Comprehensive analysis of next-generation sequencing data in COVID-19 and its secondary complications DOI Open Access
Muttanagouda Giriyappagoudar, Basavaraj Vastrad, Rajeshwari Horakeri

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Feb. 4, 2022

Abstract The ongoing pandemic of coronavirus disease 2019 (COVID-19) has made a serious public health threat globally. To discover key molecular changes in COVID-19 and its secondary complications, we analyzed next-generation sequencing (NGS) data COVID-19. NGS (GSE163151) was screened downloaded from the Gene Expression Omnibus database (GEO). Differentially expressed genes (DEGs) were identified present study, using DESeq2 package R programming software. ontology (GO) pathway enrichment analysis performed, protein-protein interaction (PPI) network, module analysis, miRNA-hub gene regulatory network TF-hub established. Subsequently, receiver operating characteristic curve (ROC) used to validate diagonostics valuesof hub genes. Firstly, 954 DEGs (477 up regulated 477 down regulated) four dataset. GO revealed related immune system process multicellular organismal process, REACTOME showed formation cornified envelope. Hub PPI network. Furthermore, ROC indicate that complications with following genes, namely, RPL10, FYN, FLNA, EEF1A1, UBA52, BMI1, ACTN2, CRMP1, TRIM42 PTCH1, had good diagnostics values. This study several associated which improves our knowledge mechanism.

Language: Английский

Pancreatic INS-1 β-Cell Response to Thapsigargin and Rotenone: A Comparative Proteomics Analysis Uncovers Key Pathways of β-Cell Dysfunction DOI

Mehari Muuz Weldemariam,

Jongmin Jacob Woo, Qibin Zhang

et al.

Chemical Research in Toxicology, Journal Year: 2022, Volume and Issue: 35(6), P. 1080 - 1094

Published: May 11, 2022

Insulin-secreting β-cells in the pancreatic islets are exposed to various endogenous and exogenous stressing conditions, which may lead β-cell dysfunction or apoptosis ultimately diabetes mellitus. However, detailed molecular mechanisms underlying β-cell's inability survive under severe stresses remain be explored. This study used two common chemical stressors, thapsigargin rotenone, induce endoplasmic reticulum (ER) mitochondria stress a rat insuloma INS-1 832/13 line, mimicking conditions experienced by dysfunctional β-cells. Proteomic changes of cells upon treatment with stressors at IC50 were profiled TMT-based quantitative proteomics further verified using label-free quantitive proteomics. The differentially expressed proteins selected for in-depth bioinformatic analysis. Thapsigargin specifically perturbed unfolded protein response (UPR) related pathways; addition, 58 not previously linked UPR pathways identified consistent upregulation induced thapsigargin. Conversely, rotenone resulted significant proteome key regulatory such as fatty acid β-oxidation, cellular respiration, citric cycle, respiratory electron transport. Our data also demonstrated that both increased reactive oxygen species production depleted adenosine triphosphate synthesis, resulting dysregulation oxidative phosphorylation signaling pathways. These novel dysregulated suggest an alternative mechanism action provide potential targets probing ER- stress-induced death.

Language: Английский

Citations

4

Epigenetic and transcriptomic alterations in offspring born to women with type 1 diabetes (the EPICOM study) DOI Creative Commons
Sine Knorr, Anne Skakkebæk, Jesper Just

et al.

BMC Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: Sept. 23, 2022

Abstract Background Offspring born to women with pregestational type 1 diabetes (T1DM) are exposed an intrauterine hyperglycemic milieu and has increased risk of metabolic disease later in life. In this present study, we hypothesize that utero exposure T1DM alters offspring DNA methylation gene expression, thereby altering their future disease. Methods Follow-up study using data from the Epigenetic, Genetic Environmental Effects on Growth, Metabolism Cognitive Functions Women Type Diabetes (EPICOM) collected between 2012 2013. Setting Exploratory sub-study nationwide EPICOM study. Participants Adolescent ( n =20) controls matched age, sex, postal code. Main outcome measures This investigates 450K-Illumina Infinium assay RNA expression (RNA sequencing) leucocytes peripheral blood samples. Results We identified 9 hypomethylated 5 hypermethylated positions p < 0.005, |Δ M -value| > 1) 38 up- downregulated genes log2FC ≥ 0.3) adolescent compared controls. None these findings remained significant after correction for multiple testing. However, differences co-expression networks, which could be biological significance, weighted correlation network analysis. Interestingly, one modules was significantly associated T1DM. Functional enrichment analysis, changes as input, revealed ontologies related diabetes, carbohydrate glucose metabolism, pathways including MAPK1/MAPK3 MAPK family signaling, T1DM, obesity, atherosclerosis, vascular pathologies. Lastly, by integrating data, six where relevant corresponded CIITA , TPM1 PXN ST8SIA1 LIPA DAXX ). Conclusions These suggest possibility maternal impact life offspring, a profile may linked

Language: Английский

Citations

4

Prebiotic inulin nanocoating for pancreatic islet surface engineering DOI

Jianghai Tang,

Xuanjin Chen,

Hang Shi

et al.

