PubMed

Front Microbiol. 2023 Jan 19;13:1029412. doi: 10.3389/fmicb.2022.1029412. eCollection 2022.ABSTRACTPseudomonas aeruginosa is one of the most important foodborne pathogens that can persist in leafy green vegetables and subsequently produce biofilms. In this study, the synergistic effect of thymoquinone and nisin in reducing biofilm formation of P. aeruginosa on lettuce was evaluated, and their anti-virulence and anti-biofilm mechanisms were also investigated. At concentrations ranging from 0.5 to 2 mg/ml, thymoquinone inhibited the production of autoinducers and virulence factors, and enhanced the susceptibility of P. aeruginosa biofilms to nisin as evidenced by the scanning electron microscopy and confocal laser scanning microscopy. Integrated transcriptomics, metabolomics, and docking analyses indicated that thymoquinone treatment disrupted the quorum sensing (QS) system, altered cell membrane component, and down-regulated the expressions of genes related to virulence, efflux pump, and antioxidation. The changed membrane component and repressed efflux pump system enhanced membrane permeability and facilitated the entrance of nisin into cells, thus improving the susceptibility of biofilms to nisin. The dysfunctional QS and repressed antioxidant enzymes lead to the enhancement of oxidative stress. The enhanced oxidative stress disrupted energy metabolism and protein metabolism and ultimately attenuated the virulence and pathogenicity of P. aeruginosa PAO1. Our study indicated that thymoquinone has the potential to function as a QS-based agent to defend against foodborne pathogens in combination with nisin.PMID:36741886 | PMC:PMC9893119 | DOI:10.3389/fmicb.2022.1029412

Front Microbiol. 2023 Jan 19;13:1075621. doi: 10.3389/fmicb.2022.1075621. eCollection 2022.ABSTRACTCyanobacterial harmful algal blooms (cHABs) dominated by Microcystis aeruginosa threaten the ecological integrity and beneficial uses of lakes globally. In addition to producing hepatotoxic microcystins (MC), M. aeruginosa exudates (MaE) contain various compounds with demonstrated toxicity to aquatic biota. Previously, we found that the ecotoxicity of MaE differed between MC-producing and MC-free strains at exponential (E-phase) and stationary (S-phase) growth phases. However, the components in these exudates and their specific harmful effects were unclear. In this study, we performed untargeted metabolomics based on liquid chromatography-mass spectrometry to reveal the constituents in MaE of a MC-producing and a MC-free strain at both E-phase and S-phase. A total of 409 metabolites were identified and quantified based on their relative abundance. These compounds included lipids, organoheterocyclic compounds, organic acid, benzenoids and organic oxygen compounds. Multivariate analysis revealed that strains and growth phases significantly influenced the metabolite profile. The MC-producing strain had greater total metabolites abundance than the MC-free strain at S-phase, whereas the MC-free strain released higher concentrations of benzenoids, lipids, organic oxygen, organic nitrogen and organoheterocyclic compounds than the MC-producing strain at E-phase. Total metabolites had higher abundance in S-phase than in E- phase in both strains. Analysis of differential metabolites (DMs) and pathways suggest that lipids metabolism and biosynthesis of secondary metabolites were more tightly coupled to growth phases than to strains. Abundance of some toxic lipids and benzenoids DMs were significantly higher in the MC-free strain than the MC-producing one. This study builds on the understanding of MaE chemicals and their biotoxicity, and adds to evidence that non-MC-producing strains of cyanobacteria may also pose a threat to ecosystem health.PMID:36741884 | PMC:PMC9894096 | DOI:10.3389/fmicb.2022.1075621

