PubMed

Free Radic Res. 2024 Dec 5:1-15. doi: 10.1080/10715762.2024.2437640. Online ahead of print.ABSTRACTOxidative stress can be alleviated by antioxidants intakes. Taraxerol acetate (TA), a natural triterpenoid extracted from dandelions, may reduce the risk of metabolic disorders by regulating oxidative stress. In the study, we investigated the effects of TA in relieving oxidative stress in murine intestinal epithelial cells using multiomics techniques. Here, we found that TA activated the antioxidant defense system. Total antioxidant capacity (T-AOC) and Catalase (CAT) activity notably increased after TA treatment. Additionally, TA treatment effectively reduced the levels of lactate dehydrogenase (LDH) and malonaldehyde (MDA) and alleviated H2O2-induced oxidative stress. Furthermore, TA induced significant changes in the levels of 30 important metabolites. Specifically, it activated the complement and coagulation cascades, NF-κB and MAPK and glycerophospholipid pathways, resulting in altered transcript levels of related genes, such as Serpinb9e, SCD2, Hspa1b, and Hspa1a. Thus, the results demonstrated that TA potentially could promote health by alleviating H2O2-induced oxidative damage and provide valuable insights for its further development.PMID:39636737 | DOI:10.1080/10715762.2024.2437640

Plant J. 2024 Dec 5. doi: 10.1111/tpj.17188. Online ahead of print.ABSTRACTFlower color change, a common phenomenon that is important in pollination ecology, has intrigued scientists for decades. While previous flower color studies have mainly focused on color diversity among different plant species, our focus is on unraveling the mechanism of post-anthesis color change (PACC) and the molecular basis for its presence and absence, respectively, in two closely related species of Lotus, Lotus filicaulis and Lotus japonicus MG20. Metabolomic analysis reveals anthocyanins as the key metabolites responsible for the observed PACC. Differential expression of anthocyanin biosynthetic and transport genes causes the variation in PACC between the two Lotus species. Crucially, the significant upregulation of a functionally characterized MYB regulator, LfPAP1, is linked to the accumulation of anthocyanins and visible color alterations in L. filicaulis flowers. Notably, we uncover a nucleotide polymorphism in the initiation codon of LjPAP1. Although this mutation does not affect transcription, we show that it has a major effect in attenuating protein translation, reducing its capacity to activate anthocyanin biosynthesis, and leading to a failure of PACC in L. japonicus MG20. Our study sheds light on mechanisms of PACC phenomenon and highlights the potential for mutations in initiation sequences to generate phenotypic differences between species in evolution.PMID:39636691 | DOI:10.1111/tpj.17188

Plant Biotechnol J. 2024 Dec 5. doi: 10.1111/pbi.14534. Online ahead of print.ABSTRACTSalinity significantly inhibits plant growth and development. While the recretohalophyte Limonium bicolor can reduce its ion content by secreting salt, the metabolic pathways it employs to adapt to high salt stress remain unclear. This study aims to unravel this enigma through integrated transcriptomic and metabolomic analyses of L. bicolor under salt stress conditions. The results showed that compared to the control (S0), low salt treatment (S1) led to a significant increase in plant growth, photosynthesis efficiency and antioxidant enzyme activity but caused no significant changes in organic soluble substance and ROS contents. However, high salt treatments (S3 and S4) led to a significant decrease in plant growth, photosynthesis efficiency and antioxidant enzyme activity, accompanied by a significant increase in organic soluble substance and ROS contents. A significant increase in phenolic compounds, such as caffeoyl shikimic acid and coniferin, upon the treatments of S1, S3 and S4, and a decrease and increase in flavonoids upon the treatments of S1 and S3 were also observed, respectively. This study also demonstrated that the expression patterns of key genes responsible for the biosynthesis of these metabolites are consistent with the observed trends in their accumulation levels. These results suggest that under low salt stress conditions, the halophyte L. bicolor experiences minimal osmotic and oxidative stress. However, under high salt stress conditions, it suffers severe osmotic and oxidative stress, and the increase in organic soluble substances and flavonoids serves as a key response to these stresses and also represents a good strategy for the alleviation of them.PMID:39636615 | DOI:10.1111/pbi.14534

