PubMed

Phytomedicine. 2023 Nov 15;126:155222. doi: 10.1016/j.phymed.2023.155222. Online ahead of print.ABSTRACTBACKGROUND: Diabetic nephropathy (DN) was one of the most popular and most significant microvascular complications of diabetes mellitus. Qingxin Lianzi Yin Decoction (QXLZY) was a traditional Chinese classical formula, suitable for chronic urinary system diseases. QXLZY had good clinical efficacy in early DN, but the underlying molecular mechanism remained unrevealed.PURPOSE: This study aimed to establish the content determination method of QXLZY index components and explore the mechanism of QXLZY on DN by network pharmacology and metabolomics studies.METHODS: Firstly, the content determination methods of QXLZY were established with calycosin-7-O-β-d-glucoside, acteoside, baicalin and glycyrrhizic acid as index components. Secondly, pharmacological experiments of QXLZY were evaluated using db/db mice. UHPLC-LTQ-Orbitrap MS was used to carry out untargeted urine metabolomics, serum metabolomics, and kidney metabolomics studies. Thirdly, employing network pharmacology, key components and targets were analyzed. Finally, targeted metabolomics studies were performed on the endogenous constituents in biological samples for validation based on untargeted metabolomics results.RESULTS: A method for the simultaneous determination of multiple index components in QXLZY was established, which passed the comprehensive methodological verification. It was simple, feasible, and scientific. The QXLZY treatment alleviated kidney injury of db/db mice, included the degree of histopathological damage and the level of urinary microalbumin/creatinine ratio. Untargeted metabolomics studies had identified metabolic dysfunction in pathways associated with amino acid metabolism in db/db mice. Treatment with QXLZY could reverse metabolite abnormalities and influence the pathways related to energy metabolism and amino acid metabolism. It had been found that pathways with a high degree were involved in signal transduction, prominently on amino acids metabolism and lipid metabolism, analyzed by network pharmacology. Disorders of amino acid metabolism did occur in db/db mice. QXLZY could revert the levels of metabolites, such as quinolinic acid, arginine, and asparagine.CONCLUSION: This study was the first time to demonstrate that QXLZY alleviated diabetes-induced pathological changes in the kidneys of db/db mice by correcting disturbances in amino acid metabolism. This work could provide a new experimental basis and theoretical guidance for the rational application of QXLZY on DN, exploring the new pharmacological effect of traditional Chinese medicine, and promoting in-depth research and development.PMID:38382279 | DOI:10.1016/j.phymed.2023.155222

Int J Parasitol Drugs Drug Resist. 2024 Feb 15;24:100526. doi: 10.1016/j.ijpddr.2024.100526. Online ahead of print.ABSTRACTAvian coccidiosis, caused by Eimeria parasites, continues to devastate the poultry industry and results in significant economic losses. Ionophore coccidiostats, such as maduramycin and monensin, are widely used for prophylaxis of coccidiosis in poultry. Nevertheless, their efficacy has been challenged by widespread drug resistance. However, the underlying mechanisms have not been revealed. Understanding the targets and resistance mechanisms to anticoccidials is critical to combat this major parasitic disease. In the present study, maduramycin-resistant (MRR) and drug-sensitive (DS) sporozoites of Eimeria tenella were purified for transcriptomic and metabolomic analysis. The transcriptome analysis revealed 5016 differentially expressed genes (DEGs) in MRR compared to DS, and KEGG pathway enrichment analysis indicated that DEGs were involved in spliceosome, carbon metabolism, glycolysis, and biosynthesis of amino acids. In the untargeted metabolomics assay, 297 differentially expressed metabolites (DEMs) were identified in MRR compared to DS, and KEGG pathway enrichment analysis indicated that these DEMs were involved in 10 pathways, including fructose and mannose metabolism, cysteine and methionine metabolism, arginine and proline metabolism, and glutathione metabolism. Targeted metabolomic analysis revealed 14 DEMs in MRR compared to DS, and KEGG pathway analysis indicated that these DEMs were involved in 20 pathways, including fructose and mannose metabolism, glycolysis/gluconeogenesis, and carbon metabolism. Compared to DS, energy homeostasis and amino acid metabolism were differentially regulated in MRR. Our results provide gene and metabolite expression landscapes of E. tenella following maduramycin induction. This study is the first work involving integrated transcriptomic and metabolomic analyses to identify the key pathways to understand the molecular and metabolic mechanisms underlying drug resistance to polyether ionophores in coccidia.PMID:38382267 | DOI:10.1016/j.ijpddr.2024.100526

