PubMed

BMC Complement Med Ther. 2024 Nov 13;24(1):394. doi: 10.1186/s12906-024-04683-z.ABSTRACTBACKGROUND: Melaleuca species (family Myrtaceae) are characterized by their wide-ranging applications as antimicrobials and in skin-related conditions. Herein, we estimated the volatile profile and biological significance of M. rugulosa (Link) leaves for the first time supported by a dereplication protocol.MATERIALS AND METHODS: Volatile components were extracted using hydrodistillation (HD), supercritical fluid (SF), and headspace (HS) techniques and identified using GC/MS. The variations among the three extracts were assessed using principal component analysis and orthogonal partial least square discriminant analysis (OPLS-DA). The extracted volatiles were tested for radical scavenging activity, anti-aging, and anti-hyperpigmentation potential. Finally, disc diffusion and broth microdilution assays were implemented to explore the antibacterial capacity against Streptococcus pyogenes, Staphylococcus aureus, Clostridium perfringens, and Pseudomonas aeruginosa.RESULTS: The yield of the SF technique (0.8%) was three times higher than HD. GC/MS analysis revealed that the oxygenated compounds are the most proponents in the three extracts being 95.93% (HD), 80.94% (HS), and 48.4% (SF). Moreover, eucalyptol (1,8-cineol) represents the major component in the HD-EO (89.60%) and HS (73.13%) volatiles, while dl-α-tocopherol (16.27%) and α-terpineol (11.89%) represent the highest percentage in SF extract. Regarding the bioactivity profile, the HD-EO and SF-extract showed antioxidant potential in terms of oxygen radical absorbance capacity, and β- carotene assays, while exerting weak activity towards DPPH. In addition, they displayed potent anti-elastase and moderate anti-collagenase activities. The HD-EO exhibited potent anti-tyrosinase activity, while the SF extract showed a moderate level compared to tested controls. OPLS-DA and dereplication studies predicted that the selective antibacterial activity of HD-EO to S. aureus was related to eucalyptol, while SF extract to C. perfringens was related to α-tocopherol.CONCLUSIONS: M. rugulosa leaves are considered a vital source of bioactive volatile components that are promoted for controlling skin aging and infection. However, further safety and clinical studies are recommended.PMID:39538246 | DOI:10.1186/s12906-024-04683-z

J Anim Sci Biotechnol. 2024 Nov 14;15(1):157. doi: 10.1186/s40104-024-01108-2.ABSTRACTBACKGROUND: Research on low-protein-level diets has indicated that even though the profiles of essential amino acids (EAAs) follow the recommendation for a normal-protein-level diet, broilers fed low-protein diets failed to achieve productive performance compared to those fed normal diets. Therefore, it is imperative to reassess the optimum profile of EAAs in low-protein diets and establish a new ideal pattern for amino acid balance. Furthermore, identifying novel sensitive biomarkers for assessing amino acid balance will greatly facilitate the development of amino acid nutrition and application technology. In this study, 12 dietary treatments [Con(+), Con(-), L&A(-), L&A(+), M&C(-), M&C(+), BCAA (-), BCAA(+), Thr(-), Thr(+), Trp(-) and Trp(+)] were established by combining different EAAs including lysine and arginine, methionine and cysteine, branched-chain amino acid (BCAA), threonine, and tryptophan to observe the growth and development of the broiler chickens fed with low-protein-level diets. Based on the biochemical parameters and untargeted metabolomic analysis of animals subjected to different treatments, biomarkers associated with optimal and suboptimal amino acid balance were identified.RESULTS: Growth performance, carcass characteristics, hepatic enzyme activity, serum biochemical parameters, and breast muscle mRNA expression differed significantly between male and female broilers under different dietary amino acid patterns. Male broilers exhibited higher sensitivity to the adjustment of amino acid patterns than female broilers. For the low-protein diet, the dietary concentrations of lysine, arginine, and tryptophan, but not of methionine, cystine, or threonine, needed to be increased. Therefore, further research on individual BCAA is required. For untargeted metabolomic analysis, Con(+) was selected as a normal diet (NP) while Con(-) represented a low-protein diet (LP). L&A(+) denotes a low-protein amino acid balanced diet (LPAB) and Thr(+) represents a low-protein amino acid imbalance diet (LPAI). The metabolites oxypurinol, pantothenic acid, and D-octopine in birds were significantly influenced by different dietary amino acid patterns.CONCLUSION: Adjusting the amino acid profile of low-protein diets is required to achieve normal growth performance in broiler chickens fed normal-protein diets. Oxypurinol, pantothenic acid, and D-octopine have been identified as potentially sensitive biomarkers for assessing amino acid balance.PMID:39538238 | DOI:10.1186/s40104-024-01108-2

