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

Frontiers in NMR metabolomics

Tue, 21/11/2023 - 12:00
Magn Reson Chem. 2023 Dec;61(12):627. doi: 10.1002/mrc.5400.NO ABSTRACTPMID:37987217 | DOI:10.1002/mrc.5400

NMR metabolomic modelling of age and lifespan: a multi-cohort analysis

Tue, 21/11/2023 - 12:00
medRxiv. 2023 Nov 8:2023.11.07.23298200. doi: 10.1101/2023.11.07.23298200. Preprint.ABSTRACTMetabolomic age models have been proposed for the study of biological aging, however they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age-related disease. 98 metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈ 31,000 individuals, age range 24-86 years). We used non-linear and penalised regression to model CA and time to all-cause mortality. We examined associations of four new and two previously published metabolomic age models, with ageing risk factors and phenotypes. Within the UK Biobank (N≈ 102,000), we tested prediction of CA, incident disease (cardiovascular disease (CVD), type-2 diabetes mellitus, cancer, dementia, chronic obstructive pulmonary disease) and all-cause mortality. Cross-validated Pearson's r between metabolomic age models and CA ranged between 0.47-0.65 in the training set (mean absolute error: 8-9 years). Metabolomic age models, adjusted for CA, were associated with C-reactive protein, and inversely associated with glomerular filtration rate. Positively associated risk factors included obesity, diabetes, smoking, and physical inactivity. In UK Biobank, correlations of metabolomic age with chronological age were modest ( r = 0.29-0.33), yet all metabolomic model scores predicted mortality (hazard ratios of 1.01 to 1.06 / metabolomic age year) and CVD, after adjustment for CA. While metabolomic age models were only moderately associated with CA in an independent population, they provided additional prediction of morbidity and mortality over CA itself, suggesting their wider applicability.PMID:37986811 | PMC:PMC10659522 | DOI:10.1101/2023.11.07.23298200

Widely targeted metabolic profiling provides insights into variations in bioactive compounds and antioxidant activity of sesame, soybean, peanut, and perilla

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113586. doi: 10.1016/j.foodres.2023.113586. Epub 2023 Oct 14.ABSTRACTOilseeds are important sources of diversified nutraceuticals with marked health attributes. Thus, a better understanding of metabolome differences between common oilseeds will be conducive to the food pharmacy. This study aimed to compare the metabolite profiles and antioxidant activity of sesame, soybean, peanut, and perilla seeds and reveal the variation in bioactive compounds. LC-MS-based widely targeted metabolic profiling identified a total of 975 metabolites, of which 753 were common to the four crops. Multivariate analyses unveiled a crop-specific accumulation of metabolites, with 298-388 DAMs (differentially accumulated metabolites) identified. Amino acid metabolism, phenylpropanoid biosynthesis, flavonoid biosynthesis, and lipid metabolism were the most differentially regulated pathways. Furthermore, we revealed the variation in the relative content of 48, 20, 18, 9, 18, 11, and 6 differentially accumulated bioactive flavonoids, phenolic acids, amino acids, vitamins, terpenoids, alkaloids, and coumarins, respectively. Most of the flavonoids accumulated highly in soybean, followed by perilla. Sesame exhibited a better amino acid profile than other oilseeds. DPPH and FRAP assays showed that the antioxidant activity of perilla seed extracts was the highest, followed by soybean, peanut, and sesame. Our results provide data support for the comprehensive use of sesame, perilla, soybean, and peanut seeds in food, and pharmaceutical industries.PMID:37986527 | DOI:10.1016/j.foodres.2023.113586

Untargeted metabolomics provide new insights into the implication of Lactobacillus helveticus strains isolated from natural whey starter in methylglyoxal-mediated browning

