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

Multi-omics analysis reveals that iron deficiency impairs spermatogenesis by gut-hormone synthesis axis

Thu, 01/12/2022 - 12:00
Ecotoxicol Environ Saf. 2022 Nov 28;248:114344. doi: 10.1016/j.ecoenv.2022.114344. Online ahead of print.ABSTRACTConsidering that research has mainly focussed on how excessive iron supplementation leads to reproductive cytotoxicity, there is a lack of in-depth research on reproductive system disorders caused by iron deficiency. To gain a better understanding of the effects of iron deficiency on the reproductive system, especially spermatogenesis, we first constructed a mouse model of iron deficiency. We employed multi-omic analysis, including transcriptomics, metabolomics, and microbiomics, to comprehensively dissect the impact of iron deficiency on spermatogenesis. Moreover, we verified our findings in detail using western blot, immunofluorescence, immunohistochemistry, qRT-PCR and other techniques. Microbiomic analysis revealed altered gut microbiota in iron-deficient mice, and functional predictive analysis showed that gut microbiota can regulate spermatogenesis. The transcriptomic data indicated that iron deficiency directly alters expression of meiosis-related genes. Transcriptome data also revealed that iron deficiency indirectly regulates spermatogenesis by affecting hormone synthesis, findings confirmed by metabolomic data, western blot and immunofluorescence. Interestingly, competing endogenous RNA networks also play a vital role in regulating spermatogenesis after iron deficiency. Taken together, the data elucidate that iron deficiency impairs spermatogenesis and increases the risk of male infertility by affecting hormone synthesis and promoting gut microbiota imbalance.PMID:36455349 | DOI:10.1016/j.ecoenv.2022.114344

Morphophysiological, proteomic and metabolomic analyses reveal cadmium tolerance mechanism in common wheat (Triticum aestivum L.)

Thu, 01/12/2022 - 12:00
J Hazard Mater. 2022 Nov 25;445:130499. doi: 10.1016/j.jhazmat.2022.130499. Online ahead of print.ABSTRACTSoil cadmium (Cd) contamination can reduce wheat yield and quality, thus threatening food security and human health. Herein, morphological physiology, Cd accumulation and distribution, proteomic and metabolomic analyses were performed (using wheat cultivars 'Luomai23' (LM, Cd-sensitive) and 'Zhongyu10' (ZY, Cd-tolerant) at the seedling stage with sand culture) to reveal Cd tolerance mechanism. Cd inhibited wheat growth, caused oxidative stress, hindered carbon and nitrogen metabolism, and altered the quantity and composition of root exudates. The root Cd concentration was lower in ZY than in LM by about 35% under 15 μM Cd treatments. ZY reduced Cd uptake through root exudation of amino acids and alkaloids. ZY also reduced Cd accumulation through specific up-regulation (twice) of major facilitator superfamily (MFS) proteins. Furthermore, ZY enhanced Cd cell wall fixation and vacuolar compartmentalization by increasing pectin contents, hemicellulose1 contents, and adenosine triphosphate binding cassette subfamily C member 1 (ABCC1) transporter expression, thus reducing the Cd organelle fraction of ZY by about 12% and 44% in root and shoot, respectively, compared with LM. Additionally, ZY had enhanced resilience to Cd due to increased antioxidant capacity, plasma membrane stability, nitrogen metabolism, and endoplasmic reticulum homeostasis, indicating that the increased Cd tolerance could be because of multi-level coordination. These findings provide a reference for exploring the molecular mechanism of Cd tolerance and accumulation, providing a basis for safe utilization of Cd-contaminated soil by breeding Cd-tolerant and low Cd-accumulating wheat varieties.PMID:36455318 | DOI:10.1016/j.jhazmat.2022.130499

Immunosuppressive Extracellular Vesicles in CLL

Thu, 01/12/2022 - 12:00
Blood Cancer Discov. 2022 Dec 1:OF1-OF3. doi: 10.1158/2643-3230.BCD-22-0161. Online ahead of print.ABSTRACTCancer cells need to evade the immune system for their progression. In this issue of Blood Cancer Discovery, Gargiulo and colleagues report that in a mouse model of chronic lymphocytic leukemia, small extracellular vesicles inhibit antitumor immunity by altering CD8 T-cell transcriptome, proteome, and metabolome. See related article by Gargiulo et al., (9).PMID:36455131 | DOI:10.1158/2643-3230.BCD-22-0161

