Search Results (23,184)

Bone diseases such as osteomyelitis, osteosarcoma, and osteoarthritis, as well as conditions caused by metabolic imbalances, including osteoporosis, require more efficient and optimized therapies. Systemic drug administration entails major disadvantages like cytotoxicity and adverse reactions, which can lead to serious complications or death. Therefore, local drug administration alternatives are currently under investigation for different pharmacological therapies. New vectors were created to improve control over administration, and 3D-printed and patient-specific drug delivery systems have been tested, revealing great potential. Moreover, 3D-printed platforms that mimic human tissues for drug testing are innovative solutions emerging for the pharmaceutical industry. Situated between in vitro and in vivo testing on human patients, they offer the advantage of reproducing functional architecture, providing results that are closer to those encountered in clinical trials performed on patients. In our article, we present the two categories of 3D systems, from the perspective of main drug groups (antibiotics, anticancer, and anti-inflammatory) as well as other categories, alongside their advantages, limitations, and their adaptations to 3D printing technologies. This article also highlights the technological drawbacks encountered in both delivery and screening systems, as well as the printing methods and materials used, including their physical and biological properties. Full article

Aphids are sap-sucking pests that cause substantial damage to fruit and fibre crops through direct feeding and transmission of plant viruses. While chemical pesticides remain the primary method of control, their use raises concerns related to human health, environmental contamination, pesticide resistance, and impacts on beneficial insects. As a sustainable alternative, spray-on double-stranded RNA (dsRNA) technology offers a promising approach to induce RNA interference (RNAi) in target pests. For RNAi to be effective against sap-sucking insects like the green peach aphid (Myzus persicae), it is essential to identify genes whose silencing disrupts vital physiological functions. In this study, artificial diet (AD)-based feeding assays were used to evaluate dsRNAs targeting eight genes involved in neural function, osmoregulation, feeding behaviour, and nucleic acid/protein metabolism. dsRNAs were administered individually, in combinations, or as a multi-target stacked construct. After 98 h of feeding, aphid mortality ranged from 14 to 72% (individual targets), 78–85% (combinations), and 54% (stacked construct). Transcript knockdown varied from 6.3% to ~54%, though a consistent correlation with mortality was not always observed. The gene targets and combinatorial dsRNA strategies identified in this study provide a foundation for developing RNAi-based crop protection technologies against M. persicae infestation. Full article

Genetic information, whether inside or outside the nucleus, is exposed to a variety of harmful physico-chemical factors. Although DNA damage repair systems have been extensively studied, little information about post-repair and non-genomic DNA damage metabolism is available in the literature. Adenosine deaminase (ADA) is an abundant enzyme found on both sides of the cell membrane that regulates the concentration of adenine derivatives. In this article, it has been shown that 7,8-dihydro-8-oxo-2′-deoxyadenosine (^OXOdAdo) and (5′R/S) 5′,8-cyclo-2′-deoxyadenosine ((5′R/S)cdAdo) are suitable substrates for ADA. For this purpose, theoretical Density Functional Tight Binding and RP-HPLC analyses were applied. The products of ADA activity, i.e., ^OXOdIno (7,8-dihydro-8-oxo-2′-deoxyinosine) and (5′R/S) cdIno ((5′R/S) 8-cyclo-2′-deoxyinosine), were identified and confirmed by high-resolution mass spectroscopy. Although the (5′R) and (5′S)cdAdo enzymatic deamination processes are much slower (34% and 32% after 168 h, respectively) than the process observed for dAdo, 5′,8-cyclo-2′-deoxyinosine should be considered when monitoring cyclopurine levels in physiological fluids. The same should be considered in the case of ^OXOdAdo, which is completely converted to ^OXOdIno within one minute and may therefore be less visible than ^OXOdGuo during mass spectroscopy analysis. Both these observations are important, given the abundance of 2′-deoxyadenosine on both sides of the cell membrane and its potential conversion into ^OXOdAdo and (5′R/S)cdAdo. They may also explain why the observed level of ^OXOdAdo is much lower than that of ^OXOdGuo in cells and physiological fluids, even though their difference in ionisation potential is only 0.25 eV. Future studies are needed to further investigate the metabolism of DNA damage and to identify the enzymes involved in nucleic acid biochemistry. Full article

