Vellore Institute of Technology (VIT) is a private university located in&nbsp;Tamil Nadu, India. Founded in 1984, as Vellore Engineering College, the institution offers 20 undergraduate, 34 postgraduate, four integrated and four research programs. It has campuses in Vellore, Amravati, Bhopal and Chennai.

VIT is one of the top ranked private universities in India according to NIRF, THE and QS Rankings.&nbsp;Govt. of India has recognized&nbsp;VIT, Vellore as an&nbsp;Institution of Eminence. This has allowed VIT to take independent quality initiatives and move up in world ranking.

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VIT University

Department of Integrative Biology

The predominance of insulin resistance, T2D linked pancreatic cancer has increased throughout the world. The insulin/IGF signaling pathway related to insulin resistance, T2D and pancreatic cancer has been described. In this context, we have demonstrated the role of miRNAs in cancer progression and control of miRNAs in insulin/IGF signaling pathway, and pancreatic cancer. In this paper, an overview was depicted about the role of following miRNAs in pancreatic development and insulin secretion (miR-375, miR-7, miR-124a2, miR-195, miR-126, miR-9, miR-96, miR-34a); insulingrowth factor-1 receptor expression (miR-7, miR-139, miR-145, miR-1); the diabetes-associated pancreatic cancer pathway genes such as IRS, PI3K, AKT/PKB (miR-128a, miR-19a, miR-21, miR-29 a/b/c); mTOR protein regulation (miR- 99, miR-21, miR-126, and miR-146a) etc. At last, we have also explained the role of miRNAs in diagnostic marker (miR- 200, miR-21, miR-103, miR-107, and miR-155) and as a therapeutic modulator (miR-34, miR-21, miR-221, and miR-101) in pancreatic cancer. © 2013 Bentham Science Publishers.

World University root node

School of Bio Sciences and Technology

Vellore Campus

Current Drug Targets

miRNAs in Insulin Resistance and Diabetes-Associated Pancreatic Cancer: The ‘Minute and Miracle’ Molecule Moving as a Monitor in the ‘Genomic Galaxy’

Cyclic-dependent kinase 2 (CDK2) is one of the primary protein kinases involved in the regulation of cell cycle progression. Flavopiridol is a flavonoid derived from an indigenous plant act as a potent antitumor drug showing increased inhibitory activity toward CDK2. The presence of deleterious variations in CDK2 may produce different effects in drug-binding adaptability. Studies on nsSNPs of CDK2 gene will provide information on the most likely variants associated with the disease. Furthermore, investigating the relationship between deleterious variants and its ripple effect in the inhibitory action with drug will provide fundamental information for the development of personalized therapies. In this study, we predicted four variants Y15S, V18L, P45L, and V69A of CDK2 as highly deleterious. Occurrence of these variations seriously affected the normal binding capacity of flavopiridol with CDK2. Analysis of 10-ns molecular dynamics (MD) simulation trajectories indicated that the predicted deleterious variants altered the CDK2 stability, flexibility, and surface area. Notably, we noticed the decrease in number of hydrogen bonds between CDK2 and flavopiridol mutant complexes in the whole dynamic period. Overall, this study explores the possible relationship between the CDK2 deleterious variants and the drug-binding ability with the help of molecular docking and MD approaches. © 2013 Springer Science+Business Media New York.

VIT Unitversity

Cell Biochemistry and Biophysics

Predicting the Impact of Single-Nucleotide Polymorphisms in CDK2–Flavopiridol Complex by Molecular Dynamics Analysis

