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1.
Food Res Int ; 188: 114476, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823866

ABSTRACT

Kimchi cabbage, the key ingredient in kimchi, is cultivated year-round to meet high production demands. This study aimed to examine the effects of seasonal harvesting (spring, summer, fall, and winter) on the microbial and metabolic profiles of kimchi during 30 days of fermentation. Lactic acid bacteria distribution is notably influenced by seasonal variations, with Latilactobacillus dominant in fall-harvested kimchi group and Weissella prevailing in spring, summer, and winter. The microbial communities of spring and fall group exhibited similar profiles before fermentation, whereas the microbial communities and metabolic profiles of spring and summer group were similar after 30 days of fermentation. Seasonal disparities in metabolite concentrations, including glutamic acid, serine, and cytosine, persist throughout fermentation. This study provides a comprehensive understanding of the substantial impact of seasonal harvesting of kimchi cabbage on the microbial and metabolic characteristics of kimchi, providing valuable insights into producing kimchi with diverse qualities.


Subject(s)
Brassica , Fermentation , Fermented Foods , Food Microbiology , Seasons , Brassica/microbiology , Brassica/metabolism , Fermented Foods/microbiology , Fermented Foods/analysis , Metabolome , Microbiota , Weissella/metabolism
2.
BMC Genomics ; 25(1): 547, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824590

ABSTRACT

BACKGROUND: Environmental temperature is critical in regulating biological functions in fish. S. prenanti is a kind of cold-water fish, but of which we have little knowledge about the metabolic adaptation and physiological responses to long-term cold acclimation. RESULTS: In this study, we determined the physiological responses of S. prenanti serum after 30 days of exposure to 6℃. Compared with the control group, the levels of TC, TG, and LDL-C in the serum were significantly (P < 0.05) increased, and the level of glucose was significantly (P < 0.05) decreased under cold acclimation. Cold acclimation had no effect on the gene expression of pro-inflammatory factors and anti-inflammatory factors of S. prenanti. Metabolomics analysis by LC-MS showed that a total of 60 differential expressed metabolites were identified after cold acclimation, which involved in biosynthesis of amino acids, biosynthesis of unsaturated fatty acids, steroid degradation, purine metabolism, and citrate cycle pathways. CONCLUSION: The results indicate that cold acclimation can alter serum metabolites and metabolic pathways to alter energy metabolism and provide insights for the physiological regulation of cold-water fish in response to cold acclimation.


Subject(s)
Acclimatization , Cold Temperature , Cyprinidae , Metabolome , Metabolomics , Animals , Cyprinidae/metabolism , Cyprinidae/physiology , Cyprinidae/blood , Cyprinidae/genetics
3.
PeerJ ; 12: e17466, 2024.
Article in English | MEDLINE | ID: mdl-38827284

ABSTRACT

Background: Tomato (Solanum lycopersicum) is an annual or perennial herb that occupies an important position in daily agricultural production. It is an essential food crop for humans and its ripening process is regulated by a number of genes. S-adenosyl-l-homocysteine hydrolase (AdoHcyase, EC 3.3.1.1) is widespread in organisms and plays an important role in regulating biological methylation reactions. Previous studies have revealed that transgenic tomato that over-express SlSAHH2 ripen earlier than the wild-type (WT). However, the differences in metabolites and the mechanisms driving how these differences affect the ripening cycle are unclear. Objective: To investigate the effects of SlSAHH2 on metabolites in over-expressed tomato and WT tomato. Methods: SlSAHH2 over-expressed tomato fruit (OE-5# and OE-6#) and WT tomato fruit at the breaker stage (Br) were selected for non-targeted metabolome analysis. Results: A total of 733 metabolites were identified by mass spectrometry using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the Human Metabolome database (HMDB). The metabolites were divided into 12 categories based on the superclass results and a comparison with the HMDB. The differences between the two databases were analyzed by PLS-DA. Based on a variable important in projection value >1 and P < 0.05, 103 differential metabolites were found between tomato variety OE-5# and WT and 63 differential metabolites were found between OE-6# and WT. These included dehydrotomatine, L-serine, and gallic acid amongst others. Many metabolites are associated with fruit ripening and eight common metabolites were found between the OE-5# vs. WT and OE-6# vs. WT comparison groups. The low L-tryptophan expression in OE-5# and OE-6# is consistent with previous reports that its content decreases with fruit ripening. A KEGG pathway enrichment analysis of the significantly different metabolites revealed that in the OE-5# and WT groups, up-regulated metabolites were enriched in 23 metabolic pathways and down-regulated metabolites were enriched in 11 metabolic pathways. In the OE-6# and WT groups, up-regulated metabolites were enriched in 29 pathways and down-regulated metabolites were enriched in six metabolic pathways. In addition, the differential metabolite changes in the L-serine to flavonoid transformation metabolic pathway also provide evidence that there is a phenotypic explanation for the changes in transgenic tomato. Discussion: The metabolomic mechanism controlling SlSAHH2 promotion of tomato fruit ripening has been further elucidated.


