PubMed

J Nutr. 2023 Jun 2:S0022-3166(23)72201-3. doi: 10.1016/j.tjnut.2023.05.030. Online ahead of print.ABSTRACTINTRODUCTION: Poor diet quality is a risk factor for type 2 diabetes and cardiovascular disease. However, knowledge of metabolites marking adherence to Dietary Guidelines for Americans (2015 version; DGA-15) are limited. The goal was to determine a pattern of metabolites associated with the Healthy Eating Index-2015 (HEI-2015), which measures adherence to the DGA.METHODS: The analysis examined 3557 adult men and women from the longitudinal cohort Multi-Ethnic Study of Atherosclerosis (MESA), without known cardiovascular disease and with complete dietary data. Fasting serum specimens, diet and demographic questionnaires were assessed at baseline. Untargeted 1H NMR 1DNMR spectroscopy (600 MHz) was used to generate metabolomics and lipidomics. A metabolome-wide association study (MWAS) specified each spectral feature as outcomes, HEI-2015 score as predictor, adjusting for age, gender, race, and study site in linear regression analyses. Subsequently, hierarchical clustering defined discrete groups of correlated NMR features associated with named metabolites and linear regression analysis assessed for associations with HEI-2015 total and component scores.RESULTS: The sample included 50% women with average age of 63 years, with 40% identifying as White, 23% Black, 24% Hispanic and 13% Chinese American. The average HEI-2015 score was 66. MWAS identified 179 spectral features significantly associated with HEI-2015 score. Cluster analysis identified seven clusters representing 4 metabolites; HEI-2015 score was significantly associated with all. HEI-2015 score was associated with proline betaine (ß 0.12 [0.02]; p=4.70 E-13) and was inversely related to proline (ß -0.13 [0.02]; p=4.45 E-14), 1,5 anhydrosorbitol (ß -0.08 [0.02]; p=4.37 E-07) and unsaturated fatty acyl chains (ß 0.08 [0.02]; p=8.98 E-07). Intake of total fruit, whole grains and seafood and plant proteins was associated with proline betaine.CONCLUSIONS: Diet quality was significantly associated with unsaturated fatty acyl chains, proline betaine, proline. Further analysis may clarify the link between diet quality, metabolites, and pathogenesis of cardiometabolic disease.PMID:37271414 | DOI:10.1016/j.tjnut.2023.05.030

Fish Shellfish Immunol. 2023 Jun 2:108876. doi: 10.1016/j.fsi.2023.108876. Online ahead of print.ABSTRACTAeromonas hydrophila frequently has harmful effects on aquatic organisms. The intestine is an important defense against stress. In this study, we investigated the intestinal microbiota and transcriptomic and metabolomic responses of Cyprinus carpio subjected to A. hydrophila infection. The results showed that obvious variation in the intestinal microbiota was observed after infection, with increased levels of Firmicutes and Bacteroidetes and decreased levels of Proteobacteria. Several genera of putatively beneficial microbiota (Cetobacterium, Bacteroides, and Lactobacillus) were abundant, while Demequina, Roseomonas, Rhodobacter, Pseudoxanthomonas, and Cellvibrio were decreased; pathogenic bacteria of the genus Vibrio were increased after microbiota infection. The intestinal transcriptome revealed several immune-related differentially expressed genes associated with the cytokines and oxidative stress. The metabolomic analysis showed that microbiota infection disturbed the metabolic processes of the carp, particularly amino acid metabolism. This study provides insight into the underlying mechanisms associated with the intestinal microbiota, immunity, and metabolism of carp response to A. hydrophila infection; eleven stress-related metabolite markers were identified, including N-acetylglutamic acid, capsidiol, sedoheptulose 7-phosphate, prostaglandin B1, 8,9-DiHETrE, 12,13-DHOME, ADP, cellobiose, 1H-Indole-3-carboxaldehyde, sinapic acid and 5,7-dihydroxyflavone.PMID:37271325 | DOI:10.1016/j.fsi.2023.108876

