Search Results (16,842)

Background: Obstructive sleep apnea (OSA) is increasingly recognized as a systemic disorder associated with insulin resistance and elevated risk of type 2 diabetes. While continuous positive airway pressure (CPAP) is the standard therapy, its long-term metabolic benefits remain inconsistent. The metabolic impact of upper airway surgery is less well defined. Methods: In this retrospective study, 49 patients with polysomnography-confirmed OSA who underwent upper airway surgery were evaluated. Respiratory and metabolic parameters—including apnea–hypopnea index (AHI), fasting plasma glucose, fasting insulin, glycated hemoglobin (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR)—were assessed preoperatively and at 6 months postoperatively. Associations between changes in AHI (ΔAHI) and insulin resistance (ΔHOMA-IR) were analyzed using correlation and receiver operating characteristic (ROC) analyses. Results: Significant improvements were observed in both respiratory and metabolic parameters. AHI decreased from 46.6 ± 25.8 to 20.7 ± 14.1 events/h (p < 0.001). Fasting plasma glucose, insulin levels, and HOMA-IR were significantly reduced postoperatively (all p < 0.05), while HbA1c showed a downward trend. Reduction in AHI was moderately correlated with improvement in insulin resistance (r = 0.527, p < 0.001). ROC analysis demonstrated modest discriminative ability of ΔAHI for identifying normalization of insulin resistance (AUC = 0.62). Conclusions: Upper airway surgery was associated with significant improvements in insulin resistance and glycemic parameters in patients with OSA. The correlation between airway improvement and metabolic change supports a physiological link between upper airway obstruction and insulin sensitivity. These findings suggest that upper airway surgery may represent a clinically relevant adjunct within multimodal strategies for metabolic risk reduction, particularly in patients unable to tolerate CPAP therapy. Full article

Gestational Diabetes Mellitus (GDM) represents a significant public health concern due to its association with adverse maternal and neonatal outcomes, as well as elevated long-term metabolic risks. Its prevalence varies substantially depending on the diagnostic criteria used and the population studied. Women with GDM frequently experience heightened stress, anxiety, and uncertainty, underscoring the need for accessible information, counseling, and ongoing support to navigate glucose monitoring, dietary adjustments, and treatment regimens. Although clinical management has been extensively studied, research has largely focused on metabolic monitoring and therapeutic interventions, often underemphasizing prevention strategies, women’s informational needs, and maternal psychological well-being. Emerging evidence and international guidelines increasingly advocate for integrating these components into structured, woman-centered GDM care plans that actively involve families. Such approaches empower women to engage in self-management, enhance health literacy, support adherence to lifestyle and pharmacological interventions, and promote sustainable behavioral changes. This narrative review presents a comprehensive, holistic model of care across the perinatal continuum, emphasizing early risk identification, preventive strategies, and multidisciplinary coordination. Core elements include individualized antenatal education, empathetic communication, and family engagement, fostering self-efficacy, continuity of care, and integration of medical, educational, and psychosocial interventions. Equipping healthcare professionals with the competencies to deliver this holistic, woman-centered framework is essential to optimize maternal and neonatal outcomes and mitigate the long-term health consequences of GDM. Full article

Background/Objectives: Sex-specific differences in the pharmacokinetics of psychotropic drugs are gaining increasing clinical relevance, but only limited data are currently available on sex-specific effects within genetically defined metabolizer phenotype categories. The objective of this study was to assess genotype-dependent sex differences in the metabolic capacity of the drug-metabolizing enzymes CYP2D6 and CYP2C19. Methods: Statistical analyses were performed using linear mixed-effects models with subject-level random intercepts to account for repeated therapeutic drug monitoring (TDM) measurements. Venlafaxine and risperidone were used as probe drugs to find differences in the metabolic capacity of CYP2D6 and escitalopram for CYP2C19. Pharmacokinetic surrogate parameters were the metabolite-to-parent ratio (MPR) for venlafaxine and risperidone and the dose-corrected serum concentration (CD) for escitalopram. Models included sex, metabolizer phenotype, and their interaction, adjusted for age and creatinine production rate (CPR). Sex-specific differences within phenotype groups were assessed using estimated marginal means. Results: Among venlafaxine samples (N = 117) and risperidone samples (N = 73), no significant sex-specific differences in MPR were observed within CYP2D6 metabolizer groups. For escitalopram samples (N = 51), a significant sex difference was observed among CYP2C19 normal metabolizers (NMs), with higher CD in males compared to females. Conclusions: Exploratory analyses suggested a higher metabolic capacity in CYP2C19 NM females treated with escitalopram. Due to the limited sample size, however, this finding should be considered hypothesis-generating. Future studies in larger samples are needed to corroborate whether sex and other factors modulate the metabolic capacity of CYP2C19, e.g., by epigenetic mechanisms. Full article