The PRK/Rubisco shunt strongly influences Arabidopsis seed metabolism and oil accumulation, affecting more than carbon recycling

Thu, 01/12/2022 - 12:00
Plant Cell. 2022 Dec 1:koac338. doi: 10.1093/plcell/koac338. Online ahead of print.ABSTRACTThe carbon efficiency of storage lipid biosynthesis from imported sucrose in green Brassicaceae seeds is proposed to be enhanced by the PRK/Rubisco shunt, in which ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) acts outside the context of the Calvin-Benson-Bassham cycle to recycle CO2 molecules released during fatty acid synthesis. This pathway utilizes metabolites generated by the nonoxidative steps of the pentose phosphate pathway. Photosynthesis provides energy for reactions such as the phosphorylation of ribulose 5-phosphate by phosphoribulokinase (PRK). Here we show that loss of PRK in Arabidopsis thaliana (Arabidopsis) blocks photoautotrophic growth and is seedling-lethal. However, seeds containing prk embryos develop normally, allowing us to use genetics to assess the importance of the PRK/Rubisco shunt. Compared to nonmutant siblings, prk embryos produce one third less lipids-a greater reduction than expected from simply blocking the proposed PRK/Rubisco shunt. However, developing prk seeds are also chlorotic and have elevated starch contents compared with their siblings, indicative of secondary effects. Overexpressing PRK did not increase embryo lipid content, but metabolite profiling suggested that Rubisco activity becomes limiting. Overall, our findings show that the PRK/Rubisco shunt is tightly integrated into the carbon metabolism of green Arabidopsis seeds, and that its manipulation affects seed glycolysis, starch metabolism, and photosynthesis.PMID:36454674 | DOI:10.1093/plcell/koac338

The octadecanoids: an emerging class of lipid mediators

Thu, 01/12/2022 - 12:00
Biochem Soc Trans. 2022 Dec 1:BST20210644. doi: 10.1042/BST20210644. Online ahead of print.ABSTRACTOxylipins are enzymatic and non-enzymatic metabolites of mono- or polyunsaturated fatty acids that encompass potent lipid mediators including the eicosanoids and docosanoids. Previously considered of low interest and often dismissed as 'just fat', octadecanoid oxylipins have only recently begun to be recognized as lipid mediators in humans. In the last few years, these compounds have been found to be involved in the mediation of multiple biological processes related to nociception, tissue modulation, cell proliferation, metabolic regulation, inflammation, and immune regulation. At the same time, the study of octadecanoids is hampered by a lack of standardization in the field, a paucity of analytical standards, and a lack of domain expertise. These issues have collectively limited the investigation of the biosynthesis and bioactivity of octadecanoids. Here, we present an overview of the primary enzymatic pathways for the oxidative metabolism of 18-carbon fatty acids in humans and of the current knowledge of the major biological activity of the resulting octadecanoids. We also propose a systematic nomenclature system based upon that used for the eicosanoids in order to avoid ambiguities and resolve multiple designations for the same octadecanoid. The aim of this review is to provide an initial framework for the field and to assist in its standardization as well as to increase awareness of this class of compounds in order to stimulate research into this interesting group of lipid mediators.PMID:36454542 | DOI:10.1042/BST20210644

AKT-driven epithelial-mesenchymal transition is affected by copper bioavailability in HER2 negative breast cancer cells via a LOXL2-independent mechanism

