PubMed

Front Microbiol. 2023 Jun 15;14:1211795. doi: 10.3389/fmicb.2023.1211795. eCollection 2023.ABSTRACTOwing to its great market potential for food and health care, white Auricularia cornea, a rare edible fungus, has received increased attention in recent years. This study presents a high-quality genome assembly of A. cornea and multi-omics analysis of its pigment synthesis pathway. Continuous Long Reads libraries, combined with Hi-C-assisted assembly were used to assemble of white A. cornea. Based on this data, we analyzed the transcriptome and metabolome of purple and white strains during the mycelium, primordium, and fruiting body stages. Finally, we obtained the genome of A.cornea assembled from 13 clusters. Comparative and evolutionary analysis suggests that A.cornea is more closely related to Auricularia subglabra than to Auricularia heimuer. The divergence of white/purple A.cornea occurred approximately 40,000 years ago, and there were numerous inversions and translocations between homologous regions of the two genomes. Purple strain synthesized pigment via the shikimate pathway. The pigment in the fruiting body of A. cornea was γ-glutaminyl-3,4-dihydroxy-benzoate. During pigment synthesis, α-D-glucose-1P, citrate, 2-Oxoglutarate, and glutamate were four important intermediate metabolites, whereas polyphenol oxidase and other 20 enzyme genes were the key enzymes. This study sheds light on the genetic blueprint and evolutionary history of the white A.cornea genome, revealing the mechanism of pigment synthesis in A.cornea. It has important theoretical and practical implications for understanding the evolution of basidiomycetes, molecular breeding of white A.cornea, and deciphering the genetic regulations of edible fungi. Additionally, it provides valuable insights for the study of phenotypic traits in other edible fungi.PMID:37396365 | PMC:PMC10308021 | DOI:10.3389/fmicb.2023.1211795

Front Nutr. 2023 Jun 15;10:1198531. doi: 10.3389/fnut.2023.1198531. eCollection 2023.ABSTRACTSCOPE: The New Nordic Diet (NND) has been shown to promote weight loss and lower blood pressure amongst obese people. This study investigates blood plasma metabolite and lipoprotein biomarkers differentiating subjects who followed Average Danish Diet (ADD) or NND. The study also evaluates how the individual response to the diet is reflected in the metabolic differences between NND subjects who lost or maintained their pre-intervention weight.METHODS: Centrally obese Danes (BMI >25) followed NND (90 subjects) or ADD (56 subjects) for 6 months. Fasting blood plasma samples, collected at three time-points during the intervention, were screened for metabolites and lipoproteins (LPs) using proton nuclear magnetic resonance spectroscopy. In total, 154 metabolites and 65 lipoproteins were analysed.RESULTS: The NND showed a relatively small but significant effect on the plasma metabolome and lipoprotein profiles, with explained variations ranging from 0.6% for lipoproteins to 4.8% for metabolites. A total of 38 metabolites and 11 lipoproteins were found to be affected by the NND. The primary biomarkers differentiating the two diets were found to be HDL-1 cholesterol, apolipoprotein A1, phospholipids, and ketone bodies (3-hydroxybutyric acid, acetone, and acetoacetic acid). The increased levels of ketone bodies detected in the NND group inversely associated with the decrease in diastolic blood pressure of the NND subjects. The study also showed that body weight loss among the NND subjects was weakly associated with plasma levels of citrate.CONCLUSION: The main plasma metabolites associated with NND were acetate, methanol and 3-hydroxybutyrate. The metabolic changes associated with the NND-driven weight loss are mostly pronounced in energy and lipid metabolism.PMID:37396134 | PMC:PMC10308042 | DOI:10.3389/fnut.2023.1198531

