PubMed

Vavilovskii Zhurnal Genet Selektsii. 2023 Apr;27(2):16-23. doi: 10.18699/VJGB-23-16.ABSTRACTThe perennial grass cocksfoot (Dactylis glomerata L.) is a valuable early highly nutritious crop used as green fodder in agricultural production. The species is widespread across the Eurasian continent; it is characterized by plasticity and high ecological and geographical variability. The article considers the metabolic profiles of 15 accessions of the cocksfoot from the collection of the N.I. Vavilov Institute of Plant Genetic Resources (VIR). The material is represented by varieties and wild forms of various origin: the European part of the Russian Federation, Norway and Finland. The study was carried out using gas-liquid chromatography coupled with mass spectrometry. The study and comparison of groups of metabolites of cocksfoot accessions of various ecological and geographical origin was carried out. Statistical processing included the calculation of the main parameters of variability, factor analysis of the correlation system (Q- and R-technique), cluster analysis by Ward's method and discriminant analysis. The variability of the quantitative and qualitative composition of the substances identified was revealed. Based on statistical processing of the results obtained, five groups of cocksfoot accessions were identified, differing in the profile of metabolites. One of the groups with a similar composition of metabolites consisted of accessions from one ecological and geographical region; another, of accessions of different origin. Significant differences were noted in the metabolomic profiles of a late-maturing wild cocksfoot accession from the Republic of Karelia at the booting stage from early- and mid-maturing accessions at the heading stage; it contained the largest number of free amino acids and the smallest number of identified primary and secondary metabolites. Wild-growing accession k-44020 from Norway surpassed other wild-growing accessions in the content of free amino acids, sugars and phosphates at the heading stage. Wild-growing accessions differed from breeding varieties with a high content of proline and threonine, indicators of high resistance to lack of moisture and high air temperature.PMID:37063510 | PMC:PMC10097600 | DOI:10.18699/VJGB-23-16

Front Microbiol. 2023 Mar 29;13:1059289. doi: 10.3389/fmicb.2022.1059289. eCollection 2022.ABSTRACTINTRODUCTION: The routine clinical diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely restricted to real-time reverse transcription quantitative PCR (RT-qPCR), and tests that detect SARS-CoV-2 nucleocapsid antigen. Given the diagnostic delay and suboptimal sensitivity associated with these respective methods, alternative diagnostic strategies are needed for acute infection.METHODS: We studied the use of a clinically validated liquid chromatography triple quadrupole method (LC/MS-MS) for detection of amino acids from plasma specimens. We applied machine learning models to distinguish between SARS-CoV-2-positive and negative samples and analyzed amino acid feature importance.RESULTS: A total of 200 samples were tested, including 70 from individuals with COVID-19, and 130 from negative controls. The top performing model overall allowed discrimination between SARS-CoV-2-positive and negative control samples with an area under the receiver operating characteristic curve (AUC) of 0.96 (95%CI 0.91, 1.00), overall sensitivity of 0.99 (95%CI 0.92, 1.00), and specificity of 0.92 (95%CI 0.85, 0.95).DISCUSSION: This approach holds potential as an alternative to existing methods for the rapid and accurate diagnosis of acute SARS-CoV-2 infection.PMID:37063449 | PMC:PMC10092816 | DOI:10.3389/fmicb.2022.1059289

Front Pharmacol. 2023 Mar 31;14:1136317. doi: 10.3389/fphar.2023.1136317. eCollection 2023.ABSTRACTClpP activators ONC201 and related small molecules (TR compounds, Madera Therapeutics), have demonstrated significant anti-cancer potential in vitro and in vivo studies, including clinical trials for refractory solid tumors. Though progress has been made in identifying specific phenotypic outcomes following ClpP activation, the exact mechanism by which ClpP activation leads to broad anti-cancer activity has yet to be fully elucidated. In this study, we utilized a multi-omics approach to identify the ClpP-dependent proteomic, transcriptomic, and metabolomic changes resulting from ONC201 or the TR compound TR-57 in triple-negative breast cancer cells. Applying mass spectrometry-based methods of proteomics and metabolomics, we identified ∼8,000 proteins and 588 metabolites, respectively. From proteomics data, 113 (ONC201) and 191 (TR-57) proteins significantly increased and 572 (ONC201) and 686 (TR-57) proteins significantly decreased in this study. Gene ontological (GO) analysis revealed strong similarities between proteins up- or downregulated by ONC201 or TR-57 treatment. Notably, this included the downregulation of many mitochondrial processes and proteins, including mitochondrial translation and mitochondrial matrix proteins. We performed a large-scale transcriptomic analysis of WT SUM159 cells, identifying ∼7,700 transcripts (746 and 1,100 significantly increasing, 795 and 1,013 significantly decreasing in ONC201 and TR-57 treated cells, respectively). Less than 21% of these genes were affected by these compounds in ClpP null cells. GO analysis of these data demonstrated additional similarity of response to ONC201 and TR-57, including a decrease in transcripts related to the mitochondrial inner membrane and matrix, cell cycle, and nucleus, and increases in other nuclear transcripts and transcripts related to metal-ion binding. Comparison of response between both compounds demonstrated a highly similar response in all -omics datasets. Analysis of metabolites also revealed significant similarities between ONC201 and TR-57 with increases in α-ketoglutarate and 2-hydroxyglutaric acid and decreased ureidosuccinic acid, L-ascorbic acid, L-serine, and cytidine observed following ClpP activation in TNBC cells. Further analysis identified multiple pathways that were specifically impacted by ClpP activation, including ATF4 activation, heme biosynthesis, and the citrulline/urea cycle. In summary the results of our studies demonstrate that ONC201 and TR-57 induce highly similar and broad effects against multiple mitochondrial processes required for cell proliferation.PMID:37063293 | PMC:PMC10103842 | DOI:10.3389/fphar.2023.1136317

