PubMed

BMC Pregnancy Childbirth. 2023 Nov 30;23(1):828. doi: 10.1186/s12884-023-06102-6.ABSTRACTBACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a prevalent pregnancy-specific complication that presents with maternal itching and elevated serum bile acid levels. ICP is associated with unfavorable pregnancy outcomes, severely decreasing the pregnant woman's quality of life. Timely identification of ICP is crucial for effective management and improved outcomes.METHODS: We collected urine samples from 8 patients with ICP and 8 healthy individuals. We used Liquid Chromatography-Mass Spectrometry (LC-MS) to detect metabolite expression levels, then conducted a series of bioinformatic analyses to explore the potential biological meanings of differentially expressed metabolites, and preliminarily discovered several candidate biomarkers. To validate these candidate biomarkers, we performed Gas Chromatography-Mass Spectrometry (GC-MS) detection and analyzed their diagnostic values using receiver operating characteristic (ROC) curve.RESULTS: Untargeted metabolomics data showed that 6129 positive peaks and 6218 negative peaks were extracted from each specimen. OPLS-DA analysis and the heat map for cluster analysis showed satisfactory capability in discriminating ICP specimens from controls. Subsequent analysis extracted 64 significantly differentially expressed metabolites, which could be potential biomarkers for diagnosis of ICP. Based on the KEGG enrichment analyses, six candidate biomarkers were preliminarily identified. Two most promising biomarkers (3-hydroxypropionic acid and uracil) were validated by targeted metabolomics analyses with the area under the curve (AUC) of 0.920 and 0.850 respectively.CONCLUSION: Based on preliminary screening from untargeted metabolomics and subsequent validation through targeted metabolomics, 3-hydroxypropionic acid and uracil were identified as promising diagnostic biomarkers for ICP.PMID:38036952 | DOI:10.1186/s12884-023-06102-6

Metabolomics. 2023 Nov 30;20(1):2. doi: 10.1007/s11306-023-02065-z.ABSTRACTINTRODUCTION: In metabolomics, the investigation of associations between the metabolome and one trait of interest is a key research question. However, statistical analyses of such associations are often challenging. Statistical tools enabling resilient verification and clear presentation are therefore highly desired.OBJECTIVES: Our aim is to provide a contribution for statistical analysis of metabolomics data, offering a widely applicable open-source statistical workflow, which considers the intrinsic complexity of metabolomics data.METHODS: We combined selected R packages tailored for all properties of heterogeneous metabolomics datasets, where metabolite parameters typically (i) are analyzed in different matrices, (ii) are measured on different analytical platforms with different precision, (iii) are analyzed by targeted as well as non-targeted methods, (iv) are scaled variously, (v) reveal heterogeneous variances, (vi) may be correlated, (vii) may have only few values or values below a detection limit, or (viii) may be incomplete.RESULTS: The code is shared entirely and freely available. The workflow output is a table of metabolites associated with a trait of interest and a compact plot for high-quality results visualization. The workflow output and its utility are presented by applying it to two previously published datasets: one dataset from our own lab and another dataset taken from the repository MetaboLights.CONCLUSION: Robustness and benefits of the statistical workflow were clearly demonstrated, and everyone can directly re-use it for analysis of own data.PMID:38036896 | DOI:10.1007/s11306-023-02065-z

Nat Biomed Eng. 2023 Nov 30. doi: 10.1038/s41551-023-01143-w. Online ahead of print.ABSTRACTThe limited availability of cytokines in solid tumours hinders maintenance of the antitumour activity of chimeric antigen receptor (CAR) T cells. Cytokine receptor signalling pathways in CAR T cells can be activated by transgenic expression or injection of cytokines in the tumour, or by engineering the activation of cognate cytokine receptors. However, these strategies are constrained by toxicity arising from the activation of bystander cells, by the suboptimal biodistribution of the cytokines and by downregulation of the cognate receptor. Here we show that replacement of the extracellular domains of heterodimeric cytokine receptors in T cells with two leucine zipper motifs provides optimal Janus kinase/signal transducer and activator of transcription signalling. Such chimeric cytokine receptors, which can be generated for common γ-chain receptors, interleukin-10 and -12 receptors, enabled T cells to survive cytokine starvation without induction of autonomous cell growth, and augmented the effector function of CAR T cells in vitro in the setting of chronic antigen exposure and in human tumour xenografts in mice. As a modular design, leucine zippers can be used to generate constitutively active cytokine receptors in effector immune cells.PMID:38036617 | DOI:10.1038/s41551-023-01143-w

