PubMed

Light Sci Appl. 2024 Feb 20;13(1):52. doi: 10.1038/s41377-024-01394-5.ABSTRACTRaman spectroscopy has tremendous potential for material analysis with its molecular fingerprinting capability in many branches of science and technology. It is also an emerging omics technique for metabolic profiling to shape precision medicine. However, precisely attributing vibration peaks coupled with specific environmental, instrumental, and specimen noise is problematic. Intelligent Raman spectral preprocessing to remove statistical bias noise and sample-related errors should provide a powerful tool for valuable information extraction. Here, we propose a novel Raman spectral preprocessing scheme based on self-supervised learning (RSPSSL) with high capacity and spectral fidelity. It can preprocess arbitrary Raman spectra without further training at a speed of ~1 900 spectra per second without human interference. The experimental data preprocessing trial demonstrated its excellent capacity and signal fidelity with an 88% reduction in root mean square error and a 60% reduction in infinite norm ([Formula: see text]) compared to established techniques. With this advantage, it remarkably enhanced various biomedical applications with a 400% accuracy elevation (ΔAUC) in cancer diagnosis, an average 38% (few-shot) and 242% accuracy improvement in paraquat concentration prediction, and unsealed the chemical resolution of biomedical hyperspectral images, especially in the spectral fingerprint region. It precisely preprocessed various Raman spectra from different spectroscopy devices, laboratories, and diverse applications. This scheme will enable biomedical mechanism screening with the label-free volumetric molecular imaging tool on organism and disease metabolomics profiling with a scenario of high throughput, cross-device, various analyte complexity, and diverse applications.PMID:38374161 | DOI:10.1038/s41377-024-01394-5

Nat Commun. 2024 Feb 19;15(1):1520. doi: 10.1038/s41467-024-45782-2.ABSTRACTFatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase expression, but the underlying mechanisms have remained unclear. Here, we show that endogenous and microbiota-dependent small molecule signals promote lipid desaturation via the nuclear receptor NHR-49/PPARα in C. elegans. Untargeted metabolomics of a β-oxidation mutant, acdh-11, in which expression of the stearoyl-CoA desaturase FAT-7/SCD1 is constitutively increased, revealed accumulation of a β-cyclopropyl fatty acid, becyp#1, that potently activates fat-7 expression via NHR-49. Biosynthesis of becyp#1 is strictly dependent on expression of cyclopropane synthase by associated bacteria, e.g., E. coli. Screening for structurally related endogenous metabolites revealed a β-methyl fatty acid, bemeth#1, which mimics the activity of microbiota-dependent becyp#1 but is derived from a methyltransferase, fcmt-1, that is conserved across Nematoda and likely originates from bacterial cyclopropane synthase via ancient horizontal gene transfer. Activation of fat-7 expression by these structurally similar metabolites is controlled by distinct mechanisms, as microbiota-dependent becyp#1 is metabolized by a dedicated β-oxidation pathway, while the endogenous bemeth#1 is metabolized via α-oxidation. Collectively, we demonstrate that evolutionarily related biosynthetic pathways in metazoan host and associated microbiota converge on NHR-49/PPARα to regulate fat desaturation.PMID:38374083 | DOI:10.1038/s41467-024-45782-2

Gene. 2024 Jan 30;893:147927. doi: 10.1016/j.gene.2023.147927. Epub 2023 Oct 30.ABSTRACTRecent semi-targeted metabolomics studies have highlighted a number of metabolites in wheat that associate with leaf rust resistance genes and/or rust infection. Here, we report the structural characterization of a novel glycosylated and partially saturated apocarotenoid, reminiscent of a reduced form of mycorradicin, (6E,8E,10E)-4,9-dimethyl-12-oxo-12-((3,4,5-trihydroxy-6-(2-hydroxyethoxy)tetrahydro-2H-pyran-2-yl)methoxy)-3-((3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)dodeca-6,8,10-trienoic acid, isolated from Triticum aestivum L. (Poaceae) variety 'Thatcher' (Tc) flag leaves. While its accumulation was not associated with any of Lr34, Lr67 or Lr22a resistance genes, infection of Tc with leaf rust was found to deplete it, consistent with the idea of this metabolite being a glycosylated-storage form of an apocarotenoid of possible relevance to plant defense. A comparative analysis of wheat transcriptomic changes shows modulation of terpenoid, carotenoid, UDP-glycosyltransferase and glycosylase -related gene expression profiles, consistent with anticipated biosynthesis and degradation mechanisms. However, details of the exact nature of the relevant pathways remain to be validated in the future. Together these findings highlight another example of the breadth of unique metabolites underlying plant host-fungal pathogen interactions.PMID:38374023 | DOI:10.1016/j.gene.2023.147927

