Food & Nutrition Research

Influence of diet on the modulation of gut microbiota and its neurobiological effects on cognition: a systematic review and meta-analysis

2026-06-16T17:02:56+00:00

Introduction: The gut microbiota, a key regulator of the gut-brain axis, is profoundly influenced by diet, and its modulation through dietary patterns may play a critical role in mitigating mild cognitive impairment (MCI).

Objective: To evaluate whether dietary interventions modify gut microbiota composition in individuals with MCI and to determine whether these microbiota changes are associated with variations in cognitive function.

Methods: A systematic review and meta-analysis were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Randomized clinical trials and observational studies evaluating dietary exposures, gut microbiota, and cognitive outcomes in adults with MCI were included. Data extraction and risk-of-bias assessment were performed using standardized and validated tools. When applicable, pooled effects on cognition were estimated using random-effects models and between-study heterogeneity was quantified.

Results: Of 3,029 records identified, 11 studies met the inclusion criteria (nine randomized trials and two observational studies), with a weighted mean age of 65.24 years. Gut microbiota differed between normal cognition and MCI-beneficial taxa (e.g. Bifidobacterium, Faecalibacterium) predominated in normal cognition, while potentially taxa more frequently reported in pro-inflammatory/dysbiosis-associated profiles (e.g. Ruminococcus, Enterobacteriaceae) were higher in MCI. The pooled effect showed a trend favoring dietary interventions (standardized mean difference = −0.32 (95% CI: −0.92 to 0.28)), although this did not reach statistical significance.

Conclusion: This review highlights the potential role of diet in modulating gut microbiota and its impact on cognition in MCI, emphasizing the need for standardized interventions and further research to clarify the underlying mechanisms.

Clinical evidence for fat-binding–mediated fecal fat excretion by RODL^TM (Red Okra–Diospyros lotus botanical combination) under a prescribed restricted diet: a randomized, double-blind, placebo-controlled trial

2026-07-06T10:17:16+00:00

Preclinical studies have demonstrated that a botanical combination of red okra (Abelmoschus esculentus) and Diospyros lotus (RODL^TM) exerts dual anti-obesity actions by both inhibiting intestinal fat absorption and stimulating adipocyte lipid metabolism. However, its clinical efficacy in promoting fecal fat excretion under controlled dietary conditions has not been validated in humans. A randomized, double-blind, placebo-controlled clinical trial was conducted in 70 healthy adults under a prescribed restricted diet containing 130–150 g/day of fat. Participants were randomly assigned to receive either RODL (N = 34, 1.5 g/day) or placebo (N = 36) for 2 days. Fecal samples were collected at baseline and post-intervention to quantify fecal fat content (mg/g wet and dry weight, and total mass). Blood lipid profiles and free fatty acids were also assessed. Data were analyzed using the full analysis set and per protocol set with appropriate statistical tests. Following 2-day administration, the RODL group showed a significantly greater increase in fecal fat excretion compared to the placebo group, as measured by wet fecal fat (28.65 ± 17.46 mg/g vs. 18.54 ± 11.86 mg/g, P = 0.0034), dry fecal fat (58.39 ± 29.95 mg/g vs. 39.54 ± 21.39 mg/g, P = 0.0025), and total fecal fat mass (3,238 ± 3,636 mg vs. 1,802 ± 1,713 mg, P = 0.0118). The botanical combination of RODL significantly enhances fecal fat excretion under a standardized fat-controlled diet without affecting fecal matrix properties or safety parameters. These findings support its potential and safe fat-sequestering agent for dietary fat management.

Sociodemographic differences in the understanding of front-of-pack nutrition labeling, perception of healthfulness, and food purchase intention in Brazil

2026-07-03T21:42:03+00:00

While nutrition claims draw attention to desirable nutrient qualities, the Brazilian Front-of-Pack Nutrition Labeling (FOPNL) system serves a contradictory purpose by signaling excessive levels of added sugar, saturated fat, and sodium.

Besides labeling, sociodemographic factors may influence the understanding of nutritional information and food choices. This experimental, controlled, and randomized study used secondary data derived from previously published research to evaluate the impact of sociodemographic variables, including region, sex, age, education, and income. Specifically, we analyzed how these factors influence the understanding of nutritional information, the perception of healthfulness, and the purchase intention of products with different FOPNL models and nutrition claims.

A sample of 720 Brazilian adults completed an online questionnaire, being randomly assigned to one of four FOPNL conditions: control (without FOPNL), octagon, triangle, or magnifying glass. Participants evaluated 12 label panels in a 3×2×2 factorial design, considering 1) food category, 2) number of nutrients in excess and 3) presence/absence of nutrition claims.

Understanding of nutritional information was measured as the ability to correctly identify nutrients in excess using a generalized linear model with binary logistic regression. Perception of healthfulness and purchase intention were assessed on a 7-point scale using mixed analysis of variance models, with the sociodemographic variables (region, sex, age, education, and income) as fixed effects and participants as random effects.

The results indicate that sociodemographic variables did not significantly affect the understanding of nutritional information. However, participants aged 25 to 34 and male participants reported higher perception of healthfulness and greater purchase intention compared to other groups. These findings suggest that, although the provision of nutritional information on packages supports informed food choices across diverse sociodemographic contexts, age and sex specifically influenced how consumers perceived product healthfulness and their likelihood of purchasing the presented items in this sample.

Maternal cafeteria diet and methyl donor supplementation modulate gut microbiota and anxiety-like behavior in male offspring

2026-06-29T15:21:21+00:00

Maternal cafeteria diet and methyl donor supplementation modulate gut microbiota and behavioral outcomes in male offspring.

Background: Maternal hypercaloric diets rich in saturated fats and refined sugars are associated with metabolic alterations, gut microbiota dysbiosis, and behavioral disturbances in offspring. Methyl donor supplementation has been proposed as a potential strategy to modulate these effects.

