Use of Molecular Modeling to Study Spermatogenesis: An Overview Using Proteins in Sertoli Cells.

Computational structure prediction and analysis helps in understanding the structure and function of varied proteins, which otherwise becomes implausible to understand by experimental procedures. Computational techniques prove to be instrumental in understanding the molecular mechanisms that underlies physiological processes and thereby also assist in identification of potent inhibitors. Spermatogenesis, being an important cellular process that decides the fate of the progeny, holds numerous molecular interaction data, which when identified and visualized with computational structural insights, might yield a cohesive and clear-cut perception to the functionality of several proteins involved.

How to Achieve Therapeutic Response in Erlotinib-Resistant Head and Neck Squamous Cell Carcinoma? New Insights from Stable Isotope Labeling with Amino Acids in Cell Culture-Based Quantitative Tyrosine Phosphoproteomics.

Resistance to cancer chemotherapy is a major global health burden. Epidermal growth factor receptor () is a proven therapeutic target for multiple cancers of epithelial origin. Despite its overexpression in >90% of head and neck squamous cell carcinoma (HNSCC) patients, tyrosine kinase inhibitors such as erlotinib have shown a modest response in clinical trials.

MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) targeted therapies have shown limited efficacy in head and neck squamous cell carcinoma (HNSCC) patients despite its overexpression. Identifying molecular mechanisms associated with acquired resistance to EGFR-TKIs such as erlotinib remains an unmet need and a therapeutic challenge. In this study, we employed an integrated multi-omics approach to delineate mechanisms associated with acquired resistance to erlotinib by carrying out whole exome sequencing, quantitative proteomic and phosphoproteomic profiling.

Chronic Exposure to Chewing Tobacco Induces Metabolic Reprogramming and Cancer Stem Cell-Like Properties in Esophageal Epithelial Cells.

Tobacco in its smoke and smokeless form are major risk factors for esophageal squamous cell carcinoma (ESCC). However, molecular alterations associated with smokeless tobacco exposure are poorly understood. In the Indian subcontinent, tobacco is predominantly consumed in chewing form.

Targeting Kinase Interaction Networks: A New Paradigm in PPI Based Design of Kinase Inhibitors.

Background: Kinases are key modulators in regulating diverse range of cellular activities and are an essential part of the protein-protein interactome. Understanding the interaction of kinases with different substrates and other proteins is vital to decode the cell signaling machinery as well as causative mechanism for disease onset and progression.

Objective: The objective of this review is to present all studies on the structure and function of few important kinases and highlight the protein-protein interaction (PPI) mechanism of kinases and the kinase specific interactome databases and how such studies could be utilized to develop anticancer drugs.

Proteomic Analysis of the Human Anterior Pituitary Gland.

The pituitary function is regulated by a complex system involving the hypothalamus and biological networks within the pituitary. Although the hormones secreted from the pituitary have been well studied, comprehensive analyses of the pituitary proteome are limited. Pituitary proteomics is a field of postgenomic research that is crucial to understand human health and pituitary diseases.

Dissecting Candida Pathobiology: Post-Translational Modifications on the Candida tropicalis Proteome.

Candida tropicalis belongs to the non-albicans group of Candida, and causes epidermal, mucosal, or systemic candidiasis in immunocompromised individuals. Although the prevalence of candidiasis has increased worldwide and non-albicans Candida (NAC) are becoming more significant, there are very few studies that focus on the NAC biology. Proteins and their post-translational modifications (PTMs) are an integral aspect in the pathobiology of such medically important fungi.

Cigarette smoke and chewing tobacco alter expression of different sets of miRNAs in oral keratinocytes.

Carcinogenic effect of tobacco in oral cancer is through chewing and/or smoking. Significant differences exist in development of oral cancer between tobacco users and non-users. However, molecular alterations induced by different forms of tobacco are yet to be fully elucidated.

Molecular alterations associated with chronic exposure to cigarette smoke and chewing tobacco in normal oral keratinocytes.

Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorly understood.

Targeting focal adhesion kinase overcomes erlotinib resistance in smoke induced lung cancer by altering phosphorylation of epidermal growth factor receptor.

EGFR-based targeted therapies have shown limited success in smokers. Identification of alternate signaling mechanism(s) leading to TKI resistance in smokers is critically important. We observed increased resistance to erlotinib in H358 NSCLC (non-small cell lung carcinoma) cells chronically exposed to cigarette smoke (H358-S) compared to parental cells.

