Journal of Nutritional Biochemistry最新文献

{"title":"The effects of docosahexaenoic acid (DHA) on plasma cytokines, oxylipins, and tumor-infiltrating lymphocytes from women with breast cancer undergoing neoadjuvant chemotherapy in the DHA-WIN trial","authors":"Jaqueline Munhoz ,&nbsp;Gilbert Bigras ,&nbsp;Marnie Newell ,&nbsp;Irma Magaly Rivas-Serna ,&nbsp;Vera Mazurak ,&nbsp;Susan Goruk ,&nbsp;Anil Abraham Joy ,&nbsp;Sunita Ghosh ,&nbsp;Kerry S. Courneya ,&nbsp;Denise G. Hemmings ,&nbsp;Catherine J. Field","doi":"10.1016/j.jnutbio.2025.110025","DOIUrl":"10.1016/j.jnutbio.2025.110025","url":null,"abstract":"<div><div>Clinical trials on docosahexaenoic acid (DHA) supplementation and immune changes during breast cancer neoadjuvant chemotherapy (NAC) are limited. This study evaluated the impact of DHA supplementation during NAC on systemic and tumor immune modulation by assessing plasma inflammatory and cardiac damage markers, tumor-infiltrating lymphocyte (TIL) proportions, and n-6- and n-3-derived oxylipins produced in response to an <em>ex vivo</em> immune challenge. Venous blood was collected at baseline, 9, and 15 weeks during NAC from participants in the DHA for Women with Breast Cancer in the Neoadjuvant Setting (DHA-WIN) trial, which compared DHA-enriched algae (4.4g/day; <em>n</em>=23) with a placebo (<em>n</em>=26) over 18 weeks. Plasma markers were measured using electrochemiluminescence assays. CD4+ and CD8+ TILs were identified in tumor tissue by immunohistochemistry, and oxylipins were quantified in the supernatant of lipopolysaccharide-stimulated peripheral blood mononuclear cells via liquid chromatography–tandem mass spectrometry. DHA supplementation resulted in greater increases in the plasma cytokines IFN-γ and TNF-α compared to placebo (<em>P</em>-interaction &lt; .05). In the DHA group, concentrations of these cytokines increased at 15 weeks compared to baseline (<em>P</em> &lt; .05). No differences were found between groups for other immune markers or the proportion of TILs. Compared to the placebo, DHA led to an overall increase in total oxylipin concentrations (<em>P</em> &lt; .05) and higher production of n-6 fatty acid-derived oxylipins, particularly prostanoids, and n-3 fatty acid-derived oxylipins, including 13-HDoHE. These results suggest that DHA may enhance immune responses by promoting an increase in oxylipin and cytokine concentrations, potentially benefiting patients during breast cancer NAC.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110025"},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary supplementation with eugenol modulates lipid metabolism in finishing pigs through the TRPV1/AMPK signaling pathway","authors":"Liping Nie,&nbsp;Yaxin Qiu,&nbsp;Xiaoling Chen,&nbsp;Ping Zheng,&nbsp;Yuheng Luo,&nbsp;Bing Yu,&nbsp;Daiwen Chen,&nbsp;Zhiqing Huang","doi":"10.1016/j.jnutbio.2025.110027","DOIUrl":"10.1016/j.jnutbio.2025.110027","url":null,"abstract":"<div><div>Eugenol (4-allyl-2-methoxyphenol), a natural phytogenic compound, exhibits physiological properties including antibacterial, anti-inflammatory, and antioxidant activities. This study aimed to evaluate the effects of dietary eugenol supplementation on lipid metabolism, carcass characteristics, and mechanism in finishing pigs. In our findings, dietary supplementation with eugenol significantly improved carcass traits in finishing pigs (<em>P</em>&lt;.05). The eugenol-supplemented diet markedly reduced serum concentrations of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) (<em>P</em>&lt;.05), while significantly increasing high-density lipoprotein (HDL) levels (<em>P</em>&lt;.05). Furthermore, eugenol supplemented diet significantly decreased the content of TC and TG in muscle tissue (<em>P</em>&lt;.05). Specifically, EUG significantly downregulated the protein expression of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and sterol regulatory element-binding protein (SREBP) in adipose tissue (<em>P</em>&lt;.05). EUG treatment upregulated protein expressions of transient receptor potential vanilloid-1 (TRPV1) and P-AMPK/AMPK (<em>P</em>&lt;.05). These results demonstrated that eugenol regulates lipid metabolism through the TRPV1/AMPK signaling pathway, effectively reducing serum TG and cholesterol levels while inhibiting lipid accumulation.