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Search Results (762)

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Keywords = metabolomics aging

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21 pages, 668 KiB  
Review
Diabetes and Sarcopenia: Metabolomic Signature of Pathogenic Pathways and Targeted Therapies
by Anamaria Andreea Danciu, Cornelia Bala, Georgeta Inceu, Camelia Larisa Vonica, Adriana Rusu, Gabriela Roman and Dana Mihaela Ciobanu
Int. J. Mol. Sci. 2025, 26(15), 7574; https://doi.org/10.3390/ijms26157574 (registering DOI) - 5 Aug 2025
Abstract
Diabetes mellites (DM) is a chronic disease with increasing prevalence worldwide and multiple health implications. Among them, sarcopenia is a metabolic disorder characterized by loss of muscle mass and function. The two age-related diseases, DM and sarcopenia, share underlying pathophysiological pathways. This narrative [...] Read more.
Diabetes mellites (DM) is a chronic disease with increasing prevalence worldwide and multiple health implications. Among them, sarcopenia is a metabolic disorder characterized by loss of muscle mass and function. The two age-related diseases, DM and sarcopenia, share underlying pathophysiological pathways. This narrative literature review aims to provide an overview of the existing evidence on metabolomic studies evaluating DM associated with sarcopenia. Advancements in targeted and untargeted metabolomics techniques could provide better insight into the pathogenesis of sarcopenia in DM and describe their entangled and fluctuating interrelationship. Recent evidence showed that sarcopenia in DM induced significant changes in protein, lipid, carbohydrate, and in energy metabolisms in humans, animal models of DM, and cell cultures. Newer metabolites were reported, known metabolites were also found significantly modified, while few amino acids and lipids displayed a dual behavior. In addition, several therapeutic approaches proved to be promising interventions for slowing the progression of sarcopenia in DM, including physical activity, newer antihyperglycemic classes, D-pinitol, and genetic USP21 ablation, although none of them were yet validated for clinical use. Conversely, ceramides had a negative impact. Further research is needed to confirm the utility of these findings and to provide potential metabolomic biomarkers that might be relevant for the pathogenesis and treatment of sarcopenia in DM. Full article
13 pages, 688 KiB  
Article
Metabolomic Patterns at Birth of Preterm Newborns with Extrauterine Growth Restriction: Towards Putative Markers of Nutritional Status
by Marta Meneghelli, Giovanna Verlato, Matteo Stocchero, Anna Righetto, Elena Priante, Lorenzo Zanetto, Paola Pirillo, Giuseppe Giordano and Eugenio Baraldi
Metabolites 2025, 15(8), 518; https://doi.org/10.3390/metabo15080518 - 1 Aug 2025
Viewed by 162
Abstract
Background: Nutrition is of paramount importance during early development, since suboptimal growth in this period of life is linked to adverse long- and mid-term outcomes. This is particularly relevant for preterm infants, who fail to thrive during the first weeks of life and [...] Read more.
Background: Nutrition is of paramount importance during early development, since suboptimal growth in this period of life is linked to adverse long- and mid-term outcomes. This is particularly relevant for preterm infants, who fail to thrive during the first weeks of life and develop extrauterine growth restriction (EUGR). This group of premature babies represents an interesting population to investigate using a metabolomic approach to optimize nutritional intake. Aims: To analyse and compare the urinary metabolomic pattern at birth of preterm infants with and without growth restriction at 36 weeks of postmenstrual age or at discharge, searching for putative markers of growth failure. Methods: We enrolled preterm infants between 23 and 32 weeks of gestational age (GA) and/or with a birth weight <1500 g, admitted to the Neonatal Intensive Care Unit (NICU) at the Department of Women’s and Children’s Health of Padova University Hospital. We collected urinary samples within 48 h of life and performed untargeted metabolomic analysis using mass spectrometry. Results: Sixteen EUGR infants were matched with sixteen non-EUGR controls. The EUGR group showed lower levels of L-cystathionine, kynurenic acid, L-carnosine, N-acetylglutamine, xanthurenic acid, aspartylglucosamine, DL5-hydroxylysine-hydrocloride, homocitrulline, and L-aminoadipic acid, suggesting a lower anti-inflammatory and antioxidant status with respect to the non-EUGR group. Conclusions: Metabolomic analysis suggests a basal predisposition to growth restriction, the identification of which could be useful for tailoring nutritional approaches. Full article
(This article belongs to the Special Issue Metabolomics-Based Biomarkers for Nutrition and Health)
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11 pages, 4085 KiB  
Article
Maturation of Eupyrene Sperm upon Ejaculation Is Influenced by a Male Accessory Gland-Derived Serine Protease in Grapholita molesta
by Jie Cheng, Tai Guo, Zhongyan Zhou, Wei Wei, Yu Liang, Huiming Xiang, Ruiyan Ma, Zhongjian Shen and Zhi-Guo Zhao
Insects 2025, 16(8), 782; https://doi.org/10.3390/insects16080782 - 30 Jul 2025
Viewed by 308
Abstract
Grapholita molesta is a globally significant fruit pest. Females achieve maximal reproductive output through efficient sperm utilization following a single copulation. Post-mating maturation of eupyrene sperm is a critical step in reproductive success. Here, we report that a male accessory gland-derived serine protease [...] Read more.