Food Chem. 2024 Feb 16;445:138746. doi: 10.1016/j.foodchem.2024.138746. Online ahead of print.ABSTRACTTo achieve salt reduction while ensuring flavor quality of Chinese horse bean-chili-paste (CHCP), we comprehensively explored the effect of indigenous strains Tetragenococcus halophilus and Candida versatilis on the aroma profiles of low-salt CHCP by metabolomics and sensomics analysis. A total of 129 volatiles and 34 aroma compounds were identified by GC × GC-MS and GC-O-MS, among which 29 and 20 volatiles were identified as significant difference compounds and aroma-active compounds, respectively. Inoculation with the two indigenous strains could effectively relieve the undesired acidic and irritative flavor brought by acetic acid and some aldehydes in salt-reduction samples. Meanwhile, inoculated fermentation provided more complex and richer volatiles in low-salt batches, especially for the accumulation of 3-methylbutanol, 1-octen-3-ol, benzeneacetaldehyde, phenylethyl alcohol, and 4-ethyl-phenol etc., which were confirmed as essential aroma compounds of CHCP by recombination and omission tests. The research elucidated the feasibility of bioturbation strategy to achieve salt-reducing fermentation of fermented foods.PMID:38382252 | DOI:10.1016/j.foodchem.2024.138746

Food Chem. 2024 Feb 10;445:138715. doi: 10.1016/j.foodchem.2024.138715. Online ahead of print.ABSTRACTThe green-tea manufacturing process showed good effect of flavor improving, debittering and shaping in making Penthorum chinensePursh leaf (PL) tea (PLT), which serves as a polyphenol dietary supplement and beverage raw material. GC-MS results showed that its unpleasant grassy odor decreased by 42.8% due to dodecanal, geranylacetone, and (E)-2-nonenal reduction, coupled with 1-hexadecanol increasing. UPLC-ESI-TOF-MS identified 95 compounds and showed that the debittering effect of green-tea manufacturing process was attributed to decreasing of flavonols and lignans, especially quercetins, kaempferols and luteolins, and increasing of dihydrochalcones which act as sweeteners bitterness-masking agents, while astringency was weakened by reducing delphinidin-3,5-O-diglucoside chloride, kaempferol-7-O-β-d-glucopyranoside, and tannins. The increase of pinocembrins and catechins in aqueous extracts of PLT, maintained its hepatoprotective, NAFLD-alleviation, and hepatofibrosis-prevention activities similar to PL in high fat-diet C57BL/6 mice, with flavonoids, tannins, tannic acids, and some newfound chemicals, including norbergenin, gomisin K2, pseudolaric acid B, tanshinol B, as functional ingredients.PMID:38382251 | DOI:10.1016/j.foodchem.2024.138715

Food Chem. 2024 Feb 20;445:138620. doi: 10.1016/j.foodchem.2024.138620. Online ahead of print.ABSTRACTGabaron green tea (GAGT) has unique flavor and health benefits through the special anaerobic treatment. However, how this composite processing affects the aroma formation of GAGT and the regulatory mechanism was rarely reported. This study used nontargeted metabolomics and molecular sensory science to overlay screen differential metabolites and key aroma contributors. The potential regulatory mechanism of anaerobic treatment on the aroma formation of GAGT was investigated by transcriptomics and correlation analyses. Five volatiles: benzeneacetaldehyde, nonanal, geraniol, linalool, and linalool oxide III, were screened as target metabolites. Through the transcriptional-level differential genes screening and analysis, some CsERF transcription factors in the ethylene signaling pathway were proposed might participate the response to the anaerobic treatment. They might regulate the expression of related genes in the metabolic pathway of the target metabolites thus affecting the GAGT flavor. The findings of this study provide novel information on the flavor and its formation of GAGT.PMID:38382249 | DOI:10.1016/j.foodchem.2024.138620

