Accumulation of endogenous Muse cells in the myocardium and its pathophysiological role in patients with fulminant myocarditis.

Multi-lineage differentiating stress-enduring (Muse) cells, identified as pluripotent surface marker SSEA-3(+) cells, are stress tolerant endogenous pluripotent-like stem cells, and are involved in tissue repair. However, the significance of Muse cells in acute myocarditis has not been evaluated. In the present study, we counted Muse cells/area in biopsied myocardial tissue samples from 17 patients with fulminant myocarditis, and 6 with non-inflammatory myocardial disease as controls.

A case of hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome with a novel frameshift variant in , p.W10Cfs40, lacks kidney malformation.

Autosomal dominant hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome are typically diagnosed by manifestations of the three features with a positive family history. Our case carried a de novo variant in causative gene, but presenting no renal dysplasia or family history. The phenotypic heterogeneity raises a caution for diagnosis.

Cancer-associated fibroblasts show heterogeneous gene expression and induce vascular endothelial growth factor A () in response to environmental stimuli.

Aim: Cancer-associated fibroblasts (CAF) play a crucial role in angiogenesis in the complex tumor microenvironment. However, fibroblasts show extensive heterogeneity and their dynamic functions against stressors remain largely unknown.

Methods: We collected patient-derived CAF and carried out perturbation-based monitoring of the dynamic functions.

Liraglutide, a GLP-1 receptor agonist, inhibits vascular smooth muscle cell proliferation by enhancing AMP-activated protein kinase and cell cycle regulation, and delays atherosclerosis in ApoE deficient mice.

Background And Aims: Several studies have demonstrated that both native glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists suppress the progression of atherosclerosis in animal models.

Methods: We investigated whether liraglutide, a GLP-1 analogue, could prevent the development of atherosclerosis in apolipoprotein E knockout mice (ApoE) on a high-fat diet. We also examined the influence of liraglutide on angiotensin II-induced proliferation of rat vascular smooth muscle cells (VSMCs) via enhancement of AMP-activated protein kinase (AMPK) signaling and regulation of cell cycle progression.

Dual pharmacological inhibition of glutathione and thioredoxin systems synergizes to kill colorectal carcinoma stem cells.

NRF2 stabilizes redox potential through genes for glutathione and thioredoxin antioxidant systems. Whether blockade of glutathione and thioredoxin is useful in eliminating cancer stem cells remain unknown. We used xenografts derived from colorectal carcinoma patients to investigate the pharmacological inhibition of glutathione and thioredoxin systems.

Empagliflozin (an SGLT2 inhibitor), alone or in combination with linagliptin (a DPP-4 inhibitor), prevents steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis and diabetes.

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are new oral antidiabetic drugs that reduce hyperglycemia by promoting urinary glucose excretion. Glycosuria produced by SGLT2 inhibitors is associated with weight loss, mainly due to reduced fat volume. We investigated the effects of empagliflozin (selective SGLT2 inhibitor) and linagliptin (DPP-4 inhibitor) on steatohepatitis and fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH) with diabetes.

Pro-B-type natriuretic peptide is cleaved intracellularly: impact of distance between O-glycosylation and cleavage sites.

We investigated the molecular mechanism underlying the processing of pro-B-type natriuretic peptide (proBNP). Rat neonatal atrial and ventricular myocytes were cultured separately. We examined the molecular forms of secreted and intracellular BNP in atrial and ventricular myocytes; levels of corin and furin mRNA in atrial and ventricular myocytes; the effect their knockdown on proBNP processing; plasma molecular forms of BNP from rats and humans with and without heart failure; and the impact of the distance between the glycosylation and cleavage sites in wild-type and mutant human proBNP, expressed in rat myocytes transfected with lentiviral vectors.

Augmented pentose phosphate pathway plays critical roles in colorectal carcinomas.

Glycolysis and the pentose phosphate pathway (PPP) are preferentially activated in cancer cells. Accumulating evidence indicated the significance of the altered glucose metabolism in cancer, but the implication for oncotherapy remains unclear. Here we report that the synthesis of glycolytic and PPP enzymes is almost ubiquitously augmented in colorectal carcinoma (CRC) specimens.

