PubMed

J Extracell Vesicles. 2024 May;13(5):e12447. doi: 10.1002/jev2.12447.ABSTRACTThe continuous emergence of multidrug-resistant bacterial pathogens poses a major global healthcare challenge, with Klebsiella pneumoniae being a prominent threat. We conducted a comprehensive study on K. pneumoniae's antibiotic resistance mechanisms, focusing on outer membrane vesicles (OMVs) and polymyxin, a last-resort antibiotic. Our research demonstrates that OMVs protect bacteria from polymyxins. OMVs derived from Polymyxin B (PB)-stressed K. pneumoniae exhibited heightened protective efficacy due to increased vesiculation, compared to OMVs from unstressed Klebsiella. OMVs also shield bacteria from different bacterial families. This was validated ex vivo and in vivo using precision cut lung slices (PCLS) and Galleria mellonella. In all models, OMVs protected K. pneumoniae from PB and reduced the associated stress response on protein level. We observed significant changes in the lipid composition of OMVs upon PB treatment, affecting their binding capacity to PB. The altered binding capacity of single OMVs from PB stressed K. pneumoniae could be linked to a reduction in the lipid A amount of their released vesicles. Although the amount of lipid A per vesicle is reduced, the overall increase in the number of vesicles results in an increased protection because the sum of lipid A and therefore PB binding sites have increased. This unravels the mechanism of the altered PB protective efficacy of OMVs from PB stressed K. pneumoniae compared to control OMVs. The lipid A-dependent protective effect against PB was confirmed in vitro using artificial vesicles. Moreover, artificial vesicles successfully protected Klebsiella from PB ex vivo and in vivo. The findings indicate that OMVs act as protective shields for bacteria by binding to polymyxins, effectively serving as decoys and preventing antibiotic interaction with the cell surface. Our findings provide valuable insights into the mechanisms underlying antibiotic cross-protection and offer potential avenues for the development of novel therapeutic interventions to address the escalating threat of multidrug-resistant bacterial infections.PMID:38766978 | DOI:10.1002/jev2.12447

Eur Rev Med Pharmacol Sci. 2024 May;28(9):3289. doi: 10.26355/eurrev_202405_36194.ABSTRACTThe article "Metabolomic profiling of amino acid alterations in anorexia nervosa: implications for appetite regulation and therapeutic strategies", by K. Donato, K. Dhuli, A. Macchia, M.C. Medori, C. Micheletti, G. Bonetti, M.R. Ceccarini, T. Beccari, P. Chiurazzi, S. Cristoni, V. Benfatti, L. Dalla Ragione, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 64-76-DOI: 10.26355/eurrev_202312_34691-PMID: 38112949 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: - Issues with ethical approval - Undeclared conflict of interest Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. The authors disagree with this retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34691.PMID:38766780 | DOI:10.26355/eurrev_202405_36194

Exposome. 2023;3(1):osad008. doi: 10.1093/exposome/osad008. Epub 2023 Nov 23.ABSTRACTThe exposome refers to all of the internal and external life-long exposures that an individual experiences. These exposures, either acute or chronic, are associated with changes in metabolism that will positively or negatively influence the health and well-being of individuals. Nutrients and other dietary compounds modulate similar biochemical processes and have the potential in some cases to counteract the negative effects of exposures or enhance their beneficial effects. We present herein the concept of Nutritional Pharmacology/Toxicology which uses high-information metabolomics workflows to identify metabolic targets associated with exposures. Using this information, nutritional interventions can be designed toward those targets to mitigate adverse effects or enhance positive effects. We also discuss the potential for this approach in precision nutrition where nutrients/diet can be used to target gene-environment interactions and other subpopulation characteristics. Deriving these "nutrient cocktails" presents an opportunity to modify the effects of exposures for more beneficial outcomes in public health.PMID:38766521 | PMC:PMC11101153 | DOI:10.1093/exposome/osad008

