PubMed

Int J Epidemiol. 2022 Nov 23:dyac218. doi: 10.1093/ije/dyac218. Online ahead of print.NO ABSTRACTPMID:36416418 | DOI:10.1093/ije/dyac218

Electrophoresis. 2022 Nov 23. doi: 10.1002/elps.202200257. Online ahead of print.ABSTRACTThe goal of integrative top-down proteomics (i.e., two-dimensional gel electrophoresis (2DE) coupled with liquid chromatography and tandem mass spectrometry (LC/MS/MS)) is a routine analytical approach that fully addresses the breadth and depth of proteomes. To accomplish this, there should be no addition, removal, or modification to any constituent proteoforms. To address two-decade old claims of protein losses during front-end proteome resolution using 2DE, here we tested an alternate rehydration method for immobilized pH gradient strips prior to isoelectric focusing (IEF; i.e., face-up compared to face-down) and quantitatively assessed losses during the front-end of 2DE (rehydration and IEF). Using a well-established high-resolution, quantitative 2DE protocol, there were no detectable proteoform losses using the alternate face-up rehydration method. While there is a <0.25% total loss of proteoforms during standard face-down rehydration, it is insignificant in terms of having any effect on overall proteome resolution (i.e., total spot count and total spot signal). This report is another milestone in integrative top-down proteomics, disproving long-held dogma in the field and confirming that quantitative front-end 2DE/LC/MS/MS is currently the only method to broadly and deeply analyze proteomes by resolving their constituent proteoforms. This article is protected by copyright. All rights reserved.PMID:36416355 | DOI:10.1002/elps.202200257

Brief Bioinform. 2022 Nov 22:bbac485. doi: 10.1093/bib/bbac485. Online ahead of print.ABSTRACTMedicinal plants are the main source of natural metabolites with specialised pharmacological activities and have been widely examined by plant researchers. Numerous omics studies of medicinal plants have been performed to identify molecular markers of species and functional genes controlling key biological traits, as well as to understand biosynthetic pathways of bioactive metabolites and the regulatory mechanisms of environmental responses. Omics technologies have been widely applied to medicinal plants, including as taxonomics, transcriptomics, metabolomics, proteomics, genomics, pangenomics, epigenomics and mutagenomics. However, because of the complex biological regulation network, single omics usually fail to explain the specific biological phenomena. In recent years, reports of integrated multi-omics studies of medicinal plants have increased. Until now, there have few assessments of recent developments and upcoming trends in omics studies of medicinal plants. We highlight recent developments in omics research of medicinal plants, summarise the typical bioinformatics resources available for analysing omics datasets, and discuss related future directions and challenges. This information facilitates further studies of medicinal plants, refinement of current approaches and leads to new ideas.PMID:36416120 | DOI:10.1093/bib/bbac485

FASEB J. 2022 Dec;36(12):e22644. doi: 10.1096/fj.202201473R.ABSTRACTMaternal obesity (MO) during pregnancy is linked to increased and premature risk of age-related metabolic diseases in the offspring. However, the underlying molecular mechanisms still remain not fully understood. Using a well-established nonhuman primate model of MO, we analyzed tissue biopsies and plasma samples obtained from post-pubertal offspring (3-6.5 y) of MO mothers (n = 19) and from control animals born to mothers fed a standard diet (CON, n = 13). All offspring ate a healthy chow diet after weaning. Using untargeted gas chromatography-mass spectrometry metabolomics analysis, we quantified a total of 351 liver, 316 skeletal muscle, and 423 plasma metabolites. We identified 58 metabolites significantly altered in the liver and 46 in the skeletal muscle of MO offspring, with 8 metabolites shared between both tissues. Several metabolites were changed in opposite directions in males and females in both liver and skeletal muscle. Several tissue-specific and 4 shared metabolic pathways were identified from these dysregulated metabolites. Interestingly, none of the tissue-specific metabolic changes were reflected in plasma. Overall, our study describes characteristic metabolic perturbations in the liver and skeletal muscle in MO offspring, indicating that metabolic programming in utero persists postnatally, and revealing potential novel mechanisms that may contribute to age-related metabolic diseases later in life.PMID:36415994 | DOI:10.1096/fj.202201473R

