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

Histidine Metabolic Pathway Contributes to Clozapine-Induced Sialorrhea Based on Nontargeted Metabolomics

Mon, 28/08/2023 - 12:00
Neuropsychobiology. 2023 Aug 28:1-16. doi: 10.1159/000528807. Online ahead of print.ABSTRACTINTRODUCTION: Clozapine-induced sialorrhea (CIS) is one of the most common side effects of clozapine use, while the mechanism remains unclear.METHODS: A total of 51 schizophrenia patients taking clozapine were selected. Among them, 32 had sialorrhea, and 19 had no sialorrhea. Saliva metabolites were identified using ultra-high-performance liquid chromatography-MS/MS (UHPLC-MS/MS), and the differences in saliva metabolites in each group were analyzed through qualitatively searching HMDB, KEGG, and self-built databases, combined with multivariate statistics. After further evaluation by receiver-operating characteristic curve (ROC) analysis, the screened differential metabolites were enriched and topologically analyzed.RESULTS: The biomarkers potentially related to CIS included 37 differential metabolites involving 17 metabolic pathways, mainly histidine metabolism (p < 0.05, impact = 0.50), pyrimidine metabolism (p < 0.05, impact = 0.08), and β-alanine metabolism (p < 0.05, impact = 0.06).CONCLUSION: Our study indicates that histidine metabolic pathway may contribute to the mechanism of CIS.PMID:37640020 | DOI:10.1159/000528807

Flavor enhancement during the drying of scallop (Patinopecten yessoensis) as revealed by integrated metabolomic and lipidomic analysis

Mon, 28/08/2023 - 12:00
Food Chem. 2023 Aug 19;432:137218. doi: 10.1016/j.foodchem.2023.137218. Online ahead of print.ABSTRACTDried scallops are a typical shellfish commodity, but the molecular change mechanism in the drying process is not clear. In this paper, the effect of drying on the flavor of scallops was revealed by integrated metabolomic and lipidomic analysis. The results showed that 70 °C was the best temperature for hot air drying, and the moisture content of the scallops was less than 20% after 12 h of drying, which meets the commercial standards for dried scallops. A total of 53 volatile compounds were detected in dried scallops, of which 2,5-dimethyl pyrazine and tetramethyl pyrazine, as characteristic flavor compounds, changed significantly during drying. In addition, taste peptides such as Arg-Gly and Gly-Gly, produced by protein degradation during drying, may contribute to the umami perception of dried scallops. This study helped to increase the overall quality of dried scallops.PMID:37639891 | DOI:10.1016/j.foodchem.2023.137218

H3K4me3 remodeling induced acquired resistance through O-GlcNAc transferase

Mon, 28/08/2023 - 12:00
Drug Resist Updat. 2023 Aug 10;71:100993. doi: 10.1016/j.drup.2023.100993. Online ahead of print.ABSTRACTAIMS: Drivers of the drug tolerant proliferative persister (DTPP) state have not been well investigated. Histone H3 lysine-4 trimethylation (H3K4me3), an active histone mark, might enable slow cycling drug tolerant persisters (DTP) to regain proliferative capacity. This study aimed to determine H3K4me3 transcriptionally active sites identifying a key regulator of DTPPs.METHODS: Deploying a model of adaptive cancer drug tolerance, H3K4me3 ChIP-Seq data of DTPPs guided identification of top transcription factor binding motifs. These suggested involvement of O-linked N-acetylglucosamine transferase (OGT), which was confirmed by metabolomics analysis and biochemical assays. OGT impact on DTPPs and adaptive resistance was explored in vitro and in vivo.RESULTS: H3K4me3 remodeling was widespread in CPG island regions and DNA binding motifs associated with O-GlcNAc marked chromatin. Accordingly, we observed an upregulation of OGT, O-GlcNAc and its binding partner TET1 in chronically treated cancer cells. Inhibition of OGT led to loss of H3K4me3 and downregulation of genes contributing to drug resistance. Genetic ablation of OGT prevented acquired drug resistance in in vivo models. Upstream of OGT, we identified AMPK as an actionable target. AMPK activation by acetyl salicylic acid downregulated OGT with similar effects on delaying acquired resistance.CONCLUSION: Our findings uncover a fundamental mechanism of adaptive drug resistance that governs cancer cell reprogramming towards acquired drug resistance, a process that can be exploited to improve response duration and patient outcomes.PMID:37639774 | DOI:10.1016/j.drup.2023.100993

