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

Effect of extrusion temperature on characteristic amino acids, fatty acids, organic acids, and phenolics of white quinoa based on metabolomics

Wed, 31/05/2023 - 12:00
Food Res Int. 2023 Jul;169:112761. doi: 10.1016/j.foodres.2023.112761. Epub 2023 Mar 31.ABSTRACTQuinoa is considered a "full nutritional food" owing to its high nutrition value. However, the whole grain form of quinoa is not always convenient direct consumption in everyday life. Extrusion is effective viable solution to this issue. In this study, the metabolic characterization of white quinoa (WQ) and extruded white quinoa (EWQ) was performed by investigating the characteristic amino acids, fatty acids, organic acids, and phenolic content of WQ after extrusion. A total of 24 amino acids, 25 organic acids, 32 fatty acids and 50 phenolics were identified in both WQ and EWQ, The results showed that extrusion and extrusion temperature significantly (p < 0.05) affect the content of amino acids, fatty acids, organic acids and phenolics in WQ. For example, the content of glutaconic acid (1231.9 μg/g of EWQ-180 to 1926.4 μg/g of WQ) and L-aspartic acid (115.47 μg/g of EWQ-140 to 643.70 μg/g of WQ) in WQ was significantly decreased, while L-serine (138.01 μg/g of WQ to 201.04 μg/g of EWQ-160) was increased respectively after extrusion. Among the EWQ samples, the highest content of glutaconic acid (1447.9 μg/g), L-aspartic acid (270.32 μg/g), and L-serine (201.04 μg/g) was observed in EWQ-160, EWQ-180 and EWQ-160, respectively. These results indicated extrusion affects the content of various amino acids differently and that the changes are dependent on the extrusion temperature. Similar result was also observed for fatty acids, organic acids, and phenolics. In conclusion, extrusion has potential in the processing of quinoas and the metabolic characterization of amino acids, fatty acids, organic acids, and phenolics in grains could be effectively analyzed using metabolomics.PMID:37254376 | DOI:10.1016/j.foodres.2023.112761

Key secondary metabolite markers for Wuchang Daohuaxiang rice discrimination in China

Wed, 31/05/2023 - 12:00
Food Res Int. 2023 Jul;169:112943. doi: 10.1016/j.foodres.2023.112943. Epub 2023 May 8.ABSTRACTThis study aimed to comprehensively elucidate the vital secondary metabolites of Wuchang Daohuaxiang (DHX) rice through widely targeted metabolomics analysis. Among the secondary metabolites detected, a total of 30 differential ones were screened out and categorized into 4 different classes, including 6 alkaloids (20%), 15 flavonoids (50%), 6 phenolic acids (20%), and 3 terpenoids (10%) between DHX and control groups. Of these, compounds as zarzissine, fagomine, arbutin, p-Hydroxypheny-β-D-allopyranoside, pimaric acid, kaurenoic acid, and isopimaric acid were more abundant in DHX than control group, with the possibility in serve as key secondary metabolites of DHX rice. Furthermore, arbutin, trigonelline and 6'-O-Feruloyl-D-sucrose were optimized as potential biomarkers for DHX rice discrimination. This study would supply data support for DHX rice authenticity and quality improvement.PMID:37254367 | DOI:10.1016/j.foodres.2023.112943

Cabernet sauvignon dry red wine ameliorates atherosclerosis in mice by regulating inflammation and endothelial function, activating AMPK phosphorylation, and modulating gut microbiota

