School Of Basic And Applied Sciences
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Item ATG5: A central autophagy regulator implicated in various human diseases(John Wiley and Sons Ltd, 2022-09-05T00:00:00) Changotra, Harish; Kaur, Sargeet; Yadav, Suresh Singh; Gupta, Girdhari Lal; Parkash, Jyoti; Duseja, AjayAutophagy, an intracellular conserved degradative process, plays a central role in the renewal/recycling of a cell to maintain the homeostasis of nutrients and energy within the cell. ATG5, a key component of autophagy, regulates the formation of the autophagosome, a hallmark of autophagy. ATG5 binds with ATG12 and ATG16L1 resulting in E3 like ligase complex, which is necessary for autophagosome expansion. Available data suggest that ATG5 is indispensable for autophagy and has an imperative role in several essential biological processes. Moreover, ATG5 has also been demonstrated to possess autophagy-independent functions that magnify its significance and therapeutic potential. ATG5 interacts with various molecules for the execution of different processes implicated during physiological and pathological conditions. Furthermore, ATG5 genetic variants are associated with various ailments. This review discusses various autophagy-dependent and autophagy-independent roles of ATG5, highlights its various deleterious genetic variants reported until now, and various studies supporting it as a potential drug target. � 2022 John Wiley & Sons Ltd.Item Association of IRGM gene promoter polymorphisms with hepatitis B virus infection(John Wiley and Sons Inc, 2022-06-04T00:00:00) Sharma, Ambika; Duseja, Ajay; Parkash, Jyoti; Changotra, HarishBackground: In response to intracellular pathogens, the autophagy gene IRGM plays an essential role in the innate immune response. Various identified IRGM gene risk loci are associated with several diseases but, so far, no study is available that shows the association of IRGM with hepatitis B virus (HBV) infection. Methods: We genotyped promoter variants (rs4958842, rs4958843, and rs4958846) of IRGM in HBV infected patients (551) and healthy controls (247) for their role in HBV infection. The genotyping was performed by applying methods developed in our laboratory and various biochemical parameters were assessed applying commercially available kits. Results: Data analysis has shown that the mutant allele A of rs4958842 plays a role in the protection from HBV infection in various genetic models that includes allelic, co-dominant and dominant models with the respective statistical data: allelic (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.48�0.78; p = 0.0003), co-dominant (OR = 0.52; 95% CI = 0.38�0.71; p = 0.0008) and dominant (OR = 0.51; 95% CI = 0.38�0.70, p = 0.0004). In chronic hepatitis B (CHB), protective association was observed in the allelic (OR = 0.48; 95% CI = 0.35�0.65, p = 0.0004), co-dominant (OR = 0.38; 95% CI = 0.26�0.54, p = 0.0004) and dominant (OR = 0.38; 95% CI = 0.26�0.54, p = 0.0002) models. Mutant allele C of rs49598843 was associated with the risk of CHB in co-dominant (OR = 1.52; 95% CI = 1.07�2.16, p = 0.04) and dominant (OR = 1.41; 95% CI = 1.00�2.00, p = 0.04) models. The mutant allele C of rs4958846 decreased the risk of HBV infection in allelic (OR = 0.74; 95% CI = 0.59�0.92, p = 0.01), dominant (OR = 0.72; 95% CI = 0.53�0.98, p = 0.05), homozygous (OR = 0.42; 95% CI = 0.24�0.74, p = 0.01) and recessive (OR = 0.42; 95% CI = 0.24�0.74, p = 0.0004) models. However, in the asymptomatic group, it was associated with the increased chance of HBV infection. Haplotypes, ATT (OR = 0.47; 95% CI = 0.33�0.68, p = 0.001) and GTC (OR = 0.68; 95% CI = 0.51�0.92, p = 0.01) protect, whereas GTT (OR = 2.01; 95% CI = 1.55�2.60, p < 0.0001) predisposes the individuals to HBV infection. All of these p�values mentioned here were obtained after performing Bonferroni correction. Conclusions: In conclusion, our findings revealed that mutant allele A of rs4958842, mutant allele C of rs4958843 and rs4958846 were associated with hepatitis B virus infection in the North Indian population. � 2022 John Wiley & Sons Ltd.Item Tinospora cordifolia: a potential neuroprotective agent against various neurodegenerative diseases(Elsevier GmbH, 2023-09-19T00:00:00) Singh, Randeep; Bhattacharyya, Chinmoyee; Prashar, Vikash; Arora, Tania; Sharma, Arti; Changotra, Harish; Parkash, JyotiIntroduction: Neurodegenerative diseases negatively affect the various neuronal populations of the central nervous system (CNS). Moreover, conventional treatment strategies are inefficient and have considerable side effects. Since Ayurveda has always been considered an effective alternative to synthetic drugs, Tinospora cordifolia, an age-old renowned herb in Ayurveda with great medicinal importance, is drawing the attention of researchers. The effect of the crude extract of T. cordifolia and its constituents in alleviating neurodegenerative diseases has been reported previously and recently. Methods: This study followed thorough research on scientific databases like PubMed, Google Scholar, and ScienceDirect regarding the