Journal of Nutritional Biochemistry最新文献

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. 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.

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 in vivo 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.

It is recognized that excessive dietary salt intake is a critical factor contributing to chronic kidney disease (CKD). A high-salt diet (HSD) disrupts the balance of the gut microbiota, but the molecular mechanisms linking gut dysbiosis to target organ damage remain unclear. This study identified dietary prebiotic inulin (INU) as a potent regulator of the gut-short-chain fatty acid-kidney axis, capable of counteracting HSD-induced CKD. Sequencing analysis showed that INU selectively enriched Bifidobacterium and Faecalibaculum while downregulating Desulfovibrio. This microbiome shift restored intestinal tight junction proteins and reduced serum lipopolysaccharide (LPS) levels, thereby inhibiting TLR4/NF-κB-mediated renal inflammation. Notably, the effects of direct SCFA supplementation align with the renal protective effects of INU, confirming the critical role of the gut-kidney axis. Our study reveals INU as a dietary strategy that combats HSD-induced CKD via SCFAs produced by the microbiota, offering new insights into the gut-SCFAs-kidney axis as a therapeutic target.

Cardiac microvascular damage exhibits a significant association with myocardial ischemia/reperfusion injury (MI/RI) development, which correlates with mitochondrial dysfunction. Lycopene has demonstrated pharmacological efficacy against cardiovascular diseases. Nevertheless, the potential roles and underlying mechanisms through which lycopene influences MI/RI remain incompletely understood. This study aimed to investigate the effect of lycopene on cardiac microvascular endothelial cell (CMEC) function in a rat model of MI/RI. This investigation sought to elucidate lycopene's role in MI/RI and its mechanistic foundation. A rat MI/RI model was employed, and multiple experimental approaches were conducted, encompassing quantitative real-time polymerase chain reaction, Western blot analysis, immunofluorescence microscopy, enzyme-linked immunosorbent assay, molecular docking, and molecular dynamics simulations. In vitro studies involved the establishment of a hypoxia-reoxygenation model using CMECs to evaluate lycopene's contribution to pyroptosis suppression and mitochondrial dysfunction prevention. Lycopene was found to enhance mitochondrial function through inhibition of the YTHDF1/E2F8/FABP3 axis in CMECs, suppress cGAS-STING signaling pathway activation, reduce cellular inflammatory responses, and inhibit cellular pyroptosis. These effects ultimately resulted in improved CMEC function, enhanced microvascular integrity, and increased perfusion and oxygen delivery to cardiomyocytes.

Background: Breastfeeding promotes improved growth and development in preterm infants, yet the mechanisms underlying these benefits remain unclear.

Objective: This study explored the interplay of breast-milk nutritional, microbiological, and environmental chemical exposure on early preterm infant growth.

Methods: In the prospective LACTACOL-cohort, growth was assessed in 137 exclusively breastfed preterm infants (including 40 twins) using Z-scores of discharge weight and fat-free mass (FFM, by air-displacement plethysmography). Breast-milk samples were analyzed for their nutriome (targeted and untargeted metabolomic and lipidomic profiling), exposome (targeting persistent organic pollutants, POPs), and microbiome (16s rRNA-sequencing). Correlation analysis and sequential random forest modelling were applied to integrate multi-omics datasets and identify determinants of discharge weight Z-score (36 observations) and FFM (21 observations).

Results: The nutriome emerged as the primary contributor to the postnatal growth in preterm infants. Choline-containing lipids (sphingolipids, phosphatidylcholines and their plasmalogen forms), positively contributed to weight Z-score. Sphingomyelin enriched in nervonic acid supported positively FFM Z-score, whereas oxylipins had a negative effect. The exposome exhibited complex effects: the dioxin-like compound 1,2,3,7,8-PeCDD negatively impacted weight, while the polychlorinated biphenyl 123 positively influenced both weight and lean mass gains. Brominated flame retardants were associated with a lower FFM Z-score. Although the microbiome showed an overall minor impact, it varied with POPs and postnatal growth terciles, highlighting the co-dependencies between milk components.

