Browsing by Author "Ashish Ashish"
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PublicationArticle Assessment of depression anxiety and stress levels among patients with epilepsy in a case control study(Discover, 2025) Shani Vishwakarma; Abhishek Pathak; Anil Kumar Maurya; Nitish Kumar Singh; Ashish Ashish; Royana SinghIntroduction: People with epilepsy frequently experience depression, anxiety, and stress, which can significantly impact their quality of life and overall well-being. This study aimed to identify psychiatric comorbidities in individuals with epilepsy by assessing their prevalence and comparing them with a healthy control group. Methodology: This case-control study was conducted in the department of Anatomy, and patients were recruited from the Out-Patient Department of Neurology, from August 2022 to February 2024. The total number of participants was 388, including 194 Cases. 194 healthy controls were matched for age and sex, with participants under the age of 18 excluded. Psychiatric comorbidity was evaluated using standardized assessment tools and analyzed with Chi-square and one-way ANOVA. Results: The study involved 194 patients and 194 healthy controls, with a mean age of 25.11 ± 10.28 years. Among the patients, 58.2% were female and 41.8% were male. A significant difference in depression levels was found between patients on monotherapy and polytherapy (p = 0.003). However, no significant differences were found in anxiety (p = 0.214) and stress (p = 0.139). There are no significant links between depression, anxiety, stress and antiepileptic drugs. Patients with epilepsy exhibited significantly higher levels of depression, anxiety, and stress compared to healthy controls, with a statistical significance of p = 0.001. Conclusion: The study highlights the elevated levels of depression, anxiety, and stress among patients with epilepsy. Clinicians and healthcare practitioners should adopt comprehensive and holistic assessment methods to address and mitigate these psychiatric comorbidities in epilepsy patients. © The Author(s) 2025.PublicationArticle BCR-ABL kinase domain mutations in CML patients, experience from a tertiary care center in North India(Elsevier Ltd, 2024) Akhilesh S; Arunim shah; Ashish Ashish; Nitish kumar Singh; Manpreet Kaur; Abhay kumar Yadav; Royana singhBackground: Chronic Myeloid Leukemia is characterized by the presence of the Philadelphia Chromosome (Ph) which contains the BCR::ABL1 fusion gene that occurs due to a reciprocal translocation between chromosomes 9 and 22. This accounts for up to 15 % of all adult leukemias [1]. Most patients treated with first line tyrosine kinase inhibitor (TKI) imatinib achieve durable response but may undergo relapse at some stage [2]. The most important mechanism that may confer imatinib resistance is point mutation within BCR::ABL kinase domain. Other generation ABL tyrosine kinase inhibitors such as dasatinib, nilotinib, bosutinib and ponatinib help to overcome imatinib resistance [3]. Sensitivity of the patient to each of the above TKIs depends upon the individual candidate mutation present. Thus, it is important to perform mutation analysis for effective therapeutic management of CML patients once they show imatinib resistance. We used direct sequencing to identify the different types of mutations responsible for resistance of imatinib treatment from north India. Methods: In this study, the patient resistance for the imatinib were analyzed for BCR::ABL kinase domain mutation by direct sequencing and the detected mutations along with their percentage prevalence were reported. Results: 329 patients with CML-CP were analyzed for BCR::ABL kinase domain mutation. Total 66 (20.06 %) patients out of 329 had mutation in at least one of the domains of BCR::ABL conferring resistance to different generations of TKI. Mutations in BCR::ABL kinase domain was observed in different domain of BCR::ABL. ATP binding P-Loop (42.42 %), Direct binding site (36.36 %), C-Loop (10.60 %), A-Loop (6.06 %), SH2 contact (3.03 %), SH3 contact (1.51 %). Conclusion: Total 20.06 % patients (66/329) show mutation in at least one of the structural motifs of BCR-ABL kinase domain, which further confer the resistance to a particular generation of TKI. © 2023 The Author(s)PublicationArticle Clinical exome sequencing (carrier screening) identifies the gene