An integrated in-silico Pharmaco-BioInformatics approaches to identify synergistic effects of COVID-19 to HIV patients

Computers in Biology and Medicine, Journal Year: 2023, Volume and Issue: 155, P. 106656 - 106656

Published: Feb. 10, 2023

With high inflammatory states from both COVID-19 and HIV conditions further result in complications. The ongoing confrontation between these two viral infections can be avoided by adopting suitable management measures.The aim of this study was to figure out the pharmacological mechanism behind apigenin's role synergetic effects progression patients.We employed computer-aided methods uncover similar biological targets signaling pathways associated with HIV, along bioinformatics network pharmacology techniques assess apigenin on as well pharmacokinetics analysis examine safety human body.Stress-responsive, membrane receptor, induction were mostly involved gene ontology (GO) pathways, whereas apoptosis significantly Kyoto encyclopedia genes genomes (KEGG). top 20 hub detected utilizing shortest path ranked degree method protein-protein interaction (PPI), molecular docking dynamics simulation performed, revealing strong proteins (MAPK3, RELA, MAPK1, EP300, AKT1). Moreover, pharmacokinetic features revealed that it is an effective therapeutic agent minimal adverse effects, for instance, hepatoxicity.Synergetic may still a danger global public health. Consequently, advanced solutions are required give valid information regarding effects. However, findings have yet confirmed patients, suggesting more vitro vivo studies.

Language: Английский

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Molecular Mimicry of SARS-CoV-2 Spike Protein in the Nervous System: A Bioinformatics Approach

Computational and Structural Biotechnology Journal, Journal Year: 2022, Volume and Issue: 20, P. 6041 - 6054

Published: Jan. 1, 2022

The development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in record time to cope with the ongoing disease 2019 (COVID-19) pandemic has led uncertainty about their use and appearance adverse neurological reactions. SARS-CoV-2 spike protein (SP) is used produce neutralizing antibodies stimulate innate immunity. However, considering alterations nervous system (NS) caused by COVID- 19, cross-reactions are plausible. To identify peptides Homo sapiens SP-like proteins involved myelin axon homeostasis that may be affected due molecular mimicry T cells induced interaction SP. A bioinformatics approach was used. select H. studied, related biological processes categorized based on gene ontology were extracted through construction a protein–protein network. Peripheral 22, major component peripheral system, as query protein. extracellular domains regions susceptible recognition from UniProt. In study cells, linear sequence similarity between SP assessed using BLASTp. This considered terms biochemical groups per residue affinity human histocompatibility complex (human leukocyte antigen I), which evaluated Needle NetMHCpan 4.1, respectively. large number shared pentapeptides identified. only small group 39 linked homeostasis. particular, some proteins, such phosphacan, attractin, teneurin-4, targets B cells. Other closely components NS, myelin-associated glycoprotein, found share at least one pentamer domains. Proteins maintenance nerve conduction central NS identified sapiens. Based these findings, re-evaluation vaccine composition recommended prevent possible side effects.

Language: Английский

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qPCR Analysis Reveals Association of Differential Expression of SRR, NFKB1, and PDE4B Genes With Type 2 Diabetes Mellitus

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 3, 2022

Type 2 diabetes mellitus (T2DM) is a heterogeneous, metabolic, and chronic condition affecting vast numbers of the world's population. The related variables T2DM associations have not been fully understood due to their diverse nature. However, functional genomics can facilitate understanding disease. This information will be useful in drug design, advanced diagnostic, prognostic markers.To understand genetic causes T2DM, this study was designed identify differentially expressed genes (DEGs) disease.We investigated 20 publicly available disease-specific cDNA datasets from Gene Expression Omnibus (GEO) containing several attributes including gene symbols clone identifiers, GenBank accession numbers, phenotypic feature coordinates. We analyzed an integrated system-level framework involving Ontology (GO), protein motifs co-expression analysis, pathway enrichment, transcriptional factors reveal biological genes. A network studied highlight that showed coordinated expression pattern across group samples. DEGs were validated by quantitative PCR (qPCR) analyze levels case control samples (50 each) using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as reference gene.From list 50 DEGs, we ranked three T2DM-related (p < 0.05): SRR, NFKB1, PDE4B. enriched terms revealed significant role amino acid metabolism, signal transduction, transmembrane intracellular transport, other vital functions. DMBX1, TAL1, ZFP161, NFIC (66.7%), NR1H4 (33.3%) are associated with regulatory mechanism. found substantial enrichment insulin signaling pathways, such valine, leucine isoleucine biosynthesis, serine threonine adipocytokine pathway, P13K/Akt Hedgehog pathway. profiles these verified qPCR level twofold change (FC) (2-ΔΔCT) SRR (FC ≤ 0.12), NFKB1 1.09), PDE4B 0.9) compared controls ≥ 1.6). downregulated pathophysiological development metabolic disorders.This would help modulate therapeutic strategies for could speed up discovery outcomes.

