Hepatocellular carcinoma (HCC) ranks the sixth most common cancer and the third cause of cancer-related mortality worldwide. Recent studies identified that circ-ITCH Suppresses mutiple cancers proliferation via inhibiting the Wnt/beta-Catenin pathway. In current study, conducted a genetic association study together with epidemiological follow-up study to delineate the role of circ-ITCH in the development and progression of HCC. we found rs10485505 (adjusted OR =1.18; 95% CI=1.06-1.31; P value =3.1×10-3) and rs4911154 (adjusted OR =1.27; 95% CI=1.14-1.43; P value =3.7×10-5) were significantly associated with increased HCC risk. The expression level of circ-ITCH was significantly lower in HCC tissues, compared with that in adjacent tissues (P value < 0.001). Cox regression analysis indicated that high expression of circ-ITCH was associated with favorable survival of HCC (HR=0.45; 95% CI=0.29-0.68; P value < 0.001). These results indicate that circ-ITCH may have an inhibitory effect on HCC, and could serve as susceptibility and prognostic biomarkers for HCC patients.

Background and Aims Hepatic ischemia‐reperfusion (I/R) injury remains a major challenge affecting the morbidity and mortality of liver transplantation. Effective strategies to improve liver function after hepatic I/R injury are limited. Six‐transmembrane epithelial antigen of the prostate 3 (Steap3), a key regulator of iron uptake, was reported to be involved in immunity and apoptotic processes in various cell types. However, the role of Steap3 in hepatic I/R‐induced liver damage remains largely unclear. Approach and Results In the present study, we found that Steap3 expression was significantly up‐regulated in liver tissue from mice subjected to hepatic I/R surgery and primary hepatocytes challenged with hypoxia/reoxygenation insult. Subsequently, global Steap3 knockout (Steap3‐KO) mice, hepatocyte‐specific Steap3 transgenic (Steap3‐HTG) mice, and their corresponding controls were subjected to partial hepatic warm I/R injury. Hepatic histology, the inflammatory response, and apoptosis were monitored to assess liver damage. The molecular mechanisms of Steap3 function were explored in vivo and in vitro. The results demonstrated that, compared with control mice, Steap3‐KO mice exhibited alleviated liver damage after hepatic I/R injury, as shown by smaller necrotic areas, lower serum transaminase levels, decreased apoptosis rates, and reduced inflammatory cell infiltration, whereas Steap3‐HTG mice had the opposite phenotype. Further molecular experiments showed that Steap3 deficiency could inhibit transforming growth factor‐β–activated kinase 1 (TAK1) activation and downstream c‐Jun N‐terminal kinase (JNK) and p38 signaling during hepatic I/R injury. Conclusions Steap3 is a mediator of hepatic I/R injury that functions by regulating inflammatory responses as well as apoptosis through TAK1‐dependent activation of the JNK/p38 pathways. Targeting hepatocytes, Steap3 may be a promising approach to protect the liver against I/R injury.

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Background and purposeAlthough high leptin concentration has been shown to be correlated with established vascular risk factors, epidemiologic studies have reported inconclusive results on the association between leptin and cardiovascular diseases (CVD). Therefore, a meta-analysis was performed to evaluate this issue.MethodsWe searched Pubmed, Embase, and the Cochrane Library from their inception to Jan 2016 for both case-control and cohort studies that assessed leptin concentration and CVD risk. Reports with odds ratio (OR), risk ratio (RR) and corresponding 95% confidence intervals (CI) were considered. The data were extracted by two investigators independently.ResultsA total of 13 epidemiologic studies totaling 4257 CVD patients and 26710 controls were included. A significant inverse association was shown between leptin and coronary heart disease (CHD), with an overall OR of 1.16 (95% CI: 1.02–1.32), but not for stroke (OR = 1.21, 95% CI 0.98–1.48) under sociodemographic adjustment. Further adjustment for additional cardiovascular risk factors resulted in ORs of 1.16 (95% CI 0.97–1.40) for CHD and 1.10 (95% CI 0.89–1.35) for stroke. The findings remained when analyses were restricted to high-quality studies and indicated OR estimates of 1.07 (95% CI 0.96–1.19) for CHD and 0.98 (95% CI 0.76–1.25) for stroke. In a subgroup meta-analysis, a high leptin level was not independently associated with CHD in both females (OR = 1.03, 95% CI 0.86–1.23) and males (OR = 1.09, 95% CI 0.95–1.26) or with stroke in both females (OR = 1.13, 95% CI 0.87–1.47) and males (OR = 0.80, 95% CI 0.59–1.09). There was no significant publication bias as suggested by Egger test outcomes.ConclusionsOur findings indicate that high leptin levels may not be associated with risks of CHD and stroke. Further large, well-designed prospective cohort studies are needed to fully evaluate the role of leptin on the risk of CVD.

