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

Comparison of <em>Balanites aegyptiaca</em> parts: metabolome providing insights into plant health benefits and valorization purposes as analyzed using multiplex GC-MS, LC-MS, NMR-based metabolomics, and molecular networking

Mon, 24/07/2023 - 12:00
RSC Adv. 2023 Jul 20;13(31):21471-21493. doi: 10.1039/d3ra03141a. eCollection 2023 Jul 12.ABSTRACTBalanites aegyptiaca (L.) Delile (Zygophyllaceae), also known as the desert date, is an edible fruit-producing tree popular for its nutritional and several health benefits. In this study, multi-targeted comparative metabolic profiling and fingerprinting approaches were conducted for the assessment of the nutrient primary and secondary metabolite heterogeneity in different parts, such as leaves, stems, seeds, unripe, and ripe fruits of B. aegyptiaca using nuclear magnetic resonance (NMR), ultra-performance liquid chromatography (UPLC-MS), and gas chromatography mass-spectrometry (GC-MS) based metabolomics coupled to multivariate analyses and in relation to its cytotoxic activities. NMR-based metabolomic study identified and quantified 15 major primary and secondary metabolites belonging to alkaloids, saponins, flavonoids, sugars, and amino and fatty acids. Principal component analysis (PCA) of the NMR dataset revealed α-glucose, sucrose, and isorhamnetin as markers for fruit and stem and unsaturated fatty acids for predominated seeds. Orthogonal projections to latent structure discriminant analysis (OPLS-DA) revealed trigonelline as a major distinctive metabolite in the immature fruit and isorhamnetin as a major distinct marker in the mature fruit. UPLC-MS/MS analysis using feature-based molecular networks revealed diverse chemical classes viz. steroidal saponins, N-containing metabolites, phenolics, fatty acids, and lipids as the constitutive metabolome in Balanites. Gas chromatography-mass spectroscopy (GC-MS) profiling of primary metabolites led to the detection of 135 peaks belonging to sugars, fatty acids/esters, amino acids, nitrogenous, and organic acids. Monosaccharides were detected at much higher levels in ripe fruit and disaccharides in predominate unripe fruits, whereas B. aegyptiaca vegetative parts (leaves and stem) were rich in amino acids and fatty acids. The antidiabetic compounds, viz, nicotinic acid, and trigonelline, were detected in all parts especially unripe fruit in addition to the sugar alcohol d-pinitol for the first time providing novel evidence for B. aegyptiaca use in diabetes. In vitro cytotoxic activity revealed the potential efficacy of immature fruit and seeds as cytotoxic agents against human prostate cancer (PC3) and human colorectal cancer (HCT-116) cell lines. Collectively, such detailed profiling of parts provides novel evidence for B. aegyptiaca medicinal uses.PMID:37485437 | PMC:PMC10359763 | DOI:10.1039/d3ra03141a

Effects of <em>Lactiplantibacillus plantarum</em> and <em>Lacticaseibacillus paracasei</em> supplementation on the faecal metabolome in children with coeliac disease autoimmunity: a randomised, double-blinded placebo-controlled clinical trial

Mon, 24/07/2023 - 12:00
Front Nutr. 2023 Jul 6;10:1183963. doi: 10.3389/fnut.2023.1183963. eCollection 2023.ABSTRACTINTRODUCTION: Coeliac disease is a lifelong immune-mediated enteropathy manifested as gluten intolerance in individuals carrying specific human leukocyte antigen (HLA) molecules. Other factors than genetics and gluten intake, however, may play a role in triggering the disease. The gut internal environment is thought to be one of these potential contributing factors, and it can be influenced throughout life.METHODS: We examine the impact of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2 supplementation on the faecal metabolome in genetically predisposed children having tissue transglutaminase autoantibodies, i.e., coeliac disease autoimmunity. Probiotic strains were selected based on their beneficial properties, including mucosal permeability and immune modulation effects. The intervention group (n = 40) and control group (n = 38) took the probiotics or placebo daily for 6 months in a double-blinded randomised trial. Faecal samples were collected at baseline and after 3 and 6 months and analysed using the 1H NMR for metabolome. The incorporation of 16S rRNA sequencing as a supportive dataset complemented the analysis of the metabolome data.RESULTS: During the 6 months of intervention, the stool concentrations of 4-hydroxyphenylacetate increased in the intervention group as compared to controls, whereas concentrations of threonine, valine, leucine, isoleucine, methionine, phenylalanine, aspartate, and fumarate decreased. Additionally, a noteworthy effect on the glycine, serine, and threonine metabolic pathway has been observed.CONCLUSION: The findings suggest a modest yet significant impact of the probiotics on the faecal metabolome, primarily influencing proteolytic processes in the gut.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03176095.PMID:37485388 | PMC:PMC10359497 | DOI:10.3389/fnut.2023.1183963

