Genes & genomics最新文献

{"title":"Exploring Cyclo (-Gly-Pro) for inflammation modulation in atopic dermatitis: a study on streptococcal postbiotics.","authors":"Haeun Lee, Yunseok Oh, Tae-Won Seo, Young-Bong Choi, Sol Kim, Sejin Cheon, Dong-Geol Lee, Seunghyun Kang, Kyudong Han, Young Mok Heo, Seyoung Mun","doi":"10.1007/s13258-026-01758-8","DOIUrl":"10.1007/s13258-026-01758-8","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itching and eczematous lesions, significantly affecting quality of life. Complex interactions involving genetic predispositions, environmental factors, and immune dysregulation contribute to AD pathogenesis, with impaired skin barriers and Staphylococcus aureus playing critical roles. Recent interest in postbiotics, beneficial compounds derived from probiotics, has opened potential therapeutic avenues.</p><p><strong>Objective: </strong>This study investigates the postbiotic solution derived from three human skin-derived Streptococcus isolates, to identify a core bioactive compound and its therapeutic role in AD.</p><p><strong>Methods: </strong>Using GC-MS and GC-FID, we quantified Cyclo (-Gly-Pro) and assessed its impact on inflammatory biomarkers in an AD-like keratinocyte cell model. The effect of different incubation temperatures on the compound's production was also analyzed. Furthermore, 16S V3-V4 amplicon sequencing was performed to analyze changes in the skin microbiome of AD patients following treatment.</p><p><strong>Results: </strong>Cyclo (-Gly-Pro) was consistently present across all strains, with production inversely related to incubation temperature, peaking at 25 °C. Our findings suggest that optimized production conditions and potential synergistic effects with other postbiotic components could enhance therapeutic efficacy.</p><p><strong>Conclusion: </strong>These results support further in vivo research to elucidate the mechanisms and validate the compound's role in AD treatment strategies, potentially leading to novel dermatological therapies.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"883-894"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide identification of the FAD gene family in Fragaria nilgerrensis reveals distinct roles of two FnFAD3 genes in peach-like aroma formation.","authors":"Ai-Hua Wang, Yi-Xuan Wang, Xiao-Cui Liu, Chao Ma, Jun Guo","doi":"10.1007/s13258-026-01762-y","DOIUrl":"10.1007/s13258-026-01762-y","url":null,"abstract":"<p><strong>Background: </strong>Fatty acid desaturases (FADs) play crucial roles in plant growth and development. Fragaria nilgerrensis Schlecht., a wild diploid strawberry species, is characterized by a distinctive peach-like aroma.</p><p><strong>Objective: </strong>To comprehensively characterize the FAD gene family in F. nilgerrensis and investigate the specific roles of FnFAD3s in peach-like aroma formation, thereby providing insights for breeding utilization.</p><p><strong>Methods: </strong>A genome-wide identification of the FAD gene family was performed using bioinformatics approaches, including phylogenetic analysis, gene structure analysis, conserved motif prediction, chromosomal localization, collinearity analysis, and cis-acting regulatory element prediction. Additionally, expression patterns and subcellular localization of FnFAD3s were investigated.</p><p><strong>Results: </strong>A total of 26 FnFAD genes were identified from the F. nilgerrensis genome and phylogenetically classified into five clades: FAB2, FAD3, FAD5, DES-1, and SLD. These genes were unevenly distributed across seven chromosomes, except for FnFAD5.2 and FnFAD5.3, which were not mapped to any specific chromosome. Both tandem and segmental duplication events contributed to the expansion of the FnFAD gene family. Members within the same subfamily exhibited relatively conserved exon-intron structures and motif compositions. Promoter analysis revealed various cis-acting elements related to hormones, stress responses, and growth and development, suggesting complex transcriptional regulatory mechanisms. Expression pattern analysis showed that FnFAD3.3 expression followed a bell-shaped curve during fruit development, peaking at the ripening stage. Notably, FnFAD3.5, which localizes to chloroplasts, was expressed at significantly higher levels in F. nilgerrensis (FN, with peach-like aroma) compared to an interspecific hybrid (IH, without peach-like aroma).</p><p><strong>Conclusions: </strong>This study provides a genome-wide characterization of the FAD gene family in F. nilgerrensis and reveals the distinct roles of FnFAD3.3 and FnFAD3.5 in peach-like aroma formation, offering insights into the molecular mechanisms underlying strawberry fruit flavor for breeding improvement.