Journal of Nutritional Biochemistry最新文献

{"title":"Molecular hydrogen mitigates acetaminophen-induced liver injury and enhances the effects of N-acetylcysteine in diabetic mice","authors":"Naomi Kamimura ,&nbsp;Katsuya Iuchi ,&nbsp;Tsutomu Igarashi ,&nbsp;Ikuroh Ohsawa ,&nbsp;Chikako Nito ,&nbsp;Jitsuo Usuda ,&nbsp;Shigeo Ohta","doi":"10.1016/j.jnutbio.2025.110176","DOIUrl":"10.1016/j.jnutbio.2025.110176","url":null,"abstract":"<div><div>Acetaminophen (APAP) overdose induces severe liver injury, especially in diabetic patients. <em>N</em>-acetylcysteine (NAC) is commonly used as an approved antidote for APAP toxicity; however, its narrow therapeutic window limits its clinical utility. This study investigated the protective effects of molecular hydrogen (H₂) against APAP-induced hepatotoxicity in diabetic mice. Diabetic <em>db/db</em> mice were provided with hydrogen-dissolved water (H₂-water) for two weeks prior to APAP administration. Consumption of H₂-water significantly attenuated APAP-induced liver injury, as evidenced by improved histological findings and decreased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Using transgenic mice expressing redox-sensitive green fluorescent protein, H₂ was shown to reduce both cytosolic and mitochondrial oxidative stress caused by APAP overdose. We observed that H₂ modulated c-Jun N-terminal kinase (JNK) activation, inhibited mitochondrial translocation of Bax, and suppressed the release of mitochondrial endonucleases. Additionally, H₂ enhanced the expression of the hepatoprotective hormone fibroblast growth factor 21 (FGF21). These findings suggest that H₂ protects against APAP-induced liver injury in diabetic mice by attenuating oxidative stress and upregulating FGF21 expression. Although NAC acts as an antioxidant, H₂ was more effective in reducing mitochondrial oxidative stress. Importantly, co-treatment with H₂ and NAC provided greater protection against APAP-induced hepatotoxicity than NAC alone. This synergistic effect may result from differences in the mechanisms by which NAC and H₂ influence FGF21 expression and mitochondrial oxidative stress. The combination of H₂ and NAC may offer an improved therapeutic strategy for treating APAP-induced liver injury in diabetic patients.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"149 ","pages":"Article 110176"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482507","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":"Inducible trophoblast-specific knockdown of mechanistic target of rapamycin impairs placental folate transport in mice","authors":"Hiroshi Shimada ,&nbsp;Johann Urschitz ,&nbsp;Theresa L Powell ,&nbsp;Thomas Jansson ,&nbsp;Fredrick J Rosario","doi":"10.1016/j.jnutbio.2025.110189","DOIUrl":"10.1016/j.jnutbio.2025.110189","url":null,"abstract":"<div><div>Folate deficiency in pregnancy is strongly associated with fetal growth restriction (FGR). Fetal folate availability is determined by maternal folate intake and the capacity of the placenta to transport folate. However, the mechanisms regulating placental folate transport remain poorly understood. The mechanistic target of rapamycin (mTOR) regulates placental function and fetal growth, but it is unknown if mTOR regulates folate transport <em>in vivo.</em> We hypothesized that trophoblast-specific mTOR knockdown inhibits placental folate transport in mice. We generated transgenic mice with a doxycycline-inducible, trophoblast-specific <em>Mtor</em> knockdown using PiggyBac transposase-enhanced pronuclear injection. Doxycycline administration on embryonic day (E) 14.5 induced placental-specific <em>Mtor</em> knockdown, resulting in reduced fetal weight, placental weight, and fetal-to-placental weight ratio. Functionally, mTOR knockdown reduced folate uptake in isolated trophoblast plasma membranes (TPM), decreased the TPM protein expression of the three main placental folate transporters (FRα, RFC, and PCFT) without affecting protein expression of theses transporters in placental homogenates, and lowered fetal plasma folate concentration. In conclusion, mTOR signaling is a positive regulator of the three main placental folate transporters <em>in vivo</em> mediated by posttranslational mechanisms, likely involving effects of plasma membrane trafficking. Trophoblast mTOR signaling is essential for maintaining adequate fetal folate supply and we propose that the inhibition of placental mTOR signaling reported in FGR contributes to fetal folate deficiency and decreased fetal growth in this pregnancy complication. Our data supports the potential to target placental mTOR signaling as a novel intervention in pregnancies affected by abnormal fetal growth.