School Of Health Sciences
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Item Neuroimaging Genomics a Predictor of Major Depressive Disorder (MDD)(Springer, 2023-11-22T00:00:00) Jindal, Manav; Chhetri, Aakash; Ludhiadch, Abhilash; Singh, Paramdeep; Peer, Sameer; Singh, Jawahar; Brar, Rahatdeep Singh; Munshi, AnjanaDepression is a complex psychiatric disorder influenced by various genetic and environmental factors. Strong evidence has established the contribution of genetic factors in depression through twin studies and the heritability rate for depression has been reported to be 37%. Genetic studies have identified genetic variations associated with an increased risk of developing depression. Imaging genetics is an integrated approach where imaging measures are combined with genetic information to explore how specific genetic variants contribute to brain abnormalities. Neuroimaging studies allow us to examine both structural and functional abnormalities in individuals with depression. This review has been designed to study the correlation of the significant genetic variants with different regions of neural activity, connectivity, and structural alteration in the brain as detected by imaging techniques to understand the scope of biomarkers in depression. This might help in developing novel therapeutic interventions targeting specific genetic pathways or brain circuits and the underlying pathophysiology of depression based on this integrated approach can be established at length. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Assessment of Resting-state functional Magnetic Resonance Imaging Connectivity Among Patients with Major Depressive Disorder: A Comparative Study(SAGE Publications Inc., 2023-08-29T00:00:00) Singh, Paramdeep; Singh, Jawahar; Peer, Sameer; Jindal, Manav; Khokhar, Sunil; Ludhiadch, Abhilash; Munshi, AnjanaBackground: Resting-state functional connectivity analysis has a potential to unearth the putative neuronal underpinnings of various disorders of the brain. Major depressive disorder (MDD) is regarded as a disorder arising from alterations in functional networks of the brain. Purpose: There is paucity of literature on resting-state functional magnetic resonance imaging (Rs-fMRI) in MDD, especially from the Indian subcontinent. The purpose of our study was to elucidate the differences in Rs-fMRI connectivity between MDD patients and age and gender matched healthy controls (HC). Methods: In this prospective single institute-based study, the patients were recruited consecutively based on Hamilton depression rating scale (HAM-D). Age and gender matched HC were also recruited. Rs-fMRI and anatomical MRI images were acquired for all the subjects (MDD and HC group) and subsequent analysis was done using the CONN toolbox. Results: A total of 49 subjects were included in the final analysis (MDD = 28 patients, HC = 21). HAM-D score was noted to be 24.4 � 4.8 in the MDD group. There was no significant difference between MDD and HC groups as far as age, gender, employment status, and level of education is concerned. Region-of-interest-based analysis of Rs-fMRI data showed a significantly lower connectivity between the left insula and left nucleus accumbens and between left paracingulate gyrus and bilateral posterior middle temporal gyri in MDD group as compared to HC group. Conclusion: There is reduced connectivity between certain key regions of the brain in MDD patients, that is, between the left insular cortex and the left nucleus accumbens and between the left paracingulate gyrus and the bilateral posterior middle temporal gyrus. These findings could explain the basis of clinical features of MDD such as anhedonia, rumination of thoughts, reduced visuo-spatial comprehension, reduced language function, and response to external stimuli. � 2023 Indian Academy of Neurosciences (IAN).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 Currently available COVID-19 management options(Elsevier, 2023-01-20T00:00:00) Ludhiadch, Abhilash; Yadav, Umesh Prasad; Munshi, AnjanaThe pandemic caused by new coronavirus (COVID-19), i.e., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started from the Wuhan state of China. COVID-19 is a novel infectious disease characterized by atypical pneumonia with the symptoms like fever, sore throat, fatigue, cough, and dyspnea. As of January 2022, more than 298 million people have been infected with SARS-CoV-2 (WHO). Changes in personal behavior like the use of face masks, proper hand hygiene, social distancing, and some interventions and control measures led by Governments all over the world resulted in decline of SARS-CoV-2 infections globally. The main concern of this pandemic is the risk of transmission and reinfection with new variants of COVID-19, and therefore, this COVID-19 pandemic is still a matter of great concern. It is a major challenge for clinicians and researchers worldwide to develop a specific strategy to eliminate this virus. The complications on account of COVID-19 disease manifest from mild to moderate. Only 5%�10% of the cases show severe and life-threatening complications with an approximately 2% of death rate worldwide [1]. Based on the severity of infection the National Institutes of Health (NIH) has classified COVID-19 into five different stages: asymptomatic infection, mild illness, moderate illness, severe illness, and critical illness [2]. Currently, many supportive measures such as ventilation systems and fluid management are being followed to save lives, but there is a dire need to develop antiviral treatment strategy to counter the spread of this virus completely. The treatment strategies also include blocking of enzymes or proteins that are essential for the survival of the virus, inhibition of viral structural proteins to prevent the affinity with human cells or virion formation, further by stimulating the immunity of the host, and inhibition of receptors in host that aid in entry of the