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

The inclusion of engineered ZnO nanoparticles and bulk ZnSO<sub>4</sub> in the growth medium distinctively modulate the root and leaf metabolome in bean plants

Mon, 12/06/2023 - 12:00
Physiol Plant. 2023 Jun 12:e13952. doi: 10.1111/ppl.13952. Online ahead of print.ABSTRACTTogether with toxicity, beneficial effects on plant growth have been ascribed to nanoparticles (NPs). This study aimed to survey the growth performance and metabolome adjustment of beans grown in a growth medium containing ZnONPs at different concentrations and compared to bulk ZnSO4 as a positive control. Growth parameters showed a reduction in shoot height starting from the lowest (25 mg l-1 ) concentration of ZnONPs. In comparison, growth was inhibited from 50 mg l-1 ZnSO4 , suggesting more toxic effects of nano forms of Zn. Untargeted metabolomics allowed us to unravel the biochemical processes involved in both promising and detrimental aspects. Multivariate statistics indicated that the tested Zn species substantially and distinctively altered the metabolic profile of both roots and leaves, with more metabolites altered in the former (435) compared to leaves (381). Despite having Zn forms in the growth medium, also leaf metabolome underwent a significant and extensive modulation. In general, the elicitation of secondary metabolism (N-containing compounds, phenylpropanoids, and phytoalexins) and the down-accumulation of fatty acid biosynthesis compounds were common responses to different Zn forms. However, an opposite trend could be observed for amino acids, fatty acids, carbohydrates, and cofactors being down-accumulated in ZnONPs treatment. Osmolytes, especially in ZnSO4 treatment, contributed to mitigating the effect of Zn toxicity and maintaining plant growth. Overall, the results indicated a complexity of tissue-specific and Zn-dependent response differences, resulting in distinctive metabolic perturbations. This article is protected by copyright. All rights reserved.PMID:37306385 | DOI:10.1111/ppl.13952

Applications of Genomics, Metabolomics, Fourier Transform Infrared in the Evaluation of Spoilage Targets of <em>Shewanella putrefaciens</em> from Spoiled Bigeye Tuna

Mon, 12/06/2023 - 12:00
J Agric Food Chem. 2023 Jun 12. doi: 10.1021/acs.jafc.3c02113. Online ahead of print.ABSTRACTShewanella putrefaciens is a typical spoiler that is commonly found in seafood and has high spoilage potential. However, the spoilage mechanism against Shewanella putrefaciens at the gene and metabolism levels has not been well elucidated. This work determined the spoilage targets on Shewanella putrefaciens XY07 from spoiled bigeye tuna by genome sequencing, metabolomics, and Fourier transform infrared (FTIR) analysis. Shewanella putrefaciens XY07 contained some genes on spoilage regulating of cys genes, his genes, spe genes and rpoS gene involved in sulfur metabolism, histidine metabolism, arginine and proline degradation, and biofilm formation at the genome level, respectively. Some spoilage genes like speC, cysM, trxB genes were identified. In addition, ABC transporters, arginine and proline metabolism; beta-alanine metabolism; glycine, serine, and threonine metabolism; histidine metabolism; sulfur metabolism; and lipid metabolism were identified as important pathways related to aquatic food during spoilage, which indicated the functions of amino acid degradation in S. putrefaciens XY 07 by metabolomics analysis. The metabolites of l-ornithine, 5-aminopentanoate, and 4-aminobutyraldehyde could be further metabolized to spermidine and spermine, producing a spoilage odor, and were involved in arginine and proline metabolism serving as key spoilage regulating metabolisms. Therefore, Shewanella putrefaciens XY07 was applied to genomics, metabolomics analysis, and FTIR to provide comprehensive insight into the investigation of spoilage targets.PMID:37306251 | DOI:10.1021/acs.jafc.3c02113

The gut microbiota in breast cancer development and treatment: The good, the bad, and the useful!

