Cells最新文献

{"title":"Disease- and Region-Specific Molecular Patterns Involving miRNAs and Associated Signalling Pathways and Epithelial Cell-Fate Responses in PSC-Associated Ulcerative Colitis.","authors":"Alicja Łaba, Joanna Abramczyk, Michał Lubkowski, Wiesława Rogoza-Mateja, Malgorzata Milkiewicz, Oktawian Knap, Piotr Milkiewicz, Agnieszka Kempinska-Podhorodecka","doi":"10.3390/cells15191821","DOIUrl":"10.3390/cells15191821","url":null,"abstract":"<p><p>Patients with primary sclerosing cholangitis-associated ulcerative colitis (PSC-UC) have an elevated risk of colorectal cancer compared with ulcerative colitis (UC), but the molecular mechanisms linking chronic inflammation to epithelial cell fate remain unclear. The present study investigated disease- and region-specific molecular patterns involving miRNAs and associated PI3K/AKT, STAT3, and NF-κB signalling pathways. miR-21, miR-181a, miR-181b, and key pathway components were analysed in paired ascending and sigmoid colon biopsies from patients with PSC, PSC-UC, UC, and controls. Functional effects were examined in HT-29 and NCM460D cells, and circulating miRNAs, including miR-155, were assessed. UC was characterised by marked miR-181a upregulation and PI3K/AKT activation, whereas PSC-UC showed reduced PDCD4, divergent p65 regulation, and altered miR-181a/miR-181b coordination. In NCM460D cells, miR-181a and miR-181b reduced viability, promoted apoptosis, impaired cell-cycle progression, and decreased PDCD4, p-AKT, and p-STAT3; miR-181b additionally reduced CYLD. Serum miR-155 was elevated in PSC-UC compared with UC and showed the strongest individual discriminatory capacity. Random forest analysis and an exploratory multivariable serum miRNA profile showed discriminatory potential. These findings support disease- and region-specific molecular patterns involving miRNAs and associated signalling pathways linked to epithelial cell-fate responses in PSC-UC and highlight molecular differences between PSC-UC and conventional UC.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GDF-15/GFRAL Axis Dynamics and Vulnerability Windows in Bariatric Surgery: Pathophysiological, Microbiomic, and Pharmacological Perspectives.","authors":"Alin Constantin Pînzariu, Ionela Lăcrămioara Șerban, Radu Petru Soroceanu, Vlad Ionuț Vlăsceanu, Madalina Maxim, Ancuta Andreea Miler, Sebastian Marian Leonte, Carmen Atodiresei, Mihaela Moscalu, Lorena Mihaela Manole, Laura Mihaela Trandafir, Dragomir Nicolae Șerban, Daniel Vasile Timofte","doi":"10.3390/cells15191823","DOIUrl":"10.3390/cells15191823","url":null,"abstract":"<p><p>Bariatric surgery (BS) and new pharmacological treatments cause significant neurometabolic changes. However, the pathways linking peripheral stress to central metabolic control remain poorly understood. This review highlights the GDF-15/GFRAL/RET complex as a key integrator of multiorgan-to-brain stress signals that shape systemic metabolic adaptation after surgical and pharmacological interventions. Based on a structured search across PubMed, Embase, Scopus, Google Scholar, and Web of Science covering 2020-2026 alongside foundational studies, we integrated translational evidence from peer-reviewed human trials and mechanistic animal models to map the GDF-15/GFRAL/RET axis across bariatric and incretin domains. We examined the neurobiology of the GDF-15/GFRAL axis to clarify variability in metabolic and behavioral outcomes after BS. This axis links metabolic stress signals from the gut, liver, and adipose tissue to the hindbrain and hypothalamic regulation of energy balance. Changes in the gut microbiome and SCFA-FFAR2/FFAR3 signaling after surgery interact with GDF-15 and incretin pathways. Future studies should critically compare BS with synergistic or alternative non-invasive neurometabolic approaches such as incretin mimetics, exogenous GDF-15 therapies, and high-protein diets.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Myotubes to Skeletal Muscle: <i>Cimicifuga racemosa</i> Extract Ze 450 Preserves Muscle Mass and Affects Skeletal Muscle Energy Metabolism Under Conditions of Metabolic Stress.","authors":"Siyu Chen, Elisabeth Habersatter, Tihomir Kostov, Jürgen Drewe, Georg Boonen, Veronika Butterweck, Patrick Diel","doi":"10.3390/cells15191816","DOIUrl":"10.3390/cells15191816","url":null,"abstract":"<p><p>Preservation of skeletal muscle is an important consideration when evaluating weight-loss interventions, particularly during menopause, when adverse changes in body composition occur. We investigated the effects of <i>Cimicifuga racemosa</i> extract Ze 450 on skeletal muscle. Differentiated C2C12 myotubes were treated with Ze 450, dexamethasone (DEX), or their combination. Non-ovariectomized female Wistar rats were assigned to one of five groups: standard diet, high-fat diet (HF), HF plus voluntary running, HF plus Ze 450 (130 mg/kg/day), or HF plus Ze 450 and voluntary running. Muscle mass and fiber cross-sectional area (CSA) were assessed in the predominantly glycolytic