PubMed

Methods Mol Biol. 2025;2853:155-171. doi: 10.1007/978-1-0716-4104-0_11.ABSTRACTFor decades, host cell proteins (HCPs) have been investigated as putative contaminants in downstream processing of biopharmaceutical products of Chinese hamster ovary (CHO) cells. However, little is still known about the composition of the entire protein and vesicle environment in CHO cultivations. Ever evolving mass spectrometry techniques allow more and more insights into cell-cell communication processes and the composition of extracellular matrix, proteases, and further actively segregated compounds such as extracellular vesicles (EVs). EVs themselves are a heterologous group consisting of exosomes, ectosomes, and apoptotic vesicles. To specifically analyze these subsets of the secretome and determine beneficial and detrimental factors for a production process, targeted separation and purification techniques are necessary.In this chapter, we present our optimized workflows for a clear differentiation between directly secreted proteins and the vesicular protein content of different fractions (especially exosomal small EVs) from CHO cell supernatant for proteomic analysis by NanoLC ESI-MS.PMID:39460920 | DOI:10.1007/978-1-0716-4104-0_11

Mol Biol Rep. 2024 Oct 26;51(1):1098. doi: 10.1007/s11033-024-10042-5.ABSTRACTBACKGROUND: High glucose level and chronic inflammation are characteristic features of diabetic cutaneous wounds. Keratinocytes make up the epidermis and play an important role in skin repair. However, metabolomic changes of keratinocytes in chronic diabetic ulcers have not been fully studied.METHODS AND RESULTS: This study used high levels of glucose combined with lipopolysaccharide to treat human HaCaT keratinocytes. Untargeted metabolomic combined with colorimetric assays were used to explore the changes of keratinocyte metabolites and related metabolic pathways caused by high glucose and lipopolysaccharide. Results demonstrated that high glucose combined with lipopolysaccharide treatment increased intracellular reactive oxygen species and impaired proliferation and migration of keratinocytes. Untargeted metabolomics analysis identified a total of 273 differential metabolites. Redox metabolism associated metabolites were largely altered. Reduced nicotinamide adenine dinucleotide, gamma-glutamylcysteine, superoxide dismutase activity and SOD2 gene expression were significantly upregulated while nicotinamide adenine dinucleotide, glutathione, glutathione peroxidase, several types of lysophosphatidylcholine, lysophosphatidylinositol, and GPR55 gene expression were downregulated. Alterations of glutathione and nicotinamide adenine dinucleotide were verified by colorimetric assays. For the first time, high glucose and LPS were observed to boost the levels of fructose, aldose reductase and sorbitol dehydrogenase of the polyol pathway in HaCaT cells. Further treatment of HaCaT with fructose leading to inhibition of cell proliferation and migration.CONCLUSIONS: Our data suggest high glucose combined with lipopolysaccharide significantly altered redox homeostasis associated metabolites and activate the polyol pathway in keratinocytes to impact cell proliferation and migration, providing new strategies for the treatment of chronic diabetic ulcers.PMID:39460853 | DOI:10.1007/s11033-024-10042-5

Mol Biol Rep. 2024 Oct 26;51(1):1097. doi: 10.1007/s11033-024-10043-4.ABSTRACTThe polyphagous phytopathogen Sclerotinia sclerotiorum causing Stem rot disease is a major biotic stress in Brassica, and affects the yield and quality in various crops of agricultural significance. It affects the crop at pre-maturity which causes a reduction in the seed yield and deteriorates the oil quality in rapeseeds and Indian mustard globally. The hemibiotrophic nature and long persistence in the soil as sclerotia have made this pathogen difficult to manage through conventional agronomical practices. Hence, for alternative strategies, it is important to understand the basic aspects of the pathogen and the pathogenesis processes in the host. The current developments in technologies for omics studies including whole-genomes, transcriptomes, proteomes, and metabolomes have deciphered various genes, transcription factors, effectors and their target molecules involved in interaction, disease establishment and pathogen progress in the host tissues. The current review encompasses the studies that were conducted to decipher the Brassica-S. sclerotiorum pathosystem and the molecular factors identified through multi-omics studies for their application in building resistance to Sclerotinia stem rot disease in the susceptible cultivars of oilseed Brassica.PMID:39460825 | DOI:10.1007/s11033-024-10043-4

