PubMed
Global metabolomic profiling of tumor tissue and paired serum samples to identify biomarkers for response to neoadjuvant FOLFIRINOX treatment of human pancreatic cancer
Mol Oncol. 2024 Nov 15. doi: 10.1002/1878-0261.13759. Online ahead of print.ABSTRACTNeoadjuvant chemotherapy (NAT) is increasingly used for the treatment of non-metastatic pancreatic ductal adenocarcinoma (PDAC) and is established as a standard of care for borderline resectable and locally advanced PDAC. However, full exploitation of its clinical benefits is limited by the lack of biomarkers that assess treatment response. To address this unmet need, global metabolomic profiling was performed on tumor tissue and paired serum samples from patients with treatment-naïve (TN; n = 18) and neoadjuvant leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride and oxaliplatin (FOLFIRINOX)-treated (NAT; n = 17) PDAC using liquid chromatography mass spectrometry. Differentially abundant metabolites (DAMs) in TN versus NAT groups were identified and their correlation with various clinical parameters was assessed. Metabolomics profiling identified 40 tissue and five serum DAMs in TN versus NAT PDAC. In general, DAMs associated with amino acid and nucleotide metabolism were lower in NAT compared to TN. Four DAMs-3-hydroxybutyric acid (BHB), 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), glycochenodeoxycholate and citrulline-were common to both tissue and serum and showed a similar pattern of differential abundance in both groups. A strong positive correlation was observed between serum carbohydrate 19-9 antigen (CA 19-9) and tissue carnitines (C12, C18, C18:2) and N8-acetylspermidine. The reduction in CA 19-9 following NAT correlated negatively with serum deoxycholate levels, and the latter correlated positively with survival. This study revealed neoadjuvant-chemotherapy-induced changes in metabolic pathways in PDAC, mainly amino acid and nucleotide metabolism, and these correlated with reduced CA 19-9 following neoadjuvant FOLFIRINOX treatment.PMID:39545923 | DOI:10.1002/1878-0261.13759
Low-Medium Polarity Ginsenosides from Wild Ginseng Improves Immunity by Activating the AhR/MAPK Pathway through Tryptophan Metabolism Driven by Gut Microbiota
J Agric Food Chem. 2024 Nov 15. doi: 10.1021/acs.jafc.4c06019. Online ahead of print.ABSTRACTThe gut microbiota contribute significantly to the immune system. Low-medium polarity ginsenosides from wild ginseng (LWG) have potential immunomodulatory effects. However, how the LWG regulates gut microbiota to enhance immunity remains unclear. To explore the interaction between gut microbes and metabolites mediating LWG's immunomodulatory effects, this study examined LWG's impact on splenocytes and CTX-induced immunosuppressed mice. Metabolomic and metagenomic analyses were conducted in vivo to explore the mechanism by which LWG regulates gut microbiota to enhance immunity. In vitro data suggest that LWG at 4 μg/mL enhances the splenocyte activity. Furthermore, LWG effectively reduces symptoms in immunocompromised mice, including weight loss and intestinal mucosal damage. LWG alleviated gut microbiota disturbance, restored tryptophan metabolites (IA, IAA, and IPA), and significantly increased JNK, ERK, and p38MAPK protein levels, which were downstream of AhR. Our study demonstrated that LWG improves the immunity by reshaping gut microbiota, restoring intestinal mucosa, and boosting the gut microbiota-related metabolism of tryptophan to activate the AhR/MAPK pathway. This research offers new insights into the mechanism by which LWG regulates immune function.PMID:39545702 | DOI:10.1021/acs.jafc.4c06019
PREVALENCE OF HYPOCALCAEMIA IN A SELECTED POPULATION IN KANO: CALL FOR METABOLOMICS AND GENETIC PROFILING FOR RISK PREDICTION
West Afr J Med. 2024 Nov 10;41(11 Suppl 1):S57.ABSTRACTINTRODUCTION: Severe acute symptomatic hypocalcemia, requiring emergency medical intervention, is a significant but poorly understood condition with high morbidity. In our setting, patients present to emergency rooms with painful carpo-pedal spasms that last for several hours, sometimes mimicking seizure disorders. Metabolomics and genetic profiling are innovative approaches that pinpoint molecular and genetic determinants of hypocalcemia risk which can be adopted to guide treatment in our population.OBJECTIVE: To determine the prevalence of hypocalcemia in urban Kano as a preliminary step towards identifying key risk factors.METHODS: We obtained retrospective data from patients who presented to a tertiary hospital between January and December 2023. Serum calcium levels were measured on Abbott Architect c4000 autoanalyzer. We analyzed data using R statistical software (version 4.3.2). Chi-square tests were used to assess significant differences (p < 0.05).RESULTS: A total of 1,270 