Comprehensive analysis of genes involved in the malignancy of gastrointestinal stromal tumors.

Background: During tumorigenesis of gastrointestinal stromal tumors (GISTs), the most frequent changes are reported to be gain-of-function mutations in the C-KIT proto-oncogene. However, we speculated that additional genetic alterations are required for the progression of GISTs.

Patients And Methods: Using 15 cases diagnosed with GISTs, we searched for novel indicator genes by microarray analyses using an Oligo GEArray(R) PI3K-AKT Signaling Pathway Microarray Kit.

Beneficial effects of a combination of Rho-kinase inhibitor and ACE inhibitor on tubulointerstitial fibrosis induced by unilateral ureteral obstruction.

We and others recently reported that long-term Rho-kinase inhibition has renoprotective effects. This study was designed to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (imidapril), a Rho-kinase inhibitor (fasudil) and a combination of them both on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). We also attempted to elucidate the mechanism involved.

Natriuretic peptide/natriuretic peptide receptor-A (NPR-A) system has inhibitory effects in renal fibrosis in mice.

Object: This study was designed to examine whether natriuretic peptide/natriuretic peptide receptor-A (NPR-A) system attenuates renal fibrosis in a unilateral ureteral obstruction (UUO) model and also examined the mechanism involved.

Methods: Three groups were studied: untreated UUO in wild-type mice; untreated UUO in NPR-A KO mice; and ANP treated (0.05 microg/kg/min) UUO in wild-type mice.

Diagnosis of an ilio-iliac arteriovenous fistula by multidetector row computed tomography and surgical repair.

An 82-year-old man presented with typical signs and symptoms of an arteriovenous fistula (AVF) associated with an aortoiliac aneurysm, such as a pulsatile abdominal mass, continuous bruit, thrill, and high output heart failure. Multidetector row computed tomography (MDCT) confirmed the presence of an AVF between the right common iliac artery aneurysm and vein. We subjected the patient to surgical repair of the AVF combined with graft replacement, which proved successful.

Stimulatory and Inhibitory regulation of lipolysis by the NPR-A/cGMP/PKG and NPR-C/G(i) pathways in rat cultured adipocytes.

Objective: Recent studies have suggested the abundant expression of natriuretic peptide receptor in adipose tissue. This study was designed to investigate the levels of natriuretic receptor-A (NPR-A) and NPR-C gene expression during the process of preadipocyte differentiation and its role in adipogenesis and lipid metabolism.

Methods: We measured mRNA levels of NPR-A and NPR-C during the process of rat preadipocyte differentiation in vitro.

Cilostazol inhibits cytokine-induced nuclear factor-kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells.

Aims: Cilostazol is a selective inhibitor of phosphodiesterase 3 that increases intracellular cyclic AMP (cAMP) levels and activates protein kinase A, thereby inhibiting platelet aggregation and inducing peripheral vasodilation. We hypothesized that cilostazol may prevent inflammatory cytokine induced-nuclear factor (NF)-kappaB activation by activating AMP-activated protein kinase (AMPK) in vascular endothelial cells.

Methods And Results: Cilostazol was observed to activate AMPK and its downstream target, acetyl-CoA carboxylase, in human umbilical vein endothelial cells (HUVEC).

Fasudil, a Rho-kinase inhibitor, reverses L-NAME exacerbated severe nephrosclerosis in spontaneously hypertensive rats.

Background: In this study, we tested the hypothesis that long-term Rho-kinase inhibition would reverse nitro-L-arginine methyl ester-exacerbated nephrosclerosis in spontaneously hypertensive rats and attempted to elucidate the mechanism involved.

Methods: Five groups (each n = 8) were studied: untreated spontaneously hypertensive rats; nitro-L-arginine methyl ester (50 mg/l in drinking water, for 3 weeks)-treated spontaneously hypertensive rats; nitro-L-arginine methyl ester with fasudil (10 mg/kg/day)-treated spontaneously hypertensive rats; nitro-L-arginine methyl ester for 3 weeks followed by fasudil for 3 weeks-treated spontaneously hypertensive rats (same doses), and nitro-L-arginine methyl ester for 3 weeks followed by untreated for 3 weeks. We examined renal function, blood pressure, histological features, oxidative stress markers, and mRNA expression in the renal cortex.

