Search Results (621)

Background/Objectives: Lifestyle modification is a cornerstone of obesity and metabolic syndrome (MetS) management, yet pharmacological agents are increasingly prescribed in the treatment of these highly prevalent issues. This meta-analysis compared the effects of diet-only, exercise-only, combined diet + exercise, and pharmacological interventions on MetS severity (MetS z-score) and related cardiometabolic outcomes in adults with overweight or obesity. Methods: A systematic search of relevant databases identified eligible studies published up to October 2025. Random-effects meta-analyses were conducted for pooled pre–post changes within intervention types and, where available, intervention-versus-control and head-to-head comparisons. Results: Forty-six studies comprising 85 intervention arms and 12,128 participants were included. Significant reductions in pooled MetS z-scores were observed following diet-only (−0.72 units; 17 arms), exercise-only (−0.63 units; 40 arms), diet + exercise (−0.68 units; 23 arms), and pharmacological interventions (−0.30 units; 5 arms) (all p < 0.001). Compared with controls, exercise-only reduced MetS z-score by −0.68 units (21 arms), and diet + exercise by −0.45 units (6 arms) (both p < 0.001), whereas pharmacotherapy showed no significant effect (−0.07 units; 5 arms; p = 0.134). Direct comparisons demonstrated that combined diet + exercise achieved greater MetS z-score reductions than diet-only (−0.75 units; 10 arms, p < 0.001). Moreover, lifestyle interventions consistently improved fasting glucose, triglycerides, HDL cholesterol, waist circumference, and blood pressure. Subgroup analyses identified caloric restriction as a key dietary moderator for cardiometabolic improvements, and meta-regression revealed exercise volume as a predictor of MetS z-score decrease. Conclusions: All intervention types improved cardiometabolic risk, but lifestyle strategies—particularly diet + exercise—demonstrated the most consistent and robust effects. While contemporary pharmacological therapies are known to induce substantial weight loss, their effects on overall cardiometabolic risk assessed by composite measures such as the MetS z-score remain insufficiently characterized, as most medication trials report single outcomes and frequently include concurrent lifestyle interventions. Therefore, there is a need for further trials evaluating the impact of anti-obesity medications on overall cardiometabolic health. Full article

Background: High-resolution computed tomography reveals a marked radiological heterogeneity in bronchiectasis; however, the clinical characteristics have not been clearly elucidated. Method: We conducted a prospective observational cohort of 334 bronchiectasis patients at Wuhan Union Hospital. Patients were classified into distal airway (DA) and proximal–intermediate airway (PIA) phenotypes and followed every six months for exacerbations. Clinical, inflammatory, microbial, and metabolic features were compared between groups. Results: Among 334 patients, 206 were classified as DA and 128 as PIA. Most allergic bronchopulmonary aspergillosis cases belonged to the PIA group (p < 0.001). The DA group showed a lower FEV₁%pred (p = 0.010) and Bhalla scores (p < 0.001), higher BSI (p = 0.003) and FACED scores (p < 0.001), more frequent exacerbations (p = 0.002), and a greater prevalence of Pseudomonas aeruginosa (PA) colonization (p < 0.001). Radiologically, the DA group exhibited more extensive structural lung damage (all p < 0.05). Inflammatory profiling showed higher neutrophil counts (p = 0.047) and elevated CRP levels (p = 0.006) in DA, whereas the PIA group was characterized by eosinophilic inflammation (p = 0.026); no significant differences were observed in inflammatory cytokine levels. Microbial interaction network analysis revealed distinct ecological structures between phenotypes. The PIA group showed strong negative correlations with Streptococcus, Rothia, and other commensal taxa, whereas the DA group exhibited no significant associations between Pseudomonas aeruginosa and other species. Furthermore, metabolomic analyses revealed elevated 4-hydroxynonenal levels in the DA group, which also experienced a higher rate of acute exacerbations during follow-up (p = 0.003). Conclusions: Distinct radiological phenotypes based on airway generation in bronchiectasis are associated with different clinical severity, inflammatory profiles, and microbiome features which enable personalized bronchiectasis management. Full article

