PubMed

Proc Biol Sci. 2023 Feb 8;290(1992):20221877. doi: 10.1098/rspb.2022.1877. Epub 2023 Feb 8.ABSTRACTAnthropogenic stressors continue to escalate worldwide, driving unprecedented declines in reef environmental conditions and coral health. One approach to better understand how corals can function in the future is to examine coral populations that thrive within present day naturally extreme habitats. We applied untargeted metabolomics (gas chromatography-mass spectrometry (GC-MS)) to contrast metabolite profiles of Pocillopora acuta colonies from hot, acidic and deoxygenated mangrove environments versus those from adjacent reefs. Under ambient temperatures, P. acuta predominantly associated with endosymbionts of the genera Cladocopium (reef) or Durusdinium (mangrove), exhibiting elevated metabolism in mangrove through energy-generating and biosynthesis pathways compared to reef populations. Under transient heat stress, P. acuta endosymbiont associations were unchanged. Reef corals bleached and exhibited extensive shifts in symbiont metabolic profiles (whereas host metabolite profiles were unchanged). By contrast, mangrove populations did not bleach and solely the host metabolite profiles were altered, including cellular responses in inter-partner signalling, antioxidant capacity and energy storage. Thus mangrove P. acuta populations resist periodically high-temperature exposure via association with thermally tolerant endosymbionts coupled with host metabolic plasticity. Our findings highlight specific metabolites that may be biomarkers of heat tolerance, providing novel insight into adaptive coral resilience to elevated temperatures.PMID:36750192 | DOI:10.1098/rspb.2022.1877

Expert Opin Ther Targets. 2023 Feb 7. doi: 10.1080/14728222.2023.2178420. Online ahead of print.NO ABSTRACTPMID:36749698 | DOI:10.1080/14728222.2023.2178420

Int J Syst Evol Microbiol. 2023 Feb;73(2). doi: 10.1099/ijsem.0.005691.ABSTRACTA novel sulphur-reducing bacterium was isolated from a pyrite-forming enrichment culture inoculated with sewage sludge from a wastewater treatment plant. Based on phylogenetic data, strain J.5.4.2-T.3.5.2T could be affiliated with the phylum Synergistota. Among type strains of species with validly published names, the highest 16S rRNA gene sequence identity value was found with Aminiphilus circumscriptus ILE-2T (89.2 %). Cells of the new isolate were Gram-negative, non-spore-forming, straight to slightly curved rods with tapered ends. Motility was conferred by lateral flagella. True branching of cells was frequently observed. The strain had a strictly anaerobic, asaccharolytic, fermentative metabolism with peptides and amino acids as preferred substrates. Sulphur was required as an external electron acceptor during fermentative growth and was reduced to sulphide, whereas it was dispensable during syntrophic growth with a Methanospirillum species. Major fermentation products were acetate and propionate. The cellular fatty acid composition was dominated by unsaturated and branched fatty acids, especially iso-C15 : 0. Its major polar lipids were phosphatidylglycerol, phosphatidylethanolamine and distinct unidentified polar lipids. Respiratory lipoquinones were not detected. Based on the obtained data we propose the novel species and genus Aminithiophilus ramosus, represented by the type strain J.5.4.2-T.3.5.2T (=DSM 107166T=NBRC 114655T) and the novel family Aminithiophilaceae fam. nov. to accommodate the genus Aminithiophilus. In addition, we suggest reclassifying certain members of the Synergistaceae into new families to comply with current standards for the classification of higher taxa. Based on phylogenomic data, the novel families Acetomicrobiaceae fam. nov., Aminiphilaceae fam. nov., Aminobacteriaceae fam. nov., Dethiosulfovibrionaceae fam. nov. and Thermovirgaceae fam. nov. are proposed.PMID:36749697 | DOI:10.1099/ijsem.0.005691