Multi-omics reveal microbial determinants impacting the treatment outcome of antidepressants in major depressive disorder

Mon, 28/08/2023 - 12:00
Microbiome. 2023 Aug 28;11(1):195. doi: 10.1186/s40168-023-01635-6.ABSTRACTBACKGROUND: There is a growing body of evidence suggesting that disturbance of the gut-brain axis may be one of the potential causes of major depressive disorder (MDD). However, the effects of antidepressants on the gut microbiota, and the role of gut microbiota in influencing antidepressant efficacy are still not fully understood.RESULTS: To address this knowledge gap, a multi-omics study was undertaken involving 110 MDD patients treated with escitalopram (ESC) for a period of 12 weeks. This study was conducted within a cohort and compared to a reference group of 166 healthy individuals. It was found that ESC ameliorated abnormal blood metabolism by upregulating MDD-depleted amino acids and downregulating MDD-enriched fatty acids. On the other hand, the use of ESC showed a relatively weak inhibitory effect on the gut microbiota, leading to a reduction in microbial richness and functions. Machine learning-based multi-omics integrative analysis revealed that gut microbiota contributed to the changes in plasma metabolites and was associated with several amino acids such as tryptophan and its gut microbiota-derived metabolite, indole-3-propionic acid (I3PA). Notably, a significant correlation was observed between the baseline microbial richness and clinical remission at week 12. Compared to non-remitters, individuals who achieved remission had a higher baseline microbial richness, a lower dysbiosis score, and a more complex and well-organized community structure and bacterial networks within their microbiota. These findings indicate a more resilient microbiota community in remitters. Furthermore, we also demonstrated that it was not the composition of the gut microbiota itself, but rather the presence of sporulation genes at baseline that could predict the likelihood of clinical remission following ESC treatment. The predictive model based on these genes revealed an area under the curve (AUC) performance metric of 0.71.CONCLUSION: This study provides valuable insights into the role of the gut microbiota in the mechanism of ESC treatment efficacy for patients with MDD. The findings represent a significant advancement in understanding the intricate relationship among antidepressants, gut microbiota, and the blood metabolome. Additionally, this study offers a microbiota-centered perspective that can potentially improve antidepressant efficacy in clinical practice. By shedding light on the interplay between these factors, this research contributes to our broader understanding of the complex mechanisms underlying the treatment of MDD and opens new avenues for optimizing therapeutic approaches. Video Abstract.PMID:37641148 | DOI:10.1186/s40168-023-01635-6

An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model

Mon, 28/08/2023 - 12:00
Hum Genomics. 2023 Aug 29;17(1):80. doi: 10.1186/s40246-023-00521-4.ABSTRACTOver the last century, outbreaks and pandemics have occurred with disturbing regularity, necessitating advance preparation and large-scale, coordinated response. Here, we developed a machine learning predictive model of disease severity and length of hospitalization for COVID-19, which can be utilized as a platform for future unknown viral outbreaks. We combined untargeted metabolomics on plasma data obtained from COVID-19 patients (n = 111) during hospitalization and healthy controls (n = 342), clinical and comorbidity data (n = 508) to build this patient triage platform, which consists of three parts: (i) the clinical decision tree, which amongst other biomarkers showed that patients with increased eosinophils have worse disease prognosis and can serve as a new potential biomarker with high accuracy (AUC = 0.974), (ii) the estimation of patient hospitalization length with ± 5 days error (R2 = 0.9765) and (iii) the prediction of the disease severity and the need of patient transfer to the intensive care unit. We report a significant decrease in serotonin levels in patients who needed positive airway pressure oxygen and/or were intubated. Furthermore, 5-hydroxy tryptophan, allantoin, and glucuronic acid metabolites were increased in COVID-19 patients and collectively they can serve as biomarkers to predict disease progression. The ability to quickly identify which patients will develop life-threatening illness would allow the efficient allocation of medical resources and implementation of the most effective medical interventions. We would advocate that the same approach could be utilized in future viral outbreaks to help hospitals triage patients more effectively and improve patient outcomes while optimizing healthcare resources.PMID:37641126 | DOI:10.1186/s40246-023-00521-4

