Journal of Nutritional Biochemistry最新文献

{"title":"Heterophyllin B alleviates diabetes-induced myocardial injury by regulating MAVS-mediated mitochondrial homeostasis","authors":"Lan Li ,&nbsp;Zheting Liu ,&nbsp;Haoran Hu ,&nbsp;Qiuru Wang ,&nbsp;Jing Wang ,&nbsp;Liang Jin ,&nbsp;Shujing Zhang ,&nbsp;Jihua Wei ,&nbsp;Lu Zhao ,&nbsp;Ziying Chen ,&nbsp;Qian Liu ,&nbsp;Keyang Zhu ,&nbsp;Ling Zhang","doi":"10.1016/j.jnutbio.2025.110075","DOIUrl":"10.1016/j.jnutbio.2025.110075","url":null,"abstract":"<div><div>Diabetic cardiomyopathy (DCM), a major cause of diabetic mortality, lacks effective therapies. This study investigated the cardioprotective role of Heterophyllin B (HET-B), a natural compound and its underlying mechanisms in DCM. Using streptozotocin-induced DCM mice and high glucose (HG)-treated H9C2/neonatal cardiomyocytes, we assessed cardiac function, mitochondrial homeostasis, and apoptosis. HET-B significantly improved cardiac function, indicated by increased ejection fraction (EF) and fractional shortening (FS). It also reduced cardiomyocyte apoptosis (<em>in vivo/vitro</em>), and ameliorated HG-induced mitochondrial damage, characterized by dysfunction, fragmentation, and excessive reactive oxygen species (ROS) production. HET-B enhanced mitochondrial fusion protein OPA1 expression and reduced Bax/Bcl2, cytochrome C (Cyt C) release and caspase-3 cleavage. Molecular docking and cellular thermal shift assays identified mitochondrial antiviral-signaling protein (MAVS) as a potential target of HET-B. HET-B reversed MAVS downregulation induced by HG/DCM <em>in vitro</em> and <em>in vivo</em>. Importantly, MAVS knockdown via siRNA abolished HET-B's protection against HG-induced apoptosis and mitochondrial damage. Furthermore, HET-B restored HG-impaired autophagic flux, reducing autolysosome accumulation and normalizing LC3-II. Collectively, the natural compound HET-B alleviates diabetic myocardial injury by targeting MAVS to enhance autophagy, maintain mitochondrial homeostasis, and inhibit cardiomyocyte apoptosis, positioning it as a promising therapeutic candidate for DCM.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110075"},"PeriodicalIF":4.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855585","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":"Immunomodulatory effects of a short-term gluten-free diet on pediatric celiac disease: Findings from a single-cell transcriptomics study","authors":"Rafael Martín-Masot ,&nbsp;Nerea Correa-López ,&nbsp;Marta Herrador-López ,&nbsp;Víctor Manuel Navas-López ,&nbsp;Francisco David Carmona ,&nbsp;Teresa Nestares ,&nbsp;Lara Bossini-Castillo","doi":"10.1016/j.jnutbio.2025.110063","DOIUrl":"10.1016/j.jnutbio.2025.110063","url":null,"abstract":"<div><div>Celiac disease (CD) is an autoimmune disorder with a strong genetic component, triggered by gluten ingestion. Although a Gluten-Free Diet (GFD) is the standard treatment, its short-term effects on immune cell modulation in pediatric CD remain largely unexplored. This study aimed to investigate transcriptional changes in peripheral blood mononuclear cells (PBMCs) of pediatric CD patients following a strict GFD for 9–10 months, using single-cell RNA sequencing (scRNA-seq). An observational longitudinal study was conducted on five pediatric CD patients pre-GFD and post-GFD (confirmed by gluten immunogenic peptide determination in feces). PBMCs were analyzed using droplet-based scRNA-seq to identify cluster markers and differentially expressed genes (DEGs) between pre-GFD and post-GFD cells. Nineteen immune cell clusters encompassing a variety of classical immune cell subtypes were identified. Key findings included the downregulation of pro-inflammatory genes and the upregulation of immune-regulatory genes after a GFD in different immune cell subsets. Changes in macrophages and monocytes suggested improved immune balance, while T cells demonstrated a shift towards reduced effector activity. Notably, post-GFD regulatory T cells transitioned into a trajectory towards enhanced immunosuppressive profiles, as evidenced by increased <em>HLA-G</em> and decreased <em>DDX5</em> expression. A strict short-term GFD induced significant immune modulation in pediatric CD patients, highlighting potential biomarkers for disease monitoring. Nevertheless, due to the small sample size, results should be interpreted with caution, and larger cohort studies are needed for further confirmation and validation. These findings provide insights into the immunological mechanisms of GFD and suggest avenues for noninvasive diagnostic strategies to enhance patient management.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110063"},"PeriodicalIF":4.