Mol Plant Microbe Interact. 2023 Feb 7. doi: 10.1094/MPMI-09-22-0178-R. Online ahead of print.ABSTRACTBroad-spectrum biocontrol by Pseudomonas protegens CHA0 and other fluorescent pseudomonads is achieved through the generation of various secondary metabolites with antibiotic activities against not only other microbes, but also nematodes and insects present in the rhizosphere. A previous metabolomic study demonstrated that intracellular low-molecular weight effectors, such as guanosine tetraphosphate and γ-aminobutyrate, function as important signals in niche adaptation by strain CHA0 to plant roots. We herein investigated the role of amino acids in the biocontrol trait of P. protegens Cab57 towards Pythium damping off and root rot in cucumber. Among the 11 amino acids tested, only glutamate markedly enhanced the efficacy of biocontrol. A RNA seq analysis revealed that glutamate up-regulated the expression of a chitinase gene cluster (c21370-c21380, where the c21370 gene was annotated as a gene encoding the chitin-binding protein cbp and the c21380 gene encoded chitinase chiC) in strain CHA0. Glutamate up-regulated the expression of the regulatory small RNA rsmZ, but reduced the production levels of other Gac/Rsm-regulated biocontrol factors, such as DAPG and pyoluteorin. The promoter activity of cbp and chitinase activity were characterized in detail; their activities were up-regulated in response to glutamate and their expression was under the control of GacA. Therefore, glutamate appears to be essential for biocontrol activity where chitinase production is regulated in response to glutamate.PMID:36749296 | DOI:10.1094/MPMI-09-22-0178-R

Microb Genom. 2023 Jan;9(1). doi: 10.1099/mgen.0.000918.ABSTRACTMesorhizobia are soil bacteria that establish nitrogen-fixing symbioses with various legumes. Novel symbiotic mesorhizobia frequently evolve following horizontal transfer of symbiosis-gene-carrying integrative and conjugative elements (ICESyms) to indigenous mesorhizobia in soils. Evolved symbionts exhibit a wide range in symbiotic effectiveness, with some fixing nitrogen poorly or not at all. Little is known about the genetic diversity and symbiotic potential of indigenous soil mesorhizobia prior to ICESym acquisition. Here we sequenced genomes of 144 Mesorhizobium spp. strains cultured directly from cultivated and uncultivated Australian soils. Of these, 126 lacked symbiosis genes. The only isolated symbiotic strains were either exotic strains used previously as legume inoculants, or indigenous mesorhizobia that had acquired exotic ICESyms. No native symbiotic strains were identified. Indigenous nonsymbiotic strains formed 22 genospecies with phylogenomic diversity overlapping the diversity of internationally isolated symbiotic Mesorhizobium spp. The genomes of indigenous mesorhizobia exhibited no evidence of prior involvement in nitrogen-fixing symbiosis, yet their core genomes were similar to symbiotic strains and they generally lacked genes for synthesis of biotin, nicotinate and thiamine. Genomes of nonsymbiotic mesorhizobia harboured similar mobile elements to those of symbiotic mesorhizobia, including ICESym-like elements carrying aforementioned vitamin-synthesis genes but lacking symbiosis genes. Diverse indigenous isolates receiving ICESyms through horizontal gene transfer formed effective symbioses with Lotus and Biserrula legumes, indicating most nonsymbiotic mesorhizobia have an innate capacity for nitrogen-fixing symbiosis following ICESym acquisition. Non-fixing ICESym-harbouring strains were isolated sporadically within species alongside effective symbionts, indicating chromosomal lineage does not predict symbiotic potential. Our observations suggest previously observed genomic diversity amongst symbiotic Mesorhizobium spp. represents a fraction of the extant diversity of nonsymbiotic strains. The overlapping phylogeny of symbiotic and nonsymbiotic clades suggests major clades of Mesorhizobium diverged prior to introduction of symbiosis genes and therefore chromosomal genes involved in symbiosis have evolved largely independent of nitrogen-fixing symbiosis.PMID:36748564 | DOI:10.1099/mgen.0.000918

