PubMed

Semin Cancer Biol. 2024 Dec 27:S1044-579X(24)00099-3. doi: 10.1016/j.semcancer.2024.12.005. Online ahead of print.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is the most lethal and common form of pancreatic cancer, it has no specific symptoms, and most of the patients are diagnosed when the disease is already at an advanced stage. Chemotherapy typically has only a modest effect, making surgery the most effective treatment option. However, only a small percentage of patients are amenable to surgery. One viable strategy to reduce PDAC death burden associated with the disease is to focus on precursor lesions and identify markers able to predict who will evolve into PDAC. While most PDACs are believed to be preceded by pancreatic intraepithelial neoplasms (PanINs), 5-10% arise from Intraductal papillary mucinous neoplasms (IPMNs), which are mass-forming cystic lesions that are very common in the general population. IPMNs offer an invaluable model of pancreatic carcinogenesis for researchers to analyse, as well as a target population for PDAC early detection by clinicians. The evolution of IPMN into cancer is a complex and multistep process, therefore the identification of individual markers will not be the solution. In recent years, multiple omics technologies have been instrumental to identify possible biomarkers of IPMN progression and carcinogenesis. The only foreseeable strategy will be to integrate multi-omics data, alongside clinical and morphological features, into a progression score or signature using either standard epidemiologic tools or artificial intelligence. The aim of this manuscript is to review the current knowledge on genetic biomarkers and to briefly mention also additional omics, such as metabolomics, the exposome, the miRNome and epigenomics of IPMNs.PMID:39733817 | DOI:10.1016/j.semcancer.2024.12.005

J Ethnopharmacol. 2024 Dec 27:119295. doi: 10.1016/j.jep.2024.119295. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a common autoimmune disease with a high clinical morbidity and leads to persistent chronic inflammation. Sanmiao wan is a classic formula for the treatment of RA, and the results of clinical and experimental studies have shown its therapeutic effect on RA. However, its mechanism of action remains unclear.AIM OF THE STUDY: The aim of this study was to evaluate the effect of Sanmiao wan on RA rats and to further explore its protective mechanism.MATERIALS AND METHODS: Research was conducted using RA models induced by Freund's adjuvant complete, and the degree of arthritis, bone destruction, histopathological and clinical chemical indexes of RA model rats were used to evaluate the animal model and the therapeutic effect of Sanmiao wan. A combination of lipid metabolomics, serum medicinal chemistry, network pharmacology, molecular docking and experimental validation was used to systematically elucidate the potential mechanism of action of Sanmiao wan in the treatment of RA.RESULT: Pharmacodynamic results showed that Sanmiao reduced joint swelling and improved immunity, and the results of non-targeted lipid metabolomics showed a total of 6 lipid core markers, which were hypothesised to play a therapeutic role in RA by modulating the Glycerophospholipid metabolism and sphingolipid metabolism pathways. Using serum medicinal chemistry, we identified 20 blood components and predicted the targets related to RA, and combined with network pharmacology, we screened a total of 59 components and disease-cross-cutting targets, and the enrichment analysis and network pharmacology and KEGG results indicated that the core targets were TNF, IL6, MMP3, and the key metabolic pathways were TNF signaling pathway, lipid and The key metabolic pathways are TNF signaling pathway, lipid and atherosclerosis, rheumatoid arthritis, IL-17 signaling pathway and sphingolipid signaling pathway, etc. It was verified by molecular docking and ELISA experiments that palmatine, cyasterone, atractylenolide I, atractylenolide III, wogonoside, wogonin, phellodendrine, and berberine in Sanmiao could reduce the activity of these targets, thereby inhibiting the expression of inflammatory factors TNF-α, IL6, IL17, RF, MMP3, STAT3.CONCLUSIONS: Sanmiao has a good therapeutic effect on RA, and for the first time, it was found that its potential mechanism of action may be to treat RA by decreasing the activities of TNF, IL6, MMP3 and modulating Glycerophospholipid metabolism and sphingolipid metabolism.It provides a solid basis for the clinical application of Sanmiao wan.PMID:39733801 | DOI:10.1016/j.jep.2024.119295