Role of protein kinase N2 (PKN2) in cigarette smoke-mediated oncogenic transformation of oral cells.

Smoking is the leading cause of preventable death worldwide. Though cigarette smoke is an established cause of head and neck cancer (including oral cancer), molecular alterations associated with chronic cigarette smoke exposure are poorly studied. To understand the signaling alterations induced by chronic exposure to cigarette smoke, we developed a cell line model by exposing normal oral keratinocytes to cigarette smoke for a period of 12 months.

Computational Methods Involved in Evaluating the Toxicity of the Reproductive Toxicants in Sertoli Cell.

The Sertoli cell, the somatic component of seminiferous tubule, provides nutritional support and immunological protection and supports overall growth and division of germ cells. Cytoskeletons, junction proteins, and kinases in Sertoli cells are prime targets for reproductive toxicants and other environmental contaminants. Among the varied targets, the kinases that are crucial for regulating varied activities in spermatogenesis such as assembly/disassembly of blood-testis barrier and apical ES and those that are involved in conferring polarity are highly targeted.

miRNA and Proteomic Dysregulation in Non-Small Cell Lung Cancer in Response to Cigarette Smoke.

Background: Dysregulation of miRNAs is associated with the development of non-small cell lung cancer (NSCLC). It is imperative to study the dysregulation of miRNAs by cigarette smoke which will affect their targets, either leading to the overexpression of oncoproteins or downregulation of tumor suppressor proteins.

Objective And Methods: In this study, we carried out miRNA sequencing and SILAC-based proteomic analysis of H358 cells chronically exposed to cigarette smoke condensate.

Chronic Exposure to Cigarette Smoke and Chewing Tobacco Alters Expression of microRNAs in Esophageal Epithelial Cells.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers with high mortality rate. Cigarette smoke and chewing tobacco are well known risk factors associated with ESCC. However, molecular mechanisms associated with development of ESCC among smokers and chewers are poorly understood.

Cigarette smoke induces mitochondrial metabolic reprogramming in lung cells.

Cellular transformation owing to cigarette smoking is due to chronic exposure and not acute. However, systematic studies to understand the molecular alterations in lung cells due to cigarette smoke are lacking. To understand these molecular alterations induced by chronic cigarette smoke exposure, we carried out tandem mass tag (TMT) based temporal proteomic profiling of lung cells exposed to cigarette smoke for upto 12months.

Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis.

Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke.

Long-Term Cigarette Smoke Exposure and Changes in MiRNA Expression and Proteome in Non-Small-Cell Lung Cancer.

Chronic exposure to cigarette smoke markedly increases the risk for lung cancer. Regulation of gene expression at the post-transcriptional level by miRNAs influences a variety of cancer-related interactomes. Yet, relatively little is known on the effects of long-term cigarette smoke exposure on miRNA expression and gene regulation.

Corrigendum: A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma.

This corrects the article DOI: 10.1038/srep36132.

In Silico Approach to Identify Potential Inhibitors for Axl-Gas6 Signaling.

Axl-Gas6 signaling plays an important role in numerous cancers. Axl kinase, a member of receptor tyrosine kinase family is activated by different mechanisms with Gas6 as its major activator. Targeting the Axl with inhibitors may block the binding of Gas6 and further hinders the activation of Axl.

Bonny light crude oil-induced alteration in levels of testicular stress proteins is accompanied by apoptosis in rats after treatment withdrawal.

Background: The folkloric use of Bonny light crude oil (BLCO) in the treatment of gastrointestinal disorders and as an anti-poison is a generally acceptable practice in the Niger Delta area of Nigeria. The testicular dysfunction induced by BLCO exposure is of public concern with a view to its folkloric usage. The present study investigated the effects of BLCO exposure and withdrawal on the levels of testicular stress proteins and apoptosis-related proteins in rats.

A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma.

Despite advances in clinical management, 5-year survival rate in patients with late-stage head and neck squamous cell carcinoma (HNSCC) has not improved significantly over the past decade. Targeted therapies have emerged as one of the most promising approaches to treat several malignancies. Though tyrosine phosphorylation accounts for a minority of total phosphorylation, it is critical for activation of signaling pathways and plays a significant role in driving cancers.