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"923-933"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone mark remodeling in cancer: an enhancer-centered perspective.","authors":"Jiyoon Park, Jinha Jeon, Sujeong Gim, Chan Chung","doi":"10.1007/s13258-026-01768-6","DOIUrl":"10.1007/s13258-026-01768-6","url":null,"abstract":"<p><p>Epigenetic deregulation is a defining feature of cancer, and histone modification remodeling plays a central role in reshaping malignant transcriptional programs. Histone marks collectively organize chromatin states that govern enhancer activity, promoter competence, and stability of repressive domains. Across diverse tumor types, redistribution of active and repressive histone modifications reconfigures regulatory landscapes that sustain oncogenic amplification, lineage plasticity, and adaptive resistance. In this review, we examine histone mark remodeling in cancer through an enhancer-centered perspective. We discuss how the gain of H3K27ac-marked enhancers, super-enhancer formation, the erosion of lineage-restrictive regulatory elements, and the redistribution of repressive marks cooperate to reorganize transcriptional circuitry. We further outline the convergent mechanisms driving these alterations, including mutations in chromatin regulators, signal-dependent modulation of epigenetic enzymes, metabolic influences on chromatin state, and changes in three-dimensional genome architecture. The functional consequences of histone mark reprogramming, ranging from cell state transitions and tumor heterogeneity to transcriptional dependency and therapy-associated chromatin adaptation, are considered in the context of tumor evolution. Finally, we highlight emerging single-cell, spatial, and integrative multi-omics approaches that enable systems-level interpretation of chromatin landscapes and identification of context-specific vulnerabilities. By framing histone modification dynamics in terms of enhancer reconfiguration, this review provides a mechanistic and translational perspective on how chromatin remodeling sustains malignant identity and offers opportunities for therapeutic intervention.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"799-815"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parametric hypothesis testing for pathway based hierarchical structural component models.","authors":"Md Kamruzzaman, Taesung Park","doi":"10.1007/s13258-026-01749-9","DOIUrl":"10.1007/s13258-026-01749-9","url":null,"abstract":"<p><p>BACKGROUND: Hierarchical Structural Component Model (HisCoM) are statistical tools developed for pathway analysis that enable the simultaneous evaluation of multiple pathways within a single model. Traditionally, HisCoM utilize permutation tests to assess the significance of pathways in relation to a phenotype of interest. While permutation tests are effective for generating exact distributions under the null hypothesis when the asymptotic distribution is unknown, they are computationally intensive, particularly for high-dimensional datasets, as they require significant time to compute p-values. OBJECTIVE: The aim of this study is to develop parametric testing procedures for HisCoM to determine pathway significance without relying on permutations. These parametric tests aim to improve statistical performance while significantly reducing computational burden. METHODS: The proposed parametric tests are built on asymptotic theory for high-dimensional frameworks with numerous biomarkers and pathways. Specifically, we introduce methods such as the standard [Formula: see text] asymptotic test, non-centrality test, degrees of freedom (df) adjustment, saddle point approximation, and modified asymptotic tests with full df and one df. RESULTS: Simulation and real data results showed substantial reductions in computational time compared to permutation-based test. Through the simulation study, the modified [Formula: see text] asymptotic test with full df shown to have higher power compare to the other methods. The real data analysis further supported its robustness and practical advantages. CONCLUSION: This study presents computationally efficient parametric testing methods for HisCoM. Based on simulation results and real data analysis, the modified [Formula: see text] asymptotic test with full df is recommended as the most reliable and effective approach for assessing pathway significance.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"831-845"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycolytic-inflammatory crosstalk mediated by Glyco-PMF-Rux hub genes drives PMF progression and ruxolitinib resistance.","authors":"Shujing Zhang, Muhammad Sameer Ashaq, Yi Wang, Yuan Li, Baobing Zhao","doi":"10.1007/s13258-026-01756-w","DOIUrl":"10.1007/s13258-026-01756-w","url":null,"abstract":"<p><strong>Background: </strong>Primary myelofibrosis (PMF) is an aggressive myeloproliferative neoplasm characterized by bone marrow fibrosis, chronic inflammation, and high leukemic risk. Although ruxolitinib (Rux) is a first-line therapy, nearly half of patients develop resistance within three years. Glycolytic reprogramming contributes to inflammatory signaling and drug resistance, while the link between metabolic reprogramming and Rux resistance remains unclear.