Front Nutr. 2023 Jun 15;10:1215836. doi: 10.3389/fnut.2023.1215836. eCollection 2023.ABSTRACTBACKGROUND: Microbiota unbalance has been proven to affect chronic kidney disease (CKD) patients and, noteworthy, microbiota composition and activity are implicated in CKD worsening. The progression of kidney failure implies an exceeding accumulation of waste compounds deriving from the nitrogenous metabolism in the intestinal milieu. Therefore, in the presence of an altered intestinal permeability, gut-derived uremic toxins, i.e., indoxyl sulfate (IS) and p-cresyl sulfate (PCS), can accumulate in the blood.METHODS: In a scenario facing the nutritional management as adjuvant therapy, the present study assessed the effectiveness of an innovative synbiotics for its ability to modulate the patient gut microbiota and metabolome by setting a randomized, single-blind, placebo-controlled, pilot trial accounting for IIIb-IV stage CKD patients and healthy controls. Metataxonomic fecal microbiota and fecal volatilome were analyzed at the run-in, after 2 months of treatment, and after 1 month of wash out.RESULTS: Significant changes in microbiota profile, as well as an increase of the saccharolytic metabolism, in feces were found for those CKD patients that were allocated in the synbiotics arm.CONCLUSIONS: Noteworthy, the here analyzed data emphasized a selective efficacy of the present synbiotics on a stage IIIb-IV CKD patients. Nonetheless, a further validation of this trial accounting for an increased patient number should be considered.CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, identifier NCT03815786.PMID:37396126 | PMC:PMC10311028 | DOI:10.3389/fnut.2023.1215836

J Agric Food Chem. 2023 Jul 3. doi: 10.1021/acs.jafc.3c01883. Online ahead of print.ABSTRACTAtlantic giant (AG, Cucurbita maxima) is a type of giant pumpkin in the Cucurbitaceae family and has the world's largest fruit. AG possesses excellent ornamental and economic value due to its well-known large fruit. However, giant pumpkins are usually thrown away after viewing, thus generating a waste of resources. To explore the additional value of giant pumpkins, a metabolome assay was performed between AG and Hubbard (a small fruit pumpkin) fruits. We found that bioactive compounds, especially flavonoids (including 8-prenylnaringenin, tetrahydrocurcumin, galangin, and acacetin) and coumarins (including coumarin, umbelliferone, 4-coumaryl alcohol, and coumaryl acetate), with extensive antioxidant and pharmacological functions, showed higher accumulation in AG fruit than in Hubbard fruits. Comparative transcriptomics of the two pumpkin fruits indicated that the differentially expressed genes (DEGs) encoding PAL, C4H, 4CL, CSE, HCT, CAD, and CCoAOMT were relatively highly expressed, which promoted an increased accumulation of the identified flavonoids and coumarins in giant pumpkins. In addition, the construction of a co-expression network and cis-element analysis of the promoter demonstrated that differentially expressed MYB, bHLH, AP2, and WRKY transcription factors might play vital roles in regulating the expression of DEGs involved in the biosynthesis of several flavonoids and coumarins. Our current results provide new insights into the accumulation of active compounds in giant pumpkins.PMID:37395666 | DOI:10.1021/acs.jafc.3c01883

Nucleic Acids Res. 2023 Jul 3:gkad565. doi: 10.1093/nar/gkad565. Online ahead of print.ABSTRACT5-Methyluridine (m5U) is one of the most abundant RNA modifications found in cytosolic tRNA. tRNA methyltransferase 2 homolog A (hTRMT2A) is the dedicated mammalian enzyme for m5U formation at tRNA position 54. However, its RNA binding specificity and functional role in the cell are not well understood. Here we dissected structural and sequence requirements for binding and methylation of its RNA targets. Specificity of tRNA modification by hTRMT2A is achieved by a combination of modest binding preference and presence of a uridine in position 54 of tRNAs. Mutational analysis together with cross-linking experiments identified a large hTRMT2A-tRNA binding surface. Furthermore, complementing hTRMT2A interactome studies revealed that hTRMT2A interacts with proteins involved in RNA biogenesis. Finally, we addressed the question of the importance of hTRMT2A function by showing that its knockdown reduces translation fidelity. These findings extend the role of hTRMT2A beyond tRNA modification towards a role in translation.PMID:37395448 | DOI:10.1093/nar/gkad565

