Insulin Receptor Substrate 1 Gly972Arg (rs1801278) Polymorphism Is Associated with Obesity and Insulin Resistance in Kashmiri Women with Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome (PCOS) is commonly associated with metabolic abnormalities such as hyperinsulinemia, insulin resistance and obesity. The genetic variants of genes regulating insulin action, expression and regulation are suggested as possible factors involved in development and severity of clinical manifestations in PCOS. Aim: We investigated whether IRS-1Gly972Arg (rs1801278) polymorphism is associated with increased risk of PCOS in Kashmiri women.

Clinical Manifestations of Hyperandrogenism and Ovulatory Dysfunction Are Not Associated with His1058 C/T SNP (rs1799817) Polymorphism of Insulin Receptor Gene Tyrosine Kinase Domain in Kashmiri Women with PCOS.

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder affecting premenopausal women. Besides primary features like anovulation, hyperandrogenism, and polycystic ovaries, women with PCOS present with multiple metabolic, cardiovascular, and psychological disorders. The etiology is multifactorial and the different genetic variants are suggested to play an important role in pathogenesis.

Androgen receptor coregulator long noncoding RNA CTBP1-AS is associated with polycystic ovary syndrome in Kashmiri women.

Objective: Polycystic ovary syndrome (PCOS) is one of the most common reproductive, endocrine, and metabolic disorder in premenopausal women. Even though the pathophysiology of PCOS is complex and obscure, the disorder is prominently considered as the syndrome of hyperandrogenism. C-Terminal binding protein 1 antisense (CTBP1-AS) acts as a novel androgen receptor regulating long noncoding RNA (lncRNA).

Active Extracts Modulate Expression of Crucial Proinflammatory Mediators/Cytokines and NFκB Cascade in Lipopolysaccharide-Induced Albino Wistar Rat Model.

Introduction: Chronic inflammation is implicated in a multitude of diseases, including arthritis, neurodegeneration, autoimmune myositis, type 2 diabetes, rheumatic disorders, spondylitis, and cancer. Therefore, strategies to explore potent anti-inflammatory regimens are pivotal from a human-health perspective. Medicinal plants represent a vast unexplored treasure trove of therapeutically active constituents with diverse pharmacological activities, including anti-inflammatory properties.

CYP17 gene polymorphic sequence variation is associated with hyperandrogenism in Kashmiri women with polycystic ovarian syndrome.

Objective: Polycystic ovarian syndrome is a complex reproductive as well as endocrinological disorder characterized by anovulatory dysfunction, androgen excess and polycystic ovarian morphology. Hyperandrogenism is regarded as a cardinal feature of the disease. It is believed that the excess androgens are produced due to abnormality in steroid biosynthesis pathway wherein cytochrome P450, 17α-hydroxylase (CYP17) plays an imperative role.

Elucidating Critical Proteinopathic Mechanisms and Potential Drug Targets in Neurodegeneration.

Neurodegeneration entails progressive loss of neuronal structure as well as function leading to cognitive failure, apathy, anxiety, irregular body movements, mood swing and ageing. Proteomic dysregulation is considered the key factor for neurodegeneration. Mechanisms involving deregulated processing of proteins such as amyloid beta (Aβ) oligomerization; tau hyperphosphorylation, prion misfolding; α-synuclein accumulation/lewy body formation, chaperone deregulation, acetylcholine depletion, adenosine 2A (A2A) receptor hyperactivation, secretase deregulation, leucine-rich repeat kinase 2 (LRRK2) mutation and mitochondrial proteinopathies have deeper implications in neurodegenerative disorders.

Assessment of PON1 activity and circulating TF levels in relation to BMI, testosterone, HOMA-IR, HDL-C, LDL-C, CHO, SOD activity and TAC in women with PCOS: An observational study.