Subject(s)
Fruit , Solanum lycopersicum , Solanum lycopersicum/metabolism , Solanum lycopersicum/genetics , Fruit/metabolism , Fruit/genetics , Plants, Genetically Modified/genetics , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Adenosylhomocysteinase/metabolism , Adenosylhomocysteinase/genetics , Metabolome , Metabolomics
4.
Anal Chim Acta ; 1312: 342758, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38834268

ABSTRACT

BACKGROUND: The selection of the sample treatment strategy is a crucial step in the metabolomics workflow. Solid phase microextraction (SPME) is a sample processing methodology with great potential for use in untargeted metabolomics of tissue samples. However, its utilization is not as widespread as other standard protocols involving steps of tissue collection, metabolism quenching, homogenization, and extraction of metabolites by solvents. Since SPME allows us to perform all these steps in one action in tissue samples, in addition to other advantages, it is necessary to know whether this methodology produces similar or comparable metabolome and lipidome coverage and performance to classical methods. RESULTS: SPME and homogenization with solid-liquid extraction (Homo-SLE) sample treatment methods were applied to healthy murine kidney tissue, followed by comprehensive metabolomics and lipidomics analyses. In addition, it has been tested whether freezing and storage of the tissue causes alterations in the renal metabolome and lipidome, so the analyses were performed on fresh and frozen tissue samples Lipidomics analysis revealed the exclusive presence of different structural membrane and intracellular lipids in the Homo-SLE group. Conversely, all annotated metabolites were detected in both groups. Notably, the freezing of the sample mainly causes a decrease in the levels of most lipid species and an increase in metabolites such as amino acids, purines, and pyrimidines. These alterations are principally detected in a statistically significant way by SPME methodology. Finally, the samples of both methodologies show a positive correlation in all the analyses. SIGNIFICANCE: These results demonstrate that in SPME processing, as long as the fundamentals of non-exhaustive extraction in a pre-equilibrium kinetic regime, extraction in a tissue localized area, the chemistry of the fiber coating and non-homogenization of the tissue are taken into account, is an excellent method to use in kidney tissue metabolomics; since this methodology presents an easy-to-use, efficient, and less invasive approach that simplifies the different sample processing steps.


Subject(s)
Kidney , Metabolomics , Solid Phase Microextraction , Solid Phase Microextraction/methods , Animals , Metabolomics/methods , Kidney/metabolism , Kidney/chemistry , Mice , Liquid-Liquid Extraction/methods , Metabolome , Male , Mice, Inbred C57BL
5.
BMC Plant Biol ; 24(1): 489, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38825671

ABSTRACT

BACKGROUND: The Fructus Ligustri Lucidi, the fruit of Ligustrum lucidum, contains a variety of bioactive compounds, such as flavonoids, triterpenoids, and secoiridoids. The proportions of these compounds vary greatly during the different fruit development periods of Fructus Ligustri Lucidi. However, a clear understanding of how the proportions of the compounds and their regulatory biosynthetic mechanisms change across the different fruit development periods of Fructus Ligustri Lucidi is still lacking. RESULTS: In this study, metabolite profiling and transcriptome analysis of six fruit development periods (45 DAF, 75 DAF, 112 DAF, 135 DAF, 170 DAF, and 195 DAF) were performed. Seventy compounds were tentatively identified, of which secoiridoids were the most abundant. Eleven identified compounds were quantified by high performance liquid chromatography. A total of 103,058 unigenes were obtained from six periods of Fructus Ligustri Lucidi. Furthermore, candidate genes involved in triterpenoids, phenylethanols, and oleoside-type secoiridoid biosynthesis were identified and analyzed. The in vitro enzyme activities of nine glycosyltransferases involved in salidroside biosynthesis revealed that they can catalyze trysol and hydroxytyrosol to salidroside and hydroxylsalidroside. CONCLUSIONS: These results provide valuable information to clarify the profile and molecular regulatory mechanisms of metabolite biosynthesis, and also in optimizing the harvest time of this fruit.