Heliyon. 2023 Jan 21;9(2):e13066. doi: 10.1016/j.heliyon.2023.e13066. eCollection 2023 Feb.ABSTRACTTryptophan and its derived metabolites have been assumed to play important roles in the development and survival of organisms. However, the links of tryptophan and its derived metabolites to temperature change remained largely cryptic. Here we presented that a class of prenyl indole alkaloids biosynthesized from tryptophan dramatically accumulated in thermophilic fungus Thermomyces dupontii under cold stress, in which lipid droplets were also highly accumulated and whose conidiophores were highly build-up. Concurrently, disruption of the key NRPS gene involved in the biosynthesis of prenyl indole alkaloids, resulted in decreased lipid and shrunken mitochondria but enlarged vacuoles. Moreover, the Fe3+ and superoxide levels in ΔNRPS were significantly increased but the reactive oxygen species lipid peroxidation and autophagy levels decreased. Metabolomics study revealed that most enriched metabolites in ΔNRPS were mainly composed of tryptophan degraded metabolites including well known ROS scavenger kynurenamines, and lipid-inhibitors, anthranilic acid and indoleacetic acid, and free radical reaction suppressor free fatty acids. Transcriptomic analysis suggested that the key gene involved in tryptophan metabolism, coinciding with the lipid metabolic processes and ion transports were most up-regulated in ΔNRPS under stress. Our results confirmed a lipid-mediated fungal response to cold stress and unveiled a link of tryptophan-based metabolic reprogramming to the fungal cold adaption.PMID:36747564 | PMC:PMC9898655 | DOI:10.1016/j.heliyon.2023.e13066

Database (Oxford). 2023 Feb 7;2023:baad002. doi: 10.1093/database/baad002.ABSTRACTSaliva as a non-invasive diagnostic fluid has immense potential as a tool for early diagnosis and prognosis of patients. The information about salivary biomarkers is broadly scattered across various resources and research papers. It is important to bring together all the information on salivary biomarkers to a single platform. This will accelerate research and development in non-invasive diagnosis and prognosis of complex diseases. We collected widespread information on five types of salivary biomarkers-proteins, metabolites, microbes, micro-ribonucleic acid (miRNA) and genes found in humans. This information was collected from different resources that include PubMed, the Human Metabolome Database and SalivaTecDB. Our database SalivaDB contains a total of 15 821 entries for 201 different diseases and 48 disease categories. These entries can be classified into five categories based on the type of biomolecules; 6067, 3987, 2909, 2272 and 586 entries belong to proteins, metabolites, microbes, miRNAs and genes, respectively. The information maintained in this database includes analysis methods, associated diseases, biomarker type, regulation status, exosomal origin, fold change and sequence. The entries are linked to relevant biological databases to provide users with comprehensive information. We developed a web-based interface that provides a wide range of options like browse, keyword search and advanced search. In addition, a similarity search module has been integrated which allows users to perform a similarity search using Basic Local Alignment Search Tool and Smith-Waterman algorithm against biomarker sequences in SalivaDB. We created a web-based database-SalivaDB, which provides information about salivary biomarkers found in humans. A wide range of web-based facilities have been integrated to provide services to the scientific community. https://webs.iiitd.edu.in/raghava/salivadb/.PMID:36747479 | DOI:10.1093/database/baad002

Nutr Metab (Lond). 2023 Feb 6;20(1):6. doi: 10.1186/s12986-023-00726-3.ABSTRACTThe use of non-drug intervention for calcium deficiency has attracted attention in recent years. Although calcium carbonate is the preferred raw material for calcium supplementation, there are few reports on the mechanism of the combined action of chondroitin sulfate and calcium to alleviate osteoporosis from the perspective of gut microbiota and metabolomics. In this study, a rat model of osteoporosis was established by feeding a low-calcium diet. The intestinal microbiota abundance, fecal and plasma metabolite expression levels of rats fed a basal diet, a low-calcium diet, a low-calcium diet plus calcium carbonate, and a low-calcium diet plus chondroitin sulfate were compared. The results showed that compared with the low calcium group, the calcium content and bone mineral density of femur were significantly increased in the calcium carbonate and chondroitin sulfate groups. 16 S rRNA sequencing and metabolomics analysis showed that chondroitin sulfate intervention could reduce short-chain fatty acid synthesis of intestinal flora, slow down inflammatory response, inhibit osteoclast differentiation, promote calcium absorption and antioxidant mechanism, and alleviate osteoporosis in low-calcium feeding rats. Correlation analysis showed that the selected intestinal flora was significantly correlated with metabolites enriched in feces and plasma. This study provides scientific evidence of the potential impact of chondroitin sulfate as a dietary supplement for patients with osteoporosis.PMID:36747190 | DOI:10.1186/s12986-023-00726-3