J Allergy Clin Immunol. 2023 Jun 2:S0091-6749(23)00706-6. doi: 10.1016/j.jaci.2023.05.013. Online ahead of print.ABSTRACTBACKGROUND: Growing up on traditional European, and U.S. Amish, dairy farms, in close contact with cows and hay, protects children against asthma, and airway administration of extracts from dust collected from cowsheds of those farms prevents allergic asthma in mice.OBJECTIVES: This study sought to begin identifying farm-derived asthma-protective agents.METHODS: Our work unfolded along two unbiased, independent but complementary discovery paths. Dust extracts from protective and non-protective farms (European and Amish cowsheds vs. European sheep sheds) were analyzed by comparative nuclear magnetic resonance fingerprinting and differential proteomics. Bioactivity-guided size fractionation focused on protective Amish cowshed dust extracts. Multiple in vitro and in vivo functional assays were used in both paths. Some of the proteins thus identified were characterized by in-solution and in-gel SDS-PAGE enzymatic digestion/peptide mapping followed by liquid chromatography/mass spectrometry. The cargo carried by these proteins was analyzed by untargeted liquid chromatography-high resolution mass spectrometry.RESULTS: Twelve carrier proteins of animal and plant origin, including the bovine lipocalins Bos d2 and odorant binding protein, were enriched in dust extracts from protective European cowsheds. A potent asthma-protective fraction of Amish cowshed dust extracts (≈0.5% of the total carbon content of unfractionated extracts) contained seven animal and plant proteins, including Bos d2 and odorant binding protein loaded with fatty acid metabolites from plants, bacteria and fungi.CONCLUSIONS: Animals and plants from traditional farms produce proteins that transport hydrophobic microbial and plant metabolites. When delivered to mucosal surfaces, these agents might regulate airway responses.PMID:37271318 | DOI:10.1016/j.jaci.2023.05.013

Free Radic Biol Med. 2023 Jun 2:S0891-5849(23)00473-2. doi: 10.1016/j.freeradbiomed.2023.05.032. Online ahead of print.ABSTRACTNAD+ and glutathione precursors are currently used as metabolic modulators for improving the metabolic conditions associated with various human diseases, including non-alcoholic fatty liver disease, neurodegenerative diseases, mitochondrial myopathy, and age-induced diabetes. Here, we performed a one-day double blinded, placebo-controlled human clinical study to assess the safety and acute effects of six different Combined Metabolic Activators (CMAs) with 1 g of different NAD+ precursors based on global metabolomics analysis. Our integrative analysis showed that the NAD+ salvage pathway is the main source for boosting the NAD+ levels with the administration of CMAs without NAD+ precursors. We observed that incorporation of nicotinamide (Nam) in the CMAs can boost the NAD+ products, followed by niacin (NA), nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), but not flush free niacin (FFN). In addition, the NA administration led to a flushing reaction, accompanied by decreased phospholipids and increased bilirubin and bilirubin derivatives, which could be potentially risky. In conclusion, this study provided a plasma metabolomic landscape of different CMA formulations, and proposed that CMAs with Nam, NMN as well as NR can be administered for boosting NAD+ levels to improve altered metabolic conditions.PMID:37271226 | DOI:10.1016/j.freeradbiomed.2023.05.032

Metabolomics. 2023 Jun 5;19(6):53. doi: 10.1007/s11306-023-02020-y.ABSTRACTINTRODUCTION: A decrease in sperm cell count has been observed along the last several decades, especially in the most developed regions of the world. The use of metabolomics to study the composition of the seminal fluid is a promising approach to gain access to the molecular mechanisms underlying this fact.OBJECTIVES: In the present work, we aimed at relating metabolomic profiles of young healthy men to their semen quality parameters obtained from conventional microscopic analysis.METHODS: An untargeted metabolomics approach focusing on low- to mid-polarity compounds was used to analyze a subset of seminal fluid samples from a cohort of over 2700 young healthy men.RESULTS: Our results show that a broad metabolic profiling comprising several families of compounds (including acyl-carnitines, steroids, and other lipids) can contribute to effectively distinguish samples provided by individuals exhibiting low or high absolute sperm counts.CONCLUSION: A number of metabolites involved in sexual development and function, signaling, and energy metabolism were highlighted as being distinctive of samples coming from either group, proving untargeted metabolomics as a promising tool to better understand the pathophysiological processes responsible for male fertility impairment.PMID:37271779 | DOI:10.1007/s11306-023-02020-y

