PubMed

Food Sci Nutr. 2024 Mar 5;12(6):4049-4062. doi: 10.1002/fsn3.4061. eCollection 2024 Jun.ABSTRACTThe primary objective of this investigation was to explore the beneficial impacts of Enteromorpha prolifera polysaccharide (EP) on dysglycemia in Zucker diabetic fatty (ZDF) rats, while also shedding light on its potential mechanism using 1H-NMR-based metabolomics. The results demonstrated a noteworthy reduction in fasting blood glucose (FBG, 46.3%), fasting insulin (50.17%), glycosylated hemoglobin A1c (HbA1c, 44.1%), and homeostatic model assessment of insulin resistance (HOMA-IR, 59.75%) following EP administration, while the insulin sensitivity index (ISI, 19.6%) and homeostatic model assessment of β-cell function (HOMA-β, 2.5-fold) were significantly increased. These findings indicate that EP enhances β-cell function, increases insulin sensitivity, and improves insulin resistance caused by diabetes. Moreover, EP significantly reduced serum lipid levels, suggesting improvement of dyslipidemia. Through the analysis of serum metabolomics, 17 metabolites were found to be altered in diabetic rats, 14 of which were upregulated and 3 of which were downregulated. Notably, the administration of EP successfully reversed the abnormal levels of 9 out of the 17 metabolites. Pathway analysis further revealed that EP treatment partially restored metabolic dysfunction, with notable effects observed in valine, leucine, and isoleucine metabolism; aminoacyl-transfer RNA (tRNA) biosynthesis; and ketone body metabolism. These findings collectively indicate the potential therapeutic efficacy of EP in preventing glycemic abnormalities and improving insulin resistance. Thus, EP holds promise as a valuable treatment option for individuals with diabetes.PMID:38873458 | PMC:PMC11167149 | DOI:10.1002/fsn3.4061

Food Sci Nutr. 2024 Apr 4;12(6):4421-4434. doi: 10.1002/fsn3.4108. eCollection 2024 Jun.ABSTRACTWith the changes of people's lifestyle, hyperlipidemia and hyperglycemia which were induced from a diet high in both fat and sugar have become serious health concerns. Tree peony seed oil (PSO) is a novel kind of edible oil that shows great potential in the food industry because of its high constituent of unsaturated fatty acids. Based 16S rRNA and gut untargeted metabolomics, this study elucidated that the mechanism of PSO regulating blood glucose (Glu) and lipids. The impact of PSO on gut microbiota balance and gut metabolites of mice with a high-fat diet (HFD) was evaluated. The findings indicated that PSO decreased HFD mice's body weight and fat accumulation, ameliorating the levels of blood lipid, reduced liver fat vacuole levels. What's more PSO modulated the proportion of gut microbiota in HFD mice and enhanced the abundance of probiotics. Furthermore, untargeted metabolomic analysis revealed that PSO not only impacted the generation of short-chain fatty acids (SCFAs) by gut microorganism and altered metabolic pathway but exerted influence on secondary bile acids (BA), amino acid metabolism, and various other metabolites. These results suggested that PSO has the potential function for mitigating HFD-induced hyperlipidemia and hyperglycemia by regulating gut microbiota and host metabolism.PMID:38873446 | PMC:PMC11167153 | DOI:10.1002/fsn3.4108

Front Pharmacol. 2024 May 30;15:1362544. doi: 10.3389/fphar.2024.1362544. eCollection 2024.ABSTRACTThe most frequent adverse event associated with bedaquiline (BDQ) is the QTc interval prolongation; however, there was no biomarkers that could be used to predict the occurrence of QTc prolongation in BDQ-treated patients. In this study, we employed the ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) to generate metabolic profiling for the discovery of potential predictive urine biomarkers of QTc prolongation in these patients. Untargeted metabolomic technique was used to concentrate the differential metabolic pathway, and targeted metabolomic technique was subsequently performed to identify predictive biomarkers for QTc prolongation. A total of 45 rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB) patients were enrolled in our study, including 15 RR/MDR-TB patients with QTc interval prolongation (QIP) and 30 RR/MDR-TB patients with QTc interval un-prolongations (QIU). Untargeted technique revealed that the lipid metabolism was the most differential metabolic pathway between two groups. Further targeted technique identified four differential metabolites, including betaine, LPE (18:2), LPE (20:3), and LPE (20:4). The combined analysis of metabolisms revealed that the combined use of LPE (20:3) and LPE (20:4) had the best performance for predicting the occurrence of QTc prolongation in TB patients, yielding a sensitivity of 87.4% and a specificity of 78.5%. In addition, with the progression of BDQ treatment, the LPEs exhibited persistent difference in the BDQ-treated TB patients experiencing QTc interval prolongation. In conclusion, our data demonstrate that the combined use of LPE (20:3) and LPE (20:4) yields promising performance for predicting the occurrence of QTc interval prolongation in BDQ-treated patients.PMID:38873419 | PMC:PMC11169739 | DOI:10.3389/fphar.2024.1362544

