Search Results (816)

Background/Objectives: Excess adipose tissue is associated with adverse changes in muscle metabolism and body composition. GLP-1 receptor agonists (GLP-1 RA) have transformed the treatment of obesity; however, concerns remain regarding the potential impact of treatment-associated weight loss on lean mass. This study aimed to evaluate the effects of GLP-1 RA on body composition in adults with obesity without type II diabetes mellitus (T2DM), with a particular focus on changes in lean mass. Methods: A database search of Medline Ultimate, Scopus, Web of Science, PubMed, and Embase was conducted to identify studies published up to December 30, 2024. Randomized controlled trials involving adults with obesity and without T2DM who received GLP-1 RA and reported changes in body composition were included. The protocol was registered with PROSPERO (CRD42025645378). Random-effects meta-analysis was performed using inverse-variance weighting. Results: A total of 2776 articles were identified, of which three trials comprising 171 participants met the inclusion criteria. Compared with controls, participants receiving GLP-1 RA treatment experienced greater reductions in lean mass (MD = −0.78 kg, 95% CI: [−1.37 to −0.16], I² = 63.2%). GLP-1 RA treatment was also associated with a significant reduction in fat mass (MD = −3.43 kg, 95% CI: [−5.94 to −0.93], I² = 78.2%). Conclusions: The loss of lean mass was greater in patients treated with GLP-1 RA than in the control group. These results highlight the importance for clinicians to incorporate lifestyle interventions, including physical activity and nutritional support, alongside therapy with GLP-1 RA. Full article

Background/Objectives: Diabetes mellitus is a chronic metabolic disorder characterized by impaired regulation of blood glucose due to defects in insulin secretion, insulin action, or both. Physiological and lifestyle factors vary among individuals. General medicine is not applicable to all patients. In this scenario, personalized medicine for each individual becomes costly. Effective management of continuous glucose levels with accurate insulin dosage is challenging. To overcome this, a digital twin (DT)-based insulin dosage simulator with an individual’s metabolic system is proposed in this work. Methods: Various machine learning techniques, mathematical models of physiology, and risk assessment using probability are used to predict the dynamics of patient-specific glucose–insulin. Parameters such as carbohydrate intake, sleep patterns, medications, and physical activity were incorporated into this model to capture real-world variations in daily life. For glucose–insulin interactions, the Bergman Minimal Model (BMM) is used; for time-of-day variability, a circadian insulin sensitivity model is used; and for predicting metabolic risks, Bayesian risk estimation (BRE) is used, which includes hyperglycemia risk. To enhance transparency and interpret model predictions, explainable artificial intelligence (XAI) methods are employed. Results: The simulation results showed improved glucose prediction accuracy, enhanced detection of hypoglycemia risk, and optimized insulin dosing strategies compared with traditional approaches. Conclusions: Overall, the proposed digital twin model offers a scalable solution using the latest techniques A “Prescriptive Analytical Framework” is provided using the BMM and BRE for personalized diabetes management and decision support for clinicians. Full article

Liver fibrosis is the common pathway through which chronic liver injury progresses to cirrhosis, portal hypertension, liver failure, hepatocellular carcinoma, and systemic complications. Its burden is increasing worldwide, driven mainly by metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, viral hepatitis, and cardiometabolic comorbidity. Current evidence supports a clinically practical approach centered on early risk recognition, non-invasive fibrosis assessment, etiologic treatment, lifestyle and metabolic risk reduction, and timely referral of patients with suspected advanced fibrosis. Although advanced cirrhosis may remain only partly reversible, fibrosis can regress when the injurious stimulus is controlled, making prevention of progression a realistic therapeutic goal. This review provides a clinically actionable framework for the assessment, management, and prevention of liver fibrosis, integrating current insights into epidemiological trends, etiopathogenesis, non-invasive and portal-hypertension assessment, sex-specific effects, hepatic and extrahepatic outcomes, and treatment strategies. It highlights the potential for fibrosis regression when the underlying etiologic factor is controlled and emphasizes the stages (F0–F2) at which reversibility is most achievable. Additionally, the paper outlines key research priorities to address current knowledge gaps in biomarker discovery, precision medicine, and artificial intelligence-assisted risk stratification, while defining priorities for personalized screening, multidisciplinary care, and combination antifibrotic research. Full article

