PubMed

J Psychiatr Res. 2022 Nov 7;156:628-638. doi: 10.1016/j.jpsychires.2022.10.072. Online ahead of print.ABSTRACTSchizophrenia (SZ) is a serious neurodevelopmental disorder. As the etiology of SZ is complex and the pathogenesis is not thoroughly understood, the diagnosis of different subtypes still depends on the subjective judgment of doctors. Therefore, there is an urgent need to develop early objective laboratory diagnostic biomarkers to screen different subtypes of patients as early as possible, and to implement targeted prevention and precision medicine to reduce the risk of SZ and improve patients' quality of life. In this study, untargeted metabolomics and 16S rDNA sequencing were used to analyze the differences in metabolites and gut microflora among 28 patients with two types of schizophrenia and 11 healthy subjects. The results showed that the metabolome and sequencing data could effectively discriminate among paranoid schizophrenia patients, undifferentiated schizophrenia patients and healthy controls. We obtained 65 metabolites and 76 microorganisms with significant changes, and fecal metabolite composition was significantly correlated with the differential genera (|r|>0.5), indicating that there was a regulatory relationship between the gut microbiota and the host metabolites. The gut microbiome, as an objective and measurable index, showed good diagnostic value for distinguishing schizophrenia patients from healthy people, especially with a combination of several differential microorganisms, which had the best diagnostic effect (AUC>0.9). Our results are conducive to understanding the complicated metabolic changes in SZ patients and providing valuable information for the clinical diagnosis of SZ.PMID:36375230 | DOI:10.1016/j.jpsychires.2022.10.072

Environ Sci Technol. 2022 Nov 14. doi: 10.1021/acs.est.2c04500. Online ahead of print.ABSTRACTContinuous CO2 emissions from human activities increase atmospheric CO2 concentrations and affect global climate change. The carbon storage capacity of the ocean is 20-fold higher than that of the land, and diatoms contribute to approximately 40% of carbon capture in the ocean. Manganese (Mn) is a major driver of marine phytoplankton growth and the marine carbon pump. Here, we discovered self-assembled manganese oxides (MnOx) for CO2 fixation in a diatom-based biohybrid system. MnOx shared key features (e.g., di-μ-oxo-bridged Mn-Mn) with the Mn4CaO5 cluster of the biological catalyst in photosystem II and promoted photosynthesis and carbon capture by diatoms/MnOx. The CO2 capture capacity of diatoms/MnOx was 1.5-fold higher than that of diatoms alone. Diatoms/MnOx easily allocated carbon into proteins and lipids instead of carbohydrates. Metabolomics showed that the contents of several metabolites (e.g., lysine and inositol) were positively associated with increased CO2 capture. Diatoms/MnOx upregulated six genes encoding photosynthesis core proteins and a key rate-limiting enzyme (Rubisco, ribulose 1,5-bisphosphate carboxylase-oxygenase) in the Calvin-Benson-Bassham carbon assimilation cycle, revealing the link between MnOx and photosynthesis. These findings provide a route for offsetting anthropogenic CO2 emissions and inspiration for self-assembled biohybrid systems for carbon capture by marine phytoplankton.PMID:36375171 | DOI:10.1021/acs.est.2c04500

Proc Natl Acad Sci U S A. 2022 Nov 22;119(47):e2117803119. doi: 10.1073/pnas.2117803119. Epub 2022 Nov 14.ABSTRACTThe formation of cell polarity is essential for many developmental processes such as polar cell growth and spatial patterning of cell division. A plant-specific ROP (Rho-like GTPases from Plants) subfamily of conserved Rho GTPase plays a crucial role in the regulation of cell polarity. However, the functional study of ROPs in angiosperm is challenging because of their functional redundancy. The Marchantia polymorpha genome encodes a single ROP gene, MpROP, providing an excellent genetic system to study ROP-dependent signaling pathways. Mprop knockout mutants exhibited rhizoid growth defects, and MpROP was localized at the tip of elongating rhizoids, establishing a role for MpROP in the control of polar cell growth and its functional conservation in plants. Furthermore, the Mprop knockout mutant showed defects in the formation of meristem notches associated with disorganized cell division patterns. These results reveal a critical function of MpROP in the regulation of plant development. Interestingly, these phenotypes were complemented not only by MpROP but also Arabidopsis AtROP2, supporting the conservation of ROP's function among land plants. Our results demonstrate a great potential for M. polymorpha as a powerful genetic system for functional and mechanistic elucidation of ROP signaling pathways during plant development.PMID:36375069 | DOI:10.1073/pnas.2117803119

