PubMed

Environ Res. 2022 Oct 28;216(Pt 3):114648. doi: 10.1016/j.envres.2022.114648. Online ahead of print.ABSTRACTEpidemiological and animal studies have shown that maternal fine particulate matters (PM2.5) exposure correlates with various adverse pregnancy outcomes such as low birth weight (LBW) of offspring. However, the underlying biological mechanisms have not been fully understood. In this study, female C57Bl/6 J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during pregestational and gestational periods, and metabolomics was performed to analyze the metabolic features in maternal serum and placenta by liquid chromatography-mass spectrometry (LC-MS). The partial least squares discriminate analysis (PLS-DA) displayed evident clustering of FA- and CAP-exposed samples for both maternal serum and placenta. In addition, pathway analysis identified that vitamin digestion and absorption was perturbed in maternal serum, while metabolic pathways including arachidonic acid metabolism, serotonergic synapse, 2-oxocarboxylic acid metabolism and cAMP signaling pathway were perturbed in placenta. Further analysis indicated that CAP exposure influenced the nutrient transportation capacity of placenta, by not only changing the ratios of some critical metabolites in placenta to maternal serum but also significantly altering the expressions of nutrition transporters in placenta. These findings reaffirm the importance of protecting women from PM2.5 exposure, and also advance our understanding of the toxic actions of ambient PM2.5.PMID:36341790 | DOI:10.1016/j.envres.2022.114648

Analyst. 2022 Nov 7. doi: 10.1039/d2an01520j. Online ahead of print.ABSTRACTLameness is a major challenge in the dairy cattle industry in terms of animal welfare and economic implications. Better understanding of metabolic alteration associated with lameness could lead to early diagnosis and effective treatment, there-fore reducing its prevalence. To determine whether metabolic signatures associated with lameness could be discovered with untargeted metabolomics, we developed a novel workflow using direct infusion-tandem mass spectrometry to rapidly analyse (2 min per sample) dried milk spots (DMS) that were stored on commercially available Whatman® FTA® DMPK cards for a prolonged period (8 and 16 days). An orthogonal partial least squares-discriminant analysis (OPLS-DA) method validated by triangulation of multiple machine learning (ML) models and stability selection was employed to reliably identify important discriminative metabolites. With this approach, we were able to differentiate between lame and healthy cows based on a set of lipid molecules and several small metabolites. Among the discriminative molecules, we identified phosphatidylglycerol (PG 35:4) as the strongest and most sensitive lameness indicator based on stability selection. Overall, this untargeted metabolomics workflow is found to be a fast, robust, and discriminating method for determining lameness in DMS samples. The DMS cards can be potentially used as a convenient and cost-effective sample matrix for larger scale research and future routine screening for lameness.PMID:36341756 | DOI:10.1039/d2an01520j

Food Funct. 2022 Nov 7. doi: 10.1039/d2fo02739a. Online ahead of print.ABSTRACTTreatment of anxiety and depression predominantly centres around pharmacological interventions, which have faced criticism for their associated side effects, lack of efficacy and low tolerability. Saffron, which is reportedly well tolerated in humans, has been recognised for its antidepressant and anti-anxiety properties. Indeed, we previously reported upon the efficacy of saffron extract supplementation in healthy adults with subclinical anxiety. However, the molecular aetiology remains unclear. In a rodent model of low-grade chronic inflammation, we explored the impact of a saffron extract (Safr'Inside™) supplemented at a physiological dose, which equated to 22 ± 1.2 mg per day human equivalent dose for a person of 60 kg. Behavioural tests (Open Field task, Y maze, Novel object recognition), caecal 16S rRNA microbial sequencing, caecal 1H NMR metabolomic analysis and 2DE brain proteomic analyses were completed to probe gut-brain axis interactions. Time occupying the centre of the Open Field maze (OF) was increased by 62% in saffron supplemented animals. This improvement in anxiety-related behaviour coincided with gut microbial shifts, notably Akkermansia, Muribaculaceae, Christensenellacae and Alloprevotella which significantly increased in response to saffron supplementation. Akkermansia and Muribaculaceae abundance negatively correlated with the neurotoxic metabolite dimethylamine which was reduced in saffron supplemented animals. Brain proteomic analysis highlighted several significantly altered proteins including ketimine reductase mu-crystallin which also correlated with dimethylamine concentration. Both dimethylamine and ketimine reductase mu-crystallin were associated with OF performance. This may be indicative of a novel interaction across the gut-brain axis which contributes to anxiety-related disorders.PMID:36341693 | DOI:10.1039/d2fo02739a