BMC Plant Biol. 2024 Nov 14;24(1):1074. doi: 10.1186/s12870-024-05773-3.ABSTRACTBACKGROUND: Chilling stress is a key abiotic stress that severely restricts the growth and quality of melon (Cucumis melo L.). Few studies have investigated the mechanism of response to chilling stress in melon.RESULTS: We characterized the physiological, transcriptomic, and metabolomic response of melon to chilling stress using two genotypes with different chilling sensitivity ("162" and "13-5A"). "162" showed higher osmotic regulation ability and antioxidant capacity to withstand chilling stress. Transcriptome analysis identified 4395 and 4957 differentially expressed genes (DEGs) in "162" and "13-5A" under chilling stress, respectively. Metabolome analysis identified 615 and 489 differential enriched metabolites (DEMs) were identified in "162" and "13-5A" under chilling stress condition, respectively. Integrated transcriptomic and metabolomic analysis showed enrichment of glutathione metabolism, and arginine (Arg) and proline (Pro) metabolism, with differential expression patterns in the two genotypes. Under chilling stress, glutathione metabolism-related DEGs, 6-phosphogluconate dehydrogenase (G6PDH), glutathione peroxidase (GPX), and glutathione s-transferase (GST) were upregulated in "162," and GSH conjugates (L-gamma-glutamyl-L-amino acid and L-glutamate) were accumulated. Additionally, "162" showed upregulation of DEGs encoding ornithine decarboxylase, Pro dehydrogenase, aspartate aminotransferase, pyrroline-5-carboxylate reductase, and spermidine synthase and increased Arg, ornithine, and Pro. Furthermore, the transcription factors (TFs), MYB, ERF, MADS-box, and bZIP were significantly upregulated, suggesting their crucial role in chilling tolerance of melon.CONCLUSIONS: These findings elucidate the molecular response mechanism to chilling stress in melon and provide insights for breeding chilling-tolerant melon.PMID:39538130 | DOI:10.1186/s12870-024-05773-3

Metabolomics. 2024 Nov 13;20(6):130. doi: 10.1007/s11306-024-02190-3.ABSTRACTINTRODUCTION: Tempeh is an antioxidant-rich soybean fermentation product from Java, Indonesia. Cooking methods have an impact on the nutritional value and bioactivity of food.OBJECTIVE: This study aims to investigate how the cooking process affects the metabolites and antioxidant activity in tempeh using ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS).METHODS: A nontargeted UHPLC-HRMS metabolomics and chemometric analysis were used to evaluate metabolite profiles and antioxidant activity changes because of food processing in tempeh.RESULTS: The score plots of tempeh produced by boiling and frying methods displayed a distinct separation from raw tempeh, revealing that the cooking process altered the metabolite composition of tempeh. Due to processing, L-glutamic acid, L-pyroglutamic acid, DL-glutamine, and D-( +)-proline became the most affected metabolites on tempeh. There were 70 metabolites that showed antioxidant activity using the DPPH assay; 23 metabolites significantly differ from DPPH and control for antioxidant activity for all processing tempeh. Metabolites with significantly different antioxidant activity in raw and processed tempeh were dominated by flavonoids, vitamin E, and bioactive lipids.CONCLUSION: The DPPH antioxidant assay using UHPLC-HRMS is promising as a fast antioxidant assay by simplifying the conventional DPPH antioxidant assay. Further, it can be used to identify the name of metabolites responsible for its antioxidant activity.PMID:39538093 | DOI:10.1007/s11306-024-02190-3

