PubMed

J Ethnopharmacol. 2023 Jun 22:116805. doi: 10.1016/j.jep.2023.116805. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Growing evidence indicates that hyperuricemia is closely associated with gut microbiota dysbiosis. Orthosiphon aristatus (Blume) Miq. (O. aristatus), as a traditional Chinese medicine, has been widely used to treat hyperuricemia in China. However, the mechanism by which O. aristatus treats hyperuricemia has not been clarified.AIM OF THE STUDY: In this study, we investigated whether the molecular mechanism underlying the anti-hyperuricemia effect of O. aristatus is related to the regulation of gut microbiota by 16S rDNA gene sequencing combined with widely targeted metabolomics.MATERIALS AND METHODS: Hyperuricemia was induced in rats by administration of 10% fructose and 20% yeast, and the uricosuric effect was assessed by measuring the uric acid (UA) levels in serum and cecal contents. Intestinal morphology was observed by hematoxylin and eosin (HE) staining. To explore the effects of O. aristatus on the gut microbiota and its metabolites, we utilized 16S rDNA gene sequencing combined with widely targeted metabolomics. Furthermore, metabolic pathway enrichment analysis was performed on the screened differential metabolites. The real time quantitative polymerase chain reaction (RT-PCR) and western blotting (WB) were used to detect the expression of relevant proteins in the key pathway.RESULTS: Our results indicated that O. aristatus intervention decreased serum UA levels and increased the UA levels in cecal contents in hyperuricemic rats. Additionally, O. aristatus improved intestinal morphology and altered the composition of the gut microbiota and its metabolites. Specifically, 16S rDNA revealed that O. aristatus treatment significantly reduced the abundance of unidentified-Ruminococcaceae and Lachnospiraceae-NK4A136-group. Meanwhile, widely targeted metabolomics showed that 17 metabolites, including lactose, 4-oxopentanoate and butyrate, were elevated, while 55 metabolites, such as flavin adenine dinucleotide and xanthine, were reduced. Metabolic pathway enrichment analysis found that O. aristatus was mainly involved in purine metabolism. Moreover, RT-PCR and WB suggested that O. aristatus could significantly up-regulate the expression of UA excretion transporter ATP-binding cassette subfamily G member 2 (ABCG2) in the intestine.CONCLUSION: O. aristatus exerts UA-lowering effect by regulating the gut microbiota and ABCG2 expression, indicating that this herb holds great promise in the treatment of hyperuricemia.PMID:37355082 | DOI:10.1016/j.jep.2023.116805

Int J Biol Macromol. 2023 Jun 22:125542. doi: 10.1016/j.ijbiomac.2023.125542. Online ahead of print.ABSTRACTPolysaccharides are one of the active components of Cistanche deserticola. Cistanche deserticola polysaccharides (CDPs) significantly regulated gut microbiota, immune activity and neuroprotective functions. However, it merely scratches the surface that the anti-depression effects of CDPs. We aimed to demonstrate the anti-depression effects of CDPs and the underlying mechanisms from the perspectives of gut homeostasis by behavioral evaluations and applying integrally microbiome, metabolome and molecular biology. CDPs showed significant effects on improving abnormal behaviors of depressed rats. Additionally, CDPs maintained Th17/Treg balance and modulated gut immunity of depressed rats. Comprehensive microbiome and metabolome analysis showed that CDPs significantly ameliorated abundances of beneficial bacteria, and increased the contents of SCFAs, consequently maintaining gut homeostasis. Besides, the anti-depression effects of CDPs involved in amino acids metabolism including BCAAs, glutamine, etc., maintaining metabolic balance. The current findings provide not only deeper understanding of depression focusing on gut, but also evidence about anti-depression effects of CDPs, broadening clinic applications of CDPs. Of note, the present study is of significance in a long run, in terms of providing novel strategies and protocols for revealing mechanisms of anti-depression drugs, and for the discovery of new antidepressants and functional foods from natural products.PMID:37355069 | DOI:10.1016/j.ijbiomac.2023.125542