Subject(s)
Fruit , Ligustrum , Metabolome , Transcriptome , Fruit/genetics , Fruit/metabolism , Fruit/chemistry , Ligustrum/genetics , Ligustrum/metabolism , Ligustrum/chemistry , Gene Expression Profiling , Gene Expression Regulation, Plant
6.
Hepatol Commun ; 8(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38836842

ABSTRACT

BACKGROUND: Patients with pediatric cirrhosis-sepsis (PC-S) attain early mortality. Plasma bacterial composition, the cognate metabolites, and their contribution to the deterioration of patients with PC-S to early mortality are unknown. We aimed to delineate the plasma metaproteome-metabolome landscape and identify molecular indicators capable of segregating patients with PC-S predisposed to early mortality in plasma, and we further validated the selected metabolite panel in paired 1-drop blood samples using untargeted metaproteomics-metabolomics by UHPLC-HRMS followed by validation using machine-learning algorithms. METHODS: We enrolled 160 patients with liver diseases (cirrhosis-sepsis/nonsepsis [n=110] and noncirrhosis [n=50]) and performed untargeted metaproteomics-metabolomics on a training cohort of 110 patients (Cirrhosis-Sepsis/Nonsepsis, n=70 and noncirrhosis, n=40). The candidate predictors were validated on 2 test cohorts-T1 (plasma test cohort) and T2 (1-drop blood test cohort). Both T1 and T2 had 120 patients each, of which 70 were from the training cohort. RESULTS: Increased levels of tryptophan metabolites and Salmonella enterica and Escherichia coli-associated peptides segregated patients with cirrhosis. Increased levels of deoxyribose-1-phosphate, N5-citryl-d-ornithine, and Herbinix hemicellulolytic and Leifsonia xyli segregated patients with PC-S. MMCN-based integration analysis of WMCNA-WMpCNA identified key microbial-metabolic modules linked to PC-S nonsurvivors. Increased Indican, Staphylobillin, glucose-6-phosphate, 2-octenoylcarnitine, palmitic acid, and guanidoacetic acid along with L. xyli, Mycoplasma genitalium, and Hungateiclostridium thermocellum segregated PC-S nonsurvivors and superseded the liver disease severity indices with high accuracy, sensitivity, and specificity for mortality prediction using random forest machine-learning algorithm. CONCLUSIONS: Our study reveals a novel metabolite signature panel capable of segregating patients with PC-S predisposed to early mortality using as low as 1-drop blood.


Subject(s)
Liver Cirrhosis , Metabolomics , Sepsis , Humans , Male , Female , Liver Cirrhosis/blood , Liver Cirrhosis/mortality , Child , Adolescent , Sepsis/blood , Sepsis/mortality , Sepsis/microbiology , Biomarkers/blood , Child, Preschool , Machine Learning , Metabolome , Bacterial Proteins/blood
7.
PLoS One ; 19(6): e0304966, 2024.
Article in English | MEDLINE | ID: mdl-38833442

ABSTRACT

PURPOSE: Out-of-hospital cardiac arrest (OHCA) carries a relatively poor prognosis and requires multimodal prognostication to guide clinical decisions. Identification of previously unrecognized metabolic routes associated with patient outcome may contribute to future biomarker discovery. In OHCA, inhaled xenon elicits neuro- and cardioprotection. However, the metabolic effects remain unknown. MATERIALS AND METHODS: In this post-hoc study of the randomised, 2-group, single-blind, phase 2 Xe-Hypotheca trial, 110 OHCA survivors were randomised 1:1 to receive targeted temperature management (TTM) at 33°C with or without inhaled xenon during 24 h. Blood samples for nuclear magnetic resonance spectroscopy metabolic profiling were drawn upon admission, at 24 and 72 h. RESULTS: At 24 h, increased lactate, adjusted hazard-ratio 2.25, 95% CI [1.53; 3.30], p<0.001, and decreased branched-chain amino acids (BCAA) leucine 0.64 [0.5; 0.82], p = 0.007, and valine 0.37 [0.22; 0.63], p = 0.003, associated with 6-month mortality. At 72 h, increased lactate 2.77 [1.76; 4.36], p<0.001, and alanine 2.43 [1.56; 3.78], p = 0.001, and decreased small HDL cholesterol ester content (S-HDL-CE) 0.36 [0.19; 0.68], p = 0.021, associated with mortality. No difference was observed between xenon and control groups. CONCLUSIONS: In OHCA patients receiving TTM with or without xenon, high lactate and alanine and decreased BCAAs and S-HDL-CE associated with increased mortality. It remains to be established whether current observations on BCAAs, and possibly alanine and lactate, could reflect neural damage via their roles in the metabolism of the neurotransmitter glutamate. Xenon did not significantly alter the measured metabolic profile, a potentially beneficial attribute in the context of compromised ICU patients. TRIAL REGISTRATION: Trial Registry number: ClinicalTrials.gov Identifier: NCT00879892.