BMC Cancer. 2023 Feb 6;23(1):122. doi: 10.1186/s12885-023-10589-9.ABSTRACTBACKGROUND: Precursor B-cell acute lymphoblastic leukemia (pre-B ALL) is the most common hematological malignancy in children. Cellular metabolic reorganization is closely related to the progression and treatment of leukemia. We found that the level of 1,5-anhydroglucitol (1,5-AG), which is structurally similar to glucose, was elevated in children with pre-B ALL. However, the effect of 1,5-AG on pre-B ALL was unclear. Here, we aimed to reveal the roles and mechanisms of 1,5-AG in pre-B ALL progression.METHODS: The peripheral blood plasma level of children with initial diagnosis of pre-B ALL and that of healthy children was measured using untargeted metabolomic analysis. Cell Counting Kit-8 assay, RNA sequencing, siRNA transfection, real-time quantitative PCR, and western blot were performed using pre-B ALL cell lines Reh and HAL-01. Cell cycle, cell apoptosis, ROS levels, and the positivity rate of CD19 were assessed using flow cytometry. Oxygen consumption rates and extracellular acidification rate were measured using XFe24 Extracellular Flux Analyzer. The lactate and nicotinamide adenine dinucleotide phosphate levels were measured using kits. The effect of 1,5-AG on pre-B ALL progression was verified using the In Vivo Imaging System in a xenotransplantation leukemia model.RESULTS: We confirmed that 1,5-AG promoted the proliferation, viability, and intracellular glycolysis of pre-B ALL cells. Mechanistically, 1,5-AG promotes glycolysis while inhibiting mitochondrial respiration by upregulating pyruvate dehydrogenase kinase 4 (PDK4). Furthermore, high levels of intracellular glycolysis promote pre-B ALL progression by activating the reactive oxygen species (ROS)-dependent mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. Conversely, N-acetylcysteine or vitamin C, an antioxidant, effectively inhibited 1,5-AG-mediated progression of leukemia cells.CONCLUSIONS: Our study reveals a previously undiscovered role of 1,5-AG in pre-B ALL, which contributes to an in-depth understanding of anaerobic glycolysis in the progression of pre-B ALL and provides new targets for the clinical treatment of pre-B ALL.PMID:36747147 | DOI:10.1186/s12885-023-10589-9

Nat Metab. 2023 Feb 6. doi: 10.1038/s42255-023-00735-9. Online ahead of print.ABSTRACTMetabolism is a fundamental cellular process that is coordinated with cell cycle progression. Despite this association, a mechanistic understanding of cell cycle phase-dependent metabolic pathway regulation remains elusive. Here we report the mechanism by which human de novo pyrimidine biosynthesis is allosterically regulated during the cell cycle. Combining traditional synchronization methods and metabolomics, we characterize metabolites by their accumulation pattern during cell cycle phases and identify cell cycle phase-dependent regulation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase and dihydroorotase (CAD), the first, rate-limiting enzyme in de novo pyrimidine biosynthesis. Through systematic mutational scanning and structural modelling, we find allostery as a major regulatory mechanism that controls the activity change of CAD during the cell cycle. Specifically, we report evidence of two Animalia-specific loops in the CAD allosteric domain that involve sensing and binding of uridine 5'-triphosphate, a CAD allosteric inhibitor. Based on homology with a mitochondrial carbamoyl-phosphate synthetase homologue, we identify a critical role for a signal transmission loop in regulating the formation of a substrate channel, thereby controlling CAD activity.PMID:36747088 | DOI:10.1038/s42255-023-00735-9