INPPL1 in a sporadic case of opsismodysplasia(Rzeszow University Press, 2025) Ashish Ashish; Shivani Mishra; Royana Singh; Sangeeta RaiIntroduction and aim. This study presents a case of opsismodysplasia in a family, characterized by skeletal dysplasia and neurological complications in two consecutive neonates. Description of the case. Genetic analysis revealed that the father carries a likely benign/variant of uncertain significance (VUS) in exon 14 of the INPPL1 gene (c.1706C>T, p.Thr569Met), while the mother carries a pathogenic variant in exon 15 (c.1809del, p.Trp604GlyfsTer17). These variants follow an autosomal recessive inheritance, confirming carrier status. Additionally, the father is a carrier of a likely pathogenic variant in the CYP17A1 gene (OMIM*609300), specifically in exon 6 (c.1040G>A, p.Arg347His, heterozygous), affecting 17,20-lyase activity and associated with isolated 17,20-lyase deficiency. Targeted sequencing and Sanger validation elucidated the genetic basis of the condition, emphasizing the importance of genetic testing and counselling in families with a history of genetic disorders. The detected variants in the INPPL1 gene disrupt SHIP2 protein function, contributing to the observed abnormalities. Conclusion. This study underscores the significance of early genetic diagnosis for reproductive counselling and timely intervention. Further research into opsismodysplasia’s genetic mechanisms may lead to improved management and therapies for affected individuals. Overall, this case highlights the critical role of genetic analysis in diagnosing and managing rare genetic disorders, offering insights into personalized care and family planning. © 2025 Publishing Office of the University of Rzeszow. All rights reserved.PublicationArticle Cytokine profiles and metabolic dysregulation in endometriosis: insights into diagnostic and therapeutic targets(Springer Science and Business Media B.V., 2025) Ashish Ashish; Sangeeta Rai; Shivani Mishra; Anil Kumar Maurya; Abhay Kumar Yadav; Shani Vishwakarma; Royana SinghIntroduction: Endometriosis is a chronic inflammatory disorder marked by the ectopic growth of endometrial-like tissue, affecting 10–15% of women of reproductive age. Pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) drive inflammation and disease progression, while anti-inflammatory cytokines (TGF-β, IL-10) maintain immune balance. Metabolic markers like homocysteine, folic acid, and vitamin B12 may influence immune regulation and contribute to endometriosis pathophysiology. Methodology: Serum levels of TNF-α, IL-1β, IL-6, IL-10, TGF-β, CRP, Ferritin, IL-4, IFN-γ, Homocysteine, Folic Acid, and Vitamin B12 were quantified using ELISA kits. Unpaired t-tests and Pearson correlation were used to assess immune-metabolic differences between endometriosis patients and healthy controls. Results: TNFα, IL-6, IL-1β, IL-10, homocysteine, ferritin, and reduced IFN-γ and CRP levels in the case group compared to controls (p < 0.05). TNFα (p = 0.0008), IL-1β (p = 0.0005), and homocysteine (p < 0.0001) were notably higher in cases. IFN-γ (p < 0.0001) and CRP (p < 0.0001) were significantly lower in cases. IL-6 (p = 0.0020), IL-10 (p = 0.0051), ferritin (p = 0.0338), and folate (p = 0.0134) also showed significant differences. TGF-β, IL-4, and Vit-B12 levels did not differ significantly (p > 0.05). These findings suggest altered cytokine and biochemical profiles in disease pathophysiology. Conclusion: The study highlights significant alterations in inflammatory cytokines and metabolic markers in endometriosis patients compared to healthy controls. Elevated pro-inflammatory and altered anti-inflammatory cytokine levels, along with metabolic imbalance, suggest immune-metabolic dysregulation in disease pathogenesis. These findings may aid in identifying potential biomarkers and therapeutic targets for endometriosis. © The Author(s), under exclusive licence to Springer Nature B.V. 2025.PublicationArticle Effects of SARS-Cov-2 infection and rhino-orbital mucormycosis on concentrations of inflammatory biomarkers in Indian populations(IP Innovative Publication Pvt. Ltd., 2022) Ajay Kumar Yadav; Shivam Tiwari; Bhupendra Kumar; Abhay Kumar Yadav; Ashish Ashish; Nitish Kumar Singh; Manpreet Kaur; Shivani Mishra; Shani Vishwakarma; Surendra Pratap Mishra; Rajendra Prakash Maurya; Nargis Khanam; Pooja