Conclusions: This integrative hypothesis-generating pilot study provides novel evidence on the richness of breast-milk composition and the interplay of nutriome, exposome, microbiome in breast-milk and their joint influence on postnatal growth in preterm infants.

Clinical trial registry: LACTACOL, ClinicalTrials.gov ID NCT NCT01493063 https://clinicaltrials.gov/study/NCT01493063.

Diet-induced thermogenesis (DIT), a critical component of energy expenditure driven by brown adipose tissue (BAT), is essential for maintaining metabolic health; however, its precise molecular regulation remains poorly understood. We investigated whether Serum Amyloid A3 (SAA3), a factor secreted by brown adipocytes, regulates DIT and protects against diet-induced obesity. Using two distinct mouse models: mice with brown adipocyte-specific Saa3 deletion and mice with lentiviral-mediated Saa3 overexpression in BAT, we examined energy expenditure (EE), substrate utilization, and thermogenic responses under chow or short-term high-fat diet (HFD) feeding. SAA3 expression in BAT was acutely induced by refeeding. Loss of SAA3 severely diminished postprandial DIT and total EE, leading to accelerated weight gain on an HFD. Mechanistically, Saa3 deletion compromised UCP1 induction, chiefly by impairing ATGL-driven lipolysis and, critically, by inhibiting Carnitine Palmitoyltransferase 1A (CPT1A)-dependent fatty acid oxidation (FAO). Conversely, SAA3 overexpression robustly enhanced DIT, stimulated lipolysis and FAO, and promoted mitochondrial oxidative phosphorylation. Studies in primary brown adipocytes confirmed that SAA3 deficiency reduced CPT1A expression, palmitate-stimulated lipolysis, and mitochondrial respiration. Together, these findings identify the SAA3-CPT1A axis as a novel, BAT-intrinsic mechanism that couples nutrient sensing to UCP1 function via enhanced FAO. By promoting lipid utilization and postprandial energy dissipation, SAA3 optimizes postprandial thermogenesis and defends against obesity, highlighting conserved SAA signaling as a potential nutritional and therapeutic target in metabolic disease.

Vitamin E, strictly defined as α-tocopherol, exhibits a complex dual role in cancer pathogenesis through its context-dependent pro-oxidant and antioxidant activities. Other members of the tocopherol and tocotrienol families (collectively referred to as tocols) have also been extensively studied for their bioactivities. At physiological levels, certain tocols such as γ-tocopherol and δ-tocotrienol act as potent antioxidants by neutralizing reactive oxygen species, inhibiting lipid peroxidation, and activating NRF2-mediated defenses, thereby suppressing tumor initiation, proliferation, and metastasis in models of colon, breast, and prostate cancers. On the contrary, under conditions such as high concentration of vitamin E in plasma, metabolic dysregulation, and the presence of transition metals (e.g., Cu²⁺), or specific genetic backgrounds, vitamin E exerts pro-oxidant effects. However, such effects are relatively rare and more often documented in vitro than in vivo. These include promoting reactive oxygen species generation, reducing p53 expression, enhancing angiogenesis, and facilitating cancer cell survival-ultimately driving tumor progression and metastasis. Critically, vitamin E modulates ferroptosis, a regulated cell death pathway pivotal in cancer; it inhibits ferroptosis via GPX4 upregulation and NRF2 activation but may paradoxically promote it in certain settings. Clinical studies highlight isomer-specific outcomes, with tocotrienols showing promise in adjuvant therapy. The dichotomy hinges on dosage, cellular microenvironment, redox balance, and vitamin E isoform. Overall, the biological impact of vitamin E is highly context-dependent, influenced by dosage, cellular microenvironment, redox status, and the specific tocol studied. Future research must prioritize isoform-specific mechanisms, optimal dosing strategies, and interactions with conventional therapies to harness vitamin E and related tocols's anticancer potential while mitigating risks.

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.