NPJ Parkinsons Dis. 2023 Jun 3;9(1):84. doi: 10.1038/s41531-023-00531-y.ABSTRACTWe performed liquid chromatography tandem mass spectrometry analysis with the targeted metabolomic kit Biocrates MxP Quant 500, in human brain cortex (Brodmann area 9) and putamen, to reveal metabolic changes characteristic of Parkinson's disease (PD) and PD-related cognitive decline. This case-control study involved 101 subjects (33 PD without dementia, 32 PD with dementia (cortex only), 36 controls). We found changes associated with PD, cognitive status, levodopa levels, and disease progression. The affected pathways include neurotransmitters, bile acids, homocysteine metabolism, amino acids, TCA cycle, polyamines, β-alanine metabolism, fatty acids, acylcarnitines, ceramides, phosphatidylcholines, and several microbiome-derived metabolites. Previously reported levodopa-related homocysteine accumulation in cortex still best explains the dementia status in PD, which can be modified by dietary supplementation. Further investigation is needed to reveal the exact mechanisms behind this pathological change.PMID:37270646 | DOI:10.1038/s41531-023-00531-y

Nat Commun. 2023 Jun 3;14(1):3215. doi: 10.1038/s41467-023-39028-w.ABSTRACTOur previous studies have shown that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the intestinal microbiome could be one of the causes of non-alcoholic fatty liver disease (NAFLD). Considering antimicrobial resistance of K. pneumoniae and dysbacteriosis caused by antibiotics, phage therapy might have potential in treatment of HiAlc Kpn-induced NAFLD, because of the specificity targeting the bacteria. Here, we clarified the effectiveness of phage therapy in male mice with HiAlc Kpn-induced steatohepatitis. Comprehensive investigations including transcriptomes and metabolomes revealed that treatment with HiAlc Kpn-specific phage was able to alleviate steatohepatitis caused by HiAlc Kpn, including hepatic dysfunction and expression of cytokines and lipogenic genes. In contrast, such treatment did not cause significantly pathological changes, either in functions of liver and kidney, or in components of gut microbiota. In addition to reducing alcohol attack, phage therapy also regulated inflammation, and lipid and carbohydrate metabolism. Our data suggest that phage therapy targeting gut microbiota is an alternative to antibiotics, with potential efficacy and safety, at least in HiAlc Kpn-caused NAFLD.PMID:37270557 | DOI:10.1038/s41467-023-39028-w

Clin Nutr. 2023 May 4:S0261-5614(23)00141-3. doi: 10.1016/j.clnu.2023.04.027. Online ahead of print.ABSTRACTBACKGROUND: Western dietary habits (WD) have been shown to promote chronic inflammation, which favors the development of many of today's non-communicable diseases. Recently, ketogenic diets (KD) have emerged as an immune-regulating countermeasure for WD-induced metaflammation. To date, beneficial effects of KD have been solely attributed to the production and metabolism of ketone bodies. Given the drastic change in nutrient composition during KD, it is reasonable to assume that there are widespread changes in the human metabolome also contributing to the impact of KD on human immunity. The current study was conducted to gain insight into the changes of the human metabolic fingerprint associated with KD. This could allow to identify metabolites that may contribute to the overall positive effects on human immunity, but also help to recognize potential health risks of KD.METHODS: We conducted a prospective nutritional intervention study enrolling 40 healthy volunteers to perform a three-week ad-libitum KD. Prior to the start and at the end of the nutritional intervention serum metabolites were quantified, untargeted mass spectrometric metabolome analyses and urine analyses of the tryptophan pathway were performed.RESULTS: KD led to a marked reduction of insulin (-21.45% ± 6.44%, p = 0.0038) and c-peptide levels (-19.29% ± 5.45%, p = 0.0002) without compromising fasting blood glucose. Serum triglyceride concentration decreased accordingly (-13.67% ± 5.77%, p = 0.0247), whereas cholesterol parameters remained unchanged. LC-MS/MS-based untargeted metabolomic analyses revealed a profound shift of the human metabolism towards mitochondrial fatty acid oxidation, comprising highly elevated levels of free fatty acids and acylcarnitines. The serum amino acid (AA) composition was rearranged with lower abundance of glucogenic AA and an increase of BCAA. Furthermore, an increase of anti-inflammatory fatty acids eicosatetraenoic acid (p < 0.0001) and docosahexaenoic acid (p = 0.0002) was detected. Urine analyses confirmed higher utilization of carnitines, indicated by lower carnitine excretion (-62.61% ± 18.11%, p = 0.0047) and revealed changes to the tryptophan pathway depicting reduced quinolinic acid (-13.46% ± 6.12%, p = 0.0478) and elevated kynurenic acid concentrations (+10.70% ± 4.25%, p = 0.0269).CONCLUSIONS: A KD fundamentally changes the human metabolome even after a short period of only three weeks. Besides a rapid metabolic switch to ketone body production and utilization, improved insulin and triglyceride levels and an increase in metabolites that mediate anti-inflammation and mitochondrial protection occurred. Importantly, no metabolic risk factors were identified. Thus, a ketogenic diet could be considered as a safe preventive and therapeutic immunometabolic tool in modern medicine.TRIAL REGISTRATION: German Clinical Trials Register; DRKS-ID: DRKS00027992 (www.drks.de).PMID:37270344 | DOI:10.1016/j.clnu.2023.04.027