PLoS One. 2022 Nov 14;17(11):e0277476. doi: 10.1371/journal.pone.0277476. eCollection 2022.ABSTRACTHistidine is an essential amino acid for broiler chickens and a precursor for the dipeptides carnosine and anserine, but little information is available about its metabolism in modern, fast-growing broilers. We used untargeted metabolomics to investigate the metabolic changes caused by the use of different standardized ileal digestible His:Lys ratios in broiler diets with and without β-alanine supplementation. A total of 2204 broilers were randomly divided into 96 pens of 23 birds each. The pens were divided into 16 blocks, each containing one pen for all six feeding groups (total of 16 pens per group). These feeding groups were fed three different His:Lys ratios (0.44, 0.54, and 0.64, respectively) without and with a combination of 0.5% β-alanine supplementation. Five randomly selected chickens of one single randomly selected pen per feeding group were slaughtered on day 35 or 54, blood was collected from the neck vessel, and plasma was used for untargeted metabolomic analysis. Here we show that up to 56.0% of all metabolites analyzed were altered by age, whereas only 1.8% of metabolites were affected by the His:Lys ratio in the diet, and 1.5% by β-alanine supplementation. Two-factor analysis and metabolic pathway analysis showed no interaction between the His:Lys ratio and β-alanine supplementation. The effect of the His:Lys ratio in the diet was limited to histidine metabolism with a greater change in formiminoglutamate concentration. Supplementation of β-alanine showed changes in metabolites of several metabolic pathways; increased concentrations of 3-aminoisobutyrate showed the only direct relationship to β-alanine metabolism. The supplementation of β-alanine indicated few effects on histidine metabolism. These results suggest that the supplements used had limited effects or interactions on both His and β-alanine metabolism. In contrast, the birds' age has the strongest influence on the metabolome.PMID:36374928 | DOI:10.1371/journal.pone.0277476

J Sport Health Sci. 2022 Oct 29:S2095-2546(22)00103-X. doi: 10.1016/j.jshs.2022.10.003. Online ahead of print.ABSTRACTExercise has long been known for its active role in improving physical fitness and sustaining health. Regular moderate-intensity exercise improves all aspects of human health and is widely accepted as a preventative and therapeutic strategy for various diseases. It is well-documented that exercise maintains and restores homeostasis at the organismal, tissue, cellular, and molecular levels to stimulate positive physiological adaptations that consequently protect against various pathological conditions. Here we mainly summarize how moderate-intensity exercise affects the major hallmarks of health, including the integrity of barriers, containment of local perturbations, recycling and turnover, integration of circuitries, rhythmic oscillations, homeostatic resilience, hormetic regulation, as well as repair and regeneration. Furthermore, we summarize the current understanding of the mechanisms responsible for beneficial adaptations in response to exercise. This review aimed at providing a comprehensive summary of the vital biological mechanisms through which moderate-intensity exercise maintains health and opens a window for its application in other health interventions. We hope that continuing investigation in this field will further increase our understanding of the processes involved in the positive role of moderate-intensity exercise and thus get us closer to the identification of new therapeutics that improve quality of life.PMID:36374766 | DOI:10.1016/j.jshs.2022.10.003

Anal Chem. 2022 Nov 14. doi: 10.1021/acs.analchem.2c02902. Online ahead of print.ABSTRACTThe accuracy and ease of metabolite assignments from a complex mixture are expected to be facilitated by employing a multispectral approach. The two-dimensional (2D) 1H-13C heteronuclear single quantum coherence (HSQC) and 2D 1H-1H-total correlation spectroscopy (TOCSY) are the experiments commonly used for metabolite assignments. The 2D 1H-13C HSQC-TOCSY and 2D 1H-13C heteronuclear multiple-bond correlation (HMBC) are routinely used by natural products chemists but have seen minimal usage in metabolomics despite the unique information, the nearly complete 1H-1H and 1H-13C and spin systems provided by these experiments that may improve the accuracy and reliability of metabolite assignments. The use of a 13C-labeled feedstock such as glucose is a routine practice in metabolomics to improve sensitivity and to emphasize the detection of specific metabolites but causes severe artifacts and an increase in spectral complexity in the HMBC experiment. To address this issue, the standard HMBC pulse sequence was modified to include carbon decoupling. Nonuniform sampling was also employed for rapid data collection. A dataset of reference 2D 1H-13C HMBC spectra was collected for 94 common metabolites. 13C-13C spin connectivity was then obtained by generating a covariance pseudo-spectrum from the carbon-decoupled HMBC and the 1H-13C HSQC-TOCSY spectra. The resulting 13C-13C pseudo-spectrum provides a connectivity map of the entire carbon backbone that uniquely describes each metabolite and would enable automated metabolite identification.PMID:36374521 | DOI:10.1021/acs.analchem.2c02902

