Yang Liu, Huihui Huang, Chi Sun, Wenhan Jia, Xuxiu Zhuang, Jia Zheng, Le Jiang, Yanan Ma, Bing Song, Joel Gittelsohn, Deliang Wen
{"title":"Skin carotenoids indicate diet, serum carotenoids, and inflammation across obesity and metabolic status in children.","authors":"Yang Liu, Huihui Huang, Chi Sun, Wenhan Jia, Xuxiu Zhuang, Jia Zheng, Le Jiang, Yanan Ma, Bing Song, Joel Gittelsohn, Deliang Wen","doi":"10.1186/s12986-026-01075-7","DOIUrl":"10.1186/s12986-026-01075-7","url":null,"abstract":"<p><p>OBJECTIVES: To validate reflection spectroscopy (RS)-based skin carotenoids (SCS) as non-invasive biomarkers of fruit and vegetable intake (FVI) in children and adolescents with obesity and metabolic dysfunction. METHODS: This case-control study (China, 2023) included 210 children and adolescents aged 7–17 years, categorized into five groups: healthy weight (n = 30), overweight (n = 23), obesity (n = 25), obesity with one metabolic disorder (n = 56), and obesity with two or more metabolic disorders (n = 76). SCS levels were measured using RS, FVI was assessed via a food frequency questionnaire, serum carotenoids were quantified by high-performance liquid chromatography, and inflammatory markers were analyzed using flow cytometry. RESULTS: SCS and serum carotenoid levels decreased significantly across groups (p for trend < 0.001). SCS correlated strongly with serum carotenoids, except for lycopene, with the strongest association observed in children and adolescents with obesity and two or more metabolic disorders. A quartile increase in FVI resulted in an 11.92–45.98 unit increase in SCS, partially mediated by total serum carotenoids, beta-carotene, and beta-cryptoxanthin. SCS also inversely correlated with inflammation in metabolically disordered groups. CONCLUSIONS: RS-based SCS is a valid, non-invasive biomarker of FVI, closely related to serum carotenoids and inflammatory status, and effectively distinguishes metabolic dysfunction in children and adolescents. </p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13032390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mehrdad Hashemi, Katayoun Heshmatzad, Ghazaleh Shahsavan, Vahid Tavakolpour, Sara Komeilie Esfahani, Pardis Karimi, Naghmeh Beikzadeh, Saba Mashhadikhan, Sevda Nasirzade, Ali Vasheghani Farahani, Neda Zali, William C Cho, Afshin Taheriazam, Ehsan Maghrebi-Ghojogh, Mina Alimohammadi, Payman Rahimzadeh, Kiavash Hushmandi, Maliheh Entezari
{"title":"Natural bioactive molecules and chemotherapeutics synergism for enhanced cancer therapy.","authors":"Mehrdad Hashemi, Katayoun Heshmatzad, Ghazaleh Shahsavan, Vahid Tavakolpour, Sara Komeilie Esfahani, Pardis Karimi, Naghmeh Beikzadeh, Saba Mashhadikhan, Sevda Nasirzade, Ali Vasheghani Farahani, Neda Zali, William C Cho, Afshin Taheriazam, Ehsan Maghrebi-Ghojogh, Mina Alimohammadi, Payman Rahimzadeh, Kiavash Hushmandi, Maliheh Entezari","doi":"10.1186/s12986-026-01094-4","DOIUrl":"10.1186/s12986-026-01094-4","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy remains a foundation of cancer care but is limited by multidrug resistance, systemic toxicities, and suboptimal selectivity, prompting interest in adjunctive strategies that improve efficacy and tolerability without adding significant burden to patients or healthcare systems.</p><p><strong>Aims/objectives: </strong>This review highlights evidence on natural bioactive compounds, including polyphenols, alkaloids, terpenoids, and fungal metabolites, as adjuvants to standard chemotherapeutics, with objectives to: first, delineate mechanisms by which these agents enhance cytotoxic efficacy and overcome resistance; second, summarize preclinical and clinical combination data; and third, evaluate their potential to mitigate chemotherapy-induced organ toxicities through pathway modulation.</p><p><strong>Results: </strong>Natural bioactives modulate key oncogenic and stress-response pathways, such as NF-κB, PI3K/AKT/mTOR, and NRF2/HO-1, thereby sensitizing tumors to chemotherapy, attenuating pro-survival signaling, and enhancing apoptosis while reducing inflammatory and oxidative injury in normal tissues. Exemplary combinations, including curcumin with 5‑fluorouracil and resveratrol with cisplatin, have demonstrated improved antitumor activity and reduced toxicity in preclinical models, with early clinical observations supporting feasibility and safety in selected settings. Additionally, several compounds exhibit organ-protective effects against cardiotoxicity, nephrotoxicity, neurotoxicity, and gastrointestinal injury induced by chemotherapy, suggesting dual benefits on efficacy and tolerability profiles.