Mol Hortic. 2024 Feb 20;4(1):6. doi: 10.1186/s43897-024-00081-8.ABSTRACTPutrescine plays a role in superficial scald development during the cold storage of pear fruit. However, the molecular mechanism behind this phenomenon has not been un-fully clarified until recently. In this study, a conjoint analysis of metabolites and gene expression profiles in the putrescine-metabolic pathway of P. bretschneideri Rehd. fruit followed by experimental validation revealed that PbrADC1, forming a homodimer in the chloroplast, was involved in putrescine biosynthesis and thus fruit chilling resistance. Additionally, the substrate-binding residue Cys546 in PbrADC1, whose activity was modified by H2O2, played a crucial role in arginine decarboxylation into agmatine. Through a combined analysis of the distribution of cis-acting elements in the PbrADC1 promoter as well as the expression profiles of related transcription factors (TFs), several TFs were identified as upstream regulators of PbrADC1 gene. Further investigation revealed that the nuclear PbrWRKY62 could directly bind to the W-box elements in the PbrADC1 promoter, activate its expression, enhance putrescine accumulation, and thus increase fruit chilling tolerance. In conclusion, our results suggest that the PbrWRKY62-PbrADC1 module is involved in the development of superficial scald in P. bretschneideri Rehd. fruit via regulating putrescine biosynthesis. Consequently, these findings could serve as valuable genetic resources for breeding scald-resistant pear fruit.PMID:38373989 | DOI:10.1186/s43897-024-00081-8

Alzheimers Res Ther. 2024 Feb 19;16(1):41. doi: 10.1186/s13195-024-01402-1.ABSTRACTBACKGROUND: The relationship between periodontitis and Alzheimer's disease (AD) has attracted more attention recently, whereas profiles of subgingival microbiomes and gingival crevicular fluid (GCF) metabolic signatures in AD patients have rarely been characterized; thus, little evidence exists to support the oral-brain axis hypothesis. Therefore, our study aimed to characterize both the microbial community of subgingival plaque and the metabolomic profiles of GCF in patients with AD and amnestic mild cognitive impairment (aMCI) for the first time.METHODS: This was a cross-sectional study. Clinical examinations were performed on all participants. The microbial community of subgingival plaque and the metabolomic profiles of GCF were characterized using the 16S ribosomal RNA (rRNA) gene high-throughput sequencing and liquid chromatography linked to tandem mass spectrometry (LC-MS/MS) analysis, respectively.RESULTS: Thirty-two patients with AD, 32 patients with aMCI, and 32 cognitively normal people were enrolled. The severity of periodontitis was significantly increased in AD patients compared with aMCI patients and cognitively normal people. The 16S rRNA gene sequencing results showed that the relative abundances of 16 species in subgingival plaque were significantly correlated with cognitive function, and LC-MS/MS analysis identified a total of 165 differentially abundant metabolites in GCF. Moreover, multiomics Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) analysis revealed that 19 differentially abundant metabolites were significantly correlated with Veillonella parvula, Dialister pneumosintes, Leptotrichia buccalis, Pseudoleptotrichia goodfellowii, and Actinomyces massiliensis, in which galactinol, sn-glycerol 3-phosphoethanolamine, D-mannitol, 1 h-indole-1-pentanoic acid, 3-(1-naphthalenylcarbonyl)- and L-iditol yielded satisfactory accuracy for the predictive diagnosis of AD progression.CONCLUSIONS: This is the first combined subgingival microbiome and GCF metabolome study in patients with AD and aMCI, which revealed that periodontal microbial dysbiosis and metabolic disorders may be involved in the etiology and progression of AD, and the differential abundance of the microbiota and metabolites may be useful as potential markers for AD in the future.PMID:38373985 | DOI:10.1186/s13195-024-01402-1