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113644. doi: 10.1016/j.foodres.2023.113644. Epub 2023 Oct 26.ABSTRACTHard cheeses may occasionally show a brown discolouration during ripening due to multifactorial phenomena that involve bacteria and give rise to pyrazines arising from methylglyoxal. The present work aimed at developing a novel approach to investigate the role of natural starters in browning. To this object, 11 strains of L. helveticus were incubated in a medium containing 10 % rennet casein dissolved in whey, and then growth was monitored by measuring pH and number of genomes/mL. Browning was assessed through CIELab analysis, methylglyoxal production was determined by targeted mass spectrometry, and untargeted metabolomics was used to extrapolate marker compounds associated with browning discoloration. The medium allowed the growth of all the strains tested and differences in colour were observed, especially for strain A7 (ΔE* value 15.92 ± 0.27). Noteworthy, this strain was also the higher producer of methylglyoxal (2.44 µg/mL). Metabolomics highlighted pyrazines and β-carboline compounds as markers of browning at 42 °C and 16 °C, respectively. Moreover, multivariate statistics pointed out differences in free amino acids and oligopeptides linked to proteolysis, while 1,2-propanediol and S-Lactoylglutathione suggested specific detoxification route in methylglyoxal-producing strains. Our model allowed detecting differences in browning amid strains, paving the way towards the study of individual L. helveticus strains to identify the variables leading to discoloration or to study the interaction between different strains in natural whey starters.PMID:37986486 | DOI:10.1016/j.foodres.2023.113644

Impact of storage time on non-volatile metabolites and fungal communities in Liupao tea using LC-MS based non-targeted metabolomics and high-throughput sequencing

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113615. doi: 10.1016/j.foodres.2023.113615. Epub 2023 Oct 25.ABSTRACTLong-term storage of Liupao tea (LPT) is usually believed to enhance its quality and commercial value. The non-volatile metabolites variations and the fungal succession play a key role for organoleptic qualities during the storage procedure. To gain in-depth understanding the impact of storage time on the quality of LPT, two different brands of LPT with different storage time, including Maosheng LPTs (MS) with 0, 5, 10 and 15 years and Tianyu LPTs (TY) with 0, 3, 5, 8 and 10 years, were resorted to investigate the changes of non-volatile metabolites and fungi as well as their correlation by multi-omics. A total of 154 and 119 differential metabolites were identified in these two different brands of MS and TY, respectively, with the aid of high-performance liquid chromatography with quadrupole-time-of-flight mass spectrometry. In both categories of LPTs, the transformation of differential metabolites in the various stages referred to the formation of alkaloids, increase of organic acids, biosynthesis of terpenoids as well as glycosylation and methylation of flavonoids. Thereinto, glycosylation and methylation of flavonoids were the critical stages for distinguishing MS and TY, which were discovered in MS and TY stored for about 10 and 8 years, respectively. Moreover, the results of high-throughput sequencing showed that the key fungal genera in the storage of LPTs consisted of Eurotium, Aspergillus, Blastobotrys, Talaromyces, Thermomyces and Trichomonascus. It was confirmed on the basis of multivariate analysis that the specific fungal genera promoted the transformation of metabolites, affecting the tea quality to some extent. Therefore, this study provided a theoretical basis for the process optimization of LPT storage.PMID:37986470 | DOI:10.1016/j.foodres.2023.113615

Metabolomic and transcriptomic integrated analysis revealed the decrease of monoterpenes accumulation in table grapes during long time low temperature storage

