Genes最新文献

{"title":"Strictosidine Synthase-like Gene <i>NMS1</i> Is Required for Male Fertility in Rice by Regulating Tapetal Degradation.","authors":"Zhiyuan He, Anping Du, Nenggang Chen, Yulin Tang, Ping Wang, Longxiang Lu, Hui Li, Yulu Bai, Shicong Yu, Jing Liang, Xiaoqing Yan, Lei Zhou, Xiaolan Liu, Zhigang Pu, Binhua Hu","doi":"10.3390/genes17080970","DOIUrl":"10.3390/genes17080970","url":null,"abstract":"<p><p><b>Background:</b> Male sterility is a critical trait for large-scale hybrid rice seed production, yet the genetic and molecular regulatory networks governing tapetal degradation during anther development remain incompletely understood. This study aimed to clone the causal gene underlying a novel rice non-pollen male sterility mutant and elucidate its role in tapetal development and microsporogenesis. <b>Methods:</b> The <i>nms1</i> (<i>non-pollen male sterility 1</i>) sterile mutant was screened from the ethyl methanesulfonate (EMS)-mutagenized progeny of the elite <i>indica</i> restorer line Shuhui 498 (R498). Map-based cloning and whole-genome resequencing-assisted bulked segregant analysis were used to identify the causal variant. Gene function was verified via cytological observation, genetic complementation testing, RNA sequencing, and quantitative real-time PCR (qRT-PCR) to profile sterility-associated transcriptional changes. <b>Results:</b> Gene mapping identified a T635A single-nucleotide substitution within <i>OsR498G0305626400.01</i> on chromosome 3, which encodes a strictosidine synthase-like protein. This nucleotide alteration causes a Val212Glu amino acid change and is associated with delayed tapetal degradation and pollen abortion. Transgenic complementation experiments verified that functional <i>NMS1</i> restores fertility in <i>nms1</i> mutant plants. Spatiotemporal expression analysis showed predominant <i>NMS1</i> expression in late-developing spikelets. Furthermore, combined RNA sequencing and qRT-PCR analyses demonstrated that loss of <i>NMS1</i> function leads to significant transcriptional dysregulation of key regulators of programmed cell death (PCD) in the tapetum (<i>PTC2</i>, <i>TIP2</i>) and pollen wall biosynthesis genes (<i>TIP3</i>, <i>OsMS2</i>). <b>Conclusions:</b> This study demonstrates that <i>NMS1</i> plays a crucial role in coordinating tapetal degradation and microspore development in rice. The discovered functional SNP of <i>NMS1</i> provides a novel theoretical foundation and a valuable sterile genetic resource for hybrid rice breeding.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTED: Wigner et al. The Impact of Chronic Mild Stress and Agomelatine Treatment on the Expression Level and Methylation Status of Genes Involved in Tryptophan Catabolic Pathway in PBMCs and Brain Structures. <i>Genes</i> 2020, <i>11</i>, 1093.","authors":"Paulina Wigner, Ewelina Synowiec, Paweł Jóźwiak, Piotr Czarny, Katarzyna Białek, Michal Bijak, Janusz Szemraj, Piotr Gruca, Mariusz Papp, Tomasz Sliwinski","doi":"10.3390/genes17080972","DOIUrl":"https://doi.org/10.3390/genes17080972","url":null,"abstract":"<p><p>The journal retracts the article titled, \"The Impact of Chronic Mild Stress and Agomelatine Treatment on the Expression Level and Methylation Status of Genes Involved in Tryptophan Catabolic Pathway in PBMCs and Brain Structures\" [...].</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13492001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Transcriptomic Remodeling of Adipose Tissue After Bariatric Surgery Revealed by Differential Expression and Explainable Machine Learning.","authors":"Soumaya Allouch, Md Shaheenur Islam Sumon, Aisha Naeem, Claus Vinter Bødker Hviid, Zumin Shi, Muhammad E H Chowdhury, Shona Pedersen","doi":"10.3390/genes17080974","DOIUrl":"10.3390/genes17080974","url":null,"abstract":"<p><p><b>Background:</b> Bariatric surgery improves metabolic health, but long-term transcriptomic remodeling of white adipose tissue (WAT) after Roux-en-Y gastric bypass (RYGB) remains incompletely defined. This study aimed to characterize longitudinal WAT gene-expression patterns after RYGB and prioritize candidate signatures of post-surgical adaptation using a publicly available dataset. <b>Methods:</b> We analyzed subcutaneous WAT transcriptomic data from women with obesity who underwent RYGB, with samples collected before surgery and at 2 and 5 years after surgery. Differential expression analysis was integrated with pathway enrichment, supervised machine-learning-based feature prioritization and classification, and SHAP-based model interpretation. <b>Results:</b> Differential expression and machine-learning analyses showed clear separation between