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Akbar, A.

Publications and source records attributed to Akbar, A..

6 recordsLinked to original sources

Relationship between SARC-F score and Peripheral Blood Lymphocytes in Juvenile Idiopathic Arthritis: An Observational Pilot Study

BackgroundGiven the relatively high prevalence of sarcopenia and immune profile abnormalities in inflammatory arthritis such as rheumatoid arthritis (RA), we investigated the relationship between exercise habits, SARC-F score and peripheral blood lymphocyte profiles in patients with Juvenile idiopathic arthritis (JIA). MethodsAll participants with JIA completed the SARC-F survey and self-reported exercise habits through online questionnaires. We defined two groups based on SARC-F scores as musculoskeletal function impaired (SARC-Fhi+) and musculoskeletal function not impaired (SARC-Fhi-). We used flow cytometry of peripheral blood mononuclear cells to define immune cell subpopulations. Statistical analyses were performed using GraphPad Prism software version10. ResultsOf the 18 participants with a median age of 24 years - five belonged to the SARC-Fhi+ group and 13 to the SARC-Fhi-group, of whom 80% and 38% were female, respectively. The SARC-Fhi + group had fewer CD45RA+CD27+ naive CD4+ T cells (26.60% vs. 45.30%, p=0.0264) and greater CD45RA-CD27-effector memory CD4+ T cells (11.90% vs. 7.00%, p=0.0350). The SARC-Fhi+ group also had fewer CD56-CD16+ NK cells compared to the SARC-Fhi-group (2.60% v. 4.28%, p = 0.0194). The moderate exercise group (n = 13) had increased numbers of total CD4+ T cells (54.06% vs. 37.30%, p=0.0140) and 3-fold fewer CD45RA+CD27-EMRA CD8+ T cells (3.17% vs. 10.40%, p=0.0350). There were no other significant differences for other immune cells / subpopulations including B cells. ConclusionsOur study findings suggest notable differences in immune profile relative to SARC-F score. Furthermore, the 3-fold lower frequency of CD8+ TEMRA subpopulation of T cells, reflective of immunosenescence, suggest a potential inverse relationship between moderate exercise and peripheral immune cell profile in JIA. Key messagesO_LISARC-F score was used as a clinically relevant tool to identify musculoskeletal function in JIA C_LIO_LISARC-Fhi+ group had fewer naive CD4+ T cells and greater effector memory CD4+ T cells C_LIO_LIModerate exercise group had 3-fold lower frequency of CD8+ TEMRA T cells C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=54 SRC="FIGDIR/small/681879v1_ufig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@1eb9d4org.highwire.dtl.DTLVardef@13a18a4org.highwire.dtl.DTLVardef@127d55corg.highwire.dtl.DTLVardef@28bddf_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

THE UNCHARTED ROLE OF ERAP2 IN AGING: A BIOINFORMATICS PERSPECTIVE

BackgroundAging is associated with significant changes in the immune system, leading to increased susceptibility to infections, reduced vaccine efficacy, and a higher risk of autoimmune diseases. However, the molecular mechanisms driving these immunological alterations remain incompletely understood. In this study, we performed differential gene expression analysis (DGEA) to identify genes implicated in immune aging and explored their functional significance through enrichment analysis. MethodsUsing publicly available transcriptomic data from aged versus young individuals, we conducted DGEA to identify significantly dysregulated genes. Functional enrichment analyses, including Gene Ontology (GO) and Reactome pathway analysis, were performed to uncover biological processes and pathways enriched in the differentially expressed genes. We specifically focused on ERAP2, a gene found to be differentially expressed in aging, and examined its expression across various tissues. Additionally, we reviewed existing literature to assess ERAP2s role in antigen presentation and immune regulation. ResultsOur analysis revealed significant enrichment of pathways related to antigen processing and presentation, peptide metabolism, and immune system regulation. ERAP2, an aminopeptidase involved in trimming peptides for MHC class I presentation, was highly associated with these processes. Interestingly, no direct KEGG pathway annotation was found for ERAP2, suggesting a potential gap in functional characterization. However, Reactome analysis confirmed its involvement in class I MHC-mediated antigen processing and immune system pathways, aligning with its known immunological role. The expression analysis across multiple tissues showed ERAP2 to be widely expressed in immune-related tissues, further supporting its relevance. ConclusionOur findings highlight the potentially underexplored role of ERAP2 in immune aging. The lack of KEGG pathway annotation suggests that its function in aging and immune modulation may not be fully characterized, presenting an opportunity for further research. Given its role in antigen presentation, ERAP2 may represent a critical factor in the declining immune function observed in aging individuals. Further experimental validation is required to establish its mechanistic involvement and potential as a therapeutic target for age-related immune dysfunction.

immunology↗

In Silico Analysis of Non-Coding RNA Regulation in Human Gene Expression: A Systematic Computational Approach to Understanding Regulatory Networks

