PubMed

Food Res Int. 2024 Jul;187:114414. doi: 10.1016/j.foodres.2024.114414. Epub 2024 Apr 21.ABSTRACTRed wine colloids, crucial in determining wine quality and stability, are understudied due to inadequate techniques for studying them effectively in the natural wine environment. Recently, Asymmetrical Flow Field-flow Fractionation (AF4) with online multidetection has emerged as a novel analytical tool for quantifying, fractionating, and characterizing red wine colloids in their native state. This study aimed to characterize the colloidal composition of 24 monovarietal Italian wines produced without filtration, oak contact, fining treatments, malolactic fermentation, macerating enzymes or ageing on yeast lees. AF4 analysis allowed quantification and characterization of wine colloids based on light scattering signal (MALS; gyration radius - Rg), size (hydrodynamic radius - Rh) and absorbance (A280 & A520 nm). The results showed that each wine contained up to five distinct colloids' populations, varying in size and gyration radii. Despite possessing very similar Rh, most colloids exhibited great differences in compactness, as indicated by their varying Rg values. Comparing the A280 signal of whole wines to those of wines containing only species larger than 5 kDa (considered colloids) allowed to calculate the percentage of molecules involved in colloidal particles assembly, ranging from 1 to 44 % of the total A280 absorbing compounds, reflecting the diversity among wines. The A520 signal indicated the presence of polymeric pigments in the colloidal fraction. Notably, colored colloids all had Rg > 20 nm, indicating their association with other colloidal-forming compounds. This observation led to the conclusion that, apart from free anthocyanins and polymeric pigments, the color of red wines is also due to colloidal particles formed by the latter bound to proteins, with their quantity being highly variable across wines of different origin. These findings, which highlight the fundamental role of proteins in shaping the colloidal status of red wines, were utilized to propose an updated hypothetical model for colloidal aggregation in red wine.PMID:38763663 | DOI:10.1016/j.foodres.2024.114414

Food Res Int. 2024 Jul;187:114409. doi: 10.1016/j.foodres.2024.114409. Epub 2024 Apr 24.ABSTRACTOchratoxin A (OTA) is a notorious mycotoxin commonly contaminating food products worldwide. In this study, an OTA-degrading strain Brevundimonas diminuta HAU429 was isolated by using hippuryl-L-phenylalanine as the sole carbon source. The biodegradation of OTA by strain HAU429 was a synergistic effect of intracellular and extracellular enzymes, which transformed OTA into ochratoxin α (OTα) through peptide bond cleavage. Cytotoxicity tests and cell metabolomics confirmed that the transformation of OTA into OTα resulted in the detoxification of its hepatotoxicity since OTA but not OTα disturbed redox homeostasis and induced oxidative damage to hepatocytes. Genome mining identified nine OTA hydrolase candidates in strain HAU429. They were heterologously expressed in Escherichia coli, and three novel amidohydrolase BT6, BT7 and BT9 were found to display OTA-hydrolyzing activity. BT6, BT7 and BT9 showed less than 45 % sequence identity with previously identified OTA-degrading amidohydrolases. BT6 and BT7 shared 60.9 % amino acid sequence identity, and exhibited much higher activity towards OTA than BT9. BT6 and BT7 could completely degrade 1 μg mL-1 of OTA within 1 h and 50 min, while BT9 hydrolyzed 100 % of OTA in the reaction mixture by 12 h. BT6 was the most thermostable retaining 38 % of activity after incubation at 70 °C for 10 min, while BT7 displayed the highest tolerance to ethanal remaining 76 % of activity in the presence of 6 % ethanol. This study could provide new insights towards microbial OTA degradation and promote the development of enzyme-catalyzed OTA detoxification during food processing.PMID:38763660 | DOI:10.1016/j.foodres.2024.114409

