PubMed

Sci Rep. 2024 Nov 5;14(1):26816. doi: 10.1038/s41598-024-78603-z.ABSTRACTAcne is a prevalent inflammatory disease in dermatology, and its pathogenesis may be associated with inflammation, immunity, and other mechanisms. It commonly manifests in young individuals and frequently imposes a heavy economic, physical, and psychological burden on patients. Gut microbes and blood metabolites, as significant immune and inflammatory regulators in the body, have been hypothesized to form the "neurocutaneous axis." Nonetheless, the precise causal relationships among the gut microbes, circulating blood metabolites, and acne development have yet to be elucidated. This study employed bidirectional two-sample Mendelian randomization (MR) to probe the causal impacts of 412 distinct gut microbes and 249 blood metabolites on acne. Single nucleotide polymorphisms (SNPs), which are closely associated with gut microbes and blood metabolites, were utilized as instrumental variables. This approach was taken to discern whether these elements serve as pathogenic or protective factors in relation to acne. Furthermore, a mediation analysis encompassing gut microbes, blood metabolites, and acne was conducted to explore potential correlations between gut microbes and blood metabolites, as well as their cumulative effects on acne. This was done to substantiate the notion of causality. Bidirectional two-sample MR analysis revealed 8 gut bacteria, 6 bacterial metabolic abundance pathways determined by birdshot, and 8 blood metabolites significantly associated with acne. The mediation MR analysis revealed 2 potential causal relationships, namely, Bifidobacterium-DHA-Acne and Bifidobacterium-Degree of Unsaturation-Acne. This study identified gut microbes and blood metabolites that are causally associated with acne. A potential causal relationship between gut microbes and blood metabolites was obtained via mediation analysis. These insights pave the way for the identification of new targets and the formulation of innovative approaches for the prevention and treatment of acne.PMID:39501024 | DOI:10.1038/s41598-024-78603-z

Cell Death Dis. 2024 Nov 6;15(11):795. doi: 10.1038/s41419-024-07177-5.ABSTRACTOsteoporosis is a major degenerative metabolic bone disease that threatens the life and health of postmenopausal women. Owing to limitations in detection methods and prevention strategy awareness, the purpose of osteoporosis treatment is more to delay further deterioration rather than to fundamentally correct bone mass. We aimed to clarify the pathogenesis of postmenopausal osteoporosis and optimize treatment plans. Our experiments were based on previous findings that oxidative stress mediates bone metabolism imbalance after oestrogen deficiency. Through energy metabolism-targeted metabolomics, we revealed that purine metabolism disorder is the main mechanism involved in inducing oxidative damage in bone tissue, which was verified via the use of machine-learning data from human databases. Xanthine and xanthine oxidase were used to treat osteoblasts to construct a purine metabolism disorder model. The activity and differentiation ability of osteoblasts decreased after X/XO treatment. Transcriptomic sequencing indicated that autophagic flux damage was involved in purine metabolism-induced oxidative stress in osteoblasts. Additionally, we performed serum metabolomics combined with network pharmacology to determine the pharmacological mechanism of metformin in the treatment of postmenopausal osteoporosis. HPRT1 was the potential target filtered from the hub genes, and FoxO1 signalling was the key pathway mediating the effect of metformin in osteoblasts. We also revealed that SIRT3-mediated deacetylation promoted the nuclear localization of FoxO1 to increase the expression of HPRT1. HPRT1 upregulation promoted purine anabolism and prevented the accumulation of ROS caused by purine catabolism to reverse oxidative damage in osteoblasts. We propose that purine metabolism disorder-induced oxidative stress is important for the pathogenesis of postmenopausal osteoporosis. The therapeutic mechanism of metformin should be confirmed through subsequent drug optimization and development studies to improve bone health in postmenopausal women.PMID:39500875 | DOI:10.1038/s41419-024-07177-5