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847163","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":"Transport of cholesterol to ovary via the Srb selective uptake pathway supports Star-mediated steroidogenesis in swimming crab (Portunus trituberculatus)","authors":"Tingting Zhu ,&nbsp;Wenli Zhao ,&nbsp;Shichao Xie ,&nbsp;Peng Sun ,&nbsp;Qicun Zhou ,&nbsp;Douglas R Tocher ,&nbsp;Min Jin","doi":"10.1016/j.jnutbio.2025.110064","DOIUrl":"10.1016/j.jnutbio.2025.110064","url":null,"abstract":"<div><div>Cholesterol, essential for steroidogenesis, is crucial in ovarian development. In crustaceans, scavenger receptor class B member (Srb) and steroidogenic acute regulatory protein (Star) may be key proteins in cholesterol transport and steroidogenesis, respectively. This study aimed to explore cholesterol's role in steroidogenesis and ovarian development in female swimming crabs through <em>in vivo</em> and <em>in vitro</em> experiments. The control diet (Ctrl, without added cholesterol) and the cholesterol diet (CH) were fed swimming crabs and sampled first (30 d) and second ovarian development (60 d). Srb and Star functions were assessed <em>via</em> knockdown and overexpression experiments. Biochemical indices, histology, immunofluorescence, gene expression and Western blot were used to evaluate cholesterol transport, steroidogenesis and ovarian development. HEK293T cells were used for immunofluorescence and co-immunoprecipitation to explore mechanisms. Cholesterol supplementation significantly increased steroid hormone and vitellogenin (VTG) concentrations, as well as mRNA and protein expression levels of cholesterol transport, steroidogenesis, and <em>vtg</em>/Vtg. After interference and overexpression of Srb, the results indicated that Srb maintained cholesterol homeostasis by regulating cholesterol efflux gene <em>abcg1</em>, but not through compensatory regulation of <em>ldlr</em>. Similar patterns were found <em>in vitro</em>, Srb-mediated cholesterol transport promoted steroid hormone production. Moreover, <em>star</em> knockdown reduced steroidogenesis and <em>vtg</em>/Vtg expression, which was reversed by Star overexpression. The findings verified the roles of Srb in cholesterol transport and Star in steroidogenesis, and revealed that cholesterol supplementation promoted cholesterol transport <em>via</em> the Srb-selective uptake pathway, and supported Star-mediated steroidogenesis, thereby promoting ovarian development in swimming crab.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110064"},"PeriodicalIF":4.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847165","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":"TRPM6 and TRPM7 genetic polymorphisms, dietary magnesium, plasma magnesium, and gestational diabetes mellitus","authors":"Xiyu Cao ,&nbsp;Huaqi Zhang ,&nbsp;Jin Liu ,&nbsp;Weiming Wang ,&nbsp;Chunrong Zhong ,&nbsp;Guofu Zhang ,&nbsp;Lixia Lin ,&nbsp;Meng Wu ,&nbsp;Tianqi Tan ,&nbsp;Sen Yang ,&nbsp;Nianhong Yang","doi":"10.1016/j.jnutbio.2025.110067","DOIUrl":"10.1016/j.jnutbio.2025.110067","url":null,"abstract":"<div><div>Genetic variation in <em>TRPM6</em> and <em>TRPM7</em> contributes to magnesium (Mg) absorption defects. We aimed to verify the combined influence of Mg intake and these genetic polymorphisms on plasma Mg concentrations and the risk of gestational diabetes mellitus (GDM). We involved 1323 pregnant women from Tongji Maternal and Child Health Cohort. Two single nucleotide polymorphisms (SNPs) in <em>TRPM6</em> (rs2274924 and rs3750425) and one SNP in <em>TRPM7</em> (rs8042919) were genotyped through Asian Screening Array bead chip. Mg intake was evaluated using food frequency questionnaires before GDM diagnosis. Plasma Mg was measured using inductively coupled plasma mass spectrometry when 75 g oral glucose tolerance test was conducted to identify GDM. The summed number of mutant alleles for rs2274924 (T&gt;C), rs3750425 (C&gt;T) and rs8042919 (G&gt;A) was associated with GDM risk, with an adjusted relative risk (RR) of 1.65 (95% confidence interval [CI]: 1.21, 2.23) for women with higher number of mutant alleles compared to those with fewer than two alleles. A significant interaction was observed between gene variants and Mg intake on GDM risk (<em>P</em>-interaction = .039). Notably, insufficient Mg intake (&lt;370.0 mg/d) significantly decreased plasma Mg concentrations (15.34 mg/L vs 15.80 mg/L; <em>P</em> &lt; .001) and increased GDM incidence (adjusted RR = 2.14; 95% CI, 1.24, 3.68) among participants with fewer mutant alleles. Sufficient Mg intake may be more beneficial to increase plasma Mg concentrations and decrease GDM risk among pregnant women with fewer mutations on <em>TRPM6, TRPM7</em> gene variants.