Front Plant Sci. 2024 May 3;15:1393438. doi: 10.3389/fpls.2024.1393438. eCollection 2024.ABSTRACTPeanuts (Arachis hypogaea) are an essential oilseed crop known for their unique developmental process, characterized by aerial flowering followed by subterranean fruit development. This crop is polyploid, consisting of A and B subgenomes, which complicates its genetic analysis. The advent and progression of omics technologies-encompassing genomics, transcriptomics, proteomics, epigenomics, and metabolomics-have significantly advanced our understanding of peanut biology, particularly in the context of seed development and the regulation of seed-associated traits. Following the completion of the peanut reference genome, research has utilized omics data to elucidate the quantitative trait loci (QTL) associated with seed weight, oil content, protein content, fatty acid composition, sucrose content, and seed coat color as well as the regulatory mechanisms governing seed development. This review aims to summarize the advancements in peanut seed development regulation and trait analysis based on reference genome-guided omics studies. It provides an overview of the significant progress made in understanding the molecular basis of peanut seed development, offering insights into the complex genetic and epigenetic mechanisms that influence key agronomic traits. These studies highlight the significance of omics data in profoundly elucidating the regulatory mechanisms of peanut seed development. Furthermore, they lay a foundational basis for future research on trait-related functional genes, highlighting the pivotal role of comprehensive genomic analysis in advancing our understanding of plant biology.PMID:38766472 | PMC:PMC11099219 | DOI:10.3389/fpls.2024.1393438

Front Plant Sci. 2024 May 3;15:1364631. doi: 10.3389/fpls.2024.1364631. eCollection 2024.ABSTRACTINTRODUCTION: Watermelon is an annual vine of the family Cucurbitaceae. Watermelon plants produce a fruit that people love and have important nutritional and economic value. With global warming and deterioration of the ecological environment, abiotic stresses, including drought, have become important factors that impact the yield and quality of watermelon plants. Previous research on watermelon drought resistance has included analyzing homologous genes based on known drought-responsive genes and pathways in other species.METHODS: However, identifying key pathways and genes involved in watermelon drought resistance through high-throughput omics methods is particularly important. In this study, RNA-seq and metabolomic analysis were performed on watermelon plants at five time points (0 h, 1 h, 6 h, 12 h and 24 h) before and after drought stress.RESULTS: Transcriptomic analysis revealed 7829 differentially expressed genes (DEGs) at the five time points. The DEGs were grouped into five clusters using the k-means clustering algorithm. The functional category for each cluster was annotated based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database; different clusters were associated with different time points after stress. A total of 949 metabolites were divided into 10 categories, with lipids and lipid-like molecules accounting for the most metabolites. Differential expression analysis revealed 22 differentially regulated metabolites (DRMs) among the five time points. Through joint analysis of RNA-seq and metabolome data, the 6-h period was identified as the critical period for watermelon drought resistance, and the starch and sucrose metabolism, plant hormone signal transduction and photosynthesis pathways were identified as important regulatory pathways involved in watermelon drought resistance. In addition, 15 candidate genes associated with watermelon drought resistance were identified through joint RNA-seq and metabolome analysis combined with weighted correlation network analysis (WGCNA). Four of these genes encode transcription factors, including bHLH (Cla97C03G068160), MYB (Cla97C01G002440), HSP (Cla97C02G033390) and GRF (Cla97C02G042620), one key gene in the ABA pathway, SnRK2-4 (Cla97C10G186750), and the GP-2 gene (Cla97C05G105810), which is involved in the starch and sucrose metabolism pathway.DISCUSSION: In summary, our study provides a theoretical basis for elucidating the molecular mechanisms underlying drought resistance in watermelon plants and provides new genetic resources for the study of drought resistance in this crop.PMID:38766468 | PMC:PMC11102048 | DOI:10.3389/fpls.2024.1364631