J Hazard Mater. 2024 Dec 25;486:136969. doi: 10.1016/j.jhazmat.2024.136969. Online ahead of print.ABSTRACTMisuse of insecticides such as thiamethoxam (TMX) not only affects the quality of tea but also leaves residues in tea. Therefore, exploring the metabolic mechanisms of TMX in tea plants can evaluate effects of pesticides on the environment and human health. Here, effects of TMX on tea plants were studied. Malondialdehyde (MDA) content reached a maximum of 12.59 nmol/g fresh weight (FW) on 1st d under X (the recommended dose: 0.015 kg a.i./ha) of TMX. Under 2 X (0.03 kg a.i./ha), the catalase, glutathione S-transferase and superoxide dismutase activity were increased by 45.0 %, 55.5 %, and 49.7 % at 7 d respectively. Metabolomic and transcriptomic analyses revealed that TMX significantly affected amino acid metabolism, flavonoid biosynthesis and glutathione metabolism, and induced the expression of 3-hydroxyisobutyric acid dehydrogenase genes (CsHDH1 and CsHDH3) and glutathione S-transferase gene (CsGST1). The three genes were transiently expressed in Nicotiana benthamiana for the first time to verify the function of TMX degradation, with the degradation rate of 59.2 %-85.3 % at X. This study elucidated the response of tea plants to abiotic stress on the molecular-scale perspective, and the molecular approaches could serve as a model for the study on pesticide metabolism in plants. SYNOPSIS: Degradation ability of CsHDH1, CsHDH3 and CsGST1 genes to thiamethoxam was verified for the first time, providing genetic resources for phytoremediation of pollutants.PMID:39733754 | DOI:10.1016/j.jhazmat.2024.136969

J Chromatogr A. 2024 Dec 20;1741:465619. doi: 10.1016/j.chroma.2024.465619. Online ahead of print.ABSTRACTKawasaki disease (KD) has emerged as the leading cause of acquired heart disease in children, primarily due to the absence of highly sensitive and specific biomarkers for early and accurate diagnosis. To address this issue, a simple and comprehensive targeted metabolomics method employing ultra high-performance liquid chromatography coupled with Q-TRAP mass spectrometry has been developed to identify new metabolite biomarkers for KD. This method enables the simultaneous quantification of 276 metabolites, covering 60 metabolic pathways, with a particular emphasis on metabolites relevant to KD. The use of nine ISs and commercial quality control samples significantly enhances both accuracy and precision. Through validation and application to serum samples from patients with KD, seventeen differential serum metabolites were identified. The altered metabolites are primarily associated with three functional metabolic pathways: tricarboxylic acid cycle, tryptophan metabolism, and bile acid metabolism, all of which are believed to be involved in the inflammatory and immune responses in KD patients. Ultimately, eight differential metabolites (indole-3-propionic acid, thiamine, indolepyruvic acid, levodopa, l-selenomethionine, isocitric acid, trans-aconitate, and N-acetylasparagine) were identified that could potentially serve as diagnostic biomarkers with the area under the curve values exceeding 0.9. Our targeted metabolomics approach demonstrates applicability in identifying potential metabolite biomarkers for KD and holds great promise in unraveling the intricate pathophysiology of the disease.PMID:39733740 | DOI:10.1016/j.chroma.2024.465619

Plant Physiol Biochem. 2024 Dec 25;219:109436. doi: 10.1016/j.plaphy.2024.109436. Online ahead of print.ABSTRACTChitinases are enzymes that hydrolyze β-1,4-glycosidic bonds in chitin. Previous studies have shown that several chitinases accumulated significantly in A. mongolicus, suggesting that chitinases might participate in the adaptation to winter climate in Ammopiptanthus mongolicus. Here, we analyzed the evolution and expression patterns of the chitinase gene family in A. mongolicus and investigated the function and regulatory mechanisms of the AmChi7 gene in response to abiotic stress. The chitinase gene family in A. mongolicus comprises 27 members, many of which arose through formed by tandem and segmental duplication. Several chitinase genes, including AmChi7 gene, were significantly upregulated in winter. Overexpression of AmChi7 gene enhanced the tolerance of yeast to freeze-thaw cycle and osmotic stress, and enhanced the tolerance of transgenic Arabidopsis to low-temperature and drought stress. Furthermore, AmWRKY59, a MeJA-induced transcription factor, bound to the W box element in the AmChi7 gene promoter, activating its expression in winter. It is speculated that chitinase AmChi7 accumulation in winter enhances adaptation to temperate winter climates in A. mongolicus. This study expands our understanding of the biological functions of chitinases and provides insights into the molecular mechanisms underlying winter climate adaptation in A. mongolicus.PMID:39733727 | DOI:10.1016/j.plaphy.2024.109436

