Medicine and Pharmacology

Abstract: The escalating global temperatures and increased frequency of heatwaves associated with climate change have intensified the risk of chronic dehydration, particularly in the Arab Gulf, Sahara, Sub-Saharan regions, and in Some part of Europe and North America during Summer. This study presents the development, biomaterial synthesis process, and comprehensive physicochemical characterization of a novel nanocomposite-based vitamin-fortified water designed as a potential approach to address hydration and nutritional needs in populations at risk of dehydration, with the vitamins included selected for their established roles in immune function and antioxidant defense. The formulation centers on a biopolymer-stabilized lipid nanocomposite incorporating concentrated vitamin extracts comprising Ascorbic Acid (Vitamin C), Riboflavin (Vitamin B₂), 25-Hydroxycholecalciferol (Vitamin D₃), and α-Tocopherol Acetate (Vitamin E). The bioactive nanocomposite is stabilized using Polyethylene Glycol (PEG)-based biocompatible surfactants and Rosmarinic acid as a natural antioxidant preservative, forming a microemulsion-based nanocomposite with a mean droplet diameter of 89.3 ± 4.7 nm and polydispersity index of 0.187, confirming colloidal stability and homogeneous nanoparticle size distribution. This Vitamin Extract concentrate is subsequently dispersed in biologically activated water (prepared using sucrase-catalyzed enzymatic treatment followed by UV-C irradiation, pH 6.9) to produce the final functional beverage. Comprehensive stability studies conducted over 12 weeks under varying storage conditions (4°C, 25°C, 40°C; light-protected versus exposed) demonstrated >90% vitamin retention under refrigeration and >85% retention at room temperature, with accelerated degradation observed at 40°C and under light exposure. The resulting product is a colorless, palatable liquid with a pH of 6.0, designed as a biomaterial-based functional beverage to support hydration, bolster immune function, and deliver essential micronutrients. This work outlines both conventional solution preparation and a non-conventional, sequential adiabatic mixing process for formulating the vitamin-loaded nanocomposite, with full analytical validation including nanoparticle size analysis, zeta potential measurement, and quantitative HPLC-DAD vitamin quantification.

Abstract: Background: Poor appetite, a major contributor to malnutrition, is highly prevalent among older adults and associated with adverse clinical outcomes. Nevertheless, no effective appetite targeted treatments are currently part of clinical practice alongside nutritional interventions. Medical cannabis has been proposed as a potential appetite stimulant in older adults with poor appetite through modulation of appetite regulating hormones such as glucagon like peptide 1 (GLP 1) and ghrelin, but the evidence remains limited. Aims: To investigate the associations between a fixed dose of Sativex® (8.1 mg Δ9-tetrahydrocannabinol (THC) and 7.5 mg cannabidiol (CBD)) versus placebo and postprandial GLP 1, total ghrelin concentrations as well as subjective appetite in older adults with poor appetite, and the associations between THC and its metabolites on these outcomes. Methods: This protocolized secondary analysis included 17 participants (≥65 years) with poor appetite from a double blinded, randomized, placebo controlled crossover trial. Participants received Sativex® or placebo on two separate study days. GLP 1 and total ghrelin were measured following a standardized breakfast, and subjective appetite was assessed repeatedly using visual analogue scales. Associations were analyzed using linear mixed effects models. Results: Sativex® administration compared with placebo was associated with an estimated 2.38 pmol/L (95% confidence intervals (CI) -0.71−5.46; p = 0.137) reduction in mean GLP 1 concentration, time dependent changes in mean total ghrelin (p = 0.054), and overall estimates of reduced subjective appetite. Increased THC and metabolite concentrations were associated with reduced estimates of mean GLP-1 concentrations and subjective appetite, and an increased mean total ghrelin. However, no clinically relevant or statistically significant associations were observed, and estimates had wide CIs, warranting cautious interpretation. Conclusions: In conclusion, the administration of medical cannabis, formulated as Sativex®, did not differ from placebo with respect to postprandial GLP-1, total ghrelin as well as subjective appetite over time in older adults with poor appetite. The same was found for associations between THC and its metabolites, and GLP-1, total-ghrelin, and subjective appetite.

