Genes & genomics最新文献

{"title":"High-quality chromosome-scale genome assembly and adaptive evolution analysis of Yangtze endemic Coreius guichenoti.","authors":"Jing Chen, Xianqi Peng, Lei Huang, Xialian Bu, Yu Zhao, Tao Qian, Jian Zhu, Huantao Qu, Jiayun Yao","doi":"10.1007/s13258-025-01713-z","DOIUrl":"10.1007/s13258-025-01713-z","url":null,"abstract":"<p><p>BACKGROUND: Coreius guichenoti is a critically endangered, nationally protected second-class endemic fish in the upper Yangtze River. Its wild population has declined sharply due to habitat degradation, overfishing, and dam construction, necessitating urgent conservation genomics resources. OBJECTIVE: To generate a high-quality chromosome-level genome assembly for C. guichenoti to elucidate its adaptive evolution and support conservation strategies. METHODS: We integrated PacBio HiFi long-read sequencing and Hi-C scaffolding technologies for de novo genome assembly. Genome annotation included repeat masking, protein-coding gene prediction, and functional characterization using public databases. Comparative genomics and phylogenetic analyses were performed with 13 related fish species. RESULTS: A 1.10 Gb genome was assembled, with 93.56% of sequences anchored to 25 chromosomes (scaffold N50 = 41.37 Mb). Repeat elements constituted 58.26% of the genome, and 25,588 protein-coding genes were predicted (96.1% functionally annotated). BUSCO completeness reached 99.7%. Phylogenetic analysis revealed that C. guichenoti diverged from Leuciscus waleckii ~ 79.8 million years ago. Synteny analysis showed significant chromosomal rearrangements between these species. Gene family expansions implicated immune adaptation (e.g., IL-17 signaling) and metabolic pathways (e.g., arachidonic acid metabolism). CONCLUSION: This high-quality genome provides a critical resource for understanding adaptive evolution and guiding conservation strategies for this imperiled species.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"559-570"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029287","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":"Transcriptomic signatures of pregnancy progression and potential early diagnostic biomarkers in peripheral blood of Hanwoo (Bos taurus coreanae) cattle.","authors":"Junhyeon Jeon, Dong-Yep Oh, Wooseok Lee, Seyoung Mun, Kyudong Han","doi":"10.1007/s13258-025-01734-8","DOIUrl":"10.1007/s13258-025-01734-8","url":null,"abstract":"<p><strong>Background: </strong>Understanding the molecular regulation of gestation is crucial for improving reproductive efficiency in Hanwoo cattle, yet the systemic changes occurring throughout pregnancy remain undefined.</p><p><strong>Objective: </strong>To identify molecular mechanisms underlying pregnancy progression and develop potential biomarkers for early detection through transcriptome profiling.</p><p><strong>Methods: </strong>Whole blood samples were collected from 15 Hanwoo cows at five physiological stages: non-pregnant, and at 2-, 4-, 16- and 40-week of gestation. RNA sequencing was performed to identify differentially expressed genes (DEGs), and their functional roles were predicted using Gene Ontology and pathway enrichment analyses. Additionally, time-series clustering was conducted to track expression patterns, and validation of candidate early pregnancy biomarkers was performed via qRT-PCR.</p><p><strong>Results: </strong>A total of 2,029 DEGs were identified across the gestation period. Early pregnancy (2-4 weeks) was characterized by immune tolerance mechanisms and the downregulation of TLR9 signaling, with ADGRE3 and OCSTAMP identified as key genes for uterine receptivity. Mid-pregnancy (16 weeks) exhibited significant upregulation of NOTCH2 and SMAD4, essential for placental maturation. Late pregnancy (40 weeks) revealed ECM remodeling and immune suppression. Validated biomarkers for early pregnancy, including HBB, HBQ1, and ADGRE3, showed strong consistency between RNA-seq and qRT-PCR data.</p><p><strong>Conclusion: </strong>This study provides comprehensive insights into the transcriptional dynamics during pregnancy in Hanwoo cattle and suggests practical biomarkers for early pregnancy diagnosis.