PubMed

RSC Adv. 2023 Oct 19;13(44):30665-30679. doi: 10.1039/d3ra04037b. eCollection 2023 Oct 18.ABSTRACTMetabolomics and molecular networking approaches have expanded rapidly in the field of biological sciences and involve the systematic identification, visualization, and high-throughput characterization of bioactive metabolites in natural products using sophisticated mass spectrometry-based techniques. The popularity of natural products in pharmaceutical therapies has been influenced by medicinal plants with a long history of ethnobotany and a vast collection of bioactive compounds. Here, we selected four medicinal plants Cleistocalyx operculatus, Terminalia chebula, Ficus lacor, and Ficus semicordata, the biochemical characteristics of which remain unclear owing to the inherent complexity of their plant metabolites. In this study, we aimed to evaluate the potential of these aforementioned plant extracts in inhibiting the enzymatic activity of α-amylase and α-glucosidase, respectively, followed by the annotation of secondary metabolites. The methanol extract of Ficus semicordata exhibited the highest α-amylase inhibition with an IC50 of 46.8 ± 1.8 μg mL-1, whereas the water fraction of Terminalia chebula fruits demonstrated the most significant α-glucosidase inhibition with an IC50 value of 1.07 ± 0.01 μg mL-1. The metabolic profiling of plant extracts was analyzed through Liquid Chromatography-Mass Spectrometry (LC-HRMS) of the active fractions, resulting in the annotation of 32 secondary metabolites. Furthermore, we applied the Global Natural Product Social Molecular Networking (GNPS) platform to evaluate the MS/MS data of Terminalia chebula (bark), revealing that there were 205 and 160 individual ion species observed as nodes in the methanol and ethyl acetate fractions, respectively. Twenty-two metabolites were tentatively identified from the network map, of which 11 compounds were unidentified during manual annotation.PMID:37869390 | PMC:PMC10585453 | DOI:10.1039/d3ra04037b

Front Aging Neurosci. 2023 Oct 6;15:1211979. doi: 10.3389/fnagi.2023.1211979. eCollection 2023.ABSTRACTA key role of the gut microbiota in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), has been identified over the past decades. Increasing clinical and preclinical evidence implicates that there is bidirectional communication between the gut microbiota and the central nervous system (CNS), which is also known as the microbiota-gut-brain axis. Nevertheless, current knowledge on the interplay between gut microbiota and the brain remains largely unclear. One of the primary mediating factors by which the gut microbiota interacts with the host is peripheral metabolites, including blood or gut-derived metabolites. However, mechanistic knowledge about the effect of the microbiome and metabolome signaling on the brain is limited. Neuroimaging techniques, such as multi-modal magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (FDG-PET), have the potential to directly elucidate brain structural and functional changes corresponding with alterations of the gut microbiota and peripheral metabolites in vivo. Employing a combination of gut microbiota, metabolome, and advanced neuroimaging techniques provides a future perspective in illustrating the microbiota-gut-brain pathway and further unveiling potential therapeutic targets for AD treatments.PMID:37869373 | PMC:PMC10587434 | DOI:10.3389/fnagi.2023.1211979

