PubMed

Biology (Basel). 2024 Jul 9;13(7):511. doi: 10.3390/biology13070511.ABSTRACTThe aim of this study was to investigate the metabolic changes associated with the anti-obesity effects of fermented blackberry extracts in the liver tissues of high-fat-diet-fed mice using mass spectrometry-based metabolomics analysis. C57BL/6J mice were divided into eight groups: normal-diet-fed mice, high-fat-diet-fed mice, high-fat diet treated with blackberry extract, high-fat-diet mice treated with blackberry fermented by L. plantarum, and high-fat diet with blackberry fermented by L. brevis. After 12 weeks, the high-fat-diet group exhibited a greater increase in liver weight compared to the control group, and among the groups, the group administered with blackberry fermented with L. plantarum showed the most pronounced reduction in liver weight. As the primary organ responsible for amino acid metabolism, the liver is crucial for maintaining amino acid homeostasis. In our study, we observed that the levels of several essential amino acids, including isoleucine and valine, were decreased by the high-fat diet, and were recovered by administration of blackberry extract fermented with L. plantarum. Our results demonstrated the potential of blackberry extract fermented with L. plantarum as a functional material for metabolic disorders by restoring some of the amino acid metabolism disturbances induced by a high-fat diet.PMID:39056704 | DOI:10.3390/biology13070511

Biology (Basel). 2024 Jun 30;13(7):488. doi: 10.3390/biology13070488.ABSTRACTThe rapid development of the mariculture industry has been hindered by limited coastal aquaculture space. To utilize the abundant inland saline-alkaline water, we studied the physiological effects of high carbonate alkalinity stress and high pH stress on Fenneropenaeus chinensis. The study employed quantitative proteomics by tandem mass tag (TMT) and non-targeted metabolomics analysis using a liquid chromatograph mass spectrometer (LC-MS) to understand the physiological and biochemical adaptive mechanisms of the hepatopancreas of F. chinensis in response to saline-alkaline stress at the molecular level. We designed two stress groups as follows: a high carbonate alkalinity (CA) group and a combined high carbonate alkalinity and high pH (CP) group. The study found that the protein and metabolic profiles of the two stress groups were changed, and the CP group, which was exposed to dual stresses, incurred more severe damage to the hepatopancreas compared to that of the CA group. After exposure to CA and CP, the hepatopancreas of F. chinensis showed significant alterations in 455 proteins and 50 metabolites, and 1988 proteins and 272 metabolites, respectively. In addition, F. chinensis upregulated the level of energy metabolism in the hepatopancreas to defend against osmotic imbalance caused by CA or CP stress, which was demonstrated by the significant upregulation of important proteins and metabolites in glycolysis, pyruvate metabolism, TCA cycle, and fatty acid oxidation. Additionally, pattern recognition receptors, the phenol oxidase system, and various immune-related metabolic enzymes and metabolites were also affected. The immune homeostasis of F. chinensis was affected by the alteration of the antioxidant system following exposure to CA or CP. These findings provide valuable information for F. chinensis saline-alkaline water cultivation practices.PMID:39056683 | DOI:10.3390/biology13070488

