Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Small High-Density Lipoprotein and Omega-3 Fatty Acid Intake Differentiates Japanese and Japanese-Americans: The INTERLIPID Study

Thu, 03/11/2022 - 11:00
J Atheroscler Thromb. 2022 Nov 3. doi: 10.5551/jat.63762. Online ahead of print.ABSTRACTAIM: To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii, in the absence of possible genetic confounders, and cross-sectionally examine the associated modifiable lifestyle factors.METHODS: Overall, 1,241 (aged 40-59 years) Japanese living in Japan and Japanese-Americans in Hawaii were included. We quantified 130 serum lipid profiles (VLDL 1-5, IDL, LDL 1-6, high-density lipoprotein [HDL] 1-4, and their subfractions) using Bruker's 1 H-nuclear magnetic resonance spectrometer for the primary outcome. Modifiable lifestyle factors included body mass index (BMI), physical activity, alcohol and smoking habits, and 70 nutrient parameters. We evaluated the different lipids between the groups using partial least squares-discriminant analysis and association between extracted lipids and lifestyle factors using multivariable linear regression analysis.RESULTS: Concentrations of HDL4, HDL with the smallest particle size, were lower in Japanese than in Japanese-Americans of both sexes. Higher fish-derived omega-3 fatty acid intake and lower alcohol intake were associated with lower HDL4 concentrations. A 1% higher kcal intake of total omega-3 fatty acids was associated with a 9.8- mg/dL lower HDL4. Fish-derived docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid intake were inversely associated with HDL4 concentration. There was no relationship between country, sex, age, or BMI.CONCLUSIONS: Japanese and Japanese-Americans can be differentiated based on HDL4 concentration. High fish intake among the Japanese may contribute to their lower HDL4 concentration. Thus, HDL particle size may be an important clinical marker for coronary artery diseases or a fish consumption biomarker.PMID:36328528 | DOI:10.5551/jat.63762

Seeking an Important Role on Metabolomics-Effects of β-Estradiol on Lipoprotein Metabolism in Mammary Tumors

Thu, 03/11/2022 - 11:00
Yakugaku Zasshi. 2022;142(11):1191-1199. doi: 10.1248/yakushi.22-00098.ABSTRACTThe role of β-estradiol (E2) in lipoprotein metabolism in mammary tumors remains unknown. Therefore the effect of E2 on secretion of lipoprotein lipase (LPL) from mouse mammary tumor FM3A cells was examined. The E2-treated FM3A cells increased active LPL secretion in a time- and dose-dependent manner. The activity of mitogen-activated protein kinase (MAPK) was elevated in the tumor cells treated with E2, and E2-stimulated secretion of LPL was suppressed by the MAPK kinase 1/2 inhibitor PD98059, extracellular signal-regulated kinase (ERK) 1/2 inhibitor FR180204, p38 MAPK inhibitor SB202190, and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. In addition, the effect of E2 on active LPL secretion was markedly suppressed by an inhibitor of mammalian target of rapamycin complex (mTORC) 1 and 2, KU0063794, but not by the mTORC1 inhibitor, rapamycin. Furthermore, a small interfering RNA (siRNA)-mediated decrease in the expression of rapamycin-insensitive companion of mTOR (Rictor), a pivotal component of mTORC2, suppressed the secretion of LPL by E2. Stimulatory secretion of LPL by E2 from the tumor cells is closely associated with activation of mTORC2 rather than mTORC1, possibly via the MAPK cascade.PMID:36328449 | DOI:10.1248/yakushi.22-00098

Proteomics reveals antiviral host response and NETosis during acute COVID-19 in high-risk patients