Cancer Lett. 2024 Feb 17:216724. doi: 10.1016/j.canlet.2024.216724. Online ahead of print.ABSTRACTCD24 is a well-characterized breast cancer (BC) stem cell (BCSC) marker. Primary breast tumor cells having CD24-negativity together with CD44-positivity is known to maintain high metastatic potential. However, the functional role of CD24 gene in triple-negative BC (TNBC), an aggressive subtype of BC, is not well understood. While the significance of CD24 in regulating immune pathways is well recognized in previous studies, the significance of CD24 low expression in onco-signaling and metabolic rewiring is largely unknown. Using CD24 knock-down and over-expression TNBC models, our in vitro and in vivo analysis suggest that CD24 is a tumor suppressor in metastatic TNBC. Comprehensive in silico gene expression analysis of breast tumors followed by lipidomic and metabolomic analyses of CD24-modulated cells revealed that CD24 negativity induces mitochondrial oxidative phosphorylation and reprograms TNBC metabolism toward the fatty acid beta-oxidation (FAO) pathway. CD24 silencing activates PPARα-mediated regulation of FAO in TNBC cells. Further analysis using reverse-phase protein array and its validation using CD24-modulated TNBC cells and xenograft models nominated CD24-NF-κB-CPT1A signaling pathway as the central regulatory mechanism of CD24-mediated FAO activity. Overall, our study proposes a novel role of CD24 in metabolic reprogramming that can open new avenues for the treatment strategies for patients with metastatic TNBC.PMID:38373689 | DOI:10.1016/j.canlet.2024.216724

J Ethnopharmacol. 2024 Feb 17:117910. doi: 10.1016/j.jep.2024.117910. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: For centuries, Shaoyao-Gancao-Fuzi decoction (SGFD) has been a reliable traditional Chinese medicine for treating rheumatoid arthritis (RA). Despite its long history of use, the specific active components and underlying mechanisms of its therapeutic effects have yet to be fully understood.AIM OF THE STUDY: The aim of this study was to investigate the active ingredients and therapeutic effects of SGFD on RA, and to further understand its underlying mechanism.MATERIALS AND METHODS: The chemical constituents in SGFD extract and in rat serum after oral administration of SGFD were identified and evaluated using ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF/MS) together with various data-processing methods, respectively. The efficacy of SGFD was assessed by using an adjuvant-induced arthritis (AIA) rat model and lipopolysaccharide-stimulated RAW 264.7 cell. Subsequently, cell metabolomic was conducted to clarify the potential biomarkers and pathways. ELISA, RT-qPCR, and WB were used to verify the anti-arthritis mechanism of SGFD.RESULTS: A total of 65 chemical constituents were identified in SGFD. 17 active components were distinguished in rat serum samples, of which 13 may be the main active ingredients for SGFD treatment of RA. The remarkable efficacy of SGFD in reducing the symptoms of RA is evident through its ability to alleviate the redness and swelling of the affected paws, as well as reduce the infiltration of inflammatory cells. Cell experiments revealed that rat serum of SGFD reduced IL-1β, IL-6, and TNF-α secretion in RAW 264.7 cells. 27 potential biomarkers were identified through cell metabolomics analysis. The arachidonic acid (AA) metabolism signaling pathway was activated in RA, which could be reversed by rat serum of SGFD. SGFD effectively inhibited the expression and transformation of AA by downregulating the expression of key enzymes, including phospholipase A and cyclooxygenase.CONCLUSION: SGFD may ameliorate RA symptoms by regulating the AA-PGH2-PGE2/PGF2α pathway. The main active components include songorine, fuziline, neoline, albiflorin, paeoniflorin, liquiritin, benzoylmesaconine, isoformononetin, liquiritigenin, isoliquiritigenin, formononetin, glycyrrhizic acid, and glycyrrhetinic acid.PMID:38373664 | DOI:10.1016/j.jep.2024.117910