The pericarp of Macadamia integrifolia represents a promising but underexplored source of functional flavonoids. To systematically elucidate their biosynthesis and enhance the industrial potential of this by-product, we conducted integrated transcriptomic and metabolomic profiling of pericarps across five developmental stages (50, 80, 110, 140, and 170 days after flowering). Our analysis reveals, for the first time, a distinct temporal shift in both gene expression and metabolite accumulation. Early stages were characterized by high expression of PAL, 4CL, CHS, and FLS, coupled with abundant flavonols and anthocyanins. In contrast, late stages exhibited upregulation of CHI and F3’5’H, redirecting the metabolic flux toward flavanones and isoflavones. This dynamic profile was closely associated with jasmonate and gibberellin signaling pathways and was likely regulated by key transcription factors (MYB, NAC, bHLH). These findings provide a multi-omics framework that elucidates the temporal flavonoid biosynthesis in macadamia pericarp, thereby laying the groundwork for its future industrial valorization. Full article

Background/Objectives: Lifestyle-related diseases such as obesity, diabetes, hypertension, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and osteoarthritis disproportionately affect women due to hormonal, metabolic, and socio-cultural factors. Emerging evidence suggests that combining structured exercise with nano-curcumin, a bioavailable phytochemical formulation with potent antioxidant and anti-inflammatory properties, may provide synergistic benefits. This scoping review systematically synthesizes available evidence on the combined effects of nano-curcumin supplementation and exercise interventions on health outcomes in women with lifestyle-related diseases. Methods: Following the Joanna Briggs Institute methodology and the PRISMA-ScR framework, a comprehensive database search was conducted in March 2025 and updated in June 2025. Records were retrieved from Scopus (n = 30), Web of Science (n = 22), PubMed (n = 18), and other sources (n = 71), yielding a total of 141 studies. After screening and deduplication, eight studies met the inclusion criteria and were included in this review. All the studies were conducted in Iran with small sample sizes (12–53 participants) and short intervention durations (6–16 weeks). Therefore, the current evidence is geographically and demographically limited. Results: Across the included trials, the combined interventions produced additive or synergistic improvements in oxidative stress markers, inflammatory cytokines, lipid and glucose metabolism, cardiovascular function, pulmonary capacity, muscle fitness, and psychological outcomes (e.g., depression). When paired with nano-curcumin supplementation at different concentrations, high-intensity interval training, aerobic exercise, Pilates, and resistance training consistently outperformed exercise or supplementation alone in modulating antioxidant defenses, reducing systemic inflammation, and improving metabolic risk factors. Conclusions: The integration of exercise and nano-curcumin supplementation appears to confer superior benefits for women with lifestyle-related diseases compared with either approach alone. These findings highlight the potential of combining phytochemicals with lifestyle interventions to optimize women’s health outcomes. However, most available evidence originates from small, short-term studies in single geographic regions. Large-scale, multicenter, randomized controlled trials with diverse populations are warranted to establish standardized protocols and optimal dosing strategies, and to assess long-term safety and efficacy. Full article

Fusarium head blight caused by Fusarium graminearum is a serious fungal disease on wheat and maize worldwide, resulting in a significant economic loss. DUG3-mediated glutathione utilization has been revealed to play important roles in fungal differentiation, metabolism, stress adaptation, and plant infection. However, functional roles of the DUG3 homolog in F. graminearum remain uncharacterized. In the present study, FgDUG3 was knocked-out via homologous recombination to investigate functions of this gene. The deletion mutant (ΔFgDUG3) was normal in mycelial growth, but showed impairments in conidiation, conidial germination, and plant infection, compared to the wild-type strain. The defects of ΔFgDUG3 were recovered in the complemented strain (ΔFgDUG3-C). Transcriptomic analysis revealed that deletion of FgDUG3 caused significantly differential expression of genes, mainly related to metabolism, catabolism, cellular structure organization, and signal transduction. Taken together, these results suggest that FgDUG3 plays important roles in the differentiation and pathogenicity of F. graminearum. Full article