samples were analyzed, consisting of 59.3% (n = 753) males, their mean age was 36.2 ± 4 years. Mean serum calcium levels were 2.05 ± 0.34 mmol/L to 2.11 ± 1.00 mmol/L. Overall prevalence of hypocalcemia (serum calcium < 2.2 mmol/L) was 52.2%. Females exhibited a significantly higher prevalence (58.8%) compared to males (p = 0.03). The highest prevalence was observed in the 40-59-year age group (p < 0.01).CONCLUSION: Hypocalcemia is highly prevalent in our population emphasizing the need for innovative approaches to better understand the genetic predictors, enable early intervention and prevent the long-term complications. These findings also provide a foundation for future multicenter studies and could inform public health policies targeting at risk groups. Keywords: Hypocalcaemia, Risk prediction,Metabolomics, Genetic markers.PMID:39545459
Multi-Omics and Physiological Analysis Reveal Crosstalk Between Aphid Resistance and Nitrogen Fertilization in Wheat
Plant Cell Environ. 2024 Nov 15. doi: 10.1111/pce.15282. Online ahead of print.ABSTRACTThe availability of nitrogen (N) can dramatically influence crops resistance to herbivorous insects. However, the interaction between N fertilization and crop resistance to insects is not well understood. In this study, the effects of N fertilization on the grain aphid (Sitobion miscanthi) were investigated using three wheat (Triticum aestivum) cultivars with different aphid resistances. We measured aphid life cycle parameters, fecundity, survival rate, weight and feeding behavior, in conjunction with wheat metabolomics, transcriptomics and alien introgression analysis. Our results demonstrated that higher N application benefits aphid feeding across all three wheat cultivars. We also reveal that the highly resistant cultivar (ZM9) can only exert its resistance-advantage under low N fertilization, losing its advantage compared to moderately resistant cultivar YN19 and susceptible cultivar YN23 under higher N fertilization. The effects of N fertilization on wheat-aphid interactions were due to changes in the regulation of carbon and nitrogen metabolism. Integration of multi-omics highlighted specific aphid-induced differentially expressed genes (DEGs, e.g., TUB6, Tubulin 6; ENODL20, Early nodulin-like protein 20; ACT7 Actin 7; Prx47, Peroxidase 47) and significantly different metabolites (SDMs, e.g., crotonoside, guanine, 2'-O-methyladenosine, ferulic acid) in ZM9. Additionally, we report the unique SDMs-DEGs interactions, associated with introgression during wheat domestication, may help infer aphid resistance. In summary, this study provides new insights into the relationships between N fertilization practices, defense responses and integrated pest management for sustainable wheat production.PMID:39545337 | DOI:10.1111/pce.15282
Integrated microbiome and metabolomic analyses revealed the antifibrotic effect of vanillic acid on thioacetamide-induced liver fibrosis in mice
Food Funct. 2024 Nov 15. doi: 10.1039/d4fo02309a. Online ahead of print.ABSTRACTVanillic acid (VA) is a natural phenolic acid compound that is widely found in various foods and medicinal plants, with a remarkable antifibrotic effect observed in animal studies, but its exact antifibrotic mechanism remains unclear. Herein, hepatic function, fibrotic index, and histopathological, microbiome, and metabolomic methods were used to investigate the potential mechanisms behind the improvement effect of vanillic acid against thioacetamide (TAA)-induced liver fibrosis in mice. Our results showed that VA reversed TAA-induced liver fibrosis manifested a decrease in collagen fiber deposition, serum transaminase, serum hepatic fibrotic index, and liver inflammation indicator levels. When analyzed, TAA injection mainly increased the abundance of Akkermansia and Roseburia and significantly reduced the abundance of Anaerotruncus. VA reversed these changes back to normal levels to varying degrees. Metabolomic profiling demonstrated that VA treatment was efficacious in modulating several key liver metabolites involved in neuroactive ligand-receptor interaction, prolactin signaling pathway, estrogen signaling pathway, and glutathione metabolism. Conclusively, VA may ameliorate liver damage and suppress the fibrogenesis caused by thioacetamide by correcting intestinal microbiota disorders and promoting normal hepatic metabolism. This research provides a novel perspective on vanillic acid as a dietary supplement for hepatic fibrosis improvement.PMID:39545308 | DOI:10.1039/d4fo02309a
Preliminary study on the potential impact of probiotic combination therapy on Helicobacter pylori infection in children using 16S gene sequencing and untargeted metabolomics approach