Objective: To evaluate the effect of maternal cafeteria diet consumption and methyl donor supplementation on gut microbiota composition and behavioral outcomes in male offspring in a murine model.

Design: Female C57BL/6 mice were assigned to four dietary groups: control, cafeteria diet, control supplemented with methyl donors, and cafeteria diet supplemented with methyl donors. Diet exposure occurred during pre-gestation, gestation, and lactation. Male offspring were evaluated at 8 weeks of age using behavioral tests and gut microbiota analysis based on 16S rRNA gene sequencing. Associations between gut microbiota and behavioral parameters were evaluated using adjusted linear regression models controlling for maternal diet and methyl donor supplementation.

Results: Offspring from cafeteria-fed dams supplemented with methyl donors showed higher microbial diversity compared to the non-supplemented cafeteria group. Cafeteria diet increased the abundance of Deferribacteres, Mucispirillum, Adlercreutzia, Butyricicoccus, and Prevotella, whereas methyl donor supplementation reduced Deferribacteres and modified the abundance of Paraprevotella and Ruminococcus_1. At the species level, Mucispirillum schaedleri and Lactobacillus reuteri were increased under cafeteria dietary conditions. No significant effects were observed in sociability-related variables after adjustment. However, Butyricicoccus remained associated with central and peripheral zone behavior, whereas Paraprevotella remained positively associated with wall-leaning behavior after adjustment for maternal diet and supplementation status.

Discussion: Maternal cafeteria diet modulated offspring gut microbiota composition and was associated with anxiety-related behavioral parameters. Methyl donor supplementation showed differential effects depending on maternal dietary context, reducing specific bacterial taxa associated with inflammatory and metabolic alterations.

Conclusions: Maternal methyl donor supplementation attenuated specific microbiota alterations induced by cafeteria diets and was associated with microbiota–behavior relationships related to anxiety-like responses in offspring.

Investigations of a multi-objective diet optimization model including human health, environment, and observed dietary intake

2026-06-26T12:52:11+00:00

Background: Food-based dietary guidelines (FBDGs) provide recommendations on diets that aim to decrease disease risk and environmental impact, while remaining culturally acceptable for the population. Using mathematical optimization to define such diets, these objectives can be operationalized as components of the objective function.

Objectives: To 1) derive an indicator that quantifies diet-related disease burden and 2) evaluate different weighting schemes within a three-dimensional diet optimization model.

Design: To address objective 1), disability-adjusted life years (DALYs) from the Global Burden of Disease Study (GBD) and a diet-specific burden estimate based on observational data were transformed into a model-compatible indicator using linear interpolation. To address objective 2), a linear diet optimization model was developed. It included constraints on nutrients and acceptability, and a three-objective function that minimized disease burden (DALYs), environmental impact (greenhouse gas emissions and land use), and, as a proxy for cultural acceptability, deviation from the observed diet. Forty-two model variations with different weighting schemes were computed and compared regarding component outcomes.

Results: In proof-of-concept analyses, the derived health indicator aligned closely with values reported in the literature: 90% (based on GBD) and 99% (based on the observational data) of diet-related DALYs were captured. Among the 42 model variations, strong synergies were observed between health and environmental outcomes. Optimizing exclusively for disease burden or environmental impact resulted in substantial deviations from the observed diet, underscoring the importance of considering cultural acceptability. Model stability improved with the inclusion of all three components.

Conclusion: The proposed methodology enables the integration of DALYs and provides insights about various weighting schemes to establish a diet optimization model that minimizes disease burden, environmental impact, and deviation from the observed diet, and serves as the basis to derive FBDG for Germany.

Maternal and infant serum ferritin concentrations across pregnancy and postpartum: a longitudinal study in Norway

2026-06-25T22:10:31+00:00

Introduction: Adequate iron status is particularly important during pregnancy and infancy, as iron deficiency can pose health risks to the woman, developing fetus, and future child. However, data in these population groups are scarce in Norway.

Aim: To describe serum ferritin concentrations in a cohort of pregnant women in Norway, followed through the postpartum period, and their infants. Further, to examine associations between maternal and infant serum ferritin concentrations, and to assess the influence of dietary supplement use and breastfeeding status on serum ferritin levels.

Methods: In this longitudinal cohort study, 137 pregnant women in Norway were enrolled and followed at gestational week 18 and 36, and at 3 and 6 months postpartum together with their infants. Infant and maternal serum ferritin concentrations were measured.

Results: At gestational week 18, 14% of pregnant women were iron deficient (serum ferritin < 15 µg/L), and 44% had depleted iron stores (< 30 µg/L). By gestational week 36, the prevalence of iron deficiency had increased to 65% and depleted stores to 95%. Infant ferritin concentrations declined between 3 and 6 months of age. At 3 months, 96% of infants had sufficient iron status (≥ 50 µg/L). At 6 months, 90% remained sufficient, while 10% were iron deficient (< 15 µg/L). No associations were observed between iron status and dietary iron supplement use or breastfeeding status.

Conclusion: A substantial proportion of the women were found to have iron deficiency, and depleted iron stores both during pregnancy and the postpartum period measured by serum ferritin concentrations. In contrast, the infants generally showed adequate iron status, and although serum ferritin levels declined between 3 and 6 months of age, the prevalence of iron deficiency remained low.

Usual nutrient intake and adherence to dietary reference values among 3–6-year-old Finnish preschoolers

2026-06-26T08:04:33+00:00

Background: Early childhood is an important period for adopting a healthy diet to support long-term health. In Finland, data on how usual nutrient intake meets requirements in young children are lacking.

Objective: We evaluated usual nutrient intake from food sources and adherence to dietary reference values among Finnish preschoolers.