Food Res Int. 2024 Jul;187:114405. doi: 10.1016/j.foodres.2024.114405. Epub 2024 Apr 25.ABSTRACTSojae semen praeparatum (SSP), a fermented product known for its distinctive flavor and medicinal properties, undergoes a complex fermentation process due to the action of various microorganisms. Despite its widespread use, the effect of these microorganisms on the flavor compounds and functional components of SSP remains poorly understood. This study aimed to shed light on this aspect by identifying 20 metabolites as potential key flavor substances in SSP. Moreover, glycine and lysine were identified as crucial flavor substances. Additionally, 24 metabolites were identified as key functional components. The dominant microorganisms involved in the fermentation process were examined, revealing six genera of fungi and 12 genera of bacteria. At the species level, 16 microorganisms were identified as dominant through metagenome sequencing. Spearman correlation analysis demonstrated a strong association between dominant microorganisms and both flavor substances and functional components. Furthermore, the study validated the significance of four core functional microorganisms in improving the flavor and quality of SSP. This comprehensive exploration of functional microorganisms of SSP on key flavor substances/functional components during SSP fermentation. The study findings serve as a valuable reference for enhancing the overall flavor and quality of SSP.PMID:38763659 | DOI:10.1016/j.foodres.2024.114405

Food Res Int. 2024 Jul;187:114392. doi: 10.1016/j.foodres.2024.114392. Epub 2024 Apr 27.ABSTRACTVariations in cultivars and cultivation altitudes have significant impacts on tea flavour compounds however lack of comprehensive understanding. This study provided insights into differential accumulation of crucial flavour compounds in response to cultivars, cultivation altitudes, and processing. Twelve flavonoids (262.4 ∼ 275.4 mg•g-1) and 20 amino acids (AAs) (56.5 ∼ 64.8 mg•g-1) were comparative analyzed in 'Longjing 43' and 'Qunti' fresh leaves harvested at low (80 m, LA) and high (500 m, HA) altitudes. Additionally, an in-depth correlation unravelling of 31 alkaloids, 25 fatty acids, 31 saccharides, 8 organic acids, and 7 vitamins and flavonoids/AAs during green tea (GT) and black tea (BT) processing was performed. Enhenced flavonoid accumulation alongside higher AAs and saccharides in HA GT promoted a sweet/mellow flavour. Abundant flavonoids, AAs, and saccharides derivates in LA BT gave rise to a sweet aftertaste. The study presents an integrated illustration of major flavour compounds' differential accumulation patterns and their interrelations, providing new insights into the influence of cultivation conditions on tea flavour.PMID:38763654 | DOI:10.1016/j.foodres.2024.114392

Food Res Int. 2024 Jul;187:114345. doi: 10.1016/j.foodres.2024.114345. Epub 2024 Apr 19.ABSTRACTLong-term consumption of Western-style diet (WSD) can lead to metabolic disorders and dysbiosis of gut microbiota, presenting a critical risk factor for various chronic conditions such as fatty liver disease. In the present study, we investigated the beneficial role of co-fermented whole grain quinoa and black barley with Lactobacillus kisonensis on rats fed a WSD. Male Sprague-Dawley (SD) rats, aged six weeks and weighing 180 ± 10 g, were randomly assigned to one of three groups: the normal control group (NC, n = 7), the WSD group (HF, n = 7), and the WSD supplemented with a co-fermented whole grain quinoa with black barley (FQB) intervention group (HFF, n = 7). The findings indicated that FQB was effective in suppressing body weight gain, mitigating hepatic steatosis, reducing perirenal fat accumulation, and ameliorating pathological damage in the livers and testicular tissues of rats. Additionally, FQB intervention led to decreased levels of serum uric acid (UA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). These advantageous effects can be ascribed to the regulation of FQB on gut microbiota dysbiosis, which includes the restoration of intestinal flora diversity, reduction of the F/B ratio, and promotion of probiotics abundance, such as Akkermansia and [Ruminococcus] at the genus level. The study employed the UPLC-Q-TOF-MSE technique to analyze metabolites in fecal and hepatic samples. The findings revealed that FQB intervention led to a regression in the levels of specific metabolites in feces, including oxoadipic acid and 20a, 22b-dihydroxycholesterol, as well as in the liver, such as pyridoxamine, xanthine and xanthosine. The transcriptome sequencing of liver tissues revealed that FQB intervention modulated the mRNA expression of specific genes, including Cxcl12, Cidea, and Gck, known for their roles in anti-inflammatory and anti-insulin resistance mechanisms in the context of WSD. Our findings indicate that co-fermented whole-grain quinoa with black barley has the potential to alleviate metabolic disorders and chronic inflammation resulting from the consumption of WSD.PMID:38763637 | DOI:10.1016/j.foodres.2024.114345

