Department Of Biochemistry And Microbial Sciences

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Acarbose Potentially Binds to the Type I Peptide Deformylase Catalytic Site and Inhibits Bacterial Growth: An In Silico and In Vitro Study
(Bentham Science Publishers, 2022-09-23T00:00:00) Singh, Atul Kumar; Prajapati, Kumari Sunita; Kumar, Shashank
Background: In bacteria, peptide deformylase (PDF), a metalloenzyme, removes N-formyl methio-nine from a nascent protein, which is a critical step in the protein maturation process. The enzyme is ubiqui-tously present in bacteria and possesses therapeutic target potential. Acarbose, an FDA-approved antidiabetic drug, is an alpha-glucosidase inhibitor of microbial origin. Clinical studies indicate that acarbose administration in humans can alter gut microbiota. As per the best of our knowledge, the antibacterial potential of acarbose has not been reported. Objective: The present study aimed to check the binding ability of acarbose to the catalytic site of E. coli PDF and assess its in vitro antibacterial activity. Methods: Molecular docking, molecular dynamic (MD) simulation, and MM-PBSA experiments were per-formed to study the binding potential of the catalytic site, and a disc diffusion assay was also employed to assess the antibacterial potential of acarbose. Results: Acarbose was found to form a hydrogen bond and interact with the metal ion present at the catalytic site. The test compound showed a better docking score in comparison to the standard inhibitor of PDF. MD simulation results showed energetically stable acarbose-PDF complex formation in terms of RMSD, RMSF, Rg, SASA, and hydrogen bond formation throughout the simulation period compared to the actinonin-PDF complex. Furthermore, MM-PBSA calculations showed better binding free energy (?G) of acarbose PDF than the actinonin-PDF complex. Moreover, acarbose showed in vitro antibacterial activity. Conclusion: Acarbose forms conformational and thermodynamically stable interaction with the E. coli peptide deformylase catalytic site. Results of the present work necessitate in-depth antimicrobial potential studies on the effect of acarbose on drug resistance and nonresistant bacteria. � 2022 Bentham Science Publishers.
Aldose Reductase: a cause and a potential target for the treatment of diabetic complications
(Pharmaceutical Society of Korea, 2021-07-19T00:00:00) Thakur, Sapna; Gupta, Sonu Kumar; Ali, Villayat; Singh, Priyanka; Verma, Malkhey
Diabetes mellitus, a disorder of metabolism, results in the elevation of glucose level in the blood. In this hyperglycaemic condition, aldose reductase overexpresses and leads to further complications of diabetes through the polyol pathway. Glucose metabolism-related disorders are the accumulation of sorbitol, overproduction of NADH and fructose, reduction in NAD+, and excessive NADPH usage, leading to diabetic pathogenesis and its complications such as�retinopathy, neuropathy, and nephropathy. Accumulation of sorbitol results in the alteration of osmotic pressure and leads to osmotic stress. The overproduction of NADH causes an increase in reactive oxygen species production which leads to oxidative stress. The overproduction of fructose causes cell death and non-alcoholic fatty liver disease. Apart from these disorders, many other complications have also been discussed in the literature. Therefore, the article overviews the aldose reductase as the causative agent and a potential target for the treatment of diabetic complications. So, aldose reductase inhibitors have gained much importance worldwide right now. Several inhibitors, like derivatives of carboxylic acid, spirohydantoin, phenolic derivatives, etc. could prevent diabetic complications are discussed in this article. � 2021, The Pharmaceutical Society of Korea.