J Immunother Cancer. 2024 Nov 5;12(11):e010422. doi: 10.1136/jitc-2024-010422.ABSTRACTBACKGROUND: Immune checkpoint inhibitors (ICIs) are therapeutically effective for hepatocellular carcinoma (HCC) but are individually selective. This study examined the role of specific common fragile sites (CFSs) related gene in HCC immunotherapy.METHODS: We analyzed HCC tissues using next-generation sequencing and flow cytometry via time-of-flight technology. A humanized orthotopic HCC mouse model, an in vitro co-culture system, untargeted metabolomics and a DNA pulldown assay were used to examine the function and mechanism of WWOX in the tumor immune response.RESULTS: WWOX was the most upregulated CFS-related gene in HCC patients responsive to ICIs. WWOX deficiency renders HCC resistant to PD-1 treatment in humanized orthotopic HCC mouse model. Macrophage infiltration is increased and CD8 T-cell subset infiltration is decreased in WWOX-deficient HCC patients. HCC-derived oleic acid (OA) promotes macrophage conversion to an immunosuppressive phenotype. Mechanistically, WWOX deficiency promoted OA synthesis primarily via competitive binding of NME2 with KAT1, which promoted acetylation of NME2 at site 31 and inhibited NME2 binding to the SCD5 promoter region. Pharmacological blockade of SCD5 enhanced the antitumor effects of anti-PD-1 therapy.CONCLUSIONS: WWOX is a key factor for immune escape in HCC patients, which suggests its use as a biomarker for stratified treatment with ICIs in clinical HCC patients.PMID:39500530 | DOI:10.1136/jitc-2024-010422

Int J Cardiol. 2024 Nov 3:132698. doi: 10.1016/j.ijcard.2024.132698. Online ahead of print.ABSTRACTBACKGROUND: Dyslipidaemia in patients with diabetes contributes to the risk of atherosclerotic cardiovascular disease. We aimed to identify a dyslipidemic profile associated with both dysglycemia and subclinical coronary atherosclerosis.METHODS: Study participants (n = 5050) were classified in three groups: normoglycemia, pre-diabetes, and diabetes. A coronary artery calcium score (CACS) > 0 defined subclinical coronary atherosclerosis. Two independent methods were used to identify, among 225 lipid biomarkers, those that were associated with pre-diabetes and diabetes and had to be further tested for association by zero inflated Poisson regression with CACS and CACS burden in those with CACS>0. Estimates were adjusted for cardiovascular risk factors with an interaction term for dispensed lipid lowering drugs.RESULTS: Thirty-two biomarkers associated with prediabetes and diabetes were further investigated for association with CACS. HDL diameter [multi-adjusted OR of 0.85 and 95 %CI (0.78-0.92)] as well as free cholesterol, phospholipids and total lipids in extra large HDL were inversely associated with CACS. There was a borderline significant interaction between small HDL and dispensed lipid lowering drugs on the presence of CACS, with and multi-adjusted OR of 0.53 and 95 %CI (0.36-0.77). None of the 32 glycemic profile-related lipid biomarkers associated with the relative increase of CACS in those with CACS>0. No consistent association was observed between non-HDL lipoproteins and CACS.CONCLUSIONS: Changes in composition and relative concentration of HDL associated with both dysglycemia and subclinical coronary atherosclerosis. Treatment with lipid lowering drugs may contribute to reduce the risk associated with high circulating levels of small HDL.PMID:39500476 | DOI:10.1016/j.ijcard.2024.132698

Poult Sci. 2024 Oct 29;103(12):104453. doi: 10.1016/j.psj.2024.104453. Online ahead of print.ABSTRACTThe differences in metabolites between fresh egg yolk (FEY), spray-dried egg yolk powder (SEY), and stored egg yolk powder (S-SEY) were quantitatively compared through metabolomic analysis. Total of 1004 metabolites were identified in the three groups of egg yolk samples. In pairwise group analysis, 242 differential metabolites were identified in FEY and SEY, 311 differential metabolites were identified in FEY and S-SEY, and 157 differential metabolites were identified in SEY and S-SEY. The analysis of differential metabolites with the highest abundance showed that amino acids, carbohydrates and lipids in FEY would undergo oxidation reactions after spray drying and storage and thus led to significant changes in the type and abundance of metabolites. The representative differential metabolites were then screened out for judging the freshness of egg yolk powder. Therefore, the results are highly important for evaluating the quality of egg yolk powder and provide important information for understanding the nutritional changes of egg yolk after spray drying and storage.PMID:39500265 | DOI:10.1016/j.psj.2024.104453

