PubMed

Hypertension. 2023 May 1. doi: 10.1161/HYPERTENSIONAHA.123.20921. Online ahead of print.ABSTRACTBACKGROUND: Primary aldosteronism is frequently caused by an adrenocortical aldosterone-producing adenoma (APA) carrying a somatic mutation that drives aldosterone overproduction. APAs with a mutation in KCNJ5 (APA-KCNJ5MUT) are characterized by heterogeneous CYP11B2 (aldosterone synthase) expression, a particular cellular composition and larger tumor diameter than those with wild-type KCNJ5 (APA-KCNJ5WT). We exploited these differences to decipher the roles of transcriptome and metabolome reprogramming in tumor pathogenesis.METHODS: Consecutive adrenal cryosections (7 APAs and 7 paired adjacent adrenal cortex) were analyzed by spatial transcriptomics (10x Genomics platform) and metabolomics (in situ matrix-assisted laser desorption/ionization mass spectrometry imaging) co-integrated with CYP11B2 immunohistochemistry.RESULTS: We identified intratumoral transcriptional heterogeneity that delineated functionally distinct biological pathways. Common transcriptomic signatures were established across all APA specimens which encompassed 2 distinct transcriptional profiles in CYP11B2-immunopositive regions (CYP11B2-type 1 or 2). The CYP11B2-type 1 signature was characterized by zona glomerulosa gene markers and was detected in both APA-KCNJ5MUT and APA-KCNJ5WT. The CYP11B2-type 2 signature displayed markers of the zona fasciculata or reticularis and predominated in APA-KCNJ5MUT. Metabolites that promote oxidative stress and cell death accumulated in APA-KCNJ5WT. In contrast, antioxidant metabolites were abundant in APA-KCNJ5MUT. Finally, APA-like cell subpopulations-negative for CYP11B2 gene expression-were identified in adrenocortical tissue adjacent to APAs suggesting the existence of tumor precursor states.CONCLUSIONS: Our findings provide insight into intra- and intertumoral transcriptional heterogeneity and support a role for prooxidant versus antioxidant systems in APA pathogenesis highlighting genotype-dependent capacities for tumor expansion.PMID:37125608 | DOI:10.1161/HYPERTENSIONAHA.123.20921

Rapid Commun Mass Spectrom. 2023 May 1:e9529. doi: 10.1002/rcm.9529. Online ahead of print.ABSTRACTRATIONALE: Thymoma is a rare malignant tumor but it is the most common primary tumor of the anterior mediastinum. The current imaging methods for thymoma screening suffer from false positive rate problem, and thymoma pathogenesis remains elusive. Study of thymoma metabolic characteristics could provide clues for improving the diagnosis and understanding the pathogenesis of thymoma.METHODS: Metabolic profiling of sera from thymoma and thymic hyperplasia patients was performed using UPLC-HRMS in both positive and negative ionization modes. After pre- and post-processing, the dataset was divided into three age groups and statistical analysis was performed to select differential metabolites of thymoma. For feature identification, experimental MS/MS spectra were matched to those of databases and available chemical standards, and also manually annotated with plausible chemical structures to ensure high identification confidence.RESULTS: A total of 47 differential metabolites were identified in thymoma. Significant higher levels of histidine, sphinganine 1-phosphate, lactic acid dimer, phenylacetylglutamine, LPC (18:3) and LPC (16:1), and significant lower levels of phenylalanine, indole-3-propionic acid (IPA), hippuric acid and mesobilirubinogen were associated with thymoma. Tryptophan level in thymoma-associated myasthenia gravis (TAMG) was significantly lower than that of the MG (-) group. IPA and hippuric acid abundances exhibited increasing trends from indolent to aggressive thymoma.CONCLUSION: Our study revealed aberrant aromatic amino acid metabolism and fatty acid oxidation might be associated with thymoma. The identified unique metabolic characteristics of thymoma may provide valuable information for study of the molecular mechanism of thymoma pathogenesis, and improvement of diagnosis and discovery of new therapeutic strategies for thymoma.PMID:37125446 | DOI:10.1002/rcm.9529