Front Cardiovasc Med. 2023 Jan 18;9:1096664. doi: 10.3389/fcvm.2022.1096664. eCollection 2022.ABSTRACTBACKGROUND: Tetralogy of Fallot (TOF) belongs to cyanotic heart damage, which is the most common in clinic. In the chronic myocardial hypoxia injury related to TOF, the potential molecular mechanism of cardiac energy metabolism remains unclear.MATERIALS AND METHODS: In our study, microarray transcriptome analysis and metabonomics methods were used to explore the energy metabolism pathway during chronic hypoxia injury. The gene expression omnibus (GEO) dataset GSE132176 was obtained for analyzing the metabolic pathways. The clinical samples (right atrial tissues) of atrial septal defect (ASD) and TOF were analyzed by metabonomics. Next, we screened important pathways and important differential metabolites related to energy metabolism to explore the pathogenesis of TOF.RESULTS: Gene set enrichment analysis (GSEA) indicated that fructose 6-phosphate metabolic process, triglyceride metabolic process, and et al. were significantly enriched. Gene set variation analysis (GSVA) results showed that significant difference of ASD group and TOF group existed in terpenoid metabolic process and positive regulation of triglyceride metabolic process. Pathways with significant enrichment (impact > 0.1) in TOF were caffeine metabolism (impact = 0.69), sphingolipid metabolism (impact = 0.46), glycerophospholipid metabolism (impact = 0.26), tryptophan metabolism (impact = 0.24), galactose metabolism (impact = 0.11). Pathways with significant enrichment (impact > 0.1) in ASD are caffeine metabolism (impact = 0.69), riboflavin metabolism (impact = 0.5), alanine, aspartate and glutamate metabolism (impact = 0.35), histidine metabolism (impact = 0.34) and et al.CONCLUSION: Disturbed energy metabolism occurs in patients with TOF or ASD, and further investigation was needed to further clarify mechanism.PMID:36741837 | PMC:PMC9889939 | DOI:10.3389/fcvm.2022.1096664

Front Physiol. 2023 Jan 18;13:1079667. doi: 10.3389/fphys.2022.1079667. eCollection 2022.ABSTRACTWhite striping (WS) is the most common myopathy in the broiler chicken industry. To reveal flavor changes of WS meat objectively, flavor precursors of WS breast muscle were evaluated systematically with integrated metabolomics and lipidomics. The results showed that WS could be distinguished from normal controls by E-nose, and four volatile compounds (o-xylene, benzene, 1,3-dimethyl, 2-heptanone and 6-methyl and Acetic acid and ethyl ester) were detected as decreased compounds by gas chromatography-mass spectrometry. Lipidomic analysis showed that WS breast fillets featured increased neutral lipid (83.8%) and decreased phospholipid molecules (33.2%). Targeted metabolomic analysis indicated that 16 hydrophilic metabolites were altered. Thereinto, some water-soluble flavor precursors, such as adenosine monophosphate, GDP-fucose and L-arginine increased significantly, but fructose 1,6-bisphosphate and L-histidine significantly decreased in the WS group. These results provided a systematic evaluation of the flavor precursors profile in the WS meat of broiler chickens.PMID:36741806 | PMC:PMC9889919 | DOI:10.3389/fphys.2022.1079667

Front Bioeng Biotechnol. 2023 Jan 20;11:1118911. doi: 10.3389/fbioe.2023.1118911. eCollection 2023.ABSTRACTIntroduction: In vitro metabolic fingerprinting encodes diverse diseases for clinical practice, while tedious sample pretreatment in bio-samples has largely hindered its universal application. Designed materials are highly demanded to construct diagnostic tools for high-throughput metabolic information extraction. Results: Herein, a ternary component chip composed of mesoporous silica substrate, plasmonic matrix, and perfluoroalkyl initiator is constructed for direct metabolic fingerprinting of biofluids by laser desorption/ionization mass spectrometry. Method: The performance of the designed chip is optimized in terms of silica pore size, gold sputtering time, and initiator loading parameter. The optimized chip can be coupled with microarrays to realize fast, high-throughput (∼second/sample), and microscaled (∼1 μL) sample analysis in human urine without any enrichment or purification. On-chip urine fingerprints further allow for differentiation between kidney stone patients and healthy controls. Discussion: Given the fast, high throughput, and easy operation, our approach brings a new dimension to designing nano-material-based chips for high-performance metabolic analysis and large-scale diagnostic use.PMID:36741764 | PMC:PMC9895787 | DOI:10.3389/fbioe.2023.1118911