baseline and post-surgery transcriptomic states. Pathway-level findings indicated reduced inflammatory and immune-related signaling, particularly across pathways related to phagosome function, lysosomal activity, antigen presentation, and host-defense responses after surgery. Gene-level analyses additionally suggested extracellular-matrix and metabolic remodeling. Machine-learning models distinguished baseline from post-surgery samples, while SHAP analysis identified genes with the strongest contributions to model predictions. Importantly, several statistically prioritized genes also showed high SHAP attribution, demonstrating concordance between univariate statistical significance and multivariate predictive relevance. This convergence suggests that the models captured biologically meaningful surgery-associated signals rather than purely data-driven classification artifacts. <b>Conclusions:</b> This study advances the interpretation of longitudinal adipose-tissue transcriptomic remodeling after RYGB by combining differential expression, pathway enrichment, supervised machine learning, and explainable AI within a unified framework. The integrated workflow prioritized candidate long-term remodeling genes, particularly immune/inflammatory and extracellular-matrix-related transcriptomic signatures, that warrant validation in independent cohorts.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13511782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA Modifications Modulate Biomolecular Condensates in Stress and Disease.","authors":"Y Sprecher, M Sevilla-Sharon, S Moshitch-Moshkovitz","doi":"10.3390/genes17080973","DOIUrl":"10.3390/genes17080973","url":null,"abstract":"<p><p>Biomolecular condensates are dynamic membraneless organelles composed of proteins and RNAs that assemble through multivalent interactions and provide cells with powerful means to regulate gene expression in space and time. Different epitranscriptomic marks such as m⁶A, m¹A, and m⁵C can reshape RNA structure-binding interfaces and multivalency and, in this manner, tuning which transcripts nucleate or partition into specific condensates and influencing their material state. This review summarizes how individual RNA modifications and their associated proteins regulate the formation and function of BMCs such as stress granules, P-bodies, nuclear bodies and disease-linked condensates in cancer and neurodegeneration. It highlights emerging concepts of combinatorial \"epitranscriptomic codes\" and bidirectional feedback between condensates and RNA-modifying enzymes and discusses the current experimental and technical gaps that still limit our understanding of modification crosstalk and condensate topology.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Genetic Diagnosis of Spinal Muscular Atrophy: Clinical Utility, Challenges, and Lessons Learned from Illustrative Cases in a Single Center.","authors":"Jinli Bai, Qinglin Jiang, Hui Jiao, Yuwei Jin, Hong Wang, Xiushan Ge, Ying Gao, Xiaoyin Peng, Fang Song, Yujin Qu, Mei Diao","doi":"10.3390/genes17080971","DOIUrl":"10.3390/genes17080971","url":null,"abstract":"<p><p><b>Background:</b> Spinal muscular atrophy (SMA) is mainly caused by biallelic <i>SMN1</i> inactivation. While most patients carry homozygous deletions, 3-5% are compound heterozygotes, making molecular diagnosis challenging. <b>Methods:</b> A tiered diagnostic strategy was applied to 17 pediatric patients, combining copy number analyses (MLPA and targeted long-read sequencing, tLRS), sequence variant detection (RT-PCR cloning and sequencing, allele-specific long-range PCR with nested PCR, and tLRS), and structural variant analysis (ultra-long-read sequencing, Ultra-LRS). <b>Results:</b> Copy numbers were concordant between MLPA and tLRS. MLPA-suggested gene conversions were confirmed by tLRS, while discordant total copy numbers were resolved as large deletions by Ultra-LRS. RT-PCR cloning, and sequencing identified <i>SMN1</i> variants in 11/12 cases and confirmed aberrant splicing in three cases, but failed for large deletions. AS-LR-PCR with nested PCR characterized the variants in 13/15 but failed in gene conversion cases. tLRS achieved definitive diagnosis in all cases, and Ultra-LRS precisely delineated breakpoint junctions of two large deletions. <b>Conclusions:</b> A hierarchical complementary strategy integrating copy number, sequence, and structural analyses is essential for the accurate diagnosis of compound heterozygous SMA.