Background: Hypertension is closely associated with excessive sodium intake, and low-sodium salt has been shown to lower blood pressure. However, whether low-sodium salt interacts with genetic variation related to salt sensitivity of blood pressure is unclear. Methods: A total of 259 hypertensive patients who completed the previous 3 years of a low-sodium salt vs. normal salt intervention were included in our study. Genetic risk scores (GRSs) of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were respectively built for each participant. A general linear regression model and a generalized mixed model were applied to identify the interaction effects between low-sodium salt intervention and ENaC genetic variation on SBP/DBP changes and trajectories over 3 years. Findings: during the 3-year intervention, both SBP and DBP levels showed a significant decline in the low-sodium salt intervention group than those in the normal salt intervention group over 3 years (Psalt intervention group = 0.001 for SBP and Psalt intervention group = 0.006 for DBP). Furthermore, a gene-diet interaction was found for the SBP change trajectory over 3 years (PSBP-GRS×salt intervention group = 0.011); specifically, significant SBP reductions were found between salt intervention groups in the high SBP-GRS group (-18.77 vs. -9.58 mmHg, Psalt intervention group = 0.001), but not in the low SBP-GRS group (-15.71 vs. -14.62 mmHg, Psalt intervention group = 0.791). No interaction effect between low-sodium salt intervention and genetic variation of ENaC was found for changes in DBP. Conclusions: Higher ENaC genetic variation is associated with a greater reduction in SBP in response to a low-sodium salt intervention. Hypertensive patients with higher ENaC genetic variation may experience a greater benefit in SBP reductions by consuming low-sodium salt. (Trial registration: chiCTR-TRC-09000538, https://www.chictr.org.cn).

Selenoprotein M (SelM), a key thioredoxin like enzyme in the endoplasmic reticulum (ER), is closely related to hepatocyte degeneration. However, the role of miR-138-5p/SelM and necroptosis in chicken SelM-deficient hepatitis and the specific biological mechanism of liver inflammation caused by SelM deficiency have not been elucidated. We established an in vivo chicken liver Se deficiency model by feeding a low-Se diet. The miR-138-5p knockdown and overexpression models and SelM knockdown models were established in LMH cells for an in vitro study. Transmission electron microscopy, H&E staining, Fluo4-AM/ER staining, and flow cytometry were used to detect the morphological changes in chicken liver tissue and the expression changes of necroptosis and inflammation in chicken liver cells. We observed that Se deficiency resulted in liver inflammation, up-regulation of miR-138-5p expression and down-regulation of SelM expression in chickens. Oxidative stress, Ca2+ overload, energy metabolism disorder and necroptosis occurred in chicken liver tissue. Importantly, ROS and the Ca2+ inhibitor could effectively alleviate the energy metabolism disorder, necroptosis and inflammatory cytokine secretion caused by miR-138-5p overexpression and SelM knockdown in LMH cells. In conclusion, selenium deficiency causes hepatitis by upregulating miR-138-5p targeting SelM. Our research findings enrich our knowledge about the biological functions of SelM and provide a theoretical basis for the lack of SelM leading to liver inflammation in chickens.

Alzheimer's disease (AD) is a common neurodegenerative disease worldwide and is accompanied by memory deficits, personality changes, anxiety, depression, and social difficulties. For treatment of AD, many researchers have attempted to find medicinal resources with high effectiveness and without side effects. Oligonol is a low molecular weight polypeptide derived from lychee fruit extract. We investigated the effects of oligonol in 5 × FAD transgenic AD mice, which developed severe amyloid pathology, through behavioral tests (Barnes maze, marble burying, and nestle shredding) and molecular experiments. Oligonol treatment attenuated blood glucose levels and increased the antioxidant response in the livers of 5 × FAD mice. Moreover, the behavioral score data showed improvements in anxiety, depressive behavior, and cognitive impairment following a 2-month course of orally administered oligonol. Oligonol treatment not only altered the circulating levels of cytokines and adipokines in 5 × FAD mice, but also significantly enhanced the mRNA and protein levels of antioxidant enzymes and synaptic plasticity in the brain cortex and hippocampus. Therefore, we highlight the therapeutic potential of oligonol to attenuate neuropsychiatric problems and improve memory deficits in the early stage of AD.

Diet is an important source of perfluoroalkyl and polyfluoroalkyl substance (PFAS) exposure, and the dietary inflammatory index (DII) is a tool used to assess the inflammatory potential of an individual's diet. However, limited research has explored the association between the DII and PFAS exposure in humans. This study is the first to analyze the association between the five PFASs and DII using the National Health and Nutrition Examination Survey (NHANES) 2007-2018 database. Additionally, we assessed the interaction between the DII and PFASs regarding oxidative stress and inflammatory markers, including alkaline phosphatase, albumin, neutrophil count, lymphocyte count, total bilirubin, and serum iron based on a previous study. A series of covariates were included in the analysis to reduce the confounding bias. The study included 7773 and 5933 participants based on the different models. The DII was significantly associated with serum perfluorooctanoic acid, perfluorononanoic acid, perfluorooctane sulfonic acid, and sum-PFAS. Some of the food parameters used to calculate the DII also showed associations with special PFAS serum concentrations. Specifically, dietary fiber, n-3 polyunsaturated fatty acids, energy intake, and vitamin D were associated with more than three PFASs. Higher DII levels in participants were linked to a more significant association between bilirubin (the interaction P-value is not significant), alkaline phosphatase, serum iron, neutrophil counts, and some PFASs. In conclusion, this study clarified the association between the three PFASs and DII, highlighting the diverse effects of PFASs on oxidative stress and inflammatory markers across different DII levels.

