PubMed

J Vet Intern Med. 2023 Jul 1. doi: 10.1111/jvim.16796. Online ahead of print.ABSTRACTBACKGROUND: Previous studies in dogs with degenerative mitral valve disease (DMVD) have identified altered myocardial energy metabolism and oxidation, which might contribute to cardiac hypertrophy. Diets rich in medium chain fatty acids and antioxidants are a potential means of treatment. A previous clinical study found significantly smaller left atrial diameter (LAD) and left atrium-to-aorta diameter ratio (LA : Ao) in dogs with subclinical DMVD fed a specially formulated diet vs control diet for 6 months.HYPOTHESIS/OBJECTIVES: A specially formulated diet will slow or arrest left heart enlargement in dogs with subclinical DMVD over 365 days.ANIMALS: One hundred twenty-seven dogs with unmedicated subclinical DMVD; 101 dogs in the per protocol cohort.METHODS: Randomized double-blinded controlled multicenter clinical trial.RESULTS: The study's primary composite outcome measure was the sum of percentage change in LAD and left ventricular internal dimension at end-diastole (LVIDd) at day 365. In the per protocol cohort, the outcome measure increased by 8.0% (95% confidence interval [CI], 2.9%-13.1%) in dogs receiving the test diet vs 8.8% (95% CI, 5.1%-12.5%) in dogs receiving control diet (P = .79). Neither component of the primary outcome measure was significantly different between groups (LAD, P = .65; LVIDd, P = .92). No difference was found in mitral valve E wave velocity (P = .36) or the proportion of dogs withdrawn from the study because of worsening DMVD and heart enlargement (P = .41).CONCLUSIONS AND CLINICAL IMPORTANCE: Feeding a specially formulated diet for 365 days was not associated with a significantly different rate of change of left heart size in dogs with subclinical DMVD as compared to control.PMID:37392086 | DOI:10.1111/jvim.16796

J Appl Physiol (1985). 2023 Jun 30. doi: 10.1152/japplphysiol.00024.2023. Online ahead of print.ABSTRACTUnderstanding changes to gut microbiota composition and metabolic output in response to acute exercise may be necessary for understanding the mechanisms mediating the long-term health and performance benefits of exercise. Our primary objective was to characterize acute changes in the fecal microbiome and metabolome following participation in an ultra-endurance (3.9km swim, 180.2km bike, 42.2km run) triathlon. An exploratory aim was to determine associations between athlete-specific factors (race performance [i.e., completion time] and lifetime years of endurance training) with pre-race gut microbiota and metabolite profiles. Stool samples from 12 triathletes (9M/3F; 43±14 yrs, 23±2 kg/m2) were collected ≤48 hours before and the first bowel movement following race completion. Intra- and inter-individual diversity of bacterial species and individual bacterial taxa were unaltered following race completion (P>0.05). However, significant reductions (P<0.05) in free and secondary bile acids (DCA, 12-ketoLCA) and short-chain fatty acids (butyric and pivalic acids), and significant increases (P<0.05) in long-chain fatty acids (oleic and palmitoleic acids) were observed. Exploratory analyses revealed several associations between pre-race bacterial taxa and fecal metabolites with race performance and lifetime history of endurance training (P<0.05). These findings suggest that 1) acute ultra-endurance exercise shifts microbial metabolism independent of changes to community composition and 2) athlete performance level and training history relate to resting-state gut microbial ecology.PMID:37391884 | DOI:10.1152/japplphysiol.00024.2023

Biomark Res. 2023 Jun 30;11(1):66. doi: 10.1186/s40364-023-00507-3.ABSTRACTCancer exerts a multitude of effects on metabolism, including the reprogramming of cellular metabolic pathways and alterations in metabolites that facilitate inappropriate proliferation of cancer cells and adaptation to the tumor microenvironment. There is a growing body of evidence suggesting that aberrant metabolites play pivotal roles in tumorigenesis and metastasis, and have the potential to serve as biomarkers for personalized cancer therapy. Importantly, high-throughput metabolomics detection techniques and machine learning approaches offer tremendous potential for clinical oncology by enabling the identification of cancer-specific metabolites. Emerging research indicates that circulating metabolites have great promise as noninvasive biomarkers for cancer detection. Therefore, this review summarizes reported abnormal cancer-related metabolites in the last decade and highlights the application of metabolomics in liquid biopsy, including detection specimens, technologies, methods, and challenges. The review provides insights into cancer metabolites as a promising tool for clinical applications.PMID:37391812 | DOI:10.1186/s40364-023-00507-3

