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

Integrated analysis of transcriptome and metabolome reveals insights for low-temperature germination in hybrid rapeseeds (Brassica napus L.)

Tue, 07/11/2023 - 12:00
J Plant Physiol. 2023 Nov 2;291:154120. doi: 10.1016/j.jplph.2023.154120. Online ahead of print.ABSTRACTRapeseed (Brassica napus L.) is an important oil-producing crop in China. However, cold stress in winter can adversely affect rapeseed germination and subsequently result in poor seed yield at the mature stage. Studies of differences in the transcriptional and metabolic levels of rapeseed under cold stress can improve our understanding of low-temperature germination (LTG). The current study aimed to identify the cold stress-responsive genes, metabolites, and metabolic pathways based on a combined transcriptome and metabolome analysis to understand the difference of LTG and tolerance mechanisms in the cold-tolerant (Yueyou1301, YY1301) and cold-normal (Fengyou737, FY737) rapeseed varieties. Compared to FY737, YY1301 had a higher germination rate, indole acetic acid (IAA) and gibberellic acid (GA)/(abscisic acid) ABA levels at 7.5 °C. A total of 951 differentially expressed genes (DEGs) and 86 differentially accumulated metabolites (DAMs) were identified in two rapeseed varieties. Conjoint analysis revealed 12 DAMs and 5 DEGs that were strongly correlated in inducing rapeseed LTG, which were mainly related to carbohydrate and amino acid metabolism, specifically the pathway of glutathione metabolism and starch and sucrose metabolism. These results suggest that the DAMs and DEGs involved in crucial biological pathways may regulate the LTG of rapeseed. It increases the understanding of the molecular mechanisms underlying the adaptation of rapeseed to LTG.PMID:37935062 | DOI:10.1016/j.jplph.2023.154120

A Data Deposition Platform for Sharing Nuclear Magnetic Resonance Data

Tue, 07/11/2023 - 12:00
J Nat Prod. 2023 Nov 7. doi: 10.1021/acs.jnatprod.3c00795. Online ahead of print.ABSTRACTNuclear magnetic resonance (NMR) data are rarely deposited in open databases, leading to loss of critical scientific knowledge. Existing data reporting methods (images, tables, lists of values) contain less information than raw data and are poorly standardized. Together, these issues limit FAIR (findable, accessible, interoperable, reusable) access to these data, which in turn creates barriers for compound dereplication and the development of new data-driven discovery tools. Existing NMR databases either are not designed for natural products data or employ complex deposition interfaces that disincentivize deposition. Journals, including the Journal of Natural Products (JNP), are now requiring data submission as part of the publication process, creating the need for a streamlined, user-friendly mechanism to deposit and distribute NMR data.PMID:37935005 | DOI:10.1021/acs.jnatprod.3c00795

Enterogenic metabolomics signatures of depression: what are the possibilities for the future

Tue, 07/11/2023 - 12:00
Expert Rev Proteomics. 2023 Nov 7. doi: 10.1080/14789450.2023.2279984. Online ahead of print.ABSTRACTINTRODUCTION: An increasing number of studies indicate that the microbiota-gut-brain axis is an important pathway involved in the onset and progression of depression. The responses of the organism (or its microorganisms) to external cues cannot be separated from a key intermediate element: their metabolites.AREAS COVERED: In recent years, with the rapid development of metabolomics, an increasing amount of metabolites has been detected and studied, especially the gut metabolites. Nevertheless, the increasing amount of metabolites described has not been reflected in a better understanding of their functions and metabolic pathways. Moreover, our knowledge of the biological interactions among metabolites is also incomplete, which limits further studies on the connections between the microbial-entero-brain axis and depression.EXPERT OPINION: This paper summarizes the current knowledge on depression-related metabolites and their involvement in the onset and progression of this disease. More importantly, this paper summarized metabolites from the intestine, and defined them as enterogenic metabolitesm, to further clarify the function of intestinal metabolites and their biochemical cross-talk, providing theoretical support and new research directions for the prevention and treatment of depression.PMID:37934939 | DOI:10.1080/14789450.2023.2279984

From Nontargeted to Targeted Analysis: Feature Selection in the Differentiation of Truffle Species (<em>Tuber</em> spp.) Using <sup>1</sup>H NMR Spectroscopy and Support Vector Machine

