Myosin light chain phosphatase is a downstream target of Rho-kinase in endothelin-1-induced transactivation of the TGF-β receptor.

Background: Rho-kinase (ROCK) regulates actomyosin contraction, coronary vasospasm, and cytoskeleton dynamics. ROCK and of NADPH oxidase (NOX) play an essential role in cardiovascular disease and proteoglycan synthesis, which promotes atherosclerosis by trapping low density lipoprotein. ROCK is activated by endothelin-1 (ET1) and transactivates the transforming growth factor beta receptor (TGFβR1), intensifying Smad signaling and proteoglycan production.

Comparison of atherogenic indices for predicting the risk of metabolic syndrome in Southwest Iran: results from the Hoveyzeh Cohort Study (HCS).

Background: Metabolic syndrome (MetS) is a cluster of risk factors related to diabetes and cardiovascular disease (CVD). Given that early identification of MetS might decrease CVD risk, it is imperative to establish a simple and cost-effective method to identify individuals at risk of MetS. The purpose of this study was to explore the relationships between several atherogenic indices (including AIP, TyG index, non-HDL-C, LDL-c/HDL-c, and TC/HDL-c) and MetS, and to assess the ability of these indices to predict MetS.

Atorvastatin's Therapeutic Potential in Atherosclerosis: Inhibiting TGF-β-Induced Proteoglycan Glycosaminoglycan Chain Elongation through ROS-ERK1/2-Smad2L Signaling Pathway Modulation in Vascular Smooth Muscle Cells.

Objective: According to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to the deposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongated glycosaminoglycan (GAG) chains. Recent studies have elucidated a signaling pathway whereby transforming growth factor-β (TGF-β) promotes the expression of genes linked to proteoglycan GAG chain elongation ( and ) via reactive oxygen species (ROS) and the downstream phosphorylation of ERK1/2 and Smad2L. Atorvastatin is known to exhibit pleiotropic effects, including antioxidant and anti-inflammatory.

The oncogenic role of SAMMSON lncRNA in tumorigenesis: A comprehensive review with especial focus on melanoma.

LncRNA Survival Associated Mitochondrial Melanoma Specific Oncogenic Non-coding RNA (SAMMSON) is located on human chromosome 3p13, and its expression is upregulated in several tumours, including melanoma, breast cancer, glioblastoma and liver cancer and has an oncogenic role in malignancy disorders. It has been reported that SAMMSON impacts metabolic regulation, cell proliferation, apoptosis, EMT, drug resistance, invasion and migration. Also, SAMMSON is involved in regulating several pathways such as Wnt, MAPK, PI3K, Akt, ERK and p53.

The expression of lncRNAs CASC2, NEAT1, LINC00299 in breast cancer tissues and their relationship with the XBP1 splicing rate in Iranian patients during 2014-2019: A cross-sectional study.

Background And Aims: Breast cancer is a leading cause of incidence and mortality in women globally. Identifying new molecular markers can aid in cancer diagnosis, targeted therapy, and treatment monitoring. This study aimed to measure the expression of the X-box binding protein 1 (XBP1) gene, an index of the unfolded protein response (UPR), and long noncoding RNAs (lncRNAs), including Nuclear Enriched Abundant Transcript 1 (NEAT1), Cancer Susceptibility Candidate 2 (CASC2), and Long Intergenic Nonprotein Coding RNA 299 (LINC00299), as possible regulators of the UPR pathway.

Impact of modifiable risk factors on prediction of 10-year cardiovascular disease utilizing framingham risk score in Southwest Iran.

Background: This cohort study was conducted to examine the association between modifiable risk factors, including hypertension, smoking, physical activity, diabetes, cholesterol, and high-density lipoprotein with Framingham risk score in the prediction of 10-year-risk of cardiovascular diseases (CVD) between men and women in an Arab community of Southwest Iran, Hoveyzeh.

Materials And Methods: A total of 8,526 people aged 35-70 participated in this cohort study. Framingham was used to estimate the 10-year risk of CVD.

Cardioprotective effect of tamoxifen and raloxifene: Preventing proteoglycan synthesis by modulating non-canonical TGF-β signalling through NADPH oxidase and ERK phosphorylation.

Atherosclerosis, a leading cause of cardiovascular disease, remains a significant global health concern. Tamoxifen and raloxifene, selective estrogen receptor modulators (SERMs), have demonstrated potential cardioprotective effects. However, the underlying molecular mechanisms by which these SERMs modulate Transforming Growth Factor-β (TGF-β) signaling in human vascular smooth muscle cells (VSMCs) remain largely unexplored.

Paradoxical effect of Aβ on protein levels of ABCA1 in astrocytes, microglia, and neurons isolated from C57BL/6 mice: an in vitro and in silico study to elucidate the effect of Aβ on ABCA1 in the brain cells.

