Glutaminase - A potential target for cancer treatment.

The overexpression of glutaminase is reported to influence cancer growth and metastasis through glutaminolysis. Upregulation of glutamine catabolism is recently recognized as a critical feature of cancer, and cancer cells are observed to reprogram glutamine metabolism to maintain its survival and proliferation. Special focus is given on the glutaminase isoform, GLS1 (kidney type glutaminase), as the other isoform GLS2 (Liver type glutaminase) acts as a tumour suppressor in some conditions.

Delayed identification of treatment failure causes high levels of acquired drug resistance and less future drug options among HIV-1-infected South Indians.

Purpose: HIV-1 Drug Resistance Mutations (DRMs) among Immunological failure (IF) on NRTI based first-line regimens, Thymidine analogue (TA) - AZT & D4T and Non-Thymidine Analogue (NTA) -TDF; and predict viral drug susceptibility to gain vision about optimal treatment strategies for second-line.

Methods: Cross-sectionally, 300 HIV-1 infected patients, failing first-line HAART were included. HIV-1 pol gene spanning 20-240 codons of RT was genotyped and mutation pattern was examined, (IAS-USA 2014 and Stanford HIV drug resistance database v7.

Role of berberine on angiogenesis and blood flow hemodynamics using zebrafish model.

Angiogenesis and hemodynamic instability created by the irregular blood vessels causes hypoperfusion and angiogenesis-mediated diseases. Therefore, therapies focusing on controlling angiogenesis will be a valuable approach to treat a broad spectrum of diseases. In this study, we explored the anti-angiogenic potential of berberine (BBR) and also analyzed blood flow hemodynamics using zebrafish embryos.

Pharmacotherapeutic values of berberine: A Chinese herbal medicine for the human cancer management.

Berberine (BBR), a traditional Chinese phytomedicine extracted from various parts of Berberis plants, is an isoquinoline alkaloid used for centuries to treat diabetes, hypercholesterolemia, hypertension, and so forth. It has recently received immense attention worldwide to treat cancer due to its potent pro-apoptotic, antiproliferative, and anti-inflammatory properties. BBR efficiently induces tumor apoptosis, replicative quiescence and abrogates cell proliferation, epithelial-mesenchymal transition, tumor neovascularization, and metastasis by modulating diverse molecular and cell signaling pathways.

Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS-COV-2 cell entry facilitator spike protein.

Background: The Transmembrane Serine Protease 2 (TMPRSS2) of human cell plays a significant role in proteolytic cleavage of SARS-Cov-2 coronavirus spike protein and subsequent priming to the receptor ACE2. Approaching TMPRSS2 as a therapeutic target for the inhibition of SARS-Cov-2 infection is highly promising. Hence, in the present study, we docked the binding efficacy of ten naturally available phyto compounds with known anti-viral potential with TMPRSS2.

A comprehensive review on high -fat diet-induced diabetes mellitus: an epigenetic view.

Modern lifestyle, genetics, nutritional overload through high-fat diet attributed prevalence and diabetes outcomes with various complications primarily due to obesity in which energy-dense diets frequently affect metabolic health. One possible issue usually associated with elevated chronic fat intake is insulin resistance, and hyperglycemia constitutes an important function in altering the carbohydrates and lipids metabolism. Similarly, in assessing human susceptibility to weight gain and obesity, genetic variations play a central role, contributing to keen interest in identifying the possible role of epigenetics as a mediator of gene-environmental interactions influencing the production of type 2 diabetes mellitus and its related concerns.

Identification of Epigenetically Modified Hub Genes and Altered Pathways Associated With Retinoblastoma.

Retinoblastoma (Rb) is the most common childhood malignancy initiated by biallelic mutation in gene and driven by various epigenetic events including DNA methylation and microRNA dysregulation. Hence, understanding the key genes that are critically modulated by epigenetic modifications in cells is very important to identify prominent biomarkers and therapeutic targets of Rb. In this study, we for the first time have integrated various Rb microarray NCBI-GEO datasets including DNA Methylation (GSE57362), miRNA (GSE7072) and mRNA (GSE110811) to comprehensively investigate the epigenetic consequences of loss in retinoblastoma tumors and identify genes with the potential to serve as early diagnostic markers and therapeutic targets for Rb.

Association of Epstein-Barr virus, cytomegalovirus and lipocalin with periodontitis in type 2 diabetic subjects.

Objective: The current study aims to evaluate and compare the lipocalin, adiponectin and periodontal viruses in the generalized periodontitis patients with and without diabetes mellitus.

Materials And Methods: Seventy subjects were grouped into 35 systemically healthy (GP) and 35 patients with diabetes mellitus (GP+DM). The periodontal parameters, demographic and diabetic variables were evaluated in both the groups.

Possible Mechanism of Human Recombinant Leptin-Induced VEGF A Synthesis via PI3K/Akt/mTOR/S6 Kinase Signaling Pathway while Inducing Angiogenesis: An Analysis Using Chicken Chorioallantoic Membrane Model.

Introduction: The present study aimed to realize human recombinant leptin 's ability to synthesize VEGF A while inducing neovascularization through PI3K/Akt/mTOR/S6 kinase involved signaling pathway.

Methods: To examine the PI3K/Akt/mTOR/S6 kinase pathway involvement in leptin-induced VEGF A synthesis, the chick chorioallantoic membrane (CAM) was incubated with human recombinant leptin and specific inhibitors of the proposed signaling molecules (rapamycin and wortmannin). We analyzed the role of specified signaling molecules in human recombinant leptin-induced physiological angiogenesis via VEGF A synthesis in detail with the support of various methodologies.