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"419-431"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959248","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":"De novo identification and differential expression of MicroRNA in the Lebbeus groenlandicus.","authors":"Du Hyeong Lee, Hae Jin Shin, Woo Ryung Kim, Eun Gyung Park, Yun Ju Lee, Hyeon-Su Jeong, Hyun-Young Roh, Ga-Ram Jeong, Tae Hwan Shin, Heui-Soo Kim","doi":"10.1007/s13258-025-01720-0","DOIUrl":"10.1007/s13258-025-01720-0","url":null,"abstract":"<p><p>BACKGROUND: Caridean shrimps remain under-studied despite their economic value. Lebbeus groenlandicus (L. groenlandicus) lacks foundational molecular resources, limiting management and aquaculture applications. MicroRNAs (miRNAs) regulate immunity and metabolism and offer biomarker potential, yet no miRNAome has been reported for this species. OBJECTIVE: To generate the first miRNAome for L. groenlandicus, characterize orthologous and novel miRNAs, and assess tissue-specific expression. METHOD: Small RNA-seq libraries (15–35 nt) were prepared from the hepatopancreas and muscle of three individuals (six libraries). Reads were aligned to human, mouse, and zebrafish miRNA references; miRDeep2 was used for discovery/quantification, with BLASTN, intersection, and MFE analyses for validation. Differential expression was tested with DESeq2; qRT-PCR evaluated species specificity of candidates. RESULTS: On average, 25.17% of reads mapped to known miRNAs, yielding average 117 known miRNAs per tissue and average 25 novel candidates per tissue. Cross-species alignment and intersection defined 61 orthologous miRNAs. Hepatopancreas showed strong up-regulation of several novel miRNAs and orthologs miR-1260a, miR-184, miR-7a-1; down-regulated sets included novel miRNAs and orthologs miR-1a-2, miR-133a-2, miR-10a, miR-5004. miR-10a was evolutionarily conserved. Candidate NM00003 exhibited a stable stem-loop structure and species-specific expression. CONCLUSION: We deliver the first miRNAome for L. groenlandicus, revealing conserved regulators of immunity and metabolism, and identify novel miRNAs as practical biomarker candidates for aquaculture monitoring and stock management.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"339-348"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699899","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":"Transcriptomic exploration unveils hub genes influencing fatty acid composition across various sections of yak meat.","authors":"Bo Hu, Haiyue Wu, Rong Hu, Zhongxin Yan, Lu Sun, Haijia Ren, Yahui Guo, Meisong Wang","doi":"10.1007/s13258-025-01729-5","DOIUrl":"10.1007/s13258-025-01729-5","url":null,"abstract":"<p><p>BACKGROUND: Yak meat, a staple in the Qinghai-Tibet Plateau, possesses unique nutritional characteristics, including its fatty acid composition. Understanding the genetic and metabolic pathways influencing these fatty acids is crucial for optimizing meat quality. OBJECTIVE: To explore the genetic and metabolic pathways affecting the fatty acid composition in different cuts of yak meat from the Qinghai-Tibet Plateau. METHODS: Twelve yaks from the Qinghai-Tibet Plateau were sampled, and three distinct meat parts (shoulder, striploin, and silverside) were analyzed. Gas chromatography was used to determine fatty acid profiles. High-throughput RNA sequencing was performed to identify differentially expressed genes (DEGs). A comprehensive bioinformatics approach, including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Set Enrichment Analysis (GSEA), Protein–Protein Interaction (PPI) network construction, and Ingenuity Pathway Analysis (IPA), was employed to analyze the genetic and metabolic pathways. RESULTS: Significant variations were observed in the ratios of saturated and unsaturated fatty acids across different yak meat parts, with notable differences in Myristic acid (C14:0) and Linoleic acid (C18:2, n-6). A total of 616 differentially expressed genes were identified. Bioinformatics analyses identified 10 candidate hub genes potentially involved in fatty acid synthesis and regulation, with PPARG showing the highest network centrality and potential regulatory importance. Key signaling pathways impacting fatty acid composition were also identified. CONCLUSION: This exploratory study identified candidate genes and signaling pathways potentially associated with fatty acid composition variation in different yak meat cuts. These findings provide preliminary insights into the transcriptomic landscape related to fatty acid metabolism in yaks, which may inform future research and strategies for improving yak meat quality.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"393-408"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892308","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":"Single-cell transcriptomic analysis reveals cellular and molecular changes in EGFR-positive lung adenocarcinoma before and after Furmonertinib treatment.","authors":"Jian Chen, Minghui Cai, Lifei Meng, Ze Hong, Wentao Hu","doi":"10.1007/s13258-025-01706-y","DOIUrl":"10.1007/s13258-025-01706-y","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) frequently harbors activating mutations in the epidermal growth factor receptor (EGFR), making EGFR tyrosine kinase inhibitors (EGFR-TKIs) a critical component of targeted therapy. Although third-generation EGFR-TKIs, such as Furmonertinib, have improved outcomes for patients with EGFR-mutant LUAD, drug resistance and tumor adaptation remain major challenges. The cellular and molecular mechanisms underlying response and adaptation to Furmonertinib, particularly within the tumor microenvironment (TME), are not fully understood.