Topical Clonidine Accelerates Cutaneous Wound Healing in Diabetic Rats by Regulating the Expression of Related Cytokine Signaling.

Based on the analgesic and anti-inflammatory effects of clonidine in previous studies, we hypothesized that clonidine could accelerate wound healing in rats by regulating the expression of related cytokines. In this study, the wound healing effect of clonidine was evaluated using an excision wound model in diabetic rats and a HaCaT cell model. The wounds were treated daily with topical clonidine.

Soluble Dipeptidyl Peptidase-4 Induces Fibroblast Activation Through Proteinase-Activated Receptor-2.

Fibroblasts are the chief secretory cells of the extracellular matrix (ECM) responsible for basal deposition and degradation of the ECM under normal conditions. During stress, fibroblasts undergo continuous activation, which is defined as the differentiation of fibroblasts into myofibroblasts, a cell type with an elevated capacity for secreting ECM proteins. Dipeptidyl peptidase-4 (DPP4) is a ubiquitously expressed transmembrane glycoprotein and exerts effects that are both dependent and independent of its enzymatic activity.

A novel isoquinoline derivative exhibits anti-inflammatory properties and improves the outcomes of endotoxemia.

Background: Sepsis initiates an inflammatory response that causes widespread injury, and candidates for related myocardial depressant factors include cytokines and nitric oxide (NO). Nuclear factor kappa-B (NF-κB) stimulated by toll-like receptor 4 activation in sepsis mediates the transcription of multiple proinflammatory genes. These inflammatory mediators can cause myocardial dysfunction, which may deteriorate sepsis outcomes.

Reduction of blood pressure elevation by losartan in spontaneously hypertensive rats through suppression of LARG expression in vascular smooth muscle cells.

Background/purpose: This study sought to elucidate the mechanism by which losartan inhibits blood pressure (BP) elevation in spontaneously hypertensive rats (SHRs).

Methods: Four-week-old Wistar-Kyoto (WKY) rats and SHRs were either treated with losartan (20 mg/kg/day) for 8 weeks or served as untreated controls. BP was measured by the tail-cuff method.

Single allele Lmbrd1 knockout results in cardiac hypertrophy.

Background/purpose: LMBD1 protein, a type IV-B plasma membrane protein possessing nine putative trans-membrane domains, was previously demonstrated at cellular level to play a critical part in the signaling cascade of insulin receptor through its involvement in regulating clathrin-mediated endocytosis. However, at physiological level, the significance of LMBD1 protein in cardiac development remains unclear.

Methods: To understand the role of Lmbrd1 gene involved in the cardiac function, heterozygous knockout mice were used as an animal model system.

Electronegative LDL-mediated cardiac electrical remodeling in a rat model of chronic kidney disease.

The mechanisms underlying chronic kidney disease (CKD)-associated higher risks for life-threatening ventricular tachyarrhythmias remain poorly understood. In rats subjected to unilateral nephrectomy (UNx), we examined cardiac electrophysiological remodeling and relevant mechanisms predisposing to ventricular arrhythmias. Adult male Sprague-Dawley rats underwent UNx (n = 6) or sham (n = 6) operations.

A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats.

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and fluid retention. Changes in myocardial structure, electrical conduction, and energy metabolism develop with heart failure, leading to contractile dysfunction, increased risk of arrhythmias, and sudden death.

Aldosterone Induces Tissue Inhibitor of Metalloproteinases-1 Expression and Further Contributes to Collagen Accumulation: From Clinical to Bench Studies.

Aldosterone induces myocardial fibrosis. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key factor of myocardial fibrosis. This study tested the hypothesis that aldosterone induces TIMP-1 expression and contributes to the fibrotic process.

Modification of Caffeic Acid with Pyrrolidine Enhances Antioxidant Ability by Activating AKT/HO-1 Pathway in Heart.

Overproduction of free radicals during ischemia/reperfusion (I/R) injury leads to an interest in using antioxidant therapy. Activating an endogenous antioxidant signaling pathway is more important due to the fact that the free radical scavenging behavior in vitro does not always correlate with a cytoprotection effect in vivo. Caffeic acid (CA), an antioxidant, is a major phenolic constituent in nature.

