PubMed

Int J Ophthalmol. 2024 Apr 18;17(4):638-645. doi: 10.18240/ijo.2024.04.05. eCollection 2024.ABSTRACTAIM: To investigate the protective effects, antioxidant potential, and anti-inflammatory mechanisms of eicosane on glutamate-induced cell damage and on N-methyl-D-aspartate (NMDA)-induced retinal ganglion cell (RGC) injury in a mouse model of glaucoma.METHODS: The protective effects of eicosane on the rat R28 retinal precursor cell line were assessed using cell counting kit-8 assays and Hoechst-propidium iodide staining. Intracellular reactive oxygen species (ROS) production was measured using the fluorescent probe 2'-7'-dichlorofluorescin diacetate and flow cytometry. The protective role of eicosane on NMDA-induced RGC injury in a mouse glaucoma model was determined by immunostaining of frozen sections of retina. The effects of eicosane on the metabolome of the retina in mice with NMDA-induced RGC damage were evaluated by liquid chromatography-mass spectroscopy (LC-MS) and untargeted metabolomics analyses.RESULTS: Eicosane treatment significantly attenuated glutamate-induced damage to R28 cells in vitro. Eicosane also protected RGCs against NMDA-induced injury in a mouse glaucoma model. Untargeted metabolomics analyses showed that eicosane increased multiple metabolites, including L-arginine and L-carnitine, in the retina.CONCLUSION: Eicosane has protective effects, antioxidant potential, and anti-inflammatory properties in an in vitro model of glutamate-induced cell damage and in an in vivo model of NMDA-induced RGC injury in mouse glaucoma through modulation of L-arginine and/or L-carnitine metabolism.PMID:38638263 | PMC:PMC10988067 | DOI:10.18240/ijo.2024.04.05

Biomed Chromatogr. 2024 Apr 18:e5872. doi: 10.1002/bmc.5872. Online ahead of print.ABSTRACTModern studies have shown that neuroendocrine disorders caused by the dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis are one of the important pathogenetic mechanisms of kidney-yang-deficiency-syndrome (KYDS). The preventive effect of Gushudan on KYDS has been reported, but its regulatory mechanisms on the HPG axis have not been elucidated. In this study, we developed an integrated untargeted and targeted metabolomics analysis strategy to investigate the regulatory mechanism of Gushudan on the HPG axis in rats with KYDS. In untargeted metabolomics, we screened 14 potential biomarkers such as glycine, lysine, and glycerol that were significantly associated with the HPG axis. To explore the effect of changes in the levels of potential biomarkers on KYDS, all of them were quantified in targeted metabolomics. With the quantitative results, correlations between potential biomarkers and testosterone, a functional indicator of the HPG axis, were explored. The results showed that oxidative stress, inflammatory response, and energy depletion, induced by metabolic disorders in rats, were responsible for the decrease in testosterone levels. Gushudan improves metabolic disorders and restores testosterone levels, thus restoring HPG axis dysfunction. This finding elucidates the special metabolic characteristics of KYDS and the therapeutic mechanism of Gushudan from a new perspective.PMID:38638009 | DOI:10.1002/bmc.5872

Aging Cell. 2024 Apr 18:e14164. doi: 10.1111/acel.14164. Online ahead of print.ABSTRACTMetabolomic age models have been proposed for the study of biological aging, however, they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age-related disease. Ninety-eight metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈31,000 individuals, age range 24-86 years). We used nonlinear and penalized regression to model CA and time to all-cause mortality. We examined associations of four new and two previously published metabolomic age models, with aging risk factors and phenotypes. Within the UK Biobank (N ≈102,000), we tested prediction of CA, incident disease (cardiovascular disease (CVD), type-2 diabetes mellitus, cancer, dementia, and chronic obstructive pulmonary disease), and all-cause mortality. Seven-fold cross-validated Pearson's r between metabolomic age models and CA ranged between 0.47 and 0.65 in the training cohort set (mean absolute error: 8-9 years). Metabolomic age models, adjusted for CA, were associated with C-reactive protein, and inversely associated with glomerular filtration rate. Positively associated risk factors included obesity, diabetes, smoking, and physical inactivity. In UK Biobank, correlations of metabolomic age with CA were modest (r = 0.29-0.33), yet all metabolomic model scores predicted mortality (hazard ratios of 1.01 to 1.06/metabolomic age year) and CVD, after adjustment for CA. While metabolomic age models were only moderately associated with CA in an independent population, they provided additional prediction of morbidity and mortality over CA itself, suggesting their wider applicability.PMID:38637937 | DOI:10.1111/acel.14164