Plant Physiol Biochem. 2023 Jun 20;201:107856. doi: 10.1016/j.plaphy.2023.107856. Online ahead of print.ABSTRACTCyclocarya paliurus (Batal.) Iljinskaja is a multiple function tree species used for functional food and valued timber production. Carbohydrates, especially water-soluble carbohydrates, play an important role in osmotic protection, signal transduction and carbon storage. Under the circumstance of global climate change the abiotic stress would restrict the development of C. paliurus plantation, whereas there is few knowledge on the regulatory mechanisms of sugar metabolism under drought stress in C. paliurus. To investigate the drought response of C. paliurus at molecular level, we conducted an integrated analysis of transcriptomic and metabolomic of C. paliurus at three PEG-induced drought stress levels (0%: control; 15%: moderate drought; 25%: severe drought) in short term. Both moderate and severe drought treatments activated the chemical defense with lowering relative water content, and enhancing the contents of soluble protein, proline and malondialdehyde in the leaves. Meanwhile, alterations in the expression of differentially expressed genes and carbohydrate metabolism profiles were observed among the treatments. Weighted gene co-expression network analysis (WGCNA) showed 3 key modules, 8 structural genes (such as genes encoding beta-fructofuranosidase (INV), sucrose synthase (SUS), raffinose synthase (RS)) and 14 regulatory transcription factors were closely linked to sugar metabolism. Our results provided the foundation to understand the response mechanism of sugar metabolism in C. paliurus under drought stress, and would drive progress in breeding of drought-tolerant varieties and plantation development of the species.PMID:37354727 | DOI:10.1016/j.plaphy.2023.107856

J Sep Sci. 2023 Jun 23:e2300264. doi: 10.1002/jssc.202300264. Online ahead of print.ABSTRACTThe fruits of Rubus chingii Hu have high medicinal and nutritional values. However, the metabolite profiles of R. chingii, especially the alterations during different development stages of fruit, have not been comprehensively analyzed, hindering the effective utilization of the unique species. In this study, we comprehensively analyzed the metabolites of R. chingii fruit at four developmental stages using systematic untargeted and targeted liquid chromatography-mass spectrometry metabolomics analysis and identified 682 metabolites. Significant changes were observed in metabolite accumulation and composition in fruits during the different developmental stages. The contents of the index components, kaempferol-3-O-rutinoside and ellagic acid, were the highest in immature fruit. The analysis identified 64 differentially expressed flavonoids and 39 differentially expressed phenolic acids; the accumulation of most of these differentially expressed metabolites decreased with the developmental stages of fruit from immaturity to maturity. These results confirmed that the developmental stages of fruit are a critical factor in determining its secondary metabolite compositions. This study elucidated the metabolic profile of R. chingii fruit at different stages of development to understand the dynamic changes in metabolites.PMID:37353914 | DOI:10.1002/jssc.202300264

BMC Plant Biol. 2023 Jun 24;23(1):337. doi: 10.1186/s12870-023-04358-w.ABSTRACTSoil salinization is a growing issue that limits agriculture globally. Understanding the mechanism underlying salt tolerance in halophytic grasses can provide new insights into engineering plant salinity tolerance in glycophytic plants. Seashore paspalum (Paspalum vaginatum Sw.) is a halophytic turfgrass and genomic model system for salt tolerance research in cereals and other grasses. However, the salt tolerance mechanism of this grass largely unknown. To explore the correlation between Na+ accumulation and salt tolerance in different tissues, we utilized two P. vaginatum accessions that exhibit contrasting tolerance to salinity. To accomplish this, we employed various analytical techniques including ICP-MS-based ion analysis, lipidomic profiling analysis, enzyme assays, and integrated transcriptomic and metabolomic analysis. Under high salinity, salt-tolerant P. vaginatum plants exhibited better growth and Na+ uptake compared to salt-sensitive plants. Salt-tolerant plants accumulated heightened Na+ accumulation in their roots, leading to increased production of root-sourced H2O2, which in turn activated the antioxidant systems. In salt-tolerant plants, metabolome profiling revealed tissue-specific metabolic changes, with increased amino acids, phenolic acids, and polyols in roots, and increased amino acids, flavonoids, and alkaloids in leaves. High salinity induced lipidome adaptation in roots, enhancing lipid metabolism in salt-tolerant plants. Moreover, through integrated analysis, the importance of amino acid metabolism in conferring salt tolerance was highlighted. This study significantly enhances our current understanding of salt-tolerant mechanisms in halophyte grass, thereby offering valuable insights for breeding and genetically engineering salt tolerance in glycophytic plants.PMID:37353755 | DOI:10.1186/s12870-023-04358-w