Dubey; Janhavi Yadav; Royana Singh; Sayeed Mehbub Ul KadirRhino-orbital mucormycosis is a rare life threatening invasive fungal infection that has recently shown a very high mortality rate in India during COVID-19 pandemic. We have designed the present study to find out associations between COVID-19 induced rhino-orbital mucormycosis and concentrations of inflammatory markers, i.e. D-dimer, Ferritin, IL-6, CRP and PCT, in blood serum of Indian population. There were four groups in the study, viz. control group with healthy subjects, treatment group-1 with patients suffering from SARS-COV-2 infection, treatment group-2 with patients suffering from both SARS-COV-2 infection and rhino-orbital mucormycosis, and treatment group-3 with patients suffering from rhino-orbital mucormycosis after SARS-COV-2 infection recovery. Inflammatory markers were quantified with standard protocols, and recorded data were subjected to statistical analyses. We found that patients suffering from SARS-COV-2 infection were more susceptible to rhino-orbital mucormycosis, as they had higher concentrations of inflammatory markers in their blood than the other subjects. Diabetes mellitus, hypertension, cardiovascular diseases and renal disorders were the associated comorbidities with the patients. We also found higher concentrations of inflammatory markers in males than the females, indicating towards their higher susceptibility in developing rhino-orbital mucormycosis than females. Present study therefore suggests that the frequent occurrence of rhino-orbital mucormycosis in India during second wave of COVID-19 was possibly due to indiscriminate use of corticosteroids by COVID-19 patients. Subjects with previous history of comorbidities like diabetes mellitus, hypertension, cardiovascular disorders and renal diseases are the most susceptible population groups for developing infection. Moreover, males are at higher risk of developing mucormycosis than the females. © 2022 Innovative Publication, All rights reserved.PublicationArticle Elevated Circulatory Proline to Glutamine Ratio (PQR) in Endometriosis and Its Potential as a Diagnostic Biomarker(American Chemical Society, 2022) Kusum Kusum; Ritu Raj; Sangeeta Rai; Pranjali Pranjali; Ashish Ashish; Sara Vicente-Muñoz; Radha Chaube; Dinesh KumarEndometriosis (EM) is a hormone-dependent gynecological disease associated with chronic pelvic pain and altered immuno-inflammatory processes. It shares some cancer-like characteristics such as increased proline biosynthesis and activated glutaminolysis. Both proline and glutamine are interconvertible metabolically, and studies have shown their roles in cancer cell metabolic reprogramming, redox homeostasis, occurrence/development of endometrial carcinoma, and its further progression toward the malignant state. So based on this, we hypothesized that the circulatory proline to glutamine ratio (PQR) would be altered in EM and may serve as an indicative biomarker to improve the clinical diagnosis of EM. In present study, the circulatory-PQR levels were estimated for 39 EM patients and 48 age matched healthy female subjects using 800 MHz NMR spectroscopy. Among 39 EM patients, 15 were in the clinical stages I to II and referred to here as moderate EM (MEM) patients and 24 were in the clinical stages III to IV and referred here as severe EM (SEM) patients. The circulatory-PQR levels were significantly increased in EM patients (0.99 ± 0.13 μM in MEM; 1.39 ± 0.22 μM in SEM) compared to normal control (NC) subjects (0.52 ± 0.05 μM in NC). Further, the circulatory PQR levels exhibit the highest diagnostic potential with area under receiver operating characteristic (AUROC) curve values equal to 0.87 ± 0.04 [95%CI = 0.79-0.96] for MEM and 0.89 ± 0.04 [95% CI = 0.82-0.96] for SEM. These results suggested that circulatory-PQR has significant potential to serve as a noninvasive biomarker for diagnostic/prognostic screening of EM and further underscored the importance of these two nonessential amino acids (proline and glutamine) in cancer metabolism. © 2022 American Chemical Society.PublicationArticle Evolution of Bioelectric Membrane Potentials: Implications in Cancer Pathogenesis and Therapeutic Strategies(Springer, 2024) Anju Shrivastava; Amit Kumar; Lalit Mohan Aggarwal; Satyajit Pradhan; Sunil Choudhary; Ashish Ashish; Keshav Kashyap; Shivani MishraElectrophysiology