Food Res Int. 2024 Jul;187:114311. doi: 10.1016/j.foodres.2024.114311. Epub 2024 Apr 23.ABSTRACTThe efficacy of amino acids as popular sports supplements has triggered debates, with their impact on athletic performance varying across sports disciplines due to diversity and heterogeneity in clinical trials. This review evaluates the ergogenic potential of amino acids, by critical appraisal of results of clinical trials of Branched chain amino acids (BCAAs), arginine, glutamine, citrulline, β-alanine, and taurine, performed on elite sportsmen from various land and water sports. Clinical trials reviewed here confirm notable physiological benefits thereby supporting the claim that BCAA, citrulline and arginine in various doses can have positive effects on endurance and overall performance in sportsperson. Furthermore, results of clinical trials and metabolomic studies indicate that in future it would be more beneficial to design precise formulations to target the requirement of specific sports. For instance, some combinations of amino acids may be more suitable for long term endurance and some others may be suitable for short burst of excessive energy. The most important insights from this review are the identification of three key areas where research is urgently needed: a) Biomarkers that can identify the physiological end points and to distinguish the specific role of amino acid as anti-fatigue or reducing muscle soreness or enhancing energy b) In-depth sports-wise clinical trials on elite sportsperson to understand the ergogenic needs for the particular sports c) Design of precision formula for similar types of sports instead of common supplements.PMID:38763626 | DOI:10.1016/j.foodres.2024.114311

Pharmacol Res. 2024 May 17:107214. doi: 10.1016/j.phrs.2024.107214. Online ahead of print.ABSTRACTStudies have shown that the microbiota-gut-brain axis is highly correlated with the pathogenesis of depression in humans. However, whether independent oral microbiome that do not depend on gut microbes could affect the progression of depression in human beings remains unclear, neither does the presence and underlying mechanisms of the microbiota-oral-brain axis in the development of the condition. Hence this study that encompasses clinical and animal experiments aims at investigating the correlation between oral microbiota and the onset of depression via mediating the microbiota-oral-brain axis. We compared the oral microbial compositions and metabolomes of 87 patients with depressive symptoms versus 70 healthy controls. We found that the oral microbial and metabolic signatures were significantly different between the two groups. Significantly, germ-free (GF) mice transplanted with saliva from mice exposing to chronic restraint stress (CRS) displayed depression-like behavior and oral microbial dysbiosis. This was characterized by a significant differential abundance of bacterial species, including the enrichment of Pseudomonas, Pasteurellaceae, and Muribacter, as well as the depletion of Streptococcus. Metabolomic analysis showed the alternation of metabolites in the plasma of CRS-exposed GF mice, especially Eicosapentaenoic Acid. Furthermore, oral and gut barrier dysfunction caused by CRS-induced oral microbiota dysbiosis may be associated with increased blood-brain barrier permeability. Pseudomonas aeruginosa supplementation exacerbated depression-like behavior, while Eicosapentaenoic Acid treatment conferred protection against depression-like states in mice. These results suggest that oral microbiome and metabolic function dysbiosis may be relevant to the pathogenesis and pathophysiology of depression. The proposed microbiota-oral-brain axis provides a new way and targets for us to study the pathogenesis of depression.PMID:38763328 | DOI:10.1016/j.phrs.2024.107214

J Pharm Biomed Anal. 2024 May 18;246:116222. doi: 10.1016/j.jpba.2024.116222. Online ahead of print.ABSTRACTZhenwu Decoction (ZWD), a classic formula from Zhang Zhongjing's "Treatise on Typhoid Fever" in the Han Dynasty, consists of five traditional Chinese medicines: Aconiti Lateralis Radix Praeparata (ALRP), Paeoniae Radix Alba, Poria Cocos, Ginger, and Rhizoma Atractylodis Macrocephalae. To evaluate the chemical constituent consistency of ZWD before and after compatibility, an ultra-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry was established to comprehensively study the constituents of ZWD. By normalizing the peak area, the pairwise compatibility of ALRP and the other four medicinal herbs, as well as the compatibility of the entire formula were studied, respectively. Multivariate statistical analysis was used to identify the differences. The processed data were analyzed by principal component analysis and supervised orthogonal partial least squared discriminant analysis, and an S-plot was generated to compare the differences in the chemical composition of the two types of decoction samples. The results showed that during the decoction process of ZWD, a total of seven components were recognized as differential compounds before and after compatibility of ZWD, namely 6-gingerol, zingerone, benzoylhypaconine, hypaconitine, benzoylaconine, paeoniflorin and fuziline. The results of this study provide basic data reference for understanding the law of ZWD compatibility and are valuable for the compatibility study of other herbal medicines.PMID:38763106 | DOI:10.1016/j.jpba.2024.116222