Wed, 31/05/2023 - 12:00
Food Res Int. 2023 Jul;169:112942. doi: 10.1016/j.foodres.2023.112942. Epub 2023 May 4.ABSTRACTLimited evidence suggests that the abundance of antioxidant polyphenols in dry red wine (DRW) may prevent cardiovascular diseases, a benefit likely attributed to abundant antioxidant polyphenols present in DRW. Here, we examined the anti-atherosclerotic effect of Cabernet Sauvignon DRW (CSDRW) in a mouse model of atherosclerosis (AS) using metabolomic profiling and molecular techniques. Oral administration of CSDRW reduced atherosclerotic lesion size in ApoE-/- mice, alleviated hyperlipidemia, ameliorated hepatic lipid accumulation mediated by AMPK activation, and promoted lipid metabolism via PPARγ-LXR-α-ABCA1 pathway regulation. CSDRW increased the relative abundance of beneficial gut microbiota, including Bacteroidetes, Verrucomicrobiota, and Akkermansiaceae. Metabolic analysis using liquid chromatography-tandem mass spectrometry revealed that CSDRW contained various polyphenols, including flavanol, phenolic acid, flavonol, and resveratrol, which possibly mediate the beneficial effects in AS by reducing inflammation, restoring normal endothelial function, regulating hepatic lipid metabolism, and modulating gut microbiota composition.PMID:37254366 | DOI:10.1016/j.foodres.2023.112942

An integrated untargeted metabolomic approach reveals the quality characteristics of black soybeans from different geographical origins in China

Wed, 31/05/2023 - 12:00
Food Res Int. 2023 Jul;169:112908. doi: 10.1016/j.foodres.2023.112908. Epub 2023 Apr 29.ABSTRACTBlack soybeans are extensively planted and consumed in China due to their high nutritional value and numerous health benefits. However, very few is known about the characteristic metabolites of black soybeans from different geographical origins in China. In the present study, 31 black soybean samples were collected from 11 main producing provinces in China. A combined metabolomics approach using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and gas chromatography coupled to an Orbitrap mass analyzer (GC-orbitrap-MS) was performed for the first time to comprehensively investigate the metabolite variability among the black soybeans from different geographical origins. A total of 48 differential non-volatile metabolites and 14 differential volatile metabolites were identified based on orthogonal partial least squares discriminant analysis (OPLS-DA) coupled with analysis of variance (ANOVA). Higher procyanidin B1, procyanidin B2, epicatechin, malonylated isoflavones, and β-pinene were observed in Gansu black soybeans. Guangxi black soybeans had higher amounts of linoleic acid and its oxidation products of hexanal and pentane. The black soybeans from Xinjiang and Yunnan were found to have higher delphinidin-derived anthocyanins, gamma-glutamyl peptides, and aromatic hydrocarbons. The characteristic metabolites of black soybeans from other geographical origins were also clarified. This study indicated that the integrated untargeted metabolomic approach can be a powerful tool to provide knowledge for developing specialty black soybeans.PMID:37254343 | DOI:10.1016/j.foodres.2023.112908

Cooperative combination of non-targeted metabolomics and targeted taste analysis for elucidating the taste metabolite profile and pathways of traditional fermented golden pompano

Wed, 31/05/2023 - 12:00
Food Res Int. 2023 Jul;169:112865. doi: 10.1016/j.foodres.2023.112865. Epub 2023 Apr 22.ABSTRACTFermentation plays a key role in taste formation in traditional fermented golden pompano and involves a series of complex metabolic reactions. Indeed, the taste profile of fermented golden pompano exhibits remarkable variation during early fermentation. Herein, nutritional fingerprinting (proteins, amino acids, lipids, etc.) was applied to discriminate the various biomolecular changes involved in golden pompano fermentation. Among the differential metabolites, amino acids, small peptides, lipids, and nucleotides were considered taste-related compounds. An increase in the amino acid content was observed during fermentation, while the peptide content decreased. Glutamic acid, alanine, and lysine had the highest taste activity values and were the main contributors to taste formation. Metabolic pathway enrichment analysis revealed that taste formation was primarily associated with alanine, aspartate, and glutamate metabolism. These findings provide a deeper understanding of taste mechanisms and establish a basis for the targeted regulation of taste formation in the fermented fish industry.PMID:37254315 | DOI:10.1016/j.foodres.2023.112865

Role in aromatic metabolites biodegradation and adverse implication of denitrifying microbiota in kitchen waste composting