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110027"},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early postnatal overnutrition as a contributor to metabolic dysregulation: Insights into hepatic epigenetic mechanisms","authors":"Wen Zheng,&nbsp;Nan Zhou,&nbsp;Jiasi Kuang,&nbsp;Susu Du,&nbsp;Dandan Zhu,&nbsp;Ru Ling,&nbsp;Chunyang Zhang,&nbsp;Yueshu Wang,&nbsp;Wei Zhou,&nbsp;Xiaonan Li","doi":"10.1016/j.jnutbio.2025.110022","DOIUrl":"10.1016/j.jnutbio.2025.110022","url":null,"abstract":"<div><div>This study evaluated the effects of postnatal overnutrition during lactation on hepatic DNA methylation patterns and their relationship with hepatic metabolic disorders. At postnatal day 3, male rats were randomly divided into normal litters (NL, 10 pups per litter) or small litters (SL, three pups per litter). Weight and insulin resistance were assessed at week 3 and week 13. Whole-genome bisulfite sequencing was used to detect alterations in hepatic DNA methylation levels, and enrichment analysis for differentially methylated genes (DMGs) was conducted. The methyl donor for DNA methylation, hepatic S-adenosylmethionine (SAMe), and serum methionine (Met) content were assessed by ELISA. The mRNA and protein expression levels of methionine adenosyltransferase I, alpha (Mat1a), a gene associated with SAMe synthesis, were examined. Rats that had postnatal overnutrition induced by small-litter rearing exhibited significant weight gain, insulin resistance and increased hepatic lipid deposition alongside reduced hepatic glycogen content. At week 3, the overall DNA methylation levels of the liver were notably reduced in the SL rats, with the differentially methylated regions (DMRs) primarily located in the genomic and intergenic regions. The DMGs were significantly enriched in the phosphatidylinositol (PI) and insulin resistance (IR) pathway. As the DNA methylation level decreased, the serum Met levels increased abnormally, while the hepatic SAMe content, glutathione (GSH) and Mat1a gene expression decreased significantly. Postnatal overnutrition leads to an aberrant hepatic DNA methylation pattern, which could contribute to persistent obesity and metabolic liver disorders by potentially regulating genes in the PI and IR pathways.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110022"},"PeriodicalIF":4.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enriched environment exposure restores behavioral alterations and transcriptional dysregulation of hippocampal steroidogenic enzymes in a small litter model","authors":"Maria Florencia Rossetti ,&nbsp;Rocío Schumacher ,&nbsp;Guillermina Canesini ,&nbsp;Pamela Fernández ,&nbsp;Luisa Gaydou ,&nbsp;Cora Stoker ,&nbsp;Jorge Guillermo Ramos","doi":"10.1016/j.jnutbio.2025.110024","DOIUrl":"10.1016/j.jnutbio.2025.110024","url":null,"abstract":"<div><div>We previously reported that rats raised in small litters (SL) exhibited increased anxiety-like behavior and poor performance in the episodic-like memory (ELM) test compared to normal litters (NL). Additionally, mRNA expression of aromatase was increased, and 5α-reductase 1 was reduced in the dentate girus (DG) of SL compared to NL rats. In this work, the objective was to analyze whether environmental enrichment (EE) can reverse or attenuate the behavioral and molecular effects observed in SL animals. Thus, male rats were raised in SL (4 pups/mother; SL), where pups consumed larger amounts of milk and gained more body weight compared to rats raised in normal litters (10 pups/mother; NL). On postnatal day (PND) 21, male rats were housed under standard conditions (SE, 4 rats/cage) or EE (8 rats/cage). For EE, cages were equipped with objects and tunnels that were changed daily. At PND75, the animals underwent locomotion activity, episodic-like memory (ELM) and elevated plus maze (EPM) tests. At PND90, the animals were euthanized, and their brains were microdissected. dentate girus (DG), CA1, and CA3 regions were isolated for mRNA quantification and methylation studies. We found that EE attenuates anxiety-like behavior and rescues spatial memory deficits in SL animals. Furthermore, EE prevented the increase in aromatase and decline in 5α-reductase 1, expression associated with SL. Some of these changes were correlated with alterations in methylation patterns of the promoter regions of these genes. These findings demonstrate that environmental interventions can mitigate the long-term effects observed in the SL model and restore brain and behavioral functions.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110024"},"PeriodicalIF":4.