Tue, 07/11/2023 - 12:00
J Agric Food Chem. 2023 Nov 7. doi: 10.1021/acs.jafc.3c05786. Online ahead of print.ABSTRACTThe price of different truffle types varies according to their culinary value, sometimes by more than a factor of 10. Nonprofessionals can hardly distinguish visually the species within the white or black truffles, making the possibility of food fraud very easy. Therefore, the identification of different truffle species (Tuber spp.) is an analytical task that could be solved in this study. The polar extract from a total of 80 truffle samples was analyzed by 1H NMR spectroscopy in combination with chemometric methods covering five commercially relevant species. All classification models were validated applying a repeated nested cross-validation. In direct comparison, the two very similar looking and closely related black representatives Tuber melanosporum and Tuber indicum could be classified 100% correctly. The most expensive truffle Tuber magnatum could be distinguished 100% from the other relevant white truffle Tuber borchii. In addition, signals for a potential Tuber borchii and a potential Tuber melanosporum marker for targeted approaches could be detected, and the corresponding molecules were identified as betaine and ribonate. A model covering all five truffle species Tuber aestivum, Tuber borchii, Tuber indicum, Tuber magnatum, and Tuber melanosporum was able to correctly discriminate between each of the species.PMID:37934755 | DOI:10.1021/acs.jafc.3c05786

Elucidating Multiple Electron-Transfer Pathways for Metavanadate Bioreduction by Actinomycetic <em>Streptomyces microflavus</em>

Tue, 07/11/2023 - 12:00
Environ Sci Technol. 2023 Nov 7. doi: 10.1021/acs.est.3c07288. Online ahead of print.ABSTRACTWhile microbial reduction has gained widespread recognition for efficiently remediating environments polluted by toxic metavanadate [V(V)], the pool of identified V(V)-reducing strains remains rather limited, with the vast majority belonging to bacteria and fungi. This study is among the first to confirm the V(V) reduction capability of Streptomyces microflavus, a representative member of ubiquitous actinomycetes in environment. A V(V) removal efficiency of 91.0 ± 4.35% was achieved during 12 days of operation, with a maximum specific growth rate of 0.073 d-1. V(V) was bioreduced to insoluble V(IV) precipitates. V(V) reduction took place both intracellularly and extracellularly. Electron transfer was enhanced during V(V) bioreduction with increased electron transporters. The electron-transfer pathways were revealed through transcriptomic, proteomic, and metabolomic analyses. Electrons might flow either through the respiratory chain to reduce intracellular V(V) or to cytochrome c on the outer membrane for extracellular V(V) reduction. Soluble riboflavin and quinone also possibly mediated extracellular V(V) reduction. Glutathione might deliver electrons for intracellular V(V) reduction. Bioaugmentation of the aquifer sediment with S. microflavus accelerated V(V) reduction. The strain could successfully colonize the sediment and foster positive correlations with indigenous microorganisms. This study offers new microbial resources for V(V) bioremediation and improve the understanding of the involved molecular mechanisms.PMID:37934564 | DOI:10.1021/acs.est.3c07288

HR-MAS DREAMTIME NMR for Slow Spinning <em>ex Vivo</em> and <em>in Vivo</em> Samples

Tue, 07/11/2023 - 12:00
Anal Chem. 2023 Nov 7. doi: 10.1021/acs.analchem.3c03800. Online ahead of print.ABSTRACTHR-MAS NMR is a powerful tool, capable of monitoring molecular changes in intact heterogeneous samples. However, one of the biggest limitations of 1H NMR is its narrow spectral width which leads to considerable overlap in complex natural samples. DREAMTIME NMR is a highly selective technique that allows users to isolate suites of metabolites from congested spectra. This permits targeted metabolomics by NMR and is ideal for monitoring specific processes. To date, DREAMTIME has only been employed in solution-state NMR, here it is adapted for HR-MAS applications. At high spinning speeds (>5 kHz), DREAMTIME works with minimal modifications. However, spinning over 3-4 kHz leads to cell lysis, and if maintaining sample integrity is necessary, slower spinning (<2.5 kHz) is required. Very slow spinning (≤500 Hz) is advantageous for in vivo analysis to increase organism survival; however, sidebands from water pose a problem. To address this, a version of DREAMTIME, termed DREAMTIME-SLOWMAS, is introduced. Both techniques are compared at 2500, 500, and 50 Hz, using ex vivo worm tissue. Following this, DREAMTIME-SLOWMAS is applied to monitor key metabolites of anoxic stress in living shrimp at 500 Hz. Thus, standard DREAMTIME works well under MAS conditions and is recommended for samples reswollen in D2O or spun >2500 Hz. For slow spinning in vivo or intact tissue samples, DREAMTIME-SLOWMAS provides an excellent way to target process-specific metabolites while maintaining sample integrity. Overall, DREAMTIME should find widespread application wherever targeted molecular information is required from complex samples with a high degree of spectral overlap.PMID:37934172 | DOI:10.1021/acs.analchem.3c03800