NRIP is newly identified as a Z-disc protein, activating calmodulin signaling for skeletal muscle contraction and regeneration.

Nuclear receptor interaction protein (NRIP, also known as DCAF6 and IQWD1) is a Ca(2+)-dependent calmodulin-binding protein. In this study, we newly identify NRIP as a Z-disc protein in skeletal muscle. NRIP-knockout mice were generated and found to have reduced muscle strength, susceptibility to fatigue and impaired adaptive exercise performance.

Caffeic acid ethanolamide prevents cardiac dysfunction through sirtuin dependent cardiac bioenergetics preservation.

Background: Cardiac oxidative stress, bioenergetics and catecholamine play major roles in heart failure progression. However, the relationships between these three dominant heart failure factors are not fully elucidated. Caffeic acid ethanolamide (CAEA), a synthesized derivative from caffeic acid that exerted antioxidative properties, was thus applied in this study to explore its effects on the pathogenesis of heart failure.

Circulating tissue inhibitor of matrix metalloproteinase-1 is associated with aldosterone-induced diastolic dysfunction.

Objective: To test if collagen markers are associated with aldosterone-induced diastolic dysfunction.

Background: Although primary aldosteronism is associated with more prominent cardiac remodeling and diastolic dysfunction, the reversibility of diastolic function is unclear. In addition, there is no known biomarker associated with aldosterone-induced diastolic dysfunction.

5-hydroxytryptamine has an endothelium-derived hyperpolarizing factor-like effect on coronary flow in isolated rat hearts.

Background: 5-hydroxytryptamine (5-HT)-induced coronary artery responses have both vasoconstriction and vasorelaxation components. The vasoconstrictive effects of 5-HT have been well studied while the mechanism(s) of how 5-HT causes relaxation of coronary arteries has been less investigated. In isolated rat hearts, 5-HT-induced coronary flow increases are partially resistant to the nitric oxide synthase inhibitor Nω-Nitro-L-arginine methyl ester (L-NAME) and are blocked by 5-HT7 receptor antagonists.

Pyrrolidinyl caffeamide against ischemia/reperfusion injury in cardiomyocytes through AMPK/AKT pathways.

Background: Coronary heart disease is a leading cause of death in the world and therapy to reduce injury is still needed. The uncoupling of glycolysis and glucose oxidation induces lactate accumulation during myocardial ischemia/reperfusion (I/R) injury. Cell death occurs and finally leads to myocardial infarction.

Increased LDL electronegativity in chronic kidney disease disrupts calcium homeostasis resulting in cardiac dysfunction.

Chronic kidney disease (CKD), an independent risk factor for cardiovascular disease, is associated with abnormal lipoprotein metabolism. We examined whether electronegative low-density lipoprotein (LDL) is mechanistically linked to cardiac dysfunction in patients with early CKD. We compared echocardiographic parameters between patients with stage 2 CKD (n = 88) and normal controls (n = 89) and found that impaired relaxation was more common in CKD patients.

The differential effects of a selective kappa-opioid receptor agonist, U50488, in guinea pig heart tissues.

The differential effects of a selective kappa- (κ-) opioid receptor agonist, U50488, were elucidated by monitoring the contraction of isolated guinea pig atrial and ventricular muscles. In electrically driven left atria, U50488 in nanomolar concentration range decreased the contractile force. Norbinaltorphimine (norBNI), a selective κ-receptor antagonist, and pertussis toxin (PTX) abolished the negative inotropic effect of U50488.

TM-1-1DP exerts protective effect against myocardial ischemia reperfusion injury via AKT-eNOS pathway.

Coronary heart disease remains a leading cause of death in the world. The demand on targeting therapy to reduce myocardial ischemia/reperfusion (I/R) injury is still urgent. The pathogenesis of I/R-induced myocardial injury is complicated.

The effect of resveratrol on protecting corneal epithelial cells from cytotoxicity caused by moxifloxacin and benzalkonium chloride.

