PubMed

Arch Toxicol. 2023 Oct 6. doi: 10.1007/s00204-023-03612-2. Online ahead of print.ABSTRACTNanoparticles have been used in neurological research in recent years because of their blood-brain barrier penetration activity. However, their potential neuronanotoxicity remains a concern. In particular, microglia, which are resident phagocytic cells, are mainly exposed to nanoparticles in the brain. We investigated the changes in lysosomal function in silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)]-treated BV2 murine microglial cells. In addition, we analyzed amyloid beta (Aβ) accumulation and molecular changes through the integration of transcriptomics, proteomics, and metabolomics (triple-omics) analyses. Aβ accumulation significantly increased in the 0.1 μg/μl MNPs@SiO2(RITC)-treated BV2 cells compared to the untreated control and 0.01 μg/μl MNPs@SiO2(RITC)-treated BV2 cells. Moreover, the MNPs@SiO2(RITC)-treated BV2 cells showed lysosomal swelling, a dose-dependent reduction in proteolytic activity, and an increase in lysosomal swelling- and autophagy-related protein levels. Moreover, proteasome activity decreased in the MNPs@SiO2(RITC)-treated BV2 cells, followed by a concomitant reduction in intracellular adenosine triphosphate (ATP). By employing triple-omics and a machine learning algorithm, we generated an integrated single molecular network including reactive oxygen species (ROS), autophagy, lysosomal storage disease, and amyloidosis. In silico analysis of the single triple omics network predicted an increase in ROS, suppression of autophagy, and aggravation of lysosomal storage disease and amyloidosis in the MNPs@SiO2(RITC)-treated BV2 cells. Aβ accumulation and lysosomal swelling in the cells were alleviated by co-treatment with glutathione (GSH) and citrate. These findings suggest that MNPs@SiO2(RITC)-induced reduction in lysosomal activity and proteasomes can be recovered by GSH and citrate treatment. These results also highlight the relationship between nanotoxicity and Aβ accumulation.PMID:37798515 | DOI:10.1007/s00204-023-03612-2

J Biosci Bioeng. 2023 Oct 3:S1389-1723(23)00301-8. doi: 10.1016/j.jbiosc.2023.09.006. Online ahead of print.ABSTRACTIn current research, yeast species Issatchenkia terricola WJL-G4 was shown to be capable of degrading citric acid, especially in the processing of fruit juice and wine. I. terricola WJL-G4 was able to use citric acid as a carbon source, but the metabolic effects of citric acid on yeast remained unclear. In this study, the metabolic effects of citric acid on I. terricola WJL-G4 were studied using liquid chromatography-mass spectrometry metabolomics technology, with glucose treatment as the control. Results showed that organic acid contents related to the extracellular tricarboxylic acid cycle (TCA) varied greatly. The metabolomics results indicated that I. terricola WJL-G4 might metabolize citric acid through the TCA pathway, and the glycolysis pathway might be inhibited; however, gluconeogenesis proceeded normally during citric acid treatment. Some fatty acids and phospholipids, along with the metabolic pathways of amino acids, vitamins, purines and nicotinamide in I. terricola WJL-G4 were also affected by the citric acid treatment. This work provided a theoretical basis for further study of the mechanism of yeast metabolism of citric acid.PMID:37798226 | DOI:10.1016/j.jbiosc.2023.09.006