PLoS Negl Trop Dis. 2024 Feb 21;18(2):e0011966. doi: 10.1371/journal.pntd.0011966. eCollection 2024 Feb.ABSTRACTSchistosomiasis is one of the most devastating human diseases worldwide. The disease is caused by six species of Schistosoma blood fluke; five of which cause intestinal granulomatous inflammation and bleeding. The current diagnostic method is inaccurate and delayed, hence, biomarker identification using metabolomics has been applied. However, previous studies only investigated infection caused by one Schistosoma spp., leaving a gap in the use of biomarkers for other species. No study focused on understanding the progression of intestinal disease. Therefore, we aimed to identify early gut biomarkers of infection with three Schistosoma spp. and progression of intestinal pathology. We infected 3 groups of mice, 3 mice each, with Schistosoma mansoni, Schistosoma japonicum or Schistosoma mekongi and collected their feces before and 1, 2, 4 and 8 weeks after infection. Metabolites in feces were extracted and identified using mass spectrometer-based metabolomics. Metabolites were annotated and analyzed with XCMS bioinformatics tool and Metaboanalyst platform. From >36,000 features in all conditions, multivariate analysis found a distinct pattern at each time point for all species. Pathway analysis reported alteration of several lipid metabolism pathways as infection progressed. Disturbance of the glycosaminoglycan degradation pathway was found with the presence of parasite eggs, indicating involvement of this pathway in disease progression. Biomarkers were discovered using a combination of variable importance for projection score cut-off and receiver operating characteristic curve analysis. Five molecules met our criteria and were present in all three species: 25-hydroxyvitamin D2, 1α-hydroxy-2β-(3-hydroxypropoxy) vitamin D3, Ganoderic acid Md, unidentified feature with m/z 455.3483, and unidentified feature with m/z 456.3516. These molecules were proposed as trans-genus biomarkers of early schistosomiasis. Our findings provide evidence for disease progression in intestinal schistosomiasis and potential biomarkers, which could be beneficial for early detection of this disease.PMID:38381759 | DOI:10.1371/journal.pntd.0011966

Stem Cells. 2024 Feb 21:sxae015. doi: 10.1093/stmcls/sxae015. Online ahead of print.ABSTRACTCardiovascular diseases (CVDs) are the leading cause of death worldwide, accounting for 31% of all deaths globally. Myocardial ischemia-reperfusion injury (IRI), a common complication of CVDs, is a major cause of mortality and morbidity. Studies have shown efficacious use of mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) to mitigate IRI in animals, but few research has been done on human-related models. In this study, human embryonic stem cell-derived chambered cardiac organoid (CCOs) was used as a model system to study the effects of MSC-derived small extracellular vesicles (sEVs) on myocardial IRI. The results revealed that MSC-sEVs treatment reduced apoptosis and improved contraction resumption of the CCOs. Metabolomics analysis showed that this effect could be attributed to sEVs' ability to prevent the accumulation of unsaturated very long chain fatty acids (VLCFAs). This was corroborated when inhibition of fatty acid synthase (FASN), which was reported to reduce VLCFAs, produced a similar protective effect to sEVs. Overall, this study uncovered the mechanistic role of sEVs in mitigating IRI that involves preventing the accumulation of unsaturated VLCFA, decreasing cell death, and improving contraction resumption in CCOs.PMID:38381602 | DOI:10.1093/stmcls/sxae015

Microb Biotechnol. 2024 Feb;17(2):e14401. doi: 10.1111/1751-7915.14401.ABSTRACTSevere acute pancreatitis (SAP) onset and development are closely associated with intestinal barrier injury. Evidence from clinical practice and research has shown that electroacupuncture (EA) at the Zusanli (ST36) acupoint can improve intestinal barrier function and abdominal symptoms in patients with SAP; however, the specific mechanisms of action remain unclear. This study aimed to observe the changes in the intestinal microbiota and metabolites in SAP rats and to explore the effect of EA at ST36 on intestinal barrier injury in SAP rats. 16S rRNA gene sequencing combined with microbial diversity analysis, short-chain fatty acids (SCFAs)-targeted metabolomics, immunohistochemistry, immunofluorescence, western blotting, and other techniques were used to explore the mechanism of EA at bilateral ST36 acupoints on SAP-related intestinal barrier injury. Our results showed that EA at ST36 could repair intestinal barrier injury by modulating intestinal microecology, thereby reducing intestinal inflammation, restoring intestinal function, and ultimately alleviating the prognosis of SAP. Our study provides new insights into the mechanisms and treatment of intestinal barrier injury in patients with SAP from the perspectives of microbiota and SCFAs regulation.PMID:38381095 | DOI:10.1111/1751-7915.14401