Inflammation. 2024 Nov 14. doi: 10.1007/s10753-024-02182-4. Online ahead of print.ABSTRACTPristimerin is a pentacyclic triterpenoid mainly derived from Celastraceae plants such as Maytenus ilicifolia, which has been traditionally used for the treatment of gastrointestinal disorders. Pharmacological studies have shown that pristimerin exhibited anti-inflammatory, antioxidant, anticancer and antibacterial activities. However, the potential mechanism of pristimerin for the treatment of ulcerative colitis (UC) remains elusive. In the present study, pristimerin could effectively inhibit the NO generation induced by LPS in RAW 264.7 cells and upregulate the decreased expression of tight junction proteins such as occludin and claudin-1. In vivo, oral administration of pristimerin (0.5 mg/kg and 1 mg/kg) could significantly relieve UC symptoms such as body weight loss, disease activity index, shortened colon length and colonic pathological damage. Meanwhile, pristimerin decreased the TNF-α, MPO and MDA levels and increased the levels of IL-10, IL-22, SOD activity, occludin and claudin-1 in colon tissues. Gut microbiota analysis of cecum contents revealed that pristimerin treatment effectively alleviated gut microbiota dysbiosis. Additionally, serum metabolomics showed that 33 potential biomarkers involving lipid and tryptophan metabolism were identified, which may account for the therapeutic effects of pristimerin on UC mice. In conclusion, our findings indicate that pristimerin attenuates UC symptoms in DSS-induced mice through modulating intestinal barrier integrity, gut microbiota composition, lipid and tryptophan metabolism.PMID:39538091 | DOI:10.1007/s10753-024-02182-4

Plant Mol Biol. 2024 Nov 13;114(6):124. doi: 10.1007/s11103-024-01517-x.ABSTRACTExistence of potent in vitro regeneration system is a prerequisite for efficient genetic transformation and functional genomics of crop plants. In this study, two contrasting cultivars differencing in their in vitro regeneration efficiency were identified. Tissue culture friendly cultivar Golden Promise (GP) and tissue culture resistant DWRB91(D91) were selected as contrasting cultivars to investigate the molecular basis of regeneration efficiency through multiomics analysis. Transcriptomics analysis revealed 1487 differentially expressed genes (DEGs), in which 795 DEGs were upregulated and 692 DEGs were downregulated in the GP-D91 transcriptome. Genes encoding proteins localized in chloroplast and involved in ROS generation were upregulated in the embryogenic calli of GP. Moreover, proteome analysis by LC-MS/MS revealed 3062 protein groups and 16,989 peptide groups, out of these 1586 protein groups were differentially expressed proteins (DEPs). Eventually, GC-MS based metabolomics analysis revealed the higher activity of plastids and alterations in key metabolic processes such as sugar metabolism, fatty acid biosynthesis, and secondary metabolism. TEM analysis also revealed differential plastid development. Higher accumulation of sugars, amino acids and metabolites corresponding to lignin biosynthesis were observed in GP as compared to D91. A comprehensive examination of gene expression, protein profiling and metabolite patterns unveiled a significant increase in the genes encompassing various functions, such as ion homeostasis, chlorophyll metabolic process, ROS regulation, and the secondary metabolic pathway.PMID:39538083 | DOI:10.1007/s11103-024-01517-x

Pflugers Arch. 2024 Nov 14. doi: 10.1007/s00424-024-03041-9. Online ahead of print.ABSTRACTWestern dietary pattern is one of the main contributors to the increased risk of obesity and chronic diseases, through oxidative stress and inflammation, that are the two key mechanisms targeting metabolic organs, such as skeletal muscle and adipose tissue. The chronic exposure to high levels of dietary fatty acids can increase the amount of intramyocellular lipids in skeletal muscle, altering glucose homeostasis and contributing to a reduction in mitochondrial oxidative capacity. Probiotic administration is a promising approach as preventive strategy to attenuate metabolic damage induced by Western diet. Here, we investigated the beneficial effect of Limosillactobacillus reuteri DSM 17938 on the inflammatory state and oxidative balance in the skeletal muscle and adipose tissue of adult rats fed a western diet for 8 weeks, focusing on the role of skeletal muscle mitochondria. Limosillactobacillus reuteri DSM 17938 administration protected the skeletal muscle from mitochondrial dysfunction and oxidative stress, preventing the establishment of inflammation and insulin resistance. Interestingly, a further beneficial effect of the probiotic was exerted on body composition, favoring the deposition of protein mass and preventing adipose tissue hypertrophy and inflammation. These results open the possibility for the use of this probiotic in therapeutic approaches for nutrition-related diseases.PMID:39537965 | DOI:10.1007/s00424-024-03041-9