Impaired cholesterol metabolism has been reported in Alzheimer's disease. Since ABCA1 is one of the main players in the brain's cholesterol homeostasis, here we used the in-vitro and in-silico experiments to investigate the effect of Aβ on ABCA1 protein levels in microglia, astrocytes, and neurons in mice. Microglia, astrocytes, and neurons were cultured and exposed to beta amyloid.

Mesenchymal Stem Cells Therapy Led to the Improvement of Spatial Memory in Rats with Alzheimer's disease Through Changing the Expression of LncRNA TUSC7/ miR-449a/ PPARγ and CD36 Genes in the Brain Tissue.

Mesenchymal stem cells (MSCs) have the ability to phagocytize amyloid beta (Aβ) plaques and lower inflammation through the activity of microglia. Peroxisome proliferator-activated receptor gamma (PPARγ) is a protein involved in reducing inflammation through the activity of microglia and the phagocytosis of Aβ plaques by scavenger receptor CD36, in this study, the effect of MSCs therapy on memory function and plaques was investigated. A total of 24 adult male Wistar rats were randomly divided into three groups:1) the control group, 2) the Aβ-treated group (Alzheimer's disease (AD)), and 3) the MSC-treated group (AD + MSC).

Endothelin-1 Stimulates PAI-1 Protein Expression via Dual Transactivation Pathway Dependent ROCK and Phosphorylation of Smad2L.

Objective: In addition to the carboxy region, Smad2 transcription factor can be phosphorylated in the linker region as
well. Phosphorylation of Smad2 linker region (Smad2L) promotes the expression of plasminogen activator inhibitor type
1 (PAI-1) which leads to cardiovascular disorders such as atherosclerosis. The purpose of this study was to evaluate the role of dual transactivation of EGF and TGF-β receptors in phosphorylation of Smad2L and protein expression of PAI-1 induced by endothelin-1 (ET-1) in bovine aortic endothelial cells (BAECs).

Reducing Proteoglycan Synthesis and NOX Activity by ROCK Inhibitors: Therapeutic Targets in Atherosclerosis.

Atherosclerosis is a chronic inflammatory disease of the arteries characterized by the accumulation of inflammatory cells in the arterial wall. Hypertension, dyslipidemia, and hyperglycemia are major risk factors of atherosclerosis. Rho-associated protein kinase (ROCK), a serine/threonine kinase, is a downstream effector of the small GTPase RhoA.

Endothelin-1 dependent expression of GAG genes involves NOX and p38 mediated Smad linker region phosphorylation.

Endothelin-1 (ET-1) is implicated in the development of atherosclerosis and mediates glycosaminoglycan (GAG) chain hyperelongation on proteoglycans. Our aim was to identify the ET-1-mediated signalling pathway involving NADPH oxidase (NOX), p38 MAP kinsae and Smad2 linker region phosphorylation (phospho-Smad2L) regulate GAG synthesising enzymes mRNA expression (C4ST-1 and ChSy1) involved in GAG chains hyperelongation in human vascular smooth muscle cells (VSMCs). Signalling intermediates were detected and quantified by Western blotting and the mRNA levels of GAG synthesising enzymes were assessed by quantitative real-time polymerase chain reaction (qRT-PCR).

Mesenchymal stem cells derived from the kidney can ameliorate diabetic nephropathy through the TGF-β/Smad signaling pathway.

Diabetic nephropathy (DN) has been introduced as one of the main microvascular complications in diabetic patients, the most common cause of end-stage renal disease (ESRD). Based on the therapeutic potential of mesenchymal stem cells in tissue repair, we aimed to test the hypothesis that kidney stem cells (KSCs) might be effective in the kidney regeneration process. Stem cells from rat kidney were separated, and the surface stem cell markers were determined by flow cytometry analysis.

Endothelin-1 mediated glycosaminoglycan synthesizing gene expression involves NOX-dependent transactivation of the transforming growth factor-β receptor.

G protein-coupled receptor (GPCR) agonist endothelin-1 (ET-1) through transactivation of the transforming growth factor (TGF) β receptor (TGFBR1) stimulates glycosaminoglycan (GAG) elongation on proteoglycans. GPCR agonists thrombin and lysophosphatidic acid (LPA) via respective receptors transactivate the TGFBR1 via Rho/ROCK dependent pathways however mechanistic insight for ET-1 transactivation of the TGFBR1 remains unknown. NADPH oxidase (NOX) generates reactive oxygen species (ROS) and is a signalling entity implicated in the pathogenesis of many diseases including atherosclerosis.

Endothelin-1 Induced Phosphorylation of Caveolin-1 and Smad2C in Human Vascular Smooth Muscle Cells: Role of NADPH Oxidases, c-Abl, and Caveolae Integrity in TGF-β Receptor Transactivation.

Caveolin-1(Cav-1) is one of the most important components of caveolae in the cell membrane, which plays an important role in cell signaling transduction, such as EGFR and TGF-β receptor transactivation. The purpose of this study was to evaluate the effect of c-Abl and NAD(P)H oxidases (NOX) on phosphorylation of Cav-1 and consequently their effect on phosphorylation of Smad2C induced by Endothelin-1 in human vascular smooth muscle cells (VSMCs). In this study, all experiments were performed using human VSMCs.

