Search Results (5,917)

Background/Objectives: Iron deficiency (ID) is a common nutritional deficiency in infancy and early childhood associated with increased risk of infection and increased likelihood of receiving antibiotic intervention. In the context of ID, antibiotics have been shown to exaggerate the growth impairments and negative impacts on metabolic health of ID itself. The objective of this research was to assess the tissue-level impact of antibiotics when provided during ID. Methods: ID was induced in piglets by withholding an iron dextran shot shortly after birth, and iron deficiency was maintained after weaning by providing an iron-deficient diet starting on postnatal day (PD) 25. Half of the ID piglets received a 3-day antibiotic course (ID + Abx) consisting of spectinomycin and gentamicin from PD34-36. The kidney, liver, skeletal muscle, and hippocampal metabolomes, as well as activity of proteins in the mTOR signaling pathway, were assessed on PD43. Results: While ID had minimal impacts on the liver, kidney, and skeletal muscle metabolomes, ID + Abx impaired energy metabolism and increased ketosis and oxidative stress in peripheral tissues. Hippocampal metabolites involved in neurotransmitter synthesis pathways were affected by ID and ID + Abx to a greater extent. Additionally, the activities of several proteins in the mTOR pathway were upregulated in the hippocampi of ID + Abx piglets compared to both ID and control piglets. Abx provided to iron-sufficient piglets had minimal effects on tissue metabolomes and did not alter the activity of proteins in the mTOR pathway. Conclusions: These results highlight that antibiotic treatment in ID alters metabolism in peripheral tissues and the developing hippocampus beyond those induced by ID alone. Considering that infants and children are develop rapidly, the combination of ID and antibiotics may have lasting impacts on neurodevelopment and cognition. Full article

Background: The bacterial wilt of tomatoes, caused by Ralstonia solanacearum, is a soil-borne plant disease that causes substantial agricultural economic losses. Various nanoparticles have been utilized as antibacterial agents to mitigate pathogenic destructiveness and improve crop yields. However, there is a lack of in-depth research on how nanoparticles affect tomato metabolite levels to regulate the bacterial wilt of tomatoes. Methods: In this study, healthy and bacterial wilt-infected tomatoes were treated with Cu-Ag nanoparticles, and a metabolomics analysis was carried out. Results: The results showed that Cu-Ag nanoparticles had a significant prevention and control effect on the bacterial wilt of tomatoes. Metabolomic analysis revealed that the nanoparticles could significantly up-regulate the expression levels of terpenol lipids, organic acids, and organic oxygen compounds in diseased tomatoes, and enhance key metabolic pathways such as amino acid metabolism, carbohydrate metabolism, secondary metabolite metabolism, and lipid metabolism. These identified metabolites and pathways could regulate plant growth and defense against pathogens. Correlation analysis between the tomato microbiome and metabolites showed that most endophytic microorganisms and rhizospheric bacteria were positively correlated with fatty acyls groups and organic oxygen compounds. Conclusions: This study reveals that Cu-Ag nanoparticles can actively regulate the bacterial wilt of tomatoes by up-regulating the levels of lipid metabolism and organic oxygen compounds, providing an important theoretical basis for the application of nanoparticles in agriculture. Full article

Background/Objectives: Levothyroxine (L-T4) replacement therapy is essential following total thyroidectomy. While liquid L-T4 formulations exhibit superior pharmacokinetic properties compared to tablets, their specific metabolic impact—particularly on insulin resistance—remains unclear. The aim of this study was to compare the short-term effects of liquid versus tablet L-T4 replacement therapy on insulin resistance indices in recently thyroidectomized women and to identify baseline predictors of metabolic response. Methods: A post hoc analysis included 130 women randomized to receive either liquid or tablet L-T4 after total thyroidectomy. Metabolic parameters—including the homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides-glucose (TyG) index, and triglycerides-to-HDL cholesterol (TG/HDL-C) ratio—were assessed at baseline and after two months. Results: Both L-T4 formulations significantly improved insulin resistance indices over two months. Liquid L-T4 induced a more pronounced reduction in HOMA-IR (treatment effect p = 0.022) and fasting insulin levels (treatment effect p = 0.017) compared to the tablet formulation. No significant between-group differences were observed for TyG index or TG/HDL-C ratio. Changes in insulin resistance markers were independent of body mass index variations and were predicted by baseline metabolic parameters including insulin, glucose, and lipid levels. Conclusions: L-T4 replacement therapy improves insulin resistance markers shortly after thyroidectomy, with the liquid formulation exerting a greater effect on hepatic insulin sensitivity. These findings support the individualized selection of L-T4 formulations to optimize both endocrine and metabolic outcomes post-thyroidectomy. Full article