Redox Biol. 2023 Sep 26;67:102907. doi: 10.1016/j.redox.2023.102907. Online ahead of print.ABSTRACTCardiac fibrosis is characterized by the excessive deposition of extracellular matrix in the myocardium with cardiac fibroblast activation, leading to chronic cardiac remodeling and dysfunction. However, little is known about metabolic alterations in fibroblasts during cardiac fibrosis, and there is a lack of pharmaceutical treatments that target metabolic dysregulation. Here, we provided evidence that fatty acid β-oxidation (FAO) dysregulation contributes to fibroblast activation and cardiac fibrosis. With transcriptome, metabolome, and functional assays, we demonstrated that FAO was downregulated during fibroblast activation and cardiac fibrosis, and that perturbation of FAO reversely affected the fibroblast-to-myofibroblast transition. The decrease in FAO may be attributed to reduced long-chain fatty acid (LCFA) uptake. Voltage-dependent anion channel 1 (VDAC1), the main gatekeeper of the outer mitochondrial membrane (OMM), serves as the transporter of LCFA into the mitochondria for further utilization and has been shown to be decreased in myofibroblasts. In vitro, the addition of exogenous VDAC1 was shown to ameliorate cardiac fibroblast activation initiated by transforming growth factor beta 1 (TGF-β1) stimuli, and silencing of VDAC1 displayed the opposite effect. A mechanistic study revealed that VDAC1 exerts a protective effect by regulating LCFA uptake into the mitochondria, which is impaired by an inhibitor of carnitine palmitoyltransferase 1A. In vivo, AAV9-mediated overexpression of VDAC1 in myofibroblasts significantly alleviated transverse aortic constriction (TAC)-induced cardiac fibrosis and rescued cardiac function in mice. Finally, we treated mice with the VDAC1-derived R-Tf-D-LP4 peptide, and the results showed that R-Tf-D-LP4 prevented TAC-induced cardiac fibrosis and dysfunction in mice. In conclusion, this study provides evidence that VDAC1 maintains FAO metabolism in cardiac fibroblasts to repress fibroblast activation and cardiac fibrosis and suggests that the VDAC1 peptide is a promising drug for rescuing fibroblast metabolism and repressing cardiac fibrosis.PMID:37797372 | DOI:10.1016/j.redox.2023.102907

Environ Sci Technol. 2023 Oct 5. doi: 10.1021/acs.est.3c04845. Online ahead of print.ABSTRACTAdverse effects associated with chemical exposures during pregnancy include several developmental and reproductive disorders. However, considering the tens of thousands of chemicals present on the market, the effects of chemical mixtures on the developing fetus is still likely underestimated. In this critical review, we discuss the potential to apply innovative biomonitoring methods using high-resolution mass spectrometry (HRMS) on placenta to improve the monitoring of chemical exposure during pregnancy. The physiology of the placenta and its relevance as a matrix for monitoring chemical exposures and their effects on fetal health is first outlined. We then identify several key parameters that require further investigations before placenta can be used for large-scale monitoring in a robust manner. Most critical is the need for standardization of placental sampling. Placenta is a highly heterogeneous organ, and knowledge of the intraplacenta variability of chemical composition is required to ensure unbiased and robust interindividual comparisons. Other important variables include the time of collection, the sex of the fetus, and mode of delivery. Finally, we discuss the first applications of HRMS methods on the placenta to decipher the chemical exposome and describe how the use of placenta can complement biofluids collected on the mother or the fetus.PMID:37796725 | DOI:10.1021/acs.est.3c04845

J Agric Food Chem. 2023 Oct 5. doi: 10.1021/acs.jafc.3c04532. Online ahead of print.ABSTRACTSustainable agriculture aims at achieving a healthy food production while reducing the use of fertilizers and greenhouse gas emissions using biostimulants and soil amendments. Untargeted metabolomics by ultra-high performance liquid chromatography-ion mobility-high-resolution mass spectrometry, operating in a high-definition MSE mode, was applied to investigate the metabolome of durum wheat in response to sustainable treatments, i.e., the addition of biochar, commercial plant growth promoting microbes, and their combination. Partial least squares-discriminant analysis provided a good discrimination among treatments with sensitivity, specificity, and a non-error rate close to 1. A total of 88 and 45 discriminant compounds having biological, nutritional, and technological implications were tentatively identified in samples grown in 2020 and 2021. The addition of biochar-biostimulants produced the highest up-regulation of lipids and flavonoids, with the glycolipid desaturation being the most impacted pathway, whereas carbohydrates were mostly down-regulated. The findings achieved suggest the safe use of the combined biochar-biostimulant treatment for sustainable wheat cultivation.PMID:37796632 | DOI:10.1021/acs.jafc.3c04532