J Hazard Mater. 2024 Oct 31;480:136381. doi: 10.1016/j.jhazmat.2024.136381. Online ahead of print.ABSTRACTDi-(2-ethylhexyl) phthalate (DEHP) and microplastics (MPs) are emerging contaminants frequently detected in the marine environment. However, the influence of MPs on DEHP bioaccumulation and their combined effects on eco-environmental risks remain underexplored. Mytilus coruscus (M. coruscus) were exposed to DEHP (200.0 µg/L), polystyrene (PS) (0.050, 0.50, and 5.0 mg/L), and their combination at environmentally relevant concentrations for 15-day, followed by a 7-day depuration period. The amount of DEHP accumulation followed the order of digestive gland > gills > muscles > gonad, with PS dose-dependently amplifying DEHP bioaccumulation in digestive gland. The changes in antioxidant enzyme activity indicated disruptions in oxidative defense. Furthermore, metabolomic analysis revealed that PS and DEHP considerably altered the lipid, energy, and citric acid cycles in digestive gland and gonad. Post-depuration analysis showed combined exposure resulted in persistent effects. Compared with single exposures, combined exposure had a greater adverse effect on the metabolism of essential amino acids, fatty acids, and volatile compounds, potentially influencing edibility and nutritional value of M. coruscus. This study underscores cumulative eco-environmental toxicity of PS and DEHP toward M. coruscus and highlights the potential increased risks of co-pollution.PMID:39500187 | DOI:10.1016/j.jhazmat.2024.136381

J Environ Manage. 2024 Nov 4;371:123176. doi: 10.1016/j.jenvman.2024.123176. Online ahead of print.ABSTRACTThe secretion, accumulation, and composition of extracellular polymeric substances (EPS) are pivotal factors influencing microalgal growth as well as wastewater recycling. Until now, the accumulation and inhibition mechanism of EPS of Chlorella vulgaris during cycling cultivation is not fully understood. The purpose of this study was to explore how different light qualities regulate the secretion, chemical composition, and structure of microalgal EPS, and subsequently influence the recycling of culture wastewater. After four cycles of cultivation, C. vulgaris under green light produced the highest EPS production and lowest biomass production, which were 82% higher and 17% lower, respectively, compared to white light, which yielded the least EPS production and the highest biomass production. EPS under different light qualities all exhibited a fibrillar structure with a sheet-like surface, but differed in composition. Compared with the other groups, EPS under green light showed a significant increase in polysaccharides, proteins, and humic acid-like compounds, as well as an increased proportion of arabinose and rhamnose, according to monosaccharide composition analysis. Transcriptome analysis indicated that the up-regulation of metabolic pathways linked to glycolysis/gluconeogenesis, TCA cycle, lipid synthesis, and ABC transporters promoted EPS accumulation. Additionally, EPS could target light-harvesting complex (LHC) and electron transport chain, down-regulating the photosynthetic pathway, which ultimately inhibited microalgal growth under green light. This study provides a theoretical foundation for the light regulation and circulation culture of microalgae, as well as for microalgal wastewater treatment.PMID:39500171 | DOI:10.1016/j.jenvman.2024.123176

J Chromatogr A. 2024 Oct 28;1738:465477. doi: 10.1016/j.chroma.2024.465477. Online ahead of print.ABSTRACTThe leaves of Pterocarpus santalinus have been identified as a good source of health-beneficial flavonoids through the amalgamation of untargeted metabolomics using UHPLC-ESI-MSn leading to the identification of flavone-glycosides bearing isorhamnetin and quercetin skeletons. To unveil the optimum ultrasonication extraction conditions required for the comprehensive extraction of major flavone-glycosides, isorhamnetin-3-O-β-d-(2-O-α-L-rhamnopyranosyl)glucopyranoside and isorhamnetin-3-O-β-d-glucopyranoside, the response surface methodology based on Box-Behnken design was adopted. The influence of input extraction parameters extraction time (X1): 15-45 min, temperature (X2): 40-60 °C and biomass-solvent ratio (X3): 60-100 on the extractive yield and comprehensive flavonoid content resulted in the optimal conditions as 19.09 min, 48.65 oC, and 72.15, respectively. The investigation provides a sustainable approach for recovering health-beneficial flavone-glycosides for utilization in various industries.PMID:39500076 | DOI:10.1016/j.chroma.2024.465477

