PubMed

J Hypertens. 2023 Apr 6. doi: 10.1097/HJH.0000000000003423. Online ahead of print.ABSTRACTBACKGROUND: Hypertension is the largest risk factor affecting global mortality. Despite available medications, uncontrolled hypertension is on the rise, whereby there is an urgent need to develop novel and sustainable therapeutics. Because gut microbiota is now recognized as an important entity in blood pressure regulation, one such new avenue is to target the gut-liver axis wherein metabolites are transacted via host-microbiota interactions. Knowledge on which metabolites within the gut-liver axis regulate blood pressure is largely unknown.METHOD: To address this, we analyzed bile acid profiles of both human and hypertensive rat models and report that conjugated bile acids are inversely correlated with blood pressure in humans and rats.RESULTS: Notably intervening with taurine rescued bile acid conjugation and reduced blood pressure in hypertensive rats. Subsequently, untargeted metabolomics uncovered lower energy metabolism following conjugation of bile acids as a mechanism alleviating high blood pressure.CONCLUSION: Together this work reveals conjugated bile acids as nutritionally re-programmable anti-hypertensive metabolites.GRAPHICAL ABSTRACT: http://links.lww.com/HJH/C165.PMID:37071431 | DOI:10.1097/HJH.0000000000003423

Dig Dis Sci. 2023 Apr 18. doi: 10.1007/s10620-023-07931-3. Online ahead of print.ABSTRACTBACKGROUND: Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis due to its therapeutic resistance. Inactivation of vitamin D/vitamin D receptor (VDR) signaling may contribute to the malignant phenotype of PDA and altered expression of oncoprotein mucin 1 (MUC1) may be involved in drug resistance of cancer cells.AIM: To determine whether vitamin D/VDR signaling regulates the expression and function of MUC1 and its effect on acquired gemcitabine resistance of pancreatic cancer cells.METHODS: Molecular analyses and animal models were used to determine the impact of vitamin D/VDR signaling on MUC1 expression and response to gemcitabine treatment.RESULTS: RPPA analysis indicated that MUC1 protein expression was significantly reduced in human PDA cells after treatment with vitamin D3 or its analog calcipotriol. VDR regulated MUC1 expression in both gain- and loss-of-function assays. Vitamin D3 or calcipotriol significantly induced VDR and inhibited MUC1 expression in acquired gemcitabine-resistant PDA cells and sensitized the resistant cells to gemcitabine treatment, while siRNA inhibition of MUC1 was associated with paricalcitol-associated sensitization of PDA cells to gemcitabine treatment in vitro. Administration of paricalcitol significantly enhanced the therapeutic efficacy of gemcitabine in xenograft and orthotopic mouse models and increased the intratumoral concentration of dFdCTP, the active metabolite of gemcitabine.CONCLUSION: These findings demonstrate a previously unidentified vitamin D/VDR-MUC1 signaling axis involved in the regulation of gemcitabine resistance in PDA and suggests that combinational therapies that include targeted activation of vitamin D/VDR signaling may improve the outcomes of patients with PDA.PMID:37071246 | DOI:10.1007/s10620-023-07931-3

Eur Radiol. 2023 Apr 18. doi: 10.1007/s00330-023-09638-5. Online ahead of print.NO ABSTRACTPMID:37071172 | DOI:10.1007/s00330-023-09638-5