Plant Cell Environ. 2023 Jul 2. doi: 10.1111/pce.14659. Online ahead of print.ABSTRACTDespite its small size, the water fern Azolla is a giant among plant symbioses. Within each of its leaflets, a specialized leaf cavity is home to a population of nitrogen-fixing cyanobacteria (cyanobionts). Although a number of plant-cyanobiont symbioses exist, Azolla is unique in that its symbiosis is perpetual: the cyanobionts are inherited during sexual and vegetative propagation. What underpins the communication between the two partners? In angiosperms, the phytohormone salicylic acid (SA) is a well-known regulator of plant-microbe interactions. Using high-performance liquid chromatography-tandem mass spectrometry, we pinpoint the presence of SA in the fern. Comparative genomics and phylogenetics on SA biosynthesis genes across Chloroplastida reveal that the entire Phenylalanine ammonia-lyase-dependent pathway likely existed in the last common ancestor of land plants. Indeed, Azolla filiculoides secondarily lost its isochorismate synthase but has the genetic competence to derive SA from benzoic acid; the presence of SA in artificially cyanobiont-free Azolla supports the existence of this route. Global gene expression data and SA levels from cyanobiont-containing and -free A. filiculoides link SA synthesis with the symbioses: SA appears to induce cyanobacterial proliferation, whereas removal of the symbiont results in reduced SA levels in a nitrogen-dependent manner.PMID:37394786 | DOI:10.1111/pce.14659

Environ Sci Technol. 2023 Jul 2. doi: 10.1021/acs.est.3c00663. Online ahead of print.ABSTRACTThe challenge of chemical exposomics in human plasma is the 1000-fold concentration gap between endogenous substances and environmental pollutants. Phospholipids are the major endogenous small molecules in plasma, thus we validated a chemical exposomics protocol with an optimized phospholipid-removal step prior to targeted and non-targeted liquid chromatography high-resolution mass spectrometry. Increased injection volume with negligible matrix effect permitted sensitive multiclass targeted analysis of 77 priority analytes; median MLOQ = 0.05 ng/mL for 200 μL plasma. In non-targeted acquisition, mean total signal intensities of non-phospholipids were enhanced 6-fold in positive (max 28-fold) and 4-fold in negative mode (max 58-fold) compared to a control method without phospholipid removal. Moreover, 109 and 28% more non-phospholipid molecular features were detected by exposomics in positive and negative mode, respectively, allowing new substances to be annotated that were non-detectable without phospholipid removal. In individual adult plasma (100 μL, n = 34), 28 analytes were detected and quantified among 10 chemical classes, and quantitation of per- and polyfluoroalkyl substances (PFAS) was externally validated by independent targeted analysis. Retrospective discovery and semi-quantification of PFAS-precursors was demonstrated, and widespread fenuron exposure is reported in plasma for the first time. The new exposomics method is complementary to metabolomics protocols, relies on open science resources, and can be scaled to support large studies of the exposome.PMID:37394749 | DOI:10.1021/acs.est.3c00663

New Phytol. 2023 Jul 2. doi: 10.1111/nph.19096. Online ahead of print.ABSTRACTMembers of the R2R3-MYB transcription factor subgroup 19 (SG19) have been extensively studied in multiple plant species using different silenced or mutated lines. Some studies have proposed a function in flower opening, others in floral organ development/maturation, or specialized metabolism production. While SG19 members are clearly key players during flower development and maturation, the resulting picture is complex, confusing our understanding in how SG19 genes function. To clarify the function of the SG19 transcription factors, we used a single system, Petunia axillaris, and targeted its two SG19 members (EOB1 and EOB2) by CRISPR-Cas9. Although EOB1 and EOB2 are highly similar, they display radically different mutant phenotypes. EOB1 has a specific role in scent emission while EOB2 has pleiotropic functions during flower development. The eob2 knockout mutants reveal that EOB2 is a repressor of flower bud senescence by inhibiting ethylene production. Moreover, partial loss-of-function mutants (transcriptional activation domain missing) show that EOB2 is also involved in both petal and pistil maturation through regulation of primary and secondary metabolism. Here, we provide new insights into the genetic regulation of flower maturation and senescence. It also emphasizes the function of EOB2 in the adaptation of plants to specific guilds of pollinators.PMID:37394728 | DOI:10.1111/nph.19096