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of saponin on testes oxidative stress, apoptosis, and steroid hormone synthesis pathway in bile duct ligation model of obstructive cholestasis in male Wistar rats","authors":"Helia Mavaddat ,&nbsp;Mahsa Ale-Ebrahim ,&nbsp;Diba Sabouni Aghdam","doi":"10.1016/j.jnutbio.2025.110020","DOIUrl":"10.1016/j.jnutbio.2025.110020","url":null,"abstract":"<div><div>Cholestasis occurs when bile flow is disrupted and toxic bile acids accumulate in the liver. This leads to systemic oxidative stress that may affect other organs including the testes. Cholestasis can cause testicular dysfunction. Saponins have antioxidant capacity and can elevate testosterone levels. In this study, a bile duct ligation (BDL) model of cholestasis has been used to assess the effects of cholestasis on antioxidant activity, apoptosis, steroid hormone synthesis pathway, and histopathological changes in testes and then evaluate the capability of saponin in attenuation of the injuries. We performed an <em>in vivo</em> study and experimental groups were as follows: control (healthy rats+0.5 mL distilled water); sham (laparotomy without BDL); saponin control (200 or 400 mg/kg); BDL; and saponin treatment (BDL rats+200 or 400 mg/kg saponin). Catalase (CAT) and superoxide dismutase (SOD) activity was evaluated by enzyme-linked immunosorbent assay (ELISA) and protein expression was assessed by Western blotting. Hematoxylin &amp; Eosin staining was done for histopathological analysis. The results indicated that BDL reduced CAT and SOD activity and stimulated apoptosis. Moreover, protein expression of Steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD), and 17β-hydroxysteroid dehydrogenase (17β-HSD) was down-regulated and histopathological changes occurred. Saponin could increase SOD and CAT activity and decrease apoptosis. Also, StAR, 17β-HSD, and 3β-HSD expression were increased by saponin. In addition, histological changes were ameliorated by saponin treatment. All these data indicate that saponin may effectively reverse the modifications caused by cholestasis in the testes.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110020"},"PeriodicalIF":4.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline 25-hydroxyvitamin D as a stronger protector against type 2 diabetes in the context of hyperuricemia and gout: a cohort study based on the UK biobank","authors":"Yingdong Han ,&nbsp;Juan Wu ,&nbsp;Menghui Yao ,&nbsp;Tiange Xie ,&nbsp;Zhikai Li ,&nbsp;He Zhao ,&nbsp;Yun Zhang ,&nbsp;Xuejun Zeng","doi":"10.1016/j.jnutbio.2025.110021","DOIUrl":"10.1016/j.jnutbio.2025.110021","url":null,"abstract":"<div><div>To elucidate the association between Vitamin D and the risk of Type 2 diabetes (T2D) in individuals with hyperuricemia or gout. A total of 43,731 patients with hyperuricemia and 9,695 with gout were included to assess the association between Vitamin D levels and T2D risk. Serum 25(OH)D (nmol/L) concentrations were measured. Multivariable logistic regression, cumulative incidence curves, Cox proportional-hazards models, and restricted cubic spline analysis were used to evaluate the relationship between 25(OH)D and T2D risk. Sensitivity and stratified analyses were performed to ensure the robustness of the findings. Higher serum 25(OH)D concentration was associated with lower risk of baseline T2D. During a median follow-up of 14.27 years for hyperuricemia patients and 14.09 years for gout patients, 4,617 and 1,072 new-onset T2D cases were documented, respectively. An inverse, nonlinear dose-response relationship was found between 25(OH)D and incident T2D in hyperuricemia patients. Compared to participants with 25(OH)D&lt;25 nmol/L, the adjusted HR for those with 25(OH)D&gt;75 nmol/L was 0.62 (0.54, 0.72). In gout patients, the protective effect of 25(OH)D was even more pronounced [HR: 0.45(0.32, 0.62)]. Sensitivity analyses confirmed the robustness of our findings. Significant interactions were observed with age, smoking, and cardiovascular disease, while genetic susceptibility showed no interaction. The protective effect of 25(OH)D (per 10 nmol/L increase) was stronger in hyperuricemia patients aged &lt;65 years [&lt;65 years: 0.91 (0.89, 0.93), ≥65 years 0.96 (0.93, 0.99)] and in never smokers [Never: 0.92 (0.89, 0.95), Current: 1.00 (0.95, 1.06)]. Among gout patients, the effect was more evident in those without cardiovascular disease [No: 0.86 (0.82, 0.90), Yes: 0.92 (0.84, 1.00)]. Higher serum 25(OH)D concentration is significantly associated with a lower risk of incident T2D in patients with hyperuricemia or gout, and this association is especially pronounced among younger individuals, nonsmokers and those without cardiovascular disease.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110021"},"PeriodicalIF":4.