Background: Irradiation-induced injury is a common fallout of radiological/nuclear accidents or therapeutic exposures to high doses of radiation at high dose rates. Currently, there are no prophylactic drugs available to mitigate radiation injury as a result of exposure to lethal doses of ionizing radiation. Gamma-tocotrienol (GT3) of vitamin E is a promising radioprotector under advanced development which has been tested for efficacy in both murine and nonhuman primate (NHP) models. Previously, we have demonstrated that GT3 has radioprotective efficacy in intestinal epithelial and crypt cells, and restores transcriptomic changes in NHPs with a supralethal dose of 12 Gy total-body irradiation (TBI). Methods: In this study, we evaluated the effect of 12 Gy partial-body irradiation (PBI) or TBI on metabolomic changes in serum samples and the extent to which GT3 was able to modulate these irradiation-induced changes. A total of 32 nonhuman primates were used for this study, and blood sample were collected 3 days (d) prior to irradiation, and 4 hours (h), 8 h, 12 h, 1 d, 2, and 6 d post-irradiation. Results: Our results demonstrate that exposure to a supralethal dose of radiation induces a complex range of metabolomic shifts with similar degrees of dysregulation in both partial- and total-body irradiated animals. The C21-steroid hormone biosynthesis and metabolism pathway was significantly dysregulated in both PBI and TBI groups, with minimal protection afforded by GT3 administration. Conclusions: GT3 offered a differential response in terms of protected metabolites and pathways in either group that was most effective at the early post-irradiation time points. Full article

Background/Objectives: Fat-free mass (FFM) loss after metabolic and bariatric surgery (MBS) is associated with adverse long-term outcomes, including osteoporosis. Identifying biomarkers that predict excessive FFM loss can improve perioperative patient management and postoperative risk stratification. This study investigated whether preoperative amino acid metabolite (AAM) levels could predict excessive FFM loss after laparoscopic sleeve gastrectomy (LSG). Methods: Forty patients with morbid obesity who underwent LSG between 2019 and 2020 were retrospectively analyzed. Based on the FFM loss to body weight loss ratio (%FFML/BWL) at 3 months postoperatively, patients were categorized into excessive (>25%) and non-excessive (≤25%) FFM loss groups. Anthropometric measurements and serum sampling were performed preoperatively and at 3, 6, and 12 months postoperatively. AAM profiles were collected before surgery. Statistical analyses, including logistic regression and receiver operating characteristic curves, were performed. Results: Twenty-five patients showed excessive FFM loss 3 months after surgery. They had significantly lower preoperative tyrosine (Tyr) levels (p = 0.025). Logistic regression revealed that higher Tyr levels were significantly associated with lower odds of being male, suggesting a potential protective effect (odds ratio (OR) =0.019, p = 0.010). Tyr profiling demonstrated acceptable predictive performance (area under the curve =0.715, p = 0.025). Despite nonsignificant p-values, trends showed lower FFM and muscle mass and higher fat mass in the excessive FFM loss group throughout follow-up. Conclusions: Preoperative Tyr profiling may help identify patients at risk for excessive FFM loss. These findings support prioritizing metabolic health alongside total weight loss in the evaluation of MBS outcomes. Full article

Objectives: Multiple myeloma and acute myeloid leukemia are severe forms of blood cancer, which lack effective therapies for treatment. In our search for new chemical lead structures from nature, we were investigating the Brazilian medicinal plant arnica-do-cerrado (Lychnophora ericoides). Methods: Repeated chromatography led to the isolation of four flavonoids and three sesquiterpenoids, which were evaluated for their cytostatic and cytotoxic properties against HL-60, MOLM-13, AMO-1, and KMS-12 PE cancer cells as well as the non-malignant HS-5 cell line. Results: Whereas the isolated flavonoids displayed only moderate activity, the three sesquiterpene lactones goyazensolide, centratherin, and lychnopholide exhibited pronounced effects against all four tested cell lines. Goyazensolide was the most effective compound, inhibiting proliferation and metabolic activity with IC₅₀ values between 1.0 and 1.6 µM, as well as 1.0 to 2.0 µM, respectively. Centratherin and lychnopholide were somewhat less active but showed higher selectivity towards malignant cell lines, which was most pronounced for MOLM-13 cells. Conclusion: The results of this study revealed interesting natural products that will be further evaluated for their potential as new lead compounds for the treatment of acute myeloid leukemia and multiple myeloma. Full article