Front Microbiol. 2024 Oct 31;15:1487978. doi: 10.3389/fmicb.2024.1487978. eCollection 2024.ABSTRACTOBJECTIVE: The purpose of this study was to explore the potential mechanism of Helicobacter pylori (Hp) eradication by probiotic therapy through 16S rRNA gene sequencing technology and untargeted metabolomics.METHODS: Twenty four Hp-infected children were recruited from the Shanxi Bethune Hospital, and 24 healthy children were recruited as a blank control group. Group A: fecal samples from 24 healthy children. Group B: fecal samples of 24 children with Hp infection. Group B1 (n = 15): fecal samples of group B treated with probiotic therapy for 2 weeks. Group B2 (n = 19): fecal samples of group B treated with probiotic therapy for 4 weeks. The above fecal samples were analyzed by 16S rRNA gene sequencing technology and untargeted metabolomics.RESULTS: There was no significant difference in alpha diversity and beta diversity among the four groups, but many bacteria with statistical difference were found in each group at the bacterial genus level and phylum level. LEfSe results showed that in group B, Porphyromonadaceae, Shigella and other microorganisms related to intestinal microecological dysbiosis were enriched. And in group B2, abundant characteristic microorganisms were found, namely Bacillales and Prevotella. KEGG metabolic pathway enrichment analysis showed that groups B1 and B2 were involved in 10 metabolic pathways potentially related to probiotic treatment: purine metabolism, nitrogen metabolism, arginine biosynthesis, alanine, aspartic acid and glutamate metabolism, glyoxylic acid and dicarboxylic acid metabolism, unsaturated fatty acid biosynthesis, fatty acid extension, fatty acid degradation, pyrimidine metabolism, fatty acid biosynthesis.CONCLUSION: Probiotic therapy can inhibit Hp to some extent and can relieve gastrointestinal symptoms, making it a preferred therapy for children with Hp infection and functional abdominal pain. Hp infection can reduce the diversity of intestinal microbes, resulting in the disturbance of intestinal microbiota and changes in the relative abundance of microbiota in children, while probiotic therapy can restore the diversity of intestinal microbes and intestinal microecological balance.PMID:39545236 | PMC:PMC11560915 | DOI:10.3389/fmicb.2024.1487978
Diagnosis of pregnancy disorder in the first-trimester patient plasma with Raman spectroscopy and protein analysis
Bioeng Transl Med. 2024 Jul 16;9(6):e10691. doi: 10.1002/btm2.10691. eCollection 2024 Nov.ABSTRACTGestational diabetes mellitus (GDM) is a pregnancy disorder associated with short- and long-term adverse outcomes in both mothers and infants. The current clinical test of blood glucose levels late in the second trimester is inadequate for early detection of GDM. Here we show the utility of Raman spectroscopy (RS) for rapid and highly sensitive maternal metabolome screening for GDM in the first trimester. Key metabolites, including phospholipids, carbohydrates, and major amino acids, were identified with RS and validated with mass spectrometry, enabling insights into associated metabolic pathway enrichment. Using classical machine learning (ML) approaches, we showed the performance of the RS metabolic model (cross-validation AUC 0.97) surpassed that achieved with patients' clinical data alone (cross-validation AUC 0.59) or prior studies with single biomarkers. Further, we analyzed novel proteins and identified fetuin-A as a promising candidate for early GDM prediction. A correlation analysis showed a moderate to strong correlation between multiple metabolites and proteins, suggesting a combined protein-metabolic analysis integrated with ML would enable a powerful screening platform for first trimester diagnosis. Our study underscores RS metabolic profiling as a cost-effective tool that can be integrated into the current clinical workflow for accurate risk stratification of GDM and to improve both maternal and neonatal outcomes.PMID:39545096 | PMC:PMC11558203 | DOI:10.1002/btm2.10691
Revealing the dynamic changes of metabolites and molecular mechanisms of chlorogenic acid accumulation during the leaf development of <em>Vaccinium dunalianum</em> based on multi-omic analyses