virus. Currently, battling COVID-19 is the top most priority in the scientific world. Various pharmaceutical companies and research fraternities around the globe are working on interventions to reduce the impact of SARS-CoV-2 and prevent subsequent infections. Many clinical trials and animal studies are being carried out to identify the most potent drug alone or combination against the disease. The management of COVID-19 is being achieved by general treatment, specific treatments, and supplementation of vitamins and essential micronutrients like zinc and magnesium. General treatment strategies basically include antiviral therapies, antiinflammatory therapies and use of corticosteroids. The treatment of critically ill patients includes specific treatment strategies such as the use of anti-SARS-CoV-2 neutralizing antibody products, immunomodulatory agents, and oxygenation and ventilation management. Supplementation with vitamin C, vitamin D, magnesium, zinc, etc., is also being used to reduce the symptoms during the course of infection. SARS-CoV-2 infection also poses a risk of developing post-COVID-19 complications in the patients who suffered severe infection [3]. The management of post-COVID complications is currently under focus and there is a need to manage such patients with proper care. The post-COVID complications affect multiple organ systems such as cardiovascular, pulmonary, gastrointestinal, hepatic, neuropsychiatric, hematologic, and several others. Developing a significantly potent treatment will help the medical fraternity to eradicate the virus without overburdening the existing healthcare system. This chapter has been compiled with an aim to sum up information on currently available treatment strategies and management for COVID-19. � 2023 Elsevier Inc. All rights reserved.Item Role of tRNA-Derived Fragments in Neurological Disorders: a Review(Springer, 2022-11-09T00:00:00) Mathew, Blessy Aksa; Katta, Madhumitha; Ludhiadch, Abhilash; Singh, Paramdeep; Munshi, AnjanatRFs are small tRNA derived fragments that are emerging as novel therapeutic targets and regulatory molecules in the pathophysiology of various neurological disorders. These are derived from precursor or mature tRNA, forming different subtypes that have been reported to be involved in neurological disorders like stroke, Alzheimer�s, epilepsy, Parkinson�s, MELAS, autism, and Huntington�s disorder. tRFs were earlier believed to be random degradation debris of tRNAs. The significant variation in the expression level of tRFs in disease conditions indicates their salient role as key players in regulation of these disorders. Various animal studies are being carried out to decipher their exact role; however, more inputs are required to transform this research knowledge into clinical application. Future investigations also call for high-throughput technologies that could help to bring out the other hidden aspects of these entities. However, studies on tRFs require further research efforts to overcome the challenges posed in quantifying tRFs, their interactions with other molecules, and the exact mechanism of function. In this review, we are abridging the current understanding of tRFs, including their biogenesis, function, relevance in clinical therapies, and potential as diagnostic and prognostic biomarkers of these neurological disorders. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Advanced molecular therapies for neurological diseases: focus on stroke, alzheimer's disease, and parkinson's disease(Springer-Verlag Italia s.r.l., 2022-09-06T00:00:00) Katta, Madhumitha; Mathew, Blessy Aksa; Chaturvedi, Pragya; Ludhiadch, Abhilash; Munshi, AnjanaNeurological diseases (NDs) are one of the leading causes of disability and the second leading cause of death globally. Among these stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) are the most common NDs. A rise in the absolute number of individuals affected with these diseases indicates that the current treatment strategies in management and prevention of these debilitating diseases are not effective sufficiently. Therefore, novel treatment strategies are being explored to cure these diseases by addressing the causative mechanisms at the molecular level. Advanced therapies like gene therapy (gene editing and gene silencing) and stem cell therapies aim to cure diseases by gene editing, gene silencing and tissue regeneration, respectively. Gene editing results in the deletion of the aberrant gene or insertion of the corrected gene which can be executed using the CRISPR/Cas gene editing tool a promising treatment strategy being explored for many other prevalent diseases. Gene silencing using siRNA silences the gene by inhibiting protein translation, thereby silencing its expression. Stem cell therapy aims to regenerate damaged cells or tissues because of their ability to divide into any type of cell in the human body. Among these approaches, gene editing and gene silencing have currently been applied in vitro and to animal models, while stem cell therapy has reached the clinical trial stage for the treatment of NDs. The current status of these strategies suggests a promising outcome in their clinical translation. � 2022, Fondazione Societ� Italiana di Neurologia.Item Role of Omics in Migraine Research and Management: A Narrative Review(Springer, 2022-07-07T00:00:00) Chaturvedi, Pragya; Khan, Rahul; Sahu, Prachi; Ludhiadch, Abhilash; Singh, Gagandeep; Munshi, AnjanaMigraine is a neurological disorder defined by episodic attacks of chronic pain associated with nausea, photophobia, and phonophobia. It is known to be a complex disease with several environmental and genetic factors contributing to its susceptibility. Risk factors for migraine include head or neck injury (Arnold, Cephalalgia 38(1):1�211, 2018). Stress and high temperature are known to trigger migraine, while sleep disorders and anxiety are considered to be the comorbid conditions with migraine. Studies