Language: Английский

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DNA methylation and expression profiles of placenta and umbilical cord blood reveal the characteristics of gestational diabetes mellitus patients and offspring

Clinical Epigenetics, Journal Year: 2022, Volume and Issue: 14(1)

Published: May 23, 2022

Abstract Background Gestational diabetes mellitus (GDM) is a common pregnancy-specific disease and growing at an alarming rate worldwide, which can negatively affect the health of pregnant women fetuses. However, most studies are limited to one tissue, placenta or umbilical cord blood, usually with omics assay. It thus difficult systematically reveal molecular mechanism GDM key influencing factors on offspring. Results We recruited group 21 20 controls without GDM. For each woman, reduced representation bisulfite sequencing RNA-seq were performed using paired neonatal blood specimens. Differentially methylated regions (DMRs) differentially expressed genes (DEGs) identified body mass index as covariate. Through comparison control samples, 2779 141 DMRs, 1442 488 DEGs from respectively. Functional enrichment analysis showed that methylation expression profiles mirrored characteristics “type II diabetes” “insulin resistance.” Methylation-altered in associated pathways “cholesterol metabolism.” Remarkably, both DMRs illustrated significant overlaps among samples. The overlapping top-ranking enriched shared include “growth hormone synthesis, secretion action” mellitus.” Conclusions Our research demonstrated epigenetic transcriptomic alternations findings emphasized importance modifications communication between offspring, provided reference for prevention, control, treatment, intervention perinatal deleterious events complications.

Language: Английский

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Bioinformatics and In silico approaches to identify novel biomarkers and key pathways for cancers that are linked to the progression of female infertility: A comprehensive approach for drug discovery

PLoS ONE, Journal Year: 2023, Volume and Issue: 18(1), P. e0265746 - e0265746

Published: Jan. 6, 2023

Despite modern treatment, infertility remains one of the most common gynecologic diseases causing severe health effects worldwide. The clinical and epidemiological data have shown that several cancerous risk factors are strongly linked to Female Infertility (FI) development, but exact causes remain unknown. Understanding how these affect FI-affected cell pathways might pave door for discovery critical signaling hub proteins may be targeted therapeutic intervention. To deal with this, we used a bioinformatics pipeline build transcriptome study FI four carcinogenic factors: Endometrial Cancer (EC), Ovarian (OC), Cervical (CC), Thyroid (TC). We identified sharing 97, 211, 87 33 differentially expressed genes (DEGs) EC, OC, CC, TC, respectively. built gene-disease association networks from based on multilayer network neighbour-based benchmarking. Identified TNF signalling pathways, ovarian genes, cholesterol metabolic process, cellular response cytokine stimulus were significant molecular GO both which improved our understanding fundamental mechanisms cancers associated progression. For intervention, two VEGFA PIK3R1, out ten Maximal Clique Centrality (MCC) value cytoscape literature analysis docking 27 phytoestrogenic compounds. Among them, sesamin, galangin coumestrol showed highest binding affinity PIK3R1 together favourable ADMET properties. recommended pathway, phytocompounds served as new targets interventions accurate diagnosis treatment multiple diseases.

Language: Английский

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Shared genetic aetiology of Alzheimer’s disease and age-related macular degeneration by APOC1 and APOE genes

BMJ Neurology Open, Journal Year: 2024, Volume and Issue: 6(1), P. e000570 - e000570

Published: April 1, 2024

Alzheimer's disease (AD) and age-related macular degeneration (AMD) share similar pathological features, suggesting common genetic aetiologies between the two. Investigating gene associations AD AMD may provide useful insights into underlying pathogenesis inform integrated prevention treatment for both diseases.