Tue, 30/05/2023 - 12:00
Environ Microbiome. 2023 May 30;18(1):44. doi: 10.1186/s40793-023-00496-8.ABSTRACTBACKGROUND: Understanding the functional diversity, composition, and dynamics of microbiome is critical for quality in composting. Denitrifying microbiota, possessing multiple metabolic pathways simultaneously. Denitrification-based biodegradation of aromatic metabolites has been widely applied in the bioremediation of sediments. However, role in biodegradation of denitrifying microbiota in kitchen waste composting remain unclear. In this study, microbiome and metabolome were used to comprehensively decipher the relationship of denitrifying microbiota and aromatic metabolites, and its implication in kitchen waste (KW) composting.RESULTS: This study was investigated by adjusting moisture content 60% as control test (CK), 70% as denitrification test (DE). In addition, one tests referred as DE + C, which received 10% of biochar to amend denitrification. Results indicated the quantities of denitrification genes narG were 1.22 × 108 copies/g in DE at the 55th day, which were significantly higher than that in CK and DE + C (P < 0.05). Similarly, the abundance of nirK gene also significantly increased in DE (P < 0.05). The relative abundance of denitrification-related microbes in DE was higher than that in CK, DE + C could weaken their abundance. Metabolomics results demonstrated that metabolites were downgraded in aromatic amino acid and catechin metabolic pathways in DE, which were identified as precursors to synthesis key product fulvic acid. The concentrations of fulvic acid dramatically decreased 21.05 mg/g in DE comparison with CK. Biochar addition alleviated the biodegradation of aromatic metabolites and reduced the utilization of fulvic acid. Integrative analyses of metabolomics and microbiome suggested that the microbiota involved in nitrite reduction pathway was vital for the biodegradation aromatic metabolites. Mantel test verified that NO3--N, moisture content, eta, environmental factors were important drivers behind the changes in the denitrifying microbiota biodegradation function.CONCLUSION: The data confirm the biodegradation function of denitrifying microbiota led to the loss of core product fulvic acid in KW composting, which highlighted the adverse role and implication of denitrification for composting humification. Control of denitrification with biochar was recommended to improve composting quality.PMID:37254173 | DOI:10.1186/s40793-023-00496-8

Metabolomic and transcriptomic analyses provide insights into variations in flavonoids contents between two Artemisia cultivars

Tue, 30/05/2023 - 12:00
BMC Plant Biol. 2023 May 30;23(1):288. doi: 10.1186/s12870-023-04295-8.ABSTRACTBACKGROUND: Plants in the genus Artemisia are rich in active ingredients and specialized metabolites. Many of these compounds, especially flavonoids, have potential medicinal and nutritional applications, and are of growing interest to scientists due to their wide range of pharmacological and biological activities. Artemisia cultivars are commonly used as raw materials for medicine, food, and moxibustion in China. However, most of the metabolites produced by Artemisia species have not been identified, and few studies have addressed differences in active compounds between species and cultivars.RESULTS: We here investigated two Artemisia cultivars, 'Nanyangshiyong' (NYSY) and 'Nanyangyaoyong' (NYYY), which are commonly used in foods and moxibustion, respectively. NYSY and NYYY were confirmed to be Artemisia argyi cultivars. Total flavonoids contents and antioxidant activities were higher in NYYY than in NYSY. A total of 882 metabolites were identified in the samples; most of the potentially medicinally active compounds, especially flavonoids (e.g., flavone, flavonol, isoflavone, and anthocyanin), were up-regulated in NYYY compared to NYSY. Furthermore, most of the genes related to flavonoids biosynthesis were up-regulated in NYYY. Correlation analysis was used to identify putative members of transcription factor families that may regulate genes encoding key flavonoids biosynthesis enzymes.CONCLUSIONS: We found that the antioxidant activities and flavonoids contents significantly varied between two Artemisia cultivars of the same species. We also uncovered metabolomic and transcriptomic evidence of the molecular phenomena underlying those differences in flavonoids contents between the two Artemisia cultivars. This study provides a wealth of data for future utilization and improvements of Artemisia cultivars, and highlights a need to study the specific metabolite profiles of plants that are used in foods and medicines.PMID:37254042 | DOI:10.1186/s12870-023-04295-8

Author Correction: Metagenomic and metabolomic remodeling in nonagenarians and centenarians and its association with genetic and socioeconomic factors

