Novel Insights into the Molecular Interaction of a Panduratin A Derivative with the Non Structural Protein (NS3) of Dengue Serotypes: A Molecular Dynamics Study.

Background: The ligand PKP10 having substitution of Cl- at R2 and R3 positions of ring A of Panduratin A i.e., ((1R,2S,5S)-5-(2,3-dichlorophenyl)-3-methyl-2-(3-methylbut-2-nyl)cyclohex-3- enyl)(2,6-dihydroxy-4-methylphenyl)methanone hydrate) has been observed to block the Nuclear Receptor Binding Protein binding site of Non Structural protein 3 in all dengue serotypes.

Promoter Hypermethylation of the ATM Gene as a Novel Biomarker for Breast Cancer.

Background: Breast cancer may be induced by activation of protooncogenes to oncogenes and in many cases inactivation of tumor suppressor genes. Ataxia telangiectasia mutated (ATM) is an important tumor suppressor gene which plays central roles in the maintenance of genomic integrity by activating cell cycle checkpoints and promoting repair of double-strand breaks of DNA. In breast cancer, decrease ATM expression correlates with a poor outcome; however, the molecular mechanisms underlying downregulation are still unclear.

Identification of symbionts in .

: Insect symbionts have the potential to block the transmission of vector-borne diseases by their hosts. The advancement of a symbiont-based transmission blocking strategy for malaria requires the identification and study of symbionts. : High throughput 16S amplicon sequencing was used to profile the bacteria associated with and identify potential symbionts.

Target-similarity search using Plasmodium falciparum proteome identifies approved drugs with anti-malarial activity and their possible targets.

Malaria causes about half a million deaths annually, with Plasmodium falciparum being responsible for 90% of all the cases. Recent reports on artemisinin resistance in Southeast Asia warrant urgent discovery of novel drugs for the treatment of malaria. However, most bioactive compounds fail to progress to treatments due to safety concerns.

Temporal genetic differentiation in Glossina pallidipes tsetse fly populations in Kenya.

Background: Glossina pallidipes is a major vector of both Human and Animal African Trypanosomiasis (HAT and AAT) in Kenya. The disease imposes economic burden on endemic regions in Kenya, including south-western Kenya, which has undergone intense but unsuccessful tsetse fly control measures. We genotyped 387 G.

Bone mineral density and risk of type 2 diabetes and coronary heart disease: A Mendelian randomization study.

Observational studies have demonstrated that increased bone mineral density is associated with a higher risk of type 2 diabetes (T2D), but the relationship with risk of coronary heart disease (CHD) is less clear. Moreover, substantial uncertainty remains about the causal relevance of increased bone mineral density for T2D and CHD, which can be assessed by Mendelian randomisation studies.  We identified 235 independent single nucleotide polymorphisms (SNPs) associated at <5×10 with estimated heel bone mineral density (eBMD) in 116,501 individuals from the UK Biobank study, accounting for 13.

Biogenic synthesis of palladium nanoparticles and their applications as catalyst and antimicrobial agent.

This paper describes a simple in-situ process of synthesizing highly dispersed palladium nanoparticles (PdNPs) using aqueous leaf extract of GarciniapedunculataRoxb as bio-reductant and starch (0.3%) as bio-stabilizer. The PdNPs are characterized by techniques like FTIR, TEM, SEM-EDX, XRD and XPS analysis.

Antioxidant and glucose metabolizing potential of edible insect, Brachytrupes orientalis via modulating Nrf2/AMPK/GLUT4 signaling pathway.

Brachytrupes orientalis (Gryllidae) is a common edible insect species eaten by the different tribes of North East India. This study investigated the potentiality of Brachytrupes orientalis extracts in different solvent hydro-alcoholic (AEBO), hexane (HEBO) and ethyl acetate (EEBO) on glucose utilization and cell viability in high glucose (HG) treated myotubes. It has been observed that AEBO supplementation significantly increased the glucose utilization against HG exposure; however, treatment HEBO and EEBO have no significant effect.

-alpha -308G/A and -238G/A polymorphisms and its protein network associated with type 2 diabetes mellitus.

Several reports document the role of tumor necrosis factor alpha () and lipid metabolism in the context of acute inflammation as a causative factor in obesity-associated insulin resistance and as one of the causative parameter of type 2 diabetes mellitus (T2DM). Our aim was to investigate the association between -308G/A and -238G/A polymorphisms located in the promoter region of the gene in T2DM in the Indian population with bioinformatics analysis of TNF-α protein networking with an aim to find new target sites for the treatment of T2DM. Demographics of 100 diabetes patients and 100 healthy volunteers were collected in a structured proforma and 3 ml blood samples were obtained from the study group, after approval of Institutional Ethics Committee of the hospital (IEC).

