School Of Basic And Applied Sciences

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    Recent advances in understanding brain cancer metabolomics: a review
    (Springer, 2023-07-10T00:00:00) Mukherjee, Anirban Goutam; Gopalakrishnan, Abilash Valsala; Jayaraj, Rama; Ganesan, Raja; Renu, Kaviyarasi; Vellingiri, Balachandar; Dey, Abhijit; Parveen, Mohamudha
    Regardless of the significant progress made in surgical techniques and adjuvant therapies, brain tumors are a major contributor to cancer-related morbidity and mortality in both pediatric and adult populations. Gliomas represent a significant proportion of cerebral neoplasms, exhibiting diverse levels of malignancy. The etiology and mechanisms of resistance of this malignancy are inadequately comprehended, and the optimization of patient diagnosis and prognosis is a challenge due to the diversity of the disease and the restricted availability of therapeutic options. Metabolomics refers to the comprehensive analysis of endogenous and exogenous small molecules, both in a targeted and untargeted manner, that enables the characterization of an individual�s phenotype and offers valuable insights into cellular activity, particularly in the context of cancer biology, including brain tumor biology. Metabolomics has garnered attention in current years due to its potential to facilitate comprehension of the dynamic spatiotemporal regulatory network of enzymes and metabolites that enables cancer cells to adapt to their environment and foster the development of tumors. Metabolic changes are widely acknowledged as a significant characteristic for tracking the advancement of diseases, treatment efficacy, and identifying novel molecular targets for successful medical management. Metabolomics has emerged as an exciting area for personalized medicine and drug discovery, utilizing advanced analytical techniques such as nuclear magnetic resonance spectroscopy (MRS) and mass spectrometry (MS) to achieve high-throughput analysis. This review examines and highlights the latest developments in MRS, MS, and other technologies in studying human brain tumor metabolomics. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Drought priming modulates ABF, GRFs, related microRNAs and induce metabolic adjustment during heat stress in chickpea
    (Elsevier Masson s.r.l., 2023-09-09T00:00:00) Juneja, Sumandeep; Saini, Rashmi; Mukit, Abdul; Kumar, Sanjeev
    Drought and high temperature stress may occur concomitantly or individually in succession causing cellular dysfunctions. Abscisic acid (ABA) is a key stress regulator, and its responsive genes are controlled by ABRE (Abscisic acid Responsive Element)-binding factors (ABFs)and G-Box Regulatory factors (GRFs). Here, we identify ABFs, GRFs and targeting miRNAs in desi and kabuli chickpea. To validate their role after drought priming and subsequent high temperature stress, two contrasting chickpea varieties (PBG1 and PBG5) were primed and exposed to 32 �C, 35 �C and 38 �C for 12, 6 and 2 h respectively and analyzed for Physio-biochemical, expression of ABFs, GRFs and MiRNAs, and GC-MS based metabolite analysis. To ascertain the ABF-GRF protein-protein interactions, docking studies were carried out between the ABF3 and GRF14. Genome-wide analysis identified total 9 & 11 ABFs, and 11 GRFsin desi and kabuli respectively. Their gene structure, and motif composition were conserved in all subfamilies and only 10 and 12 genes have undergone duplication in both desi and kabuli chickpea respectively. These genes were differentially expressed in-silico. MiR172 and miR396 were identified to target ABFs and GRFs respectively. Protein-protein interaction (ABF3 and GRF14) might be successful only when the ABF3 was phosphorylated. Drought priming downregulated miR172 and miR396 and eventually upregulated targeting ABFs, and GRFs. Metabolite profiling (GC-MS) revealed the accumulation of 87 metabolites in Primed (P) and Non-Primed (NP) Chickpea plants. Tolerant cultivar (PBG5) responded better in all respects however both severity of stress and exposure are important factors and can produce broadly similar cellular response. � 2023 Elsevier Masson SAS
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    Drought priming induced thermotolerance in wheat (Triticum aestivum L.) during reproductive stage; a multifaceted tolerance approach against terminal heat stress
    (Elsevier Masson s.r.l., 2023-06-23T00:00:00) Kumar, Rashpal; Adhikary, Arindam; Saini, Rashmi; Khan, Shahied Ahmed; Yadav, Manisha; Kumar, Sanjeev