Curr Cardiol Rep. 2023 Oct 5. doi: 10.1007/s11886-023-01971-x. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: Radiation is foundational to the treatment of cancer and improves overall survival. Yet, it is important to recognize the potential cardiovascular effects of radiation therapy and how to best minimize or manage them. Screening-both through imaging and with biomarkers-can potentially identify cardiovascular effects early, allowing for prompt initiation of treatment to mitigate late effects.RECENT FINDINGS: Cardiac echocardiography, magnetic resonance imaging (MRI), computed tomography, and measurements of troponin and natriuretic peptides serve as the initial screening tests of choice for RICD. Novel imaging applications, including positron emission tomography and specific MRI parameters, and biomarker testing, including myeloperoxidase, growth differentiation factor 15, galectin 3, micro-RNA, and metabolomics, hold promise for earlier detection and more specific characterization of RICD. Advances in imaging and novel applications of biomarkers have potential to identify subclinical RICD and may reveal opportunities for early intervention. Further research is needed to elucidate optimal imaging screening modalities, biomarkers, and surveillance strategies.PMID:37796395 | DOI:10.1007/s11886-023-01971-x

Food Funct. 2023 Oct 5. doi: 10.1039/d3fo02710d. Online ahead of print.ABSTRACTThe green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), has been studied for its potential positive health effects, but human and animal model studies have reported potential toxicity at high oral bolus doses. This study used liquid chromatography-mass spectrometry-based metabolomics to compare the urinary EGCG metabolite profile after administration of a single non-toxic (100 mg kg-1) or toxic (750 mg kg-1) oral bolus dose to male C57BL6/J mice to better understand how EGCG metabolism varies with dose. EGCG metabolites, including methyl, glucuronide, sulfate, and glucoside conjugates, were tentatively identified based on their mass to charge (m/z) ratio and fragment ion patterns. Partial least squares discriminant analysis (PLS-DA) results showed clear separation of the urine metabolite profiles between treatment groups. The most differentiating metabolites in the negative and positive ion modes were provisionally identified as di-glucuronidated EGCG quinone and di-glucuronidated EGCG, respectively. The presence of EGCG oxidation products at toxic dose is consistent with studies showing that EGCG toxicity is associated with oxidative stress. Relative amounts of methylated metabolites increased with dose to a lesser extent than glucuronide and sulfate metabolites, indicating that methylation is more prominent at low doses, whereas glucuronidation and sulfation may be more important at higher doses. One limitation of the current work is that the lack of commercially-available EGCG metabolite standards prevented absolute metabolite quantification and identification. Despite this limitation, these findings provide a basis for better understanding the dose-dependent changes in EGCG metabolism and advance studies on how these differences may contribute to the toxicity of high doses of EGCG.PMID:37796030 | DOI:10.1039/d3fo02710d

Eur J Clin Invest. 2023 Oct 5:e14101. doi: 10.1111/eci.14101. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: We aimed to assess the associations of exposure to air pollutants and standard and advanced lipoprotein measures, in a nationwide sample representative of the adult population of Spain.METHODS: We included 4647 adults (>18 years), participants in the national, cross-sectional, population-based di@bet.es study, conducted in 2008-2010. Standard lipid measurements were analysed on an Architect C8000 Analyzer (Abbott Laboratories SA). Lipoprotein analysis was made by an advanced 1 H-NMR lipoprotein test (Liposcale®). Participants were assigned air pollution concentrations for particulate matter <10 μm (PM10 ), <2.5 μm (PM2.5 ) and nitrogen dioxide (NO2 ), corresponding to the health examination year, obtained by modelling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model).RESULTS: In multivariate linear regression models, each IQR increase in PM10 , PM2.5 and NO2 was associated with 3.3%, 3.3% and 3% lower levels of HDL-c and 1.3%, 1.4% and 1.1% lower HDL particle (HDL-p) concentrations (p < .001 for all associations). In multivariate logistic regression, there was a significant association between PM10 , PM2.5 and NO2 concentrations and the odds of presenting low HDL-c (<40 mg/dL), low HDL-p (<p25) and higher LDL particle (LDL-p) concentrations (≥p75). In subgroup analyses there were stronger associations between PM10 and NO2 and low HDL-p in men (p for interaction .008 and .034), and between NO2 and low HDL-p in individuals with obesity (p for interaction .015).CONCLUSIONS: Our study shows an association between the exposure to air pollutants and blood lipids in the general population of Spain, suggesting a link to atherosclerosis.PMID:37795744 | DOI:10.1111/eci.14101

