PubMed

BMC Oral Health. 2024 Nov 29;24(1):1455. doi: 10.1186/s12903-024-05230-5.ABSTRACTBACKGROUND: Chronic apical periodontitis (CAP) has been linked to the development of atherosclerosis, although the underlying mechanisms remain unclear. This study aimed to investigate the role of gut microbiota disruption in CAP-induced atherosclerosis development, focusing on trimethylamine N-oxide (TMAO)-related metabolites.METHODS: The study utilized fecal microbiota transplantation (FMT) to transfer gut microbiota from mice with CAP to healthy mice. Atherosclerosis development was assessed by analyzing lesions in the aortic arch and aortic root. Serum lipid and inflammatory factor levels were measured. Composition and diversity of gut microbiota were analyzed using targeted metabolomics, with a focus on the ratio of Firmicutes to Bacteroidetes. The expression of hepatic flavin-containing monooxygenase 3 (FMO3) and serum TMAO levels were also evaluated.RESULTS: Mice receiving gut microbiota from CAP mice showed increased atherosclerotic lesions compared to controls, without significant differences in serum lipid or inflammatory factor levels. Alterations in gut microbiota composition were observed, characterized by an increase in the Firmicutes to Bacteroidetes ratio. Peptostreptococcaceae abundance positively correlated with atherosclerosis severity, while Odoribacteraceae showed a negative correlation. No significant differences were found in hepatic FMO3 expression or serum TMAO levels.CONCLUSIONS: The study confirms the role of gut microbiota disruption in CAP-mediated atherosclerosis development, independent of serum lipid or TMAO levels. Alterations in gut microbiota composition, particularly increased Firmicutes to Bacteroidetes ratio and specific bacterial families, were associated with atherosclerosis severity. These findings highlight the intricate interplay between gut microbiota and cardiovascular health in the context of CAP.PMID:39614243 | DOI:10.1186/s12903-024-05230-5

Sci Rep. 2024 Nov 29;14(1):29720. doi: 10.1038/s41598-024-80986-y.ABSTRACTProstate cancer (PCa) is the second most common malignancy affecting men globally. Recent advances in metabolomics have highlighted significant alterations in specific amino acid (AA) metabolism linked to PCa, indicating their potential utility in diagnosis and therapy. However, no direct causal association between serum AA levels and PCa risk has been established. A total of 35 patients with PCa and 30 individuals with benign prostatic hyperplasia (BPH) were recruited for this study. Targeted metabolomic analysis was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry on serum samples. Two-sample Mendelian randomization (MR) was applied to explore potential causal links between serum AA levels and PCa risk, including mediator effects using dual-phase MR and assessing reverse causality through reverse MR. Results Targeted metabolomic profiling identified six amino acids-glutamate (Glu), Ser, histidine (His), arginine (Arg), aspartic acid (Asp), and glycine (Gly)-that showed significant area under the ROC curve in differentiating between BPH and PCa cases. Notably, Glu demonstrated an inverse association with PCa risk, distinct from the other AAs identified. However, definitive evidence supporting a causal relationship between low Glu levels and increased PCa risk was not observed. Our results suggest a protective role of Glu against PCa development, which may have implications for disease prognosis. Increasing dietary Glu intake may present a potential preventive or therapeutic approach for PCa.PMID:39614073 | DOI:10.1038/s41598-024-80986-y

