PubMed

Gut Microbes. 2023 Jan-Dec;15(1):2192151. doi: 10.1080/19490976.2023.2192151.ABSTRACTThe development of infant gut microbiome is a pivotal process affecting the ecology and function of the microbiome, as well as host health. While the establishment of the infant microbiome has been of interest for decades, the focus on gut microbial metabolism and the resulting small molecules (metabolites) has been rather limited. However, technological and computational advances are now enabling researchers to profile the plethora of metabolites in the infant gut, allowing for improved understanding of how gut microbial-derived metabolites drive microbiome community structuring and host-microbial interactions. Here, we review the current knowledge on development of the infant gut microbiota and metabolism within the first year of life, and discuss how these microbial metabolites are key for enhancing our basic understanding of interactions during the early life developmental window.PMID:36942883 | DOI:10.1080/19490976.2023.2192151

Curr Opin Clin Nutr Metab Care. 2023 Jan 2. doi: 10.1097/MCO.0000000000000906. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: This review provides an overview of most recent research studies employing nuclear magnetic resonance (NMR)-based metabolomics in the assessment of effects of diet and food ingestion.RECENT FINDINGS: NMR metabolomics is a useful tool in the elucidation of specific diets, for example, the Mediterranean diet, the New Nordic diet types, and also for comparing vegan, vegetarian and omnivore diets where specific diet-linked metabolite perturbations have been identified. Another core area where NMR metabolomics is employed involves research focused on examining specific food components or ingredients, including dietary fibers and other functional components. In several cases, NMR metabolomics has aided to document how specific food components exert effects on the metabolic activity of the gut microbiota. Research has also demonstrated the potential use of NMR metabolomics in assessing diet quality and interactions between specific food components such as meat and diet quality. The implications of these findings are important as they address that background diet can be decisive for if food items turn out to exert either harmful or health-promoting effects.SUMMARY: NMR metabolomics can provide important mechanistic insight and aid to biomarker discovery with implications for compliance and food registration purposes.PMID:36942870 | DOI:10.1097/MCO.0000000000000906

Biotechnol Genet Eng Rev. 2023 Mar 21:1-18. doi: 10.1080/02648725.2023.2191069. Online ahead of print.ABSTRACTOBJECTIVE: To explore and analyze the diagnostic value of metabolic markers in cerebrospinal fluid (CSF) in leptomeningeal metastases (LM) of non-small cell lung cancer (NSCLC).METHODS: Forty-six CSF samples from patients with NSCLC-LM were collected. Another 48 CSF samples from patients with nonmalignant neurological diseases were selected as control group. Metabolomic analysis of CSF was performed by high-performance liquid chromatography-mass spectrometry. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were applied for modeling. A multi-criteria evaluation system (variable importance value >1, multiple of change >2 and P < 0.05 for univariate analysis) was used to find differential metabolites between two groups. The subject working characteristic curves and pathway enrichment analysis were used to screen metabolites and pathways associated with NSCLC-LM.RESULTS: The PCA model and OPLS-DA model showed good overall data quality. Thirty endogenous differential metabolites were screened, and six potential biomarkers were further identified, including tyrosine (t = 3.37, P = 0.024, AUC = 0.967), phenylalanine (t = 3.98, P < 0.001, AUC = 0.992), pyruvate (t = 4.48, P < 0.001, AUC = 0.976), tryptophan (t = -2.5, P = 0.014, AUC = 0.935), adenosine monophosphate (t = -6.13, P < 0.001, AUC = 0.932) and glucose (t = -4.00, P < 0.001, AUC = 0.993). Thirty differential metabolites screened were subjected to metabolic pathway enrichment analysis and matched to 20 relevant metabolic pathways, of which the four most likely to cause metabolite changes were as follows: glycolysis and sugar metabolism synthesis, pyruvate metabolism, phenylalanine metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis.CONCLUSIONS: Untargeted metabolomics can effectively screen for CSF metabolites specific to NSCLC-LM patients, and six potential metabolites and their metabolic pathways might be involved in the pathogenesis of NSCLC-LM.PMID:36942709 | DOI:10.1080/02648725.2023.2191069