Metabolomics. 2024 Dec 4;21(1):1. doi: 10.1007/s11306-024-02201-3.ABSTRACTINTRODUCTION: Despite the well-established efficacy of thiazolidinediones (TZDs), including pioglitazone and rosiglitazone, in type II diabetes management, their potential contribution to heart failure risk remains a significant area of uncertainty. This incomplete understanding, which persists despite decades of clinical use of TZDs, has generated ongoing controversy and unanswered questions regarding their safety profiles, ultimately limiting their broader clinical application.OBJECTIVE AND METHODS: This study presented a multi-omics approach, integrating toxicoproteomics and toxicometabolomics data with the goal of uncovering novel mechanistic insights into TZD cardiotoxicity and identifying molecular signatures predictive of side effect progression.RESULTS: Network analysis of proteo-metabolomic data revealed a distinct fingerprint of disrupted biochemical pathways, which were primarily related to energy metabolism. Downregulation of oxidative phosphorylation and fatty acid synthesis was coupled with increased activity in anaerobic glycolysis, the pentose phosphate pathway, and amino acid and purine metabolism. This suggests a potential metabolic shift in AC16 cells from fatty acid oxidation towards anaerobic glycolysis, potentially contributing to observed cardiotoxicity. Additionally, the study identified a marked disruption in the glutathione system, indicating an imbalanced redox state triggered by TZD exposure. Importantly, our analysis identified key molecular signatures across omics datasets, including prominent signatures of amino acids like L-ornithine, L-tyrosine and glutamine, which are evidently associated with heart failure, supporting their potential use for the early prediction of cardiotoxicity progression.CONCLUSION: By uncovering a novel mechanistic explanation for TZD cardiotoxicity, this study simultaneously illuminates potential therapeutic interventions, opening avenues for future research to improve the safety profile of TZD agents. (250 words).PMID:39636558 | DOI:10.1007/s11306-024-02201-3

J Mol Histol. 2024 Dec 5;56(1):31. doi: 10.1007/s10735-024-10298-y.ABSTRACTBACKGROUND: Among couples, male factors account for approximately 50% of infertility cases, with nonobstructive azoospermia (NOA) representing one of the most clinically common and severe categories of male infertility, affecting approximately 10-15% of patients. Currently, L-carnitine is clinically used to improve spermatogenesis by regulating Sertoli cell function. Multiple clinical trials have described the efficacy of L-carnitine in treating NOA. Notably, Sertoli cells rely on organic carnitine transporter 2 (OCTN2) for carnitine transport. However, it remains unknown whether OCTN2 expression is involved in the pathological process of NOA.OBJECTIVE: To investigate the expression and function of OCTN2 in Sertoli cells from patients with NOA.MATERIALS AND METHODS: Ten testicular tissue samples were collected, including five from a healthy group and five from a group of patients with NOA. Immunohistochemistry and immunofluorescence were used to detect the expression of OCTN2 in testicular tissue. Additionally, an Octn2-KO TM4 cell line (a mouse testicular Sertoli cell line) was constructed to explore the function of OCTN2 expression in Sertoli cells through transcriptomic sequencing, cell proliferation experiments, metabolomic analysis, and Western blot analysis.RESULTS: Compared with those of the healthy group, the immunohistochemistry results revealed a significant decrease in OCTN2 expression in the Sertoli cells of the NOA group. Further investigation through cell proliferation experiments revealed a reduction in the proliferative capacity of the Octn2-KO TM4 cell line. Transcriptomic sequencing and metabolomic data analysis revealed a decrease in autophagy in the Octn2-KO TM4 cell line. Western blot analysis subsequently verified the expression levels of autophagy-related proteins.CONCLUSION: In the Sertoli cells of NOA patients, decreased OCTN2 protein expression leads to decreased cell proliferation and autophagy abnormalities, which may play a crucial role in the spermatogenic dysfunction observed in NOA patients.PMID:39636482 | DOI:10.1007/s10735-024-10298-y