Evaluation of Antioxidant and Hepatoprotective Activity of Fruit Rind Extract of (Roxburgh) Kurz.

Background: Garcinia spp. belongs to the family has been traditionally used for the treatment of many ailments including the liver damage. found in North Eastern region of Assam; India can be a potential candidature to combat different ailments.

Synthesis and biological evaluation of novel 1,2,3-triazole derivatives as anti-tubercular agents.

A library of seventeen novel 1,2,3-triazole derivatives were efficiently synthesized in excellent yields by the popular 'click chemistry' approach and evaluated in vitro for their anti-tubercular activity against Mycobacterium tuberculosis H37Ra (ATCC 25177 strain). Among the series, six compounds exhibited significant activity with minimum inhibitory concentration (MIC) values ranging from 3.12 to 0.

Identification of novel human renin inhibitors through a combined approach of pharmacophore modelling, molecular DFT analysis and in silico screening.

Renin is an aspartyl protease of the renin-angiotensin system (RAS) and the first enzyme of the biochemical pathway for the generation of angiotensin II - a potent vasoconstrictor involved in the maintenance of cardiovascular homeostasis and the regulation of blood pressure. High enzymatic specificity of renin and its involvement in the catalysis of the rate-limiting step of the RAS hormone system qualify it as a good target for inhibition of hypertension and other associated diseases. Ligand-based pharmacophore model (Hypo1) was generated from a training set of 24 compounds with renin inhibitory activity.

The Global Ethics Corner: foundations, beliefs, and the teaching of biomedical and scientific ethics around the world.

The profound advances in the biomolecular sciences over the last decades have enabled similar advances in biomedicine. These advances have increasingly challenged our abilities to deploy them in an equitable and ethically acceptable manner. As such, it has become necessary and important to teach biomedical and scientific ethics to our students who will become the researchers, medical professionals, and global citizens of the future.

In vitro antibacterial activity of MGDG-palmitoyl from Oscillatoria acuminata NTAPC05 against extended-spectrum β-lactamase producers.

Extended-spectrum β-lactamase (ESBL)-producing bacteria pose a big challenge in clinical practices, warranting a new therapeutic strategy. In this study, methanol extract of the marine cyanobacterium Oscillatoria acuminata NTAPC05 was fractionated under bioassay guidance and the fractions were tested against three well-characterized ESBL-producing bacteria Escherichia coli U655, Stenotrophomonas maltophilia B929 and Enterobacter asburiae B938. Out of the four HPLC fractions, fraction 2 showed bactericidal activity against all the three ESBL producers much more efficiently (MIC 100 μg ml) than the fourth-generation cephalosporin (MIC >125 μg ml).

Potential biomarkers associated with discrimination between latent and active pulmonary tuberculosis.

Setting: A third of the world's population has latent tuberculous infection (LTBI). Current TB diagnostics used in developing countries are ineffective and are unable to distinguish LTBI from active TB. Identifying biomarkers that could aid in the early detection of TB and in distinguishing TB states could be a major breakthrough in global TB control.

Implications from predicted B-cell and T-cell epitopes of Plasmodium falciparum merozoite proteins EBA175-RII and Rh5.

The leading circumsporozoite protein (CSP) based malaria vaccine, RTS,S, though promising, has shown limited efficacy in field studies. There is therefore, still a need to identify other malaria vaccine targets. Merozoite antigens are potential vaccine candidates, since naturally acquired antibodies generated against them inhibit erythrocyte invasion and in some cases result in the clinical protection from disease.

Network pharmacology-based virtual screening of natural products from Clerodendrum species for identification of novel anti-cancer therapeutics.

Plant-derived natural products (NPs) play a vital role in the discovery of new drug molecules and these are used for development of novel therapeutic drugs for a specific disease target. Literature review suggests that natural products possess strong inhibitory efficacy against various types of cancer cells. Clerodendrum indicum and Clerodendrum serratum are reported to have anticancer activity; therefore a study was carried out to identify selective anticancer agents from these plants species.

Novel butyrylcholinesterase inhibitors through pharmacophore modeling, virtual screening and DFT-based approaches along-with design of bioisosterism-based analogues.

