Metabolites最新文献

Background/Objectives: Type 2 diabetes (T2D) and obesity are chronic metabolic disorders associated with cognitive impairment and neuronal damage. The hippocampus, a region sensitive to nutrient excess, is critical for integrating sensory and metabolic signals. This study aimed to determine the early onset of cognitive and motor deficits induced by obesity and/or hyperglycemia and to characterize associated hippocampal alterations in Zucker Diabetic Fatty (ZDF) rats. Methods: Male ZDF rats (13 weeks old) were categorized into three groups: lean control, obese normoglycemic (ZDF-NG), and obese hyperglycemic (ZDF-HG). Assessments included zoometric parameters (weight and adiposity), biochemical assays (glucose tolerance, insulin response, and lipid profile), and behavioral tests (Open Field and Novel Object Recognition). Hippocampal health was evaluated through stereological neuronal density analysis and redox balance markers. Results: Both obese groups exhibited significant visceral adiposity and hyperlipidemia. The ZDF-HG group was further characterized by glucose intolerance, hepatic insulin resistance, and reduced β-cell function. Behavioral results showed that while obesity decreased motor activity, hyperglycemia significantly exacerbated the loss of both short- and long-term recognition memory. Histologically, obesity was associated with decreased neuronal density in the hippocampal DG and CA1 regions. Furthermore, hippocampal ROS was significantly elevated in the ZDF-HG group, and glutathione reductase activity was reduced in both obese phenotypes. Conclusions: The findings demonstrate that obesity initiates hippocampal neurodegeneration and motor decline, and that hyperglycemia severely impairs recognition memory. These results emphasize the critical interplay between metabolic dysfunction and cognitive decline, highlighting the necessity of managing both obesity and T2D to prevent early neurodegenerative changes.

Background: Metabolic syndrome (MetS) is a pathological condition characterized by the co-occurrence of multiple metabolic abnormalities. The affected population is increasingly shifting toward younger age groups. Emerging digital health technologies, arising from advances in digital society, offer novel methodological tools for lifestyle-based interventions targeting metabolic risk. This systematic review aims to evaluate the effectiveness of emerging digital health technologies based on dietary and physical activity regulation in improving MetS-related outcomes among adolescents, including school-aged children. Methods: This review followed the PRISMA guidelines, systematically searched PubMed, Web of Science, Embase, MEDLINE, and Scopus, and screened eligible studies based on the PICO framework. Results: A total of 12 randomized controlled trials published between 2012 and 2025 were included in the analysis. Single device interventions (5/12) and dual device combinations (5/12) were the predominant approaches used in current digital health technology applications. Intervention content primarily focused on either physical activity alone (5/12) or combined exercise and nutrition interventions (7/12), with most programs lasting 3-6 months (7/12). Across the included digital health interventions, 13 MetS-related measures were assessed, including anthropometric/body composition measures (BMI, BMI z-score, WC, WHR, WHtR, and VFA), blood pressure measures (SBP/DBP), and biochemical markers (BG, HOMA-IR, TG, TC, HDL-C, and LDL-C). Conclusions: The available evidence supports the potential of digital health technologies to improve MetS-related outcomes. Although the selection of biochemical markers varied across studies, the findings highlight the importance of combined exercise and nutrition interventions or physical activity of moderate to high intensity in improving MetS. These results underscore the value of digital health technologies in elucidating the complex interactions among diet, physical activity, and metabolic responses. Overall, these findings support integrating digital health technologies into adolescent lifestyle interventions to facilitate more personalized monitoring and behavior support, and to potentially improve MetS-related outcomes. By promoting timely improvements in these outcome measures, such digital health interventions may have potential longer term implications for chronic disease prevention.

Background/objectives: Tributyltin (TBT) remains a persistent aquatic contaminant with documented neurotoxic effects, yet the underlying mechanisms of its neurotoxicity remain poorly understood.

Methods: We investigated the comprehensive molecular mechanisms of TBT-induced neurotoxicity in zebrafish (Danio rerio) through an integrated approach combining histopathological examination, metabolomics analysis, transcriptional profiling, and behavioral assays.

