Metabolites

16 pages, 568 KB

Open AccessArticle

Effect of Creatinine on Various Clinical Outcomes in Patients with Severe Traumatic Brain Injury (TBI)

by Sarah Dawson-Moroz, Schneider Rancy, George Agriantonis, Kate Twelker, Navin D. Bhatia, Zahra Shafaee, Jennifer Whittington and Bharti Sharma

Metabolites 2025, 15(10), 657; https://doi.org/10.3390/metabo15100657 (registering DOI) - 4 Oct 2025

Abstract

Background: Traumatic brain injury (TBI) is a major public health concern. Creatinine (Cr) has been well studied as a marker of renal function, specifically the development of acute kidney injury (AKI) in TBI patients. We aimed to evaluate the effect of Cr on [...] Read more.

Background: Traumatic brain injury (TBI) is a major public health concern. Creatinine (Cr) has been well studied as a marker of renal function, specifically the development of acute kidney injury (AKI) in TBI patients. We aimed to evaluate the effect of Cr on various clinical outcomes in patients with severe TBI. Methods: We investigated the relationship between Cr levels at various time points and a range of clinical variables, using parametric and non-parametric statistical testing. Results: 1000 patients were included in our study. We found a significant association between sex and Cr level at intensive care unit (ICU) admission and ICU discharge. Cr was positively correlated with ISS at hospital admission, ICU admission, ICU discharge, and at death. Conversely, Cr was negatively correlated with GCS at hospital admission, ICU admission, ICU discharge, and at death. Larger decreases in Cr from Hospital to ICU admission were significantly correlated with increased vent days. Larger decreases in Cr from ICU admission to ICU discharge were significantly correlated with increased hospital length of stay (LOS), ICU LOS, and vent days, likely reflecting the degree of initial hypercreatinemia. For all patients, there were significant positive correlations between Cr at admission and ICU LOS, Cr at ICU admission and ICU LOS, and Cr at ICU admission and vent days. Conclusions: Our findings support existing literature that demonstrates a positive relationship between Cr levels, ICU LOS, and vent days amongst patients with severe TBI. These data suggest renal injury is predictive of TBI outcomes. Future research should investigate the role of renal therapeutic interventions in TBI recovery. Full article

(This article belongs to the Special Issue Proteomics and Metabolomics in Human Health and Disease)

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24 pages, 6712 KB

Open AccessArticle

Biomarkers Characterizing the Onset of Dietary-Induced Hepatocellular Injury and Visceral Obesity in a Rat Experimental Model: Possible Anti-Inflammatory Effects of Steviol Glycosides

by Krastina Trifonova, Penka Yonkova and Petko Dzhelebov

Metabolites 2025, 15(10), 656; https://doi.org/10.3390/metabo15100656 (registering DOI) - 4 Oct 2025

Abstract

Background: The aim of the present study is to compare the potential of a high-fat diet, a high-carbohydrate diet, and a high-fat, high-carbohydrate diet to induce liver injury and visceral obesity within a period of five weeks, identify the pattern and degree of [...] Read more.

Background: The aim of the present study is to compare the potential of a high-fat diet, a high-carbohydrate diet, and a high-fat, high-carbohydrate diet to induce liver injury and visceral obesity within a period of five weeks, identify the pattern and degree of hepatic changes at the tissue level, identify the earliest metabolic markers of specific liver changes induced by each type of diet, and to test the possible beneficial effects of steviol glycosides in a rat experimental model. Methods: Wistar rats (n = 56) were divided into seven groups as follows: group BD (before diet), group SD (standard diet), group HFD (high-fat diet), group HCHD (high-carbohydrate diet), group HFHCHD (high-fat high-carbohydrate diet), group SDS (standard diet supplemented with Stevia extract), and group HFDS (high-fat diet supplemented with Stevia extract). Results: Total cholesterol concentrations (2.02 ± 0.22 mmol/L) increased in the HFD group (2.56 ± 0.82 mmol/L) and in the HFDS group (2.89 ± 0.48 mmol/L). The VLDL values before diets were 0.27 ± 0.11 mmol/L and increased most significantly in the HFHCHD group—1.14 ± 0.62 mmol/L. The baseline ALT values (88.4 ± 10.6 U/L) increased in the HFD group (128.13 ± 19.5 U/L) and the HFDS group (127.00 ± 17.74 U/L). Similar increases were registered in the AST/ALT ratio and ALP. Total bilirubin (7.10 ± 1.39 μmol/L) increased in HFD group (27.86 ± 17.01 μmol/L). Serum NO had the lowest values in groups fed diets supplemented with steviol glycosides. All high-calorie diets induced hepatocellular injury. The mass of the perirenal fat depot and cross-sectional area of adipocytes were highest in HFD, HFHCHD, and HFDS groups. Conclusion: High-calorie diets have the potential to induce visceral obesity and hepatocellular injury within a very short period of time, which produces characteristic histological changes and specific biochemical profile. Steviol glycosides may alleviate some aspects of the inflammatory response, but findings about lipid profile parameters and liver enzymes are controversial. Full article

(This article belongs to the Special Issue Metabolic Changes in Diet-Mediated Inflammatory Diseases)

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18 pages, 2228 KB

Open AccessArticle

Linking Elastin in Skeletal Muscle Extracellular Matrix to Metabolic and Aerobic Function in Type 2 Diabetes: A Secondary Analysis of a Lower Leg Training Intervention

by Nicholas A. Hulett, Leslie A. Knaub, Irene E. Schauer, Judith G. Regensteiner, Rebecca L. Scalzo and Jane E. B. Reusch

Metabolites 2025, 15(10), 655; https://doi.org/10.3390/metabo15100655 - 2 Oct 2025

Abstract

Background: Type 2 diabetes (T2D) is associated with reduced cardiorespiratory fitness (CRF), a critical predictor of cardiovascular disease and all-cause mortality. CRF relies upon the coordinated action of multiple systems including the skeletal muscle where the mitochondria metabolize oxygen and substrates to sustain [...] Read more.