Gene therapy through antisense technology via intracellular delivery of a gene-silencing element is a promising approach to treat critical diseases like cancers. Ras acts as molecular switch, considered as one of the proto-oncogenes whose modification or mutation may promote tumor formation. The recent trends of nano-carrier-based drug delivery have gained superiority and proved to be 100 times more potent in drug delivery compared to standard therapies. The nano-based drug delivery has provided the basis of achieving successful target-specific drug delivery. Glutathione (GSH) is considered as one of the best and ubiquitous internal stimulus for swift destabilization of nano-transporters inside cells to accomplish proficient intracellular drug release. This concept has given a new hope to oncologists of modifying the existing drugs to be delivered to their desired destination. RNA interference is a primary tool in functional genomics to selectively silence messenger RNA (mRNA) expression, which can be exploited quickly to develop novel drugs against lethal disease target. Silencing of mRNA molecules using siRNA has also come of age to become one of the latest weapons developed in the concept of gene therapy. However, this strategy has severely failed to achieve target specificity especially to a tumor cell. In this context, we have proposed the incorporation of an antisense siRNA packed inside a GSH-responsive nano-transporter to be delivered specifically to a tumor cell against the sense mRNA of the Ras protein. It will limit the Ras-mediated activation of other proteins and transcription factors. Thus, it will knock down several differential gene expressions being regulated by Ras-activated pathways like enzyme-linked receptor kinase pathway. Henceforth, gene silencing technology through nano-drug delivery can be combined as a single weapon to terminate malignancy. © 2012 Springer-Verlag.

Protoplasma

Glutathione-responsive nano-transporter-mediated siRNA delivery: silencing the mRNA expression of Ras

Silent information regulator 2 (Sir2) proteins, or sirtuins, are a family of proteins which influence several physiological responses and have implications for treating diseases of ageing. In this context, we have presented a summarized view on the discovery of Sir2 family proteins, the enzymatic activities, the role of sirtuins in aging, lifespan and onset of age-related symptoms. In addition, we have described the roles of mammalian sirtuins-with particular emphasis on their associations to aging, metabolism, and age related diseases with recent references. Current findings provide an understanding about mammalian sirtuins and their target diseases, small molecules discovery or drug discovery targeting sirtuin to tackle the serious diseases of aging. © 2013 Bentham Science Publishers.

Sirtuins Family- Recent Development as a Drug Target for Aging, Metabolism, and Age Related Diseases

The epimutational event, i.e.; ectopic methylation in tumor suppressor genes, can lead to gene silencing, thus promoting prognosis of cancer. The progression of DNA methylation is a cycle of demethylation, de novo methylation, and maintenance methylation. The enzyme responsible for maintenance of methylation status is DNA methyltransferase 1 (DNMT1), the continuous activity of which is required to maintain the pattern of epimutation; thus, its inhibition is a promising strategy for the treatment of cancer. To the best of our knowledge, this study is the first to focus on the recently developed crystal structure of the catalytic site of DNMT1. Here in this study, we have used the crystal structure for the development of non-nucleoside DNMT1 inhibitors using virtual screening (VS), absorption, distribution, metabolism, elimination/toxicology analysis, and molecular docking studies. In this study, VS was carried out on 48,531 natural products to create a subset of lead-like natural products. Three of them were found to form hydrogen bonds with the catalytic site of the DNMT1 (Cys 1226). Thus, this study adumbrates potential lead compounds for treatment of epimutation. © 2013 Springer Science+Business Media New York.

Applied Biochemistry and Biotechnology

From Natural Products to Drugs for Epimutation Computer-Aided Drug Design

Present study was aimed to screen the effect of phytochemical compounds against various medically important pathogens from Sansevieria roxburghiana and Sansevieria trifasiata majorly known as Indian herb. Sansevierias are the most popular ornamental plants with long rhizomes and fibrous roots possessing traditional healing properties. The acetone and methanol extraction was perfonned by soxhlet apparatus for the leaves of S. roxburghiana and S. trifasiata against bacterial strains. The obtained extracts were further analyzed for antimicrobial effect against Gram Positive as well as Gram negative bacteria and combined effect of extract and antibiotics was also studied. The phytochemical compounds were analyzed through thin layer chromatography and were screened for isolation of bioactive compound.

Department of Bio-Medical Sciences

Asian Journal of Plant Sciences

Screening and Characterization of Antimicrobial Agents from Sanseveria roxburghiana and Sansveria trifasiata

Various missense mutations in the VHL gene have been reported among patients with familial bilateral pheochromocytoma. However, the p.Arg82Leu mutation in the VHL gene described here among patients with familial bilateral pheochromocytoma, has never been reported previously in a germline configuration. Interestingly, long-term follow-up of these patients indicated that the mutation might have had little impact on the normal function of the VHL gene, since all of them have remained asymptomatic. We further attempted to correlate this information with the results obtained by in silico analysis of this mutation using SIFT, PhD-SNP SVM profile, MutPred, PolyPhen2, and SNPs&amp;GO prediction tools. To gain, new mechanistic insight into the structural effect, we mapped the mutation on to 3D structure (PDB ID 1LM8). Further, we analyzed the structural level changes in time scale level with respect to native and mutant protein complexes by using 12 ns molecular dynamics simulation method. Though these methods predict the mutation to have a pathogenic potential, it remains to be seen if these patients will eventually develop symptomatic disease. © 2013 John et al.