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110067"},"PeriodicalIF":4.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847091","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":"Trehalose supplementation ameliorates heat stress-induced intestinal barrier dysfunction by suppressing endoplasmic reticulum stress and modulating gut microbiota in mice","authors":"Fan Mo ,&nbsp;Xiaoyi Qin ,&nbsp;Xu Zhou,&nbsp;Haoran Jiang,&nbsp;Chong Wang,&nbsp;Yanjun Cui","doi":"10.1016/j.jnutbio.2025.110065","DOIUrl":"10.1016/j.jnutbio.2025.110065","url":null,"abstract":"<div><div>Heat stress (HS) compromises intestinal barrier integrity and microbiota homeostasis. Trehalose, a nonreducing disaccharide, is well known as a molecular chaperone to prevent protein misfolding under stress. However, whether trehalose supplementation can affect intestinal barrier integrity and microbiota under HS remains unknown. Male C57BL/6 mice (6-week-old) were randomly divided into 3 groups (7 mice/group): a normal control group (CON, 23℃), a heat stress group (HS, 42℃) and heat stress + trehalose group (HT, received 2.0% trehalose in drinking water under HS condition). Trehalose supplementation decreased rectal temperature and body weight loss in heat-stressed mice. HS-induced intestinal permeability characterized by increased <span>d</span>-lactate was inhibited by upregulating protein expression of tight junction proteins including occludin and Zo1 in mice administrated by trehalose. Supplementary trehalose significantly ameliorated HS-induced oxidative stress by elevating activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) as well as protein expression of catalase (CAT). Trehalose intervention reversed the up-regulation of endoplasmic reticulum (ER) stress proteins glucose-regulated protein 78 (GRP78), growth arrest and DNA damage-inducible protein 34 (GADD34), phosphorylated eukaryotic initiation factor 2α (p-eif2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) as well as proapoptotic proteins BAX, Cytc, and active-caspase3 in heat-stressed mice. Trehalose supplementation evidently elevated the abundance of beneficial bacteria <em>Lachnospiraceae_NK4A136_group</em> while reducing that of harmful bacteria <em>Bacteroidetes</em> in heat-stressed mice. Taken together, these results revealed that supplementary trehalose could attenuate HS-induced intestinal barrier dysfunction via reducing oxidative stress, reversing ER stress induced apoptosis and gut microbial dysbiosis, suggesting trehalose as a promising dietary additive to counteract the intestinal injury induced by HS in mice.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110065"},"PeriodicalIF":4.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847166","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":"Protective role of bovine lactoferrin in modulating the intestinal serotonergic system: Implications in intestinal inflammation","authors":"Berta Buey ,&nbsp;Inés Abad ,&nbsp;Andrea Bellés ,&nbsp;Marta Castro ,&nbsp;Marta Sofía Valero ,&nbsp;María Pilar Arruebo ,&nbsp;Laura Grasa ,&nbsp;Lourdes Sánchez ,&nbsp;Miguel Ángel Plaza ,&nbsp;José Emilio Mesonero ,&nbsp;Eva Latorre","doi":"10.1016/j.jnutbio.2025.110073","DOIUrl":"10.1016/j.jnutbio.2025.110073","url":null,"abstract":"<div><div>Bovine lactoferrin (bLf) is a multifunctional milk glycoprotein with diverse biological activities pivotal for gastrointestinal health. This study investigates the modulatory effects of bLf on the intestinal serotonergic system and its implications for intestinal inflammation and homeostasis. Intestinal serotonergic system plays a critical role in gut homeostasis, regulating various physiological processes via serotonin (5-HT) signaling. Dysregulation of this system contributes to inflammatory bowel diseases, characterized by chronic inflammation and disrupted intestinal function. We evaluated the impact of bLf on the intestinal serotonergic system <em>in vitro</em> and <em>in vivo</em>. In Caco-2/TC7 cells, bLf treatment enhanced serotonin transporter (SERT) activity and mRNA expression and modulated the mRNA levels of several serotonin receptors (5-HTRs). In mice, oral bLf administration upregulated SERT, tryptophan hydroxylase 2 (TPH2), and 5-HTRs mRNA expression in the ileum. Moreover, in a dextran sodium sulphate (DSS)-induced colitis model, bLf attenuated clinical signs of colonic inflammation, while normalizing the mRNA expression of SERT, TPH1, TPH2, and 5-HTRs in colon. These findings highlight the ability of bLf to modulate key components of the intestinal serotonergic system under both physiological and inflammatory conditions. Given the leading role of serotonin in gut-brain axis and immune regulation, bLf emerges as a promising functional food ingredient with potential for preventing or managing intestinal inflammation. Further exploration of its dietary applications may support the development of innovative nutritional strategies targeting gut-related disorders.