Role of adrenomedullin system in lipid metabolism and its signaling mechanism in cultured adipocytes.

We investigated the levels of adrenomedullin (AM) system during the process of preadipocyte differentiation and its role in lipid metabolism and cellular signaling mechanism in differentiated adipocytes. We cultured rat preadipocytes and measured the following during the process of differentiation: two molecular forms of AM in the culture medium using a specific immunoradiometric assay and gene expression of AM and its receptor component using RT-PCR analysis. In differentiated adipocytes, we measured the effects of AM on the intracellular cAMP level, lipolysis, glucose incorporation, and the protein levels.

Inhibitory effect of Agaricu blazei Murill components on abnormal collagen fiber formation in human hepatocarcinoma cells.

Hot-water extracts of the mycelial culture and fruiting bodies of Agaricus blazei Murill were fractionated by ethanol precipitation, using various ethanol concentrations. The mycelial fraction (A-4) inhibited abnormal collagen fiber formation, and fractions A-1 to A-3 showed a small inhibitory effect. The strongest inhibition was obtained by fraction A-4, and no significant inhibition was observed with fractions A-5 and A-6.

Concentrations and distribution of mercury and other heavy metals in surface sediments of the Yatsushiro Sea including Minamata Bay, Japan.

The concentrations and distribution of heavy metals, such as mercury, zinc, copper, lead, and iron in surface sediments from 234 stations of the Yatsushiro Sea including Minamata bay were investigated. High concentrations of mercury were found in sediments from Minamata bay and its vicinity, but the levels decreased gradually with distance from the bay. The concentrations of mercury in sediments decreased gradually from south to north of the Yatsushiro Sea.

Globular adiponectin induces adhesion molecule expression through the sphingosine kinase pathway in vascular endothelial cells.

The signaling pathways that couple adiponectin receptors to functional, particularly inflammatory, responses have remained elusive. We report here that globular adiponectin induces endothelial cell activation, as measured by the expression of adhesion proteins such as vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin and MCP-1, through the sphingosine kinase (SKase) signaling pathway. Treatment of human umbilical vein endothelial cells with globular adiponectin resulted in NF-kappaB activation and increased mRNA levels of VCAM-1, ICAM-1, E-selectin and MCP-1.

Inhibition of Rho-kinase attenuates nephrosclerosis and improves survival in salt-loaded spontaneously hypertensive stroke-prone rats.

Objectives: We examined whether the Rho/Rho-kinase pathway is involved in the pathogenesis of nephrosclerosis in severely hypertensive rats and assessed the effects of long-term treatment with a Rho-kinase inhibitor, fasudil, on kidney function, histological findings, gene expressions, and survival. We also attempted to elucidate the mechanisms involved.

Methods: We studied the following four groups: control Wistar-Kyoto rats (WKY), untreated salt-loaded spontaneously hypertensive stroke-prone rats (SHR-SP), low-dose fasudil (15 mg/kg per day)-treated SHR-SP, and high-dose fasudil (30 mg/kg per day)-treated SHR-SP.

Interleukin-10 regulates transforming growth factor-beta signaling in cultured human bronchial epithelial cells.

Background: The basic pathological features of bronchial asthma can be explained on the basis of chronic airway inflammation, involving inflammatory cells such as T cells (particularly type 2 helper T, Th2, cells) and mast cells, and airway remodeling. Many aspects of airway remodeling remain unclear at the molecular level. Recent attention has focused on the role of transforming growth factor (TGF)-beta, a fibrogenic cytokine, in airway remodeling.

Globular adiponectin activates nuclear factor-kappaB and activating protein-1 and enhances angiotensin II-induced proliferation in cardiac fibroblasts.

Adiponectin is present in the serum as a trimer, hexamer, or high-molecular weight form. A proteolytic cleavage product of adiponectin, known as globular adiponectin (gAd), also circulates in human plasma. The biological activities of these isoforms are not well characterized.