Molecular dynamic simulations reveal suboptimal binding of salbutamol in T164I variant of β2 adrenergic receptor.

The natural variant C491T (rs1800088) in ADRB2 gene substitutes Threonine to Isoleucine at 164th position in β2AR and results in receptor sequestration and altered binding of agonists. Present investigation pursues to identify the effect of T164I variation on function and structure of β2AR through systematic computational approaches. The study, in addition, addresses altered binding of salbutamol in T164I variant through molecular dynamic simulations.

Association of Beta 2 adrenergic receptor (Thr164Ile) polymorphism with Salbutamol refractoriness in severe asthmatics from Indian population.

Background: Thr164Ile polymorphism in the ADRB2 gene encoding β2 adrenergic receptor (β2AR) has its functional consequence in declining ligand-receptor interactions and depressed coupling of β2AR to adenylcyclase. In the present study, we sought to evaluate the possible association of Thr164Ile polymorphism with asthma susceptibility, pharmacogenetic response to Salbutamol and varying degrees of severity.

Methods: Three hundred and ninety eight clinically diagnosed patients and four hundred and fifty six healthy controls were enrolled in the study.

Association of eNOS and ACE gene polymorphisms and plasma nitric oxide with risk of non-small cell lung cancer in South India.

Introduction: The role of ACE and eNOS gene polymorphisms and their association with various cancers were reported. However, their role in the lung cancer is unclear.

Objectives: In this study, we analyzed eNOS and ACE gene polymorphisms and the risk of non-small cell lung cancer (NSCLC) in South Indian population.

Identification of Small Molecule as a High Affinity β2 Agonist Promiscuously Targeting Wild and Mutated (Thr164Ile) β 2 Adrenergic Receptor in the Treatment of Bronchial Asthma.

Background: A subset of asthmatics shows refractoriness to Salbutamol owing to ADRB2 gene C.T polymorphism (rs 1800888) that substitutes Thr to Ile at the position 164 in the β2 adrenergic receptor leading to sub-optimal binding of Salbutamol. The present study aims to associate the Salbutamol (200 mcg) refractoriness with the polymorphism and select the best existing agonist with optimal binding affinity against wild and mutated receptor and further identify high affinity compound, irrespectively targeting wild and mutated receptor through virtual screening methods.

Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of non-small cell lung cancer in Andhra Pradesh region of South India.

Background: Lung cancer is one of the most preventable causes of death globally both in developed and developing countries. Although it is well established that smokers develop lung cancer, there are some smokers who are free from the disease risk. The predisposition to lung cancer is attributed to genetic polymorphisms in xenobiotic metabolizing genes.

Identification and Pharmacological Analysis of High Efficacy Small Molecule Inhibitors of EGF-EGFR Interactions in Clinical Treatment of Non-Small Cell Lung Carcinoma: a Computational Approach.

Inhibition of EGFR-EGF interactions forms an important therapeutic rationale in treatment of non-small cell lung carcinoma. Established inhibitors have been successful in reducing proliferative processes observed in NSCLC, however patients suffer serious side effects. Considering the narrow therapeutic window of present EGFR inhibitors, the present study centred on identifying high efficacy EGFR inhibitors through structure based virtual screening strategies.

Analysis of ADRB2 (Arg16Gly) Gene Variant with Susceptibility, Pharmacogenetic Response and Disease Severity in South Indian Asthmatics.

β2-Adrenergic receptor (β2-AR) plays a crucial role in asthma pathophysiology by regulating, processes of the lung function, and clinical response to bronchodilators. The +46G>A- Gly16Arg polymorphism in the gene encoding β2 adrenergic receptor (ADRB2) has been associated with receptor non-responsiveness after β2-agonist exposure. In the present study, we sought to evaluate the possible association of Gly16Arg polymorphism with asthma susceptibility, pharmacogenetic response to Salbutamol, and varying degrees of disease severity.

Identification of high affinity bioactive Salbutamol conformer directed against mutated (Thr164Ile) beta 2 adrenergic receptor.