Grapholita molesta is a globally significant fruit pest. Females achieve maximal reproductive output through efficient sperm utilization following a single copulation. Post-mating maturation of eupyrene sperm is a critical step in reproductive success. Here, we report that a male accessory gland-derived serine protease (named GmAGSP1) is essential for this process. GmAGSP1 was only distantly related to other identified sperm-activating SPs, and its transcript was highly expressed in the AG at 48 h after emergence. RNAi-mediated knockdown of GmAGSP1 in males did not affect courtship rate, copulation duration, or mating frequency, whereas male fertility decreased significantly. Mating with GmAGSP1-knockdown males markedly impaired eupyrene sperm maturation in the spermatophores, with phenotypes including failure of eupyrene sperm bundles to dissociate normally and marked reduction in viability of the dissociated eupyrene sperm. Finally, untargeted metabolomic analysis preliminarily demonstrated marked alterations in multiple metabolic pathways within the spermatophore following mating with GmAGSP1-knockdown males. This study advances our understanding of the regulatory mechanism of “sperm activation in the spermatophore’s metabolic microenvironment mediated by male AG-derived SP” while providing critical insights for the development of novel genetic control strategies targeting G. molesta. Full article
(This article belongs to the Section Insect Pest and Vector Management)
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59 pages, 3467 KiB  
Review
Are Hippocampal Hypoperfusion and ATP Depletion Prime Movers in the Genesis of Alzheimer’s Disease? A Review of Recent Pertinent Observations from Molecular Biology
by Valerie Walker
Int. J. Mol. Sci. 2025, 26(15), 7328; https://doi.org/10.3390/ijms26157328 - 29 Jul 2025
Viewed by 259
Abstract
Alzheimer’s dementia (AD) is a disease of the ageing brain. It begins in the hippocampal region with the epicentre in the entorhinal cortex, then gradually extends into adjacent brain areas involved in memory and cognition. The events which initiate the damage are unknown [...] Read more.
Alzheimer’s dementia (AD) is a disease of the ageing brain. It begins in the hippocampal region with the epicentre in the entorhinal cortex, then gradually extends into adjacent brain areas involved in memory and cognition. The events which initiate the damage are unknown and under intense investigation. Localization to the hippocampus can now be explained by anatomical features of the blood vessels supplying this region. Blood supply and hence oxygen delivery to the area are jeopardized by poor flow through narrowed arteries. In genomic and metabolomic studies, the respiratory chain and mitochondrial pathways which generate ATP were leading pathways associated with AD. This review explores the notion that ATP depletion resulting from hippocampal hypoperfusion has a prime role in initiating damage. Sections cover sensing of ATP depletion and protective responses, vulnerable processes with very heavy ATP consumption (the malate shuttle, the glutamate/glutamine/GABA (γ-aminobutyric acid) cycle, and axonal transport), phospholipid disturbances and peroxidation by reactive oxygen species, hippocampal perfusion and the effects of hypertension, chronic hypoxia, and arterial vasospasm, and an overview of recent relevant genomic studies. The findings demonstrate strong scientific arguments for the proposal with increasing supportive evidence. These lines of enquiry should be pursued. Full article
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22 pages, 3896 KiB  
Article
Anti-Inflammatory Pharmacological Mechanism Mediated by the Conversion of Glycosides to Aglycones in Fangfeng (Saposhnikoviae Radix) in Rheumatoid Arthritis Models Based on Serum Metabolomics, Network Pharmacology, and Molecular Docking
by Wenguang Jing, Xiaoyu Lin, Wenmin Pi, Fangliang He, Haonan Wu, Xianrui Wang, Jia Chen, Xianlong Cheng, Penglong Wang and Feng Wei
Int. J. Mol. Sci. 2025, 26(15), 7088; https://doi.org/10.3390/ijms26157088 - 23 Jul 2025
Viewed by 169
Abstract
This study aims to explore the anti-inflammatory pharmacological components and anti-inflammatory mechanisms of the alcohol extract of Saposhnikoviae Radix (SR). The components of the alcohol extract of SR were analyzed using the UPLC-MS/MS system. The anti-inflammatory efficacy of the alcohol extract and core [...] Read more.