FASEB J. 2022 Dec;36(12):e22648. doi: 10.1096/fj.202200982R.ABSTRACTCyp4f18 catalyzes the conversion of n-3 polyunsaturated fatty acids (PUFAs) into omega-3 epoxides, such as 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) and 19,20-epoxydocosapentaenoic acid (19,20-EpDPE) from eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), respectively. Cyp4f18-deficient mice spontaneously develop psoriasis-like dermatitis. A significant increase in the number of IL-17A-positive gamma delta (γδ) T cells in the skin and enlargement of draining lymph nodes was observed. These symptoms were drastically suppressed by antibiotic treatment. Cyp4f18 is highly expressed in dendritic cells (DCs), and Cyp4f18-deficient bone marrow-derived dendritic cells (BMDCs) show markedly increased expression levels of cytokines such as IL-23 and IL-1β in response to lipopolysaccharide (LPS) stimulation. Lipidomic analysis of lymph nodes and BMDCs revealed a significant decrease in a series of omega-3 epoxidized metabolites. Among them, 17,18-dihydroxyeicosatetraenoic acid (17,18-diHETE), a vicinal diol derived from EPA omega-3 epoxidation suppressed IL-23 production in LPS-stimulated BMDCs in Cyp4f18-deficient mice. These results demonstrate that Cyp4f18 endogenously produces omega-3-epoxidized metabolites in the draining lymph nodes, and these metabolites contribute to skin homeostasis by suppressing the excessive activation of the IL-23/IL-17 axis initiated by DCs.PMID:36374250 | DOI:10.1096/fj.202200982R

Mol Omics. 2022 Nov 14. doi: 10.1039/d2mo00168c. Online ahead of print.ABSTRACTMetabolomics, the large-scale study of metabolites, has significant appeal as a source of information for metabolic modeling and other scientific applications. One common approach for measuring metabolomics data is gas chromatography-mass spectrometry (GC-MS). However, GC-MS metabolomics data are typically reported as relative abundances, precluding their use with approaches and tools where absolute concentrations are necessary. While chemical standards can be used to help provide quantification, their use is time-consuming, expensive, or even impossible due to their limited availability. The ability to infer absolute concentrations from GC-MS metabolomics data without chemical standards would have significant value. We hypothesized that when analyzing time-course metabolomics datasets, the mass balances of metabolism and other biological information could provide sufficient information towards inference of absolute concentrations. To demonstrate this, we developed and characterized MetaboPAC, a computational framework that uses two approaches-one based on kinetic equations and another using biological heuristics-to predict the most likely response factors that allow translation between relative abundances and absolute concentrations. When used to analyze noiseless synthetic data generated from multiple types of kinetic rate laws, MetaboPAC performs significantly better than negative control approaches when 20% of kinetic terms are known a priori. Under conditions of lower sampling frequency and high noise, MetaboPAC is still able to provide significant inference of concentrations in 3 of 4 models studied. This provides a starting point for leveraging biological knowledge to extract concentration information from time-course intracellular GC-MS metabolomics datasets, particularly for systems that are well-studied and have partially known kinetic structures.PMID:36374123 | DOI:10.1039/d2mo00168c