BMJ Open Respir Res. 2023 Jun;10(1):e001683. doi: 10.1136/bmjresp-2023-001683.ABSTRACTBACKGROUND: The L-arginine metabolome is dysregulated in asthma, though it is not understood how longitudinal changes in L-arginine metabolism differ among asthma phenotypes and relate to disease outcomes.OBJECTIVES: To determine the longitudinal associations between phenotypic characteristics with L-arginine metabolites and their relationships with asthma morbidity.METHODS: This is a prospective cohort study of 321 patients with asthma followed semiannually for over 18 months with assessments of plasma L-arginine metabolites, asthma control, spirometry, quality of life and exacerbations. Metabolite concentrations and ratios were transformed using the natural logarithm.RESULTS: There were many differences in L-arginine metabolism among asthma phenotypes in the adjusted models. Increasing body mass index was associated with increased asymmetric dimethylarginine (ADMA) and depleted L-citrulline. Latinx was associated with increased metabolism via arginase, with higher L-ornithine, proline and L-ornithine/L-citrulline levels, and was found to have higher L-arginine availability compared with white race. With respect to asthma outcomes, increasing L-citrulline was associated with improved asthma control and increasing L-arginine and L-arginine/ADMA were associated with improved quality of life. Increased variability in L-arginine, L-arginine/ADMA, L-arginine/L-ornithine and L-arginine availability index over 12 months were associated with increased exacerbations, OR 4.70 (95% CI 1.35 to 16.37), OR 8.69 (95% CI 1.98 to 38.08), OR 4.17 (95% CI 1.40 to 12.41) and OR 4.95 (95% CI 1.42 to 17.16), respectively.CONCLUSIONS: Our findings suggest that L-arginine metabolism is associated with multiple measures of asthma control and may explain, in part, the relationship between age, race/ethnicity and obesity with asthma outcomes.PMID:37270184 | DOI:10.1136/bmjresp-2023-001683

Sci Total Environ. 2023 Jun 1:164619. doi: 10.1016/j.scitotenv.2023.164619. Online ahead of print.ABSTRACTPolystyrene microplastics (PS-MPs) have emerged as a concerning pollutant in modern society due to their widespread production and usage. Despite ongoing research efforts, the impact of PS-MPs on mammalian behavior and the mechanisms driving these effects remain incompletely elucidated. Consequently, effective strategies for prevention have yet to be developed. To fill these gaps, C57BL/6 mice were orally administered with 5 μm PS-MPs for 28 consecutive days in this study. The open-field test and the elevated plus-maze test were performed to evaluate the anxiety-like behavior, 16S rRNA sequencing and untargeted metabolomics analysis were used to detect the changes of gut microbiota and serum metabolites. Our results indicated that PS-MPs exposure activated hippocampal inflammation and induced anxiety-like behavior in mice. Meanwhile, PS-MPs disturbed the gut microbiota, impaired the intestinal barrier, and aroused peripheral inflammation. Specifically, PS-MPs increased the abundance of pathogenic microbiota Tuzzerella, while lowered the abundance of probiotics Faecalibaculum and Akkermansia. Interestingly, eliminating the gut microbiota protected against the deleterious effects of PS-MPs on intestinal barrier integrity, reduced the levels of peripheral inflammatory cytokines, and ameliorated anxiety-like behavior. Additionally, green tea's primary bioactive constituent, epigallocatechin-3-gallate (EGCG), optimized gut microbial composition, improved intestinal barrier function, reduced peripheral inflammation, and exerted anti-anxiety effects by inhibiting the hippocampal TLR4/MyD88/NF-κB signaling cascade. EGCG also remodeled serum metabolism, especially modulated purine metabolism. These findings suggested that gut microbiota participates in PS-MPs-induced anxiety-like behavior by modulating the gut-brain axis, and that EGCG could serve as a potential preventive strategy.PMID:37269995 | DOI:10.1016/j.scitotenv.2023.164619