DHA Shortage Causes the Early Degeneration of Photoreceptors and RPE in Mice With Peroxisomal β-Oxidation Deficiency

Tue, 07/11/2023 - 12:00
Invest Ophthalmol Vis Sci. 2023 Nov 1;64(14):10. doi: 10.1167/iovs.64.14.10.ABSTRACTPURPOSE: Patients deficient in peroxisomal β-oxidation, which is essential for the synthesis of docosahexaenoic acid (DHA, C22:6n-3) and breakdown of very-long-chain polyunsaturated fatty acids (VLC-PUFAs), both important components of photoreceptor outer segments, develop retinopathy present with retinopathy. The representative mouse model lacking the central enzyme of this pathway, multifunctional protein 2 (Mfp2-/-), also show early-onset retinal decay and cell-autonomous retinal pigment epithelium (RPE) degeneration, accompanied by reduced plasma and retinal DHA levels. In this study, we investigated whether DHA supplementation can rescue the retinal degeneration of Mfp2-/- mice.METHODS: Mfp2+/- breeding pairs and their offspring were fed a 0.12% DHA or control diet during gestation and lactation and until sacrifice. Offspring were analyzed for retinal function via electroretinograms and for lipid composition of neural retina and plasma with lipidome analysis and gas chromatography, respectively, and histologically using retinal sections and RPE flatmounts at the ages of 4, 8, and 16 weeks.RESULTS: DHA supplementation to Mfp2-/- mice restored retinal DHA levels and prevented photoreceptor shortening, death, and impaired functioning until 8 weeks. In addition, rescue of retinal DHA levels temporarily improved the ability of the RPE to phagocytose outer segments and delayed the RPE dedifferentiation. However, despite the initial rescue of retinal integrity, DHA supplementation could not prevent retinal degeneration at 16 weeks.CONCLUSIONS: We reveal that the shortage of a systemic supply of DHA is pivotal for the early retinal degeneration in Mfp2-/- mice. Furthermore, we report that adequate retinal DHA levels are essential not only for photoreceptors but also for RPE homeostasis.PMID:37934161 | DOI:10.1167/iovs.64.14.10

Predictive performance of 1H-NMR metabolomics derived biomarkers of bacterial vaginosis

Tue, 07/11/2023 - 12:00
Sex Transm Dis. 2023 Nov 6. doi: 10.1097/OLQ.0000000000001897. Online ahead of print.ABSTRACT1H-NMR metabolomics-derived biomarkers maltose, acetate, formate and lactate have excellent potential as predictive biomarkers for BV with an AUC of 0.97 (95%CI = 0.88-1.00), sensitivity of 0.90 and specificity of 0.95.PMID:37934152 | DOI:10.1097/OLQ.0000000000001897

Exploring the in vitro anti-inflammatory activity of gross saponins of Tribulus terrestris L. fruit by using liquid chromatography-mass spectrometry-based cell metabolomics approach