have reported various biomarkers, including genetic variants, proteins, and metabolites implicated in migraine�s pathophysiology. Using the �omics� approach, which deals with genetics, transcriptomics, proteomics, and metabolomics, more specific biomarkers for various migraine can be identified. On account of its multifactorial nature, migraine is an ideal study model focusing on integrated omics approaches, including genomics, transcriptomics, proteomics, and metabolomics. The current review has been compiled with an aim to focus on the genomic alterations especially involved in the regulation of glutamatergic neurotransmission, cortical excitability, ion channels, solute carrier proteins, or receptors; their expression in migraine patients and also specific proteins and metabolites, including some inflammatory biomarkers that might represent the migraine phenotype at the molecular level. The systems biology approach holds the promise to understand the pathophysiology of the disease at length and also to identify the specific therapeutic targets for novel interventions. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Common microRNAs in Epilepsy and Migraine: Their Possibility as Can-didates for Biomarkers and Therapeutic Targets during Comorbid Onset of Both Conditions(Bentham Science Publishers, 2022-04-27T00:00:00) Ludhiadch, Abhilash; Bhardwaj, Nidhi; Gotra, Palvi; Kumar, Roshan; Munshi, AnjanaEpilepsy and migraine are chronic neurological disorders with shared clinical as well as pathophysiological mechanisms. Epileptic patients are at a higher risk of developing migraine compared to normal individuals and vice versa. Several genetic and environmental risk factors have been reported to be associated with the development of both diseases. Previous studies have already estab-lished standard genetic markers involved in various pathways implicated in the pathogenesis of both these comorbid conditions. In addition to genetic markers, epigenetic markers have also been found to be involved in the pathogenesis of epilepsy and migraine. Among the epigenetic markers, miRNAs have been explored at length and have emerged as significant players in regulating the expression of their target genes. miRNAs like miR-22, miR-34a, miR-155, miR-211, and Let-7b play a significant role in neuronal differentiation and seem to be associated with epilepsy and migraine as comorbid conditions. However, the exact shared mechanisms underlying the role of these miRNAs in these comorbid conditions are still unclear. The current review has been compiled with an aim to explore common microRNAs targeting the genes involved in shared molecular pathways leading to epilepsy and migraine as comorbid conditions. The new class of ncRNAs, i.e., tRNA transfer fragments, are also discussed. In addition, their role as potential biomarkers and therapeutic targets has also been eval-uated. However, limitations exist, and based on the current literature available, only a few microRNAs seem to be involved in the pathogenesis of both these disorders. � 2023 Bentham Science Publishers.Item Epilepsy and Migraine Shared Genetic and Molecular Mechanisms: Focus on Therapeutic Strategies(Springer, 2021-04-15T00:00:00) Gotra, Palvi; Bhardwaj, Nidhi; Ludhiadch, Abhilash; Singh, Gagandeep; Munshi, AnjanaEpilepsy and migraine are both episodic disorders and share clinical as well as pathophysiological mechanisms. The prevalence of epilepsy in migraine patients is generally higher than normal as compared to general population and vice versa. Various environmental risk factors and genetic factors have been reported to be associated with susceptibility of these comorbid diseases. Specific genes have been implicated in the pathogenesis of the two diseases. However, the shared genetic susceptibility has not been explored extensively. Previous studies have reported that the alterations in the genes encoding ion channel proteins are common risk factors for both the diseases. The alterations in ion channel-encoding genes CACNAIA (T666M) and SCNIA (Q1489K and L1649Q) have been found to be involved in the development of familial hemiplegic migraine (FHM) as well as generalized epilepsy and some cases of focal epilepsy as well. The fact that both these disorders are treated with anti-epileptic drugs (AEDs) strongly supports common underlying mechanisms. This review has been compiled with an aim to explore the alterations in common genes involved in various pathways regulating neuronal hyperexcitability, a common risk factor for both these conditions. The avenue for future treatment strategies targeting common genes and molecular mechanisms has also been discussed. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Recent advances in HER2 positive breast cancer epigenetics: Susceptibility and therapeutic strategies(Elsevier Masson SAS, 2017) Singla, Heena; Ludhiadch, Abhilash; Kaur, Raman Preet; Chander, Harish; Kumar, Vinod; Munshi, AnjanaHER2 amplification/overexpression accounts for aggressive clinical features of HER2 positive breast cancer. Epigenetic changes including DNA methylation, histone modifications and ncRNAs/miRNAs are associated with regulation of DNA chromatin and specifically, gene transcription. Hence, these produce eminent effects upon proto-oncogenes, tumor-suppressors and key cancer-regulatory signaling pathways. Understanding of epigenomic regulation of HER2 overexpression and signaling may help uncover the unmatchable physiology of HER2 gene/protein. Moreover, this may also aid in resolving the major issue of resistance-development towards HER2 targeted agents (trastuzumab and lapatinib), since epigenetic alterations are important therapeutic markers and modulate the response towards HER2 targeted therapy. Therefore, in this review the information regarding various epigenetic markers implicated in HER2 positive breast cancer susceptibility and therapeutic-strategies has been compiled. ? 2017 Elsevier Masson SAS