Sci Rep. 2023 Nov 30;13(1):21123. doi: 10.1038/s41598-023-48208-z.ABSTRACTAlthough weekend recovery sleep is common, the physiological responses to weekend recovery sleep are not fully elucidated. Identifying molecular biomarkers that represent adequate versus insufficient sleep could help advance our understanding of weekend recovery sleep. Here, we identified potential molecular biomarkers of insufficient sleep and defined the impact of weekend recovery sleep on these biomarkers using metabolomics in a randomized controlled trial. Healthy adults (n = 34) were randomized into three groups: control (CON: 9-h sleep opportunities); sleep restriction (SR: 5-h sleep opportunities); or weekend recovery (WR: simulated workweek of 5-h sleep opportunities followed by ad libitum weekend recovery sleep and then 2 days with 5-h sleep opportunities). Blood for metabolomics was collected on the simulated Monday immediately following the weekend. Nine machine learning models, including a machine learning ensemble, were built to classify samples from SR versus CON. Notably, SR showed decreased glycerophospholipids and sphingolipids versus CON. The machine learning ensemble showed the highest G-mean performance and classified 50% of the WR samples as insufficient sleep. Our findings show insufficient sleep and recovery sleep influence the plasma metabolome and suggest more than one weekend of recovery sleep may be necessary for the identified biomarkers to return to healthy adequate sleep levels.PMID:38036605 | DOI:10.1038/s41598-023-48208-z

Nat Commun. 2023 Nov 30;14(1):7873. doi: 10.1038/s41467-023-43265-4.ABSTRACTAs a red tide algal toxin with intense neurotoxicity distributed worldwide, domoic acid (DA) has attracted increasing concerns. In this work, the integrative analysis of metagenome and metabolome are applied to investigate the impact of DA on nitrogen cycling in coastal sediments. Here we show that DA can act as a stressor to induce the variation of nitrogen (N) cycling by altering the abundance of functional genes and electron supply. Moreover, microecology theory revealed that DA can increase the role of deterministic assembly in microbial dynamic succession, resulting in the shift of niches and, ultimately, the alteration in N cycling. Notably, denitrification and Anammox, the important process for sediment N removal, are markedly limited by DA. Also, variation of N cycling implies the modification in cycles of other associated elements. Overall, DA is capable of ecosystem-level effects, which require further evaluation of its potential cascading effects.PMID:38036528 | DOI:10.1038/s41467-023-43265-4

Fertil Steril. 2023 Nov 28:S0015-0282(23)02020-4. doi: 10.1016/j.fertnstert.2023.11.025. Online ahead of print.ABSTRACTOBJECTIVE: To explore the heterogeneity of CD24+ decidual stromal cells in recurrent miscarriage patients.DESIGN: We have discerned that the expression of CD24 serves to differentiate two stable and functionally distinct lineages of decidual stromal cells. The heterogeneity of CD24+ decidual stromal cells has been scrutinized, encompassing variances in stromal markers, transcriptional profile, metabolic activity, as well as immune regulation.SUBJECTS: A total of 129 early decidual samples were obtained, comprising 36 from healthy donors and 93 from recurrent miscarriage patients. Blood samples were collected prior to the surgical procedure. Paraffin-embedded segments from 20 decidual samples of recurrent miscarriage patients were obtained.INTERVENTIONS: None.MAIN OUTCOME MEASURES: The flow cytometry was utilized to quantify the expression of CD24+ decidual stromal cells in both healthy donors and recurrent miscarriage patients, while also evaluating the cellular heterogeneity. To ascertain the transcriptomic profiles of CD24+ decidual stromal cells by re-analyzing our single-cell transcriptomic data. Additionally, to measure the metabolomic activity of CD24+ decidual stromal cells from recurrent miscarriage patients, ultraperformance liquid chromatography-mass spectrometry was employed. Through the implementation of a co-culture system, we unraveled the role of CD24+ decidual stromal cells in immune regulation.RESULTS: Recurrent miscarriage patients exhibit a notable enrichment of CD24+ decidual stromal cells, revealing a pronounced heterogeneity characterized by variations in stromal markers and transcriptional profile. The heightened enrichment of CD24+ decidual stromal cells may play a pivotal role in triggering decidual inflammation and dysfunction in decidualization. Furthermore, CD24+ decidual stromal cells showed diverse metabolic activities and impeded the induction of naïve CD4+ T cells into Tregs through the abundant secretion of 3- Hydroxyisovaleric acid . Finally, our investigations have revealed that intraperitoneal administration of 3-Hydroxyisovaleric acid in mouse models can elevate the risk of recurrent miscarriage.CONCLUSION: We have successfully identified a disease-associated subset of CD24+ decidual stromal cells that potentially contribute to the development of recurrent miscarriage through the impairment of decidual immune tolerance. Targeting these specific CD24+ decidual stromal cells might hold promising prospects for therapeutic interventions in the clinical management of recurrent miscarriage.PMID:38036240 | DOI:10.1016/j.fertnstert.2023.11.025