    In wheat (Triticum aestivum L.), terminal heat stress obstructs reproductive functioning eventually leading to yield loss. Drought priming during the vegetative stage can trigger a quicker and effective defense response against impending high temperature stress and improve crop production. In the present study, two contrasting wheat cultivars (PBW670 and C306) were subjected to moderate drought stress of 50�55% ?eld capacity for eight days during the jointing stage to generate drought priming (DP) response. Fifteen days after anthesis heat stress (36 �C) was imposed for three days and physiological response of primed, and non-primed plants was assessed by analyzing membrane damage, water status and antioxidative enzymes. Heat shock transcription factors (14 TaHSFs), calmodulin (TaCaM5), antioxidative genes (TaSOD, TaPOX), polyamine biosynthesis genes and glutathione biosynthesis genes were analyzed. GC-MS based untargeted metabolite profiling was carried out to underpin the associated metabolic changes. Yield related parameters were recorded at maturity to finally assess the priming response. Heat stress response was visible from day one of exposure in terms of membrane damage and elevated antioxidative enzymes activity. DP reduced the impact of heat stress by lowering the membrane damage (ELI, MDA & LOX) and enhancing antioxidative enzyme activity except APX in both the cultivars. Drought priming upregulated the expression of HSFs, calmodulin, antioxidative genes, polyamines, and the glutathione biosynthesis genes. Drought priming altered key amino acids, carbohydrate, and fatty acid metabolism in PBW670 but also promoted thermotolerance in C306. Overall, DP provided a multifaceted approach against heat stress and positive association with yield. � 2023 Elsevier Masson SAS
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    Unravelling cross priming induced heat stress, combinatorial heat and drought stress response in contrasting chickpea varieties
    (Elsevier Masson s.r.l., 2022-04-01T00:00:00) Yadav, Renu; Saini, Rashmi; Adhikary, Arindam; Kumar, Sanjeev
    Drought and high temperature stress affect chickpea growth and productivity. Often these stresses occur simultaneously in the field and lead to a wide range of molecular and metabolic adaptations. Two chickpea varieties; GPF2 (heat sensitive) and PDG4 variety (heat tolerant) were exposed to 35 �C for 24 h individually and along with drought stress. Five heat responsive signalling genes and 11 structural genes were analyzed using qPCR along with untargeted metabolites analysis using GC MS. Expression of antioxidant genes (CaSOD and CaGPX, CaAPX and CaCAT), transcription factors (CaHSFB2, CaHSFB2A, CaHSFB2B, CaHSP17.5 and CaHSP22.7) and signalling genes (CaCAM, CaGAD, and CaMAPK) were upregulated in GPF2 as compared to PDG4 variety. Principal component analysis (PCA), partial least-square discriminant analysis (PLS-DA), and heat map analysis were applied to the metabolomics data to identify the differential response of metabolites in two chickpea varieties. GC-MS analysis identified 107 and 83 metabolites in PDG4 and GPF2 varieties respectively. PDG4 variety accumulated more sugars, amino acids, sugar alcohols, TCA cycle intermediates which provided heat resistance. Additionally, the differential metabolic pathways involved in heat tolerance were alanine, aspartate, and glutamate metabolism, pantothenate CoA biosynthesis, fructose and mannose metabolism and pentose phosphate pathway in PDG4 variety. There was less accumulation of metabolites in the primed plants of both varieties as compared to the non-primed plants indicating less damage due to heat stress. The present study gives an overview of the molecular changes occurring in response to heat stress in sensitive and tolerant chickpea. � 2022 Elsevier Masson SAS
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    Drought priming modulates ABF, GRFs, related microRNAs and induce metabolic adjustment during heat stress in chickpea
    (Elsevier Masson s.r.l., 2023-09-09T00:00:00) Juneja, Sumandeep; Saini, Rashmi; Mukit, Abdul; Kumar, Sanjeev
    Drought and high temperature stress may occur concomitantly or individually in succession causing cellular dysfunctions. Abscisic acid (ABA) is a key stress regulator, and its responsive genes are controlled by ABRE (Abscisic acid Responsive Element)-binding factors (ABFs)and G-Box Regulatory factors (GRFs). Here, we identify ABFs, GRFs and targeting miRNAs in desi and kabuli chickpea. To validate their role after drought priming and subsequent high temperature stress, two contrasting chickpea varieties (PBG1 and PBG5) were primed and exposed to 32 �C, 35 �C and 38 �C for 12, 6 and 2 h respectively and analyzed for Physio-biochemical, expression of ABFs, GRFs and MiRNAs, and GC-MS based metabolite analysis. To ascertain the ABF-GRF protein-protein interactions, docking studies were carried out between the ABF3 and GRF14. Genome-wide analysis identified total 9 & 11 ABFs, and 11 GRFsin desi and kabuli respectively. Their gene structure, and motif composition were conserved in all subfamilies and only 10 and 12 genes have undergone duplication in both desi and kabuli chickpea respectively. These genes were differentially expressed in-silico. MiR172 and miR396 were identified to target ABFs and GRFs respectively. Protein-protein interaction (ABF3 and GRF14) might be successful only when the ABF3 was phosphorylated. Drought priming downregulated miR172 and miR396 and eventually upregulated targeting ABFs, and GRFs. Metabolite profiling (GC-MS) revealed the accumulation of 87 metabolites in Primed (P) and Non-Primed (NP) Chickpea plants. Tolerant cultivar (PBG5) responded better in all respects however both severity of stress and exposure are important factors and can produce broadly similar cellular response. � 2023 Elsevier Masson SAS