Insights Imaging. 2024 Nov 29;15(1):289. doi: 10.1186/s13244-024-01859-6.ABSTRACTOBJECTIVES: Gut-brain axis dysfunction has emerged as a key contributor to the pathogenesis of Crohn's disease (CD). The elucidation of neural alterations may provide novel insights into its management. We aimed to develop a multiparameter brain MRI-based radiomics model (RM) for characterizing neural alterations in CD patients and to interpret these alterations using multiomics traits.METHODS: This prospective study enrolled 230 CD patients and 46 healthy controls (HCs). Participants voluntarily underwent brain MRI and psychological assessment (n = 155), blood metabolomics analysis (n = 260), and/or fecal 16S rRNA sequencing (n = 182). The RM was developed using 13 features selected from 13,870 first-order features extracted from multiparameter brain MRI in training cohort (CD, n = 75; HCs, n = 32) and validated in test cohort (CD, n = 34; HCs, n = 14). Multiomics data (including gut microbiomics, blood metabolomics, and brain radiomics) were compared between CD patients and HCs.RESULTS: In the training cohort, area under the receiver operating characteristic curve (AUC) of RM for distinguishing CD patients from HCs was 0.991 (95% confidence interval (CI), 0.975-1.000). In test cohort, RM showed an AUC of 0.956 (95% CI, 0.881-1.000). CD-enriched blood metabolites such as triacylglycerol (TAG) exhibited significant correlations with both brain features detected by RM and CD-enriched microbiota (e.g., Veillonella). One notable correlation was found between Veillonella and Ctx-Lh-Middle-Temporal-CBF-p90 (r = 0.41). Mediation analysis further revealed that dysbiosis, such as of Veillonella, may regulate the blood flow in the middle temporal cortex through TAG.CONCLUSION: We developed a multiparameter MRI-based RM that characterized the neural alterations of CD patients, and multiomics data offer potential evidence to support the validity of our model. Our study may offer clues to help provide potential therapeutic targets.CRITICAL RELEVANCE STATEMENT: Our brain-gut axis study developed a novel model using multiparameter MRI and radiomics to characterize brain changes in patients with Crohn's disease. We validated this model's effectiveness using multiomics data, making it a potential biomarker for better patient management.KEY POINTS: Utilizing multiparametric MRI and radiomics techniques could unveil Crohn's disease's neurophenotype. The neurophenotype radiomics model is interpreted using multiomics data. This model may serve as a novel biomarker for Crohn's disease management.PMID:39613905 | DOI:10.1186/s13244-024-01859-6

Sci Rep. 2024 Nov 29;14(1):29737. doi: 10.1038/s41598-024-81005-w.ABSTRACTFruit color is a crucial trait for bell pepper. To investigate the mechanism of color formation, three bell pepper lines with different color (yellow, orange and red) were used as materials to conduct comprehensive targeted metabolomic and transcriptomic analyses. During the process of fruit development, 54 carotenoids metabolites were discovered, exhibiting unique accumulation patterns and notable variety specificity. The types and content of carotenoids in orange fruit (OM) were notably greater compared to the other two varieties. Red pigment (capsanthin and capsorubin) was specifically enriched in red fruit (RM), and yellow pigment (lutein and zeaxanthin) is the highest in yellow fruit (YM) and OM. Five modules positively correlated with carotenoid accumulation and one negative module was determined by weighted gene co-expression network analysis (WGCNA). Additionally, transcription factors (TFs) and hub genes related to carotenoid synthesis were predicted. By elucidating the regulation of 7 key carotenoid metabolites by 14 critical genes and 5 key TFs, we constructed a comprehensive carotenoid biosynthesis metabolic network that comprehensively explains the pigment changes observed in green and mature pepper fruit. Overall, the results not only provide important insights into carotenoid synthesis pathway, but also lay a solid base for revealing the mechanism of bell pepper color transformation.PMID:39613866 | DOI:10.1038/s41598-024-81005-w

Talanta. 2024 Nov 23;285:127280. doi: 10.1016/j.talanta.2024.127280. Online ahead of print.ABSTRACTCervical cancer (CC) remains a critical public health issue, highlighting the importance of early detection. However, current methods such as cytological and HPV testing face challenges of invasiveness and low patient compliance. Exosomes, emerging as crucial in cancer diagnosis, offer promise due to their noninvasive, highly specificity, and abundant biomarkers. However, isolating exosomes efficiently remains challenging. In this study, we designed and synthesized a bifunctional affinity nanomaterial Fe3O4 @CD63-CLIKKPF, based on the synergistic interaction between its modified aptamer CD63 and peptide CLIKKPF, and CD63 protein and PS of exosomes which can achieve high specificity and high yield separation of urinary exosomes. Notably, the co-modified aptamer CD63 and peptide CLIKKPF not only enable efficient exosome isolation by leveraging dual-affinity mechanisms through a synergistic "AND" logic analysis, but also could be achieved on the Fe3O4 in one-step reaction at room temperature via Fe-S bonding. Combined with LC-MS/MS, we conducted exosome metabolomics analysis in healthy individuals and CC patients across various stages, and machine learning models demonstrated accurate classification (accuracy >0.822) and prediction capabilities for CC. Furthermore, six key metabolites indicative of CC progression were identified and validated in additional patient samples, highlighting their potential as biomarkers. Overall, this study establishes a novel method for exosome metabolomics in CC, offering insights for non-invasive early diagnosis and progression prediction on a large scale.PMID:39613490 | DOI:10.1016/j.talanta.2024.127280