Cardiovascular (CV) disease, chronic kidney disease, obesity, and diabetes mellitus have reached epidemic proportions over the past few decades. Accumulating evidence highlights the strong interconnection between these conditions, leading to the definition of a broader disease entity known as cardio-renal-metabolic (CRM) syndrome. This newly recognized clinical entity presents important challenges in identifying the optimal treatment strategy within a holistic, patient-centered framework. In line with this, sodium glucose cotransporter 2 inhibitors (SGLT2is), owing to their multifaceted pharmacological effects, have been suggested as possible treatment options in the management of CRM. SGLT2is exert their antihyperglycemic effects by impeding the renal reabsorption of sodium and glucose, causing glycosuria and natriuresis. Research has confirmed that their unique beneficial effects extend beyond glycemic control, reducing CV death and hospitalizations in patients with heart failure, and the incidence of kidney failure in dedicated kidney outcome studies—regardless of diabetes status. Furthermore, these agents contribute to weight loss and blood pressure reduction. Their benefits appear to stem from a combination of factors, which include reduced oxidative stress, lower levels of inflammation, regulated neurohormonal activation, improved endothelial function, and enhanced metabolic efficiency. This review aims to provide a comprehensive analysis of the pathophysiological mechanisms underlying the effects of SGLT2is in CRM syndrome, synthesize evidence from landmark clinical trials, evaluate current experimental and diagnostic approaches, and provide the emerging role of SGLT2is in the treatment of this new clinical entity. Full article

Novel antidiabetic drugs introduced in the last decade have not only revolutionized the treatment of type 2 diabetes mellitus but have also changed our cardiovascular risk reduction strategy. Glucagon-like peptide-1 (GLP-1) receptor agonists reduce the risk of atherosclerotic diseases primarily through their complex anti-atherosclerotic effect due to their endothelial function-improving, anti-inflammatory, anti-thrombotic, and plaque-stabilizing effects. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, on the other hand, have a favorable cardiovascular effect, mainly by increasing sodium excretion, reducing plasma volume, enhancing the use of ketone bodies as metabolic substrates in heart and kidney tissues, and reducing oxidative stress and uric acid serum levels. However, when using these two groups of drugs, important questions arise. What criteria should be used to decide on the administration of one or the other class of drugs? Which group of agents can be used more effectively to reduce our patients’ cardiovascular risk? What are the possible adverse effects? What can be gained by combining the two drugs? Our objective was to provide a current literature-based and comparative summary on the mechanisms of action, cardiovascular-risk-reducing efficacy, and safety profiles of these two drug classes, with an emphasis on identifying key factors influencing everyday clinical decision-making. Full article

Obesity is a highly complex, multifactorial disease influenced by dynamic interactions among genetic, epigenetic, environmental, and behavioral determinants that explicitly position genetics as the core. While advances in multi-omic integration have revolutionized our understanding of adiposity pathways, translation into personalized clinical nutrition remains a critical challenge. This review systematically consolidates emerging insights into the molecular and nutrigenomic architecture of obesity by integrating data from large-scale GWAS, functional epigenomics, nutrigenetic interactions, and microbiome-mediated metabolic programming. The primary aim is to systematically organize and synthesize recent genetic and genomic findings in obesity, while also highlighting how these discoveries can be contextualized within precision nutrition frameworks. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science up to July 2024 using MeSH terms, nutrigenomic-specific queries, and multi-omics filters. Eligible studies were classified into five domains: monogenic obesity, polygenic GWAS findings, epigenomic regulation, nutrigenomic signatures, and gut microbiome contributions. Over 127 candidate genes and 253 QTLs have been implicated in obesity susceptibility. Monogenic variants (e.g., LEP, LEPR, MC4R, POMC, PCSK1) explain rare, early-onset phenotypes, while FTO (polygenic) and MC4R (monogenic mutations as well as common polygenic variants) represent major loci across populations. Epigenetic mechanisms, dietary composition, physical activity, and microbial diversity significantly recalibrate obesity trajectories. Integration of genomics, functional epigenomics, precision nutrigenomics, and microbiome science presents transformative opportunities for personalized obesity interventions. However, translation into evidence-based clinical nutrition remains limited, emphasizing the need for functional validation, cross-ancestry mapping, and AI-driven precision frameworks. Specifically, this review systematically identifies and integrates evidence from genomics, epigenomics, nutrigenomics, and microbiome studies published between 2000 and 2024, applying structured inclusion/exclusion criteria and narrative synthesis to highlight translational pathways for precision nutrition. Full article

