Activated hedgehog gene pattern correlates with dismal clinical outcome and tumor microenvironment heterogeneity in hepatocellular carcinoma.

Background: Activation of the Hedgehog signaling pathway is linked to the initiation and development of human hepatocellular carcinoma (HCC). However, its impact on clinical outcomes and the HCC microenvironment remains unclear.

Methods: We performed comprehensive analyses of Hedgehog pathway genes in a large cohort of HCC patients.

Hepatitis E Virus Seroprevalence Indicated a Significantly Increased Risk Selectively in Patients with Gastric Cancer among 17 Common Malignancies.

Background: The impact of hepatitis E virus (HEV) infection on cancer development has been poorly investigated. This study aimed to explore the relationship between HEV seroprevalence and cancer risks and to identify high cancer risk subgroups in HEV-exposed populations. Methods: HEV seroprevalence status was determined in cancer and non-cancer subjects.

Proteomic Analysis of Hypoxia-Induced Senescence of Human Bone Marrow Mesenchymal Stem Cells.

Methods: Hypoxia in hBMSCs was induced for 0, 4, and 12 hours, and cellular senescence was evaluated by senescence-associated -galactosidase (SA--gal) staining. Tandem mass tag (TMT) labeling was combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for differential proteomic analysis of hypoxia in hBMSCs. Parallel reaction monitoring (PRM) analysis was used to validate the candidate proteins.

Association between hepatitis B and E virus infection and hepatocellular carcinoma risk.

The role of hepatitis E virus (HEV) in developing hepatocellular carcinoma (HCC) is unclear. Our study aimed to investigate the role of HE infection in HCC development and the effect of hepatitis B virus (HBV) and HEV coinfection on HCC risk. A hospital-based case-control study was conducted.

Hepatitis E virus re-infection accelerates hepatocellular carcinoma development and relapse in a patient with liver cirrhosis: A case report and review of literature.

Background: Hepatitis E virus (HEV) superinfection is a suspected promoting factor for hepatocellular carcinoma (HCC) in patients with chronic hepatitis and cirrhosis. However, to date, very few cases of HEV-related HCC have been reported. Nevertheless, the role of HEV re-infection in cirrhotic liver without other chronic hepatitis infections has rarely been explored.

G protein-coupled receptor kinase-2: A potential biomarker for early diabetic cardiomyopathy.

Background: G protein-coupled receptor kinase-2 (GRK2) has been shown as a key regulator of cardiac function, and the myocardial GRK2 levels are mirrored by the levels in peripheral blood mononuclear cells (PBMCs). In this study, we evaluated the myocardial and PBMCs GRK2 levels in early diabetic cardiomyopathy (DCM).

Methods: C57BL/KS-db/db male diabetic mice at 12 weeks of age, as the type 2 diabetes (T2DM) animal model of early DCM were evaluated.

Mechanisms of U46619-induced contraction in mouse intrarenal artery.

Thromboxane A (TXA ) has been implicated in the pathogenesis of vascular complications, but the underlying mechanism remains unclear. The contraction of renal arterial rings in mice was measured by a Multi Myograph System. The intracellular calcium concentration ([Ca ] ) in vascular smooth muscle cells (VSMCs) was obtained by using a fluo-4/AM dye and a confocal laser scanning microscopy.

Involvement of Orai1 in tunicamycin-induced endothelial dysfunction.

Endoplasmic reticulum (ER) stress is mediated by disturbance of Ca homeostasis. The store-operated calcium (SOC) channel is the primary Ca channel in non-excitable cells, but its participation in agent-induced ER stress is not clear. In this study, the effects of tunicamycin on Ca influx in human umbilical vein endothelial cells (HUVECs) were observed with the fluorescent probe Fluo-4 AM.

[MicroRNA-199a-3p enhances expressions of fibrosis-associated genes through targeting Smad1 in mouse cardiac fibroblasts].

Objective: To investigate the role of miR-199a-3p in cardiac fibrosis and the potential target of miR-199a-3p.

Methods: Cardiac fibroblasts were isolated from C57BL/6 mice and cultured. The miR-199a-3p mimic and Smad1 siRNA were transiently transfected into the cardiac fibroblasts via liposome.

High Plasma Exposure of Statins Associated With Increased Risk of Contrast-Induced Acute Kidney Injury in Chinese Patients With Coronary Artery Disease.

The role of statins in reducing the incidence of contrast-induced acute kidney injury (CI-AKI) remains controversial. We sought to evaluate the association between CI-AKI and high plasma exposure of statins in coronary artery disease (CAD) patients undergoing coronary angiography (CAG). This association was first evaluated in 1,219 patients with CAD receiving atorvastatin (AT) therapy and validated in 635 patients receiving rosuvastatin (RST) therapy.

Activation of miR-34a-5p/Sirt1/p66shc pathway contributes to doxorubicin-induced cardiotoxicity.

The molecular mechanisms underlying anthracyclines-induced cardiotoxicity have not been well elucidated. MiRNAs were revealed dysregulated in the myocardium and plasma of rats received Dox treatment. MicroRNA-34a-5p (miR-34a-5p) was verified increased in the myocardium and plasma of Dox-treated rats, but was reversed in rats received Dox plus DEX treatments.

