Serum protein signature of coronary artery disease in type 2 diabetes mellitus.

Background: Coronary artery disease (CAD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The purpose of the present study was to discriminate the Indian CAD patients with or without T2DM by using multiple pathophysiological biomarkers.

Methods: Using sensitive multiplex protein assays, we assessed 46 protein markers including cytokines/chemokines, metabolic hormones, adipokines and apolipoproteins for evaluating different pathophysiological conditions of control, T2DM, CAD and T2DM with CAD patients (T2DM_CAD).

Inhibition of PAI-1 attenuates perirenal fat inflammation and the associated nephropathy in high-fat diet-induced obese mice.

Plasminogen activator inhibitor-1 (PAI-1) is increasingly recognized as a mediator in extracellular matrix (ECM) accumulation in diabetic nephropathy. Previous studies have implicated PAI-1 in adipose tissue (AT) expansion, while also contributing to insulin resistance. As inflammation is also known to occur in perirenal AT during obesity, we hypothesized that in a high-fat diet (HFD)-induced obese mouse model, PAI-1 contributes to macrophage-mediated inflammation and diabetic nephropathy.

Distinct Changes in the Expression TAZ are Associated with Normal Cervix and Human Cervical Cancer.

The transcriptional coactivator with the PDZ-binding motif (TAZ) has been associated with different types of cancer. In this study, we examined the TAZ protein expression and cellular localization in 194 cases of human cervical squamous cell carcinoma (SCC). We observed that a normal cervix is characterized by higher expression levels of both nuclear and cytosolic TAZ compared to cervical SCC.

Platelet-endothelial cell interactions modulate smooth muscle cell phenotype in an in vitro model of type 2 diabetes mellitus.

Platelet (PLT)-endothelial cell (EC) interaction appears to contribute to phenotypic transition of vascular smooth muscle cells (VSMCs), which play an important role in the physiological and pathological process of vascular complications in type 2 diabetes mellitus (DM2). However, the precise mechanisms by which interactions between PLTs and ECs affect VSMC phenotype have largely remained unclear. We determined the effect of diabetic PLT-EC interaction to influence VSMC migration, proliferation, and phenotypic transformation in triple-cell coculture models using the quantitative real-time PCR, Western blot, fluorescence microscopy, wound scratch assays, CCK-8 assays, and gelatin zymography assays.

SIRT-3 Modulation by Resveratrol Improves Mitochondrial Oxidative Phosphorylation in Diabetic Heart through Deacetylation of TFAM.

Background And Purpose: Mitochondrial dysfunction remains the crucial cause for many heart diseases including diabetic cardiomyopathy (DCM). Sirtuin-3 (SIRT-3) is a protein deacetylase localized in the mitochondria and regulates mitochondrial function. Being a noteworthy mitochondrial protein deacetylase enzyme, the role of SIRT-3 in DCM is yet to be explored.

Molecular dynamics simulation reveals the possible druggable of USP7.

The plasticity in Ubiquitin Specific Proteases (USP7) inducing conformational changes at important areas has highlighted an intricate mechanism, by which USP7 is regulated. Given the importance of USP7 in oncogenic pathways and immune-oncology, identification of USP7 inhibitors has attracted considerable interest. Despite substantial efforts, the discovery of deubiquitinases (DUBs) inhibitors, knowledge of their binding site and understanding the possible mechanism of action has proven particularly challenging.

PAI-1 Exacerbates White Adipose Tissue Dysfunction and Metabolic Dysregulation in High Fat Diet-Induced Obesity.

Plasminogen activator inhibitor (PAI)-1 levels and activity are known to increase during metabolic syndrome and obesity. In addition, previous studies have implicated PAI-1 in adipose tissue (AT) expansion while also contributing to insulin resistance. As inflammation is also known to occur in AT during obesity, we hypothesized that in a high-fat diet (HFD)-induced obese mouse model PAI-1 contributes to macrophage-mediated inflammation and metabolic dysfunction.

Corrigendum: Emergence of Members of TRAF and DUB of Ubiquitin Proteasome System in the Regulation of Hypertrophic Cardiomyopathy.

[This corrects the article DOI: 10.3389/fgene.2018.