Front Pharmacol. 2023 Mar 31;14:1166635. doi: 10.3389/fphar.2023.1166635. eCollection 2023.ABSTRACTThe imbalance of gut microbiota has been confirmed to have a close pathological and physiological correlation with obesity and metabolic syndrome. Ramulus Mori (Sangzhi) Alkaloids (SZ-A) derived from twigs of mulberry was approved by the National Medical Products Administration of China in 2020 for the treatment of type 2 diabetes mellitus. In addition to its hypoglycemic effect, previous studies have confirmed that SZ-A also alleviates high-fat diet-induced obesity and non-alcoholic fatty liver disease and ameliorates obesity-linked adipose tissue metabolism and inflammation, indicating the potential of SZ-A to regulate obesity and metabolic syndrome. However, whether SZ-A can improve obesity and metabolic syndrome by regulating gut microbiota and its metabolism profiles remains unclear. The purpose of this study was to assess the effect of SZ-A on gut microbiota in obese mice and to explore the association among changes in gut microbiota, obesity, and lipid metabolism. The results showed that oral administration of SZ-A could significantly reduce body weight, fat mass, and the level of total cholesterol and low-density lipoprotein in serum in obese mice induced by a high-fat diet. Interestingly, SZ-A also regulated gut microbiota and changed the fecal metabolite composition of obese mice. Compared with the high-fat diet group, the ratio of Firmicutes to Bacteroides changed at the phylum level and the abundance of Bifidobacterium and Akkermansia muciniphila significantly increased at the genus level in the SZ-A group. The gut microbiota of the SZ-A group was reshaped and the relative abundance of microbial genes in bile acid metabolism and fatty acid metabolism were altered, which was consistent with the metabolomics results. Additionally, SZ-A greatly enriched the number of goblet cells and reduced inflammatory colon injury and pro-inflammatory macrophage infiltration induced by a high-fat diet in obese mice. In conclusion, SZ-A can alleviate obesity and metabolic syndrome by improving the gut microbiota and its metabolism profiles of obese mice induced by a high-fat diet.PMID:37063280 | PMC:PMC10102453 | DOI:10.3389/fphar.2023.1166635

Front Pharmacol. 2023 Mar 29;14:1021535. doi: 10.3389/fphar.2023.1021535. eCollection 2023.ABSTRACTBackground: Despite increasing evidence suggesting that pulmonary arterial hypertension (PAH) is a complex disease involving vasoconstriction, thrombosis, inflammation, metabolic dysregulation and vascular proliferation, all the drugs approved for PAH mainly act as vasodilating agents. Since excessive TGF-β signaling is believed to be a critical factor in pulmonary vascular remodeling, we hypothesized that blocking TGFβ-activated kinase 1 (TAK-1), alone or in combination with a vasodilator therapy (i.e., riociguat) could achieve a greater therapeutic benefit. Methods: PAH was induced in male Wistar rats by a single injection of the VEGF receptor antagonist SU5416 (20 mg/kg) followed by exposure to hypoxia (10%O2) for 21 days. Two weeks after SU5416 administration, vehicle, riociguat (3 mg/kg/day), the TAK-1 inhibitor 5Z-7-oxozeaenol (OXO, 3 mg/kg/day), or both drugs combined were administered for 7 days. Metabolic profiling of right ventricle (RV), lung tissues and PA smooth muscle cells (PASMCs) extracts were performed by magnetic resonance spectroscopy, and the differences between groups analyzed by multivariate statistical methods. Results: In vitro, riociguat induced potent vasodilator effects in isolated pulmonary arteries (PA) with negligible antiproliferative effects and metabolic changes in PASMCs. In contrast, 5Z-7-oxozeaenol effectively inhibited the proliferation of PASMCs characterized by a broad metabolic reprogramming but had no acute vasodilator effects. In vivo, treatment with riociguat partially reduced the increase in pulmonary arterial pressure (PAP), RV hypertrophy (RVH), and pulmonary vascular remodeling, attenuated the dysregulation of inosine, glucose, creatine and phosphocholine (PC) in RV and fully abolished the increase in lung IL-1β expression. By contrast, 5Z-7-oxozeaenol significantly reduced pulmonary vascular remodeling and attenuated the metabolic shifts of glucose and PC in RV but had no effects on PAP or RVH. Importantly, combined therapy had an additive effect on pulmonary vascular remodeling and induced a significant metabolic effect over taurine, amino acids, glycolysis, and TCA cycle metabolism via glycine-serine-threonine metabolism. However, it did not improve the effects induced by riociguat alone on pulmonary pressure or RV remodeling. None of the treatments attenuated pulmonary endothelial dysfunction and hyperresponsiveness to serotonin in isolated PA. Conclusion: Our results suggest that inhibition of TAK-1 induces antiproliferative effects and its addition to short-term vasodilator therapy enhances the beneficial effects on pulmonary vascular remodeling and RV metabolic reprogramming in experimental PAH.PMID:37063275 | PMC:PMC10090662 | DOI:10.3389/fphar.2023.1021535