Chemosphere. 2023 Jun 28:139375. doi: 10.1016/j.chemosphere.2023.139375. Online ahead of print.ABSTRACTThe presence of pharmaceutical active products (PhACs) in the aquatic environment is a matter of current concern, and there is an increasing trend to include these compounds in water quality monitoring programs and environmental risk assessments. Several studies have reported the presence of PhACs in environmental waters worldwide, but only a few studies have focused on Latin American countries. Thus, available information on the occurrence of parent pharmaceuticals, especially their metabolites, is very scarce. Peru is one of the less monitored countries in terms of contaminants of emerging concern (CECs) in waters, and only one study has been found, which was focused on the quantification of selected PhACs in urban wastewater and surface water. The aim of this work is to complement the previous data reported on PhACs in the aquatic environment by application of a wide-scope high-resolution (HRMS)-based screening, making use of target and suspect approaches. In the present work, 30 pharmaceuticals, drugs or other compounds (sweeteners, UV filters, etc.) and 21 metabolites have been identified, with antibiotics (and metabolites) being the most prevalent compounds. The use of liquid chromatography (LC) coupled to ion mobility-HRMS allowed the tentative identification of parent compounds and metabolites, for which the analytical reference standard was not available, with a high level of confidence in their identification. Based on the results obtained, a strategy for the monitoring of PhACs and relevant metabolites in environmental waters from Peru and for subsequent risk assessment is proposed. Our data will also help to focus future studies to evaluate the removal efficiency of wastewater treatment plants and the impact of treated water in receiving water bodies.PMID:37391080 | DOI:10.1016/j.chemosphere.2023.139375

J Hazard Mater. 2023 Jun 22;458:131910. doi: 10.1016/j.jhazmat.2023.131910. Online ahead of print.ABSTRACTHazardous chemicals, such as perfluoroalkyl substances (PFASs) and antibiotics, coexist in aquatic environments and pose a severe threat to aquatic organisms. However, research into the toxicity of these pollutants on submerged macrophytes and their periphyton is still limited. To assess their combined toxicity, Vallisneria natans (V. natans) was exposed to perfluorooctanoic acid (PFOA) and sulfadiazine (SD) at environmental concentrations. Photosynthetic parameters such as chlorophyll a, chlorophyll b, total chlorophyll, and carotenoids were lower in the SD exposure group, indicating that SD had a significant effect on the photosynthesis of aquatic plants. Single and combined exposures effectively induced antioxidant responses, with increases in superoxide dismutase, peroxidase activities, and ribulose-1,5-bisphosphate carboxylase concentrations, as well as malondialdehyde content. Accordingly, antagonistic toxicity was assessed between PFOA and SD. Furthermore, metabolomics revealed that V. natans improved stress tolerance through changes in enoic acid, palmitic acid, and palmitoleoyloxymyristic acid related to the fatty acid metabolism pathway responding to the coexisting pollutants. Additionally, PFOA and SD in combination induced more effects on the microbial community of biofilm. The alternation of α- and β-D-glucopyranose polysaccharides and the increased content of autoinducer peptides and N-acylated homoserine lactones indicated that PFOA and SD changed the structure and function of biofilm. These investigations provide a broader perspective and comprehensive analysis of the responses of aquatic plants and periphyton biofilms to PFAS and antibiotics in the environment.PMID:37390681 | DOI:10.1016/j.jhazmat.2023.131910