Thu, 03/11/2022 - 11:00
Biochim Biophys Acta Mol Basis Dis. 2022 Oct 31:166592. doi: 10.1016/j.bbadis.2022.166592. Online ahead of print.ABSTRACTSARS-CoV-2 remains an acute threat to human health, endangering hospital capacities worldwide. Previous studies have aimed at informing pathophysiologic understanding and identification of disease indicators for risk assessment, monitoring, and therapeutic guidance. While findings start to emerge in the general population, observations in high-risk patients with complex pre-existing conditions are limited. We addressed the gap of existing knowledge with regard to a differentiated understanding of disease dynamics in SARS-CoV-2 infection while specifically considering disease stage and severity. We biomedically characterized quantitative proteomics in a hospitalized cohort of COVID-19 patients with mild to severe symptoms suffering from different (co)-morbidities in comparison to both healthy individuals and patients with non-COVID related inflammation. Deep clinical phenotyping enabled the identification of individual disease trajectories in COVID-19 patients. By the use of the individualized disease phase assignment, proteome analysis revealed a severity dependent general type-2-centered host response side-by-side with a disease specific antiviral immune reaction in early disease. The identification of phenomena such as neutrophil extracellular trap (NET) formation and a pro-coagulatory response characterizing severe disease was successfully validated in a second cohort. Together with the regulation of proteins related to SARS-CoV-2-specific symptoms identified by proteome screening, we not only confirmed results from previous studies but provide novel information for biomarker and therapy development.PMID:36328146 | PMC:PMC9622026 | DOI:10.1016/j.bbadis.2022.166592

Neuroimaging uncovers neuronal and metabolic changes in pain modulatory brain areas in a rat model of chemotherapy-induced neuropathy - MEMRI and ex vivo spectroscopy studies

Thu, 03/11/2022 - 11:00
Brain Res Bull. 2022 Oct 31:S0361-9230(22)00296-9. doi: 10.1016/j.brainresbull.2022.10.018. Online ahead of print.ABSTRACTChemotherapy-induced neuropathy (CIN) is one of the most common complications of cancer treatment with sensory dysfunctions which frequently include pain. The mechanisms underlying pain during CIN are starting to be uncovered. Neuroimaging allows the identification of brain circuitry involved in pain processing and modulation and has recently been used to unravel the disruptions of that circuitry by neuropathic pain. The present study evaluates the effects of paclitaxel, a cytostatic drug frequently used in cancer treatment, at the neuronal function in the anterior cingulate cortex (ACC), hypothalamus and periaqueductal grey (PAG) using manganese-enhanced magnetic resonance imaging (MEMRI). We also studied the metabolic profile at the prefrontal cortex (PFC) and hypothalamus using ex vivo spectroscopy. Wistar male rats were intraperitoneal injected with paclitaxel or vehicle solution (DMSO). The evaluation of mechanical sensitivity using von Frey test at baseline (BL), 21 (T21), 28 (T28), 49 (T49) and 56 days (T56) after CIN induction showed that paclitaxel-injected rats presented mechanical hypersensitivity from T21 until T56 after CIN induction. The evaluation of the locomotor activity and exploratory behaviors using open-field test at T28 and T56 after the first injection of paclitaxel revealed that paclitaxel-injected rats walked higher distance with higher velocity at late point of CIN accompanied with a sustained exhibition of anxiety-like behaviors. Imaging studies performed using MEMRI at T28 and T56 showed that paclitaxel treatment increased the neuronal activation in the hypothalamus and PAG at T56 in comparison with the control group. The analysis of data from ex vivo spectroscopy demonstrated that at T28 paclitaxel-injected rats presented an increase of N-acetyl aspartate (NAA) levels in the PFC and an increase of NAA and decrease of lactate (Lac) concentration in the hypothalamus compared to the control group. Furthermore, at T56 the paclitaxel-injected rats presented lower NAA and higher taurine (Tau) levels in the PFC. Together, MEMRI and metabolomic data indicate that CIN is associated with neuroplastic changes in brain areas involved in pain modulation and suggests that other events involving glial cells may be happening.PMID:36328144 | DOI:10.1016/j.brainresbull.2022.10.018

Effects of ultrasound-assisted thawing on lamb meat quality and oxidative stability during refrigerated storage using non-targeted metabolomics