Mon, 12/06/2023 - 12:00
Gut Microbes. 2023 Jan-Dec;15(1):2221452. doi: 10.1080/19490976.2023.2221452.ABSTRACTRegardless of the global progress in early diagnosis and novel therapeutic regimens, breast carcinoma poses a devastating threat, and the advances are somewhat marred by high mortality rates. Breast cancer risk prediction models based on the known risk factors are extremely useful, but a large number of breast cancers develop in women with no/low known risk. The gut microbiome exerts a profound impact on the host health and physiology and has emerged as a pivotal frontier in breast cancer pathogenesis. Progress in metagenomic analysis has enabled the identification of specific changes in the host microbial signature. In this review, we discuss the microbial and metabolomic changes associated with breast cancer initiation and metastatic progression. We summarize the bidirectional impact of various breast cancer-related therapies on gut microbiota and vice-versa. Finally, we discuss the strategies to modulate the gut microbiota toward a more favorable state that confers anticancer effects.PMID:37305949 | DOI:10.1080/19490976.2023.2221452

Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids

Mon, 12/06/2023 - 12:00
J Pharm Anal. 2023 May;13(5):483-493. doi: 10.1016/j.jpha.2023.04.007. Epub 2023 Apr 14.ABSTRACTThree-dimensional (3D) cell spheroid models combined with mass spectrometry imaging (MSI) enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions. Herein, airflow-assisted desorption electrospray ionization-MSI (AFADESI-MSI) was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone (AMI). High-coverage imaging of >1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI. Following AMI treatment at different times, 15 metabolites of AMI involved in N-desethylation, hydroxylation, deiodination, and desaturation metabolic reactions were identified, and according to their spatiotemporal dynamics features, the metabolic pathways of AMI were proposed. Subsequently, the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis. The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism, providing considerable evidence for the mechanism of AMI hepatotoxicity. In addition, a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI. The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal information for drugs, drug metabolites, and endogenous metabolites after AMI treatment, providing an effective tool for in vitro drug hepatotoxicity evaluation.PMID:37305784 | PMC:PMC10257197 | DOI:10.1016/j.jpha.2023.04.007

Corrigendum to "Seminal plasma metabolomics signatures of normosmic congenital hypogonadotropic hypogonadism" [Heliyon 9(4) (March 2023) e14779]

Mon, 12/06/2023 - 12:00
Heliyon. 2023 Apr 25;9(5):e15657. doi: 10.1016/j.heliyon.2023.e15657. eCollection 2023 May.ABSTRACT[This corrects the article DOI: 10.1016/j.heliyon.2023.e14779.].PMID:37305512 | PMC:PMC10256820 | DOI:10.1016/j.heliyon.2023.e15657

Azelaic acid and guanosine in tears improve discrimination of proliferative from non-proliferative diabetic retinopathy in type-2 diabetes patients: A tear metabolomics study

Mon, 12/06/2023 - 12:00
Heliyon. 2023 May 18;9(5):e16109. doi: 10.1016/j.heliyon.2023.e16109. eCollection 2023 May.ABSTRACTBACKGROUND: Diabetic retinopathy (DR) is the microvascular ocular complication of diabetes mellitus (DM), which can lead to irreversible blindness and visual impairment if not properly treated. Tears can be collected non-invasively, and the compositions of tears could be the potential biomarkers for ocular diseases. Here we aimed to delineate the metabolomics signature in tears collected from Chinese type-2 DM patients with DR.METHODS: The metabolomics profiles of tear samples from 41 Chinese type-2 DM patients with DR and 21 non-diabetic subjects were determined by the untargeted liquid chromatography-mass spectrometry. The associated pathways of the differentially abundant metabolites were delineated, and the receiver operating characteristic curve analysis was conducted to identify the metabolites differentiating non-proliferative DR (NPDR) from proliferative DR (PDR).RESULTS: Total 14 differentially abundant metabolites were identified between total DR and non-diabetic subjects, and 17 differentially abundant metabolites were found between the NPDR and PDR subjects. Moreover, total 18 differentially abundant metabolites were identified between the NPDR and PDR subjects with stratification in DR duration and blood glucose level. d-Glutamine and d-glutamate metabolism was significantly highlighted in the PDR group as compared to the non-diabetic group. For the predictive performance, azelaic acid combined with guanosine achieved the area under receiver operating characteristic curve of 0.855 in the comparison between NPDR and PDR groups.CONCLUSION: This study revealed the metabolomics changes in tear samples of DR patients. The metabolites in tears could be the potential biomarkers in the DR analysis.PMID:37305454 | PMC:PMC10256905 | DOI:10.1016/j.heliyon.2023.e16109