J Biol Chem. 2023 Jun 1:104877. doi: 10.1016/j.jbc.2023.104877. Online ahead of print.ABSTRACTAbcb10 is a mitochondrial membrane protein involved in hemoglobinization of red cells. Abcb10 topology and ATPase domain localization suggest it exports a substrate, likely biliverdin, out of mitochondria that is necessary for hemoglobinization. In this study we generated Abcb10 deletion cell lines in both mouse murine erythroleukemia (MEL) and human erythroid precursor human myelogenous leukemia (K562) cells to better understand the consequences of Abcb10 loss. Loss of Abcb10 resulted in an inability to hemoglobinize upon differentiation in both K562 and MEL cells with reduced heme and intermediate porphyrins and decreased levels of aminolevulinic acid synthase 2 activity. Metabolomic and transcriptional analyses revealed that Abcb10 loss gave rise to decreased cellular arginine levels, increased transcripts for cationic and neutral amino acid transporters with reduced levels of the citrulline to arginine converting enzymes argininosuccinate synthetase and argininosuccinate lyase. The reduced arginine levels in Abcb10 null cells gave rise to decreased proliferative capacity. Arginine supplementation improved both Abcb10 null proliferation and hemoglobinization upon differentiation. Abcb10 null cells showed increased phosphorylation of Eukaryotic Translation Initiation Factor 2 Subunit Alpha (eIF2A), increased expression of nutrient sensing transcription factor ATF4 and downstream targets DNA damage inducible transcript 3 (Chop), ChaC glutathione specific gamma-glutamylcyclotransferase 1 (Chac1) and arginyl-tRNA synthetase 1 (Rars). These results suggest that when the Abcb10 substrate is trapped in the mitochondria, the nutrient sensing machinery is turned on remodeling transcription to block protein synthesis necessary for proliferation and hemoglobin biosynthesis in erythroid models.PMID:37269954 | DOI:10.1016/j.jbc.2023.104877

Food Chem. 2023 May 23;425:136434. doi: 10.1016/j.foodchem.2023.136434. Online ahead of print.ABSTRACTYoghurt fermented under sub-lethal high pressure (10, 20, 30 and 40 MPa at 43 °C), and afterward placed under refrigeration (4 °C for 23 days) was studied and compared with yoghurt fermented at atmospheric pressure (0.1 MPa). For a deeper analysis, metabolite fingerprinting by nuclear magnetic resonance (NMR), sugars and organic acids assessment by high performance liquid chromatography (HPLC), total fatty acids (TFA) determination and quantification by gas chromatography with a flame ionization detector (GC-FID) were performed. Metabolomic analyses revealed that only 2,3-butanediol, acetoin, diacetyl and formate vary with the increase of pressure and probable relation with pressure influenced diacetyl reductase, acetoin reductase and acetolactate decarboxylase. Yoghurts fermented at 40 MPa had the lowest content in lactose (39.7 % of total sugar reduction) and the less content in TFA (56.1 %). Further research is of interest to understand more about fermentation processes under sub-lethal high pressure.PMID:37269638 | DOI:10.1016/j.foodchem.2023.136434

