PubMed

J Pharm Biomed Anal. 2024 Oct 9;252:116512. doi: 10.1016/j.jpba.2024.116512. Online ahead of print.ABSTRACTSnake melon (Cucumis melo var. flexuosus, CM) is a gourd with health-promoting nutritional traits and unexplored phytochemicals. This study aims to comprehensively investigate the phytoconstituents in the fruits, leaves, roots, seeds, and stems of CM, using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. Consequently, 118 metabolites were identified, encompassing phenolic compounds, flavonoids, megastigmanes, lignans, cucurbitacins, and fatty acids. Multivariate data analysis revealed differences in the metabolite composition of CM organs and correlated these variations with the potential in-vitro anti-inflammatory properties assessed against RAW 264.7 macrophages through the down-regulation of cyclo-oxygenase-Ⅱ, nuclear factor-kappa B, and tumor necrosis factor-α. The results indicated that leaf and seed extracts showed the highest anti-inflammatory activity due to their enrichment in several flavonoids, phenolic glycosides, and a megastigmane. These findings emphasize the health benefits of CM organs as potential functional foods and functional food by-products, serving as a natural source for developing new anti-inflammatory agents.PMID:39405783 | DOI:10.1016/j.jpba.2024.116512

Drug Resist Updat. 2024 Oct 10;77:101159. doi: 10.1016/j.drup.2024.101159. Online ahead of print.ABSTRACTAlthough immune checkpoint inhibitors (ICIs) have revolutionized immuno-oncology with effective clinical responses, only 30 to 40 % of patients respond to ICIs, highlighting the need for reliable biomarkers to predict and enhance therapeutic outcomes. This study investigated how amino acid, glycolysis, and bile acid metabolism affect ICI efficacy in non-small cell lung cancer (NSCLC) patients. Through targeted metabolomic profiling and machine learning analysis, we identified amino acid metabolism as a key factor, with histidine (His) linked to favorable outcomes and homocysteine (HCys), phenylalanine (Phe), and sarcosine (Sar) linked to poor outcomes. Importantly, the His/HCys+Phe+Sar ratio emerges as a robust biomarker. Furthermore, we emphasize the role of glycolysis-related metabolites, particularly lactate. Elevated lactate levels post-immunotherapy treatment correlate with poorer outcomes, underscoring lactate as a potential indicator of treatment efficacy. Moreover, specific bile acids, glycochenodeoxycholic acid (GCDCA) and taurolithocholic acid (TLCA), are associated with better survival and therapeutic response. Particularly, TLCA enhances T cell activation and anti-tumor immunity, suggesting its utility as a predictive biomarker and therapeutic agent. We also suggest a connection between gut microbiota and TLCA levels, with the Eubacterium genus modulating this relationship. Therefore, modulating specific metabolic pathways-particularly amino acid, glycolysis, and bile acid metabolism-could predict and enhance the efficacy of ICI therapy in NSCLC patients, with potential implications for personalized treatment strategies in immuno-oncology. ONE SENTENCE SUMMARY: Our study identifies metabolic biomarkers and pathways that could predict and enhance the outcomes of immune checkpoint inhibitor therapy in NSCLC patients.PMID:39405736 | DOI:10.1016/j.drup.2024.101159

J Hazard Mater. 2024 Oct 9;480:136120. doi: 10.1016/j.jhazmat.2024.136120. Online ahead of print.ABSTRACTAlthough animal studies have evaluated lead (Pb) toxicity, they are limited to soluble forms, such as Pb-acetate, which do not reflect the range found in the exposome. Recent studies on Pb speciation of residential soils in urban areas revealed that the initial Pb sources are not persistent and are extensively repartitioned into adsorbed forms of Pb rather than insoluble phosphates. We investigated the inhalation and neurological toxicity of dusts generated from a surficial soil sample collected from a residential site with an exposomic mixture of various Pb species, both adsorbed phases (Fe and Mn oxide, humate bound Pb) and mineral phases (Pb hydroxycarbonate, pyromorphite, galena). Mice inhaled East Chicago dust (ECD) generated from a composite soil sample for 4 h/day, 7 days/week, for 4 weeks. Mice were necropsied immediately, 1, 14 and 30 days post exposure to evaluate both toxicity and recovery. Exposure to ECD caused changes in memory and spatial learning in the Morris Water Maze test. RNAseq analysis of the hippocampus region revealed multiple differentially expressed genes and impacts on pathways involved in ion channel complexes, and neuron-to-neuron synapse. Metabolomics analysis of plasma highlighted significant alterations in metabolic processes immediately after exposure that resolved after 14 days of rest.PMID:39405708 | DOI:10.1016/j.jhazmat.2024.136120

