PubMed

Tree Physiol. 2023 Jul 7:tpad087. doi: 10.1093/treephys/tpad087. Online ahead of print.ABSTRACTMetabolomics studies are becoming increasingly common for understanding how plant metabolism responds to changes in environmental conditions, genetic manipulations, and treatments. Despite the recent advances in metabolomics workflow, the sample preparation process still limits the high-throughput analysis in large-scale studies. Here, we present a highly flexible robotic system that integrates liquid handling, sonication, centrifugation, solvent evaporation, and sample transfer processed in 96-well plates to automatize the metabolite extraction from leaf samples. We transferred an established manual extraction protocol performed to a robotic system, and with this, we show the optimization steps required to improve reproducibility and obtain comparable results in terms of extraction efficiency and accuracy. We then tested the robotic system to analyze the metabolomes of wild-type and four transgenic silver birch (Betula pendula) lines under unstressed conditions. Birch trees were engineered to overexpress the poplar (Populus x canescens) isoprene synthase (PcISPS) and emit various amounts of isoprene. By fitting the different isoprene emission capacities of the transgenic trees with their leaf metabolomes, we observed an isoprene-dependent upregulation of some flavonoids and other secondary metabolites as well as carbohydrates, amino acid and lipid metabolites. In contrast, the disaccharide sucrose was found to be strongly negatively correlated to isoprene emission. The presented study illustrates the power of integrating robotics to increase sample throughput, reduce human errors and labor time, and ensure a fully controlled, monitored, and standardized sample preparation procedure. Due to its modular and flexible structure, the robotic system can be easily adapted to other extraction protocols for the analysis of various tissues or plant species to achieve high-throughput metabolomics in plant research.PMID:37418159 | DOI:10.1093/treephys/tpad087

Theor Appl Genet. 2023 Jul 7;136(8):169. doi: 10.1007/s00122-023-04412-z.ABSTRACTBy integrating QTL mapping, transcriptomics and metabolomics, 138 hub genes were identified in rapeseed root response to aluminum stress and mainly involved in metabolism of lipids, carbohydrates and secondary metabolites. Aluminum (Al) toxicity has become one of the important abiotic stress factors in areas with acid soil, which hinders the absorption of water and nutrients by roots, and consequently retards the growth of crops. A deeper understanding of the stress-response mechanism of Brassica napus may allow us to identify the tolerance gene(s) and use this information in breeding-resistant crop varieties. In this study, a population of 138 recombinant inbred lines (RILs) was subjected to aluminum stress, and QTL (quantitative trait locus) mapping was used to preliminarily locate quantitative trait loci related to aluminum stress. Root tissues from seedlings of an aluminum-resistant (R) line and an aluminum-sensitive (S) line from the RIL population were harvested for transcriptome sequencing and metabolome determination. By combining the data on quantitative trait genes (QTGs), differentially expressed genes (DEGs), and differentially accumulated metabolites (DAMs), key candidate genes related to aluminum tolerance in rapeseed were determined. The results showed that there were 3186 QTGs in the RIL population, 14,232 DEGs and 457 DAMs in the comparison between R and S lines. Lastly, 138 hub genes were selected to have a strong positive or negative correlation with 30 important metabolites (|R|≥ 0.95). These genes were mainly involved in the metabolism of lipids, carbohydrates and secondary metabolites in response to Al toxicity stress. In summary, this study provides an effective method for screening key genes by combining QTLs, transcriptome sequencing and metabolomic analysis, but also lists key genes for exploring the molecular mechanism of Al tolerance in rapeseed seedling roots.PMID:37418156 | DOI:10.1007/s00122-023-04412-z