Thu, 03/11/2022 - 11:00
Ultrason Sonochem. 2022 Oct 23;90:106211. doi: 10.1016/j.ultsonch.2022.106211. Online ahead of print.ABSTRACTThe aim of this study was to evaluate the changes of ultrasound-assisted thawing on lamb meat quality and differential metabolite profiles during refrigerated storage. Compared with flow water thawing (FW), pH, a*, C*, and sulfhydryl content of lamb were significantly increased, while L*, drip loss and cooking loss were significantly decreased after ultrasound-assisted thawing (UT). On day 1 (UT1 and FW1) and day 7 (UT7 and FW7) in the UT and FW groups, principal component analysis explained 42.22% and 39.25% of the total variance. In this study, 44 (UT1 and FW1) and 47 (UT7 and FW7) differentially expressed metabolites were identified, including amino acids, carbohydrates and their conjugates, nucleic acids, carbonyl compounds and others. The results of this study provide data to clarify the differences between UT and FW, and lay a foundation for the application of ultrasound-assisted thawing in the meat industry.PMID:36327923 | PMC:PMC9619372 | DOI:10.1016/j.ultsonch.2022.106211

Metabolomics and proteomics reveal the toxicological mechanisms of florfenicol stress on wheat (Triticum aestivum L.) seedlings

Thu, 03/11/2022 - 11:00
J Hazard Mater. 2022 Oct 31;443(Pt B):130264. doi: 10.1016/j.jhazmat.2022.130264. Online ahead of print.ABSTRACTAlthough the ecological impacts of antibiotics have received attention worldwide, research on the toxicity of florfenicol is still limited. We conducted a metabolomic and proteomic study on wheat (Triticum aestivum L.) seedlings to reveal the toxicological mechanism of florfenicol. The growth of the wheat seedlings was found to be inhibited by florfenicol. Antioxidant enzyme activities (superoxide dismutase, peroxidase and catalase), malondialdehyde content and membrane permeability increased with increasing florfenicol concentration. The contents of chlorophyll and chlorophyll synthesis precursor substances (Proto IX, Mg-proto IX and Pchlide), photosynthetic and respiration rates, and chlorophyll fluorescence parameters decreased, indicating that photosynthesis was inhibited. The ultrastructure of chloroplasts was destroyed, as evidenced by the blurred membrane surface, irregular grana arrangement, irregular thylakoid lamella structure, and increased plastoglobuli number. Proteome analysis revealed that up-regulated proteins were highly involved in protein refolding, translation, oxidation-reduction, tricarboxylic acid cycle (TCA cycle), reactive oxygen species metabolic process, cellular oxidant detoxification, and response to oxidative stress. The down-regulated proteins were mainly enriched in photosynthesis-related pathways. In the metabolome analysis, the content of most of the metabolites in wheat leaves, such as carbohydrates and amino acids increased significantly (p < 0.05). Combined pathway analysis showed that florfenicol stress stimulated the TCA cycle pathway and downregulated the photosynthesis pathway.PMID:36327828 | DOI:10.1016/j.jhazmat.2022.130264

Based on 16 S rRNA sequencing and metabonomics to reveal the new mechanism of aluminum potassium sulfate induced inflammation and abnormal lipid metabolism in mice

Thu, 03/11/2022 - 11:00
Ecotoxicol Environ Saf. 2022 Oct 31;247:114214. doi: 10.1016/j.ecoenv.2022.114214. Online ahead of print.ABSTRACTMore and more discoveries have been made about the chronic toxic effects of aluminum, but the specific mechanism of action remains unclear. In this study, we explored the perturbation of aluminum on intestinal microflora and its effects on host and microbial metabolites through a more realistic nutrient absorption model. The microorganisms Turicibacter, Lactobacillus murinus, Lactobacillus_reuteri and Bifidobacterium pseudolongum may be the main targets of the aluminum affecting microbiota. Lysine, proline, putrescine, serotonin and cholesterol may be important metabolites affected by aluminum ions after the interference of intestinal flora composition, leading to abnormal metabolism pathways of amino acids and lipids in the body, and thus promoting inflammation and lesion. The possible mechanisms of aluminum action on the body: (1) Affecting immune cell response, ROS generation and production of a series of pro-inflammatory factors to promote inflammation; (2) Through the disturbance of intestinal microbiota composition structure, change the abundance of metabolites, and then affect amino acid metabolism, lipid metabolism pathways. The joint analysis of multiple omics showed significant difference in microbiome abundance and metabolomics expression between high dose group and the control group.PMID:36327783 | DOI:10.1016/j.ecoenv.2022.114214

Toxic effects of triphenyltin on the silkworm Bombyx mori as a lepidopterous insect model