Food Funct. 2023 Oct 5. doi: 10.1039/d3fo03207h. Online ahead of print.ABSTRACTApples are rich in many nutrients and functional components. However, the mechanism of the effect of fresh apple consumption on rats remains unclear. In the present study, fresh apples (10 g kg-1) were added to the diet of Wistar rats, and changes in the microbiota and metabolite content of the cecum were analyzed after 28 days of feeding, and changes in the 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) content and indicators related to inflammation, oxidative stress, and apoptosis were detected. Subsequently, a fecal microbiota transplantation (FMT) protocol was designed and carried out to verify the relationship between the microbiota and 12(S)-HETE, the cecal structure, and inflammatory factors. The results show that apple consumption significantly reduced the serum levels of alanine aminotransferase (ALT) and immunoglobulin G (IgG), altered the cecal histomorphology, and significantly upregulated the gene expression of claudin-1 and zonula occludens-1 (ZO-1), which encode tight junction proteins. Apple consumption also changed the structure of the cecal microbiota, increasing the abundance of some species (such as Shuttleworthia) and decreasing the abundance of others (such as Alphaproteobacteria). Metabolomic screening identified 64 significantly different metabolites. The FMT results showed that apple consumption reduced 12(S)-HETE metabolite levels in the cecal contents, improved the intestinal structure, and reduced the levels of proinflammatory factor expression by altering the cecal microbiota. In conclusion, this study provides further insight into the effects of apples on animals using rats as experimental animals. It provides basic data for future exploration of the mechanisms of the effect of apple consumption on humans.PMID:37795613 | DOI:10.1039/d3fo03207h

J Appl Physiol (1985). 2023 Oct 5. doi: 10.1152/japplphysiol.00372.2023. Online ahead of print.ABSTRACTEpidemiological studies report higher risks of cardiovascular disease in humans exposed to heat stroke earlier in life. Previously, we explored mechanistic links between heat stroke and developing cardiac abnormalities using a preclinical mouse model of exertional heat stroke (EHS). Profound metabolic abnormalities developed in the ventricles of females but not males after two weeks of recovery. Here we tested whether this lack of response in males could be attributed to the lower exercise performances or reduced thermal loads they experienced with the same running protocol. We systematically altered environmental temperature (Te) during EHS to manipulate heat exposure and exercise performance in the males. Three groups of adult C57BL/6 male mice were studied: 'EHS-34' (Te=34°C), 'EHS-41' (Te=41°C), and EHS-39.5 (Te=39.5°C). Mice ran until symptom limitation (unconsciousness), reaching max core temperature (Tc,max). After a 2-wk, the mice were euthanized, and the ventricles removed for untargeted metabolomics. Results were compared against age-matched non-exercise controls. The EHS-34 mice greatly elevated their exercise performance, but reached lower Tc,max and lower thermal loads. The EHS-41 mice exhibited equivalent thermal loads, exercise times and Tc,max compared to EHS-39.5. The ventricles from EHS-34 mice exhibited the greatest metabolic disturbances in the heart, characterized by shifts toward glucose metabolism, reductions in acylcarnitines, increased amino acid metabolites, elevations in antioxidants, altered TCA cycle flux and increased xenobiotics. In conclusion, delayed metabolic disturbances following EHS in male myocardium appear to be greatly amplified by higher levels of exertion in the heat, even with lower thermal loads and max core temperatures.PMID:37795530 | DOI:10.1152/japplphysiol.00372.2023