Phytomedicine. 2024 May 11;130:155720. doi: 10.1016/j.phymed.2024.155720. Online ahead of print.ABSTRACTBACKGROUND: Ilex pubescens Hook. et Arn (IP), traditionally known for its properties of promoting blood circulation, swelling and pain relief, heat clearing, and detoxification, has been used in the treatment of thromboangiitis obliterans (TAO). Despite its traditional applications, the specific mechanisms by which IP exerts its therapeutic effects on TAO remain unclear.AIM OF THE STUDY: This study aims to uncover the underlying mechanisms in the therapeutic effects of IP on TAO, employing network pharmacology and metabolomic approaches.METHODS: In this study, a rat TAO model was established by injecting sodium laurate through the femoral artery, followed by the oral administration of IP for 7 days. Plasma coagulation parameters were measured to assess the therapeutic effects of IP. The potential influence on the femoral artery and gastrocnemius muscle was histopathologically evaluated. Network pharmacology was employed to predict relevant targets and model pathways for TAO. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was used for the metabolic profile analysis of rat plasma. Immunohistochemistry (IHC) was used to verify the mechanisms by which IP promotes blood circulation in TAO.RESULTS: The study revealed that IP improved blood biochemical function in TAO and played a significant role in vascular protection and maintaining normal blood vessels and gastrocnemius morphologies. Network pharmacology showed that IP compounds play a therapeutic role in modulating lipids and atherosclerosis. Metabolomic analysis revealed that the pathways involved in sphingolipid metabolism and steroid biosynthesis were significantly disrupted. The joint analysis showed a strong correlation between lysophosphatidylcholine and IP components, including triterpenoid and iridoid components, which support the curative action of IP through the modulation of sphingolipid metabolism. Furthermore, decreased expression levels of SPHK1/S1PR1, TNF-α, IL-1β, and IL-6 were observed in the IP-treated group, suggesting that IP exerts a protective effect on the vasculature primarily by regulating of the SPHK1/S1PR1 signaling pathway.CONCLUSION: In this study, we found that IP protects the vasculature against injury and treats TAO by regulating the steady-state disturbance of the sphingolipid pathway. These findings suggest that IP promotes vasculature by modulating sphingolipid metabolism and SPHK1/S1PR1 signaling pathway and reduce levels of inflammatory factors, offering new insights into its therapeutic potential.PMID:38763010 | DOI:10.1016/j.phymed.2024.155720

Phytomedicine. 2024 May 4;130:155712. doi: 10.1016/j.phymed.2024.155712. Online ahead of print.ABSTRACTBACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has emerged as a burgeoning health problem worldwide, but no specific drug has been approved for its treatment. Shenling Baizhu powder (SL) is extensively used to treat NAFLD in Chinese clinical practice. However, the therapeutic components and pharmacological mechanisms of SL against NAFLD have not been thoroughly investigated.PURPOSE: This study aimed to investigate the pharmacological impact and molecular mechanism of SL on NAFLD.METHODS: First, we established an animal model of NAFLD by high-fat diet (HFD) feeding, and evaluated the therapeutic efficacy of SL on NAFLD by physiological, biochemical, pathological, and body composition analysis. Next, the effect of SL on autophagic flow in NAFLD rats was evaluated by ultrastructure, immunofluorescence staining, and western blotting. Moreover, an integrated strategy of targeted energy metabolomics and network pharmacology was performed to characterize autophagy-related genes and explore the synergistic effects of SL active compounds. UPLC-MS/MS, molecular docking combined with in vivo and in vitro experiments were conducted to verify the key compounds and genes. Finally, a network was established among SL-herb-compound-genes-energy metabolites-NAFLD, which explains the complicated regulating mechanism of SL on NAFLD.RESULTS: We discovered that SL decreased hepatic lipid accumulation, hepatic steatosis, and insulin resistance, and improved systemic metabolic disorders and pathological abnormalities. Subsequently, an integrated strategy of targeted energy metabolomics and network pharmacology identified quercetin, ellagic acid, kaempferol, formononetin, stigmasterol, isorhamnetin and luteolin as key compounds; catalase (CAT), AKT serine/threonine kinase 1 (AKT), nitric oxide synthase 3 (eNOS), NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1) and hypoxia-inducible factor 1 subunit alpha (HIF-1α) were identified as key genes; while nicotinamide adenine dinucleotide phosphate (NADP) and succinate emerged as key energy metabolites. Mechanistically, we revealed that SL may exert its anti-NAFLD effect by inducing autophagy activation and forming a comprehensive regulatory network involving key compounds, key genes, and key energy metabolites, ultimately alleviating oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction.CONCLUSION: Our study demonstrated the therapeutic effect of SL in NAFLD models, and establishes a basis for the development of potential products from SL plant materials for the treatment of NAFLD.PMID:38763008 | DOI:10.1016/j.phymed.2024.155712

