School Of Basic And Applied Sciences
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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 Unveiling the mechanism of platelet dysfunction in Parkinson's disease: The effect of 6-hydroxydopamine on human blood platelets(Elsevier Ltd, 2023-05-22T00:00:00) Beura, Samir Kumar; Yadav, Pooja; Panigrahi, Abhishek Ramachandra; Singh, Sunil KumarIntroduction: Parkinson's disease (PD) is a progressive neuronal illness often linked to increased cardiovascular complications, such as myocardial infarction, cardiomyopathy, congestive heart failure, and coronary heart disease. Platelets, which are the essential components of circulating blood, are considered potential players in regulating these complications, as platelet dysfunction is evident in PD. These tiny blood cell fragments are supposed to play a crucial role in these complications, but the underlying molecular processes are still obscure. Methods: To gain a better understanding of platelet dysfunction in PD, we investigated the impact of 6-hydroxydopamine (6-OHDA), an analog of dopamine that simulates PD by destroying dopaminergic neurons, on human blood platelets. The levels of intraplatelet reactive oxygen species (ROS) were assessed using H2DCF-DA (20 ?M), while mitochondrial ROS was evaluated using MitoSOX� Red (5 ?M), and intracellular Ca2+ was measured with Fluo-4-AM (5 ?M). The data were acquired through the use of both a multimode plate reader and a laser-scanning confocal microscope. Results: Our findings showed that 6-OHDA treatment increased the production of ROS in human blood platelets. The increase in ROS was confirmed by the ROS scavenger, NAC, and was also reduced by inhibiting the NOX enzyme with apocynin. Additionally, 6-OHDA potentiated mitochondrial ROS production in platelets. Furthermore, 6-OHDA triggered the intraplatelet Ca2+ elevation. This effect was mitigated by the Ca2+ chelator BAPTA, which decreased the ROS production triggered by 6-OHDA in human blood platelets, while the IP3 receptor blocker, 2-APB, reduced the formation of ROS induced by 6-OHDA. Conclusion: Our findings suggest that the 6-OHDA-induced ROS production is regulated by the IP3 receptor-Ca2+-NOX signaling axis in human blood platelets, where the platelet mitochondria also play a significant role. This observation provides a crucial mechanistic understanding of the altered platelet activities that are commonly observed in PD patients. � 2023 Elsevier LtdItem 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 Platelet-derived microvesicles activate human platelets via intracellular calcium mediated reactive oxygen species release(Academic Press Inc., 2022-08-28T00:00:00) Yadav, Pooja; Beura, Samir Kumar; Panigrahi, Abhishek Ramachandra; Bhardwaj, Taniya; Giri, Rajanish; Singh, Sunil KumarPlatelet-derived microvesicles (PMVs) are the most abundant microvesicles in circulation, originating from blood platelets via membrane blebbing. PMVs act as biological cargo carrying key molecules from platelets, including immunomodulatory molecules, growth factors, clotting molecules, and miRNAs that can regulate recipient cellular functions. Formation and release of PMVs play an essential role in the pathophysiology of vascular diseases such as hemostasis, inflammation, and thrombosis. Platelet activation is considered the critical event in thrombosis, and a growing number of evidence suggests that oxidative stress-mediated signaling plays a significant role in platelet activation. Ca2+ is a notable player in the generation of ROS in platelets. Reports have established that microvesicles exhibit dual nature in redox mechanisms as they possess both pro-oxidant and antioxidant machinery. However, the impact of PMVs and their ROS machinery on platelets is still a limited explored area. Here, we have demonstrated that PMVs mediate platelet activation via intracellular ROS generation. PMVs interacted with platelets and induced calcium-mediated intracellular ROS production via NADPH oxidase (NOX), leading to platelet activation. Our findings will open up new insights into the tangible relationship of PMVs with platelets and will further contribute to the therapeutic aspects of PMVs in vascular injury and tissue remodeling. � 2022Item Role of platelet in Parkinson's disease: Insights into pathophysiology & theranostic solutions(Elsevier Ireland Ltd, 2022-07-04T00:00:00) Beura, Samir Kumar; Panigrahi, Abhishek Ramachandra; Yadav, Pooja; Singh, Sunil KumarParkinson's disease (PD) is the second-most-common neurodegenerative disease characterized by motor and non-motor dysfunctions, which currently affects about 10 million people worldwide. Gradual death and progressive loss of dopaminergic neurons in the pars compacta region of substantia nigra result in striatal dopamine deficiency in PD. Specific mutation with further aggregation of ??synuclein in the intraneuronal inclusion bodies is considered the neuropathological hallmark of this disease. PD is often associated with various organelle dysfunctions inside a dopaminergic neuron, including mitochondrial damage, proteasomal impairment, and production of reactive oxygen species, thus causing subsequent neuronal death. Apart from several genetic and non-genetic risk factors, emerging research establishes an association between cardiovascular diseases, including coronary heart disease, myocardial infarction, congestive heart failure, and ischemic stroke with PD. The majority of these cardiovascular diseases have an origin from atherosclerosis, where endothelial dysfunction following thrombus formation is significantly regulated by blood platelet. This non-nucleated cell fragment expresses not only neuron-specific molecules and receptors but also several PD-specific biomarkers such as ?-synuclein, parkin, PTEN-induced kinase-1, tyrosine hydroxylase, dopamine transporter, thus making platelet a suitable peripheral model for PD. Besides its similarity with a dopaminergic neuron, platelet structural alterations, as well as functional abnormalities, are also evident in PD. However, the molecular mechanism behind platelet dysfunction is still elusive and quite controversial. This state-of-the-art review describes the detailed mechanism of platelet impairment in PD, addressing the novel platelet-associated therapeutic drug candidates for plausible PD management. � 2022 Elsevier B.V.Item Evaluation of mean platelet volume and platelet count in ischemic stroke and its subtypes: focus on degree of disability and thrombus formation(Taylor and Francis Ltd., 2022-08-27T00:00:00) Ludhiadch, Abhilash; Yadav, Pooja; Singh, Sunil Kumar; Sulena; Munshi, AnjanaBackground: Platelets are crucial players in thrombus formation during ischemic stroke. Platelet (PLT) count and Mean platelet volume (MPV) are important parameters that affect platelet functions. The current study has been carried out with an aim to evaluate the association of MPV and PLT count with ischemic stroke in a population from the Malwa region of Punjab. Material and Methods: The study included one hundred and fifty ischemic stroke patients. The extent of disability occurs by stroke was measured by mRS. MPV and PLT was evaluated using cell counter. Further, PLT count was confirmed in 50% of patients using flow cytometer. Clot formation rate was evaluated using Sonoclot Coagulation and Platelet Function Analyzer. All the statistical analysis was carried out using SPSS. Results: A significant association of increased MPV (p < 0.02) was found with the ischemic stroke. However, PLT count did not show a significant association with the disease (p < 0.07). Further, a stepwise multiple logistic regression (MLR) analysis controlling the other confounding risk factors evaluated the association of hypertension and MPV with the disease. Patients with higher mRS were found to have high MPV values confirming that higher MPV is correlated with disability occurs by ischemic stroke. MPV was also found to be significantly associated with large artery atherosclerosis (p < 0.001). Clot formation analysis revealed that ischemic stroke patients bear higher clot rate (CR) and Platelet function (PF) values. Conclusions: Elevated MPV is an independent risk factor for Ischemic stroke along with hypertension. In addition, higher MPV associated significantly with stroke disability as well. � 2022 Informa UK Limited, trading as Taylor & Francis Group.Item 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.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 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.