Eng Life Sci. 2023 Sep 7;23(10):e2300219. doi: 10.1002/elsc.202300219. eCollection 2023 Oct.ABSTRACTContinuous precipitation coupled with continuous tangential flow filtration is a cost-effective alternative for the capture of recombinant antibodies from crude cell culture supernatant. The removal of surge tanks between unit operations, by the adoption of tubular reactors, maintains a continuous harvest and mass flow of product with the advantage of a narrow residence time distribution (RTD). We developed a continuous process implementing two orthogonal precipitation methods, CaCl2 precipitation for removal of host-cell DNA and polyethylene glycol (PEG) for capturing the recombinant antibody, with no influence on the glycosylation profile. Our lab-scale prototype consisting of two tubular reactors and two stages of tangential flow microfiltration was continuously operated for up to 8 days in a truly continuous fashion and without any product flow interruption, both as a stand-alone capture and as an integrated perfusion-capture. Furthermore, we explored the use of a negatively charged membrane adsorber for flow-through anion exchange as first polishing step. We obtained a product recovery of approximately 80% and constant product quality, with more than two logarithmic reduction values (LRVs) for both host-cell proteins and host-cell DNA by the combination of the precipitation-based capture and the first polishing step.PMID:37795344 | PMC:PMC10545976 | DOI:10.1002/elsc.202300219

Front Microbiol. 2023 Sep 19;14:1244004. doi: 10.3389/fmicb.2023.1244004. eCollection 2023.ABSTRACTINTRODUCTION: Heat stress can affect the production of poultry through complex interactions between genes, metabolites and microorganisms. At present, it is unclear how heat stress affects genetic, metabolic and microbial changes in poultry, as well as the complex interactions between them.METHODS: Thus, at 28 days of age a total of 200 Arbor Acres broilers with similar body weights were randomly divided into the control (CON) and heat stress treatment (HS). There were 5 replicates in CON and HS, respectively, 20 per replication. From the 28-42 days, the HS was kept at 31 ± 1°C (9:00-17:00, 8 h) and other time was maintained at 21 ± 1°C as in the CON. At the 42nd day experiment, we calculated the growth performance (n = 8) of broilers and collected 3 and 6 cecal tissues for transcriptomic and metabolomic investigation and 4 cecal contents for metagenomic investigation of each treatment.RESULTS AND DISCUSSION: The results indicate that heat stress significantly reduced the average daily gain and body weight of broilers (value of p < 0.05). Transcriptome KEGG enrichment showed that the differential genes were mainly enriched in the NF-kB signaling pathway. Metabolomics results showed that KEGG enrichment showed that the differential metabolites were mainly enriched in the mTOR signaling pathway. 16S rDNA amplicon sequencing results indicated that heat stress increased the relative abundance of Proteobacteria decreased the relative abundance of Firmicutes. Multi-omics analysis showed that the co-participating pathway of differential genes, metabolites and microorganisms KEGG enrichment was purine metabolism. Pearson correlation analysis found that ornithine was positively correlated with SULT1C3, GSTT1L and g_Lactobacillus, and negatively correlated with CALB1. PE was negatively correlated with CALB1 and CHAC1, and positively with g_Alistipes. In conclusion, heat stress can generate large amounts of reactive oxygen and increase the types of harmful bacteria, reduce intestinal nutrient absorption and antioxidant capacity, and thereby damage intestinal health and immune function, and reduce growth performance indicators. This biological process is manifested in the complex regulation, providing a foundational theoretical basis for solving the problem of heat stress.PMID:37795292 | PMC:PMC10547010 | DOI:10.3389/fmicb.2023.1244004

Psychiatry Investig. 2023 Sep;20(9):818-825. doi: 10.30773/pi.2023.0121. Epub 2023 Sep 19.ABSTRACTOBJECTIVE: Schizophrenia (SCZ) is a severe psychiatric disorder with unknown etiology and lacking specific biomarkers. Herein, we aimed to explore plasma biomarkers relevant to SCZ using targeted metabolomics.METHODS: Sixty drug-naïve SCZ patients and 36 healthy controls were recruited. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale. We analyzed the levels of 271 metabolites in plasma samples from all subjects using targeted metabolomics, and identified metabolites that differed significantly between the two groups. Then we evaluated the diagnostic power of the metabolites based on receiver operating characteristic curves, and explored metabolites associated with the psychotic symptoms in SCZ patients.RESULTS: Twenty-six metabolites showed significant differences between SCZ patients and healthy controls. Among them, 12 metabolites were phosphatidylcholines and cortisol, ceramide (d18:1/22:0), acetylcarnitine, and γ-aminobutyric acid, which could significantly distinguish SCZ from healthy controls with the area under the curve (AUC) above 0.7. Further, a panel consisting of the above 4 metabolites had an excellent performance with an AUC of 0.867. In SCZ patients, phosphatidylcholines were positively related with positive symptoms, and cholic acid was positively associated with negative symptoms.CONCLUSION: Our study provides insights into the metabolite alterations associated with SCZ and potential biomarkers for its diagnosis and symptom severity assessment.PMID:37794663 | DOI:10.30773/pi.2023.0121