Grapevine downy mildew, caused by the oomycete pathogen Plasmopara viticola (P. viticola), is one of the most devastating diseases threatening the global grape industry. The pathogen invades host plants through stomata, triggering a series of highly coordinated physiological disorders and biochemical defense events. This review systematically summarizes the dynamic changes in morphological structures (stomatal characteristics), physiological functions (photosynthesis, membrane system integrity, and carbon metabolism), and multi-level biochemical defense systems (reactive oxygen species (ROS) scavenging enzyme system, phenylpropanoid metabolic pathway, pathogenesis-related proteins, and phenolic compounds) in grapevines following infection. It focuses on analyzing the differences in the timing, intensity, and metabolic reprogramming of defense responses between resistant and susceptible cultivars, pointing out that the essence of disease resistance lies in early pathogen recognition and rapid defense induction. The conflicting conclusions regarding indicators such as soluble sugars, peroxidase (POD), and superoxide dismutase (SOD) are discussed from the perspectives of experimental systems, cultivar genetic backgrounds, and pathogen physiological race differences. Furthermore, the known physiological and biochemical alterations are linked to upstream signaling pathways, including salicylic acid and jasmonic acid (SA/JA), calcium signaling, and mitogen-activated protein kinase (MAPK) cascades. Recent advances in revealing resistance mechanisms in the omics era are also introduced. Finally, future research directions are proposed, including constructing multi-indicator dynamic evaluation models, verifying key gene functions using gene editing, exploring the potential of epigenetic regulation, and developing integrated control strategies combined with microbiome research. This review aims to provide theoretical support for grapevine downy mildew resistance breeding and sustainable disease management. Full article

Background/Objectives: Vitamin D has been implicated in lipid metabolism, but data regarding its association with atherogenic lipoproteins in elite athletes remain limited. Elite athletes represent a unique research model to investigate these associations with reduced confounding from obesity, chronic disease, smoking, and physical inactivity. Methods: This cross-sectional study included 773 male professional athletes from mixed sports disciplines (mean age 25.5 ± 5.0 years). Serum 25-hydroxyvitamin D [25(OH)D] concentrations and lipid parameters, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and lipoprotein(a) [Lp(a)], were assessed. Associations were analyzed using correlation analyses, subgroup comparisons according to predefined 25(OH)D categories (<30, 30–50, and >50 ng/mL), and multivariable linear regression models adjusted for age, body mass index, season, and training-related variables. Results: Higher serum 25(OH)D concentrations were independently associated with lower LDL-C (p = 0.028), triglyceride (p = 0.002), and Lp(a) concentrations (p = 0.036), whereas no independent association was observed with HDL-C (p = 0.559). Athletes with 25(OH)D concentrations ≥30 ng/mL demonstrated lower LDL-C, triglyceride, and Lp(a) levels compared with athletes below this threshold (all p < 0.05). Higher vitamin D status was additionally associated with greater peak exercise performance (4.29 ± 1.15 vs. 3.36 ± 0.68 W/kg; p < 0.001). Conclusions: Higher 25(OH)D concentrations were independently associated with a more favorable lipid profile in elite athletes, including lower LDL-C, triglyceride, and Lp(a) concentrations. Prospective studies are warranted to further investigate the relationship between vitamin D status and lipid metabolism in athletic populations. Full article

Background/Objectives: The transcription factor carbohydrate response element-binding protein (ChREBP) is a key glucose-sensing regulator that governs glucose and lipid metabolic homeostasis. However, its specific functions in skeletal muscle remain insufficiently clarified. The present study aimed to investigate the roles of ChREBP in skeletal muscle exercise capacity, energy metabolism, and adaptive remodeling, as well as muscle regeneration. Methods: We generated a skeletal muscle-specific ChREBP knockout mouse model, and assessed their exercise performance, energy metabolism, skeletal muscle fiber composition, and injury repair capacity. Additionally, hypoxia and high-fructose diet models were established to analyze the function of ChREBP in skeletal muscle adaptive remodeling. C2C12 myoblasts and primary muscle satellite cells were used to explore its effects on myogenic differentiation. Results: Genetic deletion of ChREBP induced no detectable alterations in myofiber composition, overall metabolic status, or muscle adaptive remodeling triggered by hypoxia and high-fructose diet. In vitro assays demonstrated that ChREBP overexpression facilitates C2C12 myogenic differentiation. Adeno-associated virus-mediated ChREBP overexpression enhanced histological markers of regeneration, including desmin-positive regenerative area and the cross-sectional area of newly formed myofibers after cardiotoxin-induced injury. Conclusions: Collectively, our experimental data indicate that ChREBP is largely dispensable for maintaining basal skeletal muscle homeostasis and stress-induced adaptive remodeling. Meanwhile, this study identifies a previously unrecognized regulatory role of ChREBP in the processes of skeletal muscle damage repair and post-injury regeneration. Full article

