Journal of Nutritional Biochemistry最新文献

{"title":"Complex interactions between stress, nutrition, gut microbiota, and infectious diseases and their impact on health in global conflicts: A narrative review","authors":"Pavlo Petakh ,&nbsp;Iryna Halabitska ,&nbsp;Halyna Petrecka ,&nbsp;Wolfgang Huber ,&nbsp;Oleksandr Kamyshnyi","doi":"10.1016/j.jnutbio.2026.110267","DOIUrl":"10.1016/j.jnutbio.2026.110267","url":null,"abstract":"<div><div>Following the global recovery from the COVID-19 pandemic, wars and conflicts have escalated to levels unseen since the Cold War. It is well known that conflict is accompanied not only by significant losses among both military personnel and civilians but also by rising levels of stress and stress-related disorders within the general population. Stress is bidirectionally connected with the state of the gut microbiota through the gut–brain axis. Dietary factors and eating behaviours also play crucial roles in shaping gut microbiota composition. On the one hand, conflict negatively affects food availability and dietary patterns, leading to reduced meal frequency and potentially diminishing microbiota diversity. On the other hand, stress-induced alterations in eating behaviour, such as bulimia or anorexia, can further impair gut microbiota composition. Additionally, individuals in conflict zones face heightened risks of infectious diseases due to disrupted vaccination schedules, poor sanitation, and limited access to clean drinking water. Stress-related immune changes may increase susceptibility to infections and raise the likelihood of adverse outcomes. Moreover, the frequent use of antibiotics to treat infections during conflicts contributes to reduced gut microbiota diversity.</div><div>This review narratively examines the complex interactions among stress, immune responses, dietary patterns, infectious diseases, and gut microbiota in conflict-affected areas, and provides new perspectives on the role of artificial intelligence in modelling such comorbid pathologies.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110267"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994268","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 naringenin alleviates experimental autoimmune encephalomyelitis in mice partially via estrogen receptor-mediated pathway","authors":"Chaolei Jin ,&nbsp;Qiaozhen Zhu ,&nbsp;Tong Wang ,&nbsp;Zejin Liu ,&nbsp;Hang Wu ,&nbsp;Xinli Niu ,&nbsp;Junpeng Wang","doi":"10.1016/j.jnutbio.2026.110266","DOIUrl":"10.1016/j.jnutbio.2026.110266","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a T-cell-mediated autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination, axonal injury, and loss of oligodendrocytes. Disease severity is influenced by sex hormones, particularly estrogens, which protects against MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, its clinical use is limited by risks such as thrombosis and reproductive tumors. Naringenin, a citrus-derived flavonoid, exhibits anti-inflammatory and neuroprotective properties and has been reported to possess phytoestrogenic activity. In this study, we investigated whether dietary naringenin alleviates autoimmune neuroinflammation in a mouse model of MS with estrogen deficiency induced by ovariectomy. Using a combination of network pharmacology, molecular docking, and <em>in vivo</em> experiments, we examined the effects of naringenin on EAE progression, immune cell responses, cytokine profiles, and estrogen receptor (ESR) signaling. Network pharmacology identified common targets of naringenin, estrogen, and MS, and molecular docking showed stable binding to ESR1. In ovariectomized EAE mice, naringenin attenuated EAE progression via dampening antigen-specific T cell responses, decreasing TNF-α, IL-6, and IL-1β, IFN-γ and IL-17A and increasing anti-inflammatory cytokines IL-10 and TGF-β. Furthermore, naringenin raised serum estradiol and CNS ESRα expression, and its benefits were partially reduced by the ESR antagonist ICI182,780, suggesting ESR signaling contributes to, but does not fully explain, naringenin’s immunomodulatory actions. Overall, these findings demonstrate that dietary naringenin ameliorates autoimmune neuroinflammation in an estrogen-deficient EAE model through mechanisms partially dependent on estrogen receptor signaling, supporting its potential as a dietary or adjunctive strategy for MS.