Pest Manag Sci. 2023 Oct 4. doi: 10.1002/ps.7813. Online ahead of print.ABSTRACTAmong the alternatives to synthetic plant protection products, biocontrol appears as a promising method. This review reports on the diversity of fungal secondary metabolites phytotoxic to weeds and on the approach generally used to extract, characterize, identify and exploit them for weed management. The 183 phytotoxic fungal secondary metabolites discussed in this review fall into five main classes of molecules: 61 polyketides, 53 terpenoids, 36 nitrogenous metabolites, 18 phenols and phenolic acids, and 15 miscellaneous. They are mainly produced by the genera Drechslera, Fusarium and Alternaria. The phytotoxic effects, more often described by the symptoms they produce on plants than by their mode of action, range from inhibition of germination to inhibition of root and vegetative growth, including tissue and organ alterations. The biochemical characterization of fungal secondary metabolites requires expertise and tools to carry out fungal cultivation and metabolite extraction, phytotoxicity tests, purification and fractionation of the extracts, and chemical identification procedures. Phytotoxicity tests are mainly carried out under controlled laboratory conditions (not always on whole plants), while effectiveness against targeted weeds and environmental impacts must be assessed in greenhouses and open fields. These steps are necessary for the formulation of effective, environment-friendly fungal secondary metabolites-derived bioherbicides using new technologies such as nanomaterials. This article is protected by copyright. All rights reserved.PMID:37794581 | DOI:10.1002/ps.7813

BMC Biol. 2023 Oct 4;21(1):207. doi: 10.1186/s12915-023-01709-9.ABSTRACTBACKGROUND: The maternal microbiota modulates fetal development, but the mechanisms of these earliest host-microbe interactions are unclear. To investigate the developmental impacts of maternal microbial metabolites, we compared full-term fetuses from germ-free and specific pathogen-free mouse dams by gene expression profiling and non-targeted metabolomics.RESULTS: In the fetal intestine, critical genes mediating host-microbe interactions, innate immunity, and epithelial barrier were differentially expressed. Interferon and inflammatory signaling genes were downregulated in the intestines and brains of the fetuses from germ-free dams. The expression of genes related to neural system development and function, translation and RNA metabolism, and regulation of energy metabolism were significantly affected. The gene coding for the insulin-degrading enzyme (Ide) was most significantly downregulated in all tissues. In the placenta, genes coding for prolactin and other essential regulators of pregnancy were downregulated in germ-free dams. These impacts on gene expression were strongly associated with microbially modulated metabolite concentrations in the fetal tissues. Aryl sulfates and other aryl hydrocarbon receptor ligands, the trimethylated compounds TMAO and 5-AVAB, Glu-Trp and other dipeptides, fatty acid derivatives, and the tRNA nucleobase queuine were among the compounds strongly associated with gene expression differences. A sex difference was observed in the fetal responses to maternal microbial status: more genes were differentially regulated in male fetuses than in females.CONCLUSIONS: The maternal microbiota has a major impact on the developing fetus, with male fetuses potentially more susceptible to microbial modulation. The expression of genes important for the immune system, neurophysiology, translation, and energy metabolism are strongly affected by the maternal microbial status already before birth. These impacts are associated with microbially modulated metabolites. We identified several microbial metabolites which have not been previously observed in this context. Many of the potentially important metabolites remain to be identified.PMID:37794486 | DOI:10.1186/s12915-023-01709-9