Diabetes Res Clin Pract. 2023 Nov 28:111031. doi: 10.1016/j.diabres.2023.111031. Online ahead of print.ABSTRACTAIMS: We aimed to determine if ketone production and excretion are increased even at mild fasting hyperglycemia in type 1 diabetes (T1D) and if these are modified by ketoacidosis risk factors, including sodium-glucose co-transporter inhibition (SGLTi) and female sex.METHODS: In secondary analysis of an 8-week single-arm open-label trial of empagliflozin (NCT01392560) we evaluated ketone concentrations during extended fasting and clamped euglycemia (4-6 mmol/L) and mild hyperglycemia (9-11 mmol/L) prior to and after treatment. Plasma and urine beta-hydroxybutyrate (BHB) concentrations and fractional excretion were analyzed by metabolomic analysis.RESULTS: Forty participants (50% female), aged 24±5 years, HbA1c 8.0±0.9% (64±0.08 mmol/mol) with T1D duration of 17.5±7 years, were studied. Increased BHB production even during mild hyperglycemia (median urine 6.3[3.5-13.6] vs. 3.5[2.2-7.0] µmol/mmol creatinine during euglycemia, p<0.001) was compensated by increased fractional excretion (0.9% [0.3-1.6] vs. 0.4% [0.2-0.9], p<0.001). SGLTi increased production and attenuated the increased BHB fractional excretion (decreased to 0.3% during mild hyperglycemia, p<0.001), resulting in higher plasma concentrations (increased to 0.21 [0.05-0.40] mmol/L, p<0.001), particularly in females (interaction p<0.001).CONCLUSIONS: Even mild hyperglycemia is associated with greater ketone production, compensated by urinary excretion, in T1D. However, SGLTi exaggerates production and partially reduces compensatory excretion, particularly in women.PMID:38036220 | DOI:10.1016/j.diabres.2023.111031

Cell Mol Gastroenterol Hepatol. 2023 Nov 28:S2352-345X(23)00213-8. doi: 10.1016/j.jcmgh.2023.11.014. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) is a common chronic liver disease worldwide. No effective pharmacological therapies for MASH have been developed; to develop such promising drugs, the underlying mechanisms regulating MASH need to be elucidated. Here, we aimed to determine the role of OTUD5 in MASH progression and identify a specific mechanism.METHODS: The expression levels of OTUD subfamily under palmitic acid/oleic acid (PAOA) stimulation were screened. OTUD5 expression was assessed in human liver tissues without steatosis, those with simple steatosis, and those with MASH. MASH models were developed in hepatocyte-specific Otud5-knockout mice that were fed high-fat high-cholesterol (HFHC) and high-fat high-cholesterol plus high-fructose/sucrose (HFF) diet for 16 weeks.RESULTS: The expression of OTUD5 was downregulated in fatty liver and was negatively related to the progression of MASH. Lipid accumulation and inflammation were exacerbated by Otud5 knockdown but attenuated by Otud5 overexpression under PAOA treatment. Hepatocyte-specific Otud5 deletion markedly exacerbated steatosis, inflammation, and fibrosis in the livers of two MASH mouse models. We identified voltage-dependent anion channel 2 (VDAC2) as an OTUD5-interacting partner; OTUD5 cleaved the K48-linked polyubiquitin chains from VDAC2, and it inhibited subsequent proteasomal degradation. The anabolic effects of OTUD5 knockdown on PAOA-induced lipid accumulation were effectively reversed by VDAC2 overexpression in primary hepatocytes. Metabolomic results revealed that VDAC2 is required for OTUD5-mediated protection against hepatic steatosis by maintaining mitochondrial function.CONCLUSIONS: OTUD5 may ameliorate MASH progression via VDAC2-maintained mitochondrial homeostasis. Targeting OTUD5 may be a viable MASH-treatment strategy.PMID:38036082 | DOI:10.1016/j.jcmgh.2023.11.014

