PubMed

Diabetologia. 2023 Jun 13. doi: 10.1007/s00125-023-05943-2. Online ahead of print.ABSTRACTAIMS/HYPOTHESIS: This study aimed to elucidate the aetiological role of plasma proteins in glucose metabolism and type 2 diabetes development.METHODS: We measured 233 proteins at baseline in 1653 participants from the Cooperative Health Research in the Region of Augsburg (KORA) S4 cohort study (median follow-up time: 13.5 years). We used logistic regression in the cross-sectional analysis (n=1300), and Cox regression accounting for interval-censored data in the longitudinal analysis (n=1143). We further applied two-level growth models to investigate associations with repeatedly measured traits (fasting glucose, 2 h glucose, fasting insulin, HOMA-B, HOMA-IR, HbA1c), and two-sample Mendelian randomisation analysis to investigate causal associations. Moreover, we built prediction models using priority-Lasso on top of Framingham-Offspring Risk Score components and evaluated the prediction accuracy through AUC.RESULTS: We identified 14, 24 and four proteins associated with prevalent prediabetes (i.e. impaired glucose tolerance and/or impaired fasting glucose), prevalent newly diagnosed type 2 diabetes and incident type 2 diabetes, respectively (28 overlapping proteins). Of these, IL-17D, IL-18 receptor 1, carbonic anhydrase-5A, IL-1 receptor type 2 (IL-1RT2) and matrix extracellular phosphoglycoprotein were novel candidates. IGF binding protein 2 (IGFBP2), lipoprotein lipase (LPL) and paraoxonase 3 (PON3) were inversely associated while fibroblast growth factor 21 was positively associated with incident type 2 diabetes. LPL was longitudinally linked with change in glucose-related traits, while IGFBP2 and PON3 were linked with changes in both insulin- and glucose-related traits. Mendelian randomisation analysis suggested causal effects of LPL on type 2 diabetes and fasting insulin. The simultaneous addition of 12 priority-Lasso-selected biomarkers (IGFBP2, IL-18, IL-17D, complement component C1q receptor, V-set and immunoglobulin domain-containing protein 2, IL-1RT2, LPL, CUB domain-containing protein 1, vascular endothelial growth factor D, PON3, C-C motif chemokine 4 and tartrate-resistant acid phosphatase type 5) significantly improved the predictive performance (ΔAUC 0.0219; 95% CI 0.0052, 0.0624).CONCLUSIONS/INTERPRETATION: We identified new candidates involved in the development of derangements in glucose metabolism and type 2 diabetes and confirmed previously reported proteins. Our findings underscore the importance of proteins in the pathogenesis of type 2 diabetes and the identified putative proteins can function as potential pharmacological targets for diabetes treatment and prevention.PMID:37308750 | DOI:10.1007/s00125-023-05943-2

J Cancer Res Clin Oncol. 2023 Jun 12. doi: 10.1007/s00432-023-04872-2. Online ahead of print.ABSTRACTINTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) is among the most common cancers in the world with a low survival rate and common diagnosis at late stages. Deubiquitination of proteins is involved in tumor growth, metastasis, apoptosis, and immunosuppressive pathways. The impact of the ubiquitin-specific protease (USP4) on survival was only scarcely investigated so far. The goal of our research was to analyze the association of USP4 expression with prognosis and clinicopathological features in HNSCC.METHODS: USP4 mRNA levels were derived from The Cancer Genome Atlas (TCGA) for a cohort of 510 patients. Protein expression of USP4 was analyzed by immunohistochemistry in a second cohort of 113 patients. Associations between USP4 levels and overall survival, disease-free survival and clinicopathological data were analyzed.RESULTS: High levels of USP4 mRNA were associated with prolonged overall survival in univariable analysis. There was no more association with survival after correction for the confounders HPV, stage and smoker status. High USP4 mRNA levels were linked to a lower T-stage, the patient's age at diagnosis, and a positive HPV status. USP4 protein levels were not associated with prognosis or other features.CONCLUSION: Since high USP4 mRNA was not an independent prognostic marker, we assume that the association is a result of the correlation of high USP4 mRNA with an HPV-positive status. Therefore, further investigation of USP4 mRNA and its association with the HPV status of HNSCC patients is warranted.PMID:37308746 | DOI:10.1007/s00432-023-04872-2