Microbiol Res. 2024 Dec 26;292:128040. doi: 10.1016/j.micres.2024.128040. Online ahead of print.ABSTRACTTemperate bacteriophages are crucial for maintaining the pathogenicity and fitness of S. aureus, which also show promise as a biocontrol agent for S. aureus. However, the fitness benefit and cost of lysogeny by S. aureus temperate phages and their underlying mechanisms remain unexplored. In this study, phage resistance, virulence, antimicrobial resistance (AMR), transcriptome, and metabolome of phage SapYZUs7 lysogenic and non-lysogenic S. aureus strains were compared. Whole-genome analysis revealed that SapYZUs7 harbouring smaII associated with a single-protein MazF-like antiphage system could be integrated into the genome of S. aureus isolates. Notably, lysogenic S. aureus exhibited higher phage resistance, a lower growth rate, and inhibited metabolic activity compared to the parental strains, indicating interference of phage reproduction by smaII. Moreover, prophages carrying smaII are widely distributed across S. aureus and harboured other virulence factor (VF) and AMR genes. Besides, the SapYZUs7-integration increased phagocytosis resistance but decreased adhesion, biofilm formation, and AMR. The combined use of SapYZUs7 and antibiotics exhibited a better bactericidal effect than SapYZUs7 or the antibiotics alone. Consistently, integrated omics analysis suggested that SapYZUs7-lysogeny downregulated multiple VF and AMR genes. Our analysis suggests that SmaII drives mutualistic phage-host interactions through lysogenic conversion. The fitness cost of SapYZUs7-integration is the downregulated expression of VF and AMR genes, serving as an alternative candidate as a biocontrol agent for methicillin-resistant S. aureus and multidrug-resistant S. aureus.PMID:39733717 | DOI:10.1016/j.micres.2024.128040

Sci Rep. 2024 Dec 28;14(1):31467. doi: 10.1038/s41598-024-83146-4.ABSTRACTWilliams Syndrome (WS) is a rare neurodevelopmental disorder with a prevalence of 1 in 7500 to 1 in 20,000 individuals, caused by a microdeletion in chromosome 7q11.23. Despite its distinctive clinical features, the underlying metabolic alterations remain largely unexplored. This study employs targeted metabolomics to investigate the metabolic characteristics of children with WS. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified significant dysregulation of 15 metabolites, with 11 upregulated and 4 downregulated. Notably, amino acids such as alanine, proline, and arginine were significantly elevated. Fatty acid metabolism showed pronounced upregulation of long-chain saturated fatty acids (C18:0, C20:0, C22:0, C24:0, C26:0, and C28:0) and downregulation of long-chain unsaturated fatty acids (C18:2 LA, C22:6 DHA, C16:1 PLA, and t-C18:1 EA), except for upregulated nervonic acid (C24:1) and arachidonic acid (C20:4). Metabolic pathway analysis highlighted disruptions in arginine synthesis, arginine/proline metabolism, alanine, aspartate and glutamate metabolism, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and arachidonic acid metabolism. This study provides the first comprehensive analysis of amino acid and fatty acid metabolism in children with WS, offering insights into the disorder's complex metabolic landscape. Further validation in larger cohorts is essential to confirm these findings and their potential as biomarkers and therapeutic targets.PMID:39733135 | DOI:10.1038/s41598-024-83146-4