Coumarin derivatives as promising xanthine oxidase inhibitors.

Xanthine oxidase (XO) is an interesting target for the synergic treatment of several diseases. Coumarin scaffold plays an important role in the design of efficient and potent inhibitors. In the current work, twenty 3-arylcoumarins and eight 3-heteroarylcoumarins were evaluated for their ability to inhibit XO.

Emergence of Members of TRAF and DUB of Ubiquitin Proteasome System in the Regulation of Hypertrophic Cardiomyopathy.

The ubiquitin proteasome system (UPS) plays an imperative role in many critical cellular processes, frequently by mediating the selective degradation of misfolded and damaged proteins and also by playing a non-degradative role especially important as in many signaling pathways. Over the last three decades, accumulated evidence indicated that UPS proteins are primal modulators of cell cycle progression, DNA replication, and repair, transcription, immune responses, and apoptosis. Comparatively, latest studies have demonstrated a substantial complexity by the UPS regulation in the heart.

Sodium Tanshinone IIA Sulfonate Prevents Angiotensin II-Induced Differentiation of Human Atrial Fibroblasts into Myofibroblasts.

Differentiation of atrial fibroblasts into myofibroblasts plays a critical role in atrial fibrosis. Sodium tanshinone IIA sulfonate (DS-201), a water-soluble derivative of tanshinone IIA, has been shown to have potent antifibrotic properties. However, the protective effects of DS-201 on angiotensin II- (Ang II-) induced differentiation of atrial fibroblasts into myofibroblasts remain to be elucidated.

Corrigendum: Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia.

[This corrects the article on p. 197 in vol. 9, PMID: 29568274.

A practically simple, catalyst free and scalable synthesis of -substituted ureas in water.

A practically simple, mild and efficient method is developed for the synthesis of -substituted ureas by nucleophilic addition of amines to potassium isocyanate in water without organic co-solvent. Using this methodology, a variety of -substituted ureas (mono-, di- and cyclic-) were synthesized in good to excellent yields with high chemical purity by applying simple filtration or routine extraction procedures avoiding silica gel purification. The developed methodology was also found to be suitable for gram scale synthesis of molecules having commercial application in large volumes.

Beneficial effects of fenofibrate in pulmonary hypertension in rats.

Pulmonary hypertension (PH) is a morbid complication of cardiopulmonary as well as several systemic diseases in humans. It is rapidly progressive and fatal if left untreated. In the present study, we investigated the effect of PPARα agonist fenofibrate (FF) on monocrotaline (MCT)-induced PH in rats.

Scavenger receptor B type 1: expression, molecular regulation, and cholesterol transport function.

Cholesterol is required for maintenance of plasma membrane fluidity and integrity and for many cellular functions. Cellular cholesterol can be obtained from lipoproteins in a selective pathway of HDL-cholesteryl ester (CE) uptake without parallel apolipoprotein uptake. Scavenger receptor B type 1 (SR-B1) is a cell surface HDL receptor that mediates HDL-CE uptake.

Synthesis and biological evaluation of certain hydrazonoindolin-2-one derivatives as new potent anti-proliferative agents.

In connection with our research program on the development of novel indolin-2-one-based anticancer candidates, herein we report the design and synthesis of different series of hydrazonoindolin-2-ones 3a-e, 5a-e, 7a-c, and 10a-l. The synthesised derivatives were in vitro evaluated for their anti-proliferative activity towards lung A-549, colon HT-29, and breast ZR-75 human cancer cell lines. Compounds 5b, 5c, 7b, and 10e emerged as the most potent derivatives with average IC values of 4.

Beneficial Effect of (Linn) against Monocrotaline-Induced Pulmonary Hypertension in Rats.

Background: The study was designed to explore any beneficial effect of Ocimum sanctum (Linn) (OS) in experimental pulmonary hypertension (PH) in rats. OS is commonly known as “holy basil” and “Tulsi” and is used in the Indian System of Medicine as antidiabetic, antioxidant, hepatoprotective, adaptogenic, and cardioprotective.

Methods: Monocrotaline (MCT) administration caused development of PH in rats after 28 days and rats were observed for 42 days.

