PubMed

Front Plant Sci. 2023 Jan 13;13:1083971. doi: 10.3389/fpls.2022.1083971. eCollection 2022.ABSTRACTHeat stress drastically affects anther tissues resulting in poor plant fertility, necessitating an urgent need to determine the key proteome regulation associated with mature anther in response to heat stress. We identified several genotype - specific protein alterations in rice anthers of Moroberekan (Japonica, heat sensitive), IR64 (Indica, moderately heat tolerant), and Nagina22 (Aus, heat tolerant) in the short-term (ST_HS; one cycle of 42°C, 4 hours before anthesis) and long-term (LT_HS; 6 cycles of 38°C, 6 hours before anthesis) heat stress. The proteins upregulated in long-term heat stress in Nagina22 were enriched in biological processes related to unfolded protein binding and carboxylic acid metabolism, including amino acid metabolism. In short-term heat stress, Nagina22 anthers were enriched in proteins associated with vitamin E biosynthesis and GTPase activator activity. In contrast, downregulated proteins were related to ribosomal proteins. The expression of different Hsp20 and DnaJ was genotype specific. Overall, the heat response in Nagina22 was associated with its capacity for adequate metabolic control and cellular homeostasis, which may be critical for its higher reproductive thermotolerance. This study improves our understanding of thermotolerance mechanisms in rice anthers during anthesis and lays a foundation for breeding thermotolerant varieties via molecular breeding.PMID:36756226 | PMC:PMC9901367 | DOI:10.3389/fpls.2022.1083971

Front Oncol. 2023 Jan 23;13:1082841. doi: 10.3389/fonc.2023.1082841. eCollection 2023.ABSTRACTINTRODUCTION: The goal of this study was to establish an optimized metabolic panel by combining serum and urine biomarkers that could reflect the malignancy of cancer tissues to improve the non-invasive diagnosis of esophageal squamous cell cancer (ESCC).METHODS: Urine and serum specimens representing the healthy and ESCC individuals, together with the paralleled ESCC cancer tissues and corresponding distant non-cancerous tissues were investigated in this study using the high-resolution 600 MHz 1H-NMR technique.RESULTS: We identified distinct 1H NMR-based serum and urine metabolic signatures respectively, which were linked to the metabolic profiles of esophageal-cancerous tissues. Creatine and glycine in both serum and urine were selected as the optimal biofluids biomarker panel for ESCC detection, as they were the overlapping discriminative metabolites across serum, urine and cancer tissues in ESCC patients. Also, the were the major metabolites involved in the perturbation of "glycine, serine, and threonine metabolism", the significant pathway alteration associated with ESCC progression. Then a visual predictive nomogram was constructed by combining creatine and glycine in both serum and urine, which exhibited superior diagnostic efficiency (with an AUC of 0.930) than any diagnostic model constructed by a single urine or serum metabolic biomarkers.DISCUSSION: Overall, this study highlighted that NMR-based biofluids metabolomics fingerprinting, as a non-invasive predictor, has the potential utility for ESCC detection. Further studies based on a lager number size and in combination with other omics or molecular biological approaches are needed to validate the metabolic pathway disturbances in ESCC patients.PMID:36756157 | PMC:PMC9900168 | DOI:10.3389/fonc.2023.1082841