Sci Rep. 2023 Jun 23;13(1):10213. doi: 10.1038/s41598-023-36895-7.ABSTRACTNovel small RNAs derived from tRNAs are continuously identified, however, their biological functions are rarely reported. Here, we accidentally found the reads peak at 32nt during statistical analysis on the miRNA-seq data of lamb skin tissue, and found that it was related to the wool type of lambs. This 32nt peak was composed of small tRNA fragments. The main component sequence of this peak was a novel small tRNA derived from Glycyl tRNA (tRNAGly), the expression level of tRNAGly-derived tRNA fragments (tRFGly) was 5.77 folds higher in the coarse wool lambs than that in the fine wool lambs. However, in contrast, the expression of tRNAGly in the skin of fine wool lambs is 6.28 folds more than that in coarse wool lambs. tRNAGly promoted the synthesis of high glycine protein including KAP6 in fine wool lamb skin. These proteins were reported as the major genes for fine curly wool. Integrative analysis of target gene prediction, proteomics and metabolomics results revealed that tRFGly reduced the level of reactive oxygen species (ROS) in the skin of coarse wool lambs by targeted inhibition of the Metabolic signal and the corresponding Glutathione metabolic pathway, on the contrary, the level of oxidative stress in the skin of fine wool lambs was significantly higher. This study revealed for the first time the relationship between tRNAGly and its derived tRFGly and animal traits. tRFGly has the function of targeting and regulating protein synthesis. At the same time, tRFGly can reduce the expression of its resource complete tRNA, thereby reducing its ability to transport specific amino acid and affecting the expression of corresponding proteins.PMID:37353550 | DOI:10.1038/s41598-023-36895-7

Sci Rep. 2023 Jun 23;13(1):10233. doi: 10.1038/s41598-023-36779-w.ABSTRACTTransportation stress is one of the most serious issues in the management of yak. Previous studies have demonstrated that transport stress is caused by a pro-oxidant state in the animal resulting from an imbalance between pro-oxidant and antioxidant status. In this context, vitamin C has the ability to regulate reactive oxygen species (ROS) synthesis and alleviate oxidative stress. Although this effect of vitamin C is useful in pigs, goats and cattle, the effect of vitamin C on the mitigation of transport stress in yaks is still unclear. The purpose of this study was to better assess the metabolic changes induced by the action of vitamin C in yaks under transportation stress, and whether these changes can influence antioxidant status. After the yaks arrived at the farm, control or baseline blood samples were collected immediately through the jugular vein (VC_CON). Then, 100 mg/kg VC was injected intramuscularly, and blood samples were collected on the 10th day before feeding in the morning (VC). Relative to the control group, the VC injection group had higher levels of VC. Compared with VC_CON, VC injection significantly (P < 0.05) decreased the blood concentrations of ALT, AST, T-Bil, D-Bil, IDBIL, UREA, CRP and LDH. However, VC injection led to greater (P < 0.05) AST/ALT and CREA-S relative to VC_CON. There was no difference (P > 0.05) in GGT, ALP, TBA, TP, ALBII, GLO, A/G, TC, TG, HDL-C, LDL-C, GLU and L-lactate between VC_CON and VC. The injection of VC led to greater (P < 0.05) concentration of MDA, but did not alter (P > 0.05) the serum concentrations of LPO and ROS. The injection of VC led to greater (P < 0.05) serum concentrations of POD, CAT and GSH-PX. In contrast, lower (P < 0.05) serum concentrations of SOD, POD and TPX were observed in VC relative to VC_CON. No difference (P > 0.05) in GSH, GSH-ST and GR was observed between VC_CON and VC. Compared with the control group, metabolomics using liquid chromatography tandem-mass spectrometry identified 156 differential metabolites with P < 0.05 and a variable importance in projection (VIP) score > 1.5 in the VC injection group. The injection of VC resulted in significant changes to the intracellular amino acid metabolism of glutathione, glutamate, cysteine, methionine, glycine, phenylalanine, tyrosine, tryptophan, alanine and aspartate. Overall, our study indicated that VC injections were able to modulate antioxidant levels by affecting metabolism to resist oxidative stress generated during transport.PMID:37353533 | DOI:10.1038/s41598-023-36779-w