J Ethnopharmacol. 2023 Nov 28:117511. doi: 10.1016/j.jep.2023.117511. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Corni Fructus, derived from the fruit of Cornus officinalis Sieb. et Zucc, is a widely utilized traditional Chinese medicine (TCM) with established efficacy in the treatment of diverse chronic kidney diseases. Crude Corni Fructus (CCF) and wine-processed Corni Fructus (WCF) are the main processed forms of Corni Fructus. Generally, TCM is often used after processing (paozhi). Despite the extensive use of processed TCM, the underlying mechanisms of processing for most TCMs have been unclear so far.AIM OF THE STUDY: In this study, an integrated strategy combined renal metabolomics with proteomics was established and investigated the potential processing mechanisms of CCF or WCF on chronic renal failure (CRF) models.MATERIALS AND METHODS: Firstly, the differences in biochemical parameters and pathological histology were compared to evaluate the effects of CCF and WCF on CRF model rats. Then, the tissue differential metabolites and proteins between CCF and WCF on CRF model rats were screened based on metabolomics and proteomics technology. Concurrently, a combined approach of metabolomics and proteomics was employed to investigate the underlying mechanisms associated with these marker metabolic products and proteins.RESULTS: Compared to the MG group, there were 27 distinct metabolites and 143 different proteins observed in the CCF-treatment group, while the WCF-treatment group exhibited 24 distinct metabolites and 379 different proteins. Further, the integration interactions analysis of the protein and lipid metabolite revealed that both WCF and CCF improved tryptophan degradation and LPS/IL-1-mediated inhibition of RXR function. WCF inhibited RXR function more than CCF via the modulation of LPS/IL-1 in the CRF model. Experimental results were validated by qRT-PCR and western blotting. Notably, the gene expression amount and protein levels of FMO3 and CYP2E1 among 8 genes influenced by WCF were higher compared to CCF.CONCLUSION: The results of this study provide a theoretical basis for further study of Corni Fructus with different processing techniques in CRF. The findings also offer guidance for investigating the mechanism of action of herbal medicines in diseases employing diverse processing techniques.PMID:38036016 | DOI:10.1016/j.jep.2023.117511

Cell Rep Med. 2023 Nov 16:101304. doi: 10.1016/j.xcrm.2023.101304. Online ahead of print.ABSTRACTBile acids are altered and associated with prognosis in patients with acute pancreatitis (AP). Here, we conduct targeted metabolomic analyses to detect bile acids changes in patients during the acute (n = 326) and the recovery (n = 133) phases of AP, as well as in healthy controls (n = 60). Chenodeoxycholic acid (CDCA) decreases in the acute phase, increases in the recovery phase, and is associated with pancreatic necrosis. CDCA and its derivative obeticholic acid exhibit a protective effect against acinar cell injury in vitro and pancreatic necrosis in murine models, and RNA sequencing reveals that the oxidative phosphorylation pathway is mainly involved. Moreover, we find that overexpression of farnesoid X receptor (FXR, CDCA receptor) inhibits pancreatic necrosis, and interfering expression of FXR exhibits an opposite phenotype in mice. Our results possibly suggest that targeting CDCA is a potential strategy for the treatment of acinar cell necrosis in AP, but further verification is needed.PMID:38035885 | DOI:10.1016/j.xcrm.2023.101304