Biomaterials Science, Journal Year: 2022, Volume and Issue: 11(4), P. 1470 - 1485

Published: Dec. 19, 2022

Pancreatic islet surface engineering has been proposed as an "easy-to-adopt" approach to enhance post-transplantation engraftment for treatment against diabetes. Inulin is FDA-approved dietary prebiotic with reported anti-diabetic, anti-inflammatory, anti-hypoxic and pro-angiogenic properties. We therefore assessed whether inulin would be a viable option engineering. was oxidized generate inulin-CHO, which bind the cell membrane via covalent bond formation between -CHO -NH2 across membrane. In vitro assessments demonstrated enhanced viability better glucose-induced insulin secretion from inulin-coated (5 mg mL-1) islets, accompanied by revascularization, shown significantly tube branching of endothelial MS1 cells following co-culture islets. Reduction cytokine-induced death also observed islets exposure pro-inflammatory cytokine LPS. LPS-induced ROS production dampened 44% in when compared controls. RNA-seq analysis control identified expression alterations genes involved function, vascular immune regulation, supporting positive impact on preservation. vivo examination using streptozotocin (STZ)-induced hyperglycemic mice further showed moderately maintained plasma glucose levels received transplantation attributable ameliorated CD45+ infiltration improved graft vascularization. propose safe beneficial, assessment required verify its applicability clinical transplantation.

Language: Английский

Citations

3

Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model DOI Creative Commons
Ahmed K. Elsayed, Noura Aldous, Nehad M. Alajez

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 16, 2024

Abstract The pathogenesis of diabetes involves complex changes in the expression profiles mRNA and non-coding RNAs within pancreatic islet cells. Recent progress induced pluripotent stem cell (iPSC) technology have allowed modeling diabetes-associated genes. Our recent study using FOXA2-deficient human iPSC models has highlighted an essential role for FOXA2 development pancreas. Here, we aimed to provide further insights on microRNAs (miRNAs) by studying miRNA-mRNA regulatory networks iPSC-derived islets lacking gene. Consistent with our previous findings, absence significantly downregulated hormones, INS, GCG, alongside other key developmental genes islets. Concordantly, RNA-Seq analysis showed significant downregulation related upregulation associated nervous system lipid metabolic pathways. Furthermore, resulted alterations miRNA expression, 61 miRNAs upregulated 99 downregulated. targeted crucial involved development. In contrary, a network targeting metabolism. These findings highlight impact suggesting intricate affecting

Language: Английский

Citations

0

Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model DOI Creative Commons
Ahmed K. Elsayed, Noura Aldous, Nehad M. Alajez

et al.

Stem Cell Reviews and Reports, Journal Year: 2024, Volume and Issue: 20(7), P. 1915 - 1931

Published: June 25, 2024

The pathogenesis of diabetes involves complex changes in the expression profiles mRNA and non-coding RNAs within pancreatic islet cells. Recent progress induced pluripotent stem cell (iPSC) technology have allowed modeling diabetes-associated genes. Our recent study using FOXA2-deficient human iPSC models has highlighted an essential role for FOXA2 development pancreas. Here, we aimed to provide further insights on microRNAs (miRNAs) by studying miRNA-mRNA regulatory networks iPSC-derived islets lacking gene. Consistent with our previous findings, absence significantly downregulated hormones, INS, GCG, alongside other key developmental genes islets. Concordantly, RNA-Seq analysis showed significant downregulation related upregulation associated nervous system lipid metabolic pathways. Furthermore, resulted alterations miRNA expression, 61 miRNAs upregulated 99 downregulated. targeted crucial involved development. In contrary, a network targeting metabolism. These findings highlight impact suggesting intricate affecting

Language: Английский

Citations

0

In-silico identification and functional characterization of common genes associated with type 2 diabetes and hypertension DOI Creative Commons