Anal Chem. 2024 Oct 26. doi: 10.1021/acs.analchem.4c02350. Online ahead of print.ABSTRACTOxylipins are a class of low-abundance lipids formed via oxygenation of fatty acids. These compounds include potent signaling molecules (e.g., octadecanoids, eicosanoids) that can exert essential functions in the pathophysiology of inflammatory diseases including asthma. While some oxylipin signaling cascades have been unraveled using LC-MS/MS-based methods, measurements in homogenate samples do not represent the spatial heterogeneity of lipid metabolism. Mass spectrometry imaging (MSI) directly detects analytes from a surface, which enables spatial mapping of oxylipin biosynthesis and migration within the tissue. MSI has lacked the sensitivity to routinely detect low-abundance oxylipins; however, new multiple-reaction-monitoring (MRM)-based MSI technologies show increased sensitivity. In this study, we developed a workflow to apply desorption electrospray ionization coupled to a triple quadrupole mass spectrometer (DESI-MRM) to spatially map oxylipins in pulmonary tissue. The targeted MSI workflow screened guinea pig lung extracts using LC-MS/MS to filter oxylipin targets based on their detectability by DESI-MRM. A panel of 5 oxylipins was then selected for DESI-MRM imaging derived from arachidonic acid (TXB2, 11-HETE, 12-HETE), linoleic acid (12,13-DiHOME), and α-linolenic acid (16-HOTrE). To parse this new data type, a custom-built R package (quantMSImageR) was developed with functionality to label regions of interest as well as quantify and analyze lipid distributions. The spatial distributions quantified by DESI-MRM were supported by LC-MS/MS analysis, with both indicating that 16-HOTrE and 12-HETE were associated with airways, while 12,13-DiHOME and arachidonic acid were mapped to parenchyma. This study realizes the potential of targeted MSI to routinely map low-abundance oxylipins with high specificity at scale.PMID:39460704 | DOI:10.1021/acs.analchem.4c02350

Eur J Endocrinol. 2024 Oct 26:lvae139. doi: 10.1093/ejendo/lvae139. Online ahead of print.ABSTRACTOBJECTIVE: The aim of this study was to investigate the gut microbial signatures and related pathophysiological implications in patients with Cushing's disease (CD).DESIGN AND METHODS: 27 patients with CD and 45 healthy controls were enrolled. Based on obtained metagenomics data, we performed correlation, network study and genome interaction group (GIG) analysis. Fecal metabolomics and serum ELISA analysis were conducted in dichotomized CD patients. Caco-2 cells were incubated with gradient concentrations of cortisol for subsequent transepithelial electrical resistance (TEER) measurement, FITC-dextran transwell permeability assay, qPCR and western blot analysis.RESULTS: Gut microbial composition in patients with CD was notably different from that in healthy controls. Network analysis revealed that Eubacterium siraeum might serve as the core specie in the gut microbial system of CD patients. Subsequent GIG analysis identified the positive correlations between GIG9 and UFC. Further serum ELISA and fecal metabolomics uncovered that CD patients with elevated UFC levels were characterized with increased lipopolysaccharide binding protein (LBP). Moreover, remarkable positive association was found between LBP level and relative abundance of Eubacterium siraeum. TEER and FITC-Dextran transwell assays demonstrated that hypercortisolism induced increased gut permeability. Further qPCR and western blot analysis suggested that dysregulated AhR/Claudin 2 axis might be involved in the development of hypercortisolism-induced defective gut barrier function.CONCLUSIONS: Disease activity associated dysbiosis and defective gut barrier might jointly facilitate the development of systemic inflammation in patients with CD.PMID:39460431 | DOI:10.1093/ejendo/lvae139

