Background: Obesity is a major risk factor for pancreatic ductal adenocarcinoma (PDAC) and is associated with poor prognosis. Although metabolic and inflammatory disturbances linking obesity to PDAC progression are well-documented, the impact of obesity-induced immune dysfunction on the tumor microenvironment remains unclear. Objective: This study aimed to elucidate the effects of obesity on the anti-tumor immune response in pancreatic cancer. Design: Splenocytes isolated from mice fed a normal chow (NC) or high-fat diet (HFD) for 12 weeks were analyzed by flow cytometry. After co-culture with Panc02 cells, both splenocytes and PDAC cells (Panc02) were subjected to flow cytometry. Results: Splenocytes derived from HFD-fed mice exhibited a markedly reduced abundance of CD8⁺ T and natural killer (NK) cells compared with those from NC-fed mice, despite unchanged cytokine-producing capacity. Co-culture experiments with Panc02 revealed that HFD-derived splenocytes significantly diminished tumor cell apoptosis, coinciding with reduced frequencies of CD8⁺ T and NK cells. Notably, while PD-1 expression on CD8⁺ T and NK cells remained stable, PD-L1 expression on Panc02 cells significantly decreased following co-culture with HFD-derived splenocytes. Conclusions: These findings indicate that obesity impairs anti-tumor immunity in PDAC by reducing the abundance of cytotoxic lymphocytes, thereby limiting tumor cell apoptosis and PD-L1 induction.
Background: Insulin resistance (IR) has been established as an independent risk factor for erectile dysfunction (ED). Objective: This study aimed to investigate the association between the estimated glucose disposal rate (eGDR) – a simple and non-invasive surrogate measure of IR – and the prevalence of ED. Design: This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2004. The association between ED prevalence and eGDR was assessed using receiver operating characteristic analysis, multivariate logistic regression, restricted cubic spline (RCS) regression, and subgroup analysis. In addition, the mediating role of the neutrophil-to-lymphocyte ratio (NLR) in the eGDR–ED relationship was evaluated through mediation analysis. Results: A total of 3,774 subjects were included, of whom 1,072 (28.4%) had ED. Multivariate logistic regression analysis revealed that eGDR was significantly and inversely associated with the risk of ED (odds ratios = 0.85, 95% confidence intervals [CI]: 0.78, 0.92). Subgroup analyses indicated that this association was more pronounced among individuals with higher educational attainment. RCS regression confirmed a linear inverse relationship. Furthermore, eGDR demonstrated superior discriminative performance for ED (area under the curve [AUC] = 0.705, 95% CI: 0.679, 0.731) compared with traditional IR and obesity indices. Mediation analysis showed that NLR mediated 10.3% (95% CI: 2.3%, 25.2%) of the total association between eGDR and ED. Conclusion: This study provides the first evidence of a significant inverse association between eGDR and ED prevalence, with NLR serving as a partial mediator.
Objective:Menopause marks the natural end of reproductive phase of women caused by decline in levels of estrogen, progesterone and other reproductive hormones. Asparagus racemosus (Shatavari) is a medicinal herb particularly known to be effective in alleviating women's reproductive health. Shatavarin IV, a steroidal saponin and a primary bioactive component in this herb, acts as a phytoestrogen by modulating the ER-alpha/ER-beta signalling, the TrkB-BDNF axis, and the Hypothalamic-Pituitary-Gonadal (HPG) and Hypothalamic-Pituitary-Adrenal (HPA) axes. In this study, the efficacy of SheVari4® on alleviating the menopause-specific endocrine dysfunction and subsequent impaired quality of life (QOL) was assessed through a randomized double-blind placebo-controlled parallel arm trial conducted on 60 pre-, peri-, and post-menopausal women. Methodology:Sixty women (age 50.0 ± 7.4 years) randomized in two equal groups were administered with 100 mg SheVari4® or placebo capsules once daily for 8 weeks. Assessment of Menopause-Specific Quality of Life (MENQOL) along with domain scores across vasomotor, psychosocial, physical, and sexual function constituted primary endpoint analysis; changes in serum estradiol E2, Follicle Stimulating Hormone (FSH), progesterone, cortisol, Anti Mullerian Hormone (AMH), Sex Hormone-Binding Globulin (SHBG) and free testosterone were assessed as secondary endpoint analysis. Safety of the formulation was evaluated in terms of body mass index, blood biochemistry and liver function test. Results:SheVari4 induced a 42.8% reduction in MENQOL versus placebo. Significant improvements in functioning (vs. placebo) were observed, respectively, across vasomotor (53.1% vs. 14.5%), psychosocial (53.6% vs. 9.9%), physical (39.2% vs. 6.5%) and sexual (29.4% vs. 10.7%) domains. The formulation also increased E2 (+36.44% vs. -2.08%) and progesterone (+0.30% vs. -2.88%) coupled with marked reduction in levels of FSH (-38.18% vs. +12.97%) and cortisol (-26.87% vs. +17.16%). Concomitantly, AMH, SHBG, and free testosterone were also favorably modulated. Blood biochemistry, liver function tests, and vital signs confirmed the broad-spectrum safety of SheVari4®. Conclusion:SheVari4® significantly improved menopause-specific QOL and endocrine parameters in peri- and post-menopausal women, with a well-established safety profile.
