PubMed

Fluids Barriers CNS. 2024 Feb 26;21(1):19. doi: 10.1186/s12987-024-00514-y.ABSTRACTBACKGROUND: Syringomyelia (SM) is characterized by the development of fluid-filled cavities, referred to as syrinxes, within the spinal cord tissue. The molecular etiology of SM post-spinal cord injury (SCI) is not well understood and only invasive surgical based treatments are available to treat SM clinically. This study builds upon our previous omics studies and in vitro cellular investigations to further understand local fluid osmoregulation in post-traumatic SM (PTSM) to highlight important pathways for future molecular interventions.METHODS: A rat PTSM model consisting of a laminectomy at the C7 to T1 level followed by a parenchymal injection of 2 μL quisqualic acid (QA) and an injection of 5 μL kaolin in the subarachnoid space was utilized 6 weeks after initial surgery, parenchymal fluid and cerebrospinal fluid (CSF) were collected, and the osmolality of fluids were analyzed. Immunohistochemistry (IHC), metabolomics analysis using LC-MS, and mass spectrometry-based imaging (MSI) were performed on injured and laminectomy-only control spinal cords.RESULTS: We demonstrated that the osmolality of the local parenchymal fluid encompassing syrinxes was higher compared to control spinal cords after laminectomy, indicating a local osmotic imbalance due to SM injury. Moreover, we also found that parenchymal fluid is more hypertonic than CSF, indicating establishment of a local osmotic gradient in the PTSM injured spinal cord (syrinx site) forcing fluid into the spinal cord parenchyma to form and/or expand syrinxes. IHC results demonstrated upregulation of betaine, ions, water channels/transporters, and enzymes (BGT1, AQP1, AQP4, CHDH) at the syrinx site as compared to caudal and rostral sites to the injury, implying extensive local osmoregulation activities at the syrinx site. Further, metabolomics analysis corroborated alterations in osmolality at the syrinx site by upregulation of small molecule osmolytes including betaine, carnitine, glycerophosphocholine, arginine, creatine, guanidinoacetate, and spermidine.CONCLUSIONS: In summary, PTSM results in local osmotic disturbance that propagates at 6 weeks following initial injury. This coincides with and may contribute to syrinx formation/expansion.PMID:38409031 | DOI:10.1186/s12987-024-00514-y

Biochim Biophys Acta Gen Subj. 2024 Feb 24:130593. doi: 10.1016/j.bbagen.2024.130593. Online ahead of print.ABSTRACTApple (Malus × domestica Borkh.) holds a prominent position among global temperate fruit crops, with flowering playing a crucial role in both production and breeding. This review delves into the intricate mechanisms governing apple flowering amidst the backdrop of climate change, acknowledging the profound influence of external and internal factors on biennial bearing, flower bud quality, and ultimately, fruit quality. Notably, the challenge faced in major apple production regions is not an inadequacy of flowers but an excess, leading to compromised fruit quality necessitating thinning practices. Climate change exacerbates these challenges, rendering apple trees more susceptible to crop failure due to unusual weather events, such as reduced winter snowfall, early spring cold weather, and hailstorms during flowering and fruit setting. Altered climatic conditions, exemplified by increased spring warming coupled with sub-freezing temperatures, negatively impact developing flower buds and decrease overall crop production. Furthermore, changing winter conditions affect chilling accumulation, disrupting flower development and synchronicity. Although the physiological perception of apple flowering has been reviewed in the past, the genetic, epigenetic, and multi-omics regulatory mechanisms governing floral induction and flowering are still rarely discussed in the case of apple flowering. This article comprehensively reviews the latest literature encompassing all aspects of apple flowering, aiming to broaden our understanding and address flowering challenges while also laying a solid foundation for future research in developing cultivars that are ideally adapted to climate change.PMID:38408683 | DOI:10.1016/j.bbagen.2024.130593