Background: Molybdenum (Mo) is an essential trace element for animals, but too much intake can cause adverse effects. Due to the metabolic characteristics of goats and other ruminants, they are more susceptible to the cumulative effects of Mo toxicity. A high Mo intake can cause multi-organ toxicity in ruminants, but the mechanism of damage to the pancreas is still unclear. The aim of this study was to systematically analyze the key regulatory pathways of pancreatic injury induced by Mo in goats using a metabolomics approach. Methods: Twenty male Yudong Black goats (22.34 ± 1.87 kg, six months) were randomly divided into a control group (fed a basal diet) and the Mo group (fed a basal diet supplemented with 50 mg·kg⁻¹ Na₂MoO₄·2H₂O). After 60 days of continuous feeding, their pancreatic tissues were collected and the mineral elements, antioxidant capacity, and inflammatory factors were examined. Untargeted metabolomics based on HILIC UHPLC-Q-EXACTIVE MS was used to analyze changes in metabolites. The core regulatory mechanisms were revealed by KEGG enrichment analysis. Results: The results demonstrated that goats in the Mo group showed obvious clinical signs, such as lethargy, loss of appetite, and unsteady gait. The pancreatic tissue of goats in the Mo group exhibited significantly elevated levels of Mo and copper, accompanied by a marked reduction in antioxidant capacity and concurrent increases in inflammatory cytokine levels. Between the Mo group and control group, 167 differentially expressed metabolites were identified. KEGG enrichment analysis showed that it disrupted multiple metabolic pathways, including glycine, serine, and threonine metabolism, cysteine and methionine metabolism, and butanoate metabolism. Conclusions: This study mainly revealed, at the metabolomics level, that Mo exposure would disrupt the metabolic pathways related to antioxidant capacity in goat pancreata. It provides new insights into the molecular mechanisms of Mo-induced pancreatic injury in goats. Full article

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) infections remain a significant challenge in healthcare. Conventional and molecular techniques used for MRSA identification are either time-consuming or costly. Alternatively, Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) offers a rapid method for microbial identification and has the potential to detect biomarkers that distinguish methicillin resistance in S. aureus isolates. The aim of this study was to identify methicillin-resistant discriminative biomarkers for S. aureus obtained using MALDI-TOF MS. Methods: A systematic review was conducted by searching databases such as PubMed and Web of Science for studies that focused on MRSA detection with biomarkers by MALDI-TOF MS, including all relevant studies published up to July 2024. The review protocol was registered in PROSPERO registry. Results: A total of 15 studies were selected for analysis. Data were extracted on study location, sample size, MALDI-TOF MS analyzer, sample preparation, methicillin resistance and sensitivity biomarkers, and the use of Artificial Intelligence (AI) models. Notably, PSM-mec and delta toxin were frequently reported as informative biomarkers, detectable at 2414 ± 2 Da and 3006 ± 2 Da, respectively. Additionally, eight studies used AI models to identify specific biomarkers differentiating methicillin-resistant and methicillin-sensitive strains, based on differences in peak intensities or the exclusive presence of certain peaks. Moreover, two studies employed detection of MRSA in low concentrations from biological samples and others employed an optimized matrix solution for improved analysis. Conclusions: Overall, MALDI-TOF MS is not only a powerful tool for the identification of bacterial isolates but also shows strong potential for rapid, cost-effective detection of methicillin resistance in S. aureus through biomarker analysis. Given that it is already implemented in several clinical laboratories, this approach could be adopted without significant additional cost. Full article

Research and innovation in metabolomics tools to measure metabolite accumulation within plants have led to important discoveries with respect to the improvement of plant stress tolerance, development, and crop yield. Traditional metabolomics analyses have commonly utilized gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry, but these methods are often performed without regard for the spatial locations of metabolites within tissues. Methods for mass spectral imaging (MSI) have recently been developed to detect and spatially resolve metabolite accumulation and are rapidly being adopted on a wider scale. Since 2010, the number of publications incorporating mass spectral imaging has grown from approximately 80 articles to over 378 on a yearly basis, constituting an increase of at least 350% during this time frame. Spatially resolved metabolite accumulation data provides unique insights into the function and regulation of plant biochemical pathways. Mass spectral imaging is commonly paired with desorption ionization technologies, including matrix-assisted laser desorption ionization (MALDI) and desorption electrospray ionization (DESI), to generate accurate, spatially resolved metabolomics data from prepared tissue segments. Here, we describe the most recent advancements in sample preparation methods, mass spectral imaging technologies, and data processing tools that have been developed to address the limits of MSI technology. Additionally, we summarize recent applications of MSI technologies in plant metabolomics and discuss potential avenues for future research advancements within the plant biology community through the use of these technologies. Full article