Gates Open Res. 2022 Jul 18;6:77. doi: 10.12688/gatesopenres.13635.1. eCollection 2022.ABSTRACTIntroduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network ( www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach. Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and 270/1140 well community children of similar age and household location) from nine sites in six countries across sub-Saharan Africa and South Asia. Systemic proteome, metabolome, lipidome, lipopolysaccharides, haemoglobin variants, toxins, pathogens, intestinal microbiome and biomarkers of enteropathy will be determined. Computational systems biology analysis will include machine learning and multivariate predictive modelling with stacked generalization approaches accounting for the different characteristics of each biological modality. This systems approach is anticipated to yield mechanistic insights, show interactions and behaviours of the components of biological entities, and help develop interventions to reduce mortality among acutely ill children. Ethics and dissemination. The CHAIN Network cohort and CNCC was approved by institutional review boards of all partner sites. Results will be published in open access, peer reviewed scientific journals and presented to academic and policy stakeholders. Data will be made publicly available, including uploading to recognised omics databases. Trial registration NCT03208725.PMID:36415883 | PMC:PMC9646488 | DOI:10.12688/gatesopenres.13635.1

Endocrinol Diabetes Metab. 2022 Nov 22. doi: 10.1002/edm2.388. Online ahead of print.ABSTRACTOBJECTIVES: Insulin resistance (IR) in adolescents with obesity is associated with a sex-dependent metabolic 'signature' comprising the branched-chain amino acids (BCAAs), glutamate/glutamine, C3/C5 acylcarnitines and uric acid. Here, we compared the levels of branched-chain α-keto acids (BCKAs) and glutamate/glutamine, which are the byproducts of BCAA catabolism and uric acid among adolescents with obesity prior to and following a 6-month lifestyle-intervention program.METHODS: Fasting plasma samples from 33 adolescents with obesity (16 males, 17 females, aged 12-18 year) were analysed by flow-injection tandem MS and LC-MS/MS. Multiple linear regression models were used to correlate changes in BCKAs, glutamate/glutamine and uric acid with changes in weight and insulin sensitivity as assessed by HOMA-IR, adiponectin and the ratio of triglyceride (TG) to HDL. In predictive models, BCKAs, glutamate/glutamine and uric acid at baseline were used as explanatory variables.RESULTS: Baseline BCKAs, glutamate/glutamine and uric acid were higher in males than females despite comparable BMI-metrics. Following lifestyle-intervention, α-keto-β-methylvalerate (α-KMV, a metabolic by product of isoleucine) decreased in males but not in females. The ratio of BCKA/BCAA trended lower in males. In the cohort as a whole, BCKAs correlated positively with the ratio of TG to HDL at baseline and HOMA-IR at 6-month-follow-up. Glutamate/glutamine was positively associated with HOMA-IR at baseline and 6-month-follow-up. A reduction in BCKAs was associated with an increase in adiponectin, and those with higher BCKAs at baseline had higher adiponectin levels at 6-month-follow-up. Interestingly those adolescents with higher uric acid levels at baseline had greater reduction in weight.CONCLUSIONS: BCKAs and glutamate/glutamine may serve as biomarkers of IR in adolescents with obesity, and uric acid might serve as a predictor of weight loss in response to lifestyle-intervention. Differential regulation of BCAA catabolism in adolescent males and females implicates critical roles for sex steroids in metabolic homeostasis.PMID:36415168 | DOI:10.1002/edm2.388