Sci Rep. 2023 Jun 12;13(1):9500. doi: 10.1038/s41598-023-36261-7.ABSTRACTChinese cordyceps was one of most valuable traditional Chinese medicine fungi. To elucidate the molecular mechanisms related to energy supply mechanism involved in the initiation and formation of primordium in Chinese cordyceps, we performed the integrated metabolomic and transcriptomic analyses of it at pre-primordium period, primordium germination period and after-primordium period, respectively. Transcriptome analysis showed that many genes related to 'starch and sucrose metabolism', 'fructose and mannose metabolism', 'linoleic acid metabolism', 'fatty acids degradation' and 'glycerophospholipid metabolism' were highly up-regulated at primordium germination period. Metabolomic analysis showed many metabolites regulated by these genes in these metabolism pathways were also markedly accumulated at this period. Consequently, we inferred that carbohydrate metabolism and β-oxidation pathway of palmitic acid and linoleic acid worked cooperatively to generate enough acyl-CoA, and then entered TCA cycle to provide energy for fruiting body initiation. Overall, our finding provided important information for further exploring the energy metabolic mechanisms of realizing the industrialization of Chinese cordyceps artificial cultivation.PMID:37308669 | DOI:10.1038/s41598-023-36261-7

Cell Death Discov. 2023 Jun 12;9(1):182. doi: 10.1038/s41420-023-01475-1.ABSTRACTMetabolic reprogramming is a hallmark of human malignancies. Dysregulation of glutamine metabolism is essential for tumorigenesis, microenvironment remodeling, and therapeutic resistance. Based on the untargeted metabolomics sequencing, we identified that the glutamine metabolic pathway was up-regulated in the serum of patients with primary DLBCL. High levels of glutamine were associated with inferior clinical outcomes, indicative of the prognostic value of glutamine in DLBCL. In contrast, the derivate of glutamine alpha-ketoglutarate (α-KG) was negatively correlated with the invasiveness features of DLBCL patients. Further, we found that treatment with the cell-permeable derivative of α-KG, known as DM-αKG, significantly suppressed tumor growth by inducing apoptosis and non-apoptotic cell death. Accumulation of a-KG promoted oxidative stress in double-hit lymphoma (DHL), which depended on malate dehydrogenase 1 (MDH1)-mediated 2-hydroxyglutarate (2-HG) conversion. High levels of reactive oxygen species (ROS) contributed to ferroptosis induction by promoting lipid peroxidation and TP53 activation. In particular, TP53 overexpression derived from oxidative DNA damage, further leading to the activation of ferroptosis-related pathways. Our study demonstrated the importance of glutamine metabolism in DLBCL progression and highlighted the potential application of α-KG as a novel therapeutic strategy for DHL patients.PMID:37308557 | DOI:10.1038/s41420-023-01475-1

Sci Rep. 2023 Jun 12;13(1):9529. doi: 10.1038/s41598-023-36618-y.ABSTRACTHeterosis contributes greatly to the worldwide agricultural yield. However, the molecular mechanism underlying heterosis remains unclear. This study took advantage of Arabidopsis intraspecific hybrids to identify heterosis-related metabolites. Forty-six intraspecific hybrids were used to examine parental effects on seed area and germination time. The degree of heterosis was evaluated based on biomass: combinations showing high heterosis of F1 hybrids exhibited a biomass increase from 6.1 to 44% over the better parent value (BPV), whereas that of the low- and no-heterosis hybrids ranged from - 19.8 to 9.8% over the BPV. Metabolomics analyses of F1 hybrids with high heterosis and those with low one suggested that changes in TCA cycle intermediates are key factors that control growth. Notably, higher fumarate/malate ratios were observed in the high heterosis F1 hybrids, suggesting they provide metabolic support associated with the increased biomass. These hybrids may produce more energy-intensive biomass by speeding up the efficiency of TCA fluxes. However, the expression levels of TCA-process-related genes in F1 hybrids were not associated with the intensity of heterosis, suggesting that the post-transcriptional or post-translational regulation of these genes may affect the productivity of the intermediates in the TCA cycle.PMID:37308530 | DOI:10.1038/s41598-023-36618-y

