PubMed

Anal Chim Acta. 2023 Oct 23;1279:341848. doi: 10.1016/j.aca.2023.341848. Epub 2023 Sep 27.ABSTRACTBACKGROUND: Recent increase in public acceptance of cannabis as a natural medical alternative for certain neurological pathologies has led to its approval in different regions of the world. However, due to its previous illegal background, little research has been conducted around its biochemical insights. Therefore, in the current framework, metabolomics may be a suitable approach for deepening the knowledge around this plant species. Nevertheless, experimental methods in metabolomics must be carefully handled, as slight modifications can lead to metabolomic coverage loss. Hence, the main objective of this work was to optimise an analytical method for appropriate untargeted metabolomic screening of cannabis.RESULTS: We present an empirically optimised experimental procedure through which the broadest metabolomic coverage was obtained, in which extraction solvents for metabolite isolation, chromatographic columns for LC-qOrbitrap analysis and plant-representative biological tissues were compared. By exploratory means, it was determined that the solvent combination composed of CHCl3:H2O:CH3OH (2:1:1, v/v) provided the highest number of features from diverse chemical classes, as it was a two-phase extractant. In addition, a reverse phase 2.6 μm C18 100 Å (150 × 3 mm) chromatographic column was determined as the appropriate choice for adequate separation and further detection of the diverse metabolite classes. Apart from that, overall chromatographic peak quality provided by each column was observed and the need for batch correction methods through quality control (QC) samples was confirmed. At last, leaf and flower tissues resulted to provide complementary metabolic information of the plant, to the detriment of stem tissue, which resulted to be negligible.SIGNIFICANCE: It was concluded that the optimised experimental procedure could significantly ease the path for future research works related to cannabis metabolomics by LC-HRMS means, as the work was based on previous plant metabolomics literature. Furthermore, it is crucial to highlight that an optimal analytical method can vary depending on the main objective of the research, as changes in the experimental factors can lead to different outcomes, regardless of whether the results are better or worse.PMID:37827627 | DOI:10.1016/j.aca.2023.341848

Anal Chim Acta. 2023 Oct 23;1279:341809. doi: 10.1016/j.aca.2023.341809. Epub 2023 Sep 8.ABSTRACTIntracellular metabolic profiling reveals real-time metabolic information useful for the study of underlying mechanisms of cells in particular conditions such as drug resistance. However, mass spectrometry (MS), one of the leading metabolomics technologies, usually requires a large number of cells and complex pretreatments. Surface enhanced Raman scattering (SERS) has an ultrahigh detection sensitivity and specificity, favorable for metabolomics analysis. However, some targeted SERS methods focus on very limited metabolite without global bioprofiling, and some label-free approaches try to fingerprint the metabolic response based on whole SERS spectral classification, but comprehensive interpretation of biological mechanisms was lacking. (95) RESULTS: We proposed a label-free SERS technique for intracellular metabolic profiling in complex cellular lysates within 3 min. We first compared three kinds of cellular lysis methods and sonication lysis shows the highest extraction efficiency of metabolites. To obtain comprehensive metabolic information, we collected a spectral set for each sample and further qualified them by the Pearson correlation coefficient (PCC) to calculate how many spectra should be acquired at least to gain the adequate information from a statistical and global view. In addition, according to our measurements with 10 pure metabolites, we can understand the spectra acquired from complex cellular lysates of different cell lines more precisely. Finally, we further disclosed the variations of 22 SERS bands in enzalutamide-resistant prostate cancer cells and some are associated with the androgen receptor signaling activity and the methionine salvage pathway in the drug resistance process, which shows the same metabolic trends as MS. (149) SIGNIFICANCE: Our technique has the capability to capture the intracellular metabolic fingerprinting with the optimized lysis approach and spectral set collection, showing high potential in rapid, sensitive and global metabolic profiling in complex biosamples and clinical liquid biopsy. This gives a new perspective to the study of SERS in insightful understanding of relevant biological mechanisms. (54).PMID:37827617 | DOI:10.1016/j.aca.2023.341809

J Proteome Res. 2023 Oct 12. doi: 10.1021/acs.jproteome.3c00255. Online ahead of print.ABSTRACTPulmonary arterial hypertension (PAH) is a severe, multifactorial, and frequently misdiagnosed disorder. The aim of this observational study was to compare the plasma and urine metabolomic profiles of PAH patients and healthy control subjects. Plasma and urine metabolomic profiles were analyzed using the GC-MS technique. Correlations between metabolite levels and clinical parameters among PAH patients, as well as the between-group differences, were evaluated. The linear discriminant analysis model, which allows for subject classification in terms of PAH with the highest possible precision, was developed and proposed. Plasma pyruvic acid, cholesterol, threonine, urine 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid, butyric acid, 1,2-benzenediol, glucoheptonic acid, and 2-oxo-glutaric acid were found to build a relatively accurate classification model for PAH patients. The model reached an accuracy of 91% and significantly improved subject classification (OR = 119 [95% CI: 20.3-698.3], p < 0.0001). Five metabolites were detected in urine that provide easily available and noninvasive tests as compared to right heart catheterization. The selected panel of metabolites has potential for early recognition of patients with dyspnea and faster referral to a reference center.PMID:37827514 | DOI:10.1021/acs.jproteome.3c00255