J Inherit Metab Dis. 2024 Oct 25. doi: 10.1002/jimd.12809. Online ahead of print.ABSTRACTAcute intermittent porphyria is an inherited error of heme synthesis. The underlying pathophysiology, involving mainly hepatic heme synthesis, is poorly understood despite its occurrence, and the severity of acute porphyria attack is still difficult to control. A better understanding of the interactions between heme synthesis and global metabolism would improve the management of AIP patients. An untargeted metabolomic analysis was performed on the urine of 114 patients with overt AIP and asymptomatic carriers using liquid chromatography coupled to high-resolution mass spectrometry. The collected data were analyzed by combining univariate and multivariate analyses. A total of 239 metabolites were annotated in urine samples by matching chromatographic and mass spectral characteristics with those from our chemical library. Twenty-six metabolites, including porphyrin precursors, intermediates of tryptophan or glycine metabolism and, unexpectedly, bile acids, showed significant concentration differences between the phenotypic groups. Dysregulation of bile acid metabolism was confirmed by targeted quantitative analysis, which revealed an imbalance in favor of hydrophobic bile acids associated with changes in conjugation, which was more pronounced in the severe phenotype. Using a random forest model, the cholic acid/chenodeoxycholic acid ratio enables the differential classification of severe patients from other patients with a diagnostic accuracy of 84%. The analysis of urine samples revealed significant modifications in the metabolome of AIP patients. Alteration in bile acids provides new insights into the pathophysiology of chronic complications, such as primary liver cancer, while also providing new biomarker candidates for predicting the most severe phenotypes.PMID:39460373 | DOI:10.1002/jimd.12809

Vaccines (Basel). 2024 Oct 17;12(10):1182. doi: 10.3390/vaccines12101182.ABSTRACTBACKGROUND/OBJECTIVES: The current Bordetella bronchiseptica (Bb) vaccine, when adjuvanted with alum, does not elicit adequate robust cellular immunity or effective antibody defense against Bb attacks. Unfortunately, antibiotic treatment generally represents an ineffective strategy due to the development of resistance against a broad range of antibiotics.METHODS: The present study was designed to investigate the immune response, protective capabilities and underlying mechanisms of a plant oil-based adjuvant E515 formulated with inactivated Bb antigen as a potential vaccine candidate against Bordetella bronchiseptica.RESULTS: Immunization studies revealed that a combination of SO, VE and GS (E515) exhibited a good synergistic adjuvant effect. The E515 adjuvanted Bb vaccine was proven to be highly efficacious and induced a mixed Th1/Th2/Th17 immune response in mice, leading to a significant increase in Bb-specific IgG, IgG1 and IgG2a antibodies, proliferative lymphocyte responses and cytokine levels (by lymphocytes and serum) and effectively induced responses by CD4+ TE, TM cells and B cells. The E515 adjuvant significantly enhanced the immune protection provided by the Bb vaccine in a mice model, as indicated by a reduced bacterial burden in the lungs. Multi-omics sequencing analysis revealed that E515 functions as an adjuvant by modulating critical pathways, including cytokine-cytokine receptor interaction, the IL-17 signaling pathway and the chemokine signaling pathway. This modulation also included interactions with beneficial species of bacteria including Alistipes, Odoribacter and Colidextribacter, as well as energy and lipid-related metabolites, thus highlighting its role as an immunomodulatory agent.CONCLUSION: Collectively, our results demonstrate the huge potential of E515-Bb vaccine candidates, thus highlighting the vegetable oil original adjuvant E515 as a promising agent for the development of new veterinary vaccines.PMID:39460348 | DOI:10.3390/vaccines12101182