Food Microbiol. 2024 Aug;121:104499. doi: 10.1016/j.fm.2024.104499. Epub 2024 Feb 22.ABSTRACTIn this study, we investigated the impact of microbial interactions on Monascus pigment (MP) production. We established diverse microbial consortia involving Monascus purpureus and Lactobacillus fermentum. The addition of Lactobacillus fermentum (4% at 48 h) to the submerged fermentation of M. purpureus resulted in a significantly higher MP production compared to that achieved using the single-fermentation system. Co-cultivation with immobilized L. fermentum led to a remarkable increase of 59.18% in extracellular MP production, while mixed fermentation with free L. fermentum caused a significant decrease of 66.93% in intracellular MPs, contrasting with a marginal increase of 4.52% observed during co-cultivation with immobilized L. fermentum and the control group respectively. The findings indicate an evident enhancement in cell membrane permeability of M. purpureus when co-cultivated with immobilized L. fementum. Moreover, integrated transcriptomic and metabolomic analyses were conducted to elucidate the regulatory mechanisms underlying MP biosynthesis and secretion following inoculation with immobilized L. fementum, with specific emphasis on glycolysis, steroid biosynthesis, fatty acid biosynthesis, and energy metabolism.PMID:38637070 | DOI:10.1016/j.fm.2024.104499

Food Microbiol. 2024 Aug;121:104497. doi: 10.1016/j.fm.2024.104497. Epub 2024 Feb 29.ABSTRACTDaqu is a saccharification agent required for fermenting Baijiu, a popular Chinese liquor. Our objective was to investigate the relationships between physicochemical indices, microbial community diversity, and metabolite profiles of strong-flavor Jinhui Daqu during different storage periods. During different storage periods of Jinhui Daqu, we combined Illumina MiSeq sequencing and non-target sequencing techniques to analyze dynamic changes of the microbial community and metabolite composition, established a symbiotic network and explored the correlation between dominant microorganisms and differential metabolites in Daqu. Fungal community diversity in 8d_Daqu was higher than that in 45d_Daqu and 90d_Daqu, whereas bacterial community diversity was higher in 90d_Daqu. Twelve bacterial and four fungal genera were dominant during storage of Daqu. Bacillus, Leuconostoc, Kroppenstedtia, Lactococcus, Thermomyces and Wickerhamomyces decreased as the storage period increased. Differences of microbiota structure led to various metabolic pathways, and 993 differential metabolites were found in all Daqu samples. Differential microorganisms were significantly related to key metabolites. Major metabolic pathways involved in the formation of amino acids and lipids, such as l-arogenate and hydroxyproline, were identified. Interactions between moisture, acidity, and microbes may drive the succession of the microbial community, which further affects the formation of metabolites.PMID:38637068 | DOI:10.1016/j.fm.2024.104497

Anal Chim Acta. 2024 May 22;1304:342535. doi: 10.1016/j.aca.2024.342535. Epub 2024 Mar 26.ABSTRACTThe implementation of ion mobility spectrometry (IMS) in liquid chromatography-high-resolution mass spectrometry (LC-HRMS) workflows has become a valuable tool for improving compound annotation in metabolomics analyses by increasing peak capacity and by adding a new molecular descriptor, the collision cross section (CCS). Although some studies reported high repeatability and reproducibility of CCS determination and only few studies reported good interplatform agreement for small molecules, standardized protocols are still missing due to the lack of reference CCS values and reference materials. We present a comparison of CCS values of approximatively one hundred lipid species either commercially available or extracted from human plasma. We used three different commercial ion mobility technologies from different laboratories, drift tube IMS (DTIMS), travelling wave IMS (TWIMS) and trapped IMS (TIMS), to evaluate both instrument repeatability and interlaboratory reproducibility. We showed that CCS discrepancies of 0.3% (average) could occur depending on the data processing software tools. Moreover, eleven CCS calibrants were evaluated yielding mean RSD below 2% for eight calibrants, ESI Low concentration tuning mix (Tune Mix) showing the lowest RSD (< 0.5%) in both ion modes. Tune Mix calibrated CCS from the three different IMS instruments proved to be well correlated and highly reproducible (R2 > 0.995 and mean RSD ≤ 1%). More than 90% of the lipid CCS had deviations of less than 1%, demonstrating high comparability between techniques, and the possibility to use the CCS as molecular descriptor. We highlighted the need of standardized procedures for calibration, data acquisition, and data processing. This work demonstrates that using harmonized analytical conditions are required for interplatform reproducibility for CCS determination of human plasma lipids.PMID:38637036 | DOI:10.1016/j.aca.2024.342535

