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Ursodeoxycholic acid alleviates high-fat diet-induced liver injury by modulating gut microbiota-mediated bile acid metabolism: an integrated microbiota-metabolomics analysis.
IF 4 2区 农林科学 Q2 NUTRITION & DIETETICS Pub Date : 2026-01-26 eCollection Date: 2026-01-01 DOI: 10.3389/fnut.2026.1714100
Xueyun Dong, Wen Sun, Hao Xu, Yunhan Xie, Jiayuan He, Xuehui Liu, Xinyu Liu, Asmaa Ali, Min Chen, Leilei Zhang, Liang Wu, Keke Shao

Purpose: Ursodeoxycholic acid (UDCA), a naturally occurring bile acid with established hepatoprotective properties, has garnered attention for its potential role in metabolic health. This study provides scientific validation for these traditional uses by demonstrating UDCA's protective mechanisms against non-alcoholic fatty liver disease (NAFLD) through gut microbiota modulation and metabolic regulation. This study elucidates the therapeutic mechanisms of UDCA against high-fat diet-induced NAFLD through integrated microbiota-metabolomics analysis.

Methods: Using a 12-week murine NAFLD model, oral UDCA (15 mg/kg/day and 30 mg/kg/day) was administered to evaluate its hepatoprotective effects. Hepatic steatosis and injury were assessed via serum ALT/AST levels, lipid profiles, and histopathology. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) quantified bile acid metabolites, while 16S rRNA sequencing analyzed gut microbiota composition. Serum metabolomics and network pharmacology were employed to identify metabolic pathways and mechanistic targets, respectively. Molecular analyses (qPCR/Western blot) assessed PPARγ/Nrf2/NF-κB signaling.

Results: UDCA treatment significantly ameliorated high-fat diet-induced NAFLD, as demonstrated by improved serum ALT/AST levels, attenuated hepatic steatosis, and reduced histopathological damage. UPLC-MS/MS analysis revealed a marked reorganization of bile acid metabolism, characterized by elevated non-12α-hydroxylated bile acids (UDCA, TUDCA) and enhanced alternative synthesis via CYP27A1 upregulation. 16S rRNA sequencing identified UDCA-driven restructuring of the gut microbiota, with specific enrichment of short-chain fatty acid-producing Muribaculum spp. and suppression of pro-inflammatory Prevotella (CAG-485). Serum metabolomics further confirmed these benefits, showing increased eicosapentaenoic acid (anti-inflammatory) and decreased long-chain acylcarnitines (lipid peroxidation markers). At the molecular level, UDCA activated PPARγ/Nrf2 antioxidative signaling while inhibiting NF-κB-mediated inflammation, and network pharmacology analysis identified 225 potential targets (including TNF-α, IL6, and NF-κB) within lipid/atherosclerosis pathways, collectively underscoring UDCA's multimodal protective mechanisms against NAFLD.

Conclusion: These findings validate UDCA's multifaceted hepatoprotection via microbiota-bile acid crosstalk and metabolic-inflammatory modulation. The study provides a mechanistic basis for UDCA's traditional use in hepatobiliary disorders by integrating microbial, metabolic, and molecular evidence.

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引用次数: 0
Guiling prescription attenuates hyperuricemia via multi-target regulation of uric acid metabolism, renal protection, and inflammation: insights from metabolomics and network pharmacology.
IF 4 2区 农林科学 Q2 NUTRITION & DIETETICS Pub Date : 2026-01-26 eCollection Date: 2025-01-01 DOI: 10.3389/fnut.2025.1738623
YuKun Wang, RenJie Ding, Yaxuan Guo, TianHui Zhou, Huichun Zhao, HuiWu Liu, XueMei Qin, XiaoXia Gao

Background: This study aims to evaluate the efficacy of Guiling Prescription (GP)-a medicinal food homologous formula-in hyperuricemic rats, its effects on uric acid excretion and renal function, and to clarify the metabolic mechanisms involved in GP's alleviation of hyperuricemia.

Methods: Sprague-Dawley (SD) rats of hyperuricemia was established using potassium oxonate (200 mg/kg, PO) and adenine (100 mg/kg) to assess the therapeutic effects of Guiling Prescription (GP). We measured body weight, serum levels of uric acid and creatinine, as well as xanthine oxidase (XOD) and adenosine deaminase (ADA) activity, alongside histopathological parameters. Serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined using ELISA kits. The expression of renal uric acid transporters was evaluated through Western blotting. Network pharmacology was utilized to predict the key drug-disease targets, and a non-targeted metabolomic assay was applied to identify the key metabolites and metabolic pathways, and validated these targets through molecular docking and western blot analyses.

Results: GP showed an improvement effect on hyperuricemia model rats, with decreased levels of serum uric acid (UA), serum urea nitrogen, and creatinine, and serum ALT, AST. Furthermore, H&E staining results showed to improve renal injury in the hyperuricemic rat, and serum interleukin-6 and tumor necrosis factor-αwere improve the body's inflammatory response after administration of GP. In addition, GP could regulate multiple serum metabolic pathways such as arachidonic acid metabolism, pyrimidine metabolism, purine metabolism, citric acid cycle. On one side, GP decreased the synthesis of uric acid by inhibiting hepatic xanthine oxidase activities and adenosine deaminase activity. On the other side, GP increased the excretion of uric acid with the upregulation of UA excretion genes ABCG2, OAT1, and OAT3 and downregulation of UA resorption genes URAT1 and GLUT9.