Background: Polycystic Ovary Syndrome (PCOS) is the most common female endocrinopathy among premenopausal women associated with hyperandrogenism, obesity, dyslipidemia, insulin resistance and inflammation. Oxidative stress is an important component of cardio-metabolic risk seen in PCOS.

Material And Methods: A total of 95 women with PCOS and 95 healthy controls were included in this observational study.

Oral contraceptive use increases risk of inflammatory and coagulatory disorders in women with Polycystic Ovarian Syndrome: An observational study.

Polycystic ovarian syndrome (PCOS) is a multispectral disorder requiring lifelong management. Its pathophysiology is still being explored which makes its treatment options restrained. Present study explores impact of oral contraceptive mode of treatment on metabolic, hormonal, inflammation and coagulation profile of PCOS women.

Elevated fasting insulin is associated with cardiovascular and metabolic risk in women with polycystic ovary syndrome.

Aims: PCOS is associated with various immediate and long term health complications. The aim of this study was to investigate the association of serum fasting insulin concentration with cardiovascular and metabolic risk factors in women with polycystic ovary syndrome.

Methods: A total of 349 women, 249 women with polycystic ovary syndrome and 100 age-matched healthy controls, were recruited in this case-control study.

Effect of six-month use of oral contraceptive pills on plasminogen activator inhibitor-1 & factor VIII among women with polycystic ovary syndrome: An observational pilot study.

Background & Objectives: Polycystic ovary syndrome (PCOS) is an endocrinopathy warranting lifelong individualized management by lifestyle and pharmacological agents mainly oral contraceptive pills (OCPs). This study was aimed to report the impact of six-month OCP use on plasminogen activator inhibitor-1 (PAI-1) and factor VIII (FVIII) in women with PCOS.

Methods: PCOS women diagnosed on the basis of Rotterdam 2003 criteria, either treated with OCPs (ethinyl estradiol-0.

Physio-chemical Characterization and Anti-microbial Activity of Serine Protease Inhibitors Purified from the Seeds.

Background And Objective: Protease inhibitors (PIs) regulate various cellular processes like cell cycle, differentiation, apoptosis and immune responses. Leguminous seeds are rich sources of protease inhibitors and many novel protease inhibitors have been purified from them. To isolate and purify protease inhibitors from seeds of Sophora japonica, characterize and investigate their anti- microbial activity.

Modern Computational Strategies for Designing Drugs to Curb Human Diseases: A Prospect.

Drug discovery is an exhaustive and time-consuming process involving numerous stages like target identification, validation, lead optimization, preclinical trials, clinical trials and finally postmarketing vigilance for drug safety. The application of computer-aided drug designing (CADD) is an indispensable approach for developing safe and effective drugs. Previous methods based on combinatorial chemistry (CC) and high throughput screening (HTS) consumed a lot of time as well as expenditure.

Impact of catechol-O-methyltransferase gene variants on methylation status of P16 and MGMT genes and their downregulation in colorectal cancer.

Globally, colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second most commonly diagnosed cancer in females, with 1.4 million new cases and almost 694 000 deaths estimated to have occurred in 2012. The development and progression of CRC is dictated by a series of alterations in diverse genes mostly proto-oncogenes and tumor suppressor genes.

The synthesis, biological evaluation and structure-activity relationship of 2-phenylaminomethylene-cyclohexane-1,3-diones as specific anti-tuberculosis agents.

The present study utilised whole cell based phenotypic screening of thousands of diverse small molecules against H37Rv () and identified the cyclohexane-1,3-dione-based structures and as hits. The selected hit molecules were used for further synthesis and a library of 37 compounds under four families was synthesized for lead generation. Evaluation of the library against lead to the identification of three lead antituberculosis agents (, and ).

Exploring Proteomic Drug Targets, Therapeutic Strategies and Protein - Protein Interactions in Cancer: Mechanistic View.