Reprod Toxicol. 2024 Nov 27:108758. doi: 10.1016/j.reprotox.2024.108758. Online ahead of print.ABSTRACTDi-(2-ethylhexyl) phthalate (DEHP) exposure has been associated with male reproductive damage, but the mechanisms involved remain incompletely defined. This study aims to investigate the effects of DEHP exposure on the testes of prepubertal rats through an integrative analysis of metabolomics and transcriptomics, combined with molecular experiments. DEHP exposure resulted in decreased testis weight and increased oxidative stress level in the testis tissues of prepubertal male rats. Moreover, our findings showed a disordered testis structure, reduced spermatogenic and Sertoli cells as well as destruction of mitochondria structure in the testis tissues of DEHP-treated prepubertal male rats. Transcriptome function analysis together with metabolome function analysis indicated that spermatogenesis, apoptosis, inflammatory, lipid metabolism as well as DNA repair signaling pathway were enriched in the testis of DEHP-treated prepubertal male rats. The integrative omics analysis further suggested that TNF-α induced apoptosis played a crucial role in mediating the detrimental effects of DEHP exposure on the testis of prepubertal rats, which was validated by ELISA, Western blotting and Tunel assays. Validation experiments conducted in vitro using GC-2 cells corroborated these findings, demonstrating that mono-(2-ethylhexyl) phthalate (MEHP), the main active metabolite of DEHP, significantly inhibits cell proliferation and increases apoptosis via activating the TNF-α apoptosis pathway. Overall, these findings provided a novel mechanism of dysregulated spermatogenesis of DEHP exposure on the testes of prepubertal rats.PMID:39613166 | DOI:10.1016/j.reprotox.2024.108758

J Ethnopharmacol. 2024 Nov 27:119158. doi: 10.1016/j.jep.2024.119158. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The current treatment for diabetic nephropathy (DN) is inadequate, and there is an urgent need for an effective and minimally adverse alternative therapy. Da-Chai-Hu Decoction (DCHD) is a time-honored herbal remedy from Chinese medicine, boasting a legacy spanning more than 1800 years. Clinical observations suggest that it may provide therapeutic benefits for individuals with type 2 diabetes mellitus (T2DM). Nonetheless, the specific advantages of DCHD in relation to diabetic nephropathy (DN) and the mechanisms through which it operates are still not well understood.AIM OF THE STUDY: This research aims to investigate whether DCHD can avert renal damage in mice with T2DM and to elucidate the mechanisms by which DCHD combats DN through the integration of metabolomics and network pharmacology.MATERIALS AND METHODS: The beneficial effects of DCHD on DN was initially evaluated using a renal injury model in T2DM mice. Subsequently, untargeted metabolomics analysis was utilized to investigate the potential mechanisms of DCHD against DN. Additionally, UPLC-MS/MS was employed to identify the chemical components in DCHD and the absorption components in DCHD-treated plasma. Network pharmacology and our newly proposed function-guided and network-based complementary methodology (FNICM) was utilized to predict the potential pathway of DCHD intervention in DN. Finally, the core pathway was validated through Western blotting analysis and ELISA.RESULTS: A total of 260 chemical components were detected in DCHD, and 41 absorption components were found in DCHD-treated plasma by UPLC-HR MS/MS for the first time. Additionally, In vivo experiments revealed that DCHD exerts the ability to regulate the disorder in glucose/lipid metabolism and improves kidney dysfunction. Furthermore, a comprehensive analysis utilizing non-targeted urine metabolomics and the FNICM method identified a total of 33 differential metabolites, which were categorized as core metabolites. Lastly, combined FNICM, network pharmacology and experimental pharmacology studies suggest that DCHD may regulate the AGEs/RAGE/AKT pathways in combating DN.CONCLUSIONS: The results indicate that DCHD treats DN through the inhibition of the AGEs/RAGE/AKT pathway and by regulating metabolic profiles.PMID:39613006 | DOI:10.1016/j.jep.2024.119158