Appl Microbiol Biotechnol. 2023 Apr 18. doi: 10.1007/s00253-023-12524-1. Online ahead of print.ABSTRACTPrevious studies regarding the gastrointestinal biogeography of microbiomes generally focused on longitudinal comparisons, whereas few studies have compared luminal and mucosal microbiomes. Investigations of the snake gut microbiome have attracted interest because of the unique digestive physiology and hibernation behavior, but adequate sampling methods must be developed. Here, we used an omics approach combining 16S rRNA gene sequencing with untargeted metabolomics to profile the luminal and mucosal gut microbiomes and metabolomes in oriental rat snakes, with the goal of revealing the heterogeneity and co-occurrence at these sites. The α-diversity of the gut microbiome was significantly higher at mucosal sites than at luminal sites. Microbial composition also differed according to sampling site, with significant differences in the abundances of dominant phyla and genera, as well as β-diversity clustering and distribution. Metabolome profiling revealed differences that were mainly related to cholinergic substances and nucleic acids. Analysis of variations in Kyoto Encyclopedia of Genes and Genomes functions of microbes and metabolites showed that the mucosal microbiome was more frequently involved in genetic information processing and cellular processes, whereas the luminal microbiome generally participated in metabolic regulation. Notably, we found a greater abundance of the opportunistic pathogen genus Escherichia-Shigella at luminal sites and higher levels of the lipid-regulator metabolite fenfluramine at mucosal sites. Despite the extensive differences between the two sampling sites, the results revealed similarities in terms of amplicon sequence variant composition and dominant core microbes. This pilot exploration of luminal and mucosal microbiomes and metabolites provides key insights to guide future research. KEY POINTS: • Snake luminal and mucosal microbiota was distinct in composition and function. • Metabolome profiling revealed differences related to different metabolites. • The pathogenic microbes are more likely to colonize the gut lumina.PMID:37071138 | DOI:10.1007/s00253-023-12524-1

Radiology. 2023 Apr 18:222010. doi: 10.1148/radiol.222010. Online ahead of print.ABSTRACTBackground Prostate-specific membrane antigen (PSMA) PET has high specificity in localizing primary tumors and metastases in patients with prostate cancer, but the individual overall survival probability is still difficult to estimate. Purpose To develop a prognostic risk score using PSMA PET-derived organ-specific total tumor volumes for predicting overall survival in patients with prostate cancer. Materials and Methods Men with prostate cancer who underwent PSMA PET/CT from January 2014 to December 2018 were evaluated retrospectively. All patients from center A were split into training (80%) and internal validation (20%) cohorts. Randomly selected patients from center B were used for external validation. Organ-specific tumor volumes were automatically quantified from PSMA PET scans by a neural network. A prognostic score was selected using multivariable Cox regression guided by the Akaike information criterion (AIC). The final prognostic risk score fitted on the training set was applied to both validation cohorts. Results A total of 1348 men (mean age, 70 years ± 8 [SD]) were included, with 918 patients in the training cohort, 230 in the internal validation cohort, and 200 in the external validation cohort. The median follow-up time was 55.7 months (IQR, 46.7-65.1 months; >4 years; 429 deaths occurred). A body weight-adjusted prognostic risk score integrating total, bone, and visceral tumor volumes obtained high C index values in the internal (0.82) and external (0.74) validation cohorts, as well as in patients with castration-resistant (0.75) and hormone-sensitive (0.68) disease. The fit of the statistical model for the prognostic score was improved compared with a model containing total tumor volume only (AIC, 3324 vs 3351; likelihood ratio test, P < .001). Calibration plots ascertained good model fit. Conclusion The newly developed risk score that included prostate-specific membrane antigen PET-derived organ-specific tumor volumes had good model fit for predicting overall survival in both internal and external validation cohorts. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Civelek in this issue.PMID:37070991 | DOI:10.1148/radiol.222010