J Anim Physiol Anim Nutr (Berl). 2022 Nov 22. doi: 10.1111/jpn.13790. Online ahead of print.ABSTRACTThis study explored the mechanism by which grape seed procyanidins (GSPs) alleviate colon inflammatory injury induced by a high-concentrate diet in lambs. Forty-eight 1/2 Dorper (♂) × 1/2 Small thin-tailed (♀) crossed male lambs were randomly assigned into four groups: the control group (CON), fed with a high-concentrate diet (concentrate:forage = 7:3) and three GSPs groups fed a high-concentrate diet + 10 (LGSP), 20 (MGSP) and 40 (HGSP) mg/kg body weight (BW) GSPs per day, respectively. The results showed that the levels of interleukin (IL)-1β and tumour necrosis factor (TNF)-α in plasma of lambs of the MGSP (0.155 and 38.52 pg/ml) and HGSP (0.165 and 39.60 pg/ml) groups were significantly lower than those in the CON (0.248 and 48.74 pg/ml) and LGSP (0.245 and 50.52 pg/ml) group (p < 0.05), and levels of IL-1β in colon tissue in the MGSP (28.49 ng/g) and HGSP (26.67 ng/g) groups were also lower (p < 0.05) than that in CON (40.55 ng/g). Metabonomics analysis of colon tissue showed that differentially expressed metabolites were mainly enriched in the arachidonic acid metabolism, citric acid cycle, glycine, serine and threonine metabolism, and peroxisome proliferator-activated receptor signalling pathway (p < 0.05). In conclusion, GSPs alleviate the colonic epithelium inflammatory response induced by a high-concentrate diet by increasing energy metabolism, amino acid metabolism, antioxidant metabolism and inhibiting arachidonic acid metabolism.PMID:36415155 | DOI:10.1111/jpn.13790

Quant Plant Biol. 2022 Nov 22;3:e26. doi: 10.1017/qpb.2022.19. eCollection 2022.ABSTRACTMobilisation of seed storage reserves is important for seedling establishment in Arabidopsis. In this process, sucrose is synthesised from triacylglycerol via core metabolic processes. Mutants with defects in triacylglycerol-to-sucrose conversion display short etiolated seedlings. We found that whereas sucrose content in the indole-3-butyric acid response 10 (ibr10) mutant was significantly reduced, hypocotyl elongation in the dark was unaffected, questioning the role of IBR10 in this process. To dissect the metabolic complexity behind cell elongation, a quantitative-based phenotypic analysis combined with a multi-platform metabolomics approach was applied. We revealed that triacylglycerol and diacylglycerol breakdown were disrupted in ibr10, resulting in low sugar content and poor photosynthetic ability. Importantly, batch-learning self-organised map clustering revealed that threonine level was correlated with hypocotyl length. Consistently, exogenous threonine supply stimulated hypocotyl elongation, indicating that sucrose levels are not always correlated with etiolated seedling length, suggesting the contribution of amino acids in this process.PMID:37077988 | PMC:PMC10095960 | DOI:10.1017/qpb.2022.19

BMC Med. 2022 Nov 21;20(1):450. doi: 10.1186/s12916-022-02653-1.ABSTRACTBACKGROUND: Glucose metabolism has been reported to be affected by dietary patterns, while the underlying mechanisms involved remain unclear. This study aimed to investigate the potential mediation role of circulating metabolites in relation to dietary patterns for prediabetes and type 2 diabetes.METHODS: Data was derived from The Maastricht Study that comprised of 3441 participants (mean age of 60 years) with 28% type 2 diabetes patients by design. Dietary patterns were assessed using a validated food frequency questionnaire (FFQ), and the glucose metabolism status (GMS) was defined according to WHO guidelines. Both cross-sectional and prospective analyses were performed for the circulating metabolome to investigate their associations and mediations with responses to dietary patterns and GMS.RESULTS: Among 226 eligible metabolite measures obtained from targeted metabolomics, 14 were identified to be associated and mediated with three dietary patterns (i.e. Mediterranean Diet (MED), Dietary Approaches to Stop Hypertension Diet (DASH), and Dutch Healthy Diet (DHD)) and overall GMS. Of these, the mediation effects of 5 metabolite measures were consistent for all three dietary patterns and GMS. Based on a 7-year follow-up, a decreased risk for apolipoprotein A1 (APOA1) and docosahexaenoic acid (DHA) (RR 0.60, 95% CI 0.55, 0.65; RR 0.89, 95% CI 0.83, 0.97, respectively) but an increased risk for ratio of ω-6 to ω-3 fatty acids (RR 1.29, 95% CI 1.05, 1.43) of type 2 diabetes were observed from prediabetes, while APOA1 showed a decreased risk of type 2 diabetes from normal glucose metabolism (NGM; RR 0.82, 95% CI 0.75, 0.89).CONCLUSIONS: In summary, this study suggests that adherence to a healthy dietary pattern (i.e. MED, DASH, or DHD) could affect the GMS through circulating metabolites, which provides novel insights into understanding the biological mechanisms of diet on glucose metabolism and leads to facilitating prevention strategy for type 2 diabetes.PMID:36414942 | DOI:10.1186/s12916-022-02653-1