Front Pharmacol. 2023 Mar 30;14:1132857. doi: 10.3389/fphar.2023.1132857. eCollection 2023.ABSTRACTBackground: Baicalein is an active ingredient extracted from the root of S. baicalensis Georgi, which exhibits cardiovascular protection, anti-inflammatory, and anti-microbial properties. Our previous study showed that chronic treatment of Baicalein ameliorated cognitive dysfunction in a mouse model of Alzheimer's disease (AD). However, it remains unknown whether Baicalein ameliorates cognitive deficits in AD mouse models by altering gut microbiota and its metabolites. Methods: Behavioral tests, metagenomic and untargeted metabolomics analyses were used to evaluate the effects of Baicalein on the APP/PS1 mice. Results: Our research showed that treatment of Baicalein for 2 weeks ameliorated cognition and memory in a dose-dependent manner, as indicated by the significant increases in the Discrimination index and Number of crossings and decrease in latency to the previous platform location in 8-month of age APP/PS1 mice in novel object recognition and water maze tests. The metagenomic analysis showed the abundance of the dominant phyla in all groups, including Bacteroidetes (14.59%-67.02%) and Firmicutes (20.19%-61.39%). LEfSe analysis of metagenomics identified three species such as s__Roseburia_sp_1XD42_69, s__Muribaculaceae_bacterium_Isolate_104_HZI, s__Muribaculaceae_bacterium_Isolate_110_HZI as Baicalein-treated potential biomarkers. Metabolite analysis revealed the increment of metabolites, including glutamate, thymine and hexanoyl-CoA. Conclusion: The effects of Baicalein on memory and cognition may relate to the metabolism of nucleotides, lipids and glucose.PMID:37063260 | PMC:PMC10101436 | DOI:10.3389/fphar.2023.1132857

Front Plant Sci. 2023 Mar 29;14:1132881. doi: 10.3389/fpls.2023.1132881. eCollection 2023.ABSTRACTTemperature affects seed germination and seedling growth, which is a critical and complex stage in plant life cycle. However, comprehensive metabolic basis on temperature implicating seed germination and seedling growth remains less known. Here, we applied the high-throughput untargeted metabolomic and advanced shotgun lipidomic approaches to profile the Arabidopsis 182 metabolites and 149 lipids under moderate (22°C, 28°C) and extreme high (34°C, 40°C) temperatures. Our results showed that a typical feature of the metabolism related to organic acids/derivates and amines was obviously enriched at the moderate temperature, which was implicated in many cellular responses towards tricarboxylic acid cycle (TCA), carbohydrates and amino acids metabolism, peptide biosynthesis, phenylpropanoid biosynthesis and indole 3-acetate (IAA) biosynthetic pathway. Whereas, under extreme high temperatures, there was no seed germination, but 148 out of total 182 metabolites were highly enriched, involving in the galactose metabolism, fatty acid degradation, tryptophan/phenylalanine metabolism, and shikimic acid-mediated pathways especially including alkaloids metabolism and glucosinolate/flavone/flavonol biosynthesis. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) also exhibited the gradually increased tendency from moderate temperatures to extreme high temperatures; whereas phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylglycerol (PG), monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG) and sulfoquinovosyldiacylglycerol (SQDG) were contrary to decrease. Another typical feature of the distinguished metabolites between 22°C and 28°C, the TCA, disaccharides, nucleotides, polypeptides, SQDG and the biosynthesis of fatty acids and glucobrassicin-mediated IAA were obviously decreased at 28°C, while amino acids, trisaccharides, PE, PC, PA, PS, MGDG, DGDG and diacylglycerol (DAG) preferred to enrich at 28°C, which characterized the alteration of metabolites and lipids during fast seedling growth. Taking together, our results provided the comprehensive metabolites phenotyping, revealed the characteristics of metabolites necessary for seed germination and/or seedling growth under different temperatures, and provided insights into the different metabolic regulation of metabolites and lipid homeostasis for seed germination and seedling growth.PMID:37063208 | PMC:PMC10090499 | DOI:10.3389/fpls.2023.1132881