Total serum <em>N</em>-glycans mark visceral leishmaniasis in human infections with <em>Leishmania infantum</em>

Mon, 24/07/2023 - 12:00
iScience. 2023 Jun 5;26(7):107021. doi: 10.1016/j.isci.2023.107021. eCollection 2023 Jul 21.ABSTRACTVisceral leishmaniasis (VL) is a clinical form of leishmaniasis with high mortality rates when not treated. Diagnosis suffers from invasive techniques and sub-optimal sensitivities. The current (affordable) treatment with pentavalent antimony as advised by the WHO is possibly harmful to the patient. There is need for an improved diagnosis to prevent possibly unnecessary treatment. N-glycan analysis may aid in diagnosis. We evaluated the N-glycan profiles from active VL, asymptomatic infections (ASYMP) and controls from non-endemic (NC) and endemic (EC) areas. Active VL has a distinct N-glycome profile that associates with disease severity. Our study suggests that the observed glycan signatures could be a valuable additive to diagnosis and assist in identifying possible markers of disease and understanding the pathogenesis of VL. Further studies are warranted to assess a possible future role of blood glycome analysis in active VL diagnosis and should aim at disease specificity.PMID:37485378 | PMC:PMC10362369 | DOI:10.1016/j.isci.2023.107021

Physical fitness, hormonal profile, nutritional and psychological aspects assessment of transgender women volleyball players submitted to physical tests: protocol paper of a prospective cohort

Mon, 24/07/2023 - 12:00
BMJ Open Sport Exerc Med. 2023 Jul 17;9(3):e001641. doi: 10.1136/bmjsem-2023-001641. eCollection 2023.ABSTRACTTo evaluate aerobic capacity, strength and other physiological, nutritional, and psychological variables which may influence the performance of transgender women (TW) athletes and compare them to cisgender women (CW) and cisgender men (CM) athletes, as well as changes in TW performance over the course of a year. Prospective cohort study including three groups: TW, CW and CM volleyball athletes. Subjects will be comprehensively assessed at two different moments: baseline and after 6-12 months of adequate hormonal therapy. Evaluation will comprise clinical, medical, nutritional and psychological interviews, incremental treadmill cardiopulmonary exercise testing, hand grip strength test, vertical jump test, analysis of sleep quality (Pittsburgh Sleep Quality Index), hormonal profile, echocardiogram, analysis of resting energy expenditure, assessment of bone mass and body composition through dual-energy X-ray absorptiometry scans, and untargeted metabolomic analysis. CW and CM matched by age, body mass index and level of physical activity will undergo a similar evaluation. The assessment of the strength, aerobic capacity, haematological, nutritional and psychological status of TW using gold-standard tests will contribute to understanding the impact of oestrogen therapy on the exercise performance of these athletes and how they compare with CW and CM.PMID:37485006 | PMC:PMC10357769 | DOI:10.1136/bmjsem-2023-001641

Chestnut polysaccharide rescues the damaged spermatogenesis process of asthenozoospermia-model mice by upregulating the level of palmitic acid

Mon, 24/07/2023 - 12:00
Front Endocrinol (Lausanne). 2023 Jul 5;14:1222635. doi: 10.3389/fendo.2023.1222635. eCollection 2023.ABSTRACTINTRODUCTION: In recent years, the quality of male semen has been decreasing, and the number of male infertilities caused by asthenozoospermia is increasing year by year, and the diagnosis and treatment of patients with asthenozoospermia are gradually receiving the attention of the whole society. Due to the unknown etiology and complex pathogenesis, there is no specific treatment for asthenozoospermia. Our previous study found that the administration of chestnut polysaccharide could alter the intestinal microbiota and thus improve the testicular microenvironment, and rescue the impaired spermatogenesis process by enhancing the expression of reproduction-related genes, but its exact metabolome-related repairment mechanism of chestnut polysaccharide is still unclear.METHODS AND RESULTS: In this study, we studied the blood metabolomic changes of busulfan-induced asthenozoospermia-model mice before and after oral administration of chestnut polysaccharide with the help of metabolome, and screened two key differential metabolites (hydrogen carbonate and palmitic acid) from the set of metabolomic changes; we then analyzed the correlation between several metabolites and between different metabolites and intestinal flora by correlation analysis, and found that palmitic acid in the blood serum of mice after oral administration of chestnut polysaccharide had different degrees of correlation with various metabolites, and palmitic acid level had a significant positive correlation with the abundance of Verrucomicrobia; finally, we verified the role of palmitic acid in rescuing the damaged spermatogenesis process by using asthenozoospermia-model mice, and screened the key target gene for palmitic acid to play the rescuing effect by integrating the analysis of multiple databases.DISCUSSION: In conclusion, this study found that chestnut polysaccharide rescued the damaged spermatogenesis in asthenozoospermia-model mice by upregulating palmitic acid level, which will provide theoretical basis and technical support for the use of chestnut polysaccharide in the treatment of asthenozoospermia.PMID:37484950 | PMC:PMC10356583 | DOI:10.3389/fendo.2023.1222635

