Zoology - Research Publications

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    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, Ajay
    Autophagy, 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.
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    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, Harish
    Background: 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.
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    Gametogenic and steroidogenic action of kisspeptin-10 in the Asian catfish, Clarias batrachus: Putative underlying mechanistic cascade
    (Elsevier Inc., 2021-06-28T00:00:00) Singh, Ankur; Lal, Bechan; Parkash, Jyoti; Millar, Robert P.
    Unlike mammals, two kisspeptins genes encoding, kiss1 and kiss2 are detected in fishes with highly varied and contradictory difference in their reproductive activities. The present study was undertaken to examine the direct action of kisspeptin-10 and its role in gonadal activities in the gonadally quiescent Asian catfish using native mammalian kisspeptin decapeptide (KP-10) involving in vivo and in vitro approaches. The in vivo KP-10 treatment caused precocious onset of gametogenesis and its rapid progression, as was evident from the appearance of advanced stages of ovarian follicles in ovary, and advanced germ cells (spermatocytes/ spermatids) in the testis of the treated Clarias batrachus in comparison to the control gonads. It also elevated the steroid levels in gonads of the catfish in vivo and in vitro conditions. Simultaneously, it increased the expressions of key steroidogenic enzymes like 3?-HSD, 17?-HSD, and StAR protein, responsible for transfer of cholesterol from outer to inner membrane of the mitochondria of steroidogenic cells. Concurrently, it augmented the activities of 3?-HSD and 17?-HSD in the ovarian explants. The expressions of MAPK component (pERK1/2 and ERK1/2) were also up-regulated by KP-10 in gonadal explants. Thus, the data suggest that kisspeptin-10 stimulates gametogenesis by enhancing gonadal steroid production. The study also describes the putative mechanistic cascade of steroidogenic actions of kisspeptin-10 in the catfish so much so in teleost fish. The study also suggests that, kisspeptin may act locally to regulate gonadal activities in an autocrine/paracine manner, independent of known extra-gonadal factors in the catfish. � 2021 Elsevier Inc.
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    Nanotoxicology: Toxicity Evaluation, Risk Assessment and Management
    (CRC Press Taylor and Francis group, 2018) Parkash, Jyoti; Sharma, Arti; Jairath, Ankur
    Nanoparticles have an interesting surface chemistry and are used in a wide variety of applications ranging from consumer products like socks, medical dressings, and computer chips. They have also been shown antimicrobial, anti-bacterial activity and wound healing properties. The small size of the particles makes nanotechnology so useful for the drug delivery system, but this small size is also one of the main factors that make them a potential threat to human health. Nanomedicines have played a very important role in the field of diagnosis and therapy in the past decade and still continue to be an important element of success in the field of medicine. The effect of nanoparticles on the proliferation and differentiation of stem cells has been studied under regeneration medicine and material science. However, advances in nanotechnology innovation related to stem cell biology and cell reprogramming remain less progressive. It is very crucial to study the cell-nanoparticle interactions in depth to eradicate any negative effects of the nanoparticles. The cellular toxicity of nanoparticles has been extensively studied in Mesenchymal-epithelial stem cells (mESCs) and human mesenchymal stem cells (hMSCs). Investigations purporting to study the toxicity of metal particulates are still in their infancy at this time and have concentrated on revealing the toxicity, tissue distribution, and antibacterial properties of metallic nanoparticles, and in addition the tissue distribution and cellular uptake of gold nanoparticles. Therefore, more study is needed to understand the role of these nanoparticles on human health.