Anal Chim Acta. 2024 May 22;1304:342533. doi: 10.1016/j.aca.2024.342533. Epub 2024 Apr 2.ABSTRACTBACKGROUND: DIA (Data-Independent Acquisition) is a powerful technique in Liquid Chromatography coupled with high-resolution tandem Mass Spectrometry (LC-MS/MS) initially developed for proteomics studies and recently emerging in metabolomics and lipidomics. It provides a comprehensive and unbiased coverage of molecules with improved reproducibility and quantitative accuracy compared to Data-Dependent Acquisition (DDA). Combined with the Zeno trap and Electron-Activated Dissociation (EAD), DIA enhances data quality and structural elucidation compared to conventional fragmentation under CID. These tools were applied to study the lipidome and metabolome of the freshwater amphipod Gammarus fossarum, successfully discriminating stages and highlighting significant biological features. Despite being underused, DIA, along with the Zeno trap and EAD, holds great potential for advancing research in the omics field.RESULTS: DIA combined with the Zeno trap enhances detection reproducibility compared to conventional DDA, improving fragmentation spectra quality and putative identifications. LC coupled with Zeno-SWATH-DIA methods were used to characterize molecular changes in reproductive cycle of female gammarids. Multivariate data analysis including Principal Component Analysis and Partial Least Square Discriminant Analysis successfully identified significant features. EAD fragmentation helped to identify unknown features and to confirm their molecular structure using fragmentation spectra database annotation or machine learning. EAD database matching accurately annotated five glycerophospholipids, including the position of double bonds on fatty acid chain moieties. SIRIUS database predicted structures of unknown features based on experimental fragmentation spectra to compensate for database incompleteness.SIGNIFICANCE: Reproducible detection of features and confident identification of putative compounds are pivotal stages within analytical pipelines. The DIA approach combined with Zeno pulsing enhances detection sensitivity and targeted fragmentation with EAD in positive polarity provides orthogonal fragmentation information. In our study, Zeno-DIA and EAD thereby facilitated a comprehensive and insightful exploration of pertinent biological molecules associated with the reproductive cycle of gammarids. The developed methodology holds great promises for identifying informative biomarkers on the health status of an environmental sentinel species.PMID:38637034 | DOI:10.1016/j.aca.2024.342533

Environ Pollut. 2024 Apr 16:123949. doi: 10.1016/j.envpol.2024.123949. Online ahead of print.ABSTRACTArsenic (As) is a heavy metal known for its detrimental effects on the kidneys, but the precise mechanisms underlying its toxicity remain unclear. In this study, we employed an integrated approach combining traditional toxicology methods with functional metabolomics to explore the nephrotoxicity induced by As in mice. Our findings demonstrated that after 28 days of exposure to sodium arsenite, blood urea nitrogen, serum creatinine levels were significantly increased, and pathological examination of the kidneys revealed dilation of renal tubules and glomerular injury. Additionally, uric acid, total cholesterol, and low-density lipoprotein cholesterol levels were significant increased while triglyceride level was decreased, resulting in renal insufficiency and lipid disorders. Subsequently, the kidney metabolomics analysis revealed that As exposure disrupted 24 differential metabolites, including 14 up-regulated and 10 down-regulated differential metabolites. Ten metabolic pathways including linoleic acid and glycerophospholipid metabolism were significantly enriched. Then, 80 metabolic targets and 168 predicted targets were identified using metabolite network pharmacology analysis. Of particular importance, potential toxicity targets, such as glycine amidinotransferase, mitochondrial (GATM), and nitric oxide synthase, and endothelial (NOS3), were prioritized through the "metabolite-target-pathway" network. Receiver operating characteristics curve and molecular docking analyses suggested that 1-palmitoyl-2-myristoyl-sn-glycero-3-PC, linoleic acid, and L-hydroxyarginine might be functional metabolites associated with GATM and NOS3. Moreover, targeted verification result showed that the level of linoleic acid in As group was 0.4951 μg/mL, which was significantly decreased compared with the control group. And in vivo and in vitro protein expression experiments confirmed that As exposure inhibited the expression of GATM and NOS3. In conclusion, these results suggest that As-induced renal injury may be associated with the inhibition of linoleic acid metabolism through the down-regulation of GATM and NOS3, resulting in decreased levels of linoleic acid, 1-palmitoyl-2-myristoyl-sn-glycero-3-PC, and L-hydroxyarginine metabolites.PMID:38636836 | DOI:10.1016/j.envpol.2024.123949