Metabolomics. 2024 Dec 4;21(1):2. doi: 10.1007/s11306-024-02197-w.ABSTRACTINTRODUCTION: The knowledge of the mode of action of an antimicrobial is essential for drug development and helps to fight against bacterial resistance. Thus, it is crucial to use analytical techniques to study the mechanism of action of substances that have potential to act as antibacterial agents OBJECTIVE: To use NMR-based metabolomics combined with chemometrics and molecular docking to identify the metabolic responses of Staphylococcus aureus following exposure to commercial antibiotics and some synthesized ω-aminoalkoxylxanthones.METHODS: Intracellular metabolites of S. aureus were extracted after treatment with four commercial antibiotics and three synthesized ω-aminoalkoxylxanthones. NMR spectra were obtained and 1H NMR data was analyzed using both unsupervised and supervised algorithms (PCA and PLS-DA, respectively). Docking simulations on DNA topoisomerase IV protein were also performed for the ω-aminoalkoxylxanthones.RESULTS: Through chemometric analysis, we distinguished between the control group and antibiotics with extracellular (ampicillin) and intracellular targets (kanamycin, tetracycline, and ciprofloxacin). We identified 21 metabolites, including important metabolites that differentiate the groups, such as betaine, acetamide, glutamate, lysine, alanine, isoleucine/leucine, acetate, threonine, proline, and ethanol. Regarding the xanthone-type derivatives (S6, S7 and S8), we observed a greater similarity between S7 and ciprofloxacin, which targets bacterial DNA replication. The molecular docking analysis showed high affinity of the ω-aminoalkoxylxanthones with the topoisomerase IV enzyme, as well as ciprofloxacin.CONCLUSION: NMR-based metabolomics has shown to be an effective technique to assess the metabolic profile of S. aureus after treatment with certain antimicrobial compounds, helping the investigation of their mechanism of action.PMID:39636460 | DOI:10.1007/s11306-024-02197-w

Metabolomics. 2024 Dec 4;21(1):3. doi: 10.1007/s11306-024-02195-y.ABSTRACTINTRODUCTION: Coronavirus disease 2019 (COVID-19) has widely varying clinical severity. Currently, no single marker or panel of markers is considered standard of care for prediction of COVID-19 disease progression. The goal of this study is to gain mechanistic insights at the molecular level and to discover predictive biomarkers of severity of infection and outcomes among COVID-19 patients.METHOD: This cohort study (n = 76) included participants aged 16-78 years who tested positive for SARS-CoV-2 and enrolled in Memphis, TN between August 2020 to July 2022. Clinical outcomes were classified as Non-severe (n = 39) or Severe (n = 37). LC/HRMS-based untargeted metabolomics/lipidomics was conducted to examine the difference in plasma metabolome and lipidome between the two groups.RESULTS: Metabolomics data indicated that the kynurenine pathway was activated in Severe participants. Significant increases in short chain acylcarnitines, and short and medium chain acylcarnitines containing OH-FA chain in Severe vs. Non-severe group, which indicates that (1) the energy pathway switched to FA β-oxidation to maintain the host energy homeostasis and to provide energy for virus proliferation; (2) ROS status was aggravated in Severe vs. Non-severe group. Based on PLS-DA and correlation analysis to severity score, IL-6, and creatine, a biomarker panel containing glucose (pro-inflammation), ceramide and S1P (inflammation related), 4-hydroxybutyric acid (oxidative stress related), testosterone sulfate (immune related), and creatine (kidney function), was discovered. This novel biomarker panel plus IL-6 with an AUC of 0.945 provides a better indication of COVID-19 clinical outcomes than that of IL-6 alone or the three clinical biomarker panel (IL-6, glucose and creatine) with AUCs of 0.875 or 0.892.PMID:39636373 | DOI:10.1007/s11306-024-02195-y

FASEB J. 2024 Dec 15;38(23):e70226. doi: 10.1096/fj.202402088R.ABSTRACTMechano-induced keratinocyte hyperproliferation is reported to be associated with various skin diseases. Enhanced cell proliferation often requires the active metabolism of nutrients to produce energy. However, how keratinocytes adapt their cellular metabolism homeostasis to mechanical cues remains unclear. Here, we first found that mechanical stretched keratinocytes showed the accumulation of metabolic arachidonic acid by metabolomic analysis. Second, we found that mechanical stretch promoted keratinocyte proliferation through the activation of cytosolic calcium-dependent phospholipase A2 (cPLA2). Knockdown or inhibition of cPLA2 could reduce the release of arachidonic acid and inhibit the proliferation of stretched keratinocytes in vitro and in vivo. Third, by analyzing overlapping transcriptomes of stretched keratinocytes and arachidonic acid-stimulated keratinocytes, we identified the upregulation of hexokinase domain-containing protein 1 (HKDC1) expression, a novel gene involved in glucose metabolism, which was associated with arachidonic acid-induced keratinocyte proliferation during stretching. Our data reveal a metabolic regulation mechanism by which mechanical stretch induces keratinocyte proliferation, thereby coupling cellular metabolism to the mechanics of the cellular microenvironment. Strategies to change the metabolism process may lead to a new way to treat skin diseases that are related to biophysical forces.PMID:39636236 | DOI:10.1096/fj.202402088R