Sea buckthorn polyphenol extract (SPE) has been reported to exert beneficial effects on lipid metabolism, yet its bioactive constituents and underlying mechanisms remain insufficiently defined. In this study, SPE was administered to db/db mice to evaluate its impact on lipid metabolism and gut microbiota, and key polyphenols were further investigated in HepG2 cells combined with a network pharmacology approach. In db/db mice, SPE restored serum high-density lipoprotein (HDL) levels and alleviated hepatic steatosis, accompanied by a tendency toward reduced body weight gain. These changes were accompanied by marked improvements in gut dysbiosis, with increased relative abundances of beneficial genera such as Lactobacillus and Akkermansia. High-performance liquid chromatography (HPLC) analysis identified isorhamnetin, myricetin, kaempferol, quercetin, and rutin as the major polyphenols in SPE, and all of these constituents decreased intracellular cholesterol and triglyceride accumulation in HepG2 cells without obvious cytotoxicity. Network pharmacology analysis focusing on isorhamnetin and myricetin revealed overlapping targets with obesity-, nonalcoholic fatty liver disease-, and diabetes-related genes that were mainly enriched in lipid-metabolism-related processes and pathways, including fatty acid metabolism, cholesterol homeostasis, nonalcoholic fatty liver disease, lipid and atherosclerosis, and PPAR/AMPK signaling. Integration of gut microbiota, fecal metabolite, and target information further suggested a gut microbiota-metabolite-host target axis involving beneficial taxa such as Akkermansia and Enterococcus and central hubs including PPARG, TNF, and IL6. Overall, these findings indicate that SPE improves lipid metabolism through coordinated modulation of gut microbiota and hepatic cholesterol-lipid homeostasis, supporting its potential use in the dietary management of obesity and dyslipidemia.
Background/Objectives:Vitamin D (VitD) plays an essential role in immune regulation, and growing evidence associates low VitD status with elevated systemic inflammation. However, large-scale, population-based evidence linking VitD status to systemic inflammatory markers in Chinese population are lacking. Objective:This study aimed to investigate the relationship between VitD levels and inflammatory markers in healthy Chinese individuals. Methods:This cross-sectional study was conducted at Zhejiang Provincial People's Hospital (March 2019-August 2023) including a total of 51,521 participants. VitD levels were categorized according to serum 25-hydroxyvitamin D concentrations, and inflammatory markers were derived using established formulas. Primary outcome measures included the systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), and aggregate index of systemic inflammation (AISI). Associations between VitD levels and inflammatory markers were assessed using Spearman's correlation and linear regression. Results:SII, PLR, and AISI were significantly higher among participants with VitD deficiency (P < 0.05). VitD levels were negatively correlated with SII (r = -0.063, P < 0.001), PLR (r = -0.095, P < 0.001), and AISI (r = -0.044, P < 0.001). In multivariable linear regression adjusting for age, sex, low-density lipoprotein cholesterol, triglycerides, uric acid, glucose, albumin, alanine transaminase, alkaline phosphatase, serum creatinine, and hemoglobin, VitD deficiency remained independently associated with SII, PLR, and AISI. Conclusion:VitD deficiency is an independent risk factor for elevated inflammatory markers, supporting a potential immunomodulatory role of VitD and highlighting the need for further research on its potential benefits in chronic disease prevention.
Background: Skeletal muscle atrophy is characterized by impaired protein synthesis, increased proteolysis, oxidative stress, and mitochondrial dysfunction. Phytoceutical interventions with antioxidant and cytoprotective properties may offer therapeutic potential in muscle-wasting conditions. Objective: To assess the effects of LI12542F6 SMI, a standardized formulation of Sphaeranthus indicus (SI) flower heads and Mangifera indica (MI) bark extracts (2:1), on dexamethasone (DEX)-induced skeletal muscle atrophy and to elucidate the underlying molecular mechanisms. Design: In vitro studies assessed antioxidant activity, endothelial nitrite production, protein synthesis, and the activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling (PI3K/AKT/mTOR) pathway, with or without DEX. In vivo, male Sprague Dawley rats received DEX (0.1 mg/kg body weight) and were supplemented with SMI (0, 45, or 90 mg/kg body weight) for 12 days. Outcomes included lean body mass, grip strength, muscle histology, antioxidant enzyme activity, and the expression of anabolic and catabolic protein markers. Results: SMI enhanced reactive oxygen species scavenging and increased endothelial nitrite production via PI3K/AKT-mediated activation of endothelial nitric oxide synthase. In DEX-treated rats, SMI attenuated declines in lean body mass, grip strength, and muscle fiber morphology. Mechanistically, SMI improved antioxidant markers, activated PI3K/AKT/mTOR signaling and myogenic markers, and suppressed catabolic and apoptotic proteins. The hepatic or renal biochemical parameters were unaltered. Discussion: These findings indicate that SMI mitigates glucocorticoid-induced muscle atrophy through coordinated modulation of oxidative stress, mitochondrial function, and anabolic signaling pathways. The activation of PI3K/AKT/mTOR signaling appears central to its effects, linking antioxidant activity with enhanced protein synthesis and the suppression of apoptotic signaling. Conclusions: SMI attenuates DEX-induced skeletal muscle atrophy and improves functional and molecular markers. These findings suggest further investigation and clinical substantiation of this phytoceutical as a possible intervention for muscle-wasting conditions.
Background:Though a healthy diet is the most effective solution for obesity, it is hindered by two main barriers: 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 measurements, biochemical parameters and eating behaviors in women with overweight or obesity who participated 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 combined 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 activity records were monitored throughout the 8-week intervention, while comprehensive assessments including 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.
Preclinical studies have demonstrated that a botanical combination of red okra (Abelmoschus esculentus) and Diospyros lotus (RODLTM) 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.
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.
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.
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.
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.
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.
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.
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; Pnon-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.
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.
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.
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.
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.
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.