EGF Receptor Transactivation by Endothelin-1 Increased CHSY-1 Mediated by NADPH Oxidase and Phosphorylation of ERK1/2.

Objective: Growth factors [transforming growth factor-β (TGF-β), epidermal growth factor (EGF), endothelin-1 (ET1)] stimulate proteoglycan synthesis resulting in retention and accumulation of low density lipoprotein (LDL) in vessel intima and leading to atherosclerosis development. This study investigated the role of ET-1 on the expression of CHSY1, proteoglycan synthesizing enzyme, through both EGF and TGF-β receptor transactivation in human vascular smooth muscle cells (VSMCs). Also, we explored the involvement of NADPH oxidase (NOX), an important intermediate of redox signaling, in ET-1 transactivated EGF receptor (EGFR) through endothelin receptors.

Amyloid beta increases ABCA1 and HMGCR protein expression, and cholesterol synthesis and accumulation in mice neurons and astrocytes.

Introduction: Imbalanced cholesterol metabolism in the brain is one of the main pathophysiological mechanisms involved in Alzheimer's disease. We investigated the effect of amyloid-beta (Aβ) on the main proteins involved in regulation of cholesterol metabolism along with cholesterol content in astrocytes and neurons.

Methods: Astrocytes and neurons were cultured and treated with Aβ.

Quercetin synergistically potentiates the anti-metastatic effect of 5-fluorouracil on the MDA-MB-231 breast cancer cell line.

Objectives: Breast cancer (BC) cells' ability to metastasize to other tissues increases mortality. The Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) facilitate cancer cell migration. 5-fluorouracil is a frequently applied chemotherapeutic agent in cancer treatment with destructive side effects on normal tissues.

Metabolic and hormonal effects of melatonin and/or magnesium supplementation in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. This study was designed to investigate the effects of melatonin and/or magnesium supplementation on metabolic profile and levels of sex hormones in PCOS women.

Methods: In an 8-week randomized double-blind placebo-controlled trial, 84 subjects with PCOS aged 18-40 years were randomly assigned based on the random block procedure to take magnesium, melatonin, magnesium plus melatonin, and placebo.

Effects of Melatonin and/or Magnesium Supplementation on Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial.

Magnesium and melatonin are known to exert multiple beneficial effects including anti-inflammatory and antioxidant actions. This study was designed to determine the effects of magnesium and/or melatonin supplementation on metabolic profiles in women with polycystic ovary syndrome (PCOS). This randomized double-blind, placebo-controlled trial was conducted among 84 subjects with PCOS aged 18-40 years old.

Impact of Methyl-β-Cyclodextrin and Apolipoprotein A-I on The Expression of ATP-Binding Cassette Transporter A1 and Cholesterol Depletion in C57BL/6 Mice Astrocytes.

Objective: Dysregulation of cholesterol metabolism in the brain is responsible for many lipid storage disorders, including Niemann-Pick disease type C (NPC). Here, we have investigated whether cyclodextrin (CD) and apolipoprotein A-I (apoA-I) induce the same signal to inhibit cell cholesterol accumulation by focusing on the main proteins involved in cholesterol homeostasis in response to CD and apoA-I treatment.

Materials And Methods: In this experimental study, astrocytes were treated with apoA-I or CD and then lysed in RIPA buffer.

Decreased lipoprotein (a) and serum high-sensitivity C-reactive protein levels in male patients with atherosclerosis after supplementation with ginger: A randomized controlled trial.

Background: Although the antioxidant properties of ginger have been revealed, there is little available information on the effectiveness of ginger on inflammatory disorders such as atherosclerosis. This study was carried out to examine the effect of ginger on improving the complication of atherosclerosis.

Methods: This study was a double-blind, placebo-controlled, randomized clinical trial conducted on patients with atherosclerosis.

Combination of Silibinin and Curcumin Reduced Leptin Receptor Expression in MCF-7 Human Breast Cancer Cell Line.

Background: Leptin and leptin receptor (Ob-R) are associated with worse prognosis, distant metastasis, and poor survival of breast cancer. We investigated the cytotoxic effect of silibinin and curcumin, individually and combined, on Ob-R expression in MCF-7 cells.

Methods: This study was performed from October 2017 to April 2018 at the Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

GPCR transactivation signalling in vascular smooth muscle cells: role of NADPH oxidases and reactive oxygen species.

The discovery and extension of G-protein-coupled receptor (GPCR) transactivation-dependent signalling has enormously broadened the GPCR signalling paradigm. GPCRs can transactivate protein tyrosine kinase receptors (PTKRs) and serine/threonine kinase receptors (S/TKRs), notably the epidermal growth factor receptor (EGFR) and transforming growth factor-β type 1 receptor (TGFBR1), respectively. Initial comprehensive mechanistic studies suggest that these two transactivation pathways are distinct.