J Hazard Mater. 2023 May 26;457:131718. doi: 10.1016/j.jhazmat.2023.131718. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS) are an important class of emerging contaminants in the environment. Most studies on the impact of PFAS mixtures considered phenotypic endpoints, which may not adequately reflect the sublethal effects on organisms. To fill this knowledge gap, we investigated the subchronic impact of environmentally relevant concentrations of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS)-as individual compounds and a mixture (PFOS+PFOA)-on earthworm (Eisenia fetida), using phenotypic and molecular endpoints. PFAS decreased the survival (12.2-16.3%), biomass (9.0-9.8%), and reproduction (15.6-19.8%) of E. fetida after 28 d of exposure. The bioaccumulation of PFOS after 28 d increased (from 2790.7 ng/g-dw to 5224.9 ng/g-dw) while that of PFOA decreased (from 780.2 ng/g-dw to 280.5 ng/g-dw) when E. fetida was exposed to the mixture compared to the individual compounds. These bioaccumulation trends were partly attributed to changes in the soil distribution coefficient (Kd) of PFOS and PFOA when present in the mixture. Eighty percent of the (p and FDR < 0.05) altered metabolites after 28 d were similarly perturbed by both PFOA and PFOS+PFOA. The pathways dysregulated are related to the metabolism of amino acids, energy, and sulfur. We showed that PFOA dominates the molecular-level impact of the binary PFAS mixture.PMID:37269561 | DOI:10.1016/j.jhazmat.2023.131718

J Mammary Gland Biol Neoplasia. 2023 Jun 3;28(1):12. doi: 10.1007/s10911-023-09540-2.ABSTRACTBreast cancer is well-known to be a highly heterogenous disease. This facet of cancer makes finding a research model that mirrors the disparate intrinsic features challenging. With advances in multi-omics technologies, establishing parallels between the various models and human tumors is increasingly intricate. Here we review the various model systems and their relation to primary breast tumors using available omics data platforms. Among the research models reviewed here, breast cancer cell lines have the least resemblance to human tumors since they have accumulated many mutations and copy number alterations during their long use. Moreover, individual proteomic and metabolomic profiles do not overlap with the molecular landscape of breast cancer. Interestingly, omics analysis revealed that the initial subtype classification of some breast cancer cell lines was inappropriate. In cell lines the major subtypes are all well represented and share some features with primary tumors. In contrast, patient-derived xenografts (PDX) and patient-derived organoids (PDO) are superior in mirroring human breast cancers at many levels, making them suitable models for drug screening and molecular analysis. While patient derived organoids are spread across luminal, basal- and normal-like subtypes, the PDX samples were initially largely basal but other subtypes have been increasingly described. Murine models offer heterogenous tumor landscapes, inter and intra-model heterogeneity, and give rise to tumors of different phenotypes and histology. Murine models have a reduced mutational burden compared to human breast cancer but share some transcriptomic resemblance, and representation of many breast cancer subtypes can be found among the variety subtypes. To date, while mammospheres and three- dimensional cultures lack comprehensive omics data, these are excellent models for the study of stem cells, cell fate decision and differentiation, and have also been used for drug screening. Therefore, this review explores the molecular landscapes and characterization of breast cancer research models by comparing recent published multi-omics data and analysis.PMID:37269418 | DOI:10.1007/s10911-023-09540-2

Planta. 2023 Jun 3;258(1):10. doi: 10.1007/s00425-023-04168-2.ABSTRACTA multi-year study of perennial Z. dumosum shows a consistent seasonal pattern in the changes of petiole metabolism, involving mainly organic acids, polyols, phenylpropanoids, sulfate conjugates, and piperazines. GC-MS and UPLC-QTOF-MS-based metabolite profiling was performed on the petioles of the perennial desert shrub Zygophyllum dumosum Boiss (Zygophyllaceae). The petioles, which are physiologically functional throughout the year and, thus, exposed to seasonal rhythms, were collected every month for 3 years from their natural ecosystem on a southeast-facing slope. Results showed a clear multi-year pattern following seasonal successions, despite different climate conditions, i.e., rainy and drought years, throughout the research period. The metabolic pattern of change encompassed an increase in the central metabolites, including most polyols, e.g., stress-related D-pinitol, organic and sugar acids, and in the dominant specialized metabolites, which were tentatively identified as sulfate, flavonoid, and piperazine conjugates during the summer-autumn period, while significantly high levels of free amino acids were detected during the winter-spring period. In parallel, the levels of most sugars (including glucose and fructose) increased in the petioles at the flowering stage at the beginning of the spring, while most of the di- and tri-saccharides accumulated at the beginning of seed development (May-June). Analysis of the conserved seasonal metabolite pattern of change shows that metabolic events are mostly related to the stage of plant development and its interaction with the environment and less to environmental conditions per se.PMID:37269337 | DOI:10.1007/s00425-023-04168-2