J Ethnopharmacol. 2023 Oct 10:117310. doi: 10.1016/j.jep.2023.117310. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Erigeron breviscapus is a common medicine of eight ethnic minorities, including Miao, Naxi, and Yi. As early as the Ming Dynasty (AD 1368-1644), Lanmao's Materia Medica of Southern Yunnan (AD 1436) recorded that the medicine is used for the treatment of "Zuo tan you huan." In modern pharmacological research, Erigeron breviscapus injection is the most commonly used preparation in the treatment of ischemic stroke caused by acute cerebral infarction, but its mechanism of action in the treatment of ischemic stroke is not well understood.AIM OF THE STUDY: In this study, a metabonomics study based on ultraperformance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) was used in investigating the effect of a traditional Chinese medicine preparation Erigeron breviscapus injection on the rat model of focal cerebral ischemia-reperfusion and the affinity of its main components with the targets of mitochondrial apoptotic pathways.MATERIALS AND METHODS: This study used molecular docking technology to verify the effective binding ability of main effective components of Erigeron breviscapus injection to target proteins related to mitochondrial apoptosis pathway. This study developed a metabonomics method based on the ultra-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS) to evaluate the efficacy and study the mechanism of traditional Chinese medicine preparation. With pattern recognition analysis (principal component analysis and partial least squares-discriminate analysis) of urinary metabolites, a clear separation of focal cerebral ischemia-reperfusion model group and healthy control group was achieved.RESULTS: Erigeron breviscapus injection can significantly reduce the area of cerebral infarction, improve tissue morphological lesion in rats, and can increase the number of Nissl bodies. It may be a promoting factor by inhibiting hippocampal nerve cell apoptosis and Bax protein expression and by exerting effects against ischemia reperfusion after the induction of apoptosis. Thus, it plays a role in brain protection. Moreover, it can considerably promote the recovery of neurological deficiency signs in advance. Meanwhile, Erigeron breviscapus decreased malondialdehyde content and T-NOS activity. Its curative effect from strong to weak order: low dose > high dose > medium dose. The representative components of Erigeron breviscapus have good affinity with the active sites of mitochondrial apoptosis-related proteins. Metabolomics found that the potential biomarkers regulated by breviscapine are kynurequinolinic acid, succinylornithine, and leucine proline. It is speculated that it may participate in TRP-kynurequinolinic acid and succinylornithine-urea cycle-NO metabolic pathways.CONCLUSIONS: This paper revealed the potential biomarkers and metabolic pathways regulated by Erigeron breviscapus. It was speculated that the mechanism is related to its inhibition of mitochondrion-mediated apoptosis. Erigeron breviscapus could restore the metabolic profiles of the model animals to normal animal levels. The mechanism may be related to the potential biomarkers of quinolinic acid, succinylornithine, and leucine proline and the metabolic pathways involved. However, the exact mechanism by which Erigeron breviscapus inhibits mitochondrion-mediated apoptosis remains to be further explored.PMID:37827296 | DOI:10.1016/j.jep.2023.117310

Radiother Oncol. 2023 Oct 10:109950. doi: 10.1016/j.radonc.2023.109950. Online ahead of print.ABSTRACTBACKGROUND: Prostate cancer patients treated with radiotherapy are susceptible to acute gastrointestinal (GI) toxicity due to substantial overlap of the intestines with the radiation volume. Due to their intimate relationship with GI toxicity, faecal microbiome and metabolome dynamics during radiotherapy were investigated.MATERIAL & METHODS: This prospective study included 50 prostate cancer patients treated with prostate (bed) only radiotherapy (PBRT) (n = 28) or whole pelvis radiotherapy (WPRT) (n = 22) (NCT04638049). Longitudinal sampling was performed prior to radiotherapy, after 10 fractions, near the end of radiotherapy and at follow-up. Patient symptoms were dichotomized into a single toxicity score. Microbiome and metabolome fingerprints were analyzed by 16S rRNA gene sequencing and ultra-high-performance liquid chromatography hybrid high-resolution mass spectrometry, respectively.RESULTS: The individual α-diversity did not significantly change over time. Microbiota composition (β-diversity) changed significantly over treatment (PERMANOVA p-value = 0.03), but there was no significant difference in stability when comparing PBRT versus WPRT. Levels of various metabolites were significantly altered during radiotherapy. Baseline α-diversity was not associated with any toxicity outcome. Based on the metabolic fingerprint, no natural clustering according to toxicity profile could be achieved.CONCLUSIONS: Radiation dose and treatment volume demonstrated limited effects on microbiome and metabolome fingerprints. In addition, no distinctive signature for toxicity status could be established. There is an ongoing need for toxicity risk stratification tools for diagnostic and therapeutic purposes, but the current evidence implies that the translation of metabolic and microbial biomarkers into routine clinical practice remains challenging.PMID:37827280 | DOI:10.1016/j.radonc.2023.109950