Metabolomics. 2024 Nov 13;20(6):131. doi: 10.1007/s11306-024-02196-x.ABSTRACTINTRODUCTION: Atopic dermatitis (AD) is a common chronic inflammatory dermatosis. However, the exact molecular mechanism underlying the development of AD remain largely unclear.OBJECTIVE: To investigate comprehensive metabolomic alterations in serum and skin tissue between 2,4-dinitrofluorobenzene (DNFB)-induced AD-like mice and healthy controls, aiming to identify the potential disease biomarkers and explore the molecular mechanisms of AD.METHODS: In this study, Untargeted metabolomics analysis was used to investigate both skin and serum metabolic abnormalities of 2,4-dinitrofluorobenzene (DNFB)-induced AD-like mice. Then, the metabolic differences among the groups were determined through the application of multivariate analysis. Additionally, the selection of predictive biomarkers was accomplished using the receiver operating characteristic (ROC) module.RESULTS: Our findings showed that levels of 220 metabolites in the skin and 94 metabolites in the serum were different in AD-like mice that were treated with DNFB compared to control mice. Uracil, N-Acetyl-L-methionine, deoxyadenosine monophoosphate, 2-acetyl-l-alkyl-sn-glycero-3-phosphcholine, and prostaglandin D2 are considered potential biomarkers of AD as obtained by integrating skin and serum differential metabolite results. Metabolomic data analysis showed that the metabolic pathways in which skin and serum are involved together include histidine metabolism, pyrimidine metabolism, alanine, aspartate, and glutamate metabolism.CONCLUSION: Our research explained the possible molecular mechanism of AD at the metabolite level and provided potential targets for the development of clinical drugs for AD.PMID:39537935 | DOI:10.1007/s11306-024-02196-x

Sci Rep. 2024 Nov 13;14(1):27891. doi: 10.1038/s41598-024-78721-8.ABSTRACTThis study presents a comprehensive multimodal analytical study of an Egyptian ritual Bes-vase, of the 2nd century BCE employing cutting-edge proteomics, metabolomics, genetics techniques, and synchrotron radiation-based Fourier Transformed Infrared microSpectroscopy (SR µ-FTIR) to characterize organic residues of its content. We successfully identified the presence of various functional, bioactive, psychotropic, and medicinal substances, shedding light on the diverse components of a liquid concoction used for ritual practices in Ptolemaic Egypt. Using LC-MS/MS with a new methodological approach, we identified key proteins and metabolites, enabling the identification of botanical sources, confirmed by genetic sequences. Our analyses revealed traces of Peganum harmala, Nimphaea nouchali var. caerulea, and a plant of the Cleome genus, all of which are traditionally proven to have psychotropic and medicinal properties. Additionally, the identification of human fluids suggests their direct involvement in these rituals. Furthermore, metabolomics and SR µ-FTIR analyses also revealed the presence of fermented fruit-based liquid and other ingredients such as honey or royal jelly. The identification of specific chemical compounds, such as alkaloids and flavonoids, provides insight into the psychoactive and therapeutic uses of these in ancient ritual practices. This multidisciplinary study highlights the complexity of ancient cultures and their interactions with psychoactive, medicinal, and bioactive substances. These findings contribute to our understanding of ancient belief systems, cultural practices, and the utilization of natural resources, ultimately enhancing our knowledge of past societies and their connection to the natural world.PMID:39537764 | DOI:10.1038/s41598-024-78721-8

Nat Commun. 2024 Nov 13;15(1):9791. doi: 10.1038/s41467-024-54072-w.ABSTRACTDrug-resistant strains of Mycobacterium tuberculosis are a major global health problem. Resistance to the front-line antibiotic isoniazid is often associated with mutations in the katG-encoded bifunctional catalase-peroxidase. We hypothesise that perturbed KatG activity would generate collateral vulnerabilities in isoniazid-resistant katG mutants, providing potential pathway targets to combat isoniazid resistance. Whole genome CRISPRi screens, transcriptomics, and metabolomics were used to generate a genome-wide map of cellular vulnerabilities in an isoniazid-resistant katG mutant strain of M. tuberculosis. Here, we show that metabolic and transcriptional remodelling compensates for the loss of KatG but in doing so generates vulnerabilities in respiration, ribosome biogenesis, and nucleotide and amino acid metabolism. Importantly, these vulnerabilities are more sensitive to inhibition in an isoniazid-resistant katG mutant and translated to clinical isolates. This work highlights how changes in the physiology of drug-resistant strains generates druggable vulnerabilities that can be exploited to improve clinical outcomes.PMID:39537607 | DOI:10.1038/s41467-024-54072-w

