Search Results (1,403)

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide and is driven by complex pathophysiological processes, including oxidative stress, chronic inflammation, complement dysregulation, and vascular endothelial growth factor (VEGF)-mediated neovascularization. Nutritional interventions—particularly supplementation with carotenoids, omega-3 fatty acids, polyphenols, and essential micronutrients—have demonstrated clinical benefits in slowing disease progression, as evidenced by landmark trials such as AREDS and AREDS2. However, many AMD-relevant bioactives exhibit poor aqueous solubility, low chemical stability, and limited gastrointestinal bioavailability, which significantly constrain their therapeutic efficacy. Food-grade microgels have emerged as versatile colloidal delivery platforms capable of addressing these limitations through rational structural and physicochemical design. This review provides a systematic roadmap for developing food-grade microgels, organized into: (1) the molecular design of protein- and polysaccharide-based networks; (2) advanced fabrication strategies such as microfluidics and atomization; (3) spatiotemporal release programming within the gastrointestinal tract; and (4) multi-nutrient synergy for retinal protection. This approach highlights how controlled crosslinking, interfacial assembly, and tunable network architectures enhance nutrient stabilization. Particular emphasis is placed on spatiotemporal release programming within the gastrointestinal tract, including diffusion-limited gastric retention, pH- and bile-responsive swelling in the small intestine, and microbiota-triggered degradation in the colon. These mechanisms collectively enable region-specific release, improved micellar incorporation, enhanced systemic absorption, and more consistent retinal delivery. Furthermore, we discuss co-encapsulation strategies that accommodate both hydrophilic and lipophilic bioactives, thereby minimizing antagonistic interactions and enabling synergistic nutritional modulation of oxidative and inflammatory pathways implicated in AMD. A central novelty of this review is the integration of the gut–eye axis, framing microgel-based oral delivery as a systemic pathway to modulate retinal health via the intestinal environment. By bridging retinal disease biology with food colloid science, this review proposes food-grade microgels as a translational platform for next-generation nutraceutical interventions. The integration of programmable release behavior with clinically validated nutrient regimens offers a promising pathway toward more effective and mechanistically informed dietary management of AMD. Full article

Background: Parathyroid hormone (PTH) is closely linked to mineral metabolism, kidney function, inflammation, and cardiovascular disease. However, its clinical significance in unselected hospitalized populations remains insufficiently characterized. We aimed to evaluate the prevalence of elevated PTH and its association with long-term mortality in a real-world cohort of internal medicine inpatients. Methods: In this retrospective cohort study, electronic records of adults hospitalized in an internal medicine department in 2019 were reviewed. Patients with available in-hospital PTH measurements were included. Elevated PTH was defined as >88 pg/mL. Clinical characteristics and laboratory parameters were recorded. The primary outcome was all-cause mortality with a minimum follow-up of 2 years. Cox proportional hazards models adjusted for clinically relevant covariates were used to examine the association between PTH and mortality. Results: A total of 1595 patients were included, of whom 567 (35.5%) had elevated PTH levels. Patients with elevated PTH were older and had a higher burden of chronic kidney disease, cardiovascular disease, and inflammatory and nutritional abnormalities. During a mean follow-up of 22 ± 13 months, mortality occurred more frequently in patients with elevated PTH than in those with normal levels (56.1% vs. 33.7%, p < 0.001). After multivariable adjustment, elevated PTH remained independently associated with increased mortality risk-adjusted HR (1.36, 95% CI 1.15–1.62, p < 0.001). Conclusions: Elevated PTH is common among hospitalized internal medicine patients and is associated with increased long-term mortality. PTH may represent an integrated biomarker reflecting disease burden, inflammation, and renal dysfunction and could contribute to risk stratification in hospitalized populations. Prospective studies are warranted to clarify underlying mechanisms and clinical implications. Full article