J Sci Food Agric. 2023 Mar 21. doi: 10.1002/jsfa.12563. Online ahead of print.ABSTRACTBACKGROUND: Panax quinquefolius L. is one of the most important foods and herbs because of its high nutritional value and medicinal potential. In our previous study we found that the content of ginsenoside in P. quinquefolius was improved by arbuscular mycorrhizal fungi (AMF). However, little research has been conducted on the molecular mechanisms in P. quinquefolius roots induced by AMF colonization. To identify the metabolomic and transcriptomic mechanisms of P. quinquefolius induced by AMF, the non-mycorrhized (Control) and mycorrhized (AMF) of P. quinquefolius were used as experimental materials for comparative analysis of transcriptome and metabolome.RESULTS: Compared with the control, 182 metabolites and 545 genes were significantly changed at the metabolic and transcriptional levels in AMF treatment. The metabolic pattern of AMF was changed, and the contents of ginsenosides (Rb1, Rg2), threonine and glutaric acid were significantly increased. There were significant differences in the expression of genes involved in plant hormone signal transduction, glutathione metabolism, and the plant-pathogen interaction pathway. In addition, several transcription factors from NAC, WRKY and bHLH families were identified in AMF vs the control. Furthermore, the combined analysis of "transcriptomic-metabolomics" analysis showed that "Plant hormone signal transduction", "Amino sugar and nucleotide sugar metabolism" and "Glutathione metabolism" pathway were the important enriched pathway in response to AMF colonization.CONCLUSION: Overall, these results provide new insights into P. quinquefolius response to AMF, which improve our understanding of the molecular mechanisms of P. quinquefolius induced by AMF. This article is protected by copyright. All rights reserved.PMID:36942522 | DOI:10.1002/jsfa.12563

Mater Today Bio. 2023 Mar 4;19:100602. doi: 10.1016/j.mtbio.2023.100602. eCollection 2023 Apr.ABSTRACTBlack phosphorus quantum dots (BPQDs) have shown potential in tumor therapy, however, their anti-angiogenic functions have not been studied. Although BPQDs are easily degraded to non-toxic phosphrous, the reported toxicity, poor stability, and non-selectivity largely limit their further application in medicine. In this study, a vascular targeting, biocompatible, and cell metabolism-disrupting nanoplatform is engineered by incorporating BPQDs into exosomes modified with the Arg-Gly-Asp (RGD) peptide (BPQDs@RGD-EXO nanospheres, BREs). BREs inhibit endothelial cells (ECs) proliferation, migration, tube formation, and sprouting in vitro. The anti-angiogenic role of BREs in vivo is evaluated using mouse retinal vascular development model and oxygen-induced retinopathy model. Combined RNA-seq and metabolomic analysis reveal that BREs disrupt glucose metabolism, which is further confirmed by evaluating metabolites, ATP production and the c-MYC/Hexokinase 2 pathway. These BREs are promising anti-angiogenic platforms for the treatment of pathological retinal angiogenesis with minimal side effects.PMID:36942311 | PMC:PMC10024194 | DOI:10.1016/j.mtbio.2023.100602