This study aims to explore the anti-inflammatory pharmacological components and anti-inflammatory mechanisms of the alcohol extract of Saposhnikoviae Radix (SR). The components of the alcohol extract of SR were analyzed using the UPLC-MS/MS system. The anti-inflammatory efficacy of the alcohol extract and core components of SR was evaluated using the LPS-induced inflammation model of RAW264.7 cells. The anti-inflammatory mechanism of SR in a mouse model of rheumatoid arthritis was expounded by means of serum metabolomics, network pharmacology, and molecular docking. A total of 12 chromones and 13 coumarins were identified in the alcohol extract of SR. The alcohol extract of SR and its components all had good anti-inflammatory activities. In the mouse model of rheumatoid arthritis, the glycoside compounds of SR were transformed into aglycones, thereby exerting anti-inflammatory effects. Moreover, the alcohol extract of SR alleviated the inflammatory response by up-regulating the expression levels of metabolites such as phenylalanine and tyrosine. Network pharmacology and molecular docking results show that SR could exert an anti-inflammatory effect by regulating AGE-RAGE, PI3K-Akt, TNF, MAPK, and Toll-like signaling pathways. In this study, the anti-inflammatory efficacy and mechanisms of the alcohol extract of SR are explored, with the aim of providing a reference for subsequent research. Full article
(This article belongs to the Section Molecular Pharmacology)
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16 pages, 1501 KiB  
Article
Effects of Modified Attapulgite on Daily Weight Gain, Serum Indexes and Serum Metabolites in Fattening Beef Cattle
by Jiajie Wang, Hanfang Zeng, Hantong Weng, Haomiao Chang, Yunfei Zhai, Zhihui Huang, Chenchen Chu, Haihui Wang and Zhaoyu Han
Animals 2025, 15(15), 2167; https://doi.org/10.3390/ani15152167 - 23 Jul 2025
Viewed by 243
Abstract
In this study, we investigated the effects of dietary supplementation with thermally modified attapulgite on the daily weight gain, serum biochemical indices, and serum metabolites of Simmental fattening cattle. A total of 30 healthy Simmental fattening beef calves of similar age (8 to [...] Read more.
In this study, we investigated the effects of dietary supplementation with thermally modified attapulgite on the daily weight gain, serum biochemical indices, and serum metabolites of Simmental fattening cattle. A total of 30 healthy Simmental fattening beef calves of similar age (8 to 9 months old) and body weight (370 ± 10 kg) were randomly divided into two groups, each containing 15 animals. A control group was fed the basal diet, and a treatment group was fed the same basal diet with the addition of 4 g/kg of thermally modified attapulgite. After 75 days of formal experiment, the calves in the two groups were weighed, and blood samples were collected by tail vein blood sampling for determinations of the serum biochemical indices and serum metabolites using liquid chromatography–mass spectrometry (LC-MS) analysis. The results indicated that the addition of thermally modified attapulgite to the diet had no significant effects on the daily weight gain of fattening beef cattle. After feeding with modified attapulgite, the glutathione peroxidase and superoxide dismutase activities in the serum of the experimental group were 55.02% (257.26 U·mL−1 to 165.95 U·mL−1, p < 0.05) and 13.11% (18.98 U·mL−1 to 16.78 U·mL−1, p < 0.05) higher than that in the control group. Compared with the control group, the tumor necrosis factor-alpha content was reduced by 14.50% (31.27 pg·mL−1 to 36.57 pg·mL−1, p < 0.01), and the concentration of interleukin-6 and lipopolysaccharide decreased by 17.00% (34.33 pg·mL−1 to 41.36 pg·mL−1, p < 0.001) and 23.05% (51.34 EU·L−1 to 66.72 EU·L−1, p < 0.001) in the serum of the experimental group. Contrastingly, the thermally modified attapulgite had no significant effects on the levels of serum total protein, albumin, or globulin in Simmental fattening cattle (p > 0.05). Furthermore, the results of serum metabolomic analyses revealed that there were a total of 98 differential metabolites, which were mainly enriched with respect to glycerophospholipid metabolism, Th1 and Th2 cell differentiation, autophagy-other, retrograde endogenous cannabinoid signaling, and the NF-κB signaling pathway. Overall, thermally modified attapulgite was found to effectively increase the activity of antioxidant enzymes, reduce serum inflammatory mediators, may suppress oxidative damage, enhance immunity, and have a positive influence on the health of Simmental fattening beef calves. Full article
(This article belongs to the Section Cattle)
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15 pages, 2281 KiB  
Article
Transcriptome and Anthocyanin Profile Analysis Reveals That Exogenous Ethylene Regulates Anthocyanin Biosynthesis in Grape Berries
by Min Liu, Boyuan Fan, Le Li, Jinmei Hao, Ruteng Wei, Hua Luo, Fei Shi, Zhiyuan Ren and Jun Wang
Foods 2025, 14(14), 2551; https://doi.org/10.3390/foods14142551 - 21 Jul 2025
Viewed by 359
Abstract
Anthocyanins are important phenolic compounds in grape skins, affecting the color, oxidation resistance, and aging ability of red wine. In recent years, global warming has had a negative effect on anthocyanin biosynthesis in grape berries. Ethylene serves as a crucial phytohormone regulating the [...] Read more.