Int J Biol Macromol. 2023 Jun 21:125459. doi: 10.1016/j.ijbiomac.2023.125459. Online ahead of print.ABSTRACTAquaporin 9 (AQP9) is the main channel by which blood glycerol enters the liver, where it plays key roles in osmotic pressure regulation and energy metabolism. Previous studies have shown that AQP9 is involved in the pathogenesis of many liver diseases. In this study, we aimed to clarify the role of AQP9 in maintaining the physiological environment of the liver using Aqp9-/- mice. We constructed Aqp9 knockout mice and used comprehensive multiomics analysis to elucidate the potential molecular effects of AQP9 expression on liver tissue. Knockout of Aqp9 reduced mouse body weight by affecting glycerol metabolism and led to hepatocyte death and inflammatory cell infiltration, which was confirmed by transcriptomics, proteomics and metabolomics. Moreover, knockout of Aqp9 triggered immune and inflammatory responses, leading to scattered and mild liver cell pyroptosis and compensatory liver cell proliferation.PMID:37353119 | DOI:10.1016/j.ijbiomac.2023.125459

Sci Total Environ. 2023 Jun 21:165009. doi: 10.1016/j.scitotenv.2023.165009. Online ahead of print.ABSTRACTThe heavy metals lead (Pb), cadmium (Cd), and mercury (Hg) that cause neurocognitive impairment have been extensively studied. These elements typically do not exist alone in the environment; they are often found with other heavy metals and can enter the body through various routes, thereby impacting health. Our previous research showed that low Pb, Cd, and Hg levels cause neurobehavioral impairments in weaning and adult rats. However, little is known about the biomarkers and mechanisms underlying Pb, Cd, and Hg mixture-induced neurological impairments. A combined analysis of metabolomic and proteomic data may reveal heavy metal-induced alterations in metabolic and protein profiles, thereby improving our understanding of the molecular mechanisms underlying heavy metal-induced neurological impairments. Therefore, brain tissue and serum samples were collected from rats exposed to a Pb, Cd, and Hg mixture for proteomic and metabolomic analyses, respectively. The analysis revealed 363 differential proteins in the brain and 206 metabolites in serum uniquely altered in the Pb, Cd, and Hg mixture exposure group, compared to those of the control group. The main metabolic impacted pathways were unsaturated fatty acids biosynthesis, linoleic acid metabolism, phenylalanine metabolism, and tryptophan metabolism. We further identified that the levels of arachidonic acid (C20:4 n-3) and, adrenic acid (C22:4 n-3) were elevated and that kynurenic acid (KA) and quinolinic acid (QA) levels and the KA/QA ratio, were decreased in the group exposed to the Pb, Cd, and Hg mixture. A joint analysis of the proteome and metabolome showed that significantly altered proteins such as LPCAT3, SLC7A11, ASCL4, and KYAT1 may participate in the neurological impairments induced by the heavy metal mixture. Overall, we hypothesize that the dysregulation of ferroptosis and kynurenine pathways is associated with neurological damage due to chronic exposure to a heavy metal mixture.PMID:37353033 | DOI:10.1016/j.scitotenv.2023.165009