Biochim Biophys Acta Mol Basis Dis. 2024 Nov 27:167567. doi: 10.1016/j.bbadis.2024.167567. Online ahead of print.ABSTRACTIt becomes increasingly clear that the tissue specificity of mitochondrial diseases might in part rely on their ability to compensate for mitochondrial defects, contributing to the heterogeneous nature of mitochondrial diseases. Here, we investigated tissue-specific responses to cytochrome c oxidase (CIV or COX) deficiency using a mouse model with heart and skeletal muscle-specific depletion of the COX assembly factor COX10. At three weeks of age, both tissues exhibit pronounced CIV depletion but respond differently to oxidative phosphorylation (OXPHOS) impairment. Heart-specific COX10 depletion caused severe dilated cardiomyopathy, while skeletal muscle experiences less damage. Cardiac CIV deficiency triggered extensive metabolic remodelling and stress response activation, potentially worsening cardiomyopathy, whereas skeletal muscle showed no stress response or significant metabolic changes. Our findings highlight distinct tissue capacities for managing CIV deficiency, explaining how identical primary defects can lead to different phenotypic outcomes and contribute to the heterogeneous progression of mitochondrial diseases.PMID:39613003 | DOI:10.1016/j.bbadis.2024.167567

J Hazard Mater. 2024 Nov 26;483:136668. doi: 10.1016/j.jhazmat.2024.136668. Online ahead of print.ABSTRACT8:2 Chlorinated polyfluoroalkyl ether sulfonate (8:2 Cl-PFESA) is a substitute for perfluorooctane sulfonate and an emerging environmental pollutant, yet its bioaccumulation and health risks are poorly understood. We established a subchronic exposure model in mice (0.04, 0.2, and 1 mg/kg/d) to evaluate its adverse effects. Our findings show extensive distribution of 8:2 Cl-PFESA in various tissues (plasma, liver, kidney, brain, heart, lung, testis, ovary, spleen, thymus, thyroid, uterus, large intestine, small intestine, muscle, and fat), with the highest accumulation in the liver, identified as the primary storage organ. Liver histopathology revealed elevated alanine aminotransferase levels, reduced triglycerides, and ballooning degeneration. Proteomics analysis indicated significant involvement of amino acid metabolism in 8:2 Cl-PFESA-induced hepatotoxicity. Metabolomics analysis further highlighted pronounced alterations in amino acid interconversion. Multi-omics integration revealed disruptions in amino acid metabolism, particularly with alanine, histidine, and tryptophan, identifying key proteins EHHADH, HAL, MAO-A, ALDH3A2, and TDO2 as crucial connectors in these metabolic processes, validated by Western blot experiments. This study provides a comprehensive analysis of 8:2 Cl-PFESA accumulation and distribution in biological systems, demonstrating that hepatotoxicity is primarily mediated through amino acid metabolism disruption, offering insights for pollution mitigation strategies and future toxicological research.PMID:39612878 | DOI:10.1016/j.jhazmat.2024.136668

Food Chem. 2024 Nov 23;466:142219. doi: 10.1016/j.foodchem.2024.142219. Online ahead of print.ABSTRACTIn this study, the flavor of egg whites was significantly improved by lactic acid fermentation, and the metabolic networks of metabolites, volatile compounds, and enzymes were established using gas chromatography-mass spectrometry, metabolomic, and proteomic. Results indicate that among ten types of common lactic acid bacteria, Streptococcus thermophilus endowed egg white with the most pleasant flavor through increasing aldehydes, ketones, alcohols, esters, terpenoids, and aromatic compounds. Amino acid catabolism was the predominant pathway for generating most aldehydes, alcohols, acids, and esters. The changes in the organic acids and derivatives (mainly amino acids, peptides, and analogues) concentration during fermentation are attributed to the hydrolysis of egg white proteins by proteinases and peptidases, and the regulation of enzymes involved in amino acid biosynthesis and other reactions. This study provides a valuable reference for future investigations focusing on regulating the flavor release of egg whites.PMID:39612849 | DOI:10.1016/j.foodchem.2024.142219