Animal. 2024 Oct 10;18(11):101354. doi: 10.1016/j.animal.2024.101354. Online ahead of print.ABSTRACTIdentification of plasma biomarkers for feed efficiency in growing beef cattle offers a promising opportunity for developing prediction models to improve precision feeding strategies. However, these models must accurately predict feed efficiency at early stages of fattening. Our study aimed to evaluate the reliability of candidate biomarkers previously identified in late-fattening cattle when analysed during early fattening stages and to develop diet-specific prediction equations for residual feed intake (RFI). From a total of 364 Charolais bulls across seven cohorts, we selected 64 animals with extreme RFI values. The animals were fed either a corn‑ or grass-silage diets. These animals were chosen from four out of the available seven cohorts. Animals from three cohorts (24 high-RFI and 24 low-RFI, having a mean RFI difference of 1.48 kg/d) were used for biomarker confirmation and prediction model training. Animals from a fourth cohort (8 high-RFI and 8 low-RFI, having a mean RFI difference of 0.98 kg/d) were used for model external validation. Blood samples were collected at the beginning of the feed efficiency test (333 ± 20 days), and plasma underwent targeted metabolomic for 630 metabolites, natural abundance of 15N (δ15N), insulin, and IGF-1 analysis. Seven previously identified plasma biomarkers for RFI in late-fattening beef cattle still kept their capability for discriminating low and high RFI animals when analysed during early fattening stages (P < 0.05). Among these confirmed biomarkers, five were common for both grass- and corn-fed animals (creatinine, β-alanine, triglyceride TG18:0_34:2, symmetric dimethyl-arginine and phosphatidylcholine PC aa C30:2) while two were diet-specific (IGF-1 for grass silage-based diet, and isoleucine for corn silage-based diet. No new plasma biomarkers of RFI were identified at early-fattening stages (false discovery rate > 0.05). Prediction models were developed based on seven confirmed RFI biomarkers analysed during early-fattening. Two logistic regression models incorporating creatinine and either IGF-1 (for grass silage-based diet) or PC aa C30:2 (for corn silage-based diet) effectively distinguished between high- and low-RFI animals with high sensitivity and specificity (area under the curve > 0.80). The biomarkers used in the models showed moderate to high repeatability between early and late fattening stages (0.45 < r < 0.65). The models were successfully externally validated, with more than 85% of animals from the fourth cohort correctly classified. Once validated in larger cohorts and utilising cost-effective and rapid analytical methods, these models could support precision feeding and breeding programmes, aiming to reduce the cost of raising beef cattle.PMID:39500057 | DOI:10.1016/j.animal.2024.101354

EBioMedicine. 2024 Nov 4;109:105400. doi: 10.1016/j.ebiom.2024.105400. Online ahead of print.ABSTRACTBACKGROUND: The ketogenic diet (KD) is a high fat, sufficient protein, and low carbohydrate dietary therapy for drug-resistant epilepsy. The underlying mechanisms of action of the KD remain unclear. In mice, the microbiota is necessary for the anti-seizure effect and specific microbes influence circulatory levels of metabolites that are linked to seizure reduction. However, it remains unclear which changes are linked to seizure reduction in patients with epilepsy.METHODS: We analysed the serum metabolome of children with drug-resistant epilepsy (n = 14) before and after three months on KD. Metabolomic changes were correlated to the gut microbiome and treatment outcome, i.e., seizure reduction.FINDINGS: In this prospective observational study, we uncovered associations between microbial species and serum metabolites that correlated with seizure reduction. Plasmalogens were most strongly linked to seizure reduction and had significant positive correlations with several gut microbes (e.g., Faecalibacterium prausnitzii, Alistipes communis, Alistipes shahii, and Christensenella minuta) while significant negative correlations were found for five strains of Escherichia coli. Infant-type Bifidobacteria correlated negatively with other metabolites associated with seizure reduction.INTERPRETATION: The microbes and metabolites identified here may contribute to the therapeutic effect of the KD in children with drug-resistant epilepsy. Several of these metabolites (e.g., plasmalogens) play important roles in neurobiology and may influence seizures. Based on our findings, anti-seizure therapeutic strategies could be developed involving the targeted manipulation of the gut microbiota and/or its metabolites.FUNDING: This study was supported by the Swedish Brain Foundation, Margarethahemmet Society, Sunnerdahls Handikappfond, Stockholm County Council Research Funds, and Linnea & Josef Carlssons Foundation.PMID:39500011 | DOI:10.1016/j.ebiom.2024.105400

Am J Respir Cell Mol Biol. 2024 Nov 5. doi: 10.1165/rcmb.2023-0249OC. Online ahead of print.ABSTRACTChanges in metabolic activity are key regulators of macrophage activity. Pro-inflammatory macrophages upregulate glycolysis, which promotes an inflammatory phenotype, whereas pro-repair macrophages rely upon oxidative metabolism and glutaminolysis to support their activity. Work to understand how metabolism regulates macrophage phenotype has been done primarily in macrophage cell lines and bone marrow-derived macrophages (BMDM). Our study sought to understand changes in metabolic activity of murine tissue-resident alveolar macrophages (AM) in response to LPS stimulation and to contrast them to BMDM. These studies also determined the contribution of glutamine metabolism using the glutamine inhibitor, DON. We found that compared to BMDM, AM have higher rates of oxygen consumption and contain a higher concentration of intracellular metabolites involved in fatty acid oxidation. In response to LPS, BMDM but not AM increased rates of glycolysis. Inhibition of glutamine metabolism using DON altered the metabolic activity of AM but not BMDM. Within AM, glutamine inhibition led to increases in intracellular metabolites involved in glycolysis, the TCA cycle, fatty acid oxidation, and amino acid metabolism. Glutamine inhibition also altered the metabolic response to LPS within AM but not BMDM. Our data reveal striking differences in the metabolic activity of AM and BMDM.PMID:39499818 | DOI:10.1165/rcmb.2023-0249OC