Anthocyanins are important phenolic compounds in grape skins, affecting the color, oxidation resistance, and aging ability of red wine. In recent years, global warming has had a negative effect on anthocyanin biosynthesis in grape berries. Ethylene serves as a crucial phytohormone regulating the development and ripening processes of fruit; however, the specific molecular mechanism and the regulatory network between ethylene signaling and the anthocyanin biosynthesis pathway remain incompletely understood. In this study, 400 mg/L ethephon (ETH) solution was sprayed onto the surface of grape berries at the lag phase (EL-34), and the changes in anthocyanin-related genes and metabolites were explored through transcriptomic and metabolomic analysis. The results showed that ETH treatment increased Brix and pH in mature berries. In total, 35 individual anthocyanins were detected, in which 21 individual anthocyanins were enhanced by ETH treatment. However, the anthocyanin profile was not affected by exogenous ethylene. Transcriptomics analysis showed that there were a total of 825 and 1399 differentially expressed genes (DEGs) 12 h and 24 h after treatment. Moreover, key structural genes in the anthocyanin synthesis pathway were strongly induced, including VvPAL, VvCHS, VvF3H, VvF3′5′H, VvDFR and VvUFGT. At the maturity stage (EL-38), the expression levels of these genes were still higher in EHT-treated berries than in the control. ETH treatment also influenced the expression of genes related to hormone biosynthesis and signal transduction. The ethylene biosynthesis gene (VvACO), ethylene receptor genes (VvETR2, VvERS1 and VvEIN4), ABA biosynthesis gene (VvNCED2), and ABA receptor gene (VvPYL4) were up-regulated by ETH treatment, while the auxin biosynthesis gene (VvTAA3) and seven genes of the auxin-responsive protein were inhibited by exogenous ethylene. Meanwhile, ETH treatment promoted the expression of the sugar transporter gene (VvEDL16) and two sucrose synthase genes (VvSUS2 and VvSUS6). In EHT-treated berries, 19 MYB and 23 ERF genes were expressed differently compared with the control (p < 0.05). This study provides the theoretical foundation and technical support for the regulation of anthocyanin synthesis in non-climacteric fruit. Full article
(This article belongs to the Section Food Physics and (Bio)Chemistry)
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27 pages, 1726 KiB  
Article
Integrated Spectroscopic Analysis of Wild Beers: Molecular Composition and Antioxidant Properties
by Dessislava Gerginova, Plamena Staleva, Zhanina Petkova, Konstantina Priboyska, Plamen Chorbadzhiev, Ralitsa Chimshirova and Svetlana Simova
Int. J. Mol. Sci. 2025, 26(14), 6993; https://doi.org/10.3390/ijms26146993 - 21 Jul 2025
Viewed by 266
Abstract
Wild ales represent a diverse category of spontaneously fermented beers, influenced by complex microbial populations and variable ingredients. This study employed an integrated metabolomic profiling approach combining proton nuclear magnetic resonance (1H NMR) spectroscopy, liquid chromatography–mass spectrometry (LC-MS), and spectrophotometric assays [...] Read more.