Front Plant Sci. 2024 Oct 31;15:1440589. doi: 10.3389/fpls.2024.1440589. eCollection 2024.ABSTRACTVaccinium dunalianum, a medicinal plant, is utilized for Quezui Tea production from its leaf buds and young leaves. Despite prior research on V. dunalianum revealing several medicinal compounds, the comprehensive variations in metabolites during its growth and development, along with the molecular mechanisms underlying high chlorogenic acid (CGA) yield, remain unclear. Through a joint analysis of transcriptomics and proteomics, our study first identified 15 key structural genes and 3 transcription factors influencing CGA biosynthesis in V. dunalianum, offering new evidence to understand its regulatory network. Furthermore, non-targeted metabolomics analysis provides the first extensive report on the metabolic profile of V. dunalianum, furnishing a valuable dataset for deeper exploration of its nutritional and medicinal value, and the development of a quality evaluation system for its product Quezui Tea. This study offers the most comprehensive molecular information on V. dunalianum, marking a significant step toward understanding and enhancing the plant's potential for medicinal and nutritional applications. Additionally, this study also reveals V. dunalianum holds promise as a natural antioxidant source for functional foods, providing data support for network pharmacology.PMID:39544533 | PMC:PMC11560443 | DOI:10.3389/fpls.2024.1440589
Analysis of blood metabolite characteristics at birth in preterm infants with bronchopulmonary dysplasia: an observational cohort study
Front Pediatr. 2024 Oct 31;12:1474381. doi: 10.3389/fped.2024.1474381. eCollection 2024.ABSTRACTBACKGROUND: To analyze the characteristics of blood metabolites within 24 h after birth in preterm infants with bronchopulmonary dysplasia (BPD) and to identify biomarkers for predicting the occurrence of BPD.METHODS: Dried blood spots (DBS) were collected at birth from preterm infants with gestational age (GA) of less than 32 weeks in the cohort. The infants were divided into the BPD group and non-BPD group based on whether they eventually developed BPD. Dried blood spot filter papers were prepared from venous blood collected within the first 24 h of life. Metabolites were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and analyzed using the R software package.RESULTS: DBS samples from 140 infants with the GA < 32 weeks were used in the study, with 4 infants who died being excluded. Among the remaining 136 preterm infants, 38 developed BPD and 98 did not. To control for GA differences, we conducted a subgroup analysis. In the GA 24+4-27+6 weeks subgroup, we observed a significant decrease in histidine levels and the ornithine/citrulline ratio in the BPD group. Additionally, the ratios of acylcarnitines C3/C0 and C5/C0 were also significantly reduced.CONCLUSIONS: Metabolic markers in DBS within 24 h after birth are promising for predicting the occurrence of BPD in preterm infants with GA < 28 weeks.CLINICAL TRIAL REGISTRATION: [https://www.chictr.org.cn/], identifier [ChiCTR2100048293, ChiCTR2400081615].PMID:39544337 | PMC:PMC11560417 | DOI:10.3389/fped.2024.1474381
Investigating the metabolomic pathways in female reproductive endocrine disorders: a Mendelian randomization study
Front Endocrinol (Lausanne). 2024 Oct 31;15:1438079. doi: 10.3389/fendo.2024.1438079. eCollection 2024.ABSTRACTINTRODUCTION: Reproductive endocrine disorders (RED), including polycystic ovary syndrome (PCOS), endometriosis (EMs), and female infertility (FI), significantly affect women's health globally, with varying prevalence across different regions. These conditions can be addressed through medication, surgical interventions, and lifestyle modifications. However, the limited understanding of RED's etiology and the substantial economic burden of its treatment highlight the importance of investigating its pathogenesis. Metabolites play a critical role in metabolic processes and are potentially linked to the development of RED. Despite existing studies suggesting correlations between metabolites and RED, conclusive evidence remains scarce, primarily due to the observational nature of these studies, which are prone to confounding factors.METHODS: This study utilized Mendelian Randomization (MR) to explore the causal relationship between metabolites and RED, leveraging genetic variants associated with metabolite levels as instrumental variables to minimize confounding and reverse causality. Data were obtained from the Metabolomics GWAS Server and the IEU OpenGWAS project. Instrumental variables were selected based on their association with the human gut microbiota composition, and the GWAS summary statistics for metabolites, PCOS, EMs, and FI were analyzed. The MR-Egger regression and random-effects inverse-variance weighted (IVW) methods were employed to validate the causal relationship. Cochran's Q test was employed to evaluate heterogeneity, sensitivity analysis was performed using leave-one-out analysis, and for pleiotropy analysis, the intercept term of MR-Egger's method was investigated.RESULTS: The MR analysis revealed significant associations between various metabolites and RED conditions. For instance, a positive association was found between 1-palmitoylglycerophosphocholine and PCOS, while a negative association was noted between phenylacetate and FI. The study identified several metabolites associated with an increased risk and others with protective effects against PCOS, EMs, and FI. These findings highlight the complex interplay between metabolites and RED, suggesting potential pathways through which these conditions could be influenced or treated.CONCLUSION: This MR study provides valuable insights into the causal relationship between metabolites and female reproductive endocrine disorders, suggesting that metabolic alterations play a significant role in the pathogenesis of PCOS, EMs, and FI, and offering a foundation for future research and therapeutic development.PMID:39544240 | PMC:PMC11560792 | DOI:10.3389/fendo.2024.1438079