</p><p><strong>Conclusions: </strong>Integrating natural bioactives with conventional chemotherapy represents a promising strategy to enhance therapeutic index by concurrently amplifying antitumor mechanisms and mitigating dose‑limiting toxicities, though broader clinical validation and standardized quality controls are needed for routine adoption.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13023180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between estimated glucose disposal rate and cardiovascular mortality in postmenopausal women: a national cohort study.","authors":"Wenguang Lai, Louyi Xiao, Jinning He, Zhidong Huang, Junhao He, Wenjun Gu","doi":"10.1186/s12986-026-01096-2","DOIUrl":"10.1186/s12986-026-01096-2","url":null,"abstract":"<p><p>BACKGROUND: The association between estimated glucose disposal rate (eGDR) and cardiovascular mortality in postmenopausal women remains unclear. METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2018. Participants were stratified by eGDR levels (< 4, 4–6, 6–8, and ≥ 8 mg/kg/min). Survey-weighted Cox proportional hazards models estimated risks of cardiovascular mortality and all-cause mortality, and logistic regression was used to evaluate the risk of having a 10-year predicted cardiovascular disease (CVD) risk ≥ 20%. RESULTS: The study enrolled 7,788 postmenopausal women with a mean age of 60.5 years. During a median follow-up of 9.1 (IQR: 4.8–14.3) years, 414 cardiovascular deaths occurred (3.9%). Compared with the reference group (eGDR < 4 mg/kg/min), multivariable-adjusted hazard ratios (95% CIs) for cardiovascular mortality were 0.37 (0.20–0.67), 0.29 (0.12–0.67), and 0.29 (0.12–0.72) for eGDR categories of 4–6, 6–8, and ≥ 8 mg/kg/min, respectively. A negative linear dose-response relationship was observed. Similar inverse associations were found for all-cause mortality and for having a predicted 10-year CVD risk ≥ 20%, with lower eGDR consistently predicting worse outcomes. CONCLUSION: Lower eGDR, reflecting higher insulin resistance, was independently associated with increased cardiovascular mortality risk among postmenopausal women. These findings support the potential utility of eGDR as a practical biomarker for early cardiovascular mortality risk stratification. </p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13032457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Obesity is the culprit behind fatty acid-induced inflammation.","authors":"Yahui Guo, Haodi Luan, Jing Lin","doi":"10.1186/s12986-026-01076-6","DOIUrl":"10.1186/s12986-026-01076-6","url":null,"abstract":"<p><p>The global prevalence of obesity has emerged as one of the most severe public health challenges of the 21st century. Research conducted over the past decade has fundamentally transformed our understanding of the pathological essence of obesity. Rather than being viewed as a static state of energy accumulation, it is now regarded as a driver of chronic low-grade inflammation. Within this inflammatory process, the composition of dietary fatty acids and metabolic dysregulation plays central roles. The considerable imbalance in the omega-6/omega-3 polyunsaturated fatty acid ratio within contemporary dietary structures, in conjunction with elevated saturated fatty acid intake, collectively establishes the metabolic foundation of the inflammatory microenvironment. This paper provides a systematic review of recent research advances, revealing how obesity reshapes the fatty acid metabolism profile, activates multi-organ inflammatory networks, and ultimately forms a vicious cycle of “obesity-fatty acids-inflammation.” This field has seen breakthrough discoveries ranging from gut microbiota-host interactions to immune cell metabolic reprogramming and from adipose tissue endocrine dysfunction to neuroinflammation. These discoveries have not only deepened our understanding of the mechanisms underlying obesity-related complications but also provided novel perspectives for developing precision anti-inflammatory strategies targeting fatty acid metabolism.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hadi Nobari, Nazila Parnian-Khajehdizaj, Kelly Johnson, Juan José Ramos-Álvarez