Abstract: Depression and anxiety increasingly look like disorders of systemic biology, where chronic stress, immune drift, and vascular dysfunction converge on brain relevant symptoms. Fermented foods are widely studied as psychobiotic candidates, yet results remain inconsistent because products vary in chemistry, viability, sodium, and biogenic amines, and trials often rely on broad symptom outcomes without exposure verification. A major gap is the lack of a reusable, mechanism first framework that links what a product delivers to barrier, endothelial, and neurovascular target engagement. This review addresses that gap by treating fermented vegetables, dairy, soy, and selected Brazilian cassava ferments and artisanal cheeses as metabolite engineering platforms mapped onto a tri-barrier remodeling axis from gut epithelium to endothelium and platelets to the blood brain barrier. We synthesize dosing grade metabolite modules, including short chain fatty acids, tryptophan derived indoles, bile acids, neuroactive small molecules, and peptide and exopolysaccharide fingerprints, and align them with interpretable readouts for permeability, endotoxemia proxies, endothelial activation, immunothrombosis, and epigenetic aging pace. Here we highlight how this modular stack converts heterogeneous food studies into testable exposure hypotheses, guides comparator design and phenotype stratification, and clarifies why null results can be informative. The framework supports trial ready product templates that can generalize across regions while making space for culturally specific foods and practical clinical translation.

Abstract: A recent Science perspective by Magkos, Forde, and Robinson critically examined five randomized controlled trials on ultraprocessed foods (UPFs) and concluded that the evidence for a processing-specific effect on energy balance is weak. Their analysis exposed a deeper problem: the reliance on the Wishnofsky rule – a fixed tissue energy density of 7,700 kcal/kg – to translate weight change into energy imbalance. This rule, though widely used, is a statistical abstraction, not a physical constant. Here, I argue that the Wishnofsky rule constitutes a structural blind spot that prevents energy balance model (EBM)-based analyses from adequately accounting for water shifts, nitrogen balance, and the varying composition of tissue change. I apply the mass balance model (MBM) to reinterpret the five UPF trials and demonstrate that MBM – by tracking mass flows directly in grams and decomposing weight change into its true components (fat, lean mass, glycogen, water) – resolves the very ambiguities that the Science perspective identified. I conclude by outlining what an MBM-informed UPF trial should measure and argue that future feeding studies must move beyond the Wishnofsky rule to direct mass accounting to yield mechanistically interpretable results.

Abstract: Background: Apulia and neighboring Southern Italian regions present a complex genetic stratification shaped by historical migrations. Phenylketonuria (PKU), caused by PAH mutations, serves as an excellent model for molecular epidemiology. This study maps the geographical distribution of PAH variants in a large Southern Italian cohort, evaluating their correlation with clinical phenotypes and long-term Body Mass Index (BMI). Methods: A retrospective cohort study was conducted on 344 patients followed for at least 10 years. Genetic characterization evolved from Sanger to Next-Generation Sequencing, and patients were stratified into micro-geographic clusters. Results: The genetic landscape was dominated by three ancestral variants (c.1208C>T, c.1066-11G>A, c.898G>T), accounting for 58% of the allelic pool. Significant micro-geographic polarization was observed: c.1222C>T clustered in Central-Northern Apulia, mirroring historical Norman-Swabian migration, whereas c.441+5G>T enriched in Southern Apulia. At final follow-up, classic PKU patients exhibited a four-fold increased risk of obesity, driven by severe null alleles enforcing lifelong dependency on engineered low-protein foods. Conclusion:PAH mutational stratification acts as a contemporary reflection of historical migratory maps. Incorporating regional and genotypic mapping provides a precision medicine framework to anticipate phenotype severity, optimize therapeutic management, and tailor long-term metabolic risk monitoring.