Scand J Gastroenterol. 2023 Apr 18:1-10. doi: 10.1080/00365521.2023.2200518. Online ahead of print.ABSTRACTBACKGROUND: The indolent course of treatment-naive patients with inflammatory bowel disease (IBD) is confirmed predictable based on clinical characteristics. Current evidences supported that bile acids (BAs) alteration might be promising biomarkers in the field of IBD. We aimed to analyze the alterations of BAs as the disease progresses and explore their predictive value for indolent course of IBD.METHODS: The indolent course of IBD was defined as a disease course without need for strict interventions throughout the entire follow-up. A targeted metabolomics method was used to detect the concentration of 27 BAs from serum sample in treatment-naive patients with IBD (Crohn's disease [CD], n = 27; ulcerative colitis [UC], n = 50). Patients with CD and UC were individually divided into two groups for further study according to the median time of indolent course. The overall BAs profile and the clinical value of BAs in predicting indolent course of IBD were identified between different groups.RESULTS: For CD, the levels of deoxycholic acid, glycodeoxycholic acid, taurodeoxycholic acid, glycolithocholic acid-3-sulfate disodium salt and iso-lithocholic acid were significantly increased in patients with indolent course > 18 M (p < 0.05). These five BAs owned 83.5% accuracy for predicting indolent course over 18 months in CD. For UC, the concentration of deoxycholic acid and glycodeoxycholic acid were significantly higher, while dehydrocholic acid were lower in patients with indolent course > 48 M (p < 0.05). These three BAs predicted indolent course over 48 months of 69.8% accuracy in UC.CONCLUSION: The specific BAs alterations might be potential biomarkers in predicting disease course of IBD patients.PMID:37070769 | DOI:10.1080/00365521.2023.2200518

Am J Physiol Lung Cell Mol Physiol. 2023 Apr 18. doi: 10.1152/ajplung.00003.2023. Online ahead of print.ABSTRACTBACKGROUND: Right ventricular (RV) adaptation is the principal determinant of outcomes in pulmonary arterial hypertension (PAH), however RV function is challenging to assess. RV responses to hemodynamic stressors are particularly difficult to interrogate without invasive testing. This study sought to identify metabolomic markers of in vivo right ventricular function and exercise performance in PAH.METHODS: Consecutive subjects with PAH (n=23) underwent rest and exercise right heart catheterization with multi-beat pressure volume loop analysis. Pulmonary arterial blood was collected at rest and during exercise. Mass spectrometry-based targeted metabolomics were performed, and metabolic associations with hemodynamics and comprehensive measures of RV function were determined using sparse partial least squares regression. Metabolite profiles were compared to pro-BNP measurements for accuracy in modeling ventriculo-arterial parameters.RESULTS: Thirteen metabolites changed in abundance with exercise, including metabolites reflecting increased arginine bioavailability, precursors of catecholamine and nucleotide synthesis, and branched chain amino acids. Higher resting arginine bioavailability predicted more favorable exercise hemodynamics and pressure-flow relationships. Subjects with more severe PAH augmented arginine bioavailability with exercise to a greater extent than subjects with less severe PAH. We identified relationships between kynurenine pathway metabolism and impaired ventriculo-arterial coupling, worse RV diastolic function, lower RV contractility, diminished RV contractility with exercise, and RV dilation with exercise. Metabolite profiles outperformed pro-BNP in modeling RV contractility, diastolic function, and exercise performance.CONCLUSIONS: Specific metabolite profiles correspond to RV functional measurements only obtainable via invasive pressure-volume loop analysis and predict RV responses to exercise. Metabolic profiling may inform discovery of RV functional biomarkers.PMID:37070742 | DOI:10.1152/ajplung.00003.2023

AIDS. 2023 Apr 12. doi: 10.1097/QAD.0000000000003574. Online ahead of print.ABSTRACTOBJECTIVE: To determine immune-metabolic dysregulation in children born to women living with HIV.METHODS: Longitudinal immune-metabolomic analyses of plasma of 32 pregnant women living with HIV (WLHIV) and 12 uninfected women and their children up to 1.5 years of age were performed.RESULTS: Using liquid chromatography-mass spectrometry and a multiplex bead assay, 280 metabolites (57 amino acids, 116 positive lipids, 107 signaling lipids) and 24 immune mediators (e.g. cytokines) were quantified. cART exposure was categorized as cART initiation preconception (long), cART initiation post-conception up to 4 weeks before birth (medium) and cART initiation within 3 weeks of birth (short). Plasma metabolite profiles differed between HEU-children with long cART exposure compared to HIV-unexposed-children (HUU). Specifically, higher levels of methionine-sulfone, which is associated with oxidative stress, were detected in HEU-children with long cART exposure compared to HUU-children. High infant methionine-sulfone levels were reflected by high prenatal plasma levels in the mother. Increased methionine-sulfone levels in the children were associated with decreased growth, including both weight and length.CONCLUSION: These findings based on longitudinal data demonstrate that dysregulation of metabolite networks associated with oxidative stress in children born to WLHIV is associated with restricted infant growth.PMID:37070556 | DOI:10.1097/QAD.0000000000003574