NPJ Vaccines. 2023 Jun 12;8(1):92. doi: 10.1038/s41541-023-00682-2.ABSTRACTMany human diseases, including metabolic diseases, are intertwined with the immune system. The understanding of how the human immune system interacts with pharmaceutical drugs is still limited, and epidemiological studies only start to emerge. As the metabolomics technology matures, both drug metabolites and biological responses can be measured in the same global profiling data. Therefore, a new opportunity presents itself to study the interactions between pharmaceutical drugs and immune system in the high-resolution mass spectrometry data. We report here a double-blinded pilot study of seasonal influenza vaccination, where half of the participants received daily metformin administration. Global metabolomics was measured in the plasma samples at six timepoints. Metformin signatures were successfully identified in the metabolomics data. Statistically significant metabolite features were found both for the vaccination effect and for the drug-vaccine interactions. This study demonstrates the concept of using metabolomics to investigate drug interaction with the immune response in human samples directly at molecular levels.PMID:37308481 | DOI:10.1038/s41541-023-00682-2

Transl Psychiatry. 2023 Jun 12;13(1):200. doi: 10.1038/s41398-023-02486-3.ABSTRACTMajor depressive disorder (MDD) is a highly heterogeneous psychiatric disorder. The pathogenesis of MDD remained unclear, and it may be associated with exposure to different stressors. Most previous studies have focused on molecular changes in a single stress-induced depression model, which limited the identification of the pathogenesis of MDD. The depressive-like behaviors were induced by four well-validated stress models in rats, including chronic unpredictable mild stress, learned helplessness stress, chronic restraint stress and social defeat stress. We applied proteomic and metabolomic to investigate molecular changes in the hippocampus of those four models and revealed 529 proteins and 98 metabolites. Ingenuity Pathways Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified differentially regulated canonical pathways, and then we presented a schematic model that simulates AKT and MAPK signaling pathways network and their interactions and revealed the cascade reactions. Further, the western blot confirmed that p-AKT, p-ERK12, GluA1, p-MEK1, p-MEK2, p-P38, Syn1, and TrkB, which were changed in at least one depression model. Importantly, p-AKT, p-ERK12, p-MEK1 and p-P38 were identified as common alterations in four depression models. The molecular level changes caused by different stressors may be dramatically different, and even opposite, between four depression models. However, the different molecular alterations converge on a common AKT and MAPK molecular pathway. Further studies of these pathways could contribute to a better understanding of the pathogenesis of depression, with the ultimate goal of helping to develop or select more effective treatment strategies for MDD.PMID:37308476 | DOI:10.1038/s41398-023-02486-3

Food Chem. 2023 Jun 5;426:136491. doi: 10.1016/j.foodchem.2023.136491. Online ahead of print.ABSTRACTLegumes and cereals as staple food are typically consumed at mature stage, though also consumed at earlier stages. UPLC/MS based molecular networking and chemometrics were employed for the first time to address metabolome composition heterogeneity amongst seeds in the context of their maturity stages. The study included 4 major cereal and leguminous seeds of different species, and cultivars i.e., Triticum aestivum, Hordeum vulgare, Vicia faba and Cicer arietinum. 146 Metabolites from various classes were identified of which several are first time to be reported. Supervised OPLS model of all datasets revealed that sugars and oxylipids were dominant in mature and immature seeds, respectively. DPPH and FRAP assays were assessed for differential secondary metabolites' correlation. Results were attributed to flavonoids, oxylipids, and amino acids/peptides. Mature barley seeds possessed the strongest antioxidant activity among examined seeds. This study provides novel insights on seeds' maturation process in context to holistic metabolic changes.PMID:37307742 | DOI:10.1016/j.foodchem.2023.136491