Conclusion: GP orchestrates uric acid metabolism through multi-target and multi-pathway regulation, highlighting its potential not only as a novel therapeutic strategy but also as a promising dietary supplement for the management of hyperuricemia.

{"title":"Guiling prescription attenuates hyperuricemia via multi-target regulation of uric acid metabolism, renal protection, and inflammation: insights from metabolomics and network pharmacology.","authors":"YuKun Wang, RenJie Ding, Yaxuan Guo, TianHui Zhou, Huichun Zhao, HuiWu Liu, XueMei Qin, XiaoXia Gao","doi":"10.3389/fnut.2025.1738623","DOIUrl":"https://doi.org/10.3389/fnut.2025.1738623","url":null,"abstract":"<p><strong>Background: </strong>This study aims to evaluate the efficacy of Guiling Prescription (GP)-a medicinal food homologous formula-in hyperuricemic rats, its effects on uric acid excretion and renal function, and to clarify the metabolic mechanisms involved in GP's alleviation of hyperuricemia.</p><p><strong>Methods: </strong>Sprague-Dawley (SD) rats of hyperuricemia was established using potassium oxonate (200 mg/kg, PO) and adenine (100 mg/kg) to assess the therapeutic effects of Guiling Prescription (GP). We measured body weight, serum levels of uric acid and creatinine, as well as xanthine oxidase (XOD) and adenosine deaminase (ADA) activity, alongside histopathological parameters. Serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined using ELISA kits. The expression of renal uric acid transporters was evaluated through Western blotting. Network pharmacology was utilized to predict the key drug-disease targets, and a non-targeted metabolomic assay was applied to identify the key metabolites and metabolic pathways, and validated these targets through molecular docking and western blot analyses.</p><p><strong>Results: </strong>GP showed an improvement effect on hyperuricemia model rats, with decreased levels of serum uric acid (UA), serum urea nitrogen, and creatinine, and serum ALT, AST. Furthermore, H&E staining results showed to improve renal injury in the hyperuricemic rat, and serum interleukin-6 and tumor necrosis factor-αwere improve the body's inflammatory response after administration of GP. In addition, GP could regulate multiple serum metabolic pathways such as arachidonic acid metabolism, pyrimidine metabolism, purine metabolism, citric acid cycle. On one side, GP decreased the synthesis of uric acid by inhibiting hepatic xanthine oxidase activities and adenosine deaminase activity. On the other side, GP increased the excretion of uric acid with the upregulation of UA excretion genes ABCG2, OAT1, and OAT3 and downregulation of UA resorption genes URAT1 and GLUT9.</p><p><strong>Conclusion: </strong>GP orchestrates uric acid metabolism through multi-target and multi-pathway regulation, highlighting its potential not only as a novel therapeutic strategy but also as a promising dietary supplement for the management of hyperuricemia.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"12 ","pages":"1738623"},"PeriodicalIF":4.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plant-based dietary patterns, micronutrient status and breast cancer outcomes: a joint analysis of UK Biobank and Chinese longitudinal healthy longevity survey.
IF 4 2区 农林科学 Q2 NUTRITION & DIETETICS Pub Date : 2026-01-26 eCollection Date: 2025-01-01 DOI: 10.3389/fnut.2025.1748611
Weizhe Xu, Wen Gu, Yanqiu Huang, Shuli Li, Honglin Liu, Xun Zhu

Background: Plant-based diets may lower breast cancer risk, but their impact on breast cancer-related mortality is unclear. We explored associations of plant-based dietary patterns (Healthful Plant-Based Diet Index [HPDI/PDI]) and micronutrient intake with breast cancer incidence and all-cause mortality in patients.

Methods: Using data of UK Biobank (UKB; 67,045 cancer-free participants; 3,397 breast cancer patients) and Chinese Longitudinal Healthy Longevity Survey (CLHLS), we analyzed dietary scores and micronutrient intake via multivariate Cox regression, restricted cubic splines, and predictive models (concordance index, Random Forest, and time-dependent ROC).

Results: Among 67,045 breast cancer-free participants, the highest HPDI tertile was associated with 11% lower breast cancer risk (HR = 0.89, 95%CI: 0.82-0.98) vs. lowest tertile (4% reduction per SD increase, HR = 0.96, 95%CI: 0.93-1.00). Among 3,397 breast cancer patients, the highest HPDI tertile showed 28% lower mortality (HR = 0.72, 95%CI: 0.55-0.95) vs. lowest (11% reduction per SD, HR = 0.89, 95%CI: 0.79-1.00). Individuals with high PDI scores exhibited a 39% lower risk of cancer compared to those with low scores in CLHLS (HR = 0.61, 95%CI: 0.41-0.92). Higher intakes of vitamins B2 and C, calcium, and magnesium were inversely associated with risk and mortality, while each SD increase in sodium raised mortality risk by 15% (HR = 1.15, 95%CI: 1.01-1.32). Predictive models showed optimal 5-year performance overall; micronutrients alone best predicted breast cancer risk across timepoints, while HPDI peaked for 5-year mortality prediction (AUC = 0.625). The combined model achieved superior 10-year prognosis.

Conclusions: High adherence to a healthful plant-based diet, together with sufficient intake of key micronutrients and reduced sodium consumption, may contribute to breast cancer prevention and improved survival outcomes.