Thu, 01/12/2022 - 12:00
Cell Oncol (Dordr). 2022 Dec 1. doi: 10.1007/s13402-022-00738-w. Online ahead of print.ABSTRACTBACKGROUND: The main mechanism underlying cancer dissemination is the epithelial to mesenchymal transition (EMT). This process is orchestrated by cytokines like TGFβ, involving "non-canonical" AKT- or STAT3-driven pathways. Recently, the alteration of copper homeostasis seems involved in the onset and progression of cancer.METHODS: We expose different breast cancer cell lines, including two triple negative (TNBC) ones, an HER2 enriched and one cell line representative of the Luminal A molecular subtype, to short- or long-term copper-chelation by triethylenetetramine (TRIEN). We analyse changes in the expression of EMT markers (E-cadherin, fibronectin, vimentin and αSMA), in the levels and activity of extracellular matrix components (LOXL2, fibronectin and MMP2/9) and of copper homeostasis markers by Western blot analyses, immunofluorescence, enzyme activity assays and RT-qPCR. Boyden Chamber and wound healing assays revealed the impact of copper chelation on cell migration. Additionally, we explored whether perturbation of copper homeostasis affects EMT prompted by TGFβ. Metabolomic and lipidomic analyses were applied to search the effects of copper chelation on the metabolism of breast cancer cells. Finally, bioinformatics analysis of data on breast cancer patients obtained from different databases was employed to correlate changes in kinases and copper markers with patients' survival.RESULTS: Remarkably, only HER2 negative breast cancer cells differently responded to short- or long-term exposure to TRIEN, initially becoming more aggressive but, upon prolonged exposure, retrieving epithelial features, reducing their invasiveness. This phenomenon may be related to the different impact of the short and prolonged activation of the AKT kinase and to the repression of STAT3 signalling. Bioinformatics analyses confirmed the positive correlation of breast cancer patients' survival with AKT activation and up-regulation of CCS. Eventually, metabolomics studies demonstrate a prevalence of glycolysis over mitochondrial energetic metabolism and of lipidome changes in TNBC cells upon TRIEN treatment.CONCLUSIONS: We provide evidence of a pivotal role of copper in AKT-driven EMT activation, acting independently of HER2 in TNBC cells and via a profound change in their metabolism. Our results support the use of copper-chelators as an adjuvant therapeutic strategy for TNBC.PMID:36454513 | DOI:10.1007/s13402-022-00738-w

Effect of Delayed Centrifugation on the Levels of NMR-Measured Lipoproteins and Metabolites in Plasma and Serum Samples

Thu, 01/12/2022 - 12:00
Anal Chem. 2022 Dec 1. doi: 10.1021/acs.analchem.2c02167. Online ahead of print.ABSTRACTMetabolic profiling is widely used for large-scale association studies, based on biobank material. The main obstacle to the translation of metabolomic findings into clinical application is the lack of standardization, making validation in independent cohorts challenging. One reason for this is sensitivity of metabolites to preanalytical conditions. We present a systematic investigation of the effect of delayed centrifugation on the levels of NMR-measured metabolites and lipoproteins in serum and plasma samples. Blood was collected from 20 anonymous donors, of which 10 were recruited from an obesity clinic. Samples were stored at room temperature until centrifugation after 30 min, 1, 2, 4, or 8 h, which is within a realistic time scenario in clinical practice. The effect of delaying centrifugation on plasma and serum metabolic concentrations, and on concentrations of lipoprotein subfractions, was investigated. Our results show that lipoproteins are only minimally affected by a delay in centrifugation while metabolite levels are more sensitive to a delay. Metabolites significantly increased or decreased in concentration depending on delay duration. Further, we describe differences in the stability of serum and plasma, showing that plasma is more stable for metabolites, while lipoprotein subfractions are equally stable for both types of matrices.PMID:36454175 | DOI:10.1021/acs.analchem.2c02167

The Application of Spearman Partial Correlation for Screening Predictors of Weight Loss in a Multiomics Dataset