{"title":"Ashwagandha (Withania Somnifera): a comprehensive narrative review of its role in enhancing physical performance and health.","authors":"Hadi Nobari, Nazila Parnian-Khajehdizaj, Kelly Johnson, Juan José Ramos-Álvarez","doi":"10.1186/s12986-026-01093-5","DOIUrl":"10.1186/s12986-026-01093-5","url":null,"abstract":"<p><p>Ashwagandha (Withania somnifera), commonly known as Indian ginseng or winter cherry, is a prominent adaptogenic herb recognized for its profound impact on physical performance and health. As an adaptogen, Ashwagandha stands out for its unique ability to restore system functions to normal, enhance the body’s resilience to stress, and elevate overall performance. This comprehensive narrative Review underscores the diverse health benefits of Ashwagandha, emphasizing its roles in immunomodulation, stress reduction, antioxidant effects, cardioprotection, anti-inflammatory, anti-tumor, and anti-cancer activities, neuroprotection, memory enhancement, cognitive function, physical performance, and sexual health improvement effects. With a rich phytochemical profile, including alkaloids and withanolides like Withaferin A, Ashwagandha showcases efficacy in mitigating stress-related markers, improving sleep quality, and regulating mitochondrial function. In addition to its anticancer potential against various types of cancer, Ashwagandha improves lipid profile and protects the heart from necrosis. Also, Ashwagandha has physical performance benefits, which indicate its potential to increase muscle strength, facilitate muscle regeneration, and improve cardiorespiratory endurance. This narrative review delves into the most recent findings and provides a comprehensive overview of the current understanding of Ashwagandha’s potential uses and effects on physical performance and health.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13032348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146227766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hong Yang, Yunda Huang, Guihua Jiang, Hang Guo, Zhiping Duan
{"title":"Middle-aged and older populations with different subtypes and definitions of metabolic syndrome face different future cardiovascular disease risks: results from a comparison of two Chinese definitions.","authors":"Hong Yang, Yunda Huang, Guihua Jiang, Hang Guo, Zhiping Duan","doi":"10.1186/s12986-026-01095-3","DOIUrl":"10.1186/s12986-026-01095-3","url":null,"abstract":"<p><p>BACKGROUND: Differences in the association between metabolic syndrome (MetS) and cardiovascular disease (CVD) across definitions and subtypes are unknown. The aim of this study was to investigate the differences between the associations of MetS defined by the Chinese Diabetes Society (CDS) and the Writing Group of 2024 Chinese Guidelines for the Management of Hypertension (WCGH) with CVD. METHODS: This cohort study included participants aged ≥ 40 years without cardiovascular disease from the 2011 survey of the China Health and Retirement Longitudinal Study. Individuals meeting different definitions of MetS based on criteria from the CDS and the WCGH were identified and followed up until 2020. Cox proportional risk models were used to analyze the association between different definitions and subtypes of MetS with CVD, and the predictive performance of the models was compared using the area under the curve (AUC) of the time-dependent receiver operating characteristic curve, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). RESULTS: Both CDS and WCGH based MetS were significantly associated with increased CVD risk, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.51 (1.38 ~ 1.66) and 1.81 (1.66 ~ 1.99), respectively, both P < 0.001. 7 of the 16 subtypes of MetS based on CDS were not associated with CVD; all 5 subtypes of MetS based on WCGH were significantly associated with an increased risk of CVD. When participants were grouped based on meeting two definitions, compared with the CDS-WCGH- group, CVD risk increased most significantly in the CDS-WCGH + group (HR and 95%CI: 2.57 [1.94 ~ 3.39], P < 0.001), showed a significant increase in the CDS + WCGH + group (HR and 95%CI: 1.66 [1.51 ~ 1.83], P < 0.001), and showed no significant increase in the CDS + WCGH- group (HR and 95%CI: 0.93 [0.7 ~ 1.23], P = 0.606). The AUC of WCGH was higher than that of CDS at all time points. IDI and NRI analyses showed that the WCGH standard demonstrated significant improvements in risk reclassification and identification compared to CDS. CONCLUSIONS: The association between MetS and CVD depends on the definition criteria and specific component combinations employed. The WCGH definition, which integrates diagnostic criteria for dyslipidemia, has been demonstrated to be more robust than the