J Hazard Mater. 2023 Jun 8;457:131811. doi: 10.1016/j.jhazmat.2023.131811. Online ahead of print.ABSTRACTGraphene oxide (GO)-promoted microbial degradation technology is considered an important strategy to eliminate polycyclic aromatic hydrocarbons (PAHs) in the environment; however, the mechanism by which GO affects microbial degradation of PAHs has not been fully studied. Thus, this study aimed to analyze the effect of GO-microbial interaction on PAHs degradation at the microbial community structure, community gene expression, and metabolic levels using multi-omics combined technology. We treated PAHs-contaminated soil samples with different concentrations of GO and analyzed the soil samples for microbial diversity after 14 and 28 days. After a short exposure, GO reduced the diversity of soil microbial community but increased potential degrading microbial abundance, promoting PAHs biodegradation. This promotion effect was further influenced by the GO concentration. In a short period of time, GO upregulated the expression of genes involved in microbial movement (flagellar assembly), bacterial chemotaxis, two-component system, and phosphotransferase system in the soil microbial community and increased the probability of microbial contact with PAHs. Biosynthesis of amino acids and carbon metabolism of microorganisms were accelerated, thereby increasing the degradation of PAHs. With the extension of time, the degradation of PAHs stagnated, which may be due to the weakened stimulation of GO on microorganisms. The results showed that screening specific degrading microorganisms, increasing the contact area between microorganisms and PAHs, and prolonging the stimulation of GO on microorganisms were important means to improve the biodegradation efficiency of PAHs in soil. This study elucidates how GO affects microbial PAHs degradation and provides important insights for the application of GO-assisted microbial degradation technology.PMID:37307733 | DOI:10.1016/j.jhazmat.2023.131811

Proc Natl Acad Sci U S A. 2023 Jun 20;120(25):e2303335120. doi: 10.1073/pnas.2303335120. Epub 2023 Jun 12.ABSTRACTSoil organic matter (SOM) is comprised of a diverse array of reactive carbon molecules, including hydrophilic and hydrophobic compounds, that impact rates of SOM formation and persistence. Despite clear importance to ecosystem science, little is known about broad-scale controls on SOM diversity and variability in soil. Here, we show that microbial decomposition drives significant variability in the molecular richness and diversity of SOM between soil horizons and across a continental-scale gradient in climate and ecosystem type (arid shrubs, coniferous, deciduous, and mixed forests, grasslands, and tundra sedges). The molecular dissimilarity of SOM was strongly influenced by ecosystem type (hydrophilic compounds: 17%, P < 0.001; hydrophobic compounds: 10% P < 0.001) and soil horizon (hydrophilic compounds: 17%, P < 0.001; hydrophobic compounds: 21%, P < 0.001), as assessed using metabolomic analysis of hydrophilic and hydrophobic metabolites. While the proportion of shared molecular features was significantly higher in the litter layer than subsoil C horizons across ecosystems (12 times and 4 times higher for hydrophilic and hydrophobic compounds, respectively), the proportion of site-specific molecular features nearly doubled from the litter layer to the subsoil horizon, suggesting greater differentiation of compounds after microbial decomposition within each ecosystem. Together, these results suggest that microbial decomposition of plant litter leads to a decrease in SOM α-molecular diversity, yet an increase in β-molecular diversity across ecosystems. The degree of microbial degradation, determined by the position in the soil profile, exerts a greater control on SOM molecular diversity than environmental factors, such as soil texture, moisture, and ecosystem type.PMID:37307452 | DOI:10.1073/pnas.2303335120