Sci Total Environ. 2024 Nov 11:176313. doi: 10.1016/j.scitotenv.2024.176313. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants known to pose significant risks to human and wildlife health. Freshwater turtles (Emydura macquarii macquarii), as long-lived species inhabiting aquatic ecosystems, are particularly vulnerable to PFAS bioaccumulation. This study investigated the multifaceted impact of PFAS contamination on these turtles, focusing on metabolic disruptions, reproductive success, hatchling health, and population impacts. Comprehensive analyses, including proteomics, lipidomics, metabolomics, and histopathology, were conducted on turtles from PFAS-impacted, control, and reference sites. The findings reveal significant metabolic disruptions in PFAS-exposed turtles, with alterations in amino acid and lipid metabolism, energy production, and oxidative stress responses. Proteomic analysis identified several health biomarkers indicative of early disease progression. Despite high levels of PFAS in tissues and organs, no gross or histopathological phenotypical abnormalities were directly linked to PFAS exposure. Gravid females from contaminated sites exhibited altered egg composition, particularly in magnesium to calcium ratios, potentially affecting eggshell strength. Biochemical profiles of egg albumin and yolk indicated significant differences in metabolites and lipids between contaminated and reference sites, suggesting potential impacts on embryo development. Hatchling deformities were notably higher and with increased frequency in terms of the types of deformities at the PFAS-impacted sites, with common defects including abnormal intergular scale shapes and marginal scale counts. Furthermore, the demographic profile of the turtle population showed a lack of juvenile turtles at contaminated sites, indicating reduced recruitment and potential long-term population declines. This indicates a field-based demonstration of an Adverse Outcome Pathway, from elevated levels of PFAS in the turtles, to biochemical perturbations within the animals, and finally population effects. These findings underscore the urgent need for regulatory measures to address PFAS contamination and its detrimental effects on wildlife.PMID:39537477 | DOI:10.1016/j.scitotenv.2024.176313

J Proteome Res. 2024 Nov 13. doi: 10.1021/acs.jproteome.4c00538. Online ahead of print.ABSTRACTAntibodies have a key role in the immune system, making their characterization essential to biomedical, biopharmaceutical, and clinical research questions. Antibody effector functions are mainly controlled by quantity, subclass, and Fc glycosylation. We describe an integrated method to measure these three critical dimensions simultaneously. The subclass-specific immunoglobulin G (IgG) Fc glycosylation analysis combines immunosorbance with glycopeptide-centered LC-MS detection. For integrated IgG1-specific quantitation, a commercial, stable isotope labeled IgG1 protein standard was spiked into the immunosorbent eluates. Robust quantitation was achieved, relying on a combination of a proteotypic peptide and the most abundant glycopeptides, generated through proteolytic cleavage from a mixture of natural IgG1 and the recombinant IgG1 standard. Method performance was demonstrated in a large coronavirus vaccination cohort at a throughput of 100 samples/day. LC-MS-derived, anti-SARS-CoV-2 spike protein IgG1 concentrations ranged from 100 to 10000 ng/mL and correlated well with a clinically relevant immunoassay. Technical variation was 200 times lower than biological variation; intermediate precision was 44%. In conclusion, we present a method capable of robustly and simultaneously assessing quantity, subclass, and Fc glycosylation of antigen-specific IgG in large clinical studies. This method will facilitate a broader understanding of immune responses, especially the important interplay among the three dimensions.PMID:39537390 | DOI:10.1021/acs.jproteome.4c00538

