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Background: Caffeine, dairy products and other food items may influence retinal microcirculation. Retinal microvascular indices provide quantitative biomarkers of systemic microvascular health and are increasingly used in clinical and research settings. The aim of this study was to elucidate the possible effects of these food products on structural and functional indices of the retinal microcirculation. Methods: Based on a registered protocol, we identified eligible interventional/observational studies examining the association of these factors with retinal biomarkers, including central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), arteriolar-to-venular diameter ratio (AVR), retinal vascular tortuosity, vessel diameter index (VDI) and retinal vessel flicker light-induced dilation (FID). Results: Fourteen studies were included addressing caffeine (4), dairy products (2) and other food (9) consumption. Acutely, caffeine intake was dose-dependently associated with narrowed CRAE, CRVE, decreased VDI and increased AVR and FID. Long-term, caffeine consumption was associated with larger CRVE and lower AVR, while decaffeinated coffee with larger CRAE and AVR and narrower CRVE. Low-fat dairy products, fish and fiber were associated with larger CRAE, smaller CRVE, and increased AVR, while red meat consumption was associated with narrower CRAE and lower AVR. Increased salt intake was associated with increased venular tortuosity, while almond consumption was associated with larger CRVE. Owing to substantial study heterogeneity, a meta-analysis was not feasible. Conclusions: Potentially clinically meaningful associations between food groups and retinal indices were identified. These associations should be considered when evaluating retinal microcirculation and assessing CVD risk since modification of these factors may be beneficial for the cardiovascular system. Full article

Background/Objectives: Branched-chain fatty acids (BCFAs) exhibit a range of biological activities; however, their limited natural abundance and high cost have constrained in vivo research. Lanolin represents a promising source for enriching BCFAs. Nevertheless, the in vivo application, safety, and dose-effect relationship of BCFAs derived from lanolin (BCFAs-DFL) remain unassessed. Methods: In this study, the acute toxicity in C57BL/6J mice was first evaluated for 7 days by a single oral administration of 5000 mg/kg BW of BCFAs-DFL. Subsequently, 40 mice were divided into four groups (control group, low dose of 100 mg/kg BW, medium dose of 300 mg/kg BW, and high dose of 600 mg/kg BW) and were continuously administered by gavage for 28 days to study the effects of BCFAs-DFL on the growth, blood biochemistry, intestinal morphology, and intestinal flora of the mice. Results: In the acute toxicity test, BCFAs-DFL exhibited no lethality or abnormalities in mice, indicating its non-toxic nature. Throughout the 28-day trial, mice in the medium- and high-dose groups experienced a notable decrease in average daily feed intake (p < 0.05), yet their weight gain remained unaffected (p > 0.05). Hemoglobin and hematocrit levels declined in the high-dose group (p < 0.05). Conversely, serum aspartate aminotransferase and total bilirubin levels escalated in the medium- and high-dose groups, while triglycerides and urea nitrogen levels decreased (p < 0.05). The serum’s total antioxidant capacity and immunoglobulin levels (IgA, IgG) rose in proportion to the dosage (p < 0.05). BCFAs-DFL notably enhanced the villus height of the jejunum and ileum in mice (p < 0.05). Gut microbiota analysis indicated no significant impact on overall α and β diversity. Conclusions: The 28-day intervention revealed that BCFAs-DFL can modulate feeding behavior, TG, T-AOC, and immunoglobulin levels in mice. Additionally, it promotes the development of intestinal villi. Based on various indicators, a dosage of 100 mg/kg BW effectively induces beneficial metabolic regulation, such as the reduction of triglycerides, without causing a burden on liver metabolism. This dosage may represent a more suitable application for potential use. Full article