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13511791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Architecture of Synaptic Failure in Dementia with Lewy Bodies: From α-Synuclein Proteoforms to GBA1-Mediated Plasticity Deficits.","authors":"Anastasia Bougea","doi":"10.3390/genes17080965","DOIUrl":"10.3390/genes17080965","url":null,"abstract":"<p><p>Dementia with Lewy bodies (DLB) is increasingly conceptualised not merely as a disorder of neuronal death but as a primary synaptopathy in which the functional collapse of synaptic transmission and plasticity precedes, and predicts, neurodegeneration and clinical decline. Two genetic determinants dominate the heritable risk architecture of DLB: the α-synuclein gene <i>SNCA</i>, in which both copy-number variation and missense mutations exert dose- and conformation-dependent effects, and GBA1, encoding the lysosomal hydrolase glucocerebrosidase (GCase), the single most influential genetic risk factor for the disease. Here we synthesise evidence that these loci converge on a shared pathogenic endpoint-the impairment of activity-dependent synaptic plasticity. We argue that <i>GBA1</i> loss-of-function and the resulting accumulation of glucosylceramide stabilise specific neurotoxic α-synuclein proteoforms, including soluble oligomers and self-templating conformational strains bearing defined post-translational modifications. These proteoforms are trafficked to, and enriched within, presynaptic terminals, where they disrupt SNARE-complex assembly and synaptic-vesicle dynamics, while postsynaptically they perturb NMDA and AMPA receptor trafficking, dysregulate dendritic calcium, and compromise synaptic mitochondrial bioenergetics. The net consequence is a metaplastic shift away from long-term potentiation (LTP) and toward aberrant long-term depression (LTD), a signature of synaptic failure detectable before frank pathology. We map these molecular events onto disease-relevant circuits-particularly the cholinergic basal forebrain and hippocampal-cortical and thalamocortical networks-and relate them to the defining neuropsychiatric features of DLB, including cognitive fluctuations and recurrent visual hallucinations. Finally, we evaluate emerging therapeutic strategies that target the GBA1-α-synuclein axis and that aim to restore synaptic plasticity directly. Positioning DLB within the framework of genetically determined plasticity deficits clarifies its kinship with other neuropsychiatric disorders and identifies the synapse as the most tractable node for early, disease-modifying intervention. We further examine how GBA1 allele severity and zygosity grade the phenotype, which genetic and environmental factors modify penetrance in carriers, and what distinguishes this synaptopathy from those driven by PSEN1/PSEN2, MAPT, or HTT, and we summarise the therapeutic pipeline-including enzyme augmentation and adeno-associated viral GBA1 gene therapy-that targets it.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GWAS-Informed Candidate Genetic Variants and Gene-Gene/Gene-Environment Interaction Patterns Associated with Intervertebral Disc Degeneration: A Chinese Han Case-Control Study.","authors":"Ridan Lei, Mengyuan Zhang, Manjun Luo, Xiaorui Ruan, Jianhui Wei, Ziye Li, Jiabi Qin","doi":"10.3390/genes17080967","DOIUrl":"10.3390/genes17080967","url":null,"abstract":"<p><strong>Background/objectives: </strong>Intervertebral disc degeneration (IDD) is a multifactorial spinal degenerative condition influenced by inherited susceptibility and environmental exposures. Genetic evidence from Chinese Han populations remains limited. This study aimed to evaluate GWAS-informed and previously reported candidate single-nucleotide polymorphisms (SNPs) associated with IDD and to explore potential gene-gene and gene-environment interaction patterns.</p><p><strong>Methods: </strong>A hospital-based case-control study was conducted in 1951 unrelated Chinese Han participants, including 929 patients with magnetic resonance imaging-confirmed IDD and 1022 control subjects without evident IDD. Candidate SNPs were genotyped using the MassARRAY platform. Multivariable logistic regression was used to assess genetic associations under different genetic models, and linkage disequilibrium, haplotype associations, additive and multiplicative interactions, and generalized multifactor dimensionality reduction (GMDR) were further evaluated.</p><p><strong>Results: </strong>Of the 60 initially selected candidate SNPs, 49 passed quality control and were retained for association analyses. Several variants showed nominal associations with IDD susceptibility. Representative associations included <i>MMP3</i> rs591058 under the recessive model (OR = 1.37, 95% CI: 1.06-1.79, <i>p</i> = 0.019) and <i>VDR</i> rs2228570 under the dominant model (OR = 1.52, 95% CI: 1.10-2.11, <i>p</i> = 0.012), whereas the <i>CCDC26</i> rs6651255-rs7816342 AC haplotype showed a protective association (OR = 0.87, 95% CI: 0.76-0.99, <i>p</i> = 0.046). Exploratory interaction analyses suggested possible gene-gene interactions involving <i>ACAN</i>, <i>IL1B</i>, <i>VDR</i>, <i>CASP3</i>, and <i>CEP162/RIPPLY2</i>, as well as gene-environment interactions involving smoking, weight-bearing workload, and duration of bending work.