Cholestasis in children is characterized by impaired bile flow that disrupts hepatic metabolism, nutrient homeostasis, and effects trace element balance. This narrative review summarizes current evidence on the metabolism, biological functions, and clinical implications of key trace elements—zinc, selenium, copper, and manganese—in pediatric cholestatic liver disease. The liver regulates trace element absorption, intracellular trafficking, storage, and biliary excretion; cholestasis alters these processes, leading to deficiencies or toxic accumulation. Zinc and selenium deficiencies are common and contribute to impaired growth, immune dysfunction, oxidative stress, and delayed hepatic regeneration. Conversely, reduced biliary excretion promotes copper and manganese accumulation, potentially exacerbating liver injury and causing manganese-related neurotoxicity. Recent advances in understanding metal-specific hepatic transporters and trafficking pathways have provided mechanistic insight into these alterations. Management strategies emphasize individualized supplementation, monitoring during enteral and parenteral nutrition, and prevention of deficiency and toxicity. Precision-based nutritional approaches may improve outcomes in pediatric cholestatic liver disease. Full article

Metabolic and bariatric surgery (MBS) has evolved into a highly effective neurohormonal intervention for severe obesity; however, it introduces unique long-term vulnerabilities, particularly regarding alcohol (AUD) and substance use disorders (SUD). This review synthesizes the epidemiological, pharmacokinetic, and neurobiological drivers of postoperative substance misuse. Procedures like Roux-en-Y gastric bypass (RYGB) radically alter ethanol metabolism, eliminating first-pass metabolism and accelerating gastric emptying, while simultaneously recalibrating reward pathways, creating a “reward gap” that facilitates addiction transfer. These physiological shifts exacerbate critical micronutrient deficiencies (thiamine, B12, iron), increase the risk of post-bariatric hypoglycemia, and correlate with higher rates of liver cirrhosis and suicide. Furthermore, substance use is a primary driver of suboptimal weight loss trajectories and weight regain. Mitigation requires a lifelong, multidisciplinary framework involving preoperative risk stratification, validated screening (e.g., AUDIT-C), and targeted nutritional supplementation to safeguard the long-term metabolic and psychological benefits of MBS. Full article

Tripartite interaction among arbuscular mycorrhizal fungi (AMF), small grain cereals—including wheat, barley, oats, and rye—and pathogenic organisms constitute a highly complex ecological system with major implications for plant health, productivity and resilience. AMF colonization increases nutrient acquisition, particularly phosphorus and nitrogen, while concurrently priming host defense mechanisms that increase resistance to a broad spectrum of pathogens. These benefits, however, are strongly context-dependent and modulated by AMF species composition, host genotype, soil characteristics, and environmental conditions. AMF activate resistance pathways and modulate the rhizosphere microbiome, underscoring their central role in shaping plant–pathogen dynamics. Importantly, the relevance of these interactions extend beyond crop protection and yield stability to encompass food security and sustainability goals aligned with the One Health framework, which recognizes the interconnectedness of plant, environmental, and human health. Field implementation of AMF-based strategies has the potential to reduce reliance on chemical fertilizers and pesticides, thereby promoting sustainable cereal production, restoring soil biodiversity, and enhancing ecosystem services, with downstream benefits for human nutrition and environmental safety. This review integrates current knowledge on AMF–cereal–pathogen interactions, synthesizing mechanistic advances and applied perspectives while identifying critical knowledge gaps that must be addressed to effectively deploy AMF in resilient and sustainable agroecosystems within a One Health context. Full article

Human milk is the optimal standard for neonatal nutrition, particularly for preterm infants. Several conditions associated with oxidative stress (OS) may be transmitted from mother to infant through milk, making the preservation of milk quality essential. When maternal milk is unavailable, donor human milk (DM) is commonly used and treated with Holder pasteurization (HoP) to ensure microbiological safety, although this process may affect bioactive components. This study aimed to evaluate the impact of HoP on OS biomarkers, specifically total antioxidant power (TAP) and 15-F2t-isoprostane, using colorimetric and ELISA methods as cost-effective alternatives to analytical gold standards. Twenty paired DM and HoP samples from the Human Milk Bank of Sant’Anna Hospital (Turin, Italy) were analyzed. No significant differences were observed in TAP levels between DM and HoP samples. In contrast, 15-F2t-isoprostane concentrations were significantly lower in DM compared to pasteurized milk (3.16 (1.59–5.27) vs. 0.76 (0.62–1.54), p-value < 0.001). This reduction remained consistent after stratification by sampling day. These findings suggest that HoP may reduce oxidative stress markers in donor milk, potentially limiting neonatal exposure to maternal oxidative imbalance. Although this effect could offer protective benefits for vulnerable preterm infants, further studies are needed to clarify the clinical implications of HoP on redox status and neonatal outcomes. Full article