Dis Model Mech. 2023 May 1;16(5):dmm049647. doi: 10.1242/dmm.049647. Epub 2022 Nov 14.ABSTRACTNicotinamide adenine dinucleotide (NAD) is a key metabolite synthesised from vitamin B3 or tryptophan. Disruption of genes encoding NAD synthesis enzymes reduces NAD levels and causes congenital NAD deficiency disorder (CNDD), characterised by multiple congenital malformations. SLC6A19 (encoding B0AT1, a neutral amino acid transporter), represents the main transporter for free tryptophan in the intestine and kidney. Here, we tested whether Slc6a19 heterozygosity in mice limits the tryptophan available for NAD synthesis during pregnancy and causes adverse pregnancy outcomes. Pregnant Slc6a19+/- mice were fed diets depleted of vitamin B3, so that tryptophan was the source of NAD during gestation. This perturbed the NAD metabolome in pregnant Slc6a19+/- females, resulting in reduced NAD levels and increased rates of embryo loss. Surviving embryos were small and exhibited specific combinations of CNDD-associated malformations. Our results show that genes not directly involved in NAD synthesis can affect NAD metabolism and cause CNDD. They also suggest that human female carriers of a SLC6A19 loss-of-function allele might be susceptible to adverse pregnancy outcomes unless sufficient NAD precursor amounts are available during gestation. This article has an associated First Person interview with the first author of the paper.PMID:36374036 | DOI:10.1242/dmm.049647

Microbiol Spectr. 2022 Nov 14:e0304322. doi: 10.1128/spectrum.03043-22. Online ahead of print.ABSTRACTHeterogeneous environments such as the chronically infected cystic fibrosis lung drive the diversification of Pseudomonas aeruginosa populations into, e.g., mucoid, alginate-overproducing isolates or small-colony variants (SCVs). In this study, we performed extensive genome and transcriptome profiling on a clinical SCV isolate that exhibited high cyclic diguanylate (c-di-GMP) levels and a mucoid phenotype. We observed a delayed, stepwise decrease of the high levels of c-di-GMP as well as alginate gene expression upon passaging the SCV under noninducing, rich medium growth conditions over 7 days. Upon prolonged passaging, this lagging reduction of the high c-di-GMP levels under noninducing planktonic conditions (reminiscent of a hysteretic response) was followed by a phenotypic switch to a large-colony morphology, which could be linked to mutations in the Gac/Rsm signaling pathway. Complementation of the Gac/Rsm signaling-negative large-colony variants with a functional GacSA system restored the SCV colony morphotype but was not able to restore the high c-di-GMP levels of the SCV. Our data thus suggest that expression of the SCV colony morphotype and modulation of c-di-GMP levels are genetically separable and follow different evolutionary paths. The delayed switching of c-di-GMP levels in response to fluctuating environmental conditions might provide a unique opportunity to include a time dimension to close the gap between short-term phenotypic and long-term genetic adaptation to biofilm-associated growth conditions. IMPORTANCE Extreme environments, such as those encountered during an infection process in the human host, make effective bacterial adaptation inevitable. While bacteria adapt individually by activating stress responses, long-term adaptation of bacterial communities to challenging conditions can be achieved via genetic fixation of favorable traits. In this study, we describe a two-pronged bacterial stress resistance strategy in the opportunistic pathogen Pseudomonas aeruginosa. We show that the production of adjusted elevated c-di-GMP levels, which drive protected biofilm-associated phenotypes in vivo, resembles a stable hysteretic response which prevents unwanted frequent switching. Cellular hysteresis might provide a link between individual adaptability and evolutionary adaptation to ensure the evolutionary persistence of host-adapted stress response strategies.PMID:36374016 | DOI:10.1128/spectrum.03043-22

Bioinformatics. 2022 Nov 14:btac726. doi: 10.1093/bioinformatics/btac726. Online ahead of print.ABSTRACTMOTIVATION: Functional interpretation of high-throughput metabolomic and transcriptomic results is a crucial step in generating insight from experimental data. However, pathway and functional information for genes and metabolites is distributed among many siloed resources, limiting the scope of analyses that rely on a single knowledge source.RESULTS: RaMP-DB 2.0 is a web interface, relational database, API, and R package designed for straightforward and comprehensive functional interpretation of metabolomic and multi-omic data. RaMP-DB 2.0 has been upgraded with an expanded breadth and depth of functional and chemical annotations (ClassyFire, LIPID MAPS, SMILES, InChIs, etc.), with new data types related to metabolites and lipids incorporated. To streamline entity resolution across multiple source databases, we have implemented a new semi-automated process, thereby lessening the burden of harmonization and supporting more frequent updates. The associated RaMP-DB 2.0 R package now supports queries on pathways, common reactions (e.g. metabolite-enzyme relationship), chemical functional ontologies, chemical classes, and chemical structures, as well as enrichment analyses on pathways (multi-omic) and chemical classes. Lastly, the RaMP-DB web interface has been completely redesigned using the Angular framework.AVAILABILITY: The code used to build all components of RaMP-DB 2.0 are freely available on GitHub at https://github.com/ncats/ramp-db, https://github.com/ncats/RaMP-Client/ and https://github.com/ncats/RaMP-Backend. The RaMP-DB front end can be accessed at https://rampdb.nih.gov/.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.PMID:36373969 | DOI:10.1093/bioinformatics/btac726