Ophthalmol Sci. 2023 Jul 1;4(1):100357. doi: 10.1016/j.xops.2023.100357. eCollection 2024 Jan-Feb.ABSTRACTPURPOSE: The most widely used classifications of age-related macular degeneration (AMD) and its severity stages still rely on color fundus photographs (CFPs). However, AMD has a wide phenotypic variability that remains poorly understood and is better characterized by OCT. We and others have shown that patients with AMD have a distinct plasma metabolomic profile compared with controls. However, all studies to date have been performed solely based on CFP classifications. This study aimed to assess if plasma metabolomic profiles are associated with OCT features commonly seen in AMD.DESIGN: Prospectively designed, cross-sectional study.PARTICIPANTS: Subjects with a diagnosis of AMD and a control group (> 50 years old) from Boston, United States, and Coimbra, Portugal.METHODS: All participants were imaged with CFP, used for AMD staging (Age-Related Eye Disease Study 2 classification scheme), and with spectral domain OCT (Spectralis, Heidelberg). OCT images were graded by 2 independent graders for the presence of characteristic AMD features, according to a predefined protocol. Fasting blood samples were collected for metabolomic profiling (using nontargeted high-resolution mass spectrometry by Metabolon Inc). Analyses were conducted using logistic regression models including the worst eye of each patient (AREDS2 classification) and adjusting for confounding factors. Each cohort (United States and Portugal) was analyzed separately and then results were combined by meta-analyses. False discovery rate (FDR) was used to account for multiple comparisons.MAIN OUTCOME MEASURES: Plasma metabolite levels associated with OCT features.RESULTS: We included data on 468 patients, 374 with AMD and 94 controls, and on 725 named endogenous metabolites. Meta-analysis identified significant associations (FDR < 0.05) between plasma metabolites and 3 OCT features: hyperreflective foci (6), atrophy (6), and ellipsoid zone disruption (3). Most associations were seen with amino acids, and all but 1 metabolite presented specific associations with the OCT features assessed.CONCLUSIONS: To our knowledge, we show for the first time that plasma metabolites have associations with specific OCT features seen in AMD. Our results support that the wide spectrum of presentations of AMD likely include different pathophysiologic mechanisms by identifying specific pathways associated with each OCT feature.FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.PMID:37869026 | PMC:PMC10587636 | DOI:10.1016/j.xops.2023.100357

Front Immunol. 2023 Oct 5;14:1225603. doi: 10.3389/fimmu.2023.1225603. eCollection 2023.ABSTRACTFetal and neonatal alloimmune thrombocytopenia (FNAIT) can occur due to maternal IgG antibodies targeting platelet antigens, causing life-threatening bleeding in the neonate. However, the disease manifests itself in only a fraction of pregnancies, most commonly with anti-HPA-1a antibodies. We found that in particular, the core fucosylation in the IgG-Fc tail is highly variable in anti-HPA-1a IgG, which strongly influences the binding to leukocyte IgG-Fc receptors IIIa/b (FcγRIIIa/b). Currently, gold-standard IgG-glycoanalytics rely on complicated methods (e.g., mass spectrometry (MS)) that are not suited for diagnostic purposes. Our aim was to provide a simplified method to quantify the biological activity of IgG antibodies targeting cells. We developed a cellular surface plasmon resonance imaging (cSPRi) technique based on FcγRIII-binding to IgG-opsonized cells and compared the results with MS. The strength of platelet binding to FcγR was monitored under flow using both WT FcγRIIIa (sensitive to Fc glycosylation status) and mutant FcγRIIIa-N162A (insensitive to Fc glycosylation status). The quality of the anti-HPA-1a glycosylation was monitored as the ratio of binding signals from the WT versus FcγRIIIa-N162A, using glycoengineered recombinant anti-platelet HPA-1a as a standard. The method was validated with 143 plasma samples with anti-HPA-1a antibodies analyzed by MS with known clinical outcomes and tested for validation of the method. The ratio of patient signal from the WT versus FcγRIIIa-N162A correlated with the fucosylation of the HPA-1a antibodies measured by MS (r=-0.52). Significantly, FNAIT disease severity based on Buchanan bleeding score was similarly discriminated against by MS and cSPRi. In conclusion, the use of IgG receptors, in this case, FcγRIIIa, on SPR chips can yield quantitative and qualitative information on platelet-bound anti-HPA-1a antibodies. Using opsonized cells in this manner circumvents the need for purification of specific antibodies and laborious MS analysis to obtain qualitative antibody traits such as IgG fucosylation, for which no clinical test is currently available.PMID:37868955 | PMC:PMC10585714 | DOI:10.3389/fimmu.2023.1225603