Endocr J. 2024 Nov 14. doi: 10.1507/endocrj.EJ24-0377. Online ahead of print.ABSTRACTObesity resulting from long-term sedentary a significant threat to human health. This study explores the effects of exercise snack intervention on body composition and plasma metabolomics in sedentary obese adults. Participants in the snack group were subjected to 4 days of sprint exercises by stair-climbing per week for 12 weeks. Systemic and regional fat mass, epicardial adipose tissue (EAT), abdominal visceral (AVFA) and subcutaneous (ASFA) fat area and plasma metabolomics data were measured before and after intervention. A higher improvement of EAT, AVFA and ASFA in the snack group compared to that in the control group, with a significant interaction effect (p < 0.05). The key differential metabolites between the two groups include isoleucine, glycine and serine. The proposed exercise snack effectively reduced the amount of AVFA and EAT. The change in body composition may be associated with the altered pathways of isoleucine, glycine, and serine metabolism.PMID:39537176 | DOI:10.1507/endocrj.EJ24-0377

Fish Shellfish Immunol. 2024 Nov 11:110016. doi: 10.1016/j.fsi.2024.110016. Online ahead of print.ABSTRACTThis study explores the impact of SYNLAC Prime probiotics on the growth performance, health status, and metabolic profile of white shrimp, Penaeus vannamei. Shrimp fed with the experimental diets, including the control diet without probiotic supplementation, and the diets supplemented with SYNLAC Prime probiotics at concentrations of 105 CFU (g diet)-1 (P5) and 106 CFU (g diet)-1 (P6) for 56 days. Results indicated a significant enhancement in growth performance in probiotic-treated shrimp relative to the control group, attributed to structural improvements in the digestive tract, particularly the increased abundances of B cells in the hepatopancreas. The administration of dietary probiotics markedly reduced the severity of Enterocytozoon hepatopenaei (EHP) infection and decreased cumulative mortalities following Vibrio alginolyticus challenge. Shrimp in the P6 group exhibited significant elevations in phenoloxidase activity, respiratory burst, lysozyme activity and phagocytic activity compared to control group. Furthermore, there was an upregulation of several immune-related genes in hepatopancreas, including serine protease (SP), prophenoloxidase (proPO) I, proPO II, and penaeidin 3a. Additionally, the expression of β-1, 3-glucan binding protein and SP mRNA was significantly increased in hemocytes. Untargeted metabolomics analysis using LC-MS/MS revealed significant changes in the hepatopancreas metabolic profile, highlighting alterations in energy metabolisms pathways, such as citrate cycle and nicotinate and nicotinamide metabolism, as well as amino acid metabolisms pathways including arginine and proline metabolism, taurine and hypotaurine metabolism, and histidine metabolism. These findings underscore the potential of SYNLAC Prime probiotics in enhancing shrimp growth, immune function, and metabolic pathways, offering valuable insights for advancing health management strategies in shrimp aquaculture.PMID:39537121 | DOI:10.1016/j.fsi.2024.110016

Life Sci. 2024 Nov 11:123231. doi: 10.1016/j.lfs.2024.123231. Online ahead of print.ABSTRACTMinor ginsenosides have demonstrated notable anti-fatigue capabilities. The aim of this study was to investigate the anti-fatigue mechanisms of total minor ginsenosides (TMGs) derived from a process involving probiotic fermentation and high-pressure steam treatment. The fatigue model was established in BALB/c male mice using weight-bearing swimming and TMGs were administered by orally at a dosage of 200 mg/kg for four weeks. The anti-fatigue mechanisms of TMGs were explored by assessing liver oxidative stress, skeletal muscle inflammation markers, as well as their impact on gut microbiota and serum metabolism. The results indicated that TMGs could significantly increase the levels of SOD, CAT, ATP and Na+-K+-ATPase and enhance the antioxidant capacity by modulating the PGC-1α/KEAP1/NRF2/HO-1 pathway. Meanwhile, TMGs reducing the levels of inflammatory factors TNF-α, IL-1β and IL-6 and inhibited inflammation by modulating the AMPK/TORC2/CREB/PGC-1α pathway. TMGs also regulated the gut microbiota, increasing the abundance of probiotic bacteria and the content of short-chain fatty acids (SCFAs) in the cecum. Serum metabolomics analyses have shown that TMGs can significantly affect the serum metabolic profile of fatigue model mice, regulating metabolic markers through affecting anti-fatigue-related metabolic pathways. In conclusion, TMGs exerted significant anti-fatigue effects through antioxidant and anti-inflammatory effects, and alleviate fatigue by regulating gut microbiota and serum metabolism.PMID:39537101 | DOI:10.1016/j.lfs.2024.123231