gastrocnemius and oxidative soleus. Markers of mitochondrial content (COX IV and CS), lipid metabolism (ATGL, HSL, FAS, and SREBP-1c), glucose transport (GLUT4), and myogenic signaling (IGF-1) were analyzed. Ze 450 had limited effects on myotube diameter under basal conditions but significantly attenuated DEX-induced myotube atrophy. In vivo, Ze 450 reduced body weight gain and fat accumulation without reducing muscle mass or fiber CSA. Ze 450 differentially affected metabolic markers in the two muscle types, decreasing markers associated with mitochondrial content in the soleus while increasing mitochondrial markers in the gastrocnemius. Taken together, these findings suggest a potential role for Ze 450 in rebalancing skeletal muscle metabolism in a muscle-type-specific manner while preserving skeletal muscle during reductions in body weight gain and adiposity.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation Between Gut Microbiota Shifts, Lipopolysaccharide Levels, and Neuroinflammatory Responses Following Ischemic Stroke.","authors":"Kemin Li, Wancong Ding, Shuang Wang, Gaowei Pan, Shengxiang Zhang","doi":"10.3390/cells15191819","DOIUrl":"10.3390/cells15191819","url":null,"abstract":"<p><strong>Background: </strong>The microbiota-gut-brain axis (MGBA) is increasingly recognized as a contributor to ischemic stroke pathophysiology, yet the relationship between gut microbial changes and neuroinflammation remains incompletely understood. This study aimed to investigate whether shifts in gut microbiota are associated with concurrent changes in lipopolysaccharide (LPS) levels and neuroinflammatory responses following ischemic stroke.</p><p><strong>Methods: </strong>Using a photothrombotic mouse model, we measured LPS in the gut, serum, and brain via ELISA and immunohistochemistry. Gentamycin was administered to deplete gut bacteria and assess its effects on LPS and stroke recovery. Upon TLR4 inhibition with TAK-242, microglial polarization and inflammatory cytokines were evaluated, and dose-dependent LPS supplementation was performed.</p><p><strong>Results: </strong>Ischemic stroke was accompanied by elevated LPS levels in the gut, circulation, and brain, paralleling <i>Verrucomicrobiota</i> expansion. Antibiotic treatment reduced <i>Verrucomicrobiota</i> and LPS in the gut and brain, and this was associated with worsened stroke outcomes. TLR4 inhibition was associated with altered microglial phenotypes and inflammatory markers. Exogenous LPS produced dose-dependent effects, whereas endogenous LPS levels remained low.</p><p><strong>Conclusions: </strong>These findings reveal a spatial correlation between gut microbial shifts, circulating LPS, and cerebral LPS immunoreactivity, suggesting LPS may serve as a correlative marker of gut-brain interactions following ischemic stroke.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pyrrole-Imidazole Polyamide Targeting Human USF1 Binding Suppresses High Glucose-Induced TGF-β1 and Osteopontin Expression in Human Renal Mesangial Cells.","authors":"Yurie Akiya, Hiroki Kobayashi, Akiko Tsunemi, Noboru Fukuda, Masanori Abe","doi":"10.3390/cells15191818","DOIUrl":"10.3390/cells15191818","url":null,"abstract":"<p><p>Transforming growth factor-β1 (TGF-β1) is a key profibrotic mediator in diabetic kidney disease. Upstream stimulatory factor 1 (USF1) enhances TGF-β1 transcription through an E-box/glucose-response element in the TGF-β1 promoter under high-glucose conditions. We designed a sequence-specific pyrrole-imidazole (PI) polyamide targeting the human USF1-binding site in the TGF-β1 promoter and evaluated its activity in human renal mesangial cells (HRMCs). A target PI polyamide and a mismatch PI polyamide were synthesized. DNA binding and inhibition of the USF1-DNA interaction were assessed by gel mobility shift assays. HRMCs were exposed to high glucose with or without PI polyamides, and TGF-β1 and osteopontin expression were quantified by real-time PCR and Western blotting. The target PI polyamide bound the intended promoter sequence and reduced recombinant USF1 binding in vitro. In high-glucose-exposed HRMCs, the target PI polyamide suppressed TGF-β1 mRNA and protein expression, whereas the mismatch PI polyamide did not suppress TGF-β1 expression. The target PI polyamide also reduced osteopontin mRNA expression. These findings provide proof-of-concept that PI polyamide-mediated targeting of the human USF1-TGF-β1 axis can attenuate high-glucose-associated profibrotic responses in HRMCs.