The regulatory networks of miRNAs, lncRNAs, and their target genes play a crucial role in controlling various cellular processes, including cell growth, apoptosis, and immune responses. In this study, we performed an in silico analysis to explore the interactions between miRNAs, lncRNAs, and their target genes in the context of disease mechanisms. We utilized multiple computational approaches, including miRNA-target interaction prediction, lncRNA-target network analysis, differential expression analysis using RNA-seq data, and validation of interactions using miRNA target prediction tools. Our results highlight key genes involved in apoptosis, cell cycle regulation, and tumorigenesis, providing valuable insights into the molecular mechanisms underlying disease progression. Non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have emerged as pivotal regulators of gene expression in human cells. Despite substantial research into their roles, there remains a critical gap in understanding how these molecules interact within complex regulatory networks. In this study, we employed a comprehensive bioinformatics approach to systematically identify and analyze ncRNA-mediated gene regulation in human cells. We utilized publicly available datasets from the ENCODE and GEO repositories, combined with computational tools such as miRBase, LNCipedia, TargetScan, and Cytoscape, to predict ncRNA-gene interactions and construct regulatory networks. Our analysis reveals several novel ncRNA regulators and their associated gene targets, which were further explored through pathway enrichment analysis. This study provides new insights into the regulatory networks of ncRNAs in human gene expression, offering a foundation for future functional studies and potential therapeutic applications.

bioinformatics↗

Phenotyping of lymphoproliferative tumours generated in xenografts of non-small cell lung cancer

Patient-derived xenograft (PDX) models involve the engraftment of tumour tissue in immunocompromised mice and represent an important pre-clinixtcal oncology research. A limitation of non-small cell lung cancer (NSCLC) PDX model derivation in NOD-scid IL2Rgammanull (NSG) mice is that a subset of initial engraftments are of lymphocytic, rather than tumour origin. In the lung TRACERx PDX pipeline, lymphoproliferations occurred in 17.8% of lung adenocarcinoma and 10% of lung squamous cell carcinoma transplantations, despite none of these patients having a prior or subsequent clinical history of lymphoproliferative disease. Lymphoproliferations were predominantly human CD20+ B cells and had the immunophenotype expected for post-transplantation diffuse large B cell lymphoma. All lymphoproliferations expressed Epstein-Barr-encoded RNAs (EBER). Analysis of immunoglobulin light chain gene rearrangements in three tumours where multiple tumour regions had resulted in lymphoproliferations suggested that each had independent clonal origins. Overall, these data suggest the presence of B cell clones with lymphoproliferative potential within primary NSCLC tumours that are under continuous immune surveillance. Since these cells can be expanded following transplantation into NSG mice, our data highlight the value of quality control measures to identify lymphoproliferations within xenograft pipelines and support the incorporation of strategies to minimise lymphoproliferations during the early stages of xenograft establishment pipelines. To present the histology data herein, we developed a Python-based tool for generating patient-level pathology overview figures from whole-slide image files; PATHOverview is available on GitHub (https://github.com/EpiCENTR-Lab/PATHOverview).

cancer biology↗

Intercellular telomere transfer extends T cell lifespan

The common view is that T-lymphocytes activate telomerase, a DNA polymerase that extends telomeres at chromosome ends, to delay senescence. We show that independently of telomerase, T cells elongate telomeres by acquiring telomere vesicles from antigen-presenting cells (APCs). Upon contact with T cells, APCs degraded shelterin to donate telomeres, which were cleaved by TZAP, and then transferred in extracellular vesicles (EVs) at the immunological synapse. Telomere vesicles retained the Rad51 recombination factor that enabled them to fuse with T cell chromosomal ends causing an average lengthening of [~]3000 base pairs. Thus, we identify a previously unknown telomere transfer program that supports T cell lifespan.

immunology↗

Differential detection of Entamoeba species in stool samples collected from children in District Swat, Khyber Pakhtunkhwa Pakistan

BackgroundAmoebiasis is an intestinal disease caused by enteric protozoan called Entamoeba histolytica belongs to the Genus Entamoeba. The main reason of infection is the contamination of food and water due to the poor sanitation. Among Entamoeba species, Entamoeba histolytica is highly pathogenic while the other species are non-pathogenic and needs no medical treatment.\n\nMethodologyA total of 400 stool samples were collected from different areas of district Swat and were processed for screening of amoebic cells. Microscopically identified samples containing amoebic cells were stored at -20 {degrees}C till DNA extraction. Extracted DNA was used in a PCR reaction with specific reference primers to amplify the target DNA.\n\nResultsOut of all 400 stool samples 111 (27.7%) were found positive through microscopy while PCR reaction confirmed 80 out of microscope positive samples. Among 80 PCR positive samples, the infection with Entamoeba dispar was most common (57.5%) followed by E. histolytica (47.5%) and Entamoeba moshkovskii (20%). The positive cases for mono-infection of E. dispar were 33 (41.25%), followed by E.histolytica 25 (31.25%) and E. moshkovskii 7 (8.75%). The co-infection of E. histolytica with E. dispar and E. moshkovskii was 6 (7.5%) and 2 (2.5%), respectively. Similarly the co-infection of Entamoeba dispar with Entamoeba moshkovskii was also 2 (2.5%) while 5 (6.25%) samples were observed with mixed infection of E. histolytica, E. dispar and E. moshkovskii.\n\nSignificance of the studyThe aim of the study was to detect and differentiate the E. histolytica, Entamoeba dispar and Entamoeba moshkovskii using conventional microscopy and polymerase chain reaction. The results suggested that the use of PCR is necessary to differentiate E. histolytica from E. dispar and E. moshkovskii and therefore, to avoid unnecessary treatment the present study recommend the use of PCR for the routine diagnosis of amoebiasis in the study area. It is also suggested that further studies from this area may also facilitate the understanding of genetic diversity of these pathogens.

microbiology↗