FEMS Microbiol Ecol. 2022 Nov 7:fiac129. doi: 10.1093/femsec/fiac129. Online ahead of print.ABSTRACTWith the increasing reliance on intensive arable agriculture, analysis of the problems associated with continuous cropping has become a global research focus. Here, high-throughput sequencing and non-targeted metabolomics were used to evaluate the responses of soil microbial community structure and soil metabolic function to continuous cucumber cultivation (from one to 18 years of continuous cultivation) in greenhouses. Continuous cucumber cropping resulted in increased soil nutrient concentrations but decreased concentrations of available nutrients. The abundance of several bacterial genera associated with nutrient cycling, such as Bacillus and Sphingomonas, was reduced by continuous cucumber cultivation. The abundance of several beneficial fungal genera, including pathogen antagonists (e.g. Chaetomium, Mortierella, Aspergillus, and Penicillium), were found to gradually decrease in response to the increased duration of continuous cropping. 3-amino-2-naphthoic acid and L-valine increased initially and then decreased as the cropping continued, which were related to fatty acid metabolism and amino acid biosynthesis. We also confirmed a close association between microbial community structure and soil metabolites. This study linked the changes in microbial community structure and metabolites in the rhizosphere soil and provided new insights into soil-microbial interactions in continuous cucumber culture systems.PMID:36341539 | DOI:10.1093/femsec/fiac129

EMBO Mol Med. 2022 Nov 7:e15200. doi: 10.15252/emmm.202115200. Online ahead of print.ABSTRACTLeukemic cutaneous T-cell lymphomas (L-CTCL) are lymphoproliferative disorders of skin-homing mature T-cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic sequencing efforts, recurrent driver mutations have not been identified, but chromosomal losses and gains are frequent and dominant. We integrated genomic landscape analyses with innovative pharmacologic interference studies to identify key vulnerable nodes in L-CTCL. We detected copy number gains of loci containing the STAT3/5 oncogenes in 74% (n = 17/23) of L-CTCL, which correlated with the increased clonal T-cell count in the blood. Dual inhibition of STAT3/5 using small-molecule degraders and multi-kinase blockers abolished L-CTCL cell growth in vitro and ex vivo, whereby PAK kinase inhibition was specifically selective for L-CTCL patient cells carrying STAT3/5 gains. Importantly, the PAK inhibitor FRAx597 demonstrated encouraging anti-leukemic activity in vivo by inhibiting tumor growth and disease dissemination in intradermally xenografted mice. We conclude that STAT3/5 and PAK kinase interaction represents a new therapeutic node to be further explored in L-CTCL.PMID:36341492 | DOI:10.15252/emmm.202115200

Front Immunol. 2022 Jul 11;13:936106. doi: 10.3389/fimmu.2022.936106. eCollection 2022.ABSTRACTSevere acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization-triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.PMID:36341434 | PMC:PMC9634751 | DOI:10.3389/fimmu.2022.936106

Front Immunol. 2022 Oct 20;13:984408. doi: 10.3389/fimmu.2022.984408. eCollection 2022.ABSTRACTMetabolomic studies show that rheumatoid arthritis (RA) is associated with metabolic disruption. Metabolic changes in fibroblast-like synoviocytes (FLS) likely contribute to FLS abnormal response and strongly contribute to joint destruction. These changes often involve increased expression of nutrient transporters to meet a high demand for energy or biomolecules. The solute carrier (SLC) transporter families are nutrient transporters and serve as 'metabolic gates' for cells by mediating the transport of several different nutrients such as glucose, amino acids, vitamins, neurotransmitters, and inorganic/metal ions. In RA FLS SLC-mediated transmembrane transport was one pathway associated with different epigenetic landscape between RA and osteoarthritis (OA) FLS. These highlight that transporters from the SLC family offer unique targets for further research and offer the promise of future therapeutic targets for RA.PMID:36341411 | PMC:PMC9632162 | DOI:10.3389/fimmu.2022.984408

