Metabolites最新文献

{"title":"Association of Shift Work and Serum Vitamin D Levels with Excessive Daytime Sleepiness, Anxiety Symptoms, and Depressive Symptoms in Female Nurses.","authors":"İbrahim Safa Karcı, Kamile Marakoğlu, Fatma Hümeyra Yerlikaya, Zeynep Ebru Şener","doi":"10.3390/metabo16100786","DOIUrl":"10.3390/metabo16100786","url":null,"abstract":"<p><strong>Background/objectives: </strong>This study evaluated the associations of shift work with serum vitamin D levels, excessive daytime sleepiness (EDS), and symptoms of anxiety and depression among female nurses working at a university hospital.</p><p><strong>Methods: </strong>This was an analytical cross-sectional study. Sociodemographic and occupational characteristics were collected via a structured questionnaire. EDS was assessed using the Epworth Sleepiness Scale (ESS), and symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Serum 25-hydroxyvitamin D [25(OH)D] levels were measured by electrochemiluminescence (Elecsys Vitamin D total II, cobas e 801). Deficiency was defined as <20 ng/mL.</p><p><strong>Results: </strong>Mean age was 32.4 ± 6.8 years; 44.9% worked night shifts. Mean 25(OH)D level was 13.16 ± 7.87 ng/mL, with deficiency in 84.3% and insufficiency in 13.5%. EDS was present in 30.8%, anxiety symptoms in 26.9%, and depressive symptoms in 46.2%. Vitamin D levels were lower in night-shift nurses, though not significantly (<i>p</i> = 0.056). In univariable logistic regression analysis, night-shift work was associated with vitamin D deficiency (OR = 2.053; 95% CI: 1.068-3.948; <i>p</i> = 0.031), but this association was not significant after adjustment (aOR = 1.136; 95% CI: 0.541-2.389; <i>p</i> = 0.736). EDS was associated with anxiety symptoms (aOR = 2.795; 95% CI: 1.553-5.031; <i>p</i> = 0.001) and depressive symptoms (aOR = 1.887; 95% CI: 1.077-3.306; <i>p</i> = 0.027). Anxiety and depressive symptoms were associated with each other (aOR = 7.332 and 7.285; <i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>A high prevalence of vitamin D deficiency, EDS, anxiety symptoms and depressive symptoms was observed among female nurses. Vitamin D status was not significantly associated with EDS, anxiety symptoms, or depressive symptoms, whereas EDS was associated with both anxiety and depressive symptoms.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13707079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270079","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":"Dietary Macronutrient Composition Is Associated with Distinct Hepatic Phenotypes During Post-Weaning Growth: An Integrated Biochemical, Histological, Immunohistochemical and Ultrastructural Study.","authors":"Emrah Zayman, Elif Kayhan, Mehmet Erman Erdemli, Zeynep Erdemli, Feyza İnceoğlu, Mehmet Gül","doi":"10.3390/metabo16100781","DOIUrl":"10.3390/metabo16100781","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The aim of this study was to compare the biochemical, histological, immunohistochemical and ultrastructural hepatic phenotypes associated with carbohydrate-, fat- and protein-enriched diets initiated during post-weaning growth. <b>Methods:</b> Forty 21-day-old male Wistar albino rats were divided into four groups: a control group and three experimental groups (carbohydrate, protein, and fat). The respective diets were fed for 13 weeks. Hepatic oxidant-antioxidant parameters, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), histopathological scores; interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) immunoreactivity and transmission electron microscopy (TEM) findings were evaluated. <b>Results:</b> The carbohydrate group showed higher thiobarbituric acid-reactive substances (TBARS), total oxidant status (TOS) and oxidative stress index (OSI), together with lower reduced glutathione (GSH) and total antioxidant status (TAS). Histology showed hydropic change, vacuolization and inflammatory cell infiltration, while TEM showed mitochondrial swelling, loss of cristae and nuclear alterations. The fat group showed prominent vacuolization, TEM-observed lipid droplets, inflammatory cell infiltration and TNF-α immunoreactivity. Most findings in the protein group were closer to control values. Thus, the carbohydrate-enriched diet was associated with the most pronounced redox and ultrastructural injury profile, whereas the fat-enriched diet was associated with a morphological and inflammatory injury profile compatible with lipid accumulation. <b>Conclusions:</b> These findings identify distinct hepatic phenotypes associated with the dietary formulations administered during post-weaning growth. The carbohydrate- and fat-enriched formulations were associated with more pronounced biochemical and morphological changes; inference is made at the level of the complete dietary formulation.