We previously established a rat model of diabetic cardiomyopathy (DCM) and found that the expression of lncRNA H19 was significantly downregulated. The present study was designed to investigate the pathogenic role of H19 in the development of DCM. Overexpression of H19 in diabetic rats attenuated oxidative stress, inflammation and apoptosis, and consequently improved left ventricular function. High glucose was associated with reduced H19 expression and increased cardiomyocyte apoptosis. To explore the molecular mechanisms involved, we performed in vitro experiments using cultured neonatal rat cardiomyocytes. Our results showed that miR-675 expression was decreased in cardiomyocytes transfected with H19 siRNA. The 3′UTR of VDAC1 was cloned downstream of a luciferase reporter construct and cotransfected into HEK293 cells with miR-675 mimic. The results of luciferase assay indicated that VDAC1 might be a direct target of miR-675. The expression of VDAC1 was upregulated in cardiomyocytes transfected with miR-675 antagomir, which consequently promotes cellular apoptosis. Moreover, enforced expression of H19 was found to reduce VDAC1 expression and inhibit apoptosis in cardiomyocytes exposed to high glucose. In conclusion, our study demonstrates that H19/miR-675 axis is involved in the regulation of high glucose-induced apoptosis by targeting VDAC1, which may provide a novel therapeutic strategy for the treatment of DCM.
Background Colorectal cancer (CRC) is one of the most common cancers of the gastrointestinal tract and ranks third in cancer-related deaths worldwide. This study was conducted to identify novel biomarkers related to the pathogenesis of CRC based upon a bioinformatics analysis, and further verify the biomarkers in clinical tumor samples and CRC cell lines. Methods A series of bioinformatics analyses were performed using datasets from NCBI-GEO and constructed a protein–protein interaction (PPI) network. This analysis enabled the identification of Hub genes, for which the mRNA expression and overall survival of CRC patients data distribution was explored in The Cancer Genome Atlas (TCGA) colon cancer and rectal cancer (COADREAD) database. Furthermore, the differential expression of HCAR3 and INLS5 was validated in clinical tumor samples by Real-time quantitative PCR analysis, western blotting analysis, and immunohistochemistry analysis. Finally, CRC cells over-expressing INSL5 were constructed and used for CCK8, cell cycle, and cell apoptosis validation assays in vitro. Results A total of 286 differentially expressed genes (DEGs) were screened, including 64 genes with increased expression and 143 genes with decreased expression in 2 CRC database, from which 10 key genes were identified: CXCL1, HCAR3, CXCL6, CXCL8, CXCL2, CXCL5, PPY, SST, INSL5, and NPY1R. Among these genes, HCAR3 and INSL5 had not previously been explored and were further verified in vitro. Conclusions HCAR3 expression was higher in CRC tissues and associated with better overall survival of CRC patients. INSL5 expression in normal tissue was higher than that in tumor tissue and its high expression was associated with a better prognosis for CRC. The overexpression of INSL5 significantly inhibited the proliferation and promoted the shearing of PARP of CRC cells. This integrated bioinformatics study presented 10 key hub genes associated with CRC. HCAR3 and INSL5 were expressed in tumor tissue and these were associated with poor survival and warrant further studies as potential therapeutic targets.
Objectives Ischemia–reperfusion injury is harmful in partial nephrectomy (PN) in renal cell carcinoma. Choosing an appropriate surgical method is important to reduce ischemia–reperfusion injury. This study aimed to compare the effect of segmental artery clamping (SAC) and main renal artery clamping (MAC) on patients who underwent PN. Methods Studies from January 2008 to November 2019 were identified by an electronic search of English and Chinese databases, including PubMed, Excerpt Medica Database, Cochrane Library, Wanfang, VIP, and Chinese National Knowledge Internet, without language restriction. Two reviewers were involved in the trial. The effects on operation time (OT), warm ischemia time (WIT), length of hospital stay (LOS), blood transfusion rate, postoperative complication rate, Clavien classification (≥ 3), and positive surgery margin (PSM) were evaluated using Stata software. Standardized mean difference (SMD, for continuous data) and pooled odds ratios (for count data) with 95% confidence interval (CI) were used as effect indicators. Results Thirty-two studies were included. SAC decreased the 1-week (SMD = − 0.973; 95% CI = − 1.414, − 0.532; P = 0.000), 1-month (SMD = − 0.411; 95% CI = − 0.769, − 0.053; P = 0.025), and 3-month (affected kidney: SMD = − 0.914; 95% CI = − 1.662, − 0.617; P = 0.000) percentages of postoperative changes in renal function (estimated glomerular filtration rate) between the SAC and MAC groups. Sub-group analysis showed that the SAC group had longer OT (SMD = 0.562; 95% CI = 0.252, 0.871; P = 0.000) than the MAC group. However, no differences were observed in the OT, WIT, LOS, blood transfusion rate, postoperative complication rate, Clavien classification (≥ 3), and PSM between the two groups. Conclusions SAC is superior to MAC in terms of short-term postoperative renal function recovery. The use of SAC or MAC depends on tumor size, location, surgical modality, and surgeon’s judgments.
Esophageal cancer is a common malignant tumor of the digestive system with a high incidence and a poor prognosis. At the present, CT-based radiomics is providing more and more valuable information. However, the heterogeneity of the study and the poor repeatability of the texture feature parameters have limited its wider clinical application. In the present study, we focused on comparing the differences in the texture features of T3 stage esophageal squamous cell carcinoma at different locations and normal esophageal wall, aiming to provide some pieces of useful information for future research on esophageal squamous cell carcinoma. Fifty seven cases with throat CT imaging, including esophageal cancer contrast enhanced CT and conventional CT of healthy control group. The texture characteristics in control group and tumor group among different parts were compared. Using Univariable analysis, we compared the difference and conducted receiver-operator curve analysis to evaluate the performance of tumor grade diagnosis model. 53 radiomic features were significantly different in control group and so as 93 features for tumor group. The upper section was the mostly different from the other 2 sections. Run-length matrix (RLM) features in tumor group accounted for the highest proportion, only Surface Volume Ratio was different. There are differences in the texture features of the tube wall in different parts of the esophagus of healthy adults, and this difference is more obvious in pT3 stage esophageal squamous cell carcinoma. In the future radiomics study of esophageal squamous cell carcinoma, we need to pay attention to this to avoid affecting the accuracy of the results.
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