J Ethnopharmacol. 2024 Apr 16:118193. doi: 10.1016/j.jep.2024.118193. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Saiga antelope horn (SAH) is a traditional Chinese medicine for treating hypertension with liver-yang hyperactivity syndrome (Gan-Yang-Shang-Kang, GYSK), that has a long history of clinical application and precise efficacy, but its mechanism and functional substances are still unknown. Based on the demand for alternative research on the rare and endangered SAH, the group designed and carried out the following studies.AIM OF THE STUDY: The purpose of this research was to demonstrate the functional substances and mechanisms of SAH in the treatment of GYSK hypertension.MATERIALS AND METHODS: The GYSK-SHR model was constructed by administering a decoction of aconite to spontaneously hypertensive rats (SHRs). Blood pressure (BP), behavioural tests related to GYSK, and pathological changes in the kidneys, heart and aorta were measured to investigate the effects of SAH on GYSK-SHRs. Proteomic analysis was used to identify the keratins and peptides of SAH. Moreover, network pharmacology and plasma metabolomics studies were carried out to reveal the mechanisms by which functional peptides in SAH regulate GYSK-hypertension.RESULTS: SAH has a significant antihypertensive effect on GYSK hypertensive animals. It has also been proven to be effective in protecting the function and structural integrity of the kidneys, heart and aorta. Moreover, SAH improved the abnormalities of 31 plasma biomarkers in rats. By constructing a "biomarker-target-peptide" network, 10 functional peptides and two key targets were screened for antihypertensive effects of SAH. The results indicated that SAH may exert a therapeutic effect by re-establishing the imbalance of renin-angiotensin (RAS) system.CONCLUSIONS: Functional peptides from keratin contained in SAH are the main material basis for the treatment of GYSK-hypertension and exhibited the protective effect on the GYSK-SHR model through the RAS system.PMID:38636578 | DOI:10.1016/j.jep.2024.118193

Dev Cell. 2024 Apr 9:S1534-5807(24)00198-9. doi: 10.1016/j.devcel.2024.03.031. Online ahead of print.ABSTRACTPatterning and growth are fundamental features of embryonic development that must be tightly coordinated. To understand how metabolism impacts early mesoderm development, we used mouse embryonic stem-cell-derived gastruloids, that co-expressed glucose transporters with the mesodermal marker T/Bra. We found that the glucose mimic, 2-deoxy-D-glucose (2-DG), blocked T/Bra expression and abolished axial elongation in gastruloids. However, glucose removal did not phenocopy 2-DG treatment despite a decline in glycolytic intermediates. As 2-DG can also act as a competitive inhibitor of mannose in protein glycosylation, we added mannose together with 2-DG and found that it could rescue the mesoderm specification both in vivo and in vitro. We further showed that blocking production and intracellular recycling of mannose abrogated mesoderm specification. Proteomics analysis demonstrated that mannose reversed glycosylation of the Wnt pathway regulator, secreted frizzled receptor Frzb. Our study showed how mannose controls mesoderm specification in mouse gastruloids.PMID:38636516 | DOI:10.1016/j.devcel.2024.03.031