J Sci Food Agric. 2024 Feb 21. doi: 10.1002/jsfa.13405. Online ahead of print.ABSTRACTBACKGROUND: Citrus flower-green tea (CT) is a scented tea processed from green tea (GT) and fresh citrus flower, which is favored by consumers due to its potential health benefits and unique citrus flavor. This study evaluated the quality of CT and revealed the mechanism of its quality formation.RESULTS: The CT had a significant citrus flavor and a good antioxidant activity, and its sensory quality was superior to that of GT. Headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) analysis revealed that the scenting process resulted in a significant increase of alkenes such as β-pinene, trans-β-ocimene, α-farnesene, isoterpinolene, and γ-terpinene, as well as a significant decrease of alcohols such as α-terpineol, L-menthol, and linalool in CT in comparision with GT. Liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis revealed that the levels of flavonoids (such as neohesperidin, hesperidin, tangeritin, hesperetin 5-O-glucoside, and nobiletin) and alkaloids (such as trigonelline and theobromine) in CT increased significantly after scenting process, while the levels of amino acids (such as valine and L-phenylalanine) and organic acids (such as ascorbic acid) decreased significantly.CONCLUSION: These observations showed that the scenting process promoted the absorption of aroma from citrus flowers by GT and the changes in its non-volatile metabolites, leading to the formation of citrus flavor quality in CT. This article is protected by copyright. All rights reserved.PMID:38380915 | DOI:10.1002/jsfa.13405

J Sci Food Agric. 2024 Feb 21. doi: 10.1002/jsfa.13403. Online ahead of print.ABSTRACTCheese, a fundamental component of the human diet and a cornerstone of the global food economy, holds significance beyond its role as a market commodity, playing a crucial part in the cultural identity of various social communities. The intricate natural aging process, known as maturation, involves a series of reactions that induce changes in physical, biochemical, microbiological, and particularly sensory characteristics, making it a complex aspect of cheese production. Recently, the adoption of omics sciences (e.g., metagenomics, metabolomics, proteomics) in PDO cheese studies has emerged as a new trend. This mini-summary aims to outline the relationship between omics studies in these food matrices and all the sustainability facets of the production chain in general, as well as discuss and recognize that the importance of these studies goes beyond comprehending the cheesebiome; it extends to fostering and ensuring the sustainability of the production chain. In this context, numerous studies in recent years have linked the identification of intrinsic characteristics of PDO cheeses through omics sciences to crucial sustainability themes such as territoriality, biodiversity, and the preservation of product authenticity. The trajectory suggests that increasingly multidisciplinary studies, spanning various omics sciences, will not only contribute to characterizing these products but also address sustainability aspects directly related to the production chain (e.g., authenticity, microbial biodiversity, functionality). This expansion underscores the multidisciplinary nature of these studies, broadening their social impact beyond the academic realm. Consequently, these pivotal studies play a crucial role in advancing discussions on PDO products and sustainability. This article is protected by copyright. All rights reserved.PMID:38380878 | DOI:10.1002/jsfa.13403

J Ethnopharmacol. 2024 Jan 30;319(Pt 3):117369. doi: 10.1016/j.jep.2023.117369. Epub 2023 Oct 28.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Shicao is the aerial part of Achillea alpina L., a common herb found mainly in Europe, Asia, and North America. Traditional Chinese medicine has a history of thousands of years and is widely used to treat various diseases.AIM OF STUDY: To explore the hepatoprotective effects of Shicao on CCl4-induced acute liver injury.METHODS: A rat model of acute liver injury was established and liver function indices were assessed to evaluate the protective effect of Shicao on the liver. Untargeted metabolomics of the serum and liver tissues was conducted using UPLC-Q-TOF/MS to identify differential metabolites related to acute liver injury. A network of metabolite-reaction-enzyme-gene constituents was constructed using network pharmacology. Hub targets and key components of the effect of Shicao on acute liver injury were screened from the network.RESULTS: Compared to the model group, Shicao improved the degree of liver damage through the assessment of the liver index, ALT and AST levels, and hepatic pathology slices, demonstrating its hepatoprotective effect against acute liver injury in rats. 10 and 38 differential metabolites involved in acute liver injury were identified in serum and liver tissues, respectively. Most of these were regulated or restored following treatment with Shicao, which mainly consisted of bile acids, lipids, and nucleotides such as taurocholic acid, LysoPC (17:0), and adenosine diphosphate ribose. Through the network of metabolite-reaction-enzyme-gene-constituents, 10 key components and 5 hub genes, along with 7 crucial differential metabolites, were mainly involved in glycerophospholipid metabolism, purine metabolism, biosynthesis of unsaturated fatty acids, and primary bile acid biosynthesis, which may play important roles in the prevention of acute liver injury by Shicao.CONCLUSION: This study revealed that Shicao had protective effects against CCl4-induced liver injury in rats. It was speculated that the ingredients of Shicao might be closely related to the hub targets, thereby regulating the levels of key metabolites, affecting inflammatory response and oxidative stress and attenuate the liver injury consequently. This study provides a basis for further investigation of its therapeutic potential and the mechanism of action.PMID:38380571 | DOI:10.1016/j.jep.2023.117369