J Sep Sci. 2023 Apr 18:e2300124. doi: 10.1002/jssc.202300124. Online ahead of print.ABSTRACTKidney-yang-deficiency-syndrome is a neuroendocrine disease caused by the dysfunction of adrenal-pituitary-target gland axis. Gushudan is a traditional Chinese medicine prescription with functions of tonifying kidney and strengthening bone, and its bone-strengthening effect has been confirmed by previous anti-osteoporosis research. However, its kidney-tonifying mechanism has not been clear so far. In this study, the renal metabolomics and lipidomics based on gas chromatography-mass and ultra-high performance liquid chromatography-high resolution mass were integrated to find the metabolic disorders in kidney-yang-deficiency-syndrome rats. Protein precipitation and liquid-liquid extraction were used to extract metabolome and lipidome from kidney. Gushudan regulated abnormal levels of amino acids, lipids, purines and carbohydrates, such as L-arginine, hypoxanine, stearic acid and phosphatidylethanolamine (P-18:1/20:4), which had effects on many metabolic pathways, such as glycerophospholipid metabolism, sphingolipid metabolism, glycine, serine and threonine metabolism and purine metabolism, etc. By integrating metabolomics and lipidomics, this study comprehensively revealed the abnormal metabolic activities of amino acids, lipids and nucleotides in kidney-yang-deficiency-syndrome, and the metabolic regulation mechanism of Gushudan in preventing kidney-yang-deficiency-syndrome, as well as the improvement of Gushudan in maintaining renal cell structure, mitochondrial function and energy supply, which also provided some new evidence and connotation for "kidney-bone" axis. This article is protected by copyright. All rights reserved.PMID:37070550 | DOI:10.1002/jssc.202300124

Circulation. 2023 Apr 18. doi: 10.1161/CIRCULATIONAHA.122.062021. Online ahead of print.ABSTRACTBACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a paramount treatment for patients with heart failure (HF), irrespective of underlying reduced or preserved ejection fraction. However, a definite cardiac mechanism of action remains elusive. Derangements in myocardial energy metabolism are detectable in all HF phenotypes, and it was proposed that SGLT2i may improve energy production. The authors aimed to investigate whether treatment with empagliflozin leads to changes in myocardial energetics, serum metabolomics, and cardiorespiratory fitness.METHODS: EMPA-VISION is a prospective, randomized, double-blind, placebo-controlled, mechanistic trial that enrolled 72 symptomatic patients with chronic HF with reduced ejection fraction (HFrEF; n=36; left ventricular ejection fraction ≤40%; New York Heart Association class ≥II; NT-proBNP [N-terminal pro-B-type natriuretic peptide] ≥125 pg/mL) and HF with preserved ejection fraction (HFpEF; n=36; left ventricular ejection fraction ≥50%; New York Heart Association class ≥II; NT-proBNP ≥125 pg/mL). Patients were stratified into respective cohorts (HFrEF versus HFpEF) and randomly assigned to empagliflozin (10 mg; n=35: 17 HFrEF and 18 HFpEF) or placebo (n=37: 19 HFrEF and 18 HFpEF) once daily for 12 weeks. The primary end point was a change in the cardiac phosphocreatine:ATP ratio (PCr:ATP) from baseline to week 12, determined by phosphorus magnetic resonance spectroscopy at rest and during peak dobutamine stress (65% of age-maximum heart rate). Mass spectrometry on a targeted set of 19 metabolites was performed at baseline and after treatment. Other exploratory end points were investigated.RESULTS: Empagliflozin treatment did not change cardiac energetics (ie, PCr:ATP) at rest in HFrEF (adjusted mean treatment difference [empagliflozin - placebo], -0.25 [95% CI, -0.58 to 0.09]; P=0.14) or HFpEF (adjusted mean treatment difference, -0.16 [95% CI, -0.60 to 0.29]; P=0.47]. Likewise, there were no changes in PCr:ATP during dobutamine stress in HFrEF (adjusted mean treatment difference, -0.13 [95% CI, -0.35 to 0.09]; P=0.23) or HFpEF (adjusted mean treatment difference, -0.22 [95% CI, -0.66 to 0.23]; P=0.32). No changes in serum metabolomics or levels of circulating ketone bodies were observed.CONCLUSIONS: In patients with either HFrEF or HFpEF, treatment with 10 mg of empagliflozin once daily for 12 weeks did not improve cardiac energetics or change circulating serum metabolites associated with energy metabolism when compared with placebo. Based on our results, it is unlikely that enhancing cardiac energy metabolism mediates the beneficial effects of SGLT2i in HF.REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifier: NCT03332212.PMID:37070436 | DOI:10.1161/CIRCULATIONAHA.122.062021