Food Chem. 2024 Apr 13;450:139354. doi: 10.1016/j.foodchem.2024.139354. Online ahead of print.ABSTRACTThe interaction between gut microbiota and muscles through the gut-muscle axis has received increasing attention. This study attempted to address existing research gaps by investigating the effects of gut microbiota on meat flavor. Specifically, lactic acid bacteria were administered to ducks, and the results of e-nose and e-tongue showed significantly enhanced meat flavor in the treatment group. Further analyses using GC-MS revealed an increase in 6 characteristic volatile flavor compounds, including pentanal, hexanal, heptanal, 1-octen-3-ol, 2,3-octanedione, and 2-pentylfuran. Linoleic acid was identified as the key fatty acid that influences meat flavor. Metagenomic and transcriptomic results further confirmed that cecal microbiota affects the duck meat flavor by regulating the metabolic pathways of fatty acids and amino acids, especially ACACB was related to fatty acid biosynthesis and ACAT2, ALDH1A1 with fatty acid degradation. This study sheds light on a novel approach to improving the flavor of animal-derived food.PMID:38636385 | DOI:10.1016/j.foodchem.2024.139354

Food Chem. 2024 Apr 12;450:139333. doi: 10.1016/j.foodchem.2024.139333. Online ahead of print.ABSTRACTCamellia saponins are important by-products of Camellia Oleifer Abel. processing. In this study, an eco-friendly method based on natural deep eutectic solvents (NaDESs, proline and glycerol at a molar ratio of 2:5) was established to extract saponins from C.oleifera cakes. The content of saponin (702.22 ± 1.28 mg/g) obtained using NaDES was higher than those extracted using water or methanol. UPLC-Q-TOF MS analysis of chemical structure showed that the difference in the extraction technique alter individual saponins. A widely targeted metabolomic approach and KEGG metabolic pathway analysis showed that the upregulated metabolites in the NaDES-based extract mainly included flavonoids, alkaloids, and phenolic acids; and they were involved in arginine and proline metabolism, metabolic pathways, phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, and flavonoid biosynthesis. The present study proposes a selective substitute for use in the extraction of camellia saponins with composition analysis.PMID:38636384 | DOI:10.1016/j.foodchem.2024.139333

Mar Environ Res. 2024 Apr 16;198:106490. doi: 10.1016/j.marenvres.2024.106490. Online ahead of print.ABSTRACTCoral bleaching events are becoming increasingly common worldwide, causing widespread coral mortality. However, not all colonies within the same coral taxa show sensitivity to bleaching events, and the current understanding of the metabolic mechanisms underlying thermal bleaching in corals remains limited. We used untargeted metabolomics to analyze the biochemical processes involved in the survival of two bleaching phenotypes of the common corals Pavona decussata and Acropora pruinosa, during a severe bleaching event in the northern South China Sea in 2020. During thermal bleaching, P. decussata and A. pruinosa significantly accumulated energy products such as succinate and EPA, antioxidants and inflammatory markers, and reduced energy storage substances like glutamate and thymidine. KEGG analysis revealed enrichment of energy production pathways such as ABC transporters, nucleotide metabolism and lipid metabolism, suggesting the occurrence of oxidative stress and energy metabolism disorders in bleached corals. Notably, heat stress exerted distinct effects on metabolic pathways in the two coral species, e.g., P. decussata activating carbohydrate metabolism pathways like glycolysis and the TCA cycle, along with amino acid metabolism pathways, whereas A. pruinosa significantly altered the content of multiple small peptides affected amino acid metabolism. Furthermore, the osmoregulatory potential of corals correlates with their ability to survive in heat-stress environments in the wild. This study provides valuable insights into the metabolic mechanisms linked to thermal tolerance in reef-building corals, contributes to the understanding of corals' adaptive potential to heat stress induced by global warming and lays the foundation for developing targeted conservation strategies in the future.PMID:38636276 | DOI:10.1016/j.marenvres.2024.106490