Life Sci. 2023 Oct 10:122166. doi: 10.1016/j.lfs.2023.122166. Online ahead of print.ABSTRACTOvarian cancer presents a significant challenge due to its high rate of chemoresistance, which complicates the effectiveness of drug-response therapy. This study provides a comprehensive metabolomic analysis of ovarian cancer cell lines OVCAR-3 and SK-OV-3, characterizing their distinct metabolic landscapes. Metabolomics coupled with chemometric analysis enabled us to discriminate between the metabolic profiles of these two cell lines. The OVCAR-3 cells, which are sensitive to doxorubicin (DOX), exhibited a preference for biosynthetic pathways associated with cell proliferation. Conversely, DOX-resistant SK-OV-3 cells favored fatty acid oxidation for energy maintenance. Notably, a marked difference in glutathione (GSH) metabolism was observed between these cell lines. Our investigations further revealed that GSH depletion led to a profound change in drug sensitivity, inducing a shift from a cytostatic to a cytotoxic response. The results derived from this comprehensive metabolomic analysis offer potential targets for novel therapeutic strategies to overcome drug resistance. Our study suggests that targeting the GSH pathway could potentially enhance chemotherapy's efficacy in treating ovarian cancer.PMID:37827232 | DOI:10.1016/j.lfs.2023.122166

Am J Pathol. 2023 Oct 10:S0002-9440(23)00366-8. doi: 10.1016/j.ajpath.2023.09.010. Online ahead of print.ABSTRACTBenign prostate hyperplasia (BPH) is caused by the non-malignant enlargement of the transition zone of the prostate gland, leading to lower urinary tract symptoms (LUTS). While current medical treatments are unsatisfactory in many patients, the limited understanding of the mechanisms driving disease progression prevents the development of alternative therapeutic strategies. The probasin-prolactin (Pb-PRL) transgenic mouse recapitulates many histopathological features of human BPH. We here show that these alterations parallel urodynamic disturbance reminiscent of LUTS. Single cell RNA-sequencing analysis of Pb-PRL mouse prostates revealed that their epithelium mainly includes low-androgen signaling cell populations analogous to Club/Hillock cells enriched in the aged human prostate. These intermediate cells are predicted to result from the reprogramming of androgen-dependent luminal cells. Pb-PRL mouse prostates exhibit increased vulnerability to oxidative stress due to reduction of antioxidant enzyme expression. One-month treatment of Pb-PRL mice with Anethole Trithione (ATT), a specific inhibitor of mitochondrial ROS production, reduced prostate weight and voiding frequency. In human BPH-1 epithelial cells, ATT decreased mitochondrial metabolism, cell proliferation and stemness features. ATT prevented the growth of organoids generated by sorted Pb-PRL basal and LSCmed cells, the two major BPH-associated, androgen-independent epithelial cell compartments. Taken together, our results support cell plasticity as a driver of BPH progression and therapeutic resistance to androgen signaling inhibition, and identify antioxidant therapy as a promising treatment of BPH.PMID:37827216 | DOI:10.1016/j.ajpath.2023.09.010