PNAS Nexus. 2022 Jul 4;1(3):pgac068. doi: 10.1093/pnasnexus/pgac068. eCollection 2022 Jul.ABSTRACTRapid population growth and increasing demand for food, feed, and bioenergy in these times of unprecedented climate change require breeding for increased biomass production on the world's croplands. To accelerate breeding programs, knowledge of the relationship between biomass features and underlying gene networks is needed to guide future breeding efforts. To this end, large-scale multiomics datasets were created with genetically diverse maize lines, all grown in long-term organic and conventional cropping systems. Analysis of the datasets, integrated using regression modeling and network analysis revealed key metabolites, elements, gene transcripts, and gene networks, whose contents during vegetative growth substantially influence the build-up of plant biomass in the reproductive phase. We found that S and P content in the source leaf and P content in the root during the vegetative stage contributed the most to predicting plant performance at the reproductive stage. In agreement with the Gene Ontology enrichment analysis, the cis-motifs and identified transcription factors associated with upregulated genes under phosphate deficiency showed great diversity in the molecular response to phosphate deficiency in selected lines. Furthermore, our data demonstrate that genotype-dependent uptake, assimilation, and allocation of essential nutrient elements (especially C and N) during vegetative growth under phosphate starvation plays an important role in determining plant biomass by controlling root traits related to nutrient uptake. These integrative multiomics results revealed key factors underlying maize productivity and open new opportunities for efficient, rapid, and cost-effective plant breeding to increase biomass yield of the cereal crop maize under adverse environmental factors.PMID:36741443 | PMC:PMC9896949 | DOI:10.1093/pnasnexus/pgac068

Front Immunol. 2023 Jan 18;13:1101130. doi: 10.3389/fimmu.2022.1101130. eCollection 2022.ABSTRACTMaternal gut microbiota is an important regulator for the metabolism and immunity of the fetus during pregnancy. Recent studies have indicated that maternal intestinal microbiota is closely linked to the development of fetus and infant health. Some bacterial metabolites are considered to be directly involved in immunoregulation of fetus during pregnancy. However, the detailed mechanisms are largely unknown. In this study, we exploited the potential correlation between the gut microbiota of pregnant sows and the occurrence of stillborn piglets by combining the 16S rRNA gene and metagenomic sequencing data, and fecal metabolome in different cohorts. The results showed that several bacterial species from Bacteroides, potential pathogens, and LPS-producing bacteria exhibited significantly higher abundances in the gut of sows giving birth to stillborn piglets. Especially, Bacteroides fragilis stood out as the key driver in both tested cohorts and showed the most significant association with the occurrence of stillborn piglets in the DN1 cohort. However, several species producing short-chain fatty acids (SCFAs), such as Prevotella copri, Clostridium butyricum and Faecalibacterium prausnitzii were enriched in the gut of normal sows. Functional capacity analysis of gut microbiome revealed that the pathways associated with infectious diseases and immune diseases were enriched in sows giving birth to stillborn piglets. However, energy metabolism had higher abundance in normal sows. Fecal metabolome profiling analysis found that Lysophosphatidylethanolamine and phosphatidylethanolamine which are the main components of cell membrane of Gram-negative bacteria showed significantly higher concentration in stillbirth sows, while SCFAs had higher concentration in normal sows. These metabolites were significantly associated with the stillborn-associated bacterial species including Bacteroides fragilis. Lipopolysaccharide (LPS), IL-1β, IL-6, FABP2, and zonulin had higher concentration in the serum of stillbirth sows, indicating increased intestinal permeability and pro-inflammatory response. The results from this study suggested that certain sow gut bacterial species in late trimester of pregnancy, e.g., an excess abundance of Bacteroides fragilis, produced high concentration of LPS which induced sow pro-inflammatory response and might cause the death of the relatively weak piglets in a farrow. This study provided novel evidences about the effect of maternal gut microbiota on the fetus development and health.PMID:36741405 | PMC:PMC9890068 | DOI:10.3389/fimmu.2022.1101130