PeerJ. 2023 Mar 15;11:e15051. doi: 10.7717/peerj.15051. eCollection 2023.ABSTRACTBACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune systemic disease, and the majority of AAV patients have renal involvement presenting as rapid progressive glomerulonephritis (GN). Currently, the clinically available AAV markers are limited, and some of the newly reported markers are still in the nascent stage. The particular mechanism of the level changes of various markers and their association with the pathogenesis of AAV are not well defined. With the help of metabolomics analysis, this study aims to explore metabolic changes in AAV patients with renal involvement and lay the foundation for the discovery of novel biomarkers for AAV-related kidney damage.METHODS: We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based on serum samples from patients with AAV (N = 33) and healthy controls (N = 33) in order to characterize the serum metabolic profiling. The principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) were used to identify the differential metabolites. Least Absolute Shrinkage and Selection Operator (LASSO) and eXtreme Gradient Boosting (XGBoost) analysis were further conducted to identify the potential diagnostic biomarker. A receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic performance of the identified potential biomarker.RESULTS: A total of 455 metabolites were detected by LC-MS analysis. PCA and OPLS-DA demonstrated a significant difference between AAV patients with renal involvement and healthy controls, and 135 differentially expressed metabolites were selected, with 121 upregulated and 14 downregulated. Ninety-two metabolic pathways were annotated and enriched based on the KEGG database. N-acetyl-L-leucine, Acetyl-DL-Valine, 5-hydroxyindole-3-acetic acid, and the combination of 1-methylhistidine and Asp-phe could accurately distinguish AAV patients with renal involvement from healthy controls. And 1-methylhistidine was found to be significantly associated with the progression and prognosis of AAV with renal impairment. Amino acid metabolism exhibits significant alternations in AAV with renal involvement.CONCLUSION: This study identified metabolomic differences between AAV patients with renal involvement and non-AAV individuals. Metabolites that could accurately distinguish patients with AAV renal impairment from healthy controls in this study, and metabolites that were significantly associated with disease progression and prognosis were screened out. Overall, this study provides information on changes in metabolites and metabolic pathways for future studies of AAV-related kidney damage and lays a foundation for the exploration of new biomarkers of AAV-related kidney damage.PMID:36942002 | PMC:PMC10024486 | DOI:10.7717/peerj.15051

Mol Ecol Resour. 2023 Mar 20. doi: 10.1111/1755-0998.13786. Online ahead of print.ABSTRACTAlthough being famous for sequestering milkweed cardenolides, the mechanism of sequestration and where cardenolides are localized in caterpillars of the monarch butterfly (Danaus plexippus, Lepidoptera: Danaini) is still unknown. While monarchs tolerate cardenolides by a resistant Na+ /K+ -ATPase, it is unclear how closely related species such as the non-sequestering common crow butterfly (Euploea core, Lepidoptera: Danaini) cope with these toxins. Using novel atmospheric-pressure scanning microprobe matrix-assisted laser/desorption ionization mass spectrometry imaging, we compared the distribution of cardenolides in caterpillars of D. plexippus and E. core. Specifically, we tested at which physiological scale quantitative differences between both species are mediated and how cardenolides distribute across body tissues. Whereas D. plexippus sequestered most cardenolides from milkweed (Asclepias curassavica), no cardenolides were found in the tissues of E. core. Remarkably, quantitative differences already manifest in the gut lumen: while monarchs retain and accumulate cardenolides above plant concentrations, the toxins are degraded in the gut lumen of crows. We visualized cardenolide transport over the monarch midgut epithelium and identified integument cells as the final site of storage where defenses might be perceived by predators. Our study provides molecular insight into cardenolide sequestration and highlights the great potential of mass spectrometry imaging for understanding the kinetics of multiple compounds including endogenous metabolites, plant toxins, or insecticides in insects.PMID:36941779 | DOI:10.1111/1755-0998.13786