Front Plant Sci. 2023 Mar 29;14:1138563. doi: 10.3389/fpls.2023.1138563. eCollection 2023.ABSTRACTIn the context of global food crisis, applying the phytohormone-brassinosteroids (BRs) in combination with the fungicide-pyraclostrobin (Pyr) was beneficial for plant quality and productivity in several field trials. However, in addition to the benefits of disease control due to the innate fungicidal activity of Pyr, it remains to be understood whether the coapplication of BL+ Pyr exerts additional growth-promoting effects. For this purpose, the effects of BL treatment, Pyr treatment, and BL+ Pyr treatment in Arabidopsis thaliana were compared. The results showed that the yield increased at a rate of 25.6% in the BL+Pyr group and 9.7% in the BL group, but no significant change was observed in the Pyr group. Furthermore, the BL+Pyr treatment increased the fresh weight of both the leaves and the inflorescences. In contrast, the Pyr and BL treatments only increased the fresh weight of leaves and inflorescences, respectively. Additionally, the BL + Pyr treatment increased the Pn, Gs, Tr, Vc, max, Jmax, VTPU, ETR, Fv'/Fm', ΦPSII, Rd, AYE and Rubisco enzyme activity by 26%, 38%, 40%, 16%, 19%, 15%, 9%, 10%, 17%, 179%, 18% and 32%, respectively. While, these paraments did not change significantly by the BL or Pyr treatments. Treatment with BL + Pyr and Pyr, rather than BL, improved the chlorophyll a and chlorophyll b contents by upregulating genes related to chlorophyll biosynthesis and downregulating genes related to chlorophyll degradation. Additionally, according to transcriptomic and metabolomic analysis, the BL+ Pyr treatment outperformed the individual BL or Pyr treatments in activating the transcription of genes involved in photosynthesis and increasing sugar accumulation. Our results first validated that the combined usage of BL and Pyr exerted striking synergistic effects on enhancing plant biomass and yield by increasing photosynthetic efficiency. These results might provide new understanding for the agricultural effects by the co-application of BL and Pyr, and it might stimulate the efforts to develop new environment-friendly replacement for Pyr to minimize the ecotoxicology of Pyr.PMID:37063198 | PMC:PMC10090558 | DOI:10.3389/fpls.2023.1138563

Front Plant Sci. 2023 Mar 31;14:1137299. doi: 10.3389/fpls.2023.1137299. eCollection 2023.ABSTRACTRice is a crucial food crop worldwide, but its yield and quality are significantly affected by Meloidogyne graminicola is a root knot nematode. No rice variety is entirely immune to this nematode disease in agricultural production. Thus, the fundamental strategy to combat this disease is to utilize rice resistance genes. In this study, we conducted transcriptome and metabolome analyses on two rice varieties, ZH11 and IR64. The results indicated that ZH11 showed stronger resistance than IR64. Transcriptome analysis revealed that the change in gene expression in ZH11 was more substantial than that in IR64 after M. graminicola infection. Moreover, GO and KEGG enrichment analysis of the upregulated genes in ZH11 showed that they were primarily associated with rice cell wall construction, carbohydrate metabolism, and secondary metabolism relating to disease resistance, which effectively enhanced the resistance of ZH11. However, in rice IR64, the number of genes enriched in disease resistance pathways was significantly lower than that in ZH11, which further explained susceptibility to IR64. Metabolome analysis revealed that the metabolites detected in ZH11 were enriched in flavonoid metabolism and the pentose phosphate pathway, compared to IR64, after M. graminicola infection. The comprehensive analysis of transcriptome and metabolome data indicated that flavonoid metabolism plays a crucial role in rice resistance to M. graminicola infection. The content of kaempferin, apigenin, and quercetin in ZH11 significantly increased after M. graminicola infection, and the expression of genes involved in the synthetic pathway of flavonoids also significantly increased in ZH11. Our study provides theoretical guidance for the precise analysis of rice resistance and disease resistance breeding in further research.PMID:37063174 | PMC:PMC10102519 | DOI:10.3389/fpls.2023.1137299