Recent Review on Selected Xenobiotics and Their Impacts on Gut Microbiome and Metabolome

Mon, 24/07/2023 - 12:00
Trends Analyt Chem. 2023 Sep;166:117155. doi: 10.1016/j.trac.2023.117155. Epub 2023 Jun 28.ABSTRACTAs it is well known, the gut is one of the primary sites in any host for xenobiotics, and the many microbial metabolites responsible for the interactions between the gut microbiome and the host. However, there is a growing concern about the negative impacts on human health induced by toxic xenobiotics. Metabolomics, broadly including lipidomics, is an emerging approach to studying thousands of metabolites in parallel. In this review, we summarized recent advancements in mass spectrometry (MS) technologies in metabolomics. In addition, we reviewed recent applications of MS-based metabolomics for the investigation of toxic effects of xenobiotics on microbial and host metabolism. It was demonstrated that metabolomics, gut microbiome profiling, and their combination have a high potential to identify metabolic and microbial markers of xenobiotic exposure and determine its mechanism. Further, there is increasing evidence supporting that reprogramming the gut microbiome could be a promising approach to the intervention of xenobiotic toxicity.PMID:37484879 | PMC:PMC10361410 | DOI:10.1016/j.trac.2023.117155

Metabolomics: a promising tool for deciphering metabolic impairment in heavy metal toxicities

Mon, 24/07/2023 - 12:00
Front Mol Biosci. 2023 Jul 6;10:1218497. doi: 10.3389/fmolb.2023.1218497. eCollection 2023.ABSTRACTHeavy metals are the metal compounds found in earth's crust and have densities higher than that of water. Common heavy metals include the lead, arsenic, mercury, cadmium, copper, manganese, chromium, nickel, and aluminum. Their environmental levels are consistently rising above the permissible limits and they are highly toxic as enter living systems via inhalation, ingestion, or inoculation. Prolonged exposures cause the disruption of metabolism, altered gene and/or protein expression, and dysregulated metabolite profiles. Metabolomics is a state of the art analytical tool widely used for pathomolecular inv22estigations, biomarkers, drug discovery and validation of biotransformation pathways in the fields of biomedicine, nutrition, agriculture, and industry. Here, we overview studies using metabolomics as a dynamic tool to decipher the mechanisms of metabolic impairment related to heavy metal toxicities caused by the environmental or experimental exposures in different living systems. These investigations highlight the key role of metabolomics in identifying perturbations in pathways of lipid and amino acid metabolism, with a critical role of oxidative stress in metabolic impairment. We present the conclusions with future perspectives on metabolomics applications in meeting emerging needs.PMID:37484533 | PMC:PMC10357477 | DOI:10.3389/fmolb.2023.1218497

How does the pattern of root metabolites regulating beneficial microorganisms change with different grazing pressures?

Mon, 24/07/2023 - 12:00
Front Plant Sci. 2023 Jul 6;14:1180576. doi: 10.3389/fpls.2023.1180576. eCollection 2023.ABSTRACTGrazing disturbance can change the structure of plant rhizosphere microbial communities and thereby alter the feedback to promote plant growth or induce plant defenses. However, little is known about how such changes occur and vary under different grazing pressures or the roles of root metabolites in altering the composition of rhizosphere microbial communities. In this study, the effects of different grazing pressures on the composition of microbial communities were investigated, and the mechanisms by which different grazing pressures changed rhizosphere microbiomes were explored with metabolomics. Grazing changed composition, functions, and co-expression networks of microbial communities. Under light grazing (LG), some saprophytic fungi, such as Lentinus sp., Ramichloridium sp., Ascobolus sp. and Hyphoderma sp., were significantly enriched, whereas under heavy grazing (HG), potentially beneficial rhizobacteria, such as Stenotrophomonas sp., Microbacterium sp., and Lysobacter sp., were significantly enriched. The beneficial mycorrhizal fungus Schizothecium sp. was significantly enriched in both LG and HG. Moreover, all enriched beneficial microorganisms were positively correlated with root metabolites, including amino acids (AAs), short-chain organic acids (SCOAs), and alkaloids. This suggests that these significantly enriched rhizosphere microbial changes may be caused by these differential root metabolites. Under LG, it is inferred that root metabolites, especially AAs such as L-Histidine, may regulate specific saprophytic fungi to participate in material transformations and the energy cycle and promote plant growth. Furthermore, to help alleviate the stress of HG and improve plant defenses, it is inferred that the root system actively regulates the synthesis of these root metabolites such as AAs, SCOAs, and alkaloids under grazing interference, and then secretes them to promote the growth of some specific plant growth-promoting rhizobacteria and fungi. To summarize, grasses can regulate beneficial microorganisms by changing root metabolites composition, and the response strategies vary under different grazing pressure in typical grassland ecosystems.PMID:37484473 | PMC:PMC10361787 | DOI:10.3389/fpls.2023.1180576