Toxicol Res (Camb). 2023 Mar 25;12(2):282-295. doi: 10.1093/toxres/tfad020. eCollection 2023 Apr.ABSTRACTBACKGROUND: Although many studies have shown that herbs containing aristolochic acids can treat various human diseases, AAΙ in particular has been implicated as a nephrotoxic agent.METHODS AND RESULTS: Here, we detail the nephrotoxic effect of AAΙ via an approach that integrated 1H NMR-based metabonomics and network pharmacology. Our findings revealed renal injury in mice after the administration of AAΙ. Metabolomic data confirmed significant differences among the renal metabolic profiles of control and model groups, with significant reductions in 12 differential metabolites relevant to 23 metabolic pathways. Among them, there were seven important metabolic pathways: arginine and proline metabolism; glycine, serine, and threonine metabolism; taurine and hypotaurine metabolism; ascorbate and aldehyde glycolate metabolism; pentose and glucosinolate interconversion; alanine, aspartate, and glutamate metabolism; and glyoxylate and dicarboxylic acid metabolism. Relevant genes, namely, nitric oxide synthase 1 (NOS1), pyrroline-5-carboxylate reductase 1 (PYCR1), nitric oxide synthase 3 (NOS3) and glutamic oxaloacetic transaminase 2 (GOT2), were highlighted via network pharmacology and molecular docking techniques. Quantitative real-time PCR findings revealed that AAI administration significantly downregulated GOT2 and NOS3 and significantly upregulated NOS1 and PYCR1 expression and thus influenced the metabolism of arginine and proline.CONCLUSION: This work provides a meaningful insight for the mechanism of AAΙ renal injury.PMID:37125334 | PMC:PMC10141773 | DOI:10.1093/toxres/tfad020

Toxicol Res (Camb). 2023 Feb 14;12(2):201-215. doi: 10.1093/toxres/tfad008. eCollection 2023 Apr.ABSTRACTINTRODUCTION: Qishenbuqi capsule (QSBQC), a listed Chinese patent prescription, comprises of 4 herbs. Clinically, it has been shown to improve immune functions.METHODS: Subjects with Qi deficiency and non-Qi deficiency were recruited, who then took QSBQC for 4 weeks. Traditional Chinese medicine (TCM) syndrome scores and the levels of white blood cells, CD3+ T cells (CD3+), CD4+ T cells (CD3+CD4+), CD8+ T cells (CD3+CD8+), and CD4+/CD8+ were determined. Serum metabolomics was used to explore the metabolic mechanisms of QSBQC on improving immunity. Meanwhile, the potential active ingredients, targets, and pathways of QSBQC on enhancing immunity were screened by network pharmacology.RESULTS: QSBQC significantly improved TCM syndrome scores and increased the number of CD8+ T cells of both Qi deficiency and non-Qi deficiency subjects. Serum metabolomics revealed that QSBQC regulated 18 differential metabolites and 8 metabolic pathways of Qi deficiency, and 12 differential metabolites and 7 metabolic pathways of non-Qi deficiency subjects. The "herbs-compounds-pathways" diagram showed that PQ-2, cimifugin, and divaricatol were the main active components. Pathways in cancer and arginine and proline metabolism could be the most important pathways.CONCLUSION: Our research revealed the immunoenhancing mechanisms of QSBQC and improved the combination of TCM theory and modern western medicine theory.PMID:37125330 | PMC:PMC10141780 | DOI:10.1093/toxres/tfad008

Front Microbiol. 2023 Apr 13;14:1155438. doi: 10.3389/fmicb.2023.1155438. eCollection 2023.ABSTRACTExamining how host cells affect metabolic behaviors of probiotics is pivotal to better understand the mechanisms underlying the probiotic efficacy in vivo. However, studies to elucidate the interaction between probiotics and host cells, such as intestinal epithelial cells, remain limited. Therefore, in this study, we performed a comprehensive metabolome analysis of a co-culture containing Bifidobacterium breve MCC1274 and induced pluripotent stem cells (iPS)-derived small intestinal-like cells. In the co-culture, we observed a significant increase in several amino acid metabolites, including indole-3-lactic acid (ILA) and phenyllactic acid (PLA). In accordance with the metabolic shift, the expression of genes involved in ILA synthesis, such as transaminase and tryptophan synthesis-related genes, was also elevated in B. breve MCC1274 cells. ILA production was enhanced in the presence of purines, which were possibly produced by intestinal epithelial cells (IECs). These findings suggest a synergistic action of probiotics and IECs, which may represent a molecular basis of host-probiotic interaction in vivo.PMID:37125172 | PMC:PMC10133457 | DOI:10.3389/fmicb.2023.1155438