Arterial stiffness is increasingly recognized as an important marker of vascular aging and an independent predictor of cardiovascular disease. Among the available methods for assessing arterial stiffness, brachial-ankle pulse wave velocity (baPWV) has gained widespread clinical acceptance because it is simple, noninvasive, highly reproducible, and suitable for routine practice and large-scale population screening. Accumulating evidence has demonstrated that baPWV is associated with hypertension-mediated target organ damage, coronary artery disease, cardiovascular events, and mortality. Beyond its prognostic value, baPWV has been investigated as a potential marker of vascular responses to pharmacological and lifestyle interventions. Emerging evidence also suggests that serial assessment and visit-to-visit variability of baPWV may provide additional prognostic information, although their clinical applicability requires further validation. Another advantage of baPWV is its simultaneous measurement of the ankle-brachial index, enabling comprehensive assessment of both arterial stiffness and peripheral artery disease without additional examination time. This review summarizes the physiological basis, measurement principles, strengths and limitations, and current clinical applications of baPWV, with particular emphasis on cardiovascular risk stratification, target organ damage, therapeutic monitoring, serial assessment, and combined ankle-brachial index evaluation. Finally, future perspectives for integrating baPWV into precision cardiovascular medicine are discussed. Full article

Background: Statins are among the most frequently prescribed medications worldwide, with proven benefits in reducing all-cause and cardiovascular mortality, preventing major adverse cardiovascular events (MACEs), and lowering healthcare costs. Despite their well-established safety and effectiveness, discontinuation of statin therapy remains a common problem in both primary and secondary prevention. Methods: A systematic literature review was conducted in accordance with PRISMA guidelines and registered in the PROSPERO database (CRD420261295172). Original studies published since 1 January 2014 were identified through searches of PubMed (MEDLINE) and Google Scholar using predefined keywords. Methodological quality and risk of bias of the included observational studies were evaluated using the Newcastle-–Ottawa Scale (NOS) and Joanna Briggs Institute (JBI) Critical Appraisal Tools. Results: Synthesized data from 29 included studies indicate that up to half of patients discontinue statin therapy within the first year (discontinuation rates ranging from 27.1% to 47.0% in primary prevention and 18.5% to 32.4% in secondary prevention), with rates increasing over time. Major factors contributing to non-adherence include fear of side effects, particularly statin-associated muscle symptoms (SAMSs), misinformation, limited patient–physician communication, socioeconomic barriers, and polypharmacy. Discontinuation is associated with significantly higher all-cause and cardiovascular mortality (Hazard Ratios ranging from 1.30 to 4.65), higher rates of cardiovascular and cerebrovascular events, worsening metabolic outcomes, reduced quality of life, and greater healthcare expenditures. Conclusions: Improving adherence requires better patient education, addressing misconceptions, strengthening patient–physician relationships, and optimising treatment regimens. A multidisciplinary approach is needed to prevent unjustified discontinuation and improve long-term clinical outcomes. Full article

Endothelial dysfunction is a key mechanism linking obesity, metabolic disturbances, and cardiovascular disease, contributing to the development and progression of atherosclerosis and other vascular complications. This review provides a comprehensive overview of the molecular mechanisms underlying endothelial dysfunction in obesity and discusses current diagnostic approaches and therapeutic strategies aimed at restoring vascular homeostasis. The available evidence indicates that chronic inflammation, oxidative stress, insulin resistance, reduced nitric oxide bioavailability, increased reactive oxygen species production, and dysregulated adipokine signaling play central roles in endothelial impairment. Recent advances in functional vascular assessment, circulating biomarkers, and imaging techniques have improved the early identification of endothelial dysfunction and cardiovascular risk. Current therapeutic strategies include pharmacological agents, such as glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter 2 inhibitors, metformin, and dipeptidyl peptidase-4 inhibitors, together with lifestyle interventions based on healthy dietary patterns and regular aerobic and resistance exercise. These approaches improve glycemic control, reduce inflammation and oxidative stress, enhance endothelial function, and contribute to cardiovascular protection. Overall, the evidence supports an integrated and personalized management strategy targeting both metabolic and vascular abnormalities to reduce cardiovascular risk and improve long-term clinical outcomes in individuals with obesity. Full article