Front Immunol. 2023 Jan 23;14:1099186. doi: 10.3389/fimmu.2023.1099186. eCollection 2023.ABSTRACTThe mitigation and prevention of acute immune stress are essential for livestock production. Clostridium butyricum (C. butyricum) has shown positive effects in stabilizing intestinal microbiota disorders, improving immune function and inhibiting disease development, but its effects on ruminants are unclear. Therefore, the current trial hypothesized that C. butyricum could improve goats' immune function and antioxidant capacity by regulating bacterial communities and blood metabolism and effectively alleviating the acute immune stress induced by Lipopolysaccharides (LPS). Sixteen healthy goats were fed C. butyricum for 70 days, and the goats were challenged with LPS on day 71. Blood and feces were collected at 0 h and 6 h after the challenge to evaluate the effects of C. butyricum on their intestinal microbiota, immune function, antioxidant function, and plasma metabolites. The results showed that C. butyricum had no significant effect on plasma biochemical parameters at the beginning of the LPS challenge. However, supplementation with C. butyricum increased plasma levels of IgA, IgG, T-SOD, and T-AOC (P < 0.05), but TNF-α, IL-6, and MDA were decreased (P < 0.05). In contrast, IL-10 showed an increasing trend (P < 0.10). Rectal microbiota analysis showed that C. butyricum significantly increased the relative abundance of Epsilonbacteraeota at the phylum level of goats; at the genus level, the relative abundances of Campylobacter and Anaerorhabdus]_furcosa_group were also significantly increased (P < 0.05). Christensenellaceae_R-7_group as the dominant microbiota also showed a significant increase in their abundance values, while Clostridium and Lachnospiraceae_UCG-001 were significantly lower (P < 0.05). When the LPS challenge continued up to 6 h, dietary supplementation with C. butyricum still resulted in significantly higher plasma concentrations of IgA, IL-10, and T-SOD in goats than in the control group, reducing TNF-α levels (P < 0.05). In addition, plasma levels of T-CHOL and LDL were significantly reduced, and the expression of d-proline was significantly upregulated according to metabolomic analysis (P < 0.05). In conclusion, dietary supplementation with C. butyricum helped optimize the expression of bacterial communities and plasma metabolites to enhance the ability of goats to alleviate acute immune stress.PMID:36756118 | PMC:PMC9899838 | DOI:10.3389/fimmu.2023.1099186

Front Nutr. 2023 Jan 23;10:1118113. doi: 10.3389/fnut.2023.1118113. eCollection 2023.ABSTRACTAIM: Evidence linking dietary patterns and the risk of gastric cancer was limited, especially in Chinese populations. This study aimed to explore the association between dietary patterns and the risk of gastric cancer in residents of the Huaihe River Basin, China.METHODS: The association between dietary patterns and the risk of gastric cancer was investigated through a case-control study. Dietary patterns were identified with factor analysis based on responses to a food frequency questionnaire (FFQ). Gastric cancer was diagnosed according to the International Classification of Diseases, 10th Revision (ICD 10). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated across the tertiles of dietary pattern scores using unconditional logistic regression models.RESULTS: A total of 2,468 participants were included in this study. Six main dietary patterns were extracted, and those patterns explained 57.09% of the total variation in food intake. After adjusting for demographic characteristics, lifestyle factors, individual disease history, family history of cancer and Helicobacter. Pylori (H. pylori) infection, comparing the highest with the lowest tertiles of dietary pattern scores, the multivariable ORs (95% CIs) were 0.786 (0.488, 1.265; P trend < 0.001) for the flavors, garlic and protein pattern, 2.133 (1.299, 3.502; P trend < 0.001) for the fast food pattern, 1.050 (0.682, 1.617; P trend < 0.001) for the vegetable and fruit pattern, 0.919 (0.659, 1.282; P trend < 0.001) for the pickled food, processed meat products and soy products pattern, 1.149 (0.804, 1.642; P trend < 0.001) for the non-staple food pattern and 0.690 (0.481, 0.989; P trend < 0.001) for the coffee and dairy pattern.CONCLUSIONS: The specific dietary patterns were associated with the risk of gastric cancer. This study has implications for the prevention of gastric cancer.PMID:36755993 | PMC:PMC9899829 | DOI:10.3389/fnut.2023.1118113

