Browsing by Author "Poddar, N.K."
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Item Deciphering the enigmatic crosstalk between prostate cancer and Alzheimer's disease: A current update on molecular mechanisms and combination therapy(Elsevier, 2022) Poddar, N.K.; Agrawal, D.; Agrawal, Y.; Wijayasinghe, Y.S.; Mukherjee, A.; Khan, S.Alzheimer's disease (AD) and prostate cancer (PCa) are considered the leading causes of death in elderly people worldwide. Although both these diseases have striking differences in their pathologies, a few underlying mechanisms are similar when cell survival is considered. In the current study, we employed an in-silico approach to decipher the possible role of bacterial proteins in the initiation and progression of AD and PCa. We further analyzed the molecular connections between these two life-threatening diseases. The androgen deprivation therapy used against PCa has been shown to promote castrate resistant PCa as well as AD. In addition, cell signaling pathways, such as Akt, IGF, and Wnt contribute to the progression of both AD and PCa. Besides, various proteins and genes are also common in disease progression. One such similarity is mTOR signaling. mTOR is the common downstream target for many signaling pathways and plays a vital role in both PCa and AD. Targeting mTOR can be a favorable line of treatment for both AD and PCa. However, drug resistance is one of the challenges in effective drug therapy. A few drugs that target mTOR have now become ineffective due to the development of resistance. In that regard, phytochemicals can be a rich source of novel drug candidates as they can act via multiple mechanisms. This review also presents mTOR targeting phytochemicals with promising anti-PCa, anti-AD activities, and approaches to overcome the issues associated with phytochemical-based therapies in clinical trials.Item Implications of trimethylamine N-oxide (TMAO) and betaine in human health: beyond being osmoprotective compounds(Frontiers Media, 2022) Ilyas, A.; Wijayasinghe, Y.S.; Khan, I.; Samaloty, N.M.E.; Adnan, M.; Dar, T.A.; Poddar, N.K.; Singh, L.R.; Sharma, H.; Khan, S.Osmolytes are naturally occurring small molecular weight organic molecules, which are accumulated in large amounts in all life forms to maintain the stability of cellular proteins and hence preserve their functions during adverse environmental conditions. Trimethylamine N-oxide (TMAO) and N,N,N-trimethylglycine (betaine) are methylamine osmolytes that have been extensively studied for their diverse roles in humans and have demonstrated opposing relations with human health. These osmolytes are obtained from food and synthesized endogenously using dietary constituents like choline and carnitine. Especially, gut microbiota plays a vital role in TMAO synthesis and contributes significantly to plasma TMAO levels. The elevated plasma TMAO has been reported to be correlated with the pathogenesis of numerous human diseases, including cardiovascular disease, heart failure, kidney diseases, metabolic syndrome, etc.; Hence, TMAO has been recognized as a novel biomarker for the detection/prediction of several human diseases. In contrast, betaine acts as a methyl donor in one-carbon metabolism, maintains cellular S-adenosylmethionine levels, and protects the cells from the harmful effects of increased plasma homocysteine. Betaine also demonstrates antioxidant and antiinflammatory activities and has a promising therapeutic value in several human diseases, including homocystinuria and fatty liver disease. The present review examines the multifarious functions of TMAO and betaine with possible molecular mechanisms towards a better understanding of their emerging and diverging functions with probable implications in the prevention, diagnosis, and treatment of human diseases.Item Nano-osmolyte conjugation: Tailoring the osmolyte-protein interactions at the nanoscale(American Chemical Society, 2023) Sharma, H.; Dar, T.A.; Wijayasinghe, Y.S.; Sahoo, D.; Poddar, N.K.Osmolytes are small organic compounds accumulated at higher concentrations in the cell under various stress conditions like high temperature, high salt, high pressure, etc. Osmolytes mainly include four major classes of compounds including sugars, polyols, methylamines, and amino acids and their derivatives. In addition to their ability to maintain protein stability and folding, these osmolytes, also termed as chemical chaperones, can prevent protein misfolding and aggregation. Although being efficient protein folders and stabilizers, these osmolytes exhibit certain unavoidable limitations such as nearly molar concentrations of osmolytes being required for their effect, which is quite difficult to achieve inside a cell or in the extracellular matrix due to nonspecificity and limited permeability of the blood-brain barrier system and reduced bioavailability. These limitations can be overcome to a certain extent by using smart delivery platforms for the targeted delivery of osmolytes to the site of action. In this context, osmolyte-functionalized nanoparticles, termed nano-osmolytes, enhance the protein stabilization and chaperone efficiency of osmolytes up to 105 times in certain cases. For example, sugars, polyols, and amino acid functionalized based nano-osmolytes have shown tremendous potential in preventing protein aggregation. The enhanced potential of nano-osmolytes can be attributed to their high specificity at low concentrations, high tunability, amphiphilicity, multivalent complex formation, and efficient drug delivery system. Keeping in view the promising potential of nano-osmolytes conjugation in tailoring the osmolyte-protein interactions, as compared to their molecular forms, the present review summarizes the recent advancements of the nano-osmolytes that enhance the protein stability/folding efficiency and ability to act as artificial chaperones with increased potential to prevent protein misfolding disorders. Some of the potential nano-osmolyte aggregation inhibitors have been highlighted for large-scale screening with future applications in aggregation disorders. The synthesis of nano-osmolytes by numerous approaches and future perspectives are also highlighted.Item Natural products: A rich source of antiviral drug lead candidates for the management of COVID-19(Bentham Science Publishers, 2021) Wijayasinghe, Y.S.; Bhansali, P.; Viola, R.E.; Kamal, M.A.; Poddar, N.K.ABSTRACT: Today, the world is suffering from the pandemic of a novel coronavirus disease (COVID-19), a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the third fatal coronavirus outbreak that has already occurred in the 21st century. Even six months after its emergence, hundreds of thousands of people are still being infected with SARS-CoV-2, and thousands of lives are lost every day across the world. No effective therapy has been approved to date for the prevention or treatment of this disease, suggesting the need to broaden the scope in the search for effective treatments. Throughout history, folk medicine has been successfully used to treat various ailments in humans and Traditional Chinese Medicine has been instrumental in the containment of a number of viral diseases. Owing to their high chemical diversity and safety profiles, natural products offer great promises as potentially effective antiviral drugs. In recent years, a large number of anti-coronaviral phytochemicals with different mechanisms of action have been identified. Among them, tetra-O-galloyl-β-D-glucose, caffeic acid, and saikosaponin B2 block viral entry. A number of flavonoids inhibit viral proteases. Silvestrol inhibits protein synthesis. Myricetin and scutellarein inhibit viral replication. Emodin, luteolin, and quercetin demonstrate anti-coronaviral activity by inhibiting multiple processes in the virus life cycle. In this review, we critically evaluate the findings of the natural product-based anti-coronaviral research that has been published during last two decades, and attempt to provide a comprehensive description about their utility as potential broad-spectrum anti-coronaviral drugs, examining leads that may guide/facilitate anti-SARS-CoV-2 drug development studies. KEYWORDS: COVID-19; Coronavirus; Natural products; Phytochemicals; SARS-CoV-2; Traditional Medicine.