Browsing by Author "Kumar S."

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    Alternate mild drought stress (−0.1 MPa PEG) immunizes sensitive chickpea cultivar against lethal chilling by accentuating the defense mechanisms
    (Polish Academy of Sciences, 2016) Kaur S.; Jairath A.; Singh I.; Nayyar H.; Kumar S.
    The changes in climate particularly, the rise in temperature and humidity affect the physiological functions of plants subsequently affecting crop productivity adversely. A strategy is required which can be directly implemented in fields to induce the tolerance in crop plants. In present study, two chickpea varieties with contrasting sensitivity PDG3 (Tolerant) and GPF2 (Sensitive) were raised hydroponically, preconditioned with mild drought stress (0.1 MPa PEG-6000) for 3 days (above 0.1 MPa is lethal) and subsequently recovered for double time (6 days) and finally exposed to lethal cold stress (4 °C) for 3 days. We hypothesize that preconditioning with non-lethal drought stress may immunize the plants to combat lethal cold stress. Membrane integrity improved in root and shoot, lipid peroxidation decreased to control level in preconditioned seedlings. Cellular respiration ability (% TTC reduction) increased in the preconditioned seedlings to almost 90 % in the shoot and 60 % in the root, concurrently it was 45 % in non-preconditioned seedlings. Proline content also increased in preconditioned seedlings, especially roots. Carbohydrate had a shift in terms of a high amount of total, reducing sugars and starch in non-preconditioned seedlings compared to preconditioned. Both PDG3 and GPF2 showed enhanced SOD, CAT and GPOX activity indicating tolerance against cold-induced oxidative stress and preconditioning induced improvement against lethal cold stress.
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    Antioxidant potential of ganoderic acid in Notch-1 protein in neuroblastoma
    (Springer New York LLC, 2019) Gill B.S.; Navgeet; Kumar S.
    Neuroblastoma is a childhood tumor arising from developing a sympathetic nervous system and causes around 10% of pediatric tumors. Despite advancement in the use of sophisticated techniques in molecular biology, neuroblastoma patient's survivability rate is very less. Notch pathway is significant in upholding cell maintenance and developmental process of organs. Notch-1 proteins are a ligand-activated transmembrane receptor which decides the fate of the cell. Notch signaling leads to transcription of genes which indulged in numerous diseases including tumor progression. Ganoderic acid, a lanosterol triterpene, isolated from fungus Ganoderma lucidum with a wide range of medicinal values. In the present study, various isoforms of the ganoderic acid and natural inhibitors were docked by molecular docking using Maestro 9 in the Notch-1 signaling pathway. The receptor-based molecular docking exposed the best binding interaction of Notch-1 with ganoderic acid A with GScore (? 8.088), kcal/mol, Lipophilic EvdW (? 1.74), Electro (? 1.18), Glide emodel (? 89.944) with the active participation of Arg 189, Arg 199, Glu 232 residues. On the other hand natural inhibitor, curcumin has GScore (? 7.644), kcal/mol, Lipophilic EvdW (? 2.19), Electro (? 0.73), Glide emodel (? 70.957) with Arg 75 residues involved in docking. The ligand binding affinity of ganoderic acid A in Notch-1 is calculated using MM-GBSA (? 76.782), whereas curcumin has (? 72.815) kcal/mol. The QikProp analyzed the various drug-likeness parameters such as absorption, distribution, metabolism, excretion, and toxicity (ADME/T) and isoforms of ganoderic acid require some modification to fall under Lipinski rule. The ganoderic acid A and curcumin were the best-docked among different compounds and exhibits downregulation in Notch-1 mRNA expression and inhibits proliferation, viability, and ROS activity in IMR-32 cells.
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    Bulbine frutescens phytochemical inhibits notch signaling pathway and induces apoptosis in triple negative and luminal breast cancer cells
    (Elsevier Inc., 2019) Kushwaha P.P.; Vardhan P.S.; Kapewangolo P.; Shuaib M.; Prajapati S.K.; Singh A.K.; Kumar S.