Elife. 2024 Dec 5;13:RP93004. doi: 10.7554/eLife.93004.ABSTRACTThe coordination of cell cycle progression and flagellar synthesis is a complex process in motile bacteria. In γ-proteobacteria, the localization of the flagellum to the cell pole is mediated by the SRP-type GTPase FlhF. However, the mechanism of action of FlhF, and its relationship with the cell pole landmark protein HubP remain unclear. In this study, we discovered a novel protein called FipA that is required for normal FlhF activity and function in polar flagellar synthesis. We demonstrated that membrane-localized FipA interacts with FlhF and is required for normal flagellar synthesis in Vibrio parahaemolyticus, Pseudomonas putida, and Shewanella putrefaciens, and it does so independently of the polar localization mediated by HubP. FipA exhibits a dynamic localization pattern and is present at the designated pole before flagellar synthesis begins, suggesting its role in licensing flagellar formation. This discovery provides insight into a new pathway for regulating flagellum synthesis and coordinating cellular organization in bacteria that rely on polar flagellation and FlhF-dependent localization.PMID:39636223 | DOI:10.7554/eLife.93004

Microbiol Spectr. 2024 Dec 5:e0122624. doi: 10.1128/spectrum.01226-24. Online ahead of print.ABSTRACTUnderstanding the extracellular electron transfer mechanisms of electroactive bacteria could help determine their potential in microbial fuel cells (MFCs) and their microbial syntrophy with redox-active minerals in natural environments. However, the mechanisms of extracellular electron transfer to electrodes by sulfate-reducing bacteria (SRB) remain underexplored. Here, we utilized double-chamber MFCs with carbon cloth electrodes to investigate the extracellular electron transfer mechanisms of Desulfovibrio vulgaris Hildenborough (DvH), a model SRB, under varying lactate and sulfate concentrations using different DvH mutants. Our MFC setup indicated that DvH can harvest electrons from lactate at the anode and transfer them to cathode, where DvH could further utilize these electrons. Patterns in current production compared with variations of electron donor/acceptor ratios in the anode and cathode suggested that attachment of DvH to the electrode and biofilm density were critical for effective electricity generation. Electron microscopy analysis of DvH biofilms indicated DvH utilized filaments that resemble pili to attach to electrodes and facilitate extracellular electron transfer from cell to cell and to the electrode. Proteomics profiling indicated that DvH adapted to electroactive respiration by presenting more pili- and flagellar-related proteins. The mutant with a deletion of the major pilus-producing gene yielded less voltage and far less attachment to both anodic and catholic electrodes, suggesting the importance of pili in extracellular electron transfer. The mutant with a deficiency in biofilm formation, however, did not eliminate current production indicating the existence of indirect extracellular electron transfer. Untargeted metabolomics profiling showed flavin-based metabolites, potential electron shuttles.IMPORTANCEWe explored the application of Desulfovibrio vulgaris Hildenborough in microbial fuel cells (MFCs) and investigated its potential extracellular electron transfer (EET) mechanism. We also conducted untargeted proteomics and metabolomics profiling, offering insights into how DvH adapts metabolically to different electron donors and acceptors. An understanding of the EET mechanism and metabolic flexibility of DvH holds promise for future uses including bioremediation or enhancing efficacy in MFCs for wastewater treatment applications.PMID:39636109 | DOI:10.1128/spectrum.01226-24