CDS. </p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Serum 25(OH)D concentration and risk of all-cause and cause-specific mortality in patients with chronic kidney disease: systematic review and dose-response meta-analysis of observational cohort studies.","authors":"Sonya Karimi Hacheso, Sina Naghshi, Sevil Kiani, Halimeh Amirazad, Naimeh Mesri Alamdari, Nazila Farrin, Neda Lotfi Yagin, Amir Bahrami, Helda Tutunchi, Farzad Najafipour","doi":"10.1186/s12986-026-01089-1","DOIUrl":"10.1186/s12986-026-01089-1","url":null,"abstract":"<p><p>BACKGROUND: To summarize the evidence on the associations between 25-hydroxyvitamin D (25(OH)D) and risk of mortality in patients with chronic kidney disease (CKD). METHODS: A comprehensive search of PubMed, Scopus, Web of Science, and Google Scholar for relevant papers published up to November 2025 that assessed the association between serum vitamin D levels and the risk of all-cause, cardiovascular disease (CVD), non-CVD, and cancer mortality was conducted. The lowest-versus-highest analysis and the linear and non-linear dose-response analyses were performed using a random-effects model. RESULTS: Overall, 36 publications (35 studies) with a total sample size of 129,135 participants, aged between 18 and 90 years, were included in the current meta-analysis. During the follow-up periods ranging between 3 months and 18 years, 117,403 cases of all-cause mortality, 2,568 cases of CVD mortality, 886 cases of non-CVD mortality, and 289 cases of cancer mortality were identified. The summary relative risk (RR) and 95% confidence intervals (CIs) comparing lowest versus highest levels of 25(OH)D was 1.61 (95% CI: 1.41–1.84, I2 = 89%, n = 28 studies, very low certainty) for all-cause mortality, 1.68 (95% CI: 1.41-2.00, I2 = 20%, n = 9, very low certainty) for CVD mortality, 1.33 (95% CI: 0.94–1.89, I2 = 26%, n = 3, very low certainty) for non-CVD mortality, and 1.51 (95% CI: 1.09–2.09, I2 = 26%, n = 1, very low certainty) for cancer mortality. There was evidence of non-linearity in the analysis of all-cause and CVD mortality, with a greater reduction in risk from serum levels of 12.5 nmol/L up to 60 nmol/L compared to higher levels, but with slight further reductions in risk with serum levels up to 110 nmol/L. CONCLUSIONS: This meta-analysis provides further evidence that lower levels of 25(OH)D are associated with a higher risk of all-cause, CVD, and cancer mortality in CKD patients. However, all outcomes were graded as very low certainty, and the observed associations may be influenced by confounding, small-study effects, and wide prediction intervals that include the null. Observed low-risk range around ~ 60 nmol/L in the non-linear dose-response analyses, should be interpreted cautiously and requires validation in randomized controlled trials. REGISTRATION: The protocol for this review was registered in PROSPERO (2025 CRD42025105350). </p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Causal relationship between obesity, leptin, and brain structure and functional connectivity: evidence based on bidirectional and mediation mendelian randomisation analyses.","authors":"Yue Wu, Fuyuan Deng, Man Bai, Guangpeng Zhang, Ziyuan Li, Mengmeng Wen, Jing Zhang, Runhua Li, Yanmin Shi, Liming Lu, Xinguang Xiao","doi":"10.1186/s12986-026-01081-9","DOIUrl":"10.1186/s12986-026-01081-9","url":null,"abstract":"<p><p>This study used Mendelian randomisation (MR) to explore the putative causal relationship between obesity, leptin, brain alternations represented by magnetic resonance imaging (MRI) phenotypes, and Mediation MR to confirm the mediating role of leptin in obesity and brain changes. The fusiform surface area (SA) (pFDR = 0.005), the bankssts SA (pFDR = 0.022), and the second principal components for fractional anisotropy (FA PC) in posterior thalamic radiation (pFDR = 0.042) had negative causal effects on obesity. Obesity risk had negative causal effects on the first FA PC in superior frontal-occipital fasciculus (pFDR = 0.020) and mean fractional anisotropy (FA) of superior frontal-occipital fasciculus (pFDR = 0.020). Leptin content was positively associated with the risk of obesity (pFDR = 0.020). The inferior parietal SA was negatively correlated with leptin content (p = 0.022). Leptin may serve as a potential mediator of obesity-induced shrinkage of the inferior parietal SA (95% CI = -0.012 to 1.111; p = 0.049). This study supports the potential bidirectional causal relationship between obesity and several aspects of brain macro- and microstructure and functional connectivity (FC), and leptin may be involved in the causal pathway from obesity to brain alterations.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chaolan Wang, Ke Lin, Hong Zhang, Tianbao Liu, Zhen Zeng, Wanpei Luo, Yan Jiang, Xiang Zhang, Shuang Du