Tue, 07/11/2023 - 12:00
J Sep Sci. 2023 Nov 7:e2300531. doi: 10.1002/jssc.202300531. Online ahead of print.ABSTRACTOur previous studies confirmed the efficacy of gross saponins of Tribulus terrestris L. fruit in treating cerebral ischemia. This study aimed to investigate the related mechanisms in vitro. The lipopolysaccharide-induced BV2 cells model was constructed and treated with gross saponins at different concentrations to explore its anti-inflammatory activity. The cell metabolite changes were tracked by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, and the metabolic biomarkers and related metabolic pathways were analyzed. Molecular biochemistry analysis was further used to verify the relevant inflammatory pathways. The results showed that the saponins reduced nitric oxide release and the secretion of tumor necrosis factor-alpha, interleukin-1β, and interleukin-6 from lipopolysaccharide-induced BV2 cells. Metabolic perturbations occurred in lipopolysaccharide-treated BV2 cells, which could be reversed by drug treatment via mainly regulating glycerophospholipid metabolism, tryptophan metabolism, purine metabolism pathways, etc. The western blot analysis demonstrated that saponin could suppress the activation of the inflammatory-related signaling pathway. The present study explored the in vitro anti-inflammatory mechanism of gross saponins of Tribulus terrestris L. fruit using an LC-MS-based cell metabolomics approach, which confirms the great potential of LC-MS for drug efficacy evaluation and can be applied in other herbal medicine-related analyses.PMID:37933967 | DOI:10.1002/jssc.202300531

Grape seed proanthocyanidin improves intestinal inflammation in canine through regulating gut microbiota and bile acid compositions

Tue, 07/11/2023 - 12:00
FASEB J. 2023 Dec;37(12):e23285. doi: 10.1096/fj.202300819RR.ABSTRACTAlthough certain progress has been made in treating canine inflammatory bowel disease (IBD), a large proportion of dogs have a poor prognosis and may develop resistance and side effects. Therefore, it is of great significance to prevent or alleviate canine IBD through nutritional intervention. Plant polyphenol can interact with intestinal bacteria and has important prospects in the intestinal health improvement. This study evaluated the effect of grape seed proanthocyanidin (GSP), a plant-derived natural polyphenol, on Labrador Retrievers with mild IBD. In Experiment 1 of this study, GSP alleviated persistent intestinal inflammation in canines by improving inflammatory indexes and reducing intestinal permeability. Moreover, GSP treatment increased the abundance of bacteria with potential anti-inflammatory properties and engaging bile acid metabolism, including Ruminococcaceae, Faecalibacterium, Ruminococcus_torques_group, and Lachnospiraceae_NK4A136_group. Notably, targeted metabolomic analysis identified elevated productions of fecal chenodeoxycholic acid and its microbial transformation product lithocholic acid, which might contribute to relieving canine intestinal inflammation. Further, in Experiment 2, fecal microbiota transplantation was used to determine whether gut microbiota is a potential mechanism for GSP efficacy. Dogs with mild IBD received the fecal microbiota from the group administered GSP and mirrored the improvement effects of GSP, which results verified that gut microbial alteration could be an underlying mechanism for GSP efficiency on canine IBD. Our findings highlight that the mechanism of the GSP function on canine IBD is mediated by altering gut microbial composition and improving bile acid metabolism. This study proposes a natural polyphenol-based dietary strategy for improving canine intestinal health.PMID:37933950 | DOI:10.1096/fj.202300819RR

Chemical composition analysis of Angelica sinensis (Oliv.) Diels and its four processed products by ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry combining with nontargeted metabolomics

Tue, 07/11/2023 - 12:00
J Sep Sci. 2023 Nov 7:e2300473. doi: 10.1002/jssc.202300473. Online ahead of print.ABSTRACTAngelica sinensis (Oliv.) Diels. has been used for women to enrich the blood, prevent and treat blood deficiency syndrome in Traditional Chinese Medicine for thousands of years. Wine-processed Angelica sinensis, soil-processed Angelica sinensis, oil-processed Angelica sinensis, and charred-processed Angelica sinensis are the most significant four processed products used in Chinese clinic. However, there have been few studies aimed at comparing their chemical differences. Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry combining with nontargeted metabolomics was applied to investigate the diversity of processed products of Angelica sinensis. A total of 74 compounds with the variable importance in the projection value more than 1.5 and P less than 0.05 in ANOVA were highlighted as the compounds that contribute most to the discrimination of Angelica sinensis and four processed products. The results showed the metabolic changes between Angelica sinensis and its four processed products, there were 19 metabolites, 3 metabolites, 6 metabolites, and 45 metabolites were tentatively assigned in soil-processed Angelica sinensis, wine-processed Angelica sinensis, oil-processed Angelica sinensis, and charred-processed Angelica sinensis, respectively. These results suggested that the proposed metabolomics approach was useful for the quality evaluation and control of processed products of Angelica sinensis.PMID:37933715 | DOI:10.1002/jssc.202300473