Nat Med. 2023 Mar 20. doi: 10.1038/s41591-023-02248-0. Online ahead of print.ABSTRACTMultiomic profiling can reveal population heterogeneity for both health and disease states. Obesity drives a myriad of metabolic perturbations and is a risk factor for multiple chronic diseases. Here we report an atlas of cross-sectional and longitudinal changes in 1,111 blood analytes associated with variation in body mass index (BMI), as well as multiomic associations with host polygenic risk scores and gut microbiome composition, from a cohort of 1,277 individuals enrolled in a wellness program (Arivale). Machine learning model predictions of BMI from blood multiomics captured heterogeneous phenotypic states of host metabolism and gut microbiome composition better than BMI, which was also validated in an external cohort (TwinsUK). Moreover, longitudinal analyses identified variable BMI trajectories for different omics measures in response to a healthy lifestyle intervention; metabolomics-inferred BMI decreased to a greater extent than actual BMI, whereas proteomics-inferred BMI exhibited greater resistance to change. Our analyses further identified blood analyte-analyte associations that were modified by metabolomics-inferred BMI and partially reversed in individuals with metabolic obesity during the intervention. Taken together, our findings provide a blood atlas of the molecular perturbations associated with changes in obesity status, serving as a resource to quantify metabolic health for predictive and preventive medicine.PMID:36941332 | DOI:10.1038/s41591-023-02248-0

Signal Transduct Target Ther. 2023 Mar 20;8(1):132. doi: 10.1038/s41392-023-01399-3.ABSTRACTMetabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks of diseases. Metabolite signatures that have close proximity to subject's phenotypic informative dimension, are useful for predicting diagnosis and prognosis of diseases as well as monitoring treatments. The lack of early biomarkers could lead to poor diagnosis and serious outcomes. Therefore, noninvasive diagnosis and monitoring methods with high specificity and selectivity are desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool for metabolic biomarker and pathway analysis, for revealing possible mechanisms of human various diseases and deciphering therapeutic potentials. It could help identify functional biomarkers related to phenotypic variation and delineate biochemical pathways changes as early indicators of pathological dysfunction and damage prior to disease development. Recently, scientists have established a large number of metabolic profiles to reveal the underlying mechanisms and metabolic networks for therapeutic target exploration in biomedicine. This review summarized the metabolic analysis on the potential value of small-molecule candidate metabolites as biomarkers with clinical events, which may lead to better diagnosis, prognosis, drug screening and treatment. We also discuss challenges that need to be addressed to fuel the next wave of breakthroughs.PMID:36941259 | DOI:10.1038/s41392-023-01399-3

Nan Fang Yi Ke Da Xue Xue Bao. 2023 Mar 20;43(3):443-453. doi: 10.12122/j.issn.1673-4254.2023.03.15.ABSTRACTOBJECTIVE: To identify potential diagnostic biomarkers of colorectal cancer (CRC) using serum metabolomic technology for minimally invasive and efficient screening for CRC.METHODS: Serum samples from 79 healthy individuals and 82 CRC patients were analyzed by metabolomics using ultra-high-performance liquid chromatography-tandem highresolution mass spectrometry (UHPLC-HRMS). The differential metabolites between the two groups were analyzed using principal component analysis and orthogonal partial least squares discriminant analysis (OPLS-DA). Receiver operating characteristic curve (ROC) analysis was performed to identify the differential metabolites with good diagnostic performance (AUC>0.80) for CRC, and targeted bile acid metabolomics was used to verify the selected bile acids as biomarkers.RESULTS: Serum metabolic profiles differed significantly between the healthy individuals and CRC patients, and a total of 82 differential metabolites (mostly fatty acids and glycerophospholipids) were selected. ROC analysis identified 10 differential metabolites, including adenine, bilirubin, ACar 12:0, ACar 10:1, ACar 9:0, PC 18:2e, deoxycholic acid, chenodeoxycholic acid, ACar 14:1 and palmitoylcarnitine. One of these metabolites was significantly up-regulated and 9 were down-regulated in the serum of CRC patients (P < 0.05). Multivariate ROC analysis with support vector machine algorithm showed that the biomarker panel consisting of 7 differential metabolites had an AUC of 0.94 for CRC diagnosis. The results of targeted bile acid metabolomics were consistent with those of untargeted metabolomics. The serum levels of deoxycholic acid and chenodeoxycholic acid were significantly down-regulated in patients with CRC as compared with the healthy individuals (P < 0.05).CONCLUSION: Metabolic disorders of fatty acids and glycerophospholipids are closely related wigh tumorigenesis of CRC. Ten differential metabolites show good performance for CRC diagnosis, and the panel consisting 7 of these metabolites has important diagnostic value for CRC. Deoxycholic acid and chenodeoxycholic acid may serve as potential diagnostic biomarkers of CRC.PMID:37087590 | DOI:10.12122/j.issn.1673-4254.2023.03.15