Front Pharmacol. 2023 Jan 23;14:1104403. doi: 10.3389/fphar.2023.1104403. eCollection 2023.ABSTRACTObjective: Leonurine is a bioactive alkaloid compound extracted from Leonurus japonicus Houtt, which potentially has immunomodulatory effects. The immunomodulatory effect and mechanism of leonurine on monocyte derived dendritic cells (moDCs) from healthy donors (HDs) and multiple myeloma (MM) patients were investigated for the first time. Methods: Peripheral blood from HDs and MM patients was isolated for peripheral blood mononuclear cells (PBMCs). The generation of moDCs was conducted by the incubation of monocytes from PBMCs in the medium consisting of RPMI 1640 medium, 2 mmol/L L-glutamine, 5% human serum, 800 U/mL GM-CSF, 500 U/mL IL-4, 100 U/mL penicillin and 0.1 mg/mL streptomycin. During the incubation of 7 days, the cells were administrated with 1 μM leonurine or 1 × PBS as the control group. On the 8th day, cells were harvested. The expression of maturation associated surface markers CD40, CD83, and HLA-DR on moDCs was analyzed by flow cytometry. Moreover, moDCs with or without 1 μM leonurine administration were evaluated by LC-MS/MS for metabolomics which was further analyzed for the potential mechanism of leonurine on moDCs. Results: The proportion of moDCs in the harvested cells was significantly higher in the HD group (n = 14) than in the MM patient group (n = 11) (p = 0.000). Leonurine significantly enhanced the median fluorescence intensity of CD83, HLA-DR and CD40 expression on HD-moDCs (n = 14; p = 0.042, p = 0.013, p = 0.084) as well as MM paitent-moDCs (n = 11; p = 0.020, p = 0.006, p = 0.025). The metabolomics data showed that in moDCs (HD, n = 15), 18 metabolites in the pathway of arachidonic acid metabolism showed significant differences between the leonurine group and the control group (VIP all >1 and P all <0.05). To be specific, 6-Keto-PGE1, 8,9-DHET, 11 (R)-HETE, 12-Keto-LTB4, 12-OxoETE, 15 (S)-HETE, 15-Deoxy-Delta12,14-PGJ2, 15-Keto-PGF2a, 20-COOH-LTB4, Lecithin, PGA2, PGB2, PGE2, PGF2a, PGG2, Prostacyclin were significantly upregulated in the leonurine group than in the control group, while Arachidonic Acid and TXB2 were significantly downregulated in the leonurine group than in the control group. Conclusion: Leonurine significantly promotes the maturation of moDCs derived from HDs and MM patients, the mechanism of which is related to arachidonic acid metabolism.PMID:36755947 | PMC:PMC9899801 | DOI:10.3389/fphar.2023.1104403

Nat Protoc. 2023 Feb 8. doi: 10.1038/s41596-023-00803-0. Online ahead of print.ABSTRACTAnalytical techniques with high sensitivity and selectivity are essential to the quantitative analysis of clinical samples. Liquid chromatography coupled to tandem mass spectrometry is the gold standard in clinical chemistry. However, tandem mass spectrometers come at high capital expenditure and maintenance costs. We recently showed that it is possible to generate very similar results using a much simpler single mass spectrometry detector by performing enhanced in-source fragmentation/annotation (EISA) combined with correlated ion monitoring. Here we provide a step-by-step protocol for optimizing the analytical conditions for EISA, so anyone properly trained in liquid chromatography-mass spectrometry can follow and apply this technique for any given analyte. We exemplify the approach by using 2-hydroxyglutarate (2-HG) which is a clinically relevant metabolite whose D-enantiomer is considered an 'oncometabolite', characteristic of cancers associated with mutated isocitrate dehydrogenases 1 or 2 (IDH1/2). We include procedures for determining quantitative robustness, and show results of these relating to the analysis of DL-2-hydroxyglutarate in cells, as well as in serum samples from patients with acute myeloid leukemia that contain the IDH1/2 mutation. This EISA-mass spectrometry protocol is a broadly applicable and low-cost approach for the quantification of small molecules that has been developed to work well for both single-quadrupole and time-of-flight mass analyzers.PMID:36755131 | DOI:10.1038/s41596-023-00803-0