Metabolomics. 2023 Jul 7;19(7):65. doi: 10.1007/s11306-023-02028-4.ABSTRACTINTRODUCTION: Absolute quantification of individual metabolites in complex biological samples is crucial in targeted metabolomic profiling.OBJECTIVES: An inter-laboratory test was performed to evaluate the impact of the NMR software, peak-area determination method (integration vs. deconvolution) and operator on quantification trueness and precision.METHODS: A synthetic urine containing 32 compounds was prepared. One site prepared the urine and calibration samples, and performed NMR acquisition. NMR spectra were acquired with two pulse sequences including water suppression used in routine analyses. The pre-processed spectra were sent to the other sites where each operator quantified the metabolites using internal referencing or external calibration, and his/her favourite in-house, open-access or commercial NMR tool.RESULTS: For 1D NMR measurements with solvent presaturation during the recovery delay (zgpr), 20 metabolites were successfully quantified by all processing strategies. Some metabolites could not be quantified by some methods. For internal referencing with TSP, only one half of the metabolites were quantified with a trueness below 5%. With peak integration and external calibration, about 90% of the metabolites were quantified with a trueness below 5%. The NMRProcFlow integration module allowed the quantification of several additional metabolites. The number of quantified metabolites and quantification trueness improved for some metabolites with deconvolution tools. Trueness and precision were not significantly different between zgpr- and NOESYpr-based spectra for about 70% of the variables.CONCLUSION: External calibration performed better than TSP internal referencing. Inter-laboratory tests are useful when choosing to better rationalize the choice of quantification tools for NMR-based metabolomic profiling and confirm the value of spectra deconvolution tools.PMID:37418094 | DOI:10.1007/s11306-023-02028-4

J Bone Miner Metab. 2023 Jul 7. doi: 10.1007/s00774-023-01449-4. Online ahead of print.ABSTRACTINTRODUCTION: The increase of ATP concentration in the extracellular space represents one of the effective signals that stimulate the physiological activities of cells when the bone is exposed to external mechanical stimulation such as stretching and shear stress force throughout life. However, the effects of ATP on osteoblast differentiation and related mechanisms are not well understood.MATERIALS AND METHODS: In this study, the roles of extracellular ATP on osteoblast differentiation, intracellular calcium ([Ca2+]i) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated.RESULTS: Our results showed that 100 μM extracellular ATP initiated intracellular calcium ([Ca2+]i) oscillations via the calcium-sensing receptor (P2R) and promoted the differentiation of MC3T3-E1 cells. Metabolomics analysis showed that the differentiation of MC3T3-E1 cells depended on aerobic oxidation, but little glycolysis. Moreover, the differentiation of MC3T3-E1 cells and aerobic oxidation were suppressed with the inhibition of AMP-activated protein kinase (AMPK).CONCLUSION: These results indicate that calcium oscillations triggered by extracellular ATP can activate aerobic oxidation through AMPK-related signaling pathways and thus promote osteoblast differentiation.PMID:37418073 | DOI:10.1007/s00774-023-01449-4

Cancer Discov. 2023 Jul 7:OF1. doi: 10.1158/2159-8290.CD-RW2023-105. Online ahead of print.ABSTRACTA database of transcriptomic and metabolomic data was assembled that reveals gene-metabolite interactions across cancers.PMID:37417838 | DOI:10.1158/2159-8290.CD-RW2023-105