{"title":"Plant-based dietary patterns, micronutrient status and breast cancer outcomes: a joint analysis of UK Biobank and Chinese longitudinal healthy longevity survey.","authors":"Weizhe Xu, Wen Gu, Yanqiu Huang, Shuli Li, Honglin Liu, Xun Zhu","doi":"10.3389/fnut.2025.1748611","DOIUrl":"https://doi.org/10.3389/fnut.2025.1748611","url":null,"abstract":"<p><strong>Background: </strong>Plant-based diets may lower breast cancer risk, but their impact on breast cancer-related mortality is unclear. We explored associations of plant-based dietary patterns (Healthful Plant-Based Diet Index [HPDI/PDI]) and micronutrient intake with breast cancer incidence and all-cause mortality in patients.</p><p><strong>Methods: </strong>Using data of UK Biobank (UKB; 67,045 cancer-free participants; 3,397 breast cancer patients) and Chinese Longitudinal Healthy Longevity Survey (CLHLS), we analyzed dietary scores and micronutrient intake via multivariate Cox regression, restricted cubic splines, and predictive models (concordance index, Random Forest, and time-dependent ROC).</p><p><strong>Results: </strong>Among 67,045 breast cancer-free participants, the highest HPDI tertile was associated with 11% lower breast cancer risk (HR = 0.89, 95%CI: 0.82-0.98) vs. lowest tertile (4% reduction per SD increase, HR = 0.96, 95%CI: 0.93-1.00). Among 3,397 breast cancer patients, the highest HPDI tertile showed 28% lower mortality (HR = 0.72, 95%CI: 0.55-0.95) vs. lowest (11% reduction per SD, HR = 0.89, 95%CI: 0.79-1.00). Individuals with high PDI scores exhibited a 39% lower risk of cancer compared to those with low scores in CLHLS (HR = 0.61, 95%CI: 0.41-0.92). Higher intakes of vitamins B2 and C, calcium, and magnesium were inversely associated with risk and mortality, while each SD increase in sodium raised mortality risk by 15% (HR = 1.15, 95%CI: 1.01-1.32). Predictive models showed optimal 5-year performance overall; micronutrients alone best predicted breast cancer risk across timepoints, while HPDI peaked for 5-year mortality prediction (AUC = 0.625). The combined model achieved superior 10-year prognosis.</p><p><strong>Conclusions: </strong>High adherence to a healthful plant-based diet, together with sufficient intake of key micronutrients and reduced sodium consumption, may contribute to breast cancer prevention and improved survival outcomes.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"12 ","pages":"1748611"},"PeriodicalIF":4.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dietary diversity and its associations with sleep quality and chronotype in young and middle-aged adults.
IF 4 2区 农林科学 Q2 NUTRITION & DIETETICS Pub Date : 2026-01-26 eCollection Date: 2025-01-01 DOI: 10.3389/fnut.2025.1743065
Anda Zhao, Yiting Chen, Zhen Li, Qing Fan, Jiang Wu

Background: While sleep quality and chronotype are critical to wellbeing, the role of dietary diversity remains scarcely investigated, particularly among young and middle-aged adults. This study aimed to examine the associations of dietary diversity with sleep quality and chronotype, and to explore whether depression mediates these relationships.

Methods: Data were derived from the 2024-2025 China Nutrition and Sleep Survey (CNSS), including 4,128 adults aged 20-59 years. Dietary diversity indices, including total dietary diversity scores (DDS), plant-based DDS, animal-based DDS, anti-inflammatory diet diversity index (AIDDI) and protein-enriched diet diversity index (PEDDI), were calculated from food frequency questionnaires. Sleep quality, chronotype, and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Morningness-Eveningness Questionnaire-5 (MEQ-5), and the Patient Health Questionnaire-9 (PHQ-9), respectively. Linear and logistic regression analyses were performed, with propensity score matching (PSM) applied to reduce confounding. Mediation and interaction analyses were further conducted.

Results: Higher dietary diversity indices were significantly associated with lower PSQI scores and higher MEQ-5 scores, both before and after PSM. Depression might be partially involved in the observed associations with sleep quality and chronotype. The associations between dietary diversity and sleep quality were stronger among females, older adults, non-drinkers, and those with regular exercise or depressive symptoms, whereas associations with chronotype were generally consistent across subgroups.

Conclusions: Greater dietary diversity is associated with better sleep quality and earlier chronotype, with depressive symptoms potentially playing a role in explaining these associations.