Pharm Biol. 2024 Dec;62(1):621-633. doi: 10.1080/13880209.2024.2378011. Epub 2024 Jul 26.ABSTRACTCONTEXT: Pyrus calleryana Decne (Rosaceae), renowned for its therapeutic properties, is known to moisturize the lungs (removing dryness; relieving cough), clear heat (acting as an antipyretic; febrifuge) and aid in detoxification (relieving pyogenic inflammation; eliminating toxins). However, scientific evidence supporting its efficacy in wound healing is lacking.OBJECTIVE: This study investigated P. calleryana samples collected over a year to explore metabolite variations and their impact on skin wound-healing activities.MATERIALS AND METHODS: P. calleryana (PC) twigs and leaves were collected from the Matsu Islands, Taiwan, spanning 2018-2020. Extracts were prepared using 95% ethanol or water, and we assessed the chemical composition, total phenolic/triterpenoid contents and antioxidant properties. Metabolites were analysed via LC-MS/MS and molecular networking. Wound healing potential was evaluated on WS-1 cells through MTT and migration assays, and gene expression analyses, with tests including control (DMSO), compounds 1 (3'-hydroxylbenzyl-4-hydroxybenzoate-4'-O-β-glucopyranoside) and 2 (vanilloylcalleryanin) (100 µM), and a positive control (ascorbic acid, 100 µM) for 24 h.RESULTS: Significant variations in extract compositions were observed based on the solvent used, with distinct metabolomic profiles in extracts collected during different months. Notably, compounds 1 and 2 showed no cytotoxic effects on human dermal fibroblast cells and significantly accelerated wound closure at 100 μM. A gene expression analysis indicated upregulation of wound healing-associated genes, including MMP-1 (matrix metalloproteinase-1) and COL1A1 (collagen, type 1, alpha 1).CONCLUSIONS: This study reports the first evidence of PC compounds aiding wound healing. Utilizing Global Natural Products Social Molecular Networking (GNPS) and principal component analysis (PCA) approaches, we unveiled metabolomic profiles, suggesting the potential to expedite wound-healing.PMID:39056547 | DOI:10.1080/13880209.2024.2378011

Anal Chem. 2024 Jul 26. doi: 10.1021/acs.analchem.4c01630. Online ahead of print.ABSTRACTTraditionally, chemical exposure has been assessed by low-resolution mass spectrometry via targeted approaches due to the typically extremely low concentration of such compounds in biological samples. Nevertheless, untargeted approaches are now becoming a promising tool for a broader investigation of the exposome, covering additional compounds, their biotransformation products, and possible metabolic alterations (metabolomics). However, despite broad compound coverage, untargeted metabolomics still underperforms in ultratrace biomonitoring analysis. To overcome these analytical limitations, we present the development of the first combined targeted/untargeted LC-MS method, merging MRM-HR and SWATH experiments in one analytical run, making use of Zeno technology for improved sensitivity. Multiple reaction monitoring transitions were optimized for 135 highly diverse toxicants including mycotoxins, plasticizers, PFAS, personal care products ingredients, and industrial side products as well as potentially beneficial xenobiotics such as phytohormones. As a proof of concept, standard reference materials of human plasma (SRM 1950) and serum (SRM 1958) were analyzed with both Zeno MRM-HR + SWATH and SWATH-only methodologies. Results demonstrated a significant increase in sensitivity represented by the detection of lower concentration levels in spiked SRM materials (mean value: 2.2 and 3 times lower concentrations for SRMs 1950 and 1958, respectively). Overall, the detection frequency was increased by 68% (19 to 32 positive detections) in the MRM-HR + SWATH mode compared to the SWATH-only. This work presents a promising avenue for addressing the outstanding key challenge in the small-molecule omics field: finding a balance between high sensitivity and broad chemical coverage. It was demonstrated for exposomic applications but might be transferred to lipidomics and metabolomics workflows.PMID:39056508 | DOI:10.1021/acs.analchem.4c01630

ACS Nano. 2024 Jul 26. doi: 10.1021/acsnano.4c05763. Online ahead of print.ABSTRACTMaterial-microbial interfaces offer a promising future in sustainable and efficient chemical-energy conversions, yet the impacts of these artificial interfaces on microbial metabolisms remain unclear. Here, we conducted detailed proteomic and metabolomic analyses to study the regulations of microbial metabolism induced by the photocatalytic material-microbial interfaces, especially the intracellular redox and energy homeostasis, which are vital for sustaining cell activity. First, we learned that the materials have a heavier weight in perturbing microbial metabolism and inducing distinctive biological pathways, like the expression of the metal-resisting system, than light stimulations. Furthermore, we observed that the materials-microbe interfaces can maintain the delicate redox balance and the energetic status of the microbial cells since the intracellular redox cofactors and energy currencies show stable levels as naturally inoculated microbes. These observations ensure the possibility of energizing microbial activities with artificial materials-microbe interfaces for diverse applications and also provide guides for future designs of materials-microbe hybrids to guard microbial activities.PMID:39056348 | DOI:10.1021/acsnano.4c05763