Front Immunol. 2022 Oct 20;13:1002536. doi: 10.3389/fimmu.2022.1002536. eCollection 2022.ABSTRACTBACKGROUND: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Dupilumab, a monoclonal antibody that targets the interleukin (IL)-4 and IL-13 receptors, has been widely used in AD because of its efficacy. However, metabolic changes occurring in patients with AD in response to dupilumab remains unknown. In this study, we integrated metabolomics and lipidomics analyses with clinical data to explore potential metabolic alterations associated with dupilumab therapeutic efficacy. In addition, we investigated whether the development of treatment side effects was linked to the dysregulation of metabolic pathways.METHODS: A total of 33 patients with AD were included in the current study, with serum samples collected before and after treatment with dupilumab. Comprehensive metabolomic and lipidomic analyses have previously been developed to identify serum metabolites (including lipids) that vary among treatment groups. An orthogonal partial least squares discriminant analysis model was established to screen for differential metabolites and metabolites with variable importance in projection > 1 and p < 0.05 were considered potential metabolic biomarkers. MetaboAnalyst 5.0 was used to identify related metabolic pathways. Patients were further classified into two groups, well responders (n = 19) and poor responders (n = 14), to identify differential metabolites between the two groups.RESULTS: The results revealed significant changes in serum metabolites before and after 16 weeks of dupilumab treatment. Variations in the metabolic profile were more significant in the well-responder group than in the poor-responder group. Pathway enrichment analysis revealed that differential metabolites derived from the well-responder group were mainly involved in glycerophospholipid metabolism, valine, leucine and isoleucine biosynthesis, the citrate cycle, arachidonic acid metabolism, pyrimidine metabolism, and sphingolipid metabolism.CONCLUSION: Serum metabolic profiles of patients with AD varied significantly after treatment with dupilumab. Differential metabolites and their related metabolic pathways may provide clues for understanding the effects of dupilumab on patient metabolism.PMID:36341398 | PMC:PMC9632449 | DOI:10.3389/fimmu.2022.1002536

Front Immunol. 2022 Oct 20;13:960709. doi: 10.3389/fimmu.2022.960709. eCollection 2022.ABSTRACTPorcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious disease that affects the global pig industry. To understand mechanisms of susceptibility/resistance to PRRSV, this study profiled the time-serial white blood cells transcriptomic and serum metabolomic responses to PRRSV in piglets from a crossbred population of PRRSV-resistant Tongcheng pigs and PRRSV-susceptible Large White pigs. Gene set enrichment analysis (GSEA) illustrated that PRRSV infection up-regulated the expression levels of marker genes of dendritic cells, monocytes and neutrophils and inflammatory response, but down-regulated T cells, B cells and NK cells markers. CIBERSORT analysis confirmed the higher T cells proportion in resistant pigs during PRRSV infection. Resistant pigs showed a significantly higher level of T cell activation and lower expression levels of monocyte surface signatures post infection than susceptible pigs, corresponding to more severe suppression of T cell immunity and inflammatory response in susceptible pigs. Differentially expressed genes between resistant/susceptible pigs during the course of infection were significantly enriched in oxidative stress, innate immunity and humoral immunity, cell cycle, biotic stimulated cellular response, wounding response and behavior related pathways. Fourteen of these genes were distributed in 5 different QTL regions associated with PRRSV-related traits. Chemokine CXCL10 levels post PRRSV infection were differentially expressed between resistant pigs and susceptible pigs and can be a promising marker for susceptibility/resistance to PRRSV. Furthermore, the metabolomics dataset indicated differences in amino acid pathways and lipid metabolism between pre-infection/post-infection and resistant/susceptible pigs. The majority of metabolites levels were also down-regulated after PRRSV infection and were significantly positively correlated to the expression levels of marker genes in adaptive immune response. The integration of transcriptome and metabolome revealed concerted molecular events triggered by the infection, notably involving inflammatory response, adaptive immunity and G protein-coupled receptor downstream signaling. This study has increased our knowledge of the immune response differences induced by PRRSV infection and susceptibility differences at the transcriptomic and metabolomic levels, providing the basis for the PRRSV resistance mechanism and effective PRRS control.PMID:36341362 | PMC:PMC9631489 | DOI:10.3389/fimmu.2022.960709