Nihon Yakurigaku Zasshi. 2023;158(4):319-325. doi: 10.1254/fpj.22133.ABSTRACTDiabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Specific remedies are needed for preventing Type 2 diabetes which causes significant changes in an array of plasma metabolites. By untargeted metabolome analysis, phenyl sulfate (PS) increased with the progression of diabetes. In experimental diabetes models, PS administration induces albuminuria and podocyte damage due to the mitochondrial dysfunction. By clinical diabetic kidney disease (DKD) cohort analysis, it was also confirmed that the PS levels significantly correlate with basal and predicted 2-year progression of albuminuria. Phenol is synthesized from dietary tyrosine by gut bacterial-specific tyrosine phenol-lyase (TPL), and absorbed phenol is metabolized into PS in the liver. Inhibition of TPL reduces not only the circulating PS level but also albuminuria in diabetic mice. TPL inhibitor did not significantly alter the major composition, showing the non-lethal inhibition of microbial-specific enzymes has a therapeutic advantage, with lower selective pressure for the development of drug resistance. Clinically, 362 patients in a multi-center clinical study in diabetic nephropathy cohort (U-CARE) were analyzed with full data. The basal plasma PS level significantly correlated with ACR, eGFR, age, duration, HbA1c and uric acid, but not with suPAR. Multiple regression analysis revealed that ACR was the only factor that significantly correlated with PS. By stratified logistic regression analysis, in the microalbuminuria group, PS was the only factor related to the amount of change in the 2-year ACR in all models. PS is not only an early diagnosis marker, but also a modifiable cause and therefore a target for the treatment of DKD. Reduction of microbiota-derived phenol by the inhibitor should represent another aspect for developing drugs of DKD prevention.PMID:37394553 | DOI:10.1254/fpj.22133

Environ Res. 2023 Jun 30:116512. doi: 10.1016/j.envres.2023.116512. Online ahead of print.ABSTRACTAnthropogenic activities are regarded as point sources of pollution entering freshwater bodies worldwide. With over 350,000 chemicals used in manufacturing, wastewater treatment and industrial effluents are comprised of complex mixtures of organic and inorganic pollutants of known and unknown origins. Consequently, their combined toxicity and mode of action are not well understood in aquatic organisms such as Daphnia magna. In this study, effluent samples from wastewater treatment and industrial sectors were used to examine molecular-level perturbations to the polar metabolic profile of D. magna. To determine if the industrial sector and/or the effluent chemistries played a role in the observed biochemical responses, Daphnia were acutely (48 h) exposed to undiluted (100%) and diluted (10, 25, and 50%) effluent samples. Endogenous metabolites were extracted from single daphnids and analyzed using targeted mass spectrometry-based metabolomics. The metabolic profile of Daphnia exposed to effluent samples resulted in significant separation compared to the unexposed controls. Linear regression analysis determined that no single pollutant detected in the effluents was significantly correlated with the responses of metabolites. Significant perturbations were uncovered across many classes of metabolites (amino acids, nucleosides, nucleotides, polyamines, and their derivatives) which serve as intermediates in keystone biochemical processes. The combined metabolic responses are consistent with oxidative stress, disruptions to energy metabolism, and protein dysregulation which were identified through biochemical pathway analysis. These results provide insight into the molecular processes driving stress responses in D. magna. Overall, we determined that the metabolic profile of Daphnia could not be predicted by the chemical composition of environmentally relevant mixtures. The findings of this study demonstrate the advantage of metabolomics in conjunction with chemical analyses to assess the interactions of industrial effluents. This work further demonstrates the ability of environmental metabolomics to characterize molecular-level perturbations in aquatic organisms exposed to complex chemical mixtures directly.PMID:37394164 | DOI:10.1016/j.envres.2023.116512