Environ Res. 2024 Feb 24:118509. doi: 10.1016/j.envres.2024.118509. Online ahead of print.ABSTRACTGlyphosate (GLY) is among the most widely used pesticides in the world. However, there are a lot of unknowns about chronic exposure to GLY's effects on Honeybee (HB) behavior and physiology. To address this, we carried out five experiments to study the impact of chronic exposure to 5 mg/kg GLY on sugar consumption, survival, gene expression, gut microbiota, and metabolites of HB workers. Our results find a significant decrease in sugar consumption and survival probability of HB after chronic exposure to GLY. Further, genes associated with immune response, energy metabolism, and longevity were conspicuously altered. In addition, a total of seven metabolites were found to be differentially expressed in the metabolomic profiles, mainly related the sucrose metabolism. There was no significant difference in the gut microbiota. Results suggest that chronic exposure to field-level GLY altered the health of HB and the intricate toxic mechanisms. Our data provided insights into the chronic effects of GLY on HB behavior in food intake and health, which represents the field conditions where HB are exposed to pesticides over extended periods.PMID:38408628 | DOI:10.1016/j.envres.2024.118509

Ageing Res Rev. 2024 Feb 24:102248. doi: 10.1016/j.arr.2024.102248. Online ahead of print.ABSTRACTTemporal lobe epilepsy (TLE) is the most common form of epileptic syndrome. It has been established that due to its complex pathogenesis, a considerable proportion of TLE patients often progress to drug-resistant epilepsy. Ferroptosis has emerged as an important neuronal death mechanism in TLE, which is primarily influenced by lipid accumulation and oxidative stress. In previous studies of ferroptosis, more attention has been focused on the impact of changes in the levels of proteins related to the redox equilibrium and signaling pathways on epileptic seizures. However, it is worth noting that the oxidative-reduction changes in different organelles may have different pathophysiological significance in the process of ferroptosis-related diseases. Mitochondria, as a key organelle involved in ferroptosis, its structural damage and functional impairment can lead to energy metabolism disorders and disruption of the excitatory inhibitory balance, significantly increasing the susceptibility to epileptic seizures. Therefore, secondary mitochondrial dysfunction in the process of ferroptosis could play a crucial role in TLE pathogenesis. This review focuses on ferroptosis and mitochondria, discussing the pathogenic role of ferroptosis-related mitochondrial dysfunction in TLE, thus aiming to provide novel insights and potential implications of ferroptosis-related secondary mitochondrial dysfunction in epileptic seizures and to offer new insights for the precise exploration of ferroptosis-related therapeutic targets for TLE patients.PMID:38408490 | DOI:10.1016/j.arr.2024.102248

Adv Sci (Weinh). 2024 Feb 26:e2309624. doi: 10.1002/advs.202309624. Online ahead of print.ABSTRACTMild-heat photothermal antibacterial therapy avoids heat-induced damage to normal tissues but causes bacterial tolerance. The use of photothermal therapy in synergy with chemodynamic therapy is expected to address this issue. Herein, two pseudo-conjugated polymers PM123 with photothermal units and PFc with ferrocene (Fc) units are designed to co-assemble with DSPE-mPEG2000 into nanoparticle NPM123/Fc . NPM123/Fc under 1064 nm laser irradiation (NPM123/Fc +NIR-II) generates mild heat and additionally more toxic ∙OH from endogenous H2 O2 , displaying a strong synergistic photothermal and chemodynamic effect. NPM123/Fc +NIR-II gives >90% inhibition rates against MDR ESKAPE pathogens in vitro. Metabolomics analysis unveils that NPM123/Fc +NIR-II induces bacterial metabolic dysregulation including inhibited nucleic acid synthesis, disordered energy metabolism, enhanced oxidative stress, and elevated DNA damage. Further, NPM123/Fc +NIR-II possesses >90% bacteriostatic rates at infected wounds in mice, resulting in almost full recovery of infected wounds. Immunodetection and transcriptomics assays disclose that the therapeutic effect is mainly dependent on the inhibition of inflammatory reactions and the promotion of wound healing. What is more, thioketal bonds in NPM123/Fc are susceptible to ROS, making it degradable with highly favorable biosafety in vitro and in vivo. NPM123/Fc +NIR-II with a unique synergistic antibacterial strategy would be much less prone to select bacterial resistance and represent a promising antibiotics-alternative anti-infective measure.PMID:38408124 | DOI:10.1002/advs.202309624