Background/Objectives: Apple pomace, a major by-product of juice production, represents both an environmental burden and an underutilized resource. This study aimed to enhance the nutritional value of apple pomace via solid-state fermentation (SSF) to develop a functional feed ingredient and systematically evaluate its effects on growth, metabolism, and intestinal health in weaned piglets. Methods: Apple pomace was fermented using a multi-species consortium (Geotrichum candidum, Saccharomyces cerevisiae, Rhizopus oryzae, Bacillus subtilis, and Trichoderma viride). A total of 180 weaned piglets were fed iso-nitrogenous diets containing 0, 2, 4, 6, 8, or 10% fermented apple pomace for 35 days. Growth performance, serum biochemical and immuno-antioxidant indices, diarrhea incidence, jejunal morphology, and fecal microbiota were analyzed. Results: Dietary fermented apple pomace supplementation showed dose-dependent effects. The 8% fermented apple pomace group exhibited optimal growth performance, with increased average daily gain and feed intake and reduced feed-to-gain ratio (p < 0.05). Serum analysis indicated enhanced protein synthesis, antioxidant capacity (T-AOC, SOD, GSH-Px), and immunoglobulin levels (IgA, IgG, IgM), along with reduced urea nitrogen and oxidative stress marker MDA. This group also had the lowest diarrhea rate, associated with improved jejunal villus morphology. Microbiota analysis revealed that 8% fermented apple pomace effectively increased α-diversity, promoted beneficial bacteria (e.g., lactic acid bacteria and butyrate-producing Clostridium sensu stricto_1), and suppressed pathogens (Escherichia coli, Salmonella, Streptococcus). Conclusions: Multi-species SSF successively enhanced the nutritional profile of apple pomace. Inclusion at 8% showed the most favorable response in terms of growth performance, metabolic profile, and immune–antioxidant status in weaned piglets, mediated through improved intestinal morphology and targeted modulation of the gut microbiota toward a more diverse and beneficial ecosystem. These findings support the high-value, functional utilization of apple pomace as a feed additive in swine nutrition. Full article

Background: Caffeine is a well-established ergogenic aid, yet most experimental evidence is based on isolated caffeine, whereas habitual intake in both the general and physically active populations occurs mainly through coffee. This gap between experimental models and everyday practice complicates the interpretation of existing findings. Objective: This review compares coffee and isolated caffeine as ergogenic aids, focusing on biological mechanisms, methodological differences, tolerability, and context-dependent use in sport and exercise. Methods: A narrative review of human studies examining the effects of coffee and isolated caffeine on exercise performance, fatigue, and post-exercise recovery was conducted, with attention being paid to dosing accuracy, bioavailability, inter-individual variability, and the influence of the coffee matrix. Results: Isolated caffeine consistently improves performance under controlled conditions. Coffee can produce similar ergogenic effects, particularly in endurance exercise, although responses are more variable due to differences in caffeine content and individual sensitivity. Emerging evidence suggests that coffee, especially when consumed with carbohydrates, may support post-exercise glycogen resynthesis. Coffee also appears to be better tolerated by many individuals and provides additional bioactive compounds with antioxidant and anti-inflammatory properties. Conclusions: Coffee and isolated caffeine should not be viewed as interchangeable ergogenic strategies. While isolated caffeine remains useful in experimental settings, coffee represents a more ecologically relevant and potentially safer source of caffeine in applied practice. Further direct comparative studies are needed to clarify their context-specific roles. Full article