Clin Nutr. 2023 Nov 14;43(1):111-123. doi: 10.1016/j.clnu.2023.11.002. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Amniotic fluid (AF) is the primary intrauterine environment for fetal growth throughout gestation. Selective fetal growth restriction (sFGR) is an adverse complication characterized by unequal growth in twins with nearly identical genetic makeup. However, the influence of AF-mediated intrauterine environment on the development and progression of sFGR remains unexplored.METHODS: High-throughput targeted metabolomics analysis (G350) was performed on AF samples collected from sFGR (n = 18) and MCDA twins with birth weight concordance (MCDA-C, n = 20) cases. Weighted correlation network analysis (WGCNA) was used to identify clinical features that may influence the metabolite composition in AF. Subsequently, partial least-squares discriminant analysis (PLS-DA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to compare the different types of sFGR and MCDA-C twins. Receiver operating characteristic (ROC) and multivariate ROC curves were utilized to explore potential AF markers in twins with sFGR.RESULTS: In our study, 182 metabolites were quantified in 76 AF samples. WGCNA indicated that the metabolite composition in late AF may not be influenced by gestational age. PLSDA demonstrated distinct variations between the metabolite profiles of AF in the sFGR and MCDA-C twins, with a significant emphasis on amino acids as the primary differential metabolite. The dissimilarities observed in sFGR twins were predominantly attributed to lipid metabolism-related metabolites. In particular, the KEGG enrichment metabolic pathway analysis revealed significant associations of both types of sFGR twins with central carbon metabolism in cancer. The multivariate ROC curves indicated that the combination of carnosine, sarcosine, l-alanine, beta-alanine, and alpha-n-phenylacetylglutamine significantly improved the AUC to 0.928. Notably, the ROC curves highlighted creatine (AUC:0.934) may be a potential biomarker for severe sFGR.CONCLUSION: The data presented in this study offer a comprehensive metabolic map of the AF in cases of sFGR, shedding light on potential biomarkers associated with fetal growth and development in MCDA twins.PMID:38035859 | DOI:10.1016/j.clnu.2023.11.002

RMD Open. 2023 Nov 30;9(4):e003560. doi: 10.1136/rmdopen-2023-003560.ABSTRACTOBJECTIVE: To investigate the relationship between metabolomic profiles, genome-wide polygenic risk scores (PRSs) and risk of rheumatoid arthritis (RA).METHODS: 143 nuclear magnetic resonance-based plasma metabolic biomarkers were measured among 93 800 participants in the UK Biobank. The Cox regression model was used to assess the associations between these metabolic biomarkers and RA risk, and genetic correlation and Mendelian randomisation analyses were performed to reveal their causal relationships. Subsequently, a metabolic risk score (MRS) comprised of the weighted sum of 17 clinically validated metabolic markers was constructed. A PRS was derived by assigning weights to genetic variants that exhibited significant associations with RA at a genome-wide level.RESULTS: A total of 620 incident RA cases were recorded during a median follow-up time of 8.2 years. We determined that 30 metabolic biomarkers were potentially associated with RA, while no further significant causal associations were found. Individuals in the top decile of MRS had an increased risk of RA (HR 3.52, 95% CI: 2.80 to 4.43) compared with those below the median of MRS. Further, significant gradient associations between MRS and RA risk were observed across genetic risk strata. Specifically, compared with the low genetic risk and favourable MRS group, the risk of incident RA in the high genetic risk and unfavourable MRS group has almost elevated by fivefold (HR 6.10, 95% CI: 4.06 to 9.14).CONCLUSION: Our findings suggested the metabolic profiles comprising multiple metabolic biomarkers contribute to capturing an elevated risk of RA, and the integration of genome-wide PRSs further improved risk stratification.PMID:38035758 | DOI:10.1136/rmdopen-2023-003560

BMJ Open. 2023 Nov 30;13(11):e074278. doi: 10.1136/bmjopen-2023-074278.ABSTRACTINTRODUCTION: Coronary heart disease is a major contributor to the global burden of disease. Appropriate nutrition is a cornerstone of the prevention and treatment of coronary heart disease; however, barriers including cost and access to recommended foods limits long-term adherence for many. We are conducting, in adults with coronary heart disease, a randomised controlled trial comparing usual care with two dietary interventions in which usual care is augmented by 12 weeks free delivered groceries.METHODS AND ANALYSIS: Three hundred adults recovering from an acute coronary event will be recruited from outpatient cardiovascular services in three regions of Aotearoa New Zealand. Participants will be randomly allocated to three arms: usual care (control group), usual care and the free delivery of foods high in dietary fibre or usual care and the free delivery of foods high in unsaturated fats. Interventions duration is 12 weeks, with a further 12 months follow-up. The primary outcome measures are change in low-density lipoprotein (LDL) cholesterol concentration following the intervention, and a cost-effectiveness analysis of healthcare access and social costs in the year after the intervention. A broad range of secondary outcome measures include other blood lipids, anthropometry, glycaemia, inflammatory markers, gut microbiome, dietary biomarkers, food acceptability, dietary change and the facilitators and barriers to dietary change. The trial will determine whether the free provision of groceries known to reduce cardiovascular risk within usual care will be clinically beneficial and justify the cost of doing so. Results may also provide an indication of the relative benefit of foods rich in dietary fibre or unsaturated fats in coronary heart disease management.ETHICS AND DISSEMINATION: This trial, The Healthy Heart Study, has Health and Disability Ethics Committee approval (20/NTB/121), underwent Māori consultation, and has locality authority to be conducted in Canterbury, Otago and Southland.TRIAL REGISTRATION NUMBER: ACTRN12620000689976, U1111-1250-1499.PMID:38035748 | DOI:10.1136/bmjopen-2023-074278