    Breast cancer (BCa) is the most commonly diagnosed lethal cancer in women worldwide. Notch signaling pathway is directly linked to BCa recurrence and aggressiveness. Natural remedies are becoming a prime choice to overcome against cancer due to lesser side effect and cost-effectiveness. Bulbine frutescens (Asphodelaceae), a traditional medicinal plant in South Africa possess bioactive flavonoids and terpenoids. Polar (methanol) and non-polar (hexane) B. frutescens plant extracts were prepared. GC–MS analysis revealed the differential presence of secondary metabolites in both methanolic and hexane extracts. We hereby first time evaluated the anticancer potential of B. frutescens methanolic and hexane extract in triple-negative and luminal BCa cells. B. frutescens extracts significantly decreased cell viability (IC50 4.8–28.4 μg/ml) and induced cell cycle arrest at G1 phase in MDA-MB-231 and T47D cells as confirmed by spectrophotometry and flow cytometry technique. RT-PCR analysis of cell cycle (cyclin D1, CDK4, and p21) and apoptosis modulating genes (caspase 3, Bcl2 and survivin) revealed upexpression of p21, and caspase 3, and down expression of cyclin D1, CDK4, Bcl2 and survivin genes in extract-treated BCa cells. Fluorescence spectrophotometry and confocal microscopy showed B. frutescens induced nuclear morphology and mitochondrial integrity disruption, and increased reactive oxygen species production in MDA-MB-231 and T47D cells. Flow cytometric apoptosis analysis of B. frutescens extracts treated MDA-MB-231 cells showed ≈13% increase in early apoptotic population in comparison to non-treated cells. Dual-Luciferase Reporter assay confirmed notch promoter inhibitory activity of B. frutescens extracts. Moreover, RTPCR analysis showed down regulation of notch responsive genes (Hes1 and Hey1) at transcription levels in extract-treated BCa cells. Western Blot analysis showed increased procaspase 3 protein expression in extract-treated BCa cells. In all the assays methanolic extract showed better anti-cancer properties. Literature-based identification of methanol soluble phytochemicals in B. frutescens and in silico docking study revealed Bulbineloneside D as a potent ϒ-secretase enzyme inhibitor. In comparison to standard notch inhibitor, lead phytochemical showed two additional hydrophobic interactions with Ala80 and Leu81 amino acids. In conclusion, B. frutescens phytochemicals have cell cycle arrest, ROS production, apoptosis induction, and mitochondria membrane potential disruption efficacy in breast cancer cells. B. frutescens phytochemicals have the ability to downregulate the notch signaling pathway in triple-negative and luminal breast cancer cells.
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    Chitin and chitosan-based support materials for enzyme immobilization and biotechnological applications
    (Springer Verlag, 2019) Verma M.L.; Kumar S.; Das A.; Randhawa J.S.; Chamundeeswari M.
    Enzymes of industrial importance are primarily employed for biotechnological applications. However, high-cost and instability issues of purified enzymes hamper their usage. Multiple reuses rather than the single use is more cost-effective. A robuster bioprocess is feasible by enzyme immobilization. Performance of immobilized enzymes depends on the nature of support materials. Chitin and its derivatives-based supports offer stability and cost-effective bioprocessing. Chitosan is biocompatible, biodegradable, non-toxic and has multiple functional groups. A variety of supports such as chitosan, chitosan film, chitosan nanoparticle and chitosan nanocomposite are employed for enzyme immobilization. Chitosan bound enzymes, as compared to free enzymes, have improved the biocatalytic performances due to exceptionally high operational stability and reusability. Here we review enzymes immobilized on chitin/chitosan supporting materials with applications ranging from agriculture to drug delivery.
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    Cross-priming accentuates key biochemical and molecular indicators of defense and improves cold tolerance in chickpea (Cicer arietinum L.)
    (Polish Academy of Sciences, Institute of Slavic Studies, 2019) Saini R.; Adhikary A.; Nayyar H.; Kumar S.