Background/Objectives: Obesity is a chronic, progressive, and relapsing disease that requires long-term, multidisciplinary management rather than episodic weight-loss treatment. Although novel incretin-based anti-obesity pharmacotherapies, including GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, have markedly improved the clinical management of obesity, weight reduction alone does not fully capture treatment success. Body composition, lean mass preservation, physical function, nutritional adequacy, psychological well-being, adherence, and long-term weight-loss maintenance are increasingly recognized as essential therapeutic outcomes. This narrative review critically examines the role of lifestyle medicine as a co-therapeutic strategy during modern anti-obesity pharmacotherapy, with particular attention to physical activity, nutrition, behavioral support, and individualized monitoring. Methods: A narrative literature search was conducted in PubMed up to June 2026. The review included studies addressing adults with overweight or obesity and evidence related to anti-obesity pharmacotherapy, physical activity, nutrition, body composition, functional outcomes, eating behavior, quality of life, treatment tolerability, adherence, weight regain, and long-term maintenance. Results: Current evidence indicates that incretin-based therapies produce substantial and clinically meaningful weight loss, but pharmacological efficacy may be limited by reductions in lean mass, gastrointestinal adverse events, inadequate nutritional intake, treatment discontinuation, and weight regain after drug withdrawal. Physical activity should be considered a therapeutic component rather than only a tool for increasing energy expenditure, as aerobic exercise supports cardiometabolic health and cardiorespiratory fitness, while resistance training helps preserve muscle strength, bone health, and functional capacity. Nutritional strategies are equally important, particularly during appetite suppression, to maintain adequate protein, fiber, fluids, micronutrients, and diet quality. Behavioral factors, including sleep, stress, mood, stigma, self-regulation, and the food environment, may influence adherence and long-term outcomes. Conclusions: Novel anti-obesity drugs should not be viewed as replacements for lifestyle medicine but as powerful tools within an integrated chronic-care model. The goal of treatment should move beyond maximal body-weight reduction to durable improvements in body composition, metabolic health, physical function, nutritional status, quality of life, and weight-loss maintenance. Full article

Glutathione is an abundant intracellular low-molecular-weight thiol that contributes importantly to cellular redox homeostasis. Besides its well-established role in the antioxidant defense of the cell, glutathione regulates mitochondrial function, metabolism of toxicants, protein thiol oxidation/reduction, redox signaling, and immunity. Disturbances in glutathione metabolism have been shown to play a role in various diseases; however, it has become clear that changes in glutathione metabolism are a part of a complex, multifactorial process. In this review, we summarize current knowledge of the molecular mechanisms governing glutathione synthesis, recycling, compartmentalization, and biological functions, with particular emphasis on redox signaling, the nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) pathway, and reversible protein S-glutathionylation. We further examine how disturbances in glutathione homeostasis interact with mitochondrial dysfunction, chronic inflammation, metabolic stress, and impaired cellular signaling in Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, multiple sclerosis, Wilson’s disease, type 2 diabetes, and nonalcoholic fatty liver disease. We also evaluate current translational interventions targeting restoration of glutathione balance through glutathione supplementation, precursor supplementation, pharmacological modulation of endogenous antioxidant mechanisms, dietary interventions, and changes in lifestyle. Despite the fact that many interventions have been promising at the mechanistic and experimental level, there are still insufficient clinical data because of the problems associated with glutathione availability, tissue specificity, disease variability, and a lack of sufficiently powered clinical trials. The conclusion of this review is that glutathione should not be viewed as a universal therapeutic target; instead, glutathione should be perceived as an important factor contributing to cellular resilience and able to help other disease-specific interventions. Future progress in glutathione-based interventions will likely depend on integrating redox biomarkers, patient stratification, and precision medicine strategies to identify individuals most likely to benefit from targeted modulation of glutathione homeostasis. Full article

Background/Objectives: Recurrent pregnancy loss (RPL) has traditionally been investigated predominantly through maternal factors, while the clinical role of paternal assessment remains inconsistently defined. Current guidelines differ substantially regarding semen analysis, sperm DNA fragmentation (SDF), genetic testing, and referral for andrological evaluation. This review aimed to compare contemporary guideline recommendations, critically appraise the directness, prognostic value, and clinical utility of the supporting evidence, and classify paternal assessment strategies as routine, selective, or investigational. Methods: A structured narrative review was conducted using PubMed and Scopus searches through June 2026. International RPL, obstetric, reproductive medicine, and andrology guidelines were compared. Evidence from systematic reviews, meta-analyses, clinical studies, and clinically relevant molecular investigations was evaluated according to its directness to RPL populations, diagnostic and prognostic value, and evidence that test-guided interventions improve miscarriage or live-birth outcomes. Results: Routine paternal assessment should include age, reproductive and medical history, body weight, lifestyle, medication exposure, and relevant environmental or occupational risks. Conventional semen analysis is appropriate primarily when RPL coexists with infertility or suspected male reproductive disease. SDF is the most extensively studied advanced paternal biomarker and is frequently elevated in RPL cohorts, but findings vary by assay and comparator population, while prospective prediction of subsequent live birth and benefit from SDF-directed treatment remain unproven. Parental karyotyping has established counselling value but should be risk-stratified. Sperm aneuploidy testing, oxidative stress assays, seminal microbiome profiling, epigenetic biomarkers, and biomarker-directed interventions remain investigational. Conclusions: Paternal assessment in RPL should be couple-based, clinically targeted, and evidence-informed. Current evidence supports routine clinical evaluation, selective use of semen analysis, SDF testing, genetic assessment, and reproductive urology referral, and restriction of unvalidated biomarkers and treatments to research settings. Full article