World J Diabetes. 2024 May 15;15(5):1021-1044. doi: 10.4239/wjd.v15.i5.1021.ABSTRACTBACKGROUND: Diabetes is a metabolic disease characterized by hyperglycemia, which has increased the global medical burden and is also the main cause of death in most countries.AIM: To understand the knowledge structure of global development status, research focus, and future trend of the relationship between diabetes and metabolomics in the past 20 years.METHODS: The articles about the relationship between diabetes and metabolomics in the Web of Science Core Collection were retrieved from 2002 to October 23, 2023, and the relevant information was analyzed using CiteSpace6.2.2R (CiteSpace), VOSviewer6.1.18 (VOSviewer), and Bibliometrix software under R language.RESULTS: A total of 3123 publications were included from 2002 to 2022. In the past two decades, the number of publications and citations in this field has continued to increase. The United States, China, Germany, the United Kingdom, and other relevant funds, institutions, and authors have significantly contributed to this field. Scientific Reports and PLoS One are the journals with the most publications and the most citations. Through keyword co-occurrence and cluster analysis, the closely related keywords are "insulin resistance", "risk", "obesity", "oxidative stress", "metabolomics", "metabolites" and "biomarkers". Keyword clustering included cardiovascular disease, gut microbiota, metabonomics, diabetic nephropathy, molecular docking, gestational diabetes mellitus, oxidative stress, and insulin resistance. Burst detection analysis of keyword depicted that "Gene", "microbiota", "validation", "kidney disease", "antioxidant activity", "untargeted metabolomics", "management", and "accumulation" are knowledge frontiers in recent years.CONCLUSION: The relationship between metabolomics and diabetes is receiving extensive attention. Diabetic nephropathy, diabetic cardiovascular disease, and kidney disease are key diseases for future research in this field. Gut microbiota, molecular docking, and untargeted metabolomics are key research directions in the future. Antioxidant activity, gene, validation, mass spectrometry, management, and accumulation are at the forefront of knowledge frontiers in this field.PMID:38766424 | PMC:PMC11099375 | DOI:10.4239/wjd.v15.i5.1021

Int J Ophthalmol. 2024 May 18;17(5):883-895. doi: 10.18240/ijo.2024.05.13. eCollection 2024.ABSTRACTAIM: To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy (DR) and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS: The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy (PDR), 23 with non-proliferative retinopathy (NPDR), 27 without retinopathy (DM), and 29 from the sex-, age- and BMI- matched healthy controls (29 HC) were analyzed by 16S rDNA gene sequencing. Sixty fecal samples from PDR, DM, and HC groups were assayed by untargeted metabolomics. Fecal metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) analysis. Associations between gut microbiota and fecal metabolites were analyzed.RESULTS: A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR, and the close correlation of the disease progression with PDR-related microbiome and metabolites were found. To be specific, the structure of gut microbiota differed in four groups. Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups, than those in DM and HC groups. A cluster of microbiome enriched in PDR group, including Pseudomonas, Ruminococcaceae-UCG-002, Ruminococcaceae-UCG-005, Christensenellaceae-R-7, was observed. Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group. Arginine, serine, ornithine, and arachidonic acid were significantly enriched in PDR group, while proline was enriched in HC group. Functional analysis illustrated that arginine biosynthesis, lysine degradation, histidine catabolism, central carbon catabolism in cancer, D-arginine and D-ornithine catabolism were elevated in PDR group. Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine, ornithine levels in fecal samples.CONCLUSION: This study elaborates the different microbiota structure in the gut from four groups. The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR. Amino acid and fatty acid catabolism is especially disordered in PDR group. This may help provide a novel diagnostic parameter for DR, especially PDR.PMID:38766339 | PMC:PMC11074191 | DOI:10.18240/ijo.2024.05.13

bioRxiv [Preprint]. 2024 May 6:2024.05.06.592725. doi: 10.1101/2024.05.06.592725.ABSTRACTCampylobacter infections are a leading cause of bacterial-derived gastroenteritis worldwide with particularly profound impacts on pediatric patients in low-and-middle income countries. It remains unclear how Campylobacter impacts these hosts, though it is becoming increasingly evident that it is a multifactorial process that depends on the host immune response, the gastrointestinal microbiota, various bacterial factors, and host nutritional status. Since these factors likely vary between adult and pediatric patients in different regions of the world, it is important that studies define these attributes in well characterized clinical cohorts in diverse settings. In this study, we analyzed the fecal microbiota and the metabolomic and micronutrient profiles of asymptomatic and symptomatic pediatric patients in Colombia that were either infected or uninfected with Campylobacter during a case-controlled study on acute diarrheal disease. Here, we report that the microbiome of Campylobacter- infected children only changed in their abundance of Campylobacter spp. despite the inclusion of children with or without diarrhea. In addition to increased Campylobacter, computational models were used to identify fecal metabolites that were associated with Campylobacter infection and found that glucose-6-phosphate and homovanillic acid were the strongest predictors of infection in these pediatric patients, which suggest that colonocyte metabolism are impacted during infection. Despite changes to the fecal metabolome, the concentrations of intestinal minerals and trace elements were not significantly impacted by Campylobacter infection, but were elevated in uninfected children with diarrhea.IMPORTANCE: Gastrointestinal infection with pathogenic Campylobacter species has long been recognized as a significant cause of human morbidity. Recently, it has been observed that pediatric populations in low-and-middle income countries are uniquely impacted by these organisms in that infected children can be persistently colonized, develop enteric dysfunction, and exhibit reduced development and growth. While the association of Campylobacter species with these long-term effects continues to emerge, the impact of infection on the gastrointestinal environment of these children remains uncharacterized. To address this knowledge gap, our group leveraged clinical samples collected during a previous study on gastrointestinal infections in pediatric patients to examine the fecal microbiota, metabolome, and micronutrient profiles of those infected with Campylobacter species, and found that the metabolome was impacted in a way that suggests gastrointestinal cell metabolism is affected during infection, which is some of the first data indicating how gastrointestinal health in these patients may be affected.PMID:38766229 | PMC:PMC11100603 | DOI:10.1101/2024.05.06.592725