Design: We used cross-sectional data from the DAGIS survey conducted in 2015–2016 among 3–6-year-old Finnish preschoolers (n = 808). Dietary intake was assessed using 3‑day food records, complemented with a 2‑day food record in a subsample. National Cancer Institute methods were applied to estimate the usual intake distributions of macronutrients, vitamins and minerals for each age group (3-, 4-, 5- and 6-year-olds) and to assess the proportions of children below and above the most recent dietary reference values.

Results: Mean protein intake was 17 E% in all age groups, and the fibre density of the diets averaged 2.5–2.6 g/MJ. High proportions of children had intakes above the recommended intake levels for saturated fatty acids (80–86% depending on age), free sugars (42–47%) and sodium (96–99%), and below the recommended intake level for polyunsaturated fatty acids (43–48%). High proportions of children had intakes below the average requirement for vitamin D (24–33%), vitamin E (61–76%) and iron (36% in 3-year-olds). Intakes above the tolerable upper intake level were detected for zinc (58% in 3-year-olds; 6.1–17% in 4–6-year-olds) and iodine (26% in 3-year-olds; 6.4–11% in 4–6-year-olds).

Conclusions: Developing strategies to reduce particularly saturated fatty acid and sodium intakes in Finnish preschoolers is essential for early prevention of chronic diseases. Our results warrant regular monitoring of usual nutrient intake in young Finnish children to support timely and evidence-based decision-making.

Effects of SRW® Stem on the functional properties, oxidative stress and inflammation of human umbilical cord mesenchymal stem cells

2026-05-25T20:52:04+00:00

Background: Global population ageing has heightened the demand for anti-ageing nutritional interventions. Science Research Wellness (SRW^®) Stem was designed by SRW^® to address this demand with ingredients that improve stem cell function, which is central to protection against age-related decline. These ingredients include mitoquinol, sea buckthorn extract, fucoidan, oleuropein, and vitamin D3.

Objectives: We compared the effects of SRW^® Stem on the functions of human umbilical cord mesenchymal stem cells (hUC-MSCs) with those of mitoquinol alone, which is known to improve these functions.

Design: In vitro assays, including CCK-8 for cell viability, trypan blue exclusion, colony formation, transwell migration, adipogenic differentiation, ROS/glutathione analysis, and cytokine profiling under oxidative stress, were used to assess proliferation, migration, and differentiation capacities, as well as antioxidant and anti-inflammatory activity of the SRW^® Stem.

Results: Results demonstrated that SRW^® Stem 5 and 10 μg/mL significantly (P < 0.05 for all) enhanced proliferation, colony formation, and migration, and promoted adipogenic differentiation in the hUC-MSCs, compared with vehicle control and mitoquinol (positive control). Under oxidative stress, SRW^® Stem significantly reduced (P < 0.001 for all) intracellular ROS, increased glutathione synthesis, suppressed IL-1β secretion, and restored IL-10 production in hUC-MSCs.

Discussions: These findings indicated that SRW^® Stem 5 and 10 μg/mL exerts antioxidant, anti-inflammatory, and pro-regenerative effects on hUC-MSCs, outperforming mitoquinol across most parameters.

Conclusions: The results highlighted the potential of SRW^® Stem as an anti-ageing intervention and a supportive agent in stem cell-based therapies. Further investigations in animal models and clinical trials are warranted to validate its efficacy.

Urolithin A supplementation alleviates osteogenic disfunction and promotes bone fracture healing in inflammatory environments

2026-05-22T12:25:06+00:00

Excessive and chronic inflammation can cause osteogenic dysfunction and disrupt the balance of the osteoimmune microenvironment, thereby increasing the risk of fracture non-union. Urolithin A (UA), a gut microbiota-derived metabolite produced from dietary sources, has been reported to inhibit RANKL-induced osteoclastogenesis and alleviate postmenopausal osteoporosis. However, the effect of UA on osteogenesis, particularly under pathogenic inflammatory conditions, remains unclear. In this study, mouse bone marrow-derived mesenchymal stromal cells (mBMSCs) were used to evaluate osteogenesis in vitro, and RAW 264.7 cells were used as macrophages in vitro. Tumour necrosis factor (TNF)-α was used to establish an inflammatory environment. In vivo, a mouse femur fracture model with local TNF-α injection was established, and UA or vehicle was administered by intragastric gavage. The UA showed no obvious effect on cell viability at concentrations ranging from 0 to 10 μM and had no direct effect on the osteogenic differentiation of mBMSCs. TNF-α treatment significantly decreased the expression of osteogenesis-related genes and proteins and inhibited calcium deposition, whereas UA reversed this inhibitory effect in a dose-dependent manner. Mechanistically, UA inhibited activation of the TNF-α-induced nuclear factor-κB signalling pathway. Furthermore, UA reduced pro-inflammatory cytokine levels and inhibited type-1 macrophage polarisation under TNF-α-induced inflammatory conditions. Conditioned medium derived from RAW 264.7 cells stimulated with TNF-α after UA treatment promoted the osteogenic differentiation of mBMSCs. In vivo, local administration of TNF-α significantly impaired bone fracture healing in the mouse femur fracture model, whereas intragastric supplementation with UA improved fracture healing and reduced pro-inflammatory responses. Collectively, these findings demonstrated that UA alleviates osteogenic dysfunction through inhibition of the nuclear factor-κB signalling pathway and regulation of macrophage-mediated inflammation under TNF-α–induced inflammatory conditions, thereby promoting osteogenesis and fracture healing.

Mediating effect of insulin resistance in the relationship between dietary inflammatory index and cardiovascular–kidney–metabolic syndrome stage in US adults, 2007–2018

2026-05-20T21:03:10+00:00

Background: Cardiovascular–kidney–metabolic (CKM) syndrome is a progressive, five-stage disease framework driven by interrelated cardiovascular, renal, and metabolic dysfunction, with chronic inflammation and insulin resistance (IR) playing key roles. The dietary inflammatory index (DII) quantifies overall dietary inflammatory potential, but its role in CKM staging remains unclear.