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"149 ","pages":"Article 110189"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557089","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":"Zinc, Fe2+, and Fe3+ differentially influence IFN-γ production in human peripheral blood mononuclear cells","authors":"Evelyn Fast ,&nbsp;Jana Jakobs ,&nbsp;Jens Bertram ,&nbsp;Inga Weßels ,&nbsp;Judith Sailer ,&nbsp;Bernhard Michalke ,&nbsp;Lothar Rink","doi":"10.1016/j.jnutbio.2025.110194","DOIUrl":"10.1016/j.jnutbio.2025.110194","url":null,"abstract":"<div><div>Iron overload is a common phenomenon in patients undergoing transfusions or organ transplantation. Clinical studies indicate that iron overload interferes with immune function. Baseless supplementation of iron leads to higher morbidity and mortality. In iron overload T-cell differentiation is skewed towards a Th2 response, with lower levels of interferon (IFN)-γ. Zinc is known for its immune balancing abilities, e.g., by induction of regulatory T cells. This study aims to investigate the interaction of iron and zinc in mixed lymphocyte cultures (MLC). MLC, peripheral blood mononuclear cells (PBMC) stimulation with phytohemagglutinin, ELISA, PCR, and ICP-MS were used as methods. Zn²⁺ supplementation leads to a significantly lower IFN-γ production in MLC compared with control (<em>P</em>&lt;.03). Fe²⁺ supplementation lowers the IFN-γ production in MLC (<em>P</em>&lt;.0017), too. However, Fe³⁺ has a slightly increasing effect on IFN-γ release which differs significantly from Fe²⁺ (<em>P</em>&lt;.03). In 2,2-Bipyridyl-induced iron deficiency IFN-γ production is lowered (<em>P</em>&lt;.0003), whereas zinc deficiency does not significantly affect IFN-γ production. Examinations of Interleukin (IL)-2 and IL-6 show comparable tendencies. The Fe²⁺ effect can be imitated by sodium sulfite. Fe³⁺ treatment increases intracellular free iron in peripheral blood mononuclear cells (PBMC) significantly compared to Fe²⁺ treatment (<em>P</em>&lt;.02). Iron (II) and zinc both suppress cytokine production in MLC. Fe³⁺ shows a significantly different effect on IFN-γ production. The underlying mechanism is likely a donation of electrons by Fe²⁺ or oxidative stress. These findings provide mechanistic insights on how the oxidation state of iron differentially modulates human immune cell function and highlights the importance of iron speciation in nutritional immunology.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"149 ","pages":"Article 110194"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634797","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":"Fermented foods and brain health: Gut–brain axis mechanisms and clinical insights","authors":"Mahmut Bodur ,&nbsp;Betül Kocaadam-Bozkurt ,&nbsp;Osman Bozkurt ,&nbsp;Serkan Aslan ,&nbsp;Duygu Ağagündüz","doi":"10.1016/j.jnutbio.2025.110195","DOIUrl":"10.1016/j.jnutbio.2025.110195","url":null,"abstract":"<div><div>The gut-brain axis represents a complex bidirectional communication network connecting the central nervous and gastrointestinal systems. Fermented foods and their phenolic compounds, which increase their bioavailability due to microbial transformation in their contents, have the potential to affect the gut microbiota and therefore the gut-brain axis positively. Fermented foods such as kefir, yogurt, miso, natto, tempeh, kombucha, and their polyphenols have an effect on the gut microbiota and on the provision of neurological activities through neuroactive components that affect the nervous system. Phenolic compounds appear to have direct or indirect effects on brain tissue through various mechanisms such as reducing neuronal oxidative stress, suppressing microglial activation, supporting synaptic plasticity, and slowing down neurodegenerative processes such as Alzheimer's and Parkinson's. In addition, the polyphenol content enriched in fermented foods has been shown to exhibit psychobiotic effects in depression and anxiety models; it has been shown in clinical studies that it improves systemic inflammation and hypothalamic–pituitary–adrenal (HPA) axis dysfunction. Current data support the inclusion of fermented, polyphenol-rich foods as a noninvasive strategy to enhance neuroprotection and mental health. However, enhanced clinical studies are needed where heterogeneity in the fermentation process and dosage adjustment are standardized. This article reviews the current literature on the effects of fermented foods and polyphenols on brain health via the microbiota and gut-brain axis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"149 ","pages":"Article 