The impact of food on immune functions has been recognized for centuries and is now being increasingly explored for therapeutic applications. Rice, in addition to being the staple food in most developing countries, exhibits diverse complexities of phytochemicals among its wide germplasm repertoire, which supports its development as a functional food. In the present study, we have explored the immunomodulatory properties of Gathuwan rice, a local rice variety grown in Chhattisgarh, India, and traditionally used for the treatment of rheumatism. Methanolic Gathuwan Brown Rice Extract (BRE) inhibits T-cell activation and proliferation and cytokine secretion (IL-2, IL-4, IL-6 and IFN-γ) without inducing cell death. BRE exhibits radical scavenging activity in a cell-free system and decreases intracellular reactive oxygen species (ROS) and glutathione levels in lymphocytes. BRE induces nuclear translocation of the immune-regulatory transcription factor Nrf2 via activation of ERK and p-38 MAP kinase and up-regulates the expression of Nrf2-dependent genes (SOD, CAT, HO-1, GPx and TrxR) in lymphocytes. BRE treatment had no effect on cytokine secretion by lymphocytes from Nrf2 knockout mice, confirming the role of Nrf2 in the immunosuppressive effects of BRE. Feeding of Gathuwan brown rice to mice had no effect on the basal haematological parameters, but lymphocytes isolated from these mice were hypo-responsive to mitogenic stimuli. Treatment of allografts with BRE significantly prevented graft-versus-host disease (GVHD)-associated mortality and morbidity in mice. Metabolic pathway enrichment analysis of ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) data revealed a high enrichment ratio of amino acid and vitamin B metabolism pathways, and among metabolite sets, pyridoxamines, phytosphingosines, hydroxybenzaldehydes, hydroxycinnamic acids and indoles were highly enriched bioactive components. In conclusion, Gathuwan BRE suppresses T-cell-mediated immune responses by altering the cellular redox balance and activating the Nrf2 signalling pathway.

High-fat diet (HFD) consumption can induce intestinal barrier dysfunction and disrupt glucose metabolism. Our previous studies have demonstrated that polysaccharides obtained from the fruits of Lycium barbarum L. (LBPs) could suppress acute experimental diabetes as well as colitis in mice. In the present study, the modulating effects of a purified fraction of LBPs, named LBPs-4, on glucose homeostasis and intestinal barrier function in mice fed with a HFD were investigated. Our results indicated that the oral administration of LBP-4 (200 mg per kg per day) improved hyperglycemia, glucose intolerance, insulin resistance and islet β-cell hyperplasia in HFD-fed mice. Moreover, LBPs-4 intervention enhanced the intestinal barrier integrity by increasing the expression levels of zonula occludens 1 and claudin-1 and the number of goblet cells in the colon. LBPs-4 also modulated the composition of gut microbiota by increasing the relative abundances of butyrate producer Allobaculum and acetate producer Romboutsia. The results of fecal transplantation experiments, transferring of microbiota from LBPs-4-fed donor mice to HFD-fed recipient mice, validated the cause-effect relationship between LBPs-4-evoked changes in the gut microbiota and improvement of glucose homeostasis and intestinal barrier function. Collectively, these findings suggested that LBPs-4 might be developed as promising prebiotics to improve glucose metabolism and gut health.

Mammalian milk proteins are known to encrypt antimicrobial peptides (AMPs) which can be passively released and exert bioactivity in the gastrointestinal and cardiovascular systems pre- or post-absorption, respectively. However, the contribution of 'passive' food-derived AMPs to the pool of endogenous and microbial AMPs has not been differentiated in previous research. Insight into the consequences of protein digestion and peptide bioactivity can be gained using in silico tools. The aim of this investigation was to use in silico methods to characterise the yields of AMPs released from major proteins in human and cow milk under infant digestion conditions, as relevant to early nutrition. The profiles of major proteins in human and cow milk from UniProtKB/Swiss-Prot, were subjected to in silico digestion by ExPASy-PeptideCutter, and the AMP activity of resulting peptides (≥4 amino acids, AAs) evaluated with the CAMPR3-RF predictive tool. The mass yields and counts of absorbing (≤10 AAs) and non-absorbing (>10 AAs) AMPs, as found in human, cow and 'humanised' ratios of cow milk proteins, were quantified. The results indicated that major whey proteins from both human and cow milks displayed a higher degree of hydrolysis than caseins, consistent with their known 'fast' digestion properties. Larger albumin and lactoferrin proteins generated relatively more and/or longer peptides. Yields of AMPs from cow milk were higher than from human milk, even after standardising the ratio of whey to casein and total protein concentration, as practiced in formulations manufactured for human newborn babies. Whereas alpha-lactalbumin (2.65 g L-1) and lactoferrin (1.75 g L-1) provided the major yields of AMPs in human milk whey proteins; beta-lactoglobulin, which is unique to cow milk, released the highest yield of AMPs in cow milk (3.25 g L-1 or 19.9% w/w of total whey protein), which may represent an important and overlooked biological function of this protein in cow milk.