Sci Rep. 2024 Dec 28;14(1):31394. doi: 10.1038/s41598-024-82995-3.ABSTRACTCoral reef sponges efficiently take up particulate and dissolved organic matter (DOM) from the water column and release compounds such as nucleosides, amino acids, and other dissolved metabolites to the surrounding reef via their exhalent seawater, but the influence of this process on reef picoplankton and nutrient processing is relatively unexplored. Here we examined the impact of sponge exhalent on the reef picoplankon community and subsequent alterations to the reef dissolved metabolite pool. We exposed reef picoplankton communities to a sponge exhalent water mixture (Niphates digitalis and Xestospongia muta) or filtered reef seawater (control) in closed, container-based dark incubations. We used 16S rRNA gene sequencing and flow cytometry-based cell counts to examine the picoplankton community and metabolomics and other analyses to examine the dissolved metabolite pool. The initial sponge exhalent was enriched in adenosine, inosine, chorismate, humic-like and amino acid-like components, and ammonium. Following 48 h of exposure to sponge exhalent, the picoplankton differed in composition, were reduced in diversity, showed doubled (or higher) growth efficiencies, and harbored increased copiotrophic and denitrifying taxa (Marinomonas, Pontibacterium, Aliiroseovarius) compared to control, reef-water based incubations. Alongside these picoplankton alterations, the sponge treatments, relative to seawater controls, had decreased adenosine, inosine, tryptophan, and ammonium, metabolites that may support the observed higher picoplankton growth efficiencies. Sponge treatments also had a net increase in several monosaccharides and other metabolites including anthranilate, riboflavin, nitrite, and nitrate. Our work demonstrates a link between sponge exhalent-associated metabolites and the picoplankton community, with exhalent water supporting an increased abundance of efficient, copiotrophic taxa that catabolize complex nutrients. The copiotrophic taxa were often different from those observed in previous algae and coral studies. These results have implications for better understanding the multifaceted role of sponges on picoplankton biomass with subsequent potential impacts to coral and other planktonic feeders in oligotrophic reef environments.PMID:39733106 | DOI:10.1038/s41598-024-82995-3

Sci Rep. 2024 Dec 28;14(1):31337. doi: 10.1038/s41598-024-82808-7.ABSTRACTMany lipid biomarkers of stroke have been identified, but the lipid metabolism in elderly patients with leukoaraiosis remains poorly understood. This study aims to explore lipid metabolic processes in stroke among leukoaraiosis patients, which could provide valuable insights for guiding future antithrombotic therapy. In a cohort of 215 individuals undergoing MRI, 13 stroke patients were matched with controls, and 48 stroke patients with leukoaraiosis were matched with 40 leukoaraiosis patients. Serum lipidomics was profiled using UPLC-TOF, and OPLS-DA was applied for metabolite identification. Partial Least Squares Path Model (PLS-PM) assessed pathway weights of novel metabolites in stroke risk, while linear regression explored correlations with clinical outcomes. Lipid profiling identified 168 distinct compounds. From these, 25 lipid molecules were associated with glycerolipid, glycerophospholipid, and sphingolipid metabolism. PLS-PM identified 12 key metabolites, including DG 36:4 (OR = 6.40) as a significant risk factor. Metabolites such as PE 38:5 and FA 16:1;O showed significant correlations with stroke in leukoaraiosis, particularly when the Fazekas score was ≥ 4. Twelve metabolites were identified as key factors in stroke incidence among leukoaraiosis patients. Lipid disturbances in glycerolipids and glycerophospholipids provide valuable insights for further studies on the progression from leukoaraiosis to stroke.PMID:39733101 | DOI:10.1038/s41598-024-82808-7