J Hazard Mater. 2024 Oct 9;480:136086. doi: 10.1016/j.jhazmat.2024.136086. Online ahead of print.ABSTRACTHeavy metals (HMs) present in the natural aquatic environment can form a ternary aggregate of "EPS-DOM-HMs" with the prevalent microalgae extracellular polymers substances (EPS) and macromolecular dissolved organic matters (DOMs), which show special molecular structure and biological interaction. This study reveals the formation of "EPS-TA-HMs" and the mechanism of their physiological and metabolic effects on Raphidocelis subcapitata. Results indicate that TA-Cr(III) can bind to EPS to form ternary aggregates with substances coexisting large and small hydrodynamic diameters and that the interactions are dominated by hydrophobic interactions of the protein binding to the pyrrole ring of the polyphenol and hydrogen bonding interactions formed by OC-(N R O). The protein structure of EPS has the largest proportion of proline, glycine, aspartic acid, and tryptophan. These interactions promoted the secretion of EPS components and reduced the growth inhibition of Raphidocelis subcapitata by 45.9 % compared with Cr(III) exposure. TEM analysis combined with EDS analysis indicated that Cr(III) was taken intracellularly and TA-Cr(III) was not. In addition, metabolomics analyses revealed that microalgae initiate adaptive mechanisms via the activation of a two-component system (i.e., maintenance of high metabolic activity). This study underscored the morphology of HMs in real aquatic environments and the mechanisms of metabolic effects on aquatic organisms.PMID:39405697 | DOI:10.1016/j.jhazmat.2024.136086

Transl Oncol. 2024 Oct 13;50:102152. doi: 10.1016/j.tranon.2024.102152. Online ahead of print.ABSTRACTBACKGROUND: Plasma-derived Extracellular Vesicles (EVs) have been suggested as novel biomarkers in melanoma, due to their ability to reflect the cell of origin and ease of collection. This study aimed to identify novel EV biomarkers that can discriminate between disease stages. This was achieved by characterising the plasma-derived EVs of patients with melanoma, and comparing their proteomic and metabolomic profile to those from healthy controls.METHODS: EVs were isolated from the plasma of 36 patients with melanoma and 13 healthy controls using Size Exclusion Chromatography. Proteomic and Metabolomic Analyses were performed, and machine learning algorithms were used to identify potential proteins and metabolites to differentiate the plasma-derived EVs from melanoma patients of different disease stages.RESULTS: The concentration and size of the EV population isolated was similar between groups. Proteins (APOC4, PRG4, PLG, TNC, VWF and SERPIND1) and metabolites (lyso PC a C18:2, PC ae C44:3) previously associated with melanoma pathogenesis were identified as relevant in differentiating between disease stages.CONCLUSION: The results further support the continued investigation of circulating plasma-derived EVs as biomarkers in melanoma. Furthermore, the potential of combined proteo-metabolomic signatures for differentiation between disease stages may provide valuable insights into early detection, prognosis, and personalised treatment strategies.PMID:39405606 | DOI:10.1016/j.tranon.2024.102152

Ticks Tick Borne Dis. 2024 Oct 13;15(6):102404. doi: 10.1016/j.ttbdis.2024.102404. Online ahead of print.ABSTRACTThe control and prevention of ticks and tick-borne diseases rely on chemical insecticides and repellents. Plant-derived compounds potentially represent new and safer repellents. Cinnamaldehyde, a component of cinnamon oil, exhibits antibacterial, anti-inflammatory, acaricidal, and repellent activity against ticks. Here we studied the molecular mechanism of the repellent effect of cinnamaldehyde on Haemaphysalis longicornis. A 2 % cinnamaldehyde treatment resulted in >90 % nymph repellency within 6 h. Nymphs were exposed to cinnamaldehyde for 30 min, and subsequent transcriptome and metabolome analyses revealed the involvement of H. longicornis Acetylcholinesterases (HL-AchEs) in the response process. HL-AchEs was transcribed in all tick developmental stages and tissues. Following cinnamaldehyde treatment, the transcript and specific activity of the enzyme of AchE were significantly altered. Following RNAi, electroantennography (EAG) tests demonstrated a significant decrease in response to various repellents as well as a significant decrease in repellency. Our findings have revealed that HL-AchEs mediates cinnamaldehyde-induced tick repellency, and the results provide insights into the mechanism of plant-derived tick repellents.PMID:39405601 | DOI:10.1016/j.ttbdis.2024.102404

