School Of Health Sciences
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Item Genomic Variation Affecting MPV and PLT Count in Association with Development of Ischemic Stroke and Its Subtypes(Springer, 2023-07-15T00:00:00) Ludhiadch, Abhilash; Sulena; Singh, Sandeep; Chakraborty, Sudip; Sharma, Dixit; Kulharia, Mahesh; Singh, Paramdeep; Munshi, AnjanaPlatelets play a significant role in the pathophysiology of ischemic stroke since they are involved in the formation of intravascular thrombus after erosion or rupture of the atherosclerotic plaques. Platelet (PLT) count and mean platelet volume (MPV) are the two significant parameters that affect the functions of platelets. In the current study, MPV and PLT count was evaluated using flow cytometry and a cell counter. SonoClot analysis was carried out to evaluate activated clot timing (ACT), clot rate (CR), and platelet function (PF). Genotyping was carried out using GSA and Sanger sequencing, and expression analysis was performed using RT-PCR. In silico analysis was carried out using the GROMACS tool and UNAFold. The interaction of significant proteins with other proteins was predicted using the STRING database. Ninety-six genes were analyzed, and a significant association of THPO (rs6141) and ARHGEF3 (rs1354034) was observed with the disease and its subtypes. Altered genotypes were associated significantly with increased MPV, decreased PLT count, and CR. Expression analysis revealed a higher expression in patients bearing the variant genotypes of both genes. In silico analysis revealed that mutation in the THPO gene leads to the reduced compactness of protein structure. mRNA encoded by mutated ARHGEF3 gene increases the half-life of mRNA. The two significant proteins interact with many other proteins, especially the ones involved in platelet activation, aggregation, erythropoiesis, megakaryocyte maturation, and cytoskeleton rearrangements, suggesting that they could be important players in the determination of MPV values. In conclusion, the current study demonstrated the role of higher MPV affected by genetic variation in the development of IS and its subtypes. The results of the current study also indicate that higher MPV can be used as a biomarker for the disease and altered genotypes, and higher MPV can be targeted for better therapeutic outcomes. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Role of lncRNAs in the Development of Ischemic Stroke and Their Therapeutic Potential(Springer, 2021-04-05T00:00:00) Vasudeva, Kanika; Dutta, Anyeasha; Munshi, AnjanaStroke is a major cause of premature mortality and disability around the world. Therefore, identification of cellular and molecular processes implicated in the pathogenesis and progression of ischemic stroke has become a priority. Long non-coding RNAs (lncRNAs) are emerging as significant players in the pathophysiology of cerebral ischemia. They are involved in different signalling pathways of cellular processes like cell apoptosis, autophagy, angiogenesis, inflammation, and cell death, impacting the progression of cerebral damage. Exploring the functions of these lncRNAs and their mechanism of action may help in the development of promising treatment strategies. In this review, the current knowledge of lncRNAs in ischemic stroke, focusing on the mechanism by which they cause cellular apoptosis, inflammation, and microglial activation, has been summarized. Very few lncRNAs have been functionally annotated. Therefore, the therapies based on lncRNAs still face many hurdles since the potential targets are likely to increase with the identification of new ones. Majority of experiments involving the identification and function of lncRNAs have been carried out in animal models, and the role of lncRNAs in human stroke presents a challenge. However, mitigating these issues through more rational experimental design might lead to the development of lncRNA-based stroke therapies to treat ischemic stroke. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Establishing molecular signatures of stroke focusing on omic approaches: a narrative review(Taylor and Francis Ltd, 2020) Ludhiadch, A; Vasudeva, K; Munshi, A.Stroke or �brain attack� is considered to be the major cause of mortality and morbidity worldwide after myocardial infraction. Inspite of the years of research and clinical practice, the pathogenesis of stroke still remains incompletely understood. Omics approaches not only enable the description of a huge number of molecular platforms but also have a potential to recognize new factors associated with various complex disorders including stroke. The most significant development among all other omics technologies over the recent years has been seen by genomics which is a powerful tool for exploring the genetic architecture of stroke. Genomics has decisively established itself in stroke research and by now wealth of data has been generated providing new insights into the physiology and pathophysiology of stroke. However, the efficacy of genomic data is restricted to risk prediction only. Omics approaches not only enable the description of a huge number of molecular platforms but also have a potential to recognize new factors associated with various complex disorders including stroke. The data generated by omics technologies enables clinicians to provide detailed insight into the makeup of stroke in individual patients, which will further help in developing diagnostic procedures to direct therapies. Present review has been compiled with an aim to understand the potential of integrated omics approach to help in characterization of mechanisms leading to stroke, to predict the patient risk of getting stroke by analyzing signature biomarkers and to develop targeted therapeutic strategies. � 2020, � 2020 Informa UK Limited, trading as Taylor & Francis Group.