J Ethnopharmacol. 2022 Nov 19:115943. doi: 10.1016/j.jep.2022.115943. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: As one of the most commonly used herbs, Artemisia capillaris Thunb. (ACT) display favorable effect in the treatment of jaundice. However, mechanism of ACT in the treatment of jaundice remains unclear at present, which limits its development and application.AIM OF THE STUDY: To investigate effect and mechanism of Artemisia capillaris Thunb. (ACT) in the treatment of jaundice using pharmacodynamics, network pharmacology and metabolomics.METHODS: Effect of ACT in treating jaundice was evaluated by biochemical assays and pathological observation using the α-naphthyl isothiocyanate (ANIT)-induced mice. Jaundice-relieving mechanism of ACT was investigated by integration of network pharmacology and metabolomics.RESULTS: After the mice with jaundice were administrated ACT extract for 9 days, compared to that of the model group, serum D-BIL, T-BIL and ALP levels of the mice in the low, medium, high dose of ACT group decreased by 39.81%, 15.30% and 16.92%; 48.06%, 42.54% and 36.91%; 26.90%, 12.34% and 16.90%, respectively. The pathologic study indicated that ACT improved the symptoms of liver injury of the mice with jaundice. The network of herb (i.e., ACT)-components-targets-disease (i.e., jaundice) was established, which consisted of 17 components classified in flavonoids, chromones, organic acids, terpenoids, and 234 targets related to treatment of jaundice. Metabolomics analysis showed that, compared to that in the model group, level of 8 differential metabolites were upregulated and level of 29 differential metabolites were downregulated in the mice liver in the ACT group, respectively. The main metabolic pathways involved in treatment of jaundice by ACT were pantothenate and CoA biosynthesis, glutathione metabolism, biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis in the liver, respectively. The integrated analysis of network pharmacology and metabolomics showed that 3α,7α,12α a-Trihydroxy-5β-cholanate, glycocholate, taurocholate, pantetheine 4'-phosphate, and d-4'-phosphopantothenate were the potential biomarkers for treatment of jaundice, and AKR1C4, ALDH2 and HSD11B were the potential drug targets in the treatment of jaundice by ACT.CONCLUSION: The study based on metabolomics and network pharmacology indicated that ACT can display favorable jaundice-relieving effect by its multiple components regulating multiple biomarkers, multiple targets and multiple pathways, and may be a rational therapy for the treatment of jaundice.PMID:36414211 | DOI:10.1016/j.jep.2022.115943

Nitric Oxide. 2022 Nov 19:S1089-8603(22)00122-7. doi: 10.1016/j.niox.2022.11.003. Online ahead of print.ABSTRACTLimited O2 availability can decrease essential processes in energy metabolism. However, cancers have developed distinct metabolic adaptations to these conditions. For example, glutaminolysis can maintain energy metabolism and hypoxia signaling. Additionally, it has been observed that nitric oxide (NO) possesses concentration-dependent, biphasic effects in cancer. NO has potent anti-tumor effects through modulating events such as angiogenesis and metastasis at low physiological concentrations and inducing cell death at higher concentrations. In this study, Ewing Sarcoma cells (A-673), MIA PaCa, and SKBR3 cells were treated with DetaNONOate (DetaNO) in a model of hypoxia (1% O2) and reoxygenation (21% O2). All 3 cell types showed NO-dependent inhibition of cellular O2 consumption which was enhanced as O2-tension decreased. L-Gln depletion suppressed the mitochondrial response to decreasing O2 tension in all 3 cell types and resulted in inhibition of Complex I activity. In A-673 cells the O2 tension dependent change in mitochondrial O2 consumption and increase in glycolysis was dependent on the presence of L-Gln. The response to hypoxia and Complex I activity were restored by α-ketoglutarate. NO exposure resulted in the A-673 cells showing greater sensitivity to decreasing O2 tension. Under conditions of L-Gln depletion, NO restored HIF-1α levels and the mitochondrial response to O2 tension possibly through the increase of 2-hydroxyglutarate. NO also resulted in suppression of cellular bioenergetics and further inhibition of Complex I which was not rescued by α-ketoglutarate. Taken together these data suggest that NO modulates the mitochondrial response to O2 differentially in the absence and presence of L-Gln. These data suggest a combination of metabolic strategies targeting glutaminolysis and Complex I in cancer cells.PMID:36414197 | DOI:10.1016/j.niox.2022.11.003