Sci Rep. 2024 Dec 28;14(1):31330. doi: 10.1038/s41598-024-82859-w.ABSTRACTThe quality of cigar tobacco leaves is profoundly affected by the timing of their harvest, with both early and late collections resulting in inferior characteristics. While the relationship between maturity and physiological metabolic processes is acknowledged, a comprehensive understanding of the physiological behavior of cigar leaves harvested at different stages remains elusive. This research investigated the physiological and metabolomic profiles of the cigar tobacco variety CX-014, grown in Danjiangkou City, Hubei Province, with leaves sampled at 35 (T1), 42 (T2), 49 (T3), and 56 (T4) days post-inflorescence removal. Leaf color transitioned from green to yellow, accompanied by the appearance of white mature spots. Notable increases in photosynthetic pigments and gas exchange parameters occurred between T1 and T2, followed by decline at T3 and T4. The optimal sugar-to-nicotine and potassium-to-chlorine ratios, critical determinants of smoking quality and tobacco combustibility, were observed at T3, indicating a superior chemical balance in leaves harvested at this stage. Metabolomic analysis revealed 2153 distinct metabolites, with the most significant changes occurring between T2 and T3, highlighting critical physiological transformations during this interval. Pathway enrichment analysis via KEGG pinpointed notable shifts in amino acid synthesis pathways, particularly those involving tryptophan, alanine, and aspartate. Tryptophan metabolism and zeatin biosynthesis were substantially altered, with compounds like indolepyruvic acid, N-formylpurine nucleotide, isopentenyladenine nucleotide, and dihydrozeatin showing marked reductions at T3. This study also explored how the timing of lower leaf harvest influences the physiological processes of middle leaves, finding that a plethora of metabolites associated with the breakdown of arachidonic acid-a primitive metazoan signaler implicated in plant stress and defense networks-were abundant in T3 leaves when lower leaves were harvested 43-38 days prior. Overall, these findings elucidates the complex physiological dynamics of cigar leaves during maturation, highlighting critical metabolites involved in essential metabolic pathways.PMID:39733066 | DOI:10.1038/s41598-024-82859-w

Sci Rep. 2024 Dec 28;14(1):31416. doi: 10.1038/s41598-024-83017-y.ABSTRACTHeat stress (HS) is an impactful condition in ruminants that negatively affects their physiological and rumen microbial composition. However, a fundamental understanding of metabolomic and metataxonomic mechanisms in goats under HS conditions is lacking. Here, we analyzed the rumen metabolomics, metataxonomics, and serum metabolomics of goats (n = 10, body weight: 41.08 ± 1.83 kg) under optimum temperature period (OTP) (HS-free, temperature humidity index (THI): 57.13 ± 3.98) and high temperature period (HTP) (HS-exposed, THI: 80.27 ± 1.22) conditions, to identify changes in key metabolites and the rumen microbiome induced by HS. Compared to the OTP and HTP conditions, metabolomic analysis revealed significant changes in rumen metabolites related to energy and amino acid metabolism, with HTP goats showing potential rumen metabolic biomarkers, such as butyrate, isopropanol, phenylacetate, and 2-oxoisocaproate (P < 0.001). Serum analysis revealed significant changes in energy metabolism and immune response, with HTP goats showing potential metabolic biomarkers, including acetate, betaine, glucuronate, and kynurenine (P < 0.05). Metataxonomic analysis revealed that HS affected the alpha diversity measurements, including the Chao1 estimate (P < 0.05) and evenness (P < 0.05) between OTP and HTP groups. Through the metabolic association of the rumen microbiome with the metabolome, we found that Fibrobacter and Ruminococcus were enriched in HTP and positively correlated with ruminal microbial metabolites, such as acetate. In addition, Prevotellaceae UCG-003, which was denoted as the keynote genus in the HTP, co-occurred with acetate-producing bacteria such as Quinella and Ruminococcus. Furthermore, we identified that Oscillospiraceae UCG-002, an enriched bacterial genus in HTP, showed a positive correlation with functional features, such as biotin and sulfur metabolism. Our study provided fundamental insights into how HS affected the physiology and rumen microbial compositions of goats and how both microbiome and host-dependent mechanisms contributed to these changes. These findings could potentially suggest strategies for mitigating the adverse effects of HS, including changes in the microbial population and energy metabolism in goats.PMID:39733052 | DOI:10.1038/s41598-024-83017-y

Sci Rep. 2024 Dec 28;14(1):31492. doi: 10.1038/s41598-024-83288-5.ABSTRACTCannabis use disorder affects up to 42% of individuals with schizophrenia, correlating with earlier onset, increased positive symptoms, and more frequent hospitalizations. This study employed an untargeted lipidomics approach to identify biomarkers in plasma samples from subjects with schizophrenia, cannabis use disorder, or both (dual diagnosis), aiming to elucidate the metabolic underpinnings of cannabis abuse and schizophrenia development. The use of liquid chromatography-high resolution mass spectrometry enabled the annotation of 119 metabolites, with the highest identification confidence level achieved for 16 compounds. Notably, a marked reduction in acylcarnitines, including octanoylcarnitine and decanoylcarnitine, was observed across all patient groups compared to controls. In cannabis use disorder patients, N-acyl amino acids (NAAAs), particularly N-palmitoyl threonine and N-palmitoyl serine, showed a strong downregulation, a pattern also seen in schizophrenia and dual diagnosis patients. Conversely, elevated levels of 7-dehydrodesmosterol were detected in schizophrenia and dual diagnosis patients relative to controls. These findings suggest a potential link between metabolic disruptions and the pathophysiology of both disorders. The untargeted lipidomics approach offers a powerful tool to identify novel biomarkers, enhancing our understanding of the biological relationship between cannabis abuse and schizophrenia, and paving the way for future therapeutic strategies targeting metabolic pathways in these conditions.PMID:39733019 | DOI:10.1038/s41598-024-83288-5