Aging Cell. 2024 Feb 21:e14125. doi: 10.1111/acel.14125. Online ahead of print.ABSTRACTIt is unclear how metabolomic age is associated with the risk of a wide range of chronic diseases. Our analysis included 110,692 participants (training: n = 27,673; testing: n = 27,673; validating: n = 55,346) aged 39-71 years at baseline (2006-2010) from the UK Biobank. Incident chronic diseases were identified using inpatient records, or death registers until January 2021. Predicted metabolomic age was trained and tested based on 168 metabolomics. Metabolomic age was linked to the risk of 50 diseases in the validation dataset. The median follow-up duration for individual diseases ranged from 11.2 years to 11.9 years. After controlling for false discovery rate, chronological age-adjusted age gap (CAAG) was significantly associated with the incidence of 25 out of 50 chronic diseases. After adjustment for full covariates, associations with 15 chronic diseases remained significant. Greater CAAG was associated with increased risk of eight cardiometabolic disorders (including cardiovascular diseases and diabetes), some cancers, alcohol use disorder, chronic obstructive pulmonary disease, chronic kidney disease, chronic liver disease and age-related macular degeneration. The association between CAAG and risk of peripheral vascular disease, other cardiac diseases, fracture, cataract and thyroid disorder was stronger among individuals with unhealthy diet than in those with healthy diet. The association between CAAG and risk of some conditions was stronger in younger individuals, those with metabolic disorders or low education. Metabolomic age plays an important role in the development of multiple chronic diseases. Healthy diet and high education may mitigate the risk for some chronic diseases due to metabolomic age acceleration.PMID:38380547 | DOI:10.1111/acel.14125

Front Mol Biosci. 2024 Feb 6;11:1343123. doi: 10.3389/fmolb.2024.1343123. eCollection 2024.ABSTRACTIntroduction: Leaf coloration in Disanthus cercidifolius var. longipes results from the interplay of various pigments undergoing complex catalytic reactions. Methods: We aimed to elucidate the mechanisms of pigment biosynthesis affecting leaf color transition in D. cercidifolius var. longipes by analyzing variations in pigment accumulation and levels of gene expression. Results: We identified 468, 577, and 215 differential metabolites in green leaves (GL), gradual-color-changing leaves (GCCL), and red leaves (RL), respectively, with 94 metabolites shared across all comparisons. Metabolite accumulation patterns were similar among GL, GCCL, and RL, with flavonoids being the main differential metabolites. Delphinidin, malvidin, and petunidin derivatives were mostly accumulated in GCCL, whereas cyanidin, pelargonidin, and peonidin derivatives accumulated in RL. Transcriptome sequencing was used to identify differentially expressed genes. The expression of anthocyanin biosynthetic pathway genes was associated with anthocyanin accumulation patterns. Discussion: Our findings reveal that the content of delphinidin, malvidin, petunidin, and carotenoids collectively determines the gradual transition of leaf color from green in spring and summer to green, purple, and orange-yellow in early autumn, whereas the content of cyanidin, peonidin, pelargonidin, and carotenoids together causes the autumnal transition to red or orange-red colors as leaves of D. cercidifolius var. longipes age.PMID:38380429 | PMC:PMC10876866 | DOI:10.3389/fmolb.2024.1343123