Background Early identification of early death for bladder cancer patients undergoing radical cystectomy based on the laboratory findings at the time of diagnosis could improve the overall survival. The study aimed to explore preoperative factors associated with higher risk of early death (within 1 year after surgery) for bladder cancer patients. Methods A total of 186 bladder cancer patients who underwent robot‐assisted radical cystectomy (RARC) were identified between October 2014 and May 2017. The probability of dying within 1 year after RARC was defined as the end point “early death.” Predictive factors including clinical features and laboratory findings at diagnosis were retrospectively collected. Results Median follow‐up time after RARC was 20.6 months (1.2‐43.7 months). Fifty‐one patients (27.4%) died during follow‐up and 31 within 1 year from surgery (1‐year mortality rate: 16.7%). All potentially prognostic factors were assessed on univariate analyses, which revealed the following factors as being associated with higher risk of early death within 1 year after RARC: older age ( P = 0.004), advanced clinical stage ( P = 0.005), presence of hydronephrosis ( P = 0.021), higher fibrinogen ( P = 0.007), higher PLR ( P = 0.031), and lower PNI ( P = 0.016). In a multivariate Cox proportional hazard regression model analysis, age >60 years (HR = 7.303, 95% CI 1.734‐30.764; P = 0.007) and fibrinogen ≥3.295 g/L (HR = 2.396, 95% CI 1.138‐5.045; P = 0.007) at diagnosis were independent prognostic factors of early death after RARC. Conclusion Age and preoperative elevated plasma fibrinogen level were independent predictors for 1‐year mortality after RARC. We believe that plasma fibrinogen levels may become a useful biomarker, which may help guide the treatment decision‐making process for patients with bladder cancer.

The mechanisms underlying severe liver injury after brain-dead (BD) donor liver transplantation (BDDLT) remain unclear. In this study, we aimed to explore the roles of lncRNAs and circRNAs in liver injury after BDDLT. Rat liver injury was detected in the sham, BD, control, and BDDLT groups. We examined the expression profiles of lncRNAs and circRNAs in the livers of the BDDLT and control group using microarray analysis. The main functions of the differentially expressed genes were analyzed by gene ontology (GO) and KEGG pathway enrichment analysis. In addition, we used bioinformatic analyses to construct related expression networks. Liver injury was aggravated in the BD and BDDLT groups. We found various mRNAs, lncRNAs, and circRNAs that were differentially expressed in the BDDLT group compared with those in the control group. Coding-noncoding gene co-expression (CNC) network analysis showed that expression of the lncRNA LOC102553657 was associated with that of the apoptosis-related genes including HMOX1 and ATF3. Furthermore, competing endogenous RNAs (ceRNAs) network analysis revealed that the lncRNA LOC103692832 and rno_circRNA_007609 were ceRNAs of rno-miR-135a-5p targeting Atf3, Per2, and Mras. These results suggest that lncRNAs and circRNAs play important roles in the pathogenesis and development of liver injury during BDDLT.

The aim of the present study was to investigate the effects and molecular mechanisms of GPR4 (G-protein-coupled receptor 4) in cell apoptosis and renal ischemia-reperfusion (IR) injury and GPR4 mice and wild-type (WT) mice underwent renal IR or sham procedures. For hypoxia/reoxygenation (HR), human umbilical vein endothelial cells (HUVECs) were subjected to 4 h of hypoxia, followed by 6 h of reoxygenation. Renal histological changes were observed by periodic acid-Schiff staining and myeloperoxidase activity. Apoptosis was detected by TUNEL staining. GPR4, C/EBP-homologous protein (CHOP) and cleaved caspase-3 protein expressions were detected by western blot. Both GPR4 and CHOP were up-regulated after renal IR in mice. GPR4-knockout mice had significantly less renal damage and decreased TUNEL-positive cells than WT controls after IR. Bone marrow chimeras demonstrated that it was due to the GPR4 inactivation in renal parenchymal cells. Moreover, GPR4 was mainly expressed in endothelial cells after renal IR. GPR4 knockdown markedly inhibited CHOP expression and cell apoptosis in the HUVECs after HR treatment. GPR4 blockade attenuated renal injury after IR and reduced the cell apoptosis through the suppression of CHOP expression.

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