</p><p><strong>Conclusions: </strong>This study provides preliminary genetic epidemiological evidence that GWAS-informed candidate variants and exploratory interaction patterns may be associated with IDD susceptibility in the Chinese Han population. These findings require further replication and functional validation.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13511863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide Characterization of the WIP Transcription Factor Gene Family in Soybean and Physiological Responses to Salt Stress.","authors":"Tianjiao Gao, Shuping Yan, Sobhi F Lamlom, Huilong Hong, Tiantian Huang, Guoqing Li, Narentuya Chen, Chunlei Zhang, Honglei Ren, Qiang Qiu, Lichun Huang","doi":"10.3390/genes17080968","DOIUrl":"10.3390/genes17080968","url":null,"abstract":"<p><strong>Background/objectives: </strong>Soybean (<i>Glycine max</i>) productivity is increasingly constrained by soil salinity. WIP transcription factors, a subfamily of C2H2-type zinc finger proteins, regulate cell division, differentiation, and tissue patterning in several plant species, but this gene family had not previously been systematically characterized in soybean or any other major legume crop. This study aimed to identify and characterize the <i>GmWIP</i> gene family genome-wide and evaluate its potential involvement in the soybean salt-stress response.</p><p><strong>Methods: </strong>Genome-wide identification of <i>GmWIP</i> genes was performed using sequence similarity and domain-based searches against the Wm82.gnm4.ann1 reference genome, followed by characterization of physicochemical properties, chromosomal distribution, phylogenetic relationships, gene duplication, conserved motifs, gene structure, and promoter cis-acting elements. Tissue-specific expression was examined using transcriptome data, and <i>GmWIP</i> responses to salt stress were profiled by RT-qPCR in roots, stems, and leaves of a salt-tolerant cultivar (HN531) and a salt-sensitive cultivar (HN563), alongside physiological measurements of oxidative stress and osmotic adjustment.</p><p><strong>Results: </strong>Thirty <i>GmWIP</i> genes were identified, with molecular weights from 26.90 to 57.52 kDa, distributed unevenly across 15 soybean chromosomes, with chromosomes 11, 12, and 13 forming a major hotspot (53.3% of the family). Duplication analysis detected 54 reconciled segmental duplicate gene pairs, all exhibiting Ka/Ks values < 1 (ranging from 0.0351 to 0.4471; mean 0.214), consistent with purifying selection acting on this gene set. GmWIP promoters were enriched for ABRE, MBS, and MeJA cis-acting elements. RT-qPCR showed genotype- and tissue-dependent differential expression under salt stress (e.g., up to 14.9-fold induction of <i>GmWIP22</i> in HN531 stems), paralleled by superior proline accumulation (+45%), soluble sugars, and CAT activity (+38%) alongside reduced MDA accumulation in the tolerant cultivar.</p><p><strong>Conclusions: </strong>The <i>GmWIP</i> gene family has expanded substantially in soybean relative to previously characterized species and shows genotype-dependent transcriptional responses to salt stress, suggesting that specific <i>GmWIP</i> members are candidate regulators of salt tolerance and warrant further functional investigation.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-27b-3p Exacerbates VCD-Induced KGN Cell Injury by Targeting PAPPA to Suppress IGF-1 Release and Inhibit the PI3K/AKT Pathway.","authors":"Manyu Zhang, Xiangyu Meng, Mengdi Shi, Pengling Ge","doi":"10.3390/genes17080966","DOIUrl":"10.3390/genes17080966","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background/objectives: &lt;/strong&gt;While currently termed premature ovarian insufficiency (POI), premature ovarian failure (POF) remains a prominent driver of female infertility with a molecular pathogenesis that is still lacking comprehensive clarification. In in vitro studies, the pathology of POI is commonly simulated through a well-characterized model involving VCD (4-vinylcyclohexene diepoxide)-mediated cytotoxicity within KGN-derived human granulosa cells. However, the key regulatory molecular networks involved in this process are still poorly characterized. Although microRNAs (miRNAs) have emerged as critical regulators in ovarian function decline, the specific role and underlying mechanism of miR-27b-3p in POI remain elusive.