</p><p><strong>Objective: </strong>This study aims to identify key genes involved in glycolytic-inflammatory crosstalk driving PMF progression and Rux resistance, with the goal of evaluating their potential as diagnostic and therapeutic targets.</p><p><strong>Methods: </strong>We integrated multiple GEO datasets to identify differentially expressed genes (DEGs) related to PMF, Rux resistance, and glycolysis. A total of 75 overlapping DEGs were identified. Protein-protein interaction analysis and centrality measures revealed four key hub genes: STAT1, EGR1, FOXO1 and SMAD7. Their diagnostic and functional relevance was assessed using GO/KEGG enrichment, ROC analysis, single-cell RNA-seq and immune infiltration analysis.</p><p><strong>Results: </strong>All four hub genes were significantly dysregulated and showed potential diagnostic value. Functional enrichment highlighted pathways of inflammation, apoptosis, and metabolic reprogramming. Single-cell analysis revealed their enrichment in hematopoietic stem/progenitor cells and correlation with resistance markers. STAT1/EGR1 were associated with pro-inflammatory immune cells, while FOXO1/SMAD7 were linked to immune evasion. Notably, STAT1 and EGR1 were significantly upregulated in ruxolitinib-resistant HEL cells. Functional assays demonstrated that STAT1 knockdown suppressed the proliferation of resistant cells, while EGR1 was further validated by its significant upregulation in PMF mouse models.</p><p><strong>Conclusions: </strong>STAT1, EGR1, FOXO1, and SMAD7 are associated with glycolytic-inflammatory crosstalk underlying PMF progression and ruxolitinib resistance, with experimental validation supporting STAT1 and EGR1 as potential diagnostic and therapeutic targets.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"867-881"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147304831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA purity over yield: optimizing extraction and PCR in degraded Asian elephant (Elephas maximus) fecal samples.","authors":"Supansa Rerkdee, Worapong Singchat, Thitipong Panthum, Trifan Budi, Warong Suksavate, Aingorn Chaiyes, Wichanon Saenphala, Kyudong Han, Prateep Duengkae, Kornsorn Srikulnath","doi":"10.1007/s13258-026-01772-w","DOIUrl":"https://doi.org/10.1007/s13258-026-01772-w","url":null,"abstract":"<p><strong>Background: </strong>Non-invasive genetic monitoring is essential for conserving the endangered Asian elephant (Elephas maximus). However, fecal DNA is highly susceptible to degradation and polymerase chain reaction (PCR) inhibition.</p><p><strong>Objective: </strong>Various DNA extraction techniques and optimized downstream PCR parameters were compared to establish a workflow that balances DNA quantity and quality.</p><p><strong>Methods: </strong>A modified phenol-chloroform-isoamyl alcohol (PCI) protocol was compared with a commercial extraction kit using 35 unpreserved, degraded fecal specimens to evaluate the trade-offs between DNA yield and purity.</p><p><strong>Results: </strong>The PCI method produced significantly higher concentrations (> 500 ng/µL in some samples) but poor purity ratios (A₂₆₀/A₂₈₀ and A₂₆₀/A₂₃₀), resulting in complete PCR failure. In contrast, the kit yielded lower DNA amounts but superior purity (A₂₆₀/A₂₃₀ = 2.0-2.2), enabling a 57.1% (20/35) amplification success rate for the mitochondrial D-loop when combined with high-processivity KOD polymerase and optimized Mg²⁺ concentrations. Sanger sequencing confirmed E. maximus mitochondrial DNA in 15 specimens, whereas environmental eDNA was detected in two samples.</p><p><strong>Conclusion: </strong>These findings demonstrate that DNA purity, rather than yield, is the critical determinant of PCR success in degraded wildlife samples, underscoring the importance of inhibitor-removal technologies for the reliable and effective management of endangered megafauna.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of spatial expression patterns of ectopic olfactory receptors.","authors":"Elina Pokharel, Jae-Kwang Jung, Jae-Young Kim, Wern-Joo Sohn","doi":"10.1007/s13258-026-01747-x","DOIUrl":"10.1007/s13258-026-01747-x","url":null,"abstract":"<p><strong>Background: </strong>The oral mucosa comprises anatomically and functionally distinct regions that differ in their degree of keratinization and barrier properties. Ectopic olfactory receptors (OR) have been detected in the oral mucosa. However, their expression patterns and potential roles remain poorly understood.