Background: Type 2 diabetes (T2D) is associated with reduced cardiorespiratory fitness (CRF), a critical predictor of cardiovascular disease and all-cause mortality. CRF relies upon the coordinated action of multiple systems including the skeletal muscle where the mitochondria metabolize oxygen and substrates to sustain ATP production. Yet, previous studies have shown that impairments in muscle bioenergetics in T2D are not solely due to mitochondrial deficits. This finding indicates that factors outside the mitochondria, particularly within the local tissue microenvironment, may contribute to reduced CRF. One such factor is the extracellular matrix (ECM), which plays structural and regulatory roles in metabolic processes. Despite its potential regulatory role, the contribution of ECM remodeling to metabolic impairment in T2D remains poorly understood. We hypothesize that pathological remodeling of the skeletal muscle ECM in overweight individuals with and without T2D impairs bioenergetics and insulin sensitivity, and that exercise may help to ameliorate these effects. Methods: Participants with T2D (n = 21) and overweight controls (n = 24) completed a 10-day single-leg exercise training (SLET) intervention. Muscle samples obtained before and after the intervention were analyzed for ECM components, including collagen, elastin, hyaluronic acid, dystrophin, and proteoglycans, using second harmonic generation imaging and immunohistochemistry. Results: Positive correlations were observed with elastin content and both glucose infusion rate (p = 0.0010) and CRF (0.0363). The collagen area was elevated in participants with T2D at baseline (p = 0.0443) and showed a trend toward reduction following a 10-day SLET (p = 0.0867). Collagen mass remained unchanged, suggesting differences in density. Dystrophin levels were increased with SLET (p = 0.0256). Conclusions: These findings identify that structural proteins contribute to aerobic capacity and identify elastin as an ECM component linked to insulin sensitivity and CRF. Full article

(This article belongs to the Special Issue Effects of Nutrition and Exercise on Cardiometabolic Health)

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16 pages, 1840 KB

Open AccessSystematic Review

The Impact of Intermittent Fasting on Metabolic and Hormonal Profile in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

by Iman Aolymat, Suhad Abumweis, Hafez Al-Momani, Diala Walid Abu-Hassan, Majd M. Albarakat, Ahmad Alzoubi, Mohammed Abu saleh, Ayah Khleaf Oleimat, Shaimaa Nasr Amin, Walaa Bayoumie El Gazzar, Ahmed Salem, Amin N. Olaimat, Heba A. Ali and Abd Al-Rahman Al-Shudiefat

Metabolites 2025, 15(10), 654; https://doi.org/10.3390/metabo15100654 - 2 Oct 2025

Abstract

Background: Polycystic ovarian syndrome (PCOS) is one of the most prevalent reproductive, endocrine, and metabolic disorders inflicting women of childbearing age. Dietary interventions have gained interest as non-pharmacological approach to control obesity and metabolic disturbances. However, the effects of intermittent fasting (IF) on [...] Read more.

Background: Polycystic ovarian syndrome (PCOS) is one of the most prevalent reproductive, endocrine, and metabolic disorders inflicting women of childbearing age. Dietary interventions have gained interest as non-pharmacological approach to control obesity and metabolic disturbances. However, the effects of intermittent fasting (IF) on metabolic and hormonal profiles of PCOS patients is debatable. Objectives: We performed this systematic review and meta-analysis to explore IF’s effect on PCOS women’s metabolic and hormonal profile (PROSPERO: CRD42024511520). Eligible studies included IF interventions in women with PCOS, with metabolic and hormonal profiles being reported. Methods: A systematic literature search using three databases, including PubMed, SCOPUS, and Web of Science, was conducted. The systematic review was performed following PRISMA guidelines. Results: A total of four studies were included (N = 4). IF is not associated with significant change in BMI (MD = −0.200, 95% CI [−0.807, 0.407], p = 0.518). The analysis revealed that IF had no statistically significant impact on FBG (MD = −0.569, 95% CI [−9.955, 8.818], p = 0.906), HOMA-IR (MD = −0.862, 95% CI [−1.737, 0.014], p = 0.054), and FINS (MD = −2.749, 95% CI [−6.441, 0.943], p = 0.145). No significant change in TG (MD = −3.120, 95% CI [−9.624, 3.385], p = 0.347), total cholesterol (MD = −0.918, 95% CI [−2.960, 1.124], p = 0.378), and LDL levels (MD = −0.433, 95% CI [−1.224, 0.359], p = 0.284) between IF and pre-fasting or non-intervention diet groups. However, the explanation is limited by the small number of studies, duration of fasting regimes, and/or variations in fasting strategies. Sex hormone data were collected but were insufficient for a pooled analysis. Conclusions: Overall, our study suggests that IF is not an effective intervention to enhance BMI, glycaemic control, and lipid metabolism in PCOS patients. Nevertheless, the current conclusion is inconclusive and preliminary, as additional well-designed studies are required to support this conclusion. Full article