Abstract: Abstract Background/Objectives: Long COVID (LC) has been associated with persistent in-flammation and impaired vascular health. Dietary minerals are involved in the regula-tion of oxidative stress, endothelial homeostasis, and arterial stiffness; however, their relationship with vascular health in LC remains poorly explored. This study aimed to examine the association between dietary mineral intake and markers of vascular stiff-ness and vascular aging in adults with LC, while exploring potential sex-specific pat-terns. Methods: A total of 304 adults with LC from the BioICOPER study were includ-ed. Dietary mineral intake was assessed using a validated 7-day dietary record from the EVIDENT tool. Vascular assessment included carotid intima–media thickness (cIMT), carotid–femoral pulse wave velocity (cfPWV), brachial–ankle pulse wave velocity (baPWV), and the vascular aging index (VAI), measured using carotid ultrasonography and validated devices, including SphygmoCor® and VaSera®. Multivariable linear re-gression models were used to evaluate the associations between dietary mineral intake and vascular outcomes, adjusting for sociodemographic, clinical, hemodynamic, an-thropometric, quality-of-life, and dietary-pattern variables. Results: Higher intakes of magnesium, selenium, potassium, and phosphorus were associated with lower cfPWV. Potassium intake was also inversely associated with baPWV, whereas selenium and phosphorus intakes were inversely associated with VAI. In sex-stratified analyses, in-verse associations were more consistent among women, particularly for cfPWV and VAI. However, formal interaction analyses did not confirm significant sex-related ef-fect modification. Conclusions: Dietary mineral intake was associated with vascular stiffness, particularly central arterial stiffness, and vascular aging in adults with LC. These findings suggest that adequate mineral intake may represent a relevant nutri-tional factor for vascular health in LC. Prospective studies and nutritional intervention trials are warranted to confirm these results and clarify their clinical relevance.

Abstract: Background/Objectives: Diabetic retinopathy (DR) is a major microvascular complication of type 2 diabetes (T2D) and a leading cause of visual impairment. While traditional risk factors contribute to DR development, the role of dietary habits and their association with vision-related quality of life remains unclear. This study investigated the relationship between dietary intake, DR, and vision-related quality of life in subjects with T2D. Methods: In this cross-sectional study, 129 subjects with T2D were classified as no DR (NDR; n = 85), non-proliferative DR (NPDR; n = 36), or proliferative DR (PDR; n = 8). Dietary intake was assessed using a food frequency questionnaire, Mediterranean diet (MD) adherence by the MD Score, and vision-related quality of life by the NEI-VFQ-25. Multivariable logistic regression identified factors associated with DR. Results: DR was present in 34.1% of participants. Subjects with DR had longer diabetes duration than those without DR (18 vs. 16 years, p < 0.01), with 12% higher odds of DR per additional year. Overall MD adherence did not differ between groups; however, lower legume consumption was independently associated with higher odds of DR (OR 2.5, 95% CI 1.1–5.8, p = 0.037). PDR was associated with poorer vision-related quality of life. Higher saturated fat intake correlated with worse questionnaire scores, whereas monounsaturated fatty acids and vitamin E showed positive associations. Conclusions: Specific dietary components, rather than overall MD adherence, were associated with DR and vision-related quality of life, supporting targeted nutritional strategies in DR management.

Abstract: Background/Objectives: Branched-chain amino acids (BCAAs) may play a protective role in the progression of heart failure; however, controversial results also exist. This study investigates the association between fasting serum BCAA levels and plasma NT-proBNP concentrations in individuals with fragmented QRS (fQRS) on ECGs within the HO-ZUGAWA health-checkup cohort in Japan, offering insights into cardiac health. Methods: This analysis included 252 participants who attended health check-ups. Fasting blood samples were analyzed using a standardized laboratory test. Internal-standard–normalized relative peak-area ratios of BCAAs and selected amino-acid–related organic acids were measured and log-transformed for analysis. Results: NT-proBNP levels did not differ significantly between individuals with and without fQRS. Among those with fQRS, higher levels of BCAAs and 2-hydroxybutyric acid (2-HB) were associated with lower NT-proBNP levels: leucine (r = -0.38, p = 0.0001), while valine (r = -0.28, p = 0.0053) and isoleucine (r =-0.21, p = 0.041); 2-HB (r = -0.21, p = 0.039). After adjustment for age, sex, BMI, and estimated glomerular filtration rate (eGFR)(n=252), leucine remained inversely associated with NT-proBNP in individuals with fQRS (r = -0.28, p = 0.00072) and positively associated in those without fQRS (r = 0.23, p = 0.0048). fQRS showed an interaction with leucine levels regarding NT-proBNP levels. Conclusions: Fasting serum leucine is an important marker of cardiac health. Leucine demonstrates an inverse correlation with NT-proBNP levels in individuals with fQRS, suggesting that lower BCAA levels may serve as potential indicators of heart failure progression and that BCAA supplementation may play a preventive role, particularly in individuals with cardiac fibrosis. Further research is warranted to explore therapeutic implications.