Editorial: Integrated omics approaches in the understanding of host-pathogen interactions

Mon, 12/06/2023 - 12:00
Front Cell Infect Microbiol. 2023 May 25;13:1215104. doi: 10.3389/fcimb.2023.1215104. eCollection 2023.NO ABSTRACTPMID:37305425 | PMC:PMC10248503 | DOI:10.3389/fcimb.2023.1215104

Mechanism and Pharmacodynamic Substance Basis of Raw and Wine-Processed <em>Evodia rutaecarpa</em> on Smooth Muscle Cells of Dysmenorrhea Mice

Mon, 12/06/2023 - 12:00
Pain Res Manag. 2023 Jun 1;2023:7711988. doi: 10.1155/2023/7711988. eCollection 2023.ABSTRACTOBJECTIVES: Evodia rutaecarpa (ER) is a well-known herbal Chinese medicine traditionally used for analgesia in dysmenorrhea, headaches, abdominal pain, etc. Notably, the analgesic effect of wine-processed Evodia rutaecarpa (PER) was more potent than that of raw ER. This research aimed to investigate the mechanism and pharmacodynamic substance basis of raw ER and PER on smooth muscle cells of dysmenorrhea mice.METHODS: Metabolomics methods based on UPLC-Q-TOF-MS were utilized to analyse the differential components of ER before and after wine processing. Afterwards, the uterine smooth muscle cells were isolated from the uterine tissue of dysmenorrhea and normal mice. The isolated dysmenorrhea uterine smooth muscle cells were randomly divided into four groups: model group, 7-hydroxycoumarin group (1 mmol/L), chlorogenic acid (1 mmol/L), and limonin (50 μmol/L). The normal group consisted of the isolated normal mouse uterine smooth muscle cells, which were repeated 3 times in each group. The cell contraction and the expression of P2X3 and Ca2+ in vitro were determined using immunofluorescence staining and laser confocal; ELISA was used for detection of PGE2, ET-1, and NO content after 7-hydroxycoumarin, chlorogenic acid, and limonin administered for 24 h.RESULTS: The metabolomics results suggested that seven differential compounds were identified in the extracts of raw ER and PER, including chlorogenic acid, 7-hydroxycoumarin, hydroxy evodiamine, laudanosine, evollionines A, limonin, and 1-methyl-2-[(z)-4-nonenyl]-4 (1H)-quinolone. The in vitro results showed that 7-hydroxycoumarin, chlorogenic acid, and limonin were able to inhibit cell contraction and PGE2, ET-1, P2X3, and Ca2+ in dysmenorrhea mouse uterine smooth muscle cells and increase the content of NO.CONCLUSION: Our finding suggested that the compounds of the PER were different from those of the raw ER, and 7-hydroxycoumarin, chlorogenic acid, and limonin could improve dysmenorrhea in mice whose uterine smooth muscle cell contraction was closed with endocrine factors and P2X3-Ca2+ pathway.PMID:37305097 | PMC:PMC10250099 | DOI:10.1155/2023/7711988

Effects of <em>Ganoderma lucidum</em> polysaccharide peptide ameliorating cyclophosphamide-induced immune dysfunctions based on metabolomics analysis

Mon, 12/06/2023 - 12:00
Front Nutr. 2023 May 25;10:1179749. doi: 10.3389/fnut.2023.1179749. eCollection 2023.ABSTRACTGanoderma lucidum polysaccharide peptide (GLPP) is one of the most abundant constituents of Ganoderma lucidum (G. lucidum), with a wide range of functional activities. The present study investigated the immunomodulatory effects of GLPP in cyclophosphamide (CTX)-induced immunosuppressive mice. The results showed that 100 mg/kg/day of GLPP administration significantly alleviated CTX-induced immune damage by improving immune organ indexes, earlap swelling rate, the index of carbon phagocytosis and clearance value, secretion of cytokines (TNF-α, IFN-γ, and IL-2), and immunoglobulin A(IgA) in the mice. Furthermore, ultra-performance liquid chromatography with mass/mass spectrometry (UPLC-MS/MS) was conducted to identify the metabolites, followed by biomarker and pathway analysis. The results showed that GLPP treatment alleviated CTX-induced alterations in the fecal metabolome profile, including arachidonic acid (AA), leukotriene D4 (LTD4), indole-3-ethanol, and formyltetrahydrofolate (CF), by reversing citric acid, malic acid, cortisol, and oleic acid. These results support the concept that GLPP exhibits immunomodulatory activity via the folate cycle, methionine cycle, TCA cycle, fatty acid biosynthesis and metabolism, glycerophospholipid metabolism, AA metabolism, and cAMP pathways. In conclusion, the results could be helpful to understand the use of GLPP to clarify the immunomodulatory mechanism and be used as immunostimulants to prevent CTX-induced side effects in the immune system.PMID:37305093 | PMC:PMC10248424 | DOI:10.3389/fnut.2023.1179749