Plant Biotechnol J. 2024 Feb 26. doi: 10.1111/pbi.14323. Online ahead of print.ABSTRACTAlthough forward-genetics-metabolomics methods such as mGWAS and mQTL have proven effective in providing myriad loci affecting metabolite contents, they are somehow constrained by their respective constitutional flaws such as the hidden population structure for GWAS and insufficient recombinant rate for QTL. Here, the combination of mGWAS and mQTL was performed, conveying an improved statistical power to investigate the flavonoid pathways in common wheat. A total of 941 and 289 loci were, respectively, generated from mGWAS and mQTL, within which 13 of them were co-mapped using both approaches. Subsequently, the mGWAS or mQTL outputs alone and their combination were, respectively, utilized to delineate the metabolic routes. Using this approach, we identified two MYB transcription factor encoding genes and five structural genes, and the flavonoid pathway in wheat was accordingly updated. Moreover, we have discovered some rare-activity-exhibiting flavonoid glycosyl- and methyl-transferases, which may possess unique biological significance, and harnessing these novel catalytic capabilities provides potentially new breeding directions. Collectively, we propose our survey illustrates that the forward-genetics-metabolomics approaches including multiple populations with high density markers could be more frequently applied for delineating metabolic pathways in common wheat, which will ultimately contribute to metabolomics-assisted wheat crop improvement.PMID:38408119 | DOI:10.1111/pbi.14323

Shock. 2024 Feb 1;61(2):322-329. doi: 10.1097/SHK.0000000000002299. Epub 2023 Dec 28.ABSTRACTObjective: We sought to identify potential drivers behind resuscitative endovascular balloon occlusion of the aorta (REBOA) induced reperfusion coagulopathy using novel proteomic methods. Background: Coagulopathy associated with REBOA is poorly defined. The REBOA Zone 1 provokes hepatic and intestinal ischemia that may alter coagulation factor production and lead to molecular pathway alterations that compromises hemostasis. We hypothesized that REBOA Zone 1 would lead to reperfusion coagulopathy driven by mediators of fibrinolysis, loss of coagulation factors, and potential endothelial dysfunction. Methods: Yorkshire swine were subjected to a polytrauma injury (blast traumatic brain injury, tissue injury, and hemorrhagic shock). Pigs were randomized to observation only (controls, n = 6) or to 30 min of REBOA Zone 1 (n = 6) or REBOA Zone 3 (n = 4) as part of their resuscitation. Thromboelastography was used to detect coagulopathy. ELISA assays and mass spectrometry proteomics were used to measure plasma protein levels related to coagulation and systemic inflammation. Results: After the polytrauma phase, balloon deflation of REBOA Zone 1 was associated with significant hyperfibrinolysis (TEG results: REBOA Zone 1 35.50% versus control 9.5% vs. Zone 3 2.4%, P < 0.05). In the proteomics and ELISA results, REBOA Zone 1 was associated with significant decreases in coagulation factor XI and coagulation factor II, and significant elevations of active tissue plasminogen activator, plasmin-antiplasmin complex complexes, and syndecan-1 (P < 0.05). Conclusion: REBOA Zone 1 alters circulating mediators of clot formation, clot lysis, and increases plasma levels of known markers of endotheliopathy, leading to a reperfusion-induced coagulopathy compared with REBOA Zone 3 and no REBOA.PMID:38407818 | DOI:10.1097/SHK.0000000000002299