BMC Genomics. 2023 Oct 4;24(1):588. doi: 10.1186/s12864-023-09666-x.ABSTRACTBACKGROUND: The fruits of Gardenia are rich in flavonoids and geniposides, which have various pharmacological effects such as antioxidant, anti-inflammatory and anticancer. In this study, we analyzed the transcriptome and metabolome of gardenia peel and kernel at different growth stages, revealed the regulatory network related to flavonoid synthesis, and identified the key regulatory genes.RESULTS: The results showed that in terms of flavonoid metabolic pathways, gardenia fruits mainly synthesized cinnamic acid through the phenylpropanoid pathway, and then synthesized flavonoids through the action of catalytic enzymes such as 4-coumaroyl-CoA ligase, chalcone synthase, chalcone isomerase and flavanol synthase, respectively. In addition, we found that the metabolomics data showed a certain spatial and temporal pattern in the expression of genes related to the flavonoid metabolism pathway and the relative content of metabolites, which was related to the development and ripening process of the fruit.CONCLUSIONS: In summary, this study successfully screened out the key genes related to the biosynthesis metabolism of flavonoids in gardenia through the joint analysis of transcriptome and metabolome. This is of certain significance to the in-depth study of the formation mechanism of gardenia efficacy components and the improvement of quality.PMID:37794356 | DOI:10.1186/s12864-023-09666-x

BMC Plant Biol. 2023 Oct 5;23(1):463. doi: 10.1186/s12870-023-04478-3.ABSTRACTBACKGROUND: Rehmannia glutinosa is a rich source of terpenoids with a high medicinal reputation. The present study compared dedifferentiated cells (DDCs) and cambial meristematic cells (CMCs) cell cultures of R. glutinosa for terpenoid (catalpol) and indole alkaloid (IA) biosynthesis. In this regard, we used widely targeted metabolomics and transcriptome sequencing approaches together with the comparison of cell morphology, cell death (%), and catalpol production at different time points.RESULTS: We were able to identify CMCs based on their morphology and hypersensitivity to zeocin. CMCs showed higher dry weight content and better catalpol production compared to DDCs. The metabolome analysis revealed higher concentrations of IA, terpenoids, and catalpol in CMCs compared to DDCs. The transcriptome sequencing analysis showed that a total of 27,201 genes enriched in 139 pathways were differentially expressed. The higher catalpol concentration in CMCs is related to the expression changes in genes involved in acetyl-CoA and geranyl-PP biosynthesis, which are precursors for monoterpenoid biosynthesis. Moreover, the expressions of the four primary genes involved in monoterpenoid biosynthesis (NMD, CYP76A26, UGT6, and CYP76F14), along with a squalene monooxygenase, exhibit a strong association with the distinct catalpol biosynthesis. Contrarily, expression changes in AADC, STR, and RBG genes were consistent with the IA biosynthesis. Finally, we discussed the phytohormone signaling and transcription factors in relation to observed changes in metabolome.CONCLUSIONS: Overall, our study provides novel data for improving the catalpol and IA biosynthesis in R. glutinosa.PMID:37794352 | DOI:10.1186/s12870-023-04478-3