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing on tumor and paired paracancerous tissues from EGFR-positive LUAD patients before and after Furmonertinib treatment, integrating both public and in-house datasets. We systematically analyzed changes in cellular composition, gene expression profiles, pathway enrichment, and ligand-receptor-mediated cell-cell communication.</p><p><strong>Results: </strong>Furmonertinib treatment led to a marked reduction in tumor cell proportion and profound remodeling of the TME. There was an increase in T cell infiltration, particularly CD4⁺ T cells, and a decrease in exhausted CD8⁺ T cells, indicating a shift toward a less immunosuppressive microenvironment. Cancer-associated fibroblasts and monocytes were also enriched post-treatment. Tumor cells exhibited increased EGFR expression, along with transcriptomic reprogramming characterized by upregulation of signaling, immune, and differentiation pathways, and downregulation of metabolic and protein synthesis genes. Cell-cell communication analysis revealed attenuation of immunosuppressive signaling (such as MIF axis) and enhancement of alternative ligand-receptor interactions, including LAMC1- and EGFR-related pathways.</p><p><strong>Conclusions: </strong>Our integrative single-cell analysis reveals that Furmonertinib therapy induces significant cellular and molecular changes in EGFR-positive LUAD, including TME remodeling, transcriptomic adaptation, and reprogramming of intercellular communication networks. These findings provide insight into the mechanisms of Furmonertinib response and resistance, and may inform strategies to optimize EGFR-TKI therapy.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"327-337"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12932405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145632068","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":"Identification of a novel nonsense variant in ARR3 in a family with early-onset high myopia.","authors":"Jiahe Yu, Jie Zhang, Yaqin Jiang, Chunli Ma, Wenjing Wang, Kaihui Zhang, Rujin Tian, Haisu Chen, Haitao Han, Huixin Sun, Chuanzhi Peng, Han Zhang, Xinyan Xu","doi":"10.1007/s13258-025-01730-y","DOIUrl":"10.1007/s13258-025-01730-y","url":null,"abstract":"<p><p>BACKGROUNDS: Early-onset high myopia (EoHM) is a severe refractive error that can result in significant vision loss. A known genetic cause involves mutations in the X-linked Arrestin-3 (ARR3) gene, which typically presents with a female-limited inheritance pattern, in which asymptomatic fathers transmit the variant to their affected daughters. OBJECTIVE: This study aims to present a unique case of EoHM characterized by paternal transmission of a novel ARR3 variant and to explore potential underlying molecular mechanisms through an exploratory bioinformatic analysis. METHODS: We collected the clinical phenotypes for the family and sequenced the blood using NGS and Sanger sequencing. Bioinformatic analysis of the GSE5338 dataset revealed a potential interaction network involving ARR3, NR2E3 (a photoreceptor development regulator), and OPN1MW (a cone opsin gene). RESULTS: The proband exhibited severe EoHM with stretched axial lengths (ALs) (24.09 and 24.43 mm) and pronounced myopic astigmatism. The asymptomatic father passed on a new nonsense variation in the ARR3 gene, c.7A > T (p.K3Ter). Exploratory bioinformatic analysis of a murine retinal dataset hinted at a possible regulatory relationship, wherein overexpression of the photoreceptor transcription factor Nr2e3 might be linked to the downregulation of Arr3 and the cone opsin gene Opn1mw. CONCLUSIONS: This study reports a novel ARR3 mutation within a family affected by EoHM, expanding the known mutational spectrum of this disease and offering vital insights for genetic counseling. Furthermore, our bioinformatic analysis has generated a hypothesis that NR2E3-mediated downregulation of both ARR3 and OPN1MW may contribute to the disease phenotype, a link that warrants future investigation in human models.