Phytochem Anal. 2023 Nov 30. doi: 10.1002/pca.3307. Online ahead of print.ABSTRACTINTRODUCTION: Pomegranate (Punica granatum L.) peels are rich in various bioactive compounds. Characterization of these compounds is crucial for the utilization of peel waste in industrial processing.OBJECTIVE: The study aimed (1) to establish and compare the metabolic profiles of the peel of seven pomegranate cultivars and (2) to identify bioactive compounds contributing to the larvicidal activity against the third instar larvae of Culex pipiens.MATERIALS AND METHODS: UPLC-ESI-MS/MS was utilized to analyze peel methanol extracts of different pomegranate cultivars. The larvicidal activity was determined by calculating the larval mortality among the third instar larvae of C. pipiens. Multivariate data analysis was conducted to identify the metabolites that exhibited a larvicidal effect.RESULTS: A total of 24 metabolites, including hydrolyzable tannins, flavonoids, and alkaloids, were tentatively identified in both negative and positive ionization modes. The extract of cultivar 'Black' exhibited the most potent larvicidal effect with LC50 values of 185.15, 156.84, and 138.12 ppm/mL after 24, 48, and 72 h of treatment, respectively. By applying chemometric techniques, the larvicidal activity could be directly correlated to the bioactive compounds punicalagin, quercetin-O-rhamnoside, quercetin-O-pentoside, and galloyl-HHDP-glucose.CONCLUSION: The present study implemented UPLC-ESI-MS/MS and chemometric techniques as potential tools for metabolomics analysis and differentiation between peels of different pomegranate cultivars. In addition, cultivar 'Black' extract could be a promising natural insecticide against mosquitoes since it is rich in bioactive compounds with larvicidal activity.PMID:38035714 | DOI:10.1002/pca.3307

Funct Plant Biol. 2023 Dec 1. doi: 10.1071/FP23206. Online ahead of print.ABSTRACTViscum schimperi is an evergreen hemiparasitic plant that can grow on stems and branches of several tree species. It penetrates the host tissues and forms a vascular bridge (haustorium) to withdraw the nutritive resources. Its relationships with hosts remain unknown. This study aimed to investigate the physiological and biochemical attributes of the host-hemiparasite association Acacia gerrardii-Viscum schimperi. The hemiparasite exhibited 2.4- and 3.0-fold lower photosynthetic activity and water use efficiency, and 1.2- and 4.1-fold higher transpiration rate and stomatal conductance. Equally, it displayed 4.9- and 2.6-fold greater water potential and osmotic potential, and in least 3.0times more accumulated 39K, 85Rb and 51V, compared to the host. Nevertheless, it had no detrimental effect on photosynthetic activity, water status and multi-element accumulations in the host. Based on metabolome profiling, V. schimperi could use xanthurenic acid and propylparaben to acquire potassium from the host, and N-1-naphthylacetamide and N-Boc-hydroxylamine to weaken or kill the distal part of the infected branch and to receive the total xylem contents. In contrast, A. gerrardii could used N-acetylserotonin, arecoline, acetophenone and 6-methoxymellein to defend against V. schimperi infection.PMID:38035483 | DOI:10.1071/FP23206