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13707318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149269995","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":"Metabolomics in Early-Phase Clinical Trials from 2010 to 2025.","authors":"Jack T Thompson, Maia Megase, Marta Boffito, Mark J Caulfield, Emma F Magavern","doi":"10.3390/metabo16100777","DOIUrl":"10.3390/metabo16100777","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Metabolomics has the potential to enhance the definition of medication response phenotypes in early-phase clinical trials, yet global uptake and distribution are not well characterised. This study provides an international assessment of metabolomics integration in registered early-phase clinical trials. <b>Methods</b>: Data were obtained from the World Health Organization's International Clinical Trials Registry Platform (ICTRP). Early-phase trials (phase 0-II) conducted from 2010 to 2025 were analysed, and metabolomics studies were identified using predefined keyword searches across trial records. <b>Results</b>: A total of 183,041 early-phase trials were identified, of which 640 (0.35%) incorporated metabolomics. Uptake has increased modestly over time but remains low overall and is concentrated predominantly in high-income countries. The United Kingdom demonstrated the highest proportional integration (1.3%), while the People's Republic of China (<i>n</i> = 237) and the United States of America (<i>n</i> = 90) contributed the greatest absolute number of trials with metabolomics. Among the included metabolomic studies: 187 (29.2%) were phase 0, 229 (35.8%) were phase I trials, 183 (28.6%) were phase II, and 41 (6.4%) were combined phase I/II studies. Metabolomics was most commonly included as a secondary, rather than primary outcome (49.7% vs. 25.3%). <b>Conclusions</b>: Metabolomics remains underutilised in early-phase clinical trials. Addressing barriers to implementation will be critical to enable broader integration of metabolomics into early-phase clinical trials and to integrate a multi-omic approach to precision medicine.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13707337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270129","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":"From Itch to Injury: An Emerging Link Between Allergic Conjunctivitis, Eye Rubbing and Lid Wiper Epitheliopathy.","authors":"Luke X Chong, Olivia Jagiello, Rinu Thomas, Ereeny Mikhail, Serap Azizoğlu, Moneisha Gokhale","doi":"10.3390/metabo16100779","DOIUrl":"10.3390/metabo16100779","url":null,"abstract":"<p><p>Allergic conjunctivitis (AC) is a common inflammatory ocular surface disease characterised by ocular itch, conjunctival redness, tearing, and frequent eye rubbing. Although the link between AC, eye rubbing and development of keratoconus is well established, the relationship between AC and lid wiper epitheliopathy (LWE) is less understood. Recent studies have identified a potential association between AC and LWE, suggesting that friction-induced damage to the lid wiper region may represent an under-recognised consequence of allergic conjunctivitis. This review synthesises current evidence linking allergic conjunctivitis, eye rubbing, ocular surface friction, and LWE, while highlighting emerging mechanistic insights from multi-omics research. LWE has potential as a novel clinical indicator of AC and may provide additional diagnostic value alongside other established biomarkers.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13706996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270102","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":"The Gut-Vascular Axis as a Therapeutic Hub: Rationale and Evidence for Combined Gut-Directed and Endothelium-Directed Interventions.","authors":"Tianyi Gu, Ruochen Wang, Shengyu Hua","doi":"10.3390/metabo16100780","DOIUrl":"10.3390/metabo16100780","url":null,"abstract":"<p><strong>Background: </strong>The gut-vascular axis linking gut microbiota, intestinal barrier, and vascular endothelium is a key pathophysiological interface in chronic metabolic diseases. Dysbiosis and \"leaky gut\" enable bacterial products and gut-derived metabolites to enter the circulation, driving systemic inflammation and endothelial dysfunction. Single-target interventions show limited efficacy; combined gut-directed and endothelium-directed strategies remain underexplored.