The metabolic and physiologic impairments underlying long COVID associated exercise intolerance
Pulm Circ. 2024 Nov 13;14(4):e70009. doi: 10.1002/pul2.70009. eCollection 2024 Oct.ABSTRACTData from invasive CPET (iCPET) revealed long COVID patients have impaired systemic oxygen extraction (EO2), suggesting impaired mitochondrial ATP production. However, it remains uncertain whether the initial severity of SARS-CoV-2 infection has implications on EO2 and exercise capacity (VO2) nor has there been assessment of anerobic ATP generation in long COVID patients. iCPET was performed on 47 long COVID patients (i.e., full cohort; n = 8 with severe SARS-CoV-2 infection). In a subset of patients (i.e., metabolomic cohort; n = 26) metabolomics on venous and arterial blood samples during iCPET was performed. In the full cohort, long COVID patients exhibited reduced peak EO2 with reduced peak VO2 (90 ± 17% predicted) relative to cardiac output (118 ± 23% predicted). Peak VO2 [88% predicted (IQR 81% - 108%) vs. 70% predicted (IQR 64% - 89%); p = 0.02] and EO2 [0.59(IQR 0.53-0.62) vs. 0.53(IQR 0.50-0.48); p = 0.01) were lower in severe versus mild infection. In the metabolomic cohort, 12 metabolites were significantly consumed, and 41 metabolites were significantly released (p-values < 0.05). Quantitative metabolomics demonstrated significant increases in inosine and succinate arteriovenous gradients during exercise. Peak VO2 was significantly correlated with peak venous succinate (r = 0.68; p = 0.0008) and peak venous lactate (r = 0.49; p = 0.0004). Peak EO2 and consequently peak VO2 impact long COVID patients in a severity dependent manner. Exercise intolerance associated with long COVID is defined by impaired aerobic and anaerobic energy production. Peak venous succinate may serve as a potential biomarker in long COVID.PMID:39544193 | PMC:PMC11560803 | DOI:10.1002/pul2.70009
Metabolomic characterization of unintentional weight loss among community-dwelling older Black and White men and women
Aging Cell. 2024 Nov 15:e14410. doi: 10.1111/acel.14410. Online ahead of print.ABSTRACTThis study aims to understand the metabolic mechanisms of unintentional weight loss in older adults. We investigated plasma metabolite associations of subsequent weight change over 2 years in 1536 previously weight stable participants (mean age 74.6 years, 50% women, 35% Black) from the Health, Aging and Body Composition (Health ABC) Study. Multinomial logistic regressions were used to examine associations of the 442 metabolites with weight loss with/without an intention and weight gain >3% annually relative to weight stability. The metabolite associations of unintentional weight loss differed from those of intentional weight loss and weight gain. Lower levels of aromatic amino acids, phospholipids, long-chain poly-unsaturated triglycerides, and higher levels of amino acid derivatives, poly-unsaturated fatty acids, and carbohydrates were associated with higher odds of unintentional weight loss after adjusting for age, sex, race, and BMI categories. Prevalent diseases attenuated four and lower mid-thigh muscle mass and poorer appetite each attenuated 2 of 77 identified metabolite associations by >20%, respectively. Other factors (e.g., energy expenditure, diet, and medication) attenuated all associations by <20%. While 16 metabolite associations were attenuated by 20%-48% when adjusting for all these risk factors, 47 metabolite associations remained significant. Altered amino acid metabolism, impaired mitochondrial fatty acid oxidation, and inflammaging implicated by identified metabolites appear to precede unintentional weight loss in Health ABC older adults. Furthermore, these pathways seem to be associated with prevalent diseases especially diabetes, lower muscle mass, and poorer appetite.PMID:39544124 | DOI:10.1111/acel.14410
UPLC-QTOF-MS based targeted metabolomics to unravel the hepatoprotective marker compounds of Swertia chirayita