Anal Bioanal Chem. 2023 Jun 3. doi: 10.1007/s00216-023-04774-9. Online ahead of print.ABSTRACTMass spectrometry imaging (MSI) is a sensitive, specific, label-free imaging analysis technique that can simultaneously obtain the spatial distribution, relative content, and structural information of hundreds of biomolecules in cells and tissues, such as lipids, small drug molecules, peptides, proteins, and other compounds. The study of molecular mapping of single cells can reveal major scientific issues such as the activity pattern of living organisms, disease pathogenesis, drug-targeted therapy, and cellular heterogeneity. Applying MSI technology to the molecular mapping of single cells can provide new insights and ideas for the study of single-cell metabolomics. This review aims to provide an informative resource for those in the MSI community who are interested in single-cell imaging. Particularly, we discuss advances in imaging schemes and sample preparation, instrumentation improvements, data processing and analysis, and 3D MSI over the past few years that have allowed MSI to emerge as a powerful technique in the molecular imaging of single cells. Also, we highlight some of the most cutting-edge studies in single-cell MSI, demonstrating the future potential of single-cell MSI. Visualizing molecular distribution at the single-cell or even sub-cellular level can provide us with richer cell information, which strongly contributes to advancing research fields such as biomedicine, life sciences, pharmacodynamic testing, and metabolomics. At the end of the review, we summarize the current development of single-cell MSI technology and look into the future of this technology.PMID:37269305 | DOI:10.1007/s00216-023-04774-9

J Sep Sci. 2023 Jun 3:e2300210. doi: 10.1002/jssc.202300210. Online ahead of print.ABSTRACTDried blood spot samples are simple to prepare and transport, enabling safe and accessible diagnostics, both locally and globally. We review dried blood spot samples for clinical analysis, focusing on liquid chromatography-mass spectrometry as a versatile measurement tool for these samples. Dried blood spot samples can provide information for, for example, metabolomics, xenobiotic analysis, and proteomics. Targeted analyses of small molecules are the main application of dried blood spot samples and liquid chromatography-mass spectrometry, but emerging applications include untargeted metabolomics and proteomics. Applications are highly varied, including analyses related to newborn screening, diagnostics and monitoring of disease progression and treatment effects of virtually any disease, as well as studies into the physiology and effects of diet, exercise, xenobiotics, and doping. A range of dried blood spot products and methods are available, and applied liquid chromatography-mass spectrometry instrumentation is varied with regard to liquid chromatography column formats and selectivity. In addition, novel approaches such as on-paper sample preparation (e.g., selective trapping of analytes with paper-immobilized antibodies) are described. We focus on research papers published in the last 5 years.PMID:37269205 | DOI:10.1002/jssc.202300210

Proteomics. 2023 Jun 3:e2200407. doi: 10.1002/pmic.202200407. Online ahead of print.ABSTRACTMultiomics approaches to studying systems biology are very powerful techniques that can elucidate changes in the genomic, transcriptomic, proteomic, and metabolomic levels within a cell type in response to an infection. These approaches are valuable for understanding the mechanisms behind disease pathogenesis and how the immune system responds to being challenged. With the emergence of the COVID-19 pandemic, the importance and utility of these tools have become evident in garnering a better understanding of the systems biology within the innate and adaptive immune response and for developing treatments and preventative measures for new and emerging pathogens that pose a threat to human health. In this review, we focus on state-of-the-art omics technologies within the scope of innate immunity.PMID:37269203 | DOI:10.1002/pmic.202200407