J Nutr. 2023 Jun 30:S0022-3166(23)72472-3. doi: 10.1016/j.tjnut.2023.06.039. Online ahead of print.ABSTRACTBACKGROUND: The consumption of poor-quality protein increases the risk of essential amino acid (EAA) deficiency, particularly for lysine and threonine. Thus, it is necessary to be able to detect easily EAA deficiency.OBJECTIVE: The purpose of this study was to develop metabolomic approaches to identify specific biomarkers for an EAA deficiency, such as lysine and threonine.METHODS: Three experiments were performed on growing rats. In Experiment 1, rats were fed for 3 weeks with lysine (L30), or threonine (T53) deficient gluten diets, or non-deficient gluten diet (LT100) in comparison with the control diet (milk protein, PLT). In Experiments 2a and 2b, rats were fed at different levels of lysine (L) or threonine (T) deficiency: L/T15, L/T25, L/T40, L/T60, L/T75, P20, L/T100 and L/T170. 24h urines and blood samples from portal vein and vena cava were analyzed using LC-MS. Data from Experiment 1 were analyzed by untargeted metabolomic and Independent Component - Discriminant Analysis (IC-DA) and data from Experiments 2a and 2b by targeted metabolomic and a quantitative PLS regression model. Each metabolite identified as significant by PLS or ICDA was then tested by one-way ANOVA to evaluate the diet effect. Two phases linear regression analysis was used to determine lysine and threonine requirements.RESULTS: ICDA and PLS found molecules that discriminated between the different diets. A common metabolite, the pipecolate, was identified in Experiments 1 and 2a, confirming that it could be specific to lysine deficiency. Another metabolite, taurine, was found in Experiments 1 and 2b, so probably specific to threonine deficiency. Pipecolate or taurine breakpoints obtained gives a value closed to the values obtained by growth indicators.CONCLUSION: Our results showed that the EAA deficiencies influenced the metabolome. Specific urinary biomarkers identified could be easily applied to detect EAA deficiency and to determine which AA is deficient.PMID:37394117 | DOI:10.1016/j.tjnut.2023.06.039

Phytochem Anal. 2023 Jul 2. doi: 10.1002/pca.3258. Online ahead of print.ABSTRACTINTRODUCTION: Selection of marker compounds for targeted chemical analysis is complicated when considering varying instrumentation and closely related plant species. High-resolution gas chromatography-mass spectrometry (GC-MS), via orbitrap detection, has yet to be evaluated for improved marker compound selection.OBJECTIVE: This study directly compares high- and low-resolution GC-MS for botanical maker compound selection using Ocimum tenuiflorum L. (OT) and Ocimum gratissimum L. (OG) for botanical ingredient authentication.METHODS: The essential oils of OT and OG were collected via hydrodistillation before untargeted chemical analysis with gas chromatography coupled to single-quadrupole (GC-SQ) and orbitrap (GC-Orbitrap) detectors. The Global Natural Products Social Molecular Networking (GNPS) software was used for compound annotation, and a manual search was used to find the 41 most common Ocimum essential oil metabolites.RESULTS: The GC-Orbitrap resulted in 1.7-fold more metabolite detection and increased dynamic range compared to the GC-SQ. Spectral matching and manual searching were improved with GC-Orbitrap data. Each instrument had differing known compound concentrations; however, there was an overlap of six compounds with higher abundance in OG than OT and three compounds with a higher abundance in OT than OG, suggesting consistent detection of the most variable compounds. An unsupervised principal component analysis (PCA) could not discern the two species with either dataset.CONCLUSION: GC-Orbitrap instrumentation improves compound detection, dynamic range, and feature annotation in essential oil analysis. However, considering both high- and low-resolution data may improve reliable marker compound selection, as GC-Orbitrap analysis alone did not improve unsupervised separation of two Ocimum species compared to GC-SQ data.PMID:37393908 | DOI:10.1002/pca.3258

