Kallistatin Improves High-Fat-Induced Insulin Resistance via Epididymal Adipose Tissue-Derived Exosomes.

Studies have found that high expression of human Kallistatin (HKS) in adipose tissue can improve obesity and its associated comorbidities, but the underlying mechanism of specific regulation is unclear. An obesity model was built by injecting 8-week-old C57BL/6 mice ( = 6 mice per group) with (Ad.Null and (Ad.

Visceral adipose tissue-directed human kallistatin gene therapy improves adipose tissue remodeling and metabolic health in obese mice.

Objective: Adipose tissue remodeling is a dynamic process that is pathologically expedited in the obese state and is closely related to obesity-associated disease progression. This study aimed to explore the effects of human kallistatin (HKS) on adipose tissue remodeling and obesity-related metabolic disorders in mice fed with a high-fat diet (HFD).

Methods: Adenovirus-mediated HKS cDNA (Ad.

Identification of major hub genes involved in high-fat diet-induced obese visceral adipose tissue based on bioinformatics approach.

High-fat diet (HFD) can cause obesity, inducing dysregulation of the visceral adipose tissue (VAT). This study aimed to explore potential biological pathways and hub genes involved in obese VAT, and for that, bioinformatic analysis of multiple datasets was performed. The expression profiles (GSE30247, GSE167311 and GSE79434) were downloaded from Gene Expression Omnibus.

Delivery of Mir-196c-3p with NIR-II light-triggered gel attenuates cardiomyocyte ferroptosis in cardiac ischemia-reperfusion injury.

Ferroptosis plays an important role in ischemia-reperfusion (I/R)-induced cardiac injury and there are many defects in current targeted delivery of miRNAs for the treatment of ferroptosis. We herein report a unique hydrogel (Gel) that can be triggered by a near-infrared-II (NIR-II) light with deep tissue penetration and biocompatible maximum permissible exposure (MPE) value for in situ treatment after I/R. The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release.

Kallistatin/Serpina3c inhibits cardiac fibrosis after myocardial infarction by regulating glycolysis via Nr4a1 activation.

Background: Fibrotic remodeling is an essential aspect of heart failure. Human kallistatin (KS, mouse Serpina3c homologs) inhibits fibrosis after myocardial infarction (MI) but the specific underlying mechanism is unknown.

Methods: A total of 40 heart failure patients (HFPs) were enrolled and their plasma KS was measured using ELISA.

Serpina3c deficiency induced necroptosis promotes non-alcoholic fatty liver disease through β-catenin/Foxo1/TLR4 signaling.

Non-alcoholic fatty liver disease (NAFLD) is a public health challenge and an increasing cause of chronic liver disease worldwide. However, the underlying molecular mechanism remains unclear. The aim of this study was to determine the precise role of serpina3c in the process of NAFLD.

Role of ferroptosis in the process of diabetes-induced endothelial dysfunction.

Background: Endothelial dysfunction, a hallmark of diabetes, is a critical and initiating contributor to the pathogenesis of diabetic cardiovascular complications. However, the underlying mechanisms are still not fully understood. Ferroptosis is a newly defined regulated cell death driven by cellular metabolism and iron-dependent lipid peroxidation.

Protective role of serpina3c as a novel thrombin inhibitor against atherosclerosis in mice.

Abnormal vascular smooth muscle cell (VSMC) proliferation is a critical step in the development of atherosclerosis. Serpina3c is a serine protease inhibitor (serpin) that plays a key role in metabolic diseases. The present study aimed to investigate the role of serpina3c in atherosclerosis and regulation of VSMC proliferation and possible mechanisms.

Serpina3c protects against high-fat diet-induced pancreatic dysfunction through the JNK-related pathway.

Background: Serpina3 is a member of the serine protease inhibitor family and is involved in the inflammatory response. In this study, we investigated the effect of Serpina3c on pancreatic function in hypercholesterolemic mice.

Methods: To investigate the role of Serpina3c in hyperlipidaemia, Serpina3c knockout mice were bred with Apoe-knockout mice (on a C57BL/6 background) to generate heterozygous Serpina3c-Apoe double knockout (Serpina3c/Apoe) mice and were then bred to obtain homozygotes.

Erythropoietin Attenuates Cardiac Dysfunction in Rats by Inhibiting Endoplasmic Reticulum Stress-Induced Diabetic Cardiomyopathy.