Environmental gradients reveal stress hubs pre-dating plant terrestrialization

Mon, 28/08/2023 - 12:00
Nat Plants. 2023 Aug 28. doi: 10.1038/s41477-023-01491-0. Online ahead of print.ABSTRACTPlant terrestrialization brought forth the land plants (embryophytes). Embryophytes account for most of the biomass on land and evolved from streptophyte algae in a singular event. Recent advances have unravelled the first full genomes of the closest algal relatives of land plants; among the first such species was Mesotaenium endlicherianum. Here we used fine-combed RNA sequencing in tandem with a photophysiological assessment on Mesotaenium exposed to a continuous range of temperature and light cues. Our data establish a grid of 42 different conditions, resulting in 128 transcriptomes and ~1.5 Tbp (~9.9 billion reads) of data to study the combinatory effects of stress response using clustering along gradients. Mesotaenium shares with land plants major hubs in genetic networks underpinning stress response and acclimation. Our data suggest that lipid droplet formation and plastid and cell wall-derived signals have denominated molecular programmes since more than 600 million years of streptophyte evolution-before plants made their first steps on land.PMID:37640935 | DOI:10.1038/s41477-023-01491-0

Comparative analysis of sucrose-embedding for whole-body zebrafish MSI by IR-MALDESI

Mon, 28/08/2023 - 12:00
Anal Bioanal Chem. 2023 Aug 29. doi: 10.1007/s00216-023-04914-1. Online ahead of print.ABSTRACTInfrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI) conventionally utilizes fresh-frozen biological tissues with an ice matrix to improve the detection of analytes. Sucrose-embedding with paraformaldehyde fixation has demonstrated feasibility as an alternative matrix for analysis by IR-MALDESI by preserving tissue features and enhancing ionization of lipids. However, investigating multi-organ systems provides broader context for a biological study and can elucidate more information about a disease state as opposed to a single organ. Danio rerio, or zebrafish, are model organisms for various disease states and can be imaged as a multi-organ sample to analyze morphological and metabolomic preservation as a result of sample preparation. Herein, whole-body zebrafish were imaged to compare sucrose-embedding with paraformaldehyde fixation against conventional fresh-frozen sample preparation. Serial sections were analyzed with and without an ice matrix to evaluate if sucrose functions as an alternative energy-absorbing matrix for IR-MALDESI applications across whole-body tissues. The resulting four conditions were compared in terms of total putative lipid annotations and category diversity, coverage across the entire m/z range, and ion abundance. Ultimately, sucrose-embedded zebrafish had an increase in putative lipid annotations for the combination of putative annotations with and without the application of an ice matrix relative to fresh-frozen tissues which require the application of an ice matrix. Upon the use of an ice matrix, a greater number of high mass putative lipid annotations (e.g., glycerophospholipids, glycerolipids, and sphingolipids) were identified. Conversely, without an ice matrix, sucrose-embedded sections elucidated more putative annotations in lower molecular weight lipids, including fatty acyls and sterol lipids. Similar to the mouse brain model, sucrose-embedding increased putative lipid annotation and abundance for whole-body zebrafish.PMID:37640826 | DOI:10.1007/s00216-023-04914-1

Spatial Metabolomics Reveals the Multifaceted Nature of Lamprey Buccal Gland and Its Diverse Mechanisms for Blood-Feeding

Mon, 28/08/2023 - 12:00
Commun Biol. 2023 Aug 28;6(1):881. doi: 10.1038/s42003-023-05250-x.ABSTRACTLampreys are blood-sucking vampires in marine environments. From a survival perspective, it is expected that the lamprey buccal gland exhibits a repository of pharmacologically active components to modulate the host's homeostasis, inflammatory and immune responses. By analyzing the metabolic profiles of 14 different lamprey tissues, we show that two groups of metabolites in the buccal gland of lampreys, prostaglandins and the kynurenine pathway metabolites, can be injected into the host fish to assist lamprey blood feeding. Prostaglandins are well-known blood-sucking-associated metabolites that act as vasodilators and anticoagulants to maintain vascular homeostasis and are involved in inflammatory responses. The vasomotor reactivity test on catfish aortic ring showed that kynurenine can also relax the blood vessels of the host fish, thus improving the blood flow of the host fish at the bite site. Finally, a lamprey spatial metabolomics database ( https://www.lampreydb.com ) was constructed to assist studies using lampreys as animal model.PMID:37640823 | DOI:10.1038/s42003-023-05250-x