Life Sci. 2024 Nov 11:123238. doi: 10.1016/j.lfs.2024.123238. Online ahead of print.ABSTRACTMetabolomics is an emerging field involving the systematic identification and quantification of numerous metabolites in biological samples. Precision medicine applies multiomics systems biology to individual patients for reliable diagnostic classification, disease monitoring, and treatment. Multiomics systems biology encompasses genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Therefore, metabolomic techniques could be highly valuable for future clinical decision-making. This review provides a technical overview of two commonly used techniques for metabolomics measurements: mass spectrometry (MS) and proton nuclear magnetic resonance (1H NMR) spectroscopy. We also discuss recent clinical advances in these techniques. Individuals with inflammatory bowel disease (IBD) exhibit significant variability in prognosis and response to treatment. Since both genetic predisposition and environmental factors contribute to this condition, targeting the metabolome may provide key insights for distinguishing and profiling patients with different clinical needs. Additionally, the considerable overlap in the clinical presentation of various disease subtypes emphasizes the need for enhanced diagnostic methods to improve patient care.PMID:39537099 | DOI:10.1016/j.lfs.2024.123238

J Nutr. 2024 Nov 11:S0022-3166(24)01171-4. doi: 10.1016/j.tjnut.2024.11.004. Online ahead of print.ABSTRACTBACKGROUND: Epidemiological evidence linking blood pressure (BP) and body weight-lowering effects with fruit and vegetable consumption mostly relies on self-reported dietary assessment prone to misreport and under- or overestimation of relationships. We characterized objective 24-hr urinary metabolites and a derived metabolite score associated with fruit and vegetable intake and assessed their associations with BP and body mass index (BMI), with validation across cohorts.METHODS: We used untargeted proton nuclear magnetic resonance spectroscopy (1H NMR) of two timed repeated 24-hr urine collections from free-living participants from the US (n=2,032) and the UK (n=449) of the cross-sectional International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP). We evaluated correlations between fruit and vegetable intake assessed by 24-hr dietary recalls with 7,100 1H NMR features, adjusted for confounders and multiple testing. We related identified metabolites and a metabolite score with BP and BMI using extensively adjusted multiple linear regression models.RESULTS: We characterized eleven 1H NMR-derived 24-hr urinary metabolites related to fruit and vegetable intake, reproducible across multiple 24-hr urine collections of both cohorts. Proline betaine, citrate, N-methylproline, scyllo-inositol, 2-hydroxy-2-(4-methyl cyclohex-3-en-1-yl) propoxyglucuronide, and proline were associated with fruit intake, specifically with Rutaceae intake, while S-methyl-L-cysteine sulfoxide and S-methyl-L-cysteine sulfoxide metabolite were associated with Brassicacea intake. The metabolite score, explaining 39.8% of fruit and vegetable intake, was inversely associated with systolic BP (-1.65 mmHg; 95% confidence interval (CI): -2.68,-0.62, P<0.002) and BMI (-1.21 kg/m2; 95% CI: -1.62,-0.78, P<0.0001). These associations were to a large extent explained by urinary citrate excretion.CONCLUSION: We identified 1H NMR-derived urinary metabolites associated with fruit and vegetable consumption, consistent and reproducible between urine collections and across populations. A higher fruit and vegetable-related metabolite score showed associations with lower systolic BP and BMI, mainly mediated by citrate, but would need confirmation in further studies.STUDY REGISTRATION: This study was registered at the clinicaltrials.gov registration (https://clinicaltrials.gov/study/NCT00005271?term=NCT00005271&rank=1) as NCT00005271.PMID:39536968 | DOI:10.1016/j.tjnut.2024.11.004