Front Immunol. 2023 Jan 19;13:1045901. doi: 10.3389/fimmu.2022.1045901. eCollection 2022.ABSTRACTUlcerative colitis (UC) is one form of inflammatory bowel disease (IBD), characterized by chronic relapsing intestinal inflammation. As increasing morbidity of UC and deficiency of conventional therapies, there is an urgent need for attractive treatment. Cassane diterpenoids, the characteristic chemical constituents of Caesalpinia genus plants, have been studied extensively owing to various and prominent biological activities. This study attempted to investigate the bioactivity of caesaldekarin e (CA), a cassane diterpenoid isolated from C. bonduc in our previous work, on dextran sulfate sodium (DSS)-induced experimental colitis and clarify the function mechanism. The results indicated that CA ameliorated mice colitis by relieving disease symptoms, suppressing inflammatory infiltration and maintaining intestinal barrier integrity. Furthermore, 16S rRNA gene sequencing analysis indicated that CA could improve the gut microbiota imbalance disrupted by DSS and especially restored abundance of Lactobacillus. In addition, untargeted metabolomics analysis suggested that CA regulated metabolism and particularly the tryptophan metabolism by inhibiting the upregulation of indoleamine 2,3-dioxygenase 1 (IDO-1). It also been proved in IFN-γ induced RAW264.7 cells. Overall, this study suggests that CA exhibits anti-UC effect through restoring gut microbiota and regulating tryptophan metabolism and has the potential to be a treatment option for UC.PMID:36741371 | PMC:PMC9893013 | DOI:10.3389/fimmu.2022.1045901

Front Genet. 2023 Jan 20;14:1023433. doi: 10.3389/fgene.2023.1023433. eCollection 2023.ABSTRACTVeratrum mengtzeanum is the main ingredient for Chinese folk medicine known as "Pimacao" due to its unique alkaloids. A diverse class of plant-specific metabolites having key pharmacological activities. There are limited studies on alkaloid synthesis and its metabolic pathways in plants. To elucidate the alkaloid pathway and identify novel biosynthetic enzymes and compounds in V. mengtzeanum, transcriptome and metabolome profiling has been conducted in leaves and roots. The transcriptome of V. mengtzeanum leaves and roots yielded 190,161 unigenes, of which 33,942 genes expressed differentially (DEGs) in both tissues. Three enriched regulatory pathways (isoquinoline alkaloid biosynthesis, indole alkaloid biosynthesis and tropane, piperidine and pyridine alkaloid biosynthesis) and a considerable number of genes such as AED3-like, A4U43, 21 kDa protein-like, 3-O-glycotransferase 2-like, AtDIR19, MST4, CASP-like protein 1D1 were discovered in association with the biosynthesis of alkaloids in leaves and roots. Some transcription factor families, i.e., AP2/ERF, GRAS, NAC, bHLH, MYB-related, C3H, FARI, WRKY, HB-HD-ZIP, C2H2, and bZIP were also found to have a prominent role in regulating the synthesis of alkaloids and steroidal alkaloids in the leaves and roots of V. mengtzeanum. The metabolome analysis revealed 74 significantly accumulated metabolites, with 55 differentially accumulated in leaves compared to root tissues. Out of 74 metabolites, 18 alkaloids were highly accumulated in the roots. A novel alkaloid compound viz; 3-Vanilloylygadenine was discovered in root samples. Conjoint analysis of transcriptome and metabolome studies has also highlighted potential genes involved in regulation and transport of alkaloid compounds. Here, we have presented a comprehensive metabolic and transcriptome profiling of V. mengtzeanum tissues. In earlier reports, only the roots were reported as a rich source of alkaloid biosynthesis, but the current findings revealed both leaves and roots as significant manufacturing factories for alkaloid biosynthesis.PMID:36741317 | PMC:PMC9895797 | DOI:10.3389/fgene.2023.1023433