Exp Ther Med. 2024 Jun 5;28(2):311. doi: 10.3892/etm.2024.12599. eCollection 2024 Aug.ABSTRACTExcessive alcohol consumption is considered to be a major risk factor of alcohol-induced osteonecrosis of the femoral head (AONFH). The gut microbiota (GM) has been reported to aid in the regulation of human physiology and its composition can be altered by alcohol consumption. The aim of the present study was to improve the understanding of the GM and its metabolites in patients with AONFH. Metabolomic sequencing and 16S rDNA analysis of fecal samples were performed using liquid chromatography-mass spectrometry to characterize the GM of patients with AONFH and healthy normal controls (NCs). Metagenomic sequencing of fecal samples was performed to identify whether GM changes on the species level were associated with the expression of gut bacteria genes or their associated functions in patients with AONFH. The abundance of 58 genera was found to differ between the NC group and the AONFH group. Specifically, Klebsiella, Holdemanella, Citrobacter and Lentilactobacillus were significantly more abundant in the AONFH group compared with those in the NC group. Metagenomic sequencing demonstrated that the majority of the bacterial species that exhibited significantly different abundance in patients with AONFH belonged to the genus Pseudomonas. Fecal metabolomic analysis demonstrated that several metabolites were present at significantly different concentrations in the AONFH group compared with those in the NC group. These metabolites were products of vitamin B6 metabolism, retinol metabolism, pentose and glucuronate interconversions and glycerophospholipid metabolism. In addition, these changes in metabolite levels were observed to be associated with the altered abundance of specific bacterial species, such as Basidiobolus, Mortierella, Phanerochaete and Ceratobasidium. According to the results of the present study, a comprehensive landscape of the GM and metabolites in patients with AONFH was revealed, suggesting the existence of interplay between the gut microbiome and metabolome in AONFH pathogenesis.PMID:38873043 | PMC:PMC11170330 | DOI:10.3892/etm.2024.12599

Front Endocrinol (Lausanne). 2024 May 30;15:1397402. doi: 10.3389/fendo.2024.1397402. eCollection 2024.ABSTRACTGraphene-based warm uterus acupoint paste (GWUAP) is an emerging non-drug alternative therapy for the treatment of primary dysmenorrhea (PD), but the underlying mechanism is still unclear. SD female rats were randomly divided into control group, model group and treatment group to explore the mechanism of GWUAP in the treatment of PD. Combined with 16S rDNA and fecal metabolomics, the diversity of microbiota and metabolites in each group was comprehensively evaluated. In this study, GWUAP reduced the torsion score of PD model rats, improved the pathological morphology of uterine tissue, reduced the pathological damage score of uterine tissue, and reversed the expression levels of inflammatory factors, pain factors and sex hormones. The 16 S rDNA sequencing of fecal samples showed that the abundance of Lactobacillus in the intestinal flora of the model group decreased and the abundance of Romboutsia increased, while the abundance of Lactobacillus in the intestinal flora of the treatment group increased and the abundance of Romboutsia decreased, which improved the imbalance of flora diversity in PD rats. In addition, 32 metabolites related to therapeutic effects were identified by metabolomics of fecal samples. Moreover, there is a close correlation between fecal microbiota and metabolites. Therefore, the mechanism of GWUAP in the treatment of PD remains to be further studied.PMID:38872962 | PMC:PMC11169635 | DOI:10.3389/fendo.2024.1397402