Cancer remains one of the leading causes of global mortality, with its incidence continuing to rise due to population growth, aging, lifestyle factors, and environmental exposures. Despite significant advances in early diagnosis and therapeutic strategies, the clinical management of cancer is still hindered by drug resistance, limited selectivity, and treatment-related toxicity. Consequently, increasing attention has been directed toward natural products as sources of novel anticancer agents with improved efficacy and reduced adverse effects. Pogostemon cablin (patchouli), a medicinal plant widely used in traditional medicine, has emerged as a promising candidate owing to its diverse bioactive constituents and broad pharmacological properties. This review systematically summarizes and critically evaluates current evidence on the anticancer potential of patchouli leaves, with particular emphasis on molecular mechanisms and translational relevance. Based on available experimental and preclinical studies, patchouli and its major phytochemicals exhibit notable anticancer activity against a wide range of malignancies, including endometrial, ovarian, liver, skin, nasopharyngeal, prostate, hematological, colorectal, and lung cancers. Mechanistically, these effects are primarily associated with the modulation of apoptosis, cell cycle regulation, oxidative stress, and key oncogenic signaling pathways, as well as potential synergistic interactions with conventional chemotherapeutic agents. Overall, this review highlights the therapeutic promise of patchouli leaves as a source of anticancer agents, identifies current knowledge gaps, and outlines future research directions to facilitate their development and clinical translation. Full article

Pediatric obesity is a complex, multifactorial pandemic with serious early-onset comorbidities, including prediabetes, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular disorders. While lifestyle modifications and the Mediterranean diet remain primary interventions, artificial intelligence (AI) is emerging as a critical tool for early diagnosis and personalized management. This review evaluates the current role of AI in predicting and treating childhood obesity and its complications. A literature search was conducted on PubMed and Google Scholar for English-language articles published from 2015 onward. Search terms included combinations of keywords related to “obesity”, “pediatric”, “comorbidities” (e.g., MASLD, diabetes), and “artificial intelligence” (e.g., machine learning, deep learning, multi-omics). Eligible study types ranged from original articles to systematic reviews and clinical guidelines. By integrating multi-omic data (genome, epigenome, transcriptome, metabolome, microbiota) with socio-psychological metrics, AI can predict obesity risk and early complications. Machine learning (ML) and deep learning have successfully identified specific metabolites, gut flora alterations, neurological pathways, and metabolic SNPs linked to obesity susceptibility. Furthermore, ML-driven prognostic models enable risk assessment for MASLD or diabetes progression, while specialized software supports remote lifestyle monitoring and tailored dietary interventions. AI has the potential to revolutionize pediatric obesity management through precision medicine. However, challenges regarding data privacy, digital literacy, and equitable access persist. Because current evidence relies heavily on limited and heterogeneous pediatric datasets, large-scale, well-characterized, and externally validated cohorts are essential to establish the clinical applicability of AI models before routine implementation. Full article

Medical students are exposed to substantial academic and psychological demands that may influence their well-being, lifestyle behaviors, and academic performance. This cross-sectional study aimed to examine the associations between smartphone-related anxiety (nomophobia), insomnia symptoms, psychological well-being, coping strategies, and academic achievement among medical students. The study was conducted among 216 students (mean age 22.03 ± 2.48 years, 72.2% female) at the University of Split School of Medicine. Data were collected through an anonymous digital questionnaire created in Google Forms, assessing general information and including the International Physical Activity Questionnaire, Nomophobia questionnaire, Insomnia Severity Index, Medical Student Well-Being Index, and Brief COPE questionnaire. Academic performance was assessed using students’ self-reported arithmetic and weighted grade point averages (GPAs), which were analyzed separately. There was a high prevalence of nomophobia and reduced well-being among participants. Nomophobia was positively associated with insomnia severity (r = 0.172, p = 0.011) and poorer psychological well-being (r = 0.268, p < 0.001), while insomnia severity (r = −0.172, p = 0.011) and avoidant coping strategies (r = −0.167, p = 0.014) were negatively correlated with academic performance. The examined demographic, lifestyle, digital, and psychological variables explained a modest 9.0% of the variance in students’ weighted GPAs, which is consistent with the multifactorial nature of academic achievement. These findings suggest that digital dependence, insomnia symptoms, coping styles, and psychological well-being are interrelated and may be relevant to academic functioning among medical students. Full article