Obesity is an increasing global public health problem. A strategy to treat obesity is the use of functional foods. Edible and medicinal mushrooms contain diverse bioactive compounds showing important antihyperlipidemic, antioxidant, and prebiotic properties. We analysed the effects of adding (10%) of Pleurotus ostreatus (Po, basidiomata), Ganoderma lucidum (Gl, basidiomata), or Ustilago maydis (Um, galls), milled, to a high fat plus saccharose diet (HFD + S) for 6 months in a model of obesity with Wistar rats. We assessed weight gain, body composition, lipid parameters, endoplasmic reticulum stress (proteins and inflammatory markers: BiP, XBP-1, JNK, p-JNK, TNF-α), and adiponectin in subcutaneous adipose tissue (SAT). The consumption of edible and medicinal mushrooms decreased weight gain (-17.2-30.1%) and fat mass (-23.7-43.1%), maintained fat-free mass, reduced levels of serum biochemical parameters (TC: -40.1-44.1%, TG: -37.7-51.6%, LDL-C: -64.5-71.1%), and prevented adipocyte hypertrophy (-30.9-36.9%) and collagen deposition (-70.9-73.7%) in SAT. Compared with the HFD + S group, mushroom consumption by Wistar rats significantly reduced the expression of proteins associated with endoplasmic reticulum stress and inflammation (BiP: -72.2-88.2%; XBP-1: -71.5-81.8%; JNK: -71.2-90.0%; p-JNK: -37.3-81.0%; TNF-α: -80.7-91.5%), whereas significantly increased adiponectin protein expression (246.4-654.2%) in SAT. These effects outperformed those obtained through the commercial lipid-lowering drug atorvastatin, contributing synergistically to prevent further obesity-related dysfunctions, such as insulin resistance derived from inflammation and ER stress in adipose tissue. Bioactive compounds from edible, functional and medicinal mushrooms represent new emerging therapies for obesity treatments using natural products.

Iron-fortified broad bean flours were obtained by vacuum impregnation during soaking. The impact of vacuum impregnation and iron fortification on the hydration kinetics of broad beans, as well as the processing (soaking, autoclaving, and dehulling) on the iron-absorption inhibitors (phytic acid and tannins), iron content, iron bioaccessibility, and physicochemical and techno-functional properties of flours was investigated. Results showed that the use of vacuum impregnation during soaking reduced the broad beans' soaking time by 77%, and using iron solution instead of water did not affect the hydration kinetics. After soaking, iron-fortified broad bean flours increased twice (without hull) or more (with hull) the iron and bioaccessible iron content regarding non-fortified flours. Cooking broad beans by autoclaving modified the tannin content, the iron content and its bioaccessible fraction, and the physicochemical and techno-functional properties of the flours. Autoclaving increased the water holding capacity and absorption rate, swelling capacity, bulk density, and particle size, while decreased the solubility index, whiteness index, emulsifying capacity, emulsion stability, and gelling capacity. Finally, dehulling did not practically affect the physicochemical and techno-functional properties of flours, but showed a decrease in iron content, although increased iron bioaccessibility was observed, occurred mainly due to the reduction in tannin concentrations. The results obtained in this study demonstrated that vacuum impregnation is a useful technology for obtaining iron-fortified broad bean flours with different physicochemical and techno-functional properties depending on the production process used.

Acrolein (ACR) is a highly reactive α,β-unsaturated aldehyde that plays a key role in the pathogenesis of human diseases, such as atherosclerosis and pulmonary, cardiovascular, and neurodegenerative disorders. We investigated the capture capacity of hesperidin (HES) and synephrine (SYN) on ACR by individual and combined means in vitro, in vivo (utilizing a mouse model), and via a human study. After proving that HES and SYN could efficiently capture ACR by generating ACR adducts in vitro, we further detected the adducts of SYN-2ACR, HES-ACR-1, and hesperetin (HESP)-ACR in mouse urine by ultraperformance liquid chromatography-tandem mass spectrometry. Quantitative assays revealed that adduct formation occurred in a dose-dependent manner, and that there was a synergistic effect of HES and SYN on capturing ACR in vivo. Moreover, quantitative analysis suggested that SYN-2ACR, HES-ACR-1, and HESP-ACR were formed and excreted through the urine of healthy volunteers consuming citrus. The maximum excretions of SYN-2ACR, HES-ACR-1, and HESP-ACR were at 2-4, 8-10, and 10-12 h, respectively, after dosing. Our findings propose a novel strategy for eliminating ACR from the human body via the simultaneous consumption of a flavonoid and an alkaloid.