Sci Total Environ. 2024 Nov 28;957:177776. doi: 10.1016/j.scitotenv.2024.177776. Online ahead of print.ABSTRACTPropranolol (PRO) has been detected in water bodies worldwide, attributed to the incomplete removal by wastewater treatment processes. Although reports exist on the removal of PRO by wetland plants such as Phragmites communis, research on the impact of PRO on soil organic carbon (SOC) components in these plants' rhizospheres remains scarce. This investigation examined the impacts of 0.5 μg/L and 50 μg/L concentrations of PRO on the rhizosphere of P. communis over a 21-day laboratory experiment. PRO exposure slightly promoted root growth, notably enhancing fine root development at a lower concentration. A notable decrease in SOC content was observed in the PRO-treated samples: specifically, the proportion of mineral-associated organic carbon (MAOC) rose (from 47.90 % to 33.17 %), whereas the proportion of particulate organic carbon (POC) significantly declined following PRO treatment (from 52.10 % to 66.83 %). Moreover, Proteobacteria and Nitrospirae experienced significant promotion in the high-concentration samples while Bacteroidetes and Verrucomicrobia were inhibited. The metabolomic analysis demonstrated that glycine, serine, and threonine metabolism was the principal differential metabolic pathway in varying concentrations of PRO exposure. Additionally, across varying PRO concentrations, plant influence emerged as the predominant factor affecting POC alterations, whereas MAOC changes resulted from the synergistic interaction of plants and associated bacteria. The outcomes of this study mark a critical advancement towards a thorough assessment of PRO's impact on the rhizosphere of wetland plants, bearing significant ramifications for evaluating PRO's environmental effects.PMID:39612712 | DOI:10.1016/j.scitotenv.2024.177776

Poult Sci. 2024 Nov 23;104(1):104556. doi: 10.1016/j.psj.2024.104556. Online ahead of print.ABSTRACTOver the past decade, metabolomic research in livestock and poultry has gained considerable momentum; however, quail metabolomics still lags behind that of livestock species such as chickens, pigs, and cattle. Quails are important models due to their low-cost protein sources-both eggs and meat-and practical benefits such as minimal space requirements, high egg production, disease resistance, and rapid reproduction. Therefore, it is necessary to systematically understand the effects of various factors on quail metabolism to provide a theoretical basis for accurate feeding and breeding practices. In this study, liquid chromatography with tandem mass spectroscopy (LC-MS/MS)-based metabolomics was used to examine the effects of age, breed, and sex on the serum metabolic profile of quails. A total of 550 metabolites were identified. Relative to breed and sex, we found that age played a crucial role in influencing quail serum metabolites. At 20 days of age (D20), quails had high levels of serum thymidine and alpha-D-glucose, while at 70 days of age (D70), the lipids, including 3-isothujone, 15-deoxy-d-12,14-PGJ2, and 2-aminobut-2-enoate dominated the serum. Additionally, xanthine, hypoxanthine, diaminopimelic acid, and 2-deoxy-scyllo-inosose appeared to be specific metabolites of Japanese quail (JAPQ). Serum levels of N-acetylglutamic acid, hydroxypyruvic acid, carnosine, alloepipregnanolone, lumichrome, 6-hydroxynicotinate, and myristic acid were higher in D70 Hengyan white feather quails (HYWQ) than those in D70 JAPQ. Notably, this study also identified 2-hydroxy-2-ethylsuccinic acid and riboflavin as potential specific metabolites in female quails. Furthermore, integration analysis showed that amino acid biosynthesis and metabolism, as well as ABC transporters, were the key pathways distinguishing D20 from D70. Purine metabolism, pyrimidine metabolism, ABC transporters, and TCA cycle were the key pathways distinguishing HYWQ from JAPQ. Differences in energy metabolism and amino acid biosynthesis and metabolism were observed between males and females. These findings enhance our understanding of the dynamic changes in quail serum metabolites influenced by various factors and address the knowledge gap regarding serum metabolic changes at different stages in quails.PMID:39612675 | DOI:10.1016/j.psj.2024.104556