Weaning stress frequently compromises intestinal integrity and nutrient absorption in piglets and induces structural perturbations in the gut microbiota. This study investigated the effects of dietary Paramylon, a linear β-1,3-glucan from Euglena gracilis, on growth and intestinal function. A total of 32 healthy, 21-day-old weaned piglets (male, castrated, Duroc × Landrace × Yorkshire) were randomly allocated to four groups: control, 0.025%, 0.05%, and 0.1% Paramylon (8 pigs/group). The results showed that 0.05% dietary Paramylon quadratically increased average daily gain and feed intake (p < 0.05). Serum TC content significantly increased, while the serum urea level significantly decreased (p < 0.05). This optimal dose was used for mechanistic exploration. Dietary 0.05% Paramylon notably enhanced ileal morphology, increasing the villus height to crypt depth ratio (p < 0.01) and significantly improving apparent nutrient digestibility and ileal β-amylase activity (p < 0.05). The expression levels of SLC7A1 and GLUT2 in ileum tissues were significantly upregulated (p < 0.05). The expression level of SLC7A7 in the liver was also increased (p < 0.05). This nutrient transport-promoting effect was further confirmed in IPEC-J2 cells, which manifested because 10 ng/mL of pure Paramylon significantly upregulated the gene expressions of SLC38A2, EAAT3, PEPT1, and GLUT2 (p < 0.05). KEGG enrichment analysis on the ileum indicated that differentially abundant metabolites were enriched in amino acid-related metabolic pathways. Furthermore, the 16s sequencing results revealed that Romboutsia was significantly enriched in the Paramylon group. In conclusion, Paramylon, as an effective dietary supplement, helps promote nutrient digestion and absorption in weaned piglets and contributes to maintaining intestinal health. Full article

Background: Early surgical intervention is associated with improved outcomes in hip fracture care, yet in patients using Direct Oral Anticoagulants (DOACs), surgery is frequently delayed due to concerns about increased intraoperative bleeding. Despite the increasing prevalence of hip fracture patients on DOACs, no consensus exists on optimal surgical timing. This has led to substantial practice variation between hospitals, with some operating within 24 h of last DOAC intake and others delaying surgery beyond 24 h. This study hypothesizes that early surgery within 24 h results in a non-inferior blood transfusion risk compared to delayed surgery 24 h or more after last DOAC intake in hip fracture patients on DOACs. This protocol describes the design and methodological rationale of a natural experiment. Methods and analysis: A multicenter cohort study designed as a natural experiment will be conducted across seven Dutch level 2 trauma centers, using predefined and standardized prospectively collected variables from electronic health records. Centers will adhere to distinct local surgical timing protocols, forming two cohorts: early surgery within 24 h and delayed surgery 24 h or more after last DOAC intake. Patients presenting with an isolated hip fracture who are using a DOAC and have taken their last dose within 24 h before admission will be included. The primary endpoint is postoperative blood transfusion. Secondary endpoints include additional bleeding-related outcomes, thrombotic and postoperative complications, and hospital length of stay. The primary analysis will be conducted on a per-protocol basis, with an intention-to-treat analysis performed as a supplementary assessment. Non-inferiority will be established if the upper bound of the one-sided 95% confidence interval for the risk difference does not exceed the predefined margin of 5%. Ethics and dissemination: Ethical approval was obtained from the Medical Ethics Committee United, Utrecht, The Netherlands. As this is a cohort study without altering clinical care, individual informed consent is not required. All data will be pseudonymized, and findings will be disseminated through peer-reviewed journals and scientific conferences. Registration details: Medical Ethics Committee United, Utrecht, The Netherlands, registration number W25.034. Full article

Long-term excessive fat intake can easily induce metabolic diseases such as fatty liver and hyperlipidemia. As a natural active ingredient, polysaccharides exhibit notable lipid-lowering effects and can serve as effective lipid regulators. Nevertheless, the lipid-lowering effect of Arabica coffee cherry peel polysaccharides (CCPPs) and the underlying regulatory mechanism remain poorly understood. This study isolated polysaccharides from coffee cherry peel, and their functional properties and the lipid-lowering effects and mechanisms on hyperlipidemic mice. In high-fat diet-fed (HFD-fed) mice, CCPP administration had significant regulatory effects on various metabolic parameters. In laboratory mice where hyperlipidemia is induced by a high-fat diet, CCPP administration improved serum lipid levels and demonstrated anti-inflammatory and antioxidant effects. These benefits were achieved by reducing pro-inflammatory cytokine expression, enhancing antioxidant enzyme activity, and lowering overall oxidative stress. Additionally, it effectively decreased fat area in liver tissues and adipocytes. Specifically, compared with the control group, after high-dose CCPP intervention, the adipocyte area of mice on a high-fat diet was significantly reduced by 41.3%. Notably, CCPP intervention resulted in a shift in the gut microbiota composition. At the phylum level, the model group showed a significant increase in Bacillota and a concomitant reduction in Bacteroidetes in comparison with the control group. Compared with the model group, CCPP intervention, especially in the CCPP-H group, resulted in an increase in the proportion of Bacteroidetes and a decrease in Bacillota. At the genus level, CCPP modulated the abundances of key bacterial genera; for instance, the relative abundance of Lachnospiraceae_NK4A136_group increased from 2.64% in the model group to 11.9% in CCPP-H group, while Faecalibaculum decreased from 62.69% to 41.27% in CCPP-L group and 25.29% in CCPP-H group. These shifts suggest that CCPP has a reparative effect on the gut microbial composition, potentially contributing to the promotion of gut health. Taken together, these factors highlight the promise of CCPP as a functional food ingredient for dietary interventions to ameliorate obesity and hyperlipidemia. Full article