J Pharm Biomed Anal. 2023 Jun 16;234:115535. doi: 10.1016/j.jpba.2023.115535. Online ahead of print.ABSTRACTBACKGROUND: Cholestasis is a commonly occurring disorder induced by impaired bile flow, for which there is no effective treatment so far. Qingre Lidan decoction (QRLD) is a clinically used herbal compound for the long-term treatment of bile circulation disorders arising from inflammation and obstruction in the gallbladder and bile ducts. The objective of this study was to investigate the protective effect of QRLD on cholestatic liver injury and its possible mechanism.METHODS: α-Naphthyl isothiocyanate (ANIT) was used to induce cholestatic liver injury in rats. Liver histopathology and serum biochemical markers were used to assess QRLD's protective impact. The possible biomarkers and mechanism of the therapeutic benefits of QRLD were investigated using a UHPLC-based Q-Exactive Orbitrap MS / MS untargeted serum metabolomics technique together with 16 S rRNA microbiota profiling. Afterwards, using RT-qPCR as well as Western Blot techniques, the expression of pertinent indicators was determined.RESULTS: The intervention effect of QRLD was stronger at medium and high dosages than at low doses, and it dramatically decreased the levels of serum biochemical markers in cholestatic rats reflecting alterations in liver function and relieving ANIT-induced abnormalities in the liver's histopathology. Serum metabolomics showed that QRLD could affect the metabolic profile of cholestatic rats, mainly related to glycerophospholipid metabolism, taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, and histidine metabolic pathway. Additionally, analysis of 16 S rRNA gene sequencing indicated that QRLD could moderate ANIT-induced microbiota disorders, particularly Romboutsia, Bifidobacterium, Fusicatenibacter, Prevotella_9, Prevotellaceae_NK3B31_group and Prevotella_1. Other experimental results showed that QRLD significantly upregulated the mRNA and protein expression of PPARα, CYP7A1 and NTCP in the liver, inhibited the expression of p-IκBα, p-p65 and TNFα while increasing the anti-inflammatory factor IL-10, and downregulated the expression of MDA (a peroxidation product) and D-lactic acid (an intestinal barrier indicator) while increasing the expression of SOD and GSH.CONCLUSIONS: QRLD can effectively regulate endogenous metabolites and microbiota disorders in cholestatic rats that are correlated with the attenuation of inflammation and oxidative stress.PMID:37390604 | DOI:10.1016/j.jpba.2023.115535

J Pharm Biomed Anal. 2023 Jun 26;234:115549. doi: 10.1016/j.jpba.2023.115549. Online ahead of print.ABSTRACTQizhiweitong particles (QZWT), a classic Chinese herbal prescription derived from the Sinisan decoction in Shang Han Za Bing Lun, has definitive clinical efficacy in treating Chronic Non-atrophic Gastritis (CNG) in China. However, its mechanism of action at the metabolic level remains unclear. The aim of this study was to explore the mechanisms of QZWT against CNG based on non-targeted metabolomics combined with network pharmacology and experimentally validated by enzyme linked immunosorbent assays (ELISA). First, CNG model rats were established by free drinking ammonia water combined with starvation and satiety disorder for 12 weeks. Taking gastric tissue as the object, ultra-high performance liquid chromatography tandem mass spectrometry based metabolomics and network pharmacology were conducted to identify the key compounds, core targets and pathways that mediate the effects of QZWT against CNG. Furthermore, the targets from network pharmacology and the metabolites from metabolomics were jointly analyzed to select crucial metabolism pathways by MetaScape. Finally, the key metabolic enzymes and metabolites were experimentally validated by ELISA. The results indicated that there were 29 differential metabolites were identified and considered to be metabolic biomarkers of QZWT in the treatment of CNG. Among them, 8 of the differential metabolites showed a significant reduction in the content of QZWT groups. Arachidonic acid (AA) metabolic and glycerophospholipid (GP) metabolic are the most crucial metabolic pathways for QZWT to treat CNG. QZWT regulated AA and GP metabolism by synergetic reducing the level of AA, Phospholipid acid and Lysophosphatidic acid and inhibiting the enzyme activity of prostaglandin endoperoxide synthase 1 and prostaglandin endoperoxide synthase 2. And a compound-reaction-enzyme-gene network of mechanism for QZWT against CNG was established. In conclusion, this study reveals the complicated mechanisms of QZWT against CNG. Our work presents a novel strategy to identify the potential mechanisms of pharmacological effects derived from a compound prescription of TCM.PMID:37390603 | DOI:10.1016/j.jpba.2023.115549