New Phytol. 2024 Jul 26. doi: 10.1111/nph.19981. Online ahead of print.ABSTRACTThe NPR proteins function as salicylic acid (SA) receptors in Arabidopsis thaliana. AtNPR1 plays a central role in SA-induced transcriptional reprogramming whereby positively regulates SA-mediated defense. NPRs are found in the genomes of nearly all land plants. However, we know little about the molecular functions and physiological roles of NPRs in most plant species. We conducted phylogenetic and alignment analyses of NPRs from 68 species covering the significant lineages of land plants. To investigate NPR functions in bryophyte lineages, we generated and characterized NPR loss-of-function mutants in the liverwort Marchantia polymorpha. Brassicaceae NPR1-like proteins have characteristically gained or lost functional residues identified in AtNPRs, pointing to the possibility of a unique evolutionary trajectory for the Brassicaceae NPR1-like proteins. We find that the only NPR in M. polymorpha, MpNPR, is not the master regulator of SA-induced transcriptional reprogramming and negatively regulates bacterial resistance in this species. The Mpnpr transcriptome suggested roles of MpNPR in heat and far-red light responses. We identify both Mpnpr and Atnpr1-1 display enhanced thermomorphogenesis. Interspecies complementation analysis indicated that the molecular properties of AtNPR1 and MpNPR are partially conserved. We further show that MpNPR has SA-binding activity. NPRs and NPR-associated pathways have evolved distinctively in diverged land plant lineages to cope with different terrestrial environments.PMID:39056290 | DOI:10.1111/nph.19981

J Med Virol. 2024 Aug;96(8):e29798. doi: 10.1002/jmv.29798.ABSTRACTAntiretroviral therapy (ART) is an effective treatment for people living with HIV (PLHIVs), requiring an extended period to achieve immune reconstitution. Metabolic alterations induced by ART are crucial for predicting long-term therapeutic responses, yet comprehensive investigation through large-scale clinical studies is still lacking. Here, we collected plasma samples from 108 PLHIVs to the untargeted plasma metabolomics study, based on the longitudinal metabolomics design. Cross-sectional analyzes were performed at pre- and post-ART to explore the metabolic transformation induced by the therapy. Subsequently, delta values between pre- and post-ART measurements were calculated to quantify metabolic alterations. Then, the optimal set of metabolic traits and clinical signatures were further identified and applied to construct random forest model for predicting the future therapeutic responses to ART. We found distinct ART-induced metabolic transformation among PLHIVs. After confounder-adjustments, five metabolites exhibited significant associations with future immune response: tetracosatetraenoic acid (24:4n-6) (pre-ART) (odds ratio [OR]: 0.978, 95% confidence interval [CI]: 0.955~0.997), 1-(3,4-dihydroxyphenyl)-5-hydroxy-3-decanone (pre-ART) (OR: 1.298, 95% CI: 1.061~1.727), beta-PC-M6 (change) (OR: 0.967, 95% CI: 0.938~0.993), d-Galactaro-1,4-lactone (change) (OR: 1.032, 95% CI: 1.007~1.063), Annuionone C (change) (OR: 1.100, 95% CI: 1.030~1.190). The addition of plasma metabolites to clinical markers accurately predicted immune response to ART with an area under curve of 0.91. Notably, most disrupted metabolites were significantly correlated with blood lipids, suggesting that metabolic transformation might contribute to dyslipidemia among PLHIVs. This study highlights the distinct metabolic transformation post-ART among PLHIVs and reveals the potential role of metabolic transformation as key determinants of ART efficacy.PMID:39056244 | DOI:10.1002/jmv.29798