Abstract: Gastrointestinal dysfunction is common in critically ill patients and frequently com-promises the delivery and tolerance of enteral nutrition. Traditional bedside markers such as gastric residual volume or nonspecific abdominal symptoms provide only lim-ited diagnostic accuracy and often fail to capture dynamic alterations in gastrointesti-nal function. Gastrointestinal ultrasound (GIUS) has emerged as a noninvasive, bed-side-applicable method that enables structural and functional assessment of the gas-trointestinal tract and may support more individualized nutritional management in intensive care. This narrative review summarizes the physiology and pathophysiology of gastric emptying and intestinal transit in critically ill patients, reviews established GIUS pro-tocols including Gastrointestinal and Urinary Tract Sonography (GUTS), Acute Gas-trointestinal Injury Ultrasound Scoring (AGIUS), the Lai protocol, and the Ultrasound Meal Accommodation Test (UMAT), and proposes pragmatic GIUS-based algorithms for enteral feeding decisions. Three clinical use cases are addressed: 8-hour monitoring during ongoing enteral nutrition, preprandial assessment of feeding readiness, and once-daily screening of gastrointestinal function. Current evidence supports the clinical relevance of key sonographic parameters such as gastric antral cross-sectional area and small-bowel diameter, whereas other measures, including mucosal thickness, colonic wall thickness, and Doppler-derived resistive indices, require further validation. UMAT adds a dynamic component to static sonographic assessment and may improve evaluation of gastric accommodation and emptying in selected patients. Structured GIUS protocols offer a promising, evidence-informed extension of bedside assessment for enteral nutrition management in the intensive care unit. However, the available literature remains heterogeneous and is largely based on physiological stud-ies, observational cohorts, and expert consensus. Prospective multicenter studies are needed to validate cut-off values, training standards, and outcome effects before GIUS-based algorithms can be adopted as stand-alone decision tools.

Abstract: Background/Objectives: Immunonutrition uses dietary bioactive compounds to support immune function while preserving systemic physiological balance. Donkey milk, bovine colostrum, and royal jelly contain complementary antimicrobial, immunoglobulin-rich, and immunoregulatory components, but their combined effects remain insufficiently characterized. Methods: A 6-week controlled study was conducted in female rabbits assigned to four groups (n = 15/group): vaccinated only (G1), immunonutraceutical only (G2), vaccination plus immunonutraceutical (G3), and pre-conditioned immunonutraceutical followed by vaccination and continued supplementation (G4). Serum total immunoglobulins and lysozyme were measured longitudinally. Biochemical indices were monitored throughout the study, and hematological parameters were evaluated at the final time point. Mixed-effects models, generalized estimating equations, principal component analysis, and correlation-based systems analyses were applied. Results: Supplementation significantly modulated both humoral and innate immune responses. The strongest terminal immunoglobulin response was observed in G4 (26.00 ± 5.80 mg/mL), whereas sustained lysozyme elevation was most pronounced in supplemented groups, particularly G3 (3.13 ± 0.44 ng/mL). Within-subject analysis demonstrated significant innate–adaptive immune coherence (p = 0.000006). Biochemical analyses showed coordinated metabolic adaptation without evidence of organ toxicity, and hematological findings indicated preserved inflammatory and hematopoietic stability. Conclusions: Multi-component immunonutraceutical supplementation enhanced humoral and innate immune dynamics in a timing-dependent manner while maintaining biochemical and hematological safety. These findings support the potential of combined donkey milk, bovine colostrum, and royal jelly as functional ingredients for coordinated immune support.