BMC Genomics. 2023 Jul 1;24(1):367. doi: 10.1186/s12864-023-09452-9.ABSTRACTBACKGROUND: Intramuscular fat (IMF) is closely related to the tenderness, marbling, juiciness, and flavor of meat. We used a combined transcriptome and metabolome analysis to investigate the molecular mechanisms underlying phenotypic variation among Qinchuan cattle.RESULTS: The IMF content was relatively high in the meat of Qinchuan cattle bulls and differed among muscle locations, namely the high rib (15.86%), ribeye (14%), striploin (10.44%), and tenderloin (8.67%). CCDC80 and the HOX gene cluster may regulate intramuscular adipose tissue deposition. Moreover, erucic acid (EA) was found to be the main metabolite in Qinchuan beef cattle, with a high concentration in IMF. The deposition of IMF could be regulated by the metabolic pathway for unsaturated fatty acids involving EA and the ACOX3, HACD2, and SCD5 genes. In addition, differentially expressed genes and metabolites were enriched in three major KEGG pathways: purine metabolism, pyrimidine metabolism, and the metabolism of glycine, serine, and threonine.CONCLUSIONS: We identified a significant metabolite, EA, with variation in IMF. Its closely related genes, ACOX3, HACD2, and SCD5, co-regulate the metabolism of unsaturated fatty acids, ultimately affecting the accumulation of intramuscular adipose tissue in Qinchuan cattle. Consequently, Qinchuan cattle are an elite cultivar for high-quality beef production and have great potential for breeding.PMID:37391702 | DOI:10.1186/s12864-023-09452-9

Chem Biodivers. 2023 Jun 30:e202300290. doi: 10.1002/cbdv.202300290. Online ahead of print.ABSTRACTSonchus oleraceus(L.) L.(Asteraceae) is an edible wild plant, known for its uses in traditional medicine. The aim of this study is to explore the phytochemical composition of the aerial parts(AP) and roots(R) of aqueous extracts of Sonchus oleraceus L. growing in Tunisia, using liquid chromatography-tandem mass spectrometry(LC-MS/MS), and determine the content of polyphenols and antioxidant activities. Results showed that aqueous extractsof AP and R contained respectively, 195.25±33µg/g and 118.66±14µg/g gallic acid equivalent(GAE), and 52.58±7µg/g and 3.2±0.3µg/g quercetin equivalent. AP and R extractsalso contained tannins, 581.78±33µg/g and 948.44±19µg/g GAE. The AP extract in the1,1-diphenyl-2-picrylhydrazyl(DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid(ABTS) scavenging activities, hydroxyl radical scavenging(OH-)and incupric reducing antioxidant activity(CUPRAC) assays were respectively 0.325±0.036mg/mL, 0.053±0.018mg/mL, 0.696±0.031mg/mL and 60.94±0.004 µMTE/g, while the R extract using the same assays showed, 0.209±0.052mg/mL, 0.034±0.002mg/mL, 0.444± 0.014mg/mL and 50.63±0.006µM Trolox equivalent/g, respectively. A total of 68 compounds were tentatively identified by LC-MS/MS in both extracts in which quinic acid, pyrogallol, osthrutin, piperine, genistic acid, fisetin, luteolin, caffeic acid, gingerol, were the most abundant in the LC-MS/MS spectrum. Many of these metabolites were found for the first time in Tunisian Sonchus oleraceus L. which may take account for the antioxidant activities exhibited by the plant.PMID:37391386 | DOI:10.1002/cbdv.202300290

J Ethnopharmacol. 2023 Jun 28:116822. doi: 10.1016/j.jep.2023.116822. Online ahead of print.NO ABSTRACTPMID:37391320 | DOI:10.1016/j.jep.2023.116822