Planta. 2024 Feb 26;259(4):74. doi: 10.1007/s00425-024-04350-0.ABSTRACTThe combined analysis of transcriptome and metabolome provided molecular insight into the dynamics of multiple active ingredients biosynthesis and accumulation across different cultivars of Lycium barbarum. Lycium barbarum L. has a high concentration of active ingredients and is well known in traditional Chinese herbal medicine for its therapeutic properties. However, there are many Lycium barbarum cultivars, and the content of active components varies, resulting in inconsistent quality between Lycium barbarum cultivars. At present, few research has been conducted to reveal the difference in active ingredient content among different cultivars of Lycium barbarum at the molecular level. Therefore, the transcriptome of 'Ningqi No.1' and 'Qixin No.1' during the three development stages (G, T, and M) was constructed in this study. A total of 797,570,278 clean reads were obtained. Between the two types of wolfberries, a total of 469, 2394, and 1531 differentially expressed genes (DEGs) were obtained in the 'G1 vs. G10,' 'T1 vs. T10,' and 'M1 vs. M10,' respectively, and were annotated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology identifiers. Using these transcriptome data, most DEGs related to the metabolism of the active ingredients in 'Ningqi No.1' and 'Qixin No.1' were identified. Moreover, a widely targeted metabolome analysis of the metabolites of 'Ningqi 1' and 'Qixin 1' fruits at the maturity stage revealed 1,135 differentially expressed metabolites (DEMs) in 'M1 vs. M10,' and many DEMs were associated with active ingredients such as flavonoids, alkaloids, terpenoids, and so on. We further quantified the flavonoid, lignin, and carotenoid contents of the two Lycium barbarum cultivars during the three developmental stages. The present outcome provided molecular insight into the dynamics of multiple active ingredients biosynthesis and accumulation across different cultivars of Lycium barbarum, which would provide the basic data for the formation of Lycium barbarum fruit quality and the breeding of outstanding strains.PMID:38407665 | DOI:10.1007/s00425-024-04350-0

Stress Biol. 2024 Feb 26;4(1):17. doi: 10.1007/s44154-024-00154-0.ABSTRACTPersimmon anthracnose, a severe disease caused by the hemibiotrophic fungus Colletotrichum horii, poses a substantial threat to China's persimmon industry. Previous research showed that 'Kangbing Jianshi' cultivar exhibits strong resistance to anthracnose. Notably, 'Kangbing Jianshi' branches exhibit greater lignification compared with the susceptible 'Fuping Jianshi' cultivar. In this study, higher lignin content was observed in 'Kangbing Jianshi' compared with 'Fuping Jianshi', and this difference was associated with disease resistance. Transcriptome and metabolome analyses revealed that the majority of differentially expressed genes and differentially accumulated metabolites were primarily enriched in the phenylpropanoid biosynthesis and lignin synthesis pathways. Furthermore, significant upregulation of DkCAD1, a pivotal gene involved in lignin metabolism, was observed in the resistant cultivar when inoculated with C. horii. Transient overexpression of DkCAD1 substantially increased lignin content and improved resistance to C. horii in a susceptible cultivar. Furthermore, through yeast one-hybrid (Y1H) assays, we identified two WRKY transcription factors, DkWRKY8 and DkWRKY10, which interacts with the DkCAD1 promoter and induces its activity. Overexpression of DkWRKY8 and DkWRKY10 not only increased leaf lignin content but also enhanced persimmon tolerance to C. horii. Moreover, the expression levels of DkCAD1, DkWRKY8, and DkWRKY10 were significantly increased in response to salicylic acid and jasmonic acid in the resistant cultivar. These findings enhance our understanding of the molecular functions of DkWRKY8, DkWRKY10, and DkCAD1 in persimmons, as well as their involvement in molecular breeding processes in persimmons.PMID:38407659 | DOI:10.1007/s44154-024-00154-0

Appl Microbiol Biotechnol. 2024 Feb 26;108(1):236. doi: 10.1007/s00253-024-13032-6.ABSTRACTTo elucidate the significant influence of microorganisms on geographically dependent flavor formation by analyzing microbial communities and volatile flavor compounds (VFCs) in cigar tobacco leaves (CTLs) obtained from China, Dominica, and Indonesia. Microbiome analysis revealed that the predominant bacteria in CTLs were Staphylococcus, Aerococcus, Pseudomonas, and Lactobacillus, while the predominant fungi were Aspergillus, Wallemia, and Sampaiozyma. The microbial communities of CTLs from different origins differed to some extent, and the diversity and abundance of bacteria were greater than fungi. Metabolomic analysis revealed that 64 VFCs were identified, mainly ketones, of which 23 VFCs could be utilized to identify the geographical origins of CTLs. Sixteen VFCs with OAV greater than 1, including cedrol, phenylacetaldehyde, damascone, beta-damascone, and beta-ionone, play important roles in shaping the flavor profile of CTLs from different origins. Combined with the correlation analysis, bacterial microorganisms were more closely related to key VFCs and favored a positive correlation. Bacillus, Vibrio, and Sphingomonas were the main flavor-related bacteria. The study demonstrated that the predominant microorganisms were essential for the formation of key flavor qualities in CTLs, which provided a theoretical reference for flavor control of CTLs by microbial technology. KEY POINTS: • It is the high OAV VFCs that determine the flavor profile of CTLs. • The methylerythritol phosphate (MEP) pathway and the carotenoid synthesis pathway are key metabolic pathways for the formation of VFCs in CTLs. • Microbial interactions influence tobacco flavor, with bacterial microorganisms contributing more to the flavor formation of CTLs.PMID:38407656 | DOI:10.1007/s00253-024-13032-6