Language: Английский

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Identification of Molecular Signatures and Candidate Drugs in Vascular Dementia by Bioinformatics Analyses

Frontiers in Molecular Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: Feb. 11, 2022

Vascular dementia (VaD) is considered to be the second most common form of after Alzheimer's disease, and no specific drugs have been approved for VaD treatment. We aimed identify shared transcriptomic signatures between frontal cortex temporal in by bioinformatics analyses. Gene ontology pathway enrichment analyses, protein-protein interaction (PPI) hub gene identification, gene-transcription factor interaction, gene-microRNA gene-drug analyses were performed. identified 159 overlapping differentially expressed genes (DEGs) that enriched mainly inflammation innate immunity, synapse pruning, regeneration, positive regulation angiogenesis, response nutrient levels, digestive system process. 10 PPI network (GNG13, CD163, C1QA, TLR2, SST, C1QB, ITGB2, CCR5, CRH, TAC1), four central regulatory transcription factors (FOXC1, CREB1, GATA2, HINFP), microRNAs (miR-27a-3p, miR-146a-5p, miR-335-5p, miR-129-2-3p). Hub analysis found (maraviroc, cenicriviroc, PF-04634817, efalizumab) could potential Together, our results may contribute understanding underlying mechanisms provide targets therapeutic intervention.

Language: Английский

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Polygenic Risk Score for Cardiovascular Diseases in Artificial Intelligence Paradigm: A Review

Journal of Korean Medical Science, Journal Year: 2023, Volume and Issue: 38(46)

Published: Jan. 1, 2023

Cardiovascular disease (CVD) related mortality and morbidity heavily strain society.The relationship between external risk factors our genetics have not been well established.It is widely acknowledged that environmental influence individual behaviours play a significant role in CVD vulnerability, leading to the development of polygenic scores (PRS).We employed PRISMA search method locate pertinent research literature extensively review artificial intelligence (AI)-based PRS models for prediction.Furthermore, we analyzed compared conventional vs. AI-based solutions PRS.We summarized recent advances understanding use prediction CVD.Our study proposes three hypotheses: i) Multiple genetic variations

Language: Английский

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Neuroinflammation mediates the progression of neonate hypoxia-ischemia brain damage to Alzheimer’s disease: a bioinformatics and experimental study

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 13, 2025

Traumatic brain injury (TBI) can generally be divided into focal damage and diffuse damage, neonate Hypoxia-Ischemia Brain Damage (nHIBD) is one of the causes damage. Patients with nHIBD are at an increased risk developing Alzheimer's disease (AD). However, shared pathogenesis patients affected both neurological disorders has not been fully elucidated. We here aim to identify molecular signatures between AD. used integrated analysis cortex gene expression data, targeting differential genes related mechanisms neurodegeneration cognitive impairment following traumatic injury. The profiles (GSE203206) that Neonate (GSE23317) were obtained from Gene Expression Omnibus (GEO) database. After identifying common differentially expressed (DEGs) by limma package analysis, five kinds analyses performed on them, namely Ontology (GO) pathway enrichment protein-protein interaction network, DEG-transcription factor interactions DEG-microRNA interactions, protein-drug protein-disease association gene-inflammation protein-inflammation analysis. In total, 12 DEGs identified including HSPB1, VIM, MVD, TUBB4A, AACS, ANXA6, DIRAS2, RPH3A, CEND1, KALM, THOP1, AREL1. also 11 hub proteins, three central regulatory transcription factors, microRNAs encoded DEGs. Protein-drug showed CYC1 UQCRFS1 associated different drugs. Gene-disease shows Mammary Neoplasms, Neoplasm Metastasis, Schizophrenia, Ischemia diseases most relevant proteins we identified. Gene-inflammation AREL1 inflammatory response, while AKT1 MAPK14 response. This study provides new insights AD nHIBD. These pathways could potentially design therapeutic interventions, reducing likelihood development in survivors neonatal Hypoxic-Ischemia

Language: Английский

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Diabetes and brain: omics approaches to study diabetic encephalopathy

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: May 12, 2025

Diabetes mellitus (DM) is a complex metabolic disorder associated with many complications, including diabetic encephalopathy (DE). DE severe neurological condition characterized by progressive decline in cognitive and motor functions, significantly impacting patients’ quality of life. Despite advancements understanding DM, the intricate pathogenetic mechanisms underlying remain incompletely elucidated. This review comprehensively analyzes application omics technologies to decipher molecular basis identify potential diagnostic biomarkers therapeutic targets. Several studies on animal models have revealed specific signatures changes gene expression key memory brain regions, like hippocampus, highlighting We explore how these “omics” approaches provided novel insights into interplay factors contributing DE. Recurrent alterations were identified upon evaluation analysis from human tissues vitro Findings indicate that this pathological impaired energy metabolism, oxidative stress, neuroinflammation, neuroendocrine dysfunction influence gut microbiota. A multi-omics approach, integrating data various limited studies, enhances translational pathogenesis, new implications for diagnosis treatment.

Language: Английский

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