Department Of Biochemistry And Microbial Sciences
Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/23
Browse
6 results
Search Results
Item Multifarious Effects of Arsenic on Plants and Strategies for Mitigation(MDPI, 2023-02-09T00:00:00) Beniwal, Rahul; Yadav, Radheshyam; Ramakrishna, WusirikaArsenic contamination in soil and water is a major problem worldwide. Inorganic arsenic is widely present as arsenate and arsenite. Arsenic is transferred to crops through the soil and irrigation water. It is reported to reduce crop production in plants and can cause a wide array of diseases in humans, including different types of cancers, premature delivery, stillbirth, and spontaneous abortion. Arsenic methyltransferase (AS3MT) in the human body converts inorganic arsenic into monomethylarsonic acid and dimethylarsinic acid, which are later excreted from the body. Arsenic transfer from the soil to grains of rice involves different transporters such as Lsi1, Lsi2, and Lsi6. These transporters are also required for the transfer of silicate, which makes them important for the plant. Different mitigation strategies have been used to mitigate arsenic from crops, such as plant growth-promoting bacteria, fungi, and nanoparticles, as well as using different plant genotypes and plant extracts. Different factors such as nitric oxide, Fe, and jasmonate also affect the response of a plant to the oxidative stress caused by arsenic. This review highlights the various effects of arsenic on plants with respect to their biochemical, molecular, and physiological aspects and the employment of classical and innovative methods for their mitigation. The current review is expected to initiate further research to improve As remediation to mitigate the effect of heavy metal pollution on the environment. � 2023 by the authors.Item Discovery of Natural Anti-Apoptotic Protein Inhibitor Using Molecular Docking and MM-GBSA Approach: An Anticancer Intervention(AMG Transcend Association, 2022-12-27T00:00:00) Dey, Sarbjit; Singh, Atul Kumar; Kumar, ShashankApoptosis is a programmed molecular phenomenon in normal cells, and "evading apoptosis" is a hallmark of cancer. Overexpression of anti-apoptotic BCL-2 promotes cancer cell survival, leading to tumor formation, its maintenance and progression, and further chemoresistance. Therefore, BCL-2 is considered an exciting drug target in clinical studies. The Cip/Kip family protein p21, which acts as an inhibitor of cyclin-CDK complexes, can also exert anti-apoptotic function and thus be involved in cancer initiation and progression. Preliminary research suggests that Piper chaba phytochemical(s) possess anticancer activity, but the underlying mechanism is yet to be established. For the first time, we explored Piper chaba phytochemicals for their anti-apoptotic protein (BCL-2 and p21) inhibition potential using molecular docking and MM-GBSA experiments. UC2288 and Venetoclax were known standards for BCL-2 and p21 proteins, respectively. We also explored the pharmacokinetics and drug-likeness properties of lead molecules using the SwissADME web tool. A total of 45 P. chaba phytochemicals were identified from published literature and docked at the drug-binding site of target proteins. Chabamide F, Piperchabaoside B, Piperundecalidiene, and Chabamide G showed ? binding affinity (-9.0 kcal/mole) than UC2288, while Brachystamide B showed lower binding affinity (-9.7 kcal/mole) than Venetoclax. MM-GBSA results revealed Chabamide F has a higher binding affinity for p21 than the standard compound. Therefore, P. chaba phytoconstituents qualify for further experiments on the drug discovery process to target anti-apoptosis proteins in cancer cells. � 2022 by the authors.Item Naringin dihydrochalcone potentially binds to catalytic domain of matrix metalloproteinase-2: molecular docking, MM-GBSA, and molecular dynamics simulation approach(Taylor and Francis Ltd., 2022-09-01T00:00:00) Singh, Atul Kumar; Kumar, ShashankMatrix metalloproteinase-2 (MMP2), an extracellular matrix remodulating protein�s increased activity causes cancer-metastasis. Potential MMP2 inhibitors showed sever side-effects in clinical trials. Present study is focused on identification natural MMP2 inhibitor by applying molecular docking, MM-GBSA binding energy estimation and molecular dynamics (MD) simulations. Commercially available flavonoid compound library was used to screen the molecules potentially binding with catalytic domain of MMP2 protein compared to standard MMP2 inhibitor ARP100. Naringin dihydrochalcone (NDC) showed interaction with the important residues (His120, Leu82 and Val117) present at the MMP2 catalytic domain in comparison to known inhibitor ARP100 (dock score ? ?13 and ?8 kcal/mole respectively). Lower ligand-protein binding energy (-67.31 kcal/mole) obtained in MM-GBSA and the MD simulation trajectory analysis showed significant stable and energetically favourable binding of NDC at the catalytic site of MMP2. In conclusion, anti-metastatic potential of NDC should be validated in in�vitro and in�vivo experiments. � 2022 Informa UK Limited, trading as Taylor & Francis Group.Item 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.Item Emerging Role of Migration and Invasion Enhancer 1 (MIEN1) in Cancer Progression and Metastasis(Frontiers Media S.A., 2019) Kushwaha, P.P; Gupta, S; Singh, A.K; Kumar, S.Tumor metastasis is a sequential event accounting for numerous cancer-related fatalities worldwide. The process of metastasis serially involves invasion, intravasation, extravasation, and tumor growth at the secondary site. Migration and invasion enhancer 1 (MIEN1) is a membrane associated protein overexpressed in various human cancers. Biological activity of MIEN1 is driven by geranylgeranyltransferase-I mediated prenylation at CAAX motif and methylation of the prenylated protein that anchors MIEN1 into the cellular membrane. Post-translationally modified MIEN1 interacts with Syk kinase and Annexin A2 protein; polymerizes G-actin and stabilizes F-actin filament; induces focal adhesion kinase phosphorylation and decrease cofilin phosphorylation implicated in both invasion and metastasis of different cancer types. In the present review, we discuss the structure, function, and involvement of MIEN1 in cancer progression. We also highlight the future prospects of MIEN1 as an emerging molecule and novel target in cancer cell invasion and metastasis.Item SNHG12: An LncRNA as a Potential Therapeutic Target and Biomarker for Human Cancer(Frontiers Media S.A., 2019) Tamang, S; Acharya, V; Roy, D; Sharma, R; Aryaa, A; Sharma, U; Khandelwal, A; Prakash, H; Vasquez, K.M; Jain, A.Limitations in current diagnostic procedures warrant identification of new methodologies to improve diagnoses of cancer patients. In this context, long non-coding RNAs (lncRNAs) have emerged as stable biomarkers which are expressed abundantly in tumors. Importantly, these can be detected at all stages of tumor development, and thus may provide potential biomarkers and/or therapeutic targets. Recently, we suggested that aberrant levels of lncRNAs can be used to determine the invasive and metastatic potential of tumor cells. Further, direct correlations of lncRNAs with cancer-derived inflammation, metastasis, epithelial-to-mesenchymal transition, and other hallmarks of cancer indicate their potential as biomarkers and targets for cancer. Thus, in this review we have discussed the importance of small nucleolar RNA host gene 12 (SNHG12), a lncRNA, as a potential biomarker for a variety of cancers. A meta-analysis of a large cohort of cancer patients revealed that SNHG12 may also serve as a potential target for cancer-directed interventions due to its involvement in unfolded protein responses, which many tumor cells exploit to both evade immune-mediated attack and enhance the polarization of effector immune cells (e.g., macrophages and T cells). Thus, we propose that SNHG12 may serve as both a biomarker and a druggable therapeutic target with promising clinical potential.