Front Oncol. 2024 Feb 6;14:1276092. doi: 10.3389/fonc.2024.1276092. eCollection 2024.ABSTRACTINTRODUCTION: Resistance to drug therapies is associated with a large majority of cancer-related deaths. ATP-binding cassette (ABC) transporter-mediated drug efflux, epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), glutathione (GSH), senescence, and vacuole-type ATPase (V-ATPase) all contribute to the resistance. We recently showed that extracellular ATP (eATP) induces and regulates EMT, CSC formation, and ABC transporters in human cancer cells and tumors. eATP also consistently upregulates Stanniocalcin-1 (STC1), a gene that significantly contributes to EMT, CSC formation, and tumor growth. We also found that eATP enhances drug resistance in cancer cells through eATP internalization mediated by macropinocytosis, leading to an elevation of intracellular ATP (iATP) levels, induction of EMT, and CSC formation. However, these factors have never been systematically investigated in the context of eATP-induced drug resistance.METHODS: In this study, we hypothesized that eATP increases drug resistance via inducing ABC efflux, EMT, CSCs, STC1, and their accompanied processes such as GSH reducing activity, senescence, and V-ATPase. RNA sequencing, metabolomics, gene knockdown and knockout, and functional assays were performed to investigate these pathways and processes.RESULTS AND DISCUSSION: Our study results showed that, in multiple human cancer lines, eATP induced genes involved in drug resistance, elevated ABC transporters' efflux activity of anticancer drugs; generated transcriptomic and metabolic profiles representing a drug resistant state; upregulated activities of GSH, senescence, and V-ATPase to promote drug resistance. Collectively, these newly found players shed light on the mechanisms of eATP-induced as well as STC1- and V-ATPase-mediated drug resistance and offer potential novel targets for combating drug resistance in cancers.PMID:38380370 | PMC:PMC10876858 | DOI:10.3389/fonc.2024.1276092

Front Microbiol. 2024 Feb 6;15:1348729. doi: 10.3389/fmicb.2024.1348729. eCollection 2024.ABSTRACTINTRODUCTION: Excessive intake of lactate caused by improper use of silage in animal husbandry has adverse effects on rumen fermentation, such as rumen acidosis. The speed of absorption and metabolism of D-lactate in rumen epithelial cells was slower than that of L-lactate, making D-lactate more prone to accumulate and induce rumen acidosis. Therefore, this study was conducted to explore the effects of dietary D-lactate levels on rumen fermentation of beef cattle and its mechanism in an in vitro system.METHODS: This experiment was adopted in single-factor random trial design, with 5 days for adaptation and 3 days for sample collection. Three treatments (n = 8/treatment) were used: (1) D-LA (0.3%), basal fermentation substrate with 0.3% (dry matter, DM basis) D-lactate; (2) D-LA (0.75%), basal fermentation substrate with 0.75% (DM basis) D-lactate; and (3) D-LA (1.2%), basal fermentation substrate with 1.2% (DM basis) D-lactate.RESULTS: With the dietary D-lactate levels increased, the daily production of total gas, hydrogen and methane, as well as the ruminal concentrations of acetate, propionate, butyrate, isobutyrate, valerate, isovalerate, total volatile fatty acid and D-lactate increased (p < 0.05), but the ruminal pH and acetate/propionate ratios decreased (p < 0.05). Principle coordinate analysis based on Bray-Curtis distance showed that increasing dietary D-lactate levels could significantly affect the structure of rumen bacterial community (p < 0.05), but had no significant effect on the structure of rumen eukaryotic community (p > 0.05). NK4A214_group, Ruminococcus_gauvreauii_group, Eubacterium_oxidoreducens_group, Escherichia-Shigella, Marvinbryantia and Entodinium were enriched in D-LA (1.2%) group (p < 0.05), as well as WCHB1-41, vadinBE97, Clostridium_sensu_stricto_1, Anaeroplasma and Ruminococcus were enriched in D-LA (0.3%) group (p < 0.05). Changes in the composition of ruminal microorganisms affected rumen metabolism, mainly focus on the biosynthesis of glycosaminoglycans (p < 0.05).DISCUSSION: Overall, feeding whole-plant corn silage with high D-lactate content could not induce rumen acidosis, and the metabolization of dietary D-lactate into volatile fatty acids increased the energy supply of beef cattle. However, it also increased the ruminal CH4 emissions and the relative abundance of opportunistic pathogen Escherichia-Shigella in beef cattle. The relative abundance of Verrucomicrobiota and Escherichia-Shigella may be influenced by glycosaminoglycans, reflecting the interaction between rumen microorganisms and metabolites.PMID:38380091 | PMC:PMC10877051 | DOI:10.3389/fmicb.2024.1348729