Fasudil may alleviate alcohol-induced astrocyte damage by modifying lipid metabolism, as determined by metabonomics analysis

Mon, 12/06/2023 - 12:00
PeerJ. 2023 Jun 6;11:e15494. doi: 10.7717/peerj.15494. eCollection 2023.ABSTRACTAlcohol dependence is a chronic, relapsing encephalopathy characterized by compulsive craving for alcohol, loss of control over alcohol use, and the presence of negative emotions and physical discomfort when alcohol is unavailable. Harmful use of alcohol is one of the greatest risk factors for death, illness, and disability. Rho kinase inhibitors have neuroprotective effects. This study used metabonomics analysis to assess untreated astrocytes, astrocytes exposed to 75 mmol/L of alcohol, and astrocytes exposed to 75 mmol/L of alcohol and treated with 15 µg/mL fasudil for 24 h. One of the clearest differences between the alcohol-exposed and fasudil-treated alcohol-exposed groups was the abundance of lipids and lipid-like molecules, although glycerophospholipid metabolism was comparable in both groups. Our findings show that fasudil may alleviate alcohol-induced astrocyte damage by modifying lipid metabolism, providing a new approach for preventing and treating alcohol dependence.PMID:37304877 | PMC:PMC10252813 | DOI:10.7717/peerj.15494

Metabolomics of Dietary Intake of Total, Animal, and Plant Protein: Results from the Atherosclerosis Risk in Communities (ARIC) Study

Mon, 12/06/2023 - 12:00
Curr Dev Nutr. 2023 Mar 24;7(4):100067. doi: 10.1016/j.cdnut.2023.100067. eCollection 2023 Apr.ABSTRACTBACKGROUND: Dietary consumption has traditionally been studied through food intake questionnaires. Metabolomics can be used to identify blood markers of dietary protein that may complement existing dietary assessment tools.OBJECTIVES: We aimed to identify associations between 3 dietary protein sources (total protein, animal protein, and plant protein) and serum metabolites using data from the Atherosclerosis Risk in Communities Study.METHODS: Participants' dietary protein intake was derived from a food frequency questionnaire administered by an interviewer, and fasting serum samples were collected at study visit 1 (1987-1989). Untargeted metabolomic profiling was performed in 2 subgroups (subgroup 1: n = 1842; subgroup 2: n = 2072). Multivariable linear regression models were used to assess associations between 3 dietary protein sources and 360 metabolites, adjusting for demographic factors and other participant characteristics. Analyses were performed separately within each subgroup and meta-analyzed with fixed-effects models.RESULTS: In this study of 3914 middle-aged adults, the mean (SD) age was 54 (6) y, 60% were women, and 61% were Black. We identified 41 metabolites significantly associated with dietary protein intake. Twenty-six metabolite associations overlapped between total protein and animal protein, such as pyroglutamine, creatine, 3-methylhistidine, and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid. Plant protein was uniquely associated with 11 metabolites, such as tryptophan betaine, 4-vinylphenol sulfate, N-δ-acetylornithine, and pipecolate.CONCLUSIONS: The results of 17 of the 41 metabolites (41%) were consistent with those of previous nutritional metabolomic studies and specific protein-rich food items. We discovered 24 metabolites that had not been previously associated with dietary protein intake. These results enhance the validity of candidate markers of dietary protein intake and introduce novel metabolomic markers of dietary protein intake.PMID:37304852 | PMC:PMC10257224 | DOI:10.1016/j.cdnut.2023.100067

Discrimination of Traditional Chinese Medicine Syndromes in Type 2 Diabetic Patients Based on Metabolomics-Proteomics Profiles