Thu, 01/12/2022 - 12:00
OMICS. 2022 Nov 28. doi: 10.1089/omi.2022.0135. Online ahead of print.ABSTRACTObesity has reached epidemic proportions in the United States, but little is known about the mechanisms of weight gain and weight loss. Integration of omics data is becoming a popular tool to increase understanding in such complex phenotypes. Biomarkers come in abundance, but small sample size remains a serious limitation in clinical trials. In the present study, we developed a strategy to screen predictors from a multiomics, high-dimensional, and longitudinal dataset from a small cohort of 10 women with obesity who were provided an identical very-low calorie diet. Our proposal explores the combinatorial space of potential predictors from transcriptomics, microbiome, metabolome, fecal bile acids, and clinical data with the application of the first-order Spearman partial correlation coefficient. Two statistics are proposed for screening predictors, the partial association score, and the persistent significance. We applied our strategy to predict rates of weight loss in our sample of participants in a hospital metabolic facility. Our method reduced an initial set of 42,000 biomarker candidates to 61 robust predictors. The results show baseline fecal bile acids and regulation in RT-polymerase chain reaction as the most predictive data sources in forecasting the rate of weight-loss. In summary, the present study proposes a strategy based on nonparametric statistics for ranking and screening predictors of weight loss from a multiomics study. The proposed biomarker screening strategy warrants further translational clinical investigation in obesity and other complex clinical phenotypes.PMID:36454164 | DOI:10.1089/omi.2022.0135

Metabolomics insights into the potential of encapsulated essential oils as multifunctional food additives

Thu, 01/12/2022 - 12:00
Crit Rev Food Sci Nutr. 2022 Dec 1:1-18. doi: 10.1080/10408398.2022.2151974. Online ahead of print.ABSTRACTGrowing consumer concern about foodborne disease outbreaks and health risks associated with chemical additives has propelled the usage of essential oils (EOs) as novel food additives, but are limited by instability. In this regard, a series of EOs nano/micro-capsules have been widely used to enhance their stability and improve food quality. However, classical food quality assessment methods are insufficient to fully characterize the effects of encapsulated EOs on food properties, including physical, biochemical, organoleptic, and microbial changes. Recently, the rapid development of high-throughput sequencing is accelerating the application of metabolomics in food safety and quality analysis. This review seeks to present the most recent achievements in the application of non-targeted metabolomics to identify and quantify the overall metabolite profile associated with food quality, which can guide the development of emerging food preservation technologies. The scientific findings confirm that metabolomics opens up exciting prospects for biomarker screening in food preservation and contributes to an in-depth understanding of the mechanisms of action (MoA) of EOs. Future research should focus on constructing food quality assessment criteria based on multi-omics technologies, which will drive the standardization and commercialization of EOs for food industry applications.PMID:36454059 | DOI:10.1080/10408398.2022.2151974

Haemophilus ducreyi Infection Induces Oxidative Stress, Central Metabolic Changes, and a Mixed Pro- and Anti-inflammatory Environment in the Human Host

Thu, 01/12/2022 - 12:00
mBio. 2022 Dec 1:e0312522. doi: 10.1128/mbio.03125-22. Online ahead of print.ABSTRACTFew studies have investigated host-bacterial interactions at sites of infection in humans using transcriptomics and metabolomics. Haemophilus ducreyi causes cutaneous ulcers in children and the genital ulcer disease chancroid in adults. We developed a human challenge model in which healthy adult volunteers are infected with H. ducreyi on the upper arm until they develop pustules. Here, we characterized host-pathogen interactions in pustules using transcriptomics and metabolomics and examined interactions between the host transcriptome and metabolome using integrated omics. In a previous pilot study, we determined the human and H. ducreyi transcriptomes and the metabolome of pustule and wounded sites of 4 volunteers (B. Griesenauer, T. M. Tran, K. R. Fortney, D. M. Janowicz, et al., mBio 10:e01193-19, 2019, https://doi.org/10.1128/mBio.01193-19). While we could form provisional transcriptional networks between the host and H. ducreyi, the study was underpowered to integrate the metabolome with the host transcriptome. To better define and integrate the transcriptomes and metabolome, we used samples from both the pilot study (n = 4) and new volunteers (n = 8) to identify 5,495 human differentially expressed genes (DEGs), 123 H. ducreyi DEGs, 205 differentially abundant positive ions, and 198 differentially abundant negative ions. We identified 42 positively correlated and 29 negatively correlated human-H. ducreyi transcriptome clusters. In addition, we defined human transcriptome-metabolome networks consisting of 9 total clusters, which highlighted changes in fatty acid metabolism and mitigation of oxidative damage. Taken together, the data suggest a mixed pro- and anti-inflammatory environment and rewired central metabolism in the host that provides a hostile, nutrient-limited environment for H. ducreyi. IMPORTANCE Interactions between the host and bacteria at sites of infection in humans are poorly understood. We inoculated human volunteers on the upper arm with the skin pathogen H. ducreyi or a buffer control and biopsied the resulting infected and sham-inoculated sites. We performed dual transcriptome sequencing (RNA-seq) and metabolic analysis on the biopsy samples. Network analyses between the host and bacterial transcriptomes and the host transcriptome-metabolome network were used to identify molecules that may be important for the virulence of H. ducreyi in the human host. Our results suggest that the pustule is highly oxidative, contains both pro- and anti-inflammatory components, and causes metabolic shifts in the host, to which H. ducreyi adapts to survive. To our knowledge, this is the first study to integrate transcriptomic and metabolomic responses to a single bacterial pathogen in the human host.PMID:36453940 | DOI:10.1128/mbio.03125-22