{"title":"Sex-specific in the nonlinear associations of hemoglobin glycation index and all-cause mortality in the general US adult population: results from NHANES 1999-2018.","authors":"Chaolan Wang, Ke Lin, Hong Zhang, Tianbao Liu, Zhen Zeng, Wanpei Luo, Yan Jiang, Xiang Zhang, Shuang Du","doi":"10.1186/s12986-026-01088-2","DOIUrl":"10.1186/s12986-026-01088-2","url":null,"abstract":"<p><strong>Background: </strong>The hemoglobin glycation index (HGI) and its association with mortality risk in the United States adults remain insufficiently understood. This research explores potential links between HGI levels and all-cause mortality using nationally representative data.</p><p><strong>Methods: </strong>>The relationship between HGI and mortality was investigated using data from National Health and Nutrition Examination Survey (NHANES) (1999-2018) covering 19,287 U.S. adults. HGI was calculated via linear regression of glycated hemoglobin A1c (HbA1c) on fasting plasma glucose (FPG). The National Death Index was utilized to link mortality outcomes, with tracking continuing through December 31, 2019. To explore sex-specific associations, we utilized weighted Cox regression models with multivariable adjustments, along with restricted cubic splines and segmented Cox analyses. Robustness was confirmed through stratified analyses and sensitivity tests.</p><p><strong>Results: </strong>In U.S. males, HGI showed a U-shaped association with mortality (threshold: -0.131). Below this, lower HGI was protective (hazard ratio (HR) 0.52; 95% confidence interval (CI) 0.42-0.66); above it, higher HGI increased risk (HR 1.34; 95% CI 1.16-1.55). In females, an L-shaped pattern emerged, where higher HGI below the threshold correlated with a decreased likelihood of mortality (HR 0.48; 95% CI 0.40-0.59). These sex-specific associations were verified through stratified and sensitivity analyses.</p><p><strong>Conclusions: </strong>The cohort study observed a U-shaped pattern between HGI and all-cause mortality in U.S. males, whereas an L-shaped association was found in females. These sex-specific patterns warrant further investigation to explore clinical implications.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12977440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianing Xu, Liang Huo, Jiatong Liu, Wei Xu, Tao Yu
{"title":"Ketogenic diet can inhibit epileptic seizures by inhibiting RGMa methylation to promote GluA1 palmitoylation in the epileptic rat model.","authors":"Jianing Xu, Liang Huo, Jiatong Liu, Wei Xu, Tao Yu","doi":"10.1186/s12986-026-01090-8","DOIUrl":"10.1186/s12986-026-01090-8","url":null,"abstract":"<p><p>BACKGROUND: This study investigated the relationship between the ketogenic diet, RGMa methylation, and GluA1 palmitoylation in a rat model of epilepsy, aiming to identify a novel mechanism for treating refractory epilepsy with the ketogenic diet. METHODS: Epileptic rats were treated with a ketogenic diet. Hippocampal tissue was analyzed to assess the expression of DNMT1 and DNMT3a proteins, RGMa DNA methylation and protein expression, FAK and zDHHC3 phosphorylation and expression, and GluA1 palmitoylation and expression. The therapeutic effects of the ketogenic diet on seizure frequency were statistically analyzed, along with the correlation between each parameter and treatment outcomes. RESULTS: The ketogenic diet treatment reduced seizure frequency in the epileptic rats. It inhibited RGMa DNA methylation in hippocampal tissue while increasing RGMa expression. Additionally, the diet enhanced GluA1 palmitoylation and reduced its expression on the neuronal membrane. These changes were associated with alterations in FAK/Src and zDHHC3 phosphorylation. CONCLUSION: The ketogenic diet inhibits RGMa DNA methylation, upregulates RGMa expression, and promotes GluA1 palmitoylation, leading to a reduction in seizure frequency and alleviation of refractory epilepsy in the rat model. These effects may be mediated through the RGMa-FAK/Src-zDHHC3 signaling axis. </p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":" ","pages":"30"},"PeriodicalIF":3.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12922386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}