NPJ Biofilms Microbiomes. 2023 Feb 8;9(1):8. doi: 10.1038/s41522-023-00374-8.ABSTRACTAlthough emerging evidence shows that gut microbiota-mediated metabolic changes regulate intestinal pathogen invasions, little is known about whether and how gut microbiota-mediated metabolites affect pathogen infection in the distal organs. In this study, untargeted metabolomics was performed to identify the metabolic changes in a subacute ruminal acidosis (SARA)-associated mastitis model, a mastitis model with increased susceptibility to Staphylococcus aureus (S. aureus). The results showed that cows with SARA had reduced cholic acid (CA) and deoxycholic acid (DCA) levels compared to healthy cows. Treatment of mice with DCA, but not CA, alleviated S. aureus-induced mastitis by improving inflammation and the blood-milk barrier integrity in mice. DCA inhibited the activation of NF-κB and NLRP3 signatures caused by S. aureus in the mouse mammary epithelial cells, which was involved in the activation of TGR5. DCA-mediated TGR5 activation inhibited the NF-κB and NLRP3 pathways and mastitis caused by S. aureus via activating cAMP and PKA. Moreover, gut-dysbiotic mice had impaired TGR5 activation and aggravated S. aureus-induced mastitis, while restoring TGR5 activation by spore-forming bacteria reversed these changes. Furthermore, supplementation of mice with secondary bile acids producer Clostridium scindens also activated TGR5 and alleviated S. aureus-induced mastitis in mice. These results suggest that impaired secondary bile acid production by gut dysbiosis facilitates the development of S. aureus-induced mastitis and highlight a potential strategy for the intervention of distal infection by regulating gut microbial metabolism.PMID:36755021 | DOI:10.1038/s41522-023-00374-8

Nat Commun. 2023 Feb 8;14(1):697. doi: 10.1038/s41467-023-36368-5.ABSTRACTHuman acetyltransferases MOZ and MORF are implicated in chromosomal translocations associated with aggressive leukemias. Oncogenic translocations involve the far amino terminus of MOZ/MORF, the function of which remains unclear. Here, we identified and characterized two structured winged helix (WH) domains, WH1 and WH2, in MORF and MOZ. WHs bind DNA in a cooperative manner, with WH1 specifically recognizing unmethylated CpG sequences. Structural and genomic analyses show that the DNA binding function of WHs targets MORF/MOZ to gene promoters, stimulating transcription and H3K23 acetylation, and WH1 recruits oncogenic fusions to HOXA genes that trigger leukemogenesis. Cryo-EM, NMR, mass spectrometry and mutagenesis studies provide mechanistic insight into the DNA-binding mechanism, which includes the association of WH1 with the CpG-containing linker DNA and binding of WH2 to the dyad of the nucleosome. The discovery of WHs in MORF and MOZ and their DNA binding functions could open an avenue in developing therapeutics to treat diseases associated with aberrant MOZ/MORF acetyltransferase activities.PMID:36754959 | DOI:10.1038/s41467-023-36368-5

Gut. 2023 Feb 8:gutjnl-2022-329297. doi: 10.1136/gutjnl-2022-329297. Online ahead of print.NO ABSTRACTPMID:36754608 | DOI:10.1136/gutjnl-2022-329297

