SR9009 attenuates TGF-β1-induced renal fibrotic responses by inhibiting the NOX4/p38 signaling pathway in NRK-49F cells.

The circadian clock protein reverse erythroblastosis virus (REV)-ERBα is implicated in the pathogenesis of various diseases, including cancer and myocardial infarction. Emerging evidence suggests that SR9009, an agonist of REV-ERBα, regulates multiple signaling molecules independent or dependent of REV-ERBα. However, the impact of SR9009 on renal fibrosis remains largely unevaluated.

Smoking-induced suppression of β-casein in milk is associated with an increase in miR-210-5p expression in mammary epithelia.

Smoking during lactation harmfully affects the amount and constituents of breast milk. Infants who consume breast milk containing miR-210-5p may have a higher risk of brain-related diseases. We investigated whether smoking during lactation decreases β-casein concentrations in milk and whether miR-210-5p expression is involved in smoking-induced β-casein suppression.

The role of tribbles homolog 2 in vascular smooth muscle cell proliferation.

Tribbles homolog 2 (TRIB2) functions as an adapter protein that regulates signal transductions involved in a variety of cellular functions, including tumorigenesis. However, the role of TRIB2 in the proliferation of vascular smooth muscle cells (VSMCs) and the underlying expression mechanisms remain unclear. The present study investigated the role of TRIB2 in VSMC proliferation and revealed that TRIB2 expression increases following vascular injury and platelet-derived growth factor (PDGF)-BB-stimulated VSMCs.

Rational design and structure-activity relationship studies reveal new esterified C-diterpenoid alkaloid analogues active against MCF-7 human breast cancer cells.

Although various diterpenoid alkaloids have been evaluated recently for antiproliferative activity against human tumor cell lines, little information is available regarding the antiproliferative effects of C-diterpenoid alkaloids against MCF-7 cells. Six new diterpenoid alkaloid derivatives (13, 14, 22, 23, 25, 26) were prepared by C-11 and 15 esterification of kobusine (6). The natural parent alkaloid 6 and all synthesized derivatives (7 - 27, 12a, 15a, 15b, 18a, 18b) were evaluated for antiproliferative activity against MCF-7 cells.

Role of Erythropoiesis-Stimulating Agents in Cardiovascular Protection in CKD Patients: Reappraisal of Their Impact and Mechanisms.

Erythropoiesis-stimulating agents (ESAs) have markedly reduced the need for blood transfusion for renal anemia and are included in standard therapies for patients with chronic kidney disease (CKD). Various protective effects of ESAs on the cardiovascular system have been discovered through basic research, and the effects have received much attention because the rates of cardiovascular events and mortality are high in CKD patients. However, randomized clinical trials did not provide strong evidence that ESAs exert cardioprotection in humans, including CKD patients.

Expression profiles of hsa-miR-148a-3p and hsa-miR-125b-5p in human breast milk and infant formulae.

Background: Milk-derived microRNAs (miRNAs), including hsa-miR-148a-3p (miR-148a) and hsa-miR-125b-5p (miR-125b), have been shown to be beneficial to the gastrointestinal function in infants. Here, we investigated their expression during lactation in humans and determined whether the infant formulae available in Japan contain these miRNAs.

Methods: Healthy Japanese women (n = 16) who gave birth vaginally or by cesarean section at the Teine Keijinkai Hospital between 1 September 2020, and 31 April 2021 were included in this study.

Norepinephrine transporter expressed on mammary epithelial cells incorporates norepinephrine in milk into the cells.

Mammary epithelial cells synthesize and secrete norepinephrine (NE) into breast milk to regulate β-casein expression through the adrenergic β receptor. We investigated the expression, localization, and roles of NE transporter (NET) in the mammary epithelium during lactation. mRNA and protein levels of NET were determined in primary normal human mammary epithelial cells (pHMECs) and non-malignant human mammary epithelial MCF-12A cells.

The role of circadian clock gene BMAL1 in vascular proliferation.

Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, is implicated in the development of cardiovascular diseases, including atherosclerosis and abdominal aortic aneurysms. However, the role of BMAL1 in vascular proliferation associated with vascular remodeling is unknown. In the present study, we investigated the mechanisms underlying BMAL1 expression in vascular smooth muscle cells (VSMCs) and the role of BMAL1 in VSMC proliferation.

Involvement of Yes-associated protein 1 (YAP1) in doxorubicin-induced cytotoxicity in H9c2 cardiac cells.

Cardiac cell death is one of the major events implicated in doxorubicin-induced cardiotoxicity, which leads to heart failure. We recently reported that Yes-associated protein 1 (YAP1) regulates cell survival and apoptosis. However, it is unclear whether YAP1 regulates doxorubicin-induced cell death in cardiomyocytes.

[Elucidation of a New Mechanism of Onset of Insulin Resistance: Effects of Statins and Tumor Necrosis Factor-α on Insulin Signal Transduction].

Impaired insulin signaling in adipose tissue and skeletal muscle causes insulin resistance associated with the development of type 2 diabetes. However, the molecular mechanisms underlying insulin resistance remain to be elucidated. In this review, we describe the current understanding of the effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and tumor necrosis factor (TNF)-α on insulin signal transduction in adipocytes.

Global Liver Gene Expression Analysis on a Murine Hepatic Steatosis Model Treated with Mulberry ( L.) Leaf Powder.

Background/aim: Mulberry (Morus alba L.) leaves (ML) contain many functional components, such as 1-deoxynojirimycin, flavonoids (rutin, quercetin, kaempferol). It is well known that 1-deoxynojirimycin functions to suppress increases in blood glucose level by α-glucosidase inhibitory activity.

The protective role of YAP1 on ER stress-induced cell death in vascular smooth muscle cells.

Apoptosis of vascular smooth muscle cells (VSMCs) has been implicated in the progression of atherosclerosis, especially in vascular remodelling and plaque rupture. Although it is known that Yes-associated protein 1 (YAP1) is a critical molecule that regulates cell proliferation, differentiation and apoptosis, the role of YAP1 in VSMCs apoptosis remains unknown. In this study, we investigated whether YAP1 modulates VSMC apoptosis induced by endoplasmic reticulum (ER) stress.

Transcriptome Analysis of Skin from SMP30/GNL Knockout Mice Reveals the Effect of Ascorbic Acid Deficiency on Skin and Hair.

Background/aim: Senescence marker protein-30/gluconolactonase knockout mice (SMP-30/GNL-KO) are a very useful model for clarifying the involvement of vitamin C (VC) in aging-related diseases. In this study, the effects of VC deficiency on skin and hair growth were investigated using SMP-30/GNL-KO mice by RNA sequencing.

Materials And Methods: SMP-30/GNL-KO mice were given water containing 1.

AMPK activation by prolonged stimulation with interleukin-1β contributes to the promotion of GLUT4 translocation in skeletal muscle cells.

Impaired insulin signaling in skeletal muscle cells causes insulin resistance associated with the onset of type 2 diabetes. Although interleukin (IL)-1β has been considered to be implicated in the pathogenesis of type 2 diabetes, the action of prolonged stimulation with IL-1β on the insulin signaling pathway in skeletal muscle cells remains poorly understood. In the current study, we investigated the effect of IL-1β stimulation on insulin signal transduction from the insulin receptor (IR), resulting in glucose transporter 4 (GLUT4) translocation in skeletal muscle cells.

Cilostazol inhibits interleukin-1-induced ADAM17 expression through cAMP independent signaling in vascular smooth muscle cells.

Increased A disintegrin and metalloprotease 17 (ADAM17) expression in vascular smooth muscle cells (VSMC) is implicated in the development of cardiovascular diseases including atherosclerosis and hypertension. Although cilostazol, type III phosphodiesterase (PDE III) inhibitor, has recently been found to inhibit VSMC proliferation, the mechanisms remain largely unclear. Here, we hypothesized that cilostazol regulates the ADAM17 expression in VSMC.