Mon, 12/06/2023 - 12:00
Int J Anal Chem. 2023 Jun 2;2023:5722131. doi: 10.1155/2023/5722131. eCollection 2023.ABSTRACTMATERIALS AND METHODS: The metabolomics-proteomics of sixty patients with T2DM were acquired by high-performance liquid chromatography (HPLC). In addition, some clinical features, containing total cholesterol (TC), triglycerides (TG), hemoglobin A1c (HbA1c), body mass index (BMI), and low-density lipoprotein (LDL) together with high-density lipoprotein (HDL), were determined via clinical detection strategies. Abundant metabolites and proteins, respectively, were identified with the analysis of liquid chromatography tandem mass spectrometry (LC-MS/MS).RESULTS: 22 differentially abundant metabolites and 15 differentially abundant proteins were determined. The analysis of bioinformatics suggested that the differentially abundant proteins were commonly associated with the renin-angiotensin system, vitamin digestion and absorption, hypertrophic cardiomyopathy, and so on. Furthermore, differentially abundant metabolites were amino acids and were associated with the biosynthesis of CoA and pantothenate, together with the metabolisms of phenylalanine, beta-alanine, proline, and arginine. Combination analysis revealed that the vitamin metabolism pathway was predominantly affected.CONCLUSIONS: DHS syndrome can be separated by certain metabolic-proteomic differences, and metabolism is particularly prominent, especially in vitamin digestion and absorption. From the molecular level, we provide preliminary data for the extensive application of TCM in the study of T2DM, and at the same time benefited in a sense diagnosis and treatment of T2DM.PMID:37304842 | PMC:PMC10256445 | DOI:10.1155/2023/5722131

Change in Metabolomic Profile Associated with an Average Increase in Plain Water Intake of &gt;+ 1 L/Day, Sustained Over 4 Weeks, in Healthy Young Men with Initial Total Water Intake Below 2 L/Day

Mon, 12/06/2023 - 12:00
Paracelsus Proc Exp Med. 2023;2(1):41-66. doi: 10.33594/000000619. Epub 2023 Apr 7.ABSTRACTBACKGROUND/AIMS: Cells adapt to chronic extracellular hypotonicity by altering metabolism. Corresponding effects of sustained hypotonic exposure at the whole-person level remain to be confirmed and characterized in clinical and population-based studies. This analysis aimed to 1) describe changes in urine and serum metabolomic profiles associated with four weeks of sustained > +1 L/d drinking water in healthy, normal weight, young men, 2) identify metabolic pathways potentially impacted by chronic hypotonicity, and 3) explore if effects of chronic hypotonicity differ by type of specimen and/or acute hydration condition.MATERIALS: Untargeted metabolomic assays were completed for specimen stored from Week 1 and Week 6 of the Adapt Study for four men (20-25 years) who changed hydration classification during that period. Each week, first-morning urine was collected after overnight food and water restriction, and urine (t+60 min) and serum (t+90 min) were collected after a 750 mL bolus of drinking water. Metaboanalyst 5.0 was used to compare metabolomic profiles.RESULTS: In association with four weeks of > + 1 L/d drinking water, urine osmolality decreased below 800 mOsm/kg H2O and saliva osmolality decreased below 100 mOsm/kg H2O. Between Week 1 and Week 6, 325 of 562 metabolic features in serum changed by 2-fold or more relative to creatinine. Based on hypergeometric test p-value <0.05 or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway impact factor >0.2, the sustained > + 1 L/d of drinking water was associated with concurrent changes in carbohydrate, protein, lipid, and micronutrient metabolism, a metabolomic pattern of carbohydrate oxidation via the tricarboxylic acid (TCA) cycle, instead of glycolysis to lactate, and a reduction of chronic disease risk factors in Week 6. Similar metabolic pathways appeared potentially impacted in urine, but the directions of impact differed by specimen type.CONCLUSION: In healthy, normal weight, young men with initial total water intake below 2 L/d, sustained > + 1 L/d drinking water was associated with profound changes in serum and urine metabolomic profile, which suggested normalization of an aestivation-like metabolic pattern and a switch away from a Warburg-like pattern. Further research is warranted to pursue whole-body effects of chronic hypotonicity that reflect cell-level effects and potential beneficial effects of drinking water on chronic disease risk.PMID:37304678 | PMC:PMC10253256 | DOI:10.33594/000000619