Environ Res. 2024 Feb 17:118485. doi: 10.1016/j.envres.2024.118485. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS) have already drawn a lot of attention for their accumulation and reproductive toxicity in organisms. Perfluorooctanoic acid (PFOA) and perfluorooctanoic sulfonate (PFOS), two representative PFAS, are toxic to humans and animals. Due to their widespread use in environmental media with multiple toxicities, PFOA and PFOS have been banned in numerous countries, and many substitutes have been produced to meet market requirements. Unfortunately, most alternatives to PFOA and PFOS have proven to be cumulative and highly toxic. Of the reported multiple organ toxicities, reproductive toxicity deserves special attention. It has been confirmed through epidemiological studies that PFOS and PFOA are not only associated with reduced testosterone levels in humans, but also with an association with damage to the integrity of the blood testicular barrier. In addition, for women, PFOA and PFOS are correlated with abnormal sex hormone levels, and increase the risk of infertility and abnormal menstrual cycle. Nevertheless, there is controversial evidence on the epidemiological relationship that exists between PFOA and PFOS as well as sperm quality and reproductive hormones, while the evidence from animal studies is relatively consistent. Based on the published papers, the potential toxicity mechanisms for PFOA, PFOS and their substitutes were reviewed. For males, PFOA and PFOS may produce reproductive toxicity in the following five ways: (1) Apoptosis and autophagy in spermatogenic cells; (2) Apoptosis and differentiation disorders of Leydig cells; (3) Oxidative stress in sperm and disturbance of Ca2+ channels in sperm membrane; (4) Degradation of delicate intercellular junctions between Sertoli cells; (5) Activation of brain nuclei and shift of hypothalamic metabolome. For females, PFOA and PFOS may produce reproductive toxicity in the following five ways: (1) Damage to oocytes through oxidative stress; (2) Inhibition of corpus luteum function; (3) Inhibition of steroid hormone synthesis; (4) Damage to follicles by affecting gap junction intercellular communication (GJIC); (5) Inhibition of placental function. Besides, PFAS substitutes show similar reproductive toxicity with PFOA and PFOS, and are even more toxic to the placenta. Finally, based on the existing knowledge, future developments and direction of efforts in this field are suggested.PMID:38373549 | DOI:10.1016/j.envres.2024.118485

Sci Total Environ. 2024 Feb 17:170980. doi: 10.1016/j.scitotenv.2024.170980. Online ahead of print.ABSTRACTGlobal rice cultivation significantly contributes to anthropogenic methane emissions. The methane emissions are caused by methane-producing microorganisms (methanogenic archaea) that are favoured by the anoxic conditions of paddy soils and small carbon molecules released from rice roots. However, different rice cultivars are associated with differences in methane emission rates suggesting that there is a considerable natural variation in this trait. Starting from the hypothesis that sugar allocation within a plant is an important factor influencing both yields and methane emissions, the aim of this study was to produce high-yielding rice lines associated with low methane emissions. In this study, the offspring (here termed progeny lines) of crosses between a newly characterized low-methane rice variety, Heijing 5, and three high-yielding elite varieties, Xiushui, Huayu and Jiahua, were selected for combined low-methane and high-yield properties. Analyses of total organic carbon and carbohydrates showed that the progeny lines stored more carbon in above-ground tissues than the maternal elite varieties. Also, metabolomic analysis of rhizospheric soil surrounding the progeny lines showed reduced levels of glucose and other carbohydrates. The carbon allocation, from roots to shoots, was further supported by a transcriptome analysis using massively parallel sequencing of mRNAs that demonstrated elevated expression of the sugar transporters SUT-C and SWEET in the progeny lines as compared to the parental varieties. Furthermore, measurement of methane emissions from plants, grown in greenhouse as well as outdoor rice paddies, showed a reduction in methane emissions by approximately 70 % in the progeny lines compared to the maternal elite varieties. Taken together, we report here on three independent low-methane-emission rice lines with high yield potential. We also provide a first molecular characterisation of the progeny lines that can serve as a foundation for further studies of candidate genes involved in sugar allocation and reduced methane emissions from rice cultivation.PMID:38373456 | DOI:10.1016/j.scitotenv.2024.170980