Invest Ophthalmol Vis Sci. 2024 Nov 4;65(13):6. doi: 10.1167/iovs.65.13.6.ABSTRACTPURPOSE: Endophthalmitis is a severe inflammatory condition due to intraocular infections that often leads to irreversible blindness. This study aimed to understand the age-dependent metabolic alterations in the vitreous of patients with bacterial endophthalmitis.METHODS: The study included the vitreous metabolome of patients with bacterial endophthalmitis (group 1, n = 15) and uninfected controls (group 2, n = 14), which were further stratified into three groups according to their age: young (0-30 years), middle (31-60 years), and elderly (>60 years). Vitreous samples were subjected to untargeted metabolomic analysis using high-resolution mass spectrometry (HRMS)m and acquired mass spectrometry data were analyzed using MetaboAnalyst 6.0. The altered metabolites with log2FC of ≥2/≤2, P < 0.05, and variable importance in projection > 1 were considered significant.RESULTS: In a total of 109 endogenous metabolites identified, young and elderly patients with endophthalmitis showed 52 (elevated, 25; reduced, 27; P < 0.05) and 27 (elevated, 19; reduced, 8; P < 0.05) significantly altered metabolites, respectively, compared to their age-matched controls. Additionally, 27 metabolites were differentially expressed in young patients with endophthalmitis compared to the older group. The crucial metabolic pathways dysregulated in the older infected population were de novo purine synthesis and salvage, carnitine, polyamine (spermidine), lipids (prostaglandins), and amino acid (taurine, methionine, histidine) which could possibly be attributed to the increased disease severity and inflammation observed in a clinical setting.CONCLUSIONS: Despite the erratic metabolic changes observed in the younger group infected with endophthalmitis when compared to age-matched controls, dysregulation in the specific pathways such as purine, carnitine, arachidonic acid, and polyamine metabolism could possibly alter the immunological exacerbation observed in the older group.PMID:39499509 | DOI:10.1167/iovs.65.13.6

Plant J. 2024 Nov 5. doi: 10.1111/tpj.17079. Online ahead of print.ABSTRACTWheat growth process has been experiencing severe challenges arising from the adverse environment. Notably, the incidence of Fusarium crown rot (FCR), a severe soil-borne disease caused by Fusarium pseudograminearum (Fp), has significantly intensified in various wheat-growing regions, resulting in a decline in grain yield. However, the identification of wheat varieties and the exploration of effective gene resources resistant to FCR have not yet been accomplished. Here, we screened and identified the tryptophan metabolism pathway to participate in wheat resistance to FCR by correlation analysis between transcriptome and metabolome, and found that indole-3-acetaldehyde (IAAld) and melatonin, two key metabolites in the tryptophan metabolic pathway, were significantly accumulated in Fp-induced wheat stem bases. Interestingly, exogenous application of these two metabolites could significantly enhance wheat resistance against Fp. Additionally, we observed that the activity of TaALDHase, a crucial enzyme responsible for catalyzing IAAld to produce indole-3-acetic acid (IAA), was inhibited. Conversely, the activity of TaMTase, a rate-limiting involved in melatonin biosynthesis, was enhanced in the Fp-induced wheat transcriptome. Further analysis showed that TaWRKY24 could regulate IAA and melatonin biosynthesis by inhibiting the expression of TaALDHase and enhancing the transcription of TaMTase, respectively. Silencing of TaALDHase could significantly increase wheat resistance to FCR. However, interference with TaWRKY24 or TaMTase could decrease wheat resistance to FCR. Collectively, our findings demonstrate the crucial role of the tryptophan metabolism pathway in conferring resistance against FCR in wheat, thereby expanding its repertoire of biological functions within the plant system.PMID:39499237 | DOI:10.1111/tpj.17079