Progress on diagnostic and prognostic markers of pancreatic cancer

Mon, 12/06/2023 - 12:00
Oncol Res. 2023 Apr 10;31(2):83-99. doi: 10.32604/or.2023.028905. eCollection 2023.ABSTRACTPancreatic cancer is a malignant disease characterized by low survival and high recurrence rate, whose patients are mostly at the stage of locally advanced or metastatic disease when first diagnosed. Early diagnosis is particularly important because prognostic/predictive markers help guide optimal individualized treatment regimens. So far, CA19-9 is the only biomarker for pancreatic cancer approved by the FDA, but its effectiveness is limited by low sensitivity and specificity. With recent advances in genomics, proteomics, metabolomics, and other analytical and sequencing technologies, the rapid acquisition and screening of biomarkers is now possible. Liquid biopsy also occupies a significant place due to its unique advantages. In this review, we systematically describe and evaluate the available biomarkers that have the greatest potential as vital tools in diagnosing and treating pancreatic cancer.PMID:37304241 | PMC:PMC10208033 | DOI:10.32604/or.2023.028905

Mass spectrometry imaging as an emerging tool for studying metabolism in human brain organoids

Mon, 12/06/2023 - 12:00
Front Mol Biosci. 2023 May 22;10:1181965. doi: 10.3389/fmolb.2023.1181965. eCollection 2023.ABSTRACTHuman brain organoids are emerging models to study human brain development and pathology as they recapitulate the development and characteristics of major neural cell types, and enable manipulation through an in vitro system. Over the past decade, with the advent of spatial technologies, mass spectrometry imaging (MSI) has become a prominent tool for metabolic microscopy, providing label-free, non-targeted molecular and spatial distribution information of the metabolites within tissue, including lipids. This technology has never been used for studies of brain organoids and here, we set out to develop a standardized protocol for preparation and mass spectrometry imaging of human brain organoids. We present an optimized and validated sample preparation protocol, including sample fixation, optimal embedding solution, homogenous deposition of matrices, data acquisition and processing to maximize the molecular information derived from mass spectrometry imaging. We focus on lipids in organoids, as they play critical roles during cellular and brain development. Using high spatial and mass resolution in positive- and negative-ion modes, we detected 260 lipids in the organoids. Seven of them were uniquely localized within the neurogenic niches or rosettes as confirmed by histology, suggesting their importance for neuroprogenitor proliferation. We observed a particularly striking distribution of ceramide-phosphoethanolamine CerPE 36:1; O2 which was restricted within rosettes and of phosphatidyl-ethanolamine PE 38:3, which was distributed throughout the organoid tissue but not in rosettes. This suggests that ceramide in this particular lipid species might be important for neuroprogenitor biology, while its removal may be important for terminal differentiation of their progeny. Overall, our study establishes the first optimized experimental pipeline and data processing strategy for mass spectrometry imaging of human brain organoids, allowing direct comparison of lipid signal intensities and distributions in these tissues. Further, our data shed new light on the complex processes that govern brain development by identifying specific lipid signatures that may play a role in cell fate trajectories. Mass spectrometry imaging thus has great potential in advancing our understanding of early brain development as well as disease modeling and drug discovery.PMID:37304070 | PMC:PMC10251497 | DOI:10.3389/fmolb.2023.1181965

Metabolomics analysis in rat hearts with ischemia/reperfusion injury after diazoxide postconditioning