Front Pharmacol. 2024 Nov 20;15:1490892. doi: 10.3389/fphar.2024.1490892. eCollection 2024.ABSTRACTBACKGROUND: Pulmonary hypertension (PH) can lead to right ventricular hypertrophy, significantly increasing mortality rates. This study aims to clarify PH-specific metabolites and their impact on genomic and post-translational modifications (PTMs) in cancer, evaluating DHA and EPA's therapeutic potential to mitigate oxidative stress and inflammation.METHODS: Data from 289,365 individuals were analyzed using Mendelian randomization to examine 1,400 metabolites' causal roles in PH. Anti-inflammatory and antioxidative effects of DHA and EPA were tested in RAW 264.7 macrophages and cancer cell lines (A549, HCT116, HepG2, LNCaP). Genomic features like CNVs, DNA methylation, tumor mutation burden (TMB), and PTMs were analyzed. DHA and EPA's effects on ROS production and cancer cell proliferation were assessed.RESULTS: We identified 57 metabolites associated with PH risk and examined key tumor-related pathways through promoter methylation analysis. DHA and EPA significantly reduced ROS levels and inflammatory markers in macrophages, inhibited the proliferation of various cancer cell lines, and decreased nuclear translocation of SUMOylated proteins during oxidative stress and inflammatory responses. These findings suggest a potential anticancer role through the modulation of stress-related nuclear signaling, as well as a regulatory function on cellular PTMs.CONCLUSION: This study elucidates metabolic and PTM changes in PH and cancer, indicating DHA and EPA's role in reducing oxidative stress and inflammation. These findings support targeting these pathways for early biomarkers and therapies, potentially improving disease management and patient outcomes.PMID:39635438 | PMC:PMC11614602 | DOI:10.3389/fphar.2024.1490892

Front Pharmacol. 2024 Nov 20;15:1428604. doi: 10.3389/fphar.2024.1428604. eCollection 2024.ABSTRACTINTRODUCTION: Type 2 diabetes (T2D) is a metabolic disorder marked by disruptions in glucolipid metabolism, with numerous signaling pathways contributing to its progression. The liver, as the hub of glycolipid metabolism, plays a pivotal role in this context. Mulberry leaf (ML), a staple in traditional Chinese medicine, is widely utilized in the clinical management of T2D. Synthesizing existing literature with the outcomes of prior research, it has become evident that ML enhances glucose metabolism via multiple pathways.METHODS: In our study, we induced T2D in rats through a regimen of high-sugar and high-fat diet supplementation, coupled with intraperitoneal injections of streptozotocin. We subsequently administered the aqueous extract of ML to these rats and assessed its efficacy using fasting blood glucose levels and other diagnostic indicators. Further, we conducted a comprehensive analysis of the rats' liver tissues using metabolomics and proteomics to gain insights into the underlying mechanisms.RESULTS: Our findings indicate that ML not only significantly alleviated the symptoms in T2D rats but also demonstrated the capacity to lower blood glucose levels. This was achieved by modulating the glucose-lipid metabolism and amino-terminal pathways within the liver. ACSL5, Dlat, Pdhb, G6pc, Mdh2, Cs, and other key enzymes in metabolic pathways regulated by ML may be the core targets of ML treatment for T2D.DISCUSSION: Mulberry leaf ameliorate STZ induced diabetic rat by regulating hepatic glycometabolism and fatty acid β-oxidation.PMID:39635431 | PMC:PMC11614592 | DOI:10.3389/fphar.2024.1428604

Front Pharmacol. 2024 Nov 20;15:1485035. doi: 10.3389/fphar.2024.1485035. eCollection 2024.ABSTRACTBackground: Polygonum multiflorum shows dual hepatoprotective and hepatotoxic effects. The bioactive components responsible for these effects are unknown. This study investigates whether cis-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (cis-TSG), a stilbene glycoside, has hepatoprotective and/or hepatotoxic effects in a liver injury model. Methods: C57BL/6J mice were administered α-naphthylisothiocyanate (ANIT) to induce cholestasis, followed by treatment with cis-TSG. Hepatoprotective and hepatotoxic effects were assessed using serum biomarkers, liver histology, and metabolomic and lipidomic profiling. Transcriptomic analysis were conducted to explore gene expression changes associated with lipid and bile acid metabolism, inflammation, and oxidative stress. Results and Discussion: ANIT administration caused significant liver injury, evident from elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and dysregulated lipid metabolism. cis-TSG treatment markedly reduced ALT and AST levels, normalized lipid profiles, and ameliorated liver damage, as seen histologically. Metabolomic and lipidomic analyses revealed that cis-TSG influenced key pathways, notably glycerophospholipid metabolism, sphingolipid metabolism, and bile acid biosynthesis. The treatment with cis-TSG increased monounsaturated and polyunsaturated fatty acids (MUFAs and PUFAs), enhancing peroxisome proliferator-activated receptor alpha (PPARα) activity. Transcriptomic data confirmed these findings, showing the downregulation of genes linked to lipid metabolism, inflammation, and oxidative stress in the cis-TSG-treated group. The findings suggest that cis-TSG has a hepatoprotective effect through modulation of lipid metabolism and PPARα activation.PMID:39635428 | PMC:PMC11614611 | DOI:10.3389/fphar.2024.1485035