RSC Adv. 2023 Jan 17;13(4):2635-2648. doi: 10.1039/d2ra07269f. eCollection 2023 Jan 11.ABSTRACTGynura segetum (Lour.) Merr. (GS), has been widely used in Chinese folk medicine and can promote circulation, relieve pain and remove stasis. In recent years, the hepatotoxicity caused by GS has been reported, however its mechanism is not fully elucidated. Metabolomic techniques are powerful means to explore the toxicological mechanism and therapeutic effects of traditional Chinese medicine. The purpose of this study was to establish a serum metabolomics method based on Gas Chromatography-Mass Spectrometry (GC-MS) to explore the hepatotoxicity mechanism of different exposure times and doses of GS in rats. Sprague Dawley (SD) rats were administered daily with distilled water, 7.5 g kg-1 GS, or 15 g kg-1 GS by intragastrical gavage for either 10 or 21 days. The methods adopted included enzyme-linked immunosorbent assay (ELISA), Hematoxylin and Eosin (H&E) staining and GC-MS-based serum metabolomics. Serum biochemistry analysis showed that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total bilirubin (TBIL) and total bile acid (TBA) significantly (P < 0.05) increased while the levels of albumin (ALB) and high-density lipoprotein (HDL) significantly (P < 0.05) decreased in GS-treated groups, compared with the control group. Interestingly, the ALT, AST, TG and ALB levels changed in a time- and dose-dependent manner. The results of H&E staining showed the degree of liver damage after administration of GS gradually deepened with the extension of administration time and the increase of the dose. According to the results of metabolomics analysis, 26 differential metabolites were identified, which were involved in 8 metabolic pathways including phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism and so on. Meanwhile, the number of differential metabolites in different GS-treated groups was associated with GS exposure time and dose. Therefore, we concluded that GS might induce hepatotoxicity depending on the exposure time and dose.PMID:36741154 | PMC:PMC9844675 | DOI:10.1039/d2ra07269f

J Clin Endocrinol Metab. 2023 Feb 6:dgad027. doi: 10.1210/clinem/dgad027. Online ahead of print.ABSTRACTCONTEXT: Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases.OBJECTIVE: We evaluated the safety and physiologic effects of NAD augmentation by administering its precursor, β-nicotinamide mononucleotide (MIB-626, Metro International Biotech, Worcester, MA), in adults at risk for age-related conditions.METHODS: Thirty overweight or obese adults, ≥ 45 years, were randomized in a 2:1 ratio to 2 MIB-626 tablets each containing 500 mg of microcrystalline β-nicotinamide mononucleotide or placebo twice daily for 28 days. Study outcomes included safety; NAD and its metabolome; body weight; liver, muscle, and intra-abdominal fat; insulin sensitivity; blood pressure; lipids; physical performance, and muscle bioenergetics.RESULTS: Adverse events were similar between groups. MIB-626 treatment substantially increased circulating concentrations of NAD and its metabolites. Body weight (difference -1.9 [-3.3, -0.5] kg, P = .008); diastolic blood pressure (difference -7.01 [-13.44, -0.59] mmHg, P = .034); total cholesterol (difference -26.89 [-44.34, -9.44] mg/dL, P = .004), low-density lipoprotein (LDL) cholesterol (-18.73 [-31.85, -5.60] mg/dL, P = .007), and nonhigh-density lipoprotein cholesterol decreased significantly more in the MIB-626 group than placebo. Changes in muscle strength, muscle fatigability, aerobic capacity, and stair-climbing power did not differ significantly between groups. Insulin sensitivity and hepatic and intra-abdominal fat did not change in either group.CONCLUSIONS: MIB-626 administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure. These data provide the rationale for larger trials to assess the efficacy of NAD augmentation in improving cardiometabolic outcomes in older adults.PMID:36740954 | DOI:10.1210/clinem/dgad027

Food Funct. 2023 Feb 6. doi: 10.1039/d2fo03509j. Online ahead of print.ABSTRACTHyperlipidemia (HLP) is one of the main factors leading to cardiovascular diseases. Quercetin (QUE) is a naturally occurring polyhydroxy flavonoid compound that has a wide range of pharmacological effects. However, the potential mechanism for treating HLP remains unclear. Thus, the study aimed to investigate the role of QUE in HLP development and its underlying mechanisms in HLP rats based on the analysis of gut microbiota and plasma metabolomics. Following the establishment of an HLP model in rats, QUE was orally administered. Plasma samples and fecal samples were collected from HLP rats for microbiome 16S rDNA sequencing and metabolic UPLC-Q-Exactive-MS analysis. The results suggested that QUE could regulate dyslipidemia and inhibit the levels of TC, TG, and LDL-c. Additionally, histopathological findings revealed that QUE could reduce lipid deposition, ameliorate hepatic injury and steatosis in HFD-induced rats, and have a protective effect on the liver. The analysis and identification of plasma metabolomics showed that the intervention effect of QUE on HLP rats was related to 60 differential metabolites and signal pathways such as lactosamine, 11b-hydroxyprogesterone, arachidonic acid, glycerophospholipid, sphingolipid, glycerolipid, and linoleic acid metabolism. Combined with fecal microbiological analysis, it was found that QUE could significantly change the composition of intestinal flora in HLP rats, increase beneficial bacteria, and reduce the composition of harmful bacteria, attenuating the Firmicutes/Bacteroidetes ratio. The results of correlation analysis showed that the relative abundance level of Firmicutes, Deironobacterium, Fusobacterium, Bacteroides, and Escherichia coli was closely related to the change of differential metabolites. In summary, combined with metabolomics and gut microbiota studies, it is found that QUE can reduce lipid levels and improve liver function. The potential mechanism may be the regulation of metabolism and intestinal flora that play a role in reducing lipid levels, to achieve the purpose of treatment of HLP.PMID:36740912 | DOI:10.1039/d2fo03509j