Mesenchymal stem cell-derived extracellular vesicles for metabolic syndrome therapy: Assessing efficacy with nuclear magnetic resonance spectroscopy

Tue, 07/11/2023 - 12:00
Cell Biochem Funct. 2023 Nov 6. doi: 10.1002/cbf.3881. Online ahead of print.ABSTRACTMetabolic syndrome (MetS) represents a cluster of metabolic abnormalities. The prevalence of MetS has surged, transforming it into a pressing public health concern that could potentially affect around 20%-25% of the global population. As MetS continues its ascent, diverse interventions, pharmacological, nonpharmacological and combined have been deployed. Yet, a comprehensive remedy that fully eradicates MetS symptoms remains elusive, compounded by the risks of polypharmacy's emergence. Acknowledging the imperative to grasp MetS's intricate pathologies, deeper insights for future research and therapy optimisation become paramount. Conventional treatments often target specific syndrome elements. However, a novel approach emerges in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) therapy, promising a holistic shift. MSC-EVs, tiny membranous vesicles secreted by mesenchymal stem cells, have garnered immense attention for their multifaceted bioactivity and regenerative potential. Their ability to modulate inflammation, enhance tissue repair and regulate metabolic pathways has prompted researchers to explore their therapeutic application in MetS. This review primarily aims to provide an overview of how MSC-EVs therapy can improve metabolic parameters in subjects with MetS disease and also introduce the usefulness of NMR spectroscopy in assessing the efficacy of MSC-EVs therapy for treating MetS.PMID:37933415 | DOI:10.1002/cbf.3881

Metabolic characterization of neurogenetic disorders involving glutamatergic neurotransmission

Tue, 07/11/2023 - 12:00
J Inherit Metab Dis. 2023 Nov 6. doi: 10.1002/jimd.12689. Online ahead of print.ABSTRACTThe study of inborn errors of neurotransmission has been mostly focused on monoamine disorders, GABAergic and glycinergic defects. The study of the glutamatergic synapse using the same approach than classic neurotransmitter disorders is challenging due to the lack of biomarkers in the CSF. A metabolomic approach can provide both insight into their molecular basis and outline novel therapeutic alternatives. We have performed a semi-targeted metabolomic analysis on CSF samples from 25 patients with neurogenetic disorders with an important expression in the glutamatergic synapse and 5 controls. Samples from patients diagnosed with MECP2, CDKL5, GRINpathies and STXBP1 related encephalopathies were included. We have performed univariate (UVA) and multivariate statistical analysis (MVA), using Wilcoxon rank-sum test, principal component analysis (PCA), and oPLS-DA. By using the results of both analyses, we have identified the metabolites that were significantly altered and that were important in clustering the respective groups. On these, we performed pathway- and network-based analyses to define which metabolic pathways were possibly altered in each pathology. We have observed alterations in the tryptophan and branched-chain amino acid metabolism pathways, which interestingly converge on LAT1 transporter-dependency to cross the blood-brain barrier (BBB). Analysis of the expression of LAT1 transporter in brain samples from a mouse model of Rett syndrome (MECP2) revealed a decrease in the transporter expression, that was already noticeable at pre-symptomatic stages. The study of the glutamatergic synapse from this perspective advances the understanding of their pathophysiology, shining light on an under-studied feature as is their metabolic signature. This article is protected by copyright. All rights reserved.PMID:37932875 | DOI:10.1002/jimd.12689

Identification of Effectors: Precipitation of Supernatant Material

Mon, 06/11/2023 - 12:00
Methods Mol Biol. 2024;2715:533-538. doi: 10.1007/978-1-0716-3445-5_32.ABSTRACTBacterial secretion systems allow the transport of proteins, called effectors, as well as external machine components in the extracellular medium or directly into target cells. Comparison of the secretome, i.e., the proteins released in the culture medium, of wild-type and mutant cells provides information on the secretion profile. In addition, mass spectrometry analyses of the culture supernatant of bacteria grown in liquid culture under secreting conditions allow the identification of secretion systems substrates. Upon identification of the substrates, the secretion profile serves as a tool to test the functionality of secretion systems. Here, we present a classical method used to concentrate the culture supernatant, based on TCA precipitation.PMID:37930549 | DOI:10.1007/978-1-0716-3445-5_32