Sci Rep. 2023 Feb 6;13(1):2139. doi: 10.1038/s41598-023-29117-7.ABSTRACTDespite of multiple systematic studies of schizophrenia based on proteomics, metabolomics, and genome-wide significant loci, reconstruction of underlying mechanism is still a challenging task. Combination of the advanced data for quantitative proteomics, metabolomics, and genome-wide association study (GWAS) can enhance the current fundamental knowledge about molecular pathogenesis of schizophrenia. In this study, we utilized quantitative proteomic and metabolomic assay, and high throughput genotyping for the GWAS study. We identified 20 differently expressed proteins that were validated on an independent cohort of patients with schizophrenia, including ALS, A1AG1, PEDF, VTDB, CERU, APOB, APOH, FASN, GPX3, etc. and almost half of them are new for schizophrenia. The metabolomic survey revealed 18 group-specific compounds, most of which were the part of transformation of tyrosine and steroids with the prevalence to androgens (androsterone sulfate, thyroliberin, thyroxine, dihydrotestosterone, androstenedione, cholesterol sulfate, metanephrine, dopaquinone, etc.). The GWAS assay mostly failed to reveal significantly associated loci therefore 52 loci with the smoothened p < 10-5 were fractionally integrated into proteome-metabolome data. We integrated three omics layers and powered them by the quantitative analysis to propose a map of molecular events associated with schizophrenia psychopathology. The resulting interplay between different molecular layers emphasizes a strict implication of lipids transport, oxidative stress, imbalance in steroidogenesis and associated impartments of thyroid hormones as key interconnected nodes essential for understanding of how the regulation of distinct metabolic axis is achieved and what happens in the conditioned proteome and metabolome to produce a schizophrenia-specific pattern.PMID:36747015 | DOI:10.1038/s41598-023-29117-7

Carbohydr Polym. 2023 Apr 15;306:120626. doi: 10.1016/j.carbpol.2023.120626. Epub 2023 Jan 26.ABSTRACTThe roots of Salvia miltiorrhiza have been used in Traditional Chinese Medicine for thousands of years. However, tons of aerial parts of this plant are usually discarded in the production of roots preparation. To make better use of these plant resources, the polysaccharide isolated from the aerial part of S. miltiorrhiza was investigated for its potential protection against intestinal diseases. A pectic polysaccharide (SMAP-1) was isolated and characterized being composed of homogalacturonan as the main chain and rhamnogalacturonan type I as ramified region, with side chains including arabinans and possible arabinogalactan type I and II. SMAP-1 exhibited robust protective effects against dextran sodium sulfate (DSS)-induced colitis and restored colitis symptoms, colonic inflammation, and barrier functions. Anti-oxidative effects were also observed by up-regulating Nrf2/Keap1 signaling pathway. Additionally, the level of serum 5-methoxyindole-3-carboxaldehyde (5-MC) was restored by SMAP-1 identified in metabolomic analysis, being correlated with the aforementioned effects. Protection against oxidative stress on intestinal porcine enterocyte cells (IPEC-J2) by 5-MC was observed through the activation of Nrf2/Keap1 system, as also shown by SMAP-1. In conclusion, SMAP-1 could be a promising candidate for colitis prevention, and 5-MC could be the signal metabolite of SMAP-1 in protecting against oxidative stress in the intestine.PMID:36746576 | DOI:10.1016/j.carbpol.2023.120626