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引用次数: 0
Association between the geriatric nutritional risk index and 28-day mortality in critically ill sepsis-associated pneumonia patients: retrospective study based on two cohorts. 危重症败血症相关肺炎患者的老年营养风险指数与28天死亡率之间的关系:基于两个队列的回顾性研究
IF 4 2区 农林科学 Q2 NUTRITION & DIETETICS Pub Date : 2026-01-26 eCollection Date: 2025-01-01 DOI: 10.3389/fnut.2025.1698973
Dandan Shao, Linyu He, Dayang Zhong, Kun Li, Xianming Zhang
<p><strong>Background: </strong>In recent years, the identification of reliable prognostic indicators for critically ill patients has become increasingly crucial. The Geriatric Nutritional Risk Index (GNRI), a simple and objective tool for assessing malnutrition risk, has demonstrated significant prognostic value across various disease conditions. This study aims to investigate and validate the clinical utility of GNRI in predicting 28-day mortality among critically ill patients with sepsis-associated pneumonia.</p><p><strong>Material and method: </strong>We conducted a retrospective analysis using two distinct cohorts. Critically ill elderly people with sepsis-associated pneumonia were included. The derivation cohort consisted of critically ill patients with sepsis-associated pneumonia extracted from the MIMIC-IV database, while the validation cohort comprised consecutively enrolled patients meeting identical criteria from Jinyang Hospital Affiliated to Guizhou Medical University between March 2023 and March 2025. Key baseline variables including demographics, comorbidities, and severity scores were analyzed. We employed restricted cubic spline regression, multivariable logistic and Cox regression, and Kaplan-Meier analysis to assess associations between GNRI and mortality. Using LASSO regression for variable selection coupled with multivariable Cox proportional hazards modeling, we developed a prognostic nomogram across three distinct risk strata. Model discrimination was evaluated using time-dependent receiver operating characteristic (ROC) analysis, with predictive performance quantified by the area under the curve (AUC).</p><p><strong>Result: </strong>The final analysis included 2,230 critically ill patients with sepsis-associated pneumonia, with observed 28-day ICU and in-hospital mortality rates of 26.64% and 26.59%, respectively. In fully adjusted models, both continuous GNRI and categorical GNRI showed significant associations with 28-day ICU mortality across cohorts. The hazard ratios were 0.99 (95% CI: 0.98-1.00) for continuous GNRI; 0.69 (0.51-0.93) for moderate vs. high nutritional risk; and 0.41 (0.25-0.69) for no vs. high nutritional risk. Similar associations were observed for 28-day in-hospital mortality (no vs. high nutritional risk: HR: 0.59, 95% CI: 0.36-0.98). Restricted cubic spline analysis revealed a nonlinear relationship between continuous GNRI and both 28-day ICU and in-hospital mortality. When combined with conventional critical illness severity scores, GNRI provided incremental predictive value for 28-day mortality. ROC curve analysis demonstrated that our risk model outperformed conventional ICU severity scores in identifying high-risk sepsis-associated pneumonia patients. Our novel nomogram demonstrated superior predictive performance for 28-day mortality, achieving area under the curve (AUC) values of 0.71 (training), 0.70 (internal validation), and 0.70 (external validation), consistently exceeding the performance
背景:近年来,确定可靠的危重患者预后指标变得越来越重要。老年人营养风险指数(GNRI)是评估营养不良风险的一种简单而客观的工具,已证明在各种疾病状况下具有重要的预后价值。本研究旨在调查和验证GNRI在预测败血症相关性肺炎危重患者28天死亡率方面的临床应用。材料和方法:我们使用两个不同的队列进行回顾性分析。患有败血症相关性肺炎的危重老年人纳入研究对象。衍生队列包括从MIMIC-IV数据库中提取的脓毒症相关性肺炎危重患者,而验证队列包括2023年3月至2025年3月期间从贵州医科大学附属金阳医院连续入组的符合相同标准的患者。主要基线变量包括人口统计学、合并症和严重程度评分进行分析。我们采用限制三次样条回归、多变量logistic和Cox回归以及Kaplan-Meier分析来评估GNRI与死亡率之间的关系。使用LASSO回归进行变量选择,并结合多变量Cox比例风险模型,我们在三个不同的风险层中建立了预后nomogram。采用随时间变化的受试者工作特征(ROC)分析来评估模型的判别性,并通过曲线下面积(AUC)来量化预测性能。结果:最终纳入2230例脓毒症相关性肺炎危重患者,28天ICU死亡率26.64%,住院死亡率26.59%。在完全调整后的模型中,连续GNRI和分类GNRI均与28天ICU死亡率显著相关。连续GNRI的风险比为0.99 (95% CI: 0.98-1.00);中等营养风险vs.高营养风险为0.69 (0.51-0.93);无营养风险与高营养风险的比值为0.41(0.25-0.69)。在住院28天死亡率中也观察到类似的关联(无营养风险vs高营养风险:HR: 0.59, 95% CI: 0.36-0.98)。限制三次样条分析显示,连续GNRI与28天ICU和住院死亡率之间存在非线性关系。当与传统的危重疾病严重程度评分相结合时,GNRI提供了28天死亡率的增量预测价值。ROC曲线分析表明,我们的风险模型在识别高危败血症相关肺炎患者方面优于传统的ICU严重程度评分。我们的新nomogram对28天死亡率的预测表现优异,达到了0.71(训练)、0.70(内部验证)和0.70(外部验证)的曲线下面积(AUC)值,始终优于传统的ICU严重程度评分。结论:我们的多中心研究表明,在两个队列中,GNRI与脓毒症相关肺炎危重患者的短期死亡率之间存在一致的负相关。这些发现将GNRI定位为一种实用的、易于获得的风险分层工具,可以帮助临床医生及时识别高危患者,进行有针对性的营养干预和加强监测。
{"title":"Association between the geriatric nutritional risk index and 28-day mortality in critically ill sepsis-associated pneumonia patients: retrospective study based on two cohorts.","authors":"Dandan Shao, Linyu He, Dayang Zhong, Kun Li, Xianming Zhang","doi":"10.3389/fnut.2025.1698973","DOIUrl":"https://doi.org/10.3389/fnut.2025.1698973","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;In recent years, the identification of reliable prognostic indicators for critically ill patients has become increasingly crucial. The Geriatric Nutritional Risk Index (GNRI), a simple and objective tool for assessing malnutrition risk, has demonstrated significant prognostic value across various disease conditions. This study aims to investigate and validate the clinical utility of GNRI in predicting 28-day mortality among critically ill patients with sepsis-associated pneumonia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Material and method: &lt;/strong&gt;We conducted a retrospective analysis using two distinct cohorts. Critically ill elderly people with sepsis-associated pneumonia were included. The derivation cohort consisted of critically ill patients with sepsis-associated pneumonia extracted from the MIMIC-IV database, while the validation cohort comprised consecutively enrolled patients meeting identical criteria from Jinyang Hospital Affiliated to Guizhou Medical University between March 2023 and March 2025. Key baseline variables including demographics, comorbidities, and severity scores were analyzed. We employed restricted cubic spline regression, multivariable logistic and Cox regression, and Kaplan-Meier analysis to assess associations between GNRI and mortality. Using LASSO regression for variable selection coupled with multivariable Cox proportional hazards modeling, we developed a prognostic nomogram across three distinct risk strata. Model discrimination was evaluated using time-dependent receiver operating characteristic (ROC) analysis, with predictive performance quantified by the area under the curve (AUC).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;The final analysis included 2,230 critically ill patients with sepsis-associated pneumonia, with observed 28-day ICU and in-hospital mortality rates of 26.64% and 26.59%, respectively. In fully adjusted models, both continuous GNRI and categorical GNRI showed significant associations with 28-day ICU mortality across cohorts. The hazard ratios were 0.99 (95% CI: 0.98-1.00) for continuous GNRI; 0.69 (0.51-0.93) for moderate vs. high nutritional risk; and 0.41 (0.25-0.69) for no vs. high nutritional risk. Similar associations were observed for 28-day in-hospital mortality (no vs. high nutritional risk: HR: 0.59, 95% CI: 0.36-0.98). Restricted cubic spline analysis revealed a nonlinear relationship between continuous GNRI and both 28-day ICU and in-hospital mortality. When combined with conventional critical illness severity scores, GNRI provided incremental predictive value for 28-day mortality. ROC curve analysis demonstrated that our risk model outperformed conventional ICU severity scores in identifying high-risk sepsis-associated pneumonia patients. Our novel nomogram demonstrated superior predictive performance for 28-day mortality, achieving area under the curve (AUC) values of 0.71 (training), 0.70 (internal validation), and 0.70 (external validation), consistently exceeding the performance","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"12 ","pages":"1698973"},"PeriodicalIF":4.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy of 42-month oral administration of glucoraphanin in preventing cognitive decline in individuals at elevated risk of dementia, including those with mild cognitive impairment: a randomized, double-blind, placebo-controlled pilot study. 一项随机、双盲、安慰剂对照的初步研究:口服葡萄糖苷42个月预防痴呆高危人群(包括轻度认知障碍患者)认知能力下降的疗效
IF 4 2区 农林科学 Q2 NUTRITION & DIETETICS Pub Date : 2026-01-26 eCollection Date: 2026-01-01 DOI: 10.3389/fnut.2026.1740494
Sunao Shimizu, Shuya Kasai, Chieko Suzuki, Tomoya Kon, Hiroyuki Suganuma, Shigenori Suzuki, Koichi Murashita, Shigeyuki Nakaji, Kazushige Ihara, Masahiko Tomiyama, Ken Itoh