Patterns of Carbon-Bound Exogenous Compounds Impact Disease Pathophysiology in Lung Cancer Subtypes in Different Ways

Mon, 28/08/2023 - 12:00
ACS Nano. 2023 Aug 28. doi: 10.1021/acsnano.2c11161. Online ahead of print.ABSTRACTCarbon-bound exogenous compounds, such as polycyclic aromatic hydrocarbons (PAHs), tobacco-specific nitrosamines, aromatic amines, and organohalogens, are known to affect both tumor characteristics and patient outcomes in lung squamous cell carcinoma (LUSC); however, the roles of these compounds in lung adenocarcinoma (LUAD) remain unclear. We analyzed 11 carbon-bound exogenous compounds in LUAD and LUSC samples using in situ high mass-resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry imaging and performed a cluster analysis to compare the patterns of carbon-bound exogenous compounds between these two lung cancer subtypes. Correlation analyses were conducted to investigate associations among exogenous compounds, endogenous metabolites, and clinical data, including patient survival outcomes and smoking behaviors. Additionally, we examined differences in exogenous compound patterns between normal and tumor tissues. Our analyses revealed that PAHs, aromatic amines, and organohalogens were more abundant in LUAD than in LUSC, whereas the tobacco-specific nitrosamine nicotine-derived nitrosamine ketone was more abundant in LUSC. Patients with LUAD and LUSC could be separated according to carbon-bound exogenous compound patterns detected in the tumor compartment. The same compounds had differential impacts on patient outcomes, depending on the cancer subtype. Correlation and network analyses indicated substantial differences between LUAD and LUSC metabolomes, associated with substantial differences in the patterns of the carbon-bound exogenous compounds. These data suggest that the contributions of these carcinogenic compounds to cancer biology may differ according to the cancer subtypes.PMID:37639684 | DOI:10.1021/acsnano.2c11161

Perspectives on the Drosophila melanogaster Model for Advances in Toxicological Science

Mon, 28/08/2023 - 12:00
Curr Protoc. 2023 Aug;3(8):e870. doi: 10.1002/cpz1.870.ABSTRACTThe use of Drosophila melanogaster for studies of toxicology has grown considerably in the last decade. The Drosophila model has long been appreciated as a versatile and powerful model for developmental biology and genetics because of its ease of handling, short life cycle, low cost of maintenance, molecular genetic accessibility, and availability of a wide range of publicly available strains and data resources. These features, together with recent unique developments in genomics and metabolomics, make the fly model especially relevant and timely for the development of new approach methodologies and movements toward precision toxicology. Here, we offer a perspective on how flies can be leveraged to identify risk factors relevant to environmental exposures and human health. First, we review and discuss fundamental toxicologic principles for experimental design with Drosophila. Next, we describe quantitative and systems genetics approaches to resolve the genetic architecture and candidate pathways controlling susceptibility to toxicants. Finally, we summarize the current state and future promise of the emerging field of Drosophila metabolomics for elaborating toxic mechanisms. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.PMID:37639638 | DOI:10.1002/cpz1.870

MYC disrupts transcriptional and metabolic circadian oscillations in cancer and promotes enhanced biosynthesis