Front Nutr. 2023 Apr 14;10:1166393. doi: 10.3389/fnut.2023.1166393. eCollection 2023.ABSTRACTBACKGROUND: To investigate the mechanism of plant protein components on nutritional value, growth performance, flesh quality, flavor, and proliferation of myocytes of yellow catfish (Pelteobagrus fulvidraco).METHODS: A total of 540 yellow catfish were randomly allotted into six experimental groups with three replicates and fed six different diets for 8 weeks.RESULTS AND CONCLUSIONS: The replacement of fish meal with cottonseed meal (CM), sesame meal (SEM), and corn gluten meal (CGM) in the diet significantly reduced growth performance, crude protein, and crude lipid, but the flesh texture (hardness and chewiness) was observably increased. Moreover, the flavor-related amino acid (glutamic acid, glycine, and proline) contents in the CM, SEM, and CGM groups of yellow catfish muscle were significantly increased compared with the fish meal group. The results of metabolomics showed that soybean meal (SBM), peanut meal (PM), CM, SEM, and CGM mainly regulated muscle protein biosynthesis by the variations in the content of vitamin B6, proline, glutamic acid, phenylalanine, and tyrosine in muscle, respectively. In addition, Pearson correlation analysis suggested that the increased glutamic acid content and the decreased tyrosine content were significantly correlated with the inhibition of myocyte proliferation genes. This study provides necessary insights into the mechanism of plant proteins on the dynamic changes of muscle protein, flesh quality, and myocyte proliferation in yellow catfish.PMID:37125039 | PMC:PMC10140373 | DOI:10.3389/fnut.2023.1166393

Front Nutr. 2023 Mar 23;10:1104685. doi: 10.3389/fnut.2023.1104685. eCollection 2023.ABSTRACTBACKGROUND: Many studies show that the intake of raspberries is beneficial to immune-metabolic health, but the responses of individuals are heterogeneous and not fully understood.METHODS: In a two-arm parallel-group, randomized, controlled trial, immune-metabolic outcomes and plasma metabolite levels were analyzed before and after an 8-week red raspberry consumption. Based on partial least squares discriminant analysis (PLS-DA) on plasma xenobiotic levels, adherence to the intervention was first evaluated. A second PLS-DA followed by hierarchical clustering was used to classify individuals into response subgroups. Clinical immune and metabolic outcomes, including insulin resistance (HOMA-IR) and sensitivity (Matsuda, QUICKI) indices, during the intervention were assessed and compared between response subgroups.RESULTS: Two subgroups of participants, type 1 responders (n = 17) and type 2 responders (n = 5), were identified based on plasma metabolite levels measured during the intervention. Type 1 responders showed neutral to negative effects on immune-metabolic clinical parameters after raspberry consumption, and type 2 responders showed positive effects on the same parameters. Changes in waist circumference, waist-to-hip ratio, fasting plasma apolipoprotein B, C-reactive protein and insulin levels as well as Matsuda, HOMA-IR and QUICKI were significantly different between the two response subgroups. A deleterious effect of two carotenoid metabolites was also observed in type 1 responders but these variables were significantly associated with beneficial changes in the QUICKI index and in fasting insulin levels in type 2 responders. Increased 3-ureidopropionate levels were associated with a decrease in the Matsuda index in type 2 responders, suggesting that this metabolite is associated with a decrease in insulin sensitivity for those subjects, whereas the opposite was observed for type 1 responders.CONCLUSION: The beneficial effects associated with red raspberry consumption are subject to inter-individual variability. Metabolomics-based clustering appears to be an effective way to assess adherence to a nutritional intervention and to classify individuals according to their immune-metabolic responsiveness to the intervention. This approach may be replicated in future studies to provide a better understanding of how interindividual variability impacts the effects of nutritional interventions on immune-metabolic health.PMID:37125033 | PMC:PMC10130762 | DOI:10.3389/fnut.2023.1104685