J Med Chem. 2024 Oct 15. doi: 10.1021/acs.jmedchem.4c01926. Online ahead of print.ABSTRACTPregnane X receptor (PXR) is a ligand-activated transcription factor that binds diverse compounds and upregulates drug metabolism machinery in response. PXR activation is detrimental to drug efficacy and safety because it reduces active drug concentrations and increases reactive metabolites, leading to toxicity and/or drug-drug interactions. Thus, effort must be expended in drug development pipelines to assess PXR activation by lead candidates and chemically modify agonists to reduce PXR liabilities while maintaining on-target potencies. Coadministration of drugs with PXR antagonists could prevent PXR-mediated metabolism events, but such compounds are rare and may themselves be converted to agonists by metabolic enzymes or PXR mutations. Here, we report the design, synthesis, optimization, and biological validation of proteolysis targeting chimeras that induce PXR degradation through E3 ubiquitin ligase recruitment. PXR degradation blocks agonist-induced gene expression and enhances anticancer effects of the chemotherapy paclitaxel, a known PXR agonist and substrate of downstream metabolic enzymes.PMID:39405362 | DOI:10.1021/acs.jmedchem.4c01926

PLoS Genet. 2024 Oct 15;20(10):e1011432. doi: 10.1371/journal.pgen.1011432. Online ahead of print.ABSTRACTSeveral protein ensembles facilitate crossover recombination and the associated assembly of synaptonemal complex (SC) during meiosis. In yeast, meiosis-specific factors including the DNA helicase Mer3, the "ZZS" complex consisting of Zip4, Zip2, and Spo16, the RING-domain protein Zip3, and the MutSγ heterodimer collaborate with crossover-promoting activity of the SC component, Zip1, to generate crossover-designated recombination intermediates. These ensembles also promote SC formation - the organized assembly of Zip1 with other structural proteins between aligned chromosome axes. We used proximity labeling to investigate spatial relationships between meiotic recombination and SC proteins in S. cerevisiae. We find that recombination initiation and SC factors are dispensable for proximity labeling of Zip3 by ZZS components, but proteins associated with early steps in recombination are required for Zip3 proximity labeling by MutSγ, suggesting that MutSγ joins Zip3 only after a recombination intermediate has been generated. We also find that zip1 separation-of-function mutants that are crossover deficient but still assemble SC fail to generate protein ensembles where Zip3 can engage ZZS and/or MutSγ. The SC structural protein Ecm11 is proximity labeled by ZZS proteins in a Zip4-dependent and Zip1-independent manner, but labeling of Ecm11 by Zip3 and MutSγ requires, at least in part, Zip1. Finally, mass spectrometry analysis of biotinylated proteins in eleven proximity labeling strains uncovered shared proximity targets of SC and crossover-associated proteins, some of which have not previously been implicated in meiotic recombination or SC formation, highlighting the potential of proximity labeling as a discovery tool.PMID:39405359 | DOI:10.1371/journal.pgen.1011432

