Xinyu Liu

This study explored potential biomarkers associated with Lauren classification of gastric cancer. We screened microarray datasets on gastric cancer with information of Lauren classification in GEO database, and compared differentially expressing genes between intestinal-type or diffuse-type gastric cancer. Four sets of microarray data (GSE2669, GSE2680, GDS3438 and GDS4007) were enrolled into analysis. By differential gene analysis, UBE2C, CDH1, CENPF, ERO1L, SCD, SOX9, CKS1B, SPP1, MMP11 and ANLN were identified as the top genes related to intestinal-type gastric cancer, and MGP, FXYD1, FAT4, SIPA1L2, MUC5AC, MMP15, RAB23, FBLN1, ANXA10 and ADH1B were genes related to diffuse-type gastric cancer. We comprehensively validated the biological functions of the intestinal-type gastric cancer related gene UBE2C and evaluated its clinical significance on 1868 cases of gastric cancer tissues from multiple medical centers of Shanghai, China. The gain of copy number on 20q was found in 4 out of 5 intestinal-type cancer cell lines, and no similar copy number variation was found in any diffuse-type cancer cell line. Interfering UBE2C expression inhibited cell proliferation, migration and invasion in vitro, and tumorigenesis in vivo. Knockdown of UBE2C resulted in G2/M blockage in intestinal-type gastric cancer cells. Overexpression of UBE2C activated ERK signal pathway and promoted cancer cell proliferation. U0126, an inhibitor of ERK signaling pathway reversed the oncogenic phenotypes caused by UBE2C. Moreover, overexpression of UBE2C was identified in human intestinal-type gastric cancer. Overexpression of UBE2C protein predicted poor clinical outcome. Taken together, we characterized a group of Lauren classification-associated biomarkers, and clarified biological functions of UBE2C, an intestinal-type gastric cancer associated gene. Overexpression of UBE2C resulted in chromosomal instability that disturbed cell cycle and led to poor prognosis of intestinal-type gastric cancer.

. Quercetin also suppressed the activation of the NF-κB pathway induced by myocardial IRI. GW9662 or PPARγ knockdown partially attenuated these cardioprotective effects of quercetin during myocardial IRI. In conclusion, our findings suggest that quercetin ameliorated IRI-induced heart damage via PPARγ activation and the underlying mechanism might involve the inhibition of NF-κB pathway by PPARγ activation.

Purpose: To evaluate the accuracy of inflammatory biomarkers in differentiating patients with asthma–COPD overlap (ACO) from those with COPD alone. Methods: Clinical data of 134 patients with COPD and 48 patients with ACO admitted to the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 were retrospectively analyzed. Receiver operating characteristic (ROC) curve analysis was performed to determine the best cut-off values of fractional exhaled nitric oxide (FeNO), blood eosinophil counts (EOS), and neutrophil to lymphocyte ratio (NLR) for differentiating between ACO and COPD alone. Spearman correlation analysis was conducted to evaluate the relationships between these inflammatory biomarkers and the forced expiratory volume in one second/prediction (FEV 1 %pred). Results: FeNO and EOS in the ACO patients were significantly higher than those in the COPD patients (FeNO: median 37.50 vs 24.50 ppb, P < 0.001; EOS: median 0.20 vs 0.10 × 10 9 /L, P = 0.004). FeNO was positively correlated with FEV 1 %pred (r = 0.314, P = 0.030), while NLR was negatively correlated with FEV 1 %pred (r = − 0.372, P = 0.009) in patients with ACO. In addition, a positive correlation between FeNO and EOS was also found in ACO, especially in patients without history of inhaled corticosteroids (ICS) use (r = 0.682, P < 0.001). The optimal cut-off value of FeNO was 31.5 ppb (AUC = 0.758, 95% CI = 0.631– 0.886) in patients with smoking history, with 70.0% sensitivity and 89.9% specificity for differentiating ACO from COPD. In patients without history of ICS use, the best cut-off value of FeNO was 39.5 ppb (AUC = 0.740, 95% CI = 0.610– 0.870), with 58.3% sensitivity and 84.9% specificity. Among patients without history of ICS use and smoking, 27.5 ppb was optimal cut-off level for FeNO (AUC = 0.744, 95% CI = 0.579– 0.908) to diagnose ACO, with 81.8% sensitivity and 60.7% specificity, and the sensitivity was improved to 91.7% when FeNO was combined with EOS. Conclusion: The inflammatory biomarkers FeNO and EOS can be used as indicators for differentiating between ACO and COPD alone. Keywords: fractional exhaled nitric oxide, blood eosinophil counts, neutrophil to lymphocyte ratio, chronic obstructive pulmonary disease, asthma–COPD overlap

BACKGROUND: Myocardial ischemia-reperfusion injury (IRI) has become one of the most serious complications after reperfusion therapy in patients with acute myocardial infarction. Small ubiquitin-like modification (SUMOylation) is a reversible process, including SUMO E1-, E2-, and E3-mediated SUMOylation and SUMO-specific protease-mediated deSUMOylation, with the latter having been shown to play a vital role in myocardial IRI previously. However, little is known about the function and regulation of SUMO E3 ligases in myocardial IRI. RESULTS: In this study, we found dramatically decreased expression of PIAS1 after ischemia/reperfusion (I/R) in mouse myocardium and H9C2 cells. PIAS1 deficiency aggravated apoptosis and inflammation of cardiomyocytes via activating the NF-κB pathway after I/R. Mechanistically, we identified PIAS1 as a specific E3 ligase for PPARγ SUMOylation. Moreover, H9C2 cells treated with hypoxia/reoxygenation (H/R) displayed reduced PPARγ SUMOylation as a result of down-regulated PIAS1, and act an anti-apoptotic and anti-inflammatory function through repressing NF-κB activity. Finally, overexpression of PIAS1 in H9C2 cells could remarkably ameliorate I/R injury. CONCLUSIONS: Collectively, our findings demonstrate the crucial role of PIAS1-mediated PPARγ SUMOylation in protecting against myocardial IRI.