Subject(s)
Out-of-Hospital Cardiac Arrest , Xenon , Humans , Out-of-Hospital Cardiac Arrest/mortality , Out-of-Hospital Cardiac Arrest/therapy , Out-of-Hospital Cardiac Arrest/metabolism , Out-of-Hospital Cardiac Arrest/blood , Male , Female , Middle Aged , Aged , Metabolome , Single-Blind Method , Biomarkers/blood , Lactic Acid/blood , Lactic Acid/metabolism , Hypothermia, Induced/methods
8.
Gigascience ; 132024 Jan 02.
Article in English | MEDLINE | ID: mdl-38837944

ABSTRACT

Hepatic steatosis is the initial manifestation of abnormal liver functions and often leads to liver diseases such as nonalcoholic fatty liver disease in humans and fatty liver syndrome in animals. In this study, we conducted a comprehensive analysis of a large chicken population consisting of 705 adult hens by combining host genome resequencing; liver transcriptome, proteome, and metabolome analysis; and microbial 16S ribosomal RNA gene sequencing of each gut segment. The results showed the heritability (h2 = 0.25) and duodenal microbiability (m2 = 0.26) of hepatic steatosis were relatively high, indicating a large effect of host genetics and duodenal microbiota on chicken hepatic steatosis. Individuals with hepatic steatosis had low microbiota diversity and a decreased genetic potential to process triglyceride output from hepatocytes, fatty acid ß-oxidation activity, and resistance to fatty acid peroxidation. Furthermore, we revealed a molecular network linking host genomic variants (GGA6: 5.59-5.69 Mb), hepatic gene/protein expression (PEMT, phosphatidyl-ethanolamine N-methyltransferase), metabolite abundances (folate, S-adenosylmethionine, homocysteine, phosphatidyl-ethanolamine, and phosphatidylcholine), and duodenal microbes (genus Lactobacillus) to hepatic steatosis, which could provide new insights into the regulatory mechanism of fatty liver development.


Subject(s)
Chickens , Fatty Liver , Gastrointestinal Microbiome , Animals , Chickens/microbiology , Gastrointestinal Microbiome/genetics , Fatty Liver/genetics , Fatty Liver/microbiology , Fatty Liver/veterinary , Fatty Liver/metabolism , Liver/metabolism , Liver/microbiology , Transcriptome , Genome , Metabolome , Poultry Diseases/microbiology , Poultry Diseases/genetics
9.
PLoS One ; 19(6): e0304522, 2024.
Article in English | MEDLINE | ID: mdl-38837993

ABSTRACT

BACKGROUND: A subset of individuals (10-20%) experience post-COVID condition (PCC) subsequent to initial SARS-CoV-2 infection, which lacks effective treatment. PCC carries a substantial global burden associated with negative economic and health impacts. This study aims to evaluate the association between plasma taurine levels with self-reported symptoms and adverse clinical outcomes in patients with PCC. METHODS AND FINDINGS: We analyzed the plasma proteome and metabolome of 117 individuals during their acute COVID-19 hospitalization and at the convalescence phase six-month post infection. Findings were compared with 28 age and sex-matched healthy controls. Plasma taurine levels were negatively associated with PCC symptoms and correlated with markers of inflammation, tryptophan metabolism, and gut dysbiosis. Stratifying patients based on the trajectories of plasma taurine levels during six-month follow-up revealed a significant association with adverse clinical events. Increase in taurine levels during the transition to convalescence were associated with a reduction in adverse events independent of comorbidities and acute COVID-19 severity. In a multivariate analysis, increased plasma taurine level between acute and convalescence phase was associated with marked protection from adverse clinical events with a hazard ratio of 0.13 (95% CI: 0.05-0.35; p<0.001). CONCLUSIONS: Taurine emerges as a promising predictive biomarker and potential therapeutic target in PCC. Taurine supplementation has already demonstrated clinical benefits in various diseases and warrants exploration in large-scale clinical trials for alleviating PCC.


Subject(s)
COVID-19 , SARS-CoV-2 , Taurine , Humans , Taurine/blood , COVID-19/blood , COVID-19/complications , Female , Male , Middle Aged , SARS-CoV-2/isolation & purification , Adult , Biomarkers/blood , Aged , Post-Acute COVID-19 Syndrome , Case-Control Studies , Metabolome , Symptom Burden
10.
Planta Med ; 90(7-08): 512-522, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38843791