Background: Fibromyalgia (FM) and eating disorders (ED) represent distinct clinical entities traditionally managed within separate medical specialties, yet emerging evidence suggests significant comorbidity and potential shared pathophysiological mechanisms. Both conditions disproportionately affect women, involve complex multifactorial etiologies and substantially impair quality of life. Despite documented clinical overlaps, the mechanistic connections linking these conditions remain poorly characterized, and integrated treatment approaches are lacking. Objective: This narrative review examines the role of oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway dysfunction as a unifying molecular mechanism connecting fibromyalgia and eating disorders, with emphasis on implications for integrated rehabilitation strategies. Methods: We synthesized current evidence on oxidative stress pathophysiology in fibromyalgia and eating disorders, focusing on Nrf2-Keap1 pathway function, clinical comorbidity patterns and rehabilitation interventions targeting antioxidant defense mechanisms. In PubMed, representative search strings included “(fibromyalgia [MeSH] OR fibromyalgia [Title/Abstract]) AND (“eating disorders” [MeSH] OR “anorexia nervosa” [MeSH] OR “bulimia nervosa” [MeSH])” and “fibromyalgia AND (“oxidative stress” OR Nrf2 OR “redox”)”. Articles in English published through December 2025 were considered, with additional records identified by manually screening reference lists. Results: Fibromyalgia patients exhibit elevated oxidative stress markers, impaired antioxidant enzyme function and compromised Nrf2 activity correlating with disease severity, with studies reporting approximately 30–50% reductions in coenzyme Q10 levels compared with healthy controls. Similarly, eating disorders demonstrate mitochondrial dysfunction and oxidative stress dysregulation, though patterns differ across eating disorder phenotypes. Nrf2 serves as the master regulator of cellular antioxidant defense, coordinating expression of over 500 genes involved in detoxification, cytoprotection, inflammation modulation and metabolic regulation. Evidence suggests Nrf2 activity is regulated by energy balance, potentially linking nutritional status with cellular stress responses. Rehabilitation interventions, including graduated exercise and nutritional optimization with Nrf2-activating foods (cruciferous vegetables, polyphenols, omega-3 fatty acids), offer mechanism-based therapeutic approaches through hormetic Nrf2 activation and direct Keap1 modification. Conclusions: Multidisciplinary rehabilitation programs integrating physical therapy, exercise prescription and nutritional strategies targeting Nrf2 activation offer evidence-based, mechanism-driven approaches to address shared oxidative stress pathophysiology. Nrf2 pathway dysfunction represents a promising and biologically plausible molecular target that may help to unify our understanding of fibromyalgia and eating disorders pending confirmation from prospective clinical studies in comorbid populations. Future research should prioritize prospective clinical trials testing Nrf2-targeted interventions in comorbid populations and collaborative patient-centered care models. Full article

Excessive sodium intake is a public health concern, although sodium chloride is technologically essential in comminuted meat systems due to its role in protein solubilization, water binding, and gel formation. This study evaluated the extent to which progressive sodium reduction combined with nutritional yeast supplementation preserves physicochemical stability, structural integrity, and sensory quality in cooked sausages. Four formulations were produced: a referent and three reduced-salt (NaCl) treatments (−15%, −25%, −35%) containing 2% nutritional yeast (1% in the referent). Water activity increased significantly with salt reduction (0.969–0.977; p < 0.05), accompanied by higher lightness (CIE L*) and yellowness (CIE b*), whereas instrumental redness (CIE a*) remained stable. Proximate composition was unaffected except for the expected decrease in ash and salt content (p < 0.05), while free glutamic acid increased significantly in reduced-salt treatments (0.67 vs. 0.87–0.91 g/kg; p < 0.05). Instrumental texture parameters indicated preserved cutting resistance, although repeated compression revealed reduced structural resilience at the 35% reduction level. Sensory evaluation showed that reductions up to 25% maintained overall typicality and balance, whereas 35% reduction decreased saltiness, slice coherence, aroma harmony, and texture typicality (p < 0.05). Principal component analysis confirmed a multivariate shift from a salt-stabilized structural domain to a softer, yeast-associated sensory domain at the highest reduction level. Moderate sodium reduction combined with nutritional yeast is therefore technologically and sensorially feasible in this product category. Full article