Front Endocrinol (Lausanne). 2023 Apr 14;14:1139725. doi: 10.3389/fendo.2023.1139725. eCollection 2023.ABSTRACTINTRODUCTION: Flaxseed oil (FO) and vitamin E (VE) both have antioxidant effects on sperm. The present study investigated the effects of dietary supplementation with FO and/or VE on semen quality.METHODS: 16 fertile Simmental bulls were selected and randomly divided into 4 groups (n = 4): the control group (control diet), FO group (control diet containing 24 g/kg FO), VE group (control diet containing 150 mg/kg VE) and FOVE group (control diet containing 150 mg/kg VE and 24 g/kg FO), and the trial lasted 10 weeks.RESULTS: The results showed that the addition of FO independently can increase sperm motion parameters, the levels of catalase (CAT), glutathione peroxidase (GSH-Px), testosterone (T) and estradiol (E2), while reduce oxidative stress in seminal plasma (P < 0.05). Supplement of VE independently can increased the motility, motility parameters, CAT and superoxide dismutase (SOD) levels, and reduce oxidative stress in seminal plasma (P < 0.05). There was an interaction effect of FO × VE on motility and reactive oxygen species (ROS), while GSH-Px and ROS were affected by week × VE 2-way interaction, levels of T and E2 were also affected by the dietary FO × week interaction (P < 0.05). The triple interaction effects of FO, VE and week were significant for malondialdehyde (MDA) (P < 0.05). Compared with the control group, sperm from the FOVE group had a significantly higher in vitro fertilization (IVF) rate, and subsequent embryos had increased developmental ability with reduced ROS levels at the eight-cell stage, then increased adenosine triphosphate (ATP) content and gene expression levels of CAT, CDX2, Nanog, and SOD at the blastocyst stage (P < 0.05). Metabolomic and transcriptomic results indicated that dietary supplementation of FO and VE increased the expression of the metabolite aconitic acid, as well as the expression of ABAT and AHDHA genes.CONCLUSION: With in-silico analysis, it can be concluded that the effects of dietary FO and VE on improving semen quality and embryo development may be related to increased aconitic acid via the ABAT and AHDHA genes involved in the propionic acid metabolism pathway.PMID:37124753 | PMC:PMC10140321 | DOI:10.3389/fendo.2023.1139725

Front Endocrinol (Lausanne). 2023 Apr 12;14:1095550. doi: 10.3389/fendo.2023.1095550. eCollection 2023.ABSTRACTOBJECTIVES: This study aimed to assess the association between plasma glutamate (Glu) and the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) and whether this association differs by gender.MATERIAL AND METHODS: We retrieved clinical information on 1032 consecutive patients with T2DM from a same tertiary care center from May 2015 to August 2016. Glu was quantified by liquid chromatography-tandem mass spectrometry analysis. Glu was converted into a categorical variable based on the median concentration in the whole population, while logistic regression was used to obtain the odds ratio (OR) and 95% confidence interval (CI), and the correlation between Glu and various biochemical indices was analyzed.RESULTS: We found that Glu was positively associated with the risk of CVD in patients with T2DM. This correlation was more significant in women. In T2DM patients, the higher the age, body mass index (BMI), weight and systolic blood pressure (SBP), the lower the glycosylated hemoglobin (HbA1C) concentration and the higher the Glu. In female patients, the correlation between age, weight, BMI, SBP, and plasma Triglycerides (TG), and Glu was also statistically significant.CONCLUSION: In conclusion, female T2DM patients with high levels of Glu have a higher risk of developing CVD.PMID:37124739 | PMC:PMC10130405 | DOI:10.3389/fendo.2023.1095550

Front Oncol. 2023 Apr 14;13:1164266. doi: 10.3389/fonc.2023.1164266. eCollection 2023.ABSTRACTMetabolomic analysis is a vital part of studying cancer progression. Metabonomic crosstalk, such as nutrient availability, physicochemical transformation, and intercellular interactions can affect tumor metabolism. Many original studies have demonstrated that metabolomics is important in some aspects of tumor metabolism. In this mini-review, we summarize the definition of metabolomics and how it can help change a tumor microenvironment, especially in pathways of three metabonomic tumors. Just as non-invasive biofluids have been identified as early biomarkers of tumor development, metabolomics can also predict differences in tumor drug response, drug resistance, and efficacy. Therefore, metabolomics is important for tumor metabolism and how it can affect oncology drugs in cancer therapy.PMID:37124524 | PMC:PMC10140396 | DOI:10.3389/fonc.2023.1164266