BMC Plant Biol. 2023 Oct 13;23(1):491. doi: 10.1186/s12870-023-04510-6.ABSTRACTBACKGROUND: Hemerocallis citrina Baroni is a traditional medical and edible plant. It is rich in flavonoid compounds, which are a kind of important bioactive components with various health benefits and pharmaceutical value. However, the flavonoid metabolomics profile and the comparison of flavonoid compounds from different parts of H. citrina is scarce.RESULTS: In this study, flavonoid metabolites were investigated from roots, stems, leaves and flowers of H. citrina. A total of 364 flavonoid metabolites were identified by UPLC-MS/MS based widely targeted metabolomics, and the four plant parts showed huge differences at flavonoid metabolic level. Compared to roots, 185, 234, and 119 metabolites accounted for upregulated differential flavonoid metabolites (DFMs) in stems, leaves, and flowers, respectively. Compared to stems, 168 and 29 flavonoid metabolites accounted for upregulated DFMs in leaves and flowers, respectively. Compared to leaves, only 29 flavonoid metabolites accounted for upregulated DFMs in flowers. A number of 35 common flavonoid metabolites were observed among six comparison groups, and each comparison group had its unique differential metabolites. The most abundant flavonoid metabolites in the four parts are flavonols and flavones, followed by flavanones, chalcones, flavanols, flavanonols, anthocyanidins, tannin, and proanthocyanidins. 6,7,8-Tetrahydroxy-5-methoxyflavone, 7,8,3',4'-tetrahydroxyflavone, 1-Hydroxy-2,3,8-trimethoxyxanthone, Farrerol-7-O-glucoside, 3',7-dihydroxy-4'-methoxyflavone, 3,3'-O-Dimethylellagic Acid, 5-Hydroxy-6,7-dimethoxyflavone, Nepetin (5,7,3',4'-Tetrahydroxy-6-methoxyflavone), (2s)-4,8,10-trihydroxy-2-methoxy-1 h,2 h-furo[3,2-a]xanthen-11-one are dominant in roots. Isorhamnetin-3-O-(6''-malonyl)glucoside-7-O-rhamnoside, 7-Benzyloxy-5-hydroxy-3',4'-methylenedioxyflavonoid, 3-Hydroxyphloretin-4'-O-glucoside are dominant in stems. Chrysoeriol-7-O-glucoside, Epicatechin glucoside, Kaempferol-3-O-rhamnoside (Afzelin)(Kaempferin)*, Azaleatin (5-O-Methylquercetin), Chrysoeriol-5-O-glucoside, Nepetin-7-O-glucoside(Nepitrin), 3,5,7,2'-Tetrahydroxyflavone; Datiscetin, Procyanidin B2*, Procyanidin B3*, Procyanidin B1, Isorhamnetin-3-O-(6''-acetylglucoside) are dominant in leaves. kaempferol-3-p-coumaroyldiglucoside, Delphinidin-3-O-sophoroside-5-O-glucoside, Limocitrin-3-O-sophoroside, Kaempferol-3-O-rutinoside(Nicotiflorin), Luteolin-7-O-(6''-malonyl)glucoside-5-O-rhamnoside are dominant in flowers.CONCLUSION: There was significant difference in flavonoid metabolites among different parts of H. citrina. Leaves had relative higher metabolites contents than other parts. This study provided biological and chemical evidence for the different uses of various plant parts of H. citrina, and these informations are important theoretical basis for the food industry, and medical treatment.PMID:37828495 | DOI:10.1186/s12870-023-04510-6

BMC Plant Biol. 2023 Oct 13;23(1):490. doi: 10.1186/s12870-023-04497-0.ABSTRACTBACKGROUND: Arbutus unedo L. is a wild tree of Mediterranean regions used as food and in traditional medicine and important for afforestation programs. There is no detailed information available on the variation of A. unedo leaves metabolome across the seasons. The leaves were analyzed by Proton nuclear magnetic resonance (1 H NMR)-based metabolomics, comparing samples harvested across the seasons and in ten different natural habitats of Sardinia (Italy).RESULTS: Multivariate analysis showed the impact of seasonal variation on the metabolome: glucose and quinic acid increased in summer, while in spring sucrose was accumulated. β-Arbutin, the main known active principle of A. unedo, generally reached the highest concentration in autumn. In winter, O-β-methylglucose, γ-aminobutyric acid (GABA), flavonols (quercetin-3-O-α-rhamnoside, myricetin-3-O-α-rhamnoside, kaempferol-3-O-α-rhamnoside), catechin, and gallocatechin increased. Characteristic metabolomic features were found also for samples collected in different locations. For instance, trees growing at the highest altitude and exposed to lower temperatures produced less flavonols and catechins. The only sample collected on trees growing on limestones, dolomites, and dolomitic limestones type of soil showed generally the highest content of arbutin. The highest phenolics content was found during spring, while samples collected on flowering branches in winter were the ones with the highest flavonoid content. The antioxidant activity was also variated, ranging from 1.3 to 10.1 mg of Trolox equivalents (TE)/mL of extract, and it was positively correlated to both total phenolics and flavonoid content. Winter samples showed the lowest antibacterial activity, while summer and autumn ones exhibited the highest activity (IC50 values ranging from 17.3 to 42.3 µg/mL against Staphylococcal species).CONCLUSION: This work provides 1 H-NMR fingerprinting of A. unedo leaves, elucidating the main metabolites and their variations during seasons. On the basis of arbutin content, autumn could be considered the balsamic period of this taxon. Samples collected in this season were also the most active ones as antibacterial. Moreover, an interesting metabolomic profile enriched in catechins and flavonols was observed in leaves collected in winter on flowering branches which were endowed with high antioxidant potential.PMID:37828439 | DOI:10.1186/s12870-023-04497-0