Backyard activities (BAs) constitute a traditional rural food production strategy, although their sustainability-related outcomes remain underexplored in rural contexts. Our objective is to analyze how BAs in rural communities in the municipality of Guasave, Sinaloa, Mexico, represent a local strategy for producing healthy food through sustainable practices, focusing on the relationship between production processes and indicators associated with waste management, water use, and environmental impact. A stratified sampling approach was employed, and a structured survey was administered to 387 households practicing BAs in the region. Instrument consistency was verified using the Kuder–Richardson coefficient. Results show that BAs are relevant in the region: 89.15% of respondents have a family garden and 67.96% raise animals for domestic consumption, supporting an additional income. Chi-square tests revealed statistically significant correlations (p < 0.05) among the study variables, ranging from moderate to strong, with backyard animal husbandry practices standing out in relation to nutritional and health management in animal production, reaffirming that these are not isolated events but complementary activities. These findings indicate that BAs involve interconnected systems rather than isolated activities, reflecting an integrated household-level system with potential implications for resource management and environmental sustainability in rural contexts. Full article

Maintenance of skeletal muscle mass is essential for mobility, metabolic homeostasis, and clinical outcomes across a wide spectrum of physiological and pathological conditions. While muscle atrophy and hypertrophy have traditionally been interpreted through upstream anabolic–catabolic signaling and proteolytic pathways, accumulating evidence indicates that ribosome biogenesis and translational control represent rate-limiting determinants of muscle plasticity. However, this regulatory layer remains insufficiently integrated into current models of muscle adaptation and disease. In this review, we synthesize recent advances in ribosomal RNA transcription, ribosomal protein dynamics, and translational regulation in skeletal muscle, with particular emphasis on signaling networks governed by mTORC1, c-Myc, AMPK, and FOXO. We highlight ribosome biogenesis as a central hub linking mechanical loading, nutrient availability, inflammatory stress, and metabolic status to protein synthesis capacity. Evidence from human and animal studies demonstrates that impaired ribosome production and translational efficiency precede and predict muscle atrophy in disuse, aging, cancer cachexia, and chronic disease, whereas ribosome expansion is a prerequisite for sustained hypertrophy. Beyond quantitative regulation, we discuss the emerging concept of ribosome heterogeneity as a qualitative layer of translational control that may enable selective mRNA translation during muscle growth, stress adaptation, and degeneration. We further examine ribosome–mitochondria crosstalk as a critical but underexplored mechanism coordinating anabolic capacity with cellular energetics. Finally, we outline therapeutic implications, highlighting exercise, nutritional strategies, and indirect pharmacological interventions that preserve ribosomal competence, and propose ribosome-based biomarkers as promising tools for precision management of muscle-wasting disorders. Collectively, this review positions ribosome biology as a translationally relevant framework bridging molecular mechanisms with therapeutic perspectives in skeletal muscle atrophy and hypertrophy. Full article