Gut Microbes. 2024 Jan-Dec;16(1):2423026. doi: 10.1080/19490976.2024.2423026. Epub 2024 Nov 5.ABSTRACTFaecal/intestinal microbiota transplant (FMT/IMT) is an efficacious treatment option for recurrent Clostridioides difficile infection, which has prompted substantial interest in FMT's potential role in the management of a much broader range of diseases associated with the gut microbiome. Despite its promise, the success rates of FMT in these other settings have been variable. This review critically evaluates the current evidence on the impact of clinical, biological, and procedural factors upon the therapeutic efficacy of FMT, and identifies areas that remain nebulous. Due to some of these factors, the optimal therapeutic approach remains unclear; for example, the preferred timing of FMT administration in a heavily antibiotic-exposed hematopoietic cell transplant recipient is not standardized, with arguments that can be made in alternate directions. We explore how these factors may impact upon more informed selection of donors, potential matching of donors to recipients, and aspects of clinical care of FMT recipients. This includes consideration of how gut microbiome composition and functionality may strategically inform donor selection criteria. Furthermore, we review how the most productive advances within the FMT space are those where clinical and translational outcomes are assessed together, and where this model has been used productively in recent years to better understand the contribution of the gut microbiome to human disease, and start the process toward development of more targeted microbiome therapeutics.PMID:39499189 | DOI:10.1080/19490976.2024.2423026

ESC Heart Fail. 2024 Nov 5. doi: 10.1002/ehf2.15135. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: The heart is a metabolic organ rich in mitochondria. The failing heart reprograms to utilize different energy substrates, which increase its oxygen consumption. These adaptive changes contribute to increased oxidative stress. Hypertrophic cardiomyopathy (HCM) is a common heart condition, affecting approximately 15% of the general cat population. Feline HCM shares phenotypical and genotypical similarities with human HCM, but the disease mechanisms for both species are incompletely understood. Our goal was to characterize global changes in metabolome between healthy control cats and cats with different stages of HCM.METHODS: Serum samples from 83 cats, the majority (70/83) of which were domestic shorthair and included 23 healthy control cats, 31 and 12 preclinical cats with American College of Veterinary Internal Medicine (ACVIM) stages B1 and B2, respectively, and 17 cats with history of clinical heart failure or arterial thromboembolism (ACVIM stage C), were collected for untargeted metabolomic analysis. Multiple linear regression adjusted for age, sex and body weight was applied to compare between control and across HCM groups.RESULTS: Our study identified 1253 metabolites, of which 983 metabolites had known identities. Statistical analysis identified 167 metabolites that were significantly different among groups (adjusted P < 0.1). About half of the differentially identified metabolites were lipids, including glycerophospholipids, sphingolipids and cholesterol. Serum concentrations of free fatty acids, 3-hydroxy fatty acids and acylcarnitines were increased in HCM groups compared with control group. The levels of creatine phosphate and multiple Krebs cycle intermediates, including succinate, aconitate and α-ketoglutarate, also accumulated in the circulation of HCM cats. In addition, serum levels of nicotinamide and tryptophan, precursors for de novo NAD+ biosynthesis, were reduced in HCM groups versus control group. Glutathione metabolism was altered. Serum levels of cystine, the oxidized form of cysteine and cysteine-glutathione disulfide, were elevated in the HCM groups, indicative of heightened oxidative stress. Further, the level of ophthalmate, an endogenous glutathione analog and competitive inhibitor, was increased by more than twofold in HCM groups versus control group. Finally, several uremic toxins, including guanidino compounds and protein bound putrescine, accumulated in the circulation of HCM cats.CONCLUSIONS: Our study provided evidence of deranged energy metabolism, altered glutathione homeostasis and impaired renal uremic toxin excretion. Altered lipid metabolism suggested perturbed structure and function of cardiac sarcolemma membrane and lipid signalling.PMID:39499136 | DOI:10.1002/ehf2.15135