Front Nutr. 2023 Nov 15;10:1282741. doi: 10.3389/fnut.2023.1282741. eCollection 2023.ABSTRACTBACKGROUND: In a 12-week randomised controlled trial, personalised nutrition delivered using a metabotype framework improved dietary intake, metabolic health parameters and the metabolomic profile compared to population-level dietary advice. The objective of the present work was to investigate the patterns of dietary advice delivered during the intervention and the alterations in dietary intake and metabolic and metabolomic profiles to obtain further insights into the effectiveness of the metabotype framework.METHODS: Forty-nine individuals were randomised into the intervention group and subsequently classified into metabotypes using four biomarkers (triacylglycerol, HDL-C, total cholesterol, glucose). These individuals received personalised dietary advice from decision tree algorithms containing metabotypes and individual characteristics. In a secondary analysis of the data, patterns of dietary advice were identified by clustering individuals according to the dietary messages received and clusters were compared for changes in dietary intake and metabolic health parameters. Correlations between changes in blood clinical chemistry and changes in metabolite levels were investigated.RESULTS: Two clusters of individuals with distinct patterns of dietary advice were identified. Cluster 1 had the highest percentage of messages delivered to increase the intake of beans and pulses and milk and dairy products. Cluster 2 had the highest percentage of messages delivered to limit the intake of foods high in added sugar, high-fat foods and alcohol. Following the intervention, both patterns improved dietary quality assessed by the Alternate Mediterranean Diet Score and the Alternative Healthy Eating Index, nutrient intakes, blood pressure, triacylglycerol and LDL-C (p ≤ 0.05). Several correlations were identified between changes in total cholesterol, LDL-C, triacylglycerol, insulin and HOMA-IR and changes in metabolites levels, including mostly lipids (sphingomyelins, lysophosphatidylcholines, glycerophosphocholines and fatty acid carnitines).CONCLUSION: The findings indicate that the metabotype framework effectively personalises and delivers dietary advice to improve dietary quality and metabolic health.CLINICAL TRIAL REGISTRATION: isrctn.com, identifier ISRCTN15305840.PMID:38035361 | PMC:PMC10684740 | DOI:10.3389/fnut.2023.1282741

Front Nutr. 2023 Nov 15;10:1251936. doi: 10.3389/fnut.2023.1251936. eCollection 2023.ABSTRACTINTRODUCTION: Undernutrition spontaneously occurs in ewes during late gestation and the pituitary is an important hinge in the neurohumoral regulatory system. However, little is known about the effect of undernutrition on pituitary metabolism.METHODS: Here, 10 multiparous ewes were restricted to a 30% feeding level during late gestation to establish an undernutrition model while another 10 ewes were fed normally as controls. All the ewes were sacrificed, and pituitary samples were collected to perform transcriptome, metabolome, and quantitative real-time PCR analysis and investigate the metabolic changes.RESULTS: PCA and PLS-DA of total genes showed that undernutrition changed the total transcriptome profile of the pituitary gland, and 581 differentially expressed genes (DEGs) were identified between the two groups. Clusters of orthologous groups for eukaryotic complete genomes demonstrated that substance transport and metabolism, including lipids, carbohydrates, and amino acids, energy production and conversion, ribosomal structure and biogenesis, and the cytoskeleton were enriched by DEGs. Kyoto encyclopedia of genes and genomes pathway enrichment analysis displayed that the phagosome, intestinal immune network, and oxidative phosphorylation were enriched by DEGs. Further analysis found that undernutrition enhanced the lipid degradation and amino acid transport, repressing lipid synthesis and transport and amino acid degradation of the pituitary gland. Moreover, the general metabolic profiles and metabolic pathways were affected by undernutrition, repressing the 60S, 40S, 28S, and 39S subunits of the ribosomal structure for translation and myosin and actin synthesis for cytoskeleton. Undernutrition was found also to be implicated in the suppression of oxidative phosphorylation for energy production and conversion into a downregulation of genes related to T cell function and the immune response and an upregulation of genes involved in inflammatory reactions enriching phagosomes.DISCUSSION: This study comprehensively analyses the effect of undernutrition on the pituitary gland in a pregnant sheep model, which provides a foundation for further research into the mechanisms of undernutrition-caused hormone secretion and metabolic disorders.PMID:38035344 | PMC:PMC10684748 | DOI:10.3389/fnut.2023.1251936