Plant Physiol Biochem. 2023 Jun 17;201:107849. doi: 10.1016/j.plaphy.2023.107849. Online ahead of print.ABSTRACTDrought is one of the major consequences of climate change and a serious threat to rice production. Drought stress activates interactions among genes, proteins and metabolites at the molecular level. A comparative multi-omics analysis of drought-tolerant and drought-sensitive rice cultivars can decipher the molecular mechanisms involved in drought tolerance/response. Here, we characterized the global-level transcriptome, proteome, and metabolome profiles, and performed integrated analyses thereof in a drought-sensitive (IR64) and a drought-tolerant (Nagina 22) rice cultivar under control and drought-stress conditions. The transcriptional dynamics and its integration with proteome analysis revealed the role of transporters in regulation of drought stress. The proteome response illustrated the contribution of translational machinery to drought tolerance in N22. The metabolite profiling revealed that aromatic amino acids and soluble sugars contribute majorly to drought tolerance in rice. The integrated transcriptome, proteome and metabolome analysis performed using statistical and knowledge-based methods revealed the preference for auxiliary carbohydrate metabolism through glycolysis and pentose phosphate pathway contributed to drought tolerance in N22. In addition, L-phenylalanine and the genes/proteins responsible for its biosynthesis were also found to contribute to drought tolerance in N22. In conclusion, our study provided mechanistic insights into the drought response/adaptation mechanism and is expected to facilitate engineering of drought tolerance in rice.PMID:37393858 | DOI:10.1016/j.plaphy.2023.107849

Phytomedicine. 2023 Jun 20;118:154937. doi: 10.1016/j.phymed.2023.154937. Online ahead of print.ABSTRACTBACKGROUND: Polygala japonica Houtt. (PJ) has been demonstrated with several biological potentials such as lipid-lowering and anti-inflammatory effects. However, the effects and mechanisms of PJ on nonalcoholic steatohepatitis (NASH) remain unclear.PURPOSE: The aim of this study was to evaluate the effects of PJ on NASH and illustrate the mechanism based on modulating gut microbiota and host metabolism.MATERIALS AND METHODS: NASH mouse model was induced using methionine and choline deficient (MCD) diet and orally treated with PJ. The therapeutic, anti-inflammatory, and anti-oxidative effects of PJ on mice with NASH were firstly assessed. Then, the gut microbiota of mice was analyzed using 16S rRNA sequencing to assess the changes. Finally, the effects of PJ on the metabolites in liver and feces were explored by untargeted metabolomics.RESULTS: The results indicated that PJ could improve hepatic steatosis, liver injury, inflammatory response, and oxidative stress in NASH mice. PJ treatment also affected the diversity of gut microbiota and changed the relative abundances of Faecalibaculum. Lactobacillus, Muribaculaceae, Dubosiella, Akkermansia, Lachnospiraceae_NK4A136_group, and Turicibacter in NASH mice. In addition, PJ treatment modulated 59 metabolites both in liver and feces. Metabolites involved in histidine, and tryptophan metabolism pathways were identified as the key metabolites according to the correlation analysis between differential gut microbiota and metabolites.CONCLUSION: Our study demonstrated the therapeutic, anti-inflammatory and anti-oxidative potentials of PJ on NASH. The mechanisms of PJ treatment were related to the improvement of gut microbiota dysbiosis and the regulation of histidine and tryptophan metabolism.PMID:37393831 | DOI:10.1016/j.phymed.2023.154937

Talanta. 2023 Jun 21;265:124859. doi: 10.1016/j.talanta.2023.124859. Online ahead of print.ABSTRACTAmino acids (AAs) are a class of important metabolites in metabolomics methodology that investigates metabolite changes in a cell, tissue, or organism for early diagnosis of diseases. Benzo[a]pyrene (BaP) is considered a priority contaminant by different environmental control agencies because it is a proven carcinogenic compound for humans. Therefore, it is important to evaluate the BaP interference in the metabolism of amino acids. In this work, a new amino acid extraction procedure (derivatized with propyl chloroformate/propanol) using functionalized magnetic carbon nanotubes was developed and optimized. A hybrid nanotube was used followed by desorption without heating, and excellent extraction of analytes was obtained. After exposure of Saccharomyces cerevisiae, the BaP concentration of 25.0 μmol L-1 caused changes in cell viability, indicating metabolic changes. A fast and efficient GC/MS method using a Phenomenex ZB-AAA column was optimized, enabling the determination of 16 AAs in yeasts exposed or not to BaP. A comparison of AA concentrations obtained in the two experimental groups showed that glycine (Gly), serine (Ser), phenylalanine (Phe), proline (Pro), asparagine (Asn), aspartic acid (Asp), glutamic acid (Glu), tyrosine (Tyr), and leucine (Leu) statistically differentiated, after subsequent application of ANOVA with Bonferroni post-hoc test, with a confidence level of 95%. This amino acid pathway analysis confirmed previous studies that revealed the potential of these AAs as toxicity biomarker candidates.PMID:37393711 | DOI:10.1016/j.talanta.2023.124859