Front Vet Sci. 2024 May 30;11:1409518. doi: 10.3389/fvets.2024.1409518. eCollection 2024.ABSTRACTOBJECTIVE: Garlic skin (GAS) has been proven to improve the growth performance of fattening sheep. However, the mechanism by which GAS affects fattening sheep is not yet clear. The aim of this study is to investigate the effects of adding GAS to feed on the growth performance, rumen and fecal microbiota, serum and urine metabolism, and transcriptomics of rumen epithelial cells in fattening sheep.METHODS: GAS with 80 g/kg dry matter (DM) was added to the diet of fattening sheep to study the effects of GAS on gut microbiota, serum and urine metabolism, and transcriptome of rumen epithelial tissue in fattening sheep. Twelve Hu sheep (body weights; BW, 23.0 ± 2.3 kg and ages 120 ± 3.5 d) were randomly divided into two groups. The CON group was the basal diet, while the GAS group was supplemented with GAS in the basal diet. The trial period was 10 weeks, with the first 2 weeks being the pre-trial period.RESULTS: The daily average weight gain of fattening sheep in the GAS group was significantly higher than that in the CON group (p < 0.05), and the serum GSH-Px of the GAS group fattening sheep was significantly increased, while MDA was significantly reduced (p < 0.05). Based on the genus classification level, the addition of garlic peel in the diet changed the intestinal microbial composition, and the relative abundance was significantly upregulated by Metanobrevibater (p < 0.05), while significantly downregulated by Akkermansia, Parasutterella, and Guggenheimella (p < 0.05). Metabolomics analysis found that there were 166 significantly different metabolites in serum and 68 significantly different metabolites in urine between the GAS and CON groups (p < 0.05). GAS had an impact on amino acid metabolism, pyrimidine metabolism, methane metabolism, riboflavin metabolism, and unsaturated fatty acid synthesis pathways (p < 0.05). Transcriptome sequencing showed that differentially expressed genes were mainly enriched in immune regulatory function, improving the health of fattening sheep.CONCLUSION: Adding GAS can improve the energy metabolism and immune function of fattening sheep by altering gut microbiota, metabolome, and transcriptome, thereby improving the growth performance of fattening sheep.PMID:38872796 | PMC:PMC11171129 | DOI:10.3389/fvets.2024.1409518

Front Aging Neurosci. 2024 May 30;16:1393721. doi: 10.3389/fnagi.2024.1393721. eCollection 2024.ABSTRACTINTRODUCTION: Gastrodia elata Blume is a widely used medicinal and edible herb with a rich chemical composition. Moreover, prescriptions containing Gastrodia elata are commonly used for the prevention and treatment of cardiovascular, cerebrovascular, and aging-related diseases. Recent pharmacological studies have confirmed the antioxidant and neuroprotective effects of Gastrodia elata, and, in recent years, this herb has also been used in the treatment of Alzheimer's disease (AD) and other neurodegenerative disorders. We have previously shown that 4,4'-methylenediphenol, a key active ingredient of Gastrodia elata, can mitigate amyloid-β (Aβ)-induced paralysis in AD model worms as well as prolong the lifespan of the animals, thus displaying potential as a treatment of AD.METHODS: We investigated the effects of 4,4'-methylenediphenol on AD and aging through paralysis, lifespan, and behavioral assays. In addition, we determined the anti-AD effects of 4,4'-methylenediphenol by reactive oxygen species (ROS) assay, lipofuscin analysis, thioflavin S staining, metabolomics analysis, GFP reporter gene worm assay, and RNA interference assay and conducted in-depth studies on its mechanism of action.RESULTS: 4,4'-Methylenediphenol not only delayed paralysis onset and senescence in the AD model worms but also enhanced their motility and stress tolerance. Meanwhile, 4,4'-methylenediphenol treatment also reduced the contents of reactive oxygen species (ROS) and lipofuscin, and decreased Aβ protein deposition in the worms. Broad-spectrum targeted metabolomic analysis showed that 4,4'-methylenediphenol administration had a positive effect on the metabolite profile of the worms. In addition, 4,4'-methylenediphenol promoted the nuclear translocation of DAF-16 and upregulated the expression of SKN-1, SOD-3, and GST-4 in the respective GFP reporter lines, accompanied by an enhancement of antioxidant activity and a reduction in Aβ toxicity; importantly, our results suggested that these effects of 4,4'-methylenediphenol were mediated, at least partly, via the activation of DAF-16.CONCLUSION: We have demonstrated that 4,4'-methylenediphenol can reduce Aβ-induced toxicity in AD model worms, suggesting that it has potential for development as an anti-AD drug. Our findings provide ideas and references for further research into the anti-AD effects of Gastrodia elata and its active ingredients.PMID:38872629 | PMC:PMC11171718 | DOI:10.3389/fnagi.2024.1393721