Objective: This study aimed to evaluate the association between DII and CKM syndrome stage and to assess the potential mediating effect of IR.

Design: This cross-sectional study used data from the National Health and Nutrition Examination Survey (2007–2018). DII was derived from 24-h dietary recall. CKM stages were defined by the American Heart Association criteria. IR was assessed using the triglyceride–glucose index (TyG), Metabolic Score for IR (METS-IR), and Homeostatic Model Assessment for IR (HOMA-IR). Statistical analyses were performed after accounting for the complex survey design.

Results: Of the 27,635 participants, 94.08% had CKM syndrome (Stage 1 or higher). Compared with Stage 0, stepwise increases in the adjusted odds ratios for a higher DII score were observed across CKM stages (Q4 vs. Q1: 1.67 [1.31–2.15] for Stage 1; 2.11 [1.63–2.73] for Stage 2; 2.32 [1.08–4.98] for Stage 3; and 4.19 [2.65–6.63] for Stage 4). Restricted cubic splines models confirmed the positive linear association between DII and each CKM stage (all P_overall < 0.05; P_non-linear > 0.05), with increasingly steep slopes at higher stages. TyG, METS-IR, and HOMA-IR mediated 30.7, 45.0, and 25.3% of the association between DII and CKM syndrome stage, respectively.

Conclusions: Pro-inflammatory diet, as indicated by a higher DII score, was positively associated with more advanced CKM syndrome stage, partly mediated by IR. The DII may serve as a practical measure of dietary inflammation in CKM management.

Salivary cortisol dynamics and their relationship with sleep and mental well-being in adults receiving a phospholipid-based Melissa officinalis supplement: a secondary analysis in a subpopulation

2026-05-13T20:58:17+00:00

Background: Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, as indicated by altered salivary cortisol secretion, has been linked to poor sleep quality, mood disturbances, and emotional distress. In the principal clinical trial, 3 weeks of Melissa phospholipids’ supplementation was associated with significant improvements in sleep quality and mood outcomes.

Objective: This study aimed to evaluate salivary cortisol dynamics in a subpopulation supplemented with Melissa officinalis extract formulated in phospholipids for 3 weeks.

Design: This secondary analysis evaluated a predefined subgroup (n = 12) receiving 400 mg/day of Melissa phospholipids for 3 weeks. Salivary cortisol was collected at 3 timepoints at baseline (T0), week 1 (T1), and week 3 (T2), and quantified by high-sensitivity enzyme-linked immunosorbent assay (ELISA). Associations between cortisol levels and psychometric outcomes were also assessed.

Results: Mean salivary cortisol levels decreased progressively over the 3-week supplementation period, with a significant main effect of time (P < 0.001). Significant correlations (P < 0.05) were also observed between psychometric domains, including PSQI, DASS-21 depression and stress, PANAS, WEMWBS, and WHOQoL-BREF scores, indicating consistent improvements in sleep quality, mood, and perceived well-being.

Discussion and conclusions: This secondary analysis provides preliminary evidence that Melissa phospholipids supplementation, is associated with a significant modulation of HPA axis activity, characterized by a reduction in daily salivary cortisol levels, in adults with poor sleep quality and emotional distress.

Gochujang elicits anti-cancer effects via distinct molecular mechanisms across different gastrointestinal cancer cell types

2026-04-22T18:55:49+00:00

Gastrointestinal (GI) cancers, including gastric, hepatic, and pancreatic cancers, account for a substantial proportion of cancer-related global morbidity and mortality. Dietary habits and bioactive food components significantly influence cancer initiation and progression. As a representative Korean traditional fermented food (KTFF), Gochujang exhibits multiple health benefits, including anti-mutagenic effects; however, its detailed cellular and molecular mechanisms of anti-cancer effects across different GI cancer cell types remain unclear.

The radical scavenging activity of Gochujang extract (GE) was ABTS: 2.86–31.84% and DPPH: 7.95–52.79%. In addition, total phenolic and flavonoid contents of GE were 6.94 ± 0.23 mg GAE/g and 9.28 ± 0.72 mg RE/g, respectively. GE markedly inhibited cell viability, migration, and colony formation in all GI cancer cell lines, including gastric cancer (AGS and SNU-668), hepatic cancer (HepG2 and Hep3B), and pancreatic cancer (MIA PaCa-2). Furthermore, GE markedly reduced the expression of cell proliferation-related proteins and changed the levels of apoptosis-involved proteins in AGS, Hep3B, and MIA PaCa-2 cells, indicating its multifaceted anti-cancer activity. Interestingly, GE significantly altered the expression of antioxidant enzymes and increased reactive oxygen species (ROS) production in gastric and hepatic cancer cells, but these effects of GE were not observed in pancreatic cancer cells. In conclusion, these findings demonstrate that Gochujang exerts comprehensive anti-cancer effects across gastric, hepatic, and pancreatic cancer cells through the coordinated inhibition of proliferation-, migration-, and survival-related mechanisms, while additionally regulating ROS metabolism in a distinctly cell type–specific manner.

Association of dietary acid load with diabetes and glucose metabolism index in Chinese adults: a cross-sectional study

2026-03-20T14:44:37+00:00

Background: Dietary acid load (DAL) has been proven to be associated with hypertension, chronic kidney disease, gout, and the prevalence of type 2 diabetes in several countries. However, its relationship with the prevalence of prediabetes and diabetes in the Chinese population, as well as with fasting blood glucose, fasting insulin levels, and insulin resistance-related indicators, remains unclear.