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113601. doi: 10.1016/j.foodres.2023.113601. Epub 2023 Oct 14.ABSTRACTLow temperature is the commonly used technique for maintaining the quality of table grapes during postharvest storage. However, this technique could strongly affect the aromatic flavor of fruit. Monoterpenes are the key compounds contributing to the Muscat aromas of grapes. The detailed information and molecular mechanisms underlying the changes in monoterpenes during postharvest low temperature storage have not been thoroughly characterized. In this study, the effects of low temperature storage on the free and bound monoterpene profiles in four cultivars of table grape were determined at both the transcriptomic and metabolomic levels. A total of 27 compounds in both free and bound forms were identified in the four cultivars and showed quantitative differences between the cultivars. Hierarchical cluster and principal component analysis indicated that the free and bound monoterpene profiles were remarkably affected by the low temperature storage. The monoterpenes in the same biosynthesis pathway were clustered together and showed similar evolution trends during low temperature storage. And the content of most of free monoterpenes underwent a rapid decline during low-temperature storage at a certain stage, but the time was different in 4 grape cultivars. Transcriptomic analysis revealed that the expression of DXS, HDR, GPPS and TPS genes involved in the monoterpene synthesis pathway were consistent with the changes in the accumulation of monoterpene compounds. While the expression of HMGS, HMGR genes in MVA pathway and branch genes GGPPS and FPPS were negatively correlated with the accumulation of monoterpenes. The findings provide new insights into the underlying mechanisms of the berry aroma flavor change during low temperature storage.PMID:37986463 | DOI:10.1016/j.foodres.2023.113601

Unveiling targeted spatial metabolome of rice seed at the dough stage using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry imaging

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113578. doi: 10.1016/j.foodres.2023.113578. Epub 2023 Oct 10.ABSTRACTRice (Oryza sativa) seeds contain a variety of metabolites, which not only provide energy for their own growth and development, but also are an important source of nutrition for humans. It is crucial to study the distribution of metabolites in rice seeds, but the spatial metabolome of rice seeds is rarely investigated. In this study, Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) imaging was used to reveal the spatial distribution of free soluble sugars (glucose, fructose, sucrose, and maltose), amino acids (9 essential amino acids and 2 amino acids affecting rice eating quality: L-aspartic acid and L-glutamic acid), and 4 metabolites in the flavonoids synthesis pathway (cinnamic acid, naringenin chalcone, naringenin, and dihydrokaempferol) in rice seed at the dough stage. It was found that the 4 free soluble sugars present similar spatial distribution, mainly distributed in the seed cortex and embryo with high abundance. The majority of amino acids are also concentrated in the rice cortex and embryo, while the others are abundant in the whole seed. Besides cinnamic acid distributed in the seed cortex and embryo, the naringenin chalcone, naringenin, and dihydrokaempferol were also found in the endosperm and had lower content. Furthermore, a colocalization phylogenetic tree according to the spatial distribution imaging of each metabolite was constructed. This study revealed the distribution diversity of metabolites in different segmentations of rice seed at the dough stage, providing clues for the nutritional differences between brown rice and white rice, and serving as a reference for people to target a healthy diet.PMID:37986446 | DOI:10.1016/j.foodres.2023.113578

Synergistic effect rescue animal model from NASH caused by diet-inflammation inducer

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113562. doi: 10.1016/j.foodres.2023.113562. Epub 2023 Oct 10.ABSTRACTExcessive intake of pro-inflammatory fatty acids is related to the development of insulin resistance, impaired oxidative stress enzymes, and lipid disorders, leading to inflammation and development of non-alcoholic steatohepatitis (NASH). Diet and physical exercise are considered to prevent and treat metabolic disorders caused by chronic inflammatory states (responsible for insulin resistance and diabetes type 2) in individuals with obesity and nonalcoholic fatty liver diseases (NAFLD). Our investigation tested the hypothesis that Hass avocado oil, a monounsaturated fatty acid and a source of phytosterol, may improve liver and metabolic parameters without adverse effects when combined with physical exercise. Rats ingested a high-fat diet for seven weeks and were then subjected to more six weeks with a standard diet, Hass avocado-oil ingestion, and swimming. The intervention showed significantly improvements by synergistic effect between Hass avocado-oil and swimming exercise (P < 0.05), including improving adiponectin, leptin, and fasting blood glucose levels, alleviating insulin resistance, reducing serum TNF-α, improving glutathione enzyme levels, and decreasing lipotoxicity in the liver and blood and serum triacylglycerides in blood (P < 0.05). Liver tissue markers of apoptosis and necrosis such as CK-18 filaments and dimethylamine (DMA) were significantly higher in the intervention group (P < 0.05). We were unable to fully confirm our hypothesis. Although the synergistic effects between Hass avocado-oil and the swimming regimen offer a promising chance of recovering liver health by improving 10 health biological markers, we must not ignore the cellular damage due to apoptosis and necrosis in liver cells and DMA. The data on metabolomic profile and avocado-oil-treated livers highlight the need for further investigation.PMID:37986439 | DOI:10.1016/j.foodres.2023.113562