bioRxiv [Preprint]. 2024 May 7:2024.05.06.592814. doi: 10.1101/2024.05.06.592814.ABSTRACTClostridioides difficile (C. difficile) strains belonging to the epidemic BI/NAP1/027 (RT027) group have been associated with increased transmissibility and disease severity. In addition to the major toxin A and toxin B virulence factors, RT027 strains also encode the CDT binary toxin. Our lab previously identified a toxigenic RT027 isolate, ST1-75, that is avirulent in mice despite densely colonizing the colon. Here, we show that co-infecting mice with the avirulent ST1-75 and virulent R20291 strains protects mice from colitis due to rapid clearance of the virulent strain and persistence of the avirulent strain. Although avirulence of ST1-75 is due to a mutation in the cdtR gene, which encodes a response regulator that modulates the production of all three C. difficile toxins, the ability of ST1-75 to protect against acute colitis is not directly attributable to the cdtR mutation. Metabolomic analyses indicate that the ST1-75 strain depletes amino acids more rapidly than the R20291 strain and supplementation with amino acids ablates ST1-75's competitive advantage, suggesting that the ST1-75 strain limits the growth of virulent R20291 bacteria by amino acid depletion. Since the germination kinetics and sensitivity to the co-germinant glycine are similar for the ST1-75 and R20291 strains, our results identify the rapidity of in vivo nutrient depletion as a mechanism providing strain-specific, virulence-independent competitive advantages to different BI/NAP1/027 strains. They also suggest that the ST1-75 strain may, as a biotherapeutic agent, enhance resistance to CDI in high-risk patients.IMPORTANCE: Clostridioides difficile infections (CDI) are prevalent in healthcare settings and are associated with high recurrence rates. Therapies to prevent CDI, including recent FDA-approved live biotherapeutic products, are costly and have not been used to prevent primary infections. While a nontoxigenic C. difficile strain (NTCD-M3) protects against virulent CDI in animals and reduced CDI recurrence in a phase 2 clinical trial, protection against CDI recurrence in humans was variable and required high doses of the nontoxigenic strain. Here we show that an avirulent C. difficile isolate, ST1-75, efficiently outcompetes virulent C. difficile strains in mice when co-infected at a 1:1 ratio. Our data suggest that inter-strain competition results from ST1-75's more rapid depletion of amino acids than the virulent R20291 strain. Our study identifies inter-strain nutrient depletion as a potentially exploitable mechanism to reduce the incidence of CDI.PMID:38766138 | PMC:PMC11100753 | DOI:10.1101/2024.05.06.592814

bioRxiv [Preprint]. 2024 May 10:2024.05.07.592801. doi: 10.1101/2024.05.07.592801.ABSTRACTKidney dysfunction often leads to neurological impairment, yet the complex kidney-brain relationship remains elusive. We employed spatial and bulk metabolomics to investigate a mouse model of rapid kidney failure induced by mouse double minute 2 ( Mdm2) conditional deletion in the kidney tubules to interrogate kidney and brain metabolism. Pathway enrichment analysis of focused plasma metabolomics panel pinpointed tryptophan metabolism as the most altered pathway with kidney failure. Spatial metabolomics showed toxic tryptophan metabolites in the kidneys and brains, revealing a novel connection between advanced kidney disease and accelerated kynurenine degradation. In particular, the excitotoxic metabolite quinolinic acid was localized in ependymal cells adjacent to the ventricle in the setting of kidney failure. These findings were associated with brain inflammation and cell death. A separate mouse model of acute kidney injury also had an increase in circulating toxic tryptophan metabolites along with altered brain inflammation. Patients with advanced CKD similarly demonstrated elevated plasma kynurenine metabolites and quinolinic acid was uniquely correlated with fatigue and reduced quality of life in humans. Overall, our study identifies the kynurenine pathway as a bridge between kidney decline, systemic inflammation, and brain toxicity, offering potential avenues for diagnosis and treatment of neurological issues in kidney disease.PMID:38766008 | PMC:PMC11100748 | DOI:10.1101/2024.05.07.592801

