Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis DOI Open Access
Basavaraj Vastrad, Chanabasayya Vastrad

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

Published: July 28, 2022

Abstract Pediatric Crohn Disease (CD) also known as inflammatory bowel diseases, affects millions of people all over the world. The aim this investigation is to identify key genes in CD and uncover their potential functions. We downloaded next generation sequencing (NGS) dataset GSE101794 from Gene Expression Omnibus (GEO) database. NGS was used screen differentially expressed (DEGs) between samples patients with healthy controls. ontology (GO) REACTOME pathway enrichment analyses were applied for DEGs. Subsequently, a protein - interaction (PPI) network, modules, miRNA- hub gene regulatory network TF constructed genes, miRNAs TFs. Receiver operating characteristic curve (ROC) analysis validate genes. A total 957 DEGs identified, including 478 up regulated 479 down GO results suggested that several Go terms pathways are involved response stimulus, extracellular region, signaling receptor binding, small molecule metabolic process, membrane, transporter activity, immune system biological oxidations. top centrality MDFI, MNDA, FBXO6, TFRC, STAT1, DPP4, MME, SLC39A4, APOA1 TMEM25 screened out critical among PPI miRNA-hub TF-hub network. This identified signal pathways, which might help us improve our understanding molecular mechanisms some novel therapeutic targets CD.

Language: Английский

Diminished Immune Response and Elevated Abundance in Gut Microbe Dubosiella in Mouse Models of Chronic Colitis with GBP5 Deficiency DOI Creative Commons
Y. Li,

Wenxia Wang,

Yuxuan Liu

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 873 - 873

Published: July 20, 2024

Guanylate binding protein 5 (GBP5) is an emerging immune component that has been increasingly recognized for its involvement in autoimmune diseases, particularly inflammatory bowel disease (IBD). IBD a complex involving inflammation of the gastrointestinal tract. Here, we explored functional significance GBP5 using

Language: Английский

Citations

5
Rosemary essential oil microemulsion prevents DSS-induced intestinal injury in mice by modulating IL-17 signaling pathway DOI Creative Commons
Jie Wang, Yanzhuo Jia, Xia Ning

et al.

Journal of Functional Foods, Journal Year: 2024, Volume and Issue: 116, P. 106180 - 106180

Published: April 24, 2024

Language: Английский

Citations

4
Macrophagic HDAC3 inhibition ameliorates Dextran Sulfate Sodium induced inflammatory bowel disease through GBP5-NLRP3 pathway DOI Creative Commons

Na Che,

Yang Zhang, Shu Zhang

et al.

International Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 21(8), P. 1385 - 1398

Published: Jan. 1, 2024

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease, characterized by dysregulated immune response. HDAC3 reported to be an epigenetic brake in inflammation, playing critical roles macrophages. However, its role IBD unclear. In our study, we found was upregulated CX3CR1-positive cells the mucosa from mice. Conditional knockout (cKO) of Hdac3 CX3CR1 positive attenuated severity Dextran Sulfate Sodium (DSS)-induced colitis. addition, inhibition with RGFP966 could also alleviate DSS-induced tissue injury and inflammation IBD. The RNA sequencing results revealed that cKO restrained upregulation genes pathways cytokine-cytokine receptor interaction, complement coagulation cascades, chemokine signaling, extracellular matrix interaction. We identified Guanylate-Binding Protein 5 (GBP5) transcriptionally regulated monocytes sequencing. Inhibition resulted decreased transcriptional activity interferon-gamma-induced expression GBP5 cells, such as macrophages microglia. Overexpression reporter. Lastly, conditional (Hdac3 mKO) conclusion, ameliorate response colitis regulating GBP5-NLRP3 axis, identifying new therapeutic avenue for treatment

Language: Английский

Citations

4
STAT1 mediates the pro-inflammatory role of GBP5 in colitis DOI Creative Commons
Yichen Li, Wenxia Wang, Ruixin Zhu

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 7, 2025

Previous studies establish guanylate binding protein 5 (GBP5) as a driver in the development of inflammatory bowel diseases (IBDs). Here, we aim to elucidate mechanism underlying pro-inflammatory role GBP5. We observe that loss Gbp5 causes reduced colonic inflammation and decreased numbers innate lymphoid cells (ILCs) colitis mice. The transcriptional alterations observed GBP5-deficient THP-1 mirrored those triggered by STAT1 activation, leading findings GBP5 is essential for stimulated expression its downstream effectors, including cytokines drive expansion ILCs. Remarkably, over-expression reverses cytokine caused deficiency. While does not directly gene transcription, it binds with facilitates nuclear translocation, thereby enhancing itself effectors. Overall, plays IBD activity STAT1.

Language: Английский

Citations

0
Role of guanylate-binding protein 5 in inflammatory diseases, immune diseases, cancers, and its potential therapeutic implications DOI

Xufan Sun,

Guiyuan Jin, Huihui Zhou

et al.