Method: This is a cross-sectional study based on the China Health and Nutrition Survey (CHNS), which uses Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) to assess DAL. Logistic regression was employed to analyze the relationship between DAL and prediabetes as well as diabetes. Linear regression was used to examine the associations between DAL and fasting blood glucose, fasting insulin levels, estimated glucose disposal rate (eGDR), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and the TyG index in the affected population. Restricted cubic spline (RCS) curves were utilized to explore potential nonlinear relationships, and mediation analysis was conducted to investigate the mediating role of insulin resistance in the effects of DAL on fasting blood glucose and insulin. Finally, the findings were validated and compared using data from the National Health and Nutrition Examination Survey (NHANES).

Results: Higher PRAL (odds ratio [OR]: 1.004, 95% confidence interval [CI]: 1.002–1.006) and NEAP (OR: 1.009, 95% CI: 1.005–1.012) were associated with an increased prevalence of diabetes and prediabetes. Elevated levels of PRAL and NEAP were also correlated with higher fasting blood glucose levels and a lower eGDR. Moreover, eGDR played a significant mediating role in the effect of DAL on fasting blood glucose (PRAL: 69.74%, P = 0.048; NEAP: 65.75%, P = 0.004). However, this phenomenon was not significant in the US population, indicating differences between Chinese and American populations.

Conclusion: High DAL is significantly associated with an increased prevalence of diabetes and prediabetes in the Chinese population, and it influences fasting blood glucose levels in affected individuals by reducing the eGDR. These findings highlight the clinical importance of regulating acid-producing diets to help manage blood glucose levels in individuals with diabetes.

SFTA2 reduced colorectal cancer ferroptosis promoting metastasis through regulating EMT transition by degradation of Nrf2

2026-03-20T15:02:41+00:00

Colon cancer is a common malignancy of the digestive system, tumor disease, and its prevalence in China shows a consistently increasing trend. This study aimed to investigate the role of surfactant associated 2 (SFTA2) in colorectal cancer (CRC) and its molecular mechanism involving ferroptosis.

Colon cancer tissues were obtained from patients and normal volunteers from our hospital, and a mouse model of CRC was established using azoxymethane (AOM)/dextran sulfate sodium (DSS) induction.

SFTA2 expression was significantly up-regulated at both the messenger RNA (mRNA) and protein levels in CRC tissues and cell lines. Patients with high SFTA2 expression exhibited a shorter survival time compared to those with low SFTA2 expression. SFTA2 was found to be expressed in cancer cells of CRC patients, associated with key signaling molecules.

Sh-SFTA2 reduced cancer proliferation in the mice model of CRC. SFTA2 up-regulation promoted cell proliferation of CRC. SFTA2 down-regulation promoted cell proliferation of CRC. SFTA2 up-regulation reduced oxidative stress and ferroptosis of CRC. SFTA2 up-regulation reduced ferroptosis of CRC through mitochondrial damage-tricarboxylic acid cycle (TAC). SFTA2 down-regulation suppressed nuclear factor erythroid 2-related factor 2 (Nrf2) expression in the model of CRC. SFTA2 up-regulation reduced Nrf2 ubiquitination in the model of CRC. Nrf2 reversed the effects of si-SFTA2 on ferroptosis of CRC. Furthermore, SFTA2 down-regulation suppressed Nrf2 expression, while SFTA2 up-regulation decreased Nrf2 ubiquitination in the CRC model. Nrf2 was shown to reverse the pro-ferroptotic effects of si-SFTA2, indicating that SFTA2 activates the Nrf2 pathway by inhibiting its ubiquitination, thereby reducing mitochondrial damage and TCA cycle disruption in CRC.

SFTA2 induced the Nrf2 pathway to reduce mitochondrial damage-TAC of the CRC model through the inhibition of Nrf2 ubiquitination. SFTA2 is thus a potentiallyeffective therapeutic strategy for patients with CRC or other cancers.

The Educational Gradient in the Adherence to the Healthy Nordic Food Index Among Adult Men and Women in Tromsø: The Tromsø study 2015–2016

2026-03-04T10:27:12+00:00

Background: There is a well-established relation between socioeconomic position (SEP) and diet. People with lower SEPs tend to eat high-calorie, low-nutrient foods, while those with a higher SEP tend to consume foods associated with better health. However, the underlying mechanisms are yet to be understood.

Objective: To examine the association between education and the Healthy Nordic Food Index (HNFI) in men and women in Tromsø, and investigate the role of three intermediate variables: household income, subjective occupational social status, and self-rated health.

Design: Dietary information from Food Frequency Questionnaires were used to construct the HNFI based on six food items and categorised as low, medium, and high adherence. Education and intermediate variables were self-reported. Multinomial logistic regression models stratified by sex were performed to assess the association between education and the HNFI among 8,610 women and 6,896 men aged 40–99 years.

Results: Median intake of all food items increased across categories of the HNFI for all participants. High adherers to the HNFI were slightly older, more educated, had higher household income, perceived their occupational social status as high, and rated their health as good/excellent. We observed an educational gradient in the adherence to the HNFI where men (odds ratios [OR] _TertiaryLong 1.92 [95% confidence intervals [CI] 1.47–2.5]) and women (OR _TertiaryLong 2.35 [1.94–2.85]) with higher education had higher odds of adhering to the HNFI compared to those with primary education. Household income partly attenuated this gradient in men only.

Conclusion: The association between education and adherence to the HNFI followed an educational gradient, which was partly attenuated by income in men but not in women. Our study highlights potential mechanisms underlying the relationship between education and diet. A deeper understanding of socioeconomic disparities in healthy eating is crucial for enhancing overall nutrition, especially among the socially disadvantaged.