Mon, 28/08/2023 - 12:00
PLoS Genet. 2023 Aug 28;19(8):e1010904. doi: 10.1371/journal.pgen.1010904. Online ahead of print.ABSTRACTThe molecular circadian clock, which controls rhythmic 24-hour oscillation of genes, proteins, and metabolites in healthy tissues, is disrupted across many human cancers. Deregulated expression of the MYC oncoprotein has been shown to alter expression of molecular clock genes, leading to a disruption of molecular clock oscillation across cancer types. It remains unclear what benefit cancer cells gain from suppressing clock oscillation, and how this loss of molecular clock oscillation impacts global gene expression and metabolism in cancer. We hypothesized that MYC or its paralog N-MYC (collectively termed MYC herein) suppress oscillation of gene expression and metabolism to upregulate pathways involved in biosynthesis in a static, non-oscillatory fashion. To test this, cells from distinct cancer types with inducible MYC were examined, using time-series RNA-sequencing and metabolomics, to determine the extent to which MYC activation disrupts global oscillation of genes, gene expression pathways, and metabolites. We focused our analyses on genes, pathways, and metabolites that changed in common across multiple cancer cell line models. We report here that MYC disrupted over 85% of oscillating genes, while instead promoting enhanced ribosomal and mitochondrial biogenesis and suppressed cell attachment pathways. Notably, when MYC is activated, biosynthetic programs that were formerly circadian flipped to being upregulated in an oscillation-free manner. Further, activation of MYC ablates the oscillation of nutrient transporter proteins while greatly upregulating transporter expression, cell surface localization, and intracellular amino acid pools. Finally, we report that MYC disrupts metabolite oscillations and the temporal segregation of amino acid metabolism from nucleotide metabolism. Our results demonstrate that MYC disruption of the molecular circadian clock releases metabolic and biosynthetic processes from circadian control, which may provide a distinct advantage to cancer cells.PMID:37639465 | DOI:10.1371/journal.pgen.1010904

Metabolomics analyses of serum metabolites perturbations associated with Naja atra bite

Mon, 28/08/2023 - 12:00
PLoS Negl Trop Dis. 2023 Aug 28;17(8):e0011507. doi: 10.1371/journal.pntd.0011507. eCollection 2023 Aug.ABSTRACTNaja atra bite is one of the most common severe snakebites in emergency departments. Unfortunately, the pathophysiological changes caused by Naja atra bite are unclear due to the lack of good animal models. In this study, an animal model of Naja atra bite in Guangxi Bama miniature pigs was established by intramuscular injection at 2 mg/kg of Naja atra venom, and serum metabolites were systematically analyzed using untargeted metabolomic and targeted metabolomic approaches. Untargeted metabolomic analysis revealed that 5045 chromatographic peaks were obtained in ESI+ and 3871 chromatographic peaks were obtained in ESI-. Screening in ESI+ modes and ESI- modes identified 22 and 36 differential metabolites compared to controls. The presence of 8 core metabolites of glutamine, arginine, proline, leucine, phenylalanine, inosine, thymidine and hippuric acid in the process of Naja atra bite was verified by targeted metabolomics significant difference (P<0.05). At the same time, during the verification process of the serum clinical samples with Naja atra bite, we found that the contents of three metabolites of proline, phenylalanine and inosine in the serum of the patients were significantly different from those of the normal human serum (P<0.05). By conducting functional analysis of core and metabolic pathway analysis, we revealed a potential correlation between changes in key metabolites after the Naja atra bite and the resulting pathophysiological alterations, and our research aims to establish a theoretical foundation for the prompt diagnosis and treatment of Naja atra bite.PMID:37639406 | DOI:10.1371/journal.pntd.0011507

A minimal kynurenine pathway was preserved for rhodoquinone but not for de novo NAD<sup><sup>+ </sup></sup> biosynthesis in parasitic worms: the essential role of NAD<sup><sup>+ </sup></sup> rescue pathways