JIMD Rep. 2022 Aug 22;63(6):593-603. doi: 10.1002/jmd2.12323. eCollection 2022 Nov.ABSTRACTAdrenomyeloneuropathy (AMN), the slow progressive phenotype of adrenoleukodystrophy (ALD), has no clinical plasma biomarker for disease progression. This feasibility study aimed to determine whether metabolomics and micro-RNA in blood plasma provide a potential source of biomarkers for AMN disease severity. Metabolomics and RNA-seq were performed on AMN and healthy human blood plasma. Biomarker discovery and pathway analyses were performed using clustering, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and regression against patient's clinical Expanded Disability Status Score (EDSS). Fourteen AMN and six healthy control samples were analyzed. AMN showed strong disease-severity-specific metabolic and miRNA clustering signatures. Strong, significant clinical correlations were shown for 7-alpha-hydroxy-3-oxo-4-cholestenoate (7-HOCA) (r 2 = 0.83, p < 0.00001), dehydroepiandrosterone sulfate (DHEA-S; r 2 = 0.82, p < 0.00001), hypoxanthine (r 2 = 0.82, p < 0.00001), as well as miRNA-432-5p (r 2 = 0.68, p < 0.00001). KEGG pathway comparison of mild versus severe disease identified affected downstream systems: GAREM, IGF-1, CALCRL, SMAD2&3, glutathione peroxidase, LDH, and NOS. This feasibility study demonstrates that miRNA and metabolomics are a source of potential plasma biomarkers for disease severity in AMN, providing both a disease signature and individual markers with strong clinical correlations. Network analyses of affected systems implicate differentially altered vascular, inflammatory, and oxidative stress pathways, suggesting disease-severity-specific mechanisms as a function of disease severity.PMID:36341174 | PMC:PMC9626672 | DOI:10.1002/jmd2.12323

STAR Protoc. 2022 Oct 29;3(4):101799. doi: 10.1016/j.xpro.2022.101799. eCollection 2022 Dec 16.ABSTRACTThis protocol describes CAROM, a computational tool that combines genome-scale metabolic networks (GEMs) and machine learning to identify enzyme targets of post-translational modifications (PTMs). Condition-specific enzyme and reaction properties are used to predict targets of phosphorylation and acetylation in multiple organisms. CAROM is influenced by the accuracy of GEMs and associated flux-balance analysis (FBA), which generate the inputs of the model. We demonstrate the protocol using multi-omics data from E. coli. For complete details on the use and execution of this protocol, please refer to Smith et al. (2022).PMID:36340881 | PMC:PMC9630780 | DOI:10.1016/j.xpro.2022.101799

JDS Commun. 2021 Oct 22;3(1):59-65. doi: 10.3168/jdsc.2021-0154. eCollection 2022 Jan.ABSTRACTThe objectives of this cross-sectional, nonintervention, observational study were to compare urine and blood parameters between cows consuming a positive dietary cation-anion difference (DCAD) diet [early dry cows, DCAD + 250 mEq/kg of dry matter (DM), n = 15] with the same cows consuming a negative DCAD diet (-220 mEq/kg of DM) 10 d after moving them from the early dry to the prepartum group. The most remarkable finding was that cows consuming the anionic diet had very low urine pH and very low base excess in blood, suggestive of uncompensated metabolic acidosis. Importantly, the metabolomics data revealed that only urine concentrations of essential and aromatic amino acids were decreased, and that concentrations of total nonessential amino acids and glucogenic amino acids were increased in plasma and reciprocally decreased in urine, suggesting that the cows fed anionic salts were attempting to meet a high glucose demand by mobilizing gluconeogenic amino acid reserves. Notably, the dietary anionic salts exerted marked effects on glycerophospholipids, with a reduction in most phosphatidylcholine containing diacyl (PC aa) and acyl-alkyl (PC ae) moieties in plasma and urine. Further characterization of these metabolomic profiles may lead to the development of novel biomarkers to identify cows susceptible to metabolic acidosis and other metabolic diseases.PMID:36340673 | PMC:PMC9623625 | DOI:10.3168/jdsc.2021-0154