Salubrious effects of Ficus carica L. leaves extract in inflammation, diabetes, and obesity: An in-vitro, in-silico, and in-vivo study

2026-02-20T02:02:39+00:00

Various traditional medicinal systems have utilized the plant-based remedies for addressing the diverse ailments worldwide. Hence, this study aimed to scientifically explore the biological and phytochemical potential of Ficus carica L. leaves. This investigation encompassed the assessments of flavonoids, total phenolic contents, as well as physicochemical and phytochemical properties. Antioxidant potential was evaluated through hydrogen peroxide, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays, while anti-inflammatory effects were determined via proteinase inhibition, bovine serum albumin (BSA) denaturation, and heat-induced hemolysis assays. Additionally, antiglycation potential was assessed through free carbonyl group estimation, fructosamine, and Congo-red assays. The impact on diabetes mellitus, obesity, and renal and hepatic functions was investigated using the high-fat high-sugar diet model. Advanced analytical techniques including Fourier-transform infrared, high-performance liquid chromatography, and liquid chromatography-tandem mass spectrometry were employed to identify the active secondary metabolites present in the F. carica L. leaf extract. Molecular docking and absorption–distribution–metabolism–excretion–toxicity analyses were performed by different computational methods. Results revealed that substantial levels of total flavonoids (123 mg rutin equivalents/g) and phenolic content (333 mg gallic acid equivalent/g) along with promising antioxidant activity (IC₅₀: 0.58 mg/mL for DPPH assay, 35.6% inhibition for H₂O₂ assay, and FRAP value of 88.769 µg/g Fe₂SO₄ solution) were found. Notably, F. carica L. leaf extract exhibited the significant inhibition in heat-induced hemolysis (55 ± 0.03%), proteinase activity (28 ± 0.01%), and BSA denaturation (51.2 ± 0.05%). Furthermore, it exhibited the significant therapeutic effects on the biomarkers related to diabetes mellitus, obesity, liver, and kidney functions. Chemical analyses unveiled the presence of chlorogenic acid, ferulic acid, thymoquinone, rutin, coumarin, as well as terpenoids, alkaloids, coumarins, and flavonoids. The key findings suggest that F. carica L. leaf extract holds significant potential as an antioxidant, antidiabetic, and hypolipidemic agent.

Legumain level in patients with gestational diabetes to promote ferroptosis through liver gluconeogenesis by HSP90 and GPX4

2026-02-28T14:04:27+00:00

Background: The incidence of gestational diabetes mellitus (GDM) is the first diabetes in pregnancy and has gradually increased worldwide, increasing the burden of social healthcare systems. In GDM, oxidative stress induced by reactive oxygen species (ROS) can disrupt the integrity of the cell membrane through lipid peroxidation reactions and trigger ferroptosis, further exacerbating pancreatic islet β-cell dysfunction and insulin resistance. Lipid peroxidation products related to ferroptosis (such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE)), along with the decrease in glutathione peroxidase 4 (GPX4) activity, may be involved in the placental oxidative damage and adverse fetal outcomes in GDM, suggesting that targeting the antioxidant pathway or regulating ferroptosis may serve as an intervention strategy. Legumain (LGMN) can serve as novel targets in diabetes mellitus genetic therapy.

Objective: This study investigated the mechanism and effects of LGMN in GDM.

Method: All blood samples of normal or patients with GDM were collected by Beijing Ditan Hospital Affiliated Capital Medical University. C57BL/6J female mice were intraperitoneally injected with streptozotocin. Sh-LGMN virus (20 μg of each) or control vector virus (20 μg of each) was injected into GDM mice. GDM mice randomly assigned to three groups (Number = 10). Sh-LGMN virus (20 μg of each) + HSP90 inhibitor or Sh-LGMN virus (20 μg of each) or control vector virus (20 μg of each) was injected into GDM mice. LGMN or si-LGMN Plasmids were transfected into HepG2 cells using Lipofectamine 2000. HepG2 cells were incubated by different insulin concentrations (100 nmol/L) treatment for 24 h. Microarray analysis, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, proliferation assay, ethynyl deoxyuridine staining, bioluminescence imaging, and Western blot were used in this study.

Results: Serum LGMN mRNA expression was significantly elevated in patients with GDM. LGMN mRNA and protein expression were also elicited in the liver tissue of GDM mice. LGMN mRNA expression exhibited a positive correlation with Body Mass Index (BMI), fasting plasma glucose, 1-h plasma glucose, or 2-h plasma glucose in patients. Sh-LGMN virus reduced blood glucose levels and body weight, inhibited fasting insulin (FINS) levels and Homeostatic Model Assessment of Beta-cell function (HOMA-β), enhanced Fasting Blood Glucose (FBG)/FINS/Total Cholesterol/Triglycerides levels, improved hepatic fibrosis (HE staining), and also upgraded HbAIc and HOMA-IR in mice of GDM. LGMN exacerbated ROS-induced oxidative stress in the in vitro model of GDM. LGMN promoted ferroptosis in vitro model of GDM. LGMN expanded ROS-induced mitochondrial damage in vitro model of GDM. LGMN inhibited the HSP90/GPX4 Signaling Pathway in the model of GDM. The inhibition of HSP90 reduced LGMN on GDM in the mice model or the in vitro model of GDM. LGMN interlinked with complex protein body of HSP90 and GPX4, which LGMN inhibited the HSP90/GPX4 Signaling Pathway.

Conclusions: The LGMN level in patients with GDM was upregulated, and LGMN facilitates ferroptosis by HSP90 and GPX4 in the mice model of GDM and may lead to therapeutic potential of ferroptosis or liver gluconeogenesis in the model of GDM.

Indole-3-carbinol ameliorates ER stress-mediated hyperleptinemia in western diet-fed apoE-/- mice

2026-02-11T10:46:23+00:00

Background: Endoplasmic reticulum (ER) stress during overnutrition causes leptin resistance in obese animals and humans. ER stress induces the activation of the unfolded protein response, which disrupts the leptin signaling pathway, accelerating atherosclerosis development and its complications.

