Department Of Biochemistry And Microbial Sciences

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Author: search.filters.author.Kushwaha, Prem Prakash

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    Anti-proliferative, apoptosis inducing, and antioxidant potential of Callistemon lanceolatus bark extracts: an in vitro and in silico study
    (Springer, 2023-05-08T00:00:00) Kumar, Ramesh; Kushwaha, Prem Prakash; Singh, Atul Kumar; Kumar, Shashank; Pandey, Abhay Kumar
    The present study reports anticancer and antioxidant activities of Callistemon lanceolatus bark extracts. Anticancer activity was studied against MDA-MB-231 cells. Antioxidant assessment of the chloroform and methanol extracts showed considerable free radical scavenging, metal ion chelating, and reducing power potential. Chloroform extract exhibited potent inhibition of cancer cell proliferation in MTT assay (IC50 9.6�?g/ml) and promoted programmed cell death. Reactive oxygen species (ROS) generation, mitochondria membrane potential (MMP) disruption ability, and nuclear morphology changes were studied using H2-DCFDA, JC-1, and Hoechst dyes, respectively, using confocal microscopy. Apoptotic cells exhibited fragmented nuclei, increased ROS generation, and altered MMP in dose- and time-dependent manner. Chloroform extract upregulated the BAX-1 and CASP3 mRNA expression coupled with downregulation of BCL-2 gene. Further, in silico docking of phytochemicals present in C. lanceolatus with anti-apoptotic Bcl-2 protein endorsed apoptosis by its inhibition and thus corroborated the experimental findings. Obatoclax, a known inhibitor of Bcl-2 was used as a reference compounds. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Ancistrobrevinium A, the first N-methylated, cationic naphthylisoquinoline alkaloid, from the tropical liana Ancistrocladus abbreviatus (Ancistrocladaceae)
    (Taylor and Francis Ltd., 2023-03-29T00:00:00) Tajuddeen, Nasir; Fayez, Shaimaa; Kushwaha, Prem Prakash; Feineis, Doris; Ak� Assi, Laurent; Kumar, Shashank; Bringmann, Gerhard
    Ancistrobrevinium A (1) is the first N-methylated and non-hydrogenated, and thus cationic naphthylisoquinoline alkaloid. It was discovered in the root bark extract of the phytochemically productive West African liana Ancistrocladus abbreviatus (Ancistrocladaceae). Its constitution was elucidated by HR-ESI-MS and 1D and 2D NMR. Due to the steric hindrance in the proximity of the linkage between the naphthalene and isoquinoline parts, the biaryl axis is rotationally hindered. It thus constitutes a stable element of chirality�the only one in the new alkaloid since, different from most other naphthylisoquinoline alkaloids, it has no stereogenic centers. The axial configuration of 1 was assigned by electronic circular dichroism (ECD) investigations, which gave a positive couplet, indicating a �positive chirality�, here corresponding to a P-configuration. Ancistrobrevinium A (1) showed a weak cytotoxic activity against A549 lung cancer cells (IC50 = 50.6 ?M). � 2023 Informa UK Limited, trading as Taylor & Francis Group.
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    Naphthylisoindolinone alkaloids: the first ring-contracted naphthylisoquinolines, from the tropical liana Ancistrocladus abbreviatus, with cytotoxic activity
    (Royal Society of Chemistry, 2022-10-12T00:00:00) Fayez, Shaimaa; Bruhn, Torsten; Feineis, Doris; Assi, Laurent Ak�; Kushwaha, Prem Prakash; Kumar, Shashank; Bringmann, Gerhard
    The West African liana Ancistrocladus abbreviatus is a rich source of structurally most diverse naphthylisoquinoline alkaloids. From its roots, a series of four novel representatives, named ancistrobrevolines A-D (14-17) have now been isolated, displaying an unprecedented heterocyclic ring system, where the usual isoquinoline entity is replaced by a ring-contracted isoindolinone part. Their constitutions were elucidated by 1D and 2D NMR and HR-ESI-MS. The absolute configurations at the chiral axis and at the stereogenic center were assigned by using experimental and computational electronic circular dichroism (ECD) investigations and a ruthenium-mediated oxidative degradation, respectively. For the biosynthetic origin of the isoindolinones from �normal� naphthyltetrahydroisoquinolines, a hypothetic pathway is presented. It involves oxidative decarboxylation steps leading to a ring contraction by a benzilic acid rearrangement. Ancistrobrevolines A (14) and B (15) were found to display moderate cytotoxic effects (up to 72%) against MCF-7 breast and A549 lung cancer cells and to reduce the formation of spheroids (mammospheres) in the breast cancer cell line. � 2022 The Royal Society of Chemistry.