Medicine (Baltimore). 2024 Nov 29;103(48):e40719. doi: 10.1097/MD.0000000000040719.ABSTRACTTo demonstrate the potential for connecting metabolomics with traditional Chinese medicine (TCM) external therapies such as acupuncture and moxibustion, we conducted a literature review on metabolomics as a measurement tool for determining the efficacy of various TCM external therapies. Human research and animal models published in the last 10 years were summarized. The investigation can be classified as follows: Using metabolomics to study metabolic profile changes produced by stimulation of a specific acupoint ST36 indicates the perturbation of metabolites produced by stimulation of acupoints by external TCM treatments can be characterized by metabolomics; and Using metabolomics to reveal the molecular mechanism of various TCM external therapy methods to treat specific diseases such as digestive system disease, cardiovascular disease, neurological disorder, bone disease, and muscle fatigue. We conclude that metabolomics has considerable potential for comprehending TCM external treatment interventions, particularly from a systems perspective. Linking TCM external therapy research with metabolomics can further bridge detailed biological mechanisms with the systematic effect of TCM external therapy, hence providing new paths for gaining a deeper knowledge of the importance of TCM in the treatment and maintenance of health.PMID:39612392 | DOI:10.1097/MD.0000000000040719

mSystems. 2024 Nov 29:e0145024. doi: 10.1128/msystems.01450-24. Online ahead of print.ABSTRACTIt is well known that gut microbial imbalance is a potential factor for the occurrence and development of diabetes mellitus (DM) and its complications. Moreover, the heart and gut microbiota can regulate each other through the gut-metabolite-heart axis. In this study, metagenomics, metabolomics, and transcriptomics were chosen to sequence the changes in gut microbiota, serum metabolite levels, and differentially expressed genes (DEGs) in leptin receptor-deficient db/db mice and analyze the correlation between serum metabolites and gut microbiota or DEGs. According to the results, there were significant differences in the 1,029 cardiac genes and 353 serum metabolites in diabetic mice of the db/db group, including DEGs enriched in the PPAR signaling pathway and increased short-chain carboxylic acids (CAs), when compared with the normal db/m group. According to metagenomics, the gut microbiota of mice in the db/db group were disrupted, and particularly Lachnospiraceae bacteria and Oscillospiraceae bacteria significantly decreased. Also, according to the Pearson correlation analysis, a significant positive correlation was found between CAs and PPAR signaling pathway-related DEGs, and a negative correlation was found between CAs and the abundance of the above-mentioned species. To sum up, type 2 diabetes mellitus (T2DM) can upregulate the expression of partial cardiac genes through the levels of serum short-chain CAs affected by gut microbiota, thus playing a role in the occurrence and development of diabetic cardiomyopathy (DCM).IMPORTANCE: Our research results clearly link the changes in heart genes of T2DM and normal mice with changes in serum metabolites and gut microbiota, indicating that some genes in biological processes are closely related to the reduction of protective microbiota in the gut microbiota. This study provides a theoretical basis for investigating the mechanism of DCM and may provide preliminary evidence for the future use of gut microbiota therapy for DCM.PMID:39611812 | DOI:10.1128/msystems.01450-24

Reproduction. 2024 Nov 1:REP-24-0051. doi: 10.1530/REP-24-0051. Online ahead of print.ABSTRACTTop-down proteomics was employed to construct proteoform atlas of sperm and seminal plasma (SP) from bulls with low (LF) and high (HF) semen freezability. Sperm and seminal proteins were fractionated by tandem size exclusion chromatography (< 30 kDa) and analyzed by reversed-phase liquid chromatography-tandem mass spectrometry. This approach enabled the identification of 299 SP (from 46 families) and 267 sperm proteoforms (from 139 families). Seventy proteoforms belonging to beta-defensin 10, c-type natriuretic peptide (NPPC), caltrin, seminal ribonuclease, osteopontin, and binder of sperm protein (BSP) 3 families were unique to HF bulls' SP. LF seminal proteins had unique 77 proteoforms, including caltrin, NPPC, osteopontin, BSP3, serpin family A member 5, and β-NGF families. Proteoform families of SP in HF and LF bulls were related to Ca2+ uptake, capacitation, acrosome reaction, sperm protection, fertilization and proteolytic processes. Thirty-three proteoforms of NPPC, caltrin, and cylicin-2 families were upregulated in HF sperm. Twenty-two proteoforms of caltrin, cylicin-2, ATP synthases, and malate dehydrogenase families were among those upregulated in LF sperm. Truncated and acetylated histone H2A and non-truncated and acetylated c-Myc binding protein were prevalent in LF sperm. Cylicin-2 proteoforms were observed in HF and LF sperm, and truncated glyceraldehyde-3-phosphate dehydrogenases, only in HF sperm. In silico analyses indicated the enrichment of mitochondrial metabolic pathways in HF sperm, including fatty acid metabolism and TCA cycle. Our study brings an unprecedented description of the bovine SP and sperm proteoforms. Post-translational processing appears to define the bio-properties of semen proteins and their associations with sperm cryoresistance.PMID:39611730 | DOI:10.1530/REP-24-0051