Pharmacol Res. 2023 Feb 4:106687. doi: 10.1016/j.phrs.2023.106687. Online ahead of print.ABSTRACTAccumulating evidence indicates gut microbiota contributes to aging-related disorders. However, the exact mechanism underlying gut dysbiosis-related pathophysiological changes during aging remains largely unclear. In the current study, we first performed gut microbiota remodeling on old mice by fecal microbiota transplantation (FMT) from young mice, and then characterized the bacteria signature that was specifically altered by FMT. Our results revealed that FMT significantly improved natural aging-related systemic disorders, particularly exerted hepatoprotective effects, and improved glucose sensitivity, hepatosplenomegaly, inflammaging, antioxidative capacity and intestinal barrier. Moreover, FMT particularly increased the abundance of fecal A.muciniphila, which was almost nondetectable in old mice. Interestingly, A.muciniphila supplementation also exerted similar benefits with FMT on old mice. Notably, targeted metabolomics on short chain fatty acids (SCFAs) revealed that only acetic acid was consistently reversed by FMT. Then, acetic acid intervention exerted beneficial actions on both Caenorhabditis elegans and natural aging mice. In conclusion, our current study demonstrated that gut microbiota remodeling improved natural aging-related disorders through A.muciniphila and its derived acetic acid, suggesting that interventions with potent stimulative capacity on A. muciniphila growth and production of acetic acid was alternative and effective way to maintain healthy aging. DATA AVAILABILITY STATEMENT: The data of RNAseq and 16S rRNA gene sequencing can be accessed in NCBI with the accession number PRJNA848996 and PRJNA849355.PMID:36746362 | DOI:10.1016/j.phrs.2023.106687

Life Sci. 2023 Feb 4:121474. doi: 10.1016/j.lfs.2023.121474. Online ahead of print.ABSTRACTAIMS: Atopic dermatitis (AD) is a common chronic inflammatory skin disorder that affects up to 20 % of children and 10 % of adults worldwide; however, the exact molecular mechanisms remain largely unknown.MATERIALS AND METHODS: In this study, we used integrated transcriptomic and metabolomic analyses to study the potential mechanisms of 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like skin lesions.KEY FINDINGS: We found that DNCB induced AD-like skin lesions, including phenotypical and histomorphological alterations and transcriptional and metabolic alterations in mice. A total of 3413 differentially expressed metabolites were detected between DNCB-induced AD-like mice and healthy controls, which includes metabolites in taurine and hypotaurine metabolism, phenylalanine metabolism, biosynthesis of unsaturated fatty acids, tryptophan metabolism, arachidonic acid metabolism, pantothenate and CoA biosynthesis, pyrimidine metabolism, and glycerophospholipid metabolism pathways. Furthermore, the differentially expressed genes associated (DEGs) with these metabolic pathways were analyzed using RNA sequencing (RNA-seq), and we found that the expression of pyrimidine metabolism-associated genes was significantly increased. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the glycolysis/gluconeogenesis, glucagon signaling pathway and pentose phosphate pathway-associated metabolic genes were dramatically altered.SIGNIFICANCE: Our results explain the possible mechanism of AD at the gene and metabolite levels and provide potential targets for the development of clinical drugs for AD.PMID:36746357 | DOI:10.1016/j.lfs.2023.121474

Biomed J. 2023 Feb 4:S2319-4170(23)00005-7. doi: 10.1016/j.bj.2023.02.001. Online ahead of print.ABSTRACTCellular senescence is a complex process involving a close-to-irreversible arrest of the cell cycle, the acquisition of the senescence-associated secretory phenotype (SASP), as well as profound changes in the expression of cell surface proteins that determine the recognition of senescent cells by innate and cognate immune effectors including macrophages, NK, NKT and T cells. It is important to note that senescence can occur in a transient fashion to improve the homeostatic response of tissues to stress. Moreover, both the excessive generation and the insufficient elimination of senescent cells may contribute to pathological aging. Attempts are being made to identify the mechanisms through which senescent cell avoid their destruction by immune effectors. Such mechanisms involve the cell surface expression of immunosuppressive molecules including PD-L1 and PD-L2 to ligate PD-1 on T cells, as well as tolerogenic MHC class-I variants. In addition, senescent cells can secrete factors that attract immunosuppressive and pro-inflammatory cells into the microenvironment. Each of these immune evasion mechanism offers a target for therapeutic intervention, e.g., by blocking the interaction between PD-1 and PD-L1 or PD-L2, upregulating immunogenic MHC class-I molecules and eliminating immunosuppressive cell types. In addition, senescent cells differ in their antigenic makeup and immunopeptidome from their normal counterparts, hence offering the opportunity to stimulate immune response against senescence-associated antigens. Ideally, immunological anti-senescence strategies should succeed in selectively eliminating pathogenic senescent cells but spare homeostatic senescence.PMID:36746349 | DOI:10.1016/j.bj.2023.02.001