(This article belongs to the Special Issue Advancements in Reproductive Medicine: Unlocking the Secrets of the Ovary and Sperm for Fertility and Beyond)

28 pages, 2613 KB

Open AccessReview

Personalized Nutrition in Pediatric Chronic Diseases

by Marlene Escobedo-Monge, Robert H. Lustig, Sergey Suchkov, Sofia Blokh, Natalya Andronova, Olga Goryacheva, Marina Borisovna Moyseyak, Timur Vlasov, Arturo Solís Herrera, Veronika Polyakova, Elena Antonova and Aleksandr Tuykavin

Metabolites 2025, 15(10), 653; https://doi.org/10.3390/metabo15100653 - 30 Sep 2025

Abstract

This narrative review examines the application of personalized nutrition (PN) through multi-OMICS and trans-OMICS in pediatric populations, particularly in relation to chronic conditions such as obesity, type 2 diabetes, and celiac disease. We synthesize evidence to identify biomarkers and gene–environment interactions and translate [...] Read more.

This narrative review examines the application of personalized nutrition (PN) through multi-OMICS and trans-OMICS in pediatric populations, particularly in relation to chronic conditions such as obesity, type 2 diabetes, and celiac disease. We synthesize evidence to identify biomarkers and gene–environment interactions and translate molecular insights into individualized dietary guidance. Even though PN represents a promising strategy for optimizing child health, significant challenges remain in translating molecular findings into practical, cost-effective, and equitable interventions. We advocate integrating this knowledge into clinical practice and developing policies and standardized methodologies that ensure accessibility for all pediatric populations. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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16 pages, 1526 KB

Open AccessArticle

Metabolic Characteristics of PGPR-Induced Growth Promotion in Alfalfa (Medicago sativa L.)

by Rina Dao, Ying Zhang, Qiang Li and Shengyan Lei

Metabolites 2025, 15(10), 652; https://doi.org/10.3390/metabo15100652 - 30 Sep 2025

Abstract

Background/Objectives: Plant growth-promoting rhizobacteria (PGPR) have demonstrated potential for enhancing plant growth; existing research inadequately characterizes the metabolic underpinnings of PGPR-induced plant phenotypes. Methods: A deeper investigation into the impact of PGPR on plant metabolic pathways is crucial for a comprehensive [...] Read more.

Background/Objectives: Plant growth-promoting rhizobacteria (PGPR) have demonstrated potential for enhancing plant growth; existing research inadequately characterizes the metabolic underpinnings of PGPR-induced plant phenotypes. Methods: A deeper investigation into the impact of PGPR on plant metabolic pathways is crucial for a comprehensive understanding of their growth-promoting mechanisms and for the development of more effective biofertilizers and plant protection strategies. Results: To clarify the core metabolic pathways targeted by PGPR strains, we selected alfalfa as the research object, employed two Pseudomonas combinations, and utilized a broad-targeted metabolomics approach to investigate the metabolic characteristics of alfalfa roots. Through the analysis of primary and secondary metabolites, a total of 2694 metabolites were identified, among which lipids were the main nutrients during the growth of alfalfa. The L-citrulline and L-arginine contents were significantly upregulated, thereby affecting nitrogen metabolism and ultimately promoting plant growth. In addition, different branches of the isoflavonoid biosynthesis pathway showed differential regulation, indicating their close relationship with plant growth promotion. Conclusions: This study provides a new perspective for a deeper understanding of the molecular mechanisms by which PGPR promotes plant growth and lays a theoretical foundation for the future development of PGPR-based agricultural biological agents. Full article

(This article belongs to the Section Plant Metabolism)

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11 pages, 1199 KB

Open AccessArticle

Metabolic Determinants of Systemic Inflammation Dynamics During Hemodialysis: Insights from the Systemic Immune–Inflammation Index in a Single-Center Observational Study

by Martina Mancinelli, Federica Moscucci, Vincenza Cofini, Anna Luisa De Nino, Raffaella Bocale, Carmine Savoia, Francesco Baratta and Giovambattista Desideri

Metabolites 2025, 15(10), 651; https://doi.org/10.3390/metabo15100651 - 30 Sep 2025

Abstract

Background/Objective: Systemic inflammation is a hallmark of end-stage renal disease (ESRD) and contributes to the high burden of cardiovascular morbidity and mortality in hemodialysis (HD) patients. The systemic immune–inflammation index (SII), derived from peripheral neutrophil, lymphocyte, and platelet counts, has emerged as a [...] Read more.

Background/Objective: Systemic inflammation is a hallmark of end-stage renal disease (ESRD) and contributes to the high burden of cardiovascular morbidity and mortality in hemodialysis (HD) patients. The systemic immune–inflammation index (SII), derived from peripheral neutrophil, lymphocyte, and platelet counts, has emerged as a promising biomarker of immune–inflammatory status. This study aimed to assess the acute effect of a single HD session on systemic inflammation and to identify metabolic predictors associated with this response. Methods: In this single-center observational before–after study, 44 chronic HD patients were enrolled. Blood samples were collected immediately before and after a single HD session. SII was calculated as platelet count × neutrophil count/lymphocyte count. Subgroup analyses were conducted based on renal disease etiology and diabetic status. Multivariable linear regression models identified baseline predictors of SII variation. Results: Median SII significantly decreased post-HD in the overall cohort (from 553.4 [342.6–847.5] to 449.1 [342.6–866.6], p = 0.001), with a more pronounced reduction in patients with cardiometabolic etiologies (from 643.4 [353.3–1360.0] to 539.1 [324.8–1083.4], p = 0.007) and diabetes (from 671.1 [408.7–1469.1] to 458.3 [285.7–1184.4], p = 0.028), but not in those with nephroangiosclerosis (p = 0.182). Baseline total cholesterol (p = 0.001) and gamma-glutamyl transferase (p = 0.034) were positively associated with smaller reductions in SII, while higher baseline glycaemia predicted a greater decrease in post-dialysis SII (p = 0.021). Conclusions: HD acutely modulates systemic inflammation, as reflected by reduction in SII. The magnitude of this response is significantly influenced by individual metabolic profiles. These findings highlight the relevance of metabolic–immune crosstalk in ESRD and suggest that SII may serve as a dynamic biomarker integrating inflammatory and metabolic signals, deserving further validation in larger, outcome-driven studies. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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20 pages, 3179 KB