Sci Total Environ. 2023 Jun 21:165018. doi: 10.1016/j.scitotenv.2023.165018. Online ahead of print.ABSTRACTThe increasing demand for rare earth elements (REEs) in modern applications has drawn significant attention. REEs can be introduced into the environment through REE-containing fertilizers, abandoned REE-rich equipment, and mining, persisting and impacting soil quality, nutrient cycles, and plant growth. Scientists have raised concerns about REEs entering the food chain from the environment and eventually accumulating in organisms. Decades of experimental evidence have shown that these effects include inhibited growth, impaired liver function, and alterations in children's intelligence quotients. However, there exists a paucity of research that has elucidated the metabolic-level biological impacts of REEs. In our study, Caenorhabditis elegans (C. elegans) was used as a model organism to investigate physiological and inherent metabolic changes under exposure to different concentrations of REEs. The diet bacteria of nematodes play a key role in their life and development. Therefore, we investigated the influence of bacterial activity on the nematodes' response to REE exposure. We observed a concentration-dependent accumulation of REEs in nematodes, which consequently led to a reduction in lifespan and alterations in body length. Exposure to a mixed solution of REEs, in comparison to a single REE solution, resulted in greater toxicity toward nematodes. The metabolic results showed that the above changes were closely related to REE-induced amino acid metabolism disorder, membrane disturbance, DNA damage, and oxidative stress. Of note, the presence of living bacteria elicits REE effects in C. elegans. These findings highlight the potential intrinsic metabolic changes occurring in nematodes under REE exposure. Our study raises awareness of the exposure risks associated with REEs, provides valuable insight into the metabolic-level biological impacts of REEs and contributes to the development of effective mitigation strategies to reduce potential risks to human health.PMID:37353023 | DOI:10.1016/j.scitotenv.2023.165018

J Adv Res. 2023 Jun 21:S2090-1232(23)00171-6. doi: 10.1016/j.jare.2023.06.008. Online ahead of print.ABSTRACTINTRODUCTION: Epidemiological evidences reveal that populations with psychological stress have an increased likelihood of respiratory viral infection involving influenza A virus (IAV) and SARS-CoV-2.OBJECTIVES: This study aims to explore the potential correlation between psychological stress and increased susceptibility to respiratory viral infections and how this may contribute to a more severe disease progression.METHODS: A chronic restraint stress (CRS) mouse model was used to infect IAV and estimate lung inflammation. Alveolar macrophages (AMs) were observed in the numbers, function and metabolic-epigenetic properties. To confirm the central importance of the gut microbiome in stress-exacerbated viral pneumonia, mice were conducted through microbiome depletion and gut microbiome transplantation.RESULTS: Stress exposure induced a decline in Lactobacillaceae abundance and hence γ-aminobutyric acid (GABA) level in mice. Microbial-derived GABA was released in the peripheral and sensed by AMs via GABAAR, leading to enhanced mitochondrial metabolism and α-ketoglutarate (αKG) generation. The metabolic intermediator in turn served as the cofactor for the epigenetic regulator Tet2 to catalyze DNA hydroxymethylation and promoted the PPARγ-centered gene program underpinning survival, self-renewing, and immunoregulation of AMs. Thus, we uncover an unappreciated GABA/Tet2/PPARγ regulatory circuitry initiated by the gut microbiome to instruct distant immune cells through a metabolic-epigenetic program. Accordingly, reconstitution with GABA-producing probiotics, adoptive transferring of GABA-conditioned AMs, or resumption of pulmonary αKG level remarkably improved AMs homeostasis and alleviated severe pneumonia in stressed mice.CONCLUSION: Together, our study identifies microbiome-derived tonic signaling tuned by psychological stress to imprint resident immune cells and defensive response in the lungs. Further studies are warranted to translate these findings, basically from murine models, into the individuals with psychiatric stress during respiratory viral infection.PMID:37353002 | DOI:10.1016/j.jare.2023.06.008