JCI Insight. 2024 Oct 15:e181172. doi: 10.1172/jci.insight.181172. Online ahead of print.ABSTRACTLeft ventricular hypertrophy (LVH) and dyslipidemia are strong, independent predictors for cardiovascular disease, but their relationship is less well-studied. A longitudinal lipidomic profiling of left ventricular mass (LVM) and LVH is still lacking. Using LC-MS, we repeatedly measured 1,542 lipids from 1,755 unique American Indians attending two exams (mean~5-year apart). Cross-sectional associations of individual lipid species with LVM index (LVMI) were examined by generalized estimating equation (GEE), followed by replication in an independent bi-racial cohort (65% white, 35% black). Baseline plasma lipids associated with LVH risk beyond traditional risk factors were identified by Cox frailty model in American Indians. Longitudinal associations between changes in lipids and changes in LVMI were examined by GEE, adjusting for baseline lipids, baseline LVMI, and covariates. Multiple lipid species (e.g., glycerophospholipids, sphingomyelins, acylcarnitines) were significantly associated with LVMI or the risk of LVH in American Indians. Some lipids were confirmed in black and white individuals. Moreover, some LVH-related lipids were inversely associated with risk of coronary heart disease (CHD). Longitudinal changes in several lipid species (e.g., glycerophospholipids, sphingomyelins, cholesterol esters) were significantly associated with changes in LVMI. These findings provide insights into the role of lipid metabolism in LV remodeling and the risk of LVH or CHD.PMID:39405119 | DOI:10.1172/jci.insight.181172

Food Funct. 2024 Oct 15. doi: 10.1039/d4fo03657c. Online ahead of print.ABSTRACTEpidemiological and animal studies have indicated that calcium and boron are essential for bone development and metabolism. However, limited information is available regarding the effects of boron supplementation on bone development and metabolism in newly weaned infants with either calcium deficiency or calcium sufficiency. This study assessed the effects of dietary boron supplementation (0 and 3 mg kg-1) on bone development and metabolism, in a newly weaned mouse model, under both calcium deficiency and sufficiency feeding conditions. The results show that mice fed a calcium sufficient diet exhibited lower fat percentage and final body weight than those fed a calcium deficient diet. Boron supplementation reduced the serum high-density lipoprotein cholesterol level and up-regulated the mRNA levels of FABP3, PPAR-γ, and CaMK in the intestinal mucosa. Importantly, boron supplementation increased the tibial weight in mice on a calcium-sufficient diet and enhanced the tibial volume in those on a calcium-deficient diet. Metabolomic analysis highlighted calcium and boron's impact on metabolites like carboxylic acids and derivatives, fatty acyls, steroids and steroid derivatives, benzene and substituted derivatives, organonitrogen compounds, organooxygen compounds, and phenols, and were related to lipid metabolism and the neural signaling pathway. Transcriptomic analysis corroborated the role of calcium and boron in modulating bone metabolism via the JAK-STAT, calcium signaling, lipid metabolism, and inflammatory pathways. Multi-omics analysis indicated a strong correlation between calcium signaling pathways, lipid metabolism signaling, and dietary calcium and boron contents. This research provides insights into these complex mechanisms, potentially paving the way for novel interventions against calcium and boron deficiencies and bone metabolism abnormalities in clinical settings.PMID:39405052 | DOI:10.1039/d4fo03657c

Crit Rev Microbiol. 2024 Oct 15:1-24. doi: 10.1080/1040841X.2024.2412007. Online ahead of print.ABSTRACTListeria monocytogenes, a resilient bacterium in diverse food conditions, such as refrigeration, reduced water activity and low pH, poses a significant threat to the food industry and public health. In recent years, it has been documented an increase in the antibiotic resistance of zoonotic pathogens, including L. monocytogenes. This review provides new insight into the molecular mechanisms involved in both intrinsic and acquired antibiotic resistance of L. monocytogenes with an emphasis on the effect of different environmental and food-related factors. It also explores the relationship of these resistance mechanisms with virulence factors. An analysis of literature data (2009-2021) was conducted to investigate statistically and graphically potential associations between specific antibiotic resistance patterns in the pathogen and food categories using an unbiased variance analysis. The results evidenced that food type had an influence on the antibiotic resistance profiles of L. monocytogenes, with meat and vegetables being the food categories exhibiting the most prevalent profiles. The frequent detection of resistance to ampicillin, penicillin, and tetracycline (non-intrinsic resistances) indicates that specific processing conditions along the food chain may induce them. Many questions remain about the impact of food chain factors (e.g. thermal treatments, cold chain, preservatives, etc.) and food type (low pH, reduced water activity, etc.) on the antibiotic resistance patterns of the pathogen, particularly concerning food-related sources, the resistance mechanisms involved (e.g. cross-protection, horizontal gene transfer, etc.), and the evolutionary processes of antibiotic-resistant microbial populations. Metagenomics, in addition to other -omics technologies (metabolomics and transcriptomics), allows a better understanding of the processes involved in the acquisition of resistance.PMID:39404832 | DOI:10.1080/1040841X.2024.2412007