Mon, 12/06/2023 - 12:00
Front Mol Biosci. 2023 May 25;10:1196894. doi: 10.3389/fmolb.2023.1196894. eCollection 2023.ABSTRACTBackground: Diazoxide is a selective mitochondrial-sensitive potassium channel opening agent that has a definite effect on reducing myocardial ischemia/reperfusion injury (MIRI). However, the exact effects of diazoxide postconditioning on the myocardial metabolome remain unclear, which might contribute to the cardioprotective effects of diazoxide postconditioning. Methods: Rat hearts subjected to Langendorff perfusion were randomly assigned to the normal (Nor) group, ischemia/reperfusion (I/R) group, diazoxide (DZ) group and 5-hydroxydecanoic acid + diazoxide (5-HD + DZ) group. The heart rate (HR), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and maximum left ventricular pressure (+dp/dtmax) were recorded. The mitochondrial Flameng scores were analysed according to the ultrastructure of the ventricular myocardial tissue in the electron microscopy images. Rat hearts of each group were used to investigate the possible metabolic changes relevant to MIRI and diazoxide postconditioning. Results: The cardiac function indices in the Nor group were better than those in the other groups at the end point of reperfusion, and the HR, LVDP and +dp/dtmax of the Nor group at T2 were significantly higher than those of the other groups. Diazoxide postconditioning significantly improved cardiac function after ischaemic injury, and the HR, LVDP and +dp/dtmax of the DZ group at T2 were significantly higher than those of the I/R group, which could be abolished by 5-HD. The HR, LVDP and +dp/dtmax of the 5-HD + DZ group at T2 were significantly lower than those of the DZ group. The myocardial tissue in the Nor group was mostly intact, while it exhibited considerable damage in the I/R group. The ultrastructural integrity of the myocardium in the DZ group was higher than that in the I/R and 5-HD + DZ groups. The mitochondrial Flameng score in the Nor group was lower than that in the I/R, DZ and 5-HD + DZ groups. The mitochondrial Flameng score in the DZ group was lower than that in the I/R and 5-HD + DZ groups. Five metabolites, namely, L-glutamic acid, L-threonine, citric acid, succinate, and nicotinic acid, were suggested to be associated with the protective effects of diazoxide postconditioning on MIRI. Conclusion: Diazoxide postconditioning may improve MIRI via certain metabolic changes. This study provides resource data for future studies on metabolism relevant to diazoxide postconditioning and MIRI.PMID:37304068 | PMC:PMC10248136 | DOI:10.3389/fmolb.2023.1196894

Soil chemistry, metabarcoding, and metabolome analyses reveal that a sugarcane-<em>Dictyophora indusiata</em> intercropping system can enhance soil health by reducing soil nitrogen loss

Mon, 12/06/2023 - 12:00
Front Microbiol. 2023 May 25;14:1193990. doi: 10.3389/fmicb.2023.1193990. eCollection 2023.ABSTRACTINTRODUCTION: Greater amounts of fertilizer are applied every year to meet the growing demand for food. Sugarcane is one of the important food sources for human beings.METHODS: Here, we evaluated the effects of a sugarcane-Dictyophora indusiata (DI) intercropping system on soil health by conducting an experiment with three different treatments: (1) bagasse application (BAS process), (2) bagasse + DI (DIS process), and (3) the control (CK). We then analyzed soil chemistry, the diversity of soil bacteria and fungi, and the composition of metabolites to clarify the mechanism underlying the effects of this intercropping system on soil properties.RESULTS AND DISCUSSION: Soil chemistry analyses revealed that the content of several soil nutrients such as nitrogen (N) and phosphorus (P) was higher in the BAS process than in the CK. In the DIS process, a large amount of soil P was consumed by DI. At the same time, the urease activity was inhibited, thus slowing down the loss of soil in the DI process, while the activity of other enzymes such as β-glucosidase and laccase was increased. It was also noticed that the content of lanthanum and calcium was higher in the BAS process than in the other treatments, and DI did not significantly alter the concentrations of these soil metal ions. Bacterial diversity was higher in the BAS process than in the other treatments, and fungal diversity was lower in the DIS process than in the other treatments. The soil metabolome analysis revealed that the abundance of carbohydrate metabolites was significantly lower in the BAS process than in the CK and the DIS process. The abundance of D(+)-talose was correlated with the content of soil nutrients. Path analysis revealed that the content of soil nutrients in the DIS process was mainly affected by fungi, bacteria, the soil metabolome, and soil enzyme activity. Our findings indicate that the sugarcane-DIS intercropping system can enhance soil health.PMID:37303785 | PMC:PMC10249477 | DOI:10.3389/fmicb.2023.1193990