typically deals with the electrical properties of excitable cells like neurons and muscles. However, all other cells (non-excitable) also possess bioelectric membrane potentials for intracellular and extracellular communications. These membrane potentials are generated by different ions present in fluids available in and outside the cell, playing a vital role in communication and coordination between the cell and its organelles. Bioelectric membrane potential variations disturb cellular ionic homeostasis and are characteristic of many diseases, including cancers. A rapidly increasing interest has emerged in sorting out the electrophysiology of cancer cells. Compared to healthy cells, the distinct electrical properties exhibited by cancer cells offer a unique way of understanding cancer development, migration, and progression. Decoding the altered bioelectric signals influenced by fluctuating electric fields benefits understanding cancer more closely. While cancer research has predominantly focussed on genetic and molecular traits, the delicate area of electrophysiological characteristics has increasingly gained prominence. This review explores the historical exploration of electrophysiology in the context of cancer cells, shedding light on how alterations in bioelectric membrane potentials, mediated by ion channels and gap junctions, contribute to the pathophysiology of cancer. Graphical Abstract: (Figure presented.) © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.PublicationBook Chapter Exploring the multifaceted links between comorbidities and cognitive aging(Elsevier, 2025) Ashish Ashish; Nitish Kumar Singh; Anil Kumar Maurya; Shivani Mishra; Royana SinghCognitive aging is a multifactorial process influenced by various physiological, psychological, pathological, and genetic factors. Comorbidities such as cardiovascular diseases, diabetes, hypertension, depression, drug addiction, family, and social environment, which are prevalent in the elderly population, have been implicated in accelerating cognitive decline. Understanding these associations is crucial for developing targeted interventions. This chapter provides a thorough review of existing literature, synthesizing data from gerontology, neurology, and psychiatry to examine the impact of comorbidities on cognitive functions. The findings highlight that cardiovascular diseases and diabetes are strongly associated with an increased risk of cognitive impairment and dementia. Hypertension contributes to vascular dementia through mechanisms involving reduced cerebral blood flow and white matter lesions. Depression, both a risk factor and a consequence of cognitive decline, is linked to shared pathophysiological pathways such as chronic inflammation and neuroendocrine dysregulation. The chapter emphasizes the bidirectional nature of these relationships, underscoring the need for holistic approaches in managing comorbidities to mitigate their impact on cognitive health. Potential mechanisms, including oxidative stress, inflammation, and vascular changes, are explored, and the role of genetic predispositions and lifestyle factors in moderating these effects is considered. Addressing comorbid conditions through integrated healthcare strategies is essential for preserving cognitive functions in aging populations. Future research should focus on personalized medicine approaches and the exploration of novel therapeutic targets to prevent or delay cognitive decline. However, the chapter’s limitations include the lack of standardized methodologies across studies and the need for further exploration into the molecular mechanisms involved. © 2026 Elsevier Inc. All rights reserved..PublicationArticle Genetic Analysis of Recurrent Pregnancy Loss: Role of Karyotyping in Understanding Pathogenesis and Management(Jaypee Brothers Medical Publishers (P) Ltd, 2025) Shivani Mishra; Royana Singh; Sangeeta Rai; Ashish Ashish; Nitish Kumar Singh; Manpreet Kaur; Nargis Khanam; Janhavi Yadav; Chetan SahniIntroduction: Recurrent pregnancy loss (RPL) is defined as two or more spontaneous pregnancy losses within 20–24 weeks of the gestational period, which typically occur in the early stages of pregnancy. Various factors can contribute to RPL, including genetic factors, hormonal imbalances, uterine abnormalities, autoimmune disorders, infections, and lifestyle