Buchwaldoboletus xylophilus is a rare saprotrophic edible mushroom in the Boletaceae and is the second bolete species to have been successfully cultivated artificially, yet its developmental molecular regulation remains unexplored. We integrated RNA-seq transcriptomics and untargeted LC-MS/MS metabolomics across five developmental stages (A–E), applying differential expression, alternative splicing, ceRNA network construction, WGCNA, machine learning, consensus clustering, and O2PLS joint modelling. Transcriptomic analysis revealed that the mycelium-to-primordium transition (stage A to C) showed the most drastic reprogramming, with 2233 differentially expressed genes, while metabolomic comparison between stage A and E revealed overwhelmingly upregulated metabolites (184 up vs. 10 down), indicating asymmetric regulation between the two omics layers. Notably, mutually exclusive exon splicing events exhibited high functional significance, and all top ceRNA hubs were lncRNAs. Unsupervised consensus clustering validated the molecular distinctness of the sampled stages. Metabolite enrichment highlighted antioxidant functions and ABC transporter pathways, and O2PLS integrative modelling confirmed a strong shared developmental signal between transcriptome and metabolome. This study provides the first multidimensional molecular atlas for B. xylophilus, revealing a non-linear developmental programme, transcriptome–metabolome decoupling, and a central role of antioxidant defence throughout development. Our findings offer mechanistic clues regarding the evolutionary transition from ectomycorrhizal to saprotrophic lifestyles in the Boletaceae and establish a multi-omics foundation for the molecular breeding of this emerging edible and medicinal mushroom. Full article

Cardiovascular disease (CVD) is the result of a complex interaction between genetic, lifestyle, and environmental factors, which may vary over the course of life. Traditional risk factors do not explain all patients’ risks; thus, the research of additional biomarkers to refine cardiovascular risk prediction has attracted considerable interest in recent years. Genetic factors, as well as air pollution exposure, among nontraditional factors, have been found to be critical determinants of CV risk. Accordingly, this narrative review aims to provide a comprehensive summary of the literature (PubMed) on the combined effects of air pollution and genetic susceptibility on CVD risk. Although different limitations and pitfalls are still to be solved, available evidence suggests that genetic variants (especially genes related to detoxification and inflammation) are involved in the association between air pollution exposure and CV adverse events. Thus, this research area could provide further knowledge of the etiology of CVD, offering new tools for targeted prevention and treatment of more susceptible subjects from a more personalized medicine point of view. Full article

Primary prevention is essential to reduce disease burden before clinical onset, yet it remains less systematically integrated into care than diagnosis and treatment. Although artificial intelligence (AI) is increasingly used in medicine, most applications have focused on secondary and tertiary prevention, including diagnosis, prognostic stratification, and disease management, while its role in primary prevention remains less defined. This narrative review examines current AI applications across four modifiable lifestyle domains relevant to prevention and healthspan promotion: nutrition, physical activity, sleep, and mental health. We synthesize evidence on machine-learning models, wearable-derived algorithms, computer-vision tools, just-in-time adaptive interventions, and conversational agents used in consumer, community, and hybrid clinical–digital settings. AI applications support postprandial glycemic prediction, automated dietary assessment, meal-planning adherence, sedentary-pattern detection, personalized exercise recommendations, adaptive behavioral nudges, sleep monitoring, circadian-aware recommendations, psychoeducation, stress-management support, and early identification of psychological vulnerability. Collectively, these tools may extend prevention beyond episodic clinical encounters toward continuous, personalized, and context-aware support. However, evidence remains limited by short follow-up, reliance on surrogate or engagement outcomes, digitally literate populations, and insufficient validation in real-world preventive-care pathways. AI is therefore a promising enabling technology for proactive, healthspan-oriented medicine, provided future studies demonstrate long-term effectiveness, equity, safety, and responsible implementation. Full article