Biomed Khim. 2022 Nov;68(5):321-338. doi: 10.18097/PBMC20226805321.ABSTRACTAging of a living organism is closely related to systemic metabolic changes. But due to the multilevel and network nature of metabolic pathways, it is difficult to understand these connections. Today, this problem is solved using one of the main approaches of metabolomics - untargeted metabolome profiling. The purpose of this publication is to systematize the results of metabolomic studies based on such profiling, both in animal models and in humans.PMID:36373879 | DOI:10.18097/PBMC20226805321

J Sci Food Agric. 2023 Jan 15;103(1):428-436. doi: 10.1002/jsfa.12157. Epub 2022 Aug 10.ABSTRACTBACKGROUND: Our previous study has demonstrated that the egg-white-derived peptide RVPSL can lower blood pressure in spontaneously hypertensive rats (SHRs), but its potential action mechanism remains unclear. In this work, the underlying mechanism of the antihypertensive effects of RVPSL in SHRs was elucidated using the widely targeted kidney metabolomics approach.RESULTS: Ten SHRs were divided into two groups: SHR-Untreated group (0.9% saline) and SHR-RVPSL group (50 mg kg-1 body weight RVPSL) for 4 weeks. After 4 weeks, kidney samples were collected and widely targeted (liquid chromatography-electrospray ionization-tandem mass spectrometry) metabolomics was used to detect metabolites. Fifty-six biomarkers were identified that may be associated with hypertension. Among them, 17 biomarkers were upregulated and 39 biomarkers were downregulated. The results suggested that eight potential biomarkers were identified in kidney samples: O-phospho-l-serine, tyramine, citric acid, 3-hydroxybutyrate, O-acetyl-l-serine, 15-oxo-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-oxoETE), dopaquinone and 3,3',5-triiodo-l-thyronine. These potential biomarkers mainly involved carbon metabolism, thyroid hormone signaling pathway, tyrosine metabolism and arachidonic acid metabolism.CONCLUSION: The study suggested that RVPSL may exert antihypertensive effects through upregulation of O-phospho-l-serine, 3-hydroxybutyrate and 15-oxoETE, and downregulation of tyramine, citric acid, O-acetyl-l-serine, 3,3',5-triiodo-l-thyronine and dopaquinone. The antihypertensive effects of RVPSL may be related to carbon metabolism, thyroid hormone signaling pathway, tyrosine metabolism and arachidonic acid metabolism. RVPSL exhibited a potent antihypertensive effect, and the antihypertensive effects were associated with inhibition of vascular smooth muscle cell proliferation, vascular remodeling, vascular endothelium dysfunction, restoring reactive oxygen species, oxidative stress, inflammation and immune reaction. © 2022 Society of Chemical Industry.PMID:36373790 | DOI:10.1002/jsfa.12157

Food Funct. 2022 Nov 14. doi: 10.1039/d2fo02871a. Online ahead of print.ABSTRACTHawthorn flavonoid (HF) exhibits potential benefits in Alzheimer's disease (AD), but its mechanism of action remains elusive. In this study, we identified the main components of HF, demonstrating that the administration of HF at a dose of 200 mg per kg per day significantly improved cognitive deficits in mice with AD induced by D-galactose and aluminum chloride. HF also effectively ameliorated β-amyloid (Aβ) accumulation and abnormal activation of hippocampal microglia. Furthermore, we investigated the effects of HF on gut microbiota and serum metabolomics in AD mice by 16S rRNA sequencing and quadrupole time-of-flight mass spectrometry. Our results showed that HF reversed the gut microbiota disturbance and metabolic disorder in AD mice by increasing the proportions of Dubosiella, Alloprevotella, and Bifidobacterium and decreasing the proportions of Acinetobacter, as well as increasing the levels of docosapentaenoic acid (DPA), sphingolipid (SM), and phosphatidylcholine (PC). Notably, a positive correlation between DPA and Bifidobacterium was observed for the first time. Therefore, HF may serve as a promising dietary supplement for improving the symptoms of Alzheimer's disease.PMID:36373486 | DOI:10.1039/d2fo02871a