J Agric Food Chem. 2023 Oct 12. doi: 10.1021/acs.jafc.3c04459. Online ahead of print.ABSTRACTThe pile fermentation process of Fuzhuan brick tea is unique in that it involves preheating without the use of starter cultures. The detailed metabolite changes and their drivers during this procedure are not known. Characterizing these unknown changes that occur in the metabolites and microbes during pile fermentation of Fuzhuan brick tea is important for industrial modernization of this traditional fermented food. Using microbial DNA amplicon sequencing, mass spectrometry-based untargeted metabolomics, and feature-based molecular networking, we herein reveal that significant changes in the microbial community occur before changes in the metabolite profile. These changes were characterized by a decrease in Klebsiella and Aspergillus, alongside an increase in Bacillus and Eurotium. The decrease in lysophosphatidylcholines, unsaturated fatty acids, and some astringent flavan-3-ols and bitter amino acids, as well as the increase in some less astringent flavan-3-ols and sweet or umami amino acids, contributed importantly to the overall changes observed in the metabolite profile. The majority of these changes was caused by bacterial metabolism and the corresponding heat generated by it.PMID:37827989 | DOI:10.1021/acs.jafc.3c04459

Plant J. 2023 Oct 12. doi: 10.1111/tpj.16497. Online ahead of print.ABSTRACTWe have developed a compendium and interactive platform, named Stress Combinations and their Interactions in Plants Database (SCIPDb; http://www.nipgr.ac.in/scipdb.php), which offers information on morpho-physio-biochemical (phenome) and molecular (transcriptome and metabolome) responses of plants to different stress combinations. SCIPDb is a plant stress informatics hub for data mining on phenome, transcriptome, trait-gene ontology, and data-driven research for advancing mechanistic understanding of combined stress biology. We analyzed global phenome data from 939 studies to delineate the effects of various stress combinations on yield in major crops and found that yield was substantially affected under abiotic-abiotic stresses. Transcriptome datasets from 36 studies hosted in SCIPDb identified novel genes, whose roles have not been earlier established in combined stress. Integretome analysis under combined drought-heat stress pinpointed carbohydrate, amino acid, and energy metabolism pathways as the crucial metabolic, proteomic, and transcriptional components in plant tolerance to combined stress. These examples illustrate the application of SCIPDb in identifying novel genes and pathways involved in combined stress tolerance. Further, we showed the application of this database in identifying novel candidate genes and pathways for combined drought and pathogen stress tolerance. To our knowledge, SCIPDb is the only publicly available platform offering combined stress-specific omics big data visualization tools, such as an interactive scrollbar, stress matrix, radial tree, global distribution map, meta-phenome analysis, search, BLAST, transcript expression pattern table, Manhattan plot, and co-expression network. These tools facilitate a better understanding of the mechanisms underlying plant responses to combined stresses.PMID:37824297 | DOI:10.1111/tpj.16497

JMIR Res Protoc. 2023 Oct 12;12:e50546. doi: 10.2196/50546.ABSTRACTBACKGROUND: Mild cognitive impairment (MCI) and Alzheimer's disease (AD) might be more frequent in patients with inflammatory bowel disease (IBD), but the relationship between these 2 entities is yet to be entirely established. Certain blood biomarkers (eg, serum amyloid A [SAA] and serum homocysteine [Hcy], which increase in IBD and MCI; brain-derived neurotrophic factor [BDNF], which decreases in MCI and AD but is not clearly modified in IBD; and S100 calcium-binding protein B [S100B], which increases in the blood-brain barrier and neuronal lesions) might predict the stage of MCI or dementia or progression to a further state. The gut-brain axis (GBA) might be the key to the development of MCI in patients with IBD, along with systemic inflammation and the possible and unknown adverse effects of disease-modifying medication.OBJECTIVE: The aim of this study is to investigate whether GBA interactions play a role in MCI development in patients with IBD.METHODS: A case-control study will be conducted on at least 100 patients diagnosed with IBD, matched with 100 healthy individual controls. The matching will include sex, age, and education. Patients will be fully examined, and a full interview and a neurological and cognitive examination will be performed. The primary clinical outcomes will be cognitive test scores (Montreal Cognitive Assessment, Trail Making Test, Digit Symbol Substitution Test, forward and backward digit span testing). Depression, stress, and anxiety screening will also be performed. Blood samples from all participants will be collected, and aliquots will be immediately stored in a biobank. Primary laboratory outcomes will include serum levels of presumed cognitive dysfunction blood biomarkers SAA, Hcy, S100B, and BDNF. Follow-up will be performed at 12, 24, 36, and 48 months.RESULTS: Data collection started in December 2021 and is ongoing. So far, 53 patients with IBD have been recruited and 50 HC matched. Data collection should end in January 2030. Intermediary analysis will be performed in April 2024. We expect patients with IBD to have lower scores on cognitive testing and a positive correlation between disease length and cognitive impairment level. In addition, the levels of stress, anxiety, and depression should be higher in the IBD group. The serum levels of the 4 biomarkers could correlate or anticorrelate with cognitive scores and serve as predictive factors for MCI or dementia development. A higher level of education, a younger age, the absence of malabsorption, and good disease control might serve as protectors against MCI.CONCLUSIONS: GBA interactions, along with systemic inflammation and the adverse effects of medication, might be a cause of MCI and AD development in patients with IBD. Serum biomarkers could prove cheap and useful predictors of MCI development.TRIAL REGISTRATION: ClinicalTrials.gov NCT05760729; https://clinicaltrials.gov/study/NCT05760729.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50546.PMID:37824197 | DOI:10.2196/50546