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"409-418"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932909","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":"Biomarkers for predominantly inattentive ADHD: potential involvement of Wnt/β-catenin/integrin signaling in a spontaneously hypertensive rat.","authors":"Nicole Bon Campomayor, Sweetie Balataria, Kwang Hee Kim, Min Yeong Lee, Jae Hoon Cheong, Mikyung Kim, Hee Jin Kim","doi":"10.1007/s13258-025-01722-y","DOIUrl":"10.1007/s13258-025-01722-y","url":null,"abstract":"<p><strong>Background: </strong>Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder marked by heterogeneous symptoms and comorbidities, complicating diagnosis and obscuring its neurobiological basis.</p><p><strong>Objective: </strong>To investigate molecular mechanisms underlying ADHD, particularly the inattentive subtype, by examining Ctnnβ1 (catenin beta 1) and Itgβ1 (integrin beta 1), key components of the Wnt/β-catenin signaling pathway implicated in neurodevelopmental disorders.</p><p><strong>Methods: </strong>Spontaneously hypertensive rats (SHR/NCrl), a validated ADHD model, were assessed for attentional performance through behavioral testing. Hippocampal and peripheral blood expression of Ctnnβ1 and Itgβ1 were quantified. A subset received atomoxetine to evaluate pharmacological effects on behavioral and molecular outcomes.</p><p><strong>Results: </strong>SHR/NCrl rats displayed attentional impairments compared with controls. These deficits were accompanied by elevated hippocampal and peripheral expression of Ctnnβ1 and Itgβ1. Atomoxetine treatment normalized gene expression and improved attentional performance, demonstrating amelioration at both molecular and behavioral levels.</p><p><strong>Conclusion: </strong>Dysregulation of Wnt/β-catenin/integrin signaling may contribute to the ADHD pathophysiology. Concordant upregulation of Ctnnβ1 and Itgβ1 in brain and peripheral blood may support their potential as peripheral biomarkers of ADHD. Responsiveness of these genetic markers to atomoxetine treatment indicates potential value for treatment monitoring and supports targeting this pathway in future therapeutic strategies.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"445-454"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010062","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":"Prevalence of germline 113 cancer genes in healthy Indonesian hospital staff.","authors":"Mega Hayati, Fahreza Saputra, Hubertus Hosti Hayuanta, Lyana Setiawan, Ahmad Rusdan H Utomo","doi":"10.1007/s13258-025-01726-8","DOIUrl":"10.1007/s13258-025-01726-8","url":null,"abstract":"<p><p>BACKGROUND: The absence of population-specific genetic variant frequency data in Indonesia complicates the interpretation of germline genetic variants of DNA repair genes critical for cancer predisposition. OBJECTIVE: to estimate baseline frequency of pathogenic/likely pathogenic germline variants (P/LP) and variant of unknown significance (VUS), we conducted an exploratory genetic screening in a convenience sample of 255 hospital staff without personal history of cancer, i.e. healthy subjects. METHODS: A cross-sectional study was conducted at Dharmais Cancer Centre, Indonesia. 156 (61%) and 99 subjects (39%) reported absence and presence of family history (FH) of cancer, respectively. Peripheral blood DNA was sequenced using the Illumina 113-gene TruSight hereditary panel, and variants were classified according to the American College of Medical Genetics (ACMG) guidelines. RESULTS: Twelve out of 255 subjects or 4.71% (95% CI: 2.45–8.09%) carried P/LP variants of MUTYH, XPA, XPC, FANCA, FANCC, CHEK2 and Homologous DNA Repair (BRCA1, BRCA2, BRIP1, and RAD51D) genes. Five out of 99 with FH (5.1%) and seven out 156 subjects (4.48%) without FH had P/LP variants. There were 4 subjects (1.56%) harboring P/LP variants of BRCA1 (1.17%) and BRCA2 (0.39%) genes. BRCA1 and FANCA P/LP variants were found exclusively in 5 subjects with FH. One subject with FH carried dual P/LP variants of BRCA1 and CHEK2 genes. 21.6% subjects with and without family history had VUS in HRR genes. CONCLUSIONS: The P/LP germline variants were detected in healthy subjects with and without family history. Furthermore, we detected several VUS that were potentially to be reclassified as benign since their prevalence in healthy subjects was more common than the rate of the disease.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"383-391"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846508","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":"Lasting bone marrow defects imprinted by hyperglycemia shape the immunological characteristics of differentiated M1 and M2 macrophages.","authors":"In-Gu Lee, Jeonghyeon Lee, Ji Young Bang, Young-Jin Seo, So-Hee Hong","doi":"10.1007/s13258-025-01736-6","DOIUrl":"10.1007/s13258-025-01736-6","url":null,"abstract":"<p><strong>Background: </strong>Hyperglycemia in type 1 diabetes (T1D) disrupts immune function, yet it remains unclear whether hyperglycemia-induced immunological defects in the bone marrow (BM) persist in BM-derived M1 and M2 macrophages.