Neurobiol Dis. 2023 Jun 21:106211. doi: 10.1016/j.nbd.2023.106211. Online ahead of print.ABSTRACTBrain tissue metabolism is distributed across several cell types and subcellular compartments, which activate at different times and with different temporal patterns. The introduction of genetically-encoded fluorescent indicators that are imaged using time-lapse microscopy has opened the possibility of studying brain metabolism at cellular and sub-cellular levels. There are indicators for sugars, monocarboxylates, Krebs cycle intermediates, amino acids, cofactors, and energy nucleotides, which inform about relative levels, concentrations and fluxes. This review offers a brief survey of the metabolic indicators that have been validated in brain cells, with some illustrative examples from the literature. Whereas only a small fraction of the metabolome is currently accessible to fluorescent probes, there are grounds to be optimistic about coming developments and the application of these tools to the study of brain disease.PMID:37352985 | DOI:10.1016/j.nbd.2023.106211

J Lipid Res. 2023 Jun 21:100405. doi: 10.1016/j.jlr.2023.100405. Online ahead of print.ABSTRACTAlpha/beta hydrolase domain-containing protein 4 (ABHD4) catalyzes the deacylation of N-acyl phosphatidyl-ethanolamine (NAPE) and lyso-NAPE to produce glycerophospho-N-acyl ethanolamine (GP-NAE). Through a variety of metabolic enzymes, NAPE, lyso-NAPE, and GP-NAE are ultimately converted into NAE, a group of bioactive lipids that control many physiological processes including inflammation, cognition, food intake, and lipolysis (i.e., oleoylethanolamide or OEA). In a diet-induced obese mouse model, adipose tissue ABHD4 gene expression positively correlated with adiposity. However, it is unknown whether ABHD4 is a causal or a reactive gene to obesity. To fill this knowledge gap, we generated an ABHD4 knockout (KO) 3T3-L1 pre-adipocyte. During adipogenic stimulation, ABHD4 KO pre-adipocytes had increased adipogenesis and lipid accumulation, suggesting ABHD4 is responding to (a reactive gene), not contributing to (not a causal gene), adiposity and may serve as a mechanism for protecting against obesity. However, we did not observe any differences in adiposity and metabolic outcomes between whole body ABHD4 KO or adipocyte specific ABHD4 KO mice and their littermate control mice (both male and female) on chow or a high fat diet. This might be because we found that deletion of ABHD4 did not affect NAE such as OEA production, even though ABHD4 was highly expressed in adipose tissue and correlated with fasting adipose OEA levels and lipolysis. These data suggest that ABHD4 plays a role in adipocyte differentiation in vitro but not in adipose tissue lipid metabolism in mice despite nutrient overload, possibly due to compensation from other NAPE and NAE metabolic enzymes.PMID:37352974 | DOI:10.1016/j.jlr.2023.100405

Food Chem. 2023 Jun 11;426:136588. doi: 10.1016/j.foodchem.2023.136588. Online ahead of print.ABSTRACTWhile the "farm to fork" strategy ticks many boxes in the sustainability agenda, it does not go far enough in addressing how we can improve crop nutraceutical quality. Here, we explored whether supplementary ultraviolet (UV) radiation exposure during growth of broccoli and Chinese cabbage can induce bioactive tryptophan- and glucosinolate-specific metabolite accumulation thereby enhancing Aryl hydrocarbon receptor (AhR) activation in human intestinal cells. By combining metabolomics analysis of both plant extracts and in vitro human colonic fermentation extracts with AhR reporter cell assay, we reveal that human colonic fermentation of UVB-exposed Chinese cabbage led to enhanced AhR activation in human intestinal cells by 23% compared to plants grown without supplementary UV. Thus, by exploring aspects beyond "from farm to fork", our study highlights a new strategy to enhance nutraceutical quality of Brassicaceae, while also providing new insights into the effects of cruciferous vegetables on human intestinal health.PMID:37352713 | DOI:10.1016/j.foodchem.2023.136588