Front Cell Infect Microbiol. 2023 Sep 12;13:1254016. doi: 10.3389/fcimb.2023.1254016. eCollection 2023.ABSTRACTBACKGROUND: Clonorchiasis is an important foodborne parasitic disease. However, eggs of Clonorchis sinensis (C. sinensis) cannot be detected in feces during biliary obstruction. Moreover, many diseases can cause biliary obstruction, such as gallstones, adenocarcinoma, cholangiocarcinoma and Ascaris lumbricoides infection. Therefore, it is of great significance to distinguish between patients of biliary obstruction and biliary obstruction with C. sinensis infection.METHODS: A total of 48 biliary obstruction patients were enrolled, including 23 infected with C. sinensis (C. sinensis) (OB+C.s) and 25 non-infected subjects (OB). The bile samples were collected by endoscopic retrograde cholangiopancreatography and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). Additionally, multivariate statistical analysis methods were employed to identify differential metabolites. Next, bile amino acid levels were determined by targeted metabolomics analysis.RESULT: A total of 146 and 132 significant metabolites were identified in electrospray ionization (ESI)+ and ESI- modes, respectively. The levels of amino acids (asparagine, glutamate, ornithine) and polyamines (spermidine and spermine) were significantly changed. Targeted analysis showed that the levels of amino acids (such as L-arginine, L-glutamine, L-lysine, L-propionic, and L-tyrosine) were lower in OB+C.s patients compared to those in OB patients. Marked metabolic pathways were involved in "Glutathione metabolism", "Caffeine metabolism", "Alanine, aspartate and glutamate metabolism", "Arginine and proline metabolism", "Purine metabolism", "Beta-Alanine metabolism", and "D-glutamine and D-glutamate metabolism".CONCLUSION: These results show that there were significant differences between OB+C.s and OB patients, especially in amino acids. The metabolic signature and perturbations in metabolic pathways may help to better distinguish OB+C.s and OB patients.PMID:37868349 | PMC:PMC10585366 | DOI:10.3389/fcimb.2023.1254016

Front Plant Sci. 2023 Oct 5;14:1216702. doi: 10.3389/fpls.2023.1216702. eCollection 2023.ABSTRACTBACKGROUND: Nicotiana tabacum is an important economic crop, which is widely planted in the world. Lignin is very important for maintaining the physiological and stress-resistant functions of tobacco. However, higher lignin content will produce lignin gas, which is not conducive to the formation of tobacco quality. To date, how to precisely fine-tune lignin content or composition remains unclear.RESULTS: Here, we annotated and screened 14 CCoAOMTs in Nicotiana tabacum and obtained homozygous double mutants of CCoAOMT6 and CCoAOMT6L through CRSIPR/Cas9 technology. The phenotype showed that the double mutants have better growth than the wild type whereas the S/G ratio increased and the total sugar decreased. Resistance against the pathogen test and the extract inhibition test showed that the transgenic tobacco has stronger resistance to tobacco bacterial wilt and brown spot disease, which are infected by Ralstonia solanacearum and Alternaria alternata, respectively. The combined analysis of metabolome and transcriptome in the leaves and roots suggested that the changes of phenylpropane and terpene metabolism are mainly responsible for these phenotypes. Furthermore, the molecular docking indicated that the upregulated metabolites, such as soyasaponin Bb, improve the disease resistance due to highly stable binding with tyrosyl-tRNA synthetase targets in Ralstonia solanacearum and Alternaria alternata.CONCLUSIONS: CAFFEOYL-COA 3-O-METHYLTRANSFERASE 6/6L can regulate the S/G ratio of lignin monomers and may affect tobacco bacterial wilt and brown spot disease resistance by disturbing phenylpropane and terpene metabolism in leaves and roots of Nicotiana tabacum, such as soyasaponin Bb.PMID:37868314 | PMC:PMC10585270 | DOI:10.3389/fpls.2023.1216702

ERJ Open Res. 2023 Oct 2;9(5):00269-2023. doi: 10.1183/23120541.00269-2023. eCollection 2023 Sep.ABSTRACTRATIONALE: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.METHODS: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study.MEASUREMENTS AND MAIN RESULTS: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12-18 months.CONCLUSION: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.PMID:37868143 | PMC:PMC10588792 | DOI:10.1183/23120541.00269-2023