Protein-Protein Interactions (PPIs) drive major signalling cascades and play critical role in cell proliferation, apoptosis, angiogenesis and trafficking. Deregulated PPIs are implicated in multiple malignancies and represent the critical targets for treating cancer. Herein, we discuss the key protein-protein interacting domains implicated in cancer notably PDZ, SH2, SH3, LIM, PTB, SAM and PH.

In vitro antimycobacterial activity of 2-(((2-hydroxyphenyl)amino)methylene)-5,5-dimethylcyclohexane-1,3-dione: a new chemical entity against Mycobacterium tuberculosis.

This study reports on the in vitro antituberculosis potential of 2-(((2-hydroxyphenyl) amino)methylene)-5,5-dimethylcyclohexane-1,3-dione (PAMCHD) against Mycobacterium tuberculosis H37Rv. PAMCHD has been proven to be a tuberculostatic as well as a tuberculocidal agent by agar and broth dilution methods with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values equivalent to some standard antituberculosis drugs (ATDs). The dynamics of M.

Design and synthesis of indolopyridone hybrids as new antituberculosis agents.

Tuberculosis continues to be the most dangerous infectious disease globally and need for development of new therapies is of utmost importance. In this study we describe the rationale design for synthesis using molecular hybridization and subsequent in-vitro antimycobacterial activity of various indolo-pyridone hybrid molecules against Mycobacterium tuberculosis H37Rv. A total of 16 indolo-pyridone hybrid molecules were synthesized with 85-90% yields and characterized by various spectroscopic techniques.

Efficacy of Aqueous and Methanolic Extracts of against Pathogenic Bacterial and Fungal Strains.

Introduction: is a newly identified edible medicinal plant of genus . The plant is used to treat various diseases on traditional levels in Kashmir Valley, India.

Aim: To evaluate the phytochemical screening, antibacterial and antifungal potential of aqueous and methanolic extracts of , a traditionally used edible medicinal plant.

Type 2 diabetes and metabolic syndrome - adipokine levels and effect of drugs.

Type 2 diabetes mellitus (T2DM) is a consequence of complex interactions among multiple genetic variants and environmental risk factors. This complex disorder is also characterized by changes in various adipokines. In this study, our objective was to estimate the levels of adiponectin, leptin, and resistin (ALR) in T2DM patients, besides studying the effect of various drugs on their levels.

Inflammation: A Multidimensional Insight on Natural Anti-Inflammatory Therapeutic Compounds.

Derailed inflammation causes severe damage to the normal tissues resulting in various pathological conditions such as auto-inflammatory disorders, neurodegenerative diseases and cancer. Cure of inflammatory diseases is a big challenge. Medicinal herbs used traditionally represent the best option for obtaining effective anti-inflammatory therapeutics.

Association between GSTM1 and GSTT1 polymorphisms and esophageal squamous cell carcinoma: results from a case-control study in Kashmir, India.

Polymorphisms in glutathione-S-transferases (GSTs), the phase II xenobiotic detoxifying enzymes, have been associated with increased cancer risk. In this study, we assessed the association of functional polymorphisms in GSTM1 and GSTT1 with esophageal cancer in Kashmir, India, an area with a high incidence of esophageal squamous cell carcinoma (ESCC). We analyzed genotypes of GSTM1 and GSTT1 using a multiplex PCR in 492 pairs of ESCC cases and individually matched controls.

Plant-derived protease inhibitors LC-pi (Lavatera cashmeriana) inhibit human lung cancer cell proliferation in vitro.

The objective of this study was to check the anticancer activity of purified protease inhibitors of Lavatera cashmeriana viz LC-pi I, II, III, and IV (Lavatera cashmeriana protease inhibitors) on A549 (lung) cell. It was found that LC-pi I and II significantly inhibited the proliferation of A549 cells with IC₅₀ value of 54 μg/ml and 38 μg/ml, respectively, whereas inhibition by LC-pi III and IV was negligible. LC-pi I and II were further found to inhibit formation of colonies in a dose-dependent manner.