</p><p><strong>Methods: </strong>PubMed was searched from database inception to 31 August 2026 using a predefined search strategy combining terms for the gut-vascular axis, intestinal barrier, microbiota/metabolites, endothelial dysfunction, and combined interventions. Preclinical and clinical studies evaluating gut barrier integrity, microbiota modulation, or endothelial protection, alone or in combination, were included. No formal risk-of-bias scoring was performed; study design, sample size, endpoint type, follow-up, and limitations were appraised.</p><p><strong>Results: </strong>(1) The axis comprises three core components: gut barrier, endothelium, and microbial metabolites. (2) Pathological activation involves leaky-gut-driven endotoxemia, dysbiosis-induced metabolic inflammation, and immune crosstalk sustaining vascular inflammation. (3) Animal models demonstrate that combined interventions can reduce atherosclerotic plaque, improve endothelium-dependent relaxation, and lower systemic inflammation to a greater extent than some monotherapies; however, most studies have not directly compared combination therapy with both corresponding monotherapies or performed formal interaction testing, so true synergy remains unproven. (4) Limited clinical studies in metabolic syndrome and heart failure suggest improvements in surrogate endpoints, but large-scale randomised trials with hard cardiovascular endpoints are lacking.</p><p><strong>Conclusions: </strong>The gut-vascular axis is a promising therapeutic framework for cardiometabolic diseases, with a strong biological rationale. Combined gut- and endothelium-directed interventions offer a rational multi-target approach, but direct evidence that they provide superior clinical outcomes remains limited. Future research must prioritise hard-endpoint trials, standardised interventions and endpoints, long-term safety, reproducibility, multi-omics-based patient stratification, and next-generation microbiome therapies.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13706681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270142","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":"Beyond Inflammatory Ratios: Age and CRP as Key Predictors of Re-Amputation in Diabetic Foot Patients.","authors":"Huseyin Bahadir Gokcen, Alp Yekta Gokalp, Sezgin Bahadir Tekin, Gizem Tekin, Onur Mercan, Umut Kahilogullari","doi":"10.3390/metabo16100778","DOIUrl":"10.3390/metabo16100778","url":null,"abstract":"<p><p><b>Background and Objectives:</b> Re-amputation is an important adverse outcome of diabetic foot disease. This study compared age and preoperative inflammatory parameters between patients with and without subsequent re-amputation and examined their adjusted associations with re-amputation group membership. <b>Materials and Methods:</b> The records of 206 patients treated between 2013 and 2024 were reviewed retrospectively, with 103 patients included in each group. Laboratory parameters obtained before the index amputation were analyzed in both groups. Between-group comparisons were performed using the Mann-Whitney U test. Three exploratory binary logistic regression models included age and C-reactive protein (CRP), together with the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), or platelet-to-lymphocyte ratio (PLR). The regression and ROC analyses were based on 197 complete cases. <b>Results:</b> Patients in the re-amputation group were older and had higher WBC, neutrophil, monocyte, CRP, NLR, MLR, and PLR values and lower lymphocyte values. In the primary model, age (adjusted OR = 1.034, 95% CI: 1.010-1.058; <i>p</i> = 0.006) and CRP (adjusted OR = 1.006 per 1 mg/L, 95% CI: 1.003-1.010; <i>p</i> = 0.001) were independently associated with re-amputation group membership, whereas NLR was not (<i>p</i> = 0.834). Neither MLR (<i>p</i> = 0.176) nor PLR (<i>p</i> = 0.446) was independently associated in the alternative models. Individual-marker AUCs ranged from 0.604 to 0.647, indicating limited discrimination. <b>Conclusions:</b> Older age and higher pre-index-amputation CRP levels were independently associated with membership in the re-amputation group. Although NLR, MLR, and PLR differed between groups, these ratios were not independently associated after adjustment for age and CRP. The limited discriminatory performance and data-derived cutoff values require validation in larger, independent cohorts.