Metabolomics. 2024 Feb 26;20(2):28. doi: 10.1007/s11306-024-02092-4.ABSTRACTINTRODUCTION: Allergies and other immune-mediated diseases are thought to result from incomplete maturation of the immune system early in life. We previously showed that infants' metabolites at birth were associated with immune cell subtypes during infancy. The placenta supplies the fetus with nutrients, but may also provide immune maturation signals.OBJECTIVES: To examine the relationship between metabolites in placental villous tissue and immune maturation during the first year of life and infant and maternal characteristics (gestational length, birth weight, sex, parity, maternal age, and BMI).METHODS: Untargeted metabolomics was measured using Liquid Chromatography-Mass Spectrometry. Subpopulations of T and B cells were measured using flow cytometry at birth, 48 h, one, four, and 12 months. Random forest analysis was used to link the metabolomics data with the T and B cell sub populations as well as infant and maternal characteristics.RESULTS: Modest associations (Q2 = 0.2-0.3) were found between the placental metabolome and kappa-deleting recombination excision circles (KREC) at birth and naïve B cells and memory T cells at 12 months. Weak associations were observed between the placental metabolome and sex and parity. Still, most metabolite features of interest were of low intensity compared to associations previously found in cord blood, suggesting that underlying metabolites were not of placental origin.CONCLUSION: Our results indicate that metabolomic measurements of the placenta may not effectively recognize metabolites important for immune maturation.PMID:38407648 | DOI:10.1007/s11306-024-02092-4

Metabolomics. 2024 Feb 26;20(2):27. doi: 10.1007/s11306-024-02095-1.ABSTRACTINTRODUCTION: The use of chemical fungicides to combat disease has made a substantial contribution to food quality and security. Nonetheless, their applications have been limited due to environmental and health concerns, unaffordability, and the fact that pathogens have acquired resistance to some of these fungicides. Alternative eco-friendly and safe control methods should be explored. The current study investigated the influence of citrus rind phenolic compounds against Phyllosticta citricarpa infection by metabolic profiling of two citrus cultivars with varying degrees of susceptibility to infection.METHODS: Chromatographic data obtained by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC) was subjected to multivariate data analysis to identify biomarkers associated with the tolerant cultivar. The identified biomarkers were tested in vitro against P. citricarpa.RESULTS: Seville oranges, a tolerant cultivar, displayed higher levels of phenolic content and lower total sugar content, that are both associated with lower susceptibility to citrus black spot infection. The generated Principal Component Analysis (PCA) and Orthogonal Projection to Latent Structures-Discriminant Analysis (OPLS-DA) models gave an overview of the data set and identified components that may be responsible for the differences in susceptibility between the two cultivars. Candidate biomarkers associated with tolerance were identified as naringin, neoeriocitrin, bruteiridin, melitidin, and lucenin-2.CONCLUSION: Naringin, a major candidate biomarker was able to inhibit the growth of the pathogen at 10 000 ppm.PMID:38407628 | DOI:10.1007/s11306-024-02095-1