Food Chem. 2023 Jun 8;426:136507. doi: 10.1016/j.foodchem.2023.136507. Online ahead of print.ABSTRACTThis work investigated microplastic (MP) pollution in a commercially-important tuna species Katsuwonus pelamis (K. pelamis) from the Eastern Pacific and health implications. 125 MPs were extracted from gills, esophagus, stomachs, intestinal tracts, and muscle of K. pelamis. MPs in the esophagus was the highest, ∼7.6 times higher than that in the gill. Polyester and polyethylene terephthalate (PET) were dominant. Molecular docking implied that PET stabilized the complex via forming 4 new hydrogen bonds that interacted with Arg83, Gln246, Thr267, and Gly268, given that PET can enter glycerol kinase protein active pocket. Metabonomic results suggested that Glycerol 3-phosphate up expressed 1.66 more times that of control groups with no MPs in the muscle. This confirmed that MPs would lie in the glycerol kinase protein active pocket, which triggered menace to K. pelamis. The results provided insights into suggested the potential influence of MPs on the sustainability of fisheries and seafood safety.PMID:37352712 | DOI:10.1016/j.foodchem.2023.136507

Plant Physiol Biochem. 2023 Jun 18;201:107839. doi: 10.1016/j.plaphy.2023.107839. Online ahead of print.ABSTRACTThe compositions and yield of flavonoid compounds of Polygonatum cyrtonema Hua (PC) are important indices of the quality of medicinal materials. However, the flavonoids compositions and accumulation mechanism are still unclear in PC. Here, we identified 22 flavonoids using widely-targeted metabolome analysis in 15 genotypes of PC. Then weighted gene co-expression network analysis based on 45 transcriptome samples was performed to construct 12 co-expressed modules, in which blue module highly correlated with flavonoids was identified. Furthermore, 4 feature genes including PcCHS1, PcCHI, PcCHS2 and PcCHR5 were identified from 94 hub genes in blue module via machine learning methods support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF), and their functions on metabolic flux of flavonoids pathway were confirmed by tobacco transient expression system. Our findings identified representative flavonoids and key enzymes in PC that provided new insight for elite breeding rich in flavonoids, and thus will be beneficial for rapid development of great potential economic and medicinal value of PC.PMID:37352696 | DOI:10.1016/j.plaphy.2023.107839

PLoS Pathog. 2023 Jun 23;19(6):e1011449. doi: 10.1371/journal.ppat.1011449. Online ahead of print.ABSTRACTMalaria parasite release (egress) from host red blood cells involves parasite-mediated membrane poration and rupture, thought to involve membrane-lytic effector molecules such as perforin-like proteins and/or phospholipases. With the aim of identifying these effectors, we disrupted the expression of two Plasmodium falciparum perforin-like proteins simultaneously and showed that they have no essential roles during blood stage egress. Proteomic profiling of parasite proteins discharged into the parasitophorous vacuole (PV) just prior to egress detected the presence in the PV of a lecithin:cholesterol acyltransferase (LCAT; PF3D7_0629300). Conditional ablation of LCAT resulted in abnormal egress and a reduced replication rate. Lipidomic profiles of LCAT-null parasites showed drastic changes in several phosphatidylserine and acylphosphatidylglycerol species during egress. We thus show that, in addition to its previously demonstrated role in liver stage merozoite egress, LCAT is required to facilitate efficient egress in asexual blood stage malaria parasites.PMID:37352369 | DOI:10.1371/journal.ppat.1011449