Front Immunol. 2023 Nov 15;14:1279846. doi: 10.3389/fimmu.2023.1279846. eCollection 2023.ABSTRACTPsoriasis is a systemic inflammatory disease that frequently coexists with various other conditions, such as essential hypertension, diabetes, metabolic syndrome, and inflammatory bowel disease. The association between these diseases may be attributed to shared inflammatory pathways and abnormal immunomodulatory mechanisms. Furthermore, metabolites also play a regulatory role in the function of different immune cells involved in psoriasis pathogenesis, particularly T lymphocytes. In this review, we have summarized the current research progress on T cell metabolism in psoriasis, encompassing the regulation of metabolites in glucose metabolism, lipid metabolism, amino acid metabolism, and other pathways within T cells affected by psoriasis. We will also explore the interaction and mechanism between psoriatic metabolites and immune cells. Moreover, we further discussed the research progress of metabolomics in psoriasis to gain a deeper understanding of its pathogenesis and identify potential new therapeutic targets through identification of metabolic biomarkers associated with this condition.PMID:38035065 | PMC:PMC10684739 | DOI:10.3389/fimmu.2023.1279846

Front Pharmacol. 2023 Nov 15;14:1255931. doi: 10.3389/fphar.2023.1255931. eCollection 2023.ABSTRACTBile acids are the main component of animal bile and are directly involved in the metabolic process of lipids in vivo. Taurochenodeoxycholic acid (TCDCA) is the primary biologically active substance in bile acids and has biological functions such as antioxidant, antipyretic, anti-inflammatory, and analgesic activities and improves immunity. In the present study, we assessed the impact of TCDCA on hyperlipidemia development in mouse models. Mice were fed a high-fat diet (HFD) to induce hyperlipidemia and orally administered different doses of TCDCA orally for 30 days. Then, indicators such as triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in mice were detected. Using HE and ORO staining techniques, the morphology of the mice's liver tissue was detected. Based on metabolomic and lipidomic analyses, we determined the mechanism of TCDCA in treating hyperlipidemia. The results showed that TCDCA had a significant ameliorating effect on dietary hyperlipidemia. In addition, it exerted therapeutic effects through glycerophospholipid metabolism.PMID:38034994 | PMC:PMC10684951 | DOI:10.3389/fphar.2023.1255931

Front Pharmacol. 2023 Nov 16;14:1236820. doi: 10.3389/fphar.2023.1236820. eCollection 2023.ABSTRACTBackground: Acute kidney injury (AKI) induced by cisplatin remains a major impediment to the clinical application of cisplatin, necessitating urgent exploration for promising solutions. Huangqi-Danshen decoction (HDD), a Chinese herbal preparation, has been shown by our group to have a reno-protective effect in adenine-induced chronic kidney disease mice and diabetic db/db mice. However, the effect of HDD on cisplatin-induced AKI and its underlying mechanisms are unknown. Methods: The AKI model was established by intraperitoneal injection of cisplatin (20 mg/kg) in C57BL/6 mice. The mice in the treatment group were administrated with HDD (6.8 g/kg/d) for 5 consecutive days before cisplatin challenge. After 72 h cisplatin injection, blood and kidney tissue were subsequently collected for biochemical detection, histopathological evaluation, Western blot analysis, immunohistochemical staining, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to detect changes in renal metabolites. Results: The results showed that HDD significantly reduced serum creatinine and blood urea nitrogen levels and alleviated renal histopathological injury in cisplatin-induced AKI mice. And HDD treatment demonstrated a significant inhibition in apoptosis, inflammation, and oxidative stress in AKI mice. Moreover, non-target metabolomics revealed that HDD significantly restored 165 altered metabolites in AKI mice. Subsequent enrichment analysis and pathway analysis of these metabolites indicated that nicotinate and nicotinamide metabolism was the primary pathway affected by HDD intervention. Further investigation showed that HDD could upregulate nicotinamide adenine dinucleotide (NAD+) biosynthesis-related enzymes quinolinate phosphoribosyltransferase, nicotinamide mononucleotide adenylyltransferase 1, and nicotinamide phosphoribosyltransferase to replenish NAD+ content in the kidney of AKI mice. Conclusion: In summary, HDD exerted a protective effect against cisplatin-induced AKI and suppressed apoptosis, inflammation, and oxidative stress in the kidney of AKI mice, which may be attributed to the modulation of NAD+ biosynthesis.PMID:38034992 | PMC:PMC10687478 | DOI:10.3389/fphar.2023.1236820