Biochem Biophys Res Commun. 2024 Feb 13;703:149683. doi: 10.1016/j.bbrc.2024.149683. Online ahead of print.ABSTRACTOsteoarthritis is the most common chronic joint disease, characterized by the abnormal remodeling of joint tissues including articular cartilage and subchondral bone. However, there are currently no therapeutic drug targets to slow the progression of disease because disease pathogenesis is largely unknown. Thus, the goals of this study were to identify metabolic differences between articular cartilage and subchondral bone, compare the metabolic shifts in osteoarthritic grade III and IV tissues, and spatially map metabolic shifts across regions of osteoarthritic hip joints. Articular cartilage and subchondral bone from 9 human femoral heads were obtained after total joint arthroplasty, homogenized and metabolites were extracted for liquid chromatography-mass spectrometry analysis. Metabolomic profiling revealed that distinct metabolic endotypes exist between osteoarthritic tissues, late-stage grades, and regions of the diseased joint. The pathways that contributed the most to these differences between tissues were associated with lipid and amino acid metabolism. Differences between grades were associated with nucleotide, lipid, and sugar metabolism. Specific metabolic pathways such as glycosaminoglycan degradation and amino acid metabolism, were spatially constrained to more superior regions of the femoral head. These results suggest that radiography-confirmed grades III and IV osteoarthritis are associated with distinct global metabolic and that metabolic shifts are not uniform across the joint. The results of this study enhance our understanding of osteoarthritis pathogenesis and may lead to potential drug targets to slow, halt, or reverse tissue damage in late stages of osteoarthritis.PMID:38373382 | DOI:10.1016/j.bbrc.2024.149683

Environ Sci Technol. 2024 Feb 19. doi: 10.1021/acs.est.3c10490. Online ahead of print.ABSTRACTAlzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease, which is currently diagnosed via clinical symptoms and nonspecific biomarkers (such as Aβ1-42, t-Tau, and p-Tau) measured in cerebrospinal fluid (CSF), which alone do not provide sufficient insights into disease progression. In this pilot study, these biomarkers were complemented with small-molecule analysis using non-target high-resolution mass spectrometry coupled with liquid chromatography (LC) on the CSF of three groups: AD, mild cognitive impairment (MCI) due to AD, and a non-demented (ND) control group. An open-source cheminformatics pipeline based on MS-DIAL and patRoon was enhanced using CSF- and AD-specific suspect lists to assist in data interpretation. Chemical Similarity Enrichment Analysis revealed a significant increase of hydroxybutyrates in AD, including 3-hydroxybutanoic acid, which was found at higher levels in AD compared to MCI and ND. Furthermore, a highly sensitive target LC-MS method was used to quantify 35 bile acids (BAs) in the CSF, revealing several statistically significant differences including higher dehydrolithocholic acid levels and decreased conjugated BA levels in AD. This work provides several promising small-molecule hypotheses that could be used to help track the progression of AD in CSF samples.PMID:38373301 | DOI:10.1021/acs.est.3c10490

J Agric Food Chem. 2024 Feb 19. doi: 10.1021/acs.jafc.3c07768. Online ahead of print.ABSTRACTSugarcane smut, caused by Sporisorium scitamineum, poses a severe threat to sugarcane production. The genetic basis of sugarcane resistance to S. scitamineum remains elusive. A comparative transcriptomic and metabolomic study was conducted on two wild Saccharum species of S. spontaneum with contrast smut resistance. Following infection, the resistant line exhibited greater down-regulation of genes and metabolites compared to the susceptible line, indicating distinct biological processes. Lignan and lignin biosynthesis and SA signal transduction were activated in the resistant line, while flavonoid biosynthesis and auxin signal transduction were enhanced in the susceptible line. TGA2.2 and ARF14 were identified as playing positive and negative roles, respectively, in plant defense. Exogenous auxin application significantly increased the susceptibility of S. spontaneum to S. scitaminum. This study established the significant switching of defense signaling pathways in contrast-resistant S. spontaneum following S. scitamineum infection, offering a hypothetical model and candidate genes for further research into sugarcane smut disease.PMID:38373255 | DOI:10.1021/acs.jafc.3c07768