Front Microbiol. 2024 Feb 6;15:1306068. doi: 10.3389/fmicb.2024.1306068. eCollection 2024.ABSTRACTUlcerative colitis (UC) is a chronic and recurrent inflammatory disease of the gastrointestinal tract. This study aimed to determine the effect of cathelicidin-related antimicrobial peptide (Cramp) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice and to investigate the underlying mechanisms. Acute UC was induced in C57BL/6 mice with 3% DSS for 7 days, 4 mg/kg b.w. synthetic Cramp peptide was administrated once daily starting on day 4 of the experimental period. Mice were evaluated for body weight, colon length, colon histopathology, and inflammatory cytokines in colon tissue. Using 16 s rRNA sequencing, the composition structure of gut microbiota was characterized. Metabolomic profiling of the serum was performed. The results showed that DSS treatment significantly induced intestinal damage as reflected by disease activity index, histopathological features, and colon length, while Cramp treatment significantly prevented these trends. Meanwhile, Cramp treatment decreased the levels of inflammatory cytokines in both serum and colonic tissue on DSS-induced colitis. It was also observed that DSS damaged the integrity of the intestinal epithelial barrier, whereas Cramp also played a protective role by attenuating these deteriorated effects. Furthermore, Cramp treatment reversed the oxidative stress by increasing the antioxidant enzymes of GSH-PX and decreasing the oxidant content of MDA. Notably, compared to the DSS group, Cramp treatment significantly elevated the abundance of Verrucomicrobiota at the phylum level. Furthermore, at the genus level, Parasutterella and Mucispirllum abundance was increased significantly in response to Cramp treatment, although Roseburia and Enterorhabdus reduced remarkably. Metabolic pathway analysis of serum metabolomics showed that Cramp intervention can regulate various metabolic pathways such as α-linolenic acid, taurine and hypotaurine, sphingolipid, and arachidonic acid metabolism. The study concluded that Cramp significantly ameliorated DSS-induced colonic injury, colonic inflammation, and intestinal barrier dysfunction in mice. The underlying mechanism is closely related to the metabolic alterations derived from gut microbiota.PMID:38380090 | PMC:PMC10877057 | DOI:10.3389/fmicb.2024.1306068

Front Pharmacol. 2024 Feb 6;15:1358626. doi: 10.3389/fphar.2024.1358626. eCollection 2024.ABSTRACTIntroduction: Idiopathic pulmonary fibrosis is a chronic interstitial lung disease characterized by excessive deposition of extracellular matrix. Cannabidiol, a natural component extracted from plant cannabis, has been shown to have therapeutic effects on lung diseases, but its exact mechanism of action is unknown, hindering its therapeutic effectiveness. Methods: To establish a pulmonary fibrosis model, combined with UPLC-Q-TOF/MS metabolomics and 16S rDNA sequencing, to explore cannabidiol's mechanism in treating pulmonary fibrosis. The rats were randomly divided into the control group, pulmonary fibrosis model group, prednisone treatment group, and cannabidiol low, medium, and high dose groups. The expression levels of HYP, SOD, and MDA in lung tissue and the expression levels of TNF-α, IL-1β, and IL-6 in serum were detected. Intestinal microbiota was detected using UPLC-QTOF/MS analysis of metabolomic properties and 16S rDNA sequencing. Results: Pathological studies and biochemical indexes showed that cannabidiol treatment could significantly alleviate IPF symptoms, significantly reduce the levels of TNF-α, IL-1β, IL-6, MDA, and HYP, and increase the expression level of SOD (p < 0.05). CBD-H can regulate Lachnospiraceae_NK4A136_group, Pseudomonas, Clostridia_UCG-014, Collinsella, Prevotella, [Eubacterium]_coprostanoligenes_group, Fusobacterium, Ruminococcus, and Streptococcus, it can restore intestinal microbiota function and reverse fecal metabolism trend. It also plays the role of fibrosis through the metabolism of linoleic acid, glycerol, linolenic acid, and sphingolipid. Discussion: Cannabidiol reverses intestinal microbiota imbalance and attenuates pulmonary fibrosis in rats through anti-inflammatory, antioxidant, and anti-fibrotic effects. This study lays the foundation for future research on the pathological mechanisms of IPF and the development of new drug candidates.PMID:38379898 | PMC:PMC10877013 | DOI:10.3389/fphar.2024.1358626