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated multiomics analysis reveals the effect of glucose selenol improves rat immunity","authors":"Xinyi Yang,&nbsp;Jinzhou Huang,&nbsp;Zhi Zeng,&nbsp;Si Sun,&nbsp;Juan Wang,&nbsp;Zhi Wang","doi":"10.1016/j.jnutbio.2025.110023","DOIUrl":"10.1016/j.jnutbio.2025.110023","url":null,"abstract":"<div><div>This study aimed to investigate the effects of glucose selenol (SeGlu) on the immune function of rats, with a particular focus on the spleen. Rats were randomly divided into CK (deionized water, oral), Se0.15 group (0.15 mg/L SeGlu, oral), and Se0.4 group (0.4 mg/L SeGlu, oral) for 30 days continuously. 0.15 mg/L SeGlu significantly increased the serum antioxidant levels and the levels of IgM and IgG. The Se0.4 group upregulated the inflammatory factor levels of IL-2 and IL-6, and both concentrations significantly reduced the serum TNF-α level. Transcriptome analysis indicated that the supplementation of SeGlu could affect three types of proteins: peptidases, tumor necrosis factor receptors, and transmembrane transport proteins. KEGG enrichment discovered pathway annotations directly or indirectly related to the immune process, especially phagosomes, natural killer cell-mediated cytotoxicity, and nod-like receptor signaling pathways. We identified 59 SeGlu target differentially expressed genes and 8 (NEG) and 20 (POS) co-expressed differentially expressed metabolites. Immunoglobulin-related DEGs were concentrated in the transcription factor family V-set, and were identified on chromosome 6. In addition, metagenome sequencing showed that SeGlu treatment increased abundance of <em>Roseburia, Ruminococcus, Eubacterium, Coprobacillus</em>, and <em>Intestinimonas</em> at the genus level. Spearman correlation analysis results showed that the modulatory effects of SeGlu on <span>d</span>-proline were related to the regulation of <em>Roseburia, Clostridium, Eubacterium Coprobacillus, Butyricimonas,</em> and <em>Muribaculum.</em> Overall, the analyses of rat physiology, transcriptome, metabolome, and metagenome offer new insights into Se on rat immunity. SeGlu provides beneficial immune protection and is a promising organic selenium enrichment additive.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110023"},"PeriodicalIF":4.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calycosin-7-O-β-D-glucoside alleviates nonalcoholic fatty liver disease by regulating short-chain fatty acids metabolism and metabolic regulators","authors":"Yanping Zeng ,&nbsp;Xinrun Huang ,&nbsp;Yuci Ma ,&nbsp;Xiaodie Di ,&nbsp;Zhao Li ,&nbsp;Hebin Wang ,&nbsp;Xiaodong Wei","doi":"10.1016/j.jnutbio.2025.110018","DOIUrl":"10.1016/j.jnutbio.2025.110018","url":null,"abstract":"<div><div>Nonalcoholic fatty liver disease (NAFLD) is a metabolic stress liver injury disease caused by excessive fat deposition in hepatocytes. <em>Astragalus memeranaceus</em> Fisch<em>.</em>, mainly consists of flavonoids, is considered to have good liver protection effects. This study aimed to explore the active ingredients and possible mechanisms of Astragalus flavone in the treatment of NAFLD. Network pharmacology and molecular docking were used to screen the active ingredients and targets of Astragalus flavone in the treatment of NAFLD, and were verified <em>in vivo</em> high-fat diet-induced mouse models. There were 89 predicted targets of 10 main compounds of Astragalus flavone in treating NAFLD, and the core genes involved PPAR-<em>γ</em>. Molecular docking results showed that all the 10 main components of Astragalus flavone had a strong binding activity with PPAR-<em>γ</em>, among which CG had the strongest binding ability. <em>In vivo</em> results showed that CG inhibited obesity, reduced the disorder of glucose and lipid metabolism, alleviated liver function injury and lipid accumulation, and improved the oxidative stress and inflammatory response of NAFLD mice, playing a positive role in the treatment of NAFLD. In addition, CG promoted the expression of AMPK, PPAR-<em>γ</em>, and Nrf2, inhibited the expressions of NF-кB, and regulated the metabolism of short-chain fatty acids (SCFAs) in NAFLD. In conclusion, CG, the main active component of Astragalus flavone, exerts a positive therapeutic effect on NAFLD, which is related to CG altering various energy sensors and metabolic regulators (PPAR-<em>γ</em>, AMPK, NF-кB, and Nrf2) that contribute to changes in intestinal SCFAs.