factors. Materials and methods: This study involved the conventional karyotyping of women facing RPL with the G-banding method and the culture procedure of leukocytes. The statistical analysis was done by IBM SPSS 20 after the biochemical data collection and karyotyping results. Results: The total samples were collected from 160 couples, out of which only 130 were successfully done with conventional karyotyping. It was noted in this study that the genetic rearrangement in female partners was found to be 11.5%, excluding the anatomical, immunogenic, and hormonal factor dysfunctions. The advanced maternal age and primary RPL were found to be more actively causing recurrent miscarriages. Conclusion: These investigations emphasize the importance of genetic analysis in RPL cases, biochemical, and cytogenetic analysis. The karyotyping must be done to rule out any chromosomal rearrangement in male and female partners. The previous family history may indicate the likelihood of carrying chromosomal rearrangements; thus, further study needs to be done in large populations. © (2025), (Jaypee Brothers Medical Publishers (P) Ltd). All rights reserved.PublicationArticle Investigation of Serum Pro-Inflammatory Markers and Trace Elements Among Short Stature in Eastern Uttar Pradesh and Bihar Populations(Dove Medical Press Ltd, 2024) Abhay Kumar Yadav; Nitish Kumar Singh; Ankur Singh; Ashish Ashish; Sachchida Nand Rai; Santosh Kumar Singh; Royana Singh; Suchitra SinghPurpose: Short stature is prevalent among children worldwide, particularly in developing countries. Various trace elements, including zinc, magnesium, iron, copper, chromium and selenium, are crucial for proper body development. The aim of this study is to explore the relationship between trace elements and TNF-α and IL-6 to elicit and possible pathway responsible for short stature. Methods: Two hundred and twenty samples were recruited for this study, 100 short statures and 120 controls were randomly selected. Six trace elements were measured using graphite furnace atomic absorption spectrometry. The concentrations of IL-6 and TNF-α in serum were assessed utilizing the Enzyme-Linked-Immunosorbent Assay (ELISA). Superoxide dismutase was also analysed to determine the oxidative stress response. Results: The study revealed notable distinctions in serum trace element levels of short stature. They exhibited significant lower levels of zinc and magnesium, alongside higher levels of copper. The altered Cu/Zn ratio seemed to have a positive correlation with short stature. Conversely, no significant disparities were observed in iron, chromium, and selenium levels. Furthermore, a significant rise was noted in proinflammatory marker TNF-α and cytokine IL-6. Additionally, superoxide dismutase was low in the short statures In silico study shows a high affinity of Zinc with TNF alpha. It may be suggested that inflammation at any time during childhood, with the rise in TNF alpha tightly binds with zinc and may have led to a decrease in zinc serum levels, altered redox homeostasis and resulted in short stature. Conclusion: The altered Cu/Zn ratio along with high TNF alpha and IL6 may be used as a marker for short stature in the initial years of growth in children before they reach maturity at the age of 18. Thereafter, introducing zinc supplementation could potentially enhance stature by mitigating TNF-alpha level. Further experimental studies will help to establish the exact role of zinc with TNF alpha in short stature. © 2024 Yadav et al.PublicationArticle The Impact of Inflammatory Cytokines on Recurrent Pregnancy Loss: A Preliminary Investigation(Springer Nature, 2025) Shivani Mishra; Ashish Ashish; Sangeeta Rai; Chetan Sahni; Shivam Tiwari; Bhupendra Kumar; Royana SinghRecurrent pregnancy loss (RPL), defined as two or more consecutive miscarriages before 20 weeks of gestation, affects 1–2% of couples worldwide. Pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6 play critical roles in early pregnancy, while anti-inflammatory cytokines like TGF-β and IL-10 promote immune tolerance to prevent harmful inflammatory responses that play important role in placental and fetal development. This aim of the study is to analyse the levels of inflammatory cytokines in blood serum from RPL patients and healthy women (control). The measured cytokines included