PLoS One. 2023 Jun 2;18(6):e0286633. doi: 10.1371/journal.pone.0286633. eCollection 2023.ABSTRACTThe aim of this work is to quantify the metabolic profile of the human putamen in vivo in a cohort of elderly subjects using single-voxel proton magnetic resonance spectroscopy. To obtain metabolite concentrations specific to the putamen, we investigated a correction method previously proposed to account for the tissue composition of the volume of interest. We compared the method with the conventional approach, which a priori assumes equal metabolite concentrations in GM and WM. Finally, we compared the concentrations acquired at 3 Tesla (T) and 7 T MRI scanners. Spectra were acquired from 15 subjects (age: 67.7 ± 8.3 years) at 3 T and 7 T, using an ultra-short echo time, stimulated echo acquisition mode sequence. To robustly estimate the WM-to-GM metabolite concentration ratio, five additional subjects were measured for whom the MRS voxel was deliberately shifted from the putamen in order to increase the covered amount of surrounding WM. The concentration and WM-to-GM concentration ratio for 16 metabolites were reliably estimated. These ratios ranged from ~0.3 for γ-aminobutyric acid to ~4 for N-acetylaspartylglutamate. The investigated correction method led to significant changes in concentrations compared to the conventional method, provided that the ratio significantly differed from unity. Finally, we demonstrated that differences in tissue voxel composition cannot fully account for the observed concentration difference between field strengths. We provide not only a fully comprehensive quantification of the neurochemical profile of the putamen in elderly subjects, but also a quantification of the WM-to-GM concentration ratio. This knowledge may serve as a basis for future studies with varying tissue voxel composition, either due to tissue atrophy, inconsistent voxel positioning or simply when pooling data from different voxel locations.PMID:37267283 | PMC:PMC10237501 | DOI:10.1371/journal.pone.0286633

J Ovarian Res. 2023 Jun 2;16(1):107. doi: 10.1186/s13048-023-01166-6.ABSTRACTBACKGROUND: Poor ovarian responders (POR) are women undergoing in-vitro fertilization who respond poorly to ovarian stimulation, resulting in the retrieval of lower number of oocytes, and subsequently lower pregnancy rates. The follicular fluid (FF) provides a crucial microenvironment for the proper development of follicles and oocytes through tightly controlled metabolism and cell signaling. Androgens such as dehydroepiandrosterone (DHEA) have been proposed to alter the POR follicular microenvironment, but the impact DHEA imposes on the FF metabolome and cytokine profiles is unknown. Therefore, the objective of this study is to profile and identify metabolomic changes in the FF with DHEA supplementation in POR patients.METHODS: FF samples collected from 52 POR patients who underwent IVF with DHEA supplementation (DHEA +) and without (DHEA-; controls) were analyzed using untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics and a large-scale multiplex suspension immunoassay covering 65 cytokines, chemokines and growth factors. Multivariate statistical modelling by partial least squares-discriminant regression (PLSR) analysis was performed for revealing metabolome-scale differences. Further, differential metabolite analysis between the two groups was performed by PLSR β-coefficient regression analysis and Student's t-test.RESULTS: Untargeted metabolomics identified 118 FF metabolites of diverse chemistries and concentrations which spanned three orders of magnitude. They include metabolic products highly associated with ovarian function - amino acids for regulating pH and osmolarity, lipids such fatty acids and cholesterols for oocyte maturation, and glucocorticoids for ovarian steroidogenesis. Four metabolites, namely, glycerophosphocholine, linoleic acid, progesterone, and valine were significantly lower in DHEA + relative to DHEA- (p < 0.05-0.005). The area under the curves of progesterone glycerophosphocholine, linoleic acid and valine are 0.711, 0.730, 0.785 and 0.818 (p < 0.05-0.01). In DHEA + patients, progesterone positively correlated with IGF-1 (Pearson r: 0.6757, p < 0.01); glycerophosphocholine negatively correlated with AMH (Pearson r: -0.5815; p < 0.05); linoleic acid correlated with estradiol and IGF-1 (Pearson r: 0.7016 and 0.8203, respectively; p < 0.01 for both). In DHEA- patients, valine negatively correlated with serum-free testosterone (Pearson r: -0.8774; p < 0.0001). Using the large-scale immunoassay of 45 cytokines, we observed significantly lower MCP1, IFNγ, LIF and VEGF-D levels in DHEA + relative to DHEA.CONCLUSIONS: In POR patients, DHEA supplementation altered the FF metabolome and cytokine profile. The identified four FF metabolites that significantly changed with DHEA may provide information for titrating and monitoring individual DHEA supplementation.PMID:37268990 | DOI:10.1186/s13048-023-01166-6