Tue, 30/05/2023 - 12:00
Nat Aging. 2022 Jul;2(7):680. doi: 10.1038/s43587-022-00258-0.NO ABSTRACTPMID:37253873 | DOI:10.1038/s43587-022-00258-0

Newborn metabolomic signatures of maternal per- and polyfluoroalkyl substance exposure and reduced length of gestation

Tue, 30/05/2023 - 12:00
Nat Commun. 2023 May 30;14(1):3120. doi: 10.1038/s41467-023-38710-3.ABSTRACTMarginalized populations experience disproportionate rates of preterm birth and early term birth. Exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to reduce length of gestation, but the underlying mechanisms are unknown. In the present study, we characterized the molecular signatures of prenatal PFAS exposure and gestational age at birth outcomes in the newborn dried blood spot metabolome among 267 African American dyads in Atlanta, Georgia between 2016 and 2020. Pregnant people with higher serum perfluorooctanoic acid and perfluorohexane sulfonic acid concentrations had increased odds of an early birth. After false discovery rate correction, the effect of prenatal PFAS exposure on reduced length of gestation was associated with 8 metabolomic pathways and 52 metabolites in newborn dried blood spots, which suggested perturbed tissue neogenesis, neuroendocrine function, and redox homeostasis. These mechanisms explain how prenatal PFAS exposure gives rise to the leading cause of infant death in the United States.PMID:37253729 | DOI:10.1038/s41467-023-38710-3

Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations

Tue, 30/05/2023 - 12:00
Nat Commun. 2023 May 30;14(1):3111. doi: 10.1038/s41467-023-38800-2.ABSTRACTCirculating metabolite levels may reflect the state of the human organism in health and disease, however, the genetic architecture of metabolites is not fully understood. We have performed a whole-genome sequencing association analysis of both common and rare variants in up to 11,840 multi-ethnic participants from five studies with up to 1666 circulating metabolites. We have discovered 1985 novel variant-metabolite associations, and validated 761 locus-metabolite associations reported previously. Seventy-nine novel variant-metabolite associations have been replicated, including three genetic loci located on the X chromosome that have demonstrated its involvement in metabolic regulation. Gene-based analysis have provided further support for seven metabolite-replicated loci pairs and their biologically plausible genes. Among those novel replicated variant-metabolite pairs, follow-up analyses have revealed that 26 metabolites have colocalized with 21 tissues, seven metabolite-disease outcome associations have been putatively causal, and 7 metabolites might be regulated by plasma protein levels. Our results have depicted the genetic contribution to circulating metabolite levels, providing additional insights into understanding human disease.PMID:37253714 | DOI:10.1038/s41467-023-38800-2

Fecal microbiota transplantation ameliorates type 2 diabetes via metabolic remodeling of the gut microbiota in db/db mice

Tue, 30/05/2023 - 12:00
BMJ Open Diabetes Res Care. 2023 May;11(3):e003282. doi: 10.1136/bmjdrc-2022-003282.ABSTRACTINTRODUCTION: Gut microbiome (GM) deregulation has been implicated in major conditions such as obesity and type 2 diabetes (T2DM). Our previous prospective study indicated that fecal microbiota transplantation (FMT) successfully improved patients with T2DM. We hypothesized that FMT may be a potential therapeutic method for T2DM, but its precise mechanisms in T2DM remains to be elucidated.RESEARCH DESIGN AND METHODS: Eight db/m mice were FMT donors and control mice, and 16 genetically diabetic db/db mice were equally divided into two groups (db/db+phosphate-buffered saline (PBS) group, db/db+FMT group). The db/db+FMT group was administered fresh fecal suspension (0.2 mL/mice) daily for 4 weeks. Analysis of the GM and serum metabolome was carried out by 16S ribosomal RNA sequencing and liquid chromatogram-mass spectrometry, respectively. Effects of FMT on the gut barrier and pancreas were assessed using protein assays, messenger RNA, immunohistology and clinical indicators testing.RESULTS: Our results showed that FMT treatment of db/db mice relieves a series of clinical indicators, including fasting plasma glucose, serum insulin and oral glucose tolerance test among others. Compared with non-diabetic control mice, db/db+PBS mice exhibited decreased abundance of Ruminococaceae, Porphyromonadaceae and increased abundance of Rikenellaceae and Lactobacillaceae. FMT treatment reversed this effect on the microbiome. Eleven metabolites were changed between the db/db+PBS and db/db+FMT groups. Correlation analysis showed that the structural changes of the GM were correlated with host metabolite levels. We further showed that FMT treatment of db/db mice improved intestinal barrier function, reduced inflammation and caused an alteration in the number of circulating immune cells.CONCLUSIONS: FMT-mediated changes in the GM, serum metabolites, intestinal epithelial barrier, inflammation and circulating immune cells play an important role in the efficacy of FMT on T2DM disease progression.PMID:37253485 | DOI:10.1136/bmjdrc-2022-003282