Role of short germination and milling on physical properties, amino acid and metabolomic profiles of high amylose rice fractions

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113556. doi: 10.1016/j.foodres.2023.113556. Epub 2023 Oct 4.ABSTRACTShort germination is a process that can improve bioactive compounds in rice. This work aimed investigate the physical properties, phenolic compounds (PC), antioxidant activity and amino acids composition of husk + bran, brown and milled rice with high amylose content after short germination (16 h). α-amylase activity (Falling Number, FN) and enthalpy (ΔH) were unchanged (p < 0.05). RVA curve profiles were similar, even though after short germination and milling. Globally, metabolomics analysis identified 117 PC, in which 111 (bound), 104 (free) and 21 revealed in both extracts. p-Coumaric, trans-ferulic and ferulic acids were the most abundant PC revealed in all fractions. The portion husk + bran showed the highest level of total antioxidant activity (709.90 µmol TE) in both free and bound fractions. In terms of total amino acids, there was no statistical difference (p < 0.05) among non-germinated and germinated samples, contrary to free amino acids content. Glutamic acid (Glu) presented the highest values combining short germination and milling (1725-1900 mg/100 g) consequently, leads to higher value of GABA (12.21 mg/100 g). The combination of short germination and milling demonstrated a good strategy to improve the nutritional quality of rice, unless the thermal and pasting properties have been altered, contribute to potential health benefits on human nutrition.PMID:37986434 | DOI:10.1016/j.foodres.2023.113556

Effect of lactic acid bacteria co-fermentation on antioxidant activity and metabolomic profiles of a juice made from wolfberry and longan

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113547. doi: 10.1016/j.foodres.2023.113547. Epub 2023 Oct 4.ABSTRACTLactic acid bacteria (LAB) fermentation is frequently employed to improve the nutritional, functional, and sensory characteristics of foods. Our study explored the effects of co-fermentation with Lacticaseibacillus paracasei ZH8 and Lactococcus lactis subsp. lactis YM313 on the physicochemical properties, antioxidant activity, and metabolomic profiles of wolfberry-longan juice (WLJ). Fermentation was carried out at 35 °C for 15 h. The results suggest that WLJ is a favorable substrate for LAB growth, reaching a total viable count exceeding 8 log CFU/mL after fermentation. LAB fermentation increased acidity, reduced the sugar content, and significantly impacted the juice color. The total phenolic and flavonoid contents of the WLJ and the antioxidant capacities based on 2,2-diphenyl-1-picrylhydrazyl (DPPH), ABTS radical scavenging abilities and FRAP were significantly improved by LAB fermentation. Nontargeted metabolomics analysis suggested that the contents of small molecule substances in WLJ were considerably affected by LAB fermentation. A total of 374 differential metabolites were identified in the juice before and after fermentation, with 193 significantly upregulated metabolites and 181 siginificantly downregulated metabolites. The regulation of metabolites is important for improving the flavor and functions of juices, such as L-eucylproline, Isovitexin, Netivudine, 3-Phenyllactic acid, vanillin, and ethyl maltol, ect. This study provides a theoretical foundation for developing plant-based foods fermented with LAB.PMID:37986427 | DOI:10.1016/j.foodres.2023.113547

Multi-omics analysis reveals the microbial interactions of S. cerevisiae and L. plantarum on Suanyu, Chinese traditional fermented fish