Sci Rep. 2024 Dec 28;14(1):31374. doi: 10.1038/s41598-024-82833-6.ABSTRACTEnhancing crops productivity to ensure food security is one of the major challenges encountering agriculture today. A promising solution is the use of biostimulants, which encompass molecules that enhance plant fitness, growth, and productivity. The regulatory metabolite zaxinone and its mimics (MiZax3 and MiZax5) showed promising results in improving the growth and yield of several crops. Here, the impact of their exogenous application on soil and rice root microbiota was investigated. Plants grown in native paddy soil were treated with zaxinone, MiZax3, and MiZax5 and the composition of bacterial and fungal communities in soil, rhizosphere, and endosphere at the tillering and the milky stage was assessed. Furthermore, shoot metabolome profile and nutrient content of the seeds were evaluated. Results show that treatment with zaxinone and its mimics predominantly influenced the root endosphere prokaryotic community, causing a partial depletion of plant-beneficial microbes at the tillering stage, followed by a recovery of the prokaryotic community structure during the milky stage. Our study provides new insights into the role of zaxinone and MiZax in the interplay between rice and its root-associated microbiota and paves the way for their practical application in the field as ecologically friendly biostimulants to enhance crop productivity.PMID:39732893 | DOI:10.1038/s41598-024-82833-6

Sci Rep. 2024 Dec 28;14(1):31262. doi: 10.1038/s41598-024-82674-3.ABSTRACTThe effect of sexual dimorphism on the metabolism of patients with Parkinson's disease has not been clarified. A group of patients with Parkinson's disease and healthy controls were recruited, and their clinical characteristics and plasma were collected. Untargeted liquid chromatography-mass spectrometry-based plasma metabolomics profiling was performed. Differentially expressed metabolites between patients and healthy controls were respectively identified in the male and female participants and metabolite set enrichment analyses were further employed. A total of 75 patients with Parkinson's disease (37 males and 38 females) and 31 healthy controls (16 males and 15 females) were enrolled while no significant differences can be discovered in clinical characteristics. The constructed male-specific metabolic model from orthogonal partial least squares-discriminant analysis can't well recognize female patients and the female-specific model also can't accurately identify male patients. There were 55 differentially expressed metabolites in the male participants, and fatty acids and conjugates and eicosanoids were the significantly enriched metabolite sets. Meanwhile, 86 metabolites were differentially expressed in the female participants while fatty acids and conjugates and glycerophosphocholines were enriched. Only 17 metabolites were simultaneously changed in both male and female patients. Significant sex differences of lipid metabolism were found in patients with Parkinson's disease.PMID:39732876 | DOI:10.1038/s41598-024-82674-3

Sci Rep. 2024 Dec 28;14(1):31336. doi: 10.1038/s41598-024-82718-8.ABSTRACTThe article is motivated by an application to the EarlyBird cohort study aiming to explore how anthropometrics and clinical and metabolic processes are associated with obesity and glucose control during childhood. There is interest in inferring the relationship between dynamically changing and high-dimensional metabolites and a longitudinal response. Important aspects of the analysis include the selection of the important set of metabolites and the accommodation of missing data in both response and covariate values. With this motivation, we propose a flexible but parsimonious Bayesian semiparametric joint model for the outcome and the covariate generating processes, making novel use of nonparametric mean processes, latent factor models, and different classes of continuous shrinkage priors. The proposed approach efficiently addresses daunting dimensionality challenges, simplifies imputation tasks, and automates the selection of important predictors. Implementation via an efficient Markov chain Monte Carlo algorithm appropriately accounts for uncertainty in various aspects of the analysis. Simulation experiments illustrate the efficacy of the proposed methodology. The application to the EarlyBird cohort study illustrates its practical utility in enabling statistical integration of different molecular processes involved in glucose production and metabolism. From this study, we were able to show that glucose levels from 5 to 16 years of age are associated with different circulating levels of metabolites in the blood serum and can be fitted over time for a wide range of shapes of trajectories. The metabolites contributing the most to explaining glucose trajectories tend to be involved in different central energy metabolomic pathways. The methodology provides a tool to generate new hypotheses related to obesity and glucose control during childhood and adolescence.PMID:39732846 | DOI:10.1038/s41598-024-82718-8