Anim Nutr. 2024 Jul 27;19:104-116. doi: 10.1016/j.aninu.2024.06.006. eCollection 2024 Dec.ABSTRACTHigh energy diets are a risk factor for intestinal barrier damage. Butyrate, a major energy source for intestinal epithelial cells, has been shown to improve barrier dysfunction and modulate the gut microbiota. In this trial, we examined the preventative effect of coated sodium butyrate (CSB) on high-energy and low-protein (HELP)-induced intestinal barrier injury in laying hens, and also worked to determine the underlying mechanisms by an integrative analysis of gut microbiota and the metabolome. A total of 216 healthy 28-week-old Huafeng laying hens were randomly assigned to 3 groups with 6 replicates each: the CON group (normal diet), HELP group (HELP diet) and CH500 group (500 mg/kg CSB added to HELP diet). The duration of the trial encompassed a period of 10 weeks. The results revealed that CSB treatment improved the laying rate and mitigated the detrimental effects on intestinal barrier function and the inflammatory response induced by the HELP diet in laying hens (P < 0.05). Microbial profiling analysis revealed that the CSB treatment reshaped the HELP-perturbed gut microbiota and promoted the growth of beneficial bacteria (P < 0.05). Untargeted metabolomics analysis revealed that CSB reduced the metabolites associated with intestinal inflammation (P < 0.05). In conclusion, CSB did not merely modulate alterations in the gut microbiota composition and microbial metabolites but also yielded increased egg production, while mitigating intestinal barrier dysfunction and inflammatory responses induced by HELP in laying hens.PMID:39635416 | PMC:PMC11615920 | DOI:10.1016/j.aninu.2024.06.006

Anim Nutr. 2024 Jul 18;19:139-152. doi: 10.1016/j.aninu.2024.06.005. eCollection 2024 Dec.ABSTRACTIn lambs, weaning imposes stress that can contribute to impaired rumen epithelial barrier functionality and immunological dysregulation. In this study, the effects of a yeast co-culture consisting of Saccharomyces cerevisiae and Kluyveromyces marxianus (NM) on rumen health in lambs was evaluated, with a focus on parameters including growth performance, ruminal fermentation, and epithelial barrier integrity, ruminal metabolic function, and the composition of the ruminal bacteria. In total, 24 lambs were grouped into four groups of six lambs including a control (C) group fed a basal diet, and N, M, and NM groups in which lambs were fed the basal diet respectively supplemented with S. cerevisiae yeast cultures (30 g/d per head), K. marxianus yeast cultures (30 g/d per head), and co-cultures of both yeasts (30 g/d per head), the experiment lasted for 42 d. Subsequent analyses revealed that relative to the C group, the average daily gain (ADG) of lambs in the NM group was significantly greater and exhibited significant increases in a range of mRNA relative expression including monocarboxylate transporter 1 (MCT1), (Na+)/hydrogen (H+) exchanger 1 (NHE1), (Na+)/hydrogen (H+) exchanger 3 (NHE3), proton-coupled amino acid transporter 1 (PAT1), vacuolar H+-ATPase (vH+ ATPase), claudin-1, occludin in the rumen epithelium (P < 0.05). Compared with the C group, the pH of the rumen contents in the NM group was significantly decreased , and the concentrations of acetate, propionate, and butyrate were significantly increased (P < 0.05). Analysis of the rumen bacteria showed that the NM group exhibited increases in the relative abundance of Prevotella, Treponema, Moryella, Fibrobacter, CF231 and Ruminococcus (P < 0.05). Metabolomics analyses revealed an increase in the relative content of phthalic acid and cinnamaldehyde in the NM group as compared to the C group (P < 0.05), together with the greater relative content of L-tyrosine, L-dopa, rosmarinic acid, and tyrosol generated by the tyrosine metabolic pathway (P < 0.05). Spearman's correlation analyses revealed relative abundance levels of Fibrobacter and Ruminococcus were positively correlated with the mRNA relative expression levels of PAT1, NHE3, and zonula occluden-1 (ZO-1), as well as with tyrosol, phthalic acid, and cinnamaldehyde levels (P < 0.05). Ultimately, these results suggest that dietary supplementation with NM has a wide range of beneficial effects on weaned lambs and is superior to single bacterial fermentation. These effects include improvements in daily gain and rumen epithelial barrier integrity, as well as improvements in the composition of the rumen microbiome, and alterations in tyrosine metabolic pathways.PMID:39635413 | PMC:PMC11615919 | DOI:10.1016/j.aninu.2024.06.005