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    Drought priming induced thermotolerance in wheat (Triticum aestivum L.) during reproductive stage; a multifaceted tolerance approach against terminal heat stress
    (Elsevier Masson s.r.l., 2023-06-23T00:00:00) Kumar, Rashpal; Adhikary, Arindam; Saini, Rashmi; Khan, Shahied Ahmed; Yadav, Manisha; Kumar, Sanjeev
    In wheat (Triticum aestivum L.), terminal heat stress obstructs reproductive functioning eventually leading to yield loss. Drought priming during the vegetative stage can trigger a quicker and effective defense response against impending high temperature stress and improve crop production. In the present study, two contrasting wheat cultivars (PBW670 and C306) were subjected to moderate drought stress of 50�55% ?eld capacity for eight days during the jointing stage to generate drought priming (DP) response. Fifteen days after anthesis heat stress (36 �C) was imposed for three days and physiological response of primed, and non-primed plants was assessed by analyzing membrane damage, water status and antioxidative enzymes. Heat shock transcription factors (14 TaHSFs), calmodulin (TaCaM5), antioxidative genes (TaSOD, TaPOX), polyamine biosynthesis genes and glutathione biosynthesis genes were analyzed. GC-MS based untargeted metabolite profiling was carried out to underpin the associated metabolic changes. Yield related parameters were recorded at maturity to finally assess the priming response. Heat stress response was visible from day one of exposure in terms of membrane damage and elevated antioxidative enzymes activity. DP reduced the impact of heat stress by lowering the membrane damage (ELI, MDA & LOX) and enhancing antioxidative enzyme activity except APX in both the cultivars. Drought priming upregulated the expression of HSFs, calmodulin, antioxidative genes, polyamines, and the glutathione biosynthesis genes. Drought priming altered key amino acids, carbohydrate, and fatty acid metabolism in PBW670 but also promoted thermotolerance in C306. Overall, DP provided a multifaceted approach against heat stress and positive association with yield. � 2023 Elsevier Masson SAS
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    Unravelling cross priming induced heat stress, combinatorial heat and drought stress response in contrasting chickpea varieties
    (Elsevier Masson s.r.l., 2022-04-01T00:00:00) Yadav, Renu; Saini, Rashmi; Adhikary, Arindam; Kumar, Sanjeev
    Drought and high temperature stress affect chickpea growth and productivity. Often these stresses occur simultaneously in the field and lead to a wide range of molecular and metabolic adaptations. Two chickpea varieties; GPF2 (heat sensitive) and PDG4 variety (heat tolerant) were exposed to 35 �C for 24 h individually and along with drought stress. Five heat responsive signalling genes and 11 structural genes were analyzed using qPCR along with untargeted metabolites analysis using GC MS. Expression of antioxidant genes (CaSOD and CaGPX, CaAPX and CaCAT), transcription factors (CaHSFB2, CaHSFB2A, CaHSFB2B, CaHSP17.5 and CaHSP22.7) and signalling genes (CaCAM, CaGAD, and CaMAPK) were upregulated in GPF2 as compared to PDG4 variety. Principal component analysis (PCA), partial least-square discriminant analysis (PLS-DA), and heat map analysis were applied to the metabolomics data to identify the differential response of metabolites in two chickpea varieties. GC-MS analysis identified 107 and 83 metabolites in PDG4 and GPF2 varieties respectively. PDG4 variety accumulated more sugars, amino acids, sugar alcohols, TCA cycle intermediates which provided heat resistance. Additionally, the differential metabolic pathways involved in heat tolerance were alanine, aspartate, and glutamate metabolism, pantothenate CoA biosynthesis, fructose and mannose metabolism and pentose phosphate pathway in PDG4 variety. There was less accumulation of metabolites in the primed plants of both varieties as compared to the non-primed plants indicating less damage due to heat stress. The present study gives an overview of the molecular changes occurring in response to heat stress in sensitive and tolerant chickpea. � 2022 Elsevier Masson SAS
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    Analysis of the Inhibitory Effect of hsa-miR-145-5p and hsa-miR-203a-5p on Imatinib-Resistant K562 Cells by GC/MS Metabolomics Method
    (American Chemical Society, 2023-09-14T00:00:00) Singh, Priyanka; Yadav, Radheshyam; Verma, Malkhey; Chhabra, Ravindresh