Brain. 2023 Apr 17:awad037. doi: 10.1093/brain/awad037. Online ahead of print.ABSTRACTReactive astrogliosis is a hallmark of Alzheimer's disease (AD). However, a clinically validated neuroimaging probe to visualize the reactive astrogliosis is yet to be discovered. Here, we show that PET imaging with 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG) functionally visualizes the reactive astrocyte-mediated neuronal hypometabolism in the brains with neuroinflammation and AD. To investigate the alterations of acetate and glucose metabolism in the diseased brains and their impact on the AD pathology, we adopted multifaceted approaches including microPET imaging, autoradiography, immunohistochemistry, metabolomics, and electrophysiology. Two AD rodent models, APP/PS1 and 5xFAD transgenic mice, one adenovirus-induced rat model of reactive astrogliosis, and post-mortem human brain tissues were used in this study. We further curated a proof-of-concept human study that included 11C-acetate and 18F-FDG PET imaging analyses along with neuropsychological assessments from 11 AD patients and 10 healthy control subjects. We demonstrate that reactive astrocytes excessively absorb acetate through elevated monocarboxylate transporter-1 (MCT1) in rodent models of both reactive astrogliosis and AD. The elevated acetate uptake is associated with reactive astrogliosis and boosts the aberrant astrocytic GABA synthesis when amyloid-β is present. The excessive astrocytic GABA subsequently suppresses neuronal activity, which could lead to glucose uptake through decreased glucose transporter-3 in the diseased brains. We further demonstrate that 11C-acetate uptake was significantly increased in the entorhinal cortex, hippocampus and temporo-parietal neocortex of the AD patients compared to the healthy controls, while 18F-FDG uptake was significantly reduced in the same regions. Additionally, we discover a strong correlation between the patients' cognitive function and the PET signals of both 11C-acetate and 18F-FDG. We demonstrate the potential value of PET imaging with 11C-acetate and 18F-FDG by visualizing reactive astrogliosis and the associated neuronal glucose hypometablosim for AD patients. Our findings further suggest that the acetate-boosted reactive astrocyte-neuron interaction could contribute to the cognitive decline in AD.PMID:37062541 | DOI:10.1093/brain/awad037

Biochimie. 2023 Apr 14:S0300-9084(23)00086-X. doi: 10.1016/j.biochi.2023.04.009. Online ahead of print.ABSTRACTType 2 diabetes mellitus (DM) poses a major burden for the treatment and control of tuberculosis (TB). Characterization of the underlying metabolic perturbations in DM patients with TB infection would yield insights into the pathophysiology of TB-DM, thus potentially leading to improvements in TB treatment. In this study, a multimodal metabolomics and lipidomics workflow was applied to investigate plasma metabolic profiles of patients with TB and TB-DM. Significantly different biological processes and biomarkers in TB-DM vs. TB were identified using a data-driven, knowledge-based framework. Changes in metabolic and signaling pathways related to carbohydrate and amino acid metabolism were mainly captured by amide HILIC column metabolomics analysis, while perturbations in lipid metabolism were identified by the C18 metabolomics and lipidomics analysis. Compared to TB, TB-DM exhibited elevated levels of bile acids and molecules related to carbohydrate metabolism, as well as the depletion of glutamine, retinol, lysophosphatidylcholine, and phosphatidylcholine. Moreover, arachidonic acid metabolism was determined as a potential important factor in the interaction between TB and DM pathophysiology. In a correlation network of the significantly altered molecules, among the central nodes, chenodeoxycholic acid was robustly associated with TB and DM. Fatty acid (22:4) was a component of all significant modules. In conclusion, the integration of multimodal metabolomics and lipidomics provides a thorough picture of the metabolic changes associated with TB-DM. The results obtained from this comprehensive profiling of TB patients with DM advance the current understanding of DM comorbidity in TB infection and contribute to the development of more effective treatment.PMID:37062470 | DOI:10.1016/j.biochi.2023.04.009

Ecotoxicol Environ Saf. 2023 Apr 14;256:114906. doi: 10.1016/j.ecoenv.2023.114906. Online ahead of print.ABSTRACTWith the detection of nano-plastics (NPs) in daily essentials and drinking water, the potential harm of NPs to human health has become the focus of global attention. Studies have shown that long term exposure to NPs can lead to disorders of glucose and lipid metabolism in organisms, while the effects of short term exposure are rarely reported. Moreover, environmental factors cause the aging of NPs, and it is unclear whether this has an effect on their toxicity. In this study, we use 100 nm polystyrene (PS) NPs and ultraviolet (UV) aging PS (aPS) NPs to gavage mice for 7 days at an exposure dose of 50 mg/kg/day. To evaluate the effects of exposure on mice hepatic glucose lipid metabolism, we performed blood biochemical, pathological and metabolomic analyses. The results showed that exposure to PS NPs and aPS NPs increased serum glucose, disrupted serum lipoprotein levels, and up-regulated the expression levels of phosphatidylinositol 3-kinase (PI3K)/ phosphoprotein kinase B (p-AKT)/Glucose transporter 4 (GLUT4) proteins in the glucose metabolism pathway. The expression levels of key proteins sterol regulatory element binding protein-1 (SREBP-1)/peroxisome proliferator-activated receptor-γ (PPARγ)/adipose triglyceride lipase (ATGL) in the lipid metabolism signaling pathway were significantly increased. These findings suggest that short term exposure to PS NPs and aPS NPs induces glycolipid metabolism disturbance in mice, which may subsequently awaken the mice to self-regulate the serum levels of various lipoproteins and the expression of related key proteins. Compared with PS NPs, the aPS NPs interfered more strongly with glucose metabolism, and the corresponding self-regulation in mice was also more obvious. These findings not only provide a basis for environmental factors to increase the health risk of NPs but also provided a reference for the selection of test substances for further studies on the toxicity of NPs.PMID:37062265 | DOI:10.1016/j.ecoenv.2023.114906