Res Sq [Preprint]. 2024 May 6:rs.3.rs-4022389. doi: 10.21203/rs.3.rs-4022389/v1.ABSTRACTVisual decline in the elderly is often attributed to retinal aging, which predisposes the tissue to pathologies such as age-related macular degeneration. Currently, effective oral pharmacological interventions for retinal degeneration are limited. We present a novel oral intervention, 8-aminoguanine (8-AG), targeting age-related retinal degeneration, utilizing the aged Fischer 344 rat model. A low-dose 8-AG regimen (5 mg/kg body weight) via drinking water, beginning at 22 months for 8 weeks, demonstrated significant retinal preservation. This was evidenced by increased retinal thickness, improved photoreceptor integrity, and enhanced electroretinogram responses. 8-AG effectively reduced apoptosis, oxidative damage, and microglial/macrophage activation associated with aging retinae. Age-induced alterations in the retinal purine metabolome, characterized by elevated levels of inosine, hypoxanthine, and xanthine, were partially mitigated by 8-AG. Transcriptomics highlighted 8-AG's anti-inflammatory effects on innate and adaptive immune responses. Extended treatment to 17 weeks further amplified the retinal protective effects. Moreover, 8-AG showed temporary protective effects in the Rho P23H/+ mouse model of retinitis pigmentosa, reducing active microglia/macrophages. Our study positions 8-AG as a promising oral agent against retinal aging. Coupled with previous findings in diverse disease models, 8-AG emerges as a promising anti-aging compound with the capability to reverse common aging hallmarks.PMID:38765984 | PMC:PMC11100887 | DOI:10.21203/rs.3.rs-4022389/v1

Res Sq [Preprint]. 2024 May 9:rs.3.rs-4344179. doi: 10.21203/rs.3.rs-4344179/v1.ABSTRACTMethods A case-control study of 97 patients hospitalized at our institution. We performed aptamer-based proteomics and metabolomics on serum biospecimens obtained within 72 hours of admission. We compared the proteome and metabolome by the AKI phenotype (i.e., HRS-AKI, ATN) and by AKI recovery (decrease in sCr within 0.3 mg/dL of baseline) using ANCOVA analyses adjusting for demographics and clinical characteristics. We completed Random Forest (RF) analyses to identify metabolites and proteins associated with AKI phenotype and recovery. Lasso regression models were developed to highlight metabolites and proteins could improve diagnostic accuracy. Results: ANCOVA analyses showed no metabolomic or proteomic differences by AKI phenotype while identifying differences by AKI recovery status. Our RF and Lasso analyses showed that metabolomics can improve the diagnostic accuracy of both AKI diagnosis and recovery, and aptamer-based proteomics can enhance the diagnostic accuracy of AKI recovery. Discussion: Our analyses provide novel insight into pathophysiologic pathways, highlighting the metabolomic and proteomic similarities between patients with cirrhosis with HRS-AKI and ATN while also identifying differences between those with and without AKI recovery.PMID:38765962 | PMC:PMC11100905 | DOI:10.21203/rs.3.rs-4344179/v1