Life (Basel). 2024 Oct 18;14(10):1323. doi: 10.3390/life14101323.ABSTRACTThe ability to analyze perilymph could allow inner ear pathologies to be studied. However, today, perilymph sampling is only performed for research purposes because of the risk of negative outcomes such as hearing loss or balance disorders. This paper aims to analyze the current literature on perilymph sampling and propose a method to collect perilymph in clinical settings. The published literature on perilymph sampling and its analyses was screened, and the results were analyzed and discussed in this mini review. Also, articles that discussed microneedle technology were reviewed and included in the analysis of the data. Based on the results of this review, we would like to propose a feasible technique to perform perilymph sampling in clinical settings. A total of eight studies analyzing perilymph were identified; data on proteomic, metabolomic and miRNA features present within human perilymph were collected and described. Two articles describing the use and auditory outcomes post microneedle drug injection into the inner ear were identified. Based on the methods for perilymph sampling described in humans and the recent innovations introduced by the use of microneedles, we suggested a feasible method to collect perilymph in the outpatient setting. The analysis of perilymph undoubtedly represents a valid instrument to fully understand inner ear diseases. A combination of traditional and innovative techniques, such as gaining access to the round window through the transcanalar approach using micro-endoscopes and microneedles to perform sampling, might simplify the sampling procedure and make it practicable in a clinical setting.PMID:39459624 | DOI:10.3390/life14101323

Life (Basel). 2024 Oct 12;14(10):1292. doi: 10.3390/life14101292.ABSTRACTINTRODUCTION: Health systems are confronted with not only the growing worldwide childhood obesity epidemic but also associated comorbidities. These subsequently cause variations in distinct metabolic pathways, leading to metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this evidence map is to systematically evaluate the evidence and to identify research gaps on glucagon-induced amino acid (AA) turnover and its metabolic interaction with MASLD.METHODOLOGY: A systematic literature search was conducted up to April 2023 in three electronic databases. Studies were required to include at least two of the main research areas, glucagon, AA metabolism and MASLD. Two independent reviewers screened titles and abstracts according to prespecified eligibility criteria, as well as full-text articles. Results are summarized in tables stratified by human and animal studies and study population age.RESULTS: Thirty-four references were ultimately included. The publication years dated back to 1965 showed a great increase from 2012 to 2023. In total, there were 19 animal studies and 15 human studies. Among the human studies, except for two studies in adolescents, all the studies were conducted in adults. In human studies, the methods used to evaluate metabolic changes differed among hyperinsulinemic-euglycemic clamp and oral glucose tolerance tests. Thirteen studies focused on the metabolic effects of MASLD, while only two studies explored the interaction between MASLD, glucagon and AA metabolism in humans. The other 19 studies focused on metabolomics, beta cell function or just one topic of a research area and not on interactions between one another.CONCLUSION: Research on the interaction between MASLD, glucagon and AA metabolism in humans is sparse and complete lacking in pediatrics. Furthermore, longitudinal studies with a focus on hyperglucagonemia independent of diabetes but related to MASLD present an unambiguous research gap.PMID:39459592 | DOI:10.3390/life14101292

Molecules. 2024 Oct 19;29(20):4947. doi: 10.3390/molecules29204947.ABSTRACTThe worm Caenorhabditis elegans, with its short lifecycle and well-known genetic and metabolic pathways, stands as an exemplary model organism for biological research. Its simplicity and genetic tractability make it an ideal system for investigating the effects of different conditions on its metabolism. The chemical analysis of this nematode was performed to identify specific metabolites produced by the worms when fed with either self- or nonself-DNA. A standard diet with OP50 feeding was used as a control. Different development stages were sampled, and their chemical composition was assessed by liquid chromatography-mass spectrometry combined with chemometrics, including both principal component analysis and orthogonal partial least squares discriminant analysis tools. The obtained data demonstrated that self-DNA-treated larvae, when arrested in their cycle, showed significant decreases in dynorphin, an appetite regulator of the nematode, and in N-formyl glycine, a known longevity promoter in C. elegans. Moreover, a substantial decrease was also recorded in the self-DNA-fed adults for the FMRF amide neuropeptide, an embryogenesis regulator, and for a dopamine derivative modulating nematode locomotion. In conclusion, this study allowed for the identification of key metabolites affected by the self-DNA diet, providing interesting hints on the main molecular pathways involved in its biological inhibitory effects.PMID:39459315 | DOI:10.3390/molecules29204947