Open AccessArticle

Development of LC-MS/MS Database Based on 250 Potentially Highly Neuroactive Compounds and Their Metabolites

by Taylor Teitelbaum, Haoduo Zhao, Lauren E. Koval, Yun-Chung Hsiao, Chih-Wei Liu, Julia E. Rager, Stephanie M. Engel and Kun Lu

Metabolites 2025, 15(10), 650; https://doi.org/10.3390/metabo15100650 - 30 Sep 2025

Abstract

Background: Environmental chemicals are hypothesized to contribute to the development of neurodevelopmental disorders; however, only a fraction of the thousands of chemicals in common commercial use have validated assays. We recently developed the Environmental NeuRoactIve Chemicals (ENRICH) list of 250 chemicals prioritized for [...] Read more.

Background: Environmental chemicals are hypothesized to contribute to the development of neurodevelopmental disorders; however, only a fraction of the thousands of chemicals in common commercial use have validated assays. We recently developed the Environmental NeuRoactIve Chemicals (ENRICH) list of 250 chemicals prioritized for further testing due to their high likelihood of neuroactivity and human exposure, as derived through analysis across eight neuroactivity, exposure, and detection databases. Measuring some of these compounds in human biological media remains challenging due to the lack of information regarding their metabolites and detection frequencies. Methods: We created an LC-MS/MS database based on the targets in the ENRICH list using S9 human liver fractions to metabolize compounds individually and in groups into newly and previously discovered phase I metabolites. Results: The final database consisted of 274 compounds with 94 parent compounds and 182 metabolites being featured. A total of 55 novel metabolites were discovered. The confidence of the compounds, which were annotated correctly within the database, was high, increasing the odds of positive identifications within future exposomic work. The confidence of the annotations fell between the levels 1–3, with levels one and two consisting of 87% of the database. Conclusions: The creation of this database creates the opportunity for future biological studies centered around the impact these compounds and their metabolites have on the brain and for a better understanding of neurodevelopmental disorders and their origins. Full article

(This article belongs to the Special Issue Advancing Metabolic/Microbial Biomarker Applications in Disease Prevention, Diagnosis and Public Health)

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25 pages, 755 KB

Open AccessReview

The Role of Omentin in Gastrointestinal Cancer: Diagnostic, Prognostic, and Therapeutic Perspectives

by Adam Mylonakis, Maximos Frountzas, Irene Lidoriki, Alexandros Kozadinos, Maria Evangelia Koloutsou, Angeliki Margoni, Areti Kalfoutzou, Dimitrios Theodorou, Konstantinos G. Toutouzas and Dimitrios Schizas

Metabolites 2025, 15(10), 649; https://doi.org/10.3390/metabo15100649 - 30 Sep 2025

Abstract

Background/Objectives: Omentin, also known as intelectin-1, is a secreted adipokine with anti-inflammatory, insulin-sensitizing, and immune-modulatory functions, primarily expressed in visceral adipose tissue. While omentin has been associated with favorable metabolic outcomes, its role in cancer pathogenesis appears context-dependent and remains poorly understood. [...] Read more.

Background/Objectives: Omentin, also known as intelectin-1, is a secreted adipokine with anti-inflammatory, insulin-sensitizing, and immune-modulatory functions, primarily expressed in visceral adipose tissue. While omentin has been associated with favorable metabolic outcomes, its role in cancer pathogenesis appears context-dependent and remains poorly understood. This review investigates the biological functions, expression patterns, and clinical relevance of omentin across gastrointestinal malignancies. Methods: A comprehensive review of the literature was conducted using PubMed, Scopus, and Web of Science up to August 2025 to evaluate the role of omentin in gastrointestinal cancers. Both preclinical and clinical studies evaluating omentin, its analogues and omentin-enhancing agents in gastric, colorectal, hepatic, pancreatic, and esophageal cancers were included. Results: Omentin exhibits anti-proliferative, anti-inflammatory, and anti-angiogenic effects within the tumor microenvironment in several GI malignancies. However, evidence also indicates a dual role. High intratumoral omentin expression correlates with improved prognosis in colorectal, gastric, and hepatic cancers; in contrast, elevated circulating levels–particularly in colorectal and pancreatic cancers–have been paradoxically associated with increased cancer risk and poor outcomes. Mechanistically, omentin modulates PI3K/Akt, NF-κB, AMPK, and oxidative stress pathways, and interacts with TMEM207. However, most available studies are small-scale and heterogeneous, with methodological inconsistencies and limited multi-omics integration, leaving major knowledge gaps. Conclusions: This review highlights omentin’s distinct systemic and local roles across GI cancers, underscoring its translational implications. Omentin emerges as a promising but context-dependent biomarker and therapeutic target, with future research needed to address heterogeneity, standardize assays, and validate its clinical utility in large-scale prospective studies. Full article