Microbiol Spectr. 2023 Oct 12:e0034423. doi: 10.1128/spectrum.00344-23. Online ahead of print.ABSTRACTQingXiaoWuWei decoction (QXWWD) exerts a prominent therapeutic effect on the methicillin-resistant Staphylococcus aureus (MRSA)-induced pneumonia model in mice; however, its pharmacological mechanisms remain unclear. This study aimed to investigate the underlying pharmacological mechanisms of QXWWD in MRSA-induced pneumonia. In the present study, 62 compounds were identified using high-resolution mass spectrometry. Network analysis, leveraging mass spectrometry, pinpointed the infection-linked, immunity-associated, and inflammation-related pathways as predominant targets. QXWWD significantly alleviated MRSA-induced pneumonia in mice and decreased the levels of pro-inflammatory cytokines and chemokines. 16S ribosomal RNA (16S rRNA) sequencing revealed that QXWWD regulated gut microbiota composition in mice with MRSA-induced pneumonia, which correlated with the enrichment of certain short-chain fatty acids (SCFAs)-producing strains. Further analysis with targeted metabolomics confirmed that the acetic, propionic, and butyric acid levels in the mice's serum were elevated significantly after QXWWD treatment. The fecal microbiota transplantation experiment suggested that gut microbiota from QXWWD-treated mice and SCFAs treatment may alleviate MRSA-induced pneumonia. Additionally, the untargeted metabolomic analysis further demonstrated that metabolic remodeling is significantly regulated by the QXWWD, particularly by the enhancement of the citrate cycle. In the case of QXWWD treatment, global transcriptome profiling revealed that genes, such as NLRP12 and CYP1A1, associated with macrophage antibacterial and immune activity, were downregulated. The results revealed that QXWWD regulated metabolic remodeling and macrophage gene expression network via the microbiota-SCFAs axis and thus alleviated MRSA-induced pneumonia in mice.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) colonizes the upper respiratory airways and is resistant to antibiotics. MRSA is a frequently acquired infection in hospital and community settings, including cases of MRSA-induced pneumonia. Multidrug-resistant Staphylococcus aureus and the limited efficacy of antibiotics necessitate alternative strategies for preventing or treating the infection. QingXiaoWuWei decoction (QXWWD) protects against both gut microbiota dysbiosis and MRSA-induced pneumonia. Furthermore, the QXWWD-regulated metabolic remodeling and macrophage gene expression network contribute to its protective effects through the microbiota-short-chain fatty acid axis. The results of this study suggest that QXWWD and its pharmacodynamic compounds might have the potential to prevent and treat pulmonary infections, especially those caused by multidrug-resistant organisms. Our study provides a theoretical basis for the future treatment of pulmonary infectious diseases by manipulating gut microbiota and their metabolites via traditional Chinese medicine.PMID:37823635 | DOI:10.1128/spectrum.00344-23

Mol Plant Pathol. 2023 Oct 12. doi: 10.1111/mpp.13396. Online ahead of print.ABSTRACTRoot-knot nematodes (RKNs) inflict extensive damage to global agricultural production. Intercropping has been identified as a viable agricultural tool for combating RKNs, but the mechanisms by which intercropped plants modulate RKN parasitism are still not well understood. Here, we focus on the cucumber-amaranth intercropping system. We used a range of approaches, including the attraction assay, in vitro RNA interference (RNAi), untargeted metabolomics, and hairy root transformation, to unveil the mechanisms by which weak host plants regulate Meloidogyne incognita chemotaxis towards host plants and control infection. Amaranth roots showed a direct repellence to M. incognita through disrupting its chemotaxis. The in vitro RNAi assay demonstrated that the Mi-flp-1 and Mi-flp-18 genes (encoding FMRFamide-like peptides) regulated M. incognita chemotaxis towards cucumber and controlled infection. Moreover, M. incognita infection stimulated cucumber and amaranth to accumulate distinct metabolites in both root tissues and rhizosphere soils. In particular, naringenin and salicin, enriched specifically in amaranth rhizosphere soils, inhibited the expression of Mi-flp-1 and Mi-flp-18. In addition, overexpression of genes involved in the biosynthesis of pantothenic acid and phloretin, both of which were enriched specifically in amaranth root tissues, delayed M. incognita development in cucumber hairy roots. Together, our results reveal that both the distinct host status and disruption of chemotaxis contribute to M. incognita inhibition in intercropping.PMID:37823341 | DOI:10.1111/mpp.13396