    Cold environment favors long vegetative phase but also impose substantial loss by damaging reproductive functioning in chickpea. Field temperature below 10��C is even more detrimental for reproductive development, enhances floral and pod abortion. In this study, contrasting chickpea varieties PDG3 and GPF2 were exposed to drought, recovered, and subsequently exposed to lethal cold stress ~ 4�5��C with an aim to induce defense response against cold shock. Physiological, biochemical, and molecular signatures related to damage and defense, i.e., membrane damage, antioxidative enzymes, fatty acid desaturase (CaFAD2.1), and small HSPs (CaHSP18.5 and CaHSP22.7), were analyzed. Drought pretreatment/preconditioning maintained the membrane stability in the cold by managing malondialdehyde (MDA) content and lipoxygenase (LOX) activity. Improved mitochondrial functioning (TTC reduction), increased activity of catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) proved better cellular functioning during cold exposure. The expression and activity of superoxide dismutase (CaSOD) were down-regulated in both varieties, but CaCAT, CaAPX, CaGR, and CaFAD2.1 expressions were up-regulated in GPF2. Small heat shock protein CaHSP22.7 was also up-regulated in drought preconditioned PDG3 and GPF2 and after cold shock. Drought pretreatment/preconditioning significantly improved membrane damage during cold exposure, induced antioxidative system, and up-regulated FAD2. This study also pointed the possible role of CaHSP22.7 in cold tolerance and CaHSP18.5 in drought stress. The sensitive variety (GPF2) was positively responsive to preconditioning as this variety showed improvement in defense-related parameters; however, genotypic variations were observed in PDG3. � 2019, Franciszek G�rski Institute of Plant Physiology, Polish Academy of Sciences, Krak�w.
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    E-pharmacophore guided discovery of pyrazolo[1,5-c]quinazolines as dual inhibitors of topoisomerase-I and histone deacetylase
    (Academic Press Inc., 2020) Joshi G.; Kalra S.; Yadav U.P.; Sharma P.; Singh P.K.; Amrutkar S.; Ansari A.J.; Kumar S.; Sharon A.; Sharma S.; Sawant D.M.; Banerjee U.C.; Singh S.; Kumar R.
    In the quest to ameliorate the camptothecin (CPT) downsides, we expedite to search for stable non-CPT analogues among 11 motifs of pyrazoloquinazolines reported. E-pharmacophore drug design approach helped filtering out pyrazolo[1,5-c]quinazolines as Topoisomerase I (TopoI) 'interfacial' inhibitors. Three compounds, 3c, 3e, and 3l were shown to be potent non-intercalating inhibitors of TopoI specifically and showed cancer cell-specific cytotoxicity in lung, breast and colon cancer cell lines. The compounds induced cell cycle arrest at S-phase, mitochondrial cell death pathway and modulated oxidative stress in cancer cells. Furthermore, a preliminary study was conducted to explore the feasibility of these compounds to be developed as dual TopoI-HDAC1 (histone deacetylase 1) inhibitors (4a) to combat resistance. Compound 4a was found to possess dual inhibitory capabilities in-vitro. Cytotoxic potential of 4a was found to be significantly higher than parent compound in 2D as well as 3D cancer cell models. Probable binding modes of 4a with TopoI and HDAC1 active sites were examined by molecular modelling.
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    Genetic engineering of poplar: Current achievements and future goals
    (Springer Singapore, 2017) Yadav R.; Yadav N.; Goutam U.; Kumar S.; Chaudhury A.
    Global biomass demand for industrial applications is ever increasing especially in biofuels and pulp industries. Poplar is likely to have great biological advantages over the other forest trees which include small genome size, large number of species, rapid juvenile growth, ease of clonal propagation, easy recovery of genetic transformants, and available genome draft. Wide and sustainable farming of rapidly growing trees such as poplars may supplement to attain the requirement of renewable resources. This chapter covers the progress in both basic and applied studies in poplar genetic tailoring. Certain advices are given for future direction of the research in poplar genetic tailoring so as to achieve the needs of environmental cleansing system and the timber industries. Emerging new thoughts for designing wood improvement approaches are discussed.
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    The great Asian security complex: China's security concerns and its responses towards the South China sea
    (Taylor and Francis, 2018) Kumar S.; Shah S.H.
    The fundamental theme of this chapter is to understand the background of the Asian Super Complex (ASC) theory that cemented the regional security architecture under the new security framework. The chapter highlights the new dynamics which are occurring in the South China Sea from the last two decades. The South China Sea (SCS) is the fulcrum of new strategic and military activities due to the availability of natural resources and the thriving maritime silk routes. The chapter analyses China's territorial disputes with the ASEAN countries in the region. It focuses on China's economic and maritime security concerns in the region. The chapter also examines the major powers involvement in the region such as the US, Japan, India, and Australia, and investigates China's strategic lookout of external security threats and challenges in the South China Sea. It also analyses China's new responses towards the new strategic dynamics in the region. The background of the chapter outlines China's upcoming diplomatic and geostrategic efforts to increase its active involvement in the region. - 2018 selection and editorial matter, Geeta Kochhar; individual chapters, the contributors.