practical implications of T. cordifolia extracts and compounds in alleviating neurodegeneration. Various search terms like �neurodegenerative diseases�, �T. cordifolia and neurodegeneration�, �signalling mechanisms of neurodegeneration�, and �neuroprotective effect of T. cordifolia� have been used. Results: Several in vitro studies have suggested that T. cordifolia extracts and compounds can improve memory, cognition, and learning deteriorated by various neurodegenerative diseases. They also enhance the potential of the antioxidant system by restoring Glutathione (GSH) and Superoxide dismutase (SOD) levels and scavenging the free radicals that cause neuronal oxidative stress and neurodegeneration. Conclusion: This review article summarises the various aspects of T. cordifolia against different neurodegenerative diseases and its future potential therapeutic values. It also emphasises the need to investigate other compounds present in T. cordifolia. Limitations and future prospects: Exploring anti-oxidative, anti-inflammatory, and neuroprotective properties proved T. cordifolia to be a life saviour. Despite this, extensive clinical and pharmacological studies are required to evaluate the precise dosage and formulation of its constituents. � 2023 Elsevier GmbHItem The Comparative Genomics and Network Analysis of eNOS by Using Different Bioinformatics Approaches(Bentham Science Publishers, 2023-01-27T00:00:00) Banerjee, Arpita; Singh, Randeep; Arora, Nymphaea; Arora, Tania; Prashar, Vikash; Godara, Priya; Sharma, Arti; Changotra, Harish; Parkash, JyotiBackground: Nitric oxide synthase (NOS) is an enzyme that catalyzes the synthesis of nitric oxide (NO) from L-arginine. It has three isoforms-(i) neuronal NOS (nNOS or NOS1), which participates in neural transmission; (ii) inducible NOS (iNOS or NOS2), which produces NO in macrophages; and (iii) endothelial NOS (eNOS or NOS3) that regulates blood pressure. The eNOS is mainly expressed in blood vessels and is a crucial regulator of endothelial homeostasis. Objective: The present study aimed to unravel the role of eNOS in different signaling pathways and its involvement as a therapeutic target in various neurodegenerative disorders. Methods: This study used various in silico methods for comprehensive genomic analysis of eNOS in 16 organisms from 7 different phyla. Prediction of conserved domains and evolutionary relationship for eNOS among 16 organisms was made. Various physical and chemical parameters, signal peptides, and transmembrane regions that helped understand its functional relevance were also studied. Results: Three transcription factor binding sites (TFBS), i.e., CP2, AR, and LDSPOLYA, were identified in human eNOS, while ATF1, T3R, and STAT1 were predicted in mouse eNOS. Transcription factors were identified for each regulatory region in human as well as mouse eNOS. eNOS protein was predicted to harbor 14 different post-translational modification (PTM) sites, most of which have phosphorylation (serine followed by threonine and tyrosine phosphorylation) followed by sumoylation and palmitoylation among all the organisms used in the current study. However, human eNOS has a relatively lower number of PTM sites for tyrosine phosphorylation. Conclusion: Structures of eNOS isoform, consistent with available biochemical and structural data, provide substantial insight into the NOS conformational changes, which give in-depth knowledge of the mechanism of eNOS, and will be helpful for better understanding the role of eNOS in pathophysiology. � 2023 Bentham Science Publishers.Item Dysregulated miRNAs in Progression and Pathogenesis of Alzheimer�s Disease(Springer, 2022-07-22T00:00:00) Arora, Tania; Prashar, Vikash; Singh, Randeep; Barwal, Tushar Singh; Changotra, Harish; Sharma, Arti; Parkash, JyotiAlzheimer�s disease (AD) is a progressive degeneration of neurons due to the accumulation of amyloid-? peptide (A?) and hyper-phosphorylation of tau protein in the neuronal milieu leading to increased oxidative stress and apoptosis. Numerous factors contribute towards the progression of AD, including miRNA, which are 22�24 nucleotides long sequence which acts as critical regulators of cellular processes by binding to 3? UTR of mRNA, regulating its expression post-transcriptionally. This review aims to determine the miRNA with the most significant dysregulation in the brain and cerebrospinal fluid (CSF) of human patients. A systemized inclusion/exclusion criterion has been utilized based on selected keywords followed by screening of those articles to conclude a list of 8 highly dysregulated miRNAs based on the fold change of AD vs control patients, which could be used in clinical testing as these miRNAs play central role in the pathophysiology of AD. Furthermore, a network study of highly dysregulated miRNA estimated the association of these miRNA in the mediation of A? generation and aggregation, inhibition of autophagy, reduction of A? clearance, microglial and astrocytic activation, neuro-inflammation, tau hyper-phosphorylation, and synaptic loss. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.