Chhatrapati Shahu Ji Maharaj University

Kānpur, India

Chhatrapati Shahu Ji Maharaj University

Kānpur, India
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Singh D.B.,Chhatrapati Shahu Ji Maharaj University | Gupta M.K.,University Institute of Engineering and Technology | Kesharwani R.K.,Indian Institute of Information Technology Allahabad | Sagar M.,University Institute of Engineering and Technology | And 2 more authors.
Translational Neuroscience | Year: 2014

Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by normal memory loss and cognitive impairment in humans. Many drug targets and disease-modulating therapies are available for treatment of AD, but none of these are effective enough in reducing problems associated with recognition and memory. Potential drug targets so far reported for AD are β-secretase, Γ-secretase, amyloid beta (Aβ) and Aβ fibrils, glycogen synthase kinase-3 (GSK-3), acyl-coenzyme A: cholesterol acyl-transferase (ACAT) and acetylcholinesterase (AChE). Herbal remedies (antioxidants) and natural metal-chelators have shown a very significant role in reducing the risk of AD, as well as lowering the effect of Aβ in AD patients. Researchers are working in the direction of antisense and stem cell-based therapies for a cure for AD, which mainly depends on the clearance of misfolded protein deposits - including Aβ, tau, and alpha-synuclein. Computational approaches for inhibitor designing, interaction analysis, principal descriptors and an absorption, distribution, metabolism, excretion and toxicity (ADMET) study could speed up the process of drug development with higher efficacy and less chance of failure. This paper reviews the known drugs, drug targets, and existing and future therapies for the treatment of AD. © 2014 Versita and Springer-Verlag.

Singh D.B.,Chhatrapati Shahu Ji Maharaj University | Singh D.B.,Gautam Buddha University | Dwivedi S.,Gautam Buddha University
Journal of Chemical Biology | Year: 2016

S-adenosyl-L-homocysteine hydrolase of Plasmodium falciparum (PfSAHH) is a potential drug target against malaria, and selective inhibition of PfSAHH is the excellent strategy to prevent the growth of parasite inside the host. Therefore, a comparative analysis of human S-adenosyl-L-homocysteine hydrolase (HsSAHH) and PfSAHH has been performed to explore the structural differences. Structural superimposition of PfSAHH and HsSAHH has generated the RMSD of 0.749 Å over 394 alpha carbon pairs. Residues of PfSAHH from position Tyr152 to Lys193 aligned with insertion/deletion region in HsSAHH, and these extra residues results in an extent of variation in cavity region of PfSAHH. Nicotinamide adenine dinucleotide (NAD) was observed to form hydrogen bonding with Thr201, Thr202, Thr203, Asn235, Val268, Glu287, Asn322, Ile343, Asn391, Lys473, and Tyr477 and also forms hydrophobic interactions with Val268, Ile288, and Thr320 of PfSAHH. In comparison to HsSAHH, Asn322, Lys473, and Tyr477 residues of PfSAHH are unique in interaction with NAD. 2-Fluoroaristeromycin and other analogues of aristeromycin have shown the good binding affinity for both enzymes. Structural differences between PfSAHH and HsSAHH might be employed to design the potential inhibitor of PfSAHH. To find the target enzyme responsible for an anti-malarial effect, molecular docking and interaction analysis of curcumin were performed with 34 drug targets of P. falciparum. Curcumin shows high affinity for binding with HGPRT of PfHGPRT, and an anti-malarial effect of curcumin might be due to binding with PfHGPRT. © 2016 Springer-Verlag Berlin Heidelberg

Naraian R.,Purvanchal University | Ram S.,Gautam Buddha University | Kaistha S.D.,Chhatrapati Shahu Ji Maharaj University | Srivastava J.,Global Group of Institutions
Cellular and Molecular Biology | Year: 2012