Alterations in cellular metabolisms after Imatinib therapy: a review
(Springer, 2022-05-16T00:00:00) Kumar, Veerandra; Singh, Priyanka; Gupta, Sonu Kumar; Ali, Villayat; Jyotirmayee; Verma, Malkhey
Chronic myeloid leukemia (CML) is characterized by the possession of the Philadelphia chromosome, which contains the Bcr-Abl oncogene that codes for the oncoprotein BCR-ABL. Through glucose metabolism, glycolysis, and the translocation of the high-affinity glucose transporter to the cell surface, BCR-ABL modulates various signaling pathways in CML cells and maintains ATP turnover in tumor cells. Given the effective results of anti-tumor drugs in normalizing abnormal cellular metabolism, Imatinib (IM) has begun to be investigated and proven to be a highly potent tyrosine kinase inhibitor (TKI) in CML therapy. Initially, IM was tested for aberrant glucose metabolism, but all four metabolisms (glucose, lipid, amino acid, and nucleotide) are interrelated and enhance tumor growth under stress; eventually, the other three metabolisms were investigated. Subsequent effects of IM therapy showed a switch from glycolysis to the tricarboxylic acid cycle, upregulation of pentose phosphate pathway-associated oxidative pathways, and internal translocation of glucose transporters. In terms of lipid metabolism, IM had contradictory results: in one study, it served as a triglyceride and total cholesterol regulator, while in another study, it had no impact. The effect of IM on altered amino acid and nucleotide metabolisms was investigated using a multi-omics approach, which revealed a decrease in sulfur-containing amino acids, aromatic amino acids, and nucleotide biosynthesis. So, despite the mixed effect on cellular metabolism, IM has more positive effects, and therefore, the drug proved to be better than other TKIs. The present study is one approach to determine the transformative activities of IM against CML-associated metabolic changes, but further investigation is still needed to uncover more potentials of IM. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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.
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.
Anti-cancer drug doxorubicin induced cardiotoxicity: Understanding the mechanisms involved in ros generation resulting in mitochondrial dysfunction
(Rasayan Journal of Chemistry, c/o Dr. Pratima Sharma, 2020) Upadhayay, S; Sharma, N; Mantha, A.K; Dhiman, M.
Doxorubicin (DOX), despite being an effective anti-cancer drug has offsite targets that affect the vital organs such as heart, brain and kidney. DOX-induced cardiotoxicity is reported as a multi-factorial process that interferes with mitochondrial bioenergetics. These responses increase the threshold of oxidant-mediated injury and redox-mediated apoptosis in the cardiomyocytes. Oxidative stress particularly mitochondrial dysfunction in cardiomyocytes associated with cardiovascular diseases. In the present study we examined the effect of DOX on H9c2 cardiomyocyte where cells were treated with 5 μM DOX. To rule out the source of reactive oxygen species (ROS) during DOX-induced toxicity, the DOX-treated cardiomyocytes were incubated with 100 ?M diphenyleneiodonium (DPI), 50 μM salicyl hydroxamic acid (SHX), 20 μM Carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP), which are specific inhibitors of NADPH oxidase (NOX), Myeloperoxidase (MPO), and mitochondrial oxidative phosphorylation respectively and 10 μM N-acetyl cysteine (NAC, free radical scavenger) was also used to perceive the role of ROS. H2O2 (100 ?M) treated H9c2 cardiomyocytes were used as positive controls. The cell viability, reactive oxygen species (ROS) level and oxidative stress were determined using MTT assay, NBT assay/Flow-cytometry and Western blotting based assays. The effect of DOX on mitochondria was evaluated using Amplex Red assay; fluorescent probes such as MitoSOX and MitoTracker were used to examine the DOX-induced ROS production from the mitochondrial matrix. The mitochondrial membrane potential was evaluated using JC-1 dye. Western blotting was performed for cytochrome c release and apoptosis was examined with Annexin V-FITC assay. DOX was found to reduce cell viability, increase ROS level followed by enhanced oxidative stress in the form of protein carbonyls. DOX also showed a reduction in the mitochondrial membrane potential and allowed the release of cytochrome c which further leads to apoptosis and cell death. Further to rule out the pathway/mechanism(s) of DOX-mediated cardiac pathologies, the treatment with inhibitors of the classical ROS sources such as NADPH oxidase, Myeloperoxidase, mitochondria and general ROS scavenger (NAC) suggested that ROS via NOX and MPO during DOX-induced toxicity plays a crucial role in cardiomyocytes. The mitochondrial integrity was conserved when the cells were treated with NOX and MPO inhibitors, the cytochrome C release and apoptosis reduced in presence of these inhibitors. Taken together, these results demonstrate that DOX leads to ROS production and oxidative stress in cardiomyocytes which ultimately affects the mitochondrial integrity and functions, most importantly the ROS released via NOX and MPO is critical during DOX-induced cardiotoxicity. - RAS?YAN. All rights reserved.
Anti-inflammatory and immune-modulating effects of rice callus suspension culture (RCSC) and bioactive fractions in an in vitro inflammatory bowel disease model
(Elsevier GmbH, 2019) Driscoll K.; Deshpande A.; Chapp A.; Li K.; Datta R.; Ramakrishna W.