Background: Evidence on the long-term impact of sapropterin in phenylketonuria (PKU) is limited. Understanding its effects on dietary restrictions, growth in children, and caregiver burden is essential to optimize PKU management. Methods: This prospective, two-year longitudinal study with a comparison group followed 33 children with PKU after sapropterin responsiveness assessment (21 responsive, 12 non-responsive). Outcomes included metabolic control, prescribed protein intake, dietary patterns, growth, psychological measures, and caregiver burden. Results: Sapropterin-responsive children increased natural protein intake from 10 g to 28 g/day at 2 years (p < 0.001), with reduced protein substitute intake (60 g [56–63] to 45 g [40–60], p < 0.05); no changes occurred in non-responsive children (p > 0.05). Animal-based foods (cheese, eggs, meat, fish) were introduced in 52% (11/21) of responsive children once tolerance exceeded approximately 25 g/day. The caregivers of responsive children reported reduced financial, familial-social, and personal burden (all p ≤ 0.05), alongside decreased food neophobia (p = 0.005) and caregiver depression (p = 0.013). In sapropterin-responsive children, weight and BMI z-scores remained stable, while height z-score increased over 24 months (p = 0.03); non-responsive children had higher weight and BMI z-scores than responsive children at 24 months (p = 0.037 and p = 0.026). Blood phenylalanine concentrations remained within recommended target ranges overall, with lower median values in responsive children at several time points. Conclusions: Sapropterin enabled more flexible, sustainable dietary management in responsive children with PKU, supporting metabolic control, growth, and improved family well-being and social participation. Equitable access to therapies and long-term dietetic support remain essential to optimize outcomes. Full article

We investigated whether antipsychotic treatment response was influenced by the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR), and A66G of methyltetrahydrofolate–homocysteine methyltransferase reductase (MTRR)—genes central to folate and homocysteine metabolism and methylation, pathways often altered in schizophrenia patients. To our knowledge, no study has examined associations of C677T and A1298C with changes in schizophrenia symptom severity after antipsychotic treatment, while studies on metabolic outcomes remain sparse and inconsistent. The MTRR A66G has been assessed only once for metabolic parameters—not symptom severity—and sex-stratified analyses are lacking for all polymorphisms. A total of 186 antipsychotic-naïve first-episode or nonadherent chronic psychosis patients and 242 controls were genotyped using PCR-RFLP. Clinical assessments—including Positive and Negative Syndrome Scale (PANSS) scores, PANSS factor scores, and metabolic parameters (fasting plasma lipids and glucose levels, and body mass index)—were conducted at baseline and after 8 weeks. Genotype and allele frequencies did not differ between patients and controls. Significant associations emerged only for symptom changes, specifically within PANSS factor domains, in a sex-dependent manner. Female MTHFR 1298-A allele carriers (AA and AC) showed greater improvement in PANSS negative factor scores, whereas male MTRR 66-G allele carriers (GG and AG) showed reduced improvement in PANSS cognitive factor scores. Effect sizes were strong to very strong, with relatively modest contributions. MTHFR A1298C and MTRR A66G have sex-dependent impacts on symptomatic improvement—but not metabolic outcomes—after antipsychotic treatment. Accordingly, folate–homocysteine genetic markers and sex-specific factors can guide the development of personalized antipsychotic treatment approaches. Full article

Background: Irisin, a recently discovered muscle-originating hormone, has been found to act as a biomarker of several ailments, while no guideline clearly indicates its testing so far in any particular population category or pathological condition. Objective: We analyzed blood (circulating) irisin in relation to the potential correlations with the evaluation of glucose and bone profile. Methods: This was a prospective, pilot, exploratory study (between December 2024 and August 2025). The enrolled patients were menopausal women aged ≥50. Exclusion criteria: Endocrine tumors, thyroid dysfunction, malignancies, or chronic kidney disease. Baseline (fasting) testing was followed by 75 g oral glucose tolerance test (OGTT). Enzyme-linked immunosorbent assay (ELISA)-based irisin assay (MyBioSource) was performed. The subjects underwent central Dual-Energy X-Ray Absorptiometry (DXA), which provided lumbar, femoral neck and total hip bone mineral density (BMD)/T-score (GE Lunar Prodigy), and lumbar DXA-based trabecular bone score (TBS iNsight). Results: We enrolled 89 females [mean age of 62.84 ± 9.33 years, average years since menopause (YSM) of 15.94 ± 9.23]. Irisin (102.69 ± 98.14 ng/mL) did not correlate with age, YSM, but with body mass index (r = 0.36, p < 0.001). Bone formation marker osteocalcin (r = −0.25, p = 0.018) was negatively associated with irisin, amidst multiple other mineral metabolism assays (including PTH and 25-hydroxyvitamin D). Irisin positively correlated with insulin (r = 0.385, p = 0.0008), HbA1c (r = 0.243, p = 0.022), and HOMA-IR (r = 0.313, p = 0.007). Additional endocrine assays pointed a statistically significant association between irisin and TSH, respectively, ACTH (r = 0.267, p = 0.01, and r = 0.309, p = 0.041, respectively). No correlation irisin-BMD/T-score/TBS was confirmed. Conclusions: Irisin correlates with markers of glucose status (insulin, HOMA-IR, and HbA1c), as well as body mass index and, to a lesser extent, bone metabolism markers. Interestingly, TSH and ACTH correlations open a new (hypothesis-generating) perspective in the endocrine frame of approaching this exerkine. To the best of our knowledge, no distinct study has so far addressed the TBS–irisin relationship or pinpointed the glucose effects on TBS, particularly in menopausal women. Full article

Background: Parkinson’s disease (PD) is increasingly recognized as a multisystem disorder in which metabolic dysfunction may contribute to disease susceptibility and progression. Peripheral insulin resistance (IR) has been implicated in PD, but data in levodopa-naïve patients are currently limited. Objective: To investigate the prevalence of IR and metabolic dysfunction in early-stage, levodopa-naïve PD patients and their association with clinical features. Methods: We conducted an exploratory case–control study including 20 levodopa-naïve PD patients and 40 age-, sex-, and BMI-matched healthy controls. Participants underwent comprehensive clinical and metabolic assessments, including fasting glucose, insulin, lipid profiles, and HOMA-IR calculation. Peripheral IR was defined using HOMA-IR cut-offs of ≥2.0 (primary analysis) and ≥2.5 (sensitivity analysis). ANCOVA adjusted for age, sex, and BMI was used for between-group comparisons. Results: PD patients exhibited higher fasting insulin (10.7 ± 5.2 vs. 8.0 ± 4.4 µIU/mL; p = 0.020) and HOMA-IR (2.63 ± 1.40 vs. 1.89 ± 1.21; p = 0.014) compared to controls. Using a HOMA-IR ≥ 2.0, IR prevalence was 70% in PD vs. 32.5% in controls (OR = 4.85, 95% CI 1.52–15.50, p = 0.012). ANCOVA analysis confirmed group differences after adjusting for covariates (respectively, p = 0.032 for insulin and p = 0.023 for HOMA-IR). A sensitivity analysis excluding six patients receiving dopaminergic therapy further supported the robustness of the results. No significant correlations were observed between IR and disease severity scores. Conclusions: Early-stage, levodopa-naïve PD patients exhibit a higher prevalence of peripheral insulin resistance compared with matched controls. These findings support the hypothesis that metabolic dysfunction is an intrinsic component of PD pathophysiology and may represent a target for early intervention. Full article

The traditional Chinese medicinal herb Gynura segetum is increasingly recognized for its hepatotoxic potential, primarily attributed to its pyrrolizidine alkaloid (PA) content. PAs are a leading cause of herb-induced liver injury (HILI) in China and are strongly linked to hepatic sinusoidal obstruction syndrome (HSOS). This review systematically summarizes the pathogenesis, diagnostic advancements, and therapeutic strategies for PA-induced HSOS. Molecular mechanisms of PA metabolism are detailed, encompassing cytochrome P450-mediated bioactivation and the subsequent formation of pyrrole-protein adducts, which trigger sinusoidal endothelial cell injury and hepatocyte apoptosis. Advances in diagnostic criteria, including the Nanjing Criteria and the Roussel Uclaf Causality Assessment Method (RUCAM)-integrated Drum Tower Severity Scoring System, are discussed. Furthermore, emerging biomarkers, such as circulating microRNAs and pyrrole-protein adducts, are examined. Imaging modalities, such as contrast-enhanced computed tomography (CT) and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI), have evolved from descriptive tools into quantitative and prognostic instruments. Therapeutic approaches have evolved from supportive care to precision interventions, including anticoagulation, transjugular intrahepatic portosystemic shunt (TIPS), and autophagy-modulating agents. A comprehensive literature review, utilizing databases such as PubMed and Web of Science, was conducted to summarize progress since the introduction of the “Nanjing Guidelines”. Ultimately, this review underscores the critical need for integrated diagnostic and therapeutic frameworks, alongside enhanced public awareness and regulatory oversight, to effectively mitigate PA-related liver injury. Full article

Background/Objectives: The gut–heart axis has garnered increasing attention. Incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), along with trimethylamine N-oxide (TMAO), have been implicated in the pathogenesis of coronary artery disease (CAD). This study aimed to investigate associations between plasma levels of GLP-1, GIP, and TMAO and the severity of CAD, alongside their correlations with serum biochemical parameters and fatty acid composition. Methods: Sixty-one patients undergoing coronary angiography were evaluated and stratified by Gensini scores into normal-coronary-artery, moderate-CAD, or severe-CAD groups. Biochemical parameters in serum and plasma GLP-1, GIP, and TMAO levels were measured. Plasma fatty acid composition was analyzed. Results: Fasting plasma GLP-1 and TMAO levels were not associated with CAD severity. Although GIP showed associations with CAD severity, these were not retained after adjustment for age and sex. Plasma myristic acid levels were positively associated with Gensini score. GLP-1 correlated positively with saturated fatty acids and negatively with monounsaturated fatty acids. TMAO levels inversely correlated with n-3 polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid, and positively with the n-6/n-3 PUFA ratio, supporting its potential role in pro-atherogenic lipid profiles. Conclusions: These findings suggest complex associations between gut-derived metabolites, lipid metabolism, and CAD severity. Full article

The increasing prevalence of metabolic dysfunction-associated fatty liver disease (MASLD) in children requires robust, non-invasive biomarkers to enable accurate disease staging and risk stratification. Elevated serum levels of homocysteine (Hcy) have emerged as potential risk factors for cardiometabolic disease in adults, including MASLD. In this observational retrospective study, we investigated the role of serum Hcy levels as a potential biomarker for disease severity and liver fibrosis in a pediatric cohort of 182 children with MASLD. In 89 patients, liver biopsy allowed the classification into metabolic dysfunction-associated steatohepatitis (MASH). Associations between Hcy, metabolic parameters, fibrosis scores, and histological features were examined, and the diagnostic performance of Hcy for liver fibrosis was evaluated using ROC analysis. Multivariate analyses identified elevated Hcy levels as independently associated with HOMA-IR (β = 0.55; p = 0.049), TG/HDL ratio (β = 3.23; p = 0.002), and liver fibrosis (β = 2.59; p = 0.04). Hcy showed a predictive accuracy of 81% for fibrosis. However, the combined diagnostic models of Hcy with non-invasive fibrotic scores (i.e., APRI and FIB-4) or TG/HDL ratio showed only a modest accuracy (AUC = 0.62–0.69). In conclusion, our data suggest that Hcy is associated with fibrosis and cardiometabolic risk. However, these results should be interpreted as exploratory and do not establish homocysteine as a diagnostic biomarker. Full article

Background/Objectives: Advanced glycation end products (AGEs) and carotenoids are systemic indicators of metabolic and oxidative status, yet their influence on ocular tissue biomechanics remains unclear. This study investigated the relationships between systemic AGEs and skin carotenoid levels, as well as corneal biomechanical properties in glaucoma patients. Methods: A retrospective observational analysis was performed on 676 patients (1278 eyes) who attended the glaucoma clinic at Shimane University Hospital between May 2019 and August 2024. Fingertip skin autofluorescence (sAF)-based AGE scores using AGE Sensor^® and skin carotenoid scores using the Veggie Meter^® were collected as part of systemic evaluation. Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal compensated intraocular pressure (IOPcc) were measured using the ocular response analyzer (ORA). Associations between systemic variables, AGEs, carotenoids, and ORA parameters were analyzed using univariate tests, mixed-effects regression models, and quartile-based comparisons. Results: The mean AGEs and carotenoid scores were 0.42 ± 0.10 arbitrary units and 338.5 ± 130.8 optical density units, respectively. Via a univariate analysis, an inverse association was found between carotenoid level and CRF; however, via multivariate analyses, neither AGEs nor carotenoid levels were associated with IOPg, IOPcc, CH, or CRF in any analysis. In contrast, demographic parameters showed significant associations with ORA parameters. Via quartile-based comparisons, a significant inverse correlation was found between AGEs and carotenoids (p < 0.0001). Conclusions: In conclusion, sAF-measured AGEs and skin carotenoids showed no remarkable associations with corneal biomechanical properties. AGEs and carotenoids demonstrated an inverse relationship with each other, and each marker was associated with several demographic parameters. Full article

Background: Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by repetitive behaviors and social interaction deficits. While the severity of ASD is classified into levels (1–3) by the DSM-5, reliable circulating biomarkers to differentiate these levels are lacking. This retrospective pilot study examines plasma amino acid levels in children with ASD to identify the potential biomarkers of disease severity. Methods: Plasma samples from 30 children diagnosed with ASD (24 males, 6 females, aged 3–12 years) were analyzed. Participants were stratified into two groups based on the Autism Diagnostic Observation Schedule Calibrated Severity Score (ADOS CSS): Group 1, presenting with mild symptoms (Level 1, n = 11), and Group 2, characterized by moderate-to-severe symptoms (Levels 2–3, n = 19). This was further confirmed by the identification of electroencephalogram (EEG) anomalies (21.1%) and magnetic resonance imaging (MRI) abnormalities (5.3%), which were detected exclusively in Group 2 and absent in Group 1. Amino acid levels were measured by ion-exchange chromatography. Statistical analyses (Mann–Whitney U test and chi-square test) were used to compare AA levels between groups. Results: Statistically significant differences were observed in the levels of phosphoethanolamine, aspartic acid, and glutamic acid between the two groups. These amino acids (AA) were significantly higher in the moderate-to-severe symptoms group (Levels 2–3) compared to the mild symptoms group (Level 1) (p < 0.05). All AA values remained within age-appropriate reference ranges. Conclusions: Plasma levels of phosphoethanolamine, aspartic acid, and glutamic acid may serve as potential biomarkers for ASD severity in children. Results from this exploratory analysis suggest that AA profiling could differentiate ASD severity and identify specific metabolic pathways, such as excitatory neurotransmission and phospholipid turnover. Further studies with larger cohorts are necessary to validate these findings and explore the role of AAs in ASD pathophysiology. Full article

Background/Objectives: Fetal growth restriction (FGR) describes the situation of a fetus that fails to reach its genetic growth potential. Postnatal catch-up growth represents a central adaptive process, yet its timing and magnitude vary widely and may influence one individual’s state of health and later metabolic risk. This study aimed to characterize longitudinal growth trajectories from birth to 10 years in children born at term, affected antenatally by growth restriction, with a particular focus on the influence of sex and FGR severity on catch-up growth. Methods: We conducted a retrospective observational study including 170 term-born children with documented FGR, admitted to a tertiary pediatric center between 2019 and 2023. Anthropometric data (weight, length/height, BMI) at birth, 1, 2, 5, and 10 years were converted to World Health Organization (WHO) age- and sex-adjusted z-scores. Catch-up growth was defined as an increase of >0.67 SD. Participants were stratified by sex and FGR severity (moderate: 10th–3rd percentile; severe: <3rd percentile). Results: Severe FGR infants exhibited significantly lower birth anthropometrics but demonstrated more pronounced early catch-up in weight and length at 1 and 2 years (p < 0.01). By 5 and 10 years, growth trajectories converged between severity groups, with no differences in BMI at any age. Sex influenced absolute anthropometric values but not the probability of achieving catch-up growth. Conclusions: Among term-born FGR infants, severity—but not sex—shapes early postnatal growth. Despite early deficits, most children achieved substantial catch-up, underscoring the need for careful monitoring to support healthy, proportionate growth and mitigate subsequent metabolic risk. Full article