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the Biomarkers: Gestation-Dependent Roles of sFLT-1 and PlGF in Human and Non-Human Mammalian Placental Development and Function.","authors":"Zoe Byrne, Sonja Brennan, David Watson, Donna Rudd, Yoga Kandasamy","doi":"10.3390/cells15191817","DOIUrl":"10.3390/cells15191817","url":null,"abstract":"<p><p>Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT-1) are established biomarkers of placental dysfunction, but their functions extend beyond the maternal circulating ratio. This structured narrative review examines the FLT1-PlGF-vascular endothelial growth factor system across implantation, trophoblast differentiation, uterine vascular transformation, foetoplacental angiogenesis, exchange capacity development and late-gestational maturation. Human evidence is integrated with selected non-human mammalian studies according to gestational stage, cellular source, anatomical compartment, molecular isoform and placental architecture. We use a compartmentalised angiogenic rheostat as a qualitative organising framework, not an experimentally validated model. It integrates established ligand-receptor biology with human observations and experimental perturbations: PlGF modifies FLT1 signalling and VEGF-A availability, whereas membrane and soluble FLT1 influence ligand distribution and vascular responses. Experimental evidence supports physiological ligand restraint and the pathogenic effects of excessive sFLT-1; human associations do not invariably establish the initiating placental lesion. Pre-eclampsia, foetal growth restriction and invasive placentation illustrate distinct contexts in which angiogenic regulation may become maladaptive. The maternal sFLT-1/PlGF ratio is therefore interpreted as a circulating indicator of placental vascular stress rather than a direct measurement of local signalling.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant Transcription-Factor Expression and Regulatory microRNAs in Metastatic Breast Cancer.","authors":"Eman Hillal Althubaiti","doi":"10.3390/cells15191815","DOIUrl":"10.3390/cells15191815","url":null,"abstract":"<p><p>Metastatic breast cancer is driven by reversible cell-state programs shaped by transcription factors (TFs) and microRNAs (miRNAs). Dysregulated TFs integrate oncogenic signaling, hypoxia, inflammation, lineage identity, mechanical cues, and chromatin state, whereas miRNAs buffer or reinforce these programs through post-transcriptional repression. Their reciprocal interactions form dynamic regulatory circuits controlling epithelial-mesenchymal plasticity, stem-like behavior, invasion, dissemination, dormancy, organ-specific colonization, immune escape, and treatment resistance. This narrative review examines major TF-miRNA modules implicated in breast cancer metastasis, including ZEB1/2-miR-200/miR-205, TWIST1-miR-10b, MYC-miR-9, FRA-1-miR-34, FOXM1-miR-671-5p, HIF-1α-miR-18a, mutant p53/HIF-1α-miR-30d, STAT3-miR-21/miR-34a, and the context-dependent FOXP3-miR-200c/miR-141 network. Evidence from experimental models, paired primary-metastatic tissues, circulating tumor cells, extracellular vesicles, and plasma cohorts is integrated with emphasis on disease stage, molecular subtype, and biological compartment. Tissue and circulating miRNA signals are not interchangeable, and FOXP3-miR-200c relationships appear compartment- and model-dependent. Clinical translation remains limited by tumor heterogeneity, pre-analytical variability, incomplete cellular resolution, and limited causal validation. Prospective, subtype-stratified studies integrating spatial, single-cell, metastatic-tissue, and standardized liquid-biopsy analyses are required before TF-miRNA signatures can guide clinical management.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Insights into the Biochemistry of Citrate and Its Transporters: Relevance to Metabolic Rewiring, Tumor Microenvironment, and Bone Metastasis in Cancer.","authors":"Vadivel Ganapathy, Sathish Sivaprakasam, Yangzom D Bhutia, Puttur D Prasad, Muthusamy Thangaraju","doi":"10.3390/cells15191811","DOIUrl":"10.3390/cells15191811","url":null,"abstract":"<p><p>Citrate intersects multiple biochemical pathways, yet its role in cancer has received limited attention. Similarly, the Na⁺-coupled citrate transporter (SLC13A5) has been investigated extensively in connection with epileptic encephalopathy, but its relevance to cancer remains understudied. This review focuses on novel insights into citrate biology and SLC13A5 that suggest a tumor-promoting role for SLC13A5/citrate. Cytosolic citrate is the building block for fatty acid and cholesterol synthesis necessary for membrane biogenesis and serves as a signaling molecule in regulating mitophagy and proteostasis in the endoplasmic reticulum. Cytosolic citrate pools derived from SLC13A5-mediated uptake across the plasma membrane and SLC25A1-mediated export from mitochondria have distinct functions. Citrate inhibits asparaginyl hydroxylase and thus potentiates transcription via hypoxia-inducible factors, consequently enhancing lactatogenic aerobic glycolysis and glutaminolysis in cancer cells. Citrate chelates iron and zinc; hence, cancer cells may be protected from ferroptosis and subjected to metabolic alterations by citrate. Human SLC13A5 is coupled to Na⁺ and H⁺, a feature that accelerates the delivery of extracellular citrate into cancer cells in the acidic tumor microenvironment (TME). SLC13A5 is also expressed in intracellular vesicles where it sequesters cytoplasmic citrate, thereby relieving citrate-mediated inhibition of glycolysis. Because the bone matrix is rich in citrate, osteolytic bone metastasis may increase citrate levels in the TME, providing a citrate-rich niche that facilitates cancer cell growth, metabolic reprogramming, and resistance to ferroptosis. Collectively, this review highlights novel biological aspects of citrate and SLC13A5 as they relate to tumor growth and bone metastasis and identifies SLC13A5 as a potential therapeutic target in cancer.