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    Role of prostate cancer stem-like cells in the development of antiandrogen resistance
    (OAE Publishing Inc., 2022-06-09T00:00:00) Kushwaha, Prem Prakash; Verma, Shiv; Kumar, Shashank; Gupta, Sanjay
    Androgen deprivation therapy (ADT) is the standard of care treatment for advance stage prostate cancer. Treatment with ADT develops resistance in multiple ways leading to the development of castration-resistant prostate cancer (CRPC). Present research establishes that prostate cancer stem-like cells (CSCs) play a central role in the development of treatment resistance followed by disease progression. Prostate CSCs are capable of self-renewal, differentiation, and regenerating tumor heterogeneity. The stemness properties in prostate CSCs arise due to various factors such as androgen receptor mutation and variants, epigenetic and genetic modifications leading to alteration in the tumor microenvironment, changes in ATP-binding cassette (ABC) transporters, and adaptations in molecular signaling pathways. ADT reprograms prostate tumor cellular machinery leading to the expression of various stem cell markers such as Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1), Prominin 1 (PROM1/CD133), Indian blood group (CD44), SRY-Box Transcription Factor 2 (Sox2), POU Class 5 Homeobox 1(POU5F1/Oct4), Nanog and ABC transporters. These markers indicate enhanced self-renewal and stemness stimulating CRPC evolution, metastatic colonization, and resistance to antiandrogens. In this review, we discuss the role of ADT in prostate CSCs differentiation and acquisition of CRPC, their isolation, identification and characterization, as well as the factors and pathways contributing to CSCs expansion and therapeutic opportunities. � The Author(s) 2022.
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    Green Synthesis of Bimetallic Au/Ag Nanostructures Using Aqueous Extract of Eichhornia crassipes for Antibacterial Activity
    (Springer, 2022-02-12T00:00:00) Halder, Arindom; Biswas, Rathindranath; Kushwaha, Prem Prakash; Halder, Krishna Kamal; Ahmed, Imtiaz; Singh, Harjinder; Kumar, Shashank; Haldar, Krishna Kanta
    Biosynthesis of nanostructured materials is an arising feature of the interdisciplinary relationship between nanotechnology and biotechnology and acquiring consideration because of developing interest to foster ecologically favorable innovations in material preparation. In the present study, we synthesized an environmentally friendly and green method for the synthesis of gold/silver bimetallic nanostructure using Eichhornia crassipes leaf extract as reducing and capping agent. Au/Ag nanostructures were characterized by UV�Visible spectroscopy, X-ray photoelectron spectroscopy, and power X-ray diffraction. Transmission electron microscopy images also confirmed the formation of Au/Ag nanostructures. Antibacterial activity of Au/Ag nanostructures was studied and it has been found that Ag/Au nanostructure at 100��M concentration significantly inhibited the bacterial growth of Escherichia coli bacteria. Moreover, the Hoechst 33342 staining method was used to study the effect of Ag/Au nanostructure particles on the morphological changes in breast cancer cell (MDA-MB-231) nucleus. Staining of the Ag/Au nanostructure particle�treated MDA-MB-231 cells (4�h treatments) showed the appearance of emblematic features of apoptosis such as cell membrane blabbing and shrinkage. Graphical Abstract: [Figure not available: see fulltext.]. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Five-Decade Update on Chemopreventive and Other Pharmacological Potential of Kurarinone: a Natural Flavanone
    (Frontiers Media S.A., 2021-09-27T00:00:00) Kumar, Shashank; Prajapati, Kumari Sunita; Shuaib, Mohd; Kushwaha, Prem Prakash; Tuli, Hardeep Singh; Singh, Atul Kumar
    In the present article we present an update on the role of chemoprevention and other pharmacological activities reported on kurarinone, a natural flavanone (from 1970 to 2021). To the best of our knowledge this is the first and exhaustive review of kurarinone. The literature was obtained from different search engine platforms including PubMed. Kurarinone possesses anticancer potential against cervical, lung (non-small and small), hepatic, esophageal, breast, gastric, cervical, and prostate cancer cells. In vivo anticancer potential of kurarinone has been extensively studied in lungs (non-small and small) using experimental xenograft models. In in vitro anticancer studies, kurarinone showed IC50 in the range of 2�62��M while in vivo efficacy was studied in the range of 20�500�mg/kg body weight of the experimental organism. The phytochemical showed higher selectivity toward cancer cells in comparison to respective normal cells. kurarinone inhibits cell cycle progression in G2/M and Sub-G1 phase in a cancer-specific context. It induces apoptosis in cancer cells by modulating molecular players involved in apoptosis/anti-apoptotic processes such as NF-?B, caspase 3/8/9/12, Bcl2, Bcl-XL, etc. The phytochemical inhibits metastasis in cancer cells by modulating the protein expression of Vimentin, N-cadherin, E-cadherin, MMP2, MMP3, and MMP9. It produces a cytostatic effect by modulating p21, p27, Cyclin D1, and Cyclin A proteins in cancer cells. Kurarinone possesses stress-mediated anticancer activity and modulates STAT3 and Akt pathways. Besides, the literature showed that kurarinone possesses anti-inflammatory, anti-drug resistance, anti-microbial (fungal, yeast, bacteria, and Coronavirus), channel and transporter modulation, neuroprotection, and estrogenic activities as well as tyrosinase/diacylglycerol acyltransferase/glucosidase/aldose reductase/human carboxylesterases 2 inhibitory potential. Kurarinone also showed therapeutic potential in the clinical study. Further, we also discussed the isolation, bioavailability, metabolism, and toxicity of Kurarinone in experimental models. � Copyright � 2021 Kumar, Prajapati, Shuaib, Kushwaha, Tuli and Singh.