Front Mol Neurosci. 2024 Nov 20;17:1383963. doi: 10.3389/fnmol.2024.1383963. eCollection 2024.ABSTRACTMicrobubble (MB)-assisted ultrasound (US) is an innovative modality for the non-invasive, targeted, and efficient delivery of therapeutic molecules into the brain. Previously, we reported the first metabolomic signature of blood-brain barrier opening (BBBO) induced by MB-assisted US. In the present study, the neurometabolic consequences of acoustically-mediated BBBO on cerebral tissue were investigated using multimodal metabolomics approaches. Sinusoid US waves (1 MHz, peak negative pressure 0.6 MPa, burst length 10 ms, total treatment time 30 s, MB bolus dose 0.7 × 105 MBs/g) were applied on the rats' right striatum (ipsilateral side). Brain was collected and both striata were then dissected 3 h, 2 days, and 1 week after BBBO. After tissue preparation, the samples were analyzed using nuclear magnetic resonance spectrometry (NMRS) and high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS). Our findings showed a slight disruption of metabolic pathways in contralateral striata of animals. Analyses of metabolic pathways indicated changes in amino acid metabolisms. In addition, tryptophan derivate dosages revealed the perturbation of a central metabolite of the kynurenine pathway (i.e., 3-hydroxy-kynurenine). In conclusion, the acoustically-mediated BBBO of the ipsilateral cerebral hemisphere induced significant change in metabolism of contralateral one.PMID:39634608 | PMC:PMC11615074 | DOI:10.3389/fnmol.2024.1383963

Food Chem X. 2024 Nov 15;24:101997. doi: 10.1016/j.fochx.2024.101997. eCollection 2024 Dec 30.ABSTRACTIn the paper, metabolomics techniques based on UHPLC-QE-MS were used to study raw black beans, steaming black beans, and their in vitro digestion products. The results show that the three groups of raw black beans, atmospheric pressure-steamed black beans, and their in vitro digests comprised 922, 945, and 878 characteristic metabolites, respectively, dominated by amino acids, organic acids, polyphenols, and sugars. After screening the differential metabolites, content comparison, the content of amino acids, sugars, and phenolics in black beans was found to be increased after atmospheric steaming. During in vitro digestion, the amino acid content increased and the phenolic content decreased, with amino acid synthesis, phenolic degradation, and conversion predominating. This study provides data to support the changes in black beans metabolites during atmospheric steam processing and in vitro digestion.PMID:39634527 | PMC:PMC11615610 | DOI:10.1016/j.fochx.2024.101997

Kidney Med. 2024 Oct 16;6(12):100920. doi: 10.1016/j.xkme.2024.100920. eCollection 2024 Dec.ABSTRACTRATIONALE & OBJECTIVE: Diabetic kidney disease (DKD) is one of the leading causes of end-stage kidney disease globally. We aim to identify proteomic and metabolomic correlates of histologically confirmed DKD that may improve our understanding of its pathophysiology.STUDY DESIGN: A cross-sectional study.SETTING & PARTICIPANTS: A total of 434 Boston Kidney Biopsy Cohort participants.PREDICTORS: Histopathological diagnosis of DKD on biopsy.OUTCOMES: Proteins and metabolites associated with DKD.ANALYTICAL APPROACH: We performed linear regression to identify circulating proteins and metabolites associated with a histopathological diagnosis of DKD (n = 81) compared with normal or thin basement membrane (n = 27), and other kidney diseases without diabetes (n = 279). Pathway enrichment analysis was used to explore biological pathways enriched in DKD. Identified proteins were assessed for their discriminative ability in cases of DKD versus a distinct set of 48 patients with diabetes but other kidney diseases.RESULTS: After adjusting for age, sex, estimated glomerular filtration, and albuminuria levels, there were 8 proteins and 1 metabolite that differed between DKD and normal/thin basement membrane, and 84 proteins and 11 metabolites that differed between DKD and other kidney diseases without diabetes. Five proteins were significant in both comparisons: C-type mannose receptor 2, plexin-A1, plexin-D1, renin, and transmembrane glycoprotein NMB. The addition of these proteins improved discrimination over clinical variables alone of a histopathological diagnosis of DKD on biopsy among patients with diabetes (change in area under the curve 0.126; P = 0.008).LIMITATIONS: A cross-sectional approach and lack of an external validation cohort.CONCLUSIONS: Distinct proteins and biological pathways are correlated with a histopathological diagnosis of DKD.PMID:39634330 | PMC:PMC11615146 | DOI:10.1016/j.xkme.2024.100920