Elife. 2024 Nov 29;13:RP96937. doi: 10.7554/eLife.96937.ABSTRACTBACKGROUND: Alcohol use disorder (AUD) is a global health problem with limited therapeutic options. The biochemical mechanisms that lead to this disorder are not yet fully understood, and in this respect, metabolomics represents a promising approach to decipher metabolic events related to AUD. The plasma metabolome contains a plethora of bioactive molecules that reflects the functional changes in host metabolism but also the impact of the gut microbiome and nutritional habits.METHODS: In this study, we investigated the impact of severe AUD (sAUD), and of a 3-week period of alcohol abstinence, on the blood metabolome (non-targeted LC-MS metabolomics analysis) in 96 sAUD patients hospitalized for alcohol withdrawal.RESULTS: We found that the plasma levels of different lipids ((lyso)phosphatidylcholines, long-chain fatty acids), short-chain fatty acids (i.e. 3-hydroxyvaleric acid) and bile acids were altered in sAUD patients. In addition, several microbial metabolites, including indole-3-propionic acid, p-cresol sulfate, hippuric acid, pyrocatechol sulfate, and metabolites belonging to xanthine class (paraxanthine, theobromine and theophylline) were sensitive to alcohol exposure and alcohol withdrawal. 3-Hydroxyvaleric acid, caffeine metabolites (theobromine, paraxanthine, and theophylline) and microbial metabolites (hippuric acid and pyrocatechol sulfate) were correlated with anxiety, depression and alcohol craving. Metabolomics analysis in postmortem samples of frontal cortex and cerebrospinal fluid of those consuming a high level of alcohol revealed that those metabolites can be found also in brain tissue.CONCLUSIONS: Our data allow the identification of neuroactive metabolites, from interactions between food components and microbiota, which may represent new targets arising in the management of neuropsychiatric diseases such as sAUD.FUNDING: Gut2Behave project was initiated from ERA-NET NEURON network (Joint Transnational Call 2019) and was financed by Academy of Finland, French National Research Agency (ANR-19-NEUR-0003-03) and the Fonds de la Recherche Scientifique (FRS-FNRS; PINT-MULTI R.8013.19, Belgium). Metabolomics analysis of the TSDS samples was supported by grant from the Finnish Foundation for Alcohol Studies.PMID:39611656 | DOI:10.7554/eLife.96937

Am J Physiol Cell Physiol. 2024 Nov 29. doi: 10.1152/ajpcell.00611.2023. Online ahead of print.ABSTRACTThe TCA cycle serves as a central hub to balance catabolic and anabolic needs of the cell, where carbon moieties can either contribute to oxidative metabolism or support biosynthetic reactions. This differential TCA cycle engagement for glucose-derived carbon has been extensively studied in cultured cells, but the fate of fatty acid (FA)-derived carbons is poorly understood. To fill the knowledge gap, we have developed a strategy to culture cells with long-chain FAs without altering cell viability. By tracing 13C-FA we show that FA oxidation (FAO) is robust in both proliferating and oxidative cells while the metabolic pathway after citrate formation is distinct. In proliferating cells, a significant portion of carbon derived from FAO exits canonical TCA cycle as citrate and converts to unlabeled malate in cytosol. Increasing FA supply or b-oxidation does not change the partition of FA-derived carbon between cytosol and mitochondria. Oxidation of glucose competes with FA derived carbon for the canonical TCA pathway thus promoting FA carbon flowing into the alternative TCA pathway. Moreover, the coupling between FAO and the canonical TCA pathway changes with the state of oxidative energy metabolism.PMID:39611618 | DOI:10.1152/ajpcell.00611.2023