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110018"},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naringin attenuates myocardial ischemia-reperfusion injury by promoting mitochondrial translocation of NDUFS1 and suppressing cardiac microvascular endothelial cell ferroptosis","authors":"Xue Guan ,&nbsp;Zhenyu Yang ,&nbsp;Jinming Wang ,&nbsp;Wei Lu ,&nbsp;Shilin Wang ,&nbsp;Mi Yang ,&nbsp;Pengbo Sun ,&nbsp;Wenfu Hu ,&nbsp;Liming Yang ,&nbsp;Hong Li","doi":"10.1016/j.jnutbio.2025.110019","DOIUrl":"10.1016/j.jnutbio.2025.110019","url":null,"abstract":"<div><div>Cardiac microvascular injury plays a pivotal role in the progression of myocardial ischemia-reperfusion injury (MI/RI). Previous studies have demonstrated the cardioprotective effects of naringin (Nar) in cardiovascular diseases. However, the involvement of cardiac microvessels in Nar-mediated protection against MI/RI remains unexplored. This study aimed to investigate the impact of Nar on the function of cardiac microvascular endothelial cells (CMECs) in MI/RI rat. An MI/RI model was established in rats through ligation of the left anterior descending artery for 45 min followed by 6 h of reperfusion. <em>In vitro</em>, a hypoxia-reoxygenation (H/R) model was established in CMECs by subjecting them to 12 h of hypoxia and 24 h of reoxygenation. A comprehensive set of experimental techniques was employed, including qRT-PCR, western blotting, transmission electron microscopy (TEM), proteomic analysis, ELISA, TTC staining, immunohistochemistry, immunofluorescence, molecular docking, and molecular dynamics simulations. Our results revealed that Nar significantly enhances cardiac microvascular function by suppressing ferroptosis in CMECs during MI/RI. Mechanistically, phosphorylation of interferon regulatory factor 3 (IRF3) was downregulated in both the hearts of MI/RI rats and CMECs exposed to H/R. Nar effectively upregulated IRF3 phosphorylation, thereby activating the SLC7A11/Gpx4 signaling pathway. Furthermore, Nar facilitated the translocation of NADH ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1) from the cytosol to the mitochondria, enhancing mitochondrial function and mitigating ferroptosis in H/R-treated CMECs. Nar promoted mitochondrial translocation of NDUFS1, thereby restoring mitochondrial function and inhibited CMECs ferroptosis <em>via</em> activation of the IRF3/SLC7A11/Gpx4 axis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110019"},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of astragalus polysaccharide alleviated experimental colitis involved mTreg cells and the mTOR/HIF-1α pathway","authors":"Miaohua Liu ,&nbsp;Jiaojiao Luo ,&nbsp;Jiaqi Huang ,&nbsp;Xiyan Zhu ,&nbsp;Duanyong Liu ,&nbsp;Jian Long ,&nbsp;Bailing Deng ,&nbsp;Bugao Zhou ,&nbsp;Haimei Zhao","doi":"10.1016/j.jnutbio.2025.110010","DOIUrl":"10.1016/j.jnutbio.2025.110010","url":null,"abstract":"<div><div>To investigate the effect of astragalus polysaccharide (APS) in the treatment of ulcerative colitis (UC) and its molecular mechanisms, particularly through the ability to regulate Treg cell-glycolytic interactions. BALB/c mice were used to establish DSS-induced UC model, and administered with APS (200 mg/kg) as a therapeutic intervention. During the study, flow cytometry was employed to analyze the changes in the proportions of Treg cells and their related subpopulations in the spleens of mice. Additionally, the expression levels of various cytokines in the colon tissues were detected simultaneously. To further investigate the mechanism of action of APS, RNA sequencing was also performed on the colon tissues, and the regulatory effects of APS on glycolysis and mTOR/HIF-1α signaling pathway were revealed by KEGG pathway analysis, western blot, RT-qPCR and other techniques. In this study, we found that APS not only substantially ameliorated the adverse symptoms in UC mice, but also promoted the expression of anti-inflammatory cytokines and suppressed the levels of pro-inflammatory cytokines by regulating the distribution of Treg cells and their subpopulations. Furthermore, the molecular mechanism by which APS exerts its protective effects by inhibiting glycolysis and mTOR/HIF-1α signaling pathway was revealed through RNA sequencing, KEGG pathway analysis, and other techniques. The study revealed that APS effectively ameliorated the symptoms of UC in mice by regulating Treg cells, inhibiting glycolysis and mTOR/HIF-1α signaling pathway, providing a scientific basis and potential therapeutic target for the application of APS in UC treatment.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110010"},"PeriodicalIF":4.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}