110195"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634720","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":"Association of poor vitamin K status with inflammation and gut microbiota in hemodialysis patients: A cross-sectional study","authors":"Ligia Soares Lima ,&nbsp;Marcia Ribeiro ,&nbsp;Ludmila F.M.F. Cardozo ,&nbsp;Rudolf Bittner ,&nbsp;Marcelo Ribeiro-Alves ,&nbsp;Júnia Schultz ,&nbsp;Alexandre Soares Rosado ,&nbsp;Paulo Emilio Correa Leite ,&nbsp;Lia S. Nakao ,&nbsp;Leon J. Schurgers ,&nbsp;Denise Mafra","doi":"10.1016/j.jnutbio.2025.110139","DOIUrl":"10.1016/j.jnutbio.2025.110139","url":null,"abstract":"<div><div>Vitamin K insufficiency is common in chronic kidney disease (CKD) and may be associated with gut dysbiosis, which decreases the number of vitamin K-producing bacteria. This insufficient status worsens inflammation, leading to vascular calcification and oxidative stress. This study investigates the correlation between vitamin K status and gut microbiota composition, and its association with inflammation in hemodialysis (HD) patients. In this cross-sectional study, patients were grouped based on dephosphorylated-uncarboxylated matrix gla-protein (dp-ucMGP) levels: adequate (≤500 pmol/L) or inadequate (&gt;500 pmol/L) vitamin K status. Plasma cytokines were analyzed using a multiplex assay, and uremic toxins <em>via</em> reverse-phase high-performance liquid chromatography (RP-HPLC). Gut microbiota composition was assessed in a subgroup using fecal DNA extraction and 16S rRNA gene sequencing on the Illumina NovaSeq PE250 platform. Among 107 patients (53 [interquartile range=16] years and 36 [interquartile range=42] months on HD) completed the study, 70 patients (53 years, BMI, 24.2 Kg/m²) exhibited insufficient vitamin K status, and 37 patients presented adequate status (52.5 years, BMI, 25.6 Kg/m²). Patients with inadequate vitamin K status exhibited significantly higher levels of interleukin (IL)-6, IL-1β, granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) compared to patients with adequate status, reflecting elevated inflammatory marker levels in patients with insufficient vitamin K. Additionally, <em>Bacteroides</em>, a key vitamin K2-producing genus, was decreased in patients with inadequate vitamin K status. Gut dysbiosis is a consequence of CKD, which can result in reduced production of vitamin K and subsequent insufficient status. Additionally, inadequate vitamin K status may contribute to the inflammatory state in patients undergoing HD.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"148 ","pages":"Article 110139"},"PeriodicalIF":4.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238847","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":"Resveratrol improves idiopathic pulmonary fibrosis by targeting IKZF3","authors":"Shuai Liu ,&nbsp;Lixin Wang ,&nbsp;Yinyan Yue ,&nbsp;DongBo Ma ,&nbsp;Xiang Deng ,&nbsp;Yuanfang Wang ,&nbsp;Dongdong Wu ,&nbsp;Yang Wang ,&nbsp;Qiuge Wu","doi":"10.1016/j.jnutbio.2025.110082","DOIUrl":"10.1016/j.jnutbio.2025.110082","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with limited treatment options. This study investigates the therapeutic potential of resveratrol, a natural compound, in treating IPF by targeting IKZF3, a transcription factor upregulated in IPF patients. Using bioinformatics analysis of the GSE110147 dataset, we identified IKZF3 as a key molecule in IPF progression. In vitro experiments with bleomycin (BLM)-treated A549 cells showed that IKZF3 overexpression exacerbated cell death and fibrosis, while its silencing reversed these effects. Resveratrol treatment significantly improved cell viability, reduced fibrosis markers, and inhibited IKZF3′s transcriptional regulation of IL-33, which in turn decreased ILC-2 activation. Molecular docking revealed a strong binding affinity between resveratrol and IKZF3. <em>In vivo</em> validation using a BLM-induced IPF mouse model demonstrated that resveratrol reduced lung fibrosis and downregulated fibrosis-related markers. Our findings suggest that targeting IKZF3 with resveratrol may offer a novel therapeutic strategy for IPF, highlighting the potential of this combination to improve disease outcomes.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"148 ","pages":"Article 110082"},"PeriodicalIF":4.