    Imatinib (IM) resistance is considered to be a significant challenge in the management of chronic myeloid leukemia (CML). Previous studies have reported that hsa-miR-145-5p and hsa-miR-203a-5p can overcome IM resistance and hsa-miR-203a-5p can alter glutathione metabolism in IM-resistant cells. The purpose of this study was to examine whether hsa-miR-145-5p or hsa-miR-203a-5p counters IM resistance by targeting the overall metabolic profile of IM-resistant K562 cells. The metablic profiling of cell lysates obtained from IM-sensitive, IM-resistant, and miR-transfected IM-resistant K562 cells was carried out using the GC-MS technique. Overall, 75 major metabolites were detected, of which 32 were present in all samples. The pathway analysis of MetaboAnalyst 5.0 revealed that the majorly enriched pathways included glucose metabolism, fatty acid biosynthesis, lipogenesis, and nucleotide metabolism. Eleven of identified metabolites, l-glutamine, l-glutamic acid, l-lactic acid, phosphoric acid, 9,12-octadecadienoic acid, 9-octadecenoic acid, myristic acid, palmitic acid, cholesterol, and ?-alanine, appeared in enriched pathways. IM-resistant cells had comparatively higher concentrations of all of these metabolites. Notably, the introduction of hsa-miR-145-5p or hsa-miR-203a-5p into resistant cells resulted in a decrease in levels of these metabolites. The efficacy of miR-203a-5p was particularly remarkable in comparison with miR-145-5p, as evidenced by partial least-squares-discriminant analysis (PLS-DA), which showed a high level of similarity in metabolic profile between IM-sensitive K562 cells and IM-resistant cells transfected with hsa-miR-203a-5p. The results indicate that GC-MS-based metabolic profiling has the potential to distinguish between drug-resistant and -sensitive cells. This approach can also be used to routinely monitor therapeutic response in drug-resistant patients, thus, enabling personalized therapy. � 2023 American Society for Mass Spectrometry. Published by American Chemical Society. All rights reserved.
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    Current Approaches and Key Applications of Plant Metabolic Engineering
    (Springer, 2018) Bharti; Reetu; Kumar, Vinay
    The diversion of carbon flux toward biosynthesis of targeted products could be achieved by manipulation of targeted biosynthesis pathway in plants. This whole process consists of many steps in stepwise manners starting with the identification and isolation of targeted metabolites, elucidation of complete biosynthetic pathway for identification of point of intervention, discovery of corresponding potential metabolic genes, and overexpression of the selected genes in heterologous system and collectively production of the metabolites. The various biochemical processes including transcriptome, translatome, proteome, and reactome are being used to assist metabolic engineering by providing new insights into novel pathways or bottlenecks of existing pathways. Apart from all these, in-depth understanding of metabolic fluxes and feedback regulations is also mandatory for plant metabolic engineering. All these different current approaches are collectively considered for investigating the plant metabolic engineering to understand, reconstruct, analyze, and annotate the targeted pathways. The key applications of plant metabolic engineering have been compiled with a few important applications including improvement of nitrogen utilization in plant, development of highly nutritive food, and generation of biofuel production. In conclusion, the plant metabolic engineering could provide comprehensive evaluation of manipulation of biosynthetic pathways for numerous applications. This compiled information could act as a resource for crop breeding and biotechnology purposes.
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    Comparative metabolic profiling of vetiver (Chrysopogon zizanioides) and maize (Zea mays) under lead stress
    (Elsevier Ltd, 2018) Pidatala, V.R.; Li, K.; Sarkar, D.; Wusirika, R.; Datta, R.
    Lead (Pb) contamination of residential soils in United States is attributed to use of Pb based paints prior to 1978 and their deterioration and accumulation in surface soils. Exposure to Pb due to ingestion and inhalation of Pb laden soil and dust causes neurological disorders, renal disorders, developmental and behavioral problems, particularly in children under the age of six. Vetiver grass is one of the leading choices for Pb remediation due to its ability to hyperaccumulate Pb, in addition to high biomass. In order to understand the effect of Pb on vetiver metabolic pathways, we compared the global metabolic changes in vetiver with that of maize, a Pb susceptible plant under Pb stress. Vetiver showed massive increase in levels of key metabolites in response to Pb, including amino acids, organic acids and coenzymes. Maize showed very modest increase in some of the same metabolites, and no change in others. The results provide the first indication of the difference in metabolic response of the hyperaccumulator, vetiver to lead stress as compared to maize. ? 2017 Elsevier Ltd