Wild ales represent a diverse category of spontaneously fermented beers, influenced by complex microbial populations and variable ingredients. This study employed an integrated metabolomic profiling approach combining proton nuclear magnetic resonance (1H NMR) spectroscopy, liquid chromatography–mass spectrometry (LC-MS), and spectrophotometric assays (DPPH and FRAP) to characterize the molecular composition and antioxidant potential of 22 wild ales from six countries. A total of 53 compounds were identified and quantified using NMR, while 62 compounds were identified by using LC-MS. The compounds in question included organic acids, amino acids, sugars, alcohols, bitter acids, phenolic compounds, and others. Ingredient-based clustering revealed that the addition of dark fruits resulted in a significant increase in the polyphenolic content and antioxidant activity. Concurrently, herb-infused and light-fruit beers exhibited divergent phytochemical profiles. Prolonged aging (>18 months) has been demonstrated to be associated with increased levels of certain amino acids, fermentation-derived aldehydes, and phenolic degradation products. However, the influence of maturation duration on the antioxidant capacity was found to be less significant than that of the type of fruit. Country-specific metabolite trends were revealed, indicating the influence of regional brewing practices on beer composition. Correlation analysis was employed to identify the major contributors to antioxidant activity, with salicylic, dihydroxybenzoic, and 4-hydroxybenzoic acids being identified as the most significant. These findings underscore the biochemical intricacy of wild ales and exemplify metabolomics’ capacity to correlate compositional variation with functionality and authenticity in spontaneously fermented beverages. Full article
(This article belongs to the Section Biochemistry)
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19 pages, 1109 KiB  
Article
Machine Learning Approach to Select Small Compounds in Plasma as Predictors of Alzheimer’s Disease
by Eleonora Stefanini, Alberto Iglesias, Joan Serrano-Marín, Juan Sánchez-Navés, Hanan A. Alkozi, Mercè Pallàs, Christian Griñán-Ferré, David Bernal-Casas and Rafael Franco
Int. J. Mol. Sci. 2025, 26(14), 6991; https://doi.org/10.3390/ijms26146991 - 21 Jul 2025
Viewed by 263
Abstract
This study employs a machine learning approach to identify a small-molecule-based signature capable of predicting Alzheimer’s disease (AD). Utilizing metabolomics data from the plasma of a well-characterized cohort of 94 AD patients and 62 healthy controls; metabolite levels were assessed using the Biocrates [...] Read more.
This study employs a machine learning approach to identify a small-molecule-based signature capable of predicting Alzheimer’s disease (AD). Utilizing metabolomics data from the plasma of a well-characterized cohort of 94 AD patients and 62 healthy controls; metabolite levels were assessed using the Biocrates MxP® Quant 500 platform. Data preprocessing involved removing low-quality samples, selecting relevant biochemical groups, and normalizing metabolite data based on demographic variables such as age, sex, and fasting time. Linear regression models were used to identify concomitant parameters that consisted of the data for a given metabolite within each of the biochemical families that were considered. Detection of these “concomitant” metabolites facilitates normalization and allows sample comparison. Residual analysis revealed distinct metabolite profiles between AD patients and controls across groups, such as amino acid-related compounds, bile acids, biogenic amines, indoles, carboxylic acids, and fatty acids. Correlation heatmaps illustrated significant interdependencies, highlighting specific molecules like carnosine, 5-aminovaleric acid (5-AVA), cholic acid (CA), and indoxyl sulfate (Ind-SO4) as promising indicators. Linear Discriminant Analysis (LDA), validated using Leave-One-Out Cross-Validation, demonstrated that combinations of four or five molecules could classify AD with accuracy exceeding 75%, sensitivity up to 80%, and specificity around 79%. Notably, optimal combinations integrated metabolites with both a tendency to increase and a tendency to decrease in AD. A multivariate strategy consistently identified included 5-AVA, carnosine, CA, and hypoxanthine as having predictive potential. Overall, this study supports the utility of combining data of plasma small molecules as predictors for AD, offering a novel diagnostic tool and paving the way for advancements in personalized medicine. Full article
(This article belongs to the Section Molecular Neurobiology)
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27 pages, 3394 KiB  
Article
Integrative Multi-Omics Profiling of Rhabdomyosarcoma Subtypes Reveals Distinct Molecular Pathways and Biomarker Signatures
by Aya Osama, Ahmed Karam, Abdelrahman Atef, Menna Arafat, Rahma W. Afifi, Maha Mokhtar, Taghreed Khaled Abdelmoneim, Asmaa Ramzy, Enas El Nadi, Asmaa Salama, Emad Elzayat and Sameh Magdeldin
Cells 2025, 14(14), 1115; https://doi.org/10.3390/cells14141115 - 20 Jul 2025
Viewed by 792
Abstract
Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, comprises embryonal (ERMS) and alveolar (ARMS) subtypes with distinct histopathological features, clinical outcomes, and therapeutic responses. To better characterize their molecular distinctions, we performed untargeted plasma proteomics and metabolomics profiling in children with ERMS [...] Read more.
Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, comprises embryonal (ERMS) and alveolar (ARMS) subtypes with distinct histopathological features, clinical outcomes, and therapeutic responses. To better characterize their molecular distinctions, we performed untargeted plasma proteomics and metabolomics profiling in children with ERMS (n = 18), ARMS (n = 17), and matched healthy controls (n = 18). Differential expression, functional enrichment (GO, KEGG, RaMP-DB), co-expression network analysis (WGCNA/WMCNA), and multi-omics integration (DIABLO, MOFA) revealed distinct molecular signatures for each subtype. ARMS displayed elevated oncogenic and stemness-associated proteins (e.g., cyclin E1, FAP, myotrophin) and metabolites involved in lipid transport, fatty acid metabolism, and polyamine biosynthesis. In contrast, ERMS was enriched in immune-related and myogenic proteins (e.g., myosin-9, SAA2, S100A11) and metabolites linked to glutamate/glycine metabolism and redox homeostasis. Pathway analyses highlighted subtype-specific activation of PI3K-Akt and Hippo signaling in ARMS and immune and coagulation pathways in ERMS. Additionally, the proteomics and metabolomics datasets showed association with clinical parameters, including disease stage, lymph node involvement, and age, demonstrating clear molecular discrimination consistent with clinical observation. Co-expression networks and integrative analyses further reinforced these distinctions, uncovering coordinated protein–metabolite modules. Our findings reveal novel, subtype-specific molecular programs in RMS and propose candidate biomarkers and pathways that may guide precision diagnostics and therapeutic targeting in pediatric sarcomas. Full article
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17 pages, 1946 KiB  
Article
Geographic Influence and Metabolomics-Driven Discovery of 5-Alpha Reductase Inhibitors in Tectona grandis L.f. (Teak) Leaves
by Nutchaninad Tanuphol, Corine Girard, Prapapan Temkitthawon, Nungruthai Suphrom, Nitra Nuengchamnong, Tongchai Saesong, Kamonlak Insumrong, Abdulaziz Wadeng, Wiyada Khangkhachit, Andy Zedet, Ratchadaree Intayot, Siriporn Jungsuttiwong, Anuchit Plubrukarn, Francois Senejoux and Kornkanok Ingkaninan
Molecules 2025, 30(14), 2895; https://doi.org/10.3390/molecules30142895 - 8 Jul 2025
Viewed by 387
Abstract
The inhibition of steroid 5-alpha reductase (S5AR), a key mechanism for managing dihydrotestosterone-dependent conditions, has been demonstrated in teak (Tectona grandis L.f.) leaf extracts. Our recent clinical study confirmed the effectiveness of a hair growth formulation containing teak leaf extract in males [...] Read more.
The inhibition of steroid 5-alpha reductase (S5AR), a key mechanism for managing dihydrotestosterone-dependent conditions, has been demonstrated in teak (Tectona grandis L.f.) leaf extracts. Our recent clinical study confirmed the effectiveness of a hair growth formulation containing teak leaf extract in males with androgenic alopecia. However, significant variability in S5AR inhibitory activity among teak leaf samples from different regions underscores the need for quality control of raw materials. This study applied a metabolomics approach to investigate the influence of leaf age, harvesting period, and geographic origin on chemical composition and S5AR inhibitory activity, as well as to identify active S5AR inhibitors. Geographic origin emerged as the primary determinant of variations in chemical profiles and S5AR inhibitory activity. Using orthogonal partial least squares analysis, six diterpenoid S5AR inhibitors were identified, including four compounds reported for the first time as S5AR inhibitors: rhinocerotinoic acid, 7-oxo-8-labden-15-oic acid, 8-hydroxy-labd-13-en-15-oic acid, and a novel diterpene, 7-hydroxy-labd-8,13-dien-15-oic acid. These findings highlight the potential of metabolomics as a powerful tool for discovering bioactive compounds and optimizing raw material selection. By prioritizing proven geographic sources, consistent bioactivity can be achieved, supporting the therapeutic potential of teak leaves in managing S5AR-related conditions. Full article
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20 pages, 12581 KiB  
Article
Metabolomics and Transcriptomics Reveal Age-Dependent Development of Meat Quality Traits in Jingyuan Chicken
by Jiahuan Hu, Wei Zhao, Jinyan Zhao, Jinli Tian, Lijuan Yang, Hua Wang, Siyu Chen, Ruimin Ma, Yaling Gu, Dawei Wei and Juan Zhang
Animals 2025, 15(13), 1938; https://doi.org/10.3390/ani15131938 - 1 Jul 2025
Viewed by 295
Abstract
In this study, we investigated the dynamic changes in muscle lipid content (MLC) deposition in the breast muscle of Jingyuan chickens at different stages (42-, 126-, and 180- days old) using metabolomics. The pH45min, a*, and L* were significantly increased in the [...] Read more.