Background: Rice callus suspension culture (RCSC) has been shown to exhibit potent antiproliferative activity in multiple cancer cell lines. RCSC and its bioactive compounds can fill the need for drugs with no side effects. Hypothesis/Purpose: The anti-inflammatory potential of RCSC and its bioactive fractions on normal colon epithelial cell lines, was investigated. Study design: Three cell lines, InEpC, NCM356 and CCD841-CoN were treated with proinflammatory cytokines followed by RCSC. Cytoplasmic and nuclear ROS were assayed with fluorescent microscopy and flow cytometer. Expression analysis of immune-related genes was performed in RCSC-treated cell lines. RCSC was fractionated using column chromatography and HPLC. Pooled fractions 10–18 was used to test for antiproliferative activity using colon adenocarcinoma cell line, SW620 and anti-inflammatory activity using CCD841-CoN. Mass spectrometric analysis was performed to identify candidate compounds in four fractions. Results: RCSC treatment showed differential effects with higher cytoplasmic ROS levels in NCM356 and CCD841-CoN and lower ROS levels in InEpC. Nuclear generated ROS levels increased in all three treated cell lines. Flow cytometry analysis of propidium iodide stained cells indicated mitigation of cell death caused by inflammation in RCSC treated groups in both NCM356 and CCD841-CoN. Genes encoding transcription factors and cytokines were differentially regulated in NCM356 and CCD841-CoN cell lines treated with RCSC which provided insights into possible pathways. Analysis of pooled fractions 10–18 by HPLC identified 8 peaks. Cell viability assay with fractions 10–18 using SW620 showed that the number of viable cells were greatly reduced which was similar to 6X and 33X RCSC with very little effect on normal cells which similar to 1X RCSC. RCSC fractions increased nuclear and cytoplasmic ROS vs. both untreated and inflammatory control. Analysis of four fractions by mass spectrometry identified 4-deoxyphloridzin, 5?-methoxycurcumin, piceid and lupeol as candidate compounds which are likely to be responsible for the antiproliferative, anti-inflammatory and immune-regulating properties of RCSC. Conclusion: RCSC and its fractions showed anti-inflammatory activity on inflamed colon epithelial cells. Downstream target candidate genes which are likely to mediate RCSC effects were identified. Candidate compounds responsible for the antiproliferative and anti-inflammatory activity of RCSC and its fractions provide possible drug targets.
Anti-inflammatory and immune-modulating effects of rice callus suspension culture (RCSC) and bioactive fractions in an in vitro inflammatory bowel disease model.
(Elsevier, 2019) Driscoll, K; Deshpande, A; Chapp, A.; Li, K.; Datta, R.,; Ramakrishna Wusirika
Background: Rice Callus Suspension Culture (RCSC) has been shown to exhibit potent antiproliferative activity in multiple cancer cell lines. RCSC and its bioactive compounds can fill the need for drugs with no side effects. Hypothesis/Purpose: The anti-inflammatory potential of RCSC and its bioactive fractions on normal colon epithelial cell lines, was investigated. Study Design: Three cell lines, InEpC, NCM356 and CCD841-CoN were treated with proinflammatory cytokines followed by RCSC. Cytoplasmic and nuclear ROS were assayed with fluorescent microscopy and flow cytometer. Expression analysis of immune-related genes was performed in RCSC-treated cell lines. RCSC was fractionated using column chromatography and HPLC. Pooled fractions 10-18 was used to test for antiproliferative activity using colon adenocarcinoma cell line, SW620 and anti-inflammatory activity using CCD841-CoN. Mass spectrometric analysis was performed to identify candidate compounds in four fractions. Results: RCSC treatment showed differential effects with higher cytoplasmic ROS levels in NCM356 and CCD841-CoN and lower ROS levels in InEpC. Nuclear generated ROS levels increased in all three treated cell lines. Flow cytometry analysis of propidium iodide stained cells indicated mitigation of cell death caused by inflammation in RCSC treated groups in both NCM356 and CCD841-CoN. Genes encoding transcription factors and cytokines were differentially regulated in NCM356 and CCD841-CoN cell lines treated with RCSC which provided insights into possible pathways. Analysis of pooled fractions 10-18 by HPLC identified 8 peaks. Cell viability assay with fractions 10-18 using SW620 showed that the number of viable cells were greatly reduced which was similar to 6X and 33X RCSC with very little effect on normal cells which similar to 1X RCSC. RCSC fractions increased nuclear and cytoplasmic ROS versus both untreated and inflammatory control. Analysis of four fractions by mass spectrometry identified 4-deoxyphloridzin, 5’-methoxycurcumin, piceid and lupeol as candidate compounds which are likely to be responsible for the antiproliferative, anti-inflammatory and immune-regulating properties of RCSC.Conclusion: RCSC and its fractions showed anti-inflammatory activity on inflamed colon epithelial cells. Downstream target candidate genes which are likely to mediate RCSC effects were identified. Candidate compounds responsible for the antiproliferative and anti-inflammatory activity of RCSC and its fractions provide possible drug targets.