Purpose: Enhanced endoplasmic reticulum (ER) stress and down-regulated SERCA2a expression play crucial roles in diabetes. We aimed to verify whether erythropoietin (EPO) attenuates cardiac dysfunction by suppressing ER stress in diabetic rats.

Methods: Forty male SD rats were randomly divided into four groups: control, EPO-treated control, vehicle-treated diabetic, and EPO-treated diabetic groups.

Transplantation of bradykinin-preconditioned human endothelial progenitor cells improves cardiac function via enhanced Akt/eNOS phosphorylation and angiogenesis.

This study determines whether preconditioning (PC) of human endothelial progenitor cells (hEPCs) with bradykinin promotes infarcted myocardium repair via enhanced activation of B2 receptor (B2R)-dependent Akt/eNOS and increased angiogenesis. hEPCs with or without bradykinin preconditioning (BK-PC) were transplanted into a nude mouse model of acute myocardial infarction. Survival of transplanted cells was assessed using DiD-labeled hEPCs.

Transplantation of bradykinin-preconditioned human endothelial progenitor cells improves cardiac function via enhanced Akt/eNOS phosphorylation and angiogenesis.

This study determines whether preconditioning (PC) of human endothelial progenitor cells (hEPCs) with bradykinin promotes infarcted myocardium repair via enhanced activation of B2 receptor (B2R)-dependent Akt/eNOS and increased angiogenesis. hEPCs with or without bradykinin preconditioning (BK-PC) were transplanted into a nude mouse model of acute myocardial infarction. Survival of transplanted cells was assessed using DiD-labeled hEPCs.

LOX-1-Targeted Iron Oxide Nanoparticles Detect Early Diabetic Nephropathy in db/db Mice.

Purpose: Activation of the low-density lipoprotein receptor 1 (LOX-1) contributes to pervasive inflammation in early diabetic nephropathy (DN). This study determined the feasibility of anti-LOX-1-ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) for noninvasive detection of inflammatory renal lesions in early DN.

Procedures: Anti-mouse LOX-1 antibody was conjugated to polyethyleneglycol-coated USPIOs.

[Impact and related mechanisms of stromal cell-derived factor-1α on serum deprivation-induced cardiac stem cells apoptosis].

Objective: To explore the impact and related mechanisms of stromal cell-derived factor-1α (SDF-1α) on serum deprivation-induced apoptosis of cardiac stem cells (CSCs).

Methods: CSCs were isolated from adult mouse heart tissue and cultured in vitro. Obtained cells were purified using magnetic-activated cell sorting (MACS) with c-kit magnetic beads.

Tissue kallikrein is related to the severity of coronary artery disease.

Background: The impairment of the tissue kallikrein (KLK1)-kinin system (KKS) may result in atheroma development. However, it remains unclear if the KKS correlates with coronary artery disease (CAD).

Methods: KLK1, VEGF and hs-CRP plasma levels were measured in 100 patients newly diagnosed with CAD and 33 CAD-free controls.

Erythropoietin attenuates cardiac dysfunction by increasing myocardial angiogenesis and inhibiting interstitial fibrosis in diabetic rats.

Background: Recent studies revealed that erythropoietin (EPO) has tissue-protective effects in the heart by increasing vascular endothelial growth factor (VEGF) expression and attenuating myocardial fibrosis in ischemia models. In this study, we investigated the effect of EPO on ventricular remodeling and blood vessel growth in diabetic rats.

Methods: Male SD rats were randomly divided into 3 groups: control rats, streptozotocin (STZ)-induced diabetic rats, and diabetic rats treated with 1000 U/kg EPO by subcutaneous injection once per week.

OxLDL-targeted iron oxide nanoparticles for in vivo MRI detection of perivascular carotid collar induced atherosclerotic lesions in ApoE-deficient mice.

Atherosclerotic disease is a leading cause of morbidity and mortality in developed countries, and oxidized LDL (OxLDL) plays a key role in the formation, rupture, and subsequent thrombus formation in atherosclerotic plaques. In the current study, anti-mouse OxLDL polyclonal antibody and nonspecific IgG antibody were conjugated to polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, and a carotid perivascular collar model in apolipoprotein E-deficient mice was imaged at 7.0 Tesla MRI before contrast administration and at 8 h and 24 h after injection of 30 mg Fe/kg.