Food Funct. 2024 Jul 26. doi: 10.1039/d4fo00210e. Online ahead of print.ABSTRACTBackground: A high-fat diet (HFD) is generally associated with an increased risk of mental disorders that constitute a sizeable worldwide health. A HFD results in the gut microbiota-brain axis being altered and linked to mental disorders. Hypocretin-1, which can promote appetite, has been previously confirmed to be associated with depression. However, no exact relationship has been found for hypocretin between depression and HFDs. Methods: Adult male SD rats were randomly assigned to either a HFD or a normal diet for eight weeks, followed by behavioral tests and plasma biochemical analyses. Then, we investigated the protein and mRNA levels of inflammation-related factors in the hippocampus. We also observed morphological changes in brain microglia and lipid accumulation. Additionally, metagenomic and metabolomic analyses of gut microbiomes were performed. 3T3-L1 cells were utilized in vitro to investigate the impact of hypocretin receptor 1 antagonists (SB334867) on lipid accumulation. To consider the connection between the brain and adipose tissue, we used a conditioned medium (CM) treated with 3T3-L1 cells to observe the activation and phagocytosis of BV2 cells. Following a 12-week period of feeding a HFD to C57BL/6 mice, a three-week intervention period was initiated during which the administration of SB334867 was observed. This was followed by a series of assessments, including monitoring of body weight changes and emotional problems, as well as attention to plasma biochemical levels and microglial cell phenotypes in the brain. Results: The HFD rats displayed anxiety and depressive-like behaviors. HFD rats exhibited increased plasma HDL, LDL, and TC levels. A HFD also causes an increase in hypocretin-1 and hypocretin-2 in the hypothalamus. Metagenomics and metabolomics revealed that the HFD caused an increase in the relative abundance of associated inflammatory bacteria and decreased the abundance of anti-inflammatory and bile acid metabolites. Compared with the CTR group, hippocampal microglia in the HFD group were significantly activated and accompanied by lipid deposition. At the same time, protein and mRNA expression levels of inflammation-related factors were increased. We found that SB334867 could significantly reduce lipid accumulation in 3T3-L1 cells after differentiation. The expression of inflammatory factors decreased in the SB334867 group. The administration of SB334867 was found to reverse the adverse effects of the HFD on body weight, depressive-like behaviour and anxiety-like mood. Furthermore, this treatment was associated with improvements in plasma biochemical levels and a reduction in the number of microglia in the brain. Conclusions: In summary, our results demonstrated that a HFD induced anxiety and depressive-like behaviors, which may be linked to the increased hypocretin-1 level and lipid accumulation. Supplementation with SB334867 improved the above. These observations highlight the possibility of hypocretin-1 inducing the risk of HFD-associated emotional dysfunctions.PMID:39056112 | DOI:10.1039/d4fo00210e

Front Mol Biosci. 2024 Jul 11;11:1420664. doi: 10.3389/fmolb.2024.1420664. eCollection 2024.ABSTRACTGestational diabetes mellitus (GDM) is a common metabolic disorder affecting approximately 16.5% of pregnancies worldwide and causing significant health concerns. GDM is a serious pregnancy complication caused by chronic insulin resistance in the mother and has been associated with the development of neurodevelopmental disorders in offspring. Emerging data support the notion that GDM affects both the maternal and fetal microbiome, altering the composition and function of the gut microbiota, resulting in dysbiosis. The observed dysregulation of microbial presence in GDM pregnancies has been connected to fetal neurodevelopmental problems. Several reviews have focused on the intricate development of maternal dysbiosis affecting the fetal microbiome. Omics data have been instrumental in deciphering the underlying relationship among GDM, gut dysbiosis, and fetal neurodevelopment, paving the way for precision medicine. Microbiome-associated omics analyses help elucidate how dysbiosis contributes to metabolic disturbances and inflammation, linking microbial changes to adverse pregnancy outcomes such as those seen in GDM. Integrating omics data across these different layers-genomics, transcriptomics, proteomics, metabolomics, and microbiomics-offers a comprehensive view of the molecular landscape underlying GDM. This review outlines the affected pathways and proposes future developments and possible personalized therapeutic interventions by integrating omics data on the maternal microbiome, genetics, lifestyle factors, and other relevant biomarkers aimed at identifying women at high risk of developing GDM. For example, machine learning tools have emerged with powerful capabilities to extract meaningful insights from large datasets.PMID:39055983 | PMC:PMC11269231 | DOI:10.3389/fmolb.2024.1420664