Curr Med Mycol. 2022 Mar;8(1):44-53. doi: 10.18502/cmm.8.1.9214.ABSTRACTMucormycosis is an opportunistic, aggressive, and angioinvasive fungal infection associated with a high mortality rate as it disseminates and infects the whole body if not treated early. Most conventional diagnostic methods require time and may also generate false-negative reports due to the several lacunae associated. On the other hand, molecular methods are rapid, reliable, and can be applied to different biological samples, such as fresh tissue, formalin-fixed paraffin-embedded blocks, serum, and urine. Mucorales are angio-invasive, and many studies have found the circulating fungal DNA (a non-invasive form of DNA) in the blood and urine of the patient. In addition, with the increase in the usage of steroid drugs in this COVID scenario, the rate of mucormycosis infection has taken a sudden rise. In light of this situation, there is an imperative need to diagnose these infections at the earliest.PMID:36340436 | PMC:PMC9548081 | DOI:10.18502/cmm.8.1.9214

Front Plant Sci. 2022 Oct 20;13:958460. doi: 10.3389/fpls.2022.958460. eCollection 2022.ABSTRACTPlants belonging to the Oxytropis genus, family Leguminosae, are found throughout the world, with about 80 species mainly distributed in northwest and northeast China. The plants have medicinal properties and many plants have been used as folk medicine for the treatment of colds, inflammation of carbuncle swelling, pain, and different types of bleeding. In recent years, due to the reduced availability of wild resources and increased clinical demand, additional Oxytropis species have been used in Mongolian medicine. This study explored the medicinal potential of four Oxytropis species, investigating their phylogeny, chemical components, and pharmacological activities. Oxytropis myriophylla (Pall) DC., Oxytropis hirta Bunge, and Oxytropis bicolor Bge. were found to be closely related at the taxonomic level. While previous investigations on the bioactive constituents of Oxytropis have been limited and have concentrated largely on flavonoids and saponins, the present study established a novel UHPLC-Q-TOF/MS based on metabolite profiling to comprehensively analyze the chemical composition of the four Oxytropis species and to identify marker compounds. A total of 75 compounds were identified from the four species, with 23 identified as characteristic marker components. Twenty-six marker compounds were identified in O. myriophylla from different geographical regions. Analysis of pharmacological activity showed that extracts of O. myriophylla and O. hirta had stronger anti-inflammatory activity than the extracts from the other species. The relationships between the chemical components, traditional curative uses, and pharmacological activities were analyzed to provide a preliminary documentation of the pharmacophylogenetic characteristics of the Oxytropis family as a whole. Several marker compounds, including licoricesaponin G2, licoricesaponin J2, and glycyrrhizic acid found in O. hirta were found to have effective anti-inflammatory activity, consistent with the traditional application of reducing swelling and healing wounds. This preliminary investigation into the pharmacophylogeny of the genus Oxytropis will contribute to the conservation and exploitation of the medicinal resources of this genus.PMID:36340402 | PMC:PMC9631219 | DOI:10.3389/fpls.2022.958460

Front Plant Sci. 2022 Oct 20;13:993682. doi: 10.3389/fpls.2022.993682. eCollection 2022.ABSTRACTSweetpotato (Ipomoea batatas L.) with different depths of yellow color contains different compositions of carotenoids, which are beneficial for human health. In this study, we performed an integrated analysis of metabolomic and transcriptomic to identify key genes playing a major role in carotenoid coloration in sweetpotato tuberous roots. Herein, 14 carotenoids were identified in five sweetpotatoes. Orange-red and orange cultivars were dominated by β-carotene (385.33 μg/g and 85.07 μg/g), yellow cultivar had a high β-cryptoxanthin (11.23 μg/g), light-yellow cultivar was rich in zeaxanthin (5.12 μg/g), whereas lutein (3.34 μg/g) was the main carotenoid in white cultivar. Furthermore, 27 differentially expressed genes involved in carotenoid metabolism were identified based on comparative transcriptome. Weighted gene co-expression network analysis identified 15 transcription factors highly associated with carotenoid content in sweetpotatoes. These results provide valuable information for revealing the regulatory mechanism of carotenoid metabolism in different-colored sweetpotato tuberous roots.PMID:36340393 | PMC:PMC9632283 | DOI:10.3389/fpls.2022.993682