Background: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates cellular defense mechanisms and has been proposed as a therapeutic target for Alzheimer's disease (AD). Preclinical studies suggest that long-term oral administration of glucoraphanin (GLR), a natural Nrf2 activator, mitigates age-related cognitive decline in animal models.

Objective: This study evaluated the long-term efficacy of GLR supplementation on cognitive function in older adults at an elevated risk for AD, including those with mild cognitive impairment (MCI).

Methods: In a 42-month randomized, double-blind, placebo-controlled trial, 26 participants aged 63-90 years with memory impairment were randomly assigned to receive either 30 mg/day of GLR (n = 13) or placebo (n = 12). The primary outcome was the change in Memory Performance Index (MPI) scores from the MCI Screen. Secondary outcomes included conversion/reversion rates between normal cognition and MCI.

Results: Ten participants in the GLR group and nine participants in the placebo group completed the trial. Analysis using a Linear Mixed Model (LMM) across the entire study period revealed a significant group by time-point interaction for MPI scores, with the GLR group showing a significantly greater improvement in MPI scores compared to the placebo (p = 0.012). No significant group difference was observed in the initial 6 months, but a marginal difference in favor of GLR appeared in the later phase (30 and 42 months), including the 42-month endpoint (p = 0.079). Conversion/reversion rates were not significantly different. The GLR group demonstrated superior performance on immediate recall and delayed free recall tests (p < 0.001 and p = 0.012, respectively). MCI participants showed a greater MPI improvement with GLR (p = 0.029). No severe adverse events related to the intervention were reported.

Conclusion: Long-term GLR supplementation may help preserve cognitive function in individuals at elevated risk for AD, particularly those with MCI. Larger trials are warranted to confirm efficacy and clarify underlying mechanisms.