ISME J. 2024 Oct 15:wrae187. doi: 10.1093/ismejo/wrae187. Online ahead of print.ABSTRACTSalmonella enterica serovar Typhimurium is a pervasive enteric pathogen and ongoing global threat to public health. Ecological studies in the Salmonella impacted gut remain underrepresented in the literature, discounting microbiome mediated interactions that may inform Salmonella physiology during colonization and infection. To understand the microbial ecology of Salmonella remodeling of the gut microbiome, we performed multi-omics on fecal microbial communities from untreated and Salmonella-infected mice. Reconstructed genomes recruited metatranscriptomic and metabolomic data providing a strain-resolved view of the expressed metabolisms of the microbiome during Salmonella infection. These data informed possible Salmonella interactions with members of the gut microbiome that were previously uncharacterized. Salmonella-induced inflammation significantly reduced the diversity of genomes that recruited transcripts in the gut microbiome, yet increased transcript mapping was observed for 7 members, among which Luxibacter and Ligilactobacillus transcript read recruitment was most prevalent. Metatranscriptomic insights from Salmonella and other persistent taxa in the inflamed microbiome further expounded the necessity for oxidative tolerance mechanisms to endure the host inflammatory responses to infection. In the inflamed gut lactate was a key metabolite, with microbiota production and consumption reported amongst members with detected transcript recruitment. We also showed that organic sulfur sources could be converted by gut microbiota to yield inorganic sulfur pools that become oxidized in the inflamed gut, resulting in thiosulfate and tetrathionate that supports Salmonella respiration. This research advances physiological microbiome insights beyond prior amplicon-based approaches, with the transcriptionally active organismal and metabolic pathways outlined here offering intriguing intervention targets in the Salmonella-infected intestine.PMID:39404095 | DOI:10.1093/ismejo/wrae187

Actas Esp Psiquiatr. 2024 Oct;52(5):641-652. doi: 10.62641/aep.v52i5.1723.ABSTRACTBACKGROUND: The pathogenesis of Alzheimer's disease (AD) is complex. Recent research suggests that AD patients have early disorders in brain cholesterol metabolism. Cholesterol and its derivatives accumulate in neurons, leading to p-Tau overproduction and synaptic dysfunction, initiating AD progression. Calycosin-7-O-β-D-glucoside (CG), a distinctive constituent of Astragali Radix, holds a representative position. Many clinical trials have demonstrated that CG can attenuate cerebral ischemia/reperfusion injury and preserve the structural integrity of the blood-brain barrier. However, whether CG alleviates tau-mediated neurodegeneration by increasing cholesterol efflux after lipid accumulation remains unexplored.METHODS: Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and multivariate data analysis were employed to investigate metabolic changes in HT22 cells induced by sodium palmitate following 24 hours of CG treatment. The potential therapeutic mechanisms of CG on AD were further examined through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.RESULTS: Metabolomic analysis characterized 24 potential biomarkers, revealing that CG could ameliorate cholesterol metabolic pathways. The results of cell experiments revealed that CG can increase the expression of enzyme cholesterol 24-hydroxylase (CYP46A1) (p < 0.05) and the level of 24 hydroxycholesterol (24-OHC) (p < 0.05), reduce the expression of p-Tau (Thr231)/Tau (p < 0.01), inhibit the formation of lipid droplets.CONCLUSION: CG may inhibit the accumulation of cholesterol and its derivatives in neurons by affecting the CYP46A1-CE-Tau axis, offering a potential therapeutic strategy for AD.PMID:39403908 | DOI:10.62641/aep.v52i5.1723

Front Endocrinol (Lausanne). 2024 Sep 30;15:1415474. doi: 10.3389/fendo.2024.1415474. eCollection 2024.ABSTRACTBACKGROUND: Pancreatitis is a serious and complex inflammatory disease that imposes a severe effect on quality of life. Links between plasma lipidome and pancreatitis have been reported, some of which have not yet been clearly elucidated.METHODS: Therefore, our study aimed to investigate the causal relationships between plasma lipidome and four types of pancreatitis by conducting a bidirectional, two-sample Mendelian randomization (MR) analysis. We obtained genetic variants associated with 179 lipid species from a Genome-wide association analysis of plasma lipidome. The aggregated statistical data of acute pancreatitis (AP), alcohol-induced acute pancreatitis (AAP), chronic pancreatitis (CP), and alcohol-induced chronic pancreatitis (ACP) from the FinnGen consortium were exploited as the outcome. The inverse variance weighted (IVW) technique as the main method was used for MR analysis and sensitivity analyses were used to evaluate heterogeneity and pleiotropy.RESULTS: After FDR correction, SE (27:1/20:4) (OR = 0.938, 95%CI = 0.906-0.972, P = 4.38 × 10-4, PFDR = 0.039) was identified to be significantly associated with AP risk. Eight lipid species were identified to be significantly associated with CP risk: SE (27:1/20:4) (OR = 0.911, 95%CI = 0.869-0.954, P = 8.89 × 10-5, PFDR = 0.016), LPC (20:4) (OR = 0.892, 95%CI = 0.843-0.945, P = 9.74 × 10-5, PFDR = 0.009), PC (16:0_22:5) (OR = 0.880, 95%CI = 0.818-0.947, P = 6.29 × 10-4, PFDR = 0.028), PC (17:0_20:4) (OR = 0.893, 95%CI = 0.842-0.948, P = 1.76 × 10-4, PFDR = 0.010), PC (18:0_20:4) (OR = 0.920, 95%CI = 0.874-0.969, P = 1.70 × 10-3, PFDR = 0.038), PC (O-16:0/20:4) (OR = 0.871, 95%CI = 0.804-0.943, P = 6.95 × 10-4, PFDR = 0.025), PC (O-16:1/20:4) (OR = 0.890, 95%CI = 0.832-0.953, P = 7.85 × 10-4, PFDR = 0.023), and PE (O-18:1/20:4) (OR = 0.866, 95%CI = 0.791-0.947, P = 1.61 × 10-3, PFDR = 0.041). Furthermore, genetically predicted increased LPC (20:4) (OR = 0.862, 95%CI = 0.796-0.934, P = 3.00 × 10-4, PFDR = 0.027) and SM (34:2;O2) (OR = 0.753, 95%CI = 0.659-0.860, P = 2.97 × 10-5, PFDR = 0.005) levels were associated with decreased risk of ACP.CONCLUSIONS: Our findings provide evidence of causal associations between the specific types of lipidome and pancreatitis, offering new insights into future clinical research.PMID:39403583 | PMC:PMC11471641 | DOI:10.3389/fendo.2024.1415474

Heliyon. 2024 Sep 28;10(19):e38551. doi: 10.1016/j.heliyon.2024.e38551. eCollection 2024 Oct 15.ABSTRACTGlucose is a major energy substrate for cellular life activities, and its metabolic pathways include glycolysis, the pentose phosphate pathway, the hexosamine biosynthesis pathway, and the polyol pathway. Here, we review the glucose uptake pathways, metabolic characteristics, glucose transport, glucose metabolism-related enzymes, and biological importance in mammalian oocyte maturation, early embryo development, and embryonic stem cell proliferation and differentiation. Moreover, the interrelationships among glucose metabolism, female reproduction-related diseases and assisted reproductive technologies are focused. In addition, we review a number of analytical methodologies with the intention to integrate a multi-tiered strategy that encompasses cutting-edge metabolomics, artificial intelligence, epigenetics, and morphological assessments, setting the stage for a pivotal approach to cultivating high-caliber embryos in the future.PMID:39403464 | PMC:PMC11471579 | DOI:10.1016/j.heliyon.2024.e38551