PeerJ. 2023 Oct 18;11:e16177. doi: 10.7717/peerj.16177. eCollection 2023.ABSTRACTTrace elements play a crucial role in the growth and bioactive substance content of medicinal plants, but their utilization efficiency in soil is often low. In this study, soil and Aconitum carmichaelii samples were collected and measured from 22 different locations, followed by an analysis of the relationship between trace elements and the yield and alkaloid content of the plants. The results indicated a significant positive correlation between zinc, trace elements in the soil, and the yield and alkaloid content of A. carmichaelii. Subsequent treatment of A. carmichaelii with both bulk zinc oxide (ZnO) and zinc oxide nanoparticles (ZnO NPs) demonstrated that the use of ZnO NPs significantly enhanced plant growth and monoester-type alkaloid content. To elucidate the underlying mechanisms responsible for these effects, metabolomic analysis was performed, resulting in the identification of 38 differentially expressed metabolites in eight metabolic pathways between the two treatments. Additionally, significant differences were observed in the rhizosphere bacterial communities, with Bacteroidota and Actinobacteriota identified as valuable biomarkers for ZnO NP treatment. Covariation analysis further revealed significant correlations between specific microbial communities and metabolite expression levels. These findings provide compelling evidence that nanoscale zinc exhibits much higher utilization efficiency compared to traditional zinc fertilizer.PMID:37868063 | PMC:PMC10590109 | DOI:10.7717/peerj.16177

Comput Struct Biotechnol J. 2023 Oct 12;21:4933-4943. doi: 10.1016/j.csbj.2023.10.016. eCollection 2023.ABSTRACTThe study of the respiratory microbiome has entered a multi-omic era. Through integrating different omic data types such as metagenome, metatranscriptome, metaproteome, metabolome, culturome and radiome surveyed from respiratory specimens, holistic insights can be gained on the lung microbiome and its interaction with host immunity and inflammation in respiratory diseases. The power of multi-omics have moved the field forward from associative assessment of microbiome alterations to causative understanding of the lung microbiome in the pathogenesis of chronic, acute and other types of respiratory diseases. However, the application of multi-omics in respiratory microbiome remains with unique challenges from sample processing, data integration, and downstream validation. In this review, we first introduce the respiratory sample types and omic data types applicable to studying the respiratory microbiome. We next describe approaches for multi-omic integration, focusing on dimensionality reduction, multi-omic association and prediction. We then summarize progresses in the application of multi-omics to studying the microbiome in respiratory diseases. We finally discuss current challenges and share our thoughts on future promises in the field.PMID:37867968 | PMC:PMC10585227 | DOI:10.1016/j.csbj.2023.10.016

iScience. 2023 Oct 4;26(11):108109. doi: 10.1016/j.isci.2023.108109. eCollection 2023 Nov 17.ABSTRACTThe host-microbiome associations occurring on the skin of vertebrates significantly influence hosts' health. However, the factors mediating their interactions remain largely unknown. Herein, we used integrated technical and ecological frameworks to investigate the skin metabolites sustaining a beneficial symbiosis between tree frogs and bacteria. We characterize macrocyclic acylcarnitines as the major metabolites secreted by the frogs' skin and trace their origin to an enzymatic unbalance of carnitine palmitoyltransferases. We found that these compounds colocalize with bacteria on the skin surface and are mostly represented by members of the Pseudomonas community. We showed that Pseudomonas sp. MPFS isolated from frogs' skin can exploit acylcarnitines as its sole carbon and nitrogen source, and this metabolic capability is widespread in Pseudomonas. We summarize frogs' multiple mechanisms to filter environmental bacteria and highlight that acylcarnitines likely evolved for another function but were co-opted to provide nutritional benefits to the symbionts.PMID:37867936 | PMC:PMC10587524 | DOI:10.1016/j.isci.2023.108109