背景:核因子红细胞2相关因子2 (Nrf2)是一种调节细胞防御机制的转录因子,已被提出作为阿尔茨海默病(AD)的治疗靶点。临床前研究表明,长期口服葡萄糖苷(GLR),一种天然Nrf2激活剂,可以减轻动物模型中与年龄相关的认知能力下降。目的:本研究评估GLR补充剂对AD高风险老年人认知功能的长期疗效,包括轻度认知障碍(MCI)患者。方法:在一项为期42个月的随机、双盲、安慰剂对照试验中,26名年龄在63-90 岁的记忆障碍患者被随机分配接受30 mg/天的GLR (n = 13)或安慰剂(n = 12)。主要结果是MCI屏幕上记忆性能指数(MPI)得分的变化。次要结果包括正常认知和轻度认知障碍之间的转换/恢复率。结果:GLR组10名参与者和安慰剂组9名参与者完成了试验。在整个研究期间,使用线性混合模型(LMM)进行分析,发现MPI评分的时间点相互作用显著,与安慰剂组相比,GLR组在MPI评分方面表现出更大的改善(p = 0.012)。在最初的6 个月没有观察到显著的组间差异,但在后期(30和42 个月)出现了有利于GLR的边际差异,包括42个月的终点(p = 0.079)。转换/逆转率无显著差异。GLR组在即时回忆和延迟自由回忆测试中表现出优异的表现(p p = 0.012)。MCI参与者在GLR的作用下MPI表现出更大的改善(p = 0.029)。没有与干预相关的严重不良事件的报道。结论:长期补充GLR可能有助于保持AD高危人群的认知功能,特别是MCI患者。有必要进行更大规模的试验以确认疗效并阐明潜在机制。
{"title":"Efficacy of 42-month oral administration of glucoraphanin in preventing cognitive decline in individuals at elevated risk of dementia, including those with mild cognitive impairment: a randomized, double-blind, placebo-controlled pilot study.","authors":"Sunao Shimizu, Shuya Kasai, Chieko Suzuki, Tomoya Kon, Hiroyuki Suganuma, Shigenori Suzuki, Koichi Murashita, Shigeyuki Nakaji, Kazushige Ihara, Masahiko Tomiyama, Ken Itoh","doi":"10.3389/fnut.2026.1740494","DOIUrl":"https://doi.org/10.3389/fnut.2026.1740494","url":null,"abstract":"<p><strong>Background: </strong>Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates cellular defense mechanisms and has been proposed as a therapeutic target for Alzheimer's disease (AD). Preclinical studies suggest that long-term oral administration of glucoraphanin (GLR), a natural Nrf2 activator, mitigates age-related cognitive decline in animal models.</p><p><strong>Objective: </strong>This study evaluated the long-term efficacy of GLR supplementation on cognitive function in older adults at an elevated risk for AD, including those with mild cognitive impairment (MCI).</p><p><strong>Methods: </strong>In a 42-month randomized, double-blind, placebo-controlled trial, 26 participants aged 63-90 years with memory impairment were randomly assigned to receive either 30 mg/day of GLR (<i>n</i> = 13) or placebo (<i>n</i> = 12). The primary outcome was the change in Memory Performance Index (MPI) scores from the MCI Screen. Secondary outcomes included conversion/reversion rates between normal cognition and MCI.</p><p><strong>Results: </strong>Ten participants in the GLR group and nine participants in the placebo group completed the trial. Analysis using a Linear Mixed Model (LMM) across the entire study period revealed a significant group by time-point interaction for MPI scores, with the GLR group showing a significantly greater improvement in MPI scores compared to the placebo (<i>p</i> = 0.012). No significant group difference was observed in the initial 6 months, but a marginal difference in favor of GLR appeared in the later phase (30 and 42 months), including the 42-month endpoint (<i>p</i> = 0.079). Conversion/reversion rates were not significantly different. The GLR group demonstrated superior performance on immediate recall and delayed free recall tests (<i>p</i> < 0.001 and <i>p</i> = 0.012, respectively). MCI participants showed a greater MPI improvement with GLR (<i>p</i> = 0.029). No severe adverse events related to the intervention were reported.</p><p><strong>Conclusion: </strong>Long-term GLR supplementation may help preserve cognitive function in individuals at elevated risk for AD, particularly those with MCI. Larger trials are warranted to confirm efficacy and clarify underlying mechanisms.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"13 ","pages":"1740494"},"PeriodicalIF":4.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Serum nutrient profile and dietary patterns as predictors of tumor grade and molecular subtype in breast cancer patients.
IF 4 2区 农林科学 Q2 NUTRITION & DIETETICS Pub Date : 2026-01-26 eCollection Date: 2026-01-01 DOI: 10.3389/fnut.2026.1745421
Xiaohu Sun, Zhihao Yu, Ran Meng, Xin Wang, Xuchen Cao

Background: Breast cancer heterogeneity is influenced by tumor grade, molecular subtype, and modifiable lifestyle factors such as diet and nutritional status. Tumor aggressiveness and oxidative stress may be influenced by dietary habits and serum nutritional profiles, according to new research.

Aim: The purpose of this study was to assess the relationship between oxidative stress markers, dietary patterns, serum nutritional profiles, and breast cancer tumor features, such as tumor grade and molecular subtype.

Methodology: Using validated questionnaires, the tumor grade, molecular subtype, serum nutrients (vitamins, trace elements, lipids, oxidative stress indicators), and food intake of 293 female patients with breast cancer were evaluated in this retrospective analysis. Dietary patterns were found using principal component analysis, and statistical analyses included correlation matrices and logistic regression.

Results: The molecular subtypes of the tumors were Luminal A (38.2%), Luminal B (24.9%), HER2-enriched (21.3%), and triple-negative (15.7%). The tumor grades were Grade I (29.8%), II (45.5%), and III (24.7%). With tumor grade, oxidative stress (MDA) rose and antioxidant nutrients decreased (p < 0.01). Plant-based, Western, Mixed, and Mediterranean-like eating patterns were found. While the Mediterranean-like diet was beneficial (OR = 0.60, p = 0.041), excessive adherence to the Western diet was linked to increased risks of aggressive tumors (OR = 2.30, p = 0.003). Antioxidant nutrients and adherence to the Mediterranean-like diet were shown to be favorably correlated; MDA was positively correlated with the Western pattern.

Conclusion: Antioxidant-rich Mediterranean-like dietary pattern showed inverse association with aggressive tumor features, suggesting potential protective biological relationship while Western dietary pattern was positively associated with oxidative stress and lower circulating antioxidant nutrients. Personalized nutrition methods to improve breast cancer prognosis may be informed by the integration of dietary and biochemical assessment.