J Infect Dis. 2024 Feb 26:jiae100. doi: 10.1093/infdis/jiae100. Online ahead of print.ABSTRACTBACKGROUND: The therapeutic challenges posed by nontuberculous mycobacterial pulmonary disease (NTM-PD) contribute to an unmet medical need. In this study, we aimed to investigate NTM-PD-specific metabolic pathways using serum metabolomics to understand disease pathogenesis.METHODS: Mass spectrometry-based untargeted metabolomic profiling of serum from patients with NTM-PD (n = 50), patients with bronchiectasis (n = 50), and healthy controls (n = 60) was performed. Selected metabolites were validated by an independent cohort and subjected to pathway analysis and classification modeling.RESULTS: Leucine, tyrosine, inosine, proline, 5-oxoproline, and hypoxanthine levels increased in the NTM-PD group compared with the healthy control group. Furthermore, levels of antioxidant metabolites (ferulic acid, α-lipoic acid, biotin, and 2,8-phenazinediamine) decreased in patients with NTM-PD. These changes were associated with arginine- and proline-related metabolism, leading to generation of reactive oxygen species. Interestingly, the observed metabolic changes in the NTM-PD group overlapped with those in the bronchiectasis group.CONCLUSION: In NTM-PD, 11 metabolites linked to increased oxidative stress were significantly altered from those in healthy controls. Our findings enhance a comprehensive understanding of NTM-PD pathogenesis and provide insights for novel treatment approaches.PMID:38407452 | DOI:10.1093/infdis/jiae100

Food Funct. 2024 Feb 26. doi: 10.1039/d3fo04076c. Online ahead of print.ABSTRACTIn this study, the antifatigue effect and mechanism of peanut sprouts were explored. BALB/c mice divided into three groups (control, dark and UV-C) were respectively supplemented with a normal diet, peanut sprouts (dark germination) added diet and stilbenes-enriched peanut sprouts (UV-C radiated germination) added diet. Results showed that swimming time and levels of blood glucose and antioxidant enzymes significantly increased, while contents of triglyceride and malondialdehyde notably decreased by peanut sprout supplementation. Besides, combined analysis of gut microbiota gene sequencing and targeted metabolomics of fecal metabolites revealed that peanut sprout supplementation up-regulated abundances and metabolic transformations of Catenibacillus, Odoribacter, Prevotellaceae-UCG-001 and Butyricicoccus while it down-regulated the abundance of Parabacteroides. Consequently, contents of sebacic acid, azelaic acid, suberic acid, heptanoic acid, pimelic acid, aminoadipic acid and mono-phenolics notably increased, which were markedly correlated with the antifatigue effect. Compared with the dark group, the swimming time, glutathione peroxidase activity, methylmalonylcarnitine content and abundances of Butyricicoccus, Catenibacillus and Lachnospiraceae NK4A136 were higher in the UV-C group, while opposite results were obtained for the levels of triglyceride, malondialdehyde, alpha-linolenic acid, gamma-linolenic acid, 10Z-heptadecenoic acid and palmitelaidic acid. Overall, peanut sprout supplementation could alleviate fatigue by modulating gut microbiota composition to promote fatty acid oxidation and lysine and stilbene catabolism to increase energy supply and regulate redox balance. UV-C-radiated peanut sprout supplementation could alleviate fatigue more effectively by up-regulating abundances of Butyricicoccus, Catenibacillus and Lachnospiraceae NK4A136 to promote long-chain fatty acid oxidation and catabolism of flavonoids and stilbenes efficiently.PMID:38407402 | DOI:10.1039/d3fo04076c

Hepatol Commun. 2024 Feb 26;8(3):e0310. doi: 10.1097/HC9.0000000000000310. eCollection 2024 Mar 1.ABSTRACTMetabolic dysfunction-associated steatotic liver disease (MASLD), a replacement of the nomenclature employed for NAFLD, is the most prevalent chronic liver disease worldwide. Despite its high global prevalence, NAFLD is often under-recognized due to the absence of reliable noninvasive biomarkers for diagnosis and staging. Growing evidence suggests that the gut microbiome plays a significant role in the occurrence and progression of NAFLD by causing immune dysregulation and metabolic alterations due to gut dysbiosis. The rapid advancement of sequencing tools and metabolomics has enabled the identification of alterations in microbiome signatures and gut microbiota-derived metabolite profiles in numerous clinical studies related to NAFLD. Overall, these studies have shown a decrease in α-diversity and changes in gut microbiota abundance, characterized by increased levels of Escherichia and Prevotella, and decreased levels of Akkermansia muciniphila and Faecalibacterium in patients with NAFLD. Furthermore, bile acids, short-chain fatty acids, trimethylamine N-oxide, and tryptophan metabolites are believed to be closely associated with the onset and progression of NAFLD. In this review, we provide novel insights into the vital role of gut microbiome in the pathogenesis of NAFLD. Specifically, we summarize the major classes of gut microbiota and metabolic biomarkers in NAFLD, thereby highlighting the links between specific bacterial species and certain gut microbiota-derived metabolites in patients with NAFLD.PMID:38407327 | DOI:10.1097/HC9.0000000000000310