Molecules. 2024 Oct 17;29(20):4924. doi: 10.3390/molecules29204924.ABSTRACTFungal endophytes, symbiotic microorganisms residing within plants, are renowned for producing bioactive secondary metabolites with diverse beneficial properties. We investigated the antimicrobial potential of fungal endophytes isolated from Solanum mauritianum, an invasive weed, against clinically significant bacterial pathogens. Selected fungal endophytes (Penicillium chrysogenum, Fusarium sp., and Paracamarosporium leucadendri) were isolated from the plant's leaves and fruits. Their crude extracts were tested against various referenced strains, such as Mycobacterium species (M. smegmatis ATCC 607 and M. bovis ATCC 27290), Staphylococcus aureus ATCC 6571, Bacillus subtilis ATCC 11774, Klebsiella species (K. pneumoniae ATCC 10031 and K. oxytoca ATCC 8724), Escherichia coli ATCC 10536, and Pseudomonas aeruginosa ATCC 10145, using the Kirby-Bauer disk diffusion method. Resazurin Microtiter Assay was used for the determination of the minimum inhibitory concentration. The chemical nature of the secondary metabolites in the crude extracts produced by fungal endophytes was evaluated using high-resolution liquid chromatography-mass spectrometry (LC-MS) using water and acetonitrile gradient. Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS/MS) was employed for untargeted metabolomics. LC-QTOF-MS/MS identified 63 bioactive compounds across the three endophytes. P. chrysogenum had the highest activity against S. aureus and M. smegmatis (1.15 mg/mL and 0.02 mg/mL, respectively), while P. leucadendri demonstrated moderate activity against M. smegmatis (2.91 mg/mL) and E. coli (1.16 mg/mL). Fusarium sp. exhibited the broadest spectrum of antibacterial activity, with MIC values ranging from 0.03 mg/mL (B. subtilis) to 10 mg/mL (M. smegmatis). P. leucadendri produced 29 metabolites, Fusarium sp. had 23 identified metabolites, and a total of 11 metabolites were identified from P. chrysogenum. The fruits of the plant, accounting for 60%, appeared to be the most abundant in the endophyte diversity when compared to the stems and leaves. This study highlights the potential of fungal endophytes from S. mauritianum as a source of novel bioactive compounds, particularly against multidrug-resistant pathogens, contributing to the ongoing efforts to combat antimicrobial resistance.PMID:39459292 | DOI:10.3390/molecules29204924

Pharmaceuticals (Basel). 2024 Oct 12;17(10):1363. doi: 10.3390/ph17101363.ABSTRACTOBJECTIVE: Gossypol is a natural polyphenolic dialdehyde product that is primarily isolated from cottonseed. It is a racemized mixture of (-)-gossypol and (+)-gossypol that has anti-infection, antimalarial, antiviral, antifertility, antitumor and antioxidant activities, among others. Gossypol optical isomers have been reported to differ in their biological activities and toxic effects.METHOD: In this study, we performed a metabolomics analysis of rat serum using 1H-NMR technology to investigate gossypol optical isomers' mechanism of action on uterine fibroids. Network toxicology was used to explore the mechanism of the liver injury caused by gossypol optical isomers. SD rats were randomly divided into a normal control group; model control group; a drug-positive group (compound gossypol acetate tablets); high-, medium- and low-dose (-)-gossypol acetate groups; and high-, medium- and low-dose (+)-gossypol acetate groups.RESULT: Serum metabolomics showed that gossypol optical isomers' pharmacodynamic effect on rats' uterine fibroids affected their lactic acid, cholesterol, leucine, alanine, glutamate, glutamine, arginine, proline, glucose, etc. According to network toxicology, the targets of the liver injury caused by gossypol optical isomers included HSP90AA1, SRC, MAPK1, AKT1, EGFR, BCL2, CASP3, etc. KEGG enrichment showed that the toxicity mechanism may be related to pathways active in cancer, such as the PPAR signaling pathway, glycolysis/glycolysis gluconeogenesis, Th17 cell differentiation, and 91 other closely related signaling pathways.CONCLUSIONS: (-)-gossypol acetate and (+)-gossypol acetate play positive roles in the treatment and prevention of uterine fibroids. Gossypol optical isomers cause liver damage through multiple targets and pathways.PMID:39459003 | DOI:10.3390/ph17101363