Trends Pharmacol Sci. 2023 Jun 28:S0165-6147(23)00131-1. doi: 10.1016/j.tips.2023.06.004. Online ahead of print.ABSTRACTRibosomally synthesized and post-translationally modified peptides (RiPPs) are a chemically diverse class of metabolites. Many RiPPs show potent biological activities that make them attractive starting points for drug development. A promising approach for the discovery of new classes of RiPPs is genome mining. However, the accuracy of genome mining is hampered by the lack of signature genes shared across different RiPP classes. One way to reduce false-positive predictions is by complementing genomic information with metabolomics data. In recent years, several new approaches addressing such integrative genomics and metabolomics analyses have been developed. In this review, we provide a detailed discussion of RiPP-compatible software tools that integrate paired genomics and metabolomics data. We highlight current challenges in data integration and identify opportunities for further developments targeting new classes of bioactive RiPPs.PMID:37391295 | DOI:10.1016/j.tips.2023.06.004

Genomics. 2023 Jun 28:110675. doi: 10.1016/j.ygeno.2023.110675. Online ahead of print.ABSTRACTMango (Mangifera indica L.) is a widely appreciated tropical fruit for its rich color and nutrition. However, knowledge on the molecular basis of color variation is limited. Here, we studied HY3 (yellowish-white pulp) and YX4 (yellow pulp), reaped with 24 h gap from the standard harvesting time. The carotenoids and total flavonoids increased with the advance of harvest time (YX4 > HY34). Transcriptome sequencing showed that higher expressions of the core carotenoid biosynthesis genes and flavonoid biosynthesis genes are correlated to their respective contents. The endogenous indole-3-acetic acid and jasmonic acid contents decreased but abscisic acid and ethylene contents increased with an increase in harvesting time (YX4 > HY34). Similar trends were observed for the corresponding genes. Our results indicate that the color differences are related to carotenoid and flavonoid contents, which in turn are influenced by phytohormone accumulation and signaling.PMID:37390936 | DOI:10.1016/j.ygeno.2023.110675

J Ethnopharmacol. 2023 Jun 28:116855. doi: 10.1016/j.jep.2023.116855. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Sargentodoxa cuneata and Patrinia villosa (S&P) are two natural herbal medicine widely used for treatment of various inflammatory diseases in Traditional Chinese Medicine, whereas the mode of action needs to be further investigated.AIM OF THE STUDY: This study aimed to explore the anti-inflammatory effects and unravel the involved mechanism of S&P extract.MATERIALS AND METHODS: The components of S&P extract were first detected using the liquid chromatography-tandem mass spectrometry (LC-MS/MS). The effects of S&P extract on the viability and migration ability of macrophages were detected using CCK8, LDH, adhesion and transwell assays. Cytokine release and macrophage phenotype transition were measured using a cytometric bead array and flow cytometry. The potential mechanism was uncovered using an integrative approach combining RNA sequencing and LC-MS/MS-based metabolic analysis. The expression of related proteins was further validated using western blotting.RESULTS: S&P extract inhibited the proliferation and migration of LPS-induced macrophages, changed the morphology of macrophages, and inhibited the production of NO and the expression of iNOS. Furthermore, the extract inhibited tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production and the expression of the M1 phenotype markers CD11c and CD16/32, whereas it promoted interleukin-10 (IL-10) production and the expression of the M2 phenotype markers CD206 and arginase 1 (Arg1). RNA sequencing analysis demonstrated that the upregulated genes by S&P extract treatment were involved in M2 macrophages: Il10, Ccl17, Ccl22, Cd68. The downregulated genes were involved in M1 macrophages and glycolysis processes: Stat1, Il18, Cd80, Cd86, Nos2, Il6, Pik3ap1, Raf1, Pdhb, etc. Metabolomics results showed that the S&P extract strongly ameliorated lipopolysaccharide (LPS)-induced metabolic disturbances. KEGG analysis indicated that most of these metabolites were involved in glucose metabolism, which is involved in the tumor necrosis factor (TNF), phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt), Glycolysis, and mitogen-activated protein kinase (MAPK) pathways. In vitro experiments further confirmed that the extract significantly inhibited the phosphorylation of focal adhesion kinase (FAK), PI3K and Akt, and the expression of glucose metabolism-related proteins. Adding a FAK inhibitor (defactinib) further inhibited the expression of M1/M2 phenotypic markers and the phosphorylation of FAK, PI3K, and Akt.CONCLUSIONS: S&P extract can induce M2 polarization and shift macrophages from M1 to M2 tissue repair in LPS-induced inflammation by regulating glucose metabolism and the FAK/PI3K/Akt pathway.PMID:37390878 | DOI:10.1016/j.jep.2023.116855