(This article belongs to the Special Issue Metabolic Biomarkers and Nutrition in Degenerative Conditions and Gastrointestinal Cancer Surgery: 2nd Edition)

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18 pages, 2427 KB

Open AccessArticle

Integrated Transcriptomic and Metabolomic Insights into Flavor-Related Metabolism in Grape Berries Across Cultivars and Developmental Stages

by Liping Huang, Linan Zhang, Min Wang, Yue Zhu, Zhili Xun, Xi Dai and Qifeng Zhao

Metabolites 2025, 15(10), 648; https://doi.org/10.3390/metabo15100648 - 29 Sep 2025

Abstract

Background: Flavor quality in grape berries is shaped by complex metabolic and regulatory networks during development. Methods: In this study, we integrated transcriptomic and LC–MS-based metabolomic analyses to investigate three cultivars (‘Mei Xiangbao’, ‘Adena Rose’, and ‘Kyoho’) at two ripening stages. Results: A [...] Read more.

Background: Flavor quality in grape berries is shaped by complex metabolic and regulatory networks during development. Methods: In this study, we integrated transcriptomic and LC–MS-based metabolomic analyses to investigate three cultivars (‘Mei Xiangbao’, ‘Adena Rose’, and ‘Kyoho’) at two ripening stages. Results: A total of 491 differentially accumulated metabolites (DAMs) were identified, mainly lipids, organic acids, and heterocyclic compounds. Among them, 33 core metabolites, including LysoPCs, malic acid, and linalool derivatives, were closely linked to aroma, membrane remodeling, and polyphenol biosynthesis. Transcriptome integration revealed 29 transcription factors (TFs) such as AP2/ERF, MYB, and bHLH, which showed strong associations with key metabolites, suggesting their involvement in lipid remodeling and phenylpropanoid-related pathways. Conclusions: These results provide new insights into the molecular regulation of grape flavor metabolism and highlight candidate genes and metabolites for improving berry sensory quality. Full article

(This article belongs to the Section Plant Metabolism)

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17 pages, 4907 KB

Open AccessArticle

Uncovering Anticancer Mechanisms of Spiramycin Derivatives Using Transcriptomic and Metabolomic Analyses

by Renyu Yang, Wuxiyar Otkur, Tingze Feng, Yirong Li, Shaojun Pei, Huan Qi, Yaopeng Zhao, Yao Lu and Hailong Piao

Metabolites 2025, 15(10), 647; https://doi.org/10.3390/metabo15100647 - 27 Sep 2025

Abstract

Background: Carrimycin is a mixture of spiramycin derivatives with antibacterial functions. However, recent studies have shown that it possesses certain anticancer properties. The specific mechanism of the anticancer activity is unknown. Methods: To study the anticancer mechanism of carrimycin, we synthesized [...] Read more.

Background: Carrimycin is a mixture of spiramycin derivatives with antibacterial functions. However, recent studies have shown that it possesses certain anticancer properties. The specific mechanism of the anticancer activity is unknown. Methods: To study the anticancer mechanism of carrimycin, we synthesized a derivative of spiramycin, n-hexyl spiramycin (h-SPM), and used a combination of metabolomics and transcriptomics methods. Capillary electrophoresis–mass spectrometry (CE-MS) was used to detect polar small molecule metabolites, and liquid chromatography–mass spectrometry (LC-MS) was used to detect lipid metabolites in cells. Transcriptomics was used to measure mRNA content in cells. Finally, by processing these data using specific bioinformatics methods, the mechanism underlying anticancer effect of carrimycin was determined. Results: Metabolomics and transcriptomic results showed that lipid metabolism and mitochondrial biogenesis pathways in the cells changed after hSPM treatment, NR1D1 genes and ceramide were enriched from these pathways, implicating the involvement of ROS and pro-inflammatory response. Western blotting verified that the protein levels of NR1D1 decreased after h-SPM treatment, and ROS stating and qPCR demonstrated that ROS levels and the mRNA levels of pro-inflammatory genes were greatly induced by h-SPM. Conclusions: h-SPM reduced the protein level of NR1D1, disrupted metabolic regulation, accumulating ceramide, and the subsequent increased ROS generation promoted apoptosis and pro-inflammatory-like response of cells. Our findings unveiled the anticancer mechanism of a potent anticancer derivative of spiramycin and unveiled its mechanism of action. Full article

(This article belongs to the Special Issue Cell Death and Cancer Metabolism)

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3 pages, 128 KB

Open AccessEditorial

Effects of Environmental Exposure on Host and Microbial Metabolism

by Bei Gao and Pengcheng Tu

Metabolites 2025, 15(10), 646; https://doi.org/10.3390/metabo15100646 - 26 Sep 2025

Abstract

Trillions of microorganisms are living in our gastrointestinal tract, known as the gut microbiota, which plays an essential role in human health and disease [...] Full article

(This article belongs to the Special Issue Effects of Environmental Exposure on Host and Microbial Metabolism)

36 pages, 1562 KB

Open AccessReview

Targeting Metabolic Dysregulation in Obesity and Metabolic Syndrome: The Emerging Role of N-Acetylcysteine

by Dorota Magdalena Radomska-Leśniewska, Justyna Niderla-Bielińska, Marek Kujawa and Ewa Jankowska-Steifer

Metabolites 2025, 15(10), 645; https://doi.org/10.3390/metabo15100645 - 26 Sep 2025

Abstract

Obesity and metabolic syndrome (MetS), growing global health concerns, are closely linked to the development of insulin resistance, type 2 diabetes, steatotic liver disease, and cardiovascular diseases (CVDs). An increase in visceral adipose tissue, the main symptom of MetS, contributes to systemic metabolic [...] Read more.