Thu, 03/11/2022 - 11:00
Ecotoxicol Environ Saf. 2022 Oct 31;247:114245. doi: 10.1016/j.ecoenv.2022.114245. Online ahead of print.ABSTRACTTriphenyltin (TPT) is a widely used reagent in various industries and agriculture, but is also known to accumulate in natural ecosystems and animal tissues. Hence, the aim of this study was to comprehensively assess the toxicity of TPT in the silkworm Bombyx mori as a model insect. The results showed that TPT exposure for the entire 5th instar larval stage significantly reduced the weight of silkworm pupa and inhibited development of the silkworm midgut. Following exposure to 2 μg/kg of TPT for 4 days, differentially expressed genes in midgut were associated with enriched pathways involved in the metabolism of carbohydrates, lipids, and amino acids, as determined by RNA sequencing. Furthermore, the metabolic profiles of the intestinal content of silkworms exposed to 2 μg/kg of TPT for 4 days were markedly altered and differential metabolites produced by metabolism of carbohydrates, lipids, and amino acids were enriched as determined by non-targeted GC-MS/MS metabolomics. This study provides novel insights into the mechanisms underlying the toxicity of TPT and emphasizes the risks posed by such pollutants released into the environment.PMID:36327780 | DOI:10.1016/j.ecoenv.2022.114245

Accurate determination for lipidomics based on LC-tandem-MS parameters modeling, prediction, and database: Monitoring the progression of hepatocellular carcinoma

Thu, 03/11/2022 - 11:00
J Pharm Biomed Anal. 2022 Oct 27;223:115126. doi: 10.1016/j.jpba.2022.115126. Online ahead of print.ABSTRACTThe unavailability of adequate lipid reference standards is a major challenge for accurate quantitative analysis of lipidomics. Based on the discovery of regularity and predictability for lipids in chromatography-mass spectrometry behaviors, "target compound-structure correlation-analytical parameter database" protocol and "modeling-prediction" strategy were carried out to calculate the relative coefficients of analytical parameters within each subclass. Then the relevant LC-tandem-MS parameters of unknown lipids were predicted and a quantification parameter database for 4081 lipids was established and validated. Reference standards-independent accurate determination for lipidomics was achieved with the parameter's database and applied to monitor the change of lipid metabolism in the plasma of whole course of health-hepatitis-cirrhosis-hepatocellular carcinoma (HCC). Combined Student's t test, orthogonal partial least squares discrimination analysis (OPLS-DA) and binary logistic regression-ROC analysis, lipid biomarkers for differentiating health from each disease and differentiating different stages of disease were identified and the pathogenesis of HCC was preliminarily clarified. The established methodology would shed light on comprehensive and accurate quantitative lipidomics and exploring the pathomechanism and potential therapeutic targets of HCC.PMID:36327578 | DOI:10.1016/j.jpba.2022.115126

In vitro fermentation characteristics of the dietary fiber in bamboo (Phyllostachys edulis) shoots and its regulatory effects on the intestinal microbiota and metabolites

Thu, 03/11/2022 - 11:00
Food Chem. 2022 Oct 21;404(Pt B):134707. doi: 10.1016/j.foodchem.2022.134707. Online ahead of print.ABSTRACTThe effects of bamboo (Phyllostachys edulis) shoot dietary fiber (BSDF-1) on ulcerative colitis (UC) are unclear. Therefore, we performed an in vitro glycolysis study of intestinal microbiota samples, based on 16S rDNA sequencing and determining the metabolites in non-targeted colonic fecal fermentation broth. After a 48 h fermentation, the pH of the fermentation broth decreased significantly (p < 0.05) with the dextran sulfate sodium group (referred to here as the Mod group). The carbohydrate utilization rate was 26.59 %, and the total short-chain fatty acid content was 16.46 ± 0.71 mmol/L. The abundances of Alistipes and Lactobacillus increased after BDSF-1 fermentation, whereas those of Escherichia-Shigella, Enterococcus, and Proteus significantly decreased. BSDF-1 altered the levels of 17 metabolites in the Mod group after fermentation for 48 h, which reduced the cadaverine increasing induced by DSS. These results indicate that BSDF-1 can regulate the metabolism of the intestinal microbiota and the host, suggesting its use as a promising therapeutic strategy.PMID:36327509 | DOI:10.1016/j.foodchem.2022.134707