Results: Histopathological analysis revealed significant TBT-induced damage to brain tissue architecture. Metabolomic profiling demonstrated that TBT exposure (500 ng/L) severely disrupted cellular energy metabolism, particularly the TCA cycle and purine/pyrimidine metabolism, while exhibiting hormetic responses at lower concentrations. Transcriptional analysis identified widespread downregulation of SNARE complex proteins and neurotransmitter transporters, indicating comprehensive deterioration of synaptic machinery.

Conclusions: These molecular perturbations corresponded with systematic disruption of antioxidant defense mechanisms and neurotransmitter signaling pathways, establishing a direct mechanistic link to observed behavioral deficits. Our findings reveal a hierarchical cascade of molecular disruptions triggered by TBT exposure, bridging the critical gap between metabolic dysregulation and synaptic dysfunction. This mechanistic framework provides fundamental insights into the neurotoxicological impact of this widespread environmental contaminant, highlighting potential therapeutic targets for intervention.

Background: Thyroid hormones regulate energy homeostasis, lipid/glucose metabolism, and protein turnover. Chronic Hepatitis C Virus (HCV) infection is highly associated with autoimmune hypothyroidism, which may have profound metabolic implications. This study evaluates thyroid dysfunction and anti-thyroid peroxidase (anti-TPO) autoimmunity in HCV patients and explores its potential metabolic implications in a high-prevalence region.

Methods: In this comparative cross-sectional study adhering to STROBE guidelines, we enrolled 100 PCR-confirmed chronic HCV patients and 100 age/gender-matched controls from District Peshawar, Pakistan. Serum TSH, fT3, fT4, and anti-TPO antibodies were quantified. Multivariable logistic regression, adjusted for age, gender, and viral load, was used to compute adjusted odds ratios (aOR) with 95% confidence intervals (CI).

Results: Thyroid dysfunction affected 41% of HCV patients vs. 12% of controls (aOR 5.2, 95% CI 2.8-9.6, p < 0.001), predominantly hypothyroidism (29% overall; 18% overt, 11% subclinical). Anti-TPO positivity was 38% in HCV vs. 8% in controls (aOR 6.7, 95% CI 3.1-14.5, p < 0.001). Anti-TPO titers correlated positively with TSH (r = +0.62, p < 0.001) and inversely with fT3/fT4. Subgroup analysis showed higher dysfunction in patients aged ≥40 years (52% vs. 28%, p = 0.012) and viral load ≥ 10⁶ IU/mL (48% vs. 32%, p = 0.041). We hypothesize that these findings may have significant metabolic implications, including impaired mitochondrial β-oxidation and insulin resistance.

Conclusions: HCV infection is strongly associated with autoimmune hypothyroidism, which may amplify cardiometabolic risk. The paper has not explicitly identified metabolic parameters, including lipid profiles, indices of insulin resistance, and metabolomic signatures, and, therefore, any metabolic inferences are speculative and based on established thyroid and HCV pathophysiology. Routine thyroid screening pre- and post-DAA therapy is recommended, alongside metabolomic profiling to validate these proposed metabolic pathways.

Background: Negative energy balance (NEB) during the transition period is associated with profound changes in the body condition and metabolic dynamics of dairy cows. However, the detailed lipidomic changes in milk induced by NEB are unclear, and lipid biomarkers that indicate the energy status of cows remain to be established.

Methods: Using a combination of GC-FID, HILIC-MS and RP-LC-MS, we performed a systematic comparison of lipid composition between early lactating (DIM: 5-14) and mid-lactating (DIM: 65-80) milk.