iScience. 2024 Jun 17;27(7):110295. doi: 10.1016/j.isci.2024.110295. eCollection 2024 Jul 19.ABSTRACTLong-term lifestyle interventions in childhood and adolescence can significantly improve cardiometabolic health, but the underlying molecular mechanisms remain poorly understood. To address this knowledge gap, we conducted an 8-year diet and physical activity intervention in a general population of children. The research revealed that the intervention influenced 80 serum metabolites over two years, with 17 metabolites continuing to be affected after eight years. The intervention primarily impacted fatty amides, including palmitic amide, linoleamide, oleamide, and others, as well as unsaturated fatty acids, acylcarnitines, phospholipids, sterols, gut microbiota-derived metabolites, amino acids, and purine metabolites. Particularly noteworthy were the pronounced changes in serum fatty amides. These serum metabolite alterations could represent molecular mechanisms responsible for the observed benefits of long-term lifestyle interventions on cardiometabolic and overall health since childhood. Understanding these metabolic changes may provide valuable insights into the prevention of cardiometabolic and other non-communicable diseases since childhood.PMID:39055945 | PMC:PMC11269805 | DOI:10.1016/j.isci.2024.110295

iScience. 2024 Jun 22;27(7):110357. doi: 10.1016/j.isci.2024.110357. eCollection 2024 Jul 19.ABSTRACTVon Hippel-Lindau (VHL) syndrome is a rare autosomal dominant disorder, where renal cell carcinoma (RCC) serves as a significant cause of mortality. We collected peripheral blood from 61 VHL-RCC patients and 31 healthy individuals, along with 19 paired RCC tumor and adjacent non-malignant samples. Using liquid chromatography-mass spectrometry, we identified 238 plasma and 241 tissue differentially abundant metabolites (DAMs), highlighting key pathways such as arginine and proline metabolism. The top 10 of the 23 DAMs, common to both plasma and tissue, were instrumental in constructing a high-performance diagnostic model. These DAMs demonstrated significant correlations with VHL gene mutation types. Cox regression analysis revealed that plasma levels of N2,N2-dimethylguanosine were associated with the timing of RCC onset in VHL patients, acting as an independent predictive factor. This study enhances diagnostic accuracy for this rare condition and opens new avenues for exploring metabolic mechanisms of the disease and potential therapeutic directions.PMID:39055909 | PMC:PMC11269943 | DOI:10.1016/j.isci.2024.110357

iScience. 2024 Jun 21;27(7):110345. doi: 10.1016/j.isci.2024.110345. eCollection 2024 Jul 19.ABSTRACTBreast cancer (BC) is currently the most prevalent malignancy worldwide, and finding effective non-invasive biomarkers for routine clinical detection of BC remains a significant challenge. Here, we performed non-targeted and targeted metabolomics analysis on the screening, training and validation cohorts of serum samples from 1,947 participants. A metabolite biomarker model including glutamate, erythronate, docosahexaenoate, propionylcarnitine, and patient's age was established for detecting BC. This model demonstrated better diagnostic performance than carbohydrate antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) alone in discriminating BC from healthy controls both in the training and validation cohorts [area under the curve (AUC), 0.954; sensitivity, 87.1% and specificity, 93.5% for the training cohort and 0.834, 68.3%, and 85.2%, respectively, for the validation cohort 1]. This study has established a noninvasive approach for the detection of BC, which shows potential as a suitable supplement to the clinical screening methods currently employed for BC.PMID:39055906 | PMC:PMC11269948 | DOI:10.1016/j.isci.2024.110345