Nat Prod Res. 2024 Nov 14:1-6. doi: 10.1080/14786419.2024.2426063. Online ahead of print.ABSTRACTSwertia chirayita is a popular hepatoprotective herb according to 'Ayurveda'. This study characterises the phytochemicals of S. chirayita responsible for hepatoprotective properties was executed using targeted metabolomics approach. Different fractions of hydro-alcoholic extract of S. chirayita were subjected to assess in-vitro antioxidant and hepatoprotective properties in HepG2 cells. Furthermore, active fraction was further subjected to UPLC-QTOF-MS based targeted metabolomics to identify the phytochemicals linked to bioactivity. A complementary in-silico experiment was also performed to understand the interactions of identified molecules with CYP2E1 enzyme. It was observed that, n-butanol fraction deciphers significant (p < .05) and maximum antioxidant and hepatocyte protection compared to other fractions. UPLC-QTOF-HRMS analysis reveals that it contains 17 secondary metabolites various classes. Identified molecules showed potential interactions with the crucial amino acid residues in the active site of CYP2E1 protein indicate the possibility of inhibition which may counter APAP induced toxicity in HepG2 cells.PMID:39544006 | DOI:10.1080/14786419.2024.2426063
F. prausnitzii potentially modulates the association between citrus intake and depression
Microbiome. 2024 Nov 14;12(1):237. doi: 10.1186/s40168-024-01961-3.ABSTRACTBACKGROUND: The gut microbiome modulates the effects of diet on host health, but it remains unclear which specific foods and microbial features interact to influence risk of depression. To understand this interplay, we leveraged decades of dietary and depression data from a longitudinal cohort of women (n = 32,427), along with fecal metagenomics and plasma metabolomics from a substudy (n = 207) nested in this cohort, as well as an independent validation cohort of men (n = 307).RESULTS: We report that citrus intake and its components are prospectively associated with a lower risk of depression and altered abundance of 15 gut microbial species, including enriched Faecalibacterium prausnitzii. In turn, we found a lower abundance of F. prausnitzii and its metabolic pathway, S-adenosyl-L-methionine (SAM) cycle I in participants with depression. To explore causality, we found that lower SAM production by F. prausnitzii may decrease intestinal monoamine oxidase A gene expression implicated in serotonin and dopamine synthesis.CONCLUSIONS: These data underscore the role of diet in the prevention of depression and offer a plausible explanation for how the intestinal microbiome modulates the influence of citrus on mental health. Video Abstract.PMID:39543781 | DOI:10.1186/s40168-024-01961-3
Analysis of variable metabolites in preterm infants with bronchopulmonary dysplasia: a systematic review and meta-analysis
Ital J Pediatr. 2024 Nov 14;50(1):246. doi: 10.1186/s13052-024-01812-9.ABSTRACTNumerous studies have attempted to identify potential biomarkers for early detection of bronchopulmonary dysplasia (BPD) in preterm infants using metabolomics techniques. However, the presence of consistent evidence remains elusive. Our study aimed to conduct a systematic review and meta-analysis to identify differences in small-molecule metabolites between BPD and non-BPD preterm infants. Through meticulous screening of numerous samples, we identified promising candidates, providing valuable insights for future research. We searched PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Internet, Wan-fang database, Chinese Science and Technique Journal Database and Chinese Biomedical Literature Database from inception until January 16, 2024. Studies were comprehensively reviewed against inclusion criteria. We included case-control studies and adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Study quality was assessed with the Newcastle-Ottawa scale. We compared the changes in metabolite levels between the BPD and non-BPD preterm infants. A meta-analysis was conducted on targeted metabolomics research data based on the strategy of standardized mean differences (MD) and 95% confidence intervals (CI).Fifteen studies (1357 participants) were included. These clinical-based metabolomics studies clarified 110 differential metabolites between BPD and non-BPD preterm infants. The meta-analysis revealed higher glutamate concentration in the BPD group compared to the non-BPD group (MD = 1, 95% CI 0.59 to 1.41, p < 0.00001). Amino acids were identified as the key metabolites distinguishing preterm infants with and without BPD, with glutamate potentially serving as a BPD predictor in this population.PMID:39543750 | DOI:10.1186/s13052-024-01812-9
An integrated approach for studying exposure, metabolism, and disposition of traditional Chinese medicine using PATBS and MDRB tools: a case study of semen Armeniacae Amarum