Curr Opin Chem Biol. 2023 Jun 30;76:102360. doi: 10.1016/j.cbpa.2023.102360. Online ahead of print.ABSTRACTMetabolomics, the global profiling of small molecules in the body, has emerged as a promising analytical approach for assessing molecular changes associated with ageing at the population level. Understanding root metabolic ageing pathways may have important implications for managing age-related disease risk. In this short review, relevant studies published in the last few years that have made valuable contributions to this field will be discussed. These include large-scale studies investigating metabolic changes with age, metabolomic clocks, and metabolic pathways associated with ageing phenotypes. Recent significant advances include the use of longitudinal study designs, populations spanning the whole life course, standardised analytical platforms of enhanced metabolome coverage and development of multivariate analyses. While many challenges remain, recent studies have demonstrated the considerable promise of this field.PMID:37393706 | DOI:10.1016/j.cbpa.2023.102360

BMC Complement Med Ther. 2023 Jul 1;23(1):217. doi: 10.1186/s12906-023-04048-y.ABSTRACTBACKGROUND: Dendrobium nobile and Dendrobium chrysotoxum are important species of the genus Dendrobium and have great economic and medicinal value. However, the medicinal properties of these two plants remain poorly understood. This study aimed to investigate the medical properties of D. nobile and D. chrysotoxum by conducting a comprehensive chemical profiling of the two plants. Additionally, active compounds and predictive targets for anti-hepatoma activity in D. chrysotoxum extracts were identified using Network Pharmacology.RESULTS: Chemical profiling showed that altogether 65 phytochemicals were identified from D. nobile and D. chrysotoxum, with major classes as alkaloids, terpenoids, flavonoids, bibenzyls and phenanthrenes. About 18 compounds were identified as the important differential metabolites in D. nobile and D. chrysotoxum. Furtherly, CCK-8 results showed that the extracts of stems and leaves of D. nobile and D. chrysotoxum could inhibit the growth of Huh-7 cells, and the anti-hepatoma activity of extracts were dose-dependent. Among the extracts, the extract of D. chrysotoxum showed significant anti-hepatoma activity. In order to find the potential mechanism of anti-hepatoma activity of D. chrysotoxum, five key compounds and nine key targets were obtained through constructing and analyzing the compound-target-pathway network. The five key compounds were chrysotobibenzyl, chrysotoxin, moscatilin, gigantol and chrysotoxene. Nine key targets, including GAPDH, EGFR, ESR1, HRAS, SRC, CCND1, HIF1A, ERBB2 and MTOR, could be considered as the core targets of the anti-hepatoma activity of D. chrysotoxum.CONCLUSIONS: In this study, the chemical composition difference and anti-hepatoma activity of stems and leaves of D. nobile and D. chrysotoxum were compared, and the potential anti-hepatoma mechanism of D. chrysotoxum was revealed in a multi-target and multi-pathway manner.PMID:37393306 | DOI:10.1186/s12906-023-04048-y

