a-doxorubicin-induced-murine-model-of-dilated-cardiomyopathy-in-vivo

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo

Dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders characterized by ventricular dilation and depressed cardiac ...

Clinical College of Nanjing Medical University

MicroRNAs (miRNAs) are classes of small, non-coding RNAs that regulate the translation of target mRNA transcripts. In this study, we demonstrated that miR-592 was downregulated in human hepatocellular carcinoma (HCC) and could suppress growth of the human HCC cell line HepG2. A tumor oncogene, DEK, was identified as a direct target of miR-592. Luciferase report assay indicated miR-592 regulates DEK expression though bind to its 3'UTR. Furthermore, knockdown of DEK also suppressed cell proliferation of HepG2 cells, which was consist with miR-592. At last, we suggested that DEK was upregulated in HCC tissues inversely with miR-592. These results demonstrated that miR-592 targets DEK transcript and suppresses HCC cell growth, and may provide potential therapeutic target in human HCC.

MicroRNA-592 targets DEK oncogene and suppresses cell growth in the hepatocellular carcinoma cell line HepG2.

Deoxyschizandrin as one of the most important component of Schisandra chinensis (Turcz.) Baill plays an immunomodulatory role in a variety of diseases, yet its role in ulcerative colitis remains to be elucidated. We aimed to investigate the role of deoxyschizandrin in DSS-induced ulcerative colitis in mice.

Deoxyschizandrin suppresses dss-induced ulcerative colitis in mice.

Angelica sinensis (Oliv) Diels (Apiaceae) is a traditional medicine that has been used for more than 2000 years in China. It exhibits various therapeutic effects including neuroprotective, anti-oxidant, anti-inflammatory, and immunomodulatory activities. Angelica polysaccharides (APs), bioactive constituents of Angelica have been shown to be responsible for these effects; however, the utility of APs for the treatment of glioma and their mechanism of action remain to be elucidated.

Angelica polysaccharides inhibit the growth and promote the apoptosis of U251 glioma cells in vitro and in vivo.

Lacking access to an affordable method of high throughput immunoblot analysis for daily use remains a big challenge for scientists worldwide. We proposed here Quantitative Dot Blot analysis (QDB) to meet this demand. With the defined linear range, QDB analysis fundamentally transforms traditional immunoblot method into a true quantitative assay. Its convenience in analyzing large number of samples also enables bench scientists to examine protein expression levels from multiple parameters. In addition, the small amount of sample lysates needed for analysis means significant saving in research sources and efforts. This method was evaluated at both cellular and tissue levels with unexpected observations otherwise would be hard to achieve using conventional immunoblot methods like Western blot analysis. Using QDB technique, we were able to observed an age-dependent significant alteration of CAPG protein expression level in TRAMP mice. We believe that the adoption of QDB analysis would have immediate impact on biological and biomedical research to provide much needed high-throughput information at protein level in this "Big Data" era.

Quantitative dot blot analysis (QDB), a versatile high throughput immunoblot method.

Previous studies showed that miR-124 had a protective role by reducing oxidant stress and preventing cell apoptosis and autophagy. However, its role in doxorubicin-induced cardiomyopathy was less known. In our study, we confirmed increased ROS and decreased expression of miR-124 in doxorubicin-treated heart tissues and primary cardiomyocytes. The oxidative stress and cell apoptosis were alleviated by overexpressing miR-124, characterized by decreased activity of MDA and increased activity of SOD. While inhibiting miR-124 generated opposed effects. Mechanistically, our bioinformatic prediction and luciferase assay confirmed that miR-124 inhibited the expression of p66Shc, a proapoptotic signaling pathway. Our results suggested that miR-124 was hopeful to become a therapeutic target in doxorubicin-related cardiomyopathy.

MiR-124 attenuates doxorubicin-induced cardiac injury via inhibiting p66Shc-mediated oxidative stress.

Diabetic nephropathy (DN) is one of the most serious complications in the development of diabetes mellitus, which has become the main cause of end-stage renal disease and one of the main causes of death in diabetic patients. With the prevalence of diabetes, the number of patients at risk for developing DN is increasing, with 20-40 percent of all patients with diabetes at risk for developing DN. Acupuncture and Chinese herbal medicine treatments are often combined to treat DN; however, there has been no meta-analysis on their synergistic effects. Therefore, we aimed to perform a systematic review and meta-analysis to estimate the effectiveness of acupuncture combined with Chinese herbal medicine for DN treatment.

Efficacy and safety of acupuncture combined with Chinese Herbal Medicine for diabetic nephropathy: A protocol for systematic review and meta-analysis.