Background: Vitamins are micronutrients involved in multiple physiological processes critical for athletic performance. Because athletes are often exposed to increased oxidative stress, higher metabolic turnover, and greater nutritional demands, which can potentially lead to deficiencies in vitamins, understanding vitamin supplementation as a function of sport discipline is of fundamental importance. Methods: This narrative review synthesizes research findings from the past decade, supplemented with earlier studies where necessary, focusing on vitamins A, C, D, E, and the B-complex vitamins. Peer-reviewed literature was evaluated for evidence on the prevalence of deficiencies in athletes, physiological mechanisms, supplementation strategies, and their effects on performance, injury prevention, and recovery. Results: Vitamin D deficiency is highly prevalent among athletes, particularly in indoor sports and during the winter months. Supplementation has been shown to improve musculoskeletal health and potentially reduce injury risk. The antioxidant vitamins C and E can attenuate exercise-induced oxidative stress and muscle damage; however, excessive intake may impair adaptive responses such as mitochondrial biogenesis and protein synthesis. Vitamin A contributes to immune modulation, metabolic regulation, and mitochondrial function, while B-complex vitamins support energy metabolism and red blood cell synthesis. Conclusions: Vitamin supplementation in athletes should be individualized, targeting confirmed deficiencies and tailored to sport-specific demands, age, sex, and training intensity. Dietary optimization should remain the primary strategy, with supplementation serving as an adjunct when intake is insufficient. Further high-quality, sport-specific, and long-term studies are needed to establish clear dosing guidelines and to assess the balance between performance benefits and potential risks associated with over-supplementation. Full article

Diabetic wounds exhibit impaired immune function, delayed neutrophils recruitment, and heightened infection risk which compromises early infection control and delays healing. We have demonstrated that topical CCL3 treatment restores neutrophil influx, reduces bacterial infection by ~99%, and accelerates wound healing in diabetic mice. As per Food and Drug Administration (FDA) Guidelines for Investigational New Drug (IND), we conducted a 14-day acute toxicity study in diabetic mice following a single topical administration of CCL3 at effective low dose (1 µg) and high dose (10 µg) per wound. Mice were monitored for clinical signs, body weight, and food intake throughout the study period. On day 14, serum biochemistry (ALT, AST, BUN, creatinine, metabolic markers) and histopathology of major organs (liver, kidney, heart, lungs, spleen) were assessed. CCL3-treated diabetic mice exhibited no adverse clinical effects. Hematological and biochemical parameters remained within normal limits, and histopathological analyses revealed no additional organ injury in CCL3-treated groups compared to diabetic control mice. Intriguingly, CCL3-treated mice showed improved ALT levels and reduced hepatic pathology, suggesting hepatoprotective effects and reduced serum IgG, indicating reduced systemic inflammation. Overall, our study demonstrates that diabetic mice tolerate topical CCL3 at doses up to 10 times the effective therapeutic concentration without evidence of systemic organ toxicity. These findings provide strong preclinical support for the translational development of CCL3 as a novel therapy for diabetic wound care. Full article

