Browsing by Author "Susheel Nidhi Chaurasia"

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Ayurvedic preparations of Raudra Rasa inhibit agonist-mediated platelet activation and restrict thrombogenicity without affecting cell viability
(John Wiley and Sons Inc, 2023) Susheel Nidhi Chaurasia; Vipin Singh; Mohammad Ekhlak; Manoj Kumar Dash; Namrata Joshi; Debabrata Dash
Ayurveda is considered to be one of the most ancient forms of medicine still practiced. The Ayurvedic preparation Raudra Rasa and its derivatives have been widely employed against cancer since the 12th century, but the effect of these traditional formulations on platelet function and signaling has not previously been examined. Here we demonstrate that Raudra Rasa and its derivatives significantly reduce thrombin-induced integrin activation and granule secretion in platelets, as observed by reduced PAC-1 binding and P-selectin externalization, respectively. These formulations also inhibited thrombin-stimulated phosphatidylserine exposure, mitochondrial reactive oxygen species generation, and mitochondrial transmembrane potential in platelets. Consistent with the above, Raudra Rasa significantly reduced thrombin-induced tyrosine phosphorylation of the platelet proteins, as well as phosphorylation of the enzymes AKT and GSK-3β. In summary, Raudra Rasa inhibits agonist-mediated platelet activation without affecting cell viability, suggesting it may have therapeutic potential as an anti-platelet/anti-thrombotic agent. © 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Casein kinase I isoforms contribute to platelet activation and thrombogenesis via RIPK3–MLKL signaling
(Nature Research, 2025) Vipin Singh; Mohammad Ekhlak; Susheel Nidhi Chaurasia; Debabrata Dash
Platelets are small, enucleate blood cells having life span of 10-12 days that play fundamental role in hemostasis and thrombosis. Casein Kinase 1 (CK1) is a serine/threonine-specific protein kinase that governs multiple cellular processes including circadian rhythm, morphogen signaling and apoptosis; however, its role in platelet biology and thrombogenesis remains unexplored. Employing a CK1-specific pharmacological inhibitors, we demonstrate here a pivotal role of CK1 in agonist-induced platelet activation. Inhibition of CK1 disrupts platelet functions that include aggregation, integrin activation, interaction with leukocytes, and thrombus formation under arterial shear ex vivo as well as in a murine model of thrombosis. CK1 maintains mitochondrial integrity by stabilizing inner mitochondrial membrane that propels energy metabolism in activated platelets. Notably, CK1 inhibition suppresses phosphorylation of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL), key arbiters of platelet activation leading to necroptosis, thus mechanistically linking CK1 activity to platelet prothrombotic responses. Downregulation of CK1 did not affect primary hemostasis nor platelet viability while significantly deferring thrombus formation, which underscores its potential as a safe therapeutic option against thrombotic disorders. This study uncovers an emerging role of CK1 in unleashing of prothrombotic phenotype and positions CK1 as a potential target for antithrombotic measures. © The Author(s) 2025.
Intermittent drought adversely impacts monogenic resistance of rice to the blast pathogen Magnaporthe oryzae and is associated with alteration in histone acetylation
(Springer Science and Business Media Deutschland GmbH, 2025) Jhumishree Meher; Srikanta K. Lenka; Umapathy Keerthana; Susheel Nidhi Chaurasia; Ankita Sarkar; Birinchi Kumar Sarma
Aims: Climate change is affecting rainfall patterns causing intermittent drought stress to rainfed rice. It is poorly understood how intermittent drought impacts the blast of rice incited by Magnaporthe oryzae. Methods: The impact of intermittent drought on virulence factors of Magnaporthe oryzae and defense responses in blast resistant (C101A51 and Tetep), susceptible (HR-12) and drought-tolerant (Vandana) rice cultivars was analyzed in stress overlapped conditions. Transcript accumulation of rice defense genes, histone acetyltransferases (OsHATs) and pathogenesis-associated genes of M. oryzae was recorded and histone acetylation at H3K9 and H4K5 was assessed through western blotting. Results: Predisposition to intermittent drought favored blast development in all rice cultivars. Higher blast resistance in C101A51 is linked to enhanced histone acetylation at H3K9 compared to Tetep. However, intermittent drought predisposition caused partial breakdown of blast resistance due to reduced OsHAT activities that led to reduced histone acetylation at H3K9. ABA signaling was predominant in drought predisposed and M. oryzae challenged plants compared to SA signaling in only M. oryzae challenged plants. Interestingly, pathogenesis-associated genes (chitin synthases, chitin deacetylases, appressorium formation) of M. oryzae were highly expressed in the drought predisposed plants compared to only M. oryzae challenged plants. Conclusions: Intermittent drought induces vulnerability of rice to blast disease. Vulnerability of rice to the pathogen in drought predisposed conditions is attributed to reduced activities of the histone acetyltransferases (OsHATs), masking of SA-signaling by ABA-signaling as well as enhanced activities of pathogenesis-associated genes in M. oryzae. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024.