Chin Med. 2024 Nov 14;19(1):158. doi: 10.1186/s13020-024-01031-8.ABSTRACTBACKGROUND: Deciphering the in vivo processes of traditional Chinese medicine (TCM) is crucial for identifying new pharmacodynamic substances and new drugs. Due to the complexity and diversity of components, investigating the exposure, metabolism, and disposition remains a major challenge in TCM research. In recent years, a number of non-targeted smart mass-spectrometry (MS) techniques, such as precise-and-thorough background-subtraction (PATBS) and metabolomics, have realized the intelligent identification of in vivo components of TCM. However, the metabolites characterization still largely relies on manual identification in combination with online databases.RESULTS: We developed a scoring approach based on the structural similarity and minimal mass defect variations between metabolites and prototypes. The current method integrates three dimensions of mass spectral data including m/z, mass defect of MS1 and MS2, and the similarity of MS2 fragments, which was sequentially analyzed by a R-based mass dataset relevance bridging (MDRB) data post-processing technique. The MDRB technology constructed a component relationship network for TCM, significantly improving metabolite identification efficiency and facilitating the mapping of translational metabolic pathways. By combining MDRB with PATBS through this non-targeted identification technology, we developed a comprehensive strategy for identification, characterization and bridging analysis of TCM metabolite in vivo. As a proof of concept, we adopted the proposed strategy to investigate the process of exposure, metabolism, and disposition of Semen Armeniacae Amarum (CKXR) in mice.SIGNIFICANCE: The currently proposed analytical approach is universally applicable and demonstrates its effectiveness in analyzing complex components of TCMs in vitro and in vivo. Furthermore, it enables the correlation of in vitro and in vivo data, providing insights into the metabolic transformations among components sharing the same parent nucleus structure. Finally, the developed MDRB platform is publicly available for ( https://github.com/933ZhangDD/MDRB ) for accelerating TCM research for the scientific community.PMID:39543720 | DOI:10.1186/s13020-024-01031-8
Effect of plant-derived microbial soil legacy in a grafting system-a turn for the better
Microbiome. 2024 Nov 14;12(1):234. doi: 10.1186/s40168-024-01938-2.ABSTRACTBACKGROUND: Plant-soil feedback arises from microbial legacies left by plants in the soil. Grafting is a common technique used to prevent yield declines in monocultures. Yet, our understanding of how grafting alters the composition of soil microbiota and how these changes affect subsequent crop performance remains limited. Our experiment involved monoculturing ungrafted and grafted watermelons to obtain conditioned soils, followed by growing the watermelons on the conditioned soils to investigate plant-soil feedback effects.RESULTS: Ungrafted plants grew better in soil previously conditioned by a different plant (heterospecific soil) while grafted plants grew better in soil conditioned by the same plant (conspecific soil). We demonstrated experimentally that these differences in growth were linked to changes in microorganisms. Using a supervised machine learning algorithm, we showed that differences in the relative abundance of certain genera, such as Rhizobium, Chryseobacterium, Fusarium, and Aspergillus, significantly influenced the conspecific plant-soil feedback. Metabolomic analyses revealed that ungrafted plants in heterospecific soil enriched arginine biosynthesis, whereas grafted plants in conspecific soil increased sphingolipid metabolism. Elsewhere, the metagenome-assembled genomes (MAGs) of ungrafted plants identified in heterospecific soil include Chryseobacterium and Lysobacter, microorganisms having been prominently identified in earlier research as contributors to plant growth. Metabolic reconstruction revealed the putative ability of Chryseobacterium to convert D-glucono-1,5-lactone to gluconic acid, pointing to distinct disease-suppressive mechanisms and hence distinct microbial functional legacies between grafted and ungrafted plants.CONCLUSIONS: Our findings show a deep impact of the soil microbial reservoir on plant growth and suggest the necessity to protect and improve this microbial community in agricultural soils. The work also suggests possibilities of optimizing microbiota-mediated benefits through grafting herein, a way that "engineered" soil microbial communities for better plant growth. Video Abstract.PMID:39543707 | DOI:10.1186/s40168-024-01938-2
Metabolomic and transcriptomic analyses reveals candidate genes and pathways involved in secondary metabolism in Bergenia purpurascens