Front Vet Sci. 2024 Jul 11;11:1442931. doi: 10.3389/fvets.2024.1442931. eCollection 2024.ABSTRACTINTRODUCTION: Gonadotropin-releasing hormone (GnRH) is widely used in the timed artificial insemination protocol for sheep. However, there remains a debate regarding its impact on pregnancy rates during artificial insemination. This study aims to evaluate the effect of GnRH on the pregnancy rates in Huyang ewes, analyze the pre-implantation metabolite changes caused by GnRH using metabolomics, and elucidate the mechanism effect on pregnancy rates.METHODS: All ewes were administered a vaginal progesterone sponge containing 45 mg of flurogestone acetate for 12 days and received 330 units of equine chorionic gonadotropin (eCG) intramuscularly after sponge removal. The experimental group (n = 69) received an intramuscular treatment of 17 μg GnRH agonist triptorelin 48 h after sponge removal on Day 0, while the control group (n = 41) received 1 mL of sterile saline solution. All ewes underwent a single vaginal insemination 58 h after the withdrawal of the progesterone sponge. The difference in pregnancy rates between the two groups was calculated. Metabolomic analysis was performed on plasma samples collected on Day 7 after the treatment of GnRH agonist.RESULTS: Gonadotropin-releasing hormone (GnRH) treatment significantly reduced the pregnancy rate in the experimental group compared with the control group (72.2 vs. 82.9%, p < 0.05). Metabolomic analysis indicated that GnRH treatment affected metabolites involved in collagen synthesis and prostaglandin synthesis in the endometrial tissue, which includes a marked decrease in hydroxyproline amino acid content and a significant increase in corticosterone and prostaglandin D2 lipids and unsaturated fatty acids.CONCLUSION: In summary, the injection of GnRH agonist Triptorelin 48 h after progesterone sponges removal reduces the pregnancy rate of Huyang ewe following artificial insemination. It also affects the metabolite levels related to endometrial collagen and prostaglandin synthesis, harming embryo implantation.PMID:39055862 | PMC:PMC11270128 | DOI:10.3389/fvets.2024.1442931

Food Sci Nutr. 2024 Apr 22;12(7):5100-5110. doi: 10.1002/fsn3.4159. eCollection 2024 Jul.ABSTRACTOur previous clinical metabolomics study illustrated that energy metabolism disorder is an underlying pathogenesis mechanism for the development of alcoholic liver disease (ALD). Supplementation of nicotinamide (NAM), the precursor of nicotinamide adenine dinucleotide (NAD+), may restore the energy metabolism homeostasis of ALD and thus serves as potential therapeutics to treat ALD. In this bedside-to-bench study, the protective effect of NAM against ALD was investigated by using the NIAAA mice model (chronic-plus-binge ethanol), and the liver regeneration boosting capability of NAM was evaluated by the partial hepatectomy mice model. Our results showed that NAM supplements not only protected the liver from alcohol-induced injury and improved alcohol-induced mitochondrial structure and function change, but also boosted liver regeneration in postpartial hepatectomy mice by increasing liver NAD+ content. These findings suggested that NAM, a water-soluble form of vitamin B3, can promote liver regeneration and improves liver function by alleviating alcohol-induced energy metabolism disorder.PMID:39055233 | PMC:PMC11266918 | DOI:10.1002/fsn3.4159

Elife. 2024 Jul 24;13:RP97289. doi: 10.7554/eLife.97289.ABSTRACTOne of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory in mice is selectively impaired following the expression of a genetically encoded Rac1 inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.PMID:39046788 | DOI:10.7554/eLife.97289