Purpose: Moxifloxacin (MOX), a fourth generation fluoroquinolone (FQ), has a wide antibacterial spectrum, but may show cytotoxicity characterized by high productions of reactive oxygen species (ROS). This study investigated the protective role of a common antioxidant agent, resveratrol (trans-3,5,4'-trihydroxystilbene), against the cytotoxicity caused by MOX.

Methods: Experiments were performed with a human corneal epithelial cell line (HCECs; ATCC-CRL-11515).

KS370G, a caffeamide derivative, attenuates unilateral ureteral obstruction-induced renal fibrosis by the reduction of inflammation and oxidative stress in mice.

Unilateral ureteral obstruction (UUO) is an established animal model used to study renal nephropathy. Caffeic acid phenethyl ester, a natural phenolic compound, possesses antifibrotic, anti-inflammation and anti-oxidative stress effects; however, rapid decomposition by esterases substantially decreases its bioavailability. The goal of this study was to investigate the beneficial effects of KS370G, a synthetic caffeamide derivative, on UUO-induced renal injury.

Activation of serotonin 5-HT₇ receptor induces coronary flow increase in isolated rat heart.

Serotonin (5-Hydroxytryptamine, 5-HT) can elicit both vasoconstrictive and relaxant responses on rat coronary artery. The constrictive response has been well discussed, but the mechanism of relaxant response is less studied. In the present study, we found serotonin (0.

Antifibrotic effects of KS370G, a caffeamide derivative, in renal ischemia-reperfusion injured mice and renal tubular epithelial cells.

Accumulating evidence suggests that renal tubulointerstitial fibrosis is a main cause of end-stage renal disease. Clinically, there are no beneficial treatments that can effectively reverse the progressive loss of renal functions. Caffeic acid phenethyl ester is a natural phenolic antifibrotic agent, but rapid decomposition by an esterase leads to its low bioavailability.

Caffeic acid phenethyl amide ameliorates ischemia/reperfusion injury and cardiac dysfunction in streptozotocin-induced diabetic rats.

Background: Caffeic acid phenethyl ester (CAPE) has been shown to protect the heart against ischemia/reperfusion (I/R) injury by various mechanisms including its antioxidant effect. In this study, we evaluated the protective effects of a CAPE analog with more structural stability in plasma, caffeic acid phenethyl amide (CAPA), on I/R injury in streptozotocin (STZ)-induced type 1 diabetic rats.

Methods: Type 1 diabetes mellitus was induced in Sprague-Dawley rats by a single intravenous injection of 60 mg/kg STZ.

Gender disparity in LDL-induced cardiovascular damage and the protective role of estrogens against electronegative LDL.

Background: Increased levels of the most electronegative type of LDL, L5, have been observed in the plasma of patients with metabolic syndrome (MetS) and ST-segment elevation myocardial infarction and can induce endothelial dysfunction. Because men have a higher predisposition to developing coronary artery disease than do premenopausal women, we hypothesized that LDL electronegativity is increased in men and promotes endothelial damage.

Methods: L5 levels were compared between middle-aged men and age-matched, premenopausal women with or without MetS.

Connective tissue growth factor and cardiac diastolic dysfunction: human data from the Taiwan diastolic heart failure registry and molecular basis by cellular and animal models.

Aims: Connective tissue growth factor (CTGF) is an emerging marker for tissue fibrosis. We investigated the association between CTGF and cardiac diastolic function using cellular and animal models and clinical human data.

Methods And Results: A total of 125 patients with a diagnosis of diastolic heart failure (DHF) were recruited from 1283 patients of the Taiwan Diastolic Heart Failure Registry.

DPP4 deficiency preserved cardiac function in abdominal aortic banding rats.

Dipeptidyl peptidase-4 (DPP4) enzyme inhibition has been reported to increase plasma glucagon-like peptide-1 (GLP-1) level for controlling postprandial glucose concentration. A prominent GLP-1 level in DPP4-deficient rats contributed to the resistance of endotoxemia and myocardial infarction. DPP4 deficiency also increased the capability against H₂O₂-induced stress in cardiomyocyte.