Health Outcomes Related to the Consumption of Olive Products: A Brief Review

Mon, 06/11/2023 - 12:00
Plant Foods Hum Nutr. 2023 Nov 6. doi: 10.1007/s11130-023-01119-w. Online ahead of print.ABSTRACTOlive oil, as well as by-products and waste that are left after production, particularly olive pomace and olive leaf, have been extensively researched as sources of phenolic compounds. These compounds are known for their biological properties and have been associated with the prevention of chronic non-communicable diseases. Metabolomics has been used as a methodological tool to elucidate the molecular mechanisms underlying these properties. The present review explores the health outcomes and changes in endogenous metabolite profiles induced by olive derivatives. A literature search was conducted using the scientific databases Scopus, Web of Science and PubMed, and the selected articles were published between the years 2012 and 2023. The reviewed studies have reported several health benefits of olive derivatives and their phenolic components, including appetite regulation, fewer cardiovascular disorders, and antiproliferative properties. This review also addressed the bioavailability of these compounds, their impact on the microbiota, and described biomarkers of their intake. Therefore, there should be further research using this methodology for a better understanding of the performance and therapeutic potential of olive derivatives.PMID:37932611 | DOI:10.1007/s11130-023-01119-w

Chromosome-level genomes of three key Allium crops and their trait evolution

Mon, 06/11/2023 - 12:00
Nat Genet. 2023 Nov 6. doi: 10.1038/s41588-023-01546-0. Online ahead of print.ABSTRACTAllium crop breeding remains severely hindered due to the lack of high-quality reference genomes. Here we report high-quality chromosome-level genome assemblies for three key Allium crops (Welsh onion, garlic and onion), which are 11.17 Gb, 15.52 Gb and 15.78 Gb in size with the highest recorded contig N50 of 507.27 Mb, 109.82 Mb and 81.66 Mb, respectively. Beyond revealing the genome evolutionary process of Allium species, our pathogen infection experiments and comparative metabolomic and genomic analyses showed that genes encoding enzymes involved in the metabolic pathway of Allium-specific flavor compounds may have evolved from an ancient uncharacterized plant defense system widely existing in many plant lineages but extensively boosted in alliums. Using in situ hybridization and spatial RNA sequencing, we obtained an overview of cell-type categorization and gene expression changes associated with spongy mesophyll cell expansion during onion bulb formation, thus indicating the functional roles of bulb formation genes.PMID:37932434 | DOI:10.1038/s41588-023-01546-0

METLIN-CCS: an ion mobility spectrometry collision cross section database

Mon, 06/11/2023 - 12:00
Nat Methods. 2023 Nov 6. doi: 10.1038/s41592-023-02078-5. Online ahead of print.NO ABSTRACTPMID:37932399 | DOI:10.1038/s41592-023-02078-5

Metronomic and single high-dose paclitaxel treatments produce distinct heterogenous chemoresistant cancer cell populations

Mon, 06/11/2023 - 12:00
Sci Rep. 2023 Nov 6;13(1):19232. doi: 10.1038/s41598-023-46055-6.ABSTRACTMore than 75% of epithelial ovarian cancer (EOC) patients experience disease recurrence after initial treatment, highlighting our incomplete understanding of how chemoresistant populations evolve over the course of EOC progression post chemotherapy treatment. Here, we show how two paclitaxel (PTX) treatment methods- a single high dose and a weekly metronomic dose for four weeks, generate unique chemoresistant populations. Using mechanically relevant alginate microspheres and a combination of transcript profiling and heterogeneity analyses, we found that these PTX-treatment regimens produce distinct and resilient subpopulations that differ in metabolic reprogramming signatures, acquisition of resistance to PTX and anoikis, and the enrichment for cancer stem cells (CSCs) and polyploid giant cancer cells (PGCCs) with the ability to replenish bulk populations. We investigated the longevity of these metabolic reprogramming events using untargeted metabolomics and found that metabolites associated with stemness and therapy-induced senescence were uniquely abundant in populations enriched for CSCs and PGCCs. Predictive network analysis revealed that antioxidative mechanisms were likely to be differentially active dependent on both time and exposure to PTX. Our results illustrate how current standard chemotherapies contribute to the development of chemoresistant EOC subpopulations by either selecting for intrinsically resistant subpopulations or promoting the evolution of resistance mechanisms. Additionally, our work describes the unique phenotypic signatures in each of these distinct resistant subpopulations and thus highlights potential vulnerabilities that can be exploited for more effective treatment.PMID:37932310 | DOI:10.1038/s41598-023-46055-6