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110073"},"PeriodicalIF":4.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847164","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":"Inhibition of advanced glycation end-products by the vitamin B6 vitamer pyridoxamine prevents systemic and skeletal muscle diet-induced metaflammation through modulation of S1P/RhoA/ROCK signalling","authors":"Patricio I. Rivas Navarrete ,&nbsp;Debora Collotta ,&nbsp;Federica Dal Bello ,&nbsp;Alessia S. Cento ,&nbsp;Manuela Aragno ,&nbsp;Massimo Collino ,&nbsp;Raffaella Mastrocola","doi":"10.1016/j.jnutbio.2025.110068","DOIUrl":"10.1016/j.jnutbio.2025.110068","url":null,"abstract":"<div><div>The typical western diet contributes to the accumulation of Advanced Glycation End-products (AGEs), reactive compounds involved in metabolic alterations and low-grade inflammation, referred as metaflammation. AGEs affect sphingolipid metabolism increasing sphingosine-1-phosphate (S1P). S1P is in turn induces pro-inflammatory M1 macrophage polarization through activation of RhoA/ROCK. The current study seeks to determine whether inhibition of AGEs by the antiglycating vitamin B6 analog pyridoxamine prevents metaflammation via modulation of S1P/RhoA/ROCK signalling. Gastrocnemius muscle was obtained from mice fed a standard diet (SD) or a western diet (WD), supplemented or not with pyridoxamine (WD+PYR, 150mg/kg bw/day). Metabolic and inflammatory profiles have been investigated in plasma, while accumulation of AGE-modified proteins, expression of RAGE, S1P-synthesizing enzymes and S1P receptors, as well as activation of RhoA/ROCK/IRS-1 pathway have been analysed in gastrocnemius muscle. Markers of local inflammatory cells infiltration and macrophage polarization were also explored. In comparison to SD mice, WD mice developed obesity, glucose intolerance, and muscle lipid accumulation with increased plasma proinflammatory cytokines and muscle M1-polarized macrophage infiltration. WD mice muscle showed higher content of AGE-modified proteins with increased S1P synthesis and S1PR1 expression, paralleled by activation of RhoA/ROCK and impairment of insulin signalling. By inhibiting AGEs production through pyridoxamine supplementation, all the WD-induced metabolic and inflammatory signalling alterations were significantly reversed towards the SD state. The present findings confirm a relevant role for AGE/S1P/RhoA/ROCK signalling in diet-induced metaflammation, suggesting the formulation of pharmacological and nutraceutical tools to prevent AGEs accumulation as a useful strategy against obesity-related metabolic and inflammatory diseases.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110068"},"PeriodicalIF":4.9,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835359","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":"Application of AI-assisted methodology to evaluate diet and ingredient formulations for rodent models in nutrition and health research","authors":"Bruce A. Watkins ,&nbsp;Jeremy R. Watkins ,&nbsp;Andrew C. Shin ,&nbsp;Guodong Zhang ,&nbsp;Eleonora Cremonini ,&nbsp;Surya Raj Niraula ,&nbsp;Robert B. Rucker","doi":"10.1016/j.jnutbio.2025.110046","DOIUrl":"10.1016/j.jnutbio.2025.110046","url":null,"abstract":"<div><div>The use of Artificial Intelligence (AI) for peer review is gaining interest by journals and editorial boards because of the length of time required for the scientific peer review process and large numbers of new submissions. The application of AI using a large language model (LLM) like OpenAI’s ChatGPT is a valid, rapid means to search published articles that examine diets in rodent studies. The information gathered can be used to evaluate rodent diets and nutrients during peer review or in developing studies and preparing appropriate experimental designs for future nutrition and biomedical research with rodents. However, it is vital that AI be used only to supplement and assist the human process of peer review and the final decision for publication. The use of ChatGPT has great potential to improve scientific peer review and assist researchers in developing experimental designs for nutrition research. The target of our AI application is improving understanding of why dietary and ingredient effects impact the interpretation of findings in metabolism, biochemistry, molecular and gene expression, physiology, health, and disease research in rodents. AI application with LLM validating diet approaches used in rodent studies can complement the human peer review process of scientific journals.