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110266"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994392","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":"Schisandrin B alleviates sulfolane-induced liver injury via the APOA1/ROS/NF-κB signaling pathway","authors":"Yuechen Xing ,&nbsp;Bo Zhang ,&nbsp;Shuo Jin ,&nbsp;Youtong Guo,&nbsp;Yueru Chen,&nbsp;Lili Chen,&nbsp;Yue Wang","doi":"10.1016/j.jnutbio.2025.110255","DOIUrl":"10.1016/j.jnutbio.2025.110255","url":null,"abstract":"<div><div>Sulfolane is a widely used industrial solvent and emerging groundwater contaminant. Sulfolane has hepatotoxicity, but the molecular mechanisms remain poorly understood. Schisandrin B (Sch B), a bioactive lignan isolated from <em>Schisandra chinensis</em>, has been shown to exert hepatoprotective effects. To elucidate the mechanisms underlying sulfolane-induced liver injury and to determine whether Sch B protects against this toxicity by modulating the APOA1/ROS/NF-κB signaling axis. Male C57BL/6 J mice were administered sulfolane (0, 10, 30 or 300 mg/kg) by oral gavage for 28 d, with or without Sch B (8 mg/kg). Liver injury was assessed using histopathology, serum biochemistry, hepatic lipid deposition, ROS levels, and inflammatory marker expression. Bioinformatic analyses integrating “sulfur compound” and “liver injury” datasets were used to identify candidate pathways. The protective effects of Sch B were investigated through APOA1 gene knockdown, APOA1 overexpression, treatment with the antioxidant NAC, and molecular docking experiments of Sch B with APOA1. Sulfolane caused dose-dependent steatosis, oxidative stress and inflammation in mouse liver and AML12 cells. sulfolane suppressed APOA1, increased ROS and activated NF-κB and downstream cytokines. Sch B restored APOA1 expression, reduced ROS accumulation and NF-κB–dependent cytokine production, and markedly improved biochemical and histological indices of liver injury <em>in vivo</em> and <em>in vitro</em>. Sulfolane-induced hepatotoxicity is mediated by suppression of APOA1 and subsequent activation of the NF-κB signaling pathway in a ROS-dependent manner. Schisandrin B protects the liver against this injury by modulating the APOA1/ROS/NF-κB axis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110255"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878572","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":"Myeloid monoamine oxidase A protects against glucose intolerance, insulin resistance and weight gain in high-fat diet-fed mice by preventing the hyperactivation of macrophages","authors":"Seonwook Kim ,&nbsp;Matthew R. Eber ,&nbsp;Alessandro G. Salerno ,&nbsp;Elena Boudyguina ,&nbsp;Reto Asmis","doi":"10.1016/j.jnutbio.2025.110257","DOIUrl":"10.1016/j.jnutbio.2025.110257","url":null,"abstract":"<div><div>The aim of this study was to determine the role of myeloid monoamine oxidase A (Mao A) in diet-induced obesity (DIO). Ten-week-old male and female LysMCre^tg/tg (CTL) and LysMCre^tg/tgMaoA^fl/fl (Mao A_Myeloid^−/−) mice were fed a high-fat diet for 20 week. Male but not female mice with myeloid Mao A deficiency showed increased weight gain, increased visceral adipose tissue (AT) weight as well as elevated fasting blood glucose and leptin levels. However, both male and female Mao A_Myeloid^−/- mice showed increased insulin resistance of the AT and glucose intolerance. Mao A mRNA levels were reduced by 90% and 94% in bone marrow-derived macrophages (BMDM) from male and female Mao A_Myeloid^−/- mice, respectively, but neither Mao A mRNA expression nor protein levels or Mao A activity in AT were altered by myeloid Mao A deficiency. Targeted gene profiling of M_TNFα+IFNγ and M_IL-4-polarized BMDM from Mao A KO mice and 129S1 strain-matched control mice revealed that Mao A deficiency amplifies the expression of polarization state-specific marker genes in BMDM from male mice but affects only a few selected marker genes in female polarized BMDM. Myeloid Mao A protects male but not female mice from AT inflammation, AT expansion and DIO, possibly by suppressing the polarization of monocyte-derived macrophages recruited into the AT. However, myeloid Mao A deficiency promoted insulin resistance in AT and glucose intolerance in both male and female mice suggesting that macrophage Mao A in other tissues contributes to the maintenance of glucose tolerance and homeostasis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110257"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900796","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":"Short-term exposure to a high-fat diet leads to neuroinflammation and impairs memory and cholinergic signaling in the hippocampal CA3 region of male mice","authors":"Suleyma Oliveira Costa ,&nbsp;Iracema