Myocardial infarction quantification with late gadolinium-enhanced magnetic resonance imaging in rats using a 7-T scanner.

Aims: The objective of this study was to noninvasively measure the volume of myocardial infarction in rats, using delayed enhancement magnetic resonance imaging (MRI) in a coronary occlusion/reperfusion model on a 7-T scanner.

Methods: At 24 h after cardiac ischemia, contrast-enhanced MRI was performed. Two distinct experimental groups were compared: one was subjected to permanent ischemia (PL) and the other was subjected to 30 min of ischemia followed by 24 h of reperfusion (IR).

Effects of heme oxygenase-1 gene modulated mesenchymal stem cells on vasculogenesis in ischemic swine hearts.

Background: Mesenchymal stem cells (MSCs) transplantation may partially restore heart function in the treatment of acute myocardial infarction (AMI). The aim of this study was to explore the beneficial effects of MSCs modified with heme xygenase-1 (HO-1) on post-infarct swine hearts to determine whether the induction of therapeutic angiogenesis is modified by the angiogenic cytokines released from the implanted cells.

Methods: In vitro, MSCs were divided into four groups: (1) non-transfected MSCs (MSCs group), (2) MSCs transfected with the pcDNA3.

[Value of in vivo monitoring of abdominal aortic atherosclerosis by high field magnetic resonance imaging in apoE-/- mice fed a high fat diet or infused with angiotensin II].

Objective: to explore the value of in vivo dynamic monitoring of abdominal aortic atherosclerosis (AS) by high field magnetic resonance (MR) imaging (MRI) in apoE-/- mice fed a high fat diet or infused with angiotensin.

Methods: high fat diet or angiotensin II infusion was applied to apoE-/- mice for establishment of abdominal aortic atherosclerosis model. Abdominal aorta MRI was performed at 3 time points (baseline, 3 and 6 months) in 13 high fat diet fed apoE-/- mice aged 10-12 months and 3 wild-type control mice; 10 apoE-/- mice aged 6 months were infused with angiotensin II (1000 or 500 ng × kg(-1)× min(-1), n = 5 each) or saline for 14 d through Osmotic minipump.

[Effects of autologous mesenchymal stem cells transfected with heme oxygenase-1 gene transplantation on ischemic Swine hearts].

Objective: To observe the effect of intracoronary transfer of autologous HO-1 overexpressed MSCs in porcine model of myocardial ischemia (1 h)/reperfusion.

Methods: Apoptosis was assayed and cytokine concentrations in supernatant were measured in cells exposed to hypoxia-reoxygen in vitro. In vivo, Chinese male mini-pigs were allocated to the following treatment groups: control group (saline), MSCs group (MSCs), MSCs transfected with pcDNA3.

[Preliminary exploration of transcription factor Nkx2.5 mutations and congenital heart diseases].

Objective: To explore the association between the gene mutation of transcription factor Nkx2.5 and Chinese patients with congenital heart disease (CHD).

Methods: Polymerase chain reaction (PCR) and DNA sequencing were used to check 99 CHD patients and 90 normal control subjects from the Zhong Da Hospital of Southeast University.

Tissue kallikrein promotes neovascularization and improves cardiac function by the Akt-glycogen synthase kinase-3beta pathway.

Aims: We investigated the role of the Akt-glycogen synthase kinase (GSK)-3beta signalling pathway in mediating the protective effects of tissue kallikrein on myocardial injury by promoting angiogenesis and blood flow in rats after myocardial infarction (MI).

Methods And Results: Human tissue kallikrein gene in an adenoviral vector, with or without co-administration of dominant-negative Akt (Ad.DN-Akt) or constitutively active GSK-3beta (Ad.

Salutary effect of kallistatin in salt-induced renal injury, inflammation, and fibrosis via antioxidative stress.

An inverse relationship exists between kallistatin levels and salt-induced oxidative stress in Dahl-salt sensitive rats. We further investigated the role of kallistatin in inhibiting inflammation and fibrosis through antioxidative stress in Dahl-salt sensitive rats and cultured renal cells. High-salt intake in Dahl-salt sensitive rats induced elevation of thiobarbituric acid reactive substances (an indicator of lipid peroxidation), malondialdehyde levels, reduced nicotinamide-adenine dinucleotide phosphate oxidase activity, and superoxide formation, whereas kallistatin gene delivery significantly reduced these oxidative stress parameters.