Mol Omics. 2023 Apr 18. doi: 10.1039/d3mo90012f. Online ahead of print.ABSTRACTCorrection for 'Metabolomics study reveals the alteration of fatty acid oxidation in the hearts of diabetic mice by empagliflozin' by Yingwei Zhang et al., Mol. Omics, 2022, 18, 643-651, https://doi.org/10.1039/D2MO00036A.PMID:37070329 | DOI:10.1039/d3mo90012f

Biomed Chromatogr. 2023 Apr 17:e5654. doi: 10.1002/bmc.5654. Online ahead of print.ABSTRACTThe efficacy of Rehmannia Radix changes after processing. However, the precise effect of processing on the property of Rehmannia Radix is an intricate topic, as this effect cannot be explained by traditional methods. The purpose of this study was to investigate how processing methods influence the property of Rehmannia Radix, as well as the changes in body function after administering dried Rehmannia Radix (RR) and processed Rehmannia Radix (PR) using a metabolomics approach. In addition, principal component analysis and orthogonal partial least squares discriminant analysis models were generated using SIMCA-P 14.0, to evaluate the property of RR and PR. Potential biomarkers were identified, and associated metabolic networks were established to clarify differences in the property and efficacies of RR and PR. The results showed that RR and PR have cold and hot property, respectively. RR can exert a hypolipidaemic effect by regulating nicotinate and nicotinamide metabolism. PR exerts a tonic effect and regulates the body's reproductive function through the regulation of alanine, aspartate, and glutamate metabolism, arachidonic acid, pentose, and glucuronate metabolism, respectively. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics is a promising approach to determine the cold/hot property of traditional Chinese medicine formulations.PMID:37070162 | DOI:10.1002/bmc.5654