Sci Total Environ. 2023 Feb 6:162042. doi: 10.1016/j.scitotenv.2023.162042. Online ahead of print.ABSTRACTWater quality and phytoplankton community composition are important factors that can indicate freshwater ecosystem health. We combined water quality, phytoplankton community, and metabolomic data from algae and water sampled from two embayments in Lake Ontario, Hamilton Harbour and the Bay of Quinte, over ten weeks from August to October in the year 2020. Metabolomics was performed using liquid chromatography tandem mass spectroscopy (LC-MS/MS) to identify changes in intracellular metabolites within algae communities over time, and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was used to characterize putative isomers of extracellular metabolites at sub-ppb mass accuracy. Results from this study indicate that Hamilton Harbour and the Bay of Quinte are two very different ecosystems with respect to water quality, phytoplankton metabolites, and phytoplankton community composition. Community composition is strongly driven by conductivity and nitrates in Hamilton Harbour, while the opposite is true in the Bay of Quinte. Metabolites including α-aminobutyric acid and glycine were found in larger abundance within algal communities at both locations, while taurine was more predominant in algal communities from the Bay of Quinte. These metabolic profiles could reflect the different communities of phytoplankton, and be alternative indicators of algal bloom growth.PMID:36754333 | DOI:10.1016/j.scitotenv.2023.162042

Biomed Chromatogr. 2023 Feb 8:e5598. doi: 10.1002/bmc.5598. Online ahead of print.ABSTRACTOBJECTIVE: This study aimed to investigate the effect of Pikang oral liquid (PK) on psoriasis and analyze its possible mechanism from the perspective of metabolism.METHODS: A psoriasis-form mouse model established using imiquimod (IMQ) was used to evaluate the anti-psoriatic effects of PK. The serum samples were analyzed by high-resolution nuclear magnetic resonance (1 H NMR) based metabonomics. Nine amino acids were furthere quantitatively analyzed by ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS).RESULTS: This study suggested that PK treatment markedly attenuated IMQ-induced psoriasis in a dose-dependent manner. 1 HNMR based multivariate trajectory analysis revealed that PK had a certain regression effect on eight differential metabolites. The quantitative results showed that PK could regulate significantly the serum levels of alanine, histidine and arginine to the healthy control levels.CONCLUSIONS: The mechanism of PK on anti-psoriasis may be associated with the restoration of the disturbance in the amino acid metabolism, energy metabolism, and lipid metabolism and so on. Quantitative results further confirmed that amino acid metabolism play an key role in the pathogenesis of psoriasis. Our investigation provided a holistic view of PK for intervention psoriasis and provided the scientific information in vivo about a clinical value of PK for psoriasis.PMID:36754046 | DOI:10.1002/bmc.5598

Cell Metab. 2023 Feb 7;35(2):299-315.e8. doi: 10.1016/j.cmet.2023.01.009.ABSTRACTFOXP3+ regulatory T cells (Tregs) are central for peripheral tolerance, and their deregulation is associated with autoimmunity. Dysfunctional autoimmune Tregs display pro-inflammatory features and altered mitochondrial metabolism, but contributing factors remain elusive. High salt (HS) has been identified to alter immune function and to promote autoimmunity. By investigating longitudinal transcriptional changes of human Tregs, we identified that HS induces metabolic reprogramming, recapitulating features of autoimmune Tregs. Mechanistically, extracellular HS raises intracellular Na+, perturbing mitochondrial respiration by interfering with the electron transport chain (ETC). Metabolic disturbance by a temporary HS encounter or complex III blockade rapidly induces a pro-inflammatory signature and FOXP3 downregulation, leading to long-term dysfunction in vitro and in vivo. The HS-induced effect could be reversed by inhibition of mitochondrial Na+/Ca2+ exchanger (NCLX). Our results indicate that salt could contribute to metabolic reprogramming and that short-term HS encounter perturb metabolic fitness and long-term function of human Tregs with important implications for autoimmunity.PMID:36754020 | DOI:10.1016/j.cmet.2023.01.009

Cell Metab. 2023 Feb 7;35(2):233-235. doi: 10.1016/j.cmet.2023.01.007.ABSTRACTIn Nature Medicine, Surendran and colleagues recently reported the analysis of human plasma metabolomic data for 913 metabolites in ∼20,000 individuals, identifying 2,599 metabolite-genetic variant associations and >400 metabolite signatures comprised of jointly regulated metabolites. This extensive atlas of variant-metabolite relationships reveals novel genomic mechanisms driving metabolic phenotypes.PMID:36754017 | DOI:10.1016/j.cmet.2023.01.007

