Ferroptosis is an iron-dependent form of regulated cell death induced by the lethal accumulation of lipid peroxidation, while the precise mechanism of ferroptosis in the pathogenesis of ulcerative colitis (UC) remains to be elucidated. This study aimed to explore the potential effect of hypoxia inducible factor-1α (HIF-1α) on ferroptosis in intestinal epithelial cells (IECs) in UC. The relationship between ferroptosis and HIF-1α was initially investigated using clinical UC colon samples. In vitro and in vivo models of acute intestinal inflammatory response were constructed using lipopolysaccharide (LPS) and dextran sulfate sodium (DSS), respectively. The effect of HIF-1α on ferroptosis in UC was determined by establishing HIF-1α overexpression (HIF1A-OE) or knockdown (shHIF1A) IEC lines, and the mechanism by which HIF-1α mediated the transcription of glutathione peroxidase 4 (GPX4) was explored by combining Co-immunoprecipitation (Co-IP) and Chromatin immunoprecipitation-qPCR (ChIP-qPCR). The results indicated that ferroptosis was present in IECs from UC patients and colitis mice. Elevated expression of HIF-1α ameliorated the secretion of inflammatory cytokines and ferroptosis in IECs in vitro. HIF-1α inhibited ferroptosis by transcriptional activation of the GPX4 gene in inflammatory IECs. HIF-1α ameliorated the general conditions of mice and intestinal barrier dysfunction and by suppressing ferroptosis in IECs of mice through upregulating the expression of GPX4. In conclusion, ferroptosis occurred in the IECs of UC patients and colitis mice. HIF-1α may improve UC by suppressing ferroptosis in IECs through regulating the transcription of GPX4.

Lupus nephritis (LN) is one of the most severe and more common organ manifestations of the autoimmune disease, systemic lupus erythematosus. Ferroptosis, a novel type of programmed cell death, so far its role in LN remains uncertain. In the present study, we explored the role of ferroptosis in LN and its relationship with the immune response. The GSE112943 LN dataset was downloaded from the Gene Expression Omnibus database. Ferroptosis-Related Genes (FRGs) that drive, suppress or mark ferroptosis were retrieved from the public FerrDb database. The gene expression matrix of the GSE112943 dataset was analyzed with the “limma” package in R to obtain differentially expressed genes (DEGs) between LN and healthy samples. Subsequently, the crossover genes between DEGs and FRGs were identified as differentially expressed ferroptosis-related genes (DE-FRGs). Protein–protein interaction (PPI) network analysis, visualization, and identification of hub lupus nephritis ferroptosis-related genes (LN-FRGs) were performed with STRING and Cytoscape, while their Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined with the clusterProfiler package. Immune cell infiltration was calculated with CIBERSORT. The relationship between hub LN-FRGs and immune-infiltrated cells in LN was determined by Pearson correlation. A total of 96 DE-FRGs and 8 hub LN-FRGs (KRAS, PIK3CA, EGFR, MAPK14, SRC, MAPK3, VEGFA, and ATM) were identified. GO and KEGG functional classification indicated these genes enrichment in apoptotic process, programmed cell death, autophagy-animal, FoxO signaling pathway, relaxin signaling pathway, and VEGF signaling pathway. Infiltration matrix analysis of immune cells showed abundant Monocytes and M0/M1/M2 macrophages in LN kidney tissues. Correlation analysis revealed 8 hub LN-FRGs associated with immune-infiltrated cells in LN. In summary, overproduction of ROS and abnormal infiltration of immune cells would be implicated in the LN caused by ferroptosis. 8 hub lupus nephritis ferroptosis-related genes (LN-FRGs) which might be good biomarkers of ferroptosis in LN were identified in this study. These findings point to the immune response playing an important role in LN caused by ferroptosis via mutual regulation between hub LN-FRGs and immune-infiltrated cells.

Introduction:Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine whose cause and underlying mechanisms are not fully understood. The aim of this study was to use bioinformatics analysis to identify differentially expressed genes (DEGs) with diagnostic and therapeutic potential in UC.Materials and methods:Three UC datasets (GSE179285, GSE75214, GSE48958) were downloaded from the Gene Expression Omnibus (GEO) database. DEGs between normal and UC tissues were identified using the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed using Metascape. Protein-protein interaction network (PPI) analysis and visualization using STRING and Cytoscape. Finally, the miRNA gene regulatory network was constructed by Cytoscape to predict potential microRNAs (miRNAs) associated with DEGs.Results:A total of 446 DEGs were identified, consisting of 309 upregulated genes and 137 downregulated genes. The enriched functions and pathways of the DEGs include extracellular matrix, regulation of cell adhesion, inflammatory response, response to cytokine, monocarboxylic acid metabolic process, response to toxic substance. The analysis of KEGG pathway indicates that the DEGs were significantly enriched in Complement and coagulation cascades, Amoebiasis, TNF signaling pathway, bile secretion, and Mineral absorption. Combining the results of the PPI network and CytoHubba, 9 hub genes including CXCL8, ICAM1, CXCR4, CD44, IL1B, MMP9, SPP1, TIMP1, and HIF1A were selected. Based on the DEG-miRNAs network construction, 7 miRNAs including miR-335-5p, mir-204-5p, miR-93-5p, miR106a-5p, miR-21-5p, miR-146a-5p, and miR-155-5p were identified as potential critical miRNAs.Conclusion:In summary, we identified DEGs that may be involved in the progression or occurrence of UC. A total of 446 DEGs,9 hub genes and 7 miRNAs were identified, which may be considered as biomarkers of UC. Further studies, however, are needed to elucidate the biological functions of these genes in UC.