Neurosci Lett. 2022 Nov 19:136972. doi: 10.1016/j.neulet.2022.136972. Online ahead of print.ABSTRACTElevated intake of fat modulates L-glutamate (L-Glu) turnover within the hippocampus (HIP). Our aim has been to investigate the effect of saturated vs unsaturated fat on the content of L-Glu and other amino acids involved in synaptic transmission within the HIP. The study was carried out in male mice fed (2 h or 8 weeks) with standard chow or with diets enriched either with saturated (SOLF) or unsaturated triglycerides (UOLF). An in vitro assay was performed in HIP slices incubated with palmitic (PA), oleic (OA), or lauric acid (LA). Amino acids were quantified by capillary electrophoresis. While both diets increased the amount of L-Glu and L-aspartate and decreased L-glutamine levels, only UOLF affected D-serine and taurine levels. γ-Aminobutyric acid was specifically decreased by SOLF. In vitro assays revealed that PA and OA modified L-Glu, glycine, L-serine and D-serine concentration. Our results suggest that fatty acids contained in SOLF and UOLF have an impact on HIP amino acid turnover that may account, at least partially, for the functional changes evoked by these diets.PMID:36414132 | DOI:10.1016/j.neulet.2022.136972

Food Chem. 2022 Nov 10;405(Pt B):134901. doi: 10.1016/j.foodchem.2022.134901. Online ahead of print.ABSTRACTMare milk(MM)production is lower than that of cow milk (CM), making it a premium product. Unfortunately, sellers adulterate MM with cheap CM to unscrupulously gain more profits. This study aimed to analyze MM adulteration with CM using proteomics and metabolomics. Using univariate and multivariate statistical analysis, the relative abundances of certain proteins of caseins and secretoglobin family 1D member were found to be higher with a higher CM admixture percentage. In addition, several metabolites, such as orotic and 4-aminonicotinic acids, increased in the mare-cow milk mixture with an increased CM percentage. Accordingly, these proteins and metabolites distinguished MM adulterated with CM at levels as low as 1 %.These findings can serve as the basis for clarifying the differences at the proteome and metabolome in milk from minor dairy animals and ensure milk authenticity.PMID:36413843 | DOI:10.1016/j.foodchem.2022.134901

Food Chem. 2022 Nov 17;405(Pt B):134962. doi: 10.1016/j.foodchem.2022.134962. Online ahead of print.ABSTRACTEpoxiconazole is widely used in agriculture to control plant diseases; however, its effect on the nutritional quality of crops is poorly understood. In the present study, the stereoselective effects of epoxiconazole and its enantiomers on leek metabolites and lipids were clarified using metabolomics and lipidomics based on ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Multivariate analysis revealed significant differences in 123 compounds of leek exposed to chiral epoxiconazole compared to the control group. The order of the degree of influence was (+)-epoxiconazole > racemic-epoxiconazole>(-)-epoxiconazole, indicating significant stereoselectivity. The differential expression of metabolites indicated the activation of stress defense systems, including the antioxidant defense system and signaling pathways and phenylpropanoid metabolism. Alterations in the levels of compounds associated with nutritional quality, such as amino acids, vitamins, phenylpropanoids, flavonoids and lipids indicated changes in the nutritional quality of leek. In general, the nutritional quality of leek decreased after exposure to epoxiconazole.PMID:36413841 | DOI:10.1016/j.foodchem.2022.134962

Anal Chem. 2022 Nov 22. doi: 10.1021/acs.analchem.2c02086. Online ahead of print.ABSTRACTAccurate metabolite characterization plays a vital role in targeted metabolomics. Nonetheless, the library of metabolites is still limited, especially for downstream conjugates, and it is time-consuming to synthesize each of these compounds due to high structural diversity. Herein, a green and smart strategy was developed to expand the scope of targeted metabolomics. The reference standards were synthesized in a one-pot microscale reaction, and the analytical method was tailored using the synthetic products. A group of new metabolites, namely bile acid-amino acid conjugates (BA-AAs), was studied as a proof-of-concept. First, in total 160 BA-AAs were synthesized using a small amount (2 mg each) of bile acids and low-toxic reagents within 4 h. Then, an ultra-high-performance liquid chromatography /Orbitrap-MS method was established to comprehensively profile 202 bile acid derivatives in 20 min. Finally, the method was applied to mice with inflammatory bowel disease (IBD) to discover the accumulation of 70 rare BA-AAs in small intestine and liver, where 55 were first reported from biosamples. These BA-AAs are farnesoid X receptor modulators and might contribute to the development of IBD. Our study demonstrated a feasible approach for the broad-spectrum targeted metabolomics of bile acids.PMID:36413803 | DOI:10.1021/acs.analchem.2c02086