Background and Objectives: Patients undergoing incisional hernia repair constitute a clinically heterogeneous population with variable postoperative outcomes. Conventional risk models based on isolated risk factors may inadequately capture this complexity. This study aimed to identify data-driven clinical phenotypes and evaluate their association with surgical outcomes. Methods and Materials: A retrospective cohort of 1262 patients undergoing retromuscular incisional hernia repair (Rives–Stoppa technique) was analyzed. Unsupervised clinical phenotyping was performed using latent class analysis based on seven preoperative variables. Model selection was guided by Akaike information criterion (AIC), Bayesian information criterion (BIC), entropy, and clinical interpretability. Postoperative outcomes were compared across phenotypes. Results: Three distinct phenotypes were identified: metabolic (34.6%), structural (33.9%), and frailty (31.5%). The structural phenotype showed the highest complication (22.7%) and recurrence rates (8.6%), while the frailty phenotype had the lowest complication burden (14.6%). The metabolic phenotype was characterized by obesity and diabetes, consistent with increased wound-related morbidity. Cluster robustness was supported by internal validation metrics and sensitivity analyses. Conclusions: In this retrospective single-center cohort, distinct clinical phenotypes with different outcome profiles were identified among patients undergoing incisional hernia repair, supporting the concept that this population comprises clinically heterogeneous subgroups with distinct patterns of vulnerability. These findings should be considered preliminary and hypothesis-generating. Further external validation and prospective studies are required to determine the clinical utility of phenotype-based risk stratification. Full article

Background: Abnormalities in energy and amino acid metabolism are potentially involved in hepatocellular carcinoma (HCC) development. This study aimed to identify serum metabolites predictive of HCC following sustained virological response (SVR) with hepatitis C virus (HCV) treatment. Methods: Comparative metabolomics was conducted using time-course serum samples from patients who failed interferon-based therapy but subsequently achieved SVR with direct-acting antivirals (DAAs), minimizing inter-individual variability. Predictive biomarkers for post-SVR HCC were extracted from the results and validated by comparing 29 patients who developed post-SVR HCC with 58 age-matched patients who remained HCC-free during follow-up. Results: Metabolite concentrations changed more markedly after treatment in SVR cases than in non-SVR cases. Significant changes in methionine (Met), methionine sulfoxide (MetO), and ornithine (Orn) levels before and after treatment (Pre- and Post-Tx) were found only in the non-HCC group. Regression and survival analyses identified high levels of Pre- and Post-Tx Orn, Pre-Tx Met, and Post-Tx MetO as predictors of post-SVR HCC and enabled risk stratification. The integration of these metabolites with the fibrosis-4 (FIB-4) index and alpha-fetoprotein (AFP) facilitated risk stratification and discriminated between high- and low-risk patients. The Pre-Tx FIB-4/Met model and the Post-Tx AFP/MetO/Orn model identified low- and high-risk groups with 3-year HCC incidence rates of 6.4% and 81.8%, respectively. Conclusions: Serum Met, MetO, and Orn were identified as candidate biomarkers associated with post-SVR HCC development, which remains a concern in the fight against hepatitis C. Combining these metabolites with established clinical markers may improve post-SVR HCC risk stratification. Full article

Ascophyllum nodosum extracts (ANE) are widely used biostimulants associated with improvements in plant growth, productivity, nutrient acquisition, and abiotic stress tolerance. However, the molecular mechanisms linking extract composition to plant signaling and physiological responses remain incompletely resolved. ANE contains a complex mixture of bioactive constituents, including polysaccharides, osmolytes, phenolic compounds, and phytohormone-like molecules. Their composition varies according to biomass source, environmental conditions, and extraction methodology, contributing to variability in biological activity. Current evidence suggests that ANE functions mainly as a signaling modulator rather than a direct nutrient source. ANE treatment has been associated with early cellular responses, including cytosolic Ca²⁺ influx, reactive oxygen species (ROS) generation, and mitogen-activated protein kinase (MAPK)-associated signaling events. However, many proposed mechanisms remain unresolved, and a considerable proportion of the available mechanistic evidence originates from studies using purified ANE-derived polysaccharides or related elicitor systems. ANE-associated responses include modulation of nutrient transport, primary metabolism, hormonal regulation, transcriptional reprogramming, and stress-responsive pathways, contributing to improved root development, nutrient acquisition, and defense-related responses. Nevertheless, limited knowledge of receptor-mediated perception mechanisms, signaling hierarchies, and extract-dependent variability continues to constrain mechanistic understanding and reproducibility. Future research should prioritize receptor identification, bioassay-guided fractionation, integrated multi-omics approaches, and improved standardization of extraction and formulation procedures. These advances will be essential for establishing robust mechanistic models and supporting the development of evidence-based ANE biostimulants for sustainable crop production. Full article