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13707061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270082","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":"The Glial Coupling in the Developing Brain: Astrocytes, Oligodendrocytes and Myelin Formation.","authors":"Maria Ester Canepa, Chiara Santucci, Daiana Mariano, Sara Mangini, Andrea Calandrino, Luigi Gagliardi, Andrea Petretto, Pasquale Striano, Luca Antonio Ramenghi","doi":"10.3390/metabo16100774","DOIUrl":"10.3390/metabo16100774","url":null,"abstract":"<p><p>Astrocytes and oligodendrocytes contribute to the metabolic, homeostatic and structural organization of the developing brain, yet their interactions evolve across development and remain incompletely characterized during the earliest stages of life. This narrative review examines astrocyte-oligodendrocyte coupling in relation to myelin development and addresses the question of which cellular and metabolic mechanisms support oligodendrocyte maturation and white-matter metabolism before mature astrocytic functions are fully established. Evidence from preterm and ill term neonates is considered together with experimental and adult or elderly studies used exclusively for secondary mechanistic comparison. Astrocytes and oligodendrocytes participate in interconnected metabolic, developmental and homeostatic processes, while perinatal white-matter injury may combine reactive astrogliosis, pre-oligodendrocyte injury and maturation arrest. Neuroimaging, including quantitative susceptibility mapping, synthetic MRI, cranial ultrasound and molecular or myelin-sensitive imaging, provides complementary but indirect information on the structural and maturational consequences of these processes, whereas omics approaches may characterize their molecular environment. Radiomics similarly provides indirect tissue-level biomarkers rather than cell-specific measures of glial biology. Dysglycaemia further illustrates the dependence of developing white matter on coordinated cellular energy handling and the potential relevance of immature astrocyte-oligodendrocyte interactions during metabolic instability. Evidence from very early development suggests that oligodendrocyte maturation occurs within a changing cellular environment in which astroglial maturation, neuronal and vascular processes, and immune and metabolic mechanisms coexist. The Crossword and Foil Effects are proposed as hypothesis-generating frameworks to organize these intersecting developmental, metabolic, cellular, imaging and molecular dimensions rather than as experimentally validated causal models. Overall, no single cellular substitute for mature astrocytic functions is identified; instead, oligodendrocyte maturation appears to emerge within a developmentally changing division of metabolic, homeostatic and signaling labour across astroglial, neuronal, vascular and immune compartments.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13707009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270113","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":"First-Trimester Thyroid-Stimulating Hormone Levels and Gestational Diabetes Mellitus: A Retrospective Cohort Study.","authors":"Büşra Şahin, Tansu Bahar Gürbüz, Fazilet Tatar, Rümeysa Uzun, Melike Özyurt Topuzoğlu, Ramazan Erda Pay, Yaprak Üstün","doi":"10.3390/metabo16100772","DOIUrl":"10.3390/metabo16100772","url":null,"abstract":"<p><p><b>Background:</b> The clinical relevance of a mildly elevated first-trimester thyroid-stimulating hormone (TSH) concentration is uncertain, recent meta-analyses disagree, and few studies have directly contrasted a TSH of 2.5-4.0 mIU/L with a TSH above 4.0 mIU/L. <b>Methods:</b> In this single-centre retrospective cohort study, 218 singleton pregnancies with a first-trimester TSH ≥ 2.5 and ≤10.0 mIU/L and a concurrent free thyroxine (fT4) measurement were classified as high-normal TSH (2.5-4.0 mIU/L; <i>n</i> = 168) or elevated TSH (>4.0-10.0 mIU/L; <i>n</i> = 50; subclinical hypothyroidism in 47 and biochemically overt hypothyroidism in 3). The primary outcome was gestational diabetes mellitus (GDM); secondary outcomes were a composite obstetric complication, individual obstetric and neonatal outcomes, and first- and