Constipation is a global health issue, with a prevalence of approximately 16%, and insufficient dietary fiber intake is a major contributing factor. Citrus peel residue contains a high proportion of dietary fiber, accounting for about 20–44% of its composition. In this study, the constipation-relieving effects of three functional components derived from citrus peel residue—cellulose (CEL), pectin (PEC), and citrus peel powder (CPP)—were systematically compared using a loperamide-induced mouse model. All groups were administered an equivalent dose of 200 mg/kg daily. The results showed that supplementation with CEL, PEC, and CPP improved defecation parameters. Among these, PEC effectively modulated the SCF/C-kit and Nrf2/HO-1 pathways. Compared with the model group, PEC increased Akkermansia abundance by approximately 34% and reduced Desulfovibrio abundance by about 26% Additionally, the smaller particle size and improved solubility of PEC promote the production of beneficial metabolites, thereby alleviating constipation. In contrast, CEL primarily alleviates constipation through its physical properties. At equivalent doses, CPP provides less constipation relief due to its lower component concentrations and a primary composition of insoluble dietary fiber. These findings provide preliminary mechanistic insights and support further exploration of citrus by-products as functional food candidates for the management of constipation. Full article

Tris(1-chloro-2-propyl) phosphate (TCIPP) is an emerging environmental pollutant associated with adverse respiratory effects, yet whether niacin has a protective effect on lung function remains unclear. Data from 1031 participants in the 2011–2012 National Health and Nutrition Examination Survey (NHANES) were analyzed using multiple linear regression to assess associations between urinary bis(1,3-dichloro-2-propyl) phosphate (BCIPP), dietary niacin intake, and pulmonary function. Animal models were established to investigate TCIPP-induced lung injury and the protective effects of niacin. Lung injury was assessed by histopathology, lung function, inflammation, and oxidative stress-related indicators. Comparative Toxicogenomics Database (CTD), molecular docking, and Western blot were performed to explore underlying mechanisms. Higher urinary BCIPP concentration was associated with reduced lung function, whereas higher dietary niacin intake was associated with improved lung function. Notably, BCIPP levels showed positive associations between dietary niacin intake and FEV₁ [β (95% CI) = 0.11 (0.06, 0.16), p_adj < 0.001] and FVC [β (95% CI) = 0.09 (0.05, 0.13), p_adj < 0.001] in males with lower BCIPP exposure. In male mice, TCIPP exposure caused dose-dependent lung injury, inflammation, and oxidative stress, while niacin supplementation alleviated lung damage, improved lung function, and restored antioxidant defenses by inhibiting NF-κB phosphorylation. Niacin supplementation alleviated TCIPP-induced lung injury in males by inhibiting oxidative stress and NF-κB activation, suggesting niacin as a potential nutritional strategy to improve lung function. Full article

Background and Objectives: There is a lack of information on the dietary intake of long-term combined oral contraceptive users (COC-users) in relation to their body composition. The aim of the pilot study was to determine the food consumption of young women using COCs for >6 months and its relationship to body composition compared to non-users. Materials and Methods: A total of 45 healthy women (21.8 ± 1.7 years) were divided into COC non-users (n = 19) and users of a low (≤20 μg) ethinylestradiol (EE) dose (n = 18) and a medium (30–35 μg) EE dose (n = 8). Anthropometric data, body composition, physical activity levels, three-consecutive-days of dietary records, and serum concentrations of calcium, magnesium, and vitamin D were assessed. Statistical methods included chi-squared, Fisher’s exact test, t-test, Mann–Whitney U test, Spearman’s correlation, and multiple linear regression. Results: There were no differences between COC-users and non-users in terms of physical activity, intake of micronutrients, body mass index, body fat percentage (BF%), or bone mineral density (BMD). COC-users consumed a higher percentage of energy from fats (p = 0.02) and had higher serum vitamin D levels (p < 0.01). BF% was negatively associated with BMD (coefficient −0.008; p = 0.027). Conclusions: The use of COCs for ˃6 months is not associated with FM or BMD, regardless of dietary differences. Further attention should be paid to possible associations between COCs use, dietary habits, and body composition (including BMD). Full article