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine, whose pathogenesis is not fully understood. Given that immune infiltration plays a key role in UC progression, our study aimed to assess the level of immune cells in UC intestinal mucosal tissues and identify potential immune-related genes. The GSE65114 UC dataset was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between healthy and UC tissues were identified using the “limma” package in R, while their Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined with the clusterProfiler package. Protein–protein interaction network analysis and visualization were performed with STRING and Cytoscape. Immune cell infiltration was calculated with CIBERSORT. The relationship between hub genes and immune-infiltrated cells in UC was determined by Pearson correlation. A total of 206 DEGs were identified, of which 174 were upregulated and 32 downregulated. GO and KEGG functional classification indicated DEG enrichment in immune response pathways, including Toll-like receptor signaling, IL-17 signaling, and immune system process and chemokine signaling. 13 hub genes were identified. Infiltration matrix analysis of immune cells showed abundant plasma cells, memory B cells, resting CD4 memory T cells, γδ T cells, M0 and M1 macrophages, and neutrophils in UC intestinal tissues. Correlation analysis revealed 13 hub genes associated with immune-infiltrated cells in UC. 13 hub genes associated with immune-infiltrated cells in UC were identified; they included CXCL13, CXCL10, CXCL9, CXCL8, CCL19, CTLA4, CCR1, CD69, CD163, IL7R, PECAM1, TLR8 and TLR2. These genes could potentially serve as markers for the diagnosis and treatment of UC.

This article presents a case of neuromyelitis optica spectrum disorder (NMOSD) secondary to systemic lupus erythematosus (SLE). The patient initially presented with unexplained nausea, vomiting, intractable hiccups, and significant bradycardia (48 bpm). Cranial and spinal MRI findings were unremarkable, while serum aquaporin-4 immunoglobulin G (AQP4-IgG) antibody titers were markedly elevated (1:320). Following exclusion of alternative etiologies through comprehensive serological and neuroimaging investigations, the diagnosis of area postrema syndrome (APS) was confirmed according to the 2015 International Panel for NMO Diagnosis (IPND) criteria as a distinct NMOSD subtype. The patient exhibited a rapid therapeutic response to high-dose glucocorticoid therapy and was discharged on maintenance methylprednisolone with adjunctive medications. At one-month follow-up, the patient reported progressive visual deterioration, prompting neuro-ophthalmologic evaluation. Clinical findings included mildly elevated intraocular pressure (22.2 mmHg OD, 22.5 mmHg OS), corrected refractive error, and abnormal visual evoked potentials (diminished amplitude with delayed waveforms). Other neuro-ophthalmic investigations revealed no abnormalities. Persistent AQP4-IgG seropositivity (titer 1:32) was noted, and gadolinium-enhanced MRI revealed focal signal abnormalities in the bilateral optic nerves, confirming optic neuritis. Intravenous rituximab therapy (500 mg every two weeks) was initiated; however, treatment was complicated by a generalized urticarial rash and pleuritic chest pain, with no significant improvement in visual acuity. The therapeutic regimen was subsequently modified to incorporate subcutaneous telitacicept (160 mg weekly) in combination with glucocorticoid taper protocol and hydroxychloroquine. After eight weeks of this combined therapy, marked visual improvement was observed. Follow-up gadolinium-enhanced MRI revealed decreased enhancement intensity in the corresponding optic nerve regions compared to baseline. The patient maintained clinical stability and continues long-term multidisciplinary surveillance. To our knowledge, this represents the third documented case validating the therapeutic efficacy of telitacicept in NMOSD. Our findings suggest that telitacicept may serve as a disease-modifying therapy for SLE patients with AQP4-IgG-seropositive NMOSD.

Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease influenced by genetic, immune, and environmental factors. This study investigates the link between ferroptosis, a cell death process related to oxidative stress and iron metabolism, and immune infiltration in UC. Materials and Methods: We analyzed UC patient transcription data from the Gene Expression Omnibus (GEO) and identified ferroptosis-related genes using FerrDB. Using STRING and Cytoscape, we analyzed protein-protein interactions to identify hub UC Differentially Expressed Genes (UCDEGs) and performed functional enrichment with GO and KEGG pathways. Machine learning helped further identify key UC Differentially Expressed Ferroptosis-related genes (UCDE-FRGs), which were validated using additional GEO datasets and immunohistochemical staining. Results: A total of 11 hub UCDEGs (CCL2, ICAM1, TLR2, CXCL9, MMP9, CXCL10, IL1B, CXCL8, PTPRC, FCGR3A, and IL1A) and 3 key UCDE-FRGs (DUOX2, LCN2 and IDO1) were identified. GO and KEGG functional enrichment indicates that these genes play a role in immunity and ferroptosis. Analysis of immune cell infiltration showed that there were a large number of Plasma cells, Monocytes, M0/M1 Macrophages and Neutrophils in the UC. Correlation analysis revealed 3 key UCDE-FRGs associated with immune-infiltrated cells in UC. IHC results showed that the expression levels of 3 key UCDE-FRGs in UC were all higher than that in the healthy controls. Conclusion: In summary, this study identified three key genes related to UC ferroptosis and immunity, namely DUOX2, IDO1 and LCN2. These findings suggest that immune infiltration plays an important role in UC caused by ferroptosis, and that there is mutual regulation between UC and immune-infiltrated cells. Our research revealed the potential application of immune and ferroptosis in the diagnosis, treatment and prognosis of UC, providing new strategies for clinical management.