</p><p><strong>Objective: </strong>This study aimed to characterize the molecular features and regional differences of structurally and functionally distinct oral mucosal tissues through unbiased transcriptomic analysis, and to explore the potential involvement of ectopic ORs as chemosensory components within this context.</p><p><strong>Methods: </strong>Gingival, buccal, and palatal mucosal tissues were collected by full-thickness excision from 8-week-old adult mice. Total RNA was extracted and sequenced. Differentially expressed genes (DEGs) and expression patterns were analyzed via bioinformatic approaches, and selected genes were validated by RT-qPCR.</p><p><strong>Results: </strong>Buccal, gingival, and palatal epithelia exhibited distinct transcriptional profiles, with gingiva and palate showing higher mutual correlation compared with buccal mucosa. Buccal tissue was enriched for genes associated with muscle activity and cytoskeletal organization, whereas genes related to keratinization and epithelial differentiation related genes were relatively underrepresented. Pairwise differential expression analysis indicated greater molecular divergence between buccal and masticatory mucosa than between gingiva and palate. Pattern-based transcriptomic analysis defined a global expression topology across oral mucosal tissues, in which ectopic ORs and associated genes were nonrandomly distributed. Several ORs displayed tissue-biased expression patterns linked to keratinization, calcium signaling, and GPCR-related pathways.</p><p><strong>Conclusion: </strong>These findings demonstrate that buccal, gingival, and palatal epithelia constitute transcriptionally and functionally distinct compartments of the oral mucosa. The regional embedding of ectopic ORs within tissue-specific expression architecture suggests a potential role for chemosensory mechanisms in shaping site-specific physiological responses, providing a molecular framework for understanding chemical sensing in the oral mucosa.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"683-696"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cochlear synaptic vulnerability scales with pathological noise intensity in a noise-induced hearing loss model.","authors":"Byeonghyeon Lee, Tae-Jun Kwon, Hyun Tae Kim, Un-Kyung Kim","doi":"10.1007/s13258-026-01748-w","DOIUrl":"10.1007/s13258-026-01748-w","url":null,"abstract":"<p><p>BACKGROUND: Noise-induced hearing loss (NIHL) has been traditionally attributed to outer hair cell (OHC) damage, but synaptic injury at inner hair cell (IHC)–spiral ganglion neuron (SGN) junctions may better explain persistent functional deficits. OBJECTIVE: To test whether IHC ribbon loss and functional synapse loss scale with pathological noise intensity and to define their longitudinal relationship to hearing function. METHODS: A rodent NIHL model was exposed to 100 dB SPL for 2 h or 110 dB SPL for 4 h. Cochleae were immunolabeled for CtBP2 (presynaptic ribbons) and GluA2 (postsynaptic AMPA receptor puncta). Putative functional synapses were quantified as closely apposed CtBP2/GluA2 pairs. Hearing function was assessed longitudinally and correlated with synaptic measures. RESULTS: Both exposure conditions produced graded reductions in IHC ribbon counts and CtBP2/GluA2 pairs, with greater losses after 110 dB/4 h. The number of CtBP2/GluA2 apposed pairs closely tracked preserved hearing function, providing a stronger association with functional outcome than ribbon counts alone. Ribbon loss remained largely stable across post-exposure intervals, whereas functional synapse loss was disproportionately larger at early time points, consistent with transient pre–post misalignment. Over time, CtBP2/GluA2 pairing partially recovered toward levels predicted by surviving ribbons, suggesting re-alignment or reconnection of a subset of remaining synaptic elements. CONCLUSION: Pathological noise intensity drives exposure-dependent IHC synaptopathy in addition to OHC injury. Functional synapse counts (CtBP2/GluA2 pairs) sensitively reflect stored hearing function and indicate a potential post-exposure window for synaptic re-establishment. </p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"697-708"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone lactatation-related genes GPR19 and SLC22A16 are important diagnostic markers and drug treatment targets for prostate cancer.","authors":"Yunkun Yan, Zhuo Li, Mushi Ye, Jianchang Li","doi":"10.1007/s13258-026-01740-4","DOIUrl":"10.1007/s13258-026-01740-4","url":null,"abstract":"<p><strong>Background: </strong>Histone lactylation is an emerging epigenetic modification involved in tumor progression, but its transcriptional characteristics and clinical relevance in prostate cancer (PCa) remain poorly understood.