Background: Parenteral nutrition (PN) is a life-sustaining therapy essential for patients who are unable to meet their nutritional needs enterally. However, individualized PN formulations impose substantial economic burdens on healthcare systems. This study aims to quantify the cost of individualized PN bags across different patient populations and identify key cost drivers to inform cost-effective clinical practice and policy development. Methods: A retrospective cohort study was conducted at King Fahad Medical City, Riyadh, Saudi Arabia, analyzing 900 unique patient-specific PN orders between February 2023 and August 2023. Patients were stratified into three groups: adults (≥18 years), pediatrics (1 month to 17 years), and neonates (<1 month), with 300 unique patients per group. The cost assessment included macronutrients, micronutrients, consumables, equipment, and personnel time, all measured using a standardized work sampling methodology. Descriptive statistics characterized demographic and clinical profiles. One-way ANOVA was used to compare costs across groups, and multivariate linear regression identified significant cost predictors, with log-transformation applied to address the skewness in the cost data. Results: Mean cost per PN bag varied significantly among patient groups (ANOVA, p < 0.001): adults 517.1 ± 274 SAR, pediatrics 383.2 ± 86.75 SAR, and neonates 243.14 ± 98 SAR. We found that PN volume, lipid dose, and the number of additives were the primary modifiable drivers of PN cost. Multivariate regression analysis identified PN volume (β = 0.182, p < 0.001), lipid dose (β = 0.145, p = 0.002), and number of additives (β = 0.098, p = 0.028) as significant predictors of cost, explaining 91.2% of the cost variance (R² = 0.912). Consumables contributed 18–22% of total costs across groups. Pediatric patients demonstrated markedly longer therapy duration (median 98 days, IQR 65–142) compared to adults (median 18 days, IQR 8–35) and neonates (median 24 days, IQR 12–42). Conclusions: This study provides the first stratified, real-world cost benchmarks for individualized PN in a Saudi tertiary-care setting and quantifies actionable cost drivers. Actionable implications include standardizing stable-patient procedures, implementing pharmacist-led appropriateness screening, and earlier transition to enteral nutrition to reduce costs while maintaining quality of care. Future research should evaluate the cost-effectiveness of standardized versus individualized formulations and investigate the relationship between cost variations and clinical outcomes. Full article

Rheumatoid arthritis is a chronic systemic autoimmune disease that arises from complex interactions among genetic susceptibility, environmental factors, and immune dysregulation. Growing evidence indicates that microorganisms residing in the oral cavity and gastrointestinal tract, together with dietary factors, play a central role in shaping inflammatory and autoimmune responses in rheumatoid arthritis, forming an interconnected microbiome–immune–nutrition axis. Alterations in the composition and function of oral and intestinal microbial communities are associated with disruption of mucosal barrier integrity, activation of innate and adaptive immune pathways, increased differentiation of proinflammatory T lymphocyte subsets, and loss of immune tolerance that promotes autoantibody production. In addition, microbially derived metabolites, particularly short-chain fatty acids, provide a mechanistic link between microbial ecology, immune regulation, and bone metabolism. Diet represents a key upstream modulator of this axis. Dietary patterns rich in anti-inflammatory nutrients support microbial diversity and immunoregulatory metabolite production, whereas diets high in processed foods and saturated fats favor proinflammatory microbial profiles. Accumulating clinical evidence suggests that nutritional strategies and microbiome-targeted dietary interventions may reduce systemic inflammation and disease-related comorbidities when used alongside standard pharmacological treatments. Taken together, the microbiome–immune–nutrition axis represents a modifiable and clinically meaningful target in rheumatoid arthritis, emphasizing the need for interdisciplinary research and well-designed clinical trials to translate these insights into personalized approaches for disease management. The aim of this review is to integrate current mechanistic and clinical evidence on the interactions between the microbiome, immune system, and nutrition in rheumatoid arthritis, with a focus on their pathogenic relevance, therapeutic potential, and implications for personalized, diet-based interventions. Full article

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome driven by systemic inflammation, persistent oxidative stress, endothelial dysfunction, and impaired mitochondrial bioenergetics. Despite recent therapeutic advances, the management of these specific pathophysiological mechanisms remains a challenge. Polyphenols, bioactive compounds found in plants, have emerged as potential modulators of these pathways. Objective: This review critically summarizes the pathophysiological and molecular evidence supporting the role of polyphenols—specifically phenolic acids, flavonoids, and lignans—in attenuating key pathways implicated in the progression of HFpEF, while also addressing the current limitations in clinical translation. Results: Preclinical evidence indicates that polyphenols regulate cellular homeostasis by activating the Keap1/Nrf2 antioxidant axis and AMPK/SIRT1 metabolic pathways, while inhibiting NF-κB-mediated pro-inflammatory signals and TGF-β fibrotic pathways. These molecular actions collectively preserve endothelial function via PI3K/Akt/eNOS, reduce interstitial fibrosis, and improve myocardial metabolic efficiency. Furthermore, the modulation of gut microbiota amplifies these systemic effects, particularly in obesity-related phenotypes. However, direct clinical application is currently hindered by low bioavailability and a scarcity of randomized trials specifically in HFpEF populations. Polyphenols represent a promising and biologically plausible nutritional therapeutic axis for the multidimensional management of HFpEF. While the molecular rationale is strong, future research should focus on improving bioavailability and conducting high-quality clinical trials to validate efficacy as an adjuvant therapy. Full article