Md. Golam Rabby,

Md Suzauddula, Md Sakib Hasan

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(16), P. e36546 - e36546

Published: Aug. 1, 2024

Type 2 diabetes (T2D) and hypertension are global public health concerns major metabolic disorders in humans. Experimental evidence indicates considerable hereditary influences on the etiology of T2D hypertension, but molecular basis these diseases is still limited. Thus, current study analyzed 185 (132 53 hypertension) GWAS catalog datasets identified 83 common genes linked to pathogenesis. These were further examined using various bioinformatics approaches elucidate their mechanisms underlying pathophysiology hypertension. Gene ontology (GO) analysis revealed biological, cellular, functions genes, which also different pathways. Specifically, seven found be crucial for T2D, nine directly associated with Protein-protein interaction (PPI) 28 candidate hub through 11 topological methods. Among 231 miRNAs, significant interacting transcription factors (TFs) out 36 genes. Additionally, two downregulated by 43 FDA-approved drugs. findings processes suggesting that targeting could lead future drug development therapeutic strategies treat

Language: Английский

Citations

0

The Effect of Vitamin D Deficiency on Immune-Related Hub Genes: A Network Analysis Associated With Type 1 Diabetes DOI Open Access
Safin Hussein, Fatemeh Bandarian, Najmeh Salehi

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Background Type 1 diabetes (T1D) is an autoimmune disorder that results in the destruction of pancreatic beta cells, causing a shortage insulin secretion. The development T1D influenced by both genetic predisposition and environmental factors, such as vitamin D. This known for its ability to regulate immune system has been associated with decreased risk T1D. However, specific ways which D affects regulation preservation cells are not yet fully understood. Gaining better understanding these interactions essential identifying potential targets preventing treating Methods analysis focused on two Gene Expression Omnibus (GEO) datasets, namely, GSE55098 GSE50012, detect differentially expressed genes (DEGs). Enrichr (Ma'ayan Laboratory, New York, NY) was used perform enrichment Ontology (GO) biological process Kyoto Encyclopedia Genes Genomes (KEGG) pathways. Search Tool Retrieval Interacting 12.0 (STRING) database generate protein-protein interaction (PPI) network. Cytoscape 3.10.1 (Cytoscape Team, San Diego, CA) analyze PPI network discover hub genes. Results DEGs datasets were identified using GEO2R tool, particular focus exhibiting contrasting regulations. Enrichment unveiled participation oppositely regulated processes relevant system. revealed five genes, MNDA, LILRB2, FPR2, HCK, FCGR2A, suggesting their role pathogenesis response Conclusion study elucidates complex between metabolism provide important knowledge molecular pathways underlie have be targeted therapeutic intervention. research underscores importance system's modulation impact development.

Language: Английский

Citations

0

Serum and urinary levels of MIF, CD74, DDT and CXCR4 among patients with type 1 diabetes mellitus, type 2 diabetes and healthy individuals: Implications for further research DOI Creative Commons
Katia Mangano,

Aristidis Diamantopoulos,

Natalia G. Vallianou

et al.

Metabolism Open, Journal Year: 2024, Volume and Issue: 24, P. 100320 - 100320

Published: Sept. 15, 2024

Language: Английский

Citations

0

UPLC-HDMSE to discover serum biomarkers in adults with type 1 diabetes DOI
Valéria Cristina Nogueira, Valzimeire do Nascimento de Oliveira, Maria Izabel Florindo Guedes

et al.

International Journal of Biological Macromolecules, Journal Year: 2022, Volume and Issue: 221, P. 1161 - 1170

Published: Sept. 14, 2022

Language: Английский

Citations

1

Comprehensive analysis of next-generation sequencing data in COVID-19 and its secondary complications DOI Open Access
Muttanagouda Giriyappagoudar, Basavaraj Vastrad, Rajeshwari Horakeri

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Feb. 4, 2022

Abstract The ongoing pandemic of coronavirus disease 2019 (COVID-19) has made a serious public health threat globally. To discover key molecular changes in COVID-19 and its secondary complications, we analyzed next-generation sequencing (NGS) data COVID-19. NGS (GSE163151) was screened downloaded from the Gene Expression Omnibus database (GEO). Differentially expressed genes (DEGs) were identified present study, using DESeq2 package R programming software. ontology (GO) pathway enrichment analysis performed, protein-protein interaction (PPI) network, module analysis, miRNA-hub gene regulatory network TF-hub established. Subsequently, receiver operating characteristic curve (ROC) used to validate diagonostics valuesof hub genes. Firstly, 954 DEGs (477 up regulated 477 down regulated) four dataset. GO revealed related immune system process multicellular organismal process, REACTOME showed formation cornified envelope. Hub PPI network. Furthermore, ROC indicate that complications with following genes, namely, RPL10, FYN, FLNA, EEF1A1, UBA52, BMI1, ACTN2, CRMP1, TRIM42 PTCH1, had good diagnostics values. This study several associated which improves our knowledge mechanism.

Language: Английский

Citations

0