Results: We found that NEB in cows caused a profound modification in the profile of all the lipid classes surveyed, including phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), sphingomyelin (SM), lysophosphatidylcholine (LPC), PC-plasmalogen (PCP), PE-plasmalogen (PEP), lactosylceramide (LacCer), acylcarnitine (AcylCar) and triglycerides (TAGs). Except for LPC and AcylCar, which were reduced and increased, respectively, by NEB, the responses of other lipid classes varied across different species. For phospholipids and TAGs, species containing de novo FAs (C4:0-C16:0) and odd-chain FAs (C15:0 and C17:0) were markedly downregulated, whereas those comprising long-chain preformed FAs were upregulated by NEB.

Conclusions: Comprehensive lipidomic profiling of early and mid-lactating milk from two large cohorts of cows allowed us to identify nine lipids (PE 33:1, LacCer 32:1, LacCer 39:1, LacCer 41:1, SM 36:1, SM 36:2, SM 37:1, PEP 38:4 and PEP 38:5) as potential biomarkers of NEB in dairy cows.

Background/Objectives: Studying the role of UV-induced metabolic changes in skin physiology, and especially skin diseases, has gained importance in both medicine and cosmetics. With the development of new technologies, a variety of approaches have been implemented to model these metabolic effects. In this study, we explore the reproducibility of the UVA1-induced metabolic changes observed in different in vitro, ex vivo, and in vivo systems with escalating complexity. Our aim is to elaborate on the role of experimental setups in the reliable representation of in vivo data in other systems. Methods: Metabolic profiles post UVA1 treatment were assessed in skin cell culture, skin explants, and intact skin. For cell culture and explants, the metabolites from the culture medium were assessed via 1D-CPMG NMR. Intact skin samples were collected via microdialysis and the resulting dialysate was measured with GC-TOF-MS. Results: Data show that, despite great metabolic variations between the systems, several metabolites, such as glutamic acid, succinic acid, and threonine, change in a similar manner across multiple systems after UVA1 irradiation, including in vivo settings. Some metabolites, like phenylalanine, citric acid, and pyruvic acid, show similar UVA-mediated metabolic patterns between corresponding in vitro and ex vivo systems, but do not overlap well with in vivo data. Conclusions: Our findings emphasize the need for a metabolite-by-metabolite approach when deciding on the proper experimental system to perform UV irradiation experiments with regard to cutaneous physiology.

Background: Non-jointed water dropwort (Oenanthe javanica (Blume) DC.) is a widely cultivated aquatic vegetable with notable nutritional and pharmacological properties. Phosphorus (P) is a key nutrient affecting plant growth, photosynthesis, and metabolic balance, yet its role in water dropwort remains understudied.

Methods: This study investigated the physiological and metabolic responses of non-jointed water dropwort under P-deficiency treatment (0 mg·L^-1) and increasing P supply levels (5, 10, and 30 mg·L^-1).

Results: Moderate P supply (10 mg·L^-1) significantly promoted plant growth, enhanced photosynthetic efficiency, and increased antioxidant enzyme activity, increasing by 55.9%, 20.2%, and 118%, respectively, compared with the P-deficiency treatment. High P levels (30 mg·L^-1) inhibited growth and induced oxidative stress. Untargeted metabolomic analysis was conducted on root samples from CK (0 mg·L^-1) and HP (30 mg·L^-1) groups using UHPLC-MS. A total of 1274 metabolites were identified, with flavonoids, phenylpropanoids, fatty acid and conjugates being predominant. A total of 842 differential metabolites were screened under HP stress, with flavonoids (e.g., narcissin) showing the most significant upregulation. KEGG enrichment revealed key pathways including biosynthesis of amino acids, ABC transporters, and aminoacyl-tRNA biosynthesis, indicating metabolic reprogramming under HP stress. Notably, flavonoid and terpenoid pathways were upregulated, while certain lipid metabolism pathways, including fatty acid conjugates and phenylpropanoids, were downregulated. These findings suggest that non-jointed water dropwort adapts to high P stress by activating defense-related secondary metabolism and adjusting carbon-nitrogen allocation.

Conclusions: This study provides a theoretical basis for P management and stress-resistant cultivar selection in non-jointed water dropwort.