Front Endocrinol (Lausanne). 2024 Nov 20;15:1481014. doi: 10.3389/fendo.2024.1481014. eCollection 2024.ABSTRACTINTRODUCTION: Microplastics (MPs) are environmental pollutants that pose potential risks to living organisms. MPs have been shown to accumulate in human organs, including the placenta. In this study, we investigated the biochemical impact of 5 μm polystyrene microplastics (PS-MPs) on term placental chorionic villi explants, focusing on cytotoxicity, oxidative stress, metabolic changes, and the potential for MPs to cross the placental barrier.METHODS: Term placental chorionic explants were cultured for 24 hours with varying concentrations of PS-MPs, with MTT assays used to determine the appropriate concentration for further analysis. Cytotoxicity was assessed using the lactate dehydrogenase (LDH) release assay over a period of up to 72 hours. Reactive oxygen species formation and antioxidant activity were evaluated using biochemical assays. Metabolomic profiling was performed using proton nuclear magnetic resonance (1H NMR).RESULTS: Placental explants exposed to 100 μg/mL of PS-MPs showed a significant increase in cytotoxicity over time (p < 0.01). Levels of mitochondrial and total superoxide anion (p < 0.01 and p < 0.05, respectively) and hydrogen peroxide (p < 0.001) were significantly elevated. PS-MP exposure resulted in a reduction in total sulfhydryl content (p < 0.05) and the activities of antioxidant enzymes superoxide dismutase (p < 0.01) and catalase (p < 0.05), while glutathione peroxidase activity increased (p < 0.05), and the oxidized/reduced glutathione ratio decreased (p < 0.05). Markers of oxidative damage, such as malondialdehyde and carbonylated proteins, also increased significantly (p < 0.001 and p < 0.01, respectively), confirming oxidative stress. Metabolomic analysis revealed significant differences between control and PS-MP-exposed groups, with reduced levels of alanine, formate, glutaric acid, and maltotriose after PS-MP exposure.DISCUSSION: This study demonstrates that high concentrations of PS-MPs induce time-dependent cytotoxicity, oxidative stress, and alterations in the TCA cycle, as well as in folate, amino acid, and energy metabolism. These findings highlight the need for further research to clarify the full impact of MP contamination on pregnancy and its implications for future generations.PMID:39634179 | PMC:PMC11614646 | DOI:10.3389/fendo.2024.1481014

Front Aging. 2024 Nov 20;5:1494095. doi: 10.3389/fragi.2024.1494095. eCollection 2024.ABSTRACTINTRODUCTION: Aging is a complex process marked by a gradual decline in physiological function and increased susceptibility to diseases. Telomere length is frequently regarded as one of the primary biomarkers of aging. Metabolic profiles are key features in longevity and have been associated with both age and age-related diseases. We previously reported an increase in the telomere length in healthy female subjects when Ramadan fasting was combined with physical training. This study aims to characterize the metabolic signature differentiating the combined effects of exercise and fasting from exercise alone and explore the correlations with the previously reported telomere length changes.METHODS: Twenty-nine young, non-obese, and healthy female subjects were previously randomized into two groups: one group followed a 4-week exercise program, while the other group followed the same 4-week exercise program but also fasted during Ramadan. Metabolic profiles were assessed pre- and post-intervention using untargeted metabolomics.RESULTS AND DISCUSSION: Our results showed a significant decrease in many lipid metabolites in the exercise-while-fasting group, particularly ceramides. Our study sheds light on the dynamic changes in lipid metabolism and its potential role in inflammation and age-related diseases, and contributes to the broader understanding of how lifestyle factors can influence cellular aging and metabolic health.PMID:39633874 | PMC:PMC11615071 | DOI:10.3389/fragi.2024.1494095