J Transl Med. 2023 Apr 17;21(1):261. doi: 10.1186/s12967-023-04114-6.ABSTRACTBACKGROUND: Acute gouty arthritis is inflammatory joint arthritis. Gouty arthritis (GA) involves multiple pathological processes. Deposition of joints by monosodium urate (MSU) crystals has been shown to play a critical role in the injury process. Due to the different effects of MSU stimulation on the joints, the exact changes in the synovial fluid are unknown. We want to explore the changes in proteins and metabolites in the joints of gouty arthritis. Regulating various functional substances in the joint can reduce inflammation and pain symptoms.METHODS: 10 patients with gouty knee arthritis and 10 normal controls were selected from clinical, surgical cases. The biological function of the metabolome was assessed by co-expression network analysis. A molecular network based on metabolomic and proteomic data was constructed to study critical molecules. The fundamental molecular changes in the relevant pathways were then verified by western blot.RESULTS: Proteomic analysis showed that the expressions of proteases Cathepsin B, Cathepsin D, Cathepsin G, and Cathepsin S in synovial fluid patients with gouty arthritis were significantly increased. Enrichment analysis showed a positive correlation between lysosomal and clinical inflammatory cell shape changes. Untargeted metabolomic analysis revealed that lipids and lipoids accumulate, inhibit autophagic flux, and modulate inflammation and immunity in gouty arthritis patients. It was determined that the accumulation of lipid substances such as phospholipase A2 led to the imbalanced state of the autophagy-lysosome complex, and the differentially expressed metabolites of Stearoylcarnitine, Tetradecanoylcarnitine, Palmitoylcarnitine were identified (|log2 fold change|> 1.5, adjusted P value < 0.05 and variable importance in prediction (VIP) > 1.5). The autophagy-lysosomal pathway was found to be associated with gouty knee arthritis. Essential molecular alterations of multi-omics networks in gouty knee arthritis patients compared with normal controls involve acute inflammatory response, exosomes, immune responses, lysosomes, linoleic acid metabolism, and synthesis.CONCLUSIONS: Comprehensive analysis of proteomic and untargeted metabolomics revealed protein and characteristic metabolite alterations in gouty arthritis, it mainly involves lipids and lipid like molecules, phospholipase A2 and autophagic lysosomes. This study describes the pathological characteristics, pathways, potential predictors and treatment goals of gouty knee arthritis.PMID:37069596 | DOI:10.1186/s12967-023-04114-6

BMC Plant Biol. 2023 Apr 18;23(1):200. doi: 10.1186/s12870-023-04206-x.ABSTRACTCasuarina equisetifolia is drought tolerant, salt tolerant, and able to grow in barren environments. It is often used to reduce wind damage, to prevent sand erosion, and to help establish plant communities in tropical and subtropical coastal zones. To determine the basis for its drought tolerance, we conducted transcriptomic and metabolic analyses of young branchlets under a non-drought treatment (D_0h) and 2-, 12-, and 24-h-long drought treatments (D_2h, D_12h, and D_24h). A total of 5033 and 8159 differentially expressed genes (DEGs) were identified in D_2h/D_0h and D_24h/D_0h. These DEGs were involved in plant hormone signal transduction, jasmonic acid (JA) biosynthesis, flavonoid biosynthesis, and phenylpropanoid biosynthesis. A total of 148 and 168 differentially accumulated metabolites (DAMs) were identified in D_12h/D_0h and D_24h/D_0h, which were mainly amino acids, phenolic acids, and flavonoids. In conclusion, C. equisetifolia responds to drought by regulating plant hormone signal transduction and the biosynthesis of JA, flavonoid, and phenylpropanoid. These results increase the understanding of drought tolerance in C. equisetifolia at both transcriptional and metabolic levels and provide new insights into coastal vegetation reconstruction and management.PMID:37069496 | DOI:10.1186/s12870-023-04206-x