Background/objectives: Although advances in understanding glaucoma have been made, early detection remains challenging due to the asymptomatic nature of the disease. The Metabolomics In Surgical Ophthalmological Patients (MISO) study previously demonstrated that aqueous humor (AH) metabolomics can distinguish glaucoma patients from controls. We aimed to determine if the metabolic profile of AH has predictive power for overall survival and glaucoma progression after surgery.

Methods: Glaucoma patients (n = 34) were retrospectively analyzed and classified into progression categories based on surgical and medical interventions and assessed for survival.

Results: Glutamine and α-ketoglutarate were significantly associated with glaucoma progression, while N-acetylglutamate, lysine, and creatine correlated with mortality. These metabolites are linked to excitotoxicity, mitochondrial dysfunction, and oxidative stress, highlighting their potential role in glaucoma pathophysiology.

Conclusions: These results suggest that metabolomic profiling of AH could provide valuable biomarkers for predicting surgical outcomes and overall survival, paving the way for individualized therapeutic approaches. Further studies are required to confirm these findings before they can be integrated into clinical practice.

Background: Myoclonus, a sudden brief shock-like involuntary movement, represents a common yet under-recognized manifestation across many inherited metabolic disorders. Although its occurrence has been reported in case series and small cohorts, the overall spectrum, pathophysiological mechanisms, and therapeutic relevance of metabolic myoclonus have not been systematically summarized. Methods: A systematic search of PubMed was conducted for English-language publications from 2014 to 2025 using predefined MeSH terms related to myoclonus, movement disorders, and inborn errors of metabolism. Titles and abstracts were screened independently by three reviewers. After removal of duplicates, 27 articles were included, complemented by 65 additional references addressing individual disorders. Data were organized according to the International Classification of Inherited Metabolic Disorders (ICIMD). Results: Myoclonus was documented across six ICIMD categories, including intermediary metabolism, mitochondrial energy metabolism, lipid metabolism, disorders of complex molecules and organelles, cofactor and mineral metabolism, and metabolic cell signaling disorders. Clinical presentation ranged from isolated jerks to progressive myoclonic epilepsies. Several conditions-such as GLUT1 deficiency, cerebrotendinous xanthomatosis, and folate receptor α deficiency-are treatable through dietary or pharmacological interventions. Conclusions: Recognition of myoclonus as a presenting feature of inherited errors of metabolism (IEMs) is critical for timely diagnosis and treatment. Metabolic screening should be considered in all unexplained cases of myoclonus, particularly when accompanied by developmental delay or systemic abnormalities.

Background/Objectives: Lenvatinib combined with anti-PD-1 therapy has shown promise in the treatment of hepatocellular carcinoma (HCC). The study evaluates changes in gut microbiota (GM) and metabolites during HCC treatment with lenvatinib combined with anti-PD-1. Methods: An HCC mouse model was established via diethylnitrosamine (DEN) injection, and the mice were then treated with lenvatinib, anti-PD-1, or their combination. GM composition and structural changes were assessed by 16S rDNA sequencing, and metabolite abundance by liquid chromatography-mass spectrometry (LC-MS). Results: Significant alterations in GM and metabolites were observed in the HCC group compared to the control group, and compared with the HCC group, both monotherapy and combination therapy resulted in varying degrees of GM and metabolites rebalancing. Specifically, compared to the HCC group, lenvatinib combined with anti-PD-1 therapy decreased the abundance of GM, including p_Patescibacteria, g_Lactobacillus, g_Clostridium_sensu_stricto_1, g_Eubacterium_siraeum_group, and g_Desulfovibrio, while the abundance of g_Prevotella_7 increased. Metabolite changes included increased 4-pyridoxic acid, deoxycholic acid, and taurochenodesoxycholic acid, and decreased myristic acid, oleic acid, riboflavin, and uric acid. Conclusions: HCC induces substantial alterations in the GM and metabolic profile of mice. Lenvatinib combined with anti-PD-1 treatment partially modulates these dysregulations. The relevant GM and metabolites may be associated with the efficacy of combined therapy and could serve as potential markers for further investigation.