Vavilovskii Zhurnal Genet Selektsii. 2023 Sep;27(5):530-538. doi: 10.18699/VJGB-23-64.ABSTRACTThe etiology of essential hypertension is intricate, since it employs simultaneously various body systems related to the regulation of blood pressure in one way or another: the sympathetic nervous system, renin-angiotensin-aldosterone and hypothalamic-pituitary-adrenal systems, renal and endothelial mechanisms. The pathogenesis of hypertension is influenced by a variety of both genetic and environmental factors, which determines the heterogeneity of the disease in human population. Hence, there is a need to perform research on experimental models - inbred animal strains, one of them being ISIAH rat strain, which is designed to simulate inherited stress-induced arterial hypertension as close as possible to primary (or essential) hypertension in humans. To determine specific markers of diseases, various omics technologies are applied, including metabolomics, which makes it possible to evaluate the content of low-molecular compounds - amino acids, lipids, carbohydrates, nucleic acids fragments - in biological samples available for clinical analysis (blood and urine). We analyzed the metabolic profile of the blood serum of male ISIAH rats with a genetic stress-dependent form of arterial hypertension in comparison with the normotensive WAG rats. Using the method of nuclear magnetic resonance spectroscopy (NMR spectroscopy), 56 metabolites in blood serum samples were identified, 18 of which were shown to have significant interstrain differences in serum concentrations. Statistical analysis of the data obtained showed that the hypertensive status of ISIAH rats is characterized by increased concentrations of leucine, isoleucine, valine, myo-inositol, isobutyrate, glutamate, glutamine, ornithine and creatine phosphate, and reduced concentrations of 2-hydroxyisobutyrate, betaine, tyrosine and tryptophan. Such a ratio of the metabolite concentrations is associated with changes in the regulation of glucose metabolism (metabolic markers - leucine, isoleucine, valine, myo-inositol), of nitric oxide synthesis (ornithine) and catecholamine pathway (tyrosine), and with inflammatory processes (metabolic markers - betaine, tryptophan), all of these changes being typical for hypertensive status. Thus, metabolic profiling of the stress-dependent form of arterial hypertension seems to be an important result for a personalized approach to the prevention and treatment of hypertensive disease.PMID:37867609 | PMC:PMC10587007 | DOI:10.18699/VJGB-23-64

Biochem Pharmacol. 2023 Oct 20:115867. doi: 10.1016/j.bcp.2023.115867. Online ahead of print.ABSTRACTTransporter-mediated drug-drug interactions (DDIs) are assessed using probe drugs and in vitro and in vivo models during drug development. The utility of endogenous metabolites as transporter biomarkers is emerging for prediction of DDIs during early phases of clinical trials. Endogenous metabolites such as pyridoxic acid and kynurenic acid have shown potential to predict DDIs mediated by organic anion transporters (OAT1 and OAT3). However, these metabolites have not been assessed in rats for their utility in prediction of DDIs. Therefore, we carried out a rat pharmacokinetic DDI study using probenecid and furosemide as OAT inhibitor and substrate, respectively. Probenecid administration led to a 3.8-fold increase in the blood concentrations and 3-fold decrease in renal clearance of furosemide. High inter-individual and intra-day variability in pyridoxic acid and kynurenic acid, and no or moderate effect of probenecid administration on these metabolites suggest their limited utility for prediction of Oat-mediated DDI in rats. Therefore, rat blood and urine samples were further analysed using untargeted metabolomics. Twenty-one m/z features (out of >8000 detected features) were identified as putative biomarkers of rat Oat1 and Oat3 using a robust biomarker qualification approach. These m/z features belong to metabolic pathways such as fatty acid analogue, peptides, prostaglandin analogues, bile acid derivatives, flavonoids, phytoconstituents, and steroids, and can be used as a panel to decrease variability caused by processes other than Oats. When validated, these putative biomarkers will be useful in predicting DDIs caused by Oats in rats.PMID:37866801 | DOI:10.1016/j.bcp.2023.115867