Mon, 28/08/2023 - 12:00
Antioxid Redox Signal. 2023 Aug 28. doi: 10.1089/ars.2023.0293. Online ahead of print.ABSTRACTAIMS: To determine the role of the kynurenine pathway in rhodoquinone and de novo NAD+ biosynthesis and whether NAD+ rescue pathways are essential in parasitic worms (helminths).RESULTS: We demonstrate that rhodoquinone, the key electron transporter used by helminths under hypoxia, derives from the tryptophan catabolism even in the presence of a minimal kynurenine pathway. We show that of the kynurenine pathway genes only the kynureninase and tryptophan/indoleamine dioxygenases are essential for rhodoquinone biosynthesis. Metabolic labeling with tryptophan revealed that the lack of the formamidase and kynurenine monooxygenase genes did not preclude rhodoquinone biosynthesis in the flatworm Mesocestoides corti. In contrast, a minimal kynurenine pathway prevented de novo NAD+ biosynthesis, as revealed by metabolic labeling in M. corti, which also lacks the 3-hydroxyanthranilate 3,4-dioxygenase gene. Our results indicate that most helminths depend solely on NAD+ rescue pathways, and some lineages rely exclusively on the nicotinamide salvage pathway. Importantly, the inhibition of the NAD+ recycling enzyme nicotinamide phosphoribosyltransferase with FK866 led cultured M. corti to death.INNOVATION: We use comparative genomics of more than 100 hundred helminth genomes, metabolic labeling, HPLC-MS targeted metabolomics, and enzyme inhibitors to define pathways that lead to rhodoquinone and NAD+ biosynthesis in helminths. We identified the essential enzymes of these pathways in helminth lineages, revealing new potential pharmacological targets for helminthiasis.CONCLUSIONS: Our results demonstrate that a minimal kynurenine pathway was evolutionary maintained for rhodoquinone and not for de novo NAD+ biosynthesis in helminths, and shed light on the essentiality of NAD+ rescue pathways in helminths.PMID:37639366 | DOI:10.1089/ars.2023.0293

Dynamic changes in the levels of metabolites and endogenous hormones during the germination of <em>Zanthoxylum nitidum</em> (Roxb.) DC. Seeds

Mon, 28/08/2023 - 12:00
Plant Signal Behav. 2023 Dec 31;18(1):2251750. doi: 10.1080/15592324.2023.2251750.ABSTRACTAccumulating experimental data have shown that endogenous hormones play important roles in regulating seed dormancy and germination. Zanthoxylum nitidum is a medicinal plant that propagates via seeds, which require a long dormancy period for normal germination, and complex changes in metabolites occur during the germination process. However, the regulatory network of endogenous hormones and metabolites during the germination of Z. nitidum seeds remains unclear. This study investigated the dynamic changes in the levels of metabolites and endogenous hormones during the germination of Z. nitidum seeds. The results revealed an increase in the levels of gibberellin 3 (GA3), 12-oxophytodienoic acid (OPDA), 1-aminocyclopropane-1-carboxylic acid (ACC) and trans-zeatin (TZ) and decrease in the levels of abscisic acid (ABA), jasmonic acid (JA), N-[(-)-jasmonoyl]-(S)-isoleucine (JA-Ile) and trans-zeatin riboside (TZR). Overall, 112 differential metabolites (DAMs) were screened from 3 seed samples (Sa, Sb and Sc), most of which are related to primary metabolism. A total of 16 DAMs (including 3 monosaccharides, 3 phosphate lipids, 3 carboxylic acids, 1 amino acid, 2 pyrimidines, and 4 nucleotides) were identified in the three sample comparison pairs (Sa vs Sb, Sa vs Sc, and Sb vs Sc); these DAMs were significantly enriched in purine metabolism; glycerophospholipid metabolism, citrate cycle (TCA cycle), alanine, aspartate and glutamate metabolism and pyruvate metabolism. OPDA, ACC and GAs were significantly positively correlated with upregulated metabolites, whereas ABA and JA were significantly positively correlated with downregulated metabolites. Finally, a hypothetical metabolic network of endogenous hormones that regulate seed germination was constructed. This study deepens our understanding of the importance of endogenous hormonal profiles that mediate seed germination.PMID:37639213 | DOI:10.1080/15592324.2023.2251750

Inhibitory Effect of Non-Saccharomyces Starmerella bacillaris CC-PT4 Isolated from Grape on MRSA Growth and Biofilm

