PubMed

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

Cell Biosci. 2023 Feb 4;13(1):24. doi: 10.1186/s13578-023-00974-z.ABSTRACTBACKGROUND: Impaired metabolic functions of gut microbiota have been demonstrated in alcohol-related liver disease (ALD), but little is known about changes in phenylalanine metabolism.METHODS: Bacterial genomics and fecal metabolomics analysis were used to recognize the changes of phenylalanine metabolism and its relationship with intestinal flora. Intestinal barrier function was detected by intestinal alkaline phosphatase (IAP) activity, levels of tight junction protein expression, colonic inflammation and levels of serum LPS. Lactobacillus acidophilus was chosen to correct phenylalanine metabolism of ALD mice by redundancy analysis and Pearson correlation analysis.RESULTS: Using 16S rRNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods, we identified elevated levels of phenylalanine and its' metabolites in the gut of alcohol-fed mice compared to control mice and were negatively correlated with the abundance of Lactobacillus, which mainly metabolized phenylalanine. The intestinal phenylalanine level was positively correlated with the colon inflammatory factors TNF-α and IL-6, and negatively correlated with ZO-1 and Occludin. While intestinal alkaline phosphatase (IAP) activity was negatively correlated with the colon inflammatory factors TNF-α, IL-6 and MCP-1, and positively correlated with ZO-1 and Occludin. Increased phenylalanine inhibited IAP activity, blocked LPS dephosphorylation, increased colonic inflammation and bacterial translocation. Phenylalanine supplementation aggravated alcohol-induced liver injury and intestinal barrier dysfunction. Among the 37 Lactobacillus species, the abundance of Lactobacillus acidophilus was most significantly decreased in ALD mice. Supplementation with L. acidophilus recovered phenylalanine metabolism and protected mice from alcohol-induced steatohepatitis.CONCLUSIONS: Recovery of phenylalanine metabolism through the oral supplementation of L. acidophilus boosted intestinal barrier integrity and ameliorated experimental ALD.PMID:36739426 | DOI:10.1186/s13578-023-00974-z

Sci Rep. 2023 Feb 4;13(1):2026. doi: 10.1038/s41598-023-28850-3.ABSTRACTWe aimed to determine the metabolomic profile of kidney cells under high glucose conditions and following sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. Targeted metabolomics using the Absolute IDQ-p180 kit was applied to quantify metabolites in kidney cells stimulated with high glucose (25 and 50 mM) and treated with SGLT2 inhibitor, dapagliflozin (2 µM). Primary cultured human tubular epithelial cells and podocytes were used to identify the metabolomic profile in high glucose conditions following dapagliflozin treatment. The levels of asparagine, PC ae C34:1, and PC ae C36:2 were elevated in tubular epithelial cells stimulated with 50 mM glucose and were significantly decreased after 2 µM dapagliflozin treatment. The level of PC aa C32:0 was significantly decreased after 50 mM glucose treatment compared with the control, and its level was significantly increased after dapagliflozin treatment in podocytes. The metabolism of glutathione, asparagine and proline was significantly changed in tubular epithelial cells under high-glucose stimulation. And the pathway analysis showed that aminoacyl-tRNA biosynthesis, arginine and proline metabolism, glutathione metabolism, valine, leucine and isoleucine biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, beta-alanine metabolism, phenylalanine metabolism, arginine biosynthesis, alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism were altered in tubular epithelial cells after dapagliflozin treatment following 50 mM glucose compared to those treated with 50 mM glucose.PMID:36739309 | DOI:10.1038/s41598-023-28850-3

Nutr Metab Cardiovasc Dis. 2023 Jan 12:S0939-4753(23)00007-8. doi: 10.1016/j.numecd.2023.01.002. Online ahead of print.ABSTRACTBACKGROUND AND AIM: Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions.METHODS AND RESULTS: Case-cohort study from the PREDIMED trial involving participants aged 55-80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20-1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12-1.58) for fumarate and 1.47 (95%CI:1.21-1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32-1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention.CONCLUSION: Plasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk.CLINICAL TRIAL NUMBER: ISRCTN35739639.PMID:36739229 | DOI:10.1016/j.numecd.2023.01.002