Arch Biochem Biophys. 2024 Nov 11:110202. doi: 10.1016/j.abb.2024.110202. Online ahead of print.ABSTRACTMagnesium (Mg2+), the second most abundant intracellular cation, plays a crucial role in cellular functions. In this study, we investigate the interaction between Mg2+ and coenzyme A (CoA), a thiol-containing cofactor central to cellular metabolism also involved in protein modifications. Isothermal titration calorimetry revealed a 1:1 binding stoichiometry between Mg2+ and free CoA under biologically relevant conditions. Association constants of (537 ± 20) M-1 and (312 ± 7) M-1 were determined at 25°C and pH 7.2 and 7.8, respectively, suggesting that a significant fraction of CoA is likely bound to Mg2+ both in the cytosol and in the mitochondrial matrix. Additionally, the process is entropically-driven, and our results support that the origin of the entropy gain is solvent-related. On the other hand, the combination of 1- and 2-dimensional nuclear magnetic resonance spectroscopy with molecular dynamics simulations and unsupervised learning demonstrate a direct coordination between Mg2+ and the phosphate groups of the 4-phosphopantothenate unit and bound to position 5' of the adenosine ring. Interestingly, the phosphate in position 3' only indirectly contributes to Mg2+ coordination. Finally, we discuss how the binding of Mg2+ to CoA perturbates the chemical environment of different CoA atoms, regardless of their apparent proximity to the coordination site, through the modulation of the CoA conformational landscape. This insight holds implications for understanding the impact on both CoA and Mg2+ functions in physiological and pathological processes.PMID:39536960 | DOI:10.1016/j.abb.2024.110202

Clin Chim Acta. 2024 Nov 11:120038. doi: 10.1016/j.cca.2024.120038. Online ahead of print.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease worldwide, affecting one-fourth of the world's population. With more than half of the world's population, the Asia-Pacific region contributed 62.6 % of liver-related fatal incidents in 2015. Currently, liver imaging techniques such as computed tomography (CT), nuclear magnetic resonance (NMR) spectroscopy, and ultrasound are non-invasive imaging methods to diagnose the disease. A liver biopsy is the gold standard test for establishing the definite diagnosis of non-alcoholic steatohepatitis (NASH). However, there are still significant problems with sample variability and the procedure's invasiveness. Numerous studies have indicated various non-invasive biomarkers for both fibrosis and steatosis to counter the invasiveness of diagnostic procedures. Metabolomics could be a promising method for detecting early liver diseases, investigating pathophysiology, and developing drugs. Metabolomics, when utilized with other omics technologies, can result in a deeper understanding of biological systems. Metabolomics has emerged as a prominent research topic, offering extensive opportunities to investigate biomarkers for liver diseases that are both sensitive and specific. In this review, we have described the recent studies involving the use of a metabolomics approach in the diagnosis of liver diseases, which would be beneficial for the early detection and treatment of liver diseases.PMID:39536895 | DOI:10.1016/j.cca.2024.120038

Microb Pathog. 2024 Nov 11:107030. doi: 10.1016/j.micpath.2024.107030. Online ahead of print.ABSTRACTAcute pancreatitis (AP) is influenced by interactions between gut microbiota and metabolic products, though the mechanisms remain unclear. This study investigates variations in gut microbiota and metabolites between severe (SAP) and mild acute pancreatitis (MAP) patients to assess their impact on disease progression. Using a cross-sectional cohort design, gut microbiota and metabolite profiles were compared in SAP and MAP patients over two weeks post-diagnosis. 16S rRNA gene sequencing and metabolomic analyses, including KEGG pathway assessments and Spearman correlation, were employed, along with Mendelian Randomization (MR) to assess the influence of specific microbiota on AP. Results showed that SAP patients had significantly reduced gut microbiota diversity, which further declined in the second week. This was marked by increases in pathogenic bacteria like Stenotrophomonas and Enterobacter and decreases in beneficial bacteria such as Blautia. Key changes included a rise in Proteobacteria and a decline in Ruminococcaceae, Enterococcus, and Faecalicatena. Metabolic shifts included lipid metabolite upregulation and antioxidant downregulation. Correlation analysis linked Stenotrophomonas to short-chain fatty acid and amino acid metabolism, highlighting its role in disease progression. MR analysis confirmed negative causal relationships between Enterococcus B, Faecalicatena torques, and AP, suggesting protective effects. Variations in Blautia species indicated differing influences on AP. This study underscores the critical role of gut microbiota and metabolites in AP progression and suggests the need for further research to confirm these findings and explore targeted therapeutic interventions.PMID:39536839 | DOI:10.1016/j.micpath.2024.107030