Exp Gerontol. 2024 Jun 11:112479. doi: 10.1016/j.exger.2024.112479. Online ahead of print.ABSTRACTPURPOSE: Trimethylamine-N-oxide (TMAO) is a gut-derived metabolite associated with cardiovascular disease (CVD). In preclinical and observational studies, resveratrol and exercise training have been suggested as potential strategies to reduce the systemic levels of TMAO. However, evidence from experimental studies in humans remains unknown. This project examined the dose-dependent effects of a combined resveratrol intervention with exercise training on circulating TMAO and other related metabolite signatures in older adults with high CVD risk.METHODS: Forty-one older adults [mean (±SD) age of 72.1 (6.8) years] participated in a 12-week supervised center-based, multi-component exercise training intervention [2×/week; 80 min/session] and were randomized to one of two resveratrol dosages [Low: 500 vs. High:1000 mg/day] or a cellulose-based placebo. Serum/plasma were collected at baseline and post-intervention and evaluated for TMAO and associated analytes.RESULTS: After the 12-week intervention, TMAO concentration increased over time, regardless of treatment [mean (±SD) Placebo: 11262 (±3970); Low:13252 (±1193); High: 12661(±3359) AUC; p = 0.04]. Each resveratrol dose produced different changes in metabolite signatures. Low dose resveratrol upregulated metabolites associated with bile acids biosynthesis (i.e., glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycocholic acid). High dose resveratrol modulated metabolites enriched for glycolysis, and pyruvate, propanoate, β-alanine, and tryptophan metabolism. Different communities tightly correlated to TMAO and resveratrol metabolites were associated with the lipid and vascular inflammatory clinical markers [|r| > 0.4, p < 0.05].CONCLUSION: These findings suggest a distinct dose-dependent adaptation response to resveratrol supplementation on circulating metabolite signatures but not on TMAO among high-risk CVD older adults when combined with an exercise training intervention.PMID:38871236 | DOI:10.1016/j.exger.2024.112479

Int J Biol Macromol. 2024 Jun 11:133060. doi: 10.1016/j.ijbiomac.2024.133060. Online ahead of print.ABSTRACTPlant-derived polysaccharides are important components for biological functions. The objective of this study is to study the mechanisms by which polysaccharides from three Huanglian (Rhizome Coptidis, HL) of Coptis chinensis, C. deltoidea, and Coptis teeta affect type 2 diabetes mellitus (T2DM) by analyzing the gut microbiome and their metabolites. A long-term high-fat diet (HFD) combined with streptozocin (STZ) induction was used to construct the T2DM mice model. The histopathology of liver, pancreas, and colon, biochemical indexes related to mice were determined to assess the ameliorative effects of these three HL polysaccharides (HLPs) on T2DM. The results indicated that oral HLPs improved hyperglycemia, insulin resistance, blood lipid levels, and β-cell function. Further, HLPs elevated the growth of advantageous beneficial bacteria within the gut microbiota and raised the concentrations of short-chain fatty acids (SCFAs), particularly butyric acid. Metabolic analyses showed that HLPs ameliorated the effects of T2DM on microbial-derived metabolites and related metabolic pathways, especially the biosynthetic pathways of phenylalanine, tyrosine, and tryptophan. In the combined analysis, many associations of T2DM-related biochemical indicators with gut microbes and their metabolites were extracted, which suggested the important role of gut microbiome and fecal metabolome in the amelioration of type 2 diabetes mellitus by HLPs.PMID:38871107 | DOI:10.1016/j.ijbiomac.2024.133060