Salbutamol forms an important and widely administered β2 agonist prescribed in the symptomatic treatment of bronchial asthma. Unfortunately, a subset of patients show refractoriness to it owing to ADRB2 gene variant (rs 1800888). The variant substitutes Thr to Ile at the position 164 in the β2 adrenergic receptor leading to sub-optimal binding of agonists.

Association of transforming growth factor-Beta 1 promoter variant -509 c/t with bronchial asthma in South Indian population.

Transforming growth factor-beta 1 (TGF-β1) is a multifunctional cytokine that plays a pivotal role in airway remodeling observed in the asthmatic airways. C to T base substitution at -509 promoter position in the TGF-β1 gene leads to its increased expression which contributes to airway remodeling in bronchial asthma. We sought to evaluate the association of TGF-β1 -509 C/T promoter variant with clinical asthma and varying degrees of disease severity.

Genetic instability in peripheral lymphocytes as biological marker for non-small cell lung cancer patients in the South Indian state of Andhra Pradesh.

Objectives: This study aims, first, at evaluating the DNA and chromosomal damage in non-small cell lung cancer (NSCLC) patients from the South Indian state of Andhra Pradesh, and then at correlating these results with possible confounding factors that might potentially play a role in causing genetic damage.

Methods: The study included 246 NSCLC patients (177 men and 69 women) and 250 healthy controls (180 men and 70 women) for the analysis of DNA and chromosomal damage using the comet assay and micronucleus test.

Results: Both DNA and chromosomal damage were found to be increased in NSCLC patients compared to healthy controls, and the extent of the damage was higher in males than female patients.

Evaluation of oxidative stress and DNA damage in traffic policemen exposed to vehicle exhaust.

Objective: We aimed to study the genotoxic effects in traffic police who are occupationally exposed due to higher free radical generation.

Methods: Ambient and breathing zone air samples were analyzed blood samples were collected for analysis of antioxidant enzymes Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and free radicals - nitric oxide (NO) and malondialdehyde (MDA) levels using a spectrophotometer. DNA damage was measured with the comet assay.

Assessment of 8-oxo-7, 8-dihydro-2'-deoxyguanosine and malondialdehyde levels as oxidative stress markers and antioxidant status in non-small cell lung cancer.

Objective: The present investigation was taken up to evaluate the 8-oxo-7,8-dihydro-2'-deoxyguanosine and malondialdehyde as markers of oxidative stress, the levels of antioxidants and the correlations between these oxidative stress markers and antioxidants in lung cancer patients.

Methods: The study included 222 patients (158 men and 64 women, age ranging from 32 to 85 years) and 207 control subjects (153 men and 54 women, aged 30-80 years) for the analysis of urinary excretion of 8-oxodG using an ELISA assay, plasma malondialdehyde using spectrophotometer and red cell Cu-Zn SOD and GPx activities by kit methods.

Results: The levels of 8-oxodG and malondialdehyde were significantly higher (p < 0.

Mutational analysis of JAG1 gene in non-syndromic tetralogy of Fallot children.

Background: JAG1 is an evolutionarily conserved ligand for Notch receptor and functions in the cell fate decisions, cell-cell interactions throughout the development of heart especially right heart development. Tetralogy of Fallot (TOF) is essentially a right sided heart disease with characteristic features of ventricular septal defect, right ventricular outflow tract obstruction, aortic dextroposition and right ventricular hypertrophy. Hence, the present study was investigated to identify mutations of JAG1 gene in an Indian cohort of patients with TOF.

Association of CYP1A1*2A polymorphism with male infertility in Indian population.

Background: The CYP1A1 gene is a polymorphic gene and encodes for the CYP1A1 enzyme that catalyzes the bioactivation of polycyclic aromatic hydrocarbons (PAHs). PAHs are ubiquitous pollutants in the natural environment, which are capable of forming DNA adducts once being activated to generate DNA reactive metabolites. DNA adducts in sperm cells could be considered as a sign of severe DNA damage, which played an important role in meiotic division during spermatogenesis and could be associated with infertility.