ABSTRACT

The use of Drosophila melanogaster as a biological platform to study the effect of diet and food bioactives on the metabolome remains a highly unexplored subject. Aiming to establish alternative solutions for the investigation of nutritional interventions with bioactive natural products by employing LC-MS-based metabolomics approaches, we assessed the effect of a phytonutrient-rich extract from the endemic Mediterranean plant Cichorium spinosum (stamnagkàthi) on a Drosophila population. The extract's modulating effect on the proteostasis network and metabolism of young D. melanogaster flies was evaluated. Furthermore, an untargeted metabolomics approach, employing a C18 UPLC-ESI-Orbitrap-HRMS/MS platform, permitted the detection of several biomarkers in the metabolic profile of Drosophila's tissues; while targeted amino acid quantification in Drosophila tissue was simultaneously performed by employing aTRAQ labeling and an ion-pairing UPLC-ESI-SWATH-HRMS/MS platform. The detected metabolites belong to different chemical classes, and statistical analysis with chemometrics tools was utilized to reveal patterns and trends, as well as to uncover potential class-distinguishing features and possible biomarkers. Our findings suggest that Drosophila can serve as a valuable in vivo model for investigating the role of bioactive phytoconstituents, like those found in C. spinosum's decoction, on diverse metabolic processes. Additionally, the fruit fly represents a highly effective platform to investigate the molecular mechanisms underlying sex differences in diverse aspects of nutrition and physiology in higher metazoans.


Subject(s)
Drosophila melanogaster , Metabolomics , Phytochemicals , Animals , Drosophila melanogaster/drug effects , Phytochemicals/pharmacology , Male , Female , Proteostasis/drug effects , Metabolic Networks and Pathways/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Metabolome/drug effects
11.
Biomed Environ Sci ; 37(5): 479-493, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38843921

ABSTRACT

Objective: To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons (PAHs) during critical brain development and explore their potential link with the intestinal microbiota. Methods: Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs (OH-PAHs) in 36-month-old children. Subsequently, 37 children were categorized into low- and high-exposure groups based on the sum of the ten OH-PAHs. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples. Furthermore, fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results: The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group (variable importance for projection > 1, P < 0.05). Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene, fluorine, and phenanthrene ( r = 0.336-0.531). The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states, including amino acid, lipid, and nucleotide metabolism. Additionally, these distinct metabolites were significantly associated with specific intestinal flora abundances ( r = 0.34-0.55), which were mainly involved in neurodevelopment. Conclusion: Higher PAH exposure in young children affected metabolic homeostasis, particularly that of certain gut microbiota-derived metabolites. Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.


Subject(s)
Gastrointestinal Microbiome , Polycyclic Aromatic Hydrocarbons , Humans , Polycyclic Aromatic Hydrocarbons/metabolism , Polycyclic Aromatic Hydrocarbons/toxicity , Polycyclic Aromatic Hydrocarbons/urine , Male , Child, Preschool , Female , Gastrointestinal Microbiome/drug effects , Environmental Exposure/adverse effects , Environmental Pollutants/toxicity , Environmental Pollutants/metabolism , Metabolomics , Metabolome/drug effects
12.
BMC Plant Biol ; 24(1): 519, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851682

ABSTRACT

Rice seeds of different varieties exhibited distinct metabolic profiles in our study. We analyzed the metabolites in seeds of six rice varieties (CH, HM, NX, YX, HY, and MX) using non-targeted GC-MS. Our findings revealed that amino acids, sugars, and organic acids were predominant in all varieties, with significant differences observed in CH compared to the others. Specifically phenylalanine and glycine content differed notably in NX and YX, respectively. Additionally, 1,5-anhydroglucitol content in NX, and glutamate, aspartate, and lactulose in NX, YX, HM, HY, and MX were up-regulated. Due to the biological functions of these amino acids and sugars, these indicated that compared to CH, rice of NX were more conducive to metabolism of carbohydrate and fat, and healthy growth maintenance in the human body, but mightThese variations suggest that NX rice may be more beneficial for carbohydrate and fat metabolism and overall health maintenance compared to CH. However, it may not be suitable for diabetic patients. YX rice may not be an ideal glycine supplement, rice ofwhile HM, HY, and MX rice could serve as potential lactulose sources. Furthermore, NX and YX rice exhibited higher levels of main storage proteins compared to CH. This study offers valuable insights into the metabolic differences among various rice varieties.


Subject(s)
Gas Chromatography-Mass Spectrometry , Metabolomics , Oryza , Seeds , Oryza/metabolism , Seeds/metabolism , Seeds/chemistry , Metabolomics/methods , Amino Acids/metabolism , Amino Acids/analysis , Metabolome
13.
Drug Des Devel Ther ; 18: 1981-1996, 2024.
Article in English | MEDLINE | ID: mdl-38855535