Anti-inflammatory Effects of Northern Highbush Blueberry Extract on an In Vitro Inflammatory Bowel Disease Model
(Routledge, 2019) Driscoll K.; Deshpande A.; Datta R.; Ramakrishna W.
Blueberry anthocyanins have the ability to efficiently reach the GI tract and exhibit a broad range of biochemical effects. In the context of inflammatory bowel disease (IBD), they remain a promising complement to current IBD treatments. Here, we investigated the anti-inflammatory and antioxidant capabilities of Highbush blueberries in-vitro on two normal colon epithelial cell lines, NCM 356 and CCD 841 CoN using fluorescent microscopy and flow cytometry following stimulation with a pro-inflammatory cytokine cocktail. Treatment with blueberry extract revealed a significant decrease in nuclear and cytoplasmic generated reactive oxygen species (ROS) compared to controls. Additionally, the blueberry extract increased cell viability following treatment with the pro-inflammatory cytokine cocktail. A comparison with previous report on rice callus suspension culture (RCSC) revealed opposing trend with reference to the levels of nuclear and cytoplasmic ROS. It is likely that blueberry extract and RCSC employ different players and pathways to mitigate inflammation.
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.
Antibacterial and Anticancer property of bioactive secondary metabolites from Actinomycetes isolated from different regions of Himachal Pradesh
(Central University of Punjab, 2018) Chambiyal, Gourav; Kushawaha Pramod K.
The prime objective of the present work is to isolate, characterize and purify soil microbes and to know about their antibacterial and anticancer properties. Soil samples were obtained from different locations in Dharamsala, Himachal Pradesh, India. Serial dilutions of the samples were made and plated on starch casein agar. Screening, purification and further tests were performed on the isolates to find the potential colonies. Biochemical and morphological characterization was done as well. Following characterization, isolates were used to extract bioactive secondary metabolites which can be anti-bacterial and anti-cancer. Secondary screening for antibacterial properties of isolates was evaluated by Agar well diffusion method. Further, the isolates were subjected to the GC-MS and MTT cytotoxic assay. Totally 7 isolates of actinomycetes were isolated and out of them only 4 were tested for antagonistic activity against 4 pathogenic microorganisms. Isolates M1,and M3 of dilution 10-1 were active, while M2 and M4 showed less activity against the pathogenic microorganisms. All actinomycetes isolates showed antibacterial activity against S. enterica and P. putida while they showed less activity against S. aureus and E.coli. These isolates showed antibacterial and anti-cancer activities and may be used for the growth of new antibiotics for pharmaceutical or agricultural purposes.