TNF-α, IL-6, IL-10, TGF-β, CRP, ferritin, IL-1β and IL-4, IFN-γ and IL-17. Using an unpaired t-test and Pearson correlation, significant difference observed between the groups. The results had significantly elevated CRP levels with decreased levels of TGF-β and ferritin (p < 0.05), whereas, IL-1β and IL-4 also found raised indicating a link between systemic inflammation and recurrent miscarriages. IL-4 and CRP increase further suggest potential oxidative stress role in RPL cases. However, no significant differences observed in IL-10, IL-6, or TNF-α level between the groups. This study highlights immune dysregulation as possible contributors to early pregnancy loss, with significant increases in CRP, IL-1β, and IL-4 levels indicating an imbalanced immune response at the maternal–fetal interface. These cytokine elevations may disrupt immune tolerance, suggesting the need for further exploration into cytokine interactions in pregnancy and their potential as an investigatory biomarker and therapeutic target in RPL. © The Author(s), under exclusive licence to Society for Reproductive Investigation 2025.PublicationArticle To determine the genotyping of Fc-gamma receptor FCGR2A polymorphism as genetic susceptibility to neonatal sepsis: A study from a tertiary center of North India(Wolters Kluwer Medknow Publications, 2022) Sarita Chowdhary; Kanika Sharma; Ashish Ashish; Abhay Kumar Yadav; Pranay Panigrahi; Akas Mishra; Deepak Kumar; Royana SinghBackground: Neonatal sepsis term is an infection of newborns <28 days of age. It is a common cause of death in developing countries. The receptor-gamma receptor FCGR2A has been shown to be associated with neonatal sepsis. It is an activating receptor found in many cell types such as monocytes, neutrophils, macrophages, platelets, and others. The receptor has a polymorphism (single-nucleotide polymorphism rs1801274) in its gene (FCGR2A) that encodes either a histidine (H) or arginine (R) at amino acid position 131. There are many studies showing the impact of these FCGR2A polymorphisms on sepsis. Our study aims to determine the prevalence of Fc-gamma receptor FCGR2A (rs1801274) polymorphism in neonatal sepsis and control in Eastern UP populations. Patients and Methods: We conducted a cross-sectional descriptive study of 590 patients (310 healthy individuals and 280 sepsis patients) to determine polymorphisms in the CD32A coding region in neonates. All individuals were genotyped for a variant at position 131 of the FcγRIIA gene. Discussion: In our study, the prevalence of FcγRIIa polymorphism is more in neonates with sepsis than in noninfected neonates. It was observed that the heterozygous allele (AG) were significantly increased in septic neonates when compared to the normal. Conclusion: Our data indicate that FcγRIIA genotyping can be used as a marker of genetic susceptibility to sepsis. © 2022 Wolters Kluwer Medknow Publications. All rights reserved.PublicationArticle Trace elements and cognitions in elderly population: a case–control study(Springer Science and Business Media B.V., 2025) Anil Kumar Maurya; Mona Srivastava; Ashish Ashish; Nitish Kumar Singh; Abhay Kumar Yadav; Shani Vishwakarma; Royana SinghThere have been almost no studies with trace elements and psychological battery in cognitively impaired elderly individuals. Such research is crucial to enhance diagnostic accuracy. We aim to identify significant differences in blood serum concentration levels of trace elements, Hindi Mini-Mental State Examination (HMMSE), and psychological battery as Hindi Mattis Dementia Rating Scale (HMDRS) scores between case and control groups in the elderly. A cross-sectional research design was conducted with a total of 240 subjects, comprising 120 each from the case and control groups. Trace elements were analyzed using Atomic Absorption Spectrometry. HMMSE and HMDRS tests were administered to assess cognition scores. The chi-square test, t-test, and appropriate statistics were utilized. Our findings indicate significant differences in demographic factors (age, gender, education level) and clinical levels (p <.001), while caste, habitat, and marital status were not significant (p <.05). Concentration levels of Iron (Fe) and Copper (Cu) was higher, Zinc (Zn), Chromium (Cr), and Selenium (Se) were lower, significantly different (p <.001), but Magnesium (Mg) was not (p <.05). Additionally, third