Metabolism. 2024 Jun 11:155941. doi: 10.1016/j.metabol.2024.155941. Online ahead of print.ABSTRACTBACKGROUND: An altered gut microbiome characterized by reduced abundance of butyrate producing bacteria and reduced gene richness is associated with type 2 diabetes (T2D). An important complication of T2D is increased risk of cognitive impairment and dementia. The biguanide metformin is a commonly prescribed medication for the control of T2D and metformin treatment has been associated with a significant reduction in the risk of dementia and improved cognition, particularly in people with T2D.AIM: To investigate the associations of metformin use with cognition exploring potential mechanisms by analyzing the gut microbiome and plasma metabolome using shotgun metagenomics and HPLC-ESI-MS/MS, respectively.METHODS: We explored two independent cohorts: an observational study (Aging Imageomics) and a phase IV, randomized, double-blind, parallel-group, randomized pilot study (MEIFLO). From the two studies, we analyzed four study groups: (1) individuals with no documented medical history or medical treatment (n = 172); (2) people with long-term T2D on metformin monotherapy (n = 134); (3) people with long-term T2D treated with oral hypoglycemic agents other than metformin (n = 45); (4) a newly diagnosed T2D subjects on metformin monotherapy (n = 22). Analyses were also performed stratifying by sex.RESULTS: Several bacterial species belonging to the Proteobacteria (Escherichia coli) and Verrucomicrobia (Akkermansia muciniphila) phyla were positively associated with metformin treatment, while bacterial species belonging to the Firmicutes phylum (Romboutsia timonensis, Romboutsia ilealis) were negatively associated. Due to the consistent increase in A. muciniphila and decrease in R.ilealis in people with T2D subjects treated with metformin, we investigated the association between this ratio and cognition. In the entire cohort of metformin-treated T2D subjects, the A.muciniphila/R.ilealis ratio was not significantly associated with cognitive test scores. However, after stratifying by sex, the A.muciniphila/R. ilealis ratio was significantly and positively associated with higher memory scores and improved memory in men. Metformin treatment was associated with an enrichment of microbial pathways involved in the TCA cycle, and butanoate, arginine, and proline metabolism in both cohorts. The bacterial genes involved inarginine metabolism, especially in production of glutamate (astA, astB, astC, astD, astE, putA), were enriched following metformin intake. In agreement, in the metabolomics analysis, metformin treatment was strongly associated with the amino acid proline, a metabolite involved in the metabolism of glutamate.CONCLUSIONS: The beneficial effects of metformin may be mediated by changes in the composition of the gut microbiota and microbial-host-derived co-metabolites.PMID:38871078 | DOI:10.1016/j.metabol.2024.155941

J Ethnopharmacol. 2024 Jun 11:118458. doi: 10.1016/j.jep.2024.118458. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi essential oil (AAEO) is a traditional herbal remedy for asthma. However, the potential effect of AAEO on asthma has not been elucidated.AIM OF THE STUDY: To investigate the protective properties of AAEO upon asthma and elucidate its mechanism.MATERIALS AND METHODS: The effects of AAEO in asthma were assessed by histology and biochemical analysis. Then, we integrated real-time reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry and metabolomics analysis to reveal its mechanism.RESULTS: In vivo, AAEO reduced the counts of white blood cells (WBCs) and cytokines in bronchoalveolar lavage fluid (BALF), ameliorated pathologic alterations in lung tissues, and inhibited secretion of OVA-sIgE and muc5ac. Metabolomics results showed that AAEO can exert therapeutic effects on asthmatic mice by regulating disordered arachidonic acid metabolism and tryptophan metabolism. Further studies shown that AAEO inhibited the expression of 5-LOX and reduced the accumulation of CysLTs in mice. Meanwhile, AAEO promoted the activity of IDO-1, facilitated the conversion of tryptophan to kynurenine, and regulated the imbalance of Treg/Th17 immunity. Immunohistochemical results showed that AAEO promoted the expression of IDO-1. RT-qPCR results showed that AAEO promoted the expression of IL-10 and Foxp3 mRNA, and inhibited the expression of IL-17A and RORγt mRNA, thus regulated the imbalance of Treg/Th17 immunity and exerted its therapeutic effects.CONCLUSION: AAEO treatment not only attenuates the clinical symptoms of asthma but is also involved in regulating lung tissue metabolism. The anti-asthmatic activity of AAEO may be achieved by reprogramming 5-LOX-CysLTs and IDO-1-KYN pathways.PMID:38871010 | DOI:10.1016/j.jep.2024.118458

Cell Host Microbe. 2024 Jun 12;32(6):786-793. doi: 10.1016/j.chom.2024.05.009.ABSTRACTSurvival strategies of human-associated microbes to drug exposure have been mainly studied in the context of bona fide pathogens exposed to antibiotics. Less well understood are the survival strategies of non-pathogenic microbes and host-associated commensal communities to the variety of drugs and xenobiotics to which humans are exposed. The lifestyle of microbial commensals within complex communities offers a variety of ways to adapt to different drug-induced stresses. Here, we review the responses and survival strategies employed by gut commensals when exposed to drugs-antibiotics and non-antibiotics-at the individual and community level. We also discuss the factors influencing the recovery and establishment of a new community structure following drug exposure. These survival strategies are key to the stability and resilience of the gut microbiome, ultimately influencing the overall health and well-being of the host.PMID:38870896 | DOI:10.1016/j.chom.2024.05.009