{"title":"Serum nutrient profile and dietary patterns as predictors of tumor grade and molecular subtype in breast cancer patients.","authors":"Xiaohu Sun, Zhihao Yu, Ran Meng, Xin Wang, Xuchen Cao","doi":"10.3389/fnut.2026.1745421","DOIUrl":"https://doi.org/10.3389/fnut.2026.1745421","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer heterogeneity is influenced by tumor grade, molecular subtype, and modifiable lifestyle factors such as diet and nutritional status. Tumor aggressiveness and oxidative stress may be influenced by dietary habits and serum nutritional profiles, according to new research.</p><p><strong>Aim: </strong>The purpose of this study was to assess the relationship between oxidative stress markers, dietary patterns, serum nutritional profiles, and breast cancer tumor features, such as tumor grade and molecular subtype.</p><p><strong>Methodology: </strong>Using validated questionnaires, the tumor grade, molecular subtype, serum nutrients (vitamins, trace elements, lipids, oxidative stress indicators), and food intake of 293 female patients with breast cancer were evaluated in this retrospective analysis. Dietary patterns were found using principal component analysis, and statistical analyses included correlation matrices and logistic regression.</p><p><strong>Results: </strong>The molecular subtypes of the tumors were Luminal A (38.2%), Luminal B (24.9%), HER2-enriched (21.3%), and triple-negative (15.7%). The tumor grades were Grade I (29.8%), II (45.5%), and III (24.7%). With tumor grade, oxidative stress (MDA) rose and antioxidant nutrients decreased (<i>p</i> < 0.01). Plant-based, Western, Mixed, and Mediterranean-like eating patterns were found. While the Mediterranean-like diet was beneficial (OR = 0.60, <i>p</i> = 0.041), excessive adherence to the Western diet was linked to increased risks of aggressive tumors (OR = 2.30, <i>p</i> = 0.003). Antioxidant nutrients and adherence to the Mediterranean-like diet were shown to be favorably correlated; MDA was positively correlated with the Western pattern.</p><p><strong>Conclusion: </strong>Antioxidant-rich Mediterranean-like dietary pattern showed inverse association with aggressive tumor features, suggesting potential protective biological relationship while Western dietary pattern was positively associated with oxidative stress and lower circulating antioxidant nutrients. Personalized nutrition methods to improve breast cancer prognosis may be informed by the integration of dietary and biochemical assessment.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"13 ","pages":"1745421"},"PeriodicalIF":4.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Shenqi compound enhances pancreatic β-cell secretion by promoting the maturation and transport of insulin secretory vesicles through the NOD1/RIP2 signaling pathway.
IF 4 2区 农林科学 Q2 NUTRITION & DIETETICS Pub Date : 2026-01-26 eCollection Date: 2025-01-01 DOI: 10.3389/fnut.2025.1690849
Nairong Yao, Yiqian Xing, Ruobing Tang, Chunguang Xie, Qiyue Yang, Ya Liu, Xiyu Zhang

Background: Shenqi compound (SQC) is an effective prescription in Chinese medicine to enhance glucose homeostasis and protect pancreatic cells from high glucose-induced damage. However, the protection mechanism remains unclear.

Objective: To investigate the effect of SQC on INS-1 cell secretion and evaluate the associated mechanisms.

Methods: INS-1 cells were cultured in serum augmented with or without NOD1 inhibitor ML130 (2μM) for 1 h, then exposed into a high glucose (50 mM) condition to simulate type 2 diabetes mellitus (T2DM) for 24 h and treated with different concentrations (0, 5, 10, 15, 20%) of SQC in serum for another 24 h. Then, the cell counting kit-8 (CCK-8) method, glucose-stimulated insulin secretion (GSIS) assay, transmission electron microscopy (TEM), real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blot were performed for further investigation.

Results: Under high glucose conditions, 15% SQC was the optimal therapeutic concentration, significantly improved INS-1 cell viability (p = 0.032) and enhanced insulin secretion (p < 0.0001). Ultrastructural analysis showed that after high glucose stimulation in GSIS, especially at 20 min, 15% SQC significantly increased both the total density (p = 0.143) and the mature ratio (p = 0.003) of insulin secretory vesicles. Furthermore, 15% SQC facilitated the dynamic transport of vesicles toward the cell membrane, evidenced by an increased vesicle density within 300 nm of the membrane at 10 min, followed by a subsequent decrease at 20 min-a trend consistent with that observed in the control group. Moreover, at the molecular level, 15% SQC intervention markedly up-regulated NOD1 and RIP2 protein expression (p = 0.029 and p < 0.0001) and transcription (p = 0.886 and p = 0.393) levels, while ML130 reversed the activation of the NOD1/RIP2 pathway.

Conclusions: SQC promotes the maturation and transport of insulin secretory vesicles, thereby enhancing the secretory function of INS-1 cells in response to high glucose-induced damage. This protective effect may be associated with the activation of the NOD1/RIP2 signaling pathway.