β-Sitosterol Circumvents Obesity Induced Inflammation and Insulin Resistance by down-Regulating IKKβ/NF-κB and JNK Signaling Pathway in Adipocytes of Type 2 Diabetic Rats.

β-sitosterol (SIT), the most abundant bioactive component of vegetable oil and other plants, is a highly potent antidiabetic drug. Our previous studies show that SIT controls hyperglycemia and insulin resistance by activating insulin receptor and glucose transporter 4 (GLUT-4) in the adipocytes of obesity induced type 2 diabetic rats. The current research was undertaken to investigate if SIT could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals.

Tumor hypoxia: The major culprit behind cisplatin resistance in cancer patients.

Cisplatin is the most commonly used first-line drug for cancer treatment. However, many patients develop resistance to cisplatin therapy which ultimately results in therapy failure and increased mortality. A growing body of evidence shows that the hypoxic microenvironment is the prime factor underlying tumor insensitivity to cisplatin treatment.

Berberine-A potent chemosensitizer and chemoprotector to conventional cancer therapies.

Chemotherapy and radiotherapy are mainstay treatments for cancer patients. However, their clinical outcomes are highly limited by the resistance of malignant tumors to these therapies and the incurrence of serious damages in vital organs. This in turn necessitates the development of adjunct drugs that overcomes chemo/radioresistance in refractory cancers and protects vital organs from the cytotoxic effects of cancer therapies.

Cytotoxic Effects of Mangosteen Pericarp Extracts on Oral Cancer and Cervical Cancer Cells.

Background: Despite immense advancements in treatment modalities, cancer remains a dreadful disease until the present. The major influencing factors behind the increased mortality rate of cancer are increased drug resistance and severe adverse effects caused by conventional cancer therapies. To overcome these limitations, the current medical field is focusing more on natural phyto-derived molecules to mitigate cancer.

Molecular docking analysis of Bcl-2 with phyto-compounds.

The Bcl-2 protein is liked in several cancers and drug resistance to therapy is also known in this context. There are many Bcl-2 inhibitors under clinical trials. It is of further interest to design new Bcl2 inhibitors from phyto compounds such as artesunate, bruceantin, maytansin, Salvicine, indicine N-oxide, kamebanin and oxyacanthine.

Molecular docking data of piperine with Bax, Caspase 3, Cox 2 and Caspase 9.

Several apoptotic signalling proteins such as Bax, Caspase 3, Cox 2 and Caspase 9 are known to be associated with colorectal cancer (CRC). It is of interest to study the interaction of these proteins with piperine a known drug candidate. We document the binding energy, hydrogen bond interaction and hydrophobic interaction between the piperine and apoptotic proteins for further consideration.

Role of Cluster of Differentiation 163 in Diabetes-Periodontitis Interplay.

Background The aim of the present study was to assess and quantify cluster of differentiation 163 (CD163) protein levels and CD163 messenger RNA (mRNA) gene expression in subgingival plaque samples of generalized chronic periodontitis subjects with and without type II diabetes mellitus (DM). Materials and methods Eighty chronic periodontitis subjects were selected and divided into 40 systemically healthy, generalized chronic periodontitis subjects (Group I) and 40 generalized chronic periodontitis subjects diagnosed with type II diabetes mellitus (Group II). Age, body mass index (BMI), income, plaque index (PI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded.

Docking analysis of importin-11 homology model with the phyto compounds towards colorectal cancer treatment.

Colorectal cancer (CRC) is the most familiar malignancy worldwide. Hence, searching for novel therapeutic options is of highest priority. Therefore, it is of interest to design inhibitors to the protein target importin-11, which transports β-catenin linked to colon cancer cells.

Herbal nutraceuticals: safe and potent therapeutics to battle tumor hypoxia.

Purpose: Growing solid tumors mostly outstrip blood supply and become hypoxic (low oxygen supply). To survive under this pathological milieu, tumors overexpress a potent oncogenic factor, hypoxia-inducible factor-1α (HIF-1α). HIF-1α up-regulate HIF-1 signaling pathways and subsequently activate genes that promote cancer growth even under hypoxia.

"Role of the adipocyte hormone leptin in cardiovascular diseases - a study from Chennai based Population".

Background: Obesity is currently regarded as a pro-inflammatory condition during which leptin (Ob gene product) might act as a risk factor for Cardiovascular Diseases (CVD) including Acute Myocardial Infarction (AMI). There is a marked increase in circulating leptin concentrations and inflammatory markers such as Tumor Necrosis Factor-α (TNF-α) in AMI patients but still the association of leptin with inflammation during AMI is not known. The present study suggest that elevated levels of leptin might elicit the risk for CVD by signaling for the secretion of inflammatory cytokines especially, TNF-α.

Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population.

Background: Obesity, characterised by increased fat mass and is currently regarded as a pro-inflammatory state and often associated with increased risk of cardiovascular diseases (CVD) including Myocardial infarction. There is an upregulation of inflammatory markers such as interleukin-6, interleukin-6 receptor and acute phase protein CRP in Acute Myocardial Infarction (AMI) patients but the exact mechanism linking obesity and inflammation is not known. It is of our interest to investigate if serum leptin (ob gene product) is associated with AMI and correlated with inflammatory proteins namely Interleukin-6 (IL-6) and high sensitivity - C reactive protein (hs-CRP).