Phytomedicine. 2024 Apr 4;129:155575. doi: 10.1016/j.phymed.2024.155575. Online ahead of print.ABSTRACTBACKGROUND: The prevalence and incidence of type 2 diabetes mellitus (T2DM) have dramatically increased. The intestinal flora and its derived metabolites are demonstrated to play vital roles in the etiology and onset of T2DM. Shouhuitongbian (SHTB) is a traditional Chinese formula to treat constipation. SHTB is composed of seven herbs and components of Colla corii asini (CCA) that are obtained from the hide of Equus asinus L.. Some of herbs in SHTB such as Aloe vera (L.) Burm.f., Cassia obtusifolia L., fruits of Lycium barbarum L., and Citrus aurantium L. have shown to improve insulin resistance (IR) and T2DM in early reports. We hypothesized that SHTB composed of these herbs has antidiabetic effects. The antidiabetic efficacy and mechanism of action of SHTB have not been previously reported.HYPOTHESIS/PURPOSE: To demonstrate the antidiabetic effect and elucidate the underlying mechanisms of SHTB from the perspective of gut microbiota.STUDY DESIGN: The main compounds were identified and quantified by high-performance liquid chromatography (HPLC)-mass spectrometry analysis. High fat diet (HFD)-fed mice and db/db mice were used to assess the antidiabetic effects and the mechanism of SHTB. The underlying mechanisms were evaluated by enzyme-linked immunosorbent assay (ELISA), western blot analysis, quantitative real time polymerase chain reaction (qPCR) analysis, 16S rRNA high-throughput sequencing, and targeted metabolome analysis.METHODS: HFD-fed mice and db/db mice were orally treated with the standard positive drug metformin (100 mg/kg/d) and with SHTB (200 and 100 mg/kg/d), which was chemically characterized according to the European Medicine Agency (EMA) guidelines. The beneficial effects of SHTB were studied by homeostasis model assessment of insulin resistance (HOMA-IR) index, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), total cholesterol (T-CHO), triglyceride (TG), and inflammation. Subsequently, 16S rDNA-based high-throughput pyrosequencing and GC-MS-based targeted metabolomics profiling were performed to analyze the gut microbiota composition and metabolites profile in the gut, respectively. Moreover, the mammalian target of rapamycin complex 1 (mTORC1) / insulin receptor substrate 1 (IRS-1) / phosphoinositide 3-kinase (PI3K) / protein kinase B (AKT) pathway was evaluated via qPCR and western blot.RESULTS: Chemically characterized SHTB, in which six markers were quantified, effectively alleviated glucose intolerance and IR, ameliorated lipid metabolism dysfunction, and reduced inflammation. In addition, 16S rDNA sequencing found that SHTB reshaped the composition of intestinal flora, as indicated by the enrichment of Akkermansia and Parabacteroides in both HFD-fed and db/db mice. Moreover, SHTB enhanced the intestinal production of short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BSCFAs), and reduced the levels of the fecal and circulating branched-chain amino acids (BCAAs). The IRS-1/PI3K/AKT signaling pathway was upregulated after treatment with SHTB.CONCLUSION: Orally administration of SHTB effectively improved IR and reduced hyperglycemia in mice. Treatment with SHTB regulated the gut BCAAs-mTORC1/IRS-1/PI3K/AKT axis by enhancing the BCAAs catabolism in the gut, which attenuated the deleterious effect of BCAAs on the IRS-1 signaling pathway.PMID:38636179 | DOI:10.1016/j.phymed.2024.155575

Anal Chem. 2024 Apr 18. doi: 10.1021/acs.analchem.3c05590. Online ahead of print.ABSTRACTChemoselective extraction strategy is an emerging and powerful means for targeted metabolomics analysis, which allows for the selective identification of biomarkers. Short-chain fatty acids (SCFAs) as functional metabolites for many diseases pose challenges in qualitative and quantitative analyses due to their high polarity and uneven abundance. In our study, we proposed the B-labeled method for the derivatization of SCFAs using easily available 3-aminobenzeneboronic acid as the derivatization reagent, which enables the introduction of recognition unit (boric acid groups). To analyze the B-labeled targeted metabolites accurately, cis-diol-based covalent organic framework (COF) was designed to specifically capture and release target compounds by pH-response borate affinity principle. The COF synthesized by the one-step Schiff base reaction possessed a large surface area (215.77 m2/g), excellent adsorption capacity (774.9 μmol/g), good selectivity, and strong regeneration ability (20 times). Combined with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, our results indicated that the detection sensitivities of SCFAs increased by 1.2-2500 folds compared with unlabeled method, and the retention time and isomer separation were improved. Using this strategy, we determined twenty-six SCFAs in the serum and urine of rats in four groups about osteoporosis and identified important biomarkers related to the tricarboxylic acid cycle and fatty acid metabolism pathways. In summary, UHPLC-MS/MS based on B-labeled derivatization with tailored COF strategy shows its high selectivity, excellent sensitivity, and good chromatographic behavior and has remarkable application prospect in targeted metabolomics study of biospecimens.PMID:38637908 | DOI:10.1021/acs.analchem.3c05590