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113525. doi: 10.1016/j.foodres.2023.113525. Epub 2023 Sep 27.ABSTRACTS. cerevisiae and L. plantarum play important roles in Suanyu fermentation. This study investigated the interaction between S. cerevisiae and L. plantarum during fermentation and its impact on metabolic pathways. Co-culturing S. cerevisiae and L. plantarum increased pH to 5.72, reduced TVB-N to 9.47 mg/mL, and achieved high utilization rates of sugars (98.9%) and proteins (73.7%). During microbial interactions, S. cerevisiae and L. plantarum produced antibiotics, including phenyllactate and Gentamicin C1a, inhibiting the growth of each other. S. cerevisiae used S-adenosyl-l-methionine to counteract acid production of L. plantarum, establishing dominance in Suanyu fermentation. Microbial interactions influenced carbohydrate and energy metabolism pathways, such as nicotinate and nicotinamide metabolism and purine metabolism. S. cerevisiae significantly impacted gene expression in protein synthesis and cell growth pathways, including ribosome, SNARE interactions, basal transcription factors, and MAPK signaling. These findings offer insights into microbial interactions and metabolic processes during Suanyu fermentation.PMID:37986426 | DOI:10.1016/j.foodres.2023.113525

Integrated metabolomics and network pharmacology to reveal antioxidant mechanisms and potential pharmacological ingredients of citrus herbs

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113514. doi: 10.1016/j.foodres.2023.113514. Epub 2023 Sep 28.ABSTRACTThe benefits of citrus herbs are strongly associated with their secondary metabolites. In the study, we conducted widely-targeted metabolomics and ultra-high performance liquid chromatography (UPLC) to compare the variability of ingredients in four citrus herbs. In total, we discovered 1126 secondary metabolites, primarily comprising flavonoids, phenolic acids, lignans and coumarins, and alkaloids. Differential metabolites of citrus herbs were searched by multivariate statistical analysis. Notably, Citri Reticulatae Pericarpium contained higher levels of flavonoids, while Zhique and Huajuhong demonstrated a greater abundance of coumarins. Among the flavonoids determined by UPLC, Guangchenpi demonstrated significantly elevated levels of polymethoxyflavones (tangeretin and nobiletin) compared to other citrus herbs. Additionally, we determined their antioxidant capacity (Chenpi > Guangchenpi > Huajuhong > Zhique) using in vitro assays. Finally, we utilized network pharmacology to explore the antioxidant mechanisms and potential pharmacological ingredients, providing a basis for future preventive and therapeutic applications of these metabolites.PMID:37986422 | DOI:10.1016/j.foodres.2023.113514

Frontiers in chronic fatigue syndrome research: An analysis of the top 100 most influential articles in the field

Tue, 21/11/2023 - 12:00
Medicine (Baltimore). 2023 Nov 17;102(46):e35754. doi: 10.1097/MD.0000000000035754.ABSTRACTChronic fatigue syndrome (CFS) is a complex constellation of symptoms that significantly reduces the quality of life among affected individuals and increases public health expenditures. We conducted a search on the Web of Science Core Collection database and selected the top 100 cited articles in the field of CFS. Several literature analysis tools, including CiteSpace 6.1.R6, VOSviewer 1.6.19, and Scimago Graphica 1.0.30, were utilized to integrate the most influential research papers and academic journals in order to obtain a comprehensive understanding of the CFS field. The top 100 highly-cited publications were published in 67 reputable journals, with contributions from 250 institutions across 26 countries/regions involved in CFS research. This demonstrates the extensive attention and coverage of CFS research by high-quality academic journals and institutions, highlighting the interdisciplinary and multidisciplinary nature of CFS studies. The journal with the highest publication volume and total citations was Lancet. The top 5 co-occurring keywords were chronic fatigue syndrome, cognitive behavior therapy, epidemiology, definition, and disorders, indicating the ongoing attention researchers have devoted to the diagnostic criteria and clinical studies of CFS. Cluster analysis results suggested that primary care, infectious retrovirus, gene expression, and metabolomics may become the focal points and trends in future CFS research. The prospective research directions in this field include the search for biological markers, with a particular focus on immunology; the advancement of diagnostic techniques; the screening of risk genes associated with CFS; and the conduct of epidemiological investigations.PMID:37986358 | DOI:10.1097/MD.0000000000035754