Objective: Indole-3-carbinol (I3C) improves metabolic dysfunction in diet-induced obesity; however, its role in protecting against ER stress-induced hyperleptinemia remains unclear. Herein, we explored whether dietary I3C alleviates ER stress in apolipoprotein E-deficient (apoE^-/-) mice fed a western diet (WD).

Design: ApoE^-/- mice were fed either WD (60 kcal from fat, n = 10) or WD supplemented with 0.05% I3C (w/w, n = 10) for 12 weeks.

Results: I3C supplementation (0.05%) resulted in reduced adipose tissue weight and plasma leptin levels compared with those in WD-fed apoE^-/- mice after 12 weeks. I3C also significantly decreased the protein expression of ER stress markers, whereas increased the mRNA expression of genes related to cholesterol efflux and fatty acid β-oxidation in the liver, despite no changes in plasma cholesterol and triglyceride levels. Immunohistochemistry revealed reduced aortic localization of glucose-related protein 78 compared with the WD group, suggesting that I3C partially alleviated ER stress in atherosclerotic lesions of WD-fed apoE^-/- mice.

Conclusion: I3C may serve as a feasible compound for preventing atherosclerosis and its associated complications.

Investigation of the immunoregulatory mechanisms of total saponins from black ginseng

2026-02-06T00:33:06+00:00

Objective: This study aimed to elucidate the immune-regulating effects and underlying mechanisms of action of total saponins extracted from black ginseng in an immunosuppressed murine model.

Methods: The chemical composition of black ginseng total saponins (BGTS) was analyzed using high-performance liquid chromatography, which revealed a high content of rare ginsenosides, such as Rk1, Rg5, and Rg3. Immunosuppressed mice were administered BGTS, and key immunological parameters were assessed, including body weight, spleen and thymus indices, cytokine and immunoglobulin levels, and the expression of immune-related genes and proteins.

Results: BGTS treatment significantly improved body weight and immune organ indices and promoted the secretion of cytokines, including interleukin (IL) 2, IL-1β, tumor necrosis factor-alpha, immunoglobulin (Ig) A, IgG, and IgM. Mechanistically, BGTS significantly activated the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88/nuclear factor-κB signaling pathway at the protein level and upregulated gene expression of TLR-4, TNF-α, IL-6, and IL-1β.

Conclusion: These findings suggest that BGTS exerts notable immunomodulatory effects by enhancing innate immune responses, primarily by activating the TLR4-mediated signaling pathway. Further studies are necessary to isolate the contribution of individual ginsenosides and evaluate the long-term safety and clinical potential of BGTS.

Melissa phospholipids improves sleep quality and mental well-being: concluding results from clinical study in adults with emotional distress

2026-01-31T12:50:50+00:00

Background: Melissa officinalis L. (lemon balm) is a botanical support widely used for its calming and sleep-promoting properties.

Objective: To evaluate the impact of daily supplementation with Melissa phospholipids (MOP) at 200 or 400 mg for 3 weeks on sleep quality and psychological well-being in adults with emotional distress and poor sleep quality.

Design: This prospective, open-label, dose-comparison clinical study enrolled 32 adults with poor sleep quality and/or clinically significant emotional distress. Participants received daily supplementation with either 200 or 400 mg/day MOP for 3 weeks. Sleep quality (primary endpoint) was assessed using the Pittsburgh Sleep Quality Index (PSQI) at baseline (T0), and week 3 (T1). Secondary endpoints included depression, anxiety, and stress, positive and negative affect, mental well-being, and quality of life. Safety was also assessed through adherence monitoring, documentation of side effects or adverse events, and by routine blood biochemistry parameters of liver and renal functions.

Results: PSQI scores significantly improved over time (P < 0.0001), with greater and earlier benefits at 400 mg/day (−30% vs. −15%; P < 0.05). The 400 mg dose also produced significant reductions in depression (−26%), anxiety (−18%), and stress (−22%) scores (all P < 0.001), together with increased positive and negative affect together with Warwick-Edinburgh Mental Well-Being Scale (+15%). Quality of life improved across total score (33%) and its four domains, with significant results in physical well-being (P < 0.05). No statistically significant changes in safety parameters were detected and no adverse effects were reported.

Discussion: MOP, particularly at 400 mg/day, confirmed to significantly improve sleep and life quality, mood, and overall mental well-being.

Conclusion: These findings support and extend the health benefits of MOP as a well-tolerated, safe natural approach in a dose-dependent frame to managing sleep quality and emotional distress. Future placebo-controlled trials are warranted to confirm these results and further elucidate the underlying mechanisms of action.

Energy drink consumption, sleep behavior, and food choices of Icelandic adolescents

2026-01-29T07:24:06+00:00

Background: The consumption of energy drinks has increased in the last decades, especially among adolescents. Caffeine and its effects on sleep are well known, but less is known about the timing of the consumption and its association with sleep and food choices.

Objective: The objective of this study was to evaluate the energy drink consumption, sleeping behavior, and food choices in Icelandic adolescents.

Design: A total of 171 participants (64 boys, 107 girls, aged 17–18 years) completed an online questionnaire on sleep, food choices, and energy drink consumption. Independent sample T-tests, Mann-Whitney U tests, and Chi-square tests were used to assess group differences.

Results: Overall, 57% reported drinking energy drinks, with higher rates among girls than boys (63 vs. 48%). Energy drink consumers were more likely to report sleeping 6 h or less. This was especially true for those drinking energy drinks after 3 PM, compared to those who avoided them after 3 PM. Participants who consumed energy drinks also ate fewer nutritious foods (fruits, vegetables, dairy, fish) and consumed more soft drinks, coffee, and alcohol compared to non-energy drink consumers.

Discussion: The results show that energy drink consumption is frequent among Icelandic 17-year-olds, particularly among girls. Consumers were more likely to report shorter sleep durations, especially when drinking after 3 PM, and had poorer dietary habits, including lower intake of nutritious foods and higher consumption of soft drinks, coffee, and alcohol.