Food Chem. 2023 Jun 25;427:136711. doi: 10.1016/j.foodchem.2023.136711. Online ahead of print.ABSTRACTRoasting is essential for processing large-leaf yellow tea (LYT). However, the effect of the roasting on the metabolic and sensory profiles of LYT remains unknown. Herein, the metabolomics and sensory quality of LYT at five roasting degrees were evaluated by liquid/gas chromatography mass spectrometry and quantitative descriptive analysis. A higher degree of roasting resulted in a significantly stronger crispy rice, fried rice, and smoky-burnt aroma (p < 0.05), which is closely associated with heterocyclic compound accumulation (concentrations: 6.47 ± 0.27 - 1065.00 ± 5.58 µg/g). Amino acids, catechins, flavonoid glycosides and N-ethyl-2-pyrrolidone-substituted flavan-3-ol varied with roasting degree. The enhancement of crispy-rice and burnt flavor coupled with the reduction of bitterness and astringency. Correlations analysis revealed the essential compounds responsible for roasting degree, including 2,3-diethyl-5-methylpyrazine, hexanal, isoleucine, N-ethyl-2-pyrrolidone-substituted flavan-3-ol (EPSF), and others. These findings provide a theoretical basis for improving the specific flavors of LYT.PMID:37390734 | DOI:10.1016/j.foodchem.2023.136711

J Pharm Biomed Anal. 2023 Jun 26;234:115548. doi: 10.1016/j.jpba.2023.115548. Online ahead of print.ABSTRACTColorectal cancer is a highly prevalent malignancy that threatens human health worldwide. Despite the availability of chemotherapy as a primary treatment option, individuals with CRC undergoing frequent chemotherapy are susceptible to developing drug resistance, which can result in poor treatment outcomes. Consequently, there is an urgent need to discover new bioactive compounds for the treatment of CRC. Capilliposide A is a triterpenoid saponin that is extracted from Lysimachia capillipes Hemsl. Although it has been reported that LC-A exhibits good bioactivity, its metabolic profile and potential mechanism underlying its anti-CRC effects remain unknown. In this study, the metabolic products of LC-A in rat plasma, feces, and urine were identified using an LC-MS platform. In addition, LC-MS-based metabolomics was employed to investigate the mechanism of LC-A against CRC. The results showed that LC-A significantly inhibited CRC cell proliferation, attenuated tumor growth, and alleviated metabolic abnormalities in CRC-bearing mice. Furthermore, the levels of p-cresol sulfate and phenylacetylglycine in CRC model plasma decreased, with an increment in sphingosine 1-phosphate, D-tryptophan, and L-2-aminoadipic acid. These metabolite levels can be reversed by LC-A treatment. These metabolite alterations were related to the sphingolipid and amino acid metabolic pathways, demonstrating that LC-A anti-CRC effects were regulated through the modulation of underlying metabolism. Additionally, seven metabolites of LC-A were characterized in rat feces, plasma, and urine. This study offers a scientific foundation for elucidating the metabolism of LC-A and its treatment of colorectal cancer.PMID:37390605 | DOI:10.1016/j.jpba.2023.115548