Anticancer Activities of Plant Secondary Metabolites: Rice Callus Suspension Culture as a New Paradigm
(Elsevier B.V., 2020-12-17T00:00:00) Ramakrishna, Wusirika; Kumari, Anuradha; Rahman, Nafeesa; Mandave, Pallavi
Plant natural products including alkaloids, polyphenols, terpenoids and flavonoids have been reported to exert anticancer activity by targeting various metabolic pathways. The biological pathways regulated by plant products can serve as novel drug targets. Plant natural compounds or their derivatives used for cancer treatment and some novel plant-based compounds which are used in clinical trials were discussed. Callus suspension culture with secondary metabolites can provide a continuous source of plant pharmaceuticals without time and space limitations. Previous research has shown that rice callus suspension culture can kill >95% cancer cells with no significant effect on the growth of normal cells. The role of candidate genes and metabolites which are likely to be involved in the process and their potential to serve as anticancer and anti-inflammatory agents were discussed. Large scale production of plant callus suspension culture and its constituents can be achieved using elicitors which enhance specific secondary metabolites combined with bioprocess technology. � 2020
Antileukemic Activity of hsa-miR-203a-5p by Limiting Glutathione Metabolism in Imatinib-Resistant K562 Cells
(MDPI, 2022-12-19T00:00:00) Singh, Priyanka; Yadav, Radheshyam; Verma, Malkhey; Chhabra, Ravindresh
Imatinib has been the first and most successful tyrosine kinase inhibitor (TKI) for chronic myeloid leukemia (CML), but many patients develop resistance to it after a satisfactory response. Glutathione (GSH) metabolism is thought to be one of the factors causing the emergence of imatinib resistance. Since hsa-miR-203a-5p was found to downregulate Bcr-Abl1 oncogene and also a link between this oncogene and GSH metabolism is reported, the present study aimed to investigate whether hsa-miR-203a-5p could overcome imatinib resistance by targeting GSH metabolism in imatinib-resistant CML cells. After the development of imatinib-resistant K562 (IR-K562) cells by gradually exposing K562 (C) cells to increasing doses of imatinib, resistant cells were transfected with hsa-miR-203a-5p (R+203). Thereafter, cell lysates from various K562 cell sets (imatinib-sensitive, imatinib-resistant, and miR-transfected imatinib-resistant K562 cells) were used for GC-MS-based metabolic profiling. L-alanine, 5-oxoproline (also known as pyroglutamic acid), L-glutamic acid, glycine, and phosphoric acid (Pi)�five metabolites from our data, matched with the enumerated 28 metabolites of the MetaboAnalyst 5.0 for the GSH metabolism. All of these metabolites were present in higher concentrations in IR-K562 cells, but intriguingly, they were all reduced in R+203 and equated to imatinib-sensitive K562 cells (C). Concludingly, the identified metabolites associated with GSH metabolism could be used as diagnostic markers. � 2022 by the authors.
Antioxidant, xanthine oxidase and monoamine oxidase inhibitory potential of coumarins: A review
(Bentham Science Publishers B.V., 2017) Dhiman, P.; Malik, N.; Khatkar, A.; Kulharia, M.
Excessive and persistent formation of ROS (reactive oxygen species) is a key factor in the origin of cancer, cardiac problems, inflammatory diseases, multiple organ dysfunction, aging and neurogenerative diseases. These ROS are produced from exogenous sources (ionizing radiation, chemicals and contaminants) and endogenous sources (Enzymes like Xanthine Oxidase and Monoamine Oxidase) which further originate a number of diseases along with genetic mutation. Due to the persistent side effects of synthetic antioxidants, there is flow towards naturally driven antioxidants as a large number of dietary supplements possess antioxidant potential. Coumarins are naturally occurring benzopyrones found in a variety of natural plants and exhibit different pharmacological properties. Among these activities the antioxidant potential of coumarins has been extensively studied that has been reviewed in this paper. ? 2017 Bentham Science Publishers.
Antitubercular drugs: possible role of natural products acting as antituberculosis medication in overcoming drug resistance and drug-induced hepatotoxicity
(Springer Science and Business Media Deutschland GmbH, 2023-09-04T00:00:00) Rana, Harvesh Kumar; Singh, Amit Kumar; Kumar, Ramesh; Pandey, Abhay K.
Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium which causes tuberculosis (TB). TB control programmes are facing threats from drug resistance. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains need longer and more expensive treatment with many medications resulting in more adverse effects and decreased chances of treatment outcomes. The World Health Organization (WHO) has emphasised the development of not just new individual anti-TB drugs, but also novel medication regimens as an alternative treatment option for the drug-resistant Mtb strains. Many plants, as well as marine creatures (sponge; Haliclona sp.) and fungi, have been continuously used to treat TB in various traditional treatment systems around the world, providing an almost limitless supply of active components. Natural products, in addition to their anti-mycobacterial action, can be used as adjuvant therapy to increase the efficacy of conventional anti-mycobacterial medications, reduce their side effects, and reverse MDR Mtb strain due to Mycobacterium�s genetic flexibility and environmental adaptation. Several natural compounds such as quercetin, ursolic acid, berberine, thymoquinone, curcumin, phloretin, and propolis have shown potential anti-mycobacterial efficacy and are still being explored in preclinical and clinical investigations for confirmation of their efficacy and safety as anti-TB medication. However, more high-level randomized clinical trials are desperately required. The current review provides an overview of drug-resistant TB along with the latest anti-TB medications, drug-induced hepatotoxicity and oxidative stress. Further, the role and mechanisms of action of first and second-line anti-TB drugs and new drugs have been highlighted. Finally, the role of natural compounds as anti-TB medication and hepatoprotectants�have been described and their mechanisms discussed. � 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Application of CRISPR�Cas9 in plant�plant growth-promoting rhizobacteria interactions for next Green Revolution
(Springer Science and Business Media Deutschland GmbH, 2021-11-13T00:00:00) Singh, Sudiksha; Ramakrishna, Wusirika
Agriculture's beginnings resulted in the domestication of numerous plant species as well as the use of natural resources. Food grain production took about 10,000�years to reach a billion tonnes in 1960, however, it took only 40�years to achieve 2 billion tonnes in year 2000. The creation of genetically modified crops, together with the use of enhanced agronomic practices, resulted in this remarkable increase, dubbed the "Green Revolution". Plants and bacteria that interact with each other in nature are co-evolving, according to Red Queen dynamics. Plant microorganisms, also known as plant microbiota, are an essential component of plant life. Plant�microbe (PM) interactions can be beneficial or harmful to hosts, depending on the health impact. The significance of microbiota in plant growth promotion (PGP) and stress resistance is well known. Our understanding of the community composition of the plant microbiome and important driving forces has advanced significantly. As a result, utilising the plant microbiota is a viable strategy for the next Green Revolution for meeting food demand. The utilisation of newer methods to understand essential genetic and molecular components of the multiple PM interactions is required for their application. The use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-mediated genome editing (GE) techniques to investigate PM interactions is of tremendous interest. The implementation of GE techniques to boost the ability of microorganisms or plants for agronomic trait development will be enabled by a comprehensive understanding of PM interactions. This review focuses on using GE approaches to investigate the principles of PM interactions, disease resistance, PGP activity, and future implications in agriculture in plants or associated microbiota. � 2021, King Abdulaziz City for Science and Technology.
Assessment of Extract of Syzygium cumini Against Doxorubicin Induced Cardiotoxicity
(Central University of Punjab, 2018) Chayan, Mukherjee; Monisha Dhiman
For the past four decades, doxorubicin (DOX) has been used to treat cancer, mainly solid tumours and haematological malignancies. However, clinical community is greatly concerned regarding the administration of this as DOX treatment is commonly associated with dose-dependent cardiotoxicity. Attempts at alleviating drug generated cardiac damage using an extract from different parts of plants with radical scavenging property are a promising area of research. Hydroalcoholic extract derived from fruit pulp of Syzygiumcumini which has a significant antiradical scavenging effect. This study aims to assess the effect of parallel administration of SC fruit pulp extract (SC) on mitigating or preventing DOX induced cardiotoxicity in vitro using H9c2 cardiomyoblast cell lines. Addition of SC fruit pulp extract and DOX were performed for both treatment and control sets on H9c2 cells. SC fruit pulp extract showed strong ABTS cation radical scavenging activity in a dose dependent manner. MTT assay was used to study the cytotoxic effect of SC fruit pulp extract and DOX. ROS levels were estimated using NBT assay and DHE assay. The results showed that DOX has significant cytotoxic effect in a dose dependent manner while SC fruit pulp extract did not display any significant cytotoxicity on H9c2 cells. The DOX induced ROS production was found to be significantly reduced in SC fruit pulp extract treated cells. Results of the current study also suggest that the treatment of SC fruit pulp extract along with DOX, displayed cardioprotective potential in H9c2 cells by: 1) reducing lipid peroxidation; 2) decreasing extracellular nitric oxide (NO); 3) decreasing the expression of the protein p47phox and iNOS/NOS-2. These results clearly suggest that treatment of SC fruit pulp extract along with DOX reduces the DOX induced toxicity and hence can be a promising therapeutic intervention in managing DOX mediated cardiotoxicity.
Assessment of risk conferred by coding and regulatory variations of TMPRSS2 and CD26 in susceptibility to SARS-CoV-2 infection in human
(Springer, 2020) Senapati, S; Kumar, S; Singh, A.K; Banerjee, P; Bhagavatula, S.