Corrigendum: Metabonomic analysis of the anti-hepatic fibrosis effect of <em>Ganlong capsules</em>

Mon, 24/07/2023 - 12:00
Front Pharmacol. 2023 Jul 7;14:1231544. doi: 10.3389/fphar.2023.1231544. eCollection 2023.ABSTRACT[This corrects the article DOI: 10.3389/fphar.2023.1122118.].PMID:37484023 | PMC:PMC10361689 | DOI:10.3389/fphar.2023.1231544

Anaphylactoid reactions induced by Shuanghuanglian injection and Shenmai injection and metabolomics analysis

Mon, 24/07/2023 - 12:00
Front Pharmacol. 2023 Jul 6;14:1200199. doi: 10.3389/fphar.2023.1200199. eCollection 2023.ABSTRACTIntroduction: Shuanghuanglian injection (lyophilized) (SHLI) is commonly used to treat respiratory tract infection. Shenmai injection (SMI) is mainly used to treat cardiovascular diseases. Despite their widespread clinical use, anaphylactoid reactions (ARs) induced by SHLI and SMI have been reported, which have attracted broad attention. However, the impact of ARs on metabolic changes and the underlying mechanisms are still unclear. Methods: ICR mice were used as model animals and were treated with normal saline, C48/80, SHLI and SMI, respectively. The behavior of mice, auricle blue staining and Evans Blue exudation were used as indexes to evaluate the sensitization of SHLI and SMI and determine the optimal sensitization dose. Anaphylactoid mice model was established based on the optimal dose and enzyme-linked immunosorbent assay (ELISA) was used to model verification. Afterwards, plasma samples of administered mice were profiled by LC-MS metabolomics and analyzed to evaluate the changes in metabolites. Results: High doses of both SHLI and SMI can induce severe anaphylactoid reactions while the reaction induced by SMI was weaker. A Partial Least-Squares Discriminant Analysis (PLS-DA) score plot indicated that following administration, significant metabolic changes occurred in mice. 23 distinct metabolites, including deoxycholic acid, histamine, and 5-hydroxytryptophan, were identified in the SHLI groups. 11 distinct metabolites, including androsterone, 17α-hydroxypregnenolone, and 5-hydroxyindoleacetate, were identified in the SMI groups. Meanwhile, different metabolic pathways of SHLI and SMI were predicted by different metabolites. The associated metabolic pathways include steroid hormone biosynthesis, tryptophan metabolism, histidine metabolism, arachidonic acid metabolism, nicotinate and nicotinamide metabolism, and primary bile acid biosynthesis. Conclusion: Study showed that both SHLI and SMI can induce varying degrees of anaphylactoid reactions, a positive correlation between response intensity and dose was observed. Metabolomics showed that SHLI and SMI may promote the simultaneous release of hormones and inflammatory factors by disturbing relevant metabolic pathways, while SMI may also inhibit the release of inflammatory factors in arachidonic acid metabolic pathway, indicating both pro-inflammatory and anti-inflammatory effects. This study will serve as a reference for developing a new approach to evaluate the safety of SHLI and SMI from perspective of susceptible drug varieties. However, ARs mechanism requires further verification.PMID:37484014 | PMC:PMC10358984 | DOI:10.3389/fphar.2023.1200199

Urinary Cytokines as Potential Biomarkers of Mild Cognitive Impairment and Alzheimer's Disease: A Pilot Study