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957937","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":"Low perinatal caffeine intake alters offspring thyroid function in a sex- and age-dependent manner","authors":"Luana Lopes de Souza ,&nbsp;Rosiane Aparecida Miranda ,&nbsp;Iala Milene Bertasso ,&nbsp;Beatriz Souza da Silva ,&nbsp;Reinaldo Röpke-Junior ,&nbsp;Leandro Miranda-Alves ,&nbsp;Egberto Gaspar Moura ,&nbsp;Patricia Cristina Lisboa","doi":"10.1016/j.jnutbio.2025.110148","DOIUrl":"10.1016/j.jnutbio.2025.110148","url":null,"abstract":"<div><div>During perinatal period, some women limit caffeine intake to 300mg/day, following the WHO recommendation. Previously, using an animal model of low perinatal caffeine exposure, correspondent to 250mg/day for human, we observed a deleterious effect on thyroid hormone (TH), with low total T3 in dams and weaned male pups and high T3 in adult offspring of both sexes. The hypothesis of the present study is that this phenotype results from alterations in TH synthesis and metabolism. Pregnant Wistar rats received vehicle or caffeine (CAF, 25mg/kg/day) by gavage during gestation and lactation. We evaluated markers of TH synthesis in dams and offspring, such as gland morphology and mRNA expression. Here, at birth, CAF males presented higher total T4 (+96%; <em>P</em> &lt; .05) and unchanged total T3 and TSH. At weaning, CAF dams presented only lower TSH. CAF male offspring presented lower colloid area, CAF female offspring presented greater thyroid epithelial height, and both sexes presented unchanged mRNA expression of TH synthesis markers, such as thyroid stimulating hormone receptor (Tshr), sodium-iodine symporter (Nis), thyroperoxidase (Tpo), dual oxidase (Duox), NADP oxidase 2 (Nox2) and iodothyronine deiodinase 1 (Dio1). Adult CAF males presented greater epithelial area, downregulation of <em>Nis</em> mRNA expression, and higher hepatic Dio1 mRNA expression. However, CAF females presented higher TSH, although genes of TH synthesis were downregulated. Perinatal low caffeine exposure promotes temporal adaptive changes in the pituitary-thyroid axis, thyroid gland and peripheral TH metabolism of offspring, supporting our hypothesis. These modifications contribute to changes in TH levels in an age- and sex-dependent manner.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"148 ","pages":"Article 110148"},"PeriodicalIF":4.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313118","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":"Bioequivalence of docosahexaenoic acid intake to a novel estimate of the dietary alpha-linolenic acid requirement in growing rats using non-esterified oxylipins and fatty acids","authors":"Anne Manson ,&nbsp;Sandrius Mirochnikov ,&nbsp;Isabel Delgado Poveda ,&nbsp;Hiu Yan Chan ,&nbsp;Tanja Winter ,&nbsp;Harold M. Aukema","doi":"10.1016/j.jnutbio.2025.110144","DOIUrl":"10.1016/j.jnutbio.2025.110144","url":null,"abstract":"<div><div>Alpha-linolenic acid (ALA) is an essential <em>n</em>-3 fatty acid that can be converted to docosahexaenoic acid (DHA), which by itself can also meet the dietary <em>n</em>-3 fatty acid requirement. However, the amount of dietary DHA that is bioequivalent to ALA remains unknown. The study objective was to estimate the DHA dose that is equivalent to a recently proposed ALA requirement assessment, using non-esterified oxylipins and fatty acids. 168 male and female Sprague-Dawley rats received graded doses of dietary ALA (0.10–2.0 g/100 g diet) or DHA (0.07–1.3 g/100 g diet). All diets contained 2 g of linoleic acid/100 g diet and were based on the AIN93G. Non-esterified fatty acids and oxylipins were analyzed in serum, liver, heart, and brain by HPLC-MS/MS. Using piecewise regression, breakpoints were calculated for ALA diets using DHA/arachidonic acid (ARA) and hydroxy‑DHA/hydroxy‑ARA oxylipins (DHA_OH/ARA_OH). Breakpoints in serum and liver were highest and deemed most suitable to determine the dietary ALA requirement, with no differences between sexes or whether the DHA/ARA or DHA_OH/ARA_OH ratio was used. These breakpoints indicated an estimated average dietary ALA requirement of 0.55 g ALA/100 g diet (1.32% energy) 95% CI (0.42, 0.69), which is higher than what is provided by the AIN93G diet. DHA was ∼4–6 (mean ± SE: 4.74±0.22) times more effective than ALA, with 0.12 g DHA/100 g diet (0.28% energy) being equivalent to the 0.55 g ALA/100 g diet that meets the ALA requirement. Hence, dietary DHA is ∼5 times more effective than ALA in meeting the proposed dietary ALA requirement in the growing rat.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"148 ","pages":"Article 110144"},"PeriodicalIF":4.