Clin Immunol. 2023 Oct 20:109812. doi: 10.1016/j.clim.2023.109812. Online ahead of print.ABSTRACTSynovial fluid (SF) extracellular vesicles (EVs) play a pathogenic role in osteoarthritis (OA). However, the surface markers, cell and tissue origins, and effectors of these EVs are largely unknown. We found that SF EVs contained 692 peptides that were positively associated with knee radiographic OA severity; 57.4% of these pathogenic peptides were from 46 proteins of the immune system, predominantly the innate immune system. CSPG4, BGN, NRP1, and CD109 are the major surface markers of pathogenic SF EVs. Genes encoding surface marker CSPG4 and CD109 were highly expressed by chondrocytes from damaged cartilage, while VISG4, MARCO, CD163 and NRP1 were enriched in the synovial immune cells. The frequency of CSPG4+ and VSIG4+ EV subpopulations in OA SF was high. We conclude that pathogenic SF EVs carry knee OA severity-associated proteins and specific surface markers, which could be developed as a new source of diagnostic biomarkers or therapeutic targets in OA.PMID:37866785 | DOI:10.1016/j.clim.2023.109812

Environ Pollut. 2023 Oct 20:122783. doi: 10.1016/j.envpol.2023.122783. Online ahead of print.ABSTRACTMice were exposed to a low dose of the model thyroid hormone disruptor, propylthiouracil. Although this had only a modest effect on maternal thyroid hormones production, postnatal analysis of the pups' plasma by mass spectrometry and the brain striatum by RNA sequencing gave evidence of low lasting changes that could reflect an adverse effect on neurodevelopment. Overall, these methods proved to be sensitive enough to detect minor disruptions of thyroid hormone signalling in vivo.PMID:37866749 | DOI:10.1016/j.envpol.2023.122783

Sci Total Environ. 2023 Oct 20:167894. doi: 10.1016/j.scitotenv.2023.167894. Online ahead of print.ABSTRACTSpontaneous plants often play important ecological roles in terrestrial environments, but impacts of contaminants on spontaneous plants are seldom investigated. Per- and polyfluoroalkyl substances (PFAS), such as perfluorooctanesulfonic acid (PFOS) are ubiquitous in rural and urban soils. In this study, we assessed the effects of PFOS on a spontaneous plant, velvetleaf (Abutilon theophrasti), using endpoints such as plant growth, stress defense, PFOS uptake, and elemental and metabolite profile. We observed stunted growth in plants grown in PFOS-contaminated soils, with PFOS accumulating in their shoots by up to 3000 times more than the control plants. The other endpoints (decreased chlorophyll a synthesis, elevated oxidative stress, reduced shoot Mg concentration, and reduced biomass production) also explained the stunted growth of velvetleaf exposed to elevated PFAS concentrations. We found that 57 metabolites involved in 13 metabolic pathways were dysregulated. The synthesis of important antioxidants such as ascorbic acid, hydroxycinnamic acids (coumaric, caffeic, ferulic, and sinapic acids), and tocopherols decreased, resulting in loss of plant's defense to stress. PFOS also reduced the levels of growth-related and stress-coping metabolites including squalene, serotonin, noradrenalin, putrescine, and indole-3-propionic acid, which further corroborated the restricted growth of velvetleaf exposed to elevated PFOS. These findings provide insights on phytotoxicity of PFOS to velvetleaf, a resilient terrestrial spontaneous plant.PMID:37866594 | DOI:10.1016/j.scitotenv.2023.167894