Mon, 24/07/2023 - 12:00
J Alzheimers Dis Rep. 2023 Jun 27;7(1):649-657. doi: 10.3233/ADR-220081. eCollection 2023.ABSTRACTBACKGROUND: Alzheimer's disease (AD) is the most common form of dementia, accounting for 80% of all cases. Mild cognitive impairment (MCI) is a transitional state between normal aging and AD. Early detection is crucial, as irreversible brain damage occurs before symptoms manifest.OBJECTIVE: This study aimed to identify potential biomarkers for early detection of AD by analyzing urinary cytokine concentrations. We investigated 37 cytokines in AD, MCI, and cognitively normal individuals (NC), assessing their associations with AD development.METHODS: Urinary cytokine concentrations were measured in AD (n = 25), MCI (n = 25), and NC (n = 26) patients. IL6ST and MMP-2 levels were compared between AD and NC, while TNFRSF8, IL6ST, and IL-19 were assessed in AD versus MCI. Diagnostic models distinguished AD from NC, and in-silico analysis explored molecular mechanisms related to AD.RESULTS: Significant perturbations in IL6ST and MMP-2 concentrations were observed in AD urine compared to NC, suggesting their potential as biomarkers. TNFRSF8, IL6ST, and IL-19 differed significantly between AD and MCI, implicating them in disease progression. Diagnostic models exhibited promising performance (AUC: 0.59-0.79, sensitivity: 0.72-0.80, specificity: 0.56-0.78) in distinguishing AD from NC. In-silico analysis revealed molecular insights, including relevant non-coding RNAs, microRNAs, and transcription factors.CONCLUSION: This study establishes significant associations between urinary cytokine concentrations and AD and MCI. IL6ST, MMP-2, TNFRSF8, IL6ST, and IL-19 emerge as potential biomarkers for early detection of AD. In-silico analysis enhances understanding of molecular mechanisms in AD. Further validation and exploration of these biomarkers in larger cohorts are warranted to assess their clinical utility.PMID:37483327 | PMC:PMC10357120 | DOI:10.3233/ADR-220081

Comparative metabolic profiling of mycelia, fermentation broth, spore powder and fruiting bodies of Ophiocordyceps gracilis by LC-MS/MS

Mon, 24/07/2023 - 12:00
Phytochem Anal. 2023 Jul 22. doi: 10.1002/pca.3266. Online ahead of print.ABSTRACTINTRODUCTION: Ophiocordyceps gracilis, a type of edible and medicinal fungus, exhibits multiple health-promoting effects. Due to the scarcity of natural O. gracilis, artificial cultures have been developed as its substitutes. However, lacking comprehension of the metabolite composition of cultures limits its utilisation.OBJECTIVE: This research aimed to evaluate the nutritional and medicinal value of four cultures of O. gracilis by analysing their metabolite composition. In addition, metabolic pathways in mycelia and fruiting bodies were analysed to explore fruiting body formation mechanism at metabolic level.METHOD: The mycelia, fermentation broth, spore powder and fruiting bodies of O. gracilis were cultivated in this study. Their metabolite composition was compared using an untargeted metabolomics approach based on liquid chromatography-tandem mass spectrometry (LC-MS/MS).RESULTS: Principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) showed that the four cultures have noticeable differences in metabolite composition. A total of 612 metabolites were identified, among which 159 metabolites showed significant differences, and these differential metabolites were classified into 13 categories. The metabolites in the fruiting bodies were the most abundant compared with other cultures. However, each culture had its own advantages and significantly accumulates some active metabolites respectively. Pearson's correlation analysed the mutual relationship among metabolites. In addition, seven metabolic pathways were closely related to fruiting body formation, such as "Biosynthesis of plant secondary metabolites", "amino acids metabolism", "tricarboxylic acid (TCA) cycle".CONCLUSION: This study offered a reference to mycelia, fermentation broth, spore powder and fruiting bodies of O. gracilis as health-promoting functional foods and medicine.PMID:37482969 | DOI:10.1002/pca.3266

Quantifying PG : VG ratio and nicotine content in commercially available e-liquids using handheld Raman spectroscopy

Mon, 24/07/2023 - 12:00
Analyst. 2023 Jul 24. doi: 10.1039/d3an00888f. Online ahead of print.ABSTRACTElectronic cigarettes are a popular nicotine consumption product that have risen in popularity as an alternative to cigarettes. However, their recent meteoric rise in market size and various controversies have resulted in the analyses of e-liquid ingredients to be focused on powerful laboratory-based slow methods such as chromatography and mass spectrometry. Here we present a complementary technology based on Raman spectroscopy combined with chemometrics as a fast, inexpensive, and highly portable screening tool to detect and quantify the propylene glycol : glycerol (PG : VG) ratio and nicotine content of e-cigarette liquids. Through this, the PG : VG ratio of 20 out of 23 commercial samples was quantified to within 3% of their stated value, while nicotine was successfully quantified to within 1 mg g-1 for 16 out of 23 samples without the need for accurate knowledge of flavonoid composition. High linearity was also achieved when flavours were kept constant. Finally, the limitations of Raman spectroscopy are discussed, and potential solutions are suggested.PMID:37482759 | DOI:10.1039/d3an00888f