Obesity and metabolic syndrome (MetS), growing global health concerns, are closely linked to the development of insulin resistance, type 2 diabetes, steatotic liver disease, and cardiovascular diseases (CVDs). An increase in visceral adipose tissue, the main symptom of MetS, contributes to systemic metabolic dysfunction, resulting in disturbances in glucose and lipid metabolism, mitochondrial dysfunction, and redox imbalance, which creates a vicious cycle of inflammation and oxidative stress, accelerating comorbidities. N-acetylcysteine (NAC), a precursor to glutathione, with antioxidant and anti-inflammatory properties, is described as a potent metabolic modulator that restores metabolic homeostasis. NAC’s ability to modulate oxidative stress and inflammation may be particularly valuable in preventing or mitigating cardiovascular complications of MetS. The aim of this narrative review is to summarize current evidence from cellular, animal, and human studies on NAC’s impact on metabolic health. MetS affects nearly one-third of the global population; therefore, there is a pressing need for accessible therapeutic strategies. NAC appears to offer potential benefits as an adjunctive agent for individuals with metabolic disturbances, but further research is needed to confirm its efficacy and establish its role in clinical practice. Full article

(This article belongs to the Special Issue Metabolic Modulators in Cardiovascular Disease Management)

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12 pages, 270 KB

Open AccessArticle

Association of Systemic Inflammation with Inflammatory mRNA Expression in Visceral Adipose Tissue in Gestational Diabetes

by Renata Saucedo, María Isabel Peña-Cano, Mary Flor Díaz-Velázquez, Alejandra Contreras-Ramos, Miranda Moleres-Orduña, Debbie López-Sánchez, Jorge Valencia-Ortega and Javier Pérez-Duran

Metabolites 2025, 15(10), 644; https://doi.org/10.3390/metabo15100644 - 26 Sep 2025

Abstract

Background/Objectives: Gestational diabetes mellitus (GDM) is characterized by a systemic inflammatory response and the expression of inflammatory factors in visceral adipose tissue (VAT). However, the association between these two inflammatory processes has not been fully elucidated. Therefore, this study aimed to (1) [...] Read more.

Background/Objectives: Gestational diabetes mellitus (GDM) is characterized by a systemic inflammatory response and the expression of inflammatory factors in visceral adipose tissue (VAT). However, the association between these two inflammatory processes has not been fully elucidated. Therefore, this study aimed to (1) investigate whether whole blood counts, the neutrophil–lymphocyte ratio (NLR), the monocyte–lymphocyte ratio (MLR), serum adiponectin levels, and the mRNA expression of inflammatory genes (TLR2, TLR4, pro-inflammatory cytokines: IL-1β, IL-6, and TNF-α, anti-inflammatory cytokines: IL-1RA, IL-10, and adiponectin) in VAT are altered in women with GDM in comparison to pregnant women with normal glucose tolerance (NGT), and (2) determine the correlations between systemic and local VAT inflammation in all, GDM, and NGT women. Methods: Study of 50 GDM and 50 women with NGT with a cross-sectional design. Standard biochemical and hematological tests were conducted and relative mRNA expression in VAT was measured by RT-qPCR. Results: Women with GDM showed higher neutrophil, monocyte, NLR, MLR, and VAT TNF-α/IL-10 mRNA expression ratios while lymphocyte and eosinophil counts, serum adiponectin, and mRNA local VAT inflammatory markers such as TLR2, TLR4, IL-1β, IL-6, IL-1RA, and IL-10 were lower in women with GDM relative to women with NGT. Additionally, the circulating monocyte count were associated with TLR2 and TLR-4 VAT mRNA expression levels and eosinophils count were associated with IL-1β, IL-6, IL-10, and IL-1RA VAT expression levels in women with GDM. Conclusions: GDM is characterized by systemic inflammation, and some circulating immune cells, such as monocytes and eosinophils, are associated with the expression of inflammatory markers in VAT. Full article

(This article belongs to the Special Issue Exploring Pathological Mechanisms in Obesity, Diabetes, and Metabolic Syndrome)

20 pages, 769 KB

Open AccessArticle

Phenolic Compounds from Hypericum cerastoides (Spach) N. Robson: Dereplication via UHPLC-HRMS/MS, Isolation, Identification, and Preliminary Biological Evaluation Focusing on Radical-Scavenging, Anti-α-Glucosidase, and Pro-Lipase Activities

by Zlatina Kokanova-Nedialkova, Yana Ilieva, Teodor Marinov and Paraskev T. Nedialkov

Metabolites 2025, 15(10), 643; https://doi.org/10.3390/metabo15100643 - 25 Sep 2025

Abstract

Background/Objectives: Hypericum cerastoides (Spach) N. Robson is a lesser-known species with potential pharmacological importance. This study aimed to profile phenolic compounds in its aerial parts and assess biological activities of isolated constituents, focusing on radical-scavenging, anti-α-glucosidase, and pro-lipase effects. Methods: Phenolic compounds [...] Read more.