Diabetol Metab Syndr. 2023 Jul 1;15(1):146. doi: 10.1186/s13098-023-01124-8.ABSTRACTINTRODUCTION: Metabolomic signatures of type 2 diabetes mellitus (T2DM) in Tibetan Chinese population, a group with high diabetes burden, remain largely unclear. Identifying the serum metabolite profile of Tibetan T2DM (T-T2DM) individuals may provide novel insights into early T2DM diagnosis and intervention.METHODS: Hence, we conducted untargeted metabolomics analysis of plasma samples from a retrospective cohort study with 100 healthy controls and 100 T-T2DM patients by using liquid chromatography-mass spectrometry.RESULTS: The T-T2DM group had significant metabolic alterations that are distinct from known diabetes risk indicators, such as body mass index, fasting plasma glucose, and glycosylated hemoglobin levels. The optimal metabolite panels for predicting T-T2DM were selected using a tenfold cross-validation random forest classification model. Compared with the clinical features, the metabolite prediction model provided a better predictive value. We also analyzed the correlation of metabolites with clinical indices and found 10 metabolites that were independently predictive of T-T2DM.CONCLUSION: By using the metabolites identified in this study, we may provide stable and accurate biomarkers for early T-T2DM warning and diagnosis. Our study also provides a rich and open-access data resource for optimizing T-T2DM management.PMID:37393287 | DOI:10.1186/s13098-023-01124-8

Aging (Albany NY). 2023 Jul 1;undefined. doi: 10.18632/aging.204880. Online ahead of print.NO ABSTRACTPMID:37393106 | DOI:10.18632/aging.204880

J Ethnopharmacol. 2023 Jun 29:116871. doi: 10.1016/j.jep.2023.116871. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: In traditional medicine, both Scutellaria baicalensis Georgi (SBG) and the traditional formulas composed of it have been used to treat a wide range of diseases, including cancer and cardiovascular. Wogonoside (Wog) is the biologically active flavonoid compound extracted from the root of SBG, with potential cardiovascular protective effects. However, the mechanisms underlying the protective effect of Wog on acute myocardial ischemia (AMI) have not yet been clearly elucidated.AIM OF THE STUDY: To explore the protective mechanism of Wog on AMI rats by comprehensively integrating traditional pharmacodynamics, metabolomics, and network pharmacology.METHODS: The rat was pretreatment with Wog at a dose of 20 mg/kg/d and 40 mg/kg/d once daily for 10 days and then ligated the left anterior descending coronary artery of rats to establish the AMI rat model. Electrocardiogram (ECG), cardiac enzyme levels, heart weight index (HWI), Triphenyltetrazolium chloride (TTC) staining, and histopathological analyses were adopted to evaluate the protective effect of Wog on AMI rats. Moreover, a serum metabolomic-based UHPLC-Q-Orbitrap MS approach was performed to find metabolic biomarkers and metabolic pathways, and network pharmacology analysis was applied to predict targets and pathways of Wog in treating AMI. Finally, the network pharmacology and metabolomic results were integrated to elucidate the mechanism of Wog in treating AMI. Finally, RT- PCR was used to detect the mRNA expression levels of PTGS1, PTGS2, ALOX5, and ALOX15 to validate the result of integrated metabolomics and network analysis.RESULTS: Pharmacodynamic studies suggest that Wog could effectively prevent the ST-segment of electrocardiogram elevation, reduce the myocardial infarct size, heart weight index, and cardiac enzyme levels, and alleviate cardiac histological damage in AMI rats. Metabolomics analysis showed that the disturbances of metabolic profile in AMI rats were partly corrected by Wog and the cardio-protection effects on AMI rats involved 32 differential metabolic biomarkers and 4 metabolic pathways. In addition, the integrated analysis of network pharmacology and metabolomics showed that 7 metabolic biomarkers, 6 targets, and 6 crucial pathways were the main mechanism for the therapeutic application of Wog for AMI. Moreover, the results of RT-PCR showed that PTGS1, PTGS2, ALOX5, and ALOX15 mRNA expression levels were reduced after treatment with Wog.CONCLUSION: Wog exerts cardio-protection effects on AMI rats via the regulation of multiple metabolic biomarkers, multiple targets, and multiple pathways, our current study will provide strong scientific evidence supporting the therapeutic application of Wog for AMI.PMID:37393028 | DOI:10.1016/j.jep.2023.116871