second-trimester screening markers. Two logistic regression models adjusted for maternal age were fitted; because levothyroxine was started after the index TSH measurement, it was treated as a potential intermediate and examined only in post hoc sensitivity analyses. <b>Results:</b> GDM occurred in 7/50 (14.0%) women with TSH > 4.0 mIU/L versus 6/168 (3.6%) with TSH 2.5-4.0 mIU/L (Fisher's exact test, <i>p</i> = 0.013; unadjusted odds ratio (OR) 4.40, 95% confidence interval (CI) 1.40-13.76; risk difference 10.4 percentage points, 95% CI 0.4-20.4). After adjustment for maternal age, TSH > 4.0 mIU/L remained associated with GDM (adjusted OR 5.24, 95% CI 1.60-17.16; <i>p</i> = 0.006), an estimate based on only 13 events; additional adjustment for levothyroxine use gave a similar estimate (adjusted OR 4.51, 95% CI 1.33-15.22). The composite obstetric complication did not differ (32.0% vs. 20.2%; χ²(1) = 3.02, <i>p</i> = 0.082; adjusted OR 1.95, 95% CI 0.96-3.98), nor did individual obstetric outcomes, neonatal outcomes or screening markers. <b>Conclusions:</b> First-trimester TSH > 4.0 mIU/L was associated with a higher frequency of GDM. Given the few events, the wide confidence interval, unmeasured body-mass index and thyroid-peroxidase-antibody status and the absence of a TSH < 2.5 mIU/L comparison group, the finding is hypothesis-generating and does not establish 4.0 mIU/L as a clinically discriminatory threshold.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13706802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270140","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":"The Multifaceted Roles of Biomarkers in Metabolic Disorders: From Diagnosis and Monitoring to Prediction, Management, and Treatment.","authors":"Prince Dadson, Miikka-Juhani Honka","doi":"10.3390/metabo16100776","DOIUrl":"10.3390/metabo16100776","url":null,"abstract":"<p><p>The rising prevalence of obesity, type 2 diabetes, and cardiovascular disease has made the identification of reliable biomarkers a central priority in metabolic research [...].</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13706853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270121","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":"L-Malate Protects Skin Against Ultraviolet-Induced Ferro-Aging.","authors":"Huanhuan Xu, Chuhui Song, Zhangqi Mao, Wenze Zhang, Hengyu Luo, Xiaoxuan Wu, Yingying Yu, Lili Huang, Liwen Zhang, Zuyong Zhang, Xuexian Fang","doi":"10.3390/metabo16100775","DOIUrl":"10.3390/metabo16100775","url":null,"abstract":"<p><p><b>Background</b>: Chronic exposure to ultraviolet (UV) radiation, particularly UVB, is the primary driver of skin photoaging. Ferro-aging, a recently identified iron-triggered, lipid peroxidation-driven cellular senescence program distinct from acute ferroptotic cell death, has emerged as a critical contributor to age-related pathologies, yet its role in skin photoaging remains largely unexplored. <b>Methods</b>: In this study, we systematically evaluated the anti-photoaging efficacy of L-malate (LM), a naturally occurring organic acid, using both in vitro human skin cell models (HaCaT keratinocytes and HSFs) and an in vivo BALB/c nude mouse model of chronic UV irradiation. <b>Results</b>: Our results demonstrate that LM treatment significantly attenuated UVB-induced cellular senescence, DNA damage, and extracellular matrix remodeling in a dose-dependent manner. Mechanistically, LM may act by increasing the expression of malic enzymes (ME1 and ME2), thereby restoring intracellular NADPH levels and glutathione homeostasis. This metabolic restoration effectively blocks the ferro-aging cascade, as evidenced by suppressed ACSL4 upregulation, the maintenance of GPX4 protein levels, and reduced lipid peroxidation. Importantly, topical application of LM in UV-irradiated mice significantly ameliorated in vivo photoaging phenotypes and suppressed ferro-aging markers. <b>Conclusions</b>: In summary, our findings demonstrate that LM may inhibit ferro-aging through the ME1/ME2-NADPH antioxidant axis. This study reveals the possibility of ferro-aging as a potential novel therapeutic target in skin photoaging and suggests that LM is a promising naturally derived ferro-aging inhibitor with translational potential in anti-aging skincare.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13707215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270052","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}