Hepatol Commun. 2024 Feb 26;8(3):e0375. doi: 10.1097/HC9.0000000000000375. eCollection 2024 Mar 1.ABSTRACTBACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as NAFLD, is the most common liver disease in children. Liver biopsy remains the gold standard for diagnosis, although more efficient screening methods are needed. We previously developed a novel NAFLD screening panel in youth using machine learning applied to high-resolution metabolomics and clinical phenotype data. Our objective was to validate this panel in a separate cohort, which consisted of a combined cross-sectional sample of 161 children with stored frozen samples (75% male, 12.8±2.6 years of age, body mass index 31.0±7.0 kg/m2, 81% with MASLD, 58% Hispanic race/ethnicity).METHODS: Clinical data were collected from all children, and high-resolution metabolomics was performed using their fasting serum samples. MASLD was assessed by MRI-proton density fat fraction or liver biopsy and cardiometabolic factors. Our previously developed panel included waist circumference, triglycerides, whole-body insulin sensitivity index, 3 amino acids, 2 phospholipids, dihydrothymine, and 2 unknowns. To improve feasibility, a simplified version without the unknowns was utilized in the present study. Since the panel was modified, the data were split into training (67%) and test (33%) sets to assess the validity of the panel.RESULTS: Our present highest-performing modified model, with 4 clinical variables and 8 metabolomics features, achieved an AUROC of 0.92, 95% sensitivity, and 80% specificity for detecting MASLD in the test set.CONCLUSIONS: Therefore, this panel has promising potential for use as a screening tool for MASLD in youth.PMID:38407264 | DOI:10.1097/HC9.0000000000000375

J Proteome Res. 2024 Feb 26. doi: 10.1021/acs.jproteome.3c00611. Online ahead of print.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose in the early stages and lacks reliable biomarkers. The scope of this project was to establish quantitative nuclear magnetic resonance (NMR) spectroscopy to comprehensively study blood serum alterations in PDAC patients. Serum samples from 34 PDAC patients obtained before and after pancreatectomy as well as 83 age- and sex-matched control samples from healthy donors were analyzed with in vitro diagnostics research (IVDr) proton NMR spectroscopy at 600 MHz. Uni- and multivariate statistics were applied to identify significant biofluid alterations. We identified 29 significantly changed metabolites and 98 lipoproteins when comparing serum from healthy controls with those of PDAC patients. The most prominent features were assigned to (i) markers of pancreatic function (e.g., glucose and blood triglycerides), (ii) markers related to surgery (e.g., ketone bodies and blood cholesterols), (iii) PDAC-associated markers (e.g., amino acids and creatine), and (iv) markers for systemic disturbances in PDAC (e.g., gut metabolites DMG, TMAO, DMSO2, and liver lipoproteins). Quantitative serum NMR spectroscopy is suited as a diagnostic tool to investigate PDAC. Remarkably, 2-hydroxybutyrate (2-HB) as a previously suggested marker for insulin resistance was found in extraordinarily high levels only after pancreatectomy, suggesting this metabolite is the strongest marker for pancreatic loss of function.PMID:38407039 | DOI:10.1021/acs.jproteome.3c00611