Food Chem X. 2024 Sep 28;24:101864. doi: 10.1016/j.fochx.2024.101864. eCollection 2024 Dec 30.ABSTRACTChinese baijiu is highly regarded for its unique flavor, and a variety of crops can be utilized as raw materials in its production. Waxy crops are essential ingredients in the brewing of high-quality baijiu; however, there is currently no comprehensive identification of volatile organic compounds (VOCs) and non-volatile compounds (N-VOCs) in waxy wheat baijiu (WWB). This study aims to investigate the dynamic changes of VOCs and N-VOCs in WWB during several important time periods from new to aged. A total of 25 amino acids underwent changes in the samples, with numerous physiologically active beneficial amino acids showing significant accumulation after aging. Additionally, 517 VOCs changed after aging, predominantly comprising esters and terpenoids, with 72 major VOCs being identified. A total of 718 metabolites were identified in the metabolome, primarily comprising alterations in lipids, amino acids, phenolic acids, organic acids, and alkaloids. These metabolites significantly influenced the levels of amino acids and VOCs. Our study is the first to provide a comprehensive examination of these aspects of WWB, highlighting its unique advantages over other crops. We believe that this research will establish a theoretical foundation for the application of waxy wheat in the baijiu industry, improve baijiu quality, and promote the development of functional baijius.PMID:39403296 | PMC:PMC11471596 | DOI:10.1016/j.fochx.2024.101864

Front Vet Sci. 2024 Sep 30;11:1425089. doi: 10.3389/fvets.2024.1425089. eCollection 2024.ABSTRACTINTRODUCTION: Red ginseng (RG), a traditional herbal remedy, has garnered attention owing to its diverse health benefits resulting from its complex composition. However, extensive research is needed to substantiate the efficacy of RG and understand the underlying mechanisms supporting these benefits. This study aimed to identify potential biomarkers and investigate the impact of RG on related metabolic pathways in horse plasma using liquid chromatography-mass spectrometry (LC-MS)-based metabolomics.METHODS: Ten horses were divided into control and RG groups, with the latter administered RG at a dose of 600 mg⋅kg-1⋅day-1 for 3 weeks. Subsequently, the plasma samples were collected and analyzed using LC-MS. Multivariate statistical analysis, volcano plots, and feature-based molecular networking were employed.RESULTS: The analysis identified 16 metabolites that substantially decreased and 21 metabolites that substantially increased following RG consumption. Among the identified metabolites were oleanolic acid, ursolic acid, and ginsenoside Rb1, which are known for their antioxidant and anti-inflammatory properties, as well as lipid species that influence sphingolipid and glycerophospholipid metabolism. Additionally, potential biomarkers, including major RG components, demonstrated distinct group clustering in principal component analysis and partial least squares-discriminant analysis, indicating their utility in assessing the physiological effects of RG consumption.DISCUSSION: This study contributes to a comprehensive understanding of the effects of RG on health.PMID:39403214 | PMC:PMC11471734 | DOI:10.3389/fvets.2024.1425089

Drug Des Devel Ther. 2024 Oct 9;18:4497-4510. doi: 10.2147/DDDT.S476273. eCollection 2024.ABSTRACTOBJECTIVE: To identify the polar parts in Rhubarb that cause hepatotoxicity and explore the underlying mechanisms.METHODS: The rat model of liver cancer was established by gavage of diethylnitrosamine (DEN; 0.002 g/rat) for 14 weeks. Starting from the 11th week, Rhubarb granule (4 g/kg), aqueous, ethyl acetate and n-butanol extract of Rhubarb or Rhein equivalent to a dose of 4 g/kg Rhubarb granule were administered intragastrically for 4 consecutive weeks. Liver tissues from rats treated with DEN and Rhubarb granules were used for non-targeted metabolomics analysis. The correlation between pyruvate kinase isozyme type M2 (PKM2) expression level and the progress and prognosis of hepatocellular carcinoma (HCC) was evaluated through bioinformatics analysis based on TCGA database. Liver tissues and blood samples from rats treated with DEN and aqueous, ethyl acetate and n-butanol extract of Rhubarb were used for the screening of hepatotoxic polar parts of Rhubarb. The liver injuries were evaluated by the changes in pathology, liver function, and the expression levels of proliferating cell nuclear antigen (PCNA) and transforming growth factor beta1 (TGF-β1). The mechanism studies focus on PKM2 expression, and the metabolic reprogramming via detecting the activities of lactate dehydrogenase A (LDHA) and isocitrate dehydrogenase (ICDH). Furthermore, molecular docking analysis was performed to validate the target interaction between Rhein and PKM2, and the hepatotoxicity of Rhein was evaluated by testing liver function in the DEN-induced liver cancer model.RESULTS: The non-targeted metabolomics analysis revealed that Rhubarb promoted aerobic glycolysis in the rat model of DEN-induced liver cancer. And bioinformatics analysis revealed that high PKM2 expression was closely related to the progression and poor prognosis of HCC. In vivo studies indicated that the aqueous extract of Rhubarb, but not ethyl acetate and n-butanol extract, promoted the liver injuries induced by DEN. The mechanism study showed that the aqueous extract of Rhubarb increased the expression of PKM2 and promoted aerobic glycolysis. Moreover, Rhein had a strong binding affinity for PKM2 and aggravated liver injury in the DEN-induced liver cancer model.CONCLUSION: Aqueous extract of Rhubarb promoted hepatotoxicity via facilitating PKM2-mediated aerobic glycolysis in the rat model of DEN-induced liver cancer.PMID:39403095 | PMC:PMC11471889 | DOI:10.2147/DDDT.S476273