ABSTRACT

Background: Polygonum capitatum Buch.-Ham. ex D. Don (P. capitatum), a traditional herb used in Miao medicine, is renowned for its heart-clearing properties. Davidiin, the primary bioactive component (approximately 1%), has been used to treat various conditions, including diabetes. Given its wide range of effects and the diverse biomolecular pathways involved in diabetes, there is a crucial need to study how davidiin interacts with these pathways to better understand its anti-diabetic properties. Materials and Methods: Diabetic rats were induced using a high-fat diet and streptozotocin (STZ) administered intraperitoneally at 35 mg/kg. Out of these, 24 rats with blood glucose levels ≥ 11.1 mmol/L and fasting blood glucose levels ≥ 7.0 mmol/L were selected for three experimental groups. These groups were then treated with either metformin (gavage, 140 mg/kg) or davidiin (gavage, 90 mg/kg) for four weeks. After the treatment period, we measured body weight, blood glucose levels, and conducted untargeted metabolic profiling using UPLC-QTOF-MS. Results: Davidiin has been shown to effectively treat diabetes by reducing blood glucose levels from 30.2 ± 2.6 mmol/L to 25.1 ± 2.4 mmol/L (P < 0.05). This effect appears stronger than that of metformin, which lowered glucose levels to 26.5 ± 2.6 mmol/L. The primary outcomes of serum metabolomics are significant changes in lipid and lipid-like molecular profiles. Firstly, davidiin may affect phosphatide metabolism by increasing levels of phosphatidylinositol and sphingosine-1-phosphate. Secondly, davidiin could influence cholesterol metabolism by reducing levels of glycocholic acid and glycochenodeoxycholic acid. Lastly, davidiin might impact steroid hormone metabolism by increasing hepoxilin B3 levels and decreasing prostaglandins. Conclusion: Our study demonstrates that davidiin modulates various lipid-related metabolic pathways to exert its anti-diabetic effects. These findings offer the first detailed metabolic profile of davidiin's action mechanism, contributing valuable insights to the field of Traditional Chinese Medicine in the context of diabetes treatment.


Subject(s)
Diabetes Mellitus, Experimental , Hypoglycemic Agents , Metabolome , Rats, Sprague-Dawley , Streptozocin , Animals , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/metabolism , Rats , Hypoglycemic Agents/pharmacology , Male , Metabolome/drug effects , Blood Glucose/drug effects , Blood Glucose/metabolism , Diet, High-Fat , Drugs, Chinese Herbal/pharmacology
14.
FASEB J ; 38(11): e23738, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38855924

ABSTRACT

Maternal nutrition contributes to gene-environment interactions that influence susceptibility to common congenital anomalies such as neural tube defects (NTDs). Supplemental myo-inositol (MI) can prevent NTDs in some mouse models and shows potential for prevention of human NTDs. We investigated effects of maternal MI intake on embryonic MI status and metabolism in curly tail mice, which are genetically predisposed to NTDs that are inositol-responsive but folic acid resistant. Dietary MI deficiency caused diminished MI in maternal plasma and embryos, showing that de novo synthesis is insufficient to maintain MI levels in either adult or embryonic mice. Under normal maternal dietary conditions, curly tail embryos that developed cranial NTDs had significantly lower MI content than unaffected embryos, revealing an association between diminished MI status and failure of cranial neurulation. Expression of inositol-3-phosphate synthase 1, required for inositol biosynthesis, was less abundant in the cranial neural tube than at other axial levels. Supplemental MI or d-chiro-inositol (DCI) have previously been found to prevent NTDs in curly tail embryos. Here, we investigated the metabolic effects of MI and DCI treatments by mass spectrometry-based metabolome analysis. Among inositol-responsive metabolites, we noted a disproportionate effect on nucleotides, especially purines. We also found altered proportions of 5-methyltetrahydrolate and tetrahydrofolate in MI-treated embryos suggesting altered folate metabolism. Treatment with nucleotides or the one-carbon donor formate has also been found to prevent NTDs in curly tail embryos. Together, these findings suggest that the protective effect of inositol may be mediated through the enhanced supply of nucleotides during neural tube closure.


Subject(s)
Inositol , Neural Tube Defects , Inositol/metabolism , Inositol/pharmacology , Neural Tube Defects/metabolism , Neural Tube Defects/prevention & control , Animals , Female , Mice , Pregnancy , Embryo, Mammalian/metabolism , Maternal Nutritional Physiological Phenomena , Metabolome , Folic Acid/metabolism
15.
PLoS Med ; 21(6): e1004388, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38843150

ABSTRACT

BACKGROUND: Frozen embryo transfer (FET) has become a widely employed assisted reproductive technology technique. There have historically been concerns regarding the long-term metabolic safety of FET technology in offspring due to pregnancy-induced hypertension and large for gestational age, both of which are well-recognized factors for metabolic dysfunction of children. Therefore, we aimed to compare the metabolic profiles of children born after frozen versus fresh embryo transfer at 2 to 5 years of age. METHODS AND FINDINGS: This was a prospective cohort study. Using data from the "Assisted Reproductive Technology borned KIDs (ARTKID)," a birth cohort of offspring born from assisted reproductive technology at the Institute of Women, Children and Reproductive Health, Shandong University, China. We included 4,246 singletons born after FET (n = 2,181) and fresh embryo transfer (n = 2,065) enrolled between 2008 and 2019 and assessed the glucose and lipid variables until the age of 2 to 5 years. During a mean follow-up of 3.6 years, no significant differences were observed in fasting blood glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance Index, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol levels between offspring conceived by fresh and frozen embryo transfer in the crude model and adjusted model (adjusted for parental age, parental body mass index, parental education level, paternal smoking, parity, offspring age and sex). These results remained consistent across subgroup analyses considering offspring age, the stage of embryo transfer, and the mode of fertilization. Results from sensitivity analysis on children matched for age within the cohort remains the same. The main limitation of our study is the young age of the offspring. CONCLUSIONS: In this study, the impact of FET on glucose and lipid profiles during early childhood was comparable to fresh embryo transfer. Long-term studies are needed to evaluate the metabolic health of offspring born after FET.