The metabolomics workbench file status website: a metadata repository promoting FAIR principles of metabolomics data

Sun, 23/07/2023 - 12:00
BMC Bioinformatics. 2023 Jul 24;24(1):299. doi: 10.1186/s12859-023-05423-9.ABSTRACTBACKGROUND: An updated version of the mwtab Python package for programmatic access to the Metabolomics Workbench (MetabolomicsWB) data repository was released at the beginning of 2021. Along with updating the package to match the changes to MetabolomicsWB's 'mwTab' file format specification and enhancing the package's functionality, the included validation facilities were used to detect and catalog file inconsistencies and errors across all publicly available datasets in MetabolomicsWB.RESULTS: The MetabolomicsWB File Status website was developed to provide continuous validation of MetabolomicsWB data files and a useful interface to all found inconsistencies and errors. This list of detectable issues/errors include format parsing errors, format compliance issues, access problems via MetabolomicsWB's REST interface, and other small inconsistencies that can hinder reusability. The website uses the mwtab Python package to pull down and validate each available analysis file and then generates an html report. The website is updated on a weekly basis. Moreover, the Python website design utilizes GitHub and GitHub.io, providing an easy to replicate template for implementing other metadata, virtual, and meta- repositories.CONCLUSIONS: The MetabolomicsWB File Status website provides a metadata repository of validation metadata to promote the FAIR use of existing metabolomics datasets from the MetabolomicsWB data repository.PMID:37482620 | DOI:10.1186/s12859-023-05423-9

Monitoring and modelling the glutamine metabolic pathway: a review and future perspectives

Sun, 23/07/2023 - 12:00
Metabolomics. 2023 Jul 23;19(8):67. doi: 10.1007/s11306-023-02031-9.ABSTRACTBACKGROUND: Analysis of the glutamine metabolic pathway has taken a special place in metabolomics research in recent years, given its important role in cell biosynthesis and bioenergetics across several disorders, especially in cancer cell survival. The science of metabolomics addresses the intricate intracellular metabolic network by exploring and understanding how cells function and respond to external or internal perturbations to identify potential therapeutic targets. However, despite recent advances in metabolomics, monitoring the kinetics of a metabolic pathway in a living cell in situ, real-time and holistically remains a significant challenge.AIM: This review paper explores the range of analytical approaches for monitoring metabolic pathways, as well as physicochemical modeling techniques, with a focus on glutamine metabolism. We discuss the advantages and disadvantages of each method and explore the potential of label-free Raman microspectroscopy, in conjunction with kinetic modeling, to enable real-time and in situ monitoring of the cellular kinetics of the glutamine metabolic pathway.KEY SCIENTIFIC CONCEPTS: Given its important role in cell metabolism, the ability to monitor and model the glutamine metabolic pathways are highlighted. Novel, label free approaches have the potential to revolutionise metabolic biosensing, laying the foundation for a new paradigm in metabolomics research and addressing the challenges in monitoring metabolic pathways in living cells.PMID:37482587 | DOI:10.1007/s11306-023-02031-9

Features of the response to subchronic low-dose exposure to copper oxide nanoparticles in rats

Sun, 23/07/2023 - 12:00
Sci Rep. 2023 Jul 23;13(1):11890. doi: 10.1038/s41598-023-38976-z.ABSTRACTCopper is an essential trace element for human health and, at the same time, a major industrial metal widely used both in its elemental form and in compounds. We conducted a dose-dependent assessment of the response of outbred albino male rats to subchronic low-dose exposure to copper oxide nanoparticles administered intraperitoneally at cumulative doses of 18 and 36 mg/kg during 6 weeks to exposure groups 1 and 2, respectively. We observed disorders at different levels of organization of the body in the exposed animals, from molecular to organismal. The observed decrease in the activity of succinate dehydrogenase in nucleated blood cells gave evidence of impaired bioenergetics processes. In view of the results of the metabolomics analysis, we assume mitochondrial damage and contribution of apoptotic processes to the pathology induced by copper poisoning. We also assume neurodegenerative effects based on the assessed morphological parameters of the nervous system, results of behavioral tests, and a decreased level of expression of genes encoding NMDA receptor subunits in the hippocampus. The hepatotoxic effect noted by a number of metabolomics-based, biochemical, and cytological indicators was manifested by the impaired protein-synthesizing function of the liver and enhanced degenerative processes in its cells. We also observed a nephrotoxic effect of nanosized copper oxide with a predominant lesion of proximal kidney tubules. At the same time, both doses tested demonstrated such positive health effects as a statistically significant decrease in the activity of alkaline phosphatase and the nucleated blood cell DNA fragmentation factor. Judging by the changes observed, the cumulative dose of copper oxide nanoparticles of 18 mg/kg body weight administered intraperitoneally approximates the threshold one for rats. The established markers of health impairments may serve as a starting point in the development of techniques of early diagnosis of copper poisoning.PMID:37482581 | DOI:10.1038/s41598-023-38976-z