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes and Extracellular Vesicles in Oncology: Next-Generation Smart Nanocarriers for Precision Cancer Therapy.","authors":"Mohd Masih Uzzaman Khan, Masood Alam Khan, Mohd Azam, Muhammad Afzal, Tariq G Alsahli","doi":"10.3390/cells15191812","DOIUrl":"10.3390/cells15191812","url":null,"abstract":"<p><p>Exosomes are an evolved sub-type of extracellular vesicles (EVs) that have gained popularity in recent years as a novel biological nanocarrier system for targeted precision therapy in cancer owing to their excellent biocompatibility, low immunogenicity, and high stability. While other artificial systems can only deliver specific types of drug, exosomes have been found to effectively carry different types of therapeutic cargo, such as chemotherapeutic agents, proteins, peptides, mRNA, siRNA, miRNA, and even CRISPR/Cas gene editing elements. Recent progress in exosome engineering technologies, such as surface modification, donor cell modification, bionic hybrid vesicles, and stimuli-responsive exosomes, has improved their targeting efficacy, cargo-loading capacity, and controlled drug release properties. Apart from their therapeutic use, exosomes play an active role in promoting tumor development by regulating the tumor microenvironment, angiogenesis, metastasis, immune escape, maintenance of cancer stem cells, and drug resistance. This review provides a brief insight into the biological properties of exosomes, recent developments in isolation and characterization methods, engineering approaches, therapeutic cargo loading, and their uses in targeted chemotherapy, gene and RNA therapy, immunotherapy, phototherapy, sonodynamic therapy, chemo-dynamic therapy, and combinational therapy. Moreover, the existing issues in exosome research, such as exosome heterogeneity, large-scale production, quality control, and regulatory issues, are addressed. Finally, new approaches involving artificial intelligence, multi-omics technology, and personalized engineering of exosomes are presented as potential solutions to enhance the clinical use of exosomes.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatiotemporal Redox Regulation of Cell-Cycle Progression: Dynamic Functions of Cellular Redox Regulatory Proteins.","authors":"Raghavendra S Patwardhan, Shruti Morjaria, Gargi Nandi, Syed Hasan, Santosh K Sandur","doi":"10.3390/cells15191814","DOIUrl":"10.3390/cells15191814","url":null,"abstract":"<p><p>Aerobic life revolves around the enigmatic role of oxygen, which sustains the life cycle by supporting energy production while simultaneously threatening its existence through the generation of reactive oxygen species (ROS). Intriguingly, ROS are not merely by-products of energy generation; cells actively invest in their production through dedicated pro-oxidant systems. A long-standing perception in the scientific community has been that cellular antioxidant systems primarily evolved as terminators of ROS to protect against oxidative damage. It appears paradoxical, however, that the complex, multilayered antioxidant defense built by cells may actually relay, propagate, and buffer ROS in a spatiotemporal manner rather than simply scavenge them. Perpetuation of life essentially depends upon the cell cycle, one of the most orderly and tightly regulated cellular events. While several elegant reviews have highlighted that cell-cycle regulatory proteins are subject to redox modifications and that changes in cellular redox state influence cell-cycle fate, the converse relationship has received relatively less attention. Proteins regulating cellular antioxidant defense themselves undergo cell-cycle phase-specific changes in their abundance, activity, and localization. There therefore appears to be a coordinated and integrated redox network operating during cell-cycle progression. Here, we examine this relationship from a protein-centric perspective, focusing on MnSOD/H₂O₂, peroxiredoxins, Nrf2, HO-1, NQO1, glutathione, glutathione peroxidases, glutaredoxins, and the thioredoxin/thioredoxin reductase system. Although these systems have often been studied independently, their functions overlap and change as cells move through G1, S, G2, and mitosis. We propose that cell-cycle progression should be viewed as a dynamically regulated redox process in which spatiotemporally organized oxidative signals provide an additional regulatory layer operating alongside the classical cell-cycle machinery.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}