Lipo-Chitooligosaccharides Induce Specialized Fungal Metabolite Profiles That Modulate Bacterial Growth

Thu, 01/12/2022 - 12:00
mSystems. 2022 Dec 1:e0105222. doi: 10.1128/msystems.01052-22. Online ahead of print.ABSTRACTLipo-chitooligosaccharides (LCOs) are historically known for their role as microbial-derived signaling molecules that shape plant symbiosis with beneficial rhizobia or mycorrhizal fungi. Recent studies showing that LCOs are widespread across the fungal kingdom have raised questions about the ecological function of these compounds in organisms that do not form symbiotic relationships with plants. To elucidate the ecological function of these compounds, we investigate the metabolomic response of the ubiquitous human pathogen Aspergillus fumigatus to LCOs. Our metabolomics data revealed that exogenous application of various types of LCOs to A. fumigatus resulted in significant shifts in the fungal metabolic profile, with marked changes in the production of specialized metabolites known to mediate ecological interactions. Using network analyses, we identify specific types of LCOs with the most significant effect on the abundance of known metabolites. Extracts of several LCO-induced metabolic profiles significantly impact the growth rates of diverse bacterial species. These findings suggest that LCOs may play an important role in the competitive dynamics of non-plant-symbiotic fungi and bacteria. This study identifies specific metabolomic profiles induced by these ubiquitously produced chemicals and creates a foundation for future studies into the potential roles of LCOs as modulators of interkingdom competition. IMPORTANCE The activation of silent biosynthetic gene clusters (BGC) for the identification and characterization of novel fungal secondary metabolites is a perpetual motion in natural product discoveries. Here, we demonstrated that one of the best-studied symbiosis signaling compounds, lipo-chitooligosaccharides (LCOs), play a role in activating some of these BGCs, resulting in the production of known, putative, and unknown metabolites with biological activities. This collection of metabolites induced by LCOs differentially modulate bacterial growth, while the LCO standards do not convey the same effect. These findings create a paradigm shift showing that LCOs have a more prominent role outside of host recognition of symbiotic microbes. Importantly, our work demonstrates that fungi use LCOs to produce a variety of metabolites with biological activity, which can be a potential source of bio-stimulants, pesticides, or pharmaceuticals.PMID:36453934 | DOI:10.1128/msystems.01052-22

Molecular mechanism of the prefrontal cortex involved in electroacupuncture against myocardial ischemia based on metabolomics

