesterol (especially decreasing VLDL + LDL cholesterol and increasing HDL cholesterol) to prevent diet-induced hypercholesterolemia, and regulating the renin-angiotensin-aldosterone system and the kallikrein-kinin system etc. to reduce blood pressure. This review summarizes the data from in vitro, animal and limited human studies of beneficial effects of taurine on obesity, dyslipidaemia, diabetes mellitus and hypertension, and addresses the possible metabolic and molecular mechanisms of the prevention of metabolic syndrome by taurine.

Colorectal cancer (CRC) is one of the principal causes of cancer-associated mortality worldwide. The high incidence of liver metastasis is the leading risk factor of mortality in patients with CRC, and the mechanisms of CRC liver metastasis are poorly understood. In the present study, 7 datasets, including 3 gene expression profile datasets and 4 microRNA (miRNA) expression profile datasets were downloaded from the NCBI Gene Expression Omnibus (GEO) database to identify potential key genes and miRNAs, which may be candidate biomarkers for CRC liver metastasis. Differentially expressed (DE) genes (DEGs) and DE miRNAs of primary CRC tumor tissues and liver metastatic CRC tumor tissues were selected using the GEO2R tool. Gene Ontology and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses were conducted using the Database for Annotation, Visualization and Integrated Discovery online database. Furthermore, Cytoscape with cytoHubba and the Molecular Complex Detection (MCODE) plug-in were used to visualize a protein-protein interaction (PPI) network for these DEGs, and to screen hub genes and gene modules in the PPI network. In addition, the online databases, TargetScan, miRanda, PITA, miRWalk and miRDB, were used to identify the target genes of the DE miRNAs. In the present study, 141 DEGs (97 upregulated and 44 downregulated) and 3 DE miRNAs (2 upregulated and 1 downregulated) were screened from the 3 gene expression microarray datasets and 4 miRNA expression microarray datasets, respectively. In total, 10 hub genes with a high degree of connectivity were selected from the PPI network, including albumin (ALB), coagulation factor II (F2), thrombin, apolipoprotein H (APOH), serpin family C member 1 (SERPINC1), apolipoprotein A1 (APOA1), α-1-microglobulin/bikunin precursor (AMBP), apolipoprotein C3 (APOC3), plasminogen (PLG), α-2 HS glycoprotein (AHSG) and apolipoprotein B (APOB). The most important module was detected in the PPI network using the MCODE plug-in. A total of 20 DEGs were identified to be potential target genes of these DE miRNAs, and novel miRNA-DEGs regulatory axes were constructed. In vitro experiments were performed to demonstrate that miR-885 promoted CRC cell migration by, at least partially, decreasing the expression of von Willebrand factor (vWF) and insulin-like growth factor binding protein 5 (IGFBP5). In conclusion, by using integrated bioinformatics analysis and in vitro experiments, key candidate genes were identified and novel miRNA-mRNA regulatory axes in CRC liver metastasis were constructed, which may improve understanding of the molecular mechanisms underlying CRC liver metastasis.

BackgroundH19 is a paternally imprinted gene that has been shown to be highly expressed in the trophoblast tissue. Results from previous studies have initiated a debate as to whether noncoding RNA H19 acts as a tumor suppressor or as a tumor promotor in trophoblast tissue. In the present study, we developed lentiviral vectors expressing H19-specific small interfering RNA (siRNA) to specifically block the expression of H19 in the human choriocarcinoma cell line JAR. Using this approach, we investigated the impact of the H19 gene on the proliferation, invasion and apoptosis of JAR cells. Moreover, we examined the effect of H19 knockdown on the expression of insulin-like growth factor 2 (IGF2), hairy and enhancer of split homologue-1 (HES-1) and dual-specific phosphatase 5 (DUSP5) genes.ResultsH19 knockdown inhibited apoptosis and proliferation of JAR cells, but had no significant impact on cell invasion. In addition, H19 knockdown resulted in significant upregulation of HES-1 and DUSP5 expression, but not IGF2 expression in JAR cells.ConclusionsThe finding that H19 downregulation could simultaneously inhibit proliferation and apoptosis of JAR cells highlights a putative dual function for H19 in choriocarcinoma and may explain the debate on whether H19 acts as a tumor suppressor or a tumor promotor in trophoblast tissue. Furthermore, upregulation of HES-1 and DUSP5 may mediate H19 downregulation-induced suppression of proliferation and apoptosis of JAR cells.

This study investigated the roles of Rho protein in epidermal growth factor (EGF)-induced trophoblast cell migration and its mechanism. Using choriocarcinoma cell lines JEG-3 and JAR and first-trimester human chorionic villus explant cultures on matrigel, we examined EGF-mediated stimulation of trophoblast migration. EGF is shown to have a dose-dependent effect on trophoblast migration. A low concentration of EGF (1 ng/ml) has a stimulatory effect on cell migration, whereas high concentrations of EGF (100 ng/ml) shows an inhibitory effect. EGF (1 ng/ml) activates RhoA and RhoC, but not RhoB, through elevated protein levels and activity. EGF-induced migration was shown to be inhibited by either cell-permeable C3 exoenzyme transferase or selective RhoA or RhoC small interfering RNAs. The inhibition was not mitigated by the addition of EGF, suggesting that RhoA and RhoC play an important role in trophoblast migration and are obligatory for EGF action. Treatment of JEG-3 and JAR cells with RhoA small interfering RNA induced F-actin cytoskeleton disruption and cell shrinkage, which is consistent with the effect of C3 exoenzyme transferase, and this action was not mitigated by EGF treatment. RhoC small interfering RNA had no apparent effect on the F-actin arrangement, suggesting that RhoA but not RhoC takes part in the EGF-induced migration through F-actin rearrangement. These results indicate that RhoA and RhoC play more important roles than RhoB in EGF-mediated migration of trophoblast cells, and RhoA but not RhoC regulates this migration through F-actin cytoskeleton reorganization.