Metabolomics. 2024 Jul 24;20(4):79. doi: 10.1007/s11306-024-02139-6.ABSTRACTINTRODUCTION: This study employs Proton-Transfer-Reaction Mass Spectrometry (PTR-MS) to analyze exhaled breath profiles of 504 healthy adults, focusing on nine common volatile organic compounds (VOCs): acetone, acetaldehyde, acetonitrile, ethanol, isoprene, methanol, propanol, phenol, and toluene. PTR-MS offers real-time VOC measurement, crucial for understanding breath biomarkers and their applications in health assessment.OBJECTIVES: The study aims to investigate how demographic factors-gender, age, and smoking history-affect VOC concentrations in exhaled breath. The objective is to enhance our understanding of breath biomarkers and their potential for health monitoring and clinical diagnosis.METHODS: Exhaled breath samples were collected using PTR-MS, measuring concentrations of nine VOCs. The data were analyzed to discern distribution patterns across demographic groups.RESULTS: Males showed higher average VOC levels for certain compounds. Propanol and methanol concentrations significantly increased with age. Smoking history influenced VOC levels, with differences among non-smokers, current smokers, and ex-smokers.CONCLUSION: This research provides valuable insights into demographic influences on exhaled VOC profiles, emphasizing the potential of breath analysis for health assessment. PTR-MS's real-time measurement capabilities are crucial for capturing dynamic VOC changes, offering advantages over conventional methods. These findings lay a foundation for advancements in non-invasive disease detection, highlighting the importance of considering demographics in breath biomarker research.PMID:39046579 | DOI:10.1007/s11306-024-02139-6

Eur J Clin Invest. 2024 Jul 24:e14289. doi: 10.1111/eci.14289. Online ahead of print.ABSTRACTBACKGROUND: Infertility is a major health issue, affecting 15% of reproductive-age couples with male factors contributing to 50% of cases. Asthenozoospermia (AS), or low sperm motility, is a common cause of male infertility with complex aetiology, involving genetic and metabolic alterations, inflammation and oxidative stress. However, the molecular mechanisms behind low motility are unclear. In this study, we used a metabolomics approach to identify metabolic biomarkers and pathways involved in sperm motility.METHODS: We compared the metabolome and lipidome of spermatozoa of men with normozoospermia (n = 44) and AS (n = 22) using untargeted LC-MS and the metabolome of seminal fluid using 1H-NMR. Additionally, we evaluated the seminal fluid redox status to assess the oxidative stress in the ejaculate.RESULTS: We identified 112 metabolites and 209 lipids in spermatozoa and 27 metabolites in the seminal fluid of normozoospermic and asthenozoospermic men. PCA analysis of the spermatozoa's metabolomics and lipidomics data showed a clear separation between groups. Spermatozoa of asthenozoospermic men presented lower levels of several amino acids, and increased levels of energetic substrates and lysophospholipids. However, the metabolome and redox status of the seminal fluid was not altered inAS.CONCLUSIONS: Our results indicate impaired metabolic pathways associated with redox homeostasis and amino acid, energy and lipid metabolism in AS. Taken together, these findings suggest that the metabolome and lipidome of human spermatozoa are key factors influencing their motility and that oxidative stress exposure during spermatogenesis or sperm maturation may be in the aetiology of decreased motility in AS.PMID:39046266 | DOI:10.1111/eci.14289

Antimicrob Agents Chemother. 2024 Jul 24:e0085024. doi: 10.1128/aac.00850-24. Online ahead of print.ABSTRACTThe metabolic state of bacteria significantly contributes to their resistance to antibiotics; however, the specific metabolic mechanisms conferring antimicrobial resistance in Helicobacter pylori remain largely understudied. Employing transcriptomic and non-targeted metabolomics, we characterized the metabolic reprogramming of H. pylori when challenged with antibiotic agents. We observed a notable increase in both genetic and key proteomic components involved in fatty acid biosynthesis. Inhibition of this pathway significantly enhanced the antibiotic susceptibility of the sensitive and multidrug-resistant H. pylori strains while also disrupting their biofilm-forming capacities. Further analysis revealed that antibiotic treatment induced a stringent response, triggering the expression of the hp0560-hp0557 operon regulated by Sigma28 (σ28). This activation in turn stimulated the fatty acid biosynthetic pathway, thereby enhancing the antibiotic tolerance of H. pylori. Our findings reveal a novel adaptive strategy employed by H. pylori to withstand antibiotic stress.PMID:39046242 | DOI:10.1128/aac.00850-24