Food Chem. 2024 Jun 8;456:140031. doi: 10.1016/j.foodchem.2024.140031. Online ahead of print.ABSTRACTLyonia ovalifolia (Wall.) Drude (LO) is mainly distributed in China with health benefits. In this study, LO buds (LOB) were extracted by ultrasonic extraction (UE) with or without ultra-high-pressure (UHP-UE), microwave (MW-UE), subcritical (SC-UE) techniques. The metabolomic result showed that a total of 960 chemical compounds and 117 differential compounds were identified from LOB extracts. The UHP-UE extract was rich in total polyphenol and flavonoid contents, followed by MW-UE, UE and SC-UE extracts, respectively. All LOB extracts increased superoxide dismutase (SOD) and catalase (CAT) activities, and glutathione (GSH) content, decreased reactive oxygen species (ROS) accumulation, levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor -α (TNF-α), and nitric oxide (NO), and alleviated apoptosis in cells. The cellular protective effect was UHP-UE > MW-UE > UE > SC-UE. This study revealed that higher pressure and lower temperature may be key factors for increasing bioactivities of LOB extracts.PMID:38870821 | DOI:10.1016/j.foodchem.2024.140031

Food Chem. 2024 May 29;456:139883. doi: 10.1016/j.foodchem.2024.139883. Online ahead of print.ABSTRACTWild soybean (Glycine soja) is known for its high flavonoid contents, yet the distribution of flavonoids in the seeds is not well understood. Herein, we utilized matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and metabolomics methods to systematically investigate flavonoid differences in the seed coats and embryos of G. soja and G. max. The results of flavonoid profiles and total flavonoid content analyses revealed that flavonoid diversity and abundance in G. soja seed coats were significantly higher than those in G. max whereas the levels were similar in embryos. Specifically, 23 unique flavonoids were identified in the seed coats of G. soja, including procyanidins, epicatechin derivatives, and isoflavones. Using MALDI-MSI, we further delineated the distribution of the important flavonoids in the cotyledons, hypocotyls, and radicles of the two species. These findings imply that G. soja holds considerable breeding potential to enhance the nutritional and stress resistance traits of G. max.PMID:38870803 | DOI:10.1016/j.foodchem.2024.139883

Talanta. 2024 Jun 6;277:126378. doi: 10.1016/j.talanta.2024.126378. Online ahead of print.ABSTRACTIn our previous study, a chemical derivatization reagent named 5-(dimethylamino) naphthalene-1-sulfonyl piperazine (Dns-PP) was developed to enhance the chromatographic retention and the mass spectrometric response of free fatty acids (FFAs) in reversed-phase liquid chromatography coupled with electrospray ionization-mass spectrometry (RPLC-ESI-MS). However, Dns-PP exhibited strong preferences for long-chain FFAs, with limited improvement for short- or medium-chain FFAs. In this study, a new series of labeling reagents targeting FFAs were designed, synthesized, and evaluated. Among these reagents, Tmt-PP (N2, N2, N4, N4-tetramethyl-6-(4-(piperazin-1-ylsulfonyl) phenyl)-1,3,5-triazine-2,4-diamine) exhibited the best MS response and was selected for further evaluations. We compared Tmt-PP with Dns-PP and four commonly used carboxyl labeling reagents from existing studies, demonstrating the advantages of Tmt-PP. Further comparisons between Tmt-PP and Dns-PP in measuring FFAs from biological samples revealed that Tmt-PP labeling enhanced the MS response for about 80 % (30/38) of the measured FFAs, particularly for short- and medium-chain FFAs. Moreover, Tmt-PP labeling significantly improved the chromatographic retention of short-chain FFAs. To ensure accurate quantification, we developed a stable isotope-labeled Tmt-PP (i.e., d12-Tmt-PP) to react with chemical standards and serve as one-to-one internal standards (IS). The method was validated for accuracy, precision, sensitivity, linearity, stability, extraction efficiency, as well as matrix effect. Overall, this study introduced a new chemical derivatization reagent Tmt-PP (d12-Tmt-PP), providing a sensitive and accurate option for quantifying FFAs in biological samples.PMID:38870757 | DOI:10.1016/j.talanta.2024.126378