Food Chem. 2022 Dec 22;412:135048. doi: 10.1016/j.foodchem.2022.135048. Online ahead of print.ABSTRACTIn this study, the anti-obesity mechanism of Ganpu tea (GPT) from the perspectives of microbiome, metabolome and transcriptome was investigated. GPT significantly reduced the high-fat-diet (HFD)-induced levels of inflammatory cytokines and the expansion of lipid droplets and white adipose tissue. GPT also improved HFD-induced gut microbiome imbalance by significantly reducing the proportion of Firmicutes to Bacteroidota. Metabolomic data showed that HFD-induced metabolic disorder was regulated by GPT and probably characterised by being related to 4-aminobutyraldehyde and 5-acetylamino-6-amino-3-methyluracil. Transcriptome showed that the improvement of obesity was mainly related to the IL-17 signaling pathway and the metabolism of xenobiotics by cytochrome P450. Spearman's correlation analysis indicated that gut microbiota were significantly correlated with inflammatory factors, genes and metabolites. Metabolome-transcriptome analysis showed that GPT reversed obesity mainly through the carbohydrate metabolism, amino acid metabolism and lipid metabolism.Collectively, GPT may be used as a health drink to prevent or treat obesity.PMID:36753939 | DOI:10.1016/j.foodchem.2022.135048

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Feb 2;1217:123626. doi: 10.1016/j.jchromb.2023.123626. Online ahead of print.ABSTRACTPien-Tze-Huang (PTH) is a well-known traditional Chinese patent medicine with excellent liver-protection effect. However, the mechanism of hepatoprotective action has not yet been entirely elucidated. The aim of this study was to investigate the mechanism of protective effect of PTH on alcohol-induced liver injury in rats using cytokine analysis and untargeted metabolomics approaches. An alcoholic liver disease (ALD) model with SD rats was established, and PTH was administered according to the prescribed dose. The hepatoprotective effect of PTH was evaluated by pathological observation of liver tissue and changes in biochemical index activity and cytokines in serum. Serum samples were analyzed by ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS), and differentially expressed metabolites were screened by multivariate statistical analysis. KEGG combined with metabolic pathway analysis were used to evaluate the underlying metabolic pathways. Results showed liver histopathology injury was attenuated. The levels of IL-6, TNF-α and NF-κB were significantly decreased in rats intervened with PTH groups, suggesting that it may alleviate inflammation via suppressing the inflammatory cytokines signaling pathway. Eighty differentially expressed metabolites were found and identified. Pathway analysis indicated that the hepatoprotective effects of PTH occurred through the regulation of inflammatory cytokines signaling pathway, primary bile acid biosynthesis, vitamin B6 metabolism pathway, cholesterol metabolism, and tyrosine metabolism. PTH showed favorable hepatoprotective effect through multiple pathways. This study has great importance in fully revealing the mechanism of hepatoprotective action and can help improve the clinical application of PTH.PMID:36753840 | DOI:10.1016/j.jchromb.2023.123626

Food Chem. 2023 Feb 2;413:135598. doi: 10.1016/j.foodchem.2023.135598. Online ahead of print.ABSTRACTFlavonoids are major nutrients in sea buckthorn berries. However, the effects of drying methods on flavonoids in sea buckthorn berries are unclear. In this study, ultra-performance liquid chromatography and metabolomics were adopted to analyse the effects of hot air drying (HAD) and infrared drying (IRD) on flavonoid compounds and antioxidant capacity in sea buckthorn berries. In total, 97 metabolites belonging to 12 classes were identified, including 26 flavones, 23 flavonols, and 11 flavanones. Additionally, 32 differential metabolites were identified among groups. Isorhamnetin and quercetin contents increased in response to HAD and IRD, while (-)-epigallocatechin and (-)-gallocatechin contents decreased. Differential metabolism of flavonoid compounds occurred mainly via the flavonoid biosynthesis and secondary metabolite biosynthesis pathways. Flavonoid compound degradation might be associated with antioxidant activity during drying. This study elucidated the effect of drying on nutritional components of sea buckthorn berries and may guide the improvement of quality during food processing.PMID:36753785 | DOI:10.1016/j.foodchem.2023.135598