J Agric Food Chem. 2022 Nov 22. doi: 10.1021/acs.jafc.2c04509. Online ahead of print.ABSTRACTThis study was designed to first verify the protective capacity of turmeric powder (TP) as a traditional cooking spice against dextran sulfate sodium (DSS)-induced intestinal inflammation and intestine microbiota imbalance. The DSS-induced mice were fed a standard rodent chow supplemented with or without TP (8%) for 37 days. The results indicated that the pathological phenotype, gut barrier disruption, and colon inflammation of DSS-induced mice were significantly improved through supplementation of TP. In addition, 16S rRNA-based microbiota or targeted metabolomics analysis indicated that TP ameliorated intestinal microbiota dysbiosis caused by DSS and particularly enhanced the abundances of probiotics correlated with tryptophan metabolism, such as Lactobacillus and Bifidobacterium, where the cecal tryptophan was metabolized to indole-3-propionic acid and indole-3-acetic acid. Consumption of TP markedly enhanced the expression levels of colonic aromatic hydrocarbon receptors and further increased the expressions of intestinal tight junction proteins and interleukin-22 in the colitis mice. Collectively, these findings manifest the protective actions of dietary TP consumption against ulcerative colitis via restoring the intestinal microbiota disorders, promoting microbial metabolism, and improving intestinal barrier damage.PMID:36413756 | DOI:10.1021/acs.jafc.2c04509

Chem Biodivers. 2022 Nov 22. doi: 10.1002/cbdv.202200745. Online ahead of print.ABSTRACTCelery is a vegetable widely consumed as a condiment to prepare diverse dishes around the world. Nevertheless, this plant is susceptible to the attack of several phytopathogens including those of the Fusarium genus which is translated into devastating losses for the production chain. Herein we report on the metabolic changes produced during the celery wilt caused by Fusarium oxysporum which was determined through untargeted 1H NMR metabolomics. The changes in the metabolite content of celery were measured at 16, 24, and 32 days post-inoculation using viable conidia obtained from the native F. oxsyporum strain FO3. Our results demonstrated that the parasitic activity of the fungus reduced the endogenous levels of free sugars (fructose, galactose, glucose isomers, mannose, Myo-inositol, mannitol, and sucrose) amino acids (alanine, aspartate GABA, glutamate, glutamine, histidine, isoleucine, leucine, methionine, proline, threonine, tyrosine, and valine), nucleosides (adenosine, cytidine, guanosine, and uridine) and organic acids (citric acid, fumaric acid, malic acid, and succinic acid). Interestingly, the levels of tyrosine and tryptophan were triggered as a consequence of F. oxysporum infection. This tendency was correlated with an increase in the levels of chlorogenic acid, apiin, and apigenin derivatives, suggesting their involvement in the chemical defense of celery against fungal colonization. According to principal component analysis (PCA) and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) methanol was the main differential metabolite and it was considered as a new chemical marker associated with F. oxysporum infection. Our results demonstrate that infected celery plants dramatically reduced their nutritional and nutraceutical contents during Fusarium wilt after 32 days post-inoculation. However, these findings also suggest that the phenylpropanoid pathway is strongly related with the chemical defense of celery against F. oxysporum.PMID:36413469 | DOI:10.1002/cbdv.202200745