Metabolomic Profile by GC-MS and Antioxidant, Antidiabetic and Anti-inflammatory Activities of Green Solvent Extracts of Heterospathe elata leaves

Tue, 30/05/2023 - 12:00
Chem Biodivers. 2023 May 30:e202300340. doi: 10.1002/cbdv.202300340. Online ahead of print.ABSTRACTPlants are the prime source of phytoconstituents that can act as potent agents for the prevention and treatment of various diseases. Heterospathe elata is a plant belonging to the Arecaceae family having numerous medicinal properties. The present study was undertaken to prepare crude extracts of Heterospathe elata leaves with solvents of different polarity dimethyl carbonate (DMC), isopropyl alcohol (IPA), hydro alcohol (HYA) and water (WTR) by using successive soxhlet extraction method. Further, the antioxidant, antidiabetic, and anti-inflammatory activities were assessed by the spectrophotometric method and possible bioactive phytoconstituents from the hydro alcohol extract of Heterospathe elata leaves using GC-MS. In our study, it was found that the GC-MS analysis revealed the presence of nineteen bioactive phytoconstituents. The highest antioxidant activity was found in the water extract. In antidiabetic and anti-inflammatory activity highest potential was shown by hydro alcohol extract and the lowest was in the dimethyl carbonate extract. These findings support the Heterospathe elata leaves showed the high biological potential attributed to a high amount of bioactive phytoconstituents and could be utilized as value-added functional food and medicine.PMID:37253201 | DOI:10.1002/cbdv.202300340

Immunogenetic metabolomics reveals key enzymes that modulate CAR T-cell metabolism and function

Tue, 30/05/2023 - 12:00
Cancer Immunol Res. 2023 May 30:CIR-22-0565. doi: 10.1158/2326-6066.CIR-22-0565. Online ahead of print.ABSTRACTImmune evasion is a critical step of cancer progression that remains a major obstacle for current T cell-based immunotherapies. Hence, we investigated whether it is possible to genetically reprogram T cells to exploit a common tumor-intrinsic evasion mechanism whereby cancer cells suppress T-cell function by generating a metabolically unfavorable tumor microenvironment (TME). In an in silico screen, we identified ADA and PDK1 as metabolic regulators. We then showed that overexpression (OE) of these genes enhanced the cytolysis of CD19-specific chimeric-antigen receptor (CAR) T cells against cognate leukemia cells, and conversely, ADA or PDK1 deficiency dampened this effect. ADA-OE in CAR T cells improved cancer cytolysis under high concentrations of adenosine, the ADA substrate and an immunosuppressive metabolite in the TME. High-throughput transcriptomics and metabolomics analysis of these CAR T cells revealed alterations of global gene expression and metabolic signatures in both ADA- and PDK1-engineered CAR T cells. Functional and immunological analyses demonstrated that ADA-OE increased proliferation and decreased exhaustion in CD19-specific and HER2-specific CAR T cells. ADA-OE improved tumor infiltration and clearance by HER2-specific CAR T cells in an in vivo colorectal cancer model. Collectively, these data unveil systematic knowledge of metabolic reprogramming directly in CAR T cells and reveal potential targets for improving CAR T-cell therapy.PMID:37253111 | DOI:10.1158/2326-6066.CIR-22-0565