{"title":"Shenqi compound enhances pancreatic β-cell secretion by promoting the maturation and transport of insulin secretory vesicles through the NOD1/RIP2 signaling pathway.","authors":"Nairong Yao, Yiqian Xing, Ruobing Tang, Chunguang Xie, Qiyue Yang, Ya Liu, Xiyu Zhang","doi":"10.3389/fnut.2025.1690849","DOIUrl":"https://doi.org/10.3389/fnut.2025.1690849","url":null,"abstract":"<p><strong>Background: </strong>Shenqi compound (SQC) is an effective prescription in Chinese medicine to enhance glucose homeostasis and protect pancreatic cells from high glucose-induced damage. However, the protection mechanism remains unclear.</p><p><strong>Objective: </strong>To investigate the effect of SQC on INS-1 cell secretion and evaluate the associated mechanisms.</p><p><strong>Methods: </strong>INS-1 cells were cultured in serum augmented with or without NOD1 inhibitor ML130 (2μM) for 1 h, then exposed into a high glucose (50 mM) condition to simulate type 2 diabetes mellitus (T2DM) for 24 h and treated with different concentrations (0, 5, 10, 15, 20%) of SQC in serum for another 24 h. Then, the cell counting kit-8 (CCK-8) method, glucose-stimulated insulin secretion (GSIS) assay, transmission electron microscopy (TEM), real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blot were performed for further investigation.</p><p><strong>Results: </strong>Under high glucose conditions, 15% SQC was the optimal therapeutic concentration, significantly improved INS-1 cell viability (<i>p</i> = 0.032) and enhanced insulin secretion (<i>p</i> < 0.0001). Ultrastructural analysis showed that after high glucose stimulation in GSIS, especially at 20 min, 15% SQC significantly increased both the total density (<i>p</i> = 0.143) and the mature ratio (<i>p</i> = 0.003) of insulin secretory vesicles. Furthermore, 15% SQC facilitated the dynamic transport of vesicles toward the cell membrane, evidenced by an increased vesicle density within 300 nm of the membrane at 10 min, followed by a subsequent decrease at 20 min-a trend consistent with that observed in the control group. Moreover, at the molecular level, 15% SQC intervention markedly up-regulated NOD1 and RIP2 protein expression (<i>p</i> = 0.029 and <i>p</i> < 0.0001) and transcription (<i>p</i> = 0.886 and <i>p</i> = 0.393) levels, while ML130 reversed the activation of the NOD1/RIP2 pathway.</p><p><strong>Conclusions: </strong>SQC promotes the maturation and transport of insulin secretory vesicles, thereby enhancing the secretory function of INS-1 cells in response to high glucose-induced damage. This protective effect may be associated with the activation of the NOD1/RIP2 signaling pathway.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"12 ","pages":"1690849"},"PeriodicalIF":4.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The relationship between dietary magnesium intake, stress level and headache in academic and administrative staff.
IF 4 2区 农林科学 Q2 NUTRITION & DIETETICS Pub Date : 2026-01-26 eCollection Date: 2026-01-01 DOI: 10.3389/fnut.2026.1694363
Naciye Kılıç, Nihal Zekiye Erdem

Background: Magnesium is an important mineral that plays a role in many biochemical reactions in the body. Since it plays a role in many mechanisms of the body, it is thought that it may also have effects on stress and headaches.

Methods: The study was conducted with the participation of a total of 150 volunteer academic and administrative staff aged between 19 and 65. Participants were evaluated through general information, anthropometric measurements, Headache Impact Test-6 (HIT-6) and Perceived Stress Level Scale-10 (PSS-10), 3-day food consumption record and frequency of consumption of magnesium-rich foods questionnaire.

Results: The mean age of the participants was 31 ± 6.283 years for men and 28.55 ± 5.294 years for women. The Headache Impact Test-6 score was higher in the group with inadequate magnesium intake (p < 0.05). Although the Perceived Stress Level Scale-10 score was also higher in the group with inadequate magnesium intake, the result was not significant (p > 0.05). A negative correlation was found between dietary magnesium and HIT-6 and PSS-10 scores (r = -0.183, r = -0.197, respectively; p < 0.05). A positive correlation was also found between the scales (r = 0.456; p < 0.01).

Conclusion: These findings suggest that lower dietary magnesium intake is associated with higher headache impact and perceived stress in academic and administrative staff.

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引用次数: 0
Precision nutrition guided by genomic and functional assessments in postmenopause: a case report. 绝经后基因组和功能评估指导的精确营养:1例报告。
IF 4 2区 农林科学 Q2 NUTRITION & DIETETICS Pub Date : 2026-01-26 eCollection Date: 2026-01-01 DOI: 10.3389/fnut.2026.1724337
Jenny Noland

Postmenopause is commonly associated with vasomotor symptoms, musculoskeletal discomfort, weight gain, gastrointestinal (GI) disturbances, and increased cardiometabolic and autoimmune risk. A 52-year-old woman presented with hot flashes, weight gain, joint stiffness and pain, and abdominal bloating. Genomic profiling revealed variants affecting methylation, detoxification, and metabolic regulation. Functional testing identified global sex hormone decline, impaired Phase II estrogen metabolism, vitamin D insufficiency, an atherogenic lipid profile, increased intestinal permeability, and elevated toxin burden. A phased, precision nutrition plan was implemented, combining dietary modification, targeted nutraceuticals, gut-directed therapy, detoxification support, sleep optimization, and stress management, alongside bioidentical hormone replacement therapy (BHRT). After 6 months, the patient experienced resolution of vasomotor symptoms and GI bloating, marked reduction in musculoskeletal pain and Medical Symptoms Questionnaire (MSQ) scores, improved sleep quality, and favorable lipid changes. This case demonstrates the potential of genomically informed precision nutrition, integrated with functional testing, to guide personalized interventions that enhance metabolic health, symptom resolution, and overall quality of life (QoL) in postmenopausal women.

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引用次数: 0
期刊
Frontiers in Nutrition
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