Front Pharmacol. 2023 Apr 12;14:1102465. doi: 10.3389/fphar.2023.1102465. eCollection 2023.ABSTRACTRecent interest in mushrooms and their components as potential therapies for mental health, along with recent government and health authority approvals, has necessitated a more comprehensive understanding of their effects on the cellular microenvironment of the brain. Amanita muscaria has been ingested as a treatment for a variety of ailments for centuries, most notably those affecting the central nervous system and conditions associated with neuroinflammation. However, the effects of these extracts on neuroinflammatory cells, such as microglia, are unknown. The effect of commercially-sourced A. muscaria extract (AME-1) on human microglial cell line (HMC3) expression of surface receptors such as CD86, CXCR4, CD45, CD125 and TLR4 was determined by flow cytometry. AME-1 upregulated expression of all of these receptors. The effect of AME-1 on HMC3 production of IL-8 and IL-6 was determined and compared to tumor necrosis factor (TNF), polyinosinic-polycytidylic acid [poly(I:C)], substance P and lipopolysaccharide (LPS), all known activators of HMC-3 and primary microglia. HMC3 produced both IL-8 and IL-6 when activated with LPS, TNF and poly(I:C) but not when they were activated with substance P. Although AME-1 at higher concentrations increased IL-8 production of HMC3 on its own, AME-1 notably potentiated HMC3 production of IL-8 in response to poly(I:C). AME-1 altered expression of toll-like receptor 3 (TLR3) mRNA but not surface protein by HMC3. AME-1 also did not significantly alter expression of retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated protein 5 (MDA5), both cytosolic sensors of dsRNA. Metabolomics analysis showed that AME-1 contained several metabolites, including the autophagy inducer, trehalose. Like AME-1, trehalose also potentiated HMC3 poly(I:C) mediated production of IL-8. This study suggests that A. muscaria extracts can modify HMC3 inflammatory responses, possibly due to their trehalose content.PMID:37124206 | PMC:PMC10130647 | DOI:10.3389/fphar.2023.1102465

AoB Plants. 2023 Apr 10;15(2):plad014. doi: 10.1093/aobpla/plad014. eCollection 2023 Feb.ABSTRACTThe dynamic trajectory of metabolites and gene expression related to phosphorus absorption and utilization in soybean seedling roots were determined under short- and long-term phosphorus deficiency stress. The metabolome results showed that TCA and GS/GOGAT cycles were enhanced after 2 days of phosphorus deficiency stress; however, they were inhibited after 15 days. GC-TOF-MS showed that phosphorus deficiency increased the accumulation of amino acids significantly after 2 days, whereas organic acids and lipid substances increased significantly after 15 days. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed that transcriptional levels of five key genes related to phosphorus activation and phosphorus starvation signal transduction increased continuously with phosphorus deficiency. The expression of GmPHT1 and GmSPX triggered the phosphorus starvation signal pathway and induced the expression of the GmPS and GmPAP genes to enhance the synthesis and secretion of organophosphorus hydrolase and organic acid in soybean roots under phosphorus deficiency. The phospholipid metabolism was enhanced significantly after 15 days of stress and when GmSQD, a crucial enzyme in lipid biosynthesis, was up-regulated. Thus, we propose that future investigations on stress caused by phosphorus deficiency should include more organs obtained at different developmental stages.PMID:37124081 | PMC:PMC10132309 | DOI:10.1093/aobpla/plad014