Effluents of three different tanneries (T-1, T-2, & T-3) were investigated to isolate and scrutinize antibiotic, chromate and salinity resistant bacteria. Total 18 isolates of 9 different bacterial genera were screened out and identified; some strains established in all effluents. Amongst the three effluents tested; T-1 exhibited largest population of all isolates compared to T-2 and T-3 effluents. The T-1 effluent contained largest 4.4 ×106 cfu/ml population of Pseudomonas aeruginosa followed by 3.9 ×106 cfu/ml in T-2 effluent. The lowest 0.7 ×106 cfu/ml count of Aeromonas spp. was recorded in T-3 effluent. Furthermore, antibiotic susceptibility tests were performed with 7 antibiotics which include ampicillin, sulfafurazole, ciprofloxacin, norfloxacin, tetracycline and amikacin. Three strains of P. aeruginosa and one strain of Escherichia coli deserved as multiple drug resistant (MDR). The P. aeruginosaT-3 and E. coliT-1 showed strongest MDR feature for 5 antibiotics. The response of chromate (50, 100, 200, 250 and 300 μg/ml) and NaCl concentrations (20, 40, 60 and 80 g/l) was incredible for 4 MDR isolates. Nearly each strain showed tolerance up to 300 μg/ml of chromate and 80 g/l of NaCl. The P. aeruginosaT-1, P. aeruginosaT-2, P. aeruginosaT-3 and E. coliT-1 were most tolerant isolates. Plasmid profiling of resistant strains was conducted with agarose gel electrophoresis. As consequence, plasmids from two strains of P. aeruginosa and E. coliT-1 represented different bands. At least for confirmation of plasmids nature; these were transformed and transformants were screened on medium having antibiotics. The study of plasmid transformation has confirmed the plasmid mediated resistance in isolates. © 2012.

Gupta P.C.,Chhatrapati Shahu Ji Maharaj University | Rao C.V.,National Botanical Research Institute
Pharmaceutical Biology | Year: 2014

Context: The leaf of Careya arborea Roxb. (Lecthidaceae) has been advocated in Ayurveda for the treatment of various disorders, including ulcers, healing of wounds and several skin diseases. Objective: The 70% ethanol (EtOH) extract of C. arborea leaves (CALE) was investigated for its gastroprotective effect in different gastric ulcer models. Materials and methods: CALE (100, 200, and 400mg/kg body weight) was administered orally, twice daily for 5d, for preventing aspirin (ASP)-, EtOH-, pylorus ligation (PL)-, and cold restraint stress (CRS)-induced ulcer in rats. The status of the antioxidant enzymes in CRS-induced ulcers, H+K+ATPase activity, gastric wall mucous in EtOH-induced ulcer, and gastric secretion parameters were estimated in the PL-induced ulcer model. Results: CALE exhibited significant (p<0.01) dose-dependent inhibition of ulcer index in ASP 12.90-51.61%, EtOH 11.97-40.35%, PL 28.63-63.92%, and CRS 38.30-66.37%, respectively. A significant (p<0.001) decrease occurred in the level of H+K+ATPase, volume of gastric juice, and acid output. Simultaneously, the level of gastric wall mucus was increased significantly (p<0.05). The antioxidant enzyme levels of LPO and SOD were decreased with concomitant increase in catalase activity in CRS-induced ulcers. High-performance thin-layer chromatography (HPTLC) showed the presence of quercetin, ellagic acid, and gallic acid (0.31%, 0.24%, and 0.71% w/w, respectively) in CALE. Conclusions: Our results show that C. arborea possesses significant gastro-protective activity, probably due to its free radical scavenging activity, and validate the folklore claim. © 2014 Informa Healthcare USA, Inc.

Mishra R.,Chhatrapati Shahu Ji Maharaj University | Singh A.,Chhatrapati Shahu Ji Maharaj University | Chandra V.,Chhatrapati Shahu Ji Maharaj University | Negi M.P.S.,Central Drug Research Institute | And 3 more authors.
Rheumatology International | Year: 2012

Progression of Rheumatoid arthritis (RA) and osteoarthritis (OA) is associated with inflammation and oxidative stress. Previous studies have shown that there was no difference between RA and OA patients regarding the percentages of the different lymphocytes subsets reflecting the abnormalities in T cells and its subsets that may contribute to the pathogenesis of OA as in RA. Therefore, the present study was aimed to analyze that whether disease activity of OA is able to affect a few serological and biochemical parameters in the same way as RA does or differently. The study was done on 36 asymptomatic controls (25 women), 28 patients with OA (20 women), 36 patients with RA (22 women). Patients with OA were screened according to radiological and clinical finding of Kellgren and Lawrence grade and ACR criteria and assessed by VAS and WOMAC score. Patients with RA were selected who were fulfilling 4/5 symptoms of ACR criteria, and their DAS28-CRP, VAS score, and RF positivity were evaluated. Participants of the groups were matched for sex, age, weight, and height (body mass index). The BMI of all three groups was also found to be the same (P > 0.05). The mean level of LDL, Cholesterol, MDA, CRP, and Triglyceride was significantly (P < 0.05 or P < 0.01) higher in both OA and RA as compared to control. The mean level of total lipid, cholesterol, MDA, CRP, and triglyceride was found to be significantly (P < 0.05 or P < 0.01) higher in RA as compared to OA. The pre-treatment CRP level of both groups of patients showed significant and direct relation with total lipid (r = 0.27, P < 0.05) and cholesterol (r = 0.66, P < 0.01). Inverse relation was observed between Uric acid and Creatinine (r = -0.26, P < 0.05) and cholesterol and HDL (r = -0.34, P < 0.01). Our study shows the similar trend in lipid profile and other parameters studied in both patients with OA and patients with RA with more pronounced changes in RA. © Springer-Verlag 2011.

Gupta M.K.,University Institute of Engineering and Technology | Singh D.B.,Chhatrapati Shahu Ji Maharaj University | Shukla R.,University Institute of Engineering and Technology | Misra K.,Sanjay Gandhi Post Graduate Institute of Medical Sciences
OMICS A Journal of Integrative Biology | Year: 2013

The thyroid pathway represents a complex interaction of different glands for thyroid hormone synthesis. Thyrotropin releasing hormone is synthesized in the hypothalamus and regulates thyrotropin stimulating hormone gene expression in the pituitary gland. In order to understand the complexity of the thyroid pathways, and using experimental data retrieved from the biomedical literature (e.g., NCBI, HuGE Navigator, Protein Data Bank, and KEGG), we constructed a metabolic map of the thyroid hormone pathway at a molecular level and analyzed it topologically. A total of five hub nodes were predicted in regards to the transcription thyroid receptor (TR), cAMP response element-binding protein (CREB), signal transducer and activator of transcription 3 (STAT 3), nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), and activator protein 1 (AP-1) as being potentially important in study of thyroid disorders and as novel putative therapeutic drug targets. Notably, the thyroid receptor is a highly connected hub node and currently used as a therapeutic target in hypothyroidism. Our analysis represents the first comprehensive description of the thyroid pathway, which pertains to understanding the function of the protein and gene interaction networks. The findings from this study are therefore informative for pathophysiology and rational therapeutics of thyroid disorders. © Mary Ann Liebert, Inc.

Singh D.B.,Chhatrapati Shahu Ji Maharaj University | Gupta M.K.,University Institute of Engineering and Technology | Singh D.V.,University Institute of Engineering and Technology | Singh S.K.,Center for Cellular and Molecular Biology | Misra K.,Indian Institute of Information Technology Allahabad
Interdisciplinary Sciences: Computational Life Sciences | Year: 2013

The Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase (pfSAHH) enzyme has been considered as a potential chemotherapeutic target against malaria due to the amino acid differences found on binding sites of pfSAHH related to human SAHH. It has been reported that noraristeromycin and some curcumin derivatives have potential binding with the largest cavity of pfSAHH, which is also related to the binding with Nicotinamide-Adenine-Dinucleotide (NAD) and Adenosine (ADN). Our present work focuses on docking and ADMET studies to select potential inhibitors of pfSAHH. The binding of the selected inhibitor of the PfSAHH active site was analyzed using Molegro Virtual Docker. In this study, curcumin and its derivatives have been found to have higher binding affinity with pfSAHH than noraristeromycin. Seven amino acid residues Leu53, His54, Thr56, Lys230, Gly397, His398 and Phe407 of pfSAHH involved in binding with curcumin, are the same as those for noraristeromycin, which reveals that curcumin and noraristeromycin bind in the same region of pfSAHH. Curcumin has shown a strong interaction with hydrophobic amino acid residues of pfSAHH. Molecular Docking and ADMET predictions suggest that curcumin can be a potent inhibitor of pfSAHH with ability to modulate the target in comparatively smaller dose. Therefore, curcumin is likely to become a good lead molecule for the development of effective drug against malaria. © 2013 International Association of Scientists in the Interdisciplinary Areas and Springer-Verlag Berlin Heidelberg.

Khare E.,Chhatrapati Shahu Ji Maharaj University | Arora N.K.,Babasaheb Bhimrao Ambedkar University
Canadian Journal of Microbiology | Year: 2011

The purified pyocyanin from Pseudomonas aeruginosa TO3 was investigated for its antagonistic activity against Macrophomina phaseolina and as a signaling molecule for development of biofilm by rhizobial strain Ca2. The antagonistic activity of purified pyocyanin, as determined by a dry mass method, showed inhibition of M. phaseolina. Biofilm formation by strain Ca2 was performed by crystal violet assay. There was an increase in biofilm development by Ca2 with an increase in pyocyanin concentration up to 0.12 nmol·L -1, followed by a reduction. Using a well-diffusion method, we determined the effect of pyocyanin on disease suppression and biofilm formation by strain Ca2 on radicles of groundnut (Arachis hypogaea L.) placed in three concentric whorls on water agar plates. Pyocyanin suppressed disease better at high concentration; however, at lower concentrations increased colony-forming units of Ca2 on radicles of seedlings was observed. A field study in soil infested with M. phaseolina showed that a coinoculant of P. aeruginosa TO3 and rhizobial strain Ca2 enhanced nodule mass and nitrogenase activity by 264.38% and 269.06%, respectively, over that of the control. This study reports that application of pyocyanin-producing pseudomonads together with rhizobia contributes to the enhancement of nodulation ability and better sustains the growth and productivity of groundnut even in the presence of M. phaseolina.

Gaur R.,National Institute of Plant Genome Research | Sethy N.K.,National Institute of Plant Genome Research | Sethy N.K.,Defence Institute of Physiology and Allied science DIPAS | Choudhary S.,National Institute of Plant Genome Research | And 4 more authors.
BMC Genomics | Year: 2011

Background: Chickpea (Cicer arietinum L.) is an economically important cool season grain legume crop that is valued for its nutritive seeds having high protein content. However, several biotic and abiotic stresses and the low genetic variability in the chickpea genome have continuously hindered the chickpea molecular breeding programs. STMS (Sequence Tagged Microsatellite Sites) markers which are preferred for the construction of saturated linkage maps in several crop species, have also emerged as the most efficient and reliable source for detecting allelic diversity in chickpea. However, the number of STMS markers reported in chickpea is still limited and moreover exhibit low rates of both inter and intraspecific polymorphism, thereby limiting the positions of the SSR markers especially on the intraspecific linkage maps of chickpea. Hence, this study was undertaken with the aim of developing additional STMS markers and utilizing them for advancing the genetic linkage map of chickpea which would have applications in QTL identification, MAS and for de novo assembly of high throughput whole genome sequence data.Results: A microsatellite enriched library of chickpea (enriched for (GT/CA)nand (GA/CT)nrepeats) was constructed from which 387 putative microsatellite containing clones were identified. From these, 254 STMS primers were designed of which 181 were developed as functional markers. An intraspecific mapping population of chickpea, [ICCV-2 (single podded) × JG-62 (double podded)] and comprising of 126 RILs, was genotyped for mapping. Of the 522 chickpea STMS markers (including the double-podding trait, screened for parental polymorphism, 226 (43.3%) were polymorphic in the parents and were used to genotype the RILs. At a LOD score of 3.5, eight linkage groups defining the position of 138 markers were obtained that spanned 630.9 cM with an average marker density of 4.57 cM. Further, based on the common loci present between the current map and the previously published chickpea intraspecific map, integration of maps was performed which revealed improvement of marker density and saturation of the region in the vicinity of sfl (double-podding) gene thereby bringing about an advancement of the current map.Conclusion: An arsenal of 181 new chickpea STMS markers was reported. The developed intraspecific linkage map defined map positions of 138 markers which included 101 new locations.Map integration with a previously published map was carried out which revealed an advanced map with improved density. This study is a major contribution towards providing advanced genomic resources which will facilitate chickpea geneticists and molecular breeders in developing superior genotypes with improved traits. © 2011 Gaur et al; licensee BioMed Central Ltd.

Yadav R.,Chhatrapati Shahu Ji Maharaj University | Jee B.,Chhatrapati Shahu Ji Maharaj University | Jee B.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Awasthi S.K.,Chhatrapati Shahu Ji Maharaj University
Indian Journal of Clinical Biochemistry | Year: 2015

Curcumin is a major bioactive compound of turmeric that exerts its anti-inflammatory effects by suppressing the many pro-inflammatory cytokines and chemokines in a number of cell types and pathologic conditions. Interleukin-18 (IL-18) is a novel pro-inflammatory cytokine which plays an important role not only in generating Th1 responses but also in inducing severe inflammatory reactions. As curcumin induced inhibition of IL-18 production in keratinocytes and mice is well known, effect of curcumin on IL-18 release in macrophages remains unknown. Hence, this present study has been designed to evaluate the effect of curcumin on IL-18 production and necrotic cell death in murine macrophages-like cells treated with or without lipopolysaccharide (LPS). The IL-18 secretion in cell culture supernatants was assayed by enzyme-linked immunosorbent assay and cytotoxicity was determined by lactate dehydrogenase release assay. Our results demonstrate that curcumin significantly inhibited the production of pro-inflammatory cytokine IL-18 in E.coli LPS stimulated murine macrophage-like cells RAW264.7 in a concentration-dependent manner. Interestingly, curcumin had no cytotoxic effect on murine macrophage-like cells. Our findings suggest that curcumin may be used as a potential therapeutic agent for the treatment of inflammatory diseases. © 2014, Association of Clinical Biochemists of India.

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