Phytomedicine. 2023 Apr 17;115:154831. doi: 10.1016/j.phymed.2023.154831. Online ahead of print.ABSTRACTBACKGROUND: The intestinal microbiota plays a key role in understanding the mechanism of traditional Chinese medicine (TCM), as it could transform the herbal ingredients to metabolites with higher bioavailability and activity comparing to their prototypes. Nevertheless, the study of the activity and mechanism of microbiota metabolites reported by the published literature still lacks viable ways. Hence a new strategy is proposed to solve this issue.PURPOSE: A new strategy to study the activity and mechanism of intestinal microbiota metabolites of TCM herbal ingredients by integrating spectrum-effect relationship, network pharmacology, metabolomics analysis and molecular docking together was developed and proposed.METHOD: Platycodin D (PD) and its microbiota metabolites with antitussive and expectorant effect were selected as an example for demonstration. First, the PD and its microbiota metabolites with important contribution to antitussive and/or expectorant effects were screened through spectrum-effect relationship analysis. Second, network pharmacology and metabolomics analysis were integrated to identify the upstream key targets of PD and its microbiota metabolites as well as the downstream endogenous metabolites. Finally, the active forms of PD were further confirmed by molecular docking.RESULTS: Results showed that PD was an active ingredient with antitussive and/or expectorant effects, and the active forms of PD were its microbiota metabolites: 3-O-β-d-glucopyranosyl platycodigenin, 3-O-β-d-glucopyranosyl isoplatycodigenin, 7‑hydroxyl-3-O-β-d-glucopyranosyl platycodigenin, platycodigenin and isoplatycodigenin. In addition, those microbiota metabolites could bind the key targets of PAH, PLA2G2A, ALOX5, CYP2C9 and CYP2D6 to exert antitussive effects by regulating four metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, glycerophospholipid metabolism and linoleic acid metabolism. Similarly, they could also bind the key targets of PLA2G1B, ALOX5, CYP2C9 and CYP2D6 to exert expectorant effect by regulating two pathways of glycerophospholipid metabolism and linoleic acid metabolism.CONCLUSION: The proposed strategy paves a new way for the illustration of the activities and mechanisms of TCM herbal ingredients, which is very important to reconcile the conundrums of TCM herbal ingredients with low oral bioavailability but high activity.PMID:37094423 | DOI:10.1016/j.phymed.2023.154831

J Alzheimers Dis. 2023 Apr 17. doi: 10.3233/JAD-220795. Online ahead of print.ABSTRACTBACKGROUND: Circulating phospholipid species have been shown to predict Alzheimer's disease (AD) prognosis but the link between phospholipid disturbances and subcortical small vessel cerebrovascular disease (CeVD) common in AD patients is not known.OBJECTIVE: This study used quantitative lipidomics to measure serum diacyl, alkenyl (ether), alkyl, and lyso phospholipid species in individuals with extensive CeVD (n = 29), AD with minimal CeVD (n = 16), and AD with extensive CeVD (n = 14), and compared them to age-matched controls (n = 27). Memory was assessed using the California Verbal Learning Test. 3.0T MRI was used to assess hippocampal volume, atrophy, and white matter hyperintensity (WMH) volumes as manifestations of CeVD.RESULTS: AD was associated with significantly higher concentrations of choline plasmalogen 18:0_18:1 and alkyl-phosphocholine 18:1. CeVD was associated with significantly lower lysophospholipids containing 16:0. Phospholipids containing arachidonic acid (AA) were associated with poorer memory in controls, whereas docosahexaenoic acid (DHA)-containing phospholipids were associated with better memory in individuals with AD+CeVD. In controls, DHA-containing phospholipids were associated with more atrophy and phospholipids containing linoleic acid and AA were associated with less atrophy. Lysophospholipids containing 16:0, 18:0, and 18:1 were correlated with less atrophy in controls, and of these, alkyl-phosphocholine 18:1 was correlated with smaller WMH volumes. Conversely, 16:0_18:1 choline plasmalogen was correlated with greater WMH volumes in controls.CONCLUSION: This study demonstrates discernable differences in circulating phospholipids in individuals with AD and CeVD, as well as new associations between phospholipid species with memory and brain structure that were specific to contexts of commonly comorbid vascular and neurodegenerative pathologies.PMID:37092220 | DOI:10.3233/JAD-220795