Front Plant Sci. 2023 Apr 14;14:1125065. doi: 10.3389/fpls.2023.1125065. eCollection 2023.ABSTRACTAbove-ground material of members of the mint family is commercially distilled to extract essential oils, which are then formulated into a myriad of consumer products. Most of the research aimed at characterizing the processes involved in the formation of terpenoid oil constituents has focused on leaves. We now demonstrate, by investigating three mint species, peppermint (Mentha ˣ piperita L.), spearmint (Mentha spicata L.) and horsemint (Mentha longifolia (L.) Huds.; accessions CMEN 585 and CMEN 584), that other organs - namely stems, rhizomes and roots - also emit volatiles and that the terpenoid volatile composition of these organs can vary substantially from that of leaves, supporting the notion that substantial, currently underappreciated, chemical diversity exists. Differences in volatile quantities released by plants whose roots had been dipped in a Verticillium dahliae-spore suspension (experimental) or dipped in water (controls) were evident: increases of some volatiles in the root headspace of mint species that are susceptible to Verticillium wilt disease (peppermint and M. longifolia CMEN 584) were detected, while the quantities of certain volatiles decreased in rhizomes of species that show resistance to the disease (spearmint and M. longifolia CMEN 585). To address the genetic and biochemical basis underlying chemical diversity, we took advantage of the newly sequenced M. longifolia CMEN 585 genome to identify candidate genes putatively coding for monoterpene synthases (MTSs), the enzymes that catalyze the first committed step in the biosynthesis of monoterpenoid volatiles. The functions of these genes were established by heterologous expression in Escherichia coli, purification of the corresponding recombinant proteins, and enzyme assays, thereby establishing the existence of MTSs with activities to convert a common substrate, geranyl diphosphate, to (+)-α-terpineol, 1,8-cineole, γ-terpinene, and (-)-bornyl diphosphate, but were not active with other potential substrates. In conjunction with previously described MTSs that catalyze the formation of (-)-β-pinene and (-)-limonene, the product profiles of the MTSs identified here can explain the generation of all major monoterpene skeletons represented in the volatiles released by different mint organs.PMID:37123862 | PMC:PMC10140540 | DOI:10.3389/fpls.2023.1125065

Front Plant Sci. 2023 Apr 14;14:1173489. doi: 10.3389/fpls.2023.1173489. eCollection 2023.ABSTRACTPyrrosia petiolosa (Christ) Ching has both medicinal and health benefits in China. The potential antioxidant activities of P. petiolosa, which are mainly attributed to its flavonoids, have attracted much attention in recent years. The present study aimed to determine the concentration of flavonoid components and evaluate the relative antioxidant activities of P. petiolosa from different geographic origins using a UPLC-MRM-MS-based metabolomics approach. In total, 97 flavonoid components were identified, and their concentrations in the samples from different geographic locations showed significant variation. Thirteen flavonoid components were identified as potential biomarkers for distinguishing between the two major regions, Guizhou (GZ) and Guangxi (GX). The GZ group showed higher total flavonoid content, free radical scavenging activities, and ferric reducing antioxidant power. The well positive correlations were found between the antioxidant capacities and some flavonoid markers. The ecogeographic factors, namely altitude and longitude, play a crucial role in the difference of antioxidant activities and flavonoids concentration. These results indicate that P. petiolosa is rich in flavonoid compounds and is a promising source of natural antioxidants, providing a basis for the quality control of P. petiolosa.PMID:37123848 | PMC:PMC10140315 | DOI:10.3389/fpls.2023.1173489

Front Plant Sci. 2023 Apr 12;14:1103413. doi: 10.3389/fpls.2023.1103413. eCollection 2023.ABSTRACTPlant-microbe interactions are a phenomenal display of symbiotic/parasitic relationships between living organisms. Plant growth-promoting rhizobacteria (PGPR) are some of the most widely investigated plant-beneficial microbes due to their capabilities in stimulating plant growth and development and conferring protection to plants against biotic and abiotic stresses. As such, PGPR-mediated plant priming/induced systemic resistance (ISR) has become a hot topic among researchers, particularly with prospects of applications in sustainable agriculture. The current study applies untargeted ultra-high performance liquid chromatography-high-definition mass spectrometry (UHPLC-HDMS) to investigate PGPR-based metabolic reconfigurations in the metabolome of primed wheat plants against Puccinia striiformis f. sp. tricti (Pst). A seed bio-priming approach was adopted, where seeds were coated with two PGPR strains namely Bacillus subtilis and Paenibacillus alvei (T22) and grown under controlled conditions in a glasshouse. The plants were infected with Pst one-week post-germination, followed by weekly harvesting of leaf material. Subsequent metabolite extraction was carried out for analysis on a UHPLC-HDMS system for data acquisition. The data was chemometrically processed to reveal the underlying trends and data structures as well as potential signatory biomarkers for priming against Pst. Results showed notable metabolic reprogramming in primary and secondary metabolism, where the amino acid and organic acid content of primed-control, primed-challenged and non-primed-challenged plants were differentially reprogrammed. Similar trends were observed from the secondary metabolism, in which primed plants (particularly primed-challenged) showed an up-regulation of phenolic compounds (flavonoids, hydroxycinnamic acids-HCAs- and HCA amides) compared to the non-primed plants. The metabolomics-based semi-quantitative and qualitative assessment of the plant metabolomes revealed a time-dependent metabolic reprogramming in primed-challenged and primed-unchallenged plants, indicating the metabolic adaptations of the plants to stripe rust infection over time.PMID:37123830 | PMC:PMC10132142 | DOI:10.3389/fpls.2023.1103413

