The roles of IRF8 in nonspecific orbital inflammation: an integrated analysis by bioinformatics and machine learning

Journal of Ophthalmic Inflammation and Infection, Год журнала: 2024, Номер 14(1)

Опубликована: Июнь 20, 2024

Abstract Background Nonspecific Orbital Inflammation (NSOI) represents a persistent and idiopathic proliferative inflammatory disorder, characterized by polymorphous lymphoid infiltration within the orbit. The transcription factor Interferon Regulatory Factor 8 (IRF8), integral to IRF protein family, was initially identified as pivotal element for commitment differentiation of myeloid cell lineage. Serving central regulator innate immune receptor signaling, IRF8 orchestrates myriad functions in hematopoietic development. However, intricate mechanisms underlying production remain be elucidated, its potential role biomarker NSOI is yet resolved. Methods extracted from intersection analysis common DEGs GSE58331 GSE105149 GEO immune- related gene lists ImmPort database using Lasso regression SVM-RFE analysis. We performed GSEA GSVA with sets coexpressed IRF8, observed that positively were enriched immune-related pathways. To further explore correlation between biological process, CIBERSORT algorithm ESTIMATE method employed evaluate TME characteristics each sample confirmed high expression might give rise infiltration. Finally, utilized confirm levels IRF8. Results Among 314 differentially expressed genes (DEGs), some found significantly different. With LASSO algorithms, we obtained 15 hub genes. For function leukocyte mediated immunity, cell-cell adhesion, negative regulation system process emphasized. B cells naive, Macrophages M0, M1, T CD4 memory activated, resting, gamma delta shown associated While, Mast Monocytes, NK Plasma cells, CD8, regulatory (Tregs) negatively linked diagnostic ability differentiating exhibited good value. Conclusions This study discovered are NSOI. shed light on new biomarkers tracking progression.

Язык: Английский

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Anti-Inflammatory Effects of miR-369-3p via PDE4B in Intestinal Inflammatory Response

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8463 - 8463

Опубликована: Авг. 2, 2024

Cyclic nucleotide phosphodiesterases (PDEs) consist of a family enzymes expressed in several types cells, including inflammatory that play pivotal role inflammation. Several studies have demonstrated the inhibition PDE4 results reduced response via PKA and CREB signaling. Hence, suppression improves feedback typical diseases, such as bowel disease (IBD). In our previous studies, we miR-369-3p regulates responses, modulating different aspects process. The aim this study was to demonstrate an additional anti-inflammatory effect targeting PDE4B, one widely isoforms immune cells. We found able reduce expression elevating intracellular levels cAMP. This accumulation increased pCREB, mitigating release pro-inflammatory cytokines promoting cytokines. To prove PDE4B is good therapeutic target IBD, also UC patients compared healthy controls, affecting infiltrate. considered important player progression; hence, show ability ameliorate inflammation by supporting its future application new approach IBD.

Язык: Английский

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Heterocyclic Nitrogen Compounds as Potential PDE4B Inhibitors in Activated Macrophages

Applied Sciences, Год журнала: 2024, Номер 14(15), С. 6747 - 6747

Опубликована: Авг. 2, 2024

Cyclic-nucleotide phosphodiesterases (PDEs) represent a superfamily of enzymes playing pivotal role in cell signaling by controlling cAMP and cGMP levels response to receptor activation. PDE activity expression are linked many diseases including inflammatory diseases. In light their specific biochemical properties, inhibition has attracted the interest several researrs this context, PDE4 induces anti-inflammatory effects. Piclamilast rolipram, well-known inhibitors, endowed with common side The selective phosphodiesterase 4B (PDE4B) inhibitors could be promising approach overcome these present study, six potential PDE4B have been investigated. Through we identified three human macrophages activated lipopolysaccharide. Interestingly, two them reduced reactive oxygen species production pro-inflammatory macrophages.

Язык: Английский

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Deciphering the role of HLF in idiopathic orbital inflammation: integrative analysis via bioinformatics and machine learning techniques

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Авг. 20, 2024

Idiopathic orbital inflammation, formerly known as NSOI (nonspecific inflammation), is characterized a spectrum disorder distinguished by the polymorphic infiltration of lymphoid tissue, presenting complex and poorly understood etiology. Recent advancements have shed light on HLF (Human lactoferrin), proposing its critical involvement in regulation hematopoiesis maintenance innate mucosal immunity. This revelation has generated significant interest exploring HLF's utility biomarker for NSOI, despite existing gaps our understanding biosynthetic pathways operational mechanisms. Intersecting multi-omic datasets—specifically, common differentially expressed genes between GSE58331 GSE105149 from Gene Expression Omnibus immune-related gene compendiums ImmPort database—we employed sophisticated analytical methodologies, including Lasso regression support vector machine-recursive feature elimination, to identify HLF. set enrichment analysis variation disclosed immune pathway within sets linked The intricate relationship expression immunological processes was further dissected through utilization CIBERSORT ESTIMATE algorithms, which assess characteristics microenvironment, highlighting noteworthy association increased enhanced cell infiltration. levels were corroborated using data dataset, reinforcing validity findings. Analysis 218 HLF-related revealed statistically discrepancies. Fifteen hub distilled LASSO SVM-RFE algorithms. Biological functions connected with HLF, such leukocyte migration, ossification, negative processes, illuminated. Immune depicted positive correlation various cells, resting mast activated NK plasma CD8 T cells. Conversely, observed gamma delta naive B M0 M1 macrophages, Diagnostic assessments distinguishing showed promising accuracy. Our investigation delineates intricately associated casting novel biomarkers diagnosis progression monitoring this perplexing condition.

Язык: Английский

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Spatial Transcriptomic Profiling of Human Saphenous Vein Exposed to Ex Vivo Arterial Haemodynamics—Implications for Coronary Artery Bypass Graft Patency and Vein Graft Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(19), С. 10368 - 10368

Опубликована: Сен. 26, 2024

Vein graft disease is the process by which saphenous vein grafts, utilised for revascularisation during coronary artery bypass surgery, undergo an inflammation-driven intimal hyperplasia and accelerated atherosclerosis in subsequent years after implantation. The role of arterial circulation, particularly haemodynamic properties’ impact on patency, have been investigated but not to date explored depth at transcriptomic level. We undertaken first-in-man spatial analysis long response ex vivo acute stimulation, utilising a combination custom 3D-printed perfusion bioreactor 10X Genomics Visium Spatial Gene Expression technology. identify total 413 significant genes (372 upregulated 41 downregulated) differentially expressed conditions. These were associated with pathways including NFkB, TNF, MAPK, PI3K/Akt, among others. are established involved initiation early pro-inflammatory response, leukocyte activation adhesion signalling, tissue remodelling, cellular differentiation. Utilising unsupervised clustering analysis, we able classify subsets expression based cell type resolution. findings allow further characterisation transcriptional landscape earliest stage implantation that contributes disease, particular validation druggable targets could contribute towards therapeutic inhibition processes underpinning disease.

Язык: Английский

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