The enhancement of TXA receptors-mediated contractile response in intrarenal artery dysfunction in type 2 diabetic mice.

Thromboxane A (TXA) has been implicated in the pathogenesis of diabetic vascular complications, although the underlying mechanism remains unclear. The present study investigated the alterations in TXA receptor signal transduction in type 2 diabetic renal arteries. The contraction of renal arterial rings in control (db/m+) mice and type 2 diabetic (db/db) mice was measured by a Multi Myograph System.

CircRNA_000203 enhances the expression of fibrosis-associated genes by derepressing targets of miR-26b-5p, Col1a2 and CTGF, in cardiac fibroblasts.

Circular RNAs (circRNAs) participate in regulating gene expression in diverse biological and pathological processes. The present study aimed to investigate the mechanism underlying the modulation of circRNA_000203 on expressions of fibrosis-associated genes in cardiac fibroblasts. CircRNA_000203 was shown upregulated in the diabetic mouse myocardium and in Ang-II-induced mouse cardiac fibroblasts.

Left ventricular deformation associated with cardiomyocyte Ca(2+) transients delay in early stage of low-dose of STZ and high-fat diet induced type 2 diabetic rats.

Background: In the early stage of diabetes, the cardiac ejection fraction is preserved, despite the existence of the subclinical cardiac dysfunction to some extent. However, the detailed phenotype of this dysfunction and the underlying mechanism remain unclear. To improve our understanding of this issue, we used low-dose STZ and high-fat diet to induce type 2 diabetic models in rats.

CDK6 mediates the effect of attenuation of miR-1 on provoking cardiomyocyte hypertrophy.

MicroRNA-1 (miR-1) is approved involved in cardiac hypertrophy, but the underlying molecular mechanisms of miR-1 in cardiac hypertrophy are not well elucidated. The present study aimed to investigate the potential role of miR-1 in modulating CDKs-Rb pathway during cardiomyocyte hypertrophy. A rat model of hypertrophy was established with abdominal aortic constriction, and a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocytes (NRVCs).

Species-specific differences in the role of L-type Ca²⁺ channels in the regulation of coronary arterial smooth muscle contraction.

The L-type calcium channel (LCC) plays a regulatory role in various physical and pathological processes. In the vasculature, LCCs mediate agonist-induced vascular smooth muscle contraction. However, whether LCC-mediated vessel responses to certain vasoconstrictors vary among species remains unclear.

Macrophage migration inhibitory factor promotes expression of GLUT4 glucose transporter through MEF2 and Zac1 in cardiomyocytes.

Objective: Evidence shows that both macrophage migration inhibitory factor (MIF) and GLUT4 glucose transporter are involved in diabetic cardiomyopathy (DCM), but it remains largely unknown whether and how MIF regulates GLUT4 expression in cardiomyocytes. The present study aims to investigate the mechanism underlying the modulation of GLUT4 by MIF in cardiomyocytes.

Material And Methods: Activations of AKT and AMPK signaling, and expressions of MIF, GLUT4 and the candidate GLUT4 regulation associated transcription factors in the diabetic mouse myocardium were determined.

Function of a novel plakophilin-2 mutation in the abnormal expression of connexin43 in a patient with arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a desmosomal disease. Desmosomes and gap junctions are important structural components of cardiac intercalated discs. The proteins plakophilin-2 (PKP-2) and connexin43 (Cx43) are components of desmosomes and gap junctions, respectively.

Attenuation of microRNA-16 derepresses the cyclins D1, D2 and E1 to provoke cardiomyocyte hypertrophy.

Cyclins/retinoblastoma protein (pRb) pathway participates in cardiomyocyte hypertrophy. MicroRNAs (miRNAs), the endogenous small non-coding RNAs, were recognized to play significant roles in cardiac hypertrophy. But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy.

Rapid determination of fenoldopam in human plasma by UPLC-MS/MS for pharmacokinetic analysis in patients.

We developed and validated a rapid, selective, and sensitive ultra-performance liquid-chromatography mass-spectrometry (UPLC-MS/MS) method for quantifying fenoldopam in human plasma for pharmacokinetic studies. Fenoldopam and the internal-standard (IS), oxazepam, were isolated from human plasma by liquid-liquid extraction using ethyl acetate after alkalization, and were separated on a 2.1×100 mm Acquity UPLC HSS T3 C18 column (inside diameter, 1.

Upregulation of 5-hydroxytryptamine receptor signaling in coronary arteries after organ culture.

Background: 5-Hydroxytryptamine (5-HT) is a powerful constrictor of coronary arteries and is considered to be involved in the pathophysiological mechanisms of coronary-artery spasm. However, the mechanism of enhancement of coronary-artery constriction to 5-HT during the development of coronary artery disease remains to be elucidated. Organ culture of intact blood-vessel segments has been suggested as a model for the phenotypic changes of smooth muscle cells in cardiovascular disease.