Transposable elements (TEs) are inserted into the genome and may change its properties; those occurring in or near regulatory regions may also alter gene expression. Given the challenges of detecting insertions in short-read sequencing, we analyzed structural variants in polar and brown bear genomes by a reciprocal alignment of one species’ sample genomes to a reference sequence of the other species, thus inferring TE insertion as the other genome’s “deletions”. With this approach, we detected short interspersed elements (SINEs) belonging to the CAN SINE family as dominant fixed TEs. We observed a non-random distribution of CAN SINE insertion positions near both protein- and RNA-coding genes, where TEs often overlap UTRs or occur in their vicinity. In contrast, SINEs avoid coding sequences, suggesting TE insertions that would disrupt such sequences are under purifying selection. We used black bear as an outgroup and determined that most of the CAN SINE insertions in the polar bear genome were derived, since they are not present in black or brown bear, while there is no dominant trend for CAN SINE insertions in brown bear relative to the outgroup. Many of the genes with UTRs affected by CAN SINEs are potentially relevant to the differences between the species (body shape, size, etc.) or to Arctic-adaptation phenotypes such as fur color, metabolism, and the immune system. This supports a model that CAN SINEs have contributed to regulatory evolution in bears and provides further evidence of such events across carnivore genomes in the animal kingdom. Full article

Background: The triglyceride–glucose (TyG) index has emerged as a simple surrogate marker of insulin resistance and metabolic disruption. In the context of ST-elevation myocardial infarction (STEMI), such disturbances have been associated with adverse cardiovascular outcomes, more complex angiographic profiles, and microvascular complications. However, data on the association between TyG and intracoronary thrombus burden (TB) in STEMI remain limited. Methods: In this prospective observational study, we included consecutive STEMI patients treated with primary percutaneous coronary intervention (pPCI). The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. TB was graded according to the modified thrombolysis in myocardial infarction (mTIMI) thrombus classification score after restoration of antegrade flow with a wire or small balloon when the culprit vessel was initially totally occluded. Patients were categorized as low-TB (LTB; mTIMI grades 1–3) and high-TB (HTB; mTIMI grade 4). The primary outcome was HTB; secondary outcomes were distal embolization and no-reflow. Associations between TyG and outcomes were assessed using univariable and multivariable logistic regression, restricted cubic spline analysis, and receiver operating characteristic (ROC) curves to evaluate incremental predictive value. Results: A total of 309 patients were analyzed. The TyG index was significantly higher in the HTB group compared with the LTB group (9.12 ± 0.62 vs. 8.92 ± 0.64, p = 0.004). In a stepwise multivariable model, TyG remained independently associated with HTB (adjusted odds ratio = 1.61; 95% confidence interval: 1.11–2.37; p = 0.014). Adding TyG to a baseline clinical model only numerically improved discrimination for HTB, as reflected by a small increase in ROC area under the curve. Restricted cubic spline analysis demonstrated a monotonic rise in the probability of HTB with higher TyG values. Higher TyG also showed non-significant trends toward increased odds of distal embolization and no-reflow. Conclusions: The TyG index was independently associated with HTB in STEMI patients undergoing pPCI and may serve as an accessible adjunctive marker for incremental risk stratification beyond conventional clinical and angiographic factors. Full article

Glutamine is a conditionally essential amino acid that is important for endothelial homeostasis, while endothelial cell dysfunction is associated with altered glutamine metabolism and shifts toward stress-responsive pathways. We investigated the role of glutamine and senescence-associated beta-galactosidase (SA-β-gal) activity in Ea.hy926 endothelial cells (ECs), together with supportive functional activity assays. We found that glutamine depletion induced a progressive decline in endothelial function. Specifically, glutamine-depleted ECs exhibited increased SA-β-gal activity, accompanied by impaired proliferative capacity, disrupted cellular morphogenesis, increased promyelocytic cell adhesion, and diminished ability to promote host tissue proliferation and EC morphogenesis in a zebrafish xenograft model. These findings suggest that glutamine availability is crucial for maintaining endothelial integrity and functional competence. Full article

Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder caused by glutaryl-CoA dehydrogenase (GCDH) deficiency, leading to the accumulation of neurotoxic metabolites that can cause both acute encephalopathic crises and progressive, insidious brain injury. Current management primarily relies on a protein-restricted diet, which remains therapeutically insufficient and burdensome for patients, highlighting the need for disease-modifying therapies. In this study, we established a novel GA1 mouse model using CRISPR/Cas9 technology and evaluated the preclinical efficacy of systemic recombinant adeno-associated virus (rAAV)-mediated gene therapy. Under standard dietary conditions without high-lysine challenge, our GA1 model exhibited sustained cerebral and hepatic glutaric acid (GA) accumulation and distinct chronic vacuolation in the hippocampus and cerebellum, mirroring the insidious-onset GA1 phenotype. Five-week-old mice received a single intravenous injection of rAAV-hGCDH using either rAAV2/8 or rAAV2/9 serotypes. Systemic rAAV-mediated gene therapy significantly reduced GA accumulation and attenuated chronic neuropathological changes in this GA1 mouse model for both serotypes. Our findings support the hypothesis that peripheral metabolic correction may play an important role in preventing the chronic neuropathological changes associated with GCDH deficiency. However, further investigation using tissue-specific expression systems is required to definitively delineate the relative contributions of hepatic versus central GCDH restoration to the observed neuroprotection. Full article

Peach (Prunus persica) fruit pigmentation is largely associated with anthocyanin accumulation, whereas colorless flavonols such as kaempferol glycosides may reflect alternative use of shared flavonoid precursors. To examine the relationship between anthocyanin and selected kaempferol glycoside accumulation, we analyzed 15 peach accessions classified by red, white, or yellow flesh pigmentation. Skin color was quantified using the a*/b* ratio, where a* represents redness/greenness and b* represents yellowness/blueness. Red-fleshed accessions showed higher skin a*/b* values and accumulated higher levels of total anthocyanins, particularly cyanidin-3-glucoside, than white and yellow accessions. In contrast, kaempferol-3-rhamnoside preferentially accumulated in white-fleshed accessions. Expression analysis of flavonoid pathway genes showed that dihydroflavonol 4-reductase (PpDFR) was more highly expressed in red accessions, whereas flavonol synthase (PpFLS) was more highly expressed in white accessions; chalcone synthase (PpCHS), flavanone 3-hydroxylase (PpF3H), flavonoid 3′-hydroxylase (PpF3′H), and anthocyanidin synthase (PpANS) showed no significant differences among color groups. Heterologous overexpression of PpF3′H in Arabidopsis thaliana, a well-characterized model plant for flavonoid biosynthesis, was associated with increased seed anthocyanin accumulation and a lower kaempferol-to-quercetin ratio, supporting its catalytic capacity to influence flavonoid composition in an exogenous system. Overall, these results indicate that differential anthocyanin and selected kaempferol glycoside accumulation in peach is associated with the relative expression patterns of branch-related flavonoid genes, particularly PpDFR and PpFLS. This study provides targeted metabolic and transcriptional evidence for understanding peach flesh and skin pigmentation and provides mechanistic insight into flavonoid branch competition linking gene expression patterns with metabolite allocation, and identifies candidate genes for improving fruit color and flavonoid-related nutritional quality. Full article

Heat stress occurs when total environmental and metabolic heat production is greater than an animal’s ability to dissipate that heat. Heat stress negatively impacts feeder cattle performance and welfare. Limited research has been conducted to determine if feeding cattle in the evening, thereby shifting their metabolic heat production to a cooler period of the day, can help mitigate heat stress. This pen-level randomized controlled trial evaluated the effects of evening feeding (PM; feedings at 2000, 2300, and 0200 h; n = 24 pens) versus morning feeding (AM; feedings at 0500, 0800, and 1200 h; n = 24 pens) on terminally sorted steer performance in a commercial feedyard in the Pacific Northwest. Data collection included feed delivery, water consumption, health events, open mouth breathing prevalence, and carcass traits. Linear and generalized linear mixed-effects models were used to determine potential differences between treatment group and temperature-humidity index (THI; <80 versus ≥80). Only 14% of the total study days had a THI ≥ 80, indicating little to no heat stress impacts. There were no differences found between PM and AM for any outcome (p < 0.05). Regardless of treatment group, water consumption tended (p = 0.07) to increase, and open mouth breathing significantly (p < 0.05) increased on days with THI ≥ 80. Further research is warranted to assess evening feeding as a heat stress mitigation strategy in a feedyard setting. Full article