Clin Nutr. 2023 Jan 14;42(3):384-393. doi: 10.1016/j.clnu.2023.01.011. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Metabolomic profiling is a systematic approach to identifying biomarkers for dietary patterns. Yet, metabolomic markers for dietary patterns in pregnant individuals have not been investigated. The aim of this study was to identify plasma metabolomic markers and metabolite panels that are associated with the Mediterranean diet in pregnant individuals.METHODS: This is a prospective study of 186 pregnant individuals who had both dietary intake and metabolomic profiles measured from the Fetal Growth Studies-Singletons cohort. Dietary intakes during the peri-conception/1st trimester and the second trimester were accessed at 8-13 and 16-22 weeks of gestation, respectively. Adherence to the Mediterranean diet was measured by the alternate Mediterranean Diet (aMED) score. Fasting plasma samples were collected at 16-22 weeks and untargeted metabolomics profiling was performed using the mass spectrometry-based platforms. Metabolites individually or jointly associated with aMED scores were identified using linear regression and least absolute shrinkage and selection operator (LASSO) regression models with adjustment for potential confounders, respectively.RESULTS: Among 459 annotated metabolites, 64 and 41 were individually associated with the aMED scores of the diet during the peri-conception/1st trimester and during the second trimester, respectively. Fourteen metabolites were associated with the Mediterranean diet in both time windows. Most Mediterranean diet-related metabolites were lipids (e.g., acylcarnitine, cholesteryl esters (CEs), linoleic acid, long-chain triglycerides (TGs), and phosphatidylcholines (PCs), amino acids, and sugar alcohols. LASSO regressions also identified a 10 metabolite-panel that were jointly associated with aMED score of the diet during the peri-conception/1st trimester (AUC: 0.74; 95% CI: 0.57, 0.91) and a 3 metabolites-panel in the 2nd trimester (AUC: 0.68; 95% CI: 0.50, 0.86).CONCLUSION: We identified plasma metabolomic markers for the Mediterranean diet among pregnant individuals. Some of them have also been reported in previous studies among non-pregnant populations, whereas others are novel. The results from our study warrant replication in pregnant individuals by future studies.CLINICAL TRIAL REGISTRATION NUMBER: This study was registered at ClinicalTrials.gov.PMID:36753781 | DOI:10.1016/j.clnu.2023.01.011

J Agric Food Chem. 2023 Feb 8. doi: 10.1021/acs.jafc.2c07844. Online ahead of print.ABSTRACTLentil seed coats are rich in antioxidant polyphenols that are important for plant defense and have potential as valorized byproducts. Although biochemical differences among lentil seed coat colors have been previously studied, differences among seed coat patterns remain largely unexplored. This study used mass spectrometry-based untargeted metabolomics to investigate polyphenol differences among lentil seed coat patterns to search for biochemical pathways potentially responsible for seed coat pattern differences. Comparing patterned with non-patterned green lentil seed coats, 28 significantly upregulated metabolites were found in patterned seed coats; 19 of them were identified as flavones. Flavones were virtually absent in non-patterned seed coats, thereby strongly suggesting a blockage in their flavone biosynthetic pathway. Although the black pattern is not readily discernible on black seed coats, many of the same flavones found in green marbled seed coats were also found in black seed coats, indicating that black seed coats likely have a marbled pattern.PMID:36753710 | DOI:10.1021/acs.jafc.2c07844