Ecotoxicol Environ Saf. 2023 Apr 14;256:114913. doi: 10.1016/j.ecoenv.2023.114913. Online ahead of print.ABSTRACTThe rapid development of nanotechnology has aroused considerable attentions toward understanding the effects of engineered nanomaterials (ENMs) on the propagation of antibiotic resistance. Molybdenum disulfide (MoS2) is an extensively used ENM and poses potential risks associated with environmental exposure; nevertheless, the role of MoS2 toward antibiotic resistance genes (ARGs) transfer remains largely unknown. Herein, it was discovered that MoS2 nanosheets accelerated the horizontal transfer of RP4 plasmid across Escherichia coli in a dose-dependent manner (0.5-10 mg/L), with the maximum transfer frequency 2.07-fold higher than that of the control. Integration of physiological, transcriptomics, and metabolomics analyses demonstrated that SOS response in bacteria was activated by MoS2 due to the elevation of oxidative damage, accompanied by cell membrane permeabilization. MoS2 promoted bacterial adhesion and intercellular contact via stimulating the secretion of extracellular polysaccharides. The ATP levels were maximally increased by 305.7 % upon exposure to MoS2, and the expression of plasmid transfer genes was up-regulated, contributing to the accelerated plasmid conjugation and increased ARG abundance in soil. Our findings highlight the roles of emerging ENMs (e.g., MoS2) in ARGs dissemination, which is significant for the safe applications and risk management of ENMs under the development scenarios of nanotechnology.PMID:37062264 | DOI:10.1016/j.ecoenv.2023.114913

Biomed Pharmacother. 2023 Apr 14;162:114703. doi: 10.1016/j.biopha.2023.114703. Online ahead of print.ABSTRACTBACKGROUND: Phenolic compounds have been associated with protective effects against type-2 diabetes (T2D). We used a metabolomics approach to determine urinary phenolic metabolites associated with T2D and fasting plasma glucose.METHODS: This case-control study within the PREDIMED trial included 200 participants at high cardiovascular risk, 102 of whom were diagnosed with T2D. A panel of urinary phenolic compounds were analysed using a novel method based on liquid chromatography coupled to mass spectrometry. Multivariate statistics and adjusted logistic regressions were applied to determine the most discriminant compounds and their association with T2D. The relationship between the discriminant phenolic compounds and plasma glucose was assessed using multivariable linear regressions.RESULTS: A total of 41 phenolic compounds were modeled in the orthogonal projection to latent structures discriminant analysis, and after applying adjusted logistic regressions two were selected as discriminant: dihydrocaffeic acid (OR = 0.22 (CI 95 %: 0.09; 0.52) per 1-SD, p-value = 0.021) and genistein diglucuronide (OR = 0.72 (CI 95%: 0.59; 0.88) per 1-SD, p-value = 0.021). Both metabolites were associated with a lower risk of suffering from T2D, but only dihydrocaffeic acid was inversely associated with plasma glucose (β = -17.12 (95 % CI: -29.92; -4.32) mg/dL per 1-SD, p-value = 0.009).CONCLUSIONS: A novel method using a metabolomics approach was developed to analyse a panel of urinary phenolic compounds for potential associations with T2D, and two metabolites, dihydrocaffeic acid and genistein diglucuronide, were found to be associated with a lower risk of this condition.PMID:37062219 | DOI:10.1016/j.biopha.2023.114703