PeerJ. 2023 Apr 17;11:e15113. doi: 10.7717/peerj.15113. eCollection 2023.ABSTRACTBACKGROUND: Chronic long-term stress is associated with a range of disorders, including depression and a variety of other chronic illnesses. It is well known that maternal exposure to psychosocial stress during pregnancy significantly increases the likelihood of adverse pregnancy outcomes. The gut microbiota has been a popular topic, it is a key mediator of the gut-brain axis and plays an important role in human health; changes in the gut microbiota have been related to chronic stress-induced health impairment, however, the relationship between maternal negative emotions and abnormal gut microbiota and its metabolites during maternal exposure to chronic stress during pregnancy remains unclear.METHODS: Pregnant rats were subjected to chronic unpredicted mild stress (CUMS) to establish the rat model of chronic stress during pregnancy. The behavioral changes were recorded using sucrose preference test (SPT) and open-field test (OFT), plasma corticosterone levels were determined by radioimmunoassay, and a comprehensive method combining 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics was used to study the effects of stress during pregnancy on the function of intestinal microbiota and its metabolites.RESULTS: Chronic stress during pregnancy not only increased maternal plasma corticosterone (P < 0.05), but also caused maternal depression-like behaviors (P < 0.05). Chronic stress during pregnancy changed the species composition at the family level of maternal gut microbiota, the species abundance of Ruminococcaceae in the stress group (23.45%) was lower than the control group (32.67%) and the species abundance of Prevotellaceae in the stress group (10.45%) was higher than the control group (0.03%) (P < 0.05). Vertical locomotion and 1% sucrose preference percentage in pregnant rats were negatively correlated with Prevotellaceae (r = - 0.90, P < 0.05). Principal component analysis with partial least squares discriminant analysis showed that the integration points of metabolic components in the stress and control groups were completely separated, indicating that there were significant differences in the metabolic patterns of the two groups, and there were seven endogenous metabolites that differed (P < 0.05).CONCLUSIONS: The negative emotional behaviors that occur in pregnant rats as a result of prenatal chronic stress may be associated with alterations in the gut microbiota and its metabolites. These findings provide a basis for future targeted metabolomics and gut flora studies on the effects of chronic stress during pregnancy on gut flora.PMID:37090110 | PMC:PMC10117386 | DOI:10.7717/peerj.15113

Food Chem. 2023 Apr 17;421:136147. doi: 10.1016/j.foodchem.2023.136147. Online ahead of print.ABSTRACTProtein glycation may occur naturally when reducing sugars and proteins coexist, which is often the case for industrial enzymes. The impact of post-translational modifications on enzyme performance (e.g., stability or function) is often not predictable, highlighting the importance of having appropriate analytical methodologies to monitor the influence of glycation on performance. Here, a boronate affinity chromatography method was developed to enrich glycated species followed by mass spectrometry for structural characterization and activity assays for functional assessment. This approach was applied to a (temperature-stressed) lipase used for food applications revealing that storage at -20 °C and 4 °C resulted in minor glycation (below 9%), whereas storage at 25 °C led to a higher glycation level with up to four sugars per lipase molecule. Remarkably, activity measurements revealed that glycation did not reduce lipase activity or stability. Altogether, this novel strategy is a helpful extension to the current analytical toolbox supporting development of enzyme products.PMID:37087987 | DOI:10.1016/j.foodchem.2023.136147

Food Chem. 2023 Apr 17;421:136150. doi: 10.1016/j.foodchem.2023.136150. Online ahead of print.ABSTRACTHydrothermal treatment is commonly used for hemicelluloses extraction from lignocellulosic materials. In this study, we thoroughly investigated with a novel approach the metabolomics of degradation compounds formed when hazelnut shells are subjected to this type of treatment. Three different complementary techniques were combined, namely GC-MS, 1H NMR, and UHPLC-IM-Q-TOF-MS. Organic acids, modified sugars and aromatic compounds, likely to be the most abundant chemical classes, were detected and quantified by NMR, whereas GC- and LC-MS-based techniques allowed to detect many molecules with low and higher Mw, respectively. Furans, polyols, N-heterocyclic compounds, aldehydes, ketones, and esters appeared, among others. Ion mobility-based LC-MS method was innovatively used for this purpose and could allow soon to create potentially useful datasets for building specific databases relating to the formation of these compounds in different process conditions and employing different matrices. This could be a very intelligent approach especially in a risk assessment perspective.PMID:37086522 | DOI:10.1016/j.foodchem.2023.136150

J Nutr. 2023 Apr 17:S0022-3166(23)35552-4. doi: 10.1016/j.tjnut.2023.04.009. Online ahead of print.NO ABSTRACTPMID:37080248 | DOI:10.1016/j.tjnut.2023.04.009