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110046"},"PeriodicalIF":4.9,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821661","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":"Syncytin-1 deficiency impairs placental nutrient transport via PI3K/Akt/mTOR signaling","authors":"Xue-ling Chen ,&nbsp;Xing-xing Gong ,&nbsp;Zhe-lei Xiong ,&nbsp;Da Zhou ,&nbsp;Ju Yang ,&nbsp;Hai-feng Zhang ,&nbsp;Yun-shan Xue ,&nbsp;Ya-nan Wang ,&nbsp;Hai-bin Chen","doi":"10.1016/j.jnutbio.2025.110060","DOIUrl":"10.1016/j.jnutbio.2025.110060","url":null,"abstract":"<div><div>The placenta, a vital organ bridging the fetus and mother, governs nutrient exchange. Syncytin-1, an endogenous retroviral envelope protein specifically expressed in placental trophoblasts, is diminished in preeclampsia and fetal growth restriction. This study aimed to investigate the effects of low syncytin-1 expression on placental transport of amino acids, fatty acids and cholesterol, and its implications for fetal and placental development, contributing to fetal growth restriction pathogenesis. Pregnant C57BL/6J mice received tamoxifen-induced conditional <em>syncytin-a</em> gene knockout at embryonic day 11.5, with controls receiving sunflower oil. Placentas and fetuses were collected and analyzed for transport efficiency. Parallelly, siRNA-mediated syncytin-1 knockdown in BeWo cells assessed trophoblast dysfunction. Nutritional content and the expression of relevant transporters for amino acids, fatty acids and cholesterol, were all evaluated in <em>vivo</em> and in <em>vitro</em>. Using conditionally induced <em>syncytin-a</em> gene knockout mouse models, we found that syncytin-A deficiency resulted in decreased fetal and placental weights, reduced placental labyrinthine layer area and syncytiotrophoblast layer structural defects. Placental amino acid (SNAT2, LAT1), fatty acid (CD36, FABP4, FATP4), and cholesterol (LDLR, SR-B1) transporters were dysregulated, aligning with altered nutrient levels in knockout mice. Similar dysfunction in amino acid and fatty acid transport was observed in syncytin-1-silenced BeWo cells. Mechanistically, syncytin-1 deficiency suppressed the PI3K/Akt/mTOR signaling, a key pathway modulating nutrient sensing and transporter activity. Our experiments demonstrate that syncytin-1 regulates the transport of amino acids, fatty acids and cholesterol in placental trophoblastic cells, providing new insights into the pathological role of decreased syncytin-1 in pregnancy-related disorders, particularly in fetal growth restriction.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110060"},"PeriodicalIF":4.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816908","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":"Madecassoside and madecassic acid mitigates diabetic nephropathy via podocyte autophagy and gut microbiota in mice","authors":"Yinhua Ni ,&nbsp;Haimei Du ,&nbsp;Xinqing Wu ,&nbsp;Yuxiang Pan ,&nbsp;Wenlong Yang ,&nbsp;Liujie Zheng ,&nbsp;Yifan Zheng ,&nbsp;Haojie Jin ,&nbsp;Zhengwei Fu ,&nbsp;Cheguo Cai ,&nbsp;Juan Jin ,&nbsp;Qiang He","doi":"10.1016/j.jnutbio.2025.110061","DOIUrl":"10.1016/j.jnutbio.2025.110061","url":null,"abstract":"<div><div>Diabetic nephropathy (DN) is a common microvascular complication of diabetes with limited treatment options available. Madecassoside (MA) and madecassic acid (MCA) exhibit various pharmacological activities, while their effects on DN remain elusive. Here, we found that MA and MCA treatment mitigated insulin resistance, alleviated metabolic disorders, and attenuated systemic inflammation in high-fat diet- and streptozotocin-induced DN mice. In addition, MA and MCA administration alleviated the biochemical indicators for kidney function and reduced renal inflammation and fibrosis, thereby mitigating the progression of DN. These renal protective effects were partly mediated by the activation of podocyte autophagy. Moreover, MA and MCA protected the integrity of the gut barrier and altered the microbial composition and their metabolites, resulting in an enrichment of beneficial bacteria and metabolites and a reduction of the pathogenic bacteria and harmful metabolites. Therefore, MA and MCA alleviated DN by activating podocyte autophagy and regulating microbiota dysbiosis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110061"},"PeriodicalIF":4.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812154","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}