Background: Type 2 diabetes mellitus (T2DM) is a major contributor to cardiovascular disease worldwide, with insulin resistance (IR) being a central pathophysiological mechanism. The triglyceride–glucose (TyG) index, derived from routine fasting measures, has emerged as a simple yet reliable proxy for IR and is increasingly recognised for its prognostic value in metabolic disorders. Despite growing interest, longitudinal evidence on TyG and incident T2DM, especially within European cohorts, remains limited and inconsistent. Therefore, we aimed to estimate the predictive role of TyG on the development of T2DM in an 8-year follow-up observation of a sample of adult men. Methods: We analysed data from 789 adult men without baseline T2DM, enrolled in the Olivetti Heart Study. Receiver operating characteristic curve analysis was used to determine the optimal TyG threshold for predicting new-onset T2DM. Results: Baseline TyG exhibited a strong, linear association with the subsequent development of T2DM. A TyG value above 4.88 was associated with an approximately twofold increase in risk, both before and after adjustment for confounding factors. Conclusions: The principal findings of this study indicate a significant predictive value of the TyG index in the development of new-onset T2DM. These observations suggest that the TyG index may serve as a low-cost, simple, and non-invasive tool for early cardio-metabolic risk assessment. Full article

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is), initially developed as antihyperglycemic agents, have emerged as multifunctional therapeutics with profound cardiorenal and metabolic benefits. Their unique insulin-independent mechanism, targeting renal glucose reabsorption, distinguishes them from conventional antidiabetic drugs. Mechanisms and Clinical Evidence: SGLT2is induce glycosuria, reduce hyperglycemia, and promote weight loss through increased caloric excretion. Beyond glycemic control, they modulate tubuloglomerular feedback, attenuate glomerular hyperfiltration, and exert systemic effects via natriuresis, ketone utilization, and anti-inflammatory pathways. Landmark trials (DAPA-HF, EMPEROR-Reduced, CREDENCE, DAPA-CKD) demonstrate robust reductions in heart failure (HF) hospitalizations, cardiovascular mortality, and chronic kidney disease (CKD) progression, irrespective of diabetes status. Adipose Tissue and Metabolic Effects: SGLT2is mitigate obesity-associated adiposopathy by shifting macrophage polarization (M1 to M2), reducing proinflammatory cytokines (TNF-α, IL-6), and enhancing adipose tissue browning (UCP1 upregulation) and mitochondrial biogenesis (via PGC-1α/PPARα). Modest weight loss (~2–4 kg) occurs, though compensatory hyperphagia may limit long-term effects. Emerging Applications: Potential roles in non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and neurodegenerative disorders are under investigation, driven by pleiotropic effects on metabolism and inflammation. Conclusions: SGLT2is represent a paradigm shift in managing T2DM, HF, and CKD, with expanding implications for metabolic syndrome. Future research should address interindividual variability, combination therapies, and non-glycemic indications to optimize their therapeutic potential. Full article

Background/Objectives: Adolescence is a critical period for the early detection of metabolic syndrome (MetS), a condition that increases the risk of cardiometabolic diseases in adulthood. Timely identification of at-risk adolescents enables targeted prevention strategies. This study aimed to analyze the discriminative capacity and accuracy of six biochemical and/or anthropometric indices related to lipid metabolism and adiposity for the early detection of MetS in a sample of Spanish adolescents. Methods: A cross-sectional study carried out according to the STROBE guidelines. A sample of 981 adolescents aged 11–16 years old were randomly recruited from schools in Southeastern Spain. The presence or absence of MetS was determined according to the International Diabetes Federation criteria. The following biochemical and/or anthropometric indices were evaluated: triglyceride glucose index, visceral adiposity index, logarithm children’s lipid accumulation product, triglyceride glucose-body mass index, triglyceride glucose-waist circumference, and triglyceride glucose-waist-to-hip ratio. Results: The triglyceride glucose-waist-to-hip ratio and triglyceride glucose-body mass index parameters were the strongest indicators associated with MetS in boys and girls, respectively, after adjusting for several factors. Moreover, all evaluated indices showed optimal AUC values, with the visceral adiposity index and triglyceride glucose-waist circumference index exhibiting the highest discriminative capacity in both genders. Conclusions: The evaluated biochemical and anthropometric indices—particularly visceral adiposity index and triglyceride-glucose-waist circumference—show promise as accessible biomarkers for identifying adolescents at metabolic risk. These indices may serve as practical tools in preventive health strategies aimed at improving metabolic health by screening adolescents at risk of MetS, thereby helping to reduce the future burden of non-communicable diseases. Full article