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    Identification of cancer stemness related miRNA(s) using integrated bioinformatics analysis and in vitro validation
    (Springer Science and Business Media Deutschland GmbH, 2021-09-23T00:00:00) Prajapati, Kumari Sunita; Shuaib, Mohd; Kushwaha, Prem Prakash; Singh, Atul Kumar; Kumar, Shsahank
    The stemness property of cells allows them to sustain their lineage, differentiation, proliferation, and regeneration. MicroRNAs are small non-coding RNAs known to regulate the stemness property of cells by regulating the expression of stem cell signaling pathway proteins at mRNA level. Dysregulated miRNA expression and associated stem cell signaling pathways in normal stem cells give rise to cancer stem cells. Thus, the present study was aimed to identify the miRNAs involved in the regulation of major stem cell signaling pathways. The proteins (n = 36) involved in the signaling pathways viz., Notch, Wnt, JAK-STAT, and Hedgehog which is associated with the stemness property was taken into the consideration. The miRNAs, having binding sites for the targeted protein-encoding gene were predicted using an online tool (TargetScan) and the common miRNA among the test pathways were identified using Venn diagram analysis. A total of 22 common miRNAs (including 8 non-studied miRNAs) were identified which were subjected to target predictions, KEGG pathway, and gene ontology (GO) analysis to study their potential involvement in the stemness process. Further, we studied the clinical relevance of the non-studied miRNAs by performing the survival analysis and their expression levels in clinical breast cancer patients using the TCGA database. The identified miRNAs showed overall poor survival in breast cancer patients. The miR-6844 showed significantly high expression in various clinical subgroups of invasive breast cancer patients compared with the normal samples. The expression levels of identified miRNA(s) were validated in breast normal, luminal A, triple-negative, and stem cells in vitro models using qRT-PCR analysis. Further treatment with the phytochemical showed excellent down regulation of the lead miRNA. Overall the study first time reports the association of four miRNAs (miR-6791, miR-4419a, miR-4251 and miR-6844) with breast cancer stemness. � 2021, King Abdulaziz City for Science and Technology.
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    Identification of miRNAs and related hub genes associated with the triple negative breast cancer using integrated bioinformatics analysis and in vitro approach
    (Taylor and Francis Ltd., 2021-08-13T00:00:00) Shuaib, Mohd; Prajapati, Kumari Sunita; Singh, Atul Kumar; Kushwaha, Prem Prakash; Waseem, Mohammad; Kumar, Shashank
    Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype generally associated with younger women. Due to the lack of suitable drugable targets in TNBC, the microRNAs are considered as a better hope as therapeutic agents for the management of the disease. In this study, we identified differentially expressed miRNAs (DEMs) and associated hub genes in TNBC microarray data (GSE38167, GSE60714, and GSE10833) using bioinformatics tools. The identified miRNAs and genes were validated in the TNBC cell line model (MDA-MB-231) compared with the normal breast cells (MCF-10A) using the qRT-PCR technique. False-positive DEMs were avoided by comparing the DEMs profile of TNBC and triple positive breast cancer (TPBC) cell line model (BT474) compared with the MCF-10A cells data. In addition, we studied the effect of anticancer phytochemicals on the differential expression of miRNAs and genes in MDA-MB-231 cells. Furthermore, target predictions, functional enrichment and KEGG pathway analysis, mutation and copy number alterations, and overall survival analysis of DEMs in TNBC sample was investigated using standard computational tools. The study identifies first time the association of hsa-miR-1250, has-miR-1273, and has-miR-635 with the TNBC. DEMs showed significant association with the Wnt, ErbB, PI3-Akt and cAMP signaling pathways having clinical implications in TNBC tumorigenesis. The DEMs and hub genes (HOXC6 and ACVR2B) showed survival disadvantages in TNBC patients. In summary, the identified miRNAs and hub genes show important implications in TNBC tumorigenesis and patient survival. We recommend further experimental studies on pathophysiological mechanism of the identified miRNAs and hub genes in TNBC. Communicated by Ramaswamy H. Sarma. � 2021 Informa UK Limited, trading as Taylor & Francis Group.