Poult Sci. 2023 Jun 14;102(9):102856. doi: 10.1016/j.psj.2023.102856. Online ahead of print.ABSTRACTThe gut microbiota is known to have significant involvement in the regulation of lipogenesis and adipogenesis, yet the mechanisms responsible for this relationship remain poorly understood. The current study aims to provide insight into the potential mechanisms by which the gut microbiota modulates lipogenesis in chickens. Using chickens fed with a normal-fat diet (NFD, n = 5) and high-fat diet (HFD, n = 5), we analyzed the correlation between gut microbiota, cecal metabolomics, and lipogenesis by 16s rRNA sequencing, miRNA and mRNA sequencing as well as targeted metabolomics analysis. The potential metabolite/miRNA/mRNA axis regulated by gut microbiota was identified using chickens treated with antibiotics (ABX, n = 5). The possible mechanism of gut microbiota regulating chicken lipogenesis was confirmed by fecal microbiota transplantation (FMT) from chickens fed with NFD to chickens fed with HFD (n = 5). The results showed that HFD significantly altered gut microbiota composition and enhanced chicken lipogenesis, with a significant correlation between 3. Furthermore, HFD significantly altered the hepatic miRNA expression profiles and reduced the abundance of hepatic butyric acid. Procrustes analysis indicated that the HFD-induced dysbiosis of the gut microbiota might affect the expression profiles of hepatic miRNA. Specifically, HFD-induced gut microbiota dysbiosis may reduce the abundance of butyric acid and downregulate the expression of miR-204 in the liver. Multiomics analysis identified ACSS2 as a target gene of miR-204. Gut microbiota depletion by an antibiotic cocktail (ABX) showed a gut microbiota-dependent manner in the abundance of butyric acid and the expression of miR-204/ACSS2, which have been observed to be significantly correlated. Fecal microbiota transplantation from NFD chickens into HFD chickens effectively attenuated the HFD-induced excessive lipogenesis, elevated the abundance of butyric acid and the relative expression of miR-204, and reduced the expression of ACSS2 in the liver. Mechanistically, our results showed that the gut microbiota plays an antiobesity role by regulating the butyric acid/miR-204/ACSS2 axis in chickens. This work contributed to a better understanding of the functions of gut microbiota in regulating chicken lipogenesis.PMID:37390560 | DOI:10.1016/j.psj.2023.102856

Anal Chem. 2023 Jun 30. doi: 10.1021/acs.analchem.3c00957. Online ahead of print.ABSTRACTGlycosylation of metabolites serves multiple purposes. Adding sugars makes metabolites more water soluble and improves their biodistribution, stability, and detoxification. In plants, the increase in melting points enables storing otherwise volatile compounds that are released by hydrolysis when needed. Classically, glycosylated metabolites were identified by mass spectrometry (MS/MS) using [M-sugar] neutral losses. Herein, we studied 71 pairs of glycosides with their respective aglycones, including hexose, pentose, and glucuronide moieties. Using liquid chromatography (LC) coupled to electrospray ionization high-resolution mass spectrometry, we detected the classic [M-sugar] product ions for only 68% of glycosides. Instead, we found that most aglycone MS/MS product ions were conserved in the MS/MS spectra of their corresponding glycosides, even when no [M-sugar] neutral losses were observed. We added pentose and hexose units to the precursor masses of an MS/MS library of 3057 aglycones to enable rapid identification of glycosylated natural products with standard MS/MS search algorithms. When searching unknown compounds in untargeted LC-MS/MS metabolomics data of chocolate and tea, we structurally annotated 108 novel glycosides in standard MS-DIAL data processing. We uploaded this new in silico-glycosylated product MS/MS library to GitHub to enable users to detect natural product glycosides without authentic chemical standards.PMID:37390485 | DOI:10.1021/acs.analchem.3c00957

Arthritis Rheumatol. 2023 Jun 30. doi: 10.1002/art.42635. Online ahead of print.ABSTRACTOBJECTIVES: To discover differential metabolites and pathways underlying infrequent gout flares (InGF) and frequent gout flares (FrGF) using metabolomics and establish a predictive model by machine learning (ML) algorithms.METHODS: Serum samples from a discovery cohort with 163 InGF and 239 FrGF patients were analyzed by mass spectrometry-based untargeted metabolomics to profile differential metabolites and explore dysregulated metabolic pathways using pathway enrichment analysis and network propagation-based algorithms. ML algorithms were performed to establish a predictive model based on selected metabolites, which was further optimized by a quantitative targeted metabolomics method and validated in an independent validation cohort with 97 participants with InGF and 139 participants with FrGF.RESULTS: 439 differential metabolites between InGF and FrGF groups were identified. Top dysregulated pathways included carbohydrates, amino acids, bile acids, and nucleotide metabolism. Subnetworks with maximum disturbances in the global metabolic networks featured cross-talk between purine metabolism and caffeine metabolism, as well as interactions among pathways involving primary bile acid biosynthesis, taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, suggesting epigenetic modifications and gut microbiome in metabolic alterations underlying InGF and FrGF. Potential metabolite biomarkers were identified using ML-based multivariable selection and further validated by targeted metabolomics. Area under receiver operating characteristics curve for differentiating InGF and FrGF achieved 0.88 and 0.67 for the discovery and validation cohorts, respectively.CONCLUSIONS: Systematic metabolic alterations underlie InGF and FrGF, and distinct profiles are associated with differences in gout flare frequencies. Predictive modeling based on selected metabolites from metabolomics can differentiate InGF and FrGF.PMID:37390372 | DOI:10.1002/art.42635