J Chromatogr A. 2023 Apr 9;1697:463985. doi: 10.1016/j.chroma.2023.463985. Online ahead of print.ABSTRACTMetabolomics is becoming increasingly popular in livestock research, but no single analytical method can cover the entire metabolome. As such, we compared similar and complementary chromatographic methods with respect to analyte coverage and chromatographic properties of mammalian metabolites. We investigated 354 biologically relevant primary metabolites from 19 compound classes including amino acids, bile acids, biogenic amines, carboxylic acids, lipids, nucleotides and sugars. A total of 2063 selected reaction monitoring transitions were optimized on a triple quadrupole mass spectrometer. We then determined the retention profiles and peak parameters of our compounds using an anion exchange chromatography (AIC), three reversed-phase (RP) and three hydrophilic interaction liquid chromatography (HILIC) methods. On average, HILIC methods covered 54% of all metabolites with retention factors >1, while average RP coverage was 41%. In contrast to RP, HILIC methods could also retain polar metabolites such as amino acids and biogenic amines. Carboxylic acids, nucleotides, and sugar related compounds were best separated by AIC or zwitterionic pHILIC with alkaline eluents. Combining two complementary HILIC and RP methods increased the library coverage to 92%. By further including important short chain fatty acids, a combination of HILIC, RP and AIC methods achieved a coverage of 97%. The resulting dataset of LC and MS/MS parameters will facilitate the development of tailor-made quantitative targeted LC-MS/MS methods to investigate the mammalian metabolome.PMID:37062154 | DOI:10.1016/j.chroma.2023.463985

Phytomedicine. 2023 Apr 10;114:154813. doi: 10.1016/j.phymed.2023.154813. Online ahead of print.ABSTRACTBACKGROUND: Tripterygium glycoside tablets (TGT) is the most common preparation from Tripterygium wilfordii Hook F, which is widely used in clinical for treating rheumatoid arthritis (RA) and other autoimmune diseases. However, its serious reproductive toxicity limits its application.PURPOSE: This study aimed to elucidate the toxic effects of TGT on the reproductive system of male RA rats and its potential toxic components and mechanism.METHODS: Collagen-induced arthritis (CIA) rat model was established, and TGT suspension was given at low, medium, and high doses. Gonadal index, pathological changes, and the number of spermatogenic cells were used to evaluate the toxic effects of TGT on the reproductive system. Non-targeted metabolomics of testicular tissue was conducted by UHPLC-QTOF/MS. Combined with network toxicology, the key targets of TGT-induced reproductive toxicity were screened and RT-qPCR was used to validation. In vitro toxicity of 19 components of TGT was evaluated using TM3 and TM4 cell lines. Molecular docking was used to predict the interaction between toxic components and key targets.RESULTS: TGT reduced testicular and epididymis weight. Pathology analysis showed a lot of deformed and atrophic spermatogenic tubules. The number of spermatogenic cells decreased significantly (P<0.0001). A total of 58 different metabolites including platelet-activating factor (PAF), lysophosphatidylcholine (Lyso PC), phosphatidylinositol (PI), glutathione (GSH), and adenosine monophosphate (AMP) were identified by testicular metabolomics. Glycerophospholipid metabolism, ether lipid metabolism, and glutathione metabolism were key pathways responsible for the reproductive toxicity of TGT. Ten key reproductive toxicity targets were screened by network toxicology. The cytotoxicity test showed that triptolide, triptonide, celastrol, and demethylzeylasteral could significantly reduce the viability of TM3 and TM4 cells. Alkaloids had no apparent toxic effects. Molecular docking showed that the four toxic components had a good affinity with 10 key targets. All binding energies were less than -7 kcal/mol. The RT-qPCR results showed the Cyp19a1 level was significantly up-regulated. Pik3ca and Pik3cg levels were significantly down-regulated.CONCLUSION: Through testicular metabolomics, we found that TGT may cause reproductive toxicity through CYP19A1, PIK3CA, and PIK3CG three target, which was preliminarily revealed. This study laid the foundation for elucidating the toxicity mechanism of TGT and evaluating its safety and quality.PMID:37062137 | DOI:10.1016/j.phymed.2023.154813

J Hazard Mater. 2023 Apr 13;453:131411. doi: 10.1016/j.jhazmat.2023.131411. Online ahead of print.ABSTRACTEngineered nanoparticles (ENPs) can resist heavy metal toxicity in plants, but their coexposure still exhibits toxicity to plants compared to plants without exposure to ENPs and heavy metals. There have been few studies on the toxic mechanism of nano TiO2-heavy metal coexposure and the effect mechanism of nano TiO2 in plants. Thus, transcriptomics and metabolomics were used to study the toxic mechanism of rutile nano TiO2 or TiO2-Cd (rutile nano TiO2 and CdCl2 mixture) on rice (Oryza sativa L.). After 40 days of exposure, the plant height and root dry weight of rice were significantly decreased in the nano TiO2-Cd group compared to the blank group (nano TiO2 and CdCl2 free). After Cd treatment, 423 differentially expressed genes (DEGs) and 16 differential metabolites were identified. Nano TiO2 exposure induced significant regulation of 299 DEGs and 6 metabolites. After nano TiO2-Cd coexposure, 1660 DEGs and 181 differential metabolites were identified. Notably, the EDGs (e.g., chalcone isomerase and hydroxycinnamoyl transferase) and differential metabolites (e.g., chrysin and galangin) demonstrated the disruption of flavonoid biosynthesis in Cd-treated rice. After rice was exposed to nano TiO2, the DEGs were related to ribosome, whereas the differential metabolites were associated with pyruvate metabolism and valine, leucine, and isoleucine biosynthesis. Furthermore, 14 DEGs (e.g., asparaginyl-tRNA synthetase and methionyl-tRNA formyltransferase) involved in aminoacyl-tRNA biosynthetic pathways were significantly upregulated in rice treated with nano TiO2-Cd, in line with the changes in related metabolites (e.g., L-asparagine and 10-formyltetrahydrofolate). Our results show that it is necessary to pay close attention to the toxicity of nano TiO2-Cd coexposure in paddy ecosystems and use ENPs with caution to combat the phytotoxicity of heavy metals.PMID:37062093 | DOI:10.1016/j.jhazmat.2023.131411