Front Plant Sci. 2023 Apr 14;14:1131735. doi: 10.3389/fpls.2023.1131735. eCollection 2023.ABSTRACTCucumber is one of the most important vegetable crops, which is widely planted all over the world. Cucumber always suffers from high-temperature stress in South China in summer. In this study, liquid chromatography-mass spectrometry (LC-MS) analysis was used to study the differential metabolites of cucumber anther between high-temperature (HT) stress and normal condition (CK). After HT, the pollen fertility was significantly reduced, and abnormal anther structures were observed by the paraffin section. In addition, the metabolomics analysis results showed that a total of 125 differential metabolites were identified after HT, consisting of 99 significantly upregulated and 26 significantly downregulated metabolites. Among these differential metabolites, a total of 26 related metabolic pathways were found, and four pathways showed significant differences, namely, porphyrin and chlorophyll metabolism; plant hormone signal transduction; amino sugar and nucleotide sugar metabolism; and glycine, serine, and threonine metabolism. In addition, pollen fertility was decreased by altering the metabolites of plant hormone signal transduction and amino acid and sugar metabolism pathway under HT. These results provide a comprehensive understanding of the metabolic changes in cucumber anther under HT.PMID:37123826 | PMC:PMC10140443 | DOI:10.3389/fpls.2023.1131735

iScience. 2023 Apr 1;26(4):106556. doi: 10.1016/j.isci.2023.106556. eCollection 2023 Apr 21.ABSTRACTThe bZIP transcription factors are well-known transcriptional regulators that are essential for regulating resistance to biotic and abiotic stresses in plants. In this study, a total of 56 putative bZIP members were identified in passion fruit (Passiflora edulis). An integrative analysis was performed using bioinformatics. Transcriptome analysis revealed that most PebZIPs respond to drought, salt, cold and heat stress. By combining the transcriptome results of two different resistant genotypes, four representative members were finally selected for differential expression validation in different tissues and cultivars. Furthermore, transcriptome and metabolome association analysis revealed consistent expression trends of PeZIP20 and PeZIP21, with only one difference at 63aa, with different metabolites including flavonoids, lipids and amino acids. This work will contribute to further studies of the functions of bZIPs and their resistance properties, as well as to the development of novel germplasm.PMID:37123220 | PMC:PMC10130921 | DOI:10.1016/j.isci.2023.106556

Livers. 2022 Dec;2(4):243-257. doi: 10.3390/livers2040020. Epub 2022 Oct 4.ABSTRACTOne carbon metabolism (1CM) can be defined as the transfer of a carbon unit from one metabolite to another and its replenishment by different sources of labile methyl-group nutrients: primarily choline, methionine, betaine, and serine. This flow of carbon units allows the biosynthesis of nucleotides, amino acids, formylated methionyl-tRNA, polyamines, glutathione, phospholipids, detoxification reactions, maintenance of the redox status and the concentration of NAD, and methylation reactions including epigenetic modifications. That is, 1CM functions as a nutrient sensor and integrator of cellular metabolism. A critical process in 1CM is the synthesis of S-adenosylmethionine (SAMe), the source of essentially all the hundreds of millions of daily methyl transfer reactions in a cell. This versatility of SAMe imposes a tight control in its synthesis and catabolism. Much of our knowledge concerning 1CM has been gained from studies in the production and prevention of nonalcoholic fatty liver disease (NAFLD). Here, we discuss in detail the function of the most important enzymes for their quantitative contribution to maintaining the flux of carbon units through 1CM in the liver and discuss how alterations in their enzymatic activity contribute to the development of NAFLD. Next, we discuss NAFLD subtypes based on serum lipidomic profiles with different risk of cardiovascular disease. Among the latter, we highlight the so-called subtype A for its serum lipidomic profile phenocopying that of mice deficient in SAMe synthesis and because its high frequency (about 50% of the NAFLD patients).PMID:37123053 | PMC:PMC10137169 | DOI:10.3390/livers2040020