Gut Microbes. 2023 Jan-Dec;15(1):2166700. doi: 10.1080/19490976.2023.2166700.ABSTRACTAlthough gut microbiota has been linked to cancer, little is known about the crosstalk between gut- and intratumoral-microbiomes. The goal of this study was to determine whether gut Akkermansia muciniphila (Akk) is involved in the regulation of intratumoral microbiome and metabolic contexture, leading to an anticancer effect on lung cancer. We evaluated the effects of gut endogenous or gavaged exogenous Akk on the tumorigenesis using the Lewis lung cancer mouse model. Feces, blood, and tumor tissue samples were collected for 16S rDNA sequencing. We then conducted spatially resolved metabolomics profiling to discover cancer metabolites in situ directly and to characterize the overall Akk-regulated metabolic features, followed by the correlation analysis of intratumoral bacteria with metabolic network. Our results showed that both endogenous and exogenous gavaged Akk significantly inhibited tumorigenesis. Moreover, we detected increased Akk abundance in blood circulation or tumor tissue by 16S rDNA sequencing in the Akk gavaged mice, compared with the control mice. Of great interest, gavaged Akk may migrate into tumor tissue and influence the composition of intratumoral microbiome. Spatially resolved metabolomics analysis revealed that the gut-derived Akk was able to regulate tumor metabolic pathways, from metabolites to enzymes. Finally, our study identified a significant correlation between the gut Akk-regulated intratumoral bacteria and metabolic network. Together, gut-derived Akk may migrate into blood circulation, and subsequently colonize into lung cancer tissue, which contributes to the suppression of tumorigenesis by influencing tumoral symbiotic microbiome and reprogramming tumoral metabolism, although more studies are needed.PMID:36740846 | DOI:10.1080/19490976.2023.2166700

Autophagy. 2023 Feb 5:1-15. doi: 10.1080/15548627.2023.2170071. Online ahead of print.ABSTRACTGuanine-quadruplex structures (G4) are unusual nucleic acid conformations formed by guanine-rich DNA and RNA sequences and known to control gene expression mechanisms, from transcription to protein synthesis. So far, a number of molecules that recognize G4 have been developed for potential therapeutic applications in human pathologies, including cancer and infectious diseases. These molecules are called G4 ligands. When the biological effects of G4 ligands are studied, the analysis is often limited to nucleic acid targets. However, recent evidence indicates that G4 ligands may target other cellular components and compartments such as lysosomes and mitochondria. Here, we summarize our current knowledge of the regulation of lysosome by G4 ligands, underlying their potential functional impact on lysosome biology and autophagic flux, as well as on the transcriptional regulation of lysosomal genes. We outline the consequences of these effects on cell fate decisions and we systematically analyzed G4-prone sequences within the promoter of 435 lysosome-related genes. Finally, we propose some hypotheses about the mechanisms involved in the regulation of lysosomes by G4 ligands.PMID:36740766 | DOI:10.1080/15548627.2023.2170071