Front Plant Sci. 2022 Oct 19;13:1045194. doi: 10.3389/fpls.2022.1045194. eCollection 2022.ABSTRACTJasmine [Jasminum sambac (L.) Aiton] is a commercially important cultivated plant species known for its fragrant flowers used in the perfume industry, medicine and cosmetics. In the present study, we obtained a draft genome for the J. sambac cultivar 'Danbanmoli' (JSDB, a single-petal phenotype). We showed that the final genome of J. sambac was 520.80 Mb in size (contig N50 = 145.43 kb; scaffold N50 = 145.53 kb) and comprised 35,363 genes. Our analyses revealed that the J. sambac genome has undergone only an ancient whole-genome duplication (WGD) event. We estimated that the lineage that has given rise to J. sambac diverged from the lineage leading to Osmanthus fragrans and Olea europaea approximately 31.1 million years ago (Mya). On the basis of a combination of genomic and transcriptomic analyses, we identified 92 transcription factors (TFs) and 206 genes related to heat stress response. Base on a combination of genomic, transcriptomic and metabolomic analyses, a range of aroma compounds and genes involved in the benzenoid/phenylpropanoid and terpenoid biosynthesis pathways were identified. In the newly assembled J. sambac genome, we identified a total of 122 MYB, 122 bHLH and 69 WRKY genes. Our assembled J. sambac JSDB genome provides fundamental knowledge to study the molecular mechanism of heat stress tolerance, and improve jasmine flowers and dissect its fragrance.PMID:36340389 | PMC:PMC9627619 | DOI:10.3389/fpls.2022.1045194

Front Plant Sci. 2022 Oct 19;13:964558. doi: 10.3389/fpls.2022.964558. eCollection 2022.ABSTRACTQuinoa (Chenopodium quinoa Willd.) contains various physiologically active substances, including vitamins, polyphenols, flavonoids, phytosterols, and saponins. Research showed that saponins were the protective substances in the outer layer of quinoa seeds to defend against microbes, herbivores, and insects. Because the aglycones of quinoa saponins are triterpenoids, they are called triterpenoid saponins (TSs). In addition, the presence of TS imparted bitterness in quinoa and resulted in anticancer and anti-inflammatory effects. In this study, the seeds of low-saponin quinoa, NT376-2 (N), and high-saponin quinoa, B-12071(B), at 30 and 60 days after flowering (DAF) were used to measure the TS content and evaluated for their transcriptomic and metabolomic profiles. The amounts of TS were found to significantly differ between all possible comparisons: N and B at 30 DAF (N1_vs_B1), N and B at 60 DAF (N2_vs_B2), N at 30 DAF and 60 DAF (N1_vs_N2), and B at 30 DAF and 60 DAF (B1_vs_B2). RNA sequencing (RNA-seq) was used to screen differentially expressed genes (DEGs) and revealed 14,703 upregulated DEGs and 26,267 downregulated DEGs in the four comparison groups. The 311 overlapping DEGs found in the four comparisons were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to screen for DEGs related to TS biosynthesis in quinoa. Metabolomics analysis identified acetyl-CoA, 1-hydroxy-2-methyl-2-butenyl-4-diphosphate, farnesal, and (S)-2,3-epoxysqualene as the key differentially accumulated metabolites (DAMs). Transcriptomics-metabolomics joint analysis showed that triterpenoid biosynthesis and terpenoid backbone biosynthesis were the enriched pathways of TS biosynthesis; farnesal were the key DAMs shared in the four comparison groups and associated with 10 key candidate DEGs related to TS biosynthesis in quinoa. These results provided important references for in-depth research on the metabolic mechanism of TS in quinoa.PMID:36340365 | PMC:PMC9627512 | DOI:10.3389/fpls.2022.964558