Mon, 28/08/2023 - 12:00
Probiotics Antimicrob Proteins. 2023 Aug 28. doi: 10.1007/s12602-023-10146-7. Online ahead of print.ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) is a notorious pathogen with biofilm-forming and drug-resistant properties that make it difficult to eradicate. In this study, the inhibition of MRSA (ATCC 43300) by Starmerella bacillaris CC-PT4 (CGMCC No. 23573) was evaluated. The results showed that the inhibition of MRSA growth and biofilm was caused by S. bacillaris CC-PT4 cell-free supernatant (CFS). The CFS of S. bacillaris CC PT4 at different times can effectively inhibit the formation of MRSA biofilm, remove the preformed biofilm, and down-regulate the related genes that promote the formation of biofilm. Afterwards, untargeted metabolomics was performed to analyze the CFS of S. bacillaris CC-PT4. Several molecules with antibacterial and inhibitory biofilm effects from the CFS were found, one of which, 2-amino-1-phenylethanol (APE), has not been reported to have antiMRSA ability before. In this study, molecular docking analysis and in vitro experiments were used to verify the function of APE to inhibit MRSA. These results indicate that S. bacillaris CC-PT4 CFS can effectively inhibit MRSA which has potential application value in controlling MRSA.PMID:37639210 | DOI:10.1007/s12602-023-10146-7

Combined Analysis of mRNA Expression and Open Chromatin in Microglia

Mon, 28/08/2023 - 12:00
Methods Mol Biol. 2024;2713:543-571. doi: 10.1007/978-1-0716-3437-0_35.ABSTRACTThe advance of single-cell RNA-sequencing technologies in the past years has enabled unprecedented insights into the complexity and heterogeneity of microglial cell states in the homeostatic and diseased brain. This includes rather complex proteomic, metabolomic, morphological, transcriptomic, and epigenetic adaptations to external stimuli and challenges resulting in a novel concept of core microglia properties and functions. To uncover the regulatory programs facilitating the rapid transcriptomic adaptation in response to changes in the local microenvironment, the accessibility of gene bodies and gene regulatory elements can be assessed. Here, we describe the application of a previously published method for simultaneous high-throughput ATAC and RNA expression with sequencing (SHARE-seq) on microglia nuclei isolated from frozen mouse brain tissue.PMID:37639146 | DOI:10.1007/978-1-0716-3437-0_35

Selenium Biofortification Impacts the Tomato Fruit Metabolome and Transcriptional Profile at Ripening

Mon, 28/08/2023 - 12:00
J Agric Food Chem. 2023 Aug 28. doi: 10.1021/acs.jafc.3c02031. Online ahead of print.ABSTRACTIn the present work, the effects of enriching tomatoes with selenium were studied in terms of physiological, metabolic, and molecular processes in the last stages of fruit development, particularly during ripening. A selenium concentration of 10 mg L-1 with sodium selenate and selenium nanoparticles was used in the spray treatments on the whole plants. No significant effects of selenium enrichment were detected in terms of ethylene production or color changes in the ripening fruit. However, selenium enrichment had an influence on both the primary and secondary metabolic processes and thus the biochemical composition of ripe tomatoes. Selenium decreased the amount of β-carotene, increased the accumulation of naringenin and chlorogenic acid, and decreased the coumaric acid level. Selenium also affected the volatile organic compound profile, with changes in the level of specific apocarotenoid compounds, such as β-ionone. These metabolomic changes may, to some extent, be due to the impact of selenium treatment on the transcription of genes involved in the metabolism of these compounds. RNA-seq analysis showed that the selenium application mostly impacted the expression of the genes involved in hormonal signaling, secondary metabolism, flavonoid biosynthesis, and glycosaminoglycan degradation.PMID:37638888 | DOI:10.1021/acs.jafc.3c02031

Compound Chenpi Tea consumption reduces obesity-related metabolic disorders by modulating gut microbiota and serum metabolites in mice

Mon, 28/08/2023 - 12:00
J Sci Food Agric. 2023 Aug 28. doi: 10.1002/jsfa.12940. Online ahead of print.ABSTRACTBACKGROUND: Compound Chenpi Tea (CCT) is a popular herbal beverage made from Citri Reticulatae Pericarpium, Ganoderma lucidum and Pu-erh tea. This study aimed to investigate the anti-obesity effect of CCT in mice fed a high-fat diet (HFD) and to explore the potential mediators by 16S rRNA sequencing and serum metabolomic analysis.RESULTS: The results showed that CCT supplementation can effectively reduce diet-induced obesity, hepatic steatosis, dyslipidemia, and insulin resistance. Further analyses revealed that CCT could reverse the changes of 28 metabolites induced by HFD, mainly affecting, amino acid metabolism, gut microbiota metabolism and glycerophospholipid metabolism. CCT could also alleviate the intestinal dysbiosis by decreasing the abundance of Romboutsia, Gemella, [Eubacterium]_fissicatena_group and Faecalibaculum, and increasing the abundance of Oscillibacter, Blautia and Acetatifactor.CONCLUSION: Collectively, these findings demonstrated that CCT supplementation modulated gut microbiota and obesity-related metabolic disorders in mice. This article is protected by copyright. All rights reserved.PMID:37638783 | DOI:10.1002/jsfa.12940