Pancreas. 2024 Feb 20. doi: 10.1097/MPA.0000000000002304. Online ahead of print.ABSTRACTOBJECTIVE: A significant number of patients experience early recurrence after surgical resection for pancreatic ductal adenocarcinoma (PDAC), negating the benefit of surgery. The present study conducted clinicopathologic and metabolomic analyses to explore the factors associated with the early recurrence of PDAC.MATERIALS AND METHODS: Patients who underwent pancreatectomy for PDAC at Kagawa University Hospital between 2011 and 2020 were enrolled. Tissue samples of PDAC and nonneoplastic pancreas were collected and frozen immediately after resection. Charged metabolites were quantified by capillary electrophoresis-mass spectrometry. Patients who relapsed within 1 year were defined as the early recurrence group.RESULTS: Frozen tumor tissue and nonneoplastic pancreas were collected from 79 patients. The clinicopathologic analysis identified 11 predictive factors, including preoperative carbohydrate antigen 19-9 levels. The metabolomic analysis revealed that only hypotaurine was a significant risk factor for early recurrence. A multivariate analysis, including clinical and metabolic factors, showed that carbohydrate antigen 19-9 and hypotaurine were independent risk factors for early recurrence (P = 0.045 and P = 0.049, respectively). The recurrence-free survival rate 1 year after surgery with both risk factors was only 25%.CONCLUSIONS: Our results suggested that tumor hypotaurine is a potential metabolite associated with early recurrence. Carbohydrate antigen 19-9 and hypotaurine showed a vital utility for predicting early recurrence.PMID:38373081 | DOI:10.1097/MPA.0000000000002304

Environ Sci Technol. 2024 Feb 19. doi: 10.1021/acs.est.3c09014. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFASs) are widely used in industrial production, causing potential health risks to the residents living around chemical industrial plants; however, the lack of data on population exposure and adverse effects impedes our understanding and ability to prevent risks. In this study, we performed screening and association analysis on exogenous PFAS pollutants and endogenous small-molecule metabolites in the serum of elderly residents living near industrial plants. Exposure levels of 11 legacy and novel PFASs were determined. PFOA and PFOS were major contributors, and PFNA, PFHxS, and 6:2 Cl-PFESA also showed high detection frequencies. Association analysis among PFASs and 287 metabolites identified via non-target screening was performed with adjustments of covariates and false discovery rate. Strongly associated metabolites were predominantly lipid and lipid-like molecules. Steroid hormone biosynthesis, primary bile acid biosynthesis, and fatty-acid-related pathways, including biosynthesis of unsaturated fatty acids, linoleic acid metabolism, α-linolenic acid metabolism, and fatty acid biosynthesis, were enriched as the metabolic pathways associated with mixed exposure to multiple PFASs, providing metabolic explanation and evidence for the potential mediating role of adverse health effects as a result of PFAS exposure. Our study achieved a comprehensive screening of PFAS exposure and associated metabolic profiling, demonstrating the promising application for integrated analysis of exposome and metabolome.PMID:38373080 | DOI:10.1021/acs.est.3c09014

J Proteome Res. 2024 Feb 19. doi: 10.1021/acs.jproteome.3c00485. Online ahead of print.ABSTRACTHuanglongbing (HLB) is a fatal citrus disease that is currently threatening citrus varieties worldwide. One putative causative agent, Candidatus Liberibacter asiaticus (CLas), is vectored by Diaphorina citri, known as the Asian citrus psyllid (ACP). Understanding the details of CLas infection in HLB disease has been hindered by its Candidatus nature and the inability to confidently detect it in diseased trees during the asymptomatic stage. To identify early changes in citrus metabolism in response to inoculation of CLas using its natural psyllid vector, leaves from Madam Vinous sweet orange (Citrus sinensis (L.) Osbeck) trees were exposed to CLas-positive ACP or CLas-negative ACP and longitudinally analyzed using transcriptomics (RNA sequencing), proteomics (liquid chromatography-tandem mass spectrometry; data available in Dryad: 10.25338/B83H1Z), and metabolomics (proton nuclear magnetic resonance). At 4 weeks postexposure (wpe) to psyllids, the initial HLB plant response was primarily to the ACP and, to a lesser extent, the presence or absence of CLas. Additionally, analysis of 4, 8, 12, and 16 wpe identified 17 genes and one protein as consistently differentially expressed between leaves exposed to CLas-positive ACP versus CLas-negative ACP. This study informs identification of early detection molecular targets and contributes to a broader understanding of vector-transmitted plant pathogen interactions.PMID:38373055 | DOI:10.1021/acs.jproteome.3c00485