Characterization of <em>Cinnamomum kanehirae</em> Extract-Stimulated Triterpenoids Synthesis in Submerged Fermentation of <em>Antrodia camphorata</em> via Untargeted Metabolomics

Tue, 30/05/2023 - 12:00
J Agric Food Chem. 2023 May 30. doi: 10.1021/acs.jafc.3c01508. Online ahead of print.ABSTRACTThe underlying mechanisms of Cinnamomum kanehirae-stimulated growth and metabolism of Antrodia camphorata remain unknown. Herein, we first observed that the methanol extract of C. kanehirae trunk (MECK) (2 g/L) showed a potent stimulatory effect on A. camphorata triterpenoids production (115.6 mg/L). Second, MECK treatment considerably increased the category and abundance of many secondary metabolites in the mycelia. We identified 93 terpenoids (8 newly formed and 49 upregulated) in the MECK-treated mycelia, wherein 21 terpenoids were the same as those in the fruiting bodies. Third, 42 out of the 93 terpenoids were annotated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, mainly involving monoterpenoids and diterpenoids syntheses. Finally, 27 monoterpenes and 16 sesquiterpenes were detected in the MECK, and the two terpenoids with the highest abundance (linalool and α-pinene) were selected for verification and found to considerably increase the terpenoids production of A. camphorata and demonstrate the regulation of mRNA expression levels of nine key genes in the mevalonate pathway via RT-qPCR. This study is beneficial for elucidating the terpenoids synthesis mechanism in A. camphorata.PMID:37252901 | DOI:10.1021/acs.jafc.3c01508

Dihydroxy-Metabolites of Dihomo-γ-linolenic Acid Drive Ferroptosis-Mediated Neurodegeneration

Tue, 30/05/2023 - 12:00
ACS Cent Sci. 2023 Mar 16;9(5):870-882. doi: 10.1021/acscentsci.3c00052. eCollection 2023 May 24.ABSTRACTEven after decades of research, the mechanism of neurodegeneration remains understudied, hindering the discovery of effective treatments for neurodegenerative diseases. Recent reports suggest that ferroptosis could be a novel therapeutic target for neurodegenerative diseases. While polyunsaturated fatty acid (PUFA) plays an important role in neurodegeneration and ferroptosis, how PUFAs may trigger these processes remains largely unknown. PUFA metabolites from cytochrome P450 and epoxide hydrolase metabolic pathways may modulate neurodegeneration. Here, we test the hypothesis that specific PUFAs regulate neurodegeneration through the action of their downstream metabolites by affecting ferroptosis. We find that the PUFA dihomo-γ-linolenic acid (DGLA) specifically induces ferroptosis-mediated neurodegeneration in dopaminergic neurons. Using synthetic chemical probes, targeted metabolomics, and genetic mutants, we show that DGLA triggers neurodegeneration upon conversion to dihydroxyeicosadienoic acid through the action of CYP-EH (CYP, cytochrome P450; EH, epoxide hydrolase), representing a new class of lipid metabolites that induce neurodegeneration via ferroptosis.PMID:37252355 | PMC:PMC10214511 | DOI:10.1021/acscentsci.3c00052

Interpretable Machine Learning on Metabolomics Data Reveals Biomarkers for Parkinson's Disease

Tue, 30/05/2023 - 12:00
ACS Cent Sci. 2023 May 9;9(5):1035-1045. doi: 10.1021/acscentsci.2c01468. eCollection 2023 May 24.ABSTRACTThe use of machine learning (ML) with metabolomics provides opportunities for the early diagnosis of disease. However, the accuracy of ML and extent of information obtained from metabolomics can be limited owing to challenges associated with interpreting disease prediction models and analyzing many chemical features with abundances that are correlated and "noisy". Here, we report an interpretable neural network (NN) framework to accurately predict disease and identify significant biomarkers using whole metabolomics data sets without a priori feature selection. The performance of the NN approach for predicting Parkinson's disease (PD) from blood plasma metabolomics data is significantly higher than other ML methods with a mean area under the curve of >0.995. PD-specific markers that predate clinical PD diagnosis and contribute significantly to early disease prediction were identified including an exogenous polyfluoroalkyl substance. It is anticipated that this accurate and interpretable NN-based approach can improve diagnostic performance for many diseases using metabolomics and other untargeted 'omics methods.PMID:37252351 | PMC:PMC10214508 | DOI:10.1021/acscentsci.2c01468