Thu, 01/12/2022 - 12:00
Zhen Ci Yan Jiu. 2022 Nov 25;47(11):962-8. doi: 10.13702/j.1000-0607.20210846.ABSTRACTOBJECTIVE: To explore the effects of electroacupuncture(EA) on metabolic patterns of the prefrontal cortex in rats with acute myocardial ischemia.METHODS: Eighteen SD rats were randomly divided into sham group, model group and EA group, with 6 rats in each group. Rats in the model and EA groups were subject to acute myocardial ischemia by ligation of the left anterior descending coronary artery. For the EA group, EA stimulation (1 mA, 2 Hz/15 Hz, 30 min) was applied to "Shenmen"(HT7) -"Tongli"(HT5) once a day for 3 consecutive days. The histopathological changes of myocardial tissue and levels of ischemia modified albumin (IMA) in serum were determined by HE staining and ELISA, respectively. The LC-MS/MS technique was used to characterize the metabolic profiling of the prefrontal cortex. The differentially expressed metabolites were screened by principal component analysis(PCA) and partial least squares-linear discriminant analysis (PLS-LDA), and subsequently Kyoto encyclopedia of genes and genomes (KEGG) metabolic pathway enrichment analysis was performed.RESULTS: Compared with the sham group, the myocardial fibers were disordered and fractured, and content of serum IMA was significantly increased in the model group (P<0.01), which, however, were significantly decreased in the EA group (P<0.01). With PCA and PLS-LDA, there were 18 differential metabolites between the model and sham groups. Forty-eight differential metabolites were emerged between the EA and model groups. Three metabolites associated to the sphingolipid metabolism were reversed by EA stimulation, as indicated by KEGG.CONCLUSION: The molecular mechanism of EA against myocardial ischemia is partially mediated by regulating sphingolipid-related metabolites in the prefrontal cortex.PMID:36453672 | DOI:10.13702/j.1000-0607.20210846

How to employ metabolomic analysis to research on functions of prebiotics and probiotics in poultry gut health?

Thu, 01/12/2022 - 12:00
Front Microbiol. 2022 Nov 14;13:1040434. doi: 10.3389/fmicb.2022.1040434. eCollection 2022.ABSTRACTGut health can be considered one of the major, manageable constituents of the animal immunity and performance. The fast spread of intestinal diseases, and increase of antimicrobial resistance have been observed, therefore the intestinal health has become not only economically relevant, but also highly important subject addressing the interest of public health. It is expected, that the strategies to control infections should be based on development of natural immunity in animals and producing resilient flocks using natural solutions, whilst eliminating antibiotics and veterinary medicinal products from action. Probiotics and prebiotics have been favored, because they have potential to directly or indirectly optimize intestinal health by manipulating the metabolism of the intestinal tract, including the microbiota. Studying the metabolome of probiotics and gut environment, both in vivo, or using the in vitro models, is required to attain the scientific understanding about the functions of bioactive compounds in development of gut health and life lasting immunity. There is a practical need to identify new metabolites being the key bioactive agents regulating biochemical pathways of systems associated with gut (gut-associated axes). Technological advancement in metabolomics studies, and increasing access to the powerful analytical platforms have paved a way to implement metabolomics in exploration of the effects of prebiotics and probiotics on the intestinal health of poultry. In this article, the basic principles of metabolomics in research involving probiotics and probiotics are introduced, together with the overview of existing strategies and suggestions of their use to study metabolome in poultry.PMID:36452931 | PMC:PMC9701725 | DOI:10.3389/fmicb.2022.1040434

Serum Metabolomics of Benign Essential Blepharospasm Using Liquid Chromatography and Orbitrap Mass Spectrometry

Thu, 01/12/2022 - 12:00
Oxid Med Cell Longev. 2022 Nov 18;2022:6876327. doi: 10.1155/2022/6876327. eCollection 2022.ABSTRACTBACKGROUND: Benign essential blepharospasm (BEB) is a form of focal dystonia that causes excessive involuntary spasms of the eyelids. Currently, the pathogenesis of BEB remains unclear. This study is aimed at investigating the serum metabolites profiles in patients with BEB and healthy control and to identify the mechanism and biomarkers of this disease.METHODS: 30 patients with BEB and 33 healthy controls were recruited for this study. We conducted the quantitative and nontargeted metabolomics analysis of the serum samples from 63 subjects by using liquid chromatography and Orbitrap mass spectrometry (LC-Orbitrap MS). Multivariate statistical analysis was performed to detect and identify different metabolites between the two groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and receiver operating characteristic (ROC) curve analysis of the altered metabolites were performed.RESULTS: A total of 134 metabolites were found and identified. The metabolites belonged to several metabolic pathways including phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, linoleic acid metabolism, tryptophan metabolism, aminoacyl-tRNA biosynthesis, sphingolipid metabolism, glycosphingolipid biosynthesis, leucine and isoleucine biosynthesis, and vitamin B6 metabolism. Eight metabolites were identified as the potential biomarkers.CONCLUSIONS: These results demonstrated that serum metabolic profiling of BEB patients was significantly different from healthy controls based on LC-Orbitrap MS. Besides, metabolomics might provide useful information for a better understanding of BEB.PMID:36452462 | PMC:PMC9704060 | DOI:10.1155/2022/6876327