Heliyon. 2024 May 4;10(9):e30632. doi: 10.1016/j.heliyon.2024.e30632. eCollection 2024 May 15.ABSTRACTLibidibia ferrea Mart, belonging to the Fabacee family, is a medicinal plant known for its biological properties and production of phenolic compounds. Previous studies reveal the biological activity of its phenolic constituents, making it very promising for the development of new medicines. Seasonality and geographic distribution of species can modify the production of secondary metabolites in Fabaceae species in terms of the preferentially activated metabolic pathways and, consequently, interfere with the medicinal properties of these species. Studying the influence of seasonality on the production of phenolic constituents is essential to establish conditions for "cultivation," species collection, standardization, production, and safety in traditional medicine. This unprecedented study proposed to evaluate the influence of seasonal variations and habitat on the production of phenolic compounds and biological properties of the ethanolic extracts of the stem bark from L. ferrea, whose specimens were collected from the Caatinga and the Atlantic Forest, biomes of Brazil. Antimicrobial activity was determined by broth microdilution. Cytotoxicity was evaluated through a colorimetric assay using MTT. ABTS and DPPH radical reduction methods estimated antioxidant capacities. Folin-Ciocalteu and AlCl3 spectrophotometric methods quantified total phenolics and flavonoids, respectively. In turn, radial diffusion quantified tannin content. PCA score plot and HCA dendogram were obtained by multivariate analysis of 1H NMR data. The cytotoxicity against C6 glioma cells was observed only for Atlantic Forest extracts (EC50 = 0.13-0.5 mg mL-1). These extracts also showed selectivity against Gram-positive bacteria Bacillus subtilis (ATCC 6633) [MICs 500-2000 μg mL-1], B. cereus CCT 0096) [MIC = 250 μg mL-1], Staphylococcus aureus (ATCC 6538) [MICs = 250-500 μg mL-1], S. epidermidis (ATCC 12228) [62.5-1000 μg mL-1], mainly to Staphylococcus sp. Caatinga extracts showed higher production of flavonoids and antioxidants in the summer [7.36 ± 0.19 μg QE mg-1 extract; IC50ABTS = 4.86 ± 0.05 μg mL-1], spring [5.96 ± 0.10 μg QE mg-1 extract; IC50ABTS = 5.96 ± 0.08 μg mL-1 ], winter [4.89 ± 0.25 μg QE mg-1 extract; IC50ABTS = 6.72 ± 0.08 μg mL-1 ]. Regarding habitat, two discriminating compound patterns in the studied biomes were revealed by NMR. The results indicated that the Caatinga biome offers better conditions for activating the production of phenolics [336.34 ± 18.1 μgGAE mg-1 extract], tannins [328.38 ± 30.19 μgTAE mg-1 extract] in the summer and flavonoids in winter, spring, and summer. The extracts that showed the best antioxidant activities were also those from the Caatinga. In turn, extracts from the Atlantic Forest are more promising for discovering antibacterial compounds against Staphylococcus sp and cytotoxic for C6 glioma cells. These findings corroborated the traditional use of L. ferrea bark powder for treating skin wounds and suggest the cytotoxic potential of these extracts for glioblastoma cell lines.PMID:38765074 | PMC:PMC11101816 | DOI:10.1016/j.heliyon.2024.e30632

Front Immunol. 2024 May 3;15:1410365. doi: 10.3389/fimmu.2024.1410365. eCollection 2024.ABSTRACTOBJECTIVE: Seronegative rheumatoid arthritis (RA) is defined as RA without circulating autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies; thus, early diagnosis of seronegative RA can be challenging. Here, we aimed to identify diagnostic biomarkers for seronegative RA by performing lipidomic analyses of sera and urine samples from patients with RA.METHODS: We performed untargeted lipidomic analysis of sera and urine samples from 111 RA patients, 45 osteoarthritis (OA) patients, and 25 healthy controls (HC). These samples were divided into a discovery cohort (n = 97) and a validation cohort (n = 84). Serum samples from 20 patients with systemic lupus erythematosus (SLE) were also used for validation.RESULTS: The serum lipidome profile of RA was distinguishable from that of OA and HC. We identified a panel of ten serum lipids and three urine lipids in the discovery cohort that showed the most significant differences. These were deemed potential lipid biomarker candidates for RA. The serum lipid panel was tested using a validation cohort; the results revealed an accuracy of 79%, a sensitivity of 71%, and a specificity of 86%. Both seropositive and seronegative RA patients were differentiated from patients with OA, SLE, and HC. Three urinary lipids showing differential expression between RA from HC were identified with an accuracy of 84%, but they failed to differentiate RA from OA. There were five lipid pathways that differed between seronegative and seropositive RA.CONCLUSION: Here, we identified a panel of ten serum lipids as potential biomarkers that can differentiate RA from OA and SLE, regardless of seropositivity. In addition, three urinary lipids had diagnostic utility for differentiating RA from HC.PMID:38765010 | PMC:PMC11099275 | DOI:10.3389/fimmu.2024.1410365