Subject(s)
Cryopreservation , Embryo Transfer , Humans , Embryo Transfer/methods , Female , Child, Preschool , Male , China/epidemiology , Prospective Studies , Metabolome , Pregnancy , Blood Glucose/metabolism , Adult , Cohort Studies , East Asian People
16.
PLoS One ; 19(6): e0304503, 2024.
Article in English | MEDLINE | ID: mdl-38843246

ABSTRACT

Drought stress is a prominent abiotic factor that adversely influences the growth and development of Bupleurum chinense during its seedling stage, negatively impacting biomass and secondary metabolite production, thus affecting yield and quality. To investigate the molecular mechanism underlying the response of B. chinense seedlings under drought stress, this study employed comprehensive physiological, transcriptomic, and metabolomic analyses. The results revealed that under drought stress, the root soluble sugar and free proline content in B. chinense seedlings significantly increased, while the activities of SOD, POD, and CAT increased in the leaves. These findings indicate the presence of distinct response mechanisms in B. chinense to cope with drought stress. Integrated analysis further identified significant correlations between genes and metabolites related to amino acid biosynthesis in the leaves, as well as genes and metabolites associated with acetaldehyde and dicarboxylic acid metabolism. In the roots, genes and metabolites related to plant hormone signaling and the tricarboxylic acid (TCA) cycle showed significant correlations. These findings provide vital views into the molecular-level response mechanisms of B. chinense under drought stress. Moreover, this study establishes the groundwork for identifying drought-tolerant genes and breeding drought-resistant varieties, which could improve the drought tolerance of medicinal plants and have broader implications for agriculture and crop production in water-scarce areas.


Subject(s)
Bupleurum , Droughts , Gene Expression Regulation, Plant , Metabolomics , Seedlings , Stress, Physiological , Bupleurum/genetics , Bupleurum/metabolism , Seedlings/metabolism , Seedlings/genetics , Stress, Physiological/genetics , Transcriptome , Plant Roots/metabolism , Plant Roots/genetics , Plant Leaves/metabolism , Plant Leaves/genetics , Gene Expression Profiling , Metabolome
17.
Environ Microbiol Rep ; 16(3): e13286, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38844388

ABSTRACT

Microorganisms in the rhizosphere, particularly arbuscular mycorrhiza, have a broad symbiotic relationship with their host plants. One of the major fungi isolated from the rhizosphere of Peucedanum praeruptorum is Penicillium restrictum. The relationship between the metabolites of P. restrictum and the root exudates of P. praeruptorum is being investigated. The accumulation of metabolites in the mycelium and fermentation broth of P. restrictum was analysed over different fermentation periods. Non-targeted metabolomics was used to compare the differences in intracellular and extracellular metabolites over six periods. There were significant differences in the content and types of mycelial metabolites during the incubation. Marmesin, an important intermediate in the biosynthesis of coumarins, was found in the highest amount on the fourth day of incubation. The differential metabolites were screened to obtain 799 intracellular and 468 extracellular differential metabolites. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the highly enriched extracellular metabolic pathways were alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism, and terpenoid backbone biosynthesis. In addition, the enrichment analysis associated with intracellular and extracellular ATP-binding cassette transporter proteins revealed that some ATP-binding cassette transporters may be involved in the transportation of certain amino acids and carbohydrates. Our results provide some theoretical basis for the regulatory mechanisms between the rhizosphere and the host plant and pave the way for the heterologous production of furanocoumarin.