Pharmaceuticals (Basel). 2024 Sep 30;17(10):1307. doi: 10.3390/ph17101307.ABSTRACTDrug development from medicinal plants constitutes an important strategy for finding natural anticancer therapies. While several plant secondary metabolites with potential antitumor activities have been identified, well-defined mechanisms of action remained uncovered. In fact, studies of medicinal plants have often focused on the genome, transcriptome, and proteome, dismissing the relevance of the metabolome for discovering effective plant-based drugs. Metabolomics has gained huge interest in cancer research as it facilitates the identification of potential anticancer metabolites and uncovers the metabolomic alterations that occur in cancer cells in response to treatment. This holds great promise for investigating the mode of action of target metabolites. Although metabolomics has made significant contributions to drug discovery, research in this area is still ongoing. In this review, we emphasize the significance of plant metabolomics in anticancer research, which continues to be a potential technique for the development of anticancer drugs in spite of all the challenges encountered. As well, we provide insights into the essential elements required for performing effective metabolomics analyses.PMID:39458949 | DOI:10.3390/ph17101307

Pharmaceuticals (Basel). 2024 Sep 27;17(10):1281. doi: 10.3390/ph17101281.ABSTRACTThe treatment of arteritic anterior ischemic optic neuropathy (AAION), non-arteritic ischemic optic neuropathy (NAAION), and posterior ischemic optic neuropathy (PION) is a topic of ongoing research with mixed evidence on some pharmacotherapies and a need for more consensus. This manuscript provides an overview of these conditions' current, potential future, and attempted pharmacotherapies. AAION's current treatment regimen consists of high-dose steroids, with methotrexate, tocilizumab, and abatacept, being the most viable steroid-sparing therapy candidates. As for NAAION, the treatments being tried are vast, with mixed evidence supporting each modality. Similarly, despite the various treatment options explored, there still needs to be a universally effective therapy for PION. More research is needed to formulate an agreed-upon treatment regimen for these conditions.PMID:39458922 | DOI:10.3390/ph17101281

Plants (Basel). 2024 Oct 15;13(20):2888. doi: 10.3390/plants13202888.ABSTRACTSodium humate (SH) is the sodium salt of humic acid. Our previous research has demonstrated that SH has the ability to enhance the levels of total flavonoids in various parts of lemons, including the leaves, peels, pulps, and seeds, thereby improving the quality of lemons. In the current study, the regulation effect of SH on the biosynthesis and content of lemon flavonoid compounds was examined using transcriptome sequencing technology and flavonoid metabolomic analysis. Following SH treatment, the transcriptome sequencing analysis revealed 320 differentially expressed genes (DEGs) between samples treated with SH and control (CK) samples, some of which were associated with the phenylalanine pathway by KEGG annotation analysis. The levels of seven flavonoid compounds identified in lemon peels were observed to increase, and eriocitrin and isoorientin were identified as differential metabolites (DMs, VIP > 1) using OPLS-DA analysis. The integrated analysis of transcriptomics and flavonoid metabolomics indicates that SH treatment induces alterations in gene expression and metabolite levels related to flavonoid synthesis. Specifically, SH influences flavonoid biosynthesis by modulating the activity of key enzymes in the phenylalanine pathway, including HCT (O-hydroxycinnamoyltransferase) and F5H (ferulate-5-hydroxylase).PMID:39458835 | DOI:10.3390/plants13202888