Talanta. 2024 May 29;277:126340. doi: 10.1016/j.talanta.2024.126340. Online ahead of print.ABSTRACTUnderstanding the contribution of new natural sources of antioxidant compounds to the stability of wines is of great interest in a context of reduction of sulfites. Here, we investigated the antioxidant potential of selected inactivated non-Saccharomyces yeast (INSY) along with related chemical fingerprints, using combined untargeted UHPLC-Q-ToF MS and DPPH analyses. 4 INSY species were compared to a reference inactivated Saccharomyces cerevisiae yeast (ISY) selected for its high antioxidant capacity. Our results show that, all the INSY can accumulate GSH during the specific production process with yields ranging from +170 % to +360 % compared to the corresponding classical production process. The principal component analysis of the 3511 ions detected by UHPLC-Q-ToF-MS clearly grouped INSY by species, independently of the production process. One INSY exhibited equivalent antioxidant capacity to the control ISY, but with a GSH concentration four times lower (4.73 ± 0.09 mg/g against 20.95 ± 0.34 mg/g, respectively). 73 specific ions presenting strong and significant spearman correlation (rho < -0.6, p-value < 0.05) with the DPPH scores, clustered the most antioxidant INSY and the control Saccharomyces in different groups, indicating that the antioxidant capacity of these two products should be driven by different pools of compounds. These results point out that, GSH alone is not relevant to explain the antioxidant capacity of INSY soluble fractions and other more reactive compounds must be considered, which opens an avenue for the selection new species with great enological potential.PMID:38870756 | DOI:10.1016/j.talanta.2024.126340

Phytomedicine. 2024 May 23;132:155755. doi: 10.1016/j.phymed.2024.155755. Online ahead of print.ABSTRACTBACKGROUND: Pulmonary fibrosis, a progressive and fatal lung disease with no effective treatment medication, is characterized by lung remodeling and fibroblastic foci caused by an oxidative imbalance with an overloading deposition of collagen. Trichodelphinine A, a hetisine-type C20-diterpenoid alkaloid, was found anti-fibrotic activity in vitro, but its effect and mechanism on pulmonary fibrosis still unknown.PURPOSE: Our study aimed to investigate and validate the anti-fibrotic properties of trichodelphinine A in pulmonary fibrosis animals induced by bleomycin (BLM), and its mechanism whether via NOX4-ARG1/TGF-β signaling pathway.METHODS: The anti-fibrotic effects of trichodelphinine A were evaluated using BLM-induced rats through indicators of lung histopathology and collagen synthesis. Dynamic metabolomics evaluated the metabolic disorder and therapeutic effect of trichodelphinine A. The interaction between trichodelphinine A and NOX4 receptor was confirmed using CETSA and molecular dynamics experiments. Molecular biology experiments were conducted in NOX4 gene knockout mice to investigate the intervention effect of trichodelphinine A.RESULTS: Trichodelphinine A could suppress histopathologic changes, collagen deposition and proinflammatory cytokine release pulmonary fibrosis in bleomycin induced rats. Dynamic metabolomics studies revealed that trichodelphinine A could correct endogenous metabolic disorders of arachidonic acid, arginine and proline during fibrosis development, which revealed that the regulation of oxidative stress and amino acid metabolism targeting NOX4 and ARG1 may be the main pharmacological mechanisms of trichodelphinine A on pulmonary fibrosis. We further determined that trichodelphinine A inhibited over oxidative stress and collagen deposition by suppressing Nrf2-keap1 and ARG1-OAT signaling pathways, respectively. Molecular dynamics studies showed that trichodelphinine A was directly binds with NOX4, in which PHE354 and THR355 residues of NOX4 are critical binding sites for trichodelphinine A. Mechanistic validation in cells or mice with NOX4 knockout or silencing suggested that the anti-fibrotic effects of trichodelphinine A depended on inhibition of NOX4 to suppress ARG1/OAT activation and TGF-β/Smads signaling pathway.CONCLUSION: Collectively, our findings indicate a powerful anti-fibrotic function of trichodelphinine A in pulmonary fibrosis via targeting NOX4. NOX4 mediates the activation of ARG1/OAT to regulate arginase-proline metabolism, and promotes TGF-β/Smads signaling pathway, thereby affecting the collagen synthesis in pulmonary fibrosis, which is a novel finding and indicates that inhibition of NOX4 is a novel therapeutic strategy for pulmonary fibrosis.PMID:38870750 | DOI:10.1016/j.phymed.2024.155755