Amyotroph Lateral Scler Frontotemporal Degener. 2024 Nov 29:1-7. doi: 10.1080/21678421.2024.2433578. Online ahead of print.ABSTRACTOBJECTIVE: Over the past years, interest in the role of gut microbiota in neurodegenerative diseases has emerged. Despite numerous publications over the past decade, both in human and pre-clinical studies, there is no clear consensus on the microbiota's role or involvement in ALS. Few studies on mouse models of ALS highlighted a correlation between specific bacteria species and the prognostic or severity of the disease. Still these results lack reproducibility and remain controverted. In this article we present a study of fecal microbiota in the SOD1G93A mouse model associated with a metabolomic analysis of cecum content, compared to controls.METHODS: Intestinal metabolomic profile and fecal microbiota were assessed in two cohorts of SODG93A mice compared to wildtype controls at the terminal stage of the ALS disease.RESULTS: Results showed a significant difference in metabolomic profile in SOD1G93A mice compared to controls but without a marked change in composition and diversity of fecal microbiota. Nevertheless, we observed an increase of Lachnospiraceae family, which are butyrate-producer bacteria, in SOD1G93A mice. Moreover, some metabolites with significantly different intestinal concentrations are partially produced and linked with intestinal bacteria, such as riboflavin, hippurate, and N-acetylputrescine, leaving us convinced of the interest in looking further into the role of the microbiota in ALS.CONCLUSIONS: Despite an alteration of the intestinal metabolome in SOD1G93A mice, microbiota data did not show significant changes, underlying the need for further research.PMID:39611550 | DOI:10.1080/21678421.2024.2433578

New Phytol. 2024 Nov 29. doi: 10.1111/nph.20323. Online ahead of print.ABSTRACTMarine microalgae demonstrate a notable capacity to adapt to high CO2 and warming in the context of global change. However, the dynamics of their evolutionary processes under simultaneous high CO₂ and warming conditions remain poorly understood. Here, we analyze the dynamics of evolution in experimental populations of a model marine diatom Phaeodactylum tricornutum. We conducted whole-genome resequencing of populations under ambient, high-CO2, warming and high CO2 + warming at 2-yr intervals over a 4-yr adaptation period. The common genes selected between 2- and 4-yr adaptation were found to be involved in protein ubiquitination and degradation and the tricarboxylic acid (TCA) cycle, and were consistently selected regardless of the experimental conditions or adaptation duration. The unique genes selected only by 4-yr adaptation function in respiration, fatty acid, and amino acid metabolism, facilitating adaptation to prolonged high CO2 with warming conditions. Corresponding changes at the metabolomic level, with significant alterations in metabolites abundances involved in these pathways, support the genomic findings. Our study, integrating genomic and metabolomic data, demonstrates that long-term adaptation of microalgae to high CO2 and/or warming can be characterized by a complex and dynamic genetic process and may advance our understanding of microalgae adaptation to global change.PMID:39611545 | DOI:10.1111/nph.20323

Biosci Biotechnol Biochem. 2024 Nov 28:zbae182. doi: 10.1093/bbb/zbae182. Online ahead of print.ABSTRACTProper diet is crucial for obesity prevention. Food health research primarily focuses on two aspects: the pathogenesis of lifestyle-related diseases caused by obesity and the identification of dietary components that can aid in the prevention and treatment of lifestyle-related diseases. Substantial knowledge has been accumulated regarding these aspects via health function evaluations based on biological experiments. However, the intricate causal relationships and specific biological metabolites or food compounds that affect health remain unclear. To address these issues, recent my studies have incorporated mass spectrometry data, particularly metabolomic data obtained via comprehensive component analysis, to enhance health function evaluation via biological experiments. These studies have revealed various biological and healthy compounds derived from different food materials for the management of obesity-induced metabolic disorders.PMID:39611358 | DOI:10.1093/bbb/zbae182