School Of Basic And Applied Sciences

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    Role of immune system in tumor progression and carcinogenesis
    (Wiley-Liss Inc., 2018) Upadhyay, S.; Sharma, N.; Gupta, K.B.; Dhiman, M.
    Tumor micro-environment has potential to customize the behavior of the immune cell according to their need. In immune-eliminating phase, immune cells eliminate transformed cells but after tumor establishment innate and adaptive immune cells synergistically provide shelter as well as fulfill their requirement that helps in progression. In between eliminating and establishment phase, equilibrium and escaping phase regulate the immune cells response. During immune-escaping, (1) the antigenic response generated is either inadequate, or focused entirely on tolerance, and (2) immune response generated is specific and effective, but the tumor skips immune recognition. In this review, we are discussing the critical role of immune cells and their cytokines before and after the establishment of tumor which might play a critical role during immunotherapy. ? 2018 Wiley Periodicals, Inc.
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    Recent trends in anticancer drug development: Challenges and opportunities
    (Bentham Science Publishers B.V., 2017) Skvortsova, Ira-Ida; Kumar, Vinod
    [No abstract available]
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    In silico study of flavonoids as DPP-4 and α-glucosidase inhibitors
    (Bentham Science Publishers B.V., 2018) Kaur, J.; Singla, Ramit; Jaitak, Vikas
    Background: Diabetes being among the most prevalent disease is being studied widely to achieve most potent drug with lesser side-effects. Numerous targets have been explored and several drugs have been developed to combat type-2 diabetes. Worldwide scenario depicts an increase in the number of diabetics at an alarming rate. Due to this critical need in the current scenario, the focus has been shifted to natural products. Amongst which flavonoids have been extensively studied for their anti-diabetic potential. Among various targets inhibition of DPP-4, ?-glucosidase arose as an advantageous methodology for the management of type-2 diabetes. DPP-4 inhibitor helps to maintain the insulin levels in the body and ?-glucosidase inhibitor aids in the control of the postprandial glycemia. Methods: In the present study, the molecular modeling of 155 flavonoids has been performed using GLIDE against Dipeptidyl Peptidase-4 (DPP-4) (PDB ID:2ONC) and ?-glucosidase (PDB ID: 2QMJ) so as to achieve lead compounds that can be further used to develop a new drug. Results: Rutin and Theaflavin-3,3'-di-O-gallate were observed to possess the best docking score for ?-glucosidase and DPP-4 respectively. Conclusions: The top scoring flavonoids show promising results, but further studies are required to be carried out including the pharmacophore mapping, SAR and QSAR studies. The results illustrated that the hydrogen bonding plays a crucial role in the binding and positioning of the molecules into the active site. Further, the rescoring of the docking values mentioned as MMGB/SA also reconfirmed that these compounds show favorable results. ? 2018 Bentham Science Publishers.
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    Genome-wide association study of 25(OH) Vitamin D concentrations in Punjabi Sikhs: Results of the Asian Indian diabetic heart study
    (Elsevier Ltd, 2016) Sapkota, B.R.; Hopkins, R.; Bjonnes, A.; Ralhan, S.; Wander, G.S.; Mehra, N.K.; Singh, J.R.; Blackett, P.R.; Saxena, R.; Sanghera, D.K.
    Vitamin D deficiency is implicated in multiple disease conditions and accumulating evidence supports that the variation in serum vitamin D (25(OH)D) levels, including deficiency, is under strong genetic control. However, the underlying genetic mechanism associated with vitamin 25(OH)D concentrations is poorly understood. We earlier reported a very high prevalence of vitamin D deficiency associated with an increased risk for type 2 diabetes and obesity in a Punjabi Sikh diabetic cohort as part of the Asian Indian diabetic heart study (AIDHS). Here we have performed the first genome-wide association study (GWAS) of serum 25(OH)D on 3538 individuals from this Punjabi Sikh population. Our discovery GWAS comprised of 1387 subjects followed by validation of 24 putative SNPs (P < 10-4) using an independent replication sample (n = 2151) from the same population by direct genotyping. A novel locus at chromosome 20p11.21 represented by rs2207173 with minor allele frequency (MAF) 0.29, [? = -0.13, p = 4.47 ? 10-9] between FOXA2 and SSTR4 was identified to be associated with 25(OH)D levels. Another suggestive association signal at rs11586313 (MAF 0.54) [? = 0.90; p = 1.36 ? 10-6] was found within the regulatory region of the IVL gene on chromosome 1q21.3. Additionally, our study replicated 3 of 5 known GWAS genes associated with 25(OH)D concentrations including GC (p = 0.007) and CYP2R1 (p = 0.019) reported in Europeans and the DAB1 (p = 0.003), reported in Hispanics. Identification of novel association signals in biologically plausible regions with 25(OH)D metabolism will provide new molecular insights on genetic drivers of vitamin D status and its implications in health disparities. ? 2015 Elsevier Ltd. All rights reserved.