Goji berry consumption provides various beneficial health effects, although little is known about the possible toxicological and pro-oxidant effects. Therefore, this study aimed to evaluate the subchronic oral toxicity of goji berry juice (GBJ) for 28 days in Wistar rats (OECD 407). The GBJ was prepared in a blender with water and then filtered. The total phenolic compounds were evaluated using the Folin method (μg equivalent of gallic acid/mL juice). Forty 90-day-old female Wistar rats were divided into four groups of 10 animals each. The control group received an oral saline solution of 1 mL/100 g, and the treatments received daily doses of 1.85, 5.68, and 11.36 μg GAE/100 g for 28 days. Our findings revealed that GBJ does not alter animal body weight or food intake, although we observed higher hepatic transaminase levels and reactive species generation in the liver and kidney, which may have led to imbalanced antioxidant defenses and damaged lipids and proteins. Additionally, we observed kidney damage with increased Bowman space. Our 28-day findings indicate that goji berry juice at doses equivalent to typical human consumption can induce early redox imbalances and hepatic and renal biochemical alterations in female Wistar rats, warranting caution and further long-term, sex-inclusive studies. Full article

Glyphosate (GLY), the active ingredient in widely used herbicides, was long considered specific to plants and bacteria, yet mounting evidence shows it can impair endocrine and reproductive functions in animals. Given its widespread use and environmental persistence, assessing its effects at regulatory-approved doses is critical. Here, adult female zebrafish (Danio rerio) were exposed for 21 days to different concentrations of dietary GLY at 0.5 mg/kg body weight/day (GLY0.5, acceptable daily intake, ADI), 5 mg/kg/day (GLY5), and 50 mg/kg/day (GLY50, no-observed-adverse-effect level, NOAEL). Our findings show that dietary GLY induces dose-dependent perturbations along the hepato-gonadal axis. At the highest dose, chronic stress responses were evident through elevated cortisol and cortisone, accompanied by hepatic glycogen accumulation and ferroptotic stress. Although follicle histology appeared normal, alterations in several genes involved in oocyte maturation and estrogen receptor signaling translated into reduced fertilization, revealing compromised gamete quality rather than overt follicular development abnormality. Likewise, the lowest dose triggered modifications in genes crucial for oogenesis without altering the follicle development, although in this case, potential compensatory mechanisms could have led to enhanced fertilization. GLY5 did not alter the number of fertilized eggs but significantly increased embryo mortality. Overall, dietary GLY disrupted hepatic metabolism, endocrine signaling, and reproduction in a non-monotonic manner, even at levels considered safe by EFSA. These findings highlight the need to reevaluate current safety thresholds with attention to female-specific reproductive risks. Full article

The interrelationship between iron metabolism and vitamin D has attracted increasing attention; however, nutritional knowledge regarding the relationship between iron and vitamin D remains scarce. We hypothesized that a continuous increase in dietary vitamin D intake would enhance biological iron levels through the regulation of hepcidin, and we investigated whether dietary vitamin D levels alter iron dynamics and blood cell status. Twenty-five male Wistar rats aged 7 and 8 weeks were used in experiments 1 (14 days) and 2 (4 days), respectively. Rats were divided into control and vitamin D-supplemented diet groups (14C vs. 14A in Experiment 1; 4C vs. 4A in Experiment 2) and fed the experimental diet ad libitum. In Experiment 2, no significant differences were observed in serum and liver iron levels, total iron-binding capacity, and serum transferrin saturation between groups; however, hepcidin (HAMP) mRNA expression was lower in the 4A group. By contrast, the 14A group showed significantly higher serum and liver iron levels and higher HAMP mRNA expression than the 14C group. These results indicate that high-dose dietary vitamin D alters iron metabolism in rats, characterized by transient suppression of hepatic hepcidin expression and increased liver iron, suggesting modulation of iron regulatory pathways. Full article