New Phytol. 2023 Oct 12. doi: 10.1111/nph.19298. Online ahead of print.ABSTRACTMeloidogyne enterolobii is an emerging root-knot nematode species that overcomes most of the nematode resistance genes in crops. Nematode effector proteins secreted in planta are key elements in the molecular dialogue of parasitism. Here, we show the MeMSP1 effector is secreted into giant cells and promotes M. enterolobii parasitism. Using co-immunoprecipitation and bimolecular fluorescent complementation assays, we identified glutathione-S-transferase phi GSTFs as host targets of the MeMSP1 effector. This protein family plays important roles in plant responses to abiotic and biotic stresses. We demonstrate that MeMSP1 interacts with all Arabidopsis GSTF. Moreover, we confirmed that the N-terminal region of AtGSTF9 is critical for its interaction, and atgstf9 mutant lines are more susceptible to root-knot nematode infection. Combined transcriptome and metabolome analyses showed that MeMSP1 affects the metabolic pathways of Arabidopsis thaliana, resulting in the accumulation of amino acids, nucleic acids, and their metabolites, and organic acids and the downregulation of flavonoids. Our study has shed light on a novel effector mechanism that targets plant metabolism, reducing the production of plant defence-related compounds while favouring the accumulation of metabolites beneficial to the nematode, and thereby promoting parasitism.PMID:37823217 | DOI:10.1111/nph.19298

Food Sci Nutr. 2023 Aug 10;11(10):6271-6287. doi: 10.1002/fsn3.3567. eCollection 2023 Oct.ABSTRACTChinese yam (Dioscorea opposite Thunb.) has been used as food and medicine to treat diarrhea for thousands of years. This article aimed to elucidate the potential mechanism of Dioscoreae Rhizoma starch in alleviating chronic diarrhea induced by rhubarb based on gut microbiotas and fecal metabolome. The administration of the Dioscoreae Rhizoma aqueous extracts, crude polysaccharides, and starch could improve diarrhea and alleviate intestinal injury in chronic diarrhea rats. The Dioscoreae Rhizoma starch displayed the most apparent effect on regulating intestinal microbiotas by increasing the abundance and diversity of microbiotas. At the genus level, there were 17 changed intestinal microbiotas in model rats, and the treatment with Dioscoreae Rhizoma starch regulated 11 microbiotas. Metabolomics analysis revealed that Dioscoreae Rhizoma starch could regulate abnormal fecal metabolites to alleviate diarrhea, and these metabolites are involved in phenylalanine, tyrosine, and tryptophan biosynthesis; tyrosine metabolism; vitamin B6 metabolism; and purine metabolism. This study will contribute to the further research and development of Dioscoreae Rhizoma starch.PMID:37823173 | PMC:PMC10563677 | DOI:10.1002/fsn3.3567

Food Sci Nutr. 2023 Jul 18;11(10):6199-6212. doi: 10.1002/fsn3.3559. eCollection 2023 Oct.ABSTRACTHuman milk oligosaccharides (HMOs) belong to a group of multifunctional glycans that are abundantly present in human breast milk. While health effects of neutral oligosaccharides have been investigated extensively, a lot remains unknown regarding health effects of acidic oligosaccharides, such as the two sialyllactoses (SLs), 3'sialyllactose (3'SL), and 6'sialyllactose (6'SL). We utilized Caenorhabditis elegans (C. elegans) to investigate the effects of SLs on exercise performance. Using swimming as an endurance-type exercise, we found that SLs decrease exhaustion, signifying an increase in endurance that is strongest for 6'SL. Through an unbiased metabolomics approach, we identified changes in energy metabolism that correlated with endurance performance. Further investigation suggested that these metabolic changes were related to adaptations of muscle mitochondria that facilitated a shift from beta oxidation to glycogenolysis during exercise. We found that the effect of SLs on endurance performance required AMPK- (aak-1/aak-2) and adenosine receptor (ador-1) signaling. We propose a model where SLs alter the metabolic status in the gut, causing a signal from the intestine to the nervous system toward muscle cells, where metabolic adaptation increases exercise performance. Together, our results underline the potential of SLs in exercise-associated health and contribute to our understanding of the molecular processes involved in nutritionally-induced health benefits.PMID:37823127 | PMC:PMC10563706 | DOI:10.1002/fsn3.3559