Abstract: Milk was designed by evolution to provide superior nutrition for support of growth and development of mammalian young. When humans domesticated dairy cattle about 10,500 years ago, they also adopted milk for adult consumption and learned to separate and utilize its constituent parts, milk proteins whey and casein for muscle growth, milk fermentation to make kefir, yogurt, and cheese, and milkfat to make butter. Research on how consumption of these different milk products affects human health has generated much factual data and some uncertainties and controversies about the extent it can be used to improve adult human body and overall metabolic health. This is important in the context of global burden of high cardiovascular morbidity and concerns about any impact of milkfat consumption on cardiovascular (CVD) and coronary heart diseases (CHD). The first theme of this review examines the involvement of milk proteins whey and casein on skeletal muscle hypertrophy (MHT). The major contribution of resistance training (RET) to MHT is contrasted to the lesser, but still important, contribution of protein supplementation (PS) and uncertainties about the efficacy of the milk proteins relative to plant proteins, along with dose, training status, and timing of PS relative to RET in producing MHT. The exceptionally rich concentration of essential and branched-chain amino acids makes whey protein and casein highly effective but not essential for MHT which can also be achieved with higher quality plant PS and is not critically dependent on either the timing of PS, the training status, or the age of users. The second theme examines the nature and importance of milk fermentation in production of full-fat and low-fat yogurt, kefir, and cheese in terms of bacteria involved, their metabolism in the gut, their beneficial influence on the gut microbiome (GM) and on overall as well as cardiovascular health. Lastly, milkfat as influence on cardiovascular health is discussed both from the perspective of its effects on blood lipids and cardiovascular physiology, but also as a component of the complex dairy matrices. As part of a rich nutrient matrix, milk products provide benefits to cardiovascular health because of their biologically active proteins and fatty acids which exert anti-inflammatory, anti-carcinogenic, antioxidative, and other beneficial actions, despite their high fat content and level of fat saturation. Fermentation usually lowers CVD and CHD risks of full-fat milk and its products, but health benefits often are greater when their fat content is reduced. Butter does not benefit from the biological activities of the milk proteins and is not fermented, so when consumed in large quantities, the balance of cardiovascular benefits shifts toward higher CVD and CHD risk. Three knowledge gaps need to be corrected for a better understanding of health benefits of consumption of milk products. Individual nutrient components in dairy food matrices need to be measured and recognized. Their identity needs to be linked to a better understanding of how they influence atherogenic lipoproteins and protein synthesis. And maximal consumption limits need to be defined for full-fat milk products to assure the benefits that their biologically active components offer, but also to reduce their detrimental effects on cardiovascular risk factors. Overall, as a food category, milk products justify acceptance as a healthy natural source of nutrition that was evolutionarily designed to support early growth and development of mammalian young but need to be prudently implemented for their lifelong consumption in adulthood.

Abstract: Background: MASLD has a prevalence of almost one-third in adults worldwide and is not currently treated pharmacologically with a first-line therapy. Lifestyle change is still the foundation of management, however, the relative effectiveness of various behavioral and dietary intervention approaches is poorly defined in both metabolic and psychobehavioral outcome areas. Objective: We compared four classes of interventions, behavioral motivation support (BMS), biomarker-guided personalized diet management (BPDM), general diet education (GDE), and prescribed diet models (PDM) against usual care (UC) in patients with MASLD using network meta-analysis (NMA). Methods: Six electronic databases and two trial registerswere searched through 31 March 2026. Eligible studies were randomized controlled trials (RCTs) in adults with MASLD/NAFLD; risk of bias was assessed with the Cochrane ROB 2 tool, and evidence certainty was graded using the CINeMA-informed GRADE framework. A frequentist random-effects NMA was conducted using the R package netmeta; interventions were ranked by P-scores. Results: Fourteen RCTs (n = 1,805; published 2016–2026) were included. BMS showed the largest ALT reduction (MD −15.63 U/L, 95% CI −27.56 to −3.69; P-score 0.89) and ranked highest for dietary behavior and self-efficacy outcomes. BPDM ranked first for BMI (MD −1.84 kg/m², 95% CI −3.48 to −0.20; P-score 0.82), body weight (MD −5.80 kg; P-score 0.76), and HbA1c improvement (P-score 0.75). All certainty ratings were very low. Conclusions: These findings suggest that BMS and BPDM may target complementary outcome domains in MASLD; however, all estimates carry very low certainty, and adequately powered direct comparative trials are essential before clinical translation.