Food Chem. 2023 Apr 11;420:136134. doi: 10.1016/j.foodchem.2023.136134. Online ahead of print.ABSTRACTSesame is a valuable crop recognized for its rich composition and myriad of health benefits. The current study attempts to characterize sesame seeds' metabolome in relation to geographical origins i.e., Egypt, Sudan, Nigeria, in addition to samples from paste production lines along its different steps. UPLC-PDA-ESI-qTOF-MS was employed for untargeted profiling and in correlation to antioxidant capacity using DPPH, FRAP and β-carotene-lineolate assays. 139 Peaks were identified, including novel phospholipids and catechol lignan in sesame. Furthermore, discriminatory markers belonging to coumarins, lignans, phenolic and organic acids were revealed among raw accessions, whereas roasted and unroasted seeds were distinguished by sugar, peptide/amino acid, and organic acid contents. Negative processing impact was observed in the loss of lignans during dehulling and decreased antioxidant capacity in sesame paste. However, malic acid in roasted seeds and verbascoside in Nigerian sesame could account for their improved antioxidant effects as revealed using chemometrics.PMID:37062083 | DOI:10.1016/j.foodchem.2023.136134

J Agric Food Chem. 2023 Apr 16. doi: 10.1021/acs.jafc.2c08486. Online ahead of print.ABSTRACTAlternaria brassicicola (Ab) can cause a major yield and quality-limiting disease of Brassica oleracea called black spot, and the genetic resources conferring complete resistance against Ab have not been identified to date. Here, comparative transcriptome and targeted metabolome analysis were performed utilizing a newly identified resistant (R) line and a broccoli susceptible (S) line at 6, 24, and 72 h post-inoculation (hpi). Kyoto encyclopedia of genes and genomes pathway enrichment and the weighted gene co-expression network analyses showed that the phenylpropanoid pathway regulates the resistance to Ab in broccoli. One metabolite, cinnamic acid, was significantly upregulated in the Ab_inoculated R line compared with the mock treatment but no significant difference in the S line, indicating that the cinnamic acid may cause the resistance difference between R and S lines. Our results also revealed that three indolic glucosinolates of I3G, 4MI3G, and 1MI3G were significantly increased in the Ab_inoculated R line compared with the mock treatment, and some related genes were differentially expressed between the R and S lines. These results provided new insights into the mechanism of Ab defense in B. oleracea and have laid a theoretical foundation for effectively utilizing resistant germplasm resources in broccoli breeding.PMID:37061924 | DOI:10.1021/acs.jafc.2c08486

Cytotherapy. 2023 Apr 14:S1465-3249(23)00067-1. doi: 10.1016/j.jcyt.2023.03.004. Online ahead of print.ABSTRACTBACKGROUND AIMS: A large part of mesenchymal stromal cell (MSC) regenerative and immunomodulatory action is mediated by paracrine signaling. Hence, an increasing body of evidence acknowledges the potential of MSC secretome in a variety of preclinical and clinical scenarios. Mid-term serum deprivation is a common approach in the pipeline of MSC secretome production. Nevertheless, up to now, little is known about the impact of this procedure on the metabolic status of donor cells.METHODS: Here, through untargeted differential metabolomics, we revealed an impairment of mitochondrial metabolism in adipose-derived MSCs exposed for 72 h to serum deprivation.RESULTS: This evidence was further confirmed by the significant accumulation of reactive oxygen species and the reduction of succinate dehydrogenase activity. Probably as a repair mechanism, an upregulation of mitochondrial superoxide dismutase was also induced.CONCLUSIONS: Of note, the analysis of mitochondrial functionality indicated that, despite a significant reduction of basal respiration and ATP production, serum-starved MSCs still responded to changes in energy demand. This metabolic phenotype correlates with the obtained evidence of mitochondrial elongation and branching upon starvation.PMID:37061899 | DOI:10.1016/j.jcyt.2023.03.004