Acta Trop. 2023 Mar 18:106875. doi: 10.1016/j.actatropica.2023.106875. Online ahead of print.ABSTRACTHepatic alveolar echinococcosis (AE) and cystic echinococcosis (CE) are severe helminthic zoonoses and leading causes of parasitic liver damage. They pose a high mortality risk due to invisible clinical signs, especially at the early inactive stage. However, the specific metabolic profiles induced by inactive AE and CE lesions remain largely unclear. Therefore, we used gas chromatography-mass spectrometry-based metabolomic profiling to identify the global metabolic variations in AE and CE patient sera to differentiate between the two diseases and reveal the mechanisms underlying their pathogenesis. In addition, specific serum biomarkers of inactive hepatic AE and CE were screened using receiver operating curves, which can contribute to the clinical diagnosis of both diseases, especially in the earlier phase. These differential metabolites are involved in glycine, serine, tyrosine, and phenylalanine metabolism. Further analysis of key metabolic pathways showed that inactive AE lesions strongly alter amino acid metabolism in the host. CE lesions have an altered metabolism of oxidative stress response. These changes suggest these metabolite-associated pathways can serve as biomarkers to distinguish individuals with inactive AE and CE from healthy populations. This study also investigated the differences in serum metabolic profiles in patients with CE and AE. The biomarkers identified belonged to different metabolic pathways, including lipid, carnitine, androgen, and bile acid metabolism. Taken together, by investigating the different phenotypes of CE and AE with metabolomic profiling, serum biomarkers facilitating early diagnosis were identified.PMID:36940858 | DOI:10.1016/j.actatropica.2023.106875

J Adv Res. 2023 Mar 18:S2090-1232(23)00086-3. doi: 10.1016/j.jare.2023.03.004. Online ahead of print.ABSTRACTINTRODUCTION: The glymphatic system offers a perivascular pathway for the clearance of pathological proteins and metabolites to optimize neurological functions. Glymphatic dysfunction plays a pathogenic role in Parkinson's disease (PD); however, the molecular mechanism of glymphatic dysfunction in PD remains elusive.OBJECTIVE: To explore whether matrix metalloproteinase-9 (MMP-9)-mediated β-dystroglycan (β-DG) cleavage is involved in the regulation of aquaporin-4 (AQP4) polarity-mediated glymphatic system in PD.METHODS: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and A53T mice were used in this study. The glymphatic function was evaluated using ex vivo imaging. TGN-020, an AQP4 antagonist, was administered to investigate the role of AQP4 in glymphatic dysfunction in PD. GM6001, an MMP-9 antagonist, was administered to investigate the role of the MMP-9/β-DG pathway in regulating AQP4. The expression and distribution of AQP4, MMP-9, and β-DG were assessed using western blotting, immunofluorescence, and co-immunoprecipitation. The ultrastructure of basement membrane (BM)-astrocyte endfeet was detected using transmission electron microscopy. Rotarod and open-field tests were performed to evaluate motor behavior.RESULTS: Perivascular influx and efflux of cerebral spinal fluid tracers were reduced in MPTP-induced PD mice with impaired AQP4 polarization. AQP4 inhibition aggravated reactive astrogliosis, glymphatic drainage restriction, and dopaminergic neuronal loss in MPTP-induced PD mice. MMP-9 and cleaved β-DG were upregulated in both MPTP-induced PD and A53T mice, with reduced polarized localization of β-DG and AQP4 to astrocyte endfeet. MMP-9 inhibition restored BM-astrocyte endfeet-AQP4 integrity and attenuated MPTP-induced metabolic perturbations and dopaminergic neuronal loss.CONCLUSION: AQP4 depolarization contributes to glymphatic dysfunction and aggravates PD pathologies, and MMP-9-mediated β-DG cleavage regulates glymphatic function through AQP4 polarization in PD, which may provide novel insights into the pathogenesis of PD.PMID:36940850 | DOI:10.1016/j.jare.2023.03.004