Sci Transl Med. 2023 Feb 8;15(682):eade3782. doi: 10.1126/scitranslmed.ade3782. Epub 2023 Feb 8.ABSTRACTPreservation quality of donor hearts is a key determinant of transplant success. Preservation duration beyond 4 hours is associated with primary graft dysfunction (PGD). Given transport time constraints, geographical limitations exist for donor-recipient matching, leading to donor heart underutilization. Here, we showed that metabolic reprogramming through up-regulation of the enzyme immune response gene 1 (IRG1) and its product itaconate improved heart function after prolonged preservation. Irg1 transcript induction was achieved by adding the histone deacetylase (HDAC) inhibitor valproic acid (VPA) to a histidine-tryptophan-ketoglutarate solution used for donor heart preservation. VPA increased acetylated H3K27 occupancy at the IRG1 enhancer and IRG1 transcript expression in human donor hearts. IRG1 converts aconitate to itaconate, which has both anti-inflammatory and antioxidant properties. Accordingly, our studies showed that Irg1 transcript up-regulation by VPA treatment increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in mice, which was accompanied by increased antioxidant protein expression [hemeoxygenase 1 (HO1) and superoxide dismutase 1 (SOD1)]. Deletion of Irg1 in mice (Irg1-/-) negated the antioxidant and cardioprotective effects of VPA. Consistent with itaconate's ability to inhibit succinate dehydrogenase, VPA treatment of human hearts increased itaconate availability and reduced succinate accumulation during preservation. VPA similarly increased IRG1 expression in pig donor hearts and improved its function in an ex vivo cardiac perfusion system both at the clinical 4-hour preservation threshold and at 10 hours. These results suggest that augmentation of cardioprotective immune-metabolomic pathways may be a promising therapeutic strategy for improving donor heart function in transplantation.PMID:36753565 | DOI:10.1126/scitranslmed.ade3782

Funct Integr Genomics. 2023 Feb 8;23(1):57. doi: 10.1007/s10142-023-00982-9.ABSTRACTThe agricultural sector and environmental safety both work hand in hand to promote sustainability in important issues like soil health, plant nutrition, food safety, and security. The conventional methods have greatly harmed the environment and people's health and caused soil fertility and quality to decline as well as deteriorate. Keeping in view the excessive exploitation and cascade of degradation events due to unsustainable farming practices, the need of the hour demands choosing an appropriate, eco-friendly strategy to restore soil health, plant nutrition, and environmental aspects. The priority highlights a need for a sustainable and environment-friendly upgradation of the present agricultural systems to utilize the beneficial aspects related to harnessing the gene-microbiome strategies which would help in the restoration and replenishment of the microbial pool. Thus, exploring the microbiome is the utmost priority which gives a deep insight into the different aspects related to soil and plant and stands out as an important contributor to plant health and productivity. "Microbes" are important drivers for the biogeochemical cycles and targets like sustainability and safety. This essential microbial bulk (soil microbiome) is greatly influenced by agricultural/farming practices. Therefore, with the help of microbiome engineering technologies like meta-transcriptomics, meta-proteomics, metabolomics, and novel gene-altering techniques, we can easily screen out the highly diverse and balanced microbial population in the bulk of soil, enhancing the soil's health and productivity. Importantly, we need to change our cultivation strategies to attain such sustainability. There is an urgent need to revert to natural/organic systems of cultivation patterns where the microbiome hub can be properly utilized to strengthen soil health, decrease insect pest and disease incidence, reduce greenhouse gas emissions, and ultimately prevent environmental degradation. Through this article, we wish to propose a shift in the cultivation pattern from chemical to the novel, upgraded gene-assisted designed eco-friendly methodologies which can help in incorporating, exploring, and harnessing the right microbiome consortium and can further help in the progression of environmentally friendly microbiome technologies for agricultural safety and productivity.PMID:36752963 | DOI:10.1007/s10142-023-00982-9