J Proteome Res. 2024 Feb 26. doi: 10.1021/acs.jproteome.3c00760. Online ahead of print.ABSTRACTThe co-occurrence of multiple chronic metabolic diseases is highly prevalent, posing a huge health threat. Clarifying the metabolic associations between them, as well as identifying metabolites which allow discrimination between diseases, will provide new biological insights into their co-occurrence. Herein, we utilized targeted serum metabolomics and lipidomics covering over 700 metabolites to characterize metabolic alterations and associations related to seven chronic metabolic diseases (obesity, hypertension, hyperuricemia, hyperglycemia, hypercholesterolemia, hypertriglyceridemia, fatty liver) from 1626 participants. We identified 454 metabolites were shared among at least two chronic metabolic diseases, accounting for 73.3% of all 619 significant metabolite-disease associations. We found amino acids, lactic acid, 2-hydroxybutyric acid, triacylglycerols (TGs), and diacylglycerols (DGs) showed connectivity across multiple chronic metabolic diseases. Many carnitines were specifically associated with hyperuricemia. The hypercholesterolemia group showed obvious lipid metabolism disorder. Using logistic regression models, we further identified distinguished metabolites of seven chronic metabolic diseases, which exhibited satisfactory area under curve (AUC) values ranging from 0.848 to 1 in discovery and validation sets. Overall, quantitative metabolome and lipidome data sets revealed widespread and interconnected metabolic disorders among seven chronic metabolic diseases. The distinguished metabolites are useful for diagnosing chronic metabolic diseases and provide a reference value for further clinical intervention and management based on metabolomics strategy.PMID:38407022 | DOI:10.1021/acs.jproteome.3c00760

J Sci Food Agric. 2024 Feb 26. doi: 10.1002/jsfa.13412. Online ahead of print.ABSTRACTBACKGROUND: Flax lignan has attracted much attention due to its potential bioactivities. However, the bioavailability of Secoisolariciresinol diglucoside(SDG), the main lignan in flaxseed, depends on the bioconversion by the colon bacteria. Lactic acid bacteria (LAB) with β-glucosidase activity found wide application in preparing bioactive aglycone.RESULTS: LAB strains with good β-glucosidase activity were isolated from fermented tofu. Their bioconversion of flax lignan extract was investigated by resting cell catalysis and microbial fermentation, and the metabolism of SDG by Lactiplantibacillus plantarum C5 following fermentation was characterized by widely targeted metabolomics. Five L. plantarum strains producing β-glucosidase with broad substrate specificity were isolated and identified, and they all can transform SDG into Secoisolariciresinol (SECO). L. plantarum C5 resting cell reached a maximum SDG conversion of 49.19 ± 3.75%, and SECO generation of 21.49 ± 1.32% (0.215 ± 0.013 mM) at an SDG substrate concentration of 1 mM and 0.477 ± 0.003 mM SECO was produced at 4 mM within 24 h. While sixteen flax lignan metabolites were identified following the fermentation of SDG extract by L. plantarum C5, among them, four were produced following the fermentation: SECO, demethyl-SECO, demethyl-dehydroxy-SECO, and isolariciresinol. Moreover, seven lignans increased significantly.CONCLUSION: Fermentation significantly increased the profile and level of flax lignan metabolites, and the resting cell catalysis benefits from higher bioconversion efficiency and more straightforward product separation. Resting cell catalysis and microbial fermentation of flax lignan extract by the isolated β-glucosidase production L. plantarum could be potentially applied in preparing flax lignan ingredients and fermented flaxseed. This article is protected by copyright. All rights reserved.PMID:38407005 | DOI:10.1002/jsfa.13412

J Vet Intern Med. 2024 Feb 26. doi: 10.1111/jvim.17015. Online ahead of print.ABSTRACTBACKGROUND: Understanding of the biochemical and morphological lesions associated with storage of equine blood is limited.OBJECTIVE: To demonstrate the temporal sequences of lipid and metabolic profiles of equine fresh and stored (up to 42 days) and leukoreduced packed red blood cells (LR-pRBC) and non-leukoreduced packed RBC (nLR-pRBC).ANIMALS: Packed RBC units were obtained from 6 healthy blood donor horses enrolled in 2 blood banks.METHODS: Observational study. Whole blood was collected from each donor using transfusion bags with a LR filter. Leukoreduction pRBC and nLR-pRBC units were obtained and stored at 4°C for up 42 days. Sterile weekly sampling was performed from each unit for analyses.RESULTS: Red blood cells and supernatants progressively accumulated lactate products while high-energy phosphate compounds (adenosine triphosphate and 2,3-Diphosphoglycerate) declined. Hypoxanthine, xanthine, and free fatty acids accumulated in stored RBC and supernatants. These lesions were exacerbated in non-LR-pRBC.CONCLUSION AND CLINICAL IMPORTANCE: Leukoreduction has a beneficial effect on RBC energy and redox metabolism of equine pRBC and the onset and severity of the metabolic storage lesions RBC.PMID:38406982 | DOI:10.1111/jvim.17015