In this study, we investigated the dynamic changes in muscle lipid content (MLC) deposition in the breast muscle of Jingyuan chickens at different stages (42-, 126-, and 180- days old) using metabolomics. The pH45min, a*, and L* were significantly increased in the breast muscle of 126-day-old chickens, and MLC and b* were significantly increased in the breast muscle of 180-day-old chickens. A total of 4643 differentially expressed metabolites (DEMs) were identified, of which 10 decreased and 29 increased with age. Key pathways associated with meat quality traits included oxidative phosphorylation, β-alanine metabolism, and glycerophospholipid metabolism. Combined transcriptomic and phenotypic correlation analyses revealed significant positive correlations of MLC, pH45min, a*, and L* with LysoPC 20:4, CD3E, TARP, IL7R, ENSGALG00010025331, and RASSF5. In the 42- and 180-day-old chickens, MLC, pH45min, a*, and L* were significantly and positively correlated with L-Anserine, Dihydroxyacetone phosphate, ENSGALG00010006904, and HSPB7. MLC, pH45min, a*, and L* were significantly and positively correlated with beta-Nicotinamide adenine dinucleotide in the 126- and 180-day-old chickens. This study deepens our understanding of the differences in MLC deposition at different stages of Jingyuan chickens and its relationship with meat quality traits. Full article
(This article belongs to the Section Poultry)
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14 pages, 3075 KiB  
Article
Plasma Metabolic and Inflammatory Protein Signatures in Psychiatric Disorders
by Manel Naifar, Franklin Ducatez, Wassim Guidara, Manel Maalej, Celine Lesueur, Carine Pilon, Thomas Plichet, Mohamed Maalej, Fatma Ayadi and Soumeya Bekri
Int. J. Mol. Sci. 2025, 26(13), 6260; https://doi.org/10.3390/ijms26136260 - 28 Jun 2025
Viewed by 358
Abstract
Psychiatric disorders, particularly schizophrenia (SCZ), bipolar disorder (BD), and schizoaffective disorder (SAD), present significant diagnostic challenges. Current diagnostic methods rely on clinical observation and self-reported symptoms, leading to under-diagnosis and delayed treatment. To address this gap, we applied mass spectrometry-based metabolomic profiling and [...] Read more.
Psychiatric disorders, particularly schizophrenia (SCZ), bipolar disorder (BD), and schizoaffective disorder (SAD), present significant diagnostic challenges. Current diagnostic methods rely on clinical observation and self-reported symptoms, leading to under-diagnosis and delayed treatment. To address this gap, we applied mass spectrometry-based metabolomic profiling and targeted analysis of inflammatory proteins to plasma samples from patients versus controls, aiming to uncover disease-related molecular patterns and enhance our understanding of the underlying pathophysiology of these complex disorders. This study included 26 patients with BD, 34 with SCZ, 16 with SAD, and age- and sex-matched controls. All diagnoses were established according to DSM-5 criteria. Unsupervised analysis shows a clear separation between controls and patients, indicating distinct metabolic and inflammatory profiles. However, the lack of clear differentiation among the three disease subgroups suggests shared biological profiles across these psychiatric disorders. Biomolecules driving this separation between controls and patients includes decreased levels of proinflammatory cytokines, amino acids, and glycerophospholipids, and increased levels of acylcarnitines. This study represents a step towards addressing the limitations of current diagnostic approaches to severe psychiatric disorders, which rely heavily on clinical symptoms, by using omics approaches to refine their diagnosis and treatment. Full article
(This article belongs to the Special Issue Molecular Advances in Mental Health and Disorders)
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15 pages, 2847 KiB  
Article
Metabolomic Profiles During and After a Hypertensive Disorder of Pregnancy: The EPOCH Study
by Mark A. Hlatky, Chi-Hung Shu, Nasim Bararpour, Brenna M. Murphy, Sabina M. Sorondo, Nicholas J. Leeper, Frank Wong, David K. Stevenson, Gary M. Shaw, Marcia L. Stefanick, Heather A. Boyd, Mads Melbye, Oshra Sedan, Ronald J. Wong, Michael P. Snyder, Nima Aghaeepour and Virginia D. Winn
Int. J. Mol. Sci. 2025, 26(13), 6150; https://doi.org/10.3390/ijms26136150 - 26 Jun 2025
Viewed by 404
Abstract
Hypertensive disorders of pregnancy are associated with a higher risk of later cardiovascular disease, but the mechanistic links are unknown. We recruited two groups of women, one during pregnancy and another at least two years after delivery, including both cases (with a hypertensive [...] Read more.