Front Cell Dev Biol. 2024 Oct 21;12:1491065. doi: 10.3389/fcell.2024.1491065. eCollection 2024.ABSTRACTBACKGROUND: Sepsis is a common disease associated with neonatal and infant mortality, and for diagnosis, blood culture is currently the gold standard method, but it has a low positivity rate and requires more than 2 days to develop. Meanwhile, unfortunately, the specific biomarkers for the early and timely diagnosis of sepsis in infants and for the determination of the severity of this disease are lacking in clinical practice.METHODS: Samples from 18 sepsis infants with comorbidities, 25 sepsis infants without comorbidities, and 25 infants with noninfectious diseases were evaluated using a serum metabolomics approach based on liquid chromatography‒mass spectrometry (LC‒MS) technology. Differentially abundant metabolites were screened via multivariate statistical analysis. In addition, least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) analyses were conducted to identify the key metabolites in infants with sepsis and without infections. The random forest algorithm was applied to determine key differentially abundant metabolites between sepsis infants with and without comorbidities. Receiver operating characteristic (ROC) curves were generated for biomarker value testing. Finally, a metabolic pathway analysis was conducted to explore the metabolic and signaling pathways associated with the identified differentially abundant metabolites.RESULTS: A total of 189 metabolites exhibited significant differences between infectious infants and noninfectious infants, while 137 distinct metabolites exhibited differences between septic infants with and without comorbidities. After screening for the key differentially abundant metabolites using LASSO and SVM-RFE analyses, hexylamine, psychosine sulfate, LysoPC (18:1 (9Z)/0:0), 2,4,6-tribromophenol, and 25-cinnamoyl-vulgaroside were retained for the diagnosis of infant sepsis. ROC curve analysis revealed that the area under the curve (AUC) was 0.9200 for hexylamine, 0.9749 for psychosine sulfate, 0.9684 for LysoPC (18:1 (9Z)/0:0), 0.7405 for 2,4,6-tribromophenol, 0.8893 for 25-cinnamoyl-vulgaroside, and 1.000 for the combination of all metabolites. When the septic infants with comorbidities were compared to those without comorbidities, four endogenous metabolites with the greatest importance were identified using the random forest algorithm, namely, 12-oxo-20-trihydroxy-leukotriene B4, dihydrovaltrate, PA (8:0/12:0), and 2-heptanethiol. The ROC curve analysis of these four key differentially abundant metabolites revealed that the AUC was 1 for all four metabolites. Pathway analysis indicated that phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and porphyrin metabolism play important roles in infant sepsis.CONCLUSION: Serum metabolite profiles were identified, and machine learning was applied to identify the key differentially abundant metabolites in septic infants with comorbidities, septic infants without comorbidities, and infants without infectious diseases. The findings obtained are expected to facilitate the early diagnosis of sepsis in infants and determine the severity of the disease.PMID:39498415 | PMC:PMC11532037 | DOI:10.3389/fcell.2024.1491065

Food Chem X. 2024 Oct 11;24:101893. doi: 10.1016/j.fochx.2024.101893. eCollection 2024 Dec 30.ABSTRACTLicorice flavonoids (LFs) exhibit potent antibacterial activities against Gram-positive bacteria. However, the related mechanism remains unclear. This study aims to illustrate the mechanisms of licochalcone A (LA), a main flavonoid in LFs, against methicillin-resistant Staphylococcus aureus (MRSA). The anti-MRSA effect of LA was comprehensively investigated by a combination of proteomics and metabolomics studies. Meanwhile, LA was loaded in glycyrrhizin (GA) micelles (GA@LA micelles) to improve its water solubility. The results demonstrated that LA could disrupt the arginine metabolism and cause the accumulation of intracellular ROS in MRSA. In addition, LA could inhibit the expression of glucokinase in MRSA, which affect the synthesis of ATP, fatty acids, and peptidoglycan. GA@LA micelles have the latent ability to inhibit the growth of MRSA on fresh pork.PMID:39498259 | PMC:PMC11532437 | DOI:10.1016/j.fochx.2024.101893

Food Chem X. 2024 Oct 15;24:101894. doi: 10.1016/j.fochx.2024.101894. eCollection 2024 Dec 30.ABSTRACTBaccaurea ramiflora has an unstable ripening period. Herein, five typical periods of fruit ripening of 'LR' Baccaurea ramiflora were analyzed by non-targeted metabolomics techniques. The results showed that ripening started 73 days after flowering and reached the ripening criterion at 93 days, a total of 451 differential metabolites were identified for the five periods. KEGG enrichment pathway showed that significant changes in citric acid were significantly correlated with changes in the downstream substance spermine (R 2 = 0.9068, y = -5.49 + 0.66×), while citric acid (R 2 = 0.9982) and spermine (R 2 = 0.9841) were negatively correlated with the sugar-acid ratio. Citric acid was the main component of titratable acid and spermine (R 2 = 0.9991) was positively correlated with titratable acid. We speculated that citric acid is a key taste marker for fruit ripening in 'LR' B. ramiflora. The results of the study provide new metabolic evidence for flavor changes and scientific basis for their quality improvement and exploitation in B. ramiflora.PMID:39498255 | PMC:PMC11532438 | DOI:10.1016/j.fochx.2024.101894