Effect of alteration of caveolin-1 expression on doxorubicin-induced apoptosis in H9c2 cardiac cells.

Doxorubicin is an anthracycline antibiotic widely used in cancer treatment. Although its antitumor efficacy appears to be dose dependent, its clinical use is greatly restricted by the development of cardiotoxicity associated with apoptosis. Although caveolin-1, the major structural protein in caveolae, can positively or negatively regulate apoptosis depending on the stimulus or cell types, the contribution of caveolin-1 to doxorubicin-induced apoptosis remains unknown.

Inhibition of the TNF-α-induced serine phosphorylation of IRS-1 at 636/639 by AICAR.

AMP-activated protein kinase (AMPK) contributes to the acceleration of insulin signaling. However, the mechanism by which AMPK regulates insulin signaling remains unclear. Serine phosphorylation of insulin receptor substrate (IRS)-1 negatively regulates insulin signaling.

ADAM17 silencing by adenovirus encoding miRNA-embedded siRNA revealed essential signal transduction by angiotensin II in vascular smooth muscle cells.

Small interfering RNA (siRNA) mediated gene silencing has been utilized as a powerful molecular tool to study the functional significance of a specific protein. However, due to transient gene silencing and insufficient transfection efficiency, this approach can be problematic in primary cell culture such as vascular smooth muscle cells. To overcome this weakness, we utilized an adenoviral-encoded microRNA (miRNA)-embedded siRNA "mi/siRNA"-based RNA interference.

A repressor protein, Mnt, is a novel negative regulator of vascular smooth muscle cell hypertrophy by angiotensin II and neointimal hyperplasia by arterial injury.

Objective: The Max-interacting protein Mnt is a transcriptional repressor that can antagonize the transcriptional and proliferation-related activities of Myc. Here, we tested the hypothesis that Mnt is a negative regulator of pathological vascular remodeling.

Methods: Adenovirus encoding Mnt or control GFP was infected to cultured rat vascular smooth muscle cells (VSMC) and carotid arteries after a balloon angioplasty.

Constitutive stimulation of vascular smooth muscle cells by angiotensin II derived from an adenovirus encoding a furin-cleavable fusion protein.

Background: To fill the gap between acute and chronic stimulation methods of angiotensin II (Ang II) and obtain relevant signaling information, we have made an adenovirus vector encoding a furin-cleavable Ang II fusion protein.

Methods: Vascular smooth muscle cells (VSMCs) were infected with adenovirus to evaluate Ang II production. Also, expression of early growth response-1 (Egr-1) and hypertrophic responses were examined in VSMCs.

A disintegrin and metalloprotease 17 mediates neointimal hyperplasia in vasculature.

The requirement of a metalloprotease, a disintegrin and metalloprotease 17 (ADAM17) for the growth of cultured vascular smooth muscle cells has been demonstrated in vitro. However, whether this metalloprotease is responsible for vascular remodeling in vivo remains unanswered. Rat carotid arteries were analyzed 2 weeks after a balloon angioplasty.

An extract from brown rice inhibits signal transduction of angiotensin II in vascular smooth muscle cells.

Background: Health benefits of brown rice over white rice have been described previously. However, whether the outer bran of rice contains an ingredient useful to prevent cardiovascular diseases remains unknown. The subaleurone layer of rice, which is usually lost by milling brown rice for whitening, is rich in varied nutrients, suggesting that some ingredient contained within this layer may be beneficial for the cardiovascular system.

Caveolin-1 negatively regulates a metalloprotease-dependent epidermal growth factor receptor transactivation by angiotensin II.

A metalloprotease, ADAM17, mediates the generation of mature ligands for the epidermal growth factor receptor (EGFR). This is the key signaling step by which angiotensin II (AngII) induces EGFR transactivation leading to hypertrophy and migration of vascular smooth muscle cells (VSMCs). However, the regulatory mechanism of ADAM17 activity remains largely unclear.