J Hazard Mater. 2024 May 16;473:134590. doi: 10.1016/j.jhazmat.2024.134590. Online ahead of print.ABSTRACTPhytoremediation, an eco-friendly approach for mitigating heavy metal contamination, is reliant on hyperaccumulators. This study focused on Leersia hexandra Swart, a known chromium (Cr) hyperaccumulator with demonstrated tolerance to multiple heavy metals. Our objective was to investigate its response to simultaneous Cr and nickel (Ni) stress over 12 days. Results from physiological experiments demonstrated a significant increase in the activities of antioxidant enzymes (APX, SOD, CAT) and glutathione (GSH) content under Cr and Ni stress, indicating enhanced antioxidant mechanisms. Transcriptome analysis revealed that stress resulted in the differential expression of 27 genes associated with antioxidant activity and metal binding, including APX, SOD, CAT, GSH, metallothionein (MT), and nicotinamide (NA). Among them, twenty differentially expressed genes (DEGs) related to GSH metabolic cycle were identified. Notably, GSTU6, GND1, and PGD were the top three related genes, showing upregulation with fold changes of 4.57, 6.07, and 3.76, respectively, indicating their crucial role in metal tolerance. The expression of selected DEGs was validated by quantitative real-time PCR, confirming the reliability of RNA-Seq data. Metabolomic analysis revealed changes in 1121 metabolites, with amino acids, flavonoids, and carbohydrates being the most affected. Furthermore, glucosinolate biosynthesis and amino acid biosynthesis pathways were represented in the KEGG pathway of differentially expressed metabolites (DEMs). This study provides insights into the tolerance mechanisms of L. hexandra under the co-stress of Cr and Ni, offering a new perspective for enhancing its remediation performance.PMID:38762990 | DOI:10.1016/j.jhazmat.2024.134590

Talanta. 2024 May 8;276:126230. doi: 10.1016/j.talanta.2024.126230. Online ahead of print.ABSTRACTColorectal cancer (CRC) is the third most common cancer in the world with a higher prevalence in the developed countries, mainly caused by environmental and lifestyle factors such as diet, particularly red meat consumption. The metabolic impact of high red meat consumption on the epithelial part of the colon was investigated using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MSI), to specifically analyze the epithelial substructure. Ten colons from rats fed for 100 days high red or white meat diet were subjected to untargeted MSI analyses using two spatial resolutions (100 μm and 10 μm) to evaluate metabolite changes in the epithelial part and to visualize the distribution of metabolites of interest within the epithelium crypts. Our results suggest a specific effect of red meat diet on the colonic epithelium metabolism, as evidenced by an increase of purine catabolism products or depletion in glutathione pool, reinforcing the hypothesis of increased oxidative stress with red meat diet. This study also highlighted cholesterol sulfate as another up-regulated metabolite, interestingly localized at the top of the crypts. Altogether, this study demonstrates the feasibility and the added value of using MSI to decipher the effect of high red meat diet on the colonic epithelium.PMID:38762974 | DOI:10.1016/j.talanta.2024.126230