Food Chem X. 2024 Apr 26;22:101423. doi: 10.1016/j.fochx.2024.101423. eCollection 2024 Jun 30.ABSTRACTColored potatoes have many health benefits because they are rich in anthocyanins. However, the constituent and property of anthocyanins in colored potatoes have not been systematically studied yet. Herein, metabolomic analysis was carried out to investigate the chemical composition of anthocyanins in the four different colored potatoes. After that, the extract and purification conditions, and the stability of the anthocyanins were further studied. The results indicated that the four colored potatoes contained abundant of polyphenols, flavonoids, and anthocyanins. Cyanidin, delphinidin, and malvidin were identified as the major anthocyanidins in purple potatoes, whereas red potatoes were mainly consisted of pelargonidin and its derivatives. 84.47 mg C3GE/100 g DW of anthocyanins was obtained at the optimal conditions, which could be effectively purified macroporous resin of D101. Moreover, the anthocyanins were sensitive to pH, temperature, light, redox agents, and divalent or trivalent metal ions, but stable to sugars and univalent metal ions.PMID:38764782 | PMC:PMC11101687 | DOI:10.1016/j.fochx.2024.101423

World J Gastroenterol. 2024 May 14;30(18):2454-2466. doi: 10.3748/wjg.v30.i18.2454.ABSTRACTBACKGROUND: Drug-induced liver injury (DILI) is one of the most common adverse events of medication use, and its incidence is increasing. However, early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.AIM: To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.METHODS: Saliva samples from 31 DILI patients and 35 healthy controls (HCs) were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry. Subsequent analyses, including partial least squares-discriminant analysis modeling, t tests and weighted metabolite coexpression network analysis (WMCNA), were conducted to identify key differentially expressed metabolites (DEMs) and metabolite sets. Furthermore, we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction. The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.RESULTS: We found 247 differentially expressed salivary metabolites between the DILI group and the HC group. Using WMCNA, we identified a set of 8 DEMs closely related to liver injury for further prediction testing. Interestingly, the distinct separation of DILI patients and HCs was achieved with five metabolites, namely, 12-hydroxydodecanoic acid, 3-hydroxydecanoic acid, tetradecanedioic acid, hypoxanthine, and inosine (area under the curve: 0.733-1).CONCLUSION: Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients. Our study may provide a potentially feasible and noninvasive diagnostic method for DILI, but further validation is needed.PMID:38764769 | PMC:PMC11099387 | DOI:10.3748/wjg.v30.i18.2454

Phytochem Anal. 2024 May 19. doi: 10.1002/pca.3362. Online ahead of print.ABSTRACTINTRODUCTION: Codonopsis Radix is a beneficial traditional Chinese medicine, and triterpenoid are the major bioactive constituents. Codonopsis pilosula var. modesta (Nannf.) L.T.Shen (CPM) is a precious variety of Codonopsis Radix, which is distributed at high mountain areas. The environment plays an important role in the synthesis and metabolism of active ingredients in medicinal plants, but there is no report elaborating on the effect of altitude on terpenoid metabolites accumulation in CPM.OBJECTIVES: This study aims to analyse the effects of altitude on triterpenoid biosynthetic pathways and secondary metabolite accumulation in CPM.MATERIAL AND METHODS: The untargeted metabolomics based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and 10 triterpenoids based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method were analysed at the low-altitude (1480 m) and high-altitude (2300 m) CPM fresh roots. The transcriptome based on high-throughput sequencing technology were combined to analyse the different altitude CPM triterpenoid biosynthetic pathways.RESULTS: A total of 17,351 differentially expressed genes (DEGs) and 55 differentially accumulated metabolites (DAMs) were detected from the different altitude CPM, and there are significant differences in the content of the 10 triterpenoids. The results of transcriptome study showed that CPM could significantly up-regulate the gene expression levels of seven key enzymes in the triterpenoid biosynthetic pathway.CONCLUSIONS: The CPM at high altitude is more likely to accumulate triterpenes than those at low altitude, which was related to the up-regulation of the gene expression levels of seven key enzymes. These results expand our understanding of how altitude affects plant metabolite biosynthesis.PMID:38764207 | DOI:10.1002/pca.3362