J Cell Mol Med. 2023 Jun 12. doi: 10.1111/jcmm.17811. Online ahead of print.ABSTRACTLipid metabolism plays an important role in the repair of skin wounds. Studies have shown that acupuncture is very effective in skin wound repair. However, there is little knowledge about the mechanism of electroacupuncture. Thirty-six SD rats were divided into three groups: sham-operated group, model group and electroacupuncture group, with 12 rats in each group. After the intervention, local skin tissues were collected for lipid metabolomics analysis, wound perfusion and ferroptosis-related indexes were detected and finally the effect of electroacupuncture on skin wound repair was comprehensively evaluated by combining wound healing rate and histology. Lipid metabolomics analysis revealed 37 differential metabolites shared by the three groups, mainly phospholipids, lysophospholipids, glycerides, acylcarnitine, sphingolipids and fatty acids, and they could be back-regulated after electroacupuncture. The recovery of blood perfusion and wound healing was faster in the electroacupuncture group than in the model group (p < 0.05). The levels of GPX4, FTH1, SOD and GSH-PX, which are related to ferroptosis, were higher in the electroacupuncture group than in the model group (p < 0.05). The levels of ACSL4 and MDA were lower in the electroacupuncture group than in the model group (p < 0.05). Electroacupuncture may promote skin wound repair by improving lipid metabolism and inhibiting ferroptosis in local tissues.PMID:37307402 | DOI:10.1111/jcmm.17811

Gut Microbes. 2023 Jan-Dec;15(1):2221098. doi: 10.1080/19490976.2023.2221098.ABSTRACTBoth growth hormone (GH) and gut microbiota play significant roles in diverse physiological processes, but the crosstalk between them is poorly understood. Despite the regulation of GH by gut microbiota, study on GH's influence on gut microbiota is limited, especially on the impacts of tissue specific GH signaling and their feedback effects on the host. In this study, we profiled gut microbiota and metabolome in tissue-specific GHR knockout mice in the liver (LKO) and adipose tissue (AKO). We found that GHR disruption in the liver rather than adipose tissue affected gut microbiota. It changed the abundance of Bacteroidota and Firmicutes at phylum level as well as abundance of several genera, such as Lactobacillus, Muribaculaceae, and Parasutterella, without affecting α-diversity. Moreover, the impaired liver bile acid (BA) profile in LKO mice was strongly associated with the change of gut microbiota. The BA pools and 12-OH BAs/non-12-OH BAs ratio were increased in the LKO mice, which was due to the induction of CYP8B1 by hepatic Ghr knockout. Consequently, the impaired BA pool in cecal content interacted with gut bacteria, which in turn increased the production of bacteria derived acetic acid, propionic acid, and phenylacetic acid that were possible to participate in the impaired metabolic phenotype of the LKO mice. Collectively, our findings suggested that the liver GH signaling regulates BA metabolism by its direct regulation on CYP8B1, which is an important factor influencing gut microbiota. Our study is significant in exploring gut microbiota modification effects of tissue-specific GH signaling as well as its involvement in gut microbiota-host interaction.PMID:37306416 | DOI:10.1080/19490976.2023.2221098

Gut Microbes. 2023 Jan-Dec;15(1):2223349. doi: 10.1080/19490976.2023.2223349.ABSTRACTThe gut metabolome acts as an intermediary between the gut microbiota and host, and has tremendous diagnostic and therapeutic potential. Several studies have utilized bioinformatic tools to predict metabolites based on the different aspects of the gut microbiome. Although these tools have contributed to a better understanding of the relationship between the gut microbiota and various diseases, most of them have focused on the impact of microbial genes on the metabolites and the relationship between microbial genes. In contrast, relatively little is known regarding the effect of metabolites on the microbial genes or the relationship between these metabolites. In this study, we constructed a computational framework of Microbe-Metabolite INteractions-based metabolic profiles Predictor (MMINP), based on the Two-Way Orthogonal Partial Least Squares (O2-PLS) algorithm to predict the metabolic profiles associated with gut microbiota. We demonstrated the predictive value of MMINP relative to that of similar methods. Additionally, we identified the features that would profoundly impact the prediction performance of data-driven methods (O2-PLS, MMINP, MelonnPan, and ENVIM), including the training sample size, host disease state, and the upstream data processing methods of the different technical platforms. We suggest that when using data-driven methods, similar host disease states and preprocessing methods, and a sufficient number of training samples are necessary to achieve accurate prediction.PMID:37306408 | DOI:10.1080/19490976.2023.2223349