Food Chem. 2024 May 15;453:139649. doi: 10.1016/j.foodchem.2024.139649. Online ahead of print.ABSTRACTThe effects of ultra-high pressure (UHP) pretreatment (50-250 MPa) on the fish curing were studied. UHP increased the overall volatile compound concentration of cured fish. Among 50-250 MPa five treatment groups, 150 MPa UHP group exhibited the highest total free amino acid content (294.34 mg/100 g) with that of the control group being 92.39 mg/100 g. The activity of cathepsin L was increased under 50-200 MPa UHP treatment (62.28-58.15 U/L), compared with that in the control group (53.80 U/L). UHP treatment resulted in a significant increase in small molecule compounds, especially the amino acid dipeptides and ATP metabolic products. Under UHP treatments, the bacterial phyla Actinobacteriota (1.04-5.25 %), Bacteroidota (0.20-4.47 %), and Deinococcota (0.00-0.05 %) exhibited an increased abundance, and they promoted taste and flavor formation. Our results indicated that UHP is a promising pretreatment method to improve taste and flavour in cured fish by affecting the microorganisms, cathepsin, and proteins.PMID:38762947 | DOI:10.1016/j.foodchem.2024.139649

Physiol Plant. 2024 May-Jun;176(3):e14352. doi: 10.1111/ppl.14352.ABSTRACTClimate change is responsible for mild winters and warm springs that can induce premature plant development, increasing the risk of exposure to cold stress with a severe reduction in plant growth. Tomato plants are sensitive to cold stress and beneficial microorganisms can increase their tolerance. However, scarce information is available on mechanisms stimulated by bacterial endophytes in tomato plants against cold stress. This study aimed to clarify metabolic changes stimulated by psychrotolerant endophytic bacteria in tomato plants exposed to cold stress and annotate compounds possibly associated with cold stress mitigation. Tomato seeds were inoculated with two bacterial endophytes isolated from Antarctic Colobanthus quitensis plants (Ewingella sp. S1.OA.A_B6 and Pseudomonas sp. S2.OTC.A_B10) or with Paraburkholderia phytofirmans PsJN, while mock-inoculated seeds were used as control. The metabolic composition of tomato plants was analyzed immediately after cold stress exposure (4°C for seven days) or after two and four days of recovery at 25°C. Under cold stress, the content of malondialdehyde, phenylalanine, ferulic acid, and p-coumaric acid was lower in bacterium-inoculated compared to mock-inoculated plants, indicating a reduction of lipid peroxidation and the stimulation of phenolic compound metabolism. The content of two phenolic compounds, five putative phenylalanine-derived dipeptides, and three further phenylalanine-derived compounds was higher in bacterium-inoculated compared to mock-inoculated samples under cold stress. Thus, psychrotolerant endophytic bacteria can reprogram polyphenol metabolism and stimulate the accumulation of secondary metabolites, like 4-hydroxybenzoic and salicylic acid, which are presumably involved in cold stress mitigation, and phenylalanine-derived dipeptides possibly involved in plant stress responses.PMID:38764037 | DOI:10.1111/ppl.14352

Cell Rep. 2024 May 18;43(6):114246. doi: 10.1016/j.celrep.2024.114246. Online ahead of print.ABSTRACTThe decidua plays a crucial role in providing structural and trophic support to the developing conceptus before placentation. Following embryo attachment, embryonic components intimately interact with the decidual tissue. While evidence indicates the participation of embryo-derived factors in crosstalk with the uterus, the extent of their impact on post-implantation decidual development requires further investigation. Here, we utilize transgenic mouse models to selectively eliminate primary trophoblast giant cells (pTGCs), the embryonic cells that interface with maternal tissue at the forefront. pTGC ablation impairs decidualization and compromises decidual interferon response and lipid metabolism. Mechanistically, pTGCs release factors such as interferon kappa (IFNK) to strengthen the decidual interferon response and lipoprotein lipase (LPL) to enhance lipid accumulation within the decidua, thereby promoting decidualization. This study presents genetic and metabolomic evidence reinforcing the proactive role of pTGC-derived factors in mobilizing maternal resources to strengthen decidualization, facilitating the normal progression of early pregnancy.PMID:38762885 | DOI:10.1016/j.celrep.2024.114246