Metabonomics and the gut microbiome analysis of the effect of 6-shogaol on improving obesity

Thu, 03/11/2022 - 11:00
Food Chem. 2022 Oct 28;404(Pt B):134734. doi: 10.1016/j.foodchem.2022.134734. Online ahead of print.ABSTRACTThis study investigated the ability of 6-shogaol to reduce obesity in C57BL/6J mice fed with high-fat diet (HFD). After 12 weeks of 6-shogaol (20, 40, 60 mg/kg/2 days) intervention, obesity related indicators, gut microbiota and metabonomics of mice were analyzed. The obesity degree and blood lipid level of mice treated with 6-shogaol were reduced, and glucose homeostasis was improved, especially in mice treated with low-dose. The intervention of 6-shogaol increased the diversity of gut microbiota and decreased the ratio of Firmicutes and Bacteroides. 6-shogaol also led to changes in metabonomics. There were 5, 4 and 6 different metabolites of 6-shogaol at low, medium and high doses. Among them, Solacauline, PE (22:5 (4Z, 7z, 10z, 13z, 13z, 16z)/14:1 (9z)) and presqualene diphosphate have strong correlation with Akkermansia, Brucella, Odoribacter and Mucispirillum. This study aims to provide a theoretical foundation for clarifying the molecular mechanism of 6-shogaol in improving obesity.PMID:36327507 | DOI:10.1016/j.foodchem.2022.134734

Presence of sarcopenia identifies a special group of lean NAFLD in middle-aged and older people

Thu, 03/11/2022 - 11:00
Hepatol Int. 2022 Nov 3. doi: 10.1007/s12072-022-10439-z. Online ahead of print.ABSTRACTBACKGROUND: Sarcopenia, the age-related loss of muscle mass and function, is closely associated and frequently concomitant with non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the clinical features of the sarcopenic NAFLD patients from middle-aged and older people.METHODS: A total of 1305 patients with NAFLD from the Shanghai Changfeng Study were included for analysis. Sarcopenia was diagnosed based on the height-adjusted appendicular skeletal muscle mass (ASM/height2). We comprehensively analyzed the metabolic phenotype, carotid artery condition, liver fibrosis score, and serum metabolomic profile of each participant.RESULTS: Among the middle-aged and older population, 68.1% of patients with sarcopenia and NAFLD were lean. Sarcopenia was independently associated with increased risk of carotid plaque (OR, 2.22; 95%CI 1.23-4.02) and liver fibrosis (OR, 2.07; 95%CI 1.24-3.44), and the sarcopenic lean NAFLD patients were characterized by a higher risk of carotid plaque (p = 0.008) and liver fibrosis (p = 0.001) than the non-sarcopenic lean NAFLD patients, despite their lower BMI and similar prevalence of metabolic syndrome and diabetes. Further serum metabolomic examination indicated that the sarcopenic lean NAFLD patients presented a distinct metabolomic profile prone to carotid plaque and liver fibrosis, with upregulated serum valine, N-acetylneuraminyl-glycoproteins, lactic acid, small LDL triglycerides and VLDL5 components, and reduced components of HDL4. A sarcopenic characterization score based on above metabolites was established and could also predict increased risk of carotid plaque and liver fibrosis.CONCLUSION: The presence of sarcopenia identifies a special subgroup of lean NAFLD with increased risk of cardiovascular disease and liver fibrosis clinically.PMID:36327053 | DOI:10.1007/s12072-022-10439-z

metabolomics; +48 new citations

Tue, 23/02/2021 - 13:22
48 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/02/23PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Metformin attenuates post-epidural fibrosis by inhibiting the TGF-β1/Smad3 and HMGB1/TLR4 signaling pathways.