The citric acid cycle disruptions are implicated in the pathogenesis of chronic diseases, including diabetes, obesity, cancer, and cardiovascular conditions. Numerous publications link TCA cycle disorders to oncological, neurodegenerative, and osteoporotic diseases, and specific single-nucleotide polymorphisms have been proposed as potential markers. Nevertheless, lifestyle and diet have been strongly linked to risk factors for mitochondrial dysfunction; thus, preventive measures that minimize these risks are a relevant field of research. This review summarizes 45 years of relevant publications on the TCA cycle, its genetics and epigenetics, and the restorative potential of certain nutrients. The review includes articles in English and Russian, registered in PubMed, Elsevier, eLIBRARY.RU. The genes encoding the TCA cycle enzymes have been collected and presented. Information is provided that a number of changes in the expression of these genes, for example, Arg18Trp, Ser87Leu, Ala252Thr, and Leu357Val of the ACO2 gene, leads to the development of neurodegenerative diseases; mutations rs121913499, rs121913500 in the IDH1, IDH2 genes, rs1270341616 and the DLST gene lead to the development of cancer. There is evidence that through epigenetic modifications, nutrition affects the activity of the TCA cycle. Niacin, α-lipoic acid, succinic acid, resveratrol, curcumin, arginine, leucine, quercetin, ursolic acid, and alternol affect the regulation of the TCA cycle at the genetic level. Further research into the effects of plant metabolites, vitamins, and bioactive supplements on the TCA cycle may improve the existing preventative and therapeutic diets. Full article

Background: Online hemodiafiltration (HDF) represents the most advanced form of kidney replacement therapy, combining diffusive and convective transport to enhance the removal of uremic toxins across a wide molecular spectrum. Achieving high convective volumes is a key determinant of treatment efficacy and has been associated with improved survival. Beyond small solutes, HDF targets middle molecules and protein-bound uremic toxins (PBUTs), including β₂-microglobulin, inflammatory cytokines, and other large uremic compounds implicated in cardiovascular and systemic complications. Aims: This narrative review examines advances in dialysis membrane materials, dialyzer design, and monitoring technologies that optimize mass transfer in HDF. It focuses on the interplay between membrane permeability, hemocompatibility, and convective dose delivery, and discusses how these engineering developments translate into clinical performance. Key mechanisms: Recent progress in synthetic polymer membranes, particularly polysulfone- and polyethersulfone-based systems, and hollow-fiber manufacturing has enabled improved control of pore size distribution, hydraulic permeability, and sieving characteristics. These developments enhance the clearance of middle molecules and selected PBUTs while preserving essential proteins such as albumin. Mechanistic insights into internal filtration, protein polarization, and Donnan effects highlight the complex transport processes occurring within the dialyzer and their interaction with automated HDF systems. Expanded hemodialysis and high-volume HDF approaches further increase the removal of larger solutes but require careful management to limit albumin loss and maintain hemocompatibility. Clinical implications: Optimized membrane design, combined with advanced HDF machine algorithms, allows delivery of high convective volumes under safe and stable conditions, improving removal of β₂-microglobulin, cytokines, and other clinically relevant toxins associated with inflammation and cardiovascular risk. However, treatment must remain individualized, considering electrolyte balance, albumin preservation, and patient-specific factors such as inflammation and nutritional status. Mechanistic modeling supports understanding of transport phenomena but must be interpreted cautiously when translated into clinical practice. Conclusions: Advances in membrane science, dialyzer engineering, and monitoring technologies have strengthened the role of HDF as a precision-based renal replacement therapy. Continued innovation aimed at optimizing middle-molecule and PBUT clearance while preserving albumin and treatment stability is essential to improve patient outcomes and support the broader implementation of HDF as a mainstream dialysis modality. Full article