Environ Pollut. 2023 Feb 4:121220. doi: 10.1016/j.envpol.2023.121220. Online ahead of print.ABSTRACTEmerging evidence suggests that exposure to PM2.5 is associated with a high risk of nonalcoholic fatty liver disease (NAFLD). NAFLD is typically characterised by hepatic steatosis. However, the underlying mechanisms and critical components of PM2.5-induced hepatic steatosis remain to be elucidated. In this study, 10-month-old C57BL/6 female mice were exposed to PM2.5 from four cities in China (Taiyuan, Beijing, Hangzhou, and Guangzhou) via oropharyngeal aspiration every other day for four weeks. After the exposure period, hepatic lipid accumulation was evaluated by biochemical and histopathological analyses. The expression levels of genes related to lipid metabolism and metabolomic profiles were assessed in the mouse liver. The association between biomarkers of hepatic steatosis (hepatic Oil Red O staining area and serum and liver triglyceride contents) and typical components of PM2.5 was identified using Pearson correlation analysis. Oil Red O staining and biochemical results indicated that PM2.5 from four cities significantly induced hepatic lipid accumulation. The most severe hepatic steatosis was observed after Guangzhou PM2.5 exposure. Moreover, Guangzhou PM2.5-induced the most significant changes in gene expression associated with lipid metabolism, including increased hepatic fatty acid uptake and lipid droplet formation and decreased fatty acid synthesis and lipoprotein secretion. Contemporaneously, exposure to Guangzhou PM2.5 significantly perturbed hepatic lipid metabolism. According to metabolomic analysis, disturbed hepatic lipid metabolism was primarily concentrated in linoleic acid, α-linoleic acid, and arachidonic acid metabolism. Finally, correlation analysis revealed that copper (Cu) and other inorganic components, as well as the majority of polycyclic aromatic hydrocarbons (PAHs), were related to changes in biomarkers of hepatic steatosis. These findings showed that PM2.5 exposure caused hepatic steatosis in aged mice, which could be related to the critical chemical components of PM2.5. This study provides critical information regarding the components of PM2.5, which cause hepatic steatosis.PMID:36746292 | DOI:10.1016/j.envpol.2023.121220

Chemosphere. 2023 Feb 4:137998. doi: 10.1016/j.chemosphere.2023.137998. Online ahead of print.ABSTRACTChronic exposure to arsenic (As) remains a global public health concern and our understanding of the biological mechanisms underlying the adverse effects of As exposure remains incomplete. Here, we used a high-resolution metabolomics approach to examine how As affects metabolic pathways in humans. We selected 60 non-smoking adults from the Folic Acid and Creatine Trial (FACT). Inorganic (AsIII, AsV) and organic (monomethylarsonous acid [MMAs], dimethylarsinous Acid [DMAs]) As species were measured in blood and urine collected at baseline and at 12 weeks. Plasma metabolome profiles were measured using untargeted high-resolution mass spectrometry. Associations of blood and urinary As with 170 confirmed metabolites and >26,000 untargeted spectral features were modeled using a metabolome-wide association study (MWAS) approach. Models were adjusted for age, sex, visit, and BMI and corrected for false discovery rate (FDR). In the MWAS screening of confirmed metabolites, 17 were associated with ≥1 blood As species (FDR<0.05), including fatty acids, neurotransmitter metabolites, and amino acids. These results were consistent across blood As species and between blood and urine As. Untargeted MWAS identified 423 spectral features associated with ≥1 blood As species. Unlike the confirmed metabolites, untargeted model results were not consistent across As species, with AsV and DMAs showing distinct association patterns. Mummichog pathway analysis revealed 12 enriched metabolic pathways that overlapped with the 17 identified metabolites, including one carbon metabolism, tricarboxylic acid cycle, fatty acid metabolism, and purine metabolism. Exposure to As may affect numerous essential pathways that underlie the well-characterized associations of As with multiple chronic diseases.PMID:36746250 | DOI:10.1016/j.chemosphere.2023.137998