Plant Reactome Knowledgebase: empowering plant pathway exploration and OMICS data analysis

Tue, 21/11/2023 - 12:00
Nucleic Acids Res. 2023 Nov 20:gkad1052. doi: 10.1093/nar/gkad1052. Online ahead of print.ABSTRACTPlant Reactome (https://plantreactome.gramene.org) is a freely accessible, comprehensive plant pathway knowledgebase. It provides curated reference pathways from rice (Oryza sativa) and gene-orthology-based pathway projections to 129 additional species, spanning single-cell photoautotrophs, non-vascular plants, and higher plants, thus encompassing a wide-ranging taxonomic diversity. Currently, Plant Reactome houses a collection of 339 reference pathways, covering metabolic and transport pathways, hormone signaling, genetic regulations of developmental processes, and intricate transcriptional networks that orchestrate a plant's response to abiotic and biotic stimuli. Beyond being a mere repository, Plant Reactome serves as a dynamic data discovery platform. Users can analyze and visualize omics data, such as gene expression, gene-gene interaction, proteome, and metabolome data, all within the rich context of plant pathways. Plant Reactome is dedicated to fostering data interoperability, upholding global data standards, and embracing the tenets of the Findable, Accessible, Interoperable and Re-usable (FAIR) data policy.PMID:37986220 | DOI:10.1093/nar/gkad1052

Expression of concern on 'PMhub 1.0: a comprehensive plant metabolome database'

Tue, 21/11/2023 - 12:00
Nucleic Acids Res. 2023 Nov 20:gkad1137. doi: 10.1093/nar/gkad1137. Online ahead of print.NO ABSTRACTPMID:37986219 | DOI:10.1093/nar/gkad1137

Alzheimer's genes in microglia: a risk worth investigating

Tue, 21/11/2023 - 12:00
Mol Neurodegener. 2023 Nov 20;18(1):90. doi: 10.1186/s13024-023-00679-4.ABSTRACTDespite expressing many key risk genes, the role of microglia in late-onset Alzheimer's disease pathophysiology is somewhat ambiguous, with various phenotypes reported to be either harmful or protective. Herein, we review some key findings from clinical and animal model investigations, discussing the role of microglial genetics in mediating perturbations from homeostasis. We note that impairment to protective phenotypes may include prolonged or insufficient microglial activation, resulting in dysregulated metabolomic (notably lipid-related) processes, compounded by age-related inflexibility in dynamic responses. Insufficiencies of mouse genetics and aggressive transgenic modelling imply severe limitations in applying current methodologies for aetiological investigations. Despite the shortcomings, widely used amyloidosis and tauopathy models of the disease have proven invaluable in dissecting microglial functional responses to AD pathophysiology. Some recent advances have brought modelling tools closer to human genetics, increasing the validity of both aetiological and translational endeavours.PMID:37986179 | DOI:10.1186/s13024-023-00679-4

Tracking the effect of roasting and fermentation on the metabolites of licorice root (Glycyrrhiza glabra L.) using UPLC-MS analysis combined with multivariate statistical analysis