Introduction: Sarcopenia, the progressive age-related decline in skeletal muscle mass, strength, and function, represents a major contributor to morbidity, frailty, and reduced quality of life in older adults. Oxidative stress and chronic low-grade inflammation are increasingly recognized as central mechanisms driving its onset and progression, through pathways involving mitochondrial dysfunction, impaired satellite cell activity, and dysregulated protein turnover. Objective: The purpose of the following manuscript is to summarize current research on the molecular and cellular interactions between oxidative stress and inflammation in sarcopenia, as well as to assess Aronia melanocarpa’s potential as a nutritional intervention. Methods: A narrative review was conducted by searching PubMed, Scopus, and Web of Science for peer-reviewed literature published between 2000 and 2024. Keywords included “sarcopenia”, “oxidative stress”, “inflammation”, “Aronia melanocarpa”, “polyphenols”, and even “functional foods”. Eligible publications provided mechanistic, preclinical, or clinical findings on skeletal muscle biology and A. melanocarpa bioactivity. Results: This narrative review examines the relationship between oxidative stress and inflammation in sarcopenia, focusing on NF-κB-mediated inflammatory signaling, Nrf-2-dependent antioxidant defenses, myokines like myostatin and irisin, and macrophage polarization in muscle homeostasis. Aronia melanocarpa (black chokeberry) is highlighted as a polyphenol-rich fruit with a distinct profile of anthocyanins and proanthocyanidins that have strong antioxidant and anti-inflammatory properties. According to preclinical, clinical, and nutritional studies, A. melanocarpa bioactives modulate redox balance, suppress pro-inflammatory cytokine production, increase antioxidant enzyme activity, and regulate metabolic and regenerative signaling pathways important for skeletal muscle health. Conclusions: Overall, the data suggest A. melanocarpa’s potential as a functional food and nutraceutical candidate for the prevention and treatment of sarcopenia. However, further translational and clinical research is needed to determine the appropriate intake, bioavailability, and long-term efficacy in human populations. Full article

Ectomycorrhizal fungal sporomes represent complex microuniverses harboring structurally and functionally eclectic microbiomes with significant ecological roles and potential anthropogenic applications. Nevertheless, the factors governing the assembly of these microbial communities remain poorly understood, and numerous fungal taxa, including many ectomycorrhizal species, remain uninvestigated. This study characterizes the bacteriome of the socioculturally and economically important yet hallucinogenic-if-raw ectomycorrhizal bolete Lanmoa asiatica. We analyzed 36 basidiomata from four geographic locations within China, partitioning each into pileus, stipe, and hymenophore tissues, and sequenced the V5–V7 region of the bacterial 16S rRNA gene. Proteobacteria dominated (>85%), with Pantoea, Sphingomonas, and the Burkholderia complex identified as core genera. Contrary to expectations, α-diversity was highest in the stipe (Chao1 index up to 1934) rather than the exposed hymenophore. PERMANOVA indicated that geographic origin (R² = 0.46, p < 0.001) was a stronger structuring force than tissue type (R² = 0.28, p < 0.01). Functional prediction via PICRUSt2 revealed enrichments in lipid metabolism, antimicrobial resistance, and apoptosis pathways across sites, while tissue-specific functions involved carbohydrate and nitrogen metabolism. These findings support a hierarchical model of bacteriome assembly where broad-scale environmental filters override micro-niche differentiation, providing a biogeographic framework for the conservation of this highly valued edible mushroom. Full article

A significant gap in specific nutritional guidelines for ruminants with compromised health exists. Due to their unique anatomy, physiology, and metabolic processes, further research is needed to establish accurate, evidence-based recommendations tailored to these animals. This review highlights the critical role of clinical ruminant nutrition and provides provisional recommendations based on studies in other species (e.g., changes in nutrient requirements in different morbidities available for humans and less for companion animals). These suggestions should be interpreted cautiously until more definitive, species-specific data become available. The review includes the foundational principles of clinical nutrition in ruminants, with particular emphasis on the pathophysiology of nutrient utilization. It explores the roles of energy, protein, vitamins, and minerals during illness or injury and discusses how these nutrients can be strategically applied in clinical interventions. Considerations for designing diets for compromised ruminants are also addressed, considering both physiological needs and the challenges posed by illness and injury states. Practical aspects of diet delivery during treatment are examined, including the indications, benefits, limitations, and potential side effects of route of feeding. Clinical nutrition can be administered orally, enterally (including rumen delivery) or parenteral, depending on the localization of the pathology and the integrity of the alimentary tract. Nutrients should be provided based on livestock requirements and pathophysiology and severity of the primary morbidity. Oral or ruminal provision of diet should be prioritized to maintain rumen functionality. Additionally, a list of pharmaconutrients with potential clinical applications in ruminant medicine is presented to encourage future research and integration into veterinary practice. The success of clinical nutritional interventions can be measured by improvements in appetite, behavior, and health of the compromised ruminant. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder worldwide and a key driver of cardiometabolic complications. Despite its growing burden, the underlying metabolic perturbations remain incompletely understood. The Fatty Liver Index (FLI) provides a validated non-invasive tool for stratifying MASLD in large-scale and clinical studies. Methods: This study utilized data from the Qatar Biobank, applying strict exclusion criteria and propensity score matching, to select 110 adults stratified by FLI into the MASLD group (≥60, n = 55) and the control group (<30, n = 55) with balanced age, sex, and BMI. Untargeted serum metabolomics was performed. Differential metabolite profiles were identified using linear regression adjusted for covariates and validated by multivariate modeling. Functional enrichment analyses were conducted to highlight perturbed metabolic pathways. Results: Metabolomic profiling revealed distinct metabolic signatures: the MASLD group was characterized by elevated glutamate and phospholipids, while the control group showed enrichment of gamma-glutamyl amino acids, plasmalogens, and sphingomyelins. Conclusions: This contrasting pattern reflects disruption of the gamma-glutamyl cycle and consistent depletion of antioxidant plasmalogen species, suggesting impaired redox homeostasis and lipid remodeling as hallmarks of MASLD pathogenesis. These findings provide a foundation for future research into targeted metabolic biomarkers and therapeutic strategies. Longitudinal and mechanistic studies are warranted to determine causal relationships and clinical utility. Full article