Tue, 23/02/2021 - 10:21
Related Articles Metformin attenuates post-epidural fibrosis by inhibiting the TGF-β1/Smad3 and HMGB1/TLR4 signaling pathways. J Cell Mol Med. 2021 Feb 21;: Authors: Song Z, Wu T, Sun J, Wang H, Hua F, Nicolas YSM, Kc R, Chen K, Jin Z, Liu J, Zhang M Abstract Excessive post-epidural fibrosis is a common cause of recurrent back pain after spinal surgery. Though various treatment methods have been conducted, the safe and effective drug for alleviating post-epidural fibrosis remains largely unknown. Metformin, a medicine used in the treatment of type 2 diabetes, has been noted to relieve fibrosis in various organs. In the present study, we aimed to explore the roles and mechanisms of metformin in scar formation in a mouse model of laminectomy. Post-epidural fibrosis developed in a mouse model of laminectomy by spinous process and the T12-L2 vertebral plate with a rongeur. With the administration of metformin, post-epidural fibrosis was reduced, accompanied with decreased collagen and fibronectin in the scar tissues. Mechanistically, metformin decreased fibronectin and collagen deposition in fibroblast cells, and this effect was dependent on the HMGB1/TLR4 and TGF-β1/Smad3 signalling pathways. In addition, metformin influenced the metabolomics of the fibroblast cells. Taken together, our study suggests that metformin may be a potential option to mitigate epidural fibrosis after laminectomy. PMID: 33611840 [PubMed - as supplied by publisher]

Comparative physiological and metabolic analyses of two Italian ryegrass (Lolium multiflorum) cultivars with contrasting salinity tolerance.

Tue, 23/02/2021 - 10:21
Related Articles Comparative physiological and metabolic analyses of two Italian ryegrass (Lolium multiflorum) cultivars with contrasting salinity tolerance. Physiol Plant. 2021 Feb 21;: Authors: Feng Q, Song S, Yang Y, Amee M, Chen L, Xie Y Abstract Italian ryegrass (Lolium multiflorum) is a widely cultivated forage with high nutritional value and good palatability. Salinity, however, is a negative factor to lessen output and quality in Italian ryegrass. The aim of this study was to elucidate the salt tolerance mechanism of two Italian ryegrass cultivars, 'Abundant' and 'Angus'. Under hydroponic conditions, two cultivars of Italian ryegrass with different salt tolerance were exposed to 0 and 300 mM NaCl solution for one week, respectively. The results showed that salt stress decreased relative growth rate and relative water content, especially in salt-sensitive 'Angus'. The salt-tolerant 'Abundant' cultivar alleviated reactive oxygen species (ROS) induced burst and cell damage. However, 'Angus' exhibited a greater activity of superoxide dismutase (SOD) and peroxidase (POD) than 'Abundant'. Additionally, 'Abundant' exhibited higher photosynthetic efficiency than 'Angus' under salt stress condition. Salt treatment significantly increased the Na/K, Na/Mg and Na/Ca ratios in the leaves and roots of both cultivars, with a pronounced effect in salt-sensitive 'Angus'. The metabolite analysis of leaf polar extracts revealed 41 salt responsive metabolites in both cultivars, mainly consisting of amino acids, organic acids, fatty acids, and sugars. Following exposure to salt conditions, salt-sensitive 'Angus' had a higher level of metabolites and more uniquely up-regulated metabolites were detected. Based on these findings, we conclude that the 'Abundant' cultivar emerged as a favorite in saline-alkali soil, while the 'Angus' cultivar is suitable for planting in normal soil. It appears that the high salt tolerance of 'Abundant' is partly to prevent the plant from ionic homeostasis disruption. This article is protected by copyright. All rights reserved. PMID: 33611798 [PubMed - as supplied by publisher]

Wood profiling by non-targeted high-resolution mass spectrometry: Part 1, Metabolite profiling in Cedrela wood for the determination of the geographical origin.

Tue, 23/02/2021 - 10:21
Related Articles Wood profiling by non-targeted high-resolution mass spectrometry: Part 1, Metabolite profiling in Cedrela wood for the determination of the geographical origin. J Chromatogr A. 2021 Feb 12;1641:461993 Authors: Creydt M, Ludwig L, Köhl M, Fromm J, Fischer M Abstract The determination of the geographical origin of wood can be highly relevant for several reasons: On the one hand, it can help to prevent illegal logging and timber trade, on the other hand, it is of special interest for archaeological artefacts made of wood, as well as for a variety of biological questions. For this reason, different extraction methods were first tested for the analysis of polar and non-polar metabolites using liquid chromatography coupled electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). A two-phase extraction with chloroform, methanol and water proved to be particularly successful. Subsequently, cedrela (Cedrela odorata) samples from South America were measured to distinguish geographic origin. Using multivariate data analysis, numerous origin-dependent differences could be extracted. The identification of the marker substances indicated that several metabolic pathways were affected by the geographical influences, some of them probably indicating pest infections. PMID: 33611119 [PubMed - as supplied by publisher]

Evaluation of a nanoflow interface based on the triple-tube coaxial sheath-flow sprayer for capillary electrophoresis-mass spectrometry coupling in metabolomics.