Buckwheat OMICS: present status and future prospects

Sun, 23/07/2023 - 12:00
Crit Rev Biotechnol. 2023 Jul 23:1-18. doi: 10.1080/07388551.2023.2229511. Online ahead of print.ABSTRACTBuckwheat (Fagopyrum spp.) is an underutilized resilient crop of North Western Himalayas belonging to the family Polygonaceae and is a source of essential nutrients and therapeutics. Common Buckwheat and Tatary Buckwheat are the two main cultivated species used as food. It is the only grain crop possessing rutin, an important metabolite with high nutraceutical potential. Due to its inherent tolerance to various biotic and abiotic stresses and a short life cycle, Buckwheat has been proposed as a model crop plant. Nutritional security is one of the major concerns, breeding for a nutrient-dense crop such as Buckwheat will provide a sustainable solution. Efforts toward improving Buckwheat for nutrition and yield are limited due to the lack of available: genetic resources, genomics, transcriptomics and metabolomics. In order to harness the agricultural importance of Buckwheat, an integrated breeding and OMICS platforms needs to be established that can pave the way for a better understanding of crop biology and developing commercial varieties. This, coupled with the availability of the genome sequences of both Buckwheat species in the public domain, should facilitate the identification of alleles/QTLs and candidate genes. There is a need to further our understanding of the molecular basis of the genetic regulation that controls various economically important traits. The present review focuses on: the food and nutritional importance of Buckwheat, its various omics resources, utilization of omics approaches in understanding Buckwheat biology and, finally, how an integrated platform of breeding and omics will help in developing commercially high yielding nutrient rich cultivars in Buckwheat.PMID:37482536 | DOI:10.1080/07388551.2023.2229511

Multi-walled carbon nanotubes enhance the toxicity effects of dibutyl phthalate on early life stages of zebrafish (Danio rerio): Research in physiological, biochemical and molecular aspects

Sun, 23/07/2023 - 12:00
Sci Total Environ. 2023 Jul 21:165684. doi: 10.1016/j.scitotenv.2023.165684. Online ahead of print.ABSTRACTPhthalate esters (PAEs) are widely used as plasticizers. PAEs are ubiquitous in natural water bodies, with dibutyl phthalate (DBP) being one of the most common PAEs. DBP is prone to leaching or migration into the environment, posing serious health and environmental risks. Carbon nanotubes (CNTs) have been widely used in various fields with the rapid development of nanotechnology. CNTs could alter the environmental behavior and toxicity of co-existing pollutants. CNTs have been shown to rapidly adsorb PEAs. However, current knowledge about the effects of CNTs on DBP toxicity is limited. Here we show that the toxic effects of single and combined exposure to DBP (0.1, 0.5, 1.0 mg/L) and different CNTs (MWCNTs/MWCNTs-COOH, 0.5 mg/L) on the early growth stage of zebrafish. The results suggested that a significant increase in heart rate and heart malformation rate was observed after co-exposure of DBP and MWCNTs/MWCNTs-COOH (p < 0.05). Furthermore, combined exposure increased antioxidant enzyme activity during early developmental stages in zebrafish (p < 0.05). The qRT-PCR results revealed that DBP and MWCNTs/MWCNTs-COOH co-exposure significantly interfered with the expression of genes related to oxidative stress, energy metabolism, development of cardiac function and apoptosis (p < 0.05). In addition, for oxidative stress and cardiotoxicity, MWCNTs/MWCNTs-COOH aggravated the toxic effects of 0.5 mg/L DBP on embryos/larvae. The metabolomics results showed that co-exposure mitigated the disturbance of amino acid metabolism mediated by single DBP exposure. In general, MWCNTs/MWCNTs-COOH increased the impact of DBP in the early developmental stages of zebrafish. This study provides new insights into the toxicology of early developmental stages of aquatic organisms exposed to co-exist pollutants of DBP and CNTs.PMID:37482360 | DOI:10.1016/j.scitotenv.2023.165684

Paternal cadmium exposure induces glucolipid metabolic reprogramming in offspring mice via PPAR signaling pathway