Background/Objectives: Hypericum cerastoides (Spach) N. Robson is a lesser-known species with potential pharmacological importance. This study aimed to profile phenolic compounds in its aerial parts and assess biological activities of isolated constituents, focusing on radical-scavenging, anti-α-glucosidase, and pro-lipase effects. Methods: Phenolic compounds from H. cerastoides aerial parts were dereplicated via UHPLC-HRMS/MS. The structures of isolated compounds were determined using spectroscopic methods (1D and 2D NMR, UV, and HRMS-ESI). Radical-scavenging was evaluated by DPPH and ABTS assays; anti-α-glucosidase and pro-lipase activities were measured by LC-MS. Results: UHPLC-HRMS profiling of a hydroalcoholic extract tentatively identified and quantified 39 phenolic compounds, mainly flavonoids and hydroxycinnamic acid derivatives. Furthermore, two new phenolic compounds, namely hypercerastoside A (HC4) and hypercerastoside B (HC6), together with three known compounds, coumaroylquinic acid (HC1), myricetin-3-O-glycoside (HC2), and myricetin-3-O-galactoside (HC3), as well as two artifacts, namely methyl ester of chlorogenic acid (HC5) and hypercerastoside C (HC7), were isolated from the ethylacetate extract of the aerial parts of title plant. Compounds HC2, HC3, and HC5 displayed the highest radical-scavenging activity. The anti-α-glucosidase test showed that compounds HC1 (IC₅₀ = 44 µM) and HC3 (IC₅₀ = 206 µM) possessed similar activity to acarbose (IC₅₀ = 206 µM). Myricetin glycosides HC2 and HC3 enhanced lipase activity fivefold at 200 µM. Conclusions: H. cerastoides is a promising source of bioactive phenolic compounds with significant radical-scavenging and enzyme-modulating activities. These preliminary findings support further exploration of its therapeutic potential, especially for oxidative stress-related disorders, type 2 diabetes, and cachexia. Full article

(This article belongs to the Special Issue Bioactive Plant Extracts: Phytochemical Characterization, Isolation and Biological Evaluation)

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22 pages, 3716 KB

Open AccessArticle

Precision Probiotics Regulate Blood Glucose, Cholesterol, Body Fat Percentage, and Weight Under Eight-Week High-Fat Diet

by Jinhua Chi, Jeffrey S. Patterson, Lingjun Li, Nicole Lalime, Daniella Hawley, Kyle Joohyung Kim, Li Liu, Julia Yue Cui, Dorothy D. Sears, Paniz Jasbi and Haiwei Gu

Metabolites 2025, 15(10), 642; https://doi.org/10.3390/metabo15100642 - 25 Sep 2025

Abstract

Background/Objectives: Poor glycemic control is reaching an epidemic prevalence globally. It is associated with significantly morbid health concerns including retinopathy, neuropathy, nephropathy, cancer, and cardiovascular disease. Probiotics have shown promise in reducing health complications associated with poor blood glucose control. We tested [...] Read more.

Background/Objectives: Poor glycemic control is reaching an epidemic prevalence globally. It is associated with significantly morbid health concerns including retinopathy, neuropathy, nephropathy, cancer, and cardiovascular disease. Probiotics have shown promise in reducing health complications associated with poor blood glucose control. We tested a novel approach to designing a precision probiotic cocktail for improving blood glucose homeostasis. Methods: We tested the in vitro glucose consumption rate of twelve mouse microbiome bacterial strains and selected three with the greatest glucose consumption for the probiotic cocktail. The in vivo metabolic impact of ingesting the selected probiotic cocktail was evaluated in twelve C57BL/6J male mice fed a high-fat diet for eight weeks. Results: Compared to a control group, the probiotic group (L. rhamnosus, L. reuteri, and L. salivarius) exhibited significantly lower blood glucose levels, body weight, and body fat percentage. Moreover, the probiotic cocktail also demonstrated the ability to reduce serum insulin, total cholesterol, very-low-density lipoprotein/low-density lipoprotein cholesterol, and total cholesterol to high-density lipoprotein ratio. For further mechanistic investigation, untargeted metabolomics analyses uncovered overall downregulations in energy substrates and producing pathways like gluconeogenesis, acylcarnitine synthesis, glycolysis, the mitochondrial electron transport chain, the TCA cycle, and the building blocks for ATP formation. Partial least squares-discriminant analyses also confirmed clear group differences in metabolic activity. 16S rRNA sequencing from extracted gut microbiota also showed significant increases in Faith’s phylogenetic diversity, Lachnospiraceae bacterium 609-strain, and the genus Muribaculaceae as well as group β-diversity differences after probiotic intake. Conclusions: As such, we successfully developed a blend of three probiotics to effectively reduce blood glucose levels in male mice, which could further mitigate adverse health effects in the host. Full article

(This article belongs to the Special Issue Role of Nutraceuticals in Metabolic Disorders: Mechanisms and Benefits)

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13 pages, 1004 KB

Open AccessArticle

Matched Metabolic Stress Preserves Myokine Responses Regardless of Mechanical Load: A Randomized, Controlled Crossover Trial

by Yuji Maki, Hiroo Matsuse, Ryuki Hashida, Norika Matsukuma, Hiroshi Tajima, Eriko Baba, Yuji Kaneyuki, Sohei Iwanaga, Masayuki Omoto, Yoshio Takano, Matsuo Shigeaki, Takeshi Nago and Koji Hiraoka

Metabolites 2025, 15(10), 641; https://doi.org/10.3390/metabo15100641 - 25 Sep 2025

Abstract

Background/Objectives: Skeletal muscle functions as an endocrine organ by secreting myokines in response to exercise, with interleukin-6 (IL-6) recognized as a representative intensity-dependent biomarker that rapidly increases immediately after exercise and is strongly dependent on exercise intensity. However, it is unclear how [...] Read more.

Background/Objectives: Skeletal muscle functions as an endocrine organ by secreting myokines in response to exercise, with interleukin-6 (IL-6) recognized as a representative intensity-dependent biomarker that rapidly increases immediately after exercise and is strongly dependent on exercise intensity. However, it is unclear how changes in mechanical stress affect the response of myokines after exercise. This randomized crossover study aimed to investigate the effect of mechanical stress on acute myokine secretion during matched metabolic exercise under different mechanical stress. Methods: Ten healthy adult males performed 30 min of cycling at 60% of peak

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O₂ in both semi-recumbent position and side-lying positions. Blood samples were collected before, immediately after, and at 30 and 60 min post-exercise to evaluate IL-6, brain-derived neurotrophic factor (BDNF), and lactate. Results: BDNF and lactate levels peaked immediately after exercise, and IL-6 reached its peak at 30 min post-exercise in both the semi-recumbent position and side-lying positions. All markers showed significant elevations in response to exercise. However, no significant differences were found between the two postures in any of the measured variables. Conclusions: These findings suggest that reduced mechanical load does not impair endocrine responses when the intensity of metabolic stress is maintained. This study provides scientific evidence that, regardless of posture or environment, sufficient exercise intensity can induce adequate IL-6 and BDNF secretion, through which the beneficial effects of exercise may be expected. Full article

(This article belongs to the Special Issue Muscle Metabolic Response and Adaptation to Exercise, Diet, and Environment: 2nd Edition)

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12 pages, 1928 KB

Open AccessArticle

Chemometric Discrimination of Korean and Chinese Kimchi Using Untargeted Metabolomics

by Quynh-An Nguyen, Dong-Shin Kim, Hyo-Dong Kim, Kyu-Bin Kim, Kyung-Sik Ham, Yonghoon Lee and Hyun-Jin Kim

Metabolites 2025, 15(10), 640; https://doi.org/10.3390/metabo15100640 - 25 Sep 2025

Abstract

Background/Objectives: Kimchi has gained global recognition for its unique taste and health benefits, but its quality is totally different according to its geographical origin of materials and production methods. Methods: In this study, differences between Korean (53 samples) and Chinese kimchi (72 samples) [...] Read more.

Background/Objectives: Kimchi has gained global recognition for its unique taste and health benefits, but its quality is totally different according to its geographical origin of materials and production methods. Methods: In this study, differences between Korean (53 samples) and Chinese kimchi (72 samples) were investigated through comprehensive metabolomic analysis using gas chromatography–mass spectrometry (GC-MS) and ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF MS). Results: Multivariate statistical analyses revealed a clear separation between the two groups. Thirty-four metabolites contributing to the separation were identified. Korean kimchi was enriched in sucrose, quinic acid, sinapic acid derivatives, rutin, capsicosin, and capsianoside, while Chinese kimchi contained higher levels of trihydroxy octadecenoic acid, 2-hydroxypalmitic acid, pinellic acid, maltose, glucuronic acid, and corchorifatty acid F. In particular, the univariate Bayesianlogistic regression analysis revealed that among these metabolites, rutin, capsicosin derivatives, and sinapic acid derivatives showed strong potential as origin-discriminant markers of kimchi, providing insights into how these metabolites influence its nutritional and sensory properties. Conclusions: These compositional differences may be attributed to variations in raw materials and production methods of kimchi. Full article

(This article belongs to the Section Food Metabolomics)

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11 pages, 255 KB

Open AccessReview

Vitamin D Metabolism and the Risk of Renal Stones: A Focus on PHPT

by Elena Castellano and Federica Saponaro

Metabolites 2025, 15(10), 639; https://doi.org/10.3390/metabo15100639 - 24 Sep 2025

Abstract

Primary hyperparathyroidism is nowadays a common endocrine disorder. Over time, the clinical manifestation has shifted from symptomatic cases to mostly asymptomatic diagnoses. Despite this, nephrolithiasis remains significant, often presenting as bilateral and recurrent, with the literature reporting prevalence rates of up to 40%. [...] Read more.

Primary hyperparathyroidism is nowadays a common endocrine disorder. Over time, the clinical manifestation has shifted from symptomatic cases to mostly asymptomatic diagnoses. Despite this, nephrolithiasis remains significant, often presenting as bilateral and recurrent, with the literature reporting prevalence rates of up to 40%. The nephrolithiasis pathogenesis in PHPT is multifactorial and not fully understood. While elevated PTH increases urinary calcium load, additional urinary abnormalities and demographic factors, including age and sex, influence the risk. Vitamin D status has also been explored as a possible contributor to stone formation both in the general population and in PHPT patients. The relationship between serum 25OHD levels and nephrolithiasis remains unclear, and the impact of vitamin D supplementation on stone risk in PHPT is still under investigation. The relationship between vitamin D status, supplementation and renal stones in PHPT is explored in the present review. Full article

(This article belongs to the Special Issue Primary Hyperparathyroidism: Mechanisms and Treatment)

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