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    Chemical composition and antiproliferative, antioxidant, and proapoptotic effects of fruiting body extracts of the lingzhi or reishi medicinal mushroom, ganoderma lucidum (Agaricomycetes), from India
    (Begell House Inc., 2016) Gill, B.S.; Sharma, P.; Navgeet, Kumar, S.
    Ganoderma lucidum is a renowned medicinal mushroom exploited as a panacea because of the broad spectrum of its bioactivities, which give it invaluable nutritional and clinical implications. This research was implemented with an incentive to explore and quantify various macromolecules encompassed in the oriental fungus; these vary in concentration with respect to the development/growth phase, host plants, and geographic location of collection. Chemical profiling of G. lucidum confirmed the presence of myco-constituents, their amounts varying in response to extreme climatic conditions. G. lucidum extract exhibited elevated levels of all myco-constituents but flavonoids, which were more pronounced when in a parasitic relationship with their host plants. Proapoptotic efficiency portrayed by the extracts against a prostate cancer cell line (PC-3) was also found to be similar. The samples collected from the Bathinda region, with Azadirachta and Acacia trees as the host plants, showed several-fold augmentation in levels of G. lucidum gredients compared with other variants. Elevated levels of myco-constituents highlight their significance in inhibiting prostate cancer cell proliferation, reducing reactive oxygen species, suppressing invasive potential, and inducing apoptosis. It was thus concluded that G. lucidum grown on Azadirachta plants was more efficient in exhibiting potent biological activities than G. lucidum grown on other host plants. ? 2016 Begell House, Inc.
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    Cellular uptake, intracellular trafficking and cytotoxicity of silver nanoparticles
    (2012) Singh, R.P.; Ramarao, P.
    Silver nanoparticles (Ag NPs) are used in consumer products and wound dressings due to their antimicrobial properties. However, in addition to toxic effects on microbes, Ag NPs can also induce stress responses as well as cytotoxicity in mammalian cells. We observed that Ag NPs are efficiently internalized via scavenger receptor-mediated phagocytosis in murine macrophages. Confocal and electron microscopy analysis revealed that internalized Ag NPs localize in the cytoplasm. Ag NPs cause mitochondrial damage, induce apoptosis and cell death. These effects were abrogated in presence of Ag ion-reactive, thiol-containing compounds suggesting the central of Ag ions in Ag NP toxicity. Quantitative image analysis revealed that intracellular dissolution of Ag NPs occurs about 50 times faster than in water. In conclusion, we demonstrate for the first time that Ag NPs are internalized by scavenger receptors, trafficked to cytoplasm and induce toxicity by releasing Ag ions. ? 2012 Elsevier Ireland Ltd.
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    Geminin a multi task protein involved in cancer pathophysiology and developmental process: A review
    (Elsevier B.V., 2016) Kushwaha, Prem Prakash; Rapalli, Krishna Chaitanya; Kumar, Shashank
    DNA replicates in a timely manner with each cell division. Multiple proteins and factors are involved in the initiation of DNA replication including a dynamic interaction between Cdc10-dependent transcript (Cdt1) and Geminin (GMNN). A conformational change between GMNN-Cdt1 heterotrimer and heterohexamer complex is responsible for licensing or inhibition of the DNA replication. This molecular switch ensures a faithful DNA replication during each S phase of cell cycle. GMNN inhibits Cdt1-mediated minichromosome maintenance helicases (MCM) loading onto the chromatin-bound origin recognition complex (ORC) which results in the inhibition of pre-replication complex assembly. GMNN modulates DNA replication by direct binding to Cdt1, and thereby alters its stability and activity. GMNN is involved in various stages of development such as pre-implantation, germ layer formation, cell commitment and specification, maintenance of genome integrity at mid blastula transition, epithelial to mesenchymal transition during gastrulation, neural development, organogenesis and axis patterning. GMNN interacts with different proteins resulting in enhanced hematopoietic stem cell activity thereby activating the development-associated genes' transcription. GMNN expression is also associated with cancer pathophysiology and development. In this review we discussed the structure and function of GMNN in detail. Inhibitors of GMNN and their role in DNA replication, repair, cell cycle and apoptosis are reviewed. Further, we also discussed the role of GMNN in virus infected host cells. ? 2016 Elsevier B.V. and Soci?t? Fran?aise de Biochimie et Biologie Mol?culaire (SFBBM)
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    Novel potent inhibitors of Plasmodium vivax dihydrofolate reductase: An in silico antimalarial drug discovery