Plants (Basel). 2024 Oct 14;13(20):2865. doi: 10.3390/plants13202865.ABSTRACTChestnut (Castanea mollissima) is an economically important forest tree species, and its flowers possess functions such as repelling mosquitoes, killing bacteria, and clearing heat. However, the regulatory mechanisms of floral volatile organic compounds (VOCs) in chestnut are still unclear. This study analyzed the contents of major volatile compounds and related gene expression levels in chestnut flowers during the initial flowering stage (IFS) and full-flowering stage (FFS) using metabolomics and transcription techniques. In total, 926 volatile compounds were detected, mainly terpenes, heterocyclic compounds, and esters. Acetylenone, styrene, and β-pinene had contents that exceeded 5% in FFS chestnut flowers. In total, 325 differential metabolites between the IFS and FFS were significantly (p < 0.05) enriched in the biosynthetic pathways of sesquiterpenes and triterpenes, as well as the ethylbenzene metabolic pathway. In total, 31 differentially expressed genes (DEGs) were related to terpenoid biosynthesis. There were only two DEGs related to the ethylbenzene metabolic pathway. In summary, we identified the volatile components of chestnut flowers and analyzed the changes in the contents of major volatile compounds in the flowers and the expression patterns of the related genes. The research results are helpful for understanding the regulation of VOCs in chestnut flowers.PMID:39458813 | DOI:10.3390/plants13202865

Nutrients. 2024 Oct 19;16(20):3553. doi: 10.3390/nu16203553.ABSTRACTBACKGROUND: Although healthy lifestyle has been linked with a reduced risk of cardiovascular diseases (CVDs), the potential metabolic mechanism underlying this association remains unknown.METHODS: We included 161,018 CVD-free participants from the UK Biobank. Elastic net regression was utilized to generate a healthy lifestyle-related metabolic signature. The Cox proportional hazards model was applied to investigate associations of lifestyle-related metabolic signature with incident CVDs, and mediation analysis was conducted to evaluate the potential mediating role of metabolic profile on the healthy lifestyle-CVD association. Mendelian randomization (MR) analysis was conducted to detect the causality.RESULTS: During 13 years of follow-up, 17,030 participants developed incident CVDs. A healthy lifestyle-related metabolic signature comprising 123 metabolites was established, and it was inversely associated with CVDs. The hazard ratio (HR) was 0.83 (95% confidence interval [CI]: 0.81, 0.84) for CVD, 0.83 (95% CI: 0.81, 0.84) for ischemic heart disease (IHD), 0.86 (95% CI: 0.83, 0.90) for stroke, 0.86 (95% CI: 0.82, 0.89) for myocardial infarction (MI), and 0.75 (95% CI: 0.72, 0.77) for heart failure (HF) per standard deviation increase in the metabolic signature. The metabolic signature accounted for 20% of the association between healthy lifestyle score and CVD. Moreover, MR showed a potential causal association between the metabolic signature and stroke.CONCLUSIONS: Our study revealed a potential link between a healthy lifestyle, metabolic signatures, and CVD. This connection suggests that identifying an individual's metabolic status and implementing lifestyle modifications may provide novel insights into the prevention of CVD.PMID:39458547 | DOI:10.3390/nu16203553

Nutrients. 2024 Oct 18;16(20):3543. doi: 10.3390/nu16203543.ABSTRACTBACKGROUND/OBJECTIVES: Metabolic dysfunction-associated fatty liver disease (MAFLD) is currently the most common cause of chronic liver disease. Systemic inflammatory status and peripheral metabolic symptoms in the clinical picture have an impact on gut commensal bacteria.METHODS: Our designed clinical trial was based on a cohort of patients with MAFLD whose diet included the daily consumption of 400 g of "Navelina" oranges for 28 days, compared with a control group of patients with the same pathologic conditions whose diet did not include the consumption of oranges and other foods containing similar nutrients/micronutrients. We used 16S metataxonomics and GC/MS analyses to identify taxa and urine/fecal VOCs, respectively.RESULTS: A set of micronutrients from the diet were inspected, and some specific fatty acids were identified as the main contributors in terms of cluster sample separation. Metataxonomics and metabolomics profiles were obtained, and a stringent statistical approach allowed for the identification of significant taxa/VOCs, which emerged from pairwise group comparisons in both fecal and urine samples.CONCLUSIONS: In conclusion, a set of taxa/VOCs can be directly referred to as a marker of dysbiosis status and other comorbidities that, together, make up the pathologic burden associated with MAFLD. The investigated variables can be a target of therapeutic strategies.PMID:39458536 | DOI:10.3390/nu16203543