Conclusion: Future research should explore the long-term effects of these behaviors and assess interventions to reduce energy drink use and promote healthier habits in adolescents.

Estrogen promotes the angiogenesis and osteogenesis of bone marrow stromal cells via regulating ESR1/RUNX2 axis

2026-01-16T09:15:02+00:00

Osteoporosis (OP) is a common bone disease characterized by decreased bone mass and microarchitectural deterioration. This study aimed to investigate the effects of estrogen on OP. Bilateral ovariectomy (OVX) surgery was performed to establish the OP mouse model. Histological analysis was performed using hema- toxylin and eosin (HE) staining and alizarin red S (ARS) staining. Angiogenetic factors were determined using enzyme-linked immunosorbent assay (ELISA). Messenger RNA (mRNA) levels were determined using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Protein expression was determined using Western blot. Cellular functions were analyzed using Transwell, tube formation, alkaline phosphatase staining, and ARS staining assay. The co-localization of estrogen receptor alpha (ESR1) and runt-related transcription factor 2 (RUNX2) was determined using the fluorescence in situ hybridization (FISH) assay. The interaction between ESR1 and RUNX2 was determined using the co-immunoprecipi- tation (Co-IP) assay. We found that 17β-estradiol (E2) alleviated the decrease in bone intensity and mass induced by OVX. E2 promoted the angiogenesis and osteogenesis of bone marrow stromal cells (BMSCs). Mechanistically, E2 predominantly upregulated ESR1. Moreover, mediated nuclear-localization of ESR1 promoted the interaction between ESR1 and RUNX2. Furthermore, ESR1 overexpression promoted the angiogenesis and osteogenesis of BMSCs. Estrogen exerts a protective effect on OP. Estrogen mediates the angiogenesis and osteogenesis of BMSCs by regulating the ESR1/RUNX2 axis.

Enhanced bioavailability of a krill oil-based milk thistle extract formulation: in vitro and human studies

2026-01-08T02:08:35+00:00

Background/Objectives: The milk thistle plant (Silybum marianum) is known for its hepatoprotective properties. However, the poor water solubility of silymarin limits its dissolution in the intestinal tract and restricts its bioavailability following oral administration.

Methods: To improve bioavailability, special formulations, in particular micellar solubilization, are explored. In this study, we examined the transport rate of silymarin in a krill oil-based formulation across a Caco-2 epithelial barrier after upstream digestion simulation in vitro. Furthermore, in a randomized cross-over design study the bioavailability of the krill oil-based formulation was investigated after single dose intake in fasting conditions in healthy participants.

Results: We could demonstrate that the apparent transport coefficient of silybin, measured as lead substance of milk thistle extract, across the epithelium is efficiently boosted by a krill oil formulation, resulting in a 28% increase compared to silymarin powder. Consistent with these findings, a significant enhancement of bioavailability (P < 0.0001) was demonstrated for the krill oil-based formulation in comparison to the milk thistle extract resulting in an 8.59-fold higher AUC_0-8h and a 15.08-fold greater C_max of silybin and faster uptake kinetic after single dose intake.

Discussion and Conclusions: These findings suggest that phospholipid-based delivery systems offer a promising strategy for improving the efficacy of lipophilic bioactives. Furthermore, the combination of krill oil with milk thistle extracts efficiently provides silybin, PUFAs, and choline, which are important nutrients contributing to liver and heart health.

Evaluating home-delivered meal service programs for obesity: a randomized controlled approach

2026-05-07T09:59:34+00:00

Background: Though a healthy diet is the most effective solution for obesity, it is hindered by two main barri-
ers: difficulty in accessing or preparing healthy meals and lack of portion control knowledge.

Objective: This study compared two different medical nutrition therapies (home-delivered diet meal service
[HDMS] combined with dietary counseling and dietary counseling solely) in terms of anthropometric mea-
surements, biochemical parameters and eating behaviors in women with overweight or obesity who partici-
pated in a weight loss program.

Design: A non-randomized, controlled, parallel-group intervention study was conducted with 60 women aged
25–45 years, having a Body Mass Index (BMI) of 25–35 kg/m², representing individuals with overweight
and class I obesity. Participants were divided into two groups: an intervention group receiving HDMS com-
bined with dietary counseling (n = 30) and a control group receiving dietary counseling solely (n = 30).
Anthropometric measurements, bioelectrical impedance analysis (BIA), and dietary and physical activ-
ity records were monitored throughout the 8-week intervention, while comprehensive assessments includ-
ing biochemical parameters (fasting blood glucose, homeostatic model assessment for insulin resistance
(HOMA-IR), lipid profile), resting metabolic rate (RMR) (FITMATE), and eating behaviors assessed using
the Three-Factor Eating Questionnaire (TFEQ) were conducted at baseline, week 4, and week 8.

Results: Both groups showed significant reductions over time in body weight, BMI, waist circumference,
hip circumference, body fat percentage, RMR, blood glucose, lipid parameters, and blood pressure values
(P < 0.001). Although greater reductions were observed in the HDMS group, the differences between groups
were not statistically significant (P > 0.05). When considering the group-time interaction, changes in waist
circumference (P < 0.001), hip circumference (P < 0.05), RMR (P < 0.05), fasting blood glucose (P < 0.05),
low-density lipoprotein (LDL), cholesterol (P < 0.05), and systolic blood pressure (P < 0.05) were found
to be significant in the HDMS group. In addition, when examining eating behaviors, statistically significant
changes were observed in the intervention group for both time effects and behavior outcomes. Uncontrolled
eating and emotional eating behaviors decreased, while cognitive restraint increased (P < 0.001).

Conclusion: Both interventions improved anthropometric and metabolic parameters, with greater reductions observed in the HDMS group; however, the differences between groups were not statistically significant. HDMS may be considered a practical approach to support weight management.