Physiol Plant. 2023 Jun 12:e13952. doi: 10.1111/ppl.13952. Online ahead of print.ABSTRACTTogether with toxicity, beneficial effects on plant growth have been ascribed to nanoparticles (NPs). This study aimed to survey the growth performance and metabolome adjustment of beans grown in a growth medium containing ZnONPs at different concentrations and compared to bulk ZnSO4 as a positive control. Growth parameters showed a reduction in shoot height starting from the lowest (25 mg l-1 ) concentration of ZnONPs. In comparison, growth was inhibited from 50 mg l-1 ZnSO4 , suggesting more toxic effects of nano forms of Zn. Untargeted metabolomics allowed us to unravel the biochemical processes involved in both promising and detrimental aspects. Multivariate statistics indicated that the tested Zn species substantially and distinctively altered the metabolic profile of both roots and leaves, with more metabolites altered in the former (435) compared to leaves (381). Despite having Zn forms in the growth medium, also leaf metabolome underwent a significant and extensive modulation. In general, the elicitation of secondary metabolism (N-containing compounds, phenylpropanoids, and phytoalexins) and the down-accumulation of fatty acid biosynthesis compounds were common responses to different Zn forms. However, an opposite trend could be observed for amino acids, fatty acids, carbohydrates, and cofactors being down-accumulated in ZnONPs treatment. Osmolytes, especially in ZnSO4 treatment, contributed to mitigating the effect of Zn toxicity and maintaining plant growth. Overall, the results indicated a complexity of tissue-specific and Zn-dependent response differences, resulting in distinctive metabolic perturbations. This article is protected by copyright. All rights reserved.PMID:37306385 | DOI:10.1111/ppl.13952

J Agric Food Chem. 2023 Jun 12. doi: 10.1021/acs.jafc.3c02113. Online ahead of print.ABSTRACTShewanella putrefaciens is a typical spoiler that is commonly found in seafood and has high spoilage potential. However, the spoilage mechanism against Shewanella putrefaciens at the gene and metabolism levels has not been well elucidated. This work determined the spoilage targets on Shewanella putrefaciens XY07 from spoiled bigeye tuna by genome sequencing, metabolomics, and Fourier transform infrared (FTIR) analysis. Shewanella putrefaciens XY07 contained some genes on spoilage regulating of cys genes, his genes, spe genes and rpoS gene involved in sulfur metabolism, histidine metabolism, arginine and proline degradation, and biofilm formation at the genome level, respectively. Some spoilage genes like speC, cysM, trxB genes were identified. In addition, ABC transporters, arginine and proline metabolism; beta-alanine metabolism; glycine, serine, and threonine metabolism; histidine metabolism; sulfur metabolism; and lipid metabolism were identified as important pathways related to aquatic food during spoilage, which indicated the functions of amino acid degradation in S. putrefaciens XY 07 by metabolomics analysis. The metabolites of l-ornithine, 5-aminopentanoate, and 4-aminobutyraldehyde could be further metabolized to spermidine and spermine, producing a spoilage odor, and were involved in arginine and proline metabolism serving as key spoilage regulating metabolisms. Therefore, Shewanella putrefaciens XY07 was applied to genomics, metabolomics analysis, and FTIR to provide comprehensive insight into the investigation of spoilage targets.PMID:37306251 | DOI:10.1021/acs.jafc.3c02113