Tue, 23/02/2021 - 10:21
Related Articles Evaluation of a nanoflow interface based on the triple-tube coaxial sheath-flow sprayer for capillary electrophoresis-mass spectrometry coupling in metabolomics. J Chromatogr A. 2021 Feb 09;1641:461982 Authors: Ferré S, Drouin N, González-Ruiz V, Rudaz S Abstract The performance of an original CE-MS interface that allows the in-axis positioning of the electrospray with respect to the MS inlet was evaluated. The variations in the geometrical alignment of this configuration in the absence of a nebulizing gas afforded a significant reduction in the sheath-liquid flow rate from 3 µL/min to as low as 300 nL/min. The sheath liquid and BGE were respectively composed of H2O-iPrOHCH3COOH 50:50:1 (v/v/v) and 10% acetic acid (pH 2.2). A significant gain in sensitivity was obtained, and it was correlated to the effective mobility of the analytes. Compounds with low mobility values showed a greater sensitivity gain. Special attention was paid to the detection of proteinogenic amino acids. Linear response functions were obtained from 15 ng/mL to 500 ng/mL. The limits of quantification, as low as 34.3 ng/mL, were improved by a factor of up to six compared to the conventional configuration. The in-axis setup was ultimately applied to the absolute quantification of four important amino acids, alanine, tyrosine, methionine and valine, in standard reference material (NIST plasma). The accuracies ranged from 78 to 113%, thus demonstrating the potential of this configuration for metabolomics. PMID: 33611118 [PubMed - as supplied by publisher]

Identification of the metabolites regulated in soybean-Rhizobia symbiosis through solid phase microextraction coupled with LC-MS.

Tue, 23/02/2021 - 10:21
Related Articles Identification of the metabolites regulated in soybean-Rhizobia symbiosis through solid phase microextraction coupled with LC-MS. J Chromatogr A. 2021 Jan 30;1641:461934 Authors: Onat B, Rosales-Solano H, Ferrier L, Pawliszyn J Abstract Legumes provide one of the uniquely nutrient-rich food sources to the population and are one of the primary field crops that play significant roles in agricultural sustainability. Inoculation with Bradyrhizobium japonicum is necessary for the high yield of leguminous crops, i.e. soybean. Nodulation of soybean by Bradyrhizobium japonicum is a complex process that is essential for cultivation of these legumes and external stress factors, such as draught and soil acidity, that influence the nodulation and crop yield. Alterations in the nodule metabolites are known to identify the type of stress that mitigates nodulation and lowers crop yield. Current techniques aimed at understanding the metabolic activities in the symbiont, such as in the case of metabolic regulations in varying nodule growth phases, rely on exhaustive techniques based on the removal of nodules or other plant tissue. Aiming to capture a more in-depth, accurate profile of this system without quenching the metabolic activity in the nodules, or removing the nodules, a workflow was prepared for the metabolite sampling through in vivo solid phase microextraction in thin film format (TF-SPME). This technique was followed by LC-QTOF-MS instrumental analysis with subsequent metabolite annotation and reference standard validation. Our approach is unique in terms of eliminating the effects that arise due to analyte partition coefficients. We show that the symbiont undergoes metabolic regulations throughout the cultivation period, displaying the efficacy of TF-SPME as a non-exhaustive sampling method that can be used as a tool to investigate the metabolic alterations in nodules. These alterations would potentially fingerprint the environmental effects on soybean yield. PMID: 33611117 [PubMed - as supplied by publisher]

Metabolomics analysis reveals the effect of copper on autophagy in myocardia of pigs.