Serum-free alginate-C2C12 cells microcapsule as a model of alternative animal protein source

Tue, 30/05/2023 - 12:00
Front Nutr. 2023 May 11;10:1184178. doi: 10.3389/fnut.2023.1184178. eCollection 2023.ABSTRACTDue to the climate change crisis, and environmental impacts of the traditional meat sector, the production of artificial animal protein based on in vitro cell culture technology is proposed as an alternative. Furthermore, since traditional animal serum-supplemented cultures pose scientific challenges such as batch variation and contamination risks, artificial animal protein cultures are currently in urgent need of not only serum-free cultures, but also microcarrier culture systems for scalability. However, serum-free microcarrier-based culture system for the differentiation of muscle cells is not available to date. Therefore, we established an edible alginate microcapsules culture system for the differentiation of C2C12 cells in serum-free conditions. Furthermore, metabolites related to central carbon metabolism were profiled based on targeted metabolomics using mass spectrometry. The C2C12 cells cultured in alginate microcapsules displayed high viability throughout 7 days and successfully differentiated within 4 days in serum and serum-free cultures except for AIM-V cultures, which was confirmed by CK activity and MHC immunostaining. Lastly, to the best of our knowledge, this is the first report to compare metabolite profiles between monolayer and alginate microcapsule culture systems. Alginate microcapsule culture showed higher levels of intracellular glycolysis and TCA cycle intermediates, lactate, and the contribution of essential amino acids compared to the monolayer culture. We believe our serum-free alginate microcapsule culture system is adaptable to different species of muscle cells and contributes to future food technology as a proof of concept for the scalability of alternative animal protein source production.PMID:37252232 | PMC:PMC10213942 | DOI:10.3389/fnut.2023.1184178

Using a multi-omic approach to investigate the mechanism of 12-bis-THA activity against <em>Burkholderia thailandensis</em>

Tue, 30/05/2023 - 12:00
Front Microbiol. 2023 May 12;13:1092230. doi: 10.3389/fmicb.2022.1092230. eCollection 2022.ABSTRACTBurkholderia pseudomallei is the causative agent of the tropical disease, melioidosis. It is intrinsically resistant to many antimicrobials and treatment requires an onerous regimen of intravenous and orally administered drugs. Relapse of disease and high rates of mortality following treatment are common, demonstrating the need for new anti-Burkholderia agents. The cationic bola-amphiphile, 12,12'-(dodecane-1,12-diyl) bis (9-amino-1,2,3,4-tetrahydroacridinium), referred to as 12-bis-THA, is a molecule with the potential to treat Burkholderia infections. 12-bis-THA spontaneously forms cationic nanoparticles that bind anionic phospholipids in the prokaryotic membrane and are readily internalized. In this study, we examine the antimicrobial activity of 12-bis-THA against strains of Burkholderia thailandensis. As B. pseudomallei produces a polysaccharide capsule we first examined if this extra barrier influenced the activity of 12-bis-THA which is known to act on the bacterial envelope. Therefore two strains of B. thailandensis were selected for further testing, strain E264 which does not produce a capsule and strain E555 which does produce a capsule that is chemically similar to that found in B. pseudomallei. In this study no difference in the minimum inhibitory concentration (MIC) was observed when capsulated (E555) and unencapsulated (E264) strains of B. thailandensis were compared, however time-kill analysis showed that the unencapsulated strain was more susceptible to 12-bis-THA. The presence of the capsule did not affect the membrane permeation of 12-bis-THA at MIC concentrations. Proteomic and metabolomic analyses showed that 12-bis-THA causes a shift in central metabolism away from glycolysis and glyoxylate cycle, and suppressed the production of the F1 domain of ATP synthase. In summary, we provide insight into the molecular mechanisms underpinning the activity of 12-bis-THA against B. thailandensis and discuss its potential for further development.PMID:37252207 | PMC:PMC10213367 | DOI:10.3389/fmicb.2022.1092230