Poult Sci. 2024 May 25;103(8):103905. doi: 10.1016/j.psj.2024.103905. Online ahead of print.ABSTRACTIncreasing evidence has indicated that the gut microbiome plays an important role in chicken growth traits. However, the cecal microbial taxa associated with the growth rates of the Chinese Ningdu yellow chickens are unknown. In this study, shotgun metagenomic sequencing was used to identify cecal bacterial species associated with the growth rate of the Chinese Ningdu yellow chickens. We found that nine cecal bacterial species differed significantly between high and low growth rate chickens, including three species (Succinatimonas hippei, Phocaeicola massiliensis, and Parabacteroides sp. ZJ-118) that were significantly enriched in high growth rate chickens. We identified six Bacteroidales that were significantly enriched in low growth rate chickens, including Barnesiella sp. An22, Barnesiella sp. ET7, and Bacteroidales bacterium which were key biomarkers in differentiating high and low growth rate chickens and were associated with alterations in the functional taxa of the cecal microbiome. Untargeted serum metabolome analysis revealed that 8 metabolites showing distinct enrichment patterns between high and low growth rate chickens, including triacetate lactone and N-acetyl-a-neuraminic acid, which were at higher concentrations in low growth rate chickens and were positively and significantly correlated with Barnesiella sp. An22, Barnesiella sp. ET7, and Bacteroidales bacterium. Furthermore, the results suggest that serum cytokines, such as IL-5, may reduce growth rate and are related to changes in serum metabolites and gut microbes (e.g., Barnesiella sp. An22 and Barnesiella sp. ET7). These results provide important insights into the effects of the cecal microbiome, serum metabolism and cytokines in Ningdu yellow chickens.PMID:38870614 | DOI:10.1016/j.psj.2024.103905

Theriogenology. 2024 Jun 8;226:95-103. doi: 10.1016/j.theriogenology.2024.06.003. Online ahead of print.ABSTRACTMelatonin, a hormone synthesized in various tissues, plays a crucial role in modulating sperm characteristics, yet its protective function on boar sperm remains poorly understood. This study aimed to investigate the expression and localization of melatonin-related proteins (AANAT, ASMT, MT1, MT2, and NQO2) in pig tissues, assess the impact of melatonin on pig sperm motility parameters and quality, and elucidate the underlying molecular mechanisms. Our results revealed widespread expression of AANAT, ASMT, MT1, MT2, and NQO2 proteins in pig tissues, particularly in the testis. Specific localization patterns were observed in Leydig cells, reproductive epithelium, and columnar epithelium cells in the testis and cauda epididymis. Additionally, melatonin membrane receptors MT1 and MT2 were detected in boar sperm. Melatonin treatment significantly enhanced boar sperm motility parameters and quality, particularly with 10 nM melatonin treatment. Inhibition of the MT1 receptor, but not the MT2 receptor, resulted in decreased sperm motility, highlighting the pivotal role of the MT1 receptor in mediating melatonin's effects on boar sperm. Metabolomic analysis revealed significant alterations in sperm metabolites following melatonin supplementation, particularly in amino acid metabolism. Overall, our findings provide comprehensive insights into melatonin's mechanisms in improving boar sperm quality, suggesting its potential as a therapeutic agent for enhancing male fertility.PMID:38870584 | DOI:10.1016/j.theriogenology.2024.06.003

Sci Rep. 2024 Jun 13;14(1):13651. doi: 10.1038/s41598-024-64312-0.ABSTRACTTraumatic brain injury (TBI) is a ubiquitous, common sequela of accidents with an annual prevalence of several million cases worldwide. In forensic pathology, structural proteins of the cellular compartments of the CNS in serum and cerebrospinal fluid (CSF) have been predominantly used so far as markers of an acute trauma reaction for the biochemical assessment of neuropathological changes after TBI. The analysis of endogenous metabolites offers an innovative approach that has not yet been considered widely in the assessment of causes and circumstances of death, for example after TBI. The present study, therefore, addresses the question whether the detection of metabolites by liquid-chromatography-mass spectrometry (LC/MS) analysis in post mortem CSF is suitable to identify TBI and to distinguish it from acute cardiovascular control fatalities (CVF). Metabolite analysis of 60 CSF samples collected during autopsies was performed using high resolution (HR)-LC/MS. Subsequent statistical and graphical evaluation as well as the calculation of a TBI/CVF quotient yielded promising results: numerous metabolites were identified that showed significant concentration differences in the post mortem CSF for lethal acute TBI (survival times up to 90 min) compared to CVF. For the first time, this forensic study provides an evaluation of a new generation of biomarkers for diagnosing TBI in the differentiation to other causes of death, here CVF, as surrogate markers for the post mortem assessment of complex neuropathological processes in the CNS ("neuroforensomics").PMID:38871842 | DOI:10.1038/s41598-024-64312-0