Gut Microbes. 2023 Jan-Dec;15(1):2221452. doi: 10.1080/19490976.2023.2221452.ABSTRACTRegardless of the global progress in early diagnosis and novel therapeutic regimens, breast carcinoma poses a devastating threat, and the advances are somewhat marred by high mortality rates. Breast cancer risk prediction models based on the known risk factors are extremely useful, but a large number of breast cancers develop in women with no/low known risk. The gut microbiome exerts a profound impact on the host health and physiology and has emerged as a pivotal frontier in breast cancer pathogenesis. Progress in metagenomic analysis has enabled the identification of specific changes in the host microbial signature. In this review, we discuss the microbial and metabolomic changes associated with breast cancer initiation and metastatic progression. We summarize the bidirectional impact of various breast cancer-related therapies on gut microbiota and vice-versa. Finally, we discuss the strategies to modulate the gut microbiota toward a more favorable state that confers anticancer effects.PMID:37305949 | DOI:10.1080/19490976.2023.2221452

J Pharm Anal. 2023 May;13(5):483-493. doi: 10.1016/j.jpha.2023.04.007. Epub 2023 Apr 14.ABSTRACTThree-dimensional (3D) cell spheroid models combined with mass spectrometry imaging (MSI) enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions. Herein, airflow-assisted desorption electrospray ionization-MSI (AFADESI-MSI) was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone (AMI). High-coverage imaging of >1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI. Following AMI treatment at different times, 15 metabolites of AMI involved in N-desethylation, hydroxylation, deiodination, and desaturation metabolic reactions were identified, and according to their spatiotemporal dynamics features, the metabolic pathways of AMI were proposed. Subsequently, the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis. The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism, providing considerable evidence for the mechanism of AMI hepatotoxicity. In addition, a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI. The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal information for drugs, drug metabolites, and endogenous metabolites after AMI treatment, providing an effective tool for in vitro drug hepatotoxicity evaluation.PMID:37305784 | PMC:PMC10257197 | DOI:10.1016/j.jpha.2023.04.007

Heliyon. 2023 Apr 25;9(5):e15657. doi: 10.1016/j.heliyon.2023.e15657. eCollection 2023 May.ABSTRACT[This corrects the article DOI: 10.1016/j.heliyon.2023.e14779.].PMID:37305512 | PMC:PMC10256820 | DOI:10.1016/j.heliyon.2023.e15657

Heliyon. 2023 May 18;9(5):e16109. doi: 10.1016/j.heliyon.2023.e16109. eCollection 2023 May.ABSTRACTBACKGROUND: Diabetic retinopathy (DR) is the microvascular ocular complication of diabetes mellitus (DM), which can lead to irreversible blindness and visual impairment if not properly treated. Tears can be collected non-invasively, and the compositions of tears could be the potential biomarkers for ocular diseases. Here we aimed to delineate the metabolomics signature in tears collected from Chinese type-2 DM patients with DR.METHODS: The metabolomics profiles of tear samples from 41 Chinese type-2 DM patients with DR and 21 non-diabetic subjects were determined by the untargeted liquid chromatography-mass spectrometry. The associated pathways of the differentially abundant metabolites were delineated, and the receiver operating characteristic curve analysis was conducted to identify the metabolites differentiating non-proliferative DR (NPDR) from proliferative DR (PDR).RESULTS: Total 14 differentially abundant metabolites were identified between total DR and non-diabetic subjects, and 17 differentially abundant metabolites were found between the NPDR and PDR subjects. Moreover, total 18 differentially abundant metabolites were identified between the NPDR and PDR subjects with stratification in DR duration and blood glucose level. d-Glutamine and d-glutamate metabolism was significantly highlighted in the PDR group as compared to the non-diabetic group. For the predictive performance, azelaic acid combined with guanosine achieved the area under receiver operating characteristic curve of 0.855 in the comparison between NPDR and PDR groups.CONCLUSION: This study revealed the metabolomics changes in tear samples of DR patients. The metabolites in tears could be the potential biomarkers in the DR analysis.PMID:37305454 | PMC:PMC10256905 | DOI:10.1016/j.heliyon.2023.e16109

Front Cell Infect Microbiol. 2023 May 25;13:1215104. doi: 10.3389/fcimb.2023.1215104. eCollection 2023.NO ABSTRACTPMID:37305425 | PMC:PMC10248503 | DOI:10.3389/fcimb.2023.1215104