Front Microbiol. 2024 Oct 21;15:1458090. doi: 10.3389/fmicb.2024.1458090. eCollection 2024.ABSTRACTBACKGROUND: Microbial-derived secondary bile acids (SBAs) are reabsorbed and sensed via host receptors modulating cellular inflammation and fibrosis. Feline chronic kidney disease (CKD) occurs with progressive renal inflammation and fibrosis, mirroring the disease pathophysiology of human CKD patients.METHODS: Prospective cross-sectional study compared healthy cats (n = 6) with CKD (IRIS Stage 2 n = 17, Stage 3 or 4 n = 11). Single timepoint fecal samples from all cats underwent targeted bile acid metabolomics. 16S rRNA gene amplicon sequencing using DADA2 with SILVA taxonomy characterized the fecal microbiota.RESULTS: CKD cats had significantly reduced fecal concentrations (median 12.8 ng/mg, Mann-Whitney p = 0.0127) of the SBA ursodeoxycholic acid (UDCA) compared to healthy cats (median 39.4 ng/mg). Bile acid dysmetabolism characterized by <50% SBAs was present in 8/28 CKD and 0/6 healthy cats. Beta diversity significantly differed between cats with <50% SBAs and > 50% SBAs (PERMANOVA p < 0.0001). Twenty-six amplicon sequence variants (ASVs) with >97% nucleotide identity to Peptacetobacter hiranonis were identified. P. hiranonis combined relative abundance was significantly reduced (median 2.1%) in CKD cats with <50% SBAs compared to CKD cats with >50% SBAs (median 13.9%, adjusted p = 0.0002) and healthy cats with >50% SBAs (median 15.5%, adjusted p = 0.0112). P. hiranonis combined relative abundance was significantly positively correlated with the SBAs deoxycholic acid (Spearman r = 0.5218, adjusted p = 0.0407) and lithocholic acid (Spearman r = 0.5615, adjusted p = 0.0156). Three Oscillospirales ASVs and a Roseburia ASV were also identified as significantly correlated with fecal SBAs.CLINICAL AND TRANSLATIONAL IMPORTANCE: The gut-kidney axis mediated through microbial-derived SBAs appears relevant to the spontaneous animal CKD model of domestic cats. This includes reduced fecal concentrations of the microbial-derived SBA UDCA, known to regulate inflammation and fibrosis and be reno-protective. Microbes correlated with fecal SBAs include bai operon containing P. hiranonis, as well as members of Oscillospirales, which also harbor a functional bai operon. Ultimately, CKD cats represent a translational opportunity to study the role of SBAs in the gut-kidney axis, including the potential to identify novel microbial-directed therapeutics to mitigate CKD pathogenesis in veterinary patients and humans alike.PMID:39498133 | PMC:PMC11532117 | DOI:10.3389/fmicb.2024.1458090

Front Microbiol. 2024 Oct 21;15:1461821. doi: 10.3389/fmicb.2024.1461821. eCollection 2024.ABSTRACTINTRODUCTION: Organic fertilizers (OF) are crucial for enhancing soil quality and fostering plant growth, offering a more eco-friendly and enduring solution compared to chemical fertilizers (CF). However, few studies have systematically analyzed the effects of OF/CF on root microbiome of medicinal plants, especially in combination with active ingredients.METHODS: In this study, we investigated the composition and function of bacteria and fungi in the rhizosphere or within the root of traditional Chinese medicinal plants, Citri Grandis Exocarpium (Huajuhong), which were treated with OF or CF over 1, 3, and 5 years (starting from 2018). Additionally, we conducted metabolome analysis to evaluate the effects of different fertilizers on the medicinal properties of Huajuhong.RESULTS: The results indicated that extended fertilization could enhance the microbial population and function in plant roots. Notably, OF demonstrated a stronger influence on bacteria, whereas CF enhanced the cohesion of fungal networks and the number of fungal functional enzymes, and even potentially reduced the proliferation of harmful rhizosphere pathogens. By adopting distancebased redundancy analysis, we identified the key physicochemical characteristics that significantly influence the distribution of endophytes, particularly in the case of OF. In contrast, CF was found to exert a more pronounced impact on the composition of the rhizosphere microbiome. Although the application of OF resulted in a broader spectrum of compounds in Huajuhong peel, CF proved to be more efficacious in elevating the concentrations of flavonoids and polysaccharides in the fruit.DISCUSSION: Consequently, the effects of long-term application of OF or CF on medicinal plants is different in many ways. This research provides a guide for OF/CF selection from the perspective of soil microecology and aids us to critically assess and understand the effects of both fertilizers on the soil environment, and promotes sustainable development of organic agriculture.PMID:39498128 | PMC:PMC11532108 | DOI:10.3389/fmicb.2024.1461821