Environ Res. 2023 Oct 20:117435. doi: 10.1016/j.envres.2023.117435. Online ahead of print.ABSTRACTBACKGROUND: Neonatal per- and polyfluoroalkyl substance (PFAS) exposure can disrupt hormonal homeostasis and induce neuro- and immunotoxicity in children. In this exploratory study, we investigated associations between PFAS levels in neonatal dried blood spots and retinoblastoma risk.MATERIALS AND METHODS: This study included 501 retinoblastoma cases born from 1983 to 2011 and 899 controls frequency-matched by birth year (20:1 matching ratio), born to 755 US-born and 366 Mexico-born mothers in California. Perfluorooctanesulfonic acid (PFOS), perflurooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) feature intensities were identified from neonatal blood spots from California newborn Genetic Disease Screening Program. Using logistic regression, we assessed whether an interquartile range (IQR) increase of PFAS levels or having above-mean levels of PFAS in blood affects retinoblastoma risk overall or its subtypes (i.e., unilateral, bilateral). We assessed children of US-born and Mexico-born mothers, separately.RESULTS: and Discussion: Among all children, above-mean PFOS levels at birth increased the odds of retinoblastoma overall by 29% (95% Confidence Interval (CI): 1.00, 1.67) and unilateral retinoblastoma by 42% (95% CI: 1.03, 1.97). For children of Mexico-born mothers, we estimated the highest odds of retinoblastoma overall (adjusted odds ratio (aOR): 1.67; 95% CI: 1.06, 2.66) and bilateral retinoblastoma (aOR: 2.06; 95% CI: 1.12, 3.92) with above-mean PFOS levels. Among children of US-born mothers, higher PFOS levels increased the odds of unilateral retinoblastoma by 15% (95% CI: 0.99, 1.35) for each IQR increase and by 71% among children with above-mean PFOS levels (95% CI: 1.04, 2.90). In addition, for children of US-born mothers, PFOA increased the odds of retinoblastoma overall (aOR: 1.41; 95% CI: 1.00, 2.02 for above-mean levels, aOR: 1.09; 95% CI: 0.98, 1.23 per IQR increase). PFNA was not associated with retinoblastoma risk.CONCLUSIONS: Our results suggested that PFOS and PFOA might contribute to retinoblastoma risk in children born in California.PMID:37866539 | DOI:10.1016/j.envres.2023.117435

Food Chem. 2023 Oct 18;437(Pt 1):137793. doi: 10.1016/j.foodchem.2023.137793. Online ahead of print.ABSTRACTThe hypoglycemic effect of Porphyra is well known. Based on in vitro digestion and metabolomics, the bioaccessibility, antidiabetic activity and phenolic conversion of P. haitanensis were investigated at different harvests. Total polyphenol content (TPC), α-glucosidase inhibition and oxygen radical absorbance capacity (ORAC) increased with harvesting and digestion stages, reaching maximum at the fourth harvest. TPC and α-glucosidase inhibition after digestion reached 130-150 mg/g and 50-90 %, ORAC was 8.7-13.5 times higher than the undigestion. However, bioaccessibility in the first and second harvests was 10-80 % higher than other harvests. The phenolic content in the fourth harvest was up-regulated to 2-30 times than the first and mostly were citrus flavonoids. Redundancy analysis indicated significant correlation between phenolic metabolites and bioactivities in different harvests of P. haitanensis during digestion, with the strongest correlation coefficients were apigenin and genistein. This study provides reference for the application of P. haitanensis in treating type 2 diabetes.PMID:37866341 | DOI:10.1016/j.foodchem.2023.137793