Hypertensive disorders of pregnancy are associated with a higher risk of later cardiovascular disease, but the mechanistic links are unknown. We recruited two groups of women, one during pregnancy and another at least two years after delivery, including both cases (with a hypertensive disorder of pregnancy) and controls (with a normotensive pregnancy). We measured metabolites using liquid chromatography–mass spectroscopy and applied machine learning to identify metabolomic signatures at three time points: antepartum, postpartum, and mid-life. The mean ages of the pregnancy cohort (58 cases, 46 controls) and the mid-life group (71 cases, 74 controls) were 33.8 and 40.8 years, respectively. The levels of 157 metabolites differed significantly between the cases and the controls antepartum, including 19 acylcarnitines, 12 gonadal steroids, 11 glycerophospholipids, nine fatty acids, six vitamin D metabolites, and four corticosteroids. The machine learning model developed using all antepartum metabolite levels discriminated well between the cases and the controls antepartum (c-index = 0.96), postpartum (c-index = 0.63), and in mid-life (c-index = 0.60). Levels of 10,20-dihydroxyeicosanoic acid best distinguished the cases from the controls both antepartum and postpartum. These data suggest that the pattern of differences in metabolites found antepartum continues to distinguish women who had a hypertensive disorder of pregnancy from women with a normotensive pregnancy for years after delivery. Full article
(This article belongs to the Special Issue Molecular Links Between Pregnancy and Chronic Diseases)
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Article
Insomnia, Cognitive Impairment, or a Combination of Both, Alter Lipid Metabolism Due to Changes in Acylcarnitine Concentration in Older Persons
by Selma Karime Castillo-Vazquez, Berenice Palacios-González, Marcela Vela-Amieva, Isabel Ibarra-González, Ricardo Morales, Paola García-delaTorre, Sergio Sánchez-García, Carmen García-Peña, Ricardo Reyes-Chilpa, Raúl Hernán Medina-Campos, Jessica Hernández-Pineda, Juan Carlos Gomez-Verjan and Nadia Alejandra Rivero-Segura
Metabolites 2025, 15(6), 417; https://doi.org/10.3390/metabo15060417 - 19 Jun 2025
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Abstract
Background/Objectives: Insomnia has been widely associated with cognitive impairment (CI). However, the relationship between the two entities (insomnia and CI) is poorly understood. In this context, adults with insomnia show metabolic changes, including alterations in the catabolism of branched-chain amino acids, glycerophospholipids, and [...] Read more.
Background/Objectives: Insomnia has been widely associated with cognitive impairment (CI). However, the relationship between the two entities (insomnia and CI) is poorly understood. In this context, adults with insomnia show metabolic changes, including alterations in the catabolism of branched-chain amino acids, glycerophospholipids, and glutathione and glutamate biosynthesis. Nevertheless, aging itself induces metabolic changes that may be amplified by chronic diseases that compromise the health of the elderly. Therefore, in the present study we aim to characterise metabolomic profiles of insomnia and CI alone in order to address a significant gap in current research regarding the pathways through which insomnia may lead to CI in older persons. Methods: In this study we perform a targeted metabolomics analysis (UPLC-MS) on 80 serum samples from the Cohort of Obesity, Sarcopenia, and Frailty of Older Mexican Adults (COSFOMA); these samples were classified into four groups (control, insomnia, CI, and insomnia + CI). Results: Our results show that insomnia increases the concentration of acylcarnitines (C10, C8, C14, C12:1, C18:1 and C18) as compared to CI group, while older persons with CI show a decrease the concentration of the acylcarnitines C16, C10 and C8. Finally, individuals with both conditions (insomnia + CI) show that only the concentration of the acylcarnitine C16 decreases compared to controls. Conclusions: Taken together, our results shed light on the relevance of insomnia on lipid metabolism in older persons. Full article
(This article belongs to the Special Issue Lipid Metabolism in Age-Related Diseases)
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