Nephrology (Carlton). 2024 Apr 18. doi: 10.1111/nep.14308. Online ahead of print.ABSTRACTAIM: Saliva can reflect an individual's physiological status or susceptibility to systemic disease. However, little attention has been given to salivary analysis in children with idiopathic nephrotic syndrome (INS). We aimed to perform a comprehensive analysis of saliva from INS children.METHODS: A total of 18 children (9 children with INS and 9 normal controls) were recruited. Saliva was collected from each INS patient in the acute and remission phases. 16S rRNA gene sequencing, widely targeted metabolomics, and 4D-DIA proteomics were performed.RESULTS: Actinobacteria and Firmicutes were significantly enriched in the pretreatment group compared with the normal control group, while Bacteroidota and Proteobacteria were significantly decreased. A total of 146 metabolites were identified as significantly different between INS children before treatment and normal controls, which covers 17 of 23 categories. KEGG enrichment analysis revealed three significantly enriched pathways, including ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and terpenoid backbone biosynthesis (P < 0.05). A total of 389 differentially expressed proteins were selected between INS children before treatment and normal controls. According to the KEGG and GO enrichment analyses of the KOGs, abnormal ribosome structure and function and humoral immune disorders were the most prominent differences between INS patients and normal controls in the proteomic analysis.CONCLUSION: Oral microbiota dysbiosis may modulate the metabolic profile of saliva in children with INS. It is hypothesized that children with INS might have "abnormal ribosome structure and function" and "humoral immune disorders".PMID:38637907 | DOI:10.1111/nep.14308

Sci Rep. 2024 Apr 18;14(1):8933. doi: 10.1038/s41598-024-59388-7.ABSTRACTPlasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50-80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.PMID:38637659 | DOI:10.1038/s41598-024-59388-7

Commun Biol. 2024 Apr 18;7(1):475. doi: 10.1038/s42003-024-06165-x.ABSTRACTMaternal investment influences the survival and reproduction of both mothers and their progeny and plays a crucial role in understanding individuals' life-history and population ecology. To reveal the complex mechanisms associated with reproduction and investment, it is necessary to examine variations in maternal investment across species. Comparisons across species call for a standardised method to quantify maternal investment, which remained to be developed. This paper addresses this limitation by introducing the maternal investment metric - MI - for mammalian species, established through the allometric scaling of the litter mass at weaning age by the adult mass and investment duration (i.e. gestation + lactation duration) of a species. Using a database encompassing hundreds of mammalian species, we show that the metric is not highly sensitive to the regression method used to fit the allometric relationship or to the proxy used for adult body mass. The comparison of the maternal investment metric between mammalian subclasses and orders reveals strong differences across taxa. For example, our metric confirms that Eutheria have a higher maternal investment than Metatheria. We discuss how further research could use the maternal investment metric as a valuable tool to understand variation in reproductive strategies.PMID:38637653 | DOI:10.1038/s42003-024-06165-x