Talanta. 2023 Oct 9;268(Pt 1):125295. doi: 10.1016/j.talanta.2023.125295. Online ahead of print.ABSTRACTBACKGROUND: The COVID-19 pandemic challenged the management of technical and human resources in intensive care units (ICU) across the world. Several long-term predictors for COVID-19 disease progression have been discovered. However, predictors to support short-term planning of resources and medication that can be translated to future pandemics are still missing. A workflow was established to identify a predictor for short-term COVID-19 disease progression in the acute phase of intensive care patients to support clinical decision-making.METHODS: Thirty-two patients with SARS-CoV-2 infection were recruited on admission to the ICU and clinical data collected. During their hospitalization, plasma samples were acquired from each patient on multiple occasions, excepting one patient for which only one time point was possible, and the proteome (Inflammation, Immune Response and Organ Damage panels from Olink® Target 96), metabolome and lipidome (flow injection analysis and liquid chromatography-mass spectrometry) analyzed for each sample. Patient visits were grouped according to changes in disease severity based on their respiratory and organ function, and evaluated using a combination of statistical analysis and machine learning. The resulting short-term predictor from this multi-omics approach was compared to the human assessment of disease progression. Furthermore, the potential markers were compared to the baseline levels of 50 healthy subjects with no known SARS-CoV-2 or other viral infections.RESULTS: A total of 124 clinical parameters, 271 proteins and 782 unique metabolites and lipids were assessed. The dimensionality of the dataset was reduced, selecting 47 from the 1177 parameters available following down-selection, to build the machine learning model. Subsequently, two proteins (C-C motif chemokine 7 (CCL7) and carbonic anhydrase 14 (CA14)) and one lipid (hexosylceramide 18:2; O2/20:0) were linked to disease progression in the studied SARS-CoV-2 infections. Thus, a predictor delivering the prognosis of an upcoming worsening of the patient's condition up to five days in advance with a reasonable accuracy (79 % three days prior to event, 84 % four to five days prior to event) was found. Interestingly, the predictor's performance was complementary to the clinicians' capabilities to foresee a worsening of a patient.CONCLUSION: This study presents a workflow to identify omics-based biomarkers to support clinical decision-making and resource management in the ICU. This was successfully applied to develop a short-term predictor for aggravation of COVID-19 symptoms. The applied methods can be adapted for future small cohort studies.PMID:37866305 | DOI:10.1016/j.talanta.2023.125295

Water Res. 2023 Oct 12;246:120738. doi: 10.1016/j.watres.2023.120738. Online ahead of print.ABSTRACTTraditional research on biodegradation of emerging organic pollutants involves slow and labor-intensive experimentation. Currently, fast-developing metagenome, metatranscriptome, and metabolome technologies promise to expedite mechanistic research on biodegradation of emerging organic pollutants. Integrating the metagenome, metatranscriptome, and metabolome (i.e., tri-omics) makes it possible to link gene abundance and expression with the biotransformation of the contaminant and the formation of metabolites from this biotransformation. In this study, we used this tri-omics approach to study the biotransformation pathways for cetyltrimethylammonium bromide (CTAB) under aerobic conditions. The tri-omics analysis showed that CTAB undergoes three parallel first-step mono-/di-oxygenations (to the α, β, and ω-carbons); intermediate metabolites and expressed enzymes were identified for all three pathways, and the β-carbon mono-/di-oxygenation is a novel pathway; and the genes related to CTAB biodegradation were associated with Pseudomonas spp. Four metabolites - palmitic acid, trimethylamine N-oxide (TMAO), myristic acid, and betaine - were the key identified biodegradation intermediates of CTAB, and they were associated with first-step mono-/di-oxygenations at the α/β-C. This tri-omics approach with CTAB demonstrates its power for identifying promising paths for future research on the biodegradation of complex organics by microbial communities.PMID:37866246 | DOI:10.1016/j.watres.2023.120738

Cell Immunol. 2023 Oct 15;393-394:104777. doi: 10.1016/j.cellimm.2023.104777. Online ahead of print.ABSTRACTVaccinations in early life elicit variable antibody and cellular immune responses, sometimes leaving fully vaccinated children unprotected against life-threatening infectious diseases. Specific immune cell populations and immune networks may have a critical period of development and calibration in a window of opportunity occurring during the first 100 days of early life. Among the early life determinants of vaccine responses, this review will focus on modifiable factors involving development of the infant microbiota and metabolome: antibiotic exposure, breast versus formula feeding, and Caesarian section versus vaginal delivery of newborns. How microbiota may serve as natural adjuvants for vaccine responses and how microbiota-derived metabolites influence vaccine responses are also reviewed. Early life poor vaccine responsiveness can be linked to increased infection susceptibility because both phenotypes share similar immunity dysregulation profiles. An early life pre-vaccination endotype, when interventions have the highest potential for success, should be sought that predicts vaccine response trajectories.PMID:37866234 | DOI:10.1016/j.cellimm.2023.104777