Tue, 23/02/2021 - 10:21
Related Articles Metabolomics analysis reveals the effect of copper on autophagy in myocardia of pigs. Ecotoxicol Environ Saf. 2021 Feb 18;213:112040 Authors: Li Q, Liao J, Lei C, Shi J, Zhang H, Han Q, Guo J, Hu L, Li Y, Pan J, Tang Z Abstract Among different synthetic compounds copper (Cu) is persistently and frequently used as growth promoter, antibacterial, antifungal and antiparasitic agent and has become common environmental pollutant. Therefore, this study explores the cardio-toxic effects of control group (10 mg/kg bw Cu) and treatment group (125 and 250 mg/kg bw Cu), and it association with process of autophagy and metabolomics in myocardium of pigs kept in three different experimental treatments for a period of 80 days. The results of serum biochemical parameters showed a significantly increase in creatinine kinase (CK), creatine kinase-MB (CK-MB), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and aspartate aminotransferase (AST) in pigs exposed to 125 mg/kg bw and 250 mg/kg bw Cu. Meanwhile, the severe structural abnormalities in cardiomyocytes were found when exposed to 250 mg/kg Cu at day 80. In addition, the mRNA and proteins (Beclin1, ATG5 and LC3II) expression levels were significantly increased and p62 was significantly decreased in cardiomyocytes exposed to 250 mg/kg Cu at day 80 of the trial. Further, UPLC-QTOF/MS technique showed that 7 metabolites were up-regulated and 37 metabolites were down-regulated in cardiomyocytes after 250 mg/kg Cu treatment, with a principal impact on the metabolic pathways including glycerophospholipid metabolism, one carbon pool by folate, fatty acid elongation and fatty acid degradation, which were related to autophagy. Overall, our study identified the autophagy processes and metabolites in metabolic pathways in Cu-induced myocardium injury, which provided useful evidence of myocardium toxicity caused by Cu exposure via metabolomics and multiple bioanalytic methods. PMID: 33610943 [PubMed - as supplied by publisher]

M. tuberculosis curli pili (MTP) is associated with alterations in carbon, fatty acid and amino acid metabolism in a THP-1 macrophage infection model.

Tue, 23/02/2021 - 10:21
Related Articles M. tuberculosis curli pili (MTP) is associated with alterations in carbon, fatty acid and amino acid metabolism in a THP-1 macrophage infection model. Microb Pathog. 2021 Feb 18;:104806 Authors: Ashokcoomar S, Loots DT, Beukes D, van Reenen M, Pillay B, Pillay M Abstract The initial host-pathogen interaction is crucial for the establishment of infection. An improved understanding of the pathophysiology of Mycobacterium tuberculosis (M. tuberculosis) during macrophage infection can aid the development of intervention therapeutics against tuberculosis. M. tuberculosis curli pili (MTP) is a surface located adhesin, involved in the first point-of-contact between pathogen and host. This study aimed to better understand the role of MTP in modulating the intertwined metabolic pathways of M. tuberculosis and its THP-1 macrophage host. Metabolites were extracted from pelleted wet cell mass of THP-1 macrophages infected with M. tuberculosis wild-type V9124 (WT), Δmtp-deletion mutant and the mtp-complemented strains, respectively, via a whole metabolome extraction method using a 1:3:1 ratio of chloroform:methanol:water. Metabolites were detected by two-dimensional gas chromatography time-of-flight mass spectrometry. Significant metabolites were determined through univariate and multivariate statistical tests and online pathway databases. Relative to the WT, a total of nine and ten metabolites were significantly different in the Δmtp and complement strains, respectively. All nine significant metabolites were found in elevated levels in the Δmtp relative to the WT. Additionally, of the ten significant metabolites, eight were detected in lower levels and two were detected in higher levels in the complement relative to the WT. The absence of the MTP adhesin resulted in reduced virulence of M. tuberculosis leading to alterations in metabolites involved in carbon, fatty acid and amino acid metabolism during macrophage infection, suggesting that MTP plays an important role in the modulation of host metabolic activity. These findings support the prominent role of the MTP adhesin as a virulence factor as well as a promising biomarker for possible diagnostic and therapeutic intervention. PMID: 33610716 [PubMed - as supplied by publisher]

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