Front Microbiol. 2024 Sep 30;15:1450085. doi: 10.3389/fmicb.2024.1450085. eCollection 2024.ABSTRACTINTRODUCTION: Staphylococcus aureus is one of the chief pathogens that cause chronic and recurrent infections. Failure of the antibiotics to curb the infections contributes to relapse and is an important reason for the high mortality rate. Treatment failure may also be due to antibiotic tolerance. Accumulating evidence suggests that t the host immune environment plays an important role in inducing antibiotic tolerance of S. aureus, but research in this area has been limited.METHODS: In this study,the minimum inhibitory concentration (MIC) of the antibiotics against S. aureus was determined using the standard broth microdilution method.The study evaluated whether itaconate induces antibiotic tolerance in S. aureus through an antibiotic bactericidal activity assay.The effect of itaconate on the growth of S. aureus was evaluated by monitoring the growth of S. aureus in medium supplemented with itaconate. Additionally, RNA sequencing and metabolomics analyses were used to determine transcriptional and metabolic changes in S. aureus when exposed to itaconate.RESULTS AND DISCUSSION: According to the study,we found that the immune metabolite itaconate can induce tolerance in both methicillin-resistant and -susceptible S. aureus to aminoglycosides. When S. aureus was exposed to itaconate, its growth slowed down and transcriptomic and metabolomic alterations associated with decreased energy metabolism, including the tricarboxylate cycle, glycolysis, pyruvate metabolism, and arginine biosynthesis, were observed. These changes are associated with aminoglycoside tolerance. This study highlights the role of immune signaling metabolites in bacterial antibiotic tolerance and suggests new strategies to improve antibiotic treatment by modulating the host immune response and stimulating the metabolism of bacteria.PMID:39403084 | PMC:PMC11471559 | DOI:10.3389/fmicb.2024.1450085

Plant Direct. 2024 Oct 14;8(10):e70012. doi: 10.1002/pld3.70012. eCollection 2024 Oct.ABSTRACTC3 photosynthesis can be complemented with a C4 carbon concentrating mechanism (CCM) to minimize photorespiratory losses. C4 photosynthesis is often more efficient than C3 under steady-state conditions. However, the C4 CCM depends on inter-cellular metabolite concentration gradients, which must increase following increases in light intensity and could decrease rates of C4 photosynthesis under fluctuating light. Additionally, incomplete flux through photorespiration could prove beneficial to C4 assimilation during light induction of the CCM. Here, we compare metabolic profiles in the closely related C3 Flaveria robusta and C4 Flaveria bidentis during a light transient from low to high light to determine if these non-steady state accumulation patterns provide insight to the induction of the metabolite gradients needed to drive C4 intermediate transport and if there is incomplete cycling of photorespiratory intermediates. In these C3 and C4 species, metabolite steady-state pool sizes suggest that C4 transport acids maintain concentration gradients across the bundle sheath and mesophyll cell types under these light fluctuations. However, there was incomplete flux through photorespiration in the C4 F. bidentis, which could reduce photorespiratory CO2 loss via glycine decarboxylation and help maintain higher rates of assimilation during following induction periods.PMID:39403073 | PMC:PMC11473189 | DOI:10.1002/pld3.70012