J Trauma Acute Care Surg. 2024 May 20. doi: 10.1097/TA.0000000000004342. Online ahead of print.ABSTRACTBACKGROUND: Platelets are well known for their roles in hemostasis, but they also play a key role in thromboinflammatory pathways by regulating endothelial health, stimulating angiogenesis, and mediating host defense through both contact dependent and independent signaling. When activated, platelets degranulate releasing multiple active substances. We hypothesized that the soluble environment formed by trauma platelet releasates attenuates thromboinflammation via mitigation of trauma induced endothelial permeability and metabolomic reprogramming.METHODS: Blood was collected from injured and healthy patients to generate platelet releasates and plasma in parallel. Permeability of endothelial cells when exposed to trauma platelet releasates (TPR) and plasma (TP) was assessed via resistance measurement by Electric Cell-substrate Impedance Sensing (ECIS). Endothelial cells treated with TPR and TP were subjected to mass spectrometry-based metabolomics.RESULTS: TP increased endothelial permeability, whereas TPR decreased endothelial permeability when compared to untreated cells. When TP and TPR were mixed ex vivo, TPR mitigated TP-induced permeability, with significant increase in AUC compared to TP alone. Metabolomics of TPR and TP demonstrated disrupted redox reactions and anti-inflammatory mechanisms.CONCLUSION: TPRs provide endothelial barrier protection against TP-induced endothelial permeability. Our findings highlight a potential beneficial action of activated platelets on the endothelium in injured patients through disrupted redox reactions and increased antioxidants. Our findings support that soluble signaling from platelet degranulation may mitigate the endotheliopathy of trauma. The clinical implications of this are that activated platelets may prove a promising therapeutic target in the complex integration of thrombosis, endotheliopathy, and inflammation in trauma.LEVEL OF EVIDENCE: Prognostic/Epidemiological, Level III.PMID:38764145 | DOI:10.1097/TA.0000000000004342

Carbohydr Polym. 2024 Aug 15;338:122168. doi: 10.1016/j.carbpol.2024.122168. Epub 2024 Apr 21.ABSTRACTEnzymatic functionalization of oligosaccharides is a useful and environmentally friendly way to expand their structural chemical space and access to a wider range of applications in the health, food, feed, cosmetics and other sectors. In this work, we first tested the laccase/TEMPO system to generate oxidized forms of cellobiose and methyl β-D-cellobiose, and obtained high yields of novel anionic disaccharides (>60 %) at pH 6.0. Laccase/TEMPO system was then applied to a mix of cellooligosaccharides and to pure D-cellopentaose. The occurrence of carbonyl and carboxyl groups in the oxidation products was shown by LC-HRMS, MALDI-TOF and reductive amination of the carbonyl groups was attempted with p-toluidine a low molar mass amine to form the Schiff base, then reduced by 2-picoline borane to generate a more stable amine bond. The new grafted products were characterized by LC-HRMS, LC-UV-MS/MS and covalent grafting was evidenced. Next, the same procedure was adopted to successfully graft a dye, the rhodamine 123, larger in size than toluidine. This two-step chemo-enzymatic approach, never reported before, for functionalization of oligosaccharides, offers attractive opportunities to anionic cellooligosaccharides and derived glucoconjugates of interest for biomedical or neutraceutical applications. It also paves the way for more environmentally-friendly cellulose fabric staining procedures.PMID:38763718 | DOI:10.1016/j.carbpol.2024.122168

Food Res Int. 2024 Jul;187:114455. doi: 10.1016/j.foodres.2024.114455. Epub 2024 May 3.ABSTRACTDendrobium officinale flower tea (DFT) is a traditional health product of geographical identity known for its unique aroma and taste. The effects of different drying methods on sensory properties, metabolic profiles and antioxidant activity of DFT were compared using sensomics and metabolomics approaches. Twenty-seven aroma-active compounds were identified and more than half of the volatiles responsible for the "green" and "floral" scent lost after drying. Sensory evaluations revealed that vacuum freeze-dried DFT showed a significant preference in taste and fifty-eight metabolites with higher levels of glutamine were observed, possibly contributing to a "fresh" taste and increased preference. Among the three drying methods, natural air drying retained the fresh flower scent better, while freeze drying preserved the color and shape of the flowers better and enhanced the taste and antioxidant activity of DFT. The research results may provide a foundation for the selection of DFT processing method and quality detection.PMID:38763691 | DOI:10.1016/j.foodres.2024.114455