Front Med. 2023 Jun 30. doi: 10.1007/s11684-023-0989-7. Online ahead of print.ABSTRACTMigraine is one of the most prevalent and disabling neurological disease, but the current pharmacotherapies show limited efficacy and often accompanied by adverse effects. Acupuncture is a promising complementary therapy, but further clinical evidence is needed. The influence of acupuncture on migraine is not an immediate effect, and its mechanism remains unclear. This study aims to provide further clinical evidence for the anti-migraine effects of acupuncture and explore the mechanism involved. A randomized controlled trial was performed among 10 normal controls and 38 migraineurs. The migraineurs were divided into blank control, sham acupuncture, and acupuncture groups. Patients were subjected to two courses of treatment, and each treatment lasted for 5 days, with an interval of 1 day between the two courses. The effectiveness of treatment was evaluated using pain questionnaire. The functional magnetic resonance imaging (fMRI) data were analyzed for investigating brain changes induced by treatments. Blood plasma was collected for metabolomics and proteomics studies. Correlation and mediation analyses were performed to investigate the interaction between clinical, fMRI and omics changes. Results showed that acupuncture effectively relieved migraine symptoms in a way different from sham acupuncture in terms of curative effect, affected brain regions, and signaling pathways. The anti-migraine mechanism involves a complex network related to the regulation of the response to hypoxic stress, reversal of brain energy imbalance, and regulation of inflammation. The brain regions of migraineurs affected by acupuncture include the lingual gyrus, default mode network, and cerebellum. The effect of acupuncture on patients' metabolites/proteins may precede that of the brain.PMID:37389804 | DOI:10.1007/s11684-023-0989-7

Ann Surg. 2023 Jun 30. doi: 10.1097/SLA.0000000000005973. Online ahead of print.ABSTRACTOBJECTIVE AND SUMMARY BACKGROUND DATA: Propranolol, a non-selective beta receptor blocker, improves outcomes of severely burned patients. While the clinical and physiological benefits of beta blockade are well characterized, the underlying metabolic mechanisms are less well defined. We hypothesized that propranolol improves outcomes after burn injury by profoundly modulating metabolic pathways.METHODS: In this phase II randomized controlled trial, patients with burns ≥20% of total body surface area were randomly assigned to control or propranolol (dose given to decrease heart rate <100 bpm). Outcomes included clinical markers, inflammatory and lipidomic profiles, untargeted metabolomics, and molecular pathways.RESULTS: Fifty-two severely burned patients were enrolled in this trial (propranolol n=23 and controls n=29). There were no significant differences in demographics or injury severity between groups. Metabolomic pathway analyses of the adipose tissue showed that propranolol substantially alters several essential metabolic pathways involved in energy and nucleotide metabolism, as well as catecholamine degradation (P<0.05). Lipidomic analysis revealed that propranolol-treated patients had lower levels of pro-inflammatory palmitic acid (P<0.05) and saturated fatty acids (P<0.05) with an increased ratio of polyunsaturated fatty acids (P<0.05), thus shifting the lipidomic profile towards an anti-inflammatory phenotype after burn (P<0.05). These metabolic effects were mediated by decreased activation of hormone-sensitive lipase at serine 660 (P<0.05) and significantly reduced ER stress by decreasing p-JNK (P<0.05).CONCLUSIONS: Propranolol's ability to mitigate pathophysiological changes to essential metabolic pathways results in significantly improved stress responses.PMID:37389480 | DOI:10.1097/SLA.0000000000005973