Glob Chang Biol. 2023 Feb 5. doi: 10.1111/gcb.16614. Online ahead of print.ABSTRACTPeatlands are among the largest natural sources of atmospheric methane (CH4 ) worldwide. Microbial processes play a key role in regulating CH4 emissions from peatland ecosystems, yet the complex interplay between soil substrates and microbial communities in controlling CH4 emissions as a function of global change remains unclear. Herein, we performed an integrated analysis of multi-omics data sets to provide a comprehensive understanding of the molecular processes driving changes in greenhouse gas (GHG) emissions in peatland ecosystems with increasing temperature and sulfate deposition in a laboratory incubation study. We sought to first investigate how increasing temperatures (4, 21, and 35°C) impact soil microbiome-metabolome interactions; then explore the competition between methanogens and sulfate-reducing bacteria (SRBs) with increasing sulfate concentrations at the optimum temperature for methanogenesis. Our results revealed that peat soil organic matter degradation, mediated by biotic and potentially abiotic processes, is the main driver of the increase in CO2 production with temperature. In contrast, the decrease in CH4 production at 35°C was linked to the absence of syntrophic communities and the potential inhibitory effect of phenols on methanogens. Elevated temperatures further induced the microbial communities to develop high growth yield and stress tolerator trait-based strategies leading to a shift in their composition and function. On the other hand, SRBs were able to outcompete methanogens in the presence of non-limiting sulfate concentrations at 21°C, thereby reducing CH4 emissions. At higher sulfate concentrations, however, the prevalence of communities capable of producing sufficient low-molecular-weight carbon substrates for the coexistence of SRBs and methanogens was translated into elevated CH4 emissions. The use of omics in this study enhanced our understanding of the structure and interactions among microbes with the abiotic components of the system that can be useful for mitigating GHG emissions from peatland ecosystems in the face of global change.PMID:36740729 | DOI:10.1111/gcb.16614

Pestic Biochem Physiol. 2023 Feb;190:105320. doi: 10.1016/j.pestbp.2022.105320. Epub 2022 Dec 16.ABSTRACTProthioconazole (PTC) is a widely used agricultural fungicide. In recent years, studies have confirmed that it exerts adverse effects on various species, including aquatic organisms, mammals, and reptiles. However, the toxicological effects of PTC on soil organisms are poorly understood. Here, we investigated the toxic effects, via oxidative stress and metabolic responses, of PTC on earthworms (Eisenia fetida). PTC exposure can induce significant changes in oxidative stress indicators, including the activities of superoxide dismutase (SOD) and catalase (CAT) and the content of glutathione (GSH), which in turn affect the oxidative defense system of earthworms. In addition, metabolomics revealed that PTC exposure caused significant changes in the metabolic profiles of earthworms. The relative abundances of 16 and 21 metabolites involved in amino acids, intermediates of the tricarboxylic acid (TCA) cycle and energy metabolism were significantly altered after 7 and 14 days of PTC exposure, respectively. Particularly, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that multiple different metabolic pathways could be disturbed after 7 and 14 days of PTC exposure. Importantly, these alterations in oxidative stress and metabolic responses in earthworms reveal that the effects of PTC on earthworms were time dependent, and vary with exposure time. In conclusion, this study highlights that the effects of PTC on soil organisms are of serious concern.PMID:36740340 | DOI:10.1016/j.pestbp.2022.105320

Am J Obstet Gynecol. 2023 Feb 3:S0002-9378(23)00075-3. doi: 10.1016/j.ajog.2023.01.035. Online ahead of print.NO ABSTRACTPMID:36740032 | DOI:10.1016/j.ajog.2023.01.035

Ecotoxicol Environ Saf. 2023 Feb 3;252:114597. doi: 10.1016/j.ecoenv.2023.114597. Online ahead of print.ABSTRACTMaternal exposure to antibiotics existing in the environment is a predisposing factor for developmental malformation with metabolic disorders in offspring. In this study, female zebrafish (3 months) were exposed to 0.05 mg/L and 0.5 mg/L florfenicol (FF) for 28 days. After pairing and spawning with healthy male fish, F1 embryos were collected and developed to 5 d post-fertilization (dpf) in clear water. And the adverse effects on the F1 generation were examined thoroughly. The fecundity of F0 female fish and the hatchability, mortality, and body length of F1 larvae significantly decreased in the treatment group. Meanwhile, multi-malformation types were found in the exposure group, including delayed yolk sac absorption, lack of swim bladder, and spinal curvature. Metabolomic and transcriptomic results revealed alterations in metabolism with dysregulation in tricarboxylase acid cycle, amino acid metabolism, and disordered lipid metabolism with elevated levels of glycerophospholipid and sphingolipid. Accompanying these metabolic derangements, decreased levels of ATP and disordered oxidative-redox state were observed. These results were consistent with the damaged mitochondrial membrane potential and respiratory chain function, suggesting that the developmental toxicity and perturbed metabolic signaling in the F1 generation were related to the mitochondrial injury after exposing F0 female zebrafish to FF. Our findings highlighted the potential toxicity of FF to offspring generations even though they were not directly exposed to environmental contaminants.PMID:36739738 | DOI:10.1016/j.ecoenv.2023.114597