J Phys Chem A. 2022 Nov 22. doi: 10.1021/acs.jpca.2c06858. Online ahead of print.ABSTRACTAnalysis of small molecules is essential to metabolomics, natural products, drug discovery, food technology, and many other areas of interest. Current barriers preclude from identifying the constituent molecules in a mixture as overlapping clusters of NMR lines pose a major challenge in resolving signature frequencies for individual molecules. While homonuclear decoupling techniques produce much simplified pure shift spectra, they often affect sensitivity. Conversion of typical NMR spectra to pure shift spectra by signal processing without a priori knowledge about the coupling patterns is essential for accurate analysis. We developed a super-resolved wavelet packet transform based 1H NMR spectroscopy that can be used in high-throughput studies to reliably decouple individual constituents of small molecule mixtures. We demonstrate the efficacy of the method on the model mixtures of saccharides and amino acids in the presence of significant noise.PMID:36413171 | DOI:10.1021/acs.jpca.2c06858

mSystems. 2022 Nov 22:e0090322. doi: 10.1128/msystems.00903-22. Online ahead of print.ABSTRACTCurrently, the regulation of Lactobacillus on intestinal stem cells (ISCs) attracts broad attention, but their active ingredients and the underlying mechanism are worthy of further study. Previously, host intestinal commensal bacteria were verified to drive the differentiation of ISCs. In this study, the strong bacteriostatic activity of Lactobacillus salivarius and Lactobacillus agilis were illustrated, and the components (supernatant, precipitation) of L. salivarius or L. agilis were further demonstrated to decrease the differentiation of ISCs in vivo. Interestingly, antibiotics feeding decreased ISCs differentiation in vivo as well. However, the administration of L. salivarius supernatant following antibiotics feeding was shown to promote ISCs differentiation dramatically when compared with the antibiotics feeding group, indicating that some active ingredients existed in its supernatant to promote ISCs activity. Strikingly, in vitro, the treatment of L. salivarius supernatant was further confirmed to promote the intestinal organoids' size, budding, and LGR5 expression. Next, the metabolomics analysis of Lactobacilli' supernatants suggested that succinate might be a crucial metabolite to promote ISCs activity. Further, the succinate treatment in vitro (1000 μM) and in vivo (50 mM) was confirmed to enhance the expression of LGR5 and PCNA. SLC13A3 (a sodium/dicarboxylate cotransporter) was detected in the intestinal organoids and demonstrated to transport succinate into ISCs, as confirmed by the contact of FITC-succinate with ISCs nucleus. Subsequently, high mitochondrial membrane potential and reactive oxygen species levels appeared in the intestinal organoids upon succinate treatment. Collectively, the promotion of L. salivarius on ISCs activity is associated with succinate-induced mitochondrial energy metabolism. IMPORTANCE In our previous study, Lactobacillus salivarius and Lactobacillus agilis were demonstrated to regulate intestinal stem cell activity in hens, but their active ingredients and the underlying mechanism remain unclear. In this study, L. salivarius supernatant was shown to directly promote intestinal stem cell activity. Furthermore, the succinate (a critical metabolite of L. salivarius) was screened out to promote intestinal stem cell activity. Moreover, the succinate was confirmed to enter intestinal stem cells and induce high mitochondrial energy metabolism, finally promoting intestinal stem cell activity. These findings will advance uncovering the mechanism by which Lactobacillus regulate intestinal stem cell activity in chickens.PMID:36413033 | DOI:10.1128/msystems.00903-22

J Agric Food Chem. 2022 Nov 22. doi: 10.1021/acs.jafc.2c06287. Online ahead of print.ABSTRACTNitrogen (N) and potassium (K) have significant effects on apple peel color. To further understand the molecular mechanism of N-K regulation of apple color, we analyzed the apple peel under different N and K treatments using isotope labeling, transcriptomics, and metabolomics. Under high N treatments, fruit red color and anthocyanin content decreased significantly. High N decreased the 13C distribution rate and increased the Ndff values of fruits, while K increased the expression of MdSUTs and MdSOTs and promoted 13C transportation to fruits. Anthocyanin-targeted metabonomics and transcriptome analysis revealed that high N downregulated the expression of structural genes related to the anthocyanin synthesis pathway (MdPAL, Md4CL, MdF3H, MdANS, and MdUFGT) and their regulators (MdMYBs and MdbHLHs), and also decreased some metabolites contents. K alleviated this inhibition and seven anthocyanins were regulated by N-K. Our results improve the understanding of the synergistic regulation of apple fruit coloring by N-K.PMID:36412927 | DOI:10.1021/acs.jafc.2c06287