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    Identification of Natural Inhibitors Against SARS-CoV-2 Drugable Targets Using Molecular Docking, Molecular Dynamics Simulation, and MM-PBSA Approach
    (Frontiers Media S.A., 2021-08-12T00:00:00) Kushwaha, Prem Prakash; Singh, Atul Kumar; Bansal, Tanya; Yadav, Akansha; Prajapati, Kumari Sunita; Shuaib, Mohd; Kumar, Shashank
    The present study explores the SARS-CoV-2 drugable target inhibition efficacy of phytochemicals from Indian medicinal plants using molecular docking, molecular dynamics (MD) simulation, and MM-PBSA analysis. A total of 130 phytochemicals were screened against SARS-CoV-2 Spike (S)-protein, RNA-dependent RNA polymerase (RdRp), and Main protease (Mpro). Result of molecular docking showed that Isoquercetin potentially binds with the active site/protein binding site of the Spike, RdRP, and Mpro targets with a docking score of -8.22, -6.86, and -9.73 kcal/mole, respectively. Further, MS�3, 7-Hydroxyaloin B, 10-Hydroxyaloin A, showed -9.57, -7.07, -8.57 kcal/mole docking score against Spike, RdRP, and Mpro targets respectively. The MD simulation was performed to study the favorable confirmation and energetically stable complex formation ability of Isoquercetin and 10-Hydroxyaloin A phytochemicals in Mpro-unbound/ligand bound/standard inhibitor bound system. The parameters such as RMSD, RMSF, Rg, SASA, Hydrogen-bond formation, energy landscape, principal component analysis showed that the lead phytochemicals form stable and energetically stabilized complex with the target protein. Further, MM-PBSA analysis was performed to compare the Gibbs free energy of the Mpro-ligand bound and standard inhibitor bound complexes. The analysis revealed that the His-41, Cys145, Met49, and Leu27 amino acid residues were majorly responsible for the lower free energy of the complex. Drug likeness and physiochemical properties of the test compounds showed satisfactory results. Taken together, the study concludes that that the Isoquercetin and 10-Hydroxyaloin A phytochemical possess significant efficacy to bind SARS-Cov-2 Mpro active site. The study necessitates further in vitro and in vivo experimental validation of these lead phytochemicals to assess their anti-SARS-CoV-2 potential. � Copyright � 2021 Kushwaha, Singh, Bansal, Yadav, Prajapati, Shuaib and Kumar.
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    miRNAs as Therapeutic Target in Obesity and Cancer
    (Springer Singapore, 2021-07-18T00:00:00) Prajapati, Kumari Sunita; Shuaib, Mohd; Kushwaha, Prem Prakash; Singh, Atul Kumar; Sharma, Rahul; Kumar, Shashank
    MicroRNAs are small non-coding RNAs that regulate the expression of many genes. Alteration of microRNA expressions is associated with the occurrence of diseases including cancer, obesity, and obesity-related cancer. miRNAs are also known to regulate different cancer-related gene expressions indicating microRNAs could function as tumor suppressors and oncogenes. Obesity and cancer are the two critical diseases affecting millions of people all over the world. Obesity has been associated with incidence and a major risk factor for the occurrence of diseases like diabetes, cardiovascular disease, and various cancers. Synthesis of miRNAs-based therapeutics like miRNA mimics, anti-miR oligonucleotides is going on to cure obesity, cancer, and obesity-associated cancer. miRNAs emerged as a potential biomarker and being considered as a diagnostic, prognostic, and therapeutic target for the treatment of obesity, cancer, and obesity-associated cancer. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Taylor and Francis Pte Ltd. 2021.