Food Chem X. 2024 Feb 10;21:101221. doi: 10.1016/j.fochx.2024.101221. eCollection 2024 Mar 30.ABSTRACTWolfberry, known as Goji berry, is the fruit of Lycium barbarum L. (LB). As a famous functional food and TCM, the cost and efficacy of LB are closely linked to its geographical origin. The present study aimed to establish an effective method for distinguishing LB from different geographical origins. By employing UHPLC-QTOF-MS/MS combined with multivariate analysis, the metabolite profiling of LB (199 batches) obtained from Ningxia, Gansu, Qinghai, and Xinjiang, was evaluated. The results demonstrated that the method effectively distinguished LB from the four regions, with a total of 148 different metabolites being detected. Subsequent assessment using heat maps, Venn analysis, receiver operating characteristics curves and dot plots revealed 21 of these metabolites exhibited exceptional sensitivity and specificity, with under-curve values approaching 1, thus indicating their potential as biomarkers for LB. These findings strongly support the suitability of UHPLC-QTOF-MS/MS-based metabolomics as an effective approach to identify the source of LB.PMID:38379804 | PMC:PMC10877177 | DOI:10.1016/j.fochx.2024.101221

Food Chem X. 2024 Feb 6;21:101175. doi: 10.1016/j.fochx.2024.101175. eCollection 2024 Mar 30.ABSTRACTIn this work, we employed a global untargeted metabolomics technique to explore the intricate composition of anthocyanin constituents in bayberry wine and elucidate their alteration during the maceration process. Our analysis uncovered 20 distinct forms of anthocyanins in bayberry wine, including cyanidin-type, delphinidin-type, peonidin-type, malvidin-type, and other-type. 'Dongkui' (DK) bayberry wine was characterized by a predominance of glycoside forms of cyanidin-type and delphinidin-type anthocyanins, while 'Shuijing' (SJ) bayberry wine mainly contained other-type anthocyanins. Additionally, differential anthocyanins analyses conducted across various maceration periods demonstrated the different fate of the components in the wine, with a conspicuous decline in most glycosidic form anthocyanins. Moreover, correlation analysis revealed that the red hue of bayberry wine was primarily associated with cyanidin-3-O-glucoside, cyanidin-3-O-rhamnoside, delphinidin-3-O-arabinoside, and delphinidin-3-O-galactoside. This research contributes to our understanding of the anthocyanin composition and the dynamic variations in bayberry wine, opening avenues for further exploration and optimization of production techniques in the future.PMID:38379795 | PMC:PMC10876708 | DOI:10.1016/j.fochx.2024.101175

J Am Soc Mass Spectrom. 2024 Feb 21. doi: 10.1021/jasms.3c00418. Online ahead of print.ABSTRACTUntargeted metabolomics based on reverse phase LC-MS (RPLC-MS) plays a crucial role in biomarker discovery across physiological and disease states. Standardizing the development process of untargeted methods requires paying attention to critical factors that are under discussed or easily overlooked, such as injection parameters, performance assessment, and matrix effect evaluation. In this study, we developed an untargeted metabolomics method for plasma and fecal samples with the optimization and evaluation of these factors. Our results showed that optimizing the reconstitution solvent and sample injection amount was critical for achieving the balance between metabolites coverage and signal linearity. Method validation with representative stable isotopically labeled standards (SILs) provided insights into the analytical performance evaluation of our method. To tackle the issue of the matrix effect, we implemented a postcolumn infusion (PCI) approach to monitor the overall absolute matrix effect (AME) and relative matrix effect (RME). The monitoring revealed distinct AME and RME profiles in plasma and feces. Comparing RME data obtained for SILs through postextraction spiking with those monitored using PCI compounds demonstrated the comparability of these two methods for RME assessment. Therefore, we applied the PCI approach to predict the RME of 305 target compounds covered in our in-house library and found that targets detected in the negative polarity were more vulnerable to the RME, regardless of the sample matrix. Given the value of this PCI approach in identifying the strengths and weaknesses of our method in terms of the matrix effect, we recommend implementing a PCI approach during method development and applying it routinely in untargeted metabolomics.PMID:38379502 | DOI:10.1021/jasms.3c00418