</p><p><strong>Purpose: </strong>To preliminarily explore histone lactylation-related transcriptional features in prostate cancer and identify potential diagnostic biomarkers.</p><p><strong>Methods: </strong>The TCGA-PRAD dataset was used as the training cohort and the GSE46602 dataset as the validation cohort. Based on histone lactylation-related genes (HLRGs) reported in the literature, single-sample gene set enrichment analysis (ssGSEA) scores were calculated to characterize histone lactylation-related transcriptional states. Differentially expressed genes were identified between tumor and normal tissues, as well as between highand low-ssGSEA score groups, and overlapping genes were selected for further analysis. Mendelian randomization (MR) analysis was then applied to identify genes significantly associated with PCa, and receiver operating characteristic (ROC) curves were used to evaluate their discriminatory performance. Functional enrichment and regulatory network analyses were also performed. In addition, gene expression was examined in prostate-related cell lines, and gene knockdown experiments were conducted to preliminarily assess the effects on prostate cancer cell viability and proliferation.</p><p><strong>Results: </strong>GPR19 and SLC22A16 were ultimately identified as candidate biomarkers. Both genes were significantly upregulated in prostate cancer tissues and cell lines. Functional analyses indicated that GPR19 and SLC22A16 were associated with the \"cell cycle\" and \"aminoacyl-tRNA biosynthesis\" pathways, respectively. In vitro experiments showed that knockdown of SLC22A16 significantly suppressed the viability and proliferation of PC-3 cells.</p><p><strong>Conclusion: </strong>Based on histone lactylation-related transcriptional features, this study preliminarily identified GPR19 and SLC22A16 as genes associated with prostate cancer and provided supportive evidence for their potential biological relevance. Further studies are required to elucidate their regulatory mechanisms and clinical significance.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"659-671"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147283357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis modulation by Toxoplasma gondii suppresses sodium iodate-driven age-related macular degeneration.","authors":"Xin-Cheng Wang, Guan-Hao Hong, Yu-Sun Yun, In-Wook Choi, Jaemin Yuk, Guang-Ho Cha","doi":"10.1007/s13258-026-01757-9","DOIUrl":"10.1007/s13258-026-01757-9","url":null,"abstract":"<p><p>BACKGROUND: Oxidative stress is a central driver of retinal pigment epithelium (RPE) degeneration and a defining pathological feature of age-related macular degeneration (AMD). Sodium iodate (NaIO3) is widely used to model oxidative injury in RPE cells, yet the molecular checkpoints that determine whether oxidatively stressed RPE cells succumb or survive remain poorly defined. OBJECTIVE: This study aimed to investigate whether Toxoplasma gondii (T. gondii) infection modulates NaIO3-induced oxidative stress and ferroptotic vulnerability in human RPE cells, and to elucidate the role of ferroptosis in RPE degeneration. METHODS: ARPE-19 cells were exposed to NaIO3 to induce oxidative stress and ferroptosis-associated injury, followed by infection with T. gondii. Cellular viability, cytosolic and mitochondrial reactive oxygen species (ROS), lipid peroxidation, iron homeostasis, and the expression of key ferroptosis-related regulators, including GPX4 and SLC7A11, were assessed using biochemical assays, fluorescence imaging, and immunoblotting. RESULTS: NaIO3 exposure impaired ferroptosis-associated antioxidant defenses in ARPE-19 cells by suppressing GPX4 and SLC7A11, disrupting iron homeostasis, and amplifying cytosolic and mitochondrial ROS production. T. gondii infection reversed this ferroptotic priming, markedly reduced oxidative stress, and protected RPE cells from lipid peroxidation–driven apoptotic execution. This parasite-driven cytoprotective conversion identifies ferroptosis as a pivotal regulatory node in host–pathogen interactions within the retina. CONCLUSIONS: Our findings demonstrate that T. gondii counteracts oxidative–ferroptotic stress to preserve RPE integrity, highlighting ferroptosis modulation as a key mechanism linking oxidative stress, retinal degeneration, and parasite-driven host cell reprogramming. These results expand the conceptual framework for understanding how host–pathogen interactions shape tissue vulnerability and survival in retinal disease contexts.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"767-781"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}