Fish Shellfish Immunol. 2023 Feb 4:108590. doi: 10.1016/j.fsi.2023.108590. Online ahead of print.ABSTRACTThe molecular processes underlying skin wound healing in several fish species have been elucidated in the last years, however, metabolomic insights are scarce. Here we report the skin mucus metabolome of wounded and non-wounded gilthead seabream (Sparus aurata) fed with silk fibroin microparticles, a functional additive considered to accelerate the wound healing process. The three experimental diets (commercial diet enriched with 0 mg (control), 50 mg or 100 mg of silk fibroin microparticles Kg-1) were administered for 30 days and thereafter, a skin wound was inflicted. Skin mucus was collected on day 30 of feeding and 7 days post-wounding and subjected to metabolomic analysis by Ultra Performance Liquid Chromatography coupled with a high-resolution quadrupole-orbitrap mass spectrometry. The most enriched metabolite class was amino acids and derivatives, followed by nucleotides, nucleosides and analogues and carbohydrates and their derivatives. Metabolomic profiles revealed that the diet had a more profound effect than wounding in skin mucus. Metabolic pathway analysis of significantly affected metabolites revealed perturbations in the aminoacyl t-RNA biosynthesis in the skin. In particular, skin wound resulted in a decreased methionine level in mucus. Further, silk fibroin supplementation increased methionine level in skin mucus, which correlated with several wound morphometric parameters that characterized the epithelial healing capacity in seabream. The results provided new insight into the physiological consequences of skin wounds and how these processes could be influenced by dietary manipulation.PMID:36746227 | DOI:10.1016/j.fsi.2023.108590

Bioresour Technol. 2023 Feb 4:128705. doi: 10.1016/j.biortech.2023.128705. Online ahead of print.ABSTRACTCordycepin is the key pharmacologically active compound of Cordyceps militaris, and various fermentation strategies have been developed to increase cordycepin production. This study aimed to investigate the effect of rotenone on cordycepin biosynthesis in submerged fermentation of C. militaris, and also to explore its possible induction mechanisms via multi-omics analysis. Adding 5 mg/L rotenone significantly increased the cordycepin production by 316.09%, along with mycelial growth inhibition and cell wall destruction. Moreover, transcriptomic analysis and metabolomic analysis revealed the accumulation of cordycepin was promoted by alterations in energy metabolism and amino acid metabolism pathways. Finally, the integration analysis of the two omics confirmed rotenone altered the nucleotide metabolism pathway toward adenosine and up-regulated the cordycepin synthesis genes (cns1-3) to convert adenosine to cordycepin. This work reports, for the first time, rotenone could act as an effective inducer of cordycepin synthesis.PMID:36746212 | DOI:10.1016/j.biortech.2023.128705

Aquat Toxicol. 2023 Feb 2;256:106415. doi: 10.1016/j.aquatox.2023.106415. Online ahead of print.ABSTRACTThe ecotoxicological and environmental impacts of glyphosate-based herbicides have received considerable attention due to their extensive use globally. However, the potential for adverse effects in cultured non-fish vertebrate species are commonly ignored. In this study, effects on growth, indicators of functional performance, gut microbial diversity, liver antioxidant responses and metabolite profiles were evaluated in soft-shelled turtle hatchlings (Pelodiscus sinensis) exposed to different concentrations of glyphosate-isopropylammonium (0, 0.02, 0.2, 2 and 20 mg/L). No significant changes in growth or functional performance (food intake, swimming speed), gut microbiota, and liver antioxidant responses (SOD and CAT activities, MDA content) were observed in exposed turtles. However, hepatic metabolite profiles revealed distinct perturbations that primarily involved amino acid metabolism in turtles exposed to environmentally relevant concentrations. Overall, our results suggested that metabolite profiles may be more sensitive than phenotypic or general physiological endpoints and gut microbiota profiling, and indicate a potential mechanism of hepatotoxicity caused by glyphosate-isopropylammonium based on untargeted metabolomics analysis. Furthermore, the toxicity of glyphosate at environmentally relevant concentrations might be relatively minor in aquatic turtle species.PMID:36746075 | DOI:10.1016/j.aquatox.2023.106415