Widely targeted metabolomic analysis reveals that volatile metabolites in cigar tobacco leaves dynamically change during fermentation

Mon, 28/08/2023 - 12:00
Biochem Biophys Rep. 2023 Aug 19;35:101532. doi: 10.1016/j.bbrep.2023.101532. eCollection 2023 Sep.ABSTRACTChanges in volatile metabolites during cigar tobacco leaves fermentation as well as the metabolic pathways of metabolites with significant differences were investigated to determine the influence of cigar tobacco leaves fermentation on its flavor. The volatile substances in cigar tobacco leaves at different stages were detected by headspace-solid phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), and the main differences in volatile substances in cigar tobacco leaves at different fermentation stages of Yunxue1 in Yuxi production area were analyzed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The results show that in the process of cigar tobacco leaves fermentation (YXF0, YXF1, YXF2, YXF3, YXF4, YXF5), a total of 613 volatile metabolites were detected, and a significant difference was found in 263 kinds of metabolites. Among them, the main upregulated differential metabolites were 1,3,6,10-Cyclotetradecatetraene, 3,7,11-trimethyl-14-(1-methylethyl)-, [S-(E,Z,E,E)]-, Benzoic acid, Benzaldehyde, etc. While the main downregulated differential metabolites included beta.-Myrcene, trans-Farnesol, etc. The metabolites with significant differences are mainly concentrated in the biosynthesis of monoterpenes, diterpenes, sesquiterpenes and triterpenes, the degradation metabolism of amino acids, such as valine, leucine and isoleucine, and the biosynthesis of phenylpropyl. There were 8 different metabolites in 5 groups, including 4- (1-methylethyl) -1-cyclohexene-1-formaldehyde、2, 4-dihydroxyacetophenone、2-methylbutyl 3-methylbutyrate and methylpyrazine, all of which showed upregulation trend during fermentation. In the fermentation process, volatile metabolites participate in various synthesis and degradation pathways. The biosynthesis pathway of terpenes and amino acid synthesis and degradation pathway are connected to produce various terpenes, aldehydes and other substances, such as 1,3,6,10-Cyclotetradecatetraene, 3,7,11-trimethyl-14-(1-methylethyl)-, [S-(E,Z,E,E)]-、benzaldehyde and 4-hydroxybenzaldehyde, which are conducive to the overall flavor and quality of cigar tobacco leaves.PMID:37637940 | PMC:PMC10457684 | DOI:10.1016/j.bbrep.2023.101532

Untargeted metabolite profiling of serum in rats exposed to pyrraline

Mon, 28/08/2023 - 12:00
Food Sci Biotechnol. 2023 Jan 26;32(11):1541-1549. doi: 10.1007/s10068-023-01256-7. eCollection 2023 Oct.ABSTRACTPyrraline, one of advanced glycation end-products, is formed in advanced Maillard reactions. It was reported that the presence of pyrraline was tested to be associated with nephropathy and diabetes. Pyrraline might result in potential health risks because many modern diets are heat processed. In the study, an integrated metabolomics by ultra-high-performance liquid chromatography with mass spectrometry was used to evaluate the effects of pyrraline on metabolism in rats. Thirty-two metabolites were identified as differential metabolites. Linolenic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, tyrosine metabolism and glycerophospholipid metabolism were the main perturbed networks in this pathological process. Differential metabolites and metabolic pathways we found give new insights into studying the toxic molecular mechanisms of pyrraline.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-023-01256-7.PMID:37637845 | PMC:PMC10449741 | DOI:10.1007/s10068-023-01256-7

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