Environ Pollut. 2023 Feb 2:121199. doi: 10.1016/j.envpol.2023.121199. Online ahead of print.ABSTRACTFreshwater ecosystems are gradually becoming sinks for terrestrial microplastics (MPs), posing a potential ecological risk. Although the effects of MPs on plankton and aquatic animals in freshwater ecosystems have been given increasing attention, the phytotoxicity of MPs to the metabolism of aquatic plants remains unclear. Here, the model aquatic plant Spirodela polyrhiza (L.) Schleid. (S. polyrhiza) was exposed to polyvinyl chloride (PVC; 0, 10, 100 and 1000 mg/L) MPs, and changes in the plant functional traits and physiological metabolism were monitored. The results showed that the high dose of PVC MPs decreased the adventitious root elongation ratio by 41.68% and leaf multiplication ratio by 61.03% of S. polyrhiza, and resulted in the decrease in anthocyanin and nitrogen contents to 63.45% and 84.21% of the control group, respectively. Moreover, the widely targeted metabolomics analysis results showed 37 differential metabolites in the low-dose treatment and 119 differential metabolites in the high-dose treatment. PVC MPs interfered with organic matter accumulation by affecting carbon metabolism, nitrogen metabolism, amino acid metabolism and lipid metabolism, and S. polyrhiza resists PVC MP stress by regulating the synthesis and metabolism of secondary metabolites. PVC MPs had concentration-related toxicological effects on plant functional traits, inhibited plant growth and reproduction, affected plant nutrient metabolism, and exhibited profound effects on the nitrogen fate of aquatic plant habitats. Overall, we systematically summarized the metabolic response mechanisms of aquatic plants to PVC MP stress, providing a new perspective for studying the effects of MPs on plant trait function and ecological risks.PMID:36738884 | DOI:10.1016/j.envpol.2023.121199

Steroids. 2023 Feb 2:109188. doi: 10.1016/j.steroids.2023.109188. Online ahead of print.ABSTRACTIn our process of studying fusidane-type antibiotics, metabolomics-guided chemical investigation on the endophytic Acremonium pilosum F47 led to the isolation of two unique heterodimers, acremonidiols B and C (1 and 2) consisting of a fusidane-type triterpenoid motif and a steroid unit. Four biosynthetically related known natural products including fusidic acid (FA, 3), as well as ergosterol derivatives (4-6) were also obtained. Their structures were determined by the analyses of ESI-HRMS and NMR data. Compounds 1 and 2, as hybrid molecules comprising the fusidane triterpenoid and steroid, are rare in nature. Compared with the clinically used antibiotic FA (3), new compounds 1 and 2 showed no obvious antibiotic activity, indicating the importance of free C-21 carboxyl group for antibacterial activity.PMID:36738818 | DOI:10.1016/j.steroids.2023.109188

Lancet Healthy Longev. 2023 Feb;4(2):e72-e82. doi: 10.1016/S2666-7568(23)00001-6.ABSTRACTBACKGROUND: Complex and incompletely understood metabolic dysfunction associated with inflammation and protein-energy wasting contribute to the increased mortality risk of older patients and those with chronic organ diseases affected by cachexia, sarcopenia, malnutrition, and frailty. However, these wasting syndromes have uncertain relevance for patients with cardiovascular disease or people at lower risk. Studies are hampered by imperfect objective clinical assessment tools for these intertwined metabolic malnutrition and inflammation syndromes. We aimed to assess, in two independent cohorts of patients who underwent cardiac catheterisation, the mortality risk associated with the metabolic vulnerability index (MVX), a multimarker derived from six simultaneously measured serum biomarkers plausibly linked to these dysmetabolic syndromes.METHODS: In this prospective, longitudinal, observational study, we included patients aged ≥18 years recruited into the CATHGEN biorepository (Jan 2, 2001, to Dec 30, 2011) and the Intermountain Heart Collaborative Study (Sept 12, 2000, to Sept 21, 2006) who underwent coronary angiography and had clinical nuclear magnetic resonance metabolomic profiling done on frozen plasma obtained at catheterisation. We aggregated six mortality risk biomarkers (GlycA, small HDL, valine, leucine, isoleucine, and citrate concentrations) into sex-specific MVX multimarker scores using coefficients from predictive models for all-cause mortality in the CATHGEN cohort. We assessed associations of biomarkers and MVX with mortality in both cohorts using Cox proportional hazards models adjusted for 15 clinical covariates.FINDINGS: We included 5876 participants from the CATHGEN biorepository and 2888 from the Intermountain Heart study. Median follow-up was 6·2 years (IQR 4·4-8·9) in CATHGEN and 8·2 years (6·9-9·2) in the Intermountain Heart study. The six nuclear magnetic resonance biomarkers and MVX made strong, independent contributions to 5-year mortality risk prediction in both cohorts (hazard ratio 2·18 [95% CI 2·03-2·34] in the CATHGEN cohort and 1·67 [1·50-1·87] in the Intermountain Heart cohort). CATHGEN subgroup analyses showed similar MVX associations in men and women, older and younger individuals, for death from cardiovascular or non-cardiovascular causes, and in patients with or without multiple comorbidities.INTERPRETATION: MVX made a dominant contribution to mortality prediction in patients with cardiovascular disease and in low-risk subgroups without pre-existing disease, suggesting that metabolic malnutrition-inflammation syndromes might have a more universal role in survival than previously thought.FUNDING: Labcorp.PMID:36738747 | DOI:10.1016/S2666-7568(23)00001-6