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    Lysine and ?-Aminoisobutyric Acid Conjugated Bioinspired Polydopamine Surfaces for the Enhanced Antibacterial Performance of the Foley Catheter
    (American Chemical Society, 2019) Patel K.; Kushwaha P.; Kumar S.; Kumar R.
    Microbial adhesion onto implanted devices was reduced by the immobilization of amino acid lysine and ?-aminoisobutyric acid to polydopamine functionalized PET films and Foley catheters. The polydopamine functionalized film was prepared by a dip coating method followed by incorporation of biocompatible amino acids to prepared films. The purpose of development of the modified pDA film is to improve the anti-biofouling and antibacterial activity of the film which can be successfully applied for medical devices. The characterization of modification was done using different techniques such as contact angle measurement, ATR-FTIR, FE-SEM, AFM, and XPS analysis. ATR-FTIR spectroscopy and XPS confirmed the successful amino modification of film. The anti-biofouling and antimicrobial behavior of the prepared surfaces were evaluated using the bacterial attachment and death assay. The resulting coatings repelled bacterial cell attachment and killed clinically applicable Gram-negative and Gram-positive strains. The developed coatings were applied to the Foley catheters to study the antibacterial activity by the log reduction method. The results demonstrate that tested amino acid-modified film increases the antibacterial activity of the catheters and can significantly help in reduction of nosocomial infections.
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    MicroRNA Targeting Nicotinamide Adenine Dinucleotide Phosphate Oxidases in Cancer
    (Mary Ann Liebert Inc., 2020) Kushwaha P.P.; Gupta S.; Singh A.K.; Prajapati K.S.; Shuaib M.; Kumar S.
    Significance: Reactive oxygen species (ROS) production occurs primarily in the mitochondria as a by-product of cellular metabolism. ROS are also produced by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases in response to growth factors and cytokines by normal physiological signaling pathways. NADPH oxidase, a member of NADPH oxidase (NOX) family, utilizes molecular oxygen (O2) to generate ROS such as hydrogen peroxide and superoxide. Imbalance between ROS production and its elimination is known to be the major cause of various human diseases. NOX family proteins are exclusively involved in ROS production, which makes them attractive target(s) for the treatment of ROS-mediated diseases including cancer. Recent Advances: Molecules such as Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2), N-methyl-d-aspartic acid (NMDA) receptors, nuclear factor-kappaB, KRAS, kallistatin, gene associated with retinoic-interferon-induced mortality-19, and deregulated metabolic pathways are involved in ROS production in association with NADPH oxidase. Critical Issues: Therapeutic strategies targeting NADPH oxidases in ROS-driven cancers are not very effective due to its complex regulatory circuit. Tumor suppressor microRNAs (miRNAs) viz. miR-34a, miR-137, miR-99a, and miR-21a-3p targeting NADPH oxidases are predominantly downregulated in ROS-driven cancers. miRNAs also regulate other cellular machineries such as Keap1/Nrf2 pathway and NMDA receptors involved in ROS production and consequently drug resistance. Here, we discuss the structure, function, and metabolic role of NADPH oxidase, NOX family protein-protein interaction, their association with other pathways, and NADPH oxidase alteration by miRNAs. Moreover, we also discuss and summarize studies on NADPH oxidase associated with various malignancies and their therapeutic implications. Future Directions: Targeting NADPH oxidases through miRNAs appears to be a promising strategy for the treatment of ROS-driven cancer.
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    Space time fractional Drinfel'd-Sokolov-Wilson system with time-dependent variable coefficients: Symmetry analysis, power series solutions and conservation laws
    (Springer Verlag, 2019) Kour B.; Kumar S.
    In this work we aim to apply the Lie-symmetry method via the Riemann-Liouville fractional derivative based on continuous group of transformations to examine the symmetry reduction of space time fractional Drinfel'd-Sokolov-Wilson (DSW) system with time-dependent variable coefficients. The reduced Nonlinear fractional ordinary differential equations (NLFODEs) with variable coefficients are further studied for the exact solution by using the power series method. The exact solutions obtained in form of power series and their convergence show the accuracy and efficiency of the proposed method, which is simple and accurate in comparison to other methods to find the exact solution of nonlinear fractional partial differential equations (NLFPDEs). Also, the new conservation theorem and Noether's operators are used to construct conservation laws of the governing system.