Monteiro Silva ,&nbsp;Wenicios Ferreira Chaves ,&nbsp;Andrea Maculano Esteves ,&nbsp;Beatriz Franco ,&nbsp;Leticia Martins Ignácio-Souza ,&nbsp;Marciane Milanski ,&nbsp;Michael Glenn Ross ,&nbsp;Mina Desai ,&nbsp;Marcio Alberto Torsoni ,&nbsp;Adriana Souza Torsoni","doi":"10.1016/j.jnutbio.2026.110274","DOIUrl":"10.1016/j.jnutbio.2026.110274","url":null,"abstract":"<div><div>Consumption of a high-fat diet (HFD) can lead to cognitive dysfunction and neuroinflammation in the hippocampus, particularly the CA3 region, which is vital for associative memory. Cholinergic input from the basal forebrain to the hippocampus is critical for regulating excitability, plasticity, and overall cognitive function in this area. Neuroinflammation may disrupt the expression of the α7 nicotinic acetylcholine receptor (α7nAChR), essential for the anti-inflammatory cholinergic pathway. We sought to assess the effects of brief HFD exposure on hippocampal cholinergic function and neurobehavior. Adult Swiss male mice were fed either a standard chow diet (Control; CTR) or a 60% HFD for 3 d. The Open Field (OF) and Novel Object Recognition (NOR) tests were used to evaluate anxiety-like behavior and memory performance, respectively. Following testing, the CA3 region of the hippocampus was analyzed using Western Blotting, PCR, and immunofluorescence techniques. Additionally, HFD-fed mice treated intracerebroventricularly with the α7nAChR-selective agonist PNU-282987 and α7nAChR knockout (<em>Chrna7</em>^-/-) mice were evaluated to elucidate the role of cholinergic signaling in cognition. Results showed that HFD-fed mice performed worse on the NOR test compared to CTR mice and exhibited reduced α7nAChR expression and increased acetylcholinesterase (AChE) levels, along with signs of neuroinflammation in the CA3 area. Treatment with PNU-282987 for 3 d mitigated memory impairments and neuroinflammation. In contrast, <em>Chrna7</em>^-/- mice fed a HFD displayed poorer performance on the NOR test. Our findings suggest that short-term HFD intake is linked to cholinergic impairment and inflammation in the CA3 region, indicating that targeted agonist therapy may help alleviate HFD-induced memory deficits. These results highlight the critical role of α7nAChR activation in memory regulation during neuroinflammatory episodes.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110274"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018868","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 phospholipids alleviate high fat diet-induced intestinal lipid deposition through ATF4-PPARα-MTTP/SAR1B pathway in yellow catfish","authors":"Hua Zheng ,&nbsp;Xiao-Ying Tan ,&nbsp;Biao Wang ,&nbsp;Chong-Chao Zhong ,&nbsp;Xiao-Lei Wei ,&nbsp;Chang-Chun Song ,&nbsp;Zhi Luo","doi":"10.1016/j.jnutbio.2026.110261","DOIUrl":"10.1016/j.jnutbio.2026.110261","url":null,"abstract":"<div><div>Phospholipids serve as an efficient emulsifier and transport carrier for lipids. However, the regulatory mechanism by which phospholipids ameliorate lipid metabolic disorders induced by high-fat diet (HFD) remains unclear. The study aimed to investigate the effects and regulatory mechanisms of dietary phospholipids and HFD on intestinal lipid metabolism. We found that dietary phospholipids alleviated HFD-induced intestinal lipid deposition by inhibiting sterol regulatory element binding proteins 1 (SREBP1)-dependent lipogenesis and promoting peroxisome proliferator-activated receptor α (PPARα)-dependent lipolysis. Dietary phospholipids alleviated HFD-induced impairment in chylomicrons (CMs) synthesis and secretion by promoting microsomal triglyceride transfer protein (MTTP), apolipoprotein B and secretion-associated, Ras-related GTPase 1b (SAR1B) mRNA and protein expression. Moreover, dietary phospholipids alleviated the reduction in phosphatidylcholine synthesis induced by HFD <em>via</em> promoting cytidine triphosphate: phosphocholine cytidylyltransferase (CCTα) protein expression and mitigated HFD-induced ER stress by inhibiting glucose-regulated protein 78 (GRP78), protein kinase R like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4) mRNA and protein expression. Mechanistically, phosphatidylcholine promoted CCTα protein expression to alleviate the obstruction of CMs synthesis and secretion caused by fatty acid (palmitic acid and oleic acid). Moreover, phosphatidylcholine enhanced the transcription of <em>mttp</em> and <em>sar1b</em> genes by PPARα through reducing the interaction between ATF4 and PPARα, thereby promoting the CMs assembly and secretion to alleviate fatty acid-induced lipid deposition in primary intestinal cells of yellow catfish. Overall, this study reveals that phospholipids alleviate HFD-induced intestinal lipid accumulation through the ATF4-PPARα-MTTP/SAR1B pathway, and provides strong basis for phospholipids in the prevention of obesity-related metabolic diseases.