Front Nutr. 2023 Sep 26;10:1242301. doi: 10.3389/fnut.2023.1242301. eCollection 2023.ABSTRACTRuminants' milk is commonly used for supplying nutrients to infants when breast milk is unavailable or limited. Previous studies have highlighted the differences between ruminants' milk composition, digestion, absorption, and fermentation. However, whether consuming different ruminants' milk impact the appearance of the circulatory blood metabolites in the early postnatal life is not well understood. The analysis conducted here aimed to determine the effect of feeding exclusively whole milk from bovine, caprine or ovine species to pigs, approximately 7 days-old for 15 days, on circulatory blood plasma metabolites. Relative intensities of plasma metabolites were detected using a liquid chromatography-mass spectrometry based metabolomic approach. Seven polar and 83 non-polar (lipids) metabolites in plasma were significantly different (false discovery rate < 0.05) between milk treatments. These included polar metabolites involved in amino acid metabolism and lipids belonging to phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, and triglycerides. Compared to the caprine or bovine milk group, the relative intensities of polar metabolites and unsaturated triglycerides were higher in the peripheral circulation of the ovine milk group. In contrast, relative intensities of saturated triglycerides and phosphatidylcholine were higher in the bovine milk group compared to the ovine or caprine milk group. In addition, correlations were identified between amino acid and lipid intake and their appearance in peripheral blood circulation. The results highlighted that consuming different ruminants' milk influences the plasma appearance of metabolites, especially lipids, that may contribute to early postnatal life development in pigs.PMID:37823089 | PMC:PMC10564076 | DOI:10.3389/fnut.2023.1242301

Exposome. 2023 May 26;3(1):osad006. doi: 10.1093/exposome/osad006.ABSTRACTChildhood obesity is an increasingly severe public health problem, with a prospective impact on health. We propose an exposome approach to identify actionable risk factors for this condition. Our assumption is that relationships between external exposures and outcomes such as rapid growth, overweight, or obesity in children can be better understood through a "meet-in-the-middle" model. This is based on a combination of external and internal exposome-based approaches, that is, the study of multiple exposures (in our case, dietary patterns) and molecular pathways (metabolomics and epigenetics). This may strengthen causal reasoning by identifying intermediate markers that are associated with both exposures and outcomes. Our biomarker-based studies in the STOP consortium suggest (in several ways, including mediation analysis) that branched-chain amino acids (BCAAs) could be mediators of the effect of dietary risk factors on childhood overweight/obesity. This is consistent with intervention and animal studies showing that higher intake of BCAAs has a positive impact on body composition, glycemia, and satiety. Concerning food, of particular concern is the trend of increasing intake of ultra-processed food (UPF), including among children. Several mechanisms have been proposed to explain the impact of UPF on obesity and overweight, including nutrient intake (particularly proteins), changes in appetite, or the role of additives. Research from the Avon Longitudinal Study of Parents and Children cohort has shown a relationship between UPF intake and trajectories in childhood adiposity, while UPF was related to lower blood levels of BCAAs. We suggest that an exposome-based approach can help strengthening causal reasoning and support policies. Intake of UPF in children should be restricted to prevent obesity.PMID:37823001 | PMC:PMC7615122 | DOI:10.1093/exposome/osad006

Front Vet Sci. 2023 Sep 26;10:1273944. doi: 10.3389/fvets.2023.1273944. eCollection 2023.ABSTRACTHexavalent chromium Cr (VI) is one of the most hazardous heavy metals in the environment and is toxic to living organisms causing tissue damage, disruption of the intestinal microbiota and cancer. However, there is little information on the relationship between the Cr (VI) and broiler chickens. The current study was performed to investigate the effect of Cr (VI) on growth performance, serum biochemical analysis, histopathological observations, and metabolomics analysis in broilers. Results show that Cr (VI) exposure significantly decreased the body weight (p < 0.01) and caused liver damages in broilers. With the extension of Cr (VI) action time, the liver appeared obvious pathological changes, including hepatic cord disorder, incomplete hepatocyte additionally, decreased serum biochemical indices of calcium (Ca), phosphorus (P), total protein (TP), phosphatase (ALP), and globin (GLB) significantly (p < 0.01). Moreover, metabolomics analysis indicated that 29 differential metabolites were identified, such as phytosphingosine, L-Serine, 12, 13-DHOME, Alpha-dimorphecolic acid, L-Methionine, L-Phenylalanine, 3-Dehydroshikimate, L-Tyrosine, and N-Acetyl-L-phenylalanine were significantly decreased under the action of Cr (VI) (p < 0.05). These 29 differential metabolites are mainly involved in 35 metabolic pathways, such as aminoacyl-tRNA biosynthesis, phenylalanine metabolism, sphingolipid, and linoleic metabolism. The study revealed that exposure to Cr (VI) resulted in a decrease in growth performance and metabolism, with the hazards and toxicity in broiler chicken. The findings provided new insight and a comprehensive understanding of the relationship between Cr (VI) and broiler chickens.PMID:37822955 | PMC:PMC10562699 | DOI:10.3389/fvets.2023.1273944