EMBO J. 2022 Nov 14:e110780. doi: 10.15252/embj.2022110780. Online ahead of print.ABSTRACTIL-1β can exit the cytosol as an exosomal cargo following inflammasome activation in intestinal epithelial cells (IECs) in a Gasdermin D (GSDMD)-dependent manner. The mechanistic connection linking inflammasome activation and the biogenesis of exosomes has so far remained largely elusive. Here, we report the Ras GTPase-activating-like protein IQGAP1 functions as an adaptor, bridging GSDMD to the endosomal sorting complexes required for transport (ESCRT) machinery to promote the biogenesis of pro-IL-1β-containing exosomes in response to NLPR3 inflammasome activation. We identified IQGAP1 as a GSDMD-interacting protein through a non-biased proteomic analysis. Functional investigation indicated the IQGAP1-GSDMD interaction is required for LPS and ATP-induced exosome release. Further analysis revealed that IQGAP1 serves as an adaptor which bridges GSDMD and associated IL-1β complex to Tsg101, a component of the ESCRT complex, and enables the packaging of GSDMD and IL-1β into exosomes. Importantly, this process is dependent on an LPS-induced increase in GTP-bound CDC42, a small GTPase known to activate IQGAP1. Taken together, this study reveals IQGAP1 as a link between inflammasome activation and GSDMD-dependent, ESCRT-mediated exosomal release of IL-1β.PMID:36373462 | DOI:10.15252/embj.2022110780

J Clin Endocrinol Metab. 2022 Nov 14:dgac655. doi: 10.1210/clinem/dgac655. Online ahead of print.NO ABSTRACTPMID:36373423 | DOI:10.1210/clinem/dgac655

NMR Biomed. 2022 Nov 13:e4865. doi: 10.1002/nbm.4865. Online ahead of print.ABSTRACTIn communicating scientific results, convincing data visualization is of utmost importance. Especially in metabolomics, results based on large numbers of dimensions and variables necessitate particular attention in order to convey their message unambiguously to the reader; and in the era of open science, traceability and reproducibility are becoming increasingly important. This paper describes the use of the R programming language to visualize published metabolomics data resulting from ex-vivo NMR spectroscopy and mass spectrometry experiments with a special focus on reproducibility, including example figures as well as associated R code for ease of reuse. Examples include various types of plots (bar plots, swarm plots, and violin plots; volcano plots, heatmaps, Euler diagrams, Kaplan-Meier survival plots) and annotations (groupings, intra-group line connections, significance brackets, text annotations). Advantages of code-generated plots as well as advanced techniques and best practices are discussed.PMID:36373190 | DOI:10.1002/nbm.4865

J Appl Toxicol. 2022 Nov 13. doi: 10.1002/jat.4415. Online ahead of print.ABSTRACTE-cigarette, or vaping product use-associated lung injury (EVALI), is a severe respiratory disorder that caused a sudden outbreak of hospitalized young people in 2019. Using cannabis oil containing vaping products, including vitamin E acetate contaminants, was found to be strongly associated with EVALI. However, the underlying tissue impacts of the condition are still largely unknown. Here, we focused on the vehicle cannabinoid oil (CBD oil) and contaminant vitamin E acetate (VEA) effects on airway epithelial cells. Primary human bronchial epithelial (HBE) cultures were exposed to e-liquid aerosols that contained CBD oil and VEA in combination or the common e-liquid components PG/VG with and without nicotine. Cell viability analysis indicated dramatically increased cell death counts after three days of CBD exposure, and this effect was even higher after CBD+VEA exposure. Microscopic examination of the cultures revealed cannabinoid and VEA depositions on the epithelial surfaces and cannabinoid accumulation in exposed cells, followed by cell death. These observations were supported by proteomic analysis of the cell secretions that exhibited increases in known markers of airway epithelial toxicity, such as xenobiotic enzymes, factors related to oxidative stress response and cell death indicators. Overall, our study provides insights into the association between cannabinoid oil and vitamin E acetate vaping and lung injury. Collectively, our results suggest that the adherent accumulation of CBD oil on airway surfaces and the cellular uptake of both CBD oil- and VEA-containing condensates cause elevated metabolomic stress, leading to increased cell death rates in human airway epithelial cultures.PMID:36372912 | DOI:10.1002/jat.4415