Cocultivation of Chinese prescription and intestine microbiota: SJZD alleviated the major symptoms of IBS-D subjects by tuning neurotransmitter metabolism

Thu, 01/12/2022 - 12:00
Front Endocrinol (Lausanne). 2022 Nov 14;13:1053103. doi: 10.3389/fendo.2022.1053103. eCollection 2022.ABSTRACTOBJECTIVE: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a recurrent and common disease featuring dysbiotic intestinal microbiota, with limited treatments. Si-Jun-Zi Decoction (SJZD), a classic Chinese prescription, has been extensively used for IBS-D. This work aimed to explore the ex vivo interactions of SJZD and IBS-D's intestinal microbiota.METHODS: Five samples of intestinal microbiota collected from IBS-D volunteers and five age-matched healthy controls were recruited from the Affiliated Hospital, Chengdu University of Traditional Chinese Medicine (TCM). A representative mixture of intestinal microbiota was composed of an equal proportion of these fecal samples. To simulate the clinical interaction, this microbiota was cocultivated with SJZD at clinical dosage in an anaerobic incubator at 37°C for 35 h. Microbiota and metabolic alterations were assessed by 16S rRNA gene sequencing in the V3/V4 regions and a nontargeted metabolome platform, respectively.RESULTS: After being cocultivated with SJZD, the dysbiotic intestine microbiota from IBS-D subjects was largely restored to those of the healthy controls. A total of 624 differentially expressed metabolites were detected by nontargeted metabolomics, of which 16 biomarkers were identified. These metabolites were then enriched into 11 pathways by KEGG, particularly those involved in neurotransmitter metabolism responses for the major symptom of IBS-D. Correlation analysis of bacterial metabolites demonstrated a synergistic pattern of neurotransmitter metabolism between Streptococcus and E. Shigella.CONCLUSION: SJZD rescued the dysbiotic intestinal microbiota and ameliorated the dysfunctional neurotransmitter metabolism involved in IBS-D's major symptoms.PMID:36452327 | PMC:PMC9704418 | DOI:10.3389/fendo.2022.1053103

Application of metabolomics in osteoporosis research

Thu, 01/12/2022 - 12:00
Front Endocrinol (Lausanne). 2022 Nov 14;13:993253. doi: 10.3389/fendo.2022.993253. eCollection 2022.ABSTRACTOsteoporosis (OP) is a systemic disease characterized by bone metabolism imbalance and bone microstructure destruction, which causes serious social and economic burden. At present, the diagnosis and treatment of OP mainly rely on imaging combined with drugs. However, the existing pathogenic mechanisms, diagnosis and treatment strategies for OP are not clear and effective enough, and the disease progression that cannot reflect OP further restricts its effective treatment. The application of metabolomics has facilitated the study of OP, further exploring the mechanism and behavior of bone cells, prevention, and treatment of the disease from various metabolic perspectives, finally realizing the possibility of a holistic approach. In this review, we focus on the application of metabolomics in OP research, especially the newer systematic application of metabolomics and treatment with herbal medicine and their extracts. In addition, the prospects of clinical transformation in related fields are also discussed. The aim of this study is to highlight the use of metabolomics in OP research, especially in exploring the pathogenesis of OP and the therapeutic mechanisms of natural herbal medicine, for the benefit of interdisciplinary researchers including clinicians, biologists, and materials engineers.PMID:36452325 | PMC:PMC9702081 | DOI:10.3389/fendo.2022.993253

Editorial: The application of OMICS technologies to interrogate host-virus interactions