Subject(s)
Fermentation , Mycelium , Penicillium , Rhizosphere , Mycelium/metabolism , Mycelium/growth & development , Penicillium/metabolism , Penicillium/genetics , Plant Roots/microbiology , Metabolome , Metabolomics , Soil Microbiology , Metabolic Networks and Pathways/genetics
18.
BMC Plant Biol ; 24(1): 507, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844853

ABSTRACT

BACKGROUND: Powdery mildew, caused by Eeysiphe heraclei, seriously threatens Heracleum moellendorffii Hance. Plant secondary metabolites are essential to many activities and are necessary for defense against biotic stress. In order to clarify the functions of these metabolites in response to the pathogen, our work concentrated on the variations in the accumulation of secondary metabolites in H. moellendorffii during E. heraclei infection. RESULTS: Following E. heraclei infection, a significant upregulation of coumarin metabolites-particularly simple coumarins and associated genes was detected by RNA-seq and UPLC-MS/MS association analysis. Identifying HmF6'H1, a Feruloyl CoA 6'-hydroxylase pivotal in the biosynthesis of the coumarin basic skeleton through ortho-hydroxylation, was a significant outcome. The cytoplasmic HmF6'H1 protein was shown to be able to catalyze the ortho-hydroxylation of p-coumaroyl-CoA and caffeoyl-CoA, resulting in the formation of umbelliferone and esculetin, respectively. Over-expression of the HmF6'H1 gene resulted in increased levels of simple coumarins, inhibiting the biosynthesis of furanocoumarins and pyranocoumarins by suppressing PT gene expression, enhancing H. moellendorffii resistance to powdery mildew. CONCLUSIONS: These results established HmF6'H1 as a resistance gene aiding H. moellendorffii in combatting E. heraclei infection, offering additional evidence of feruloyl-CoA 6'-hydroxylase role in catalyzing various types of simple coumarins. Therefore, this work contributes to our understanding of the function of simple coumarins in plants' defense against powdery mildew infection.


Subject(s)
Ascomycota , Coumarins , Metabolome , Plant Diseases , Transcriptome , Coumarins/metabolism , Plant Diseases/microbiology , Plant Diseases/genetics , Ascomycota/physiology , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Apiaceae/metabolism , Apiaceae/genetics , Disease Resistance/genetics
19.
Pediatr Allergy Immunol ; 35(5): e14133, 2024 May.
Article in English | MEDLINE | ID: mdl-38727629

ABSTRACT

Food allergy (FA) is a widespread issue, affecting as many as 10% of the population. Over the past two to three decades, the prevalence of FA has been on the rise, particularly in industrialized and westernized countries. FA is a complex, multifactorial disease mediated by type 2 immune responses and involving environmental and genetic factors. However, the precise mechanisms remain inadequately understood. Metabolomics has the potential to identify disease endotypes, which could beneficially promote personalized prevention and treatment. A metabolome approach would facilitate the identification of surrogate metabolite markers reflecting the disease activity and prognosis. Here, we present a literature overview of recent metabolomic studies conducted on children with FA.


Subject(s)
Food Hypersensitivity , Metabolomics , Humans , Food Hypersensitivity/immunology , Food Hypersensitivity/diagnosis , Metabolomics/methods , Child , Biomarkers/metabolism , Metabolome , Allergens/immunology
20.
Molecules ; 29(9)2024 May 06.
Article in English | MEDLINE | ID: mdl-38731650

ABSTRACT

The present study investigates the chemical composition variances among Pinelliae Rhizoma, a widely used Chinese herbal medicine, and its common adulterants including Typhonium flagelliforme, Arisaema erubescens, and Pinellia pedatisecta. Utilizing the non-targeted metabolomics technique of employing UHPLC-Q-Orbitrap HRMS, this research aims to comprehensively delineate the metabolic profiles of Pinelliae Rhizoma and its adulterants. Multivariate statistical methods including PCA and OPLS-DA are employed for the identification of differential metabolites. Volcano plot analysis is utilized to discern upregulated and downregulated compounds. KEGG pathway analysis is conducted to elucidate the differences in metabolic pathways associated with these compounds, and significant pathway enrichment analysis is performed. A total of 769 compounds are identified through metabolomics analysis, with alkaloids being predominant, followed by lipids and lipid molecules. Significant differential metabolites were screened out based on VIP > 1 and p-value < 0.05 criteria, followed by KEGG enrichment analysis of these differential metabolites. Differential metabolites between Pinelliae Rhizoma and Typhonium flagelliforme, as well as between Pinelliae Rhizoma and Pinellia pedatisecta, are significantly enriched in the biosynthesis of amino acids and protein digestion and absorption pathways. Differential metabolites between Pinelliae Rhizoma and Arisaema erubescens are mainly enriched in tyrosine metabolism and phenylalanine metabolism pathways. These findings aim to provide valuable data support and theoretical references for further research on the pharmacological substances, resource development and utilization, and quality control of Pinelliae Rhizoma.


Subject(s)
Metabolomics , Pinellia , Rhizome , Chromatography, High Pressure Liquid/methods , Metabolomics/methods , Pinellia/metabolism , Pinellia/chemistry , Rhizome/metabolism , Rhizome/chemistry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/metabolism , Mass Spectrometry/methods , Drug Contamination , Metabolome , Metabolic Networks and Pathways
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