Cardiovasc Diabetol. 2024 May 18;23(1):174. doi: 10.1186/s12933-024-02264-5.ABSTRACTBACKGROUND: Growth differentiation factor 15 (GDF15) is a mitokine, the role of which, total or H-specific, in modulating energy metabolism and homeostasis in obesity-related diseases, such as metabolic dysfunction associated steatotic liver disease (MASLD), has not been fully elucidated in adult humans. We aimed to investigate the fasting and stimulated levels of GDF15, total and H-specific, glucose-dependent insulinotropic polypeptide (GIP) and C-peptide, in two physiology interventional studies: one focusing on obesity, and the other on MASLD.METHODS: Study 1 investigated individuals with normal weight or with obesity, undergoing a 3-h mixed meal test (MMT); and study 2, examined adults with MASLD and controls undergoing a 120-min oral glucose tolerance test (OGTT). Exploratory correlations of total and H-specific GDF15 with clinical, hormonal and metabolomic/lipidomic parameters were also performed.RESULTS: In study 1, 15 individuals were included per weight group. Fasting and postprandial total and H-specific GDF15 were similar between groups, whereas GIP was markedly higher in leaner individuals and was upregulated following a MMT. Baseline and postprandial C-peptide were markedly elevated in people with obesity compared with lean subjects. GIP was higher in leaner individuals and was upregulated after a MMT, while C-peptide and its overall AUC after a MMT was markedly elevated in people with obesity compared with lean subjects. In study 2, 27 individuals were evaluated. Fasting total GDF15 was similar, but postprandial total GDF15 levels were significantly higher in MASLD patients compared to controls. GIP and C-peptide remained unaffected. The postprandial course of GDF15 was clustered among those of triglycerides and molecules of the alanine cycle, was robustly elevated under MASLD, and constituted the most notable differentiating molecule between healthy and MASLD status. We also present robust positive correlations of the incremental area under the curve of total and H-specific GDF15 with a plethora of lipid subspecies, which remained significant after adjusting for confounders.CONCLUSION: Serum GDF15 levels do not differ in relation to weight status in hyperlipidemic but otherwise metabolically healthy individuals. In contrast, GDF15 levels are significantly increased in MASLD patients at baseline and they remain significantly higher compared to healthy participants during OGTT, pointing to a role for GDF15 as a mitokine with important roles in the pathophysiology and possibly therapeutics of MASLD. Trial registration ClinicalTrials.gov NCT03986684, NCT04430946.PMID:38762719 | DOI:10.1186/s12933-024-02264-5

Metabolomics. 2024 May 18;20(3):56. doi: 10.1007/s11306-024-02123-0.ABSTRACTINTRODUCTION: Preeclampsia (PreE) remains a major source of maternal and newborn complications. Prenatal prediction of these complications could significantly improve pregnancy management.OBJECTIVES: Using metabolomic analysis we investigated the prenatal prediction of maternal and newborn complications in early and late PreE and investigated the pathogenesis of such complications.METHODS: Serum samples from 76 cases of PreE (36 early-onset and 40 late-onset), and 40 unaffected controls were collected. Direct Injection Liquid Chromatography-Mass Spectrometry combined with Nuclear Magnetic Resonance (NMR) spectroscopy was performed. Logistic regression analysis was used to generate models for prediction of adverse maternal and neonatal outcomes in patients with PreE. Metabolite set enrichment analysis (MSEA) was used to identify the most dysregulated metabolites and pathways in PreE.RESULTS: Forty-three metabolites were significantly altered (p < 0.05) in PreE cases with maternal complications and 162 metabolites were altered in PreE cases with newborn adverse outcomes. The top metabolite prediction model achieved an area under the receiver operating characteristic curve (AUC) = 0.806 (0.660-0.952) for predicting adverse maternal outcomes in early-onset PreE, while the AUC for late-onset PreE was 0.843 (0.712-0.974). For the prediction of adverse newborn outcomes, regression models achieved an AUC = 0.828 (0.674-0.982) in early-onset PreE and 0.911 (0.828-0.994) in late-onset PreE. Profound alterations of lipid metabolism were associated with adverse outcomes.CONCLUSION: Prenatal metabolomic markers achieved robust prediction, superior to conventional markers for the prediction of adverse maternal and newborn outcomes in patients with PreE. We report for the first-time the prediction and metabolomic basis of adverse maternal and newborn outcomes in patients with PreE.PMID:38762675 | DOI:10.1007/s11306-024-02123-0