Design and synthesis of novel annulated thienopyrimidines as phosphodiesterase 5 (PDE5) inhibitors.

Novel cycloalkene-fused thienopyrimidine analogues with enhanced phosphodiesterase 5 (PDE5) inhibitory properties are presented. The structure of the reported scaffold was modulated through variation of the terminal cycloalkene ring size, as well as by varying the substituents at position 4 through the attachment of different groups including aniline, benzylamine, cyclohexylethylamine, methyl/acetyl/aryl piperazines, and aryl hydrazones. Compound 15Y with a benzylamine substituent and cycloheptene as terminal ring showed the highest PDE5 inhibitory activity with an IC value as low as 190 nM and with good selectivity versus PDE7 and PDE9.

miR-503 suppresses the proliferation and metastasis of esophageal squamous cell carcinoma by triggering autophagy via PKA/mTOR signaling.

MicroRNA (miR)-503 is involved in the regulation of the malignant phenotype in multiple tumor types, and has been proven to be a novel diagnostic and therapeutic target; however, its function and mechanisms of action have not yet been fully elucidated in esophageal squamous cell carcinoma (ESCC). In the current study, we detected miR‑503 expression by RT‑qPCR and found that miR‑503 expression was increased in ESCC, but negatively correlated with lymph node metastasis, TNM stage and tumor differentiation. Functionally, we confirmed that miR‑503 inhibited the proliferation and metastasis of ESCC cells by triggering cellular autophagy.

Computational modeling suggests impaired interactions between NKX2.5 and GATA4 in individuals carrying a novel pathogenic D16N NKX2.5 mutation.

, a homeobox containing gene, plays an important role in embryonic heart development and associated mutations are linked with various cardiac abnormalities. We sequenced the gene in 100 congenital heart disease (CHD) patients and 200 controls. Our analysis revealed a total of 7 mutations, 3 in intronic region, 3 in coding region and 1 in 3' UTR.

Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia.

Fat deposition is associated with peripheral arterial disease. Adipose tissue has recently been implicated in vascular remodeling and angiogenic activity. We hypothesized that the transplantation of adipose tissues from normal mice improves blood flow perfusion and neovascularization in high-fat diet fed mice.

Rb interactome data and its modulations during cell cycle progression in HEK 293 cells.

The Rb protein is a tumor suppressor protein that regulates the key G1S checkpoint consequently blocking the progression of cell cycle into S-phase. Despite its pertinent role in cell cycle regulation, comprehensive information on its interacting partners across cell cycle progression is lacking. Here, we aim to submit a comprehensive set of Rb interactors as the cell progresses from G0 through G1 and S into G2 phase in HEK 293 cell line.

ε-Poly-l-Lysine/plasmid DNA nanoplexes for efficient gene delivery in vivo.

The present work addresses the development and characterization of ε-Poly-l-Lysine/pDNA polyplexes and evaluation for their improved transfection efficacy and safety as compared to polyplexes prepared using Poly-l-Lysine and SuperFect®. Self-assembling polyplexes were prepared by varying the N/P ratio to obtain the optimum size, a net positive zeta potential and gel retardation. The stability in presence of DNase I and serum was assured using gel retardation assay.

Potent ACE inhibitors from 5-hydroxy indanone derivatives.

A novel triazole derivatives(±)-2-(hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b]furan-6(2H)-one (12a-j) were designed and synthesized by the reaction between racemic azide and terminal acetylenes under click chemistry reaction conditions followed by biological evaluation as angiotensin converting enzyme (ACE) inhibitors. β-Amino alcohol derivatives of 1-indanone (15a-l) were synthesized from 5-hydroxy indanone, it was reacted with epichlorohydrin and followed by oxirane ring opening with various piperazine derivatives. Among the newly synthesized compounds 12b (IC: 1.

Defining the Akt1 interactome and its role in regulating the cell cycle.

Cell growth and proliferation are two diverse processes yet always linked. Akt1, a serine/threonine kinase, is a multi-functional protein implicated in regulation of cell growth, survival and proliferation. Though it has a role in G1/S progression, the manner by which Akt1 controls cell cycle and blends cell growth with proliferation is not well explored.