Microbiome and metabolome features in inflammatory bowel disease via multi-omics integration analyses across cohorts

Mon, 06/11/2023 - 12:00
Nat Commun. 2023 Nov 6;14(1):7135. doi: 10.1038/s41467-023-42788-0.ABSTRACTThe perturbations of the gut microbiota and metabolites are closely associated with the progression of inflammatory bowel disease (IBD). However, inconsistent findings across studies impede a comprehensive understanding of their roles in IBD and their potential as reliable diagnostic biomarkers. To address this challenge, here we comprehensively analyze 9 metagenomic and 4 metabolomics cohorts of IBD from different populations. Through cross-cohort integrative analysis (CCIA), we identify a consistent characteristic of commensal gut microbiota. Especially, three bacteria, namely Asaccharobacter celatus, Gemmiger formicilis, and Erysipelatoclostridium ramosum, which are rarely reported in IBD. Metagenomic functional analysis reveals that essential gene of Two-component system pathway, linked to fecal calprotectin, are implicated in IBD. Metabolomics analysis shows 36 identified metabolites with significant differences, while the roles of these metabolites in IBD are still unknown. To further elucidate the relationship between gut microbiota and metabolites, we construct multi-omics biological correlation (MOBC) maps, which highlights gut microbial biotransformation deficiencies and significant alterations in aminoacyl-tRNA synthetases. Finally, we identify multi-omics biomarkers for IBD diagnosis, validated across multiple global cohorts (AUROC values ranging from 0.92 to 0.98). Our results offer valuable insights and a significant resource for developing mechanistic hypotheses on host-microbiome interactions in IBD.PMID:37932270 | DOI:10.1038/s41467-023-42788-0

Defence mechanisms of Pinctada fucata martensii to Vibrio parahaemolyticus infection: Insights from proteomics and metabolomics

Mon, 06/11/2023 - 12:00
Fish Shellfish Immunol. 2023 Nov 4:109204. doi: 10.1016/j.fsi.2023.109204. Online ahead of print.ABSTRACTSurvival of pearl oysters is not only challenged by coastal pollution, but also pathogen infection that may eventually incur substantial economic losses in the pearl farming industry. Yet, whether pearl oysters can defend themselves against pathogen infection through molecular mechanisms remains largely unexplored. By using iTRAQ proteomic and metabolomic analyses, we analysed the proteins and metabolites in the serum of pearl oysters (Pinctada fucata martensii) when stimulated by pathogenic bacteria (Vibrio parahaemolyticus). Proteomic results found that a total of 2,242 proteins were identified in the experimental (i.e., Vibrio-stimulated) and control groups, where 166 of them were differentially expressed (120 upregulated and 46 downregulated in the experimental group). Regarding the immune response enrichment results, the pathway of signal transduction was significantly enriched, such as cytoskeleton and calcium signalling pathways. Proteins, including cathepsin L, heat shock protein 20, myosin and astacin-like protein, also contributed to the immune response of oysters. Pathogen stimulation also altered the metabolite profile of oysters, where 49 metabolites associated with metabolism of energy, fatty acids and amino acids were found. Integrated analysis suggests that the oysters could respond to pathogen infection by coordinating multiple cellular processes. Thus, the proteins and metabolites identified herein not only represent valuable genetic resources for developing molecular biomarkers and genetic breeding research, but also open new avenues for studies on the molecular defence mechanisms of pearl oysters to pathogen infection.PMID:37931889 | DOI:10.1016/j.fsi.2023.109204

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