Coronary artery disease (CAD) is the most common cardiovascular disease worldwide. In this study, we investigated the pathogenesis of CAD. We downloaded the GSE98583 dataset, including 12 CAD samples and 6 normal samples, from the Gene Expression Omnibus (GEO) database and screened differentially expressed genes (DEGs) in CAD versus normal samples. Next, we performed functional enrichment analysis, protein-protein interaction (PPI) network, and functional module analyses to explore potential functions and regulatory functions of identified DEGs. Next, transcription factors (TFs) and microRNAs (miRNAs) targeting DEGs were predicted. In total, 456 DEGs were identified in CAD and normal samples, including 175 upregulated and 281 downregulated genes. These genes were enriched in the intestinal immune network for immunoglobulin A production and the mitogen-activated protein kinase signaling pathway (e.g.,  and ). The PPI network contained 212 genes, and , , , and  were hub genes with degrees higher than 10. Four significant modules were identified from the PPI network, with genes in the modules mainly enriched in the inflammatory response, protein ubiquitination involved in ubiquitin-dependent protein catabolic processes, protein transport, and mitochondrial translational elongation, respectively. Two TFs (E2F1 and FOXK1) and five miRNAs (, , , , and ) were predicted to target 112 DEGs.  reportedly targets both  and  in the TF-miRNA target regulatory network. The abnormal expression of , , , and  may be implicated in CAD pathogenesis. Our study provides targets and potential regulators for investigating CAD pathogenesis.

Abnormal expression of , , , and  is involved in the pathogenesis of coronary artery disease.

We intended to explore the potential molecular mechanisms underlying the cardiac conduction block inducted by urea transporter (UT)-B deletion at the transcriptome level. The heart tissues were harvested from UT-B null mice and age-matched wild-type mice for lncRNA sequencing analysis. Based on the sequencing data, the differentially expressed mRNAs (DEMs) and lncRNAs (DELs) between UT-B knockout and control groups were identified, followed by function analysis and mRNA-lncRNA co-expression analysis. The miRNAs were predicted, and then the competing endogenous RNA (ceRNA) network was constructed. UT-B deletion results in the aberrant expression of 588 lncRNAs and 194 mRNAs. These DEMs were significantly enriched in the inflammation-related pathway. A lncRNA-mRNA co-expression network and a ceRNA network were constructed on the basis of the DEMs and DELs. The complement 7 (C7)-NONMMUT137216.1 co-expression pair had the highest correlation coefficient in the co-expression network. NONMMUT140591.1 had the highest degree in the ceRNA network and was involved in the ceRNA of NONMMUT140591.1-mmu-miR-298-5p- (GATA binding protein 5). UT-B deletion may promote cardiac conduction block via inflammatory process. The ceRNA NONMMUT140591.1-mmu-miR-298-5p- may be a potential molecular mechanism of UT-B knockout-induced cardiac conduction block.

NONMMUT140591.1 may serve as a ceRNA to regulate Gata5 in UT-B knockout-induced cardiac conduction block.

To evaluate the efficacy and potential pharmacological mechanisms of Danggui Buxue Decoction (DGBXD) in the treatment of diabetic nephropathy.

The efficacy and potential mechanism of Danggui Buxue Decoction in treating diabetic nephropathy: A meta-analysis and network pharmacology.

The link between diabetes and dementia risk is not well understood. This study evaluates the factors linking diabetes to dementia onset, providing guidance for preventing dementia in diabetic patients.

Article	Year
MicroRNA-592 targets DEK oncogene and suppresses cell growth in the hepatocellular carcinoma cell line HepG2. International journal of clinical and experimental pathology\| PubMed ID: 26722432	2015
Deoxyschizandrin suppresses dss-induced ulcerative colitis in mice. Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association\| PubMed ID: 27976641	2016
Angelica polysaccharides inhibit the growth and promote the apoptosis of U251 glioma cells in vitro and in vivo. Phytomedicine : international journal of phytotherapy and phytopharmacology\| PubMed ID: 28887916	2017
Quantitative dot blot analysis (QDB), a versatile high throughput immunoblot method. Oncotarget\| PubMed ID: 28938578	2017
MiR-124 attenuates doxorubicin-induced cardiac injury via inhibiting p66Shc-mediated oxidative stress. Biochemical and biophysical research communications\| PubMed ID: 31672275	2020
Efficacy and safety of acupuncture combined with Chinese Herbal Medicine for diabetic nephropathy: A protocol for systematic review and meta-analysis. Medicine\| PubMed ID: 34477143	2021
Abnormal expression of , , , and is involved in the pathogenesis of coronary artery disease. Reviews in cardiovascular medicine\| PubMed ID: 34565095	2021
NONMMUT140591.1 may serve as a ceRNA to regulate Gata5 in UT-B knockout-induced cardiac conduction block. Open life sciences\| PubMed ID: 34901457	2021
The efficacy and potential mechanism of Danggui Buxue Decoction in treating diabetic nephropathy: A meta-analysis and network pharmacology. Medicine\| PubMed ID: 37026924	2023
The relationship between diabetes and the dementia risk: a meta-analysis. Diabetology & metabolic syndrome\| PubMed ID: 38745237	2024

Wenfeng Zhang

Biography

JoVE Journal Publications

Other Publications