Thu, 01/12/2022 - 12:00
Front Cell Infect Microbiol. 2022 Nov 14;12:1050012. doi: 10.3389/fcimb.2022.1050012. eCollection 2022.NO ABSTRACTPMID:36452297 | PMC:PMC9703051 | DOI:10.3389/fcimb.2022.1050012

Editorial: Secondary metabolism and fruit quality

Thu, 01/12/2022 - 12:00
Front Plant Sci. 2022 Nov 14;13:1072193. doi: 10.3389/fpls.2022.1072193. eCollection 2022.NO ABSTRACTPMID:36452114 | PMC:PMC9704809 | DOI:10.3389/fpls.2022.1072193

Untargeted metabolomic profiling of fresh and dried leaf extracts of young and mature <em>Eucalyptus globulus</em> trees indicates differences in the presence of specialized metabolites

Thu, 01/12/2022 - 12:00
Front Plant Sci. 2022 Nov 14;13:986197. doi: 10.3389/fpls.2022.986197. eCollection 2022.ABSTRACTAqueous extracts from Eucalyptus globulus leaves contain a wide variety of specialized metabolites, mainly polyphenols and appreciable amounts of volatile compounds, which are responsible for their diverse biological activities, such as antioxidant, antimicrobial, and allelopathic features. For this reason, several studies have been conducted to explore the composition of E. globulus leaf extracts for multiple therapeutic and commercial applications. However, so far, the available bibliographic reports only refer to the chemical composition of extracts prepared with leaves from mature trees, leaving much to clarify about the composition of juvenile eucalyptus leaf extracts. Furthermore, there is no consensus regarding the type of leaves, fresh or dried ones, to be used in the extraction procedure, considering the highest recovery of biologically active compounds. In this sense, this study aimed to characterize the chemical composition of aqueous extracts prepared with fresh and dried leaves from young and mature E. globulus trees. For this, leaf biomass from young and mature E. globulus trees was collected in three distinct places from a forest area, and after oven-drying a portion of the leaves, an extraction in hot water was carried out, followed by GC-MS and HPLC-MS/MS analyses. The results revealed that the maturity of eucalyptus trees and biomass drying significantly influenced the volatile and non-volatile composition of the aqueous extracts. Accordingly, while fresh leaf extracts of young trees had great levels of hydrolysable tannins, extracts prepared with fresh leaves from mature trees presented a wide range of terpenes. When dried leaf material was used, extracts had notorious contents of amino acids derivatives, C13 norisoprenoids, fatty and other organic acids. Overall, this study showed, for the first time, that plant maturity (young vs mature) and pre-processing (fresh vs dried) of foliar biomass of E. globulus trees need to be considered in the preparation of leaf aqueous extracts depending on the desired purposes, since major changes in what regards biologically active compounds were found.PMID:36452102 | PMC:PMC9702574 | DOI:10.3389/fpls.2022.986197

Gibberellin delays metabolic shift during tomato ripening by inducing auxin signaling

Thu, 01/12/2022 - 12:00
Front Plant Sci. 2022 Nov 14;13:1045761. doi: 10.3389/fpls.2022.1045761. eCollection 2022.ABSTRACTFruit ripening involves the dynamic interaction of phytohormones. Ethylene (ET) and gibberellin (GA) antagonistically affect fruit ripening. However, the mechanism of GA and its potential interaction with ET during fruit ripening remain unknown. To identify the potential molecular mechanism of ET and GA interplay in tomato (Solanum lycopersicum L.) fruit ripening, transcriptome and metabolomic profiling was carried out in tomato fruit treated with GA, ET or the combination of the two hormones (GA+ET). ET accelerated fruit ripening with the simultaneous repression of auxin signaling. In contrast, gibberellin delayed ripening by the upregulation of auxin signaling. ET signaling and response was inhibited by GA or combined with ET. At the metabolite level, while GA treatment inhibited metabolite shift during ripening, ET treatment promoted. In the combined hormone treatment, ET reduced or recovered GA inhibitory effect on specific metabolites. This study provided insight into ET and GA interaction, highlighting the importance of auxin signaling in metabolic shifts during tomato ripening progression.PMID:36452096 | PMC:PMC9703062 | DOI:10.3389/fpls.2022.1045761

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