At present, more than 200 countries and territories are directly affected by the coronavirus disease-19 (COVID-19) pandemic. Incidence and case fatality rate are significantly higher among elderly individuals (age > 60 years), type 2 diabetes and hypertension patients. Cellular receptor ACE2, serine protease TMPRSS2 and exopeptidase CD26 (also known as DPP4) are the three membrane bound proteins potentially implicated in SARS-CoV-2 infection. We hypothesised that common variants from TMPRSS2 and CD26 may play critical role in infection susceptibility of predisposed population or group of individuals. Coding (missense) and regulatory variants from TMPRSS2 and CD26 were studied across 26 global populations. Two missense and five regulatory SNPs were identified to have differential allelic frequency. Significant linkage disequilibrium (LD) signature was observed in different populations. Modelled protein?protein interaction (PPI) predicted strong molecular interaction between these two receptors and SARS-CoV-2 spike protein (S1 domain). However, two missense SNPs, rs12329760 (TMPRSS2) and rs1129599 (CD26), were not found to be involved physically in the said interaction. Four regulatory variants (rs112657409, rs11910678, rs77675406 and rs713400) from TMPRSS2 were found to influence the expression of TMPRSS2 and pathologically relevant MX1. rs13015258 a 5? UTR variant from CD26 have significant role in regulation of expression of key regulatory genes that could be involved in SARS-CoV-2 internalization. Overexpression of CD26 through epigenetic modification at rs13015258-C allele was found critical and could explain the higher SARS-CoV-2 infected fatality rate among type 2 diabetes. 2020, Indian Academy of Sciences.
Association of elevated levels of C-reactive protein with breast cancer, breast cancer subtypes, and poor outcome
(Mosby Inc., 2019) Kaur R.P.; Rubal; Banipal R.P.S.; Vashistha R.; Dhiman M.; Munshi A.
Background and Purpose: Inflammation and caner are linked in a bidirectional manner. C-reactive protein (CRP) is an important inflammatory marker. The aim of the study was to test whether the inflammatory marker, CRP at the time of diagnosis of breast cancer is associated with metastasis, recurrence, and death in breast cancer patients from Malwa region of Punjab where breast cancer is widely feared. Material and Methods: Two hundred and forty-two breast cancer patients and 242 age and sex matched controls were included in the study. CRP levels were estimated using fully automated bio analyzer Erba200. Follow up interviews were conducted at an interval of 3, 6, 9, 12, 15, 18, 21, 24, and 27 months to determine the outcome among breast cancer patients. Results: Elevated levels of CRP were found among the diseased in comparison with controls (P < 0.0001). Higher CRP levels associated significantly with poor outcome including metastasis and recurrence among breast cancer patients [P = 0.03; 95% confidence interval; odds ratio: 2.954 (0.9125-9.561)]. Conclusion: Elevated levels of CRP associated significantly with increased risk of breast cancer and poor outcome. CRP estimation may be a simple and inexpensive tool for the risk assessment and outcome of the disease in Malwa region of Punjab where incidence of breast cancer is reported to be very high.
Association of elevated levels of C-reactive protein with breast cancer, breast cancer subtypes, and poor outcome
(Mosby Inc., 2018) Kaur, R.P.; Rubal, Banipal,; Vashistha, R.; Dhiman, Monisha; Munshi, Anjana
Background and Purpose: Inflammation and caner are linked in a bidirectional manner. C-reactive protein (CRP) is an important inflammatory marker. The aim of the study was to test whether the inflammatory marker, CRP at the time of diagnosis of breast cancer is associated with metastasis, recurrence, and death in breast cancer patients from Malwa region of Punjab where breast cancer is widely feared. Material and Methods: Two hundred and forty-two breast cancer patients and 242 age and sex matched controls were included in the study. CRP levels were estimated using fully automated bio analyzer Erba200. Follow up interviews were conducted at an interval of 3, 6, 9, 12, 15, 18, 21, 24, and 27 months to determine the outcome among breast cancer patients. Results: Elevated levels of CRP were found among the diseased in comparison with controls (P < 0.0001). Higher CRP levels associated significantly with poor outcome including metastasis and recurrence among breast cancer patients [P = 0.03; 95% confidence interval; odds ratio: 2.954 (0.9125-9.561)]. Conclusion: Elevated levels of CRP associated significantly with increased risk of breast cancer and poor outcome. CRP estimation may be a simple and inexpensive tool for the risk assessment and outcome of the disease in Malwa region of Punjab where incidence of breast cancer is reported to be very high. ? 2018