Sci Rep. 2024 Apr 18;14(1):8950. doi: 10.1038/s41598-024-59491-9.ABSTRACTDetailed knowledge regarding the associations between intake of different types of seafood and meat and the risk of type 2 diabetes (T2D), and insight into possible mechanisms are warranted. In this study we aimed to evaluate the associations between intake of different types of seafood and meat and the subsequent risk of T2D using the Norwegian Mother, Father, and Child Cohort Study (MoBa), and furthermore, by using a mouse model to gain further insight into possible molecular mechanisms contributing to the associated metabolic changes. Women in MoBa who were free of pharmacologically treated diabetes at baseline (n = 60,777) were prospectively evaluated for incident T2D, identified on the basis of medication usages > 90 days after delivery, ascertained by the Norwegian Prescription Database. Dietary intake was obtained with a validated 255-item food frequency questionnaire which assessed habitual diet during the first 4-5 months of pregnancy. Metabolic phenotypes and plasma metabolome were investigated in female mice fed isocaloric diets with different types of seafood and meat mimicking the dietary intake in the human cohort. During maximum 10-year and mean (SD) 7.2 (1.6) years follow-up time, 681 (1.1%) women developed pharmacologically treated T2D. All statistical models identified a higher risk of T2D with increased shellfish intake, whereas no associations were observed for total seafood, fatty fish, total meat and red meat in the adjusted models. In mice, the shellfish-based western diet induced reduced glucose tolerance and insulin secretion compared to the diet based on lean fish, and we identified a number of metabolites elevated in plasma from shellfish-fed mice that correlated with glucose intolerance. Mice fed a western diet based on meat also exhibited reduced glucose tolerance in comparison to lean fish fed mice, whereas mice fed fatty fish, total seafood or red meat did not differ from lean fish fed mice. We observed a diet-specific metabolic signature in plasma demonstrating five distinct metabolite profiles in mice fed shellfish, fatty fish, total seafood/lean fish, a mixed diet and meat. In conclusion, these findings demonstrate that different types of seafood have different outcome on T2D risk. In women, intake of shellfish was associated with higher risk of T2D. In female mice, a shellfish enriched diet reduced glucose tolerance and altered the abundance of several distinct plasma metabolites correlating with glucose tolerance.PMID:38637574 | DOI:10.1038/s41598-024-59491-9

Zhonghua Yi Xue Za Zhi. 2024 Apr 16;104(15):1316-1322. doi: 10.3760/cma.j.cn112137-20230810-00199.ABSTRACTObjective: To explore the relationship between gut microbiota and its metabolite dysregulation and postoperative cognitive dysfunction in elderly male C57BL/6J mice after laparotomy exploration. Methods: A total of 48 specific pathogen-free (SPF) male C57BL/6J mice, aged 16-17 months, were divided into two groups by random number table method: control group (n=24) and operation group (n=24). Mice in the operation group were induced with 1.4% isoflurane for 15 minutes, followed by a 10 minutes exploratory laparotomy anesthetized with 1.4% isoflurane and 100% oxygen, and anesthesia continued for 2 hours after surgery. Mice in control group were put in 100% oxygen for 2 hours. Feces and venous blood samples of both groups were collected 48 hours after surgery. Changes in the abundance and diversity of intestinal bacteria in the feces were detected by 16S rDNA gene sequencing. Functional changes of fecal metabolic profiles were detected by liquid chromatography tandem mass spectrometry (LC/MS) metabolomics and differential metabolite functions were analyzed. The serum level of interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were detected by Enzyme-linked immunosorbent assay (ELISA). The cognitive function of the mice was detected by Morris water maze test 3 days after operation. Results: The postoperative escape latency of mice in control group and operation group was (22.0±4.9) and (35.0±5.1) s, and the target quadrant residence time was (26.0±3.7) and (16.0±2.9) s, respectively. Compared with the control group, the postoperative escape latency of mice in the operation group was prolonged (P=0.035), and the residence time in the target quadrant was reduced (P=0.006). The difference of intestinal flora between the two groups was comparable. The expression levels of Escherichia coli, shigella and clostridium in the operation group were up-regulated, while the expression levels of rumen bacteria and butyricobacteria were down-regulated. Fecal metabolic profiles of mice in control group and operation group were obtained by LC/MS, and 14 and 21 different metabolites were screened in positive and negative ion modes, respectively. The different metabolites in positive ion mode were glutamic acid, 2-indoleic acid, kynuuric acid and glyceraldehyde. The negative ion pattern differential metabolites are methionine, aspartic acid, L-threonine, tyrosyl-threonine and 5-hydroxyindole-3-acetic acid. The identified differential metabolite pathways are mainly involved in amino acid, fatty acid and tryptophan metabolism and nucleotide synthesis. There were no significant differences in serum levels of IL-1β, IL-6 and TNF-α between the two groups (all P>0.05). Conclusion: The dysregulated changes of gut microbiota and its metabolites are correlated with the occurrence of postoperative cognitive dysfunction in elderly male C57BL/6J mice. Anesthesia and surgery alter the structure of mice intestinal bacteria on the level of abundance, and change the metabolic balance and feces metabolomic phenotype.PMID:38637168 | DOI:10.3760/cma.j.cn112137-20230810-00199