Ultrason Sonochem. 2023 Jan 25;94:106311. doi: 10.1016/j.ultsonch.2023.106311. Online ahead of print.ABSTRACTMung bean seeds were treated by a combination of ultrasound and γ-aminobutyric acid (GABA). Effect of these treatments on the free polyphenols content, antioxidant activity, and digestibility of mung bean sprouts was evaluated. Additionally, phenolic compounds were analyzed and identified using a metabolomics approach. The combined ultrasound and GABA treatments significantly enhanced the free polyphenols and flavonoids content (P < 0.05) of mung bean sprouts depending on sprouting duration. Besides, a positive correlation (P < 0.05) was found between the polyphenols content and in vitro antioxidant activity of mung bean sprouts. Moreover, a total number of 608 metabolites were detected, and 55 polyphenol compounds were identified, including flavonoids, isoflavones, phenols, and coumarins. Also, the KEGG metabolic pathway analysis revealed 10 metabolic pathways of phenols, including flavonoid, isoflavone, and phenylpropanoid biosynthesis. Powder of 48 h sprouted mung bean released polyphenols during simulated gastric digestion and possessed antioxidant activity.PMID:36738696 | DOI:10.1016/j.ultsonch.2023.106311

Water Res. 2023 Jan 29;232:119678. doi: 10.1016/j.watres.2023.119678. Online ahead of print.ABSTRACTHematite (the most abundant iron oxide polymorph) is widely detected in the water environment and has attracted considerable attention. Natural nanocolloids (Ncs) exist ubiquitously in surface waters and play critical roles in biogeochemical processes. However, the influences of Ncs on the fate and phytotoxicity of hematite remain unknown. In this study, the infrared absorption spectra coupled with two-dimensional correlation spectroscopy analysis reveal that the specific binding interactions between Ncs and hematite primarily occur via hydrophilic effects and π-π interactions with an increase in the Ncs contact time. Moreover, binding with Ncs slightly promoted the aggregation rates of hematite particles in the BG-11 medium. Interestingly, Ncs remarkably mitigate the phytotoxicity (e.g., growth inhibition, oxidative stress, and mitochondrial toxicity) of nanosized and submicrosized hematite particles to Chlorella vulgaris after a 96 h exposure. The integrating metabolomic and transcriptomic analysis reveals that the regulated urea cycle, amino acids, and fatty acid-related metabolites (e.g., urea, serine, glutamate, and hexadecenoic acid) and genes (e.g., ACY1, CysC, and GLA) contribute to persistent phytotoxicity. This study provides new insights into the roles and mechanisms of natural Ncs in regulating the environmental risk of iron oxide minerals in aqueous media.PMID:36738560 | DOI:10.1016/j.watres.2023.119678

Plant Physiol Biochem. 2023 Jan 28;196:302-317. doi: 10.1016/j.plaphy.2023.01.042. Online ahead of print.ABSTRACTPhosphorus (P) is an essential nutrient controlling plant growth and development through the regulation of basic metabolic processes; however, the molecular details of these pathways remain largely unknown. In this study, physiological, transcriptome, and metabolome analysis were compared for two cotton genotypes with different low P tolerance under P starvation and resupply. The results showed that the glucose, fructose, sucrose, and starch contents increased by 18.2%, 20.4%, 20.2%, and 14.3% in the roots and 18.3%, 23.3%, 11.0%, and 13.6% in the shoot of Jimian169 than DES926, respectively. Moreover, the activities of enzymes related to carbon and phosphorus metabolism were higher in the roots and shoots of Jimian169 than DES926. In addition, transcriptome analysis revealed that the number of differentially expressed genes (DEGs) was higher in both roots (830) and shoots (730) under P starvation and the DEGs drastically reduced upon P resupply. The KEGG analysis indicated that DEGs were mainly enriched in phenylpropanoid biosynthesis, carbon metabolism, and photosynthesis. The metabolome analysis showed the enrichment of phenylpropanoid, organic acids and derivatives, and lipids in all the pairs at a given time point. The combined transcriptome and metabolome analysis revealed that carbon metabolism and flavonoid biosynthesis are involved in the P starvation response in cotton. Moreover, co-expression network analysis identified 3 hub genes in the roots and shoots that regulate the pathways involved in the P starvation response. This study provides the foundation for understanding the mechanisms of low P tolerance and the hub genes as a potential target for the development of low P tolerant genotypes.PMID:36738510 | DOI:10.1016/j.plaphy.2023.01.042