Sci Rep. 2024 Dec 28;14(1):31211. doi: 10.1038/s41598-024-82596-0.ABSTRACTHigh SARS-CoV-2-specific antibody levels can protect against SARS-CoV-2 reinfection. The gut microbiome can affect a host's immune response. However, its role in the antibody response to SARS-CoV-2 in people living with HIV (PLWH) remains poorly understood. Here, we categorised PLWH and healthy individuals into high- and low-antibody-response groups. Shotgun metagenomic sequencing and targeted metabolomic assays were used to investigate the differences in the gut microbiome and metabolic functions between the high- and low-antibody-response groups. PLWH demonstrated a higher abundance of short-chain fatty acid (SCFA)-producing species, accompanied by high serum levels of several SCFAs, in the high-antibody-response group than in the low-antibody-response group. In contrast, healthy individuals demonstrated higher enrichment of pilus-bearing bacterial species, with flagella-expressing genes, in the high-antibody-response group than in the low-antibody-response group. Therefore, gut-microbiota-derived SCFAs play a key role in antibody responses in PLWH but not in healthy individuals. Our results afford a novel understanding of how the gut microbiome and its metabolites are associated with host immunity. Moreover, they may facilitate the exploration of modalities to prevent SARS-CoV-2 reinfection through various gut-microbiota-targeted interventions tailored to different populations.PMID:39732792 | DOI:10.1038/s41598-024-82596-0

Sci Rep. 2024 Dec 28;14(1):31240. doi: 10.1038/s41598-024-82553-x.ABSTRACTUnregulated, systemic inflammation negatively impacts health and production in dairy cows. Soluble mediators and platelets have been studied for their expansive role in mediating inflammation. Our objectives were to compare the plasma oxylipin and endocannabinoid profiles, and the platelet and plasma proteomic profiles of healthy cows to cows experiencing elevated systemic inflammation as indicated by plasma haptoglobin (Hp) concentrations. Postpartum cows at 3 DIM with plasma Hp concentrations [Formula: see text] 0.50 g/L and no clinical disease were enrolled into the high-inflammation group (n = 8). Cows with plasma Hp concentrations [Formula: see text] 0.1 g/L and no clinical disease were enrolled into the low-inflammation group (n = 8). Targeted lipidomic analysis revealed differences in the plasma oxylipin and endocannabinoid profile between high- and low-inflammation cows. Cows in the high-inflammation group had increased plasma concentrations of the oxylipins 9(S)-HpOTrE, 9(S)-HOTrE, 13(S)-HpOTrE, and 9,10-EpOME, and the endocannabinoid anandamide. In-depth proteomic analysis of platelets between the high- and low-inflammation groups revealed significant differences in protein categories related to platelet granule release and cellular iron uptake. Proteomic outputs from plasma revealed 24 proteins to be different between high and low-inflammation groups, including proteins involved in autophagy and immune mediation. Together, our results indicate that cows experiencing an exacerbated systemic inflammatory response in the postpartum may have impaired disease resistance, and platelets could be contributors to their inflammatory state.PMID:39732778 | DOI:10.1038/s41598-024-82553-x