Sun, 23/07/2023 - 12:00
Chemosphere. 2023 Jul 21:139592. doi: 10.1016/j.chemosphere.2023.139592. Online ahead of print.ABSTRACTIn industrialized societies, the prevalence of metabolic diseases has substantially increased over the past few decades, yet the underlying causes remain unclear. Cadmium (Cd) is a hazardous heavy metal and pervasive environmental endocrine disruptor. Here, we investigate the effects of paternal Cd exposure on offspring glucolipid metabolism. Paternal Cd exposure (1 mg kg-1 body weight) impaired glucose tolerance, increased random serum glucose and fasting serum insulin, elevated serum total cholesterol, and low-density lipoprotein in offspring mice. Untargeted metabolomics analysis of male offspring liver tissue revealed that paternal Cd exposure can affect offspring glucolipid metabolic reprogramming, which involved biosynthesis of phenylalanine, tyrosine and tryptophan, biosynthesis of unsaturated fatty acids, metabolism of linoleic acid, arachidonic acid and α-linolenic acid. Transcriptome sequencing of male offspring liver tissue showed that arachidonic acid metabolism, AMPK signaling pathway, PPAR signaling pathway and adipocytokine signaling pathway were significantly inhibited in the Cd-exposed group. The mRNA expression levels of PPAR signaling pathway related genes (Acsl1, Cyp4a14, Cyp4a10, Cd36, Ppard and Pck1) were significantly decreased. The protein expression levels of ACSL1, CD36, PPARD and PCK1 were also significantly reduced. Collectively, our findings suggest that paternal Cd exposure affect offspring glucolipid metabolic reprogramming via PPAR signaling pathway.PMID:37482320 | DOI:10.1016/j.chemosphere.2023.139592

Protective effects of scutellaria-coptis herb couple against non-alcoholic steatohepatitis via activating NRF2 and FXR pathways in vivo and in vitro

Sun, 23/07/2023 - 12:00
J Ethnopharmacol. 2023 Jul 21:116933. doi: 10.1016/j.jep.2023.116933. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria-coptis herb couple (SC) is a classic herbal pair used in many Traditional Chinese Medicine (TCM) formulations in the treatment of endocrine and metabolic deseases. Diabetes mellitus and non-alcoholic steatohepatitis (NASH) are both endocrine and metabolic diseases. Previous studies have shown that SC has anti-diabetic effects. However, the effect and mechanism of SC against NASH remains unclear.AIM OF THE STUDY: This study aimed to demonstrate the effect and mechanism of SC against NASH through the nuclear factor-erythroid 2-related factor 2 (Nrf2) and farnesoid X receptor (FXR) dual signaling pathways in vivo and in vitro.MATERIALS AND METHODS: The high fat diet-fed rat model, and HepG2 and RAW264.7 cell models were used. Serum biochemical indexes and liver histopathological changes were examined. Metabolomics, transcriptomics, and flow cytometry were performed. RT-qPCR and western blot analysis were performed to provide expression of NRF2 and FXR pathway signal molecules during SC's anti-NASH treatment in vivo and in vitro.RESULTS: SC had anti-NASH effects in vivo with significantly improvement of serum NASH biochemical index and hepatopathological structure; meanwhile, SC significantly elevated the expression levels of FXR protein in liver and intestinal tissues, and cholesterol 7a-hydroxylase (CYP7A1) protein in liver. The mRNA expression levels of Takeda G protein receptor 5 (TGR5), CYP7A1, fibroblast growth factor receptor-4 (FGFR4), FXR, small heterodimer partner (SHP), fibroblast growth factor 15/19 (FGF15/19) and glucagon-like peptide-1 (GLP-1) were significantly elevated by SC. SC reduced the levels of NorCA, isoLCA and α-MCA in the feces of NAFLD rats. In vitro, SC-containing serum (SC-CS) was found to significantly reduce intracellular lipid deposition, inhibit ROS production, reduce intracellular Malondialdehyde (MDA) and IL-1β levels, and enhance the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Six differential genes closely related to oxidative stress and Nrf2 were identified by transcriptomic analysis. SC-CS up-regulated the expression of NRF2, and reduced the expression of TXNIP and Caspase-1 genes in RAW264.7 cells. In addition, SC-CS reduced the expression of Keap1 and NF-κB, and up-regulated the expression of Nrf2, heme oxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO1), and SOD; SC-CS elevated the protein level of NRF2, and reduced the protein level of TXNIP in HepG2 cells.CONCLUSIONS: the mechanisms of SC action against NASH was closely related to the simultaneous activations of both NRF2 and FXR signaling pathways. These findings provide a new insight into the anti-NASH application of SC in clinical settings and demonstrate the potential of SC in the treatment of NASH.PMID:37482263 | DOI:10.1016/j.jep.2023.116933

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