BMC Genomics. 2023 Oct 4;24(1):589. doi: 10.1186/s12864-023-09662-1.ABSTRACTBACKGROUND: The Q-426 strain isolated from compost samples has excellent antifungal activities against a variety of plant pathogens. However, the complete genome of Q-426 is still unclear, which limits the potential application of Q-426.RESULTS: Genome sequencing revealed that Q-426 contains a single circular chromosome 4,086,827 bp in length, with 4691 coding sequences and an average GC content of 46.3%. The Q-426 strain has a high degree of collinearity with B. velezensis FZB42, B. velezensis SQR9, and B. amyloliquefaciens DSM7, and the strain was reidentified as B. velezensis Q-426 based on the homology analysis results. Many genes in the Q-426 genome have plant growth-promoting activity, including the secondary metabolites of lipopeptides. Genome mining revealed 14 clusters and 732 genes encoding secondary metabolites with predicted functions, including the surfactin, iturin, and fengycin families. In addition, twelve lipopeptides (surfactin, iturin and fengycin) were successfully detected from the fermentation broth of B. velezensis Q-426 by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS), which is consistent with the genome analysis results. We found that Q-426 produced indole-3-acetic acid (IAA) at 1.56 mg/l on the third day of incubation, which might promote the growth of plants. Moreover, we identified eighteen volatile compounds (VOCs, including 2-heptanone, 6-methylheptan-2-one, 5-methylheptan-2-one, 2-nonanone, 2-decanone, 2-undecanone, 2-dodecanone, 2-tridecanone, 2-tetradecanone, 2-nonadecanone, pentadecanoic acid, oleic acid, dethyl phthalate, dibutyl phthalate, methyl (9E,12E)-octadeca-9,12-dienoate), pentadecane, (6E,10E)-1,2,3,4,4a,5,8,9,12,12a-decahydro-1,4-methanobenzo[10]annulene, and nonanal) based on gas chromatograph-mass spectrometer (GC/MS) results.CONCLUSIONS: We mined secondary metabolite-related genes from the genome based on whole-genome sequence results. Our study laid the theoretical foundation for the development of secondary metabolites and the application of B. velezensis Q-426. Our findings provide insights into the genetic characteristics responsible for the bioactivities and potential application of B. velezensis Q-426 as a plant growth-promoting strain in ecological agriculture.PMID:37794314 | DOI:10.1186/s12864-023-09662-1

Environ Geochem Health. 2023 Oct 4. doi: 10.1007/s10653-023-01764-9. Online ahead of print.ABSTRACTRespiratory diseases continue to be a major global concern, with allergies and asthma often discussed as critical areas of study. While the role of environmental risk factors, such as non-allergenic pollutants and high humidity, in asthma induction is often mentioned, there is still a lack of thorough research on their co-exposure. This study aims to investigate the adjuvant effect of ultrafine carbon black (30-50 nm) and high humidity (70% relative humidity) on the induction of allergic asthma. A mouse model of asthma was established using ovalbumin, and airway hyperresponsiveness, remodeling, and inflammation were measured as the endpoint effects of asthma. The mediating role of the oxidative stress pathway and the transient receptor potential vanilloid 1 pathway in asthma induction was validated using pathway inhibitors vitamin E and capsaicin, respectively. Co-exposure to ultrafine carbon black and high humidity had a significant impact on metabolic pathways in the lung, including aminoacyl-tRNA biosynthesis, glycerophospholipid metabolism, and ATP-binding cassette transporters. However, administering vitamin E and capsaicin altered the effects of co-exposure on the lung metabolome. These results offer new insights into the health risk assessment of co-exposure to environmental risk factors and provide an important reference point for the prevention and treatment of allergic asthma.PMID:37794280 | DOI:10.1007/s10653-023-01764-9

Reprod Sci. 2023 Oct 4. doi: 10.1007/s43032-023-01353-2. Online ahead of print.ABSTRACTThe purpose of the study is to investigate the metabolic characteristics of placental tissue in patients diagnosed with gestational diabetes mellitus (GDM). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was employed to qualitatively and quantitatively analyze the metabolites in placental tissues obtained from 25 healthy pregnant women and 25 pregnant women diagnosed with GDM. Multilevel statistical methods are applied to process intricate metabolomics data. Meanwhile, we applied machine learning techniques to identify biomarkers that could potentially predict the risk of long-term complications in patients with GDM as well as their offspring. We identified 1902 annotated metabolites, out of which 212 metabolites exhibited significant differences in GDM placentas. In addition, the study identifies a set of risk biomarkers that effectively predict the likelihood of long-term complications in both pregnant women with GDM and their offspring. The accuracy of this panel was measured by the area under the receiver operating characteristic curve (ROC), which was found to be 0.992 and 0.960 in the training and validation sets, respectively. This study enhances our understanding of GDM pathogenesis through metabolomics. Furthermore, the panel of risk markers identified could prove to be a valuable tool in predicting potential long-term complications for both GDM patients and their offspring.PMID:37794198 | DOI:10.1007/s43032-023-01353-2