Nutrition. 2023 Feb 10;110:112002. doi: 10.1016/j.nut.2023.112002. Online ahead of print.ABSTRACTNutrigenetics and nutrigenomics, combined with the omics technologies, are a demanding and an increasingly important field in personalizing nutrition-based care to understand an individual's response to nutrition-guided therapy. Omics is defined as the analysis of the large data sets of the biological system featuring transcriptomics, proteomics, and metabolomics and providing new insights into cell regulation. The effect of combining nutrigenetics and nutrigenomics with omics will give insight into molecular analysis, as human nutrition requirements vary per individual. Omics measures modest intraindividual variability and is critical to exploit these data for use in the development of precision nutrition. Omics, combined with nutrigenetics and nutrigenomics, is instrumental in the creation of goals for improving the accuracy of nutrition evaluations. Although dietary-based therapies are provided for various clinical conditions such as inborn errors of metabolism, limited advancement has been done to expand the omics data for a more mechanistic understanding of cellular networks dependent on nutrition-based expression and overall regulation of genes. The greatest challenge remains in the clinical sector to integrate the current data available, overcome the well-established limits of self-reported methods in research, and provide omics data, combined with nutrigenetics and nutrigenomics research, for each individual. Hence, the future seems promising if a design for personalized, nutrition-based diagnosis and care can be implemented practically in the health care sector.PMID:36940623 | DOI:10.1016/j.nut.2023.112002

Talanta. 2023 Mar 11;258:124446. doi: 10.1016/j.talanta.2023.124446. Online ahead of print.ABSTRACTDoping control is essential for sports, and untargeted detection of doping agents (UDDA) is the holy grail for anti-doping strategies. The present study examined major factors impacting UDDA with metabolomic data processing, including the use of blank samples, signal-to-noise ratio thresholds, and the minimum chromatographic peak intensity. Contrary to data processing in metabolomics studies, both blank sample use (either blank solvent or plasma) and marking of background compounds were found to be unnecessary for UDDA in biological samples, the first such report to the authors' knowledge. The minimum peak intensity required to detect chromatographic peaks affected the limit of detection (LOD) and data processing time for untargeted detection of 57 drugs spiked into equine plasma. The ratio of the mean (ROM) of the extracted ion chromatographic peak area of a compound in the sample group (SG) to that in the control group (CG) impacted its LOD, and a small ROM value such as 2 is recommended for UDDA. Mathematical modeling of the required signal-to-noise ratio (S/N) for UDDA provided insights into the effect of the number of samples in the SG, the number of positive samples, and the ROM on the required S/N, highlighting the power of mathematics in addressing issues in analytical chemistry. The UDDA method was validated by its successful identification of untargeted doping agents in real-world post-competition equine plasma samples. This advancement in UDDA methodology will be a useful addition to the arsenal of approaches used to combat doping in sports.PMID:36940570 | DOI:10.1016/j.talanta.2023.124446

Mar Environ Res. 2023 Mar 15;187:105944. doi: 10.1016/j.marenvres.2023.105944. Online ahead of print.ABSTRACTWhile offshore wind power has support from countries around the world, studies show that offshore wind farms (OWFs) may affect marine organisms. Environmental metabolomics is a high-throughput method that provides a snapshot of an organism's metabolic state. To elucidate the effects of OWFs on aquatic organisms, we studied, in situ, Crassostrea gigas and Mytilus edulis attached within and outside of OWFs and their reef areas. Our results show that epinephrine, sulphaniline, and inosine 5'-monophosphate were significantly increased and L-carnitine was significantly reduced in both Crassostrea and Mytilus species from the OWFs. This may be related to immune response, oxidative stress, energy metabolism and osmotic pressure regulation of aquatic organisms. Our study shows that active selection of biological monitoring methods for risk assessment is necessary and that metabolomics of attached shellfish is useful in elucidating the metabolic pathways of aquatic organisms in OWFs.PMID:36940557 | DOI:10.1016/j.marenvres.2023.105944