HMMSE and HMDRS were significant (p <.001) between the case and control groups in the elderly. The study suggested that higher levels of Fe and Cu, while lower Zn, Cr, and Se blood serum concentrations increased the risk of cognitive impairments in the elderly population, demonstrated by the HMMSE and HMDRS test scores which were lower in the case group. © The Author(s), under exclusive licence to Springer Nature B.V. 2025.PublicationBook Chapter Unlocking cognitive vitality: the interplay of stimulation, sleep, and brain aging(Elsevier, 2025) Nitish Kumar Singh; Ashish Ashish; Surbhi Singh; Pooja Dubey; Royana SinghCognitive vitality is a crucial component of healthy aging, influenced by cognitive stimulation, sleep quality, and the natural aging process of the brain. This chapter explores the interplay between these factors, integrating findings from empirical and neuroimaging studies to provide a comprehensive perspective on their impact on brain aging. Research shows that participating in cognitive activities like reading, solving problems, and engaging in social interactions boosts neural plasticity and helps slow down cognitive decline. At the same time, quality sleep, defined by sufficient duration and few interruptions, is crucial for memory consolidation, synaptic balance, and the removal of neural waste. In contrast, inadequate sleep speeds up brain aging and raises the likelihood of neurodegenerative diseases. Research indicates that the combined effects of mental stimulation and sleep may yield synergistic benefits for cognitive health. However, several limitations must be acknowledged. Despite strong empirical support, variability in study methodologies, sample sizes, and assessment tools may influence the generalizability of findings. Additionally, while neuroimaging studies provide valuable insights, they cannot fully capture the complexity of individual cognitive trajectories. The long-term impact of specific interventions remains an area requiring further exploration, particularly in diverse populations. Future research should focus on refining personalized intervention strategies and examining the bidirectional relationship between cognitive stimulation and sleep in brain aging. Addressing these gaps will enhance our understanding of cognitive resilience and inform effective approaches to maintaining cognitive function in aging populations. © 2026 Elsevier Inc. All rights reserved..PublicationArticle Unveiling immune and signalling proteins in recurrent pregnancy loss: GEO2R analysis sheds light(Elsevier Ltd, 2025) Shivani Mishra; Surbhi Singh; Ashish Ashish; Sangeeta Rai; Royana SinghBackground: Recurrent pregnancy loss (RPL) is defined as the spontaneous loss of two or more pregnancies on or before 24 weeks of gestation. It has multifactorial aetiology, including genetic abnormalities, immune dysfunction, hormonal imbalances, and environmental factors. The Gene Expression Omnibus (GEO) database and its analytical tool GEO2R enable differential gene expression analysis to identify potential biomarkers in RPL. Objective: This study aims to identify differentially expressed genes (DEGs) and pathways contributing to RPL pathogenesis using transcriptome data mining and in silico approaches. Methodology: High-throughput gene expression data from four datasets (GSE141716, GSE204721, GSE161969, and GSE139180) were analysed. Enrichment analysis of DEGs conducted using the KEGG database and the BINGO plugin in Cytoscape. Protein-protein interaction (PPI) networks constructed using STRING, and molecular docking of key hub genes performed using HDOCK and Discovery Studio. ELISA validation of TNF-α, CD44, and MMP2 analysed on serum samples. Results: Pathway analysis revealed immune-related pathways, including TNF-α, CD44, MMP2, VEGFR, and IL-17 signalling. Ten hub genes identified TNF, CD44, MMP2, CCL2, FN1, IL1A, THBS1, STAT1, ICAM1, and PXDN. Docking analysis confirmed TNFα-CD44 interactions, emphasizing their role in immune tolerance. ELISA results showed significantly elevated TNF-α (p = 0.001) and MMP2 (p = 0.0001) levels in RPL cases, while CD44 was not found significant (p = 0.632). Conclusion: This transcriptomic study highlights immune modulation as a key factor in RPL, identifying potential biomarkers and therapeutic targets for improved diagnosis and management. © 2025 Elsevier Ltd