Pharm Biol. 2023 Dec;61(1):1054-1064. doi: 10.1080/13880209.2023.2229379.ABSTRACTCONTEXT: Hydroxysafflor yellow A (HSYA) is the main bioactive ingredient of safflower (Carthamus tinctorius L., [Asteraceae]) for traumatic brain injury (TBI) treatment.OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of HSYA on post-TBI neurogenesis and axon regeneration.MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly assigned into Sham, controlled cortex impact (CCI), and HSYA groups. Firstly, the modified Neurologic Severity Score (mNSS), foot fault test, hematoxylin-eosin staining, Nissl's staining, and immunofluorescence of Tau1 and doublecortin (DCX) were used to evaluate the effects of HSYA on TBI at the 14th day. Next, the effectors of HSYA on post-TBI neurogenesis and axon regeneration were screened out by pathology-specialized network pharmacology and untargeted metabolomics. Then, the core effectors were validated by immunofluorescence.RESULTS: HSYA alleviated mNSS, foot fault rate, inflammatory cell infiltration, and Nissl's body loss. Moreover, HSYA increased not only hippocampal DCX but also cortical Tau1 and DCX following TBI. Metabolomics demonstrated that HSYA significantly regulated hippocampal and cortical metabolites enriched in 'arginine metabolism' and 'phenylalanine, tyrosine and tryptophan metabolism' including l-phenylalanine, ornithine, l-(+)-citrulline and argininosuccinic acid. Network pharmacology suggested that neurotrophic factor (BDNF) and signal transducer and activator of transcription 3 (STAT3) were the core nodes in the HSYA-TBI-neurogenesis and axon regeneration network. In addition, BDNF and growth-associated protein 43 (GAP43) were significantly elevated following HSYA treatment in the cortex and hippocampus.DISCUSSION AND CONCLUSIONS: HSYA may promote TBI recovery by facilitating neurogenesis and axon regeneration through regulating cortical and hippocampal metabolism, BDNF and STAT3/GAP43 axis.PMID:37416997 | DOI:10.1080/13880209.2023.2229379

Front Plant Sci. 2023 Jun 19;14:1135000. doi: 10.3389/fpls.2023.1135000. eCollection 2023.ABSTRACTPlants are continuously threatened by a plethora of biotic stresses caused by microbes, pathogens, and pests, which often act as the major constraint in crop productivity. To overcome such attacks, plants have evolved with an array of constitutive and induced defense mechanisms- morphological, biochemical, and molecular. Volatile organic compounds (VOCs) are a class of specialized metabolites that are naturally emitted by plants and play an important role in plant communication and signaling. During herbivory and mechanical damage, plants also emit an exclusive blend of volatiles often referred to as herbivore-induced plant volatiles (HIPVs). The composition of this unique aroma bouquet is dependent upon the plant species, developmental stage, environment, and herbivore species. HIPVs emitted from infested and non-infested plant parts can prime plant defense responses by various mechanisms such as redox, systemic and jasmonate signaling, activation of mitogen-activated protein (MAP) kinases, and transcription factors; mediate histone modifications; and can also modulate the interactions with natural enemies via direct and indirect mechanisms. These specific volatile cues mediate allelopathic interactions leading to altered transcription of defense-related genes, viz., proteinase inhibitors, amylase inhibitors in neighboring plants, and enhanced levels of defense-related secondary metabolites like terpenoids and phenolic compounds. These factors act as deterrents to feeding insects, attract parasitoids, and provoke behavioral changes in plants and their neighboring species. This review presents an overview of the plasticity identified in HIPVs and their role as regulators of plant defense in Solanaceous plants. The selective emission of green leaf volatiles (GLVs) including hexanal and its derivatives, terpenes, methyl salicylate, and methyl jasmonate (MeJa) inducing direct and indirect defense responses during an attack from phloem-sucking and leaf-chewing pests is discussed. Furthermore, we also focus on the recent developments in the field of metabolic engineering focused on modulation of the volatile bouquet to improve plant defenses.PMID:37416879 | PMC:PMC10322200 | DOI:10.3389/fpls.2023.1135000

Front Plant Sci. 2023 Jun 21;14:1186816. doi: 10.3389/fpls.2023.1186816. eCollection 2023.ABSTRACTINTRODUCTION: Metabolic engineering of anthocyanin synthesis is an active research area for pigment breeding and remains a research hotspot involving AtPAP1 and ZmLc transcription factors. Caladium bicolor is a desirable anthocyanin metabolic engineering receptor, with its abundant leaf color and stable genetic transformation system.METHODS: We transformed C. bicolor with AtPAP1 and ZmLc and successfully obtained transgenic plants. We then used a combination of metabolome, transcriptome, WGCNA and PPI co-expression analyses to identify differentially expressed anthocyanin components and transcripts between wild-type and transgenic lines.RESULTS: Cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside and peonidin-3-O-rutinoside are the main components of anthocyanins in the leaves and petioles of C. bicