Search Results (8,318)

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age, often associated with metabolic issues, causing infertility. Although it is common, the cause of PCOS remains unknown, and early diagnosis is challenging. MicroRNAs (miRNAs) serve as post-transcriptional regulators of gene expression, play a significant role in PCOS development, and have emerged as biomarkers for reproductive and metabolic disorders. However, research on miRNA signatures in the Indian population is limited. This pilot exploratory study aims to compare the candidate differentially expressed miRNAs (DE miRNAs) in serum samples from individuals with and without PCOS using high-throughput miRNA sequencing. Methods: In the study, patients with PCOS and age-matched controls were included; small RNAs were isolated from their serum, libraries were prepared, and the libraries were analyzed by next-generation sequencing. Bioinformatics analysis, including miRBase annotation, differential expression analysis, target prediction, GO/KEGG enrichment, and hub gene network analysis, was performed. Results: A total of 967 miRNAs were identified, with seven showing differential expression (log2FC > 1, p < 0.05). Among these, six miRNAs of hsa-miR-219a-2-3p, hsa-mir-384, hsa-miR-149-5p, hsa-miR-3182, hsa-miR-3960, and hsa-miR-4508 were upregulated, whereas hsa-mir-139 was downregulated. Functional enrichment and hub gene analyses identified key targets, including TP53, FOXO1, HIF1A, and HDAC1, that are crucial to the cell cycle, insulin signaling, and hypoxia. Conclusions: These preliminary findings identify candidate serum miRNA signatures in Indian women that may be associated with PCOS’s reproductive and metabolic issues. These pilot study results suggest potential miRNAs and their target pathway links with PCOS that need validation in larger cohorts for diagnostic or therapeutic applications. Full article

Background/Objectives: Ambient fine particulate matter (PM_2.5) poses significant health risks to older adult populations, yet the specific contributions of its chemical constituents, particularly non-phthalate and non-organophosphate ester compounds, remain poorly understood. This study aimed to elucidate the mechanistic links between PM_2.5-bound ester exposures and metabolic pathway alterations in elderly individuals. Methods: A total of 258 elderly residents aged 60 years or older from Fuzhou, China, were recruited. Personal PM_2.5 exposure was monitored over 72 h using UPAS V2 samplers, with chemical components analyzed via gas chromatography–mass spectrometry (GC–MS). Plasma metabolomic profiling was conducted using liquid chromatography–mass spectrometry (LC–MS), and metabolic pathway enrichment was performed using MetaboAnalyst 5.0. Linear regression models adjusted for covariates (age, sex, BMI, lifestyle factors) assessed associations between ester exposures and metabolite abundance. Results: The mean PM_2.5 concentration was 38.06 μg/m³, with ester compounds dominating the chemical composition. Twenty high-concentration non-target esters were prioritized for analysis. PM_2.5 ester exposure was associated with alterations in key metabolic pathways, including steroid biosynthesis, glycolysis/gluconeogenesis, glycerophospholipid metabolism, and purine/pyrimidine metabolism. When interpreted alongside prior epidemiological evidence, these alterations represent putative links to increased risks of insulin resistance, cardiovascular dysfunction, and metabolic syndrome—relationships that require confirmation in prospective cohort studies and controlled toxicological experiments. Conclusions: Putatively annotated PM_2.5-bound ester compounds, particularly non-regulated subclasses, are associated with systemic metabolic alterations in older adults, coincident with perturbations in steroid and lipid metabolism. While these findings are exploratory and hypothesis-generating, they highlight the need to incorporate specific ester profiles into PM_2.5 risk assessments and develop targeted interventions for vulnerable aging populations. Full article

Introduction: Hepatitis C virus (HCV) infection often coexists with comorbidities, increasing vulnerability, complications, and adverse events. Direct-acting antivirals (DAAs) have dramatically improved HCV management, but they differ in drug–drug interaction (DDI) profiles. Sofosbuvir/velpatasvir (SOF/VEL) is associated with minimal clinically relevant interactions. Areas covered: A narrative review of the literature was conducted by searching PubMed and major international guidelines, focusing on studies published in the DAA era addressing HCV patients with major comorbidities, focusing on diabetes, metabolic syndrome, and cardiovascular disease; neuropsychiatric disorders; cancer; transplants; and use of substances or treatment with opioid agonists; and patients requiring hormone therapy including transgender patients. Expert opinion: Based on the literature and real-world data, managing polypharmacy in HCV patients with comorbidities is effective and well-tolerated, provided thorough drug review, potential DDI analysis, proactive monitoring, and coordinated multidisciplinary care are ensured. DAAs have dramatically improved the management of HCV patients; however, they have different DDI profiles that should be carefully checked. SOF/VEL has been shown to be associated with minimal clinically relevant interactions and offers a simple dosing regimen. DAA treatment is strongly advised in HCV comorbid patients not only to cure HCV but also to improve the course of comorbidities, provided that DDIs are no longer considered mere minor details. Full article

Long COVID (LC) is a heterogeneous post-infectious syndrome characterized by persistent symptoms, yet the biological basis underlying its interindividual variability remains poorly understood. Given the clinical overlap between LC and myalgic encephalomyelitis (ME), and prior demonstration that haptoglobin (Hp) phenotypes modulate symptom severity in ME, we investigated whether Hp phenotypes similarly stratify post-exertional cognitive dysfunction in LC. In this longitudinal observational study, 44 individuals with LC and 20 short-course COVID controls, who recovered rapidly from SARS-CoV-2 infection without persistent symptoms or sequelae, underwent Hp phenotyping alongside metabolomic and physiological profiling before and after a standardized 90 min passive post-exertional challenge. Hp phenotypes identified clinically distinct LC subgroups. Compared with Hp1-1 individuals, Hp2 allele carriers exhibited greater fatigue, poorer physical function, and more severe post-exertional symptoms. Immediately following the challenge, Hp2-2 participants with LC showed significant cognitive decline, whereas Hp1-1 individuals demonstrated cognitive resilience and more favorable longitudinal cognitive trajectories. This differential susceptibility was accompanied by higher post-exertional cerebral fractional tissue oxygen extraction in the right hemisphere in Hp1-1 individuals and by distinct metabolic signatures, with Hp2 allele carriers exhibiting lower post-exertional plasma concentrations of citric acid, isethionate, and glucosamine. Lower metabolite levels were associated with poorer cognitive performance. These findings support Hp phenotypes as promising candidate biomarkers for biological stratification in Long COVID, pending validation in larger independent cohorts. Full article

Background/Objectives: Cardiovascular–kidney–metabolic (CKM) syndrome, characterized by disturbances in glucose and lipid metabolism as its core pathophysiological feature, is a major driver of target organ damage. While early risk stratification in CKM stages 0–3 is critical to intercept renal decline, the practical utility of accessible metabolic surrogates remains poorly characterized. This study evaluated and compared the prospective capacity of the atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, and C-reactive protein–triglyceride glucose index (CTI) for predicting renal deterioration in early-stage CKM. Methods: Data were extracted from the China Health and Retirement Longitudinal Study (2011–2015). In total, 4064 participants aged ≥ 45 with CKM stages 0–3 (with exclusion of participants with baseline CKM stage 4) were prospectively followed. Renal function decline was defined as an estimated glomerular filtration rate (eGFR) decrease of ≥30% over 4 years, calculated using the CKD-EPI 2012 cystatin C equation. Multivariable logistic regression, restricted cubic splines (RCSs), and receiver operating characteristic (ROC) curves were applied. Results: Overall, 122 participants developed the renal outcome. In fully adjusted models, AIP, TyG, and CTI were valid independent risk factors for renal decline, with the lipid-driven AIP exhibiting the strongest association (OR = 5.54, 95% CI: 3.30–9.29; TyG: OR = 1.97, 95% CI: 1.49–2.59; CTI: OR = 1.63, 95% CI: 1.30–2.05; all p < 0.001). RCS analysis demonstrated significant non-linear dose–response trajectories, with renal risk escalating sharply past specific exploratory inflection points (AIP = 0.97, TyG = 7.80, CTI = 8.07). ROC curves confirmed robust predictive performance (AUCs > 0.75), with AIP performing optimally (AUC = 0.773). Conclusions: AIP, TyG, and CTI are independent longitudinal predictors of renal decline in early-stage CKM, with AIP demonstrating superior discriminatory power. Monitoring these composite indices and maintaining them within observed metabolic ranges may aid in early renal risk stratification and monitoring, though the exploratory statistical inflection points identified require validation in independent cohorts before clinical application. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide and represents the hepatic manifestation of a systemic cardiometabolic-inflammatory syndrome rather than an isolated organ disease. In parallel, anticancer therapies carry a well-recognised burden of cancer therapy-related cardiovascular toxicity (CTR-CVT). Evidence suggests that the metabolic-inflammatory cascade driving steatosis → steatohepatitis → fibrosis may also contribute to endothelial dysfunction, myocardial remodelling and cardiomyocyte vulnerability to chemotherapy-induced oxidative stress. This narrative review proposes a unifying conceptual framework in which MASLD may act as a potential amplifier of cardiotoxicity in oncology patients and examines whether lifestyle and dietary interventions could mitigate this cumulative risk. Methods: A structured literature search of PubMed, Scopus and Web of Science was performed, prioritising systematic reviews, meta-analyses, randomised controlled trials, large cohort studies and recent international guidelines on MASLD, cardio-oncology and nutritional interventions. Results: Four converging molecular axes were identified as plausible links between MASLD and cardiomyocyte susceptibility to anticancer therapy: mitochondrial dysfunction with reactive oxygen species overproduction, NLRP3 inflammasome activation and metaflammation, endothelial nitric oxide impairment, and pro-fibrotic TGF-β/hepatic stellate cell signalling. Mediterranean-style dietary patterns, selected micronutrients and emerging metabolic therapies modulate the same network and may offer translational opportunities. Conclusions: Reframing MASLD as a potentially modifiable amplifier of CTR-CVT supports the integration of hepatic phenotyping into baseline cardio-oncology risk stratification and the use of personalised nutrition as a precision tool acting on shared mitochondrial, inflammatory, endothelial and fibrotic pathways. Multidisciplinary framework and prospective interventional studies, adopting composite hepato-cardio-oncological endpoints, are warranted. Full article

Objective: Pain in psoriatic arthritis (PsA) is multifactorial and may persist despite apparently controlled inflammatory activity. Metabolic syndrome (MetS), a frequent comorbidity in PsA, could contribute to increased pain burden beyond inflammatory disease activity. The objective was to investigate the association between MetS and pain burden in PsA, focusing on pain intensity (BPI severity; primary outcome) and pain-related functional impact (BPI interference; secondary outcome), and to assess whether these associations are independent of disease activity (DAPSA) and fibromyalgia. Methods: PSABRAIN is a cross-sectional, monocentric study including consecutive adult patients with PsA (CASPAR criteria). MetS was defined according to modified ATP III criteria. Pain outcomes were assessed using the Brief Pain Inventory (BPI) severity and interference subscales. Group comparisons (MetS vs. no MetS) were performed using appropriate parametric/non-parametric tests. Univariable and multivariable linear regression models were fitted for BPI severity and BPI interference. Multivariable models were adjusted for age, sex, disease duration, fibromyalgia, and DAPSA. Robustness analyses replaced MetS with BMI (continuous), obesity, and overweight. Results: A total of 187 PsA patients were included (44 with MetS; 143 without). MetS patients were older (median 62 vs. 57 years, p = 0.0017), had higher BMI (median 30.1 vs. 25.5 kg/m², p < 0.001) and a higher prevalence of obesity (56.8% vs. 15.4%, p < 0.001), while DAPSA did not differ between groups (p = 0.819). MetS patients reported higher BPI severity (median 5.75 vs. 4.5, p = 0.038) and BPI interference (median 6.86 vs. 5.5, p = 0.044). In univariable regression, MetS was associated with higher BPI severity (β = 0.93, 95% CI 0.08 to 1.77; p = 0.032) but not with BPI interference (β = 0.81, 95% CI −0.13 to 1.75; p = 0.091). In adjusted models, MetS remained independently associated with BPI severity (β = 0.99, 95% CI 0.23 to 1.75; p = 0.011), whereas its association with BPI interference was not significant (β = 0.69, 95% CI −0.20 to 1.57; p = 0.126). In alternative models, BMI and obesity were independently associated with both outcomes (BPI severity: BMI β = 0.097/kg/m², p = 0.004; obesity β = 0.91, p = 0.010; BPI interference: BMI β = 0.095/kg/m², p = 0.015; obesity β = 1.22, p = 0.003). Conclusions: In PsA, MetS is independently associated with higher pain severity but not with pain interference after adjustment for disease activity and fibromyalgia. Adiposity measures show consistent independent associations, particularly with pain interference, supporting the relevance of metabolic and weight-related factors in the multidimensional assessment of pain in PsA. Full article

The association between Down syndrome (DS) and Hodgkin lymphoma (HL) is rare, with only a few cases reported in the literature. Here, we report the case of a pediatric patient with DS diagnosed with HL. In addition, a literature review was conducted, identifying only seven pediatric cases. We highlight treatment-related toxicity in this group of patients. Given the high survival rates of patients with HL, current strategies focus on individualizing treatment intensity based on the initial disease characteristics and the patient’s response. This consideration becomes even more important in patients with DS. The patient described in this report achieved complete metabolic remission after chemotherapy, experienced manageable grade 3 treatment-related toxicities, and remains in complete remission after 27 months of follow-up. Full article

Skeletal deformities remain a major challenge in marine fish hatcheries, affecting larval quality, animal welfare, production efficiency, and market value. In European seabass (Dicentrarchus labrax), saddleback syndrome (SBS) is a relevant skeletal abnormality that develops during larval ontogeny and has been associated with defects of the primordial marginal finfold around the flexion stage. This study investigated whether gene expression markers, combined with machine learning, could provide a stage-specific molecular approach for assessing SBS-associated larval batch quality. Larval populations from commercial hatcheries were classified as GOOD or POOR according to SBS incidence at mid-metamorphosis. Gene expression was analyzed at first feeding, flexion, post-flexion, and mid-metamorphosis, targeting genes involved in osteogenesis, myogenesis, metabolism, oxidative phosphorylation, and stress response. Stage-specific random forest models were used to classify gene expression profiles derived from larval populations with contrasting SBS incidence and to identify candidate informative genes. The models showed cross-validated area under the receiver operating characteristic curve (ROC AUC) values ranging from 0.83 to 0.962, with the highest performance at flexion. Reduced models based on the three most informative genes retained comparable internal cross-validation performance. Key candidate genes were mainly related to mitochondrial energy production, iron metabolism, stress response, muscle development, and extracellular matrix formation. These findings suggest that gene expression profiling combined with machine learning may support stage-aware discrimination of larval populations with contrasting SBS incidence, although validation in larger independent datasets is required before hatchery application. Full article

Patients with autoimmune rheumatic diseases, particularly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), experience excess cardiovascular risk that is not fully captured by conventional lipid measurements. In active RA, lower cholesterol may coexist with higher vascular risk, a pattern known as the lipid paradox. We propose that systemic inflammation can uncouple lipid concentration from lipoprotein function and organize the evidence along five mechanistic axes. Inflammatory cytokines, mainly interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), IL-1β, IL-17/IL-23 and type I interferons, remodel lipoprotein metabolism. High-density lipoproteins (HDL) lose protective functions and may become pro-inflammatory. Apolipoprotein-B particles are oxidized or otherwise modified, linking lipid metabolism to autoimmunity. Macrophage cholesterol imbalance and cholesterol crystals activate inflammasome pathways in experimental atherosclerosis, while immune-cell metabolic rewiring may amplify cytokine output; these mechanisms are treated as extrapolated when direct rheumatic-disease evidence is limited. The pathways converge on endothelial dysfunction and thrombo-inflammation. RA and SLE are the mechanistic anchors, whereas psoriatic disease, axial spondyloarthritis, systemic sclerosis, vasculitides and antiphospholipid syndrome are weighted by evidence category. Standard lipid panels may therefore underestimate risk in selected contexts, especially during active inflammatory disease. Full article

Agave angustifolia Haw. is one of the primary sources for the production of mezcals such as raicilla and tuxca, in western Mexico. In Jalisco, Agave angustifolia evolved from being a pre-Hispanic ritual and food resource (200–1500 CE) to becoming the primary basis for 16th-century vino mezcal, the precursor to all modern mezcals, including raicilla and tequila. This review synthesizes current genomic, epigenetic, and metabolic evidence to elucidate the species’ evolutionary and adaptive potential. Our analysis suggests that the domestication of A. angustifolia is characterized by a “domestication paradox,” where intensive clonal management ensures short-term productivity but creates genetic bottlenecks that limit long-term adaptive capacity. We synthesize empirical evidence to show that adaptive plasticity is driven by the integration of Crassulacean Acid Metabolism (CAM) flexibility and dynamic global DNA methylation (GDM) profiles, which, while currently correlative, suggest an environmental response mechanism. We conclude that securing the socio-economic viability of Agave spirits requires a transition from intensive monocultures to regenerative agroforestry, incorporating sexual propagation to maintain evolutionary potential. Furthermore, we outline a roadmap for Genomics-Assisted Breeding (GAB 4.0), integrating marker-assisted selection for juvenile traits to accelerate the release of resilient biotypes, and precision diagnostic tools to reduce the ecological footprint of Agave production. This framework secures the genomic integrity of traditional spirits within a circular, climate-resilient bioeconomy. Full article

Background: Adolescence represents an essential stage of life for the prevention of metabolic changes associated with diseases, especially cardiovascular diseases. Objectives: The objectives of this study were to identify nutritional status and associate it with metabolic alterations in adolescent girls. Methods: We conducted a cross-sectional study that included adolescent 10–14-year-old girls from public schools. The research was undertaken with 79 girls. Results: We identified that over half of the girls were sedentary, excessively exposed to screens, physically inactive, and did not practice physical activities in sunlight. The menarche age was significantly lower in girls with overweight and obesity. Most girls skipped breakfast (53.1%) and watched television (84.8%). We observed a high percentage of adolescents with overweight (65.7%), hypovitaminosis D (78.4%) and high levels of triglycerides (69.6%). We did not find an association between hypovitaminosis D and some recorded metabolic parameters (glycemia, glycated hemoglobin, insulin, total cholesterol, HDL-c, LDL-c and triglycerides). However, insulin levels, HOMA-IR, HDL-c, and systolic blood pressure were significantly associated with overweight and obesity, and our results may reflect the characteristics of the study sample and suggest that obese children may already exhibit early signs and risk factors for these chronic diseases during childhood, consistent with national and international data. Conclusions: The identification of metabolic alterations, nutritional status and lifestyle enables early and directed interventions, which may lead to the present and future cardiometabolic health improvements relative to adolescents. Full article

Background/Objectives: The cardiometabolic consequences of sarcopenic obesity (SO) remain poorly characterized in Latin America. We hypothesized that SO uniquely concentrates aortic stiffness, metabolic syndrome, and vitamin D deficiency in older Mexican adults, and that handgrip strength exhibits a dose–response relationship with cardiometabolic risk independent of adiposity. Methods: We conducted a cross-sectional analysis of 2087 adults ≥ 50 years from the Mexican Health and Aging Study (MHAS) 2012. Four phenotypes were defined using EWGSOP2 criteria: lean–fit, lean–sarcopenic, obese–non-sarcopenic, and obese–sarcopenic (BMI ≥ 30 kg/m²). Outcomes were pulse pressure (PP, aortic stiffness proxy), metabolic syndrome (modified IDF criteria), and serum 25(OH)D. Normality tests confirmed non-normal distribution (p < 0.001). Given heteroscedasticity (Breusch–Pagan p < 0.001), HC3 robust standard errors were used. Regression models were sex-adjusted and sex-stratified. Results: The sample showed high cardiometabolic burden: mean HbA1c 6.91% (35.3% ≥ 6.5%); metabolic syndrome 57.6%; mean PP 60.7 ± 17.9 mmHg; mean gait speed 0.708 m/s (70.4% slow). Phenotype distribution: lean–fit 12.3%; lean–sarcopenic 47.3%; obese–non-sarcopenic 8.7%; obese–sarcopenic 31.7%. In multivariable models, handgrip strength was an independent protective predictor of PP (beta = −0.09 per kg; 95% CI: −0.17 to −0.01; p = 0.033), with a sex-specific effect in women (beta = −0.13; p = 0.010). Conclusions: SO is highly prevalent in older Mexican adults and associates with an adverse cardiometabolic profile. Handgrip strength shows a protective dose–response association with cardiometabolic risk independent of adiposity, identifying muscle function as a candidate modifiable factor that warrants confirmation in longitudinal and interventional studies. The obese–non-sarcopenic phenotype exhibited the lowest PP, unveiling the sarcopenic obesity paradox: adiposity without muscle function loss does not promote arterial stiffening. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent disease closely linked to dietary habits and body composition, particularly reflected in lean mass and markers such as appendicular skeletal muscle mass (ASM). Low ASM can subsequently trigger metabolic abnormalities such as metabolic syndrome (MetS). This study aimed to evaluate the relationships between the diet quality index, ASM, and MetS in individuals with MASLD from the Yucatan Peninsula. Methods: A cross-sectional study was conducted in subjects with a MASLD diagnosis. Diet quality index, anthropometric and biochemical parameters were evaluated. Body composition analysis was utilized to estimate ASM. Correlations between ASM and anthropometric/biochemical parameters were analyzed. Furthermore, comparative analyses were performed between groups stratified by the presence of MetS and low ASM. Results: Fifty subjects were included in the study. Participants exhibited a significantly low diet quality index (57.6 ± 9.78 vs. 100, p < 0.001), alongside a high prevalence of both low ASM and MetS. ASM was positively correlated with BW, WC, and protein mass (p < 0.001), as well as with creatinine and ALT (p < 0.05), and negatively correlated with body fat percentage and TG (p < 0.05). Subjects with low ASM showed significant differences in BW, waist circumference, protein mass, and energy intake compared to those with normal ASM (p < 0.05). Individuals with MetS had higher glucose and blood pressure compared to non-MetS (p < 0.05). Additionally, among patients with MASLD and MetS, those with low ASM exhibited higher glucose and systolic blood pressure compared to those with normal ASM (p < 0.05). Conclusions: Our study demonstrates that adults with MASLD from the Yucatan Peninsula exhibited suboptimal diet quality according to the DQI-I, with a high prevalence of low ASM and MetS. These findings highlight the potential role of the muscle–liver axis in metabolic dysfunction in MASLD. Full article

Pediatric obstructive sleep apnea (OSA) is a common disorder associated with significant neurocognitive, behavioral, cardiovascular, and metabolic consequences. Although adenotonsillectomy remains first-line therapy for many children, residual OSA is common, particularly among those with obesity, craniofacial abnormalities, genetic syndromes, neuromuscular disease, or other forms of medical complexity. Continuous positive airway pressure (CPAP) is the standard non-surgical treatment; however, long-term effectiveness is frequently limited by poor tolerance and adherence. Heated high-flow nasal cannula (HFNC) therapy has emerged as a potential alternative for selected children with sleep-disordered breathing, particularly those who are unable to tolerate conventional positive airway pressure therapy. Unlike CPAP, HFNC delivers heated, humidified gas through an open nasal interface and may improve sleep-disordered breathing through a combination of flow-dependent positive airway pressure generation, dead-space washout, improved ventilatory efficiency, enhanced gas conditioning, and reductions in inspiratory resistance. However, the relative contribution of these mechanisms during sleep remains incompletely understood. Current clinical evidence consists primarily of physiological studies, retrospective cohorts, case series, and a limited number of prospective comparative studies. Collectively, these data suggest that HFNC can reduce obstructive respiratory events and improve oxygenation in selected pediatric populations, including children with persistent OSA, CPAP intolerance, medical complexity, and syndromic conditions. Nevertheless, important uncertainties remain regarding optimal patient selection, titration strategies, patient monitoring, long-term adherence and comparative effectiveness relative to CPAP. This review summarizes the physiological basis of HFNC therapy, critically appraises the current clinical evidence, discusses practical considerations related to adherence and implementation, and highlights key knowledge gaps and future research priorities. Overall, HFNC should be viewed as an alternative for selected children who cannot tolerate CPAP, rather than as a universal substitute for pressure-based therapy. Full article