Front Plant Sci. 2022 Oct 20;13:937927. doi: 10.3389/fpls.2022.937927. eCollection 2022.ABSTRACTTranscriptomics and metabolomics are methodologies being increasingly chosen to perform molecular studies in grapevine (Vitis vinifera L.), focusing either on plant and fruit development or on interaction with abiotic or biotic factors. Currently, the integration of these approaches has become of utmost relevance when studying key plant physiological and metabolic processes. The results from these analyses can undoubtedly be incorporated in breeding programs whereby genes associated with better fruit quality (e.g., those enhancing the accumulation of health-promoting compounds) or with stress resistance (e.g., those regulating beneficial responses to environmental transition) can be used as selection markers in crop improvement programs. Despite the vast amount of data being generated, integrative transcriptome/metabolome meta-analyses (i.e., the joint analysis of several studies) have not yet been fully accomplished in this species, mainly due to particular specificities of metabolomic studies, such as differences in data acquisition (i.e., different compounds being investigated), unappropriated and unstandardized metadata, or simply no deposition of data in public repositories. These meta-analyses require a high computational capacity for data mining a priori, but they also need appropriate tools to explore and visualize the integrated results. This perspective article explores the universe of omics studies conducted in V. vinifera, focusing on fruit-transcriptome and metabolome analyses as leading approaches to understand berry physiology, secondary metabolism, and quality. Moreover, we show how omics data can be integrated in a simple format and offered to the research community as a web resource, giving the chance to inspect potential gene-to-gene and gene-to-metabolite relationships that can later be tested in hypothesis-driven research. In the frame of the activities promoted by the COST Action CA17111 INTEGRAPE, we present the first grapevine transcriptomic and metabolomic integrated database (TransMetaDb) developed within the Vitis Visualization (VitViz) platform (https://tomsbiolab.com/vitviz). This tool also enables the user to conduct and explore meta-analyses utilizing different experiments, therefore hopefully motivating the community to generate Findable, Accessible, Interoperable and Reusable (F.A.I.R.) data to be included in the future.PMID:36340350 | PMC:PMC9630917 | DOI:10.3389/fpls.2022.937927

Front Plant Sci. 2022 Oct 20;13:970410. doi: 10.3389/fpls.2022.970410. eCollection 2022.ABSTRACTModelling higher plant growth is of strategic interest for modern agriculture as well as for the development of bioregenerative life support systems for space applications, where crop growth is expected to play an essential role. The capability of constraint-based metabolic models to cope the diel dynamics of plants growth is integrated into a multilevel modelling approach including mass and energy transfer and enzyme kinetics. Lactuca sativa is used as an exemplary crop to validate, with experimental data, the approach presented as well as to design a novel model-based predictive control strategy embedding metabolic information. The proposed modelling strategy predicts with high accuracy the dynamics of gas exchange and the distribution of fluxes in the metabolic network whereas the control architecture presented can be useful to manage higher plants chambers and open new ways of merging metabolome and control algorithms.PMID:36340344 | PMC:PMC9632494 | DOI:10.3389/fpls.2022.970410

Front Pharmacol. 2022 Oct 21;13:1002269. doi: 10.3389/fphar.2022.1002269. eCollection 2022.ABSTRACTColitis-associated cancer (CAC) is a subtype of inflammatory bowel disease (IBD)-associated colorectal cancer. Huoxiang Zhengqi (HXZQ) is a classical Chinese herbal medicine and has been used to treat intestinal disorders, however, anti-CAC effects and underlying mechanisms of HXZQ have not been reported. An azoxymethane/dextran sulfate sodium-induced CAC mice model was used to investigate the anti-CAC effect of HXZQ. HXZQ significantly reduced colonic inflammation, suppressed the size and number of tumors, and reduced the levels of pro-inflammatory cytokines (interleukin [IL]-1α, IL-1β, IL-6, IL-17A, IL-21, IL-23, granulocyte macrophage-colony stimulating factor, and tumor necrosis factor-α) and oxidative stress markers (reactive oxygen species and malondialdehyde), and increased the levels of anti-inflammatory cytokines (IL-10 and IL-27) in CAC mice. Intestinal microbiota and serum metabolomics analyses indicated that HXZQ altered the gut microbial composition and the abundance of 29 serum metabolites in CAC mice. Additionally, HXZQ activated the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) signaling pathway and increased the levels of antioxidants such as catalase (CAT), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductases-1 (NQO-1), and superoxide dismutase-1 (SOD-1). HXZQ inhibited the activation of the nuclear factor kappa-B (NF-κB) signaling pathway and decreased the expression of NLR family pyrin domain containing 3 (NLRP3) by inhibiting the phosphorylation of inhibitor of nuclear factor kappa-B (IκB), inhibitor of nuclear factor kappa-B kinase (IKK), and NF-κB. In conclusion, HXZQ alleviated CAC in mice by modulating the intestinal microbiota and metabolism, activating Nrf2-mediated antioxidant response, and inhibiting NF-κB-mediated NLRP3 inflammasome activation against inflammation. The present data provide a reference for the use of HXZQ as a therapeutic or combination agent for clinical CAC treatment.PMID:36339623 | PMC:PMC9634060 | DOI:10.3389/fphar.2022.1002269