Browsing by Author "Singh, Sunil K."
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Item 2D Nanomaterials in Diagnostics and Therapy of Cardiovascular Diseases(CRC Press, 2022-09-26T00:00:00) Yadav, Pooja; Beura, Samir K.; Panigrahi, Abhishek R.; Chatterjee, Abhinaba; Yadav, Jyoti; Singh, Sunil K.[No abstract available]Item Antiplatelet drugs: Potential therapeutic options for the management of neurodegenerative diseases(John Wiley and Sons Inc, 2023-05-03T00:00:00) Beura, Samir K.; Dhapola, Rishika; Panigrahi, Abhishek R.; Yadav, Pooja; Kumar, Reetesh; Reddy, Dibbanti H.; Singh, Sunil K.The blood platelet plays an important role but often remains under-recognized in several vascular complications and associated diseases. Surprisingly, platelet hyperactivity and hyperaggregability have often been considered the critical risk factors for developing vascular dysfunctions in several neurodegenerative diseases (NDDs) like Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. In addition, platelet structural and functional impairments promote prothrombotic and proinflammatory environment that can aggravate the progression of several NDDs. These findings provide the rationale for using antiplatelet agents not only to prevent morbidity but also to reduce mortality caused by NDDs. Therefore, we thoroughly review the evidence supporting the potential pleiotropic effects of several novel classes of synthetic antiplatelet drugs, that is, cyclooxygenase inhibitors, adenosine diphosphate receptor antagonists, protease-activated receptor blockers, and glycoprotein IIb/IIIa receptor inhibitors in NDDs. Apart from this, the review also emphasizes the recent developments of selected natural antiplatelet phytochemicals belonging to key classes of plant-based bioactive compounds, including polyphenols, alkaloids, terpenoids, and flavonoids as potential therapeutic candidates in NDDs. We believe that the broad analysis of contemporary strategies and specific approaches for plausible therapeutic treatment for NDDs presented in this review could be helpful for further successful research in this area. � 2023 Wiley Periodicals LLC.Item Blood Coagulation System and Carbon-Based Nanoengineering for Biomedical Application(Springer Nature, 2021-10-01T00:00:00) Panigrahi, Abhishek R.; Yadav, Pooja; Beura, Samir K.; Singh, Sunil K.Carbon-based nanomaterials (CBNs) acquired unique physiochemical properties, due to which they were examined for various biomedical applications such as bio-imaging, bio-sensing, targeted drug delivery, etc. CBNs first experience the complex blood system during their intravenous administration for controlled delivery of drugs. In blood, CBNs triggers a cascade of events such as biocorona formation, complement activation, hemolysis, and thrombosis. During thrombosis, CBNs interact with blood coagulation system. Coagulation systems include platelets and clotting factors. The current book chapter is highlighting the impact of different CBNs on blood coagulation system with brief description of the various allotropes of carbon nanomaterials along with coagulation cascade mechanism. Encounter of CBNs with platelets induces its activation, aggregation, and adhesion properties whereas while interacting with coagulation cascade they mostly affect the intrinsic pathway rather than extrinsic pathways of coagulation. CBNs mediated blood coagulation system activation depends on its shape, size, and composition, which can be characterized using various sophisticated techniques such as flow cytometry, electron microscopy as well as platelet aggregometer. � 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.Item Implicative role of cytokines in neuroinflammation mediated AD and associated signaling pathways: Current progress in molecular signaling and therapeutics(Elsevier Ireland Ltd, 2023-10-30T00:00:00) Kumari, Sneha; Dhapola, Rishika; Sharma, Prajjwal; Singh, Sunil K.; Reddy, Dibbanti HariKrishnaAlzheimer's Disease (AD) is one of the most devastating age-related disorder causing significant social and economic burden worldwide. It affects the cognitive and social behavior of individuals and characterized by accumulation of A?, phosphorylated tau and cytokines formation. The synthesis and release of cytokines are regulated by specific groups of immune and non-immune cells in response to microglia or astrocyte activation through multiple pathways. Physiologically, microglia assert an anti-inflammatory, quiescent state with minimal cytokine expression and little phagocytic activity in motion to carry out their housekeeping role to eliminate pathogens, aggregated A? and tau protein. However, they develop a phagocytic nature and overexpress cytokine gene modules in response to certain stimuli in AD. Microglia and astrocytes upon chronic activation release an enormous amount of inflammatory cytokines due to interaction with formed A? and neurofibrillary tangle. Gut microbiota dysbiosis also stimulates the release of inflammatory cytokines contributing to AD pathogenesis. In addition, the dysregulation of few signaling