Abstract: Background/Objectives: Oxidative stress is a key pathogenic factor in gastric diseases (GDs). Nutraceuticals with antioxidant activity derived from macroalgae represent promising preventive strategies. However, Chilean macroalgae remains poorly explored in the context of GDs, particularly associated with oxidative stress. This study evaluated the antioxidant and cytoprotective properties of crude aqueous and ethanolic extracts from green, brown, and red macroalgae collected along the north-central coast of Chile. Methods: Crude extracts were prepared from green, brown, and red macroalgae and evaluated for antioxidant activity via ABTS, DPPH, and FRAP assays. Using hydrogen peroxide-induced oxidative stress in GES-1 gastric epithelial cells, we assessed cell viability (MTS assay), intracellular reactive oxygen species (ROS) levels (time-lapse confocal microscopy), and apoptosis (active caspase-3 detection). Results: All extracts exhibited antioxidant activity; the red macroalgae Gracilaria chilensis displayed the highest flavonoid content (up to 2.236 mg QE/g dw). Notably, extracts from G. chilensis, S. gaudichaudii, and M. canaliculata preserved GES-1 cell viability under hydrogen peroxide-induced stress, outperforming green and brown species, demonstrating the superior cytoprotective capacity of red macroalgae compared to other groups. Furthermore, G. chilensis extracts significantly reduced intracellular ROS levels and attenuated ROS-induced apoptosis. Conclusions: Red macroalgae extracts, particularly G. chilensis, exhibit strong antioxidant and cytoprotective effects. Our findings demonstrate that these species outperform green and brown macroalgae, addressing a gap in knowledge regarding Chilean marine resources. These results support their potential development as nutraceuticals for the prevention of oxidative stress-related gastric diseases and highlight red macroalgae as a valuable source of bioactive compounds for diet-based preventive strategies.

Abstract: The energy balance model (EBM) has dominated human body weight regulation research for nearly a century, yet its reliance on indirect mass-to-energy conversions introduces propagated uncertainties that obscure the stoichiometric mechanisms governing tissue accretion and loss. A mass balance model (MBM), which tracks macronutrient mass flows directly in grams without intermediary energy-unit transformations, has recently been proposed as a conceptually simpler, mathematically consistent, and mechanistically faithful alternative. However, widespread adoption of the MBM has been hindered by the absence of standardized protocols, validated analytical frameworks, and practical implementation guidance. This paper fills that gap. I provide a comprehensive, step-by-step guide to MBM implementation, organized into five interdependent modules: (1) quantification of mass intake via precise food and beverage weighing with macronutrient composition analysis, (2) respiratory gas exchange measurement by indirect calorimetry for stoichiometric determination of substrate oxidation, (3) 24-hour urine and fecal collection protocols for nitrogen and carbon outflow quantification, (4) body composition assessment methods for independent validation of MBM predictions, and (5) data integration and computational workflows that produce complete daily mass balances for carbon, nitrogen, and water. The mathematical and computational framework is fully specified, including the core dynamic equation, derivation of the mass clearance coefficient, and prediction of body composition trajectories via Forbes's relationship. Translational applications are discussed, including early detection of lean tissue loss, real-time dietary monitoring, personalized protein prescription, and pharmacotherapy evaluation. By equipping researchers and clinicians with the tools necessary to adopt direct mass accounting, this paper aims to accelerate the transition from an energy-centric to a mass-centric paradigm in human metabolism research.

Abstract: Background: Vitamin D optimizes musculoskeletal function and athletic performance, yet optimal supplementation protocols remain unclear. Methods: In this double-blind RCT, 18 professional female soccer players were randomized during autum preparatory period (August-September) to receive vitamin D₃ (4000 IU/day; n=9) or placebo (n=9) for 8 weeks. Outcomes included serum 25(OH)D/1,25(OH)₂D, hematology, RAST, 5/30-m sprints, and CMJ. Results: At baseline, after summer exposure, four players had 25(OH)D ≤ 30 ng/mL, and fifteen had levels between 30–50 ng/mL; none exceeded 50 ng/mL. After eight weeks of supplementation, no significant differences were observed between groups in 25(OH)D, and metabolites (Δ25(OH)D: EG +12.4±8.2 vs. PG +3.1±6.5 ng/mL; p=0.12), perfomance, or morphology. Training improved RAST (p=0.001) and 30-m sprint (p=0.005). Conclu-sions: Vitamin D₃ supplementation at 4000 IU/day for eight weeks did not significantly improve strength, speed, or CMJ performance in professional female soccer players. Persistently suboptimal vitamin D status suggests that higher doses may be required to improve anaerobic capacity. Further studies in this specific population are warranted, and higher supplementation doses, as observed in studies on male football players, may potentially lead to more pronounced improvements in physical performance tests.