Fulltext

PLoS ONE

p.Arg82Leu von Hippel-Lindau (VHL) Gene Mutation among Three Members of a Family with Familial Bilateral Pheochromocytoma in India: Molecular Analysis and In Silico Characterization

The aim of the study was to predict and analyze the molecular interactions between the drug target named γ-hemolysin of <a href="http://www.scialert.net/asci/result.php?searchin=Keywords&amp;cat=&amp;ascicat=ALL&amp;Submit=Search&amp;keyword=Staphylococcus+aureus">Staphylococcus aureus</a> and various flavonoid compounds. Binding affinity for the complexes were calculated based on the free binding energies and the number of interactions. The receptor is a bicomponent, β-barrel pore forming toxin associated with several clinical diseases. The cytolytic and hemolytic activity of the toxin and its involvement in the pathogenesis by damaging the host membranes proved γ-hemolysin to be a valid drug target. The 3D structure of γ-hemolysin downloaded from PDB database (PDB ID: 2QK7) was docked with flavonoid compounds having antimicrobial property. The SMILES of the twenty compounds were obtained from NCBI Pubchem Compound database and downloaded PDB files from Corina tool. Drug-like property and drug-likeness of the compounds were checked by Lipinski’s Rule. Molecular docking was done using Autodock 4.0 resulting in binding energies and the docked complexes were analyzed by PyMol which revealed the binding pattern of <a href="http://www.scialert.net/asci/result.php?searchin=Keywords&amp;cat=&amp;ascicat=ALL&amp;Submit=Search&amp;keyword=amino+acid">amino acid</a>s of the receptor with the ligands. Docking analysis revealed that the residue SER90 play an important role in binding with the ligands. The binding energy values of the docked complexes ranged between -6.49 to -5.02 kcal moL-1. A more negative binding energy was found with Ponciretin compound with -6.49 kcal moL-1. The lower energy indicated that the compound was in stable conformation and had higher affinity towards the receptor. Thus, Ponciretin compound would be a possible drug compound for inhibiting the cytotoxic and hemolytic activity of the toxin.

Mechanical

School of Mechanical Engineering

Chennai Campus

Trends in Bioinformatics

In silico Molecular Interaction Studies of Gamma-hemolysin of Staphylococcus aureus with Flavonoid Compounds

Signal transducer and activators of transcription (STAT) gene, suppressors of cytokine signaling (SOCS) has been isolated from kuruma shrimp, Marsupenaeus japonicus and characterized. The kuruma shrimp STAT (MjSTAT) cDNA was composed of 2901 bp consisting of 801 amino acid residues which includes a protein interaction domain, all alpha domain, DNA binding domain and SH2 domain. Homology analysis of MjSTAT showed 94.1% and 34.0% identities with Penaeus monodon STAT (PmSTAT) and Drosophila melanogaster STAT92E (DmSTAT), respectively. The kuruma shrimp SOCS (MjSOCS) cDNA was composed of 1675 bp consisting of 342 amino acid residues including a SH2 domain and C-terminal SOCS domain. Homology analysis of MjSOCS showed 52.6% and 21.3% identities with Chinese mitten crab (Eriocheir sinensis) SOCS2 and fruit fly (D. melanogaster) SOCS44A, respectively. The MjSTAT and MjSOCS genes are constitutively expressed in the muscle, stomach, brain and gill of kuruma shrimp. In lymphoid organ cells, an enhanced expression of both MjSTAT and MjSOCS genes are observed following stimulation with peptidoglycan and polycytidylic acid. These observations suggest that MjSTAT and MjSOCS might play a major role in the innate immune defense of kuruma shrimp. The discovery of JAK/STAT signaling pathway in shrimp will allow a complete and concrete understanding of shrimp cytokine signaling. © 2012 Elsevier Ltd.