The effects of ambient temperature exposure on feline fecal metabolome

Mon, 12/06/2023 - 12:00
Front Vet Sci. 2023 May 26;10:1141881. doi: 10.3389/fvets.2023.1141881. eCollection 2023.ABSTRACTINTRODUCTION: The fecal metabolome provides insight into overall gastrointestinal and microbial health. Methods for fecal sample storage in metabolomics research vary, however, making comparisons within current literature difficult. This study investigated the effect of ambient temperature exposure on microbial-derived metabolites of feline fecal samples.METHODS: Fecal samples were collected from 11 healthy cats from a local boarding facility. Samples were manually homogenized and aliquoted. The first aliquot was frozen at -80°C within 1 hour of defecation, and remaining samples were exposed to ambient temperature for 2, 4, 6, 8, 12, and 24 h prior to freezing at -80°C. Fecal metabolites were quantified using 1H NMR spectroscopy. Fifty metabolites were grouped into six categories (27 amino acids, 8 fatty acids, 5 sugars, 3 alcohols, 2 nitrogenous bases, 5 miscellaneous).RESULTS: Concentrations of 20 out of 50 metabolites significantly differed due to ambient temperature exposure (7 amino acids, 6 fatty acids, 2 alcohols, 1 nitrogenous base, 4 miscellaneous). The earliest detected changes occurred 6 h post-defecation for cadaverine and fumaric acid.DISCUSSION: This study shows ambient temperature exposure alters the composition of the feline fecal metabolome, but short-term (up to 4 h) exposure prior to storage in the freezer seems to be acceptable.PMID:37303717 | PMC:PMC10250732 | DOI:10.3389/fvets.2023.1141881

Acetate is a beneficial nutrient for E. coli at low glycolytic flux

Mon, 12/06/2023 - 12:00
EMBO J. 2023 Jun 12:e113079. doi: 10.15252/embj.2022113079. Online ahead of print.ABSTRACTAcetate, a major by-product of glycolytic metabolism in Escherichia coli and many other microorganisms, has long been considered a toxic waste compound that inhibits microbial growth. This counterproductive auto-inhibition represents a major problem in biotechnology and has puzzled the scientific community for decades. Recent studies have however revealed that acetate is also a co-substrate of glycolytic nutrients and a global regulator of E. coli metabolism and physiology. Here, we used a systems biology strategy to investigate the mutual regulation of glycolytic and acetate metabolism in E. coli. Computational and experimental analyses demonstrate that decreasing the glycolytic flux enhances co-utilization of acetate with glucose. Acetate metabolism thus compensates for the reduction in glycolytic flux and eventually buffers carbon uptake so that acetate, rather than being toxic, actually enhances E. coli growth under these conditions. We validated this mechanism using three orthogonal strategies: chemical inhibition of glucose uptake, glycolytic mutant strains, and alternative substrates with a natively low glycolytic flux. In summary, acetate makes E. coli more robust to glycolytic perturbations and is a valuable nutrient, with a beneficial effect on microbial growth.PMID:37303231 | DOI:10.15252/embj.2022113079

Epigenetic and Metabolomic Biomarkers for Biological Age: A Comparative Analysis of Mortality and Frailty Risk

Mon, 12/06/2023 - 12:00
J Gerontol A Biol Sci Med Sci. 2023 Jun 12:glad137. doi: 10.1093/gerona/glad137. Online ahead of print.ABSTRACTBiological age captures a person's age-related risk of unfavorable outcomes using biophysiological information. Multivariate biological age measures include frailty scores and molecular biomarkers. These measures are often studied in isolation, but here we present a large-scale study comparing them. In two prospective cohorts (n=3,222), we compared epigenetic (DNAm Horvath, DNAm Hannum, DNAm Lin, DNAm epiTOC, DNAm PhenoAge, DNAm DunedinPoAm, DNAm GrimAge, and DNAm Zhang) and metabolomic-based (MetaboAge, MetaboHealth) biomarkers in reflection of biological age, as represented by five frailty measures and overall mortality. Biomarkers trained on outcomes with biophysiological and/or mortality information outperformed age-trained biomarkers in frailty reflection and mortality prediction. DNAm GrimAge and MetaboHealth, trained on mortality, showed the strongest association with these outcomes. The associations of DNAm GrimAge and MetaboHealth with frailty and mortality were independent of each other and of the frailty score mimicking clinical geriatric assessment. Epigenetic, metabolomic, and clinical biological age markers seem to capture different aspects of aging. These findings suggest that mortality-trained molecular markers may provide novel phenotype reflecting biological age and strengthen current clinical geriatric health and well-being assessment.PMID:37303208 | DOI:10.1093/gerona/glad137

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