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Language: Английский

Citations

0
Adolescent gut microbiome imbalance and its association with immune response in inflammatory bowel diseases and obesity DOI Creative Commons

Minjae Joo,

Seungyoon Nam

BMC Microbiology, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 19, 2024

Abstract Background Recently, there has been an increase in the number of studies focusing on association between gut microbiome and obesity or inflammatory diseases, especially adults. However, is a lack investigating gastrointestinal (GI) diseases adolescents. Method We obtained 16S rRNA-seq datasets for analysis from 202 adolescents, comprising ulcerative colitis (UC), Crohn’s disease (CD), (Ob), healthy controls (HC). utilized Quantitative Insights Into Microbial Ecology (QIIME) Phylogenetic Investigation Communities by Reconstruction Unobserved States (PICRUSt) to acquire Operational Taxonomic Units (OTUs). Subsequently, we analyzed Kyoto Encyclopedia Genes Genomes (KEGG) Orthology (KO) terms pathway enrichment identified OTUs. Results In this study, investigated difference microbiomes adolescents with GI those using samples rRNA sequencing data. The distribution six main microbiota (i.e., unclassified Dorea , Lachnospiraceae Ruminococcus Faecalibacterium prausnitzii Prevotella copri Sutterella ) was different based status diseases. Dysbiosis observed within UC CD), . More specifically, our results showed that relative abundance more than 10% 8% higher, respectively, group compared CD, Ob, HC groups. Additionally, Ob had over 20% 3% higher levels UC, Also, inspecting associations specific KO terms, found -relating were associated NOD-like receptor signaling. These taxa differences may affect immune system response affecting signaling host during critical adolescence. Conclusion discovered dysbiosis microbial community varying degrees influence pathways obesity.

Language: Английский

Citations

2
Identification and Validation of the Diagnostic Markers for Inflammatory Bowel Disease by Bioinformatics Analysis and Machine Learning DOI
Qiong Tang, Xiang Shi,

Ying Xu

et al.

Biochemical Genetics, Journal Year: 2023, Volume and Issue: 62(1), P. 371 - 384

Published: June 23, 2023

Language: Английский

Citations

5
Crosstalk Between Microbiota, Microbial Metabolites, and Interferons in the Inflammatory Bowel Disease Gut DOI Creative Commons

Vi To Diep Vu,

Ramsha Mahmood, Heather Armstrong

et al.

Journal of the Canadian Association of Gastroenterology, Journal Year: 2023, Volume and Issue: 7(1), P. 78 - 87

Published: Dec. 25, 2023

Abstract With the prevalence of inflammatory bowel diseases (IBD) continuing to rise in Canada and globally, developing improved therapeutics that successfully treat greater percentages patients with reduced complications is paramount. A better understanding pertinent immune pathways IBD will improve our ability both dampen inflammation promote gut healing, beyond just inhibiting specific proteins; success combination therapies supports this approach. Interferons (IFNs) are key cytokines protect mucosal barrier surfaces, their roles regulating homeostasis differ between three IFN families (type I, II, III). Interestingly, microbiota microbial metabolites impact IFN-signaling, yet how system impacted remains unclear. In review, we discuss current knowledge directly or indirectly levels/responses, what known about IFNs differentially animal models IBD.

Language: Английский

Citations

4
Modulatory Effects of IFN-γ and IL-22 on Inflammatory Signaling and Cellular Responses in Intestinal Epithelial Cells DOI

Asia Johnson,

Timothy L. Denning

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

Published: May 14, 2024

Abstract Inflammatory bowel disease (IBD) continues to affect millions worldwide, with an increasing prevalence that highlights the urgent need for deeper understanding of its underlying immune mechanisms. The cytokine interactions, especially those mediated by cells from TH1 and TH17 lymphocyte subsets, are crucial in orchestrating landscape IBD. well known producing TNF-α IFNγ, which have been extensively studied their roles conjunction each other within context secrete IL-22 IL-17, existing studies primarily focusing on IL-22’s interaction IL-17 rather than interplay cytokines such as IFNγ. Our study focuses co-stimulatory effects IFNγ using organoids derived mouse small intestines model epithelial interactions. We found interferes capacity up-regulate antimicrobial peptides, is essential mucosal defense. Additionally, higher concentrations enhance IFNγ’s ability stimulate gene expression CXCL10 protein production, indicating a dose-dependent relationship. This co-stimulation also led increased rate cell death, influenced partly TNF-α. These findings suggest IL-22, typically seen anti-inflammatory agent, can assume pro-inflammatory role when combined complicating cells. consider specific interactions developing more effective IBD treatments.

Language: Английский

Citations

0
Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis DOI Open Access
Basavaraj Vastrad, Chanabasayya Vastrad

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

Published: July 28, 2022

Abstract Pediatric Crohn Disease (CD) also known as inflammatory bowel diseases, affects millions of people all over the world. The aim this investigation is to identify key genes in CD and uncover their potential functions. We downloaded next generation sequencing (NGS) dataset GSE101794 from Gene Expression Omnibus (GEO) database. NGS was used screen differentially expressed (DEGs) between samples patients with healthy controls. ontology (GO) REACTOME pathway enrichment analyses were applied for DEGs. Subsequently, a protein - interaction (PPI) network, modules, miRNA- hub gene regulatory network TF constructed genes, miRNAs TFs. Receiver operating characteristic curve (ROC) analysis validate genes. A total 957 DEGs identified, including 478 up regulated 479 down GO results suggested that several Go terms pathways are involved response stimulus, extracellular region, signaling receptor binding, small molecule metabolic process, membrane, transporter activity, immune system biological oxidations. top centrality MDFI, MNDA, FBXO6, TFRC, STAT1, DPP4, MME, SLC39A4, APOA1 TMEM25 screened out critical among PPI miRNA-hub TF-hub network. This identified signal pathways, which might help us improve our understanding molecular mechanisms some novel therapeutic targets CD.

Language: Английский

Citations

0