J Agric Food Chem. 2023 Mar 20. doi: 10.1021/acs.jafc.2c08864. Online ahead of print.ABSTRACTAreca catechu L., of the Arecaceae family, is widely distributed in tropical Asia. In A. catechu, the extracts and compounds, including flavonoids, have various pharmacological activities. Although there are many studies of flavonoids, the molecular mechanism of their biosynthesis and regulation remains unclear in A. catechu. In this study, 331 metabolites were identified from the root, stem, and leaf of A. catechu using untargeted metabolomics, including 107 flavonoids, 71 lipids, 44 amino acids and derivatives, and 33 alkaloids. The transcriptome analysis identified 6119 differentially expressed genes, and some were enriched in the flavonoid pathway. To analyze the biosynthetic mechanism of the metabolic differences in A. catechu tissues, 36 genes were identified through combined transcriptomic and metabolomic analysis, in which glycosyltransferase genes Acat_15g017010 and Acat_16g013670 were annotated as being involved in the glycosylation of kaempferol and chrysin by their expression and in vitro activities. Flavonoid biosynthesis could be regulated by the transcription factors, AcMYB5 and AcMYB194. This study laid a foundation for further research on the flavonoid biosynthetic pathway of A. catechu.PMID:36940468 | DOI:10.1021/acs.jafc.2c08864

J Agric Food Chem. 2023 Mar 20. doi: 10.1021/acs.jafc.2c08654. Online ahead of print.ABSTRACTIn this study, the soil effect on the micro-component composition of Nero d'Avola wines obtained from different locations was investigated through 1H NMR-based metabolomics. Two different approaches were applied: the targeted (TA) and the non-targeted one (NTA). The former differentiated the wines by profiling (i.e., by identifying and quantifying) a number of different metabolites. The latter provided wine fingerprinting by processing the entire spectra with multivariate statistical analysis. NTA also allowed investigation of the hydrogen bond network inside wines via the analysis of 1H NMR chemical shift dispersions. Results showed that the differences among wines were due not only to the concentrations of various analytes but also to the characteristics of the H-bond network where different solutes were involved. The H-bond network affects both gustatory and olfactory perceptions by modulating the way how solutes interact with the human sensorial receptors. Moreover, the aforementioned H-bond network is also related to the soil properties from which the grapes were taken. Therefore, the present study can be considered a good attempt to investigate terroir, i.e., the relationship between wine quality and soil characteristics.PMID:36940311 | DOI:10.1021/acs.jafc.2c08654

Phenomics. 2022 Oct 27;3(1):34-49. doi: 10.1007/s43657-022-00069-8. eCollection 2023 Feb.ABSTRACTEpoxyeicosatrienoic acids (EETs) have pleiotropic endogenous cardiovascular protective effects and can be hydrolyzed to the corresponding dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Heart failure with preserved ejection fraction (HFpEF) has shown an increased prevalence and worse prognosis over the decades. However, the role of sEH activity in HFpEF remains unclear. We enrolled 500 patients with HFpEF and 500 healthy controls between February 2010 and March 2016. Eight types of sEH-related eicosanoids were measured according to target metabolomics, and their correlation with clinical endpoints was also analyzed. The primary endpoint was cardiac mortality, and the secondary endpoint was a composite of cardiac events, including heart failure (HF) readmission, cardiogenic hospitalization, and all-cause mortality. Furthermore, the effect of sEH inhibitors on cardiac diastolic function in HFpEF was investigated in vivo and in vitro. Patients with HFpEF showed significantly enhanced EET degradation by the sEH enzyme compared with healthy controls. More importantly, sEH activity was positively correlated with cardiac mortality in patients with HFpEF, especially in older patients with arrhythmia. A consistent result was obtained in the multiple adjusted models. Decreased sEH activity by the sEH inhibitor showed a significant effective effect on the improvement of cardiac diastolic function by ameliorating lipid disorders in cardiomyocytes of HFpEF mouse model. This study demonstrated that increased sEH activity was associated with cardiac mortality in patients with HFpEF and suggested that sEH inhibition could be a promising therapeutic strategy to improve diastolic cardiac function. Clinical trial identifier: NCT03461107 (https://clinicaltrials.gov).SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-022-00069-8.PMID:36939801 | PMC:PMC9883375 | DOI:10.1007/s43657-022-00069-8