FASEB J. 2024 Feb 29;38(4):e23478. doi: 10.1096/fj.202302163R.ABSTRACTCarnitine derivatives of disease-specific acyl-CoAs are the diagnostic hallmark for long-chain fatty acid β-oxidation disorders (lcFAOD), including carnitine shuttle deficiencies, very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and mitochondrial trifunctional protein deficiency (MPTD). The exact consequence of accumulating lcFAO-intermediates and their influence on cellular lipid homeostasis is, however, still unknown. To investigate the fate and cellular effects of the accumulating lcFAO-intermediates and to explore the presence of disease-specific markers, we used tracer-based lipidomics with deuterium-labeled oleic acid (D9-C18:1) in lcFAOD patient-derived fibroblasts. In line with previous studies, we observed a trend towards neutral lipid accumulation in lcFAOD. In addition, we detected a direct connection between the chain length and patterns of (un)saturation of accumulating acylcarnitines and the various enzyme deficiencies. Our results also identified two disease-specific candidate biomarkers. Lysophosphatidylcholine(14:1) (LPC(14:1)) was specifically increased in severe VLCADD compared to mild VLCADD and control samples. This was confirmed in plasma samples showing an inverse correlation with enzyme activity, which was better than the classic diagnostic marker C14:1-carnitine. The second candidate biomarker was an unknown lipid class, which we identified as S-(3-hydroxyacyl)cysteamines. We hypothesized that these were degradation products of the CoA moiety of accumulating 3-hydroxyacyl-CoAs. S-(3-hydroxyacyl)cysteamines were significantly increased in LCHADD compared to controls and other lcFAOD, including MTPD. Our findings suggest extensive alternative lipid metabolism in lcFAOD and confirm that lcFAOD accumulate neutral lipid species. In addition, we present two disease-specific candidate biomarkers for VLCADD and LCHADD, that may have significant relevance for disease diagnosis, prognosis, and monitoring.PMID:38372965 | DOI:10.1096/fj.202302163R

Parasite Immunol. 2024 Feb;46(2):e13026. doi: 10.1111/pim.13026.ABSTRACTES-62, a protein secreted by Acanthocheilonema viteae, is anti-inflammatory by virtue of covalently attached phosphorylcholine (PC) residues and thus a library of drug-like small molecule analogues (SMAs) based on its PC moieties has been designed for therapeutic purposes. Two members, SMAs 11a and 12b, were previously found to suppress production of pro-inflammatory cytokines by mouse bone marrow-derived macrophages (BMMs) exposed to cytosine-phosphate-guanosine oligodeoxynucleotides (CpG), agonists for Toll-like receptor 9. In order to explore the mechanism of action underlying such activities, an untargeted mass spectrometry-based metabolomics screen was undertaken. Stimulation of BMMs with CpG produced significant metabolic changes relating to glycolysis and the TCA cycle but the SMAs had little impact on this. Also, the SMAs did not promote alterations in metabolites known to be associated with macrophage M1/M2 polarization. Rather, BMMs exposed to SMAs 11a or 12b prior to CpG treatment, or even alone, revealed downregulation of metabolites of creatine, a molecule whose major role is in the transport of high energy phosphate from the mitochondria to the cytosol. These data therefore provide insight into a possible mechanism of action of molecules with significant therapeutic potential that has not previously been described for parasitic worm products.PMID:38372616 | DOI:10.1111/pim.13026

Analyst. 2024 Feb 19. doi: 10.1039/d3an01723k. Online ahead of print.ABSTRACTArachidonic acid metabolites are a family of bioactive lipids derived from membrane phospholipids. They are involved in cancer progression, but arachidonic acid metabolite profiles and their related biosynthetic pathways remain uncertain in colorectal cancer (CRC). To compare the arachidonic acid metabolite profiles between CRC patients and healthy controls, quantification was performed using a liquid chromatography-mass spectrometry-based analysis of serum and tissue samples. Metabolomics analysis delineated the distinct oxidized lipids in CRC patients and healthy controls. Prostaglandin (PGE2)-derived metabolites were increased, suggesting that the PGE2 biosynthetic pathway was upregulated in CRC. The qRT-PCR and immunohistochemistry analyses showed that the expression level of PGE2 synthases, the key protein of PGE2 biosynthesis, was upregulated in CRC and positively correlated with the CD68+ macrophage density and CRC development. Our study indicates that the PGE2 biosynthetic pathway is associated with macrophage infiltration and progression of CRC tumors.PMID:38372525 | DOI:10.1039/d3an01723k