Metabolic acidosis is common after kidney transplantation and has been linked to adverse renal outcomes. However, its relationship with histological injury in kidney allografts remains poorly characterized. We aimed to explore the association between metabolic acidosis and histopathological features in kidney allograft biopsies. This single-center, cross-sectional observational study included 63 adult kidney transplant recipients who underwent clinically indicated allograft biopsies. Metabolic acidosis was defined as a serum bicarbonate level < 22 mmol/L at the time of biopsy. Histological lesions were assessed according to the Banff classification. Lesion severity was evaluated using descriptive statistics, nonparametric comparisons, ordinal logistic regression, and multivariable logistic regression models adjusted for renal function, proteinuria, and time from transplantation. Sensitivity analyses additionally adjusted for hemoglobin and donor-related variables. Patients with metabolic acidosis exhibited numerically higher severity scores for both acute inflammatory lesions and chronic histological changes, including total inflammation and interstitial fibrosis/tubular atrophy (IFTA). Across ordinal analyses and multivariable regression models, consistent directional trends toward a greater histological injury burden were observed among acidotic patients; however, none of these associations reached statistical significance, and confidence intervals were wide. Sensitivity analyses yielded directionally consistent effect estimates. In this biopsy-based analysis, metabolic acidosis showed consistent directional trends toward a higher burden of inflammatory and chronic histological lesions, although these findings did not reach statistical significance. Full article

The Yan goose (YE, Anser cygnoides) is a valuable indigenous poultry genetic resource, renowned for its superior meat quality and environmental adaptability. Despite its economic importance, the genetic basis underlying these adaptive traits remains unclear. In this study, we employed whole-genome resequencing (WGS) to perform high-throughput sequencing on a conserved population of 15 samples. Bioinformatic analyses were conducted to systematically evaluate the population’s genetic structure, and a genome-wide scan for selection signals related to economically significant traits was performed using the integrated haplotype score (iHS) method. An average of 4.43 million high-quality SNPs were identified, which were predominantly located in intergenic and intronic regions. Population structure analysis revealed a close genetic relationship within the conserved population of YE, with no significant lineage stratification observed. Pairwise sequentially Markovian coalescent (PSMC) analysis indicated that the YE underwent a severe genetic bottleneck during the Last Glacial Maximum (LGM), followed by gradual population recovery in the early Neolithic period. Genome-wide selection signal scanning identified multiple genomic regions under strong selection, annotating key genes associated with growth and development (e.g., GHRL, AKT1, and MAPK3), lipid deposition (e.g., PLPP4, SAMD8, and LPIN1), and disease resistance and stress resilience (e.g., TP53, STAT3). Functional enrichment analysis revealed significant enrichment of these genes in pathways related to glycerophospholipid metabolism (p < 0.01), purine metabolism (p < 0.01), and immune response (p < 0.01). This study not only provides a theoretical foundation for the scientific conservation of the YE germplasm resources but also offers valuable genomic resources for identifying functional genes underlying important economic traits and advancing molecular breeding strategies. Full article

Psoriasis is a chronic inflammatory disorder with immunological, metabolic, and environmental components. It affects not only the skin but also the nails, joints, and vascular system. A total of 50 patients with psoriasis and 28 healthy controls took part in this study. Serum samples were gathered both from the psoriatic group and the control group. Serum zyxin concentrations were measured via enzyme-linked immunosorbent assay (ELISA). Our results revealed that serum zyxin amounts were significantly higher in patients with psoriasis compared with the controls. However, no statistically significant correlations were found between serum zyxin levels and inflammatory or metabolic parameters in the psoriasis group. Similarly, there was no significant correlation between zyxin level and disease severity as assessed by the Psoriasis Area and Severity Index (PASI) score. To sum up, our study demonstrates that serum zyxin levels are significantly elevated in patients with psoriasis compared with controls. Nevertheless, the precise role of zyxin in the aetiology of psoriasis remains unclear. Further research is needed to clarify the function of this protein in the disease process and to explore its potential as a therapeutic target. Full article