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110261"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933847","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":"Discovery of myristic acid, from chick early amniotic fluid for the treatment of acute gastric ulcers by targeting pyruvate carboxylase to improve TCA cycle","authors":"Fan Chen ,&nbsp;Ke-jia Wu ,&nbsp;Ziru Zhou ,&nbsp;Jiajun Yin ,&nbsp;Xuezheng Gao ,&nbsp;Yanfa Dai ,&nbsp;Lin Shao ,&nbsp;YaNan Zhu ,&nbsp;Zhenhe Zhou ,&nbsp;Ning Sun","doi":"10.1016/j.jnutbio.2026.110264","DOIUrl":"10.1016/j.jnutbio.2026.110264","url":null,"abstract":"<div><div>Gastric ulcer (GU) is a common digestive disease. We recently identified early chicken embryo amniotic fluid (ceAF) as a potent antioxidant, which exerts effects via its active components. This study demonstrates the potential of ceAF and one of its active components, myristic acid (MA), as GU protectants. UPLC-MS and GC-MS identified the key components and fatty acid contents in ceAF. In absolute ethanol-induced acute gastric ulcer (AGU) mice, ceAF and MA treatment significantly reduced ulcer area, while improving histopathology and inflammatory factor infiltration. Further, proteomics was used to elucidate the molecular mechanism by which MA ameliorates AGU: the gastroprotective potential of MA is mediated by targeting pyruvate carboxylase (PCX) to improve the Tricarboxylic acid cycle (TCA cycle). Our findings indicate that ceAF and MA show potential as candidate substances for GU prevention in preclinical studies, providing a new direction for the development of functional foods.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110264"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985015","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":"Type 3 resistant starch from Canna edulis improves Parkinson’s symptoms, including behavioral function and nerve damage, in Parkinson’s model rats by regulating the gut–brain axis","authors":"Nan Zhang,&nbsp;Fangyuan Zhao,&nbsp;Tingting Miao,&nbsp;Nan Wang,&nbsp;Jiahui Wu,&nbsp;Shuting Tan,&nbsp;Xiang Wang,&nbsp;Xier Lihou,&nbsp;Yan Li,&nbsp;Yang Li,&nbsp;Feng Ou,&nbsp;Maochun Xiao,&nbsp;Aji Li,&nbsp;Rongting Min,&nbsp;Shiyao Su,&nbsp;Xueyong Wang","doi":"10.1016/j.jnutbio.2025.110191","DOIUrl":"10.1016/j.jnutbio.2025.110191","url":null,"abstract":"<div><div>Intestinal microorganisms affect the pathogenesis of Parkinson’s disease (PD) and, therefore, are a new research focus of PD treatment. Type 3 resistant starch from <em>Canna edulis</em> (Ce-RS3) regulates gut microbes and has prebiotic properties. The effects include decreased blood lipids, weight, and inflammation, as well as increased glycolipid metabolism. There are few reports on the use of prebiotics alone in the treatment of Parkinson's. In this study, based on the gut–brain axis, the pharmacological effects and related mechanisms of Ce-RS3 on PD were studied by analyzing intestinal bacteria and brain transcriptomics. Ce-RS3 improved motor function in PD model rats over a defined period and repaired PD-induced inflammation-related organ and neural damage. In addition, Ce-RS3 increased the number of short-chain fatty acid-producing, and other beneficial, bacteria. Transcriptomics showed that Ce-RS3 decreased inflammatory gene expression, upregulated the expression of the protein homeostasis-related gene <em>Hspb1</em> and downregulated the expression levels of the protein aggregation-related genes <em>Hdac6</em> and <em>Ubd</em>. Therefore, we hypothesized that Ce-RS3 plays a role in the treatment of PD by regulating the α-synuclein-related pathway through the brain–gut axis and protecting the neural tissues. This study provides a new intervention plan for the prevention and treatment of PD.