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A VCD-induced KGN cell injury model was established by treating cells with 1.0 mM VCD for 24 h. Cell viability, apoptosis rate, and miR-27b-3p expression were assessed by CCK-8 assay, flow cytometry, and RT-qPCR, respectively. Overexpression and targeted suppression of miR-27b-3p were achieved by introducing its specific mimics and inhibitors, respectively. Target identification was conducted via bioinformatic prediction, EdU incorporation, Western blot, and dual-luciferase reporter assays. Functional rescue experiments were carried out by co-transfection with a PAPPA-overexpressing plasmid (oe-PAPPA). IGF-1 secretion was quantified by ELISA, and phosphorylation of IGF1R and AKT was analyzed by Western blot to determine whether miR-27b-3p modulates cellular phenotypes via the PAPPA-IGF-1-PI3K/AKT axis. Exogenous IGF-1 supplementation was further applied to confirm pathway dependence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;VCD treatment dose-dependently restrained cellular growth and stimulated apoptotic pathways in KGN cells; paralleling these phenotypic changes, miR-27b-3p abundance was remarkably increased. Ectopic expression of miR-27b-3p exacerbated VCD-induced growth inhibition and apoptosis, whereas its inhibition conferred cytoprotective effects. Through the integration of computational predictions and dual-luciferase reporter systems, PAPPA was definitively established as a direct downstream target of miR-27b-3p. miR-27b-3p negatively regulated both PAPPA mRNA and protein levels, thereby impairing PAPPA-mediated cleavage of IGF-binding proteins (e.g., IGFBP4) and subsequent release of free IGF-1. This led to reduced IGF-1 secretion and significantly diminished phosphorylation of IGF1R and AKT. Remarkably, PAPPA overexpression effectively reversed the detrimental effects of miR-27b-3p, and exogenous IGF-1 supplementation similarly attenuated miR-27b-3p-mediated proliferation arrest and pro-apoptotic phenotypes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study uncovers a novel pathogenic mechanism whereby miR-27b-3p exacerbates VCD-induced granulosa cell injury by directly targeting PAPPA, suppressing IGF-1 release, and consequently inhibiting the PI3K/AKT pro-survival signaling p","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Skeletal Muscle Memory: The Impact of Physical Activity on Aging and Post-Injury Regeneration.","authors":"Antoni Godlewski, Marcin Wróblewski, Julia Kuk, Magdalena Moritz, Filip Dobrak, Renata Kołodziejska, Alina Woźniak","doi":"10.3390/genes17080964","DOIUrl":"10.3390/genes17080964","url":null,"abstract":"<p><p>Skeletal muscle retains adaptive information from previous mechanical loading, enabling faster responses to subsequent training and regenerative challenges. This review synthesizes current evidence on the cellular and epigenetic mechanisms underlying skeletal muscle memory and examines how these mechanisms are modified by aging and post-injury regeneration. Muscle memory emerges from complementary structural and molecular components, including myonuclear retention, persistent DNA methylation changes, chromatin remodeling, transcriptional priming, non-coding RNA regulation, and mitochondrial epigenetic adaptations. These mechanisms interact with muscle satellite cells (MuSCs), fibro-adipogenic progenitors (FAPs), immune cells, and extracellular matrix remodeling to maintain regenerative competence. During aging, epigenetic drift, chronic low-grade inflammation, altered macrophage states, MuSC dysfunction, persistent FAP activity, fibrosis, mitochondrial impairment, and anabolic resistance progressively reduce this plasticity, thereby contributing to sarcopenia. Training-detraining-retraining studies indicate that parts of the exercise-induced epigenetic landscape remain detectable after training cessation and can be reactivated during renewed loading, although the persistence and functional importance of individual molecular signatures remain incompletely defined. Physical exercise remains the most established intervention for preserving muscle function and epigenetic responsiveness, whereas caloric restriction, modulation of nutrient-sensing pathways, senolytic strategies, and direct targeting of epigenetic regulators remain promising but translationally less mature approaches. Overall, the preservation of epigenetic plasticity may be a key determinant of healthy skeletal muscle aging and effective regeneration.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}