PubMed

Food Funct. 2023 Mar 21. doi: 10.1039/d2fo04085a. Online ahead of print.ABSTRACTTo investigate the prebiotic potential of two Laminaria japonica polysaccharide (LJP) fractions with different molecular weights and structures, we conducted in vitro simulated digestion and fermentation with hyperlipidemia-associated human gut microbiota. The results indicated that the LJP fraction with higher molecular weight (HLJP) appeared to have a more complex monosaccharide composition and microstructure than did the LJP fraction with lower molecular weight (LLJP), and both fractions could not be digested by in vitro simulated digestion. After in vitro fermentation, HLJP generated more short-chain fatty acids (SCFAs) and showed stronger ability to regulate core metabolites. Intriguingly, LLJP is better at promoting the proliferation of Akkermansiaceae, while HLJP is more effective in reducing the Firmicutes/Bacteroidetes ratio and increasing the content of Bacteroidaceae and Tannerellaceae. The present study indicates that LLJP and HLJP may have probiotic effects through different approaches and these differences may be related to the molecular weight and structure of the polysaccharides.PMID:36943742 | DOI:10.1039/d2fo04085a

Microbiol Spectr. 2023 Mar 21:e0469122. doi: 10.1128/spectrum.04691-22. Online ahead of print.ABSTRACTOuter membrane vesicles (OMVs) are a primary means of communication for Gram-negative bacteria. The specific role of vesicle components in cellular communication and how components are packaged are still under investigation, but a correlation exists between OMV biogenesis and content. The two primary mechanisms of OMV biogenesis are membrane blebbing and explosive cell lysis, and vesicle content is based on the biogenesis mechanism. Hypervesiculation, which can be induced by stress conditions, also influences OMV content. Norovirus interaction with Enterobacter cloacae induces stress responses leading to increased OMV production and changes in DNA content, protein content, and vesicle size. The presence of genomic DNA and cytoplasmic proteins in these OMVs suggests some of the vesicles are formed by explosive cell lysis, so reduction or loss of these components indicates a shift away from this mechanism of biogenesis. Based on this, further investigation into bacterial stability and OMV content was conducted. Results showed that norovirus induced a dramatic shift in OMV lipid content. Specifically, the increased accumulation of phospholipids is associated with increased blebbing, thereby supporting previous observations that noroviruses shift the mechanism of OMV biogenesis. Slight differences in OMV metabolite content were also observed. While norovirus induced changes in OMV content, it did not change the lipid content of the bacterial outer membrane or the metabolite content of the bacterial cell. Overall, these results indicate that norovirus induces significant changes to OMV lipid architecture and cargo, which may be linked to a change in the mechanism of vesicle biogenesis. IMPORTANCE Extracellular vesicles from commensal bacteria are recognized for their importance in modulating host immune responses, and vesicle content is related to their impact on the host. Therefore, understanding how vesicles are formed and how their content shifts in response to stress conditions is necessary for elucidating their downstream functions. Our recent work has demonstrated that interactions between noroviruses and Enterobacter cloacae induce bacterial stress responses leading to hypervesiculation. In this article, we characterize and compare the lipid and metabolomic cargo of E. cloacae vesicles generated in the presence and absence of norovirus and show that viral interactions induce significant changes in vesicle content. Furthermore, we probe how these changes and changes to the bacterial cell may be indicative of a shift in the mechanism of vesicle biogenesis. Importantly, we find that noroviruses induce significant changes in vesicle lipid architecture and cargo that may be responsible for the immunogenic activity of these vesicles.PMID:36943087 | DOI:10.1128/spectrum.04691-22

Microbiol Spectr. 2023 Mar 21:e0333022. doi: 10.1128/spectrum.03330-22. Online ahead of print.ABSTRACTThe Integrative Human Microbiome Project and other cohort studies have indicated that inflammatory bowel disease is accompanied by dysbiosis of gut microbiota, decreased production of secondary bile acids, and increased levels of primary bile acids. Secondary bile acids, such as ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), have been reported to be anti-inflammatory, yet it remains to be studied whether introducing selected bacteria strains to restore bile acid metabolism of the gut microbiome can alleviate intestinal inflammation. In this study, we screened human gut bacterial strains for bile acid metabolism and designed a consortium of three species, including Clostridium AP sp000509125, Bacteroides ovatus, and Eubacterium limosum, and named it BAC (bile acid consortium). We showed that the three-strain gut bacterial consortium BAC is capable of converting conjugated primary bile acids taurochenodeoxycholic acid and glycochenodeoxycholic acid to secondary bile acids UDCA and LCA in vitro. Oral gavage treatment with BAC in mice resulted in protective effects against dextran sulfate sodium (DSS)-induced colitis, including reduced weight loss and increased colon length. Furthermore, BAC treatment increased the fecal level of bile acids, including UDCA and LCA. BAC treatment enhanced intestinal barrier function, which may be attributed to the increased activation of the bile acid receptor TGR5 by secondary bile acids. Finally, we examined the remodeling of gut microbiota by BAC treatment. Taken together, the three-strain gut bacterial consortium BAC restored the dysregulated bile acid metabolism and alleviated DSS-induced colitis. Our study provides a proof-of-concept demonstration that a rationally designed bacterial consortium can reshape the metabolism of the gut microbiome to treat diseases. IMPORTANCE Secondary bile acids have been reported to be anti-inflammatory, yet it remains to be studied whether introducing selected bacteria strains to restore bile acid metabolism of the gut microbiome can alleviate intestinal inflammation. To address this gap, we designed a consortium of human gut bacterial strains based on their metabolic capacity to produce secondary bile acids UDCA and LCA, and we evaluated the efficacy of single bacterial strains and the bacterial consortium in treating the murine colitis model. We found that oral gavage of the bacterial consortium to mice restored secondary bile acid metabolism to increase levels of UDCA and LCA, which induced the activation of TGR5 to improve gut-barrier integrity and reduced the inflammation in murine colitis. Overall, our study demonstrates that rationally designed bacterial consortia can reshape the metabolism of the gut microbiome and provides novel insights into the application of live biotherapeutics for treating IBD.PMID:36943054 | DOI:10.1128/spectrum.03330-22

Biomed Chromatogr. 2023 Mar 21:e5620. doi: 10.1002/bmc.5620. Online ahead of print.ABSTRACTCitronella is used as a spice and traditional herbal medicine. Dried citronella is easy to store and transport, and it is unclear whether dried citronella has increased or decreased medicinal components compared to fresh citronella. In the present study, various metabolites in fresh and dry citronella were detected using a widely targeted metabolomics strategy. we identified 712 metabolites, and classified as 31 categories, and discovered 132 flavonoids. After the drying of citronella, the contents of most kinds of flavonoids increased, but the contents of amino acids, organic acids and vitamins decreased, and the content of quercetin increased significantly. Therefore, the medicinal value of citronella after drying treatment may be increased, but the nutritional value of amino acids and vitamins may be decreased. The results of this study may serve as a new theoretical reference for deal with citronella and promote the nutrition and medicinal chemical composition of citronella.PMID:36942894 | DOI:10.1002/bmc.5620

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