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313146","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":"Multi-omics analysis of ketogenic diet-mediated neural repair in spinal cord injury: Targeting of lysosomal autophagy through CTSB/LAMP2 regulation","authors":"Jiayu Chen ,&nbsp;Haoxin Lian ,&nbsp;Ruqin Guo ,&nbsp;Kai Chen ,&nbsp;Hao Ma ,&nbsp;Jiachen Yang ,&nbsp;Zhiping Huang ,&nbsp;Lijia Chen ,&nbsp;Kinon Chen ,&nbsp;Jie Liu ,&nbsp;Qing’an Zhu ,&nbsp;Junhao Liu ,&nbsp;Hui Jiang ,&nbsp;Zucheng Huang","doi":"10.1016/j.jnutbio.2025.110152","DOIUrl":"10.1016/j.jnutbio.2025.110152","url":null,"abstract":"<div><div>Spinal cord injury (SCI) initiates secondary pathologies characterized by dysregulated autophagy and neuroinflammation Although the ketogenic diet (KD) has shown potential in promoting functional recovery after SCI, the mechanisms underlying KD-mediated neural repair remain unclear. We employed an integrated multi-omics approach combining 4D proteomics, transcriptomics, and single-cell RNA sequencing in a C5 hemi-contusion mouse model. This was combined with in vitro validation using β-hydroxybutyrate (β-OHB)-treated BV2 microglia cells to investigate KD’s effects on lysosome-mediated autophagy and microglial dynamics. Behavioral assessments and histopathological analyses were conducted over acute to chronic phases, spanning from 0 to 8 weeks post-injury. KD attenuated maladaptive lysosomal activation by downregulating cathepsin B (CTSB) and lysosomal-associated membrane protein 2 (LAMP2). This suppression concurrently reduced pro-inflammatory cytokines levels (IL-1β, TNF-α, IL-6) while facilitating M2 microglia polarization. Proteomic analysis identified 73 proteins responsive to KD that are associated with endoplasmic reticulum stress and chaperone-mediated autophagy. Single-cell transcriptomics revealed co-upregulation of CTSB and LAMP2 in injury-associated microglia subpopulations. Importantly, β-OHB partially replicated the effects of KD in vitro, reducing autophagy hyperactivity and enhancing M2 polarization. By targeting CTSB/LAMP2 axis, KD orchestrates dual neuroprotective mechanisms: lysosomal homeostasis restoration and immunomodulatory reprogramming. This coordinated action reconciles proteostatic regulation with microglial M1/M2 polarization dynamics, establishing KD as a multimodal metabolic intervention capable of simultaneously addressing autophagy dysregulation and neuroinflammation following SCI. These findings hold significant translational potential for neurotrauma management.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"148 ","pages":"Article 110152"},"PeriodicalIF":4.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337155","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":"Iron homeostasis: effects of different levels of protein iron on placental iron handling in sows","authors":"Deyuan Wu ,&nbsp;Jiawei Nie ,&nbsp;Shijian Zhou ,&nbsp;Liudan Liu ,&nbsp;Lili Wang ,&nbsp;Songfeng Yang ,&nbsp;Jie Peng ,&nbsp;Chengquan Tan","doi":"10.1016/j.jnutbio.2025.110141","DOIUrl":"10.1016/j.jnutbio.2025.110141","url":null,"abstract":"<div><div>Pregnant sows suffer from iron deficiency; however, excessive iron supplementation can induce tissue damage through ferroptosis. This study aimed to identify the optimal iron supplementation dose for gestating sows and investigate the mechanisms underlying iron deficiency and overdose, which contribute to reduced reproductive performance in sows. 84 sows with similar farrowing times were selected and stratified by body weight at day 85 of gestation. They were randomly assigned to one of three dietary treatments (<em>n</em>=28 per treatment): basal diet (L-Iron), basal diet supplemented with 0.13% protein iron (N-Iron) or 0.27% protein iron (H-Iron). Obviously, the rate of live-born piglets and placental vascular development in the N-Iron group were significantly higher than those in the <span>l</span>-Iron and H-Iron groups. Further analysis revealed that the expression levels of Transferrin (TF) and Transferrin receptor 1(TFR1) in the placenta of the H-Iron group were significantly reduced, while the expression levels of ferritin and nuclear receptor coactivator 4 were significantly increased. Importantly, the expression levels of lipid peroxidation and inflammatory markers such as lysophosphatidylcholine acyltransferase 3 and tumor necrosis factor-α were also significantly increased in the H-Iron group. In summary, our results indicate that supplementation of iron at an appropriate dose in iron-deficient pregnant sows promotes iron transfer between the sow and piglets and supports placental vascularization. Conversely, excessive iron supplementation leads to iron accumulation in the placenta, causing lipid peroxidation and mitochondrial damage, ultimately reducing the number of liveborn piglets.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"148 ","pages":"Article 110141"},"PeriodicalIF":4.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280461","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}