pathways significantly influences the development of disease, and the pace of advancement also rises with age. This review sheds light on multiple pathways results into neuroinflammation triggered by activated cytokines worsening AD pathology and making it an appropriate target for AD treatment. This review also included drugs targeting different neuroinflammation pathways under clinical and preclinical studies that are found to be effective in attenuating the disease pathology. � 2023 Elsevier B.V.Item Phytochemicals as Potential Therapeutics for SARS-CoV-2�Induced Cardiovascular Complications: Thrombosis and Platelet Perspective(Frontiers Media S.A., 2021-04-26T00:00:00) Beura, Samir K.; Panigrahi, Abhishek R.; Yadav, Pooja; Singh, Sunil K.After gaining entry through ACE2 aided by TMPRSS2, the SARS-CoV-2 causes serious complications of the cardiovascular system leading to myocarditis and other myocardial injuries apart from causing lung, kidney and brain dysfunctions. Here in this review, we are going to divulge the cellular and immunological mechanisms behind the cardiovascular, thrombotic and platelet impairments that are caused in COVID-19. In addition, we also propose the significance of various anti-platelet and anti-thrombotic phytochemicals in the treatment of COVID-19. The virus induces many immune-modulatory cytokines and chemokines which help in the intravascular coagulation and create a pro-thrombotic environment along with pulmonary embolism and thrombocytopenia. Different types of innate and adaptive immune cells and their granular contents regulate the pathophysiology of SARS-CoV-2 induced endothelial and platelet dysfunctions which correlate the involvement of platelets with myocardial injury and intravascular thrombi directly or indirectly. Hence, by exploiting the natural bioactive compounds from medicinal plants and inhibiting the platelet mediated thrombus formation can be beneficial for the treatment of SARS-CoV-2 infection. � Copyright � 2021 Beura, Panigrahi, Yadav and Singh.Item Platelet-derived microvesicles induce intracellular calcium mobilization in human platelets(John Wiley and Sons Inc, 2023-08-31T00:00:00) Yadav, Pooja; Panigrahi, Abhishek R.; Beura, Samir K.; Singh, Sunil K.Platelet-derived microvesicles (PMVs) represent a significant proportion of microvesicles in circulation and have been linked to various pathophysiological complications. Recent research suggests that PMVs carry significant amounts of cargo that can affect cellular functions by influencing calcium oscillations in target cells. As calcium is involved in multiple cellular processes, including hemostasis and thrombosis, this study aimed to investigate the impact of PMVs on platelet calcium mobilization. The study found that PMVs increase platelet intracellular calcium levels via both intracellular storage and extracellular space in a dose-dependent manner. The study highlighted the critical role of the dense tubular system, acidic vacuoles, mitochondrial stores, and store-operated calcium entry (SOCE) in PMV-mediated calcium release in human platelets. Moreover, the study revealed that PMV-induced calcium rise in platelets does not occur via sarcoendoplasmic reticulum calcium ATPase, and extracellular calcium addition further increases the calcium level in platelets, demonstrating the involvement of SOCE. These findings provide insights into the platelet stimulation signaling mechanisms and contributes to our understanding of platelet and cell behavior when exposed to PMV-rich environments. � 2023 International Federation of Cell Biology.Item Probing interaction of atherogenic lysophosphatidylcholine with functionalized graphene nanosheets: theoretical modelling and experimental validation(Springer Science and Business Media Deutschland GmbH, 2023-09-09T00:00:00) Panigrahi, Abhishek R.; Yadav, Pooja; Beura, Samir K.; Singh, Jyoti; Dastider, Saptarshi G.; Singh, Sunil K.; Mondal, KrishnakantaContext: The potential of graphene derivatives for theranostic applications depends on their compatibility with cellular and biomolecular components. Lysophosphatidylcholine (LPC), a lipid component present in oxidized low-density lipoproteins, microvesicles and free circulation in blood, plays a critical role in the pathophysiology of various diseases. Using�density functional theory-based methods, we systematically investigated the interaction of atherogenic LPC molecule with different derivatives of graphene, including pristine graphene, graphene with defect, N-doped graphene, amine-functionalized graphene, various graphene oxides and hydroxylated graphene oxides. We observed that the adsorption of LPC on graphene derivatives is highly selective based on the orientation of the functional groups of LPC interacting with the surface of the derivatives. Hydroxylated graphene oxide exhibited the strongest interaction with LPC with adsorption energy of ? 