Front Endocrinol (Lausanne). 2024 Feb 2;14:1332406. doi: 10.3389/fendo.2023.1332406. eCollection 2023.ABSTRACTAIMS: This study aimed to assess the gingival crevicular fluid (GCF) microbiome and metabolome of adults with type 1 diabetes (T1D) treated with continuous subcutaneous insulin infusion (CSII).METHODS: In this cross-sectional study, the GCF of adults with T1D treated with CSII and non-diabetic controls were sampled, and metagenomic/metabolomic analyses were performed.RESULTS: In total, 65 participants with T1D and 45 healthy controls with a mean age of 27.05 ± 5.95 years were investigated. There were 22 cases of mild gingivitis (G) in the T1D group. There were no differences considering the Shannon and Chao indices and β-diversity between people with T1D and G, with T1D without G, and healthy controls. Differential taxa were identified, which were mainly enriched in people with T1D and G. Acetic acid concentration was higher in people with T1D, regardless of the presence of G, than in healthy controls. Propionic acid was higher in people with T1D and G than in healthy controls. Isobutyric and isovaleric acid levels were higher in individuals with T1D and G than in the other two subgroups. The concentration of valeric acid was lower and that of caproic acid was higher in people with T1D (regardless of gingival status) than in healthy controls.CONCLUSIONS: The identification of early changes in periodontal tissues by targeting the microbiome and metabolome could potentially enable effective prevention and initial treatment of periodontal disease in people with T1D.PMID:38371896 | PMC:PMC10871129 | DOI:10.3389/fendo.2023.1332406

Front Vet Sci. 2024 Feb 2;11:1347585. doi: 10.3389/fvets.2024.1347585. eCollection 2024.ABSTRACTThis study aims to investigate differences in metabolism regarding the transition cows. Eight cows were selected for the test. Serum was collected on antepartum days 14th (ap14) and 7th (ap7) and postpartum days 1st (pp1), 7th (pp7), and 14th (pp14) to detect biochemical parameters. The experiment screened out differential metabolites in the antepartum (ap) and postpartum (pp) periods and combined with metabolic pathway analysis to study the relationship and role between metabolites and metabolic abnormalities. Results: (1) The glucose (Glu) levels in ap7 were significantly higher than the other groups (p < 0.01). The insulin (Ins) levels of ap7 were significantly higher than pp7 (p = 0.028) and pp14 (p < 0.01), and pp1 was also significantly higher than pp14 (p = 0.016). The insulin resistance (HOMA-IR) levels of ap7 were significantly higher than ap14, pp7, and pp14 (p < 0.01). The cholestenone (CHO) levels of ap14 and pp14 were significantly higher than pp1 (p < 0.01). The CHO levels of pp14 were significantly higher than pp7 (p < 0.01). The high density lipoprotein cholesterol (DHDL) levels of pp1 were significantly lower than ap14 (p = 0.04), pp7 (p < 0.01), and pp14 (p < 0.01), and pp14 was also significantly higher than ap14 and ap7 (p < 0.01). (2) The interferon-gamma (IFN-γ) and tumor necrosis factor α (TNF-α) levels of ap7 were significantly higher than pp1 and pp7 (p < 0.01); the immunoglobulin A (IgA) levels of pp1 were significantly higher than ap7 and pp7 (p < 0.01); the interleukin-4 (IL-4) levels of pp7 were significantly higher than ap7 and pp1 (p < 0.01), the interleukin-6 (IL-6) levels of ap7 and pp1 were significantly higher than pp7 (p < 0.01). (3) Metabolomics identified differential metabolites mainly involved in metabolic pathways, such as tryptophan metabolism, alpha-linolenic acid metabolism, tyrosine metabolism, and lysine degradation. The main relevant metabolism was concentrated in lipid and lipid-like molecules, organic heterocyclic compounds, organic acids, and their derivatives. The results displayed the metabolic changes in the transition period, which laid a foundation for further exploring the mechanism of metabolic abnormalities in dairy cows in the transition period.PMID:38371596 | PMC:PMC10869552 | DOI:10.3389/fvets.2024.1347585