Brain Pathol. 2024 Jul 24:e13289. doi: 10.1111/bpa.13289. Online ahead of print.ABSTRACTPostoperative cognitive dysfunction (POCD) is a major concern, particularly among older adults. This study used social isolation (ISO) and multiomics analyses in aged mice to investigate potential mechanisms underlying POCD development. Aged mice were divided into two groups: ISO and paired housing (PH). Oleamide and the cannabinoid receptor type 2 (CB2R) antagonist AM630 were administered intraperitoneally, while Foxq1 adeno-associated viral (AAV) vector was injected directly into the hippocampus. Intramedullary tibial surgeries were subsequently performed to establish the POCD models. Behavioral tests comprising the Y-maze, open field test, and novel object recognition were conducted 2 days after surgery. Hippocampal and serum inflammatory cytokines were assessed. Following surgery, ISO mice demonstrated intensified cognitive impairments and escalated inflammatory markers. Integrative transcriptomic and metabolomic analysis revealed elevated oleamide concentrations in the hippocampus and serum of PH mice, with associative investigations indicating a close relationship between the Foxq1 gene and oleamide levels. While oleamide administration and Foxq1 gene overexpression substantially ameliorated postoperative cognitive performance and systemic inflammation in mice, CB2R antagonist AM630 impeded these enhancements. The Foxq1 gene and oleamide may be crucial in alleviating POCD. While potentially acting through CB2R-mediated pathways, these factors may modulate neuroinflammation and attenuate proinflammatory cytokine levels within the hippocampus, substantially improving cognitive performance postsurgery. This study lays the groundwork for future research into therapeutic approaches targeting the Foxq1-oleamide-CB2R axis, with the ultimate goal of preventing or mitigating POCD.PMID:39046224 | DOI:10.1111/bpa.13289

Liver Int. 2024 Jul 24. doi: 10.1111/liv.16052. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) is a growing cause of chronic liver disease, characterized by fat accumulation, inflammation and fibrosis, which development depends on mitochondrial dysfunction and oxidative stress. Highly expressed in the liver during fasting, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) regulates mitochondrial and oxidative metabolism. Given the relevant role of mitochondrial function in MASH, we investigated the relationship between PGC-1α and steatohepatitis.METHODS: We measured the hepatic expression of Pgc-1α in both MASH patients and wild-type mice fed a western diet (WD) inducing steatosis and fibrosis. We then generated a pure C57BL6/J strain loss of function mouse model in which Pgc-1α is selectively deleted in the liver and we fed these mice with a WD supplemented with sugar water that accurately mimics human MASH.RESULTS: We observed that the hepatic expression of Pgc-1α is strongly reduced in MASH, in both humans and mice. Moreover, the hepatic ablation of Pgc-1α promotes a considerable reduction of the hepatic mitochondrial respiratory capacity, setting up a bioenergetic harmful environment for liver diseases. Indeed, the lack of Pgc-1α decreases mitochondrial function and increases inflammation, fibrosis and oxidative stress in the scenario of MASH. Intriguingly, this profibrotic phenotype is not linked with obesity, insulin resistance and lipid disbalance.CONCLUSIONS: In a MASH model the hepatic ablation of Pgc-1α drives fibrosis independently from lipid and glucose metabolism. These results add a novel mechanistic piece to the puzzle of the specific and crucial role of mitochondrial function in MASH development.PMID:39046166 | DOI:10.1111/liv.16052