2.1 eV due to the interaction between the hydroxyl group on graphene and the phosphate group of LPC. The presence of aqueous medium further enhanced this interaction indicating favourable adsorption of LPC and graphene oxide in biological systems. Such strong interaction leads to substantial change in the electronic structure of the LPC molecule, which results in the activation of this molecule. In contrast, amine-modified graphene showed the least interaction. These theoretical results are in line with our experimental fluorescence spectroscopic data of LPC/1-anilino-8-napthalene sulfonic acid complex. Our present comprehensive investigation employing both theoretical and experimental methods provides a deeper understanding of graphene-lipid interaction, which holds paramount importance in the design and fabrication of graphene-based nanomaterials for biomedical applications. Methods: In this study, we employed the density functional theory-based methods to investigate the electronic and structural properties of graphene derivatives and LPC molecule using the Quantum Espresso package. The exchange�correlation functional was described within generalized gradient approximation (GGA) as parameterized by Perdew, Burke and Ernzerhof (PBE). The valence electrons were represented using plane wave basis sets. `The Grimme�s dispersion method was used to include the van der Waals dispersion correction. � 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Item Quantification and optimization of clot retraction in washed human platelets by Sonoclot coagulation analysis(John Wiley and Sons Inc, 2021-10-07T00:00:00) Yadav, Pooja; Beura, Samir K.; Panigrahi, Abhishek R.; Singh, Sunil K.Introduction: Clot retraction is a pivotal process for haemostasis, where platelets develop a contractile force in fibrin meshwork and lead to the increased rigidity of clot. The pathophysiological alteration in contractile forces generated by the platelet-fibrin meshwork can lead to haemostatic disorders. Regardless of its utter significance, clot retraction remains a limited understood process owing to lack of quantification methodology. Sonoclot analysis is a point-of-care technique used in clinical laboratories for whole blood analysis that provides�in vitro�qualitative as well as quantitative assessment of coagulation process from initial fibrin formation to clot retraction. Methods: Human washed platelets were isolated by differential centrifugation method and analysed via optical imaging, microscopy and Sonoclot analysis using 1-2�נ108/mL of washed platelets, 1�U/mL of thrombin, 1�mg/mL of fibrinogen and 1�mM of calcium chloride. Results: In this study, we demonstrate the novelty of this instrument in the quantitative evaluation of clot retraction in washed platelets and attempted to optimize the reference range of Sonoclot parameters including ACT - 87.3���20.997, CR - 16.23���3.538 and PF - 3.57���0.629, (n�=�10). Discussion: Sonoclot analysis provides a simple and quantitative method to better understand in vitro clot retraction and its modulation by retraction components including platelet count, fibrinogen and platelet�fibrin interaction compared with existing conventional methods. Sonoclot may prove to be a valuable tool in thrombus biology research to understand fundamental basis of blood clot retraction. � 2021 John Wiley & Sons LtdItem Role of Neurons and Glia Cells in Wound Healing as a Novel Perspective Considering Platelet as a Conventional Player(Springer, 2021-10-11T00:00:00) Beura, Samir K.; Panigrahi, Abhishek R.; Yadav, Pooja; Agrawal, Siwani; Singh, Sunil K.Wound healing is a complex physiological process in which the damaged or injured tissue is replaced or regenerated by new cells or existing cells respectively in their synthesized and secreted matrices. Several cells modulate the process of wound healing including macrophages, fibroblasts, and keratinocytes. Apart from these cells, platelet has been considered as a major cellular fragment to be involved in wound healing at several stages by secreting its granular contents including growth factors, thus resulting in coagulation, inflammation, and angiogenesis. A distant cell, which is gaining significant attention nowadays due to its resemblance with platelet in several aspects, is the neuron. Not only neurons but also glia cells are also confirmed to regulate wound healing at different stages in an orchestrated manner. Furthermore, these neurons and glia cells mediate wound healing inducing tissue repair and regeneration apart from hemostasis, angiogenesis, and inflammation by secreting various growth factors, coagulation molecules, immunomodulatory molecules as well as neurohormones, neuropeptides, and neurotrophins. Therefore, in wound healing platelets, neurons and glia cells not only contribute to tissue repair but are also responsible for establishing the wound microenvironment, thus affecting the proliferation of immune cells, fibroblast, and keratinocytes. Here in this review, we will enlighten the physiological roles of neurons and glia cells in coordination with platelets to understand various cellular and molecular mechanism in brain injury and associated neurocognitive impairments. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.