Tue, 21/11/2023 - 12:00
BMC Complement Med Ther. 2023 Nov 20;23(1):419. doi: 10.1186/s12906-023-04239-7.ABSTRACTBACKGROUND: Roasting, honey-roasting and fermentation are the most common pre-processing procedures of licorice roots. They were shown to noticeably change the composition of extracts. In this work, the common alterations in licorice secondary metabolites by processing were interpreted. Comprehensive metabolic profiling of different studied samples was undergone.METHODS: UPLC-QqQ-MS/MS analysis coupled to various chemometric analysis models was implemented to unravel the effect of different pre-processing procedures on the chemical profile of licorice samples.RESULTS: UPLC-QqQ-MS/MS analysis designated 133 chromatographic peaks with saponins, flavonoids, chalcones and pterocarpans being the most abundant groups. Triterpene saponins dominated the secondary metabolites in the aqueous extracts, with fermented samples showing the highest relative amounts. Meanwhile the ethanol extracts showed significant amounts of chalcones. Melanoidins were only detected in roasted and honey roasted samples. Multivariate models indicated that roasting of samples induced a greater effect on the polar metabolites rather than nonpolar ones. Variable of importance (VIP) plot indicated that glycyrrhizin and its hydrolysis product glycyrrhetinic acid, trihdroxychalcone diglycoside, glabrone and glabridin are the main chemical features responsible for the discrimination of samples.CONCLUSION: Coupling UPLC-MS/MS to multivariate analysis was a successful tool that unveiled the significant effect of different pre-processing methods on the chemical profile of processed and unprocessed licorice samples. Moreover, such coupling unraveled the discriminatory chemical compounds among tested samples that can be employed as markers for the processing procedure of licorice.PMID:37986059 | DOI:10.1186/s12906-023-04239-7

Omics data integration suggests a potential idiopathic Parkinson's disease signature

Tue, 21/11/2023 - 12:00
Commun Biol. 2023 Nov 20;6(1):1179. doi: 10.1038/s42003-023-05548-w.ABSTRACTThe vast majority of Parkinson's disease cases are idiopathic. Unclear etiology and multifactorial nature complicate the comprehension of disease pathogenesis. Identification of early transcriptomic and metabolic alterations consistent across different idiopathic Parkinson's disease (IPD) patients might reveal the potential basis of increased dopaminergic neuron vulnerability and primary disease mechanisms. In this study, we combine systems biology and data integration approaches to identify differences in transcriptomic and metabolic signatures between IPD patient and healthy individual-derived midbrain neural precursor cells. Characterization of gene expression and metabolic modeling reveal pyruvate, several amino acid and lipid metabolism as the most dysregulated metabolic pathways in IPD neural precursors. Furthermore, we show that IPD neural precursors endure mitochondrial metabolism impairment and a reduced total NAD pool. Accordingly, we show that treatment with NAD precursors increases ATP yield hence demonstrating a potential to rescue early IPD-associated metabolic changes.PMID:37985891 | DOI:10.1038/s42003-023-05548-w

Genome mining for macrolactam-encoding gene clusters allowed for the network-guided isolation of β-amino acid-containing cyclic derivatives and heterologous production of ciromicin A

Tue, 21/11/2023 - 12:00
Commun Chem. 2023 Nov 20;6(1):257. doi: 10.1038/s42004-023-01034-w.ABSTRACTβ-Amino acid-containing macrolactams represent a structurally diverse group of bioactive natural products derived from polyketides; however we are currently lacking a comprehensive overview about their abundance across bacterial families and the underlying biosynthetic diversity. In this study, we employed a targeted β-amino acid-specific homology-based multi-query search to identify potential bacterial macrolactam producers. Here we demonstrate that approximately 10% of each of the identified actinobacterial genera harbor a biosynthetic gene cluster (BGC) encoding macrolactam production. Based on our comparative study, we propose that mutations occurring in specific regions of polyketide synthases (PKS) are the primary drivers behind the variation in macrolactam ring sizes. We successfully validated two producers of ciromicin A from the genus Amycolatopsis, revised the composition of the biosynthetic gene cluster region mte of macrotermycins, and confirmed the ciromicin biosynthetic pathway through heterologous expression. Additionally, network-based metabolomic analysis uncovered three previously unreported macrotermycin congeners from Amycolatopsis sp. M39. The combination of targeted mining and network-based analysis serves as a powerful tool for identifying macrolactam producers and our studies will catalyze the future discovery of yet unreported macrolactams.PMID:37985888 | DOI:10.1038/s42004-023-01034-w

Characterizing the metabolomes of phase-separated condensates

Tue, 21/11/2023 - 12:00
Nat Chem Biol. 2023 Nov 20. doi: 10.1038/s41589-023-01487-z. Online ahead of print.NO ABSTRACTPMID:37985884 | DOI:10.1038/s41589-023-01487-z

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