BMC Plant Biol. 2022 Nov 14;22(1):524. doi: 10.1186/s12870-022-03867-4.ABSTRACTBACKGROUND: Phosphorus (P) is one of the most essential macronutrients for crops. The growth and yield of peanut (Arachis hypogaea L.) are always limited by P deficiency. However, the transcriptional and metabolic regulatory mechanisms were less studied. In this study, valuable phenotype, transcriptome and metabolome data were analyzed to illustrate the regulatory mechanisms of peanut under P deficiency stress.RESULT: In present study, two treatments of P level in deficiency with no P application (-P) and in sufficiency with 0.6 mM P application (+ P) were used to investigate the response of peanut on morphology, physiology, transcriptome, microRNAs (miRNAs), and metabolome characterizations. The growth and development of plants were significantly inhibited under -P treatment. A total of 6088 differentially expressed genes (DEGs) were identified including several transcription factor family genes, phosphate transporter genes, hormone metabolism related genes and antioxidant enzyme related genes that highly related to P deficiency stress. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that 117 genes were annotated in the phenylpropanoid biosynthesis pathway under P deficiency stress. A total of 6 miRNAs have been identified significantly differential expression between + P and -P group by high-throughput sequencing of miRNAs, including two up-regulated miRNAs (ahy-miR160-5p and ahy-miR3518) and four down-regulated miRNAs (ahy-miR408-5p, ahy-miR408-3p, ahy-miR398, and ahy-miR3515). Further, the predicted 22 target genes for 6 miRNAs and cis-elements in 2000 bp promoter region of miRNA genes were analyzed. A total of 439 differentially accumulated metabolites (DAMs) showed obviously differences in two experimental conditions.CONCLUSIONS: According to the result of transcripome and metabolome analyses, we can draw a conclusion that by increasing the content of lignin, amino acids, and levan combining with decreasing the content of LPC, cell reduced permeability, maintained stability, raised the antioxidant capacity, and increased the P uptake in struggling for survival under P deficiency stress.PMID:36372886 | DOI:10.1186/s12870-022-03867-4

Chemosphere. 2022 Nov 10:137228. doi: 10.1016/j.chemosphere.2022.137228. Online ahead of print.ABSTRACTMillions of people are at risk of consuming arsenic (As) contaminated drinking water in Pakistan. The current study aimed to investigate urinary arsenic species [iAsIII, iAsV, dimethylarsinic acid (DMA), methylarsonic acid (MMA)] and their potential toxicity biomarkers (based on urinary metabolome) in order to characterize the health effects in general adult male participants (n = 588) exposed to various levels of arsenic in different floodplain areas of Pakistan. The total urinary arsenic concentration (mean; 161 μg/L) of studied participants was lower and/or comparable than those values reported from other highly contaminated regions, but exceeded the Agency for Toxic Substances and Disease Registry (ATSDR) limits. For all the participants, the most excreted species was DMA accounting for 65% of the total arsenic, followed by MMA (20%) and iAs (16%). The percentage of MMA detected in this study was higher than those of previously reported data from other countries. These results suggested that studied population might have high risk of developing arsenic exposure related adverse health outcomes. Furthermore, random forest machine learning algorithm, partial correlation and binary logistic regression analysis were performed to screen the arsenic species-related urinary metabolites. A total of thirty-eight metabolites were extracted from 2776 metabolic features and identified as the potential arsenic toxicity biomarkers. The metabolites were mainly classified into xanthines, purines, and amino acids, which provided the clues linking the arsenic exposure with oxidative stress, one-carbon metabolism, purine metabolism, caffeine metabolism and hormone metabolism. These results would be helpful to develop early health warning system in context of arsenic exposure among the general populations of Pakistan.PMID:36372340 | DOI:10.1016/j.chemosphere.2022.137228