PLoS Comput Biol. 2023 Jun 23;19(6):e1011221. doi: 10.1371/journal.pcbi.1011221. Online ahead of print.ABSTRACTThe intricate dependency structure of biological "omics" data, particularly those originating from longitudinal intervention studies with frequently sampled repeated measurements renders the analysis of such data challenging. The high-dimensionality, inter-relatedness of multiple outcomes, and heterogeneity in the studied systems all add to the difficulty in deriving meaningful information. In addition, the subtle differences in dynamics often deemed meaningful in nutritional intervention studies can be particularly challenging to quantify. In this work we demonstrate the use of quantitative longitudinal models within the repeated-measures ANOVA simultaneous component analysis+ (RM-ASCA+) framework to capture the dynamics in frequently sampled longitudinal data with multivariate outcomes. We illustrate the use of linear mixed models with polynomial and spline basis expansion of the time variable within RM-ASCA+ in order to quantify non-linear dynamics in a simulation study as well as in a metabolomics data set. We show that the proposed approach presents a convenient and interpretable way to systematically quantify and summarize multivariate outcomes in longitudinal studies while accounting for proper within subject dependency structures.PMID:37352364 | DOI:10.1371/journal.pcbi.1011221

Metabolomics. 2023 Jun 23;19(7):61. doi: 10.1007/s11306-023-02025-7.ABSTRACTINTRODUCTION: Polar metabolites in Caenorhabditis elegans (C. elegans) have predominantly been analyzed using hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC-MS). Capillary electrophoresis coupled to mass spectrometry (CE-MS) represents another complementary analytical platform suitable for polar and charged analytes.OBJECTIVE: We compared CE-MS and HILIC-MS for the analysis of a set of 60 reference standards relevant for C. elegans and specifically investigated the strengths of CE separation. Furthermore, we employed CE-MS as a complementary analytical approach to study polar metabolites in C. elegans samples, particularly in the context of longevity, in order to address a different part of its metabolome.METHOD: We analyzed 60 reference standards as well as metabolite extracts from C. elegans daf-2 loss-of-function mutants and wild-type (WT) samples using HILIC-MS and CE-MS employing a Q-ToF-MS instrument.RESULTS: CE separations showed narrower peak widths and a better linearity of the estimated response function across different concentrations which is linked to less saturation of the MS signals. Additionally, CE exhibited a distinct selectivity in the separation of compounds compared to HILIC-MS, providing complementary information for the analysis of the target compounds. Analysis of C. elegans metabolites of daf-2 mutants and WT samples revealed significant alterations in shared metabolites identified through HILIC-MS, as well as the presence of distinct metabolites.CONCLUSION: CE-MS was successfully applied in C. elegans metabolomics, being able to recover known as well as identify novel putative biomarkers of longevity.PMID:37351740 | DOI:10.1007/s11306-023-02025-7

Metabolomics. 2023 Jun 23;19(7):62. doi: 10.1007/s11306-023-02026-6.ABSTRACTINTRODUCTION: Assessing intraspecific variation in plant volatile organic compounds (VOCs) involves pitfalls that may bias biological interpretation, particularly when several laboratories collaborate on joint projects. Comparative, inter-laboratory ring trials can inform on the reproducibility of such analyses.OBJECTIVES: In a ring trial involving five laboratories, we investigated the reproducibility of VOC collections with polydimethylsiloxane (PDMS) and analyses by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). As model plant we used Tanacetum vulgare, which shows a remarkable diversity in terpenoids, forming so-called chemotypes. We performed our ring-trial with two chemotypes to examine the sources of technical variation in plant VOC measurements during pre-analytical, analytical, and post-analytical steps.METHODS: Monoclonal root cuttings were generated in one laboratory and distributed to five laboratories, in which plants were grown under laboratory-specific conditions. VOCs were collected on PDMS tubes from all plants before and after a jasmonic acid (JA) treatment. Thereafter, each laboratory (donors) sent a subset of tubes to four of the other laboratories (recipients), which performed TD-GC-MS with their own established procedures.RESULTS: Chemotype-specific differences in VOC profiles were detected but with an overall high variation both across donor and recipient laboratories. JA-induced changes in VOC profiles were not reproducible. Laboratory-specific growth conditions led to phenotypic variation that affected the resulting VOC profiles.CONCLUSION: Our ring trial shows that despite large efforts to standardise each VOC measurement step, the outcomes differed both qualitatively and quantitatively. Our results reveal sources of variation in plant VOC research and may help to avoid systematic errors in similar experiments.PMID:37351733 | DOI:10.1007/s11306-023-02026-6