Nutrients. 2024 Oct 17;16(20):3518. doi: 10.3390/nu16203518.ABSTRACTObjectives: Highland barley (HB) consumption offers numerous health benefits; however, its impact on glycolipid metabolism abnormalities induced by a high-fat diet remains unclear. Consequently, this study aimed to investigate the therapeutic effects and underlying molecular mechanisms of HB in the context of obesity; Methods: Rats were fed either a high-fat diet (HFD) to induce obesity or a standard diet (SD) for six weeks. The rats in the HFD group were randomly assigned into five groups: HFD+HFD, HFD+SD, and low (30%), medium (45%), and high (60%) doses of the HB diet for an additional ten weeks. Analyses of serum lipid profiles, liver histology, transcriptomes, and untargeted metabolomes were conducted; Results: HB intake resulted in decreased weight gain, reduced feed intake, lower serum triglyceride and cholesterol levels, and diminished hepatic lipid accumulation. It also improved insulin and fasting blood glucose levels, and antioxidant capacity in the HFD-fed rats. Transcriptome analysis revealed that HB supplementation significantly suppressed the HFD-induced increase in the expression of Angptl8, Apof, CYP7A1, GDF15, Marveld1, and Nr0b2. Furthermore, HB supplementation reversed the HFD-induced decrease in Pex11a expression. Untargeted metabolome analysis indicated that HB primarily influenced the pentose phosphate pathway, the Warburg effect, and tryptophan metabolism. Additionally, integrated transcriptome and metabolome analyses demonstrated that the treatments affected the expression of genes associated with glycolipid metabolism, specifically ABCG8, CYP2C12, CYP2C24, CYP7A1, and IRS2. Western blotting confirmed that HB supplementation impacted the IRS2/PI3K/AKT signaling pathway; Conclusions: HB alleviates HFD-induced obesity and liver injury in an obese rat model possibly through the IRS2/PI3K/Akt signaling pathway.PMID:39458511 | DOI:10.3390/nu16203518

Nutrients. 2024 Oct 16;16(20):3501. doi: 10.3390/nu16203501.ABSTRACTDifferences in metabolic regulation among obesity phenotypes, specifically metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) women, may lead to varied responses to interventions, which could be elucidated through metabolomics. Therefore, this study aims to investigate the differences in metabolite profiles between MHO and MUO women and the changes following a lifestyle intervention. Serum samples from 36 MHO and 34 MUO women who participated in a lifestyle intervention for weight loss were analysed using untargeted proton nuclear magnetic resonance spectroscopy (1H NMR) at baseline and 6 months post-intervention. Anthropometric, clinical, and dietary intake parameters were assessed at both time points. Both groups showed differential metabolite profiles at baseline and after six months. Seven metabolites, including trimethylamine-N-oxide (TMAO), arginine, ribose, aspartate, carnitine, choline, and tyrosine, significantly changed between groups post-intervention, which all showed a decreasing pattern in MHO. Significant reductions in body weight and body mass index (BMI) in the MUO correlated with changes in the carnitine and tyrosine levels. In conclusion, metabolite profiles differed significantly between MHO and MUO women before and after a lifestyle intervention. The changes in carnitine and tyrosine levels in MUO were correlated with weight loss, suggesting potential targets for therapeutic intervention.PMID:39458496 | DOI:10.3390/nu16203501