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110191"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668641","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":"Curcumin alleviates murine ulcerative colitis by modulating Tfh-B cell crosstalk via the CD40/CD40L costimulatory pathway","authors":"Ji Yu ,&nbsp;Yazhen Liu ,&nbsp;Jiaqi Huang ,&nbsp;Xiyan Zhu ,&nbsp;Duanyong Liu ,&nbsp;Haimei Zhao ,&nbsp;Bailing Deng ,&nbsp;Youbao Zhong","doi":"10.1016/j.jnutbio.2025.110256","DOIUrl":"10.1016/j.jnutbio.2025.110256","url":null,"abstract":"<div><div>Ulcerative colitis (UC) progression is closely associated with dysregulated T follicular helper (Tfh)-B cell crosstalk, a process are centrally mediated through the CD40/CD40L costimulatory pathway. This study aimed to investigate whether curcumin (Cur) alleviates UC by regulating Tfh-B cell crosstalk via modulation of this pathway. Mice with dextran sulfate sodium (DSS)-induced UC were administered were treated with Cur for 14 consecutive days. Tfh and B cell subsets were analyzed using flow cytometry, while CD40/CD40L gene and protein expression were assessed via qRT-PCR and WB. Cellular spatial interactions were examined through immunofluorescence. Additionally, molecular docking, molecular dynamics simulations and surface plasmon resonance (SPR) were performed to evaluate Cur's binding to the CD40/CD40L complex. Cur treatment significantly reduced the disease activity index, restored colon length, ameliorated histological damage, and suppressed proinflammatory cytokines (<em>e.g.</em>, IL-6, IL-21) as well as IgG levels. Mechanistically, Cur downregulated significantly CD40L⁺ Tfh cells and CD40⁺ B cells, and inhibited significantly key GC transcription factor Bcl-6 and plasma cell differentiation regulator Blimp-1. Molecular simulations confirmed that Cur stably binds to the CD40/CD40L interface through van der Waals forces and electrostatic complementarity, effectively blocking their interaction. The evidence from kinetic and competitive SPR assays demonstrates that Cur not only exhibits strong binding affinity by directly targeting CD40L, but also concentration-dependently blocks its interaction with CD40, resulting in significant functional inhibition of the CD40/CD40L signaling axis. Collectively, these findings demonstrate that Cur ameliorates UC by inhibiting the CD40/CD40L complex, which disrupts pathological Tfh-B cell crosstalk and ultimately restores gut immune homeostasis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110256"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889540","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 disodium fumarate relieves high-concentrate diet-induced hepatic injury by inhibiting endoplasmic reticulum stress, mitochondrial dysfunction and autophagy via epigenetic modifications in lactating hu sheep","authors":"Nana Ma,&nbsp;Wan Xie,&nbsp;Huimin Shi,&nbsp;Shendong Zhou,&nbsp;Hongzhu Zhang,&nbsp;Guangjun Chang,&nbsp;Xiangzhen Shen","doi":"10.1016/j.jnutbio.2025.110254","DOIUrl":"10.1016/j.jnutbio.2025.110254","url":null,"abstract":"<div><div>A high-concentrate diet fed to ruminants induced the release of LPS from the rumen to the liver. Dietary disodium fumarate (DF) fed to ruminants helps restore rumen homeostasis by improving the pH of the rumen fluid. However, the effects of dietary disodium fumarate on hepatic injury induced by high-concentrate diet have not been thoroughly explored. Eighteen lactating Hu sheep with rumen fistula were randomly divided into three groups: the low-concentrate diet group (LC, forage:concentrate=7:3, <em>n</em>=6), the high-concentrate diet group (HC, forage:concentrate=3:7, <em>n</em>=6) and the high-concentrate diet with DF supplementation group (FHC, 10g DF per sheep daily, <em>n</em>=6). After 8 weeks, the rumen fluid, portal vein and hepatic blood and liver tissue were collected for analysis. A high-concentrate diet decreased the pH of the rumen fluid and increased the LPS concentration in portal vein blood, resulting in morphological damage and an inflammatory response. GRP78-regulated unfolded protein response receptors and CHOP were upregulated, indicating ER stress; The imbalance between fusion and fission, mitophagy and PGAM5 upregulation indicated the mitochondrial damage in the liver of the HC group. Dietary DF supplementation relieved these hepatic injuries, accompanied by reduced autophagy. The level of methylation and chromatin compaction of ER stress- and autophagy-related genes were also increased by DF supplementation. These epigenetic modifications were negatively correlated with the mRNA expression of the target genes. Therefore, DF supplementation alleviated the inflammatory response, ER stress, and mitochondrial damage, not only by reducing LPS release but also through epigenetic modifications in the livers of Hu sheep fed a high-concentrate diet.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110254"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900715","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}