Vascular Endothelial Growth Factor Genetic Variant Is Associated with in-Stent Restenosis after Percutaneous Coronary Intervention

Tue, 30/05/2023 - 12:00
J Tehran Heart Cent. 2022 Jul;17(3):119-126. doi: 10.18502/jthc.v17i3.10844.ABSTRACTBACKGROUND: In-stent restenosis (ISR) is an inevitable complication of percutaneous coronary intervention, with genetic factors thought to play a role in its pathogenesis. The vascular endothelial growth factor (VEGF) gene can have an inhibitory effect on ISR development. Accordingly, in the present study, we investigated the role of -2549 VEGF (insertion/deletion [I/D]) variants in ISR formation.METHODS: Patients with ISR (ISR+) (n=53) and patients without ISR (ISR-) (n=67) were enrolled in this case-control study based on follow-up angiography 1 year after percutaneous coronary intervention between 2019 and 2020. The clinical characteristics of the patients were evaluated, and the frequencies of the alleles and genotypes of -2549 VEGF (I/D) variants were determined using polymerase chain reaction. The χ2 test was performed for the calculation of genotypes and alleles. A P value of less than 0.05 was considered the level of significance.RESULTS: This study recruited 120 individuals at a mean age of 61.43±8.91 years in the ISR+ group and 62.09±7.94 years in the ISR- group. Women and men, respectively, comprised 26.4% and 73.6% of the ISR+ group and 43.3% and 56.7% of the ISR- group. A significant association was observed between the VEGF -2549 genotype frequency and ISR. The frequency of the insertion/insertion (I/I) allele was significantly higher in the ISR+ group than in the ISR- group, while the frequency of the D/D allele was higher in the latter group.CONCLUSION: Regarding ISR development, the I/I allele may be a risk allele and the D/D allele a protective allele.PMID:37252077 | PMC:PMC10222935 | DOI:10.18502/jthc.v17i3.10844

Comprehensive analysis of untargeted metabolomics and lipidomics in girls with central precocious puberty

Tue, 30/05/2023 - 12:00
Front Pediatr. 2023 May 12;11:1157272. doi: 10.3389/fped.2023.1157272. eCollection 2023.ABSTRACTOBJECTIVE: Central precocious puberty (CPP) is a rare condition that causes early sexual development in children. Although the cure is effective, the etiology of central precocious puberty is unclear.METHODS: In total, 10 girls with central precocious puberty and same number of age-matched female controls were enrolled. Plasma samples were collected from each participant and subjected to untargeted metabolomics and lipidomics. Student's t-tests were employed to compare the mean of each metabolite and lipid. Furthermore, orthogonal partial least-squares discriminant analysis was conducted and the variable importance in the projection was calculated to identify differentially expressed metabolites or lipids. Subsequent bioinformatics was conducted to investigate the potential function of differentially expressed metabolites and lipids.RESULTS: Fifty-nine differentially expressed metabolites were identified based on the criteria used (variable importance in the projection >1 and a P value < 0.05). Kyoto Encyclopedia Genes and Genome (KEGG) enrichment analysis showed that differentially expressed metabolites were enriched in four pathways: beta-alanine metabolism, histidine metabolism, bile secretion, and steroid hormone biosynthesis. As for the lipidomics, 41 differentially expressed lipids were observed and chain length analysis and lipid saturation analysis yielded similar results. Significant differences between the two groups were only observed in (O-acyl) ω-hydroxy fatty acids (OAHFA).CONCLUSION: The present study showed that antibiotic overuse, increased meat consumption, and obesity may have potential roles in the development of central precocious puberty in girls. Several metabolites have diagnostic value but further research is required.PMID:37252040 | PMC:PMC10213437 | DOI:10.3389/fped.2023.1157272

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