</p><p><strong>Objective: </strong>We investigated the immunological and metabolic features of BM-derived M1 and M2 macrophages from prediabetic and diabetic non-obese diabetic (NOD) mice to determine the impact of hyperglycemic memory on polarized macrophages.</p><p><strong>Methods: </strong>Macrophages were differentiated from BM cells of prediabetic and diabetic NOD mice and subsequently polarized with lipopolysaccharide (LPS; M1 macrophages) or interleukin-4 (IL-4; M2 macrophages). Transcriptomic profiles were assessed using RNA sequencing and gene set enrichment analysis of differentially expressed genes (DEGs). In parallel, glycolysis, oxygen consumption, and cytokine production were evaluated.</p><p><strong>Results: </strong>Hyperglycemia induced pronounced transcriptomic alterations in both M1 and M2 macrophages, modifying immune and metabolic gene expression. Immune pathways, including inflammatory responses and cytokine production, were consistently suppressed in both subsets from diabetic mice compared with those from prediabetic mice. Metabolically, M1 macrophages preserved mitochondrial and glycolytic activity under diabetic conditions, whereas M2 macrophages exhibited impaired oxidative phosphorylation and glycolysis, resulting in diminished energy production. Functionally, both subsets from diabetic mice secreted lower levels of inflammatory cytokines upon stimulation relative to prediabetic counterparts.</p><p><strong>Conclusion: </strong>These findings demonstrate that hyperglycemia imprints persistent transcriptomic and functional defects in BM-derived M1 and M2 macrophages. This work provides new insights into how chronic hyperglycemia contributes to impaired host defense and dysregulated inflammation in diabetes.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"433-444"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959228","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":"Alpha-defensins promote macrophage inflammatory activation via RNF31 signaling.","authors":"Jungnam Lee, Naweed Mohammad, Seyoung Mun, Kyudong Han, Tammy Flagg-Dowie, Maria Magallon, Mark L Brantly, Karina A Serban","doi":"10.1007/s13258-025-01735-7","DOIUrl":"10.1007/s13258-025-01735-7","url":null,"abstract":"<p><strong>Background: </strong>Defensins, small cationic peptides with strong antimicrobial activity, are key effectors of innate immunity. α-defensins, human neutrophil peptides, are produced primarily by neutrophils and serve as an essential component of the airway defense system against invading pathogens. However, accumulating evidence indicates that α-defensins released from human neutrophils are markedly elevated in various lung diseases, where excessive α-defensins exert cytotoxic effects on epithelial and immune cells.</p><p><strong>Objective: </strong>We investigated how α-defensins influence macrophage inflammatory responses and aimed to elucidate the molecular mechanisms underlying α-defensin-induced macrophage activation.</p><p><strong>Methods: </strong>Through RNA-seq analysis, we identified key molecules potentially involved in α-defensin-induced inflammatory signaling and validated these candidates using qRT-PCR and western blotting.</p><p><strong>Results: </strong>Our results show that α-defensins significantly upregulate both the gene expression and protein levels of RNF31 in macrophages, leading to enhanced phosphorylation of NF-κB p65 and increased production of pro-inflammatory cytokines. Furthermore, when co-cultured with lung epithelial cells, α-defensin-stimulated macrophages induced NLRP3 expression in epithelial cells, suggesting that macrophage-epithelial crosstalk contributes to α-defensin-driven airway inflammation.</p><p><strong>Conclusion: </strong>Together, our results reveal that α-defensins promote macrophage-driven inflammation through RNF31-dependent NF-κB activation and subsequent macrophage-epithelial communication, providing new insight into the inflammatory mechanisms of lung injury. These findings uncover a previously unrecognized α-defensin-RNF31 signaling pathway that amplifies macrophage-mediated airway inflammation, highlighting RNF31 as a potential therapeutic target for inflammatory lung diseases.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"455-470"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010111","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}