Front Immunol. 2023 Apr 14;14:1114586. doi: 10.3389/fimmu.2023.1114586. eCollection 2023.ABSTRACTBACKGROUND: Gut dysbiosis and gut microbiome-derived metabolites have been implicated in both disease onset and treatment response, but this has been rarely demonstrated in pemphigus vulgaris (PV). Here, we aim to systematically characterize the gut microbiome to assess the specific microbial species and metabolites associated with PV.METHODS: We enrolled 60 PV patients and 19 matched healthy family members, and collected 100 fecal samples (60 treatment-naïve, 21 matched post-treatment, and 19 controls). Metagenomic shotgun sequencing and subsequent quality control/alignment/annotation were performed to assess the composition and microbial species, in order to establish the association between gut microbiome with PV onset and treatment response. In addition, we evaluated short-chain fatty acids (SCFAs) in PV patients through targeted metabolomics analysis.RESULTS: The diversity of the gut microbiome in PV patients deviates from the healthy family members but not between responder and non-responder, or before and after glucocorticoid treatment. However, the relative abundance of several microbial species, including the pathogenic bacteria (e.g., Escherichia coli) and some SCFA-producing probiotics (e.g., Eubacterium ventriosum), consistently differed between the two groups in each comparison. Escherichia coli was enriched in PV patients and significantly decreased after treatment in responders. In contrast, Eubacterium ventriosum was enriched in healthy family members and significantly increased particularly in responders after treatment. Consistently, several gut microbiome-derived SCFAs were enriched in healthy family members and significantly increased after treatment (e.g., butyric acid and valeric acid).CONCLUSIONS: This study supports the association between the gut microbiome and PV onset, possibly through disrupting the balance of gut pathogenic bacteria and probiotics and influencing the level of gut microbiome-derived SCFAs. Furthermore, we revealed the potential relationship between specific microbial species and glucocorticoid treatment.PMID:37122759 | PMC:PMC10140300 | DOI:10.3389/fimmu.2023.1114586

Front Immunol. 2023 Apr 14;14:1139249. doi: 10.3389/fimmu.2023.1139249. eCollection 2023.ABSTRACTINTRODUCTION: The present study assessed whether asinine milk supplementation improved the immune and behavioral responses of piglets during an early life weaning stress event as a model for its future use in humans.METHODS: For this, 48 piglets from 4 different litters were used. At 20 days of age, piglets were weighed and allocated with their litter and dam into group pens until 28 days of age. Four piglets from each litter were then randomly assigned to either (1) asinine milk supplementation (n = 16) (2), skimmed cow milk supplementation (n = 16) or (3) no supplementation (n = 16; control group). The supplementations were voluntarily administered for 3 days preweaning and 3 days postweaning using a baby bottle. The effects on the weaning stress response were assessed through salivary cortisol measurements; behavioral tests such as the open field, novel object end elevated plus maze tests; and gene expression of HSD11B1, NR3C1 and IL1B in PBMCs, which was determined by RT-qPCR and normalized to GAPDH and UBB. To test the effect of the supplementations on weight, milk intake, gene expression, and behavior, a randomized block design was used with repeated measurements over time by the PROC MIXED procedure.RESULTS AND DISCUSSION: The effects on salivary cortisol were determined using the ratio between the morning and afternoon concentrations, considering the time before and after the weaning event. Principal component analysis (PCA) and Fisher's test were performed to evaluate the behavior test data. When comparing salivary cortisol concentrations between the pre- and postweaning periods, there was a difference (p < 0.05) between the supplementation groups in the afternoon period, suggesting that piglets fed asinine milk had lower afternoon cortisol concentrations postweaning than their counterparts. For the behavioral tests, the supplementations had no measurable effects. No difference was between groups pre- and postweaning for the expression of HSD11B2, which codes for an enzyme that breaks down cortisol. However, the expression of NR3C1, which encodes the glucocorticoid receptor, was significantly upregulated in piglets supplemented with cow milk (mean 1.245; p < 0.05).CONCLUSION: Asinine milk downregulated 1L1B gene expression, which codes for an inflammatory cytokine. In conclusion, these results suggest that supplementation with asinine milk may represent a strategy to diminish the damage associated with an early life event by modulating IL1B expression and reducing salivary cortisol levels in piglets undergoing weaning stress. Further transcriptomic and metabolomic studies may improve our understanding of the molecular pathways that mediate this systemic immune-mediated response.PMID:37122716 | PMC:PMC10140756 | DOI:10.3389/fimmu.2023.1139249