Ligand and structure-based pharmacophore models were used to identify the important chemical features of butyrylcholinesterase (BChE) inhibitors. A training set of 16 known structurally diverse compounds with a wide range of inhibitory activity against BChE was used to develop a quantitative ligand-based pharmacophore (Hypo1) model to identify novel BChE inhibitors in virtual screening databases. A structure-based pharmacophore hypothesis (Phar1) was also developed with the ligand-binding site of BChE in consideration.

3D pharmacophore-based virtual screening, docking and density functional theory approach towards the discovery of novel human epidermal growth factor receptor-2 (HER2) inhibitors.

Human epidermal growth factor receptor 2 (HER2) is one of the four members of the epidermal growth factor receptor (EGFR) family and is expressed to facilitate cellular proliferation across various tissue types. Therapies targeting HER2, which is a transmembrane glycoprotein with tyrosine kinase activity, offer promising prospects especially in breast and gastric/gastroesophageal cancer patients. Persistence of both primary and acquired resistance to various routine drugs/antibodies is a disappointing outcome in the treatment of many HER2 positive cancer patients and is a challenge that requires formulation of new and improved strategies to overcome the same.

Prevalence and Identification of Burkholderia pseudomallei and Near-Neighbor Species in the Malabar Coastal Region of India.

Accurate identification of pathogens with biowarfare importance requires detection tools that specifically differentiate them from near-neighbor species. Burkholderia pseudomallei, the causative agent of a fatal disease melioidosis, is one such biothreat agent whose differentiation from its near-neighbor species is always a challenge. This is because of its phenotypic similarity with other Burkholderia species which have a wide spread geographical distribution with shared environmental niches.

Role of collectins and complement protein C1q in pregnancy and parturition.

Collectins such as surfactant proteins SP-A, SP-D, and mannan-binding lectin (MBL), as well as complement protein C1q are evolutionarily conserved innate immune molecules. They are known to opsonize a range of microbial pathogens (bacteria, fungi, virus, and parasites) and trigger effector clearance mechanisms involving phagocytosis and/or complement activation. Collectins and C1q have also attracted attention in studies involving pregnancy as they are expressed in the female reproductive tissues during pregnancy; a unique state of immune suppression with increased susceptibility to infectious diseases.

An efficient approach to BAC based assembly of complex genomes.

Background: There has been an exponential growth in the number of genome sequencing projects since the introduction of next generation DNA sequencing technologies. Genome projects have increasingly involved assembly of whole genome data which produces inferior assemblies compared to traditional Sanger sequencing of genomic fragments cloned into bacterial artificial chromosomes (BACs). While whole genome shotgun sequencing using next generation sequencing (NGS) is relatively fast and inexpensive, this method is extremely challenging for highly complex genomes, where polyploidy or high repeat content confounds accurate assembly, or where a highly accurate 'gold' reference is required.

Association of The Common CYP1A1*2C Variant (Ile462Val Polymorphism) with Chronic Myeloid Leukemia (CML) in Patients Undergoing Imatinib Therapy.

Objective: Cytochrome P450 is one of the major drug metabolizing enzyme families and its role in metabolism of cancer drugs cannot be less emphasized. The association be- tween single nucleotide polymorphisms (SNPs) in CYP1A1 and pathogenesis of chronic myeloid leukemia (CML) has been investigated in several studies, but the results observed vary based on varied risk factors. The objective of this study was to investigate the risk factors associated with the CYP1A1*2C [rs1048943: A>G] polymorphism in CML patients and its role in therapeutic response to imatinib mesylate (IM) affecting clinico-pathological parameters, in the Indian population.

Expression of surfactant proteins SP-A and SP-D in murine decidua and immunomodulatory effects on decidual macrophages.

Surfactant proteins SP-A and SP-D are pattern recognition innate immune molecules that belong to the C-type lectin family. In lungs, they play an important role in the clearance of pathogens and control of inflammation. SP-A and SP-D are also expressed in the female reproductive tract where they play an important role in pregnancy and parturition.

Proteomics Approach to Identify Biomarkers in Neurodegenerative Diseases.

This chapter examines the use of proteomics in understanding pathogenesis and identifying possible biomarkers in a range of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and prion diseases. We have attempted to look at the neuroproteomic approach from a biomarker discovery point of view. Novel biomarkers can pave the way for new therapeutic targets and lead us to a better understanding of the pathogenesis involved in the neurodegenerative diseases.