Kardiol Pol. 2023 Feb 5. doi: 10.33963/KP.a2023.0037. Online ahead of print.ABSTRACTHypertension (HT) is a modifiable risk factor for life-threatening cardiovascular diseases (CVDs) including coronary artery disease, heart failure or stroke. Despite significant progress in understanding of the pathophysiological mechanisms of the disease, the molecular pathways targeted by HT treatment still remain largely unchanged. This warrants the necessity for searching novel biomarkers, which are causally related to persistent high blood pressure (BP) and may be pharmacologically targeted. Data from large-scale biobanks, containing high-throughput genetic and biochemical data, such as OLINK and SomaScan-based proteomics or Nuclear Magnetic Resonance-based metabolomics, as well as novel analytical tools including Mendelian randomisation (MR) approach enabling genetic casual inference, may create new treatment opportunities for HT and related CVDs. MR analysis may constitute an additional proof for observational studies and facilitate selection of druggable targets for clinical testing and have been already used to nominate potentially causal biomarkers for HT and CVDs such as circulating glycine, branched-chain amino acids, insulin-like growth factor 1 or fibronectin 1. Using MR framework, genetic proxies for targets of already known drugs, such as statins, PCSK9 and ACE inhibitors, may additionally inform about potential side effects and eventually contribute to a more personalized medicine. Finally, genetic causal inference may disentangle independent, direct effects of correlated traits such as lipid classes or markers of inflammation on cardiovascular clinical outcomes such as atherosclerosis and HT. While several novel HT-targeting drugs are currently under clinical investigation (e.g. brain renin-angiotensin-aldosterone system inhibitors or endothelin-1 receptor antagonists), analysis of high-throughput proteomic and metabolomic data from well-powered studies may deliver novel druggable molecular targets for HT and associated CVDs.PMID:36739654 | DOI:10.33963/KP.a2023.0037

J Intern Med. 2023 Feb 5. doi: 10.1111/joim.13612. Online ahead of print.ABSTRACTBACKGROUND: Anisocytosis reflects unequal-sized red blood cells and is quantified using red blood cell distribution width (RDW). RDW increases with age and has been consistently associated with adverse health outcomes, such as cardiovascular disease and mortality. Why RDW increases with age is not understood. We aimed to identify plasma metabolomic markers mediating anisocytosis with aging.METHODS: We performed mediation analyses of plasma metabolomics on the association between age and RDW using resampling techniques after covariate adjustment. We analyzed data from adults aged 70 or older from the main discovery cohort of the Baltimore Longitudinal Study of Aging (BLSA, n = 477, 46% women) and validation cohorts of the Health, Aging and Body Composition Study (Health ABC, n = 620, 52% women) and Invecchiare in Chianti, Aging in the Chianti Area (InCHIANTI) study (n = 735, 57% women). Plasma metabolomics were assayed using the Biocrates MxP Quant 500 kit in BLSA and Health ABC and liquid chromatography with tandem mass spectrometry in InCHIANTI.RESULTS: In all three cohorts, symmetric dimethylarginine (SDMA) significantly mediated the association between age and RDW. Asymmetric dimethylarginine (ADMA) and 1-methylhistidine were also significant mediators in the discovery cohort and one validation cohort. In the discovery cohort, we also found choline, homoarginine, and several long-chain triglycerides significantly mediated the association between age and RDW.CONCLUSIONS AND RELEVANCE: This metabolomics study of three independent aging cohorts identified a specific set of metabolites mediating anisocytosis with aging. Whether SDMA, ADMA, and 1-methylhistidine are released by the damaged erythrocytes with high RDW or they affect the physiology of erythrocytes causing high RDW should be further investigated. This article is protected by copyright. All rights reserved.PMID:36739565 | DOI:10.1111/joim.13612