Phenomics. 2022 Oct 10;2(6):363-382. doi: 10.1007/s43657-022-00073-y. eCollection 2022 Dec.ABSTRACTSkin is a complex ecosystem colonized by millions of microorganisms, including bacteria, fungi, and viruses. Skin microbiota is believed to exert critical functions in maintaining host skin health. Profiling the structure of skin microbial community is the first step to overview the ecosystem. However, the community composition is highly individualized and extremely complex. To explore the fundamental factors driving the complexity of the ecosystem, namely the selection pressures, we review the present studies on skin microbiome from the perspectives of ecology. This review summarizes the following: (1) the composition of substances/nutrients in the cutaneous ecological environment that are derived from the host and the environment, highlighting their proposed function on skin microbiota; (2) the features of dominant skin commensals to occupy ecological niches, through self-adaptation and microbe-microbe interactions; (3) how skin microbes, by their structures or bioactive molecules, reshape host skin phenotypes, including skin immunity, maintenance of skin physiology such as pH and hydration, ultraviolet (UV) protection, odor production, and wound healing. This review aims to re-examine the host-microbe interactions from the ecological perspectives and hopefully to give new inspiration to this field.PMID:36939800 | PMC:PMC9712873 | DOI:10.1007/s43657-022-00073-y

Invest Ophthalmol Vis Sci. 2023 Mar 1;64(3):28. doi: 10.1167/iovs.64.3.28.ABSTRACTPURPOSE: Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles of patients with intermediate AMD using untargeted metabolomics.METHODS: We performed metabolomics using high-resolution liquid chromatography mass spectrometry on the vitreous humor of 31 patients with intermediate AMD and 30 controls who underwent vitrectomy for epiretinal membrane with or without cataract surgery. Univariate analyses after false discovery rate correction were performed to discriminate the metabolites and identify the significant metabolites of intermediate AMD. For biologic interpretation, enrichment and pathway analysis were conducted using MetaboAnalyst 5.0.RESULTS: Of the 858 metabolites analyzed in the vitreous humor, 258 metabolites that distinguished patients with AMD from controls were identified (P values < 0.05). Ascorbic acid and uric acid levels increased in the AMD group (all P values < 0.05). The acyl carnitines, such as acetyl L-carnitine (1.37-fold), and fatty amides, such as anandamide (0.9-fold) and docosanamide (0.67-fold), were higher in patients with intermediate AMD. In contrast, nicotinamide (-0.55-fold), and succinic acid (-1.69-fold) were lower in patients with intermediate AMD. The metabolic pathway related oxidation of branched chain fatty acids and carnitine synthesis showed enrichment.CONCLUSIONS: Multiple metabolites related to fatty amides and acyl carnitine were found to be increased in the vitreous humor of patients with intermediate AMD, whereas succinic acid and nicotinamide were reduced, suggesting that altered metabolites related to fatty amides and acyl carnitines and energy metabolism may be implicated in the etiology of AMD.PMID:36939720 | DOI:10.1167/iovs.64.3.28