Abstract: The role of the gut-brain axis is crucial in maintaining homeostasis and regulating neural, hormonal, and immunological activity. This study aimed to evaluate the effects of prebiotic or synbiotic on serum markers related to emotional disorders in individuals with morbid obesity in a triple-blind randomized trial. The sample consisted of 22 subjects, 16 women and 6 men, with a mean age of 41.8 ± 8.5 years and a mean BMI of 47.7 ± 6.8 kg/m². Serum BDNF concentrations decreased significantly after 30 days of prebiotic supplementation (p=0.017), and when analyzing the difference between the evaluated moments, only this group showed a reduction in this parameter. Serum cortisol concentrations were increased in all groups between the moments evaluated, being statistically significant in the synbiotic supplemented group (p=0.028). Serum TNF-α concentrations increased significantly after 30 days of prebiotic supplementation when compared to the baseline of the group itself (p=0.035): however, this variation did not promote significant difference between the groups evaluated after 30 days of supplementation. The results suggest that low grade chronic inflammatory state may be related to neuroendocrine changes present in emotional disorders, but studies with greater sampling power and correlations with clinical findings are necessary to strengthen this evidence.

Abstract: Dietary emulsifiers, common in processed and ultra-processed foods, improve food texture and shelf-life but may affect gut health by interacting with the microbiota and intestinal barrier. While emulsifiers have long been considered safe, growing evi-dence links their presence in ultra-processed foods to chronic disease risk. This review aims to evaluate the current understanding of the factors and mechanisms underlying individual differences in intestinal mucosal susceptibility to dietary emulsifiers. A search of PubMed and Embase through February 2026 identified eight relevant studies. Overall, the available evidence indicates a heterogeneous and highly individ-ualized host response to dietary emulsifiers. These differences appear to be strongly in-fluenced by the gut microbiota and its functional properties, while animal studies fur-ther suggest that host factors such as sex-related differences in microbial composition may also contribute to variability in response. Importantly, not all emulsifiers have the same effects, underscoring compound-specific impacts on gut physiology. The findings demonstrate that sensitivity to dietary emulsifiers varies substantially between individuals, challenging the long-standing assumption that these additives are universally safe. Given the multifactorial nature of this susceptibility, particularly the role of the gut microbiota, future research should adopt an integrative approach that combines microbial profiling with host genetics, immune responses, and early-life exposures. Such efforts will be essential to identify at-risk individuals and to inform more personalized dietary recommendations aimed at preserving intestinal health and reducing disease risk. Importantly, there is a clear need for larger, well-powered studies that can validate and expand upon these initial observations.

Abstract: Background/Objectives: Disease-related malnutrition is highly prevalent in oncology and is associated with poor clinical outcomes. Early detection through nutritional screening is essential; however, the optimal screening tool for ambulatory cancer patients remains uncertain. This study aimed to evaluate the agreement and diagnostic performance of the Malnutrition Screening Tool (MST) and NUTRISCORE compared with the Global Leadership Initiative on Malnutrition (GLIM) criteria in a large nationwide cohort of ambulatory cancer patients. Methods: In this multicenter, observational, cross-sectional nationwide study, adult patients attending oncology day hospitals for intravenous antineoplastic treatment between April and November 2021 were included. Nutritional risk was assessed using MST (cut-off ≥ 2) and NUTRISCORE (cut-off ≥ 5). Malnutrition was diagnosed according to GLIM criteria. Agreement between tools was assessed with Cohen’s kappa, and diagnostic performance was evaluated by sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. Analyses were stratified by tumor nutritional risk and cancer stage. Results: Among 4440 patients from 86 hospitals, 50.7% met the GLIM criteria for malnutrition; 72.5% had moderate and 27.5% severe malnutrition. MST identified 37.5% of patients as being at nutritional risk, compared with 17.3% identified by NUTRISCORE. Agreement between MST and NUTRISCORE was moderate overall (κ = 0.48; 95% CI, 0.45–0.51), but varied markedly according to tumor nutritional risk, ranging from high agreement in high-risk tumors (κ = 0.82) to low agreement in low-risk tumors (κ = 0.28). Relative to GLIM, MST was more sensitive than NUTRISCORE (0.51 vs. 0.27), whereas NUTRISCORE was more specific (0.92 vs. 0.76) and had a higher positive predictive value (0.77 vs. 0.68). Negative predictive value was low for both tools. Conclusions: GLIM-defined malnutrition was highly prevalent in this large cohort of ambulatory patients with cancer. MST provided greater case detection, whereas NUTRISCORE showed a more conservative profile with higher specificity but substantially lower sensitivity. These findings suggest that the choice of screening tool should consider clinical context and tumor-related nutritional risk, and that neither instrument alone reliably excludes malnutrition in outpatient oncology settings.

Abstract: Background: Obesity arises from complex interactions beyond energy imbalance, with the gut microbiome increasingly recognised as a key modulator of metabolic function in obesity. This narrative review examines microbiome-targeted interventions for obesity prevention and treatment. Objective: To synthesise evidence on diet, exercise, biotics (pre/pro/post/synbiotics) and faecal microbiota transplantation (FMT) as modulators of gut microbiota composition and function to improve body composition and metabolic health. Methods: A structured literature search of PubMed, Scopus and Web of Science (2015–2026) informed this narrative review, focusing on studies evaluating the role of the gut microbiome in obesity and the impact of microbiome-targeted interventions. Randomised controlled trials, systematic reviews, meta-analyses and key observational and preclinical studies were prioritised. Evidence was synthesised narratively. Results: Microbiome-targeted interventions including dietary modification, physical activity and biotic therapies demonstrate modest and variable effects on adiposity but may improve metabolic outcomes through mechanisms involving short-chain fatty acids (SCFA), inflammation and gut barrier function. High-fibre diets (e.g., resistant starch, Mediterranean) consistently enhance SCFA-producing taxa and reduce fat mass. Exercise induces modest microbiome shifts favouring beneficial bacteria such as Akkermansia / Bifidobacterium. Biotics (Lactobacillus / Bifidobacterium strains) yield small-moderate reductions in BMI / fat mass with next-generation strains (A. muciniphila, F. prausnitzii) showing promise in preclinical / human pilots. Evidence for FMT in obesity remains limited and inconsistent in humans. Mechanisms converge on energy harvesting, barrier integrity, endotoxemia reduction and GLP-1 / bile signalling. Conclusions: Microbiome modulation appears to complement lifestyle and therapeutic interventions but translation into clinical practice requires strain-specific, well-designed randomised controlled trials and longitudinal data. Personalised multiomics approaches offer future potential.

Abstract: Oxidative stress is an important component of cancer biology with an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense systems. Excess ROS can cause molecular damage and genomic instability. At the same time, ROS signaling remains necessary for normal cellular function. Redox homeostasis is of particular importance in this balance. The role of dietary antioxidants in cancer prevention is complex, depending on the biological context. This narrative review used preclinical and clinical studies to synthetize the current literature. We performed an extensive literature search of Scopus, Web of Science, and PubMed. We focused on articles published between 2021 and 2026. Dietary antioxidants influence redox biology in cancer. It focuses on major redox-sensitive pathways, including Nrf2-Keap1-ARE signaling, AMPK-mTOR regulation, NF-κB-mediated inflammation, mitochondrial quality control (autophagy and mitophagy), and inflammasome activation. These pathways involved in tumor initiation and progression link oxidative stress to metabolic and inflammatory processes. Current evidence suggests that dietary antioxidants act primarly by supporting endogenous defense systems. This may help explain the “antioxidant paradox,” in which antioxidant-rich dietary patterns are associated with a lower risk of cancer. In some studies, high-dose supplementation with isolated antioxidants has produced inconsistent or sometimes adverse results. These effects depend on dose, chemical form, metabolic context, and initial redox state. The gut microbiota is also an important mediator of antioxidant bioactivity. The gut microbiota modulates systemic redox balance by converting dietary polyphenols into bioactive metabolites, not acting only as simple scavengers. This contributes to inter-individual variability. Dietary antioxidants act as modulators of redox signaling. Personalized redox modulation may guide future cancer prevention strategies, emphasizing whole-diet approaches and biomarkers.