Schools constitute strategic settings for shaping eating behaviors among youth. Given the profound environmental, health, and social challenges associated with current food systems, there is an urgent need to explore dietary patterns that simultaneously support human well-being, ecological sustainability, and ethical principles. This comprehensive review provides a contemporary overview of the role of plant-based diets as an instrumental pathway to a healthier and more sustainable future by examining (i) environmental and social impacts of current food systems; (ii) the effects of plant-based diets on health; (iii) determinants of plant-based diet implementation in schools, including barriers and facilitators to their adoption; and (iv) the development of future-oriented dietary guidelines. Transitioning to plant-based diets, combined with sustainable agricultural practices, can reduce resource use and promote ecological sustainability. Promoting plant-based diets can also encourage the development of a more responsible and equitable social culture. Plant-based diets consistently provide metabolic, cardiovascular, and anti-inflammatory benefits across diverse populations, contributing to healthy weight and glycemic regulation. Well-planned plant-based diets may also improve cognitive function and promote psychological well-being. The integration of plant-based diets in schools is limited by barriers such as children’s food preferences, habitual eating patterns, peer influence, time and resource constraints, limited knowledge, cultural attachment to meat, and low family involvement. Conversely, facilitators including experiential learning, nutrition education, teacher and family engagement, social norms, ethical or environmental motivations, and institutional support promote acceptance and implementation. Ongoing research is required to refine dietary recommendations, assess long-term health outcomes, and ensure nutritional adequacy across pediatric populations. Continued evaluation of school-based interventions and policy frameworks will be essential to optimize the integration of plant-based diets and to monitor their health, ethical, and environmental impacts. Full article

Sepsis remains one of the major challenges in modern intensive care, characterized by high mortality and complex metabolic and immunological disturbances. Given the limited effectiveness of current therapeutic strategies, increasing attention has been directed toward supportive interventions aimed at restoring metabolic homeostasis. Particular interest has been focused on selected vitamins that exhibit pleiotropic biological effects. Thus, we summarized the current evidence on the role of selected vitamins (C, D, B1, B9, B12) in the treatment and supportive management of sepsis, highlighting their mechanisms of action, potential clinical benefits, and limitations derived from available studies. A comprehensive analysis of the literature was performed, including clinical trials and meta-analyses evaluating the efficacy of vitamin supplementation in sepsis, with particular emphasis on combined interventions and randomized controlled trials in severe sepsis and septic shock. Vitamin D might demonstrate the greatest therapeutic potential, particularly in patients with severe sepsis and respiratory failure, with benefits associated with achieving appropriate therapeutic concentrations. Thiamine (vitamin B1) appears to provide potential advantages primarily in deficient patients, improving mitochondrial function and reducing the risk of renal failure. Evidence regarding folic acid (vitamin B9) and cobalamin (vitamin B12) remains inconclusive, as both deficiency and elevated serum levels have been linked to adverse outcomes. Vitamin C, despite its well-documented antioxidant and microcirculatory effects, has not yet shown consistent evidence of mortality reduction. In conclusion, current evidence suggests that vitamin supplementation might represent an adjunct to standard sepsis therapy, particularly within a personalized approach that considers nutritional status and metabolic phenotype. The development of standardized dosing protocols and well-designed clinical trials is essential to determine the efficacy and safety of phenotype-driven individualized approaches in sepsis management. Full article