BMC Genomics. 2024 Nov 14;25(1):1083. doi: 10.1186/s12864-024-10953-4.ABSTRACTBergenia purpurascens is an important medicinal, edible and ornamental plant. The lack of omics information hinders the study of its metabolic pathways and related genes. In order to investigate candidate genes and pathways involved in secondary metabolism in B. purpurascens, roots, stems and leaves of B. purpurascens were subjected to metabolomic and transcriptomic analyses in this study. A total of 351 differentially accumulated secondary metabolites were identified. We identified 120 candidate genes involved in phenylpropanoid and flavonoid biosynthesis pathway, from which 29 key candidate genes were obtained by WGCNA. Five UDP-Glycosyltransferases and four O-methyltransferases were suggested to be the candidate enzymes involved in synthetic pathway from gallic acid to bergenin by correlation analysis between transcriptional and metabolic levels and phylogenetic analysis. This study provides data resources and new insights for further studies on the biosynthesis of major active components in B. purpurascens.PMID:39543501 | DOI:10.1186/s12864-024-10953-4
Integrative hyperspectral, transcriptomic, and metabolomic analysis reveals the mechanism of tea plants in response to sooty mold disease
BMC Plant Biol. 2024 Nov 15;24(1):1079. doi: 10.1186/s12870-024-05806-x.ABSTRACTBACKGROUND: Sooty mold (SM), caused by Cladosporium species, is a pervasive threat to tea plant health, affecting both canopy structure and crop yield. Despite its significance, understanding the complex interplay between defense genes and metabolites in tea plants across various SM-infected canopy layers remains limited. Our study employed hyperspectral imaging, transcriptomic profiling, and metabolomic analysis to decipher the intricate mechanisms underlying the tea plant's response to SM infection.RESULTS: Our hyperspectral imaging identified three critical wavelengths (552, 673, and 800 nm) inflection points associated with varying degrees of SM infection. This non-invasive method allows for the precise assessment of disease progression. Concurrently, transcriptome analysis revealed a wealth of differentially expressed genes (DEGs) enriched in metabolic pathways, secondary metabolite biosynthesis, and plant-pathogen interactions. Cluster analysis highlighted an intensified immune response in A2 and A3 samples. A comprehensive metabolomic profile identified 733 co-changed metabolites in SM-infected leaves, with alcohols, lipids (free fatty acids), hydrocarbons, and amino acids significantly accumulating in A1, while flavonoids were predominantly upregulated in A2 and A3. Weighted Gene Co-Expression Network Analysis (WGCNA) uncovered five hub genes (Dormancy-associated protein, Serine/threonine-protein phosphatase, ABC transporter, and some uncharacterized proteins) and two hub metabolites (D-Mannitol and 17-Hydroxylinolenic Acid) that exhibit significant relationships with DEGs and metabolites. Further co-expression analysis indicated that tea plants mainly employed genes and metabolites related to the biosynthesis of secondary metabolites, plant hormone signal transduction, and plant-pathogen interaction to combat SM.CONCLUSION: This study establishes a foundation for understanding the immune mechanisms of tea plants across different canopy layers in response to SM infection. It not only sheds light on the complex defense strategies employed by tea plants but also identifies candidate genes and metabolites crucial for enhancing tea plant breeding and resistance to SM.PMID:39543476 | DOI:10.1186/s12870-024-05806-x
Analysis of metabolites associated with ADIPOQ genotypes in individuals with type 2 diabetes mellitus
Sci Rep. 2024 Nov 15;14(1):28093. doi: 10.1038/s41598-024-79686-4.ABSTRACTDiabetes mellitus (DM) is a significant public health problem and it is known that the identification of molecular markers involved in glycemic control can impact disease control. Although the rs266729 polymorphism located in the promoter of the adiponectin gene (ADP) has been shown to be a candidate for involvement in glycemic control, the genotypic groups have never been characterized in terms of metabolomic aspects. Objective: Analyze the metabolites present in the rs266729 genotype groups. 127 diabetic individuals were compared according to the rs266729 genotype groups CC and GC + GG (RFLP-PCR). Blood plasma metabolites were classified by nuclear magnetic resonance (NMR), and the metabolic pathways of each group using the MetaboAnalyst tool. Insulin therapy (p = 0.049) was more frequent in the GC + GG rs266729 group. Lactate, alanine, glutamine, aspartate, lipid, lysine, isoleucine, citrulline, cholesterol, and fucose impacted the CC group and aspartate, beta-glucose, glutamate, pyruvate, proline, and 2-oxoglutarate impacted the CG + GG group. The glucose-alanine pathway, malate-aspartate transport, and urea cycle impacted the CC group (D-glucose, glutamic acid, L-alanine, oxoglutaric acid, and pyruvic acid). The glutamine/glutamate ratio is likely to be related to the causes of rs266729 influencing the risk of diabetes.PMID:39543306 | DOI:10.1038/s41598-024-79686-4