Sci Rep. 2024 May 18;14(1):11382. doi: 10.1038/s41598-024-62131-x.ABSTRACTThe annual increase in myopia prevalence poses a significant economic and health challenge. Our study investigated the effect of calcitriol role in myopia by inducing the condition in guinea pigs through form deprivation for four weeks. Untargeted metabolomics methods were used to analyze the differences in metabolites in the vitreous body, and the expression of vitamin D receptor (VDR) in the retina was detected. Following form deprivation, the guinea pigs received intraperitoneal injections of calcitriol at different concentrations. We assessed myopia progression using diopter measurements and biometric analysis after four weeks. Results indicated that form deprivation led to a pronounced shift towards myopia, characterized by reduced choroidal and scleral thickness, disorganized collagen fibers, and decreased scleral collagen fiber diameter. Notably, a reduction in calcitriol expression in vitreous body, diminished vitamin D and calcitriol levels in the blood, and decreased VDR protein expression in retinal tissues were observed in myopic guinea pigs. Calcitriol administration effectively slowed myopia progression, preserved choroidal and scleral thickness, and prevented the reduction of scleral collagen fiber diameter. Our findings highlight a significant decrease in calcitriol and VDR expressions in myopic guinea pigs and demonstrate that exogenous calcitriol supplementation can halt myopia development, enhancing choroidal and scleral thickness and scleral collagen fiber diameter.PMID:38762668 | DOI:10.1038/s41598-024-62131-x

Metabolomics. 2024 May 18;20(3):55. doi: 10.1007/s11306-024-02121-2.ABSTRACTINTRODUCTION: The world is experiencing exponential growth in communication, especially wireless communication. Wireless connectivity has recently become a part of everyone's daily life. Recent developments in low-cost, low-power, and miniature devices contribute to a significant rise in radiofrequency-electromagnetic field (RF-EM) radiation exposure in our environment, raising concern over its effect on biological systems. The inconsistent and conflicting research results make it difficult to draw definite conclusions about how RF-EM radiation affects living things.OBJECTIVES: This study identified two micro-environments based on their level of exposure to cellular RF-EM radiation, one with significantly less exposure and another with very high exposure to RF-EM radiation. Emphasis is given to studying the metabolites in the urine samples of humans naturally exposed to these two different microenvironments to understand short-term metabolic dysregulations.METHODS: Untargeted 1H NMR spectroscopy was employed for metabolomics analyses to identify dysregulated metabolites. A total of 60 subjects were recruited with 5 ml urine samples each. These subjects were divided into two groups: one highly exposed to RF-EM (n = 30) and the other consisting of low-exposure populations (n = 30).RESULTS: The study found that the twenty-nine metabolites were dysregulated. Among them, 19 were downregulated, and 10 were upregulated. In particular, Glyoxylate and dicarboxylate and the TCA cycle metabolism pathway have been perturbed. The dysregulated metabolites were validated using the ROC curve analysis.CONCLUSION: Untargeted urine metabolomics was conducted to identify dysregulated metabolites linked to RF-EM radiation exposure. Preliminary findings suggest a connection between oxidative stress and gut microbiota imbalance. However, further research is needed to validate these biomarkers and understand the effects of RF-EM radiation on human health. Further research is needed with a diverse population.PMID:38762651 | DOI:10.1007/s11306-024-02121-2

NPJ Precis Oncol. 2024 May 18;8(1):105. doi: 10.1038/s41698-024-00596-9.ABSTRACTThe diagnostic spectrum for AML patients is increasingly based on genetic abnormalities due to their prognostic and predictive value. However, information on the AML blast phenotype regarding their maturational arrest has started to regain importance due to its predictive power for drug responses. Here, we deconvolute 1350 bulk RNA-seq samples from five independent AML cohorts on a single-cell healthy BM reference and demonstrate that the morphological differentiation stages (FAB) could be faithfully reconstituted using estimated cell compositions (ECCs). Moreover, we show that the ECCs reliably predict ex-vivo drug resistances as demonstrated for Venetoclax, a BCL-2 inhibitor, resistance specifically in AML with CD14+ monocyte phenotype. We validate these predictions using LUMC proteomics data by showing that BCL-2 protein abundance is split into two distinct clusters for NPM1-mutated AML at the extremes of CD14+ monocyte percentages, which could be crucial for the Venetoclax dosing patients. Our results suggest that Venetoclax resistance predictions can also be extended to AML without recurrent genetic abnormalities and possibly to MDS-related and secondary AML. Lastly, we show that CD14+ monocytic dominated Ven/Aza treated patients have significantly lower overall survival. Collectively, we propose a framework for allowing a joint mutation and maturation stage modeling that could be used as a blueprint for testing sensitivity for new agents across the various subtypes of AML.PMID:38762545 | DOI:10.1038/s41698-024-00596-9