Stem Cell Res Ther. 2024 Dec 29;15(1):414. doi: 10.1186/s13287-024-04028-0.ABSTRACTBACKGROUND: Complex perianal fistulas, challenging to treat and prone to recurrence, often require surgical intervention that may cause fecal incontinence and lower quality of life due to large surgical wounds and potential sphincter damage. Human umbilical cord-derived MSCs (hUC-MSCs) and their exosomes (hUCMSCs-Exo) may promote wound healing.METHODS: This study assessed the efficacy, mechanisms, and safety of these exosomes in treating complex perianal fistulas in SD rats. We established a rat model, divided rats with fistulas into the control and the exosome groups. We assessed treatment efficacy through ultrasound, clinical observations, and histopathological analysis. We also evaluated the activation of the HIF-1α/TGF-β/Smad signaling pathway via PCR and Western blot and assessed serological markers for HIF-1α and inflammatory indices through ELISA. We analyzed gut microbiota and the systemic metabolic environment via untargeted metabolomics.RESULTS: The hUCMSCs-Exo effectively promoted healing of wound, regulated the immune balance enhanced collagen synthesis and angiogenesis in the perianal fistulas model of rats, and regulated the gut microbiota and metabolomic profiles. Results of PCR and Western blot analyses indicated that the exosomes activated HIF-1α/TGF-β/Smad signaling pathways. To the dosages tested, the 10ug/100ul concentration (medium dose) was found to be the most effective to the treatment of complex perianal fistulas.CONCLUSIONS: The hUCMSCs-Exo significantly promoted the healing of wound in perianal fistulas of rats and demonstrated higher safety. The underlying mechanism facilitating the healing process was likely associated with the activation of the HIF-1α/TGF-β/Smad signaling pathway.PMID:39732731 | DOI:10.1186/s13287-024-04028-0

Biomed Chromatogr. 2025 Jan;39(1):e6061. doi: 10.1002/bmc.6061.ABSTRACTAn animal model of radiation-induced lung injury (RILI) was established using female rats given sublethal whole-thorax X-ray irradiation (15 Gy) at a dose rate of 2.7 Gy/min. The rats were studied for up to day 45 and compared with sham-irradiated controls. Time-series lung tissue samples during the progression of RILI were collected for dynamic metabolomics studies based on gas chromatography-mass spectrometry (GC-MS). Differential metabolites associated with radiation-induced lung injury were identified, followed by metabolite set enrichment analysis to uncover pathway changes in RILI. The results revealed dynamic metabolic alterations in the progression of RILI, primarily involving in glycine and serine metabolism, the urea cycle, the Warburg effect, glutamate metabolism, arginine and proline metabolism, glucose-alanine cycle, and ammonia recycling. In addition, the potential panel of biomarkers including taurine, lysine, and tyrosine of RILI was selected and then applied to evaluate the diagnostic potential for RILI based on the receiving operator characteristic curve (ROC) at the early-stage of RILI. The better sensitivity, specificity, and accuracy indicate the potential of early diagnosis for RILI. These findings suggest that dynamic metabolomics data could provide new insights into understanding the complex metabolic dysregulation underlying RILI, facilitating the selection of biomarkers for early diagnosis.PMID:39732522 | DOI:10.1002/bmc.6061

Exp Eye Res. 2024 Dec 26:110227. doi: 10.1016/j.exer.2024.110227. Online ahead of print.ABSTRACTChoroid neovascularization (CNV) is a distinct type of age-related macular degeneration (AMD) with a poor prognosis and responsible for the majority of vision loss in the elderly population. The laser-induced CNV model is a well-established animal model frequently used to study CNV. In this study, we performed an integrated analysis of metabolomic and transcriptomic data from CNV samples, utilizing multiple approaches including single-sample gene set enrichment analysis (ssGSEA), correlation analysis, and weighted gene co-expression network analysis (WGCNA), alongside various bioinformatics platforms, to identify key metabolic and immune signatures and to investigate their interplay during angiogenesis. Dominant infiltration of macrophages and monocytes was detected and a positive correlation between dysregulated riboflavin metabolism and angiogenesis pathways was characterized. Hub genes such as ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) and acid phosphatase 5, tartrate resistant (ACP5) emerged as potential central regulators of immune-metabolic crosstalk in CNV. The classification of the immune and metabolic landscape and their critical interactions in CNV models will enhance the understanding of the pathogenesis of neovascular AMD and other neovascular eye diseases, contributing to the development of multi-targeted therapeutic strategies with better efficacy.PMID:39732424 | DOI:10.1016/j.exer.2024.110227