    (Association of Pharmaceutical Teachers of India, 2018) Pushpendra, Singh; Kushwaha, Prem Prakash; Shashank, Kumar
    Objectives: In the present study, we targeted the dihydrofolate reductase enzyme that catalyzes the reduction of dihydrofolate to tetrahydrofolate which is required for the purines and pyrimidine synthesis. Malaria is one of the severe diseases throughout the world caused by blood-borne parasite Plasmodium vivax. Materials and Methods: Eighty-five parthenin analogs were docked against P. vivax and Homo sapiens dihydrofolate reductase proteins (PDB 2BL9 and 1KMS respectively) by using Maestro 9.6 program to evaluate the binding affinities of ligands with the protein. Results and Discussion: Docking analysis revealed some best hit ligands against P. vivax such as CID3467446 and CID56671343 but not inhibited the mammalian dihydrofolate reductase. The Dock score of parthenin analogs ranged from -7.31 to -9.3 while for standard dihydrofolate reductase inhibitors it was -4.78 to -8.04. Structural analysis of docked complexes of selected parthenin like compounds with P. vivax and mammalian dihydrofolate reductase revealed the involvement of Arg 115, Leu 136, Lys 138, Gly 175, Ser 117, Gln 177 and Ile 7, Ala 9, Thr 56, Ile 60, Pro 61 amino acid residues respectively in strong interactions. Absorption, distribution, metabolism, and excretion properties of best-docked compounds were predicted using QikProp application of Maestro 9.6. The results indicated that all the best-docked lead compounds followed Lipinski?s rule of five. Conclusion: Based on the results of the present study it has been concluded that parthenin like compounds may serve as potent dihydrofolate reductase inhibition based anti-malarial drug lead. ? 2018, Association of Pharmaceutical Teachers of India. All rights reserved.
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    The emerging role of long non-coding RNA in gallbladder cancer pathogenesis
    (Elsevier B.V., 2017) Khandelwal, Akanksha; Malhotra, Akshay; Jain, Manju; Vasquez, Karen M.; Jain, Aklank; Khandelwal, A.; Malhotra, A.; Jain, M.; Vasquez, K.M.; Jain, A.
    Gallbladder cancer (GBC) is the most common and aggressive form of biliary tract carcinoma with an alarmingly low 5-year survival rate. Despite its high mortality rate, the underlying mechanisms of GBC pathogenesis are not completely understood. Recently, from a growing volume of literature, long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression and appear to play vital roles in many human cancers. To date, a number of lncRNAs have been implicated in GBC, but their potential roles in GBC have not been systematically examined. Thus, in this review, we critically discuss the emerging roles of lncRNAs in GBC, and the pathways involved. Specifically, we note that some lncRNAs show greater expression in T1 and T2 tumor stages compared to T3 and T4 tumor stages and that their dysregulation leads to alterations in cell cycle progression and can cause an increase in GBC cell proliferation or apoptosis. In addition, some lncRNAs control the epithelial-mesenchymal transition process, while others take part in the regulation of ERK/MAPK and Ras cancer-associated signaling pathways. We also present their potential utility in diagnosis, prognosis, and/or treatment of GBC. The overall goal of this review is to stimulate interest in the role of lncRNAs in GBC, which may open new avenues in the determination of GBC pathogenesis and may lead to the development of new preventive and therapeutic strategies for GBC. ? 2016 Elsevier B.V. and Soci?t? Fran?aise de Biochimie et Biologie Mol?culaire (SFBBM)
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    The regulatory roles of long non-coding RNAs in the development of chemoresistance in breast cancer
    (Impact Journals LLC, 2017) Malhotra, Akshay; Jain, Manju; Prakash, Hridayesh; Vasquez, Karen M.; Jain, Aklank; Malhotra, A.; Jain, M.; Prakash, H.; Vasquez, K.M.; Jain, A.
    Chemoresistance is one of the major hurdles in the treatment of breast cancer, which limits the effect of both targeted and conventional therapies in clinical settings. Therefore, understanding the mechanisms underpinning resistance is paramount for developing strategies to circumvent resistance in breast cancer patients. Several published reports have indicated that lncRNAs play a dynamic role in the regulation of both intrinsic and acquired chemoresistance through a variety of mechanisms that endow cells with a drug-resistant phenotype. Although a number of lncRNAs have been implicated in chemoresistance of breast cancer, their mechanistic roles have not been systematically reviewed. Thus, here we present a detailed review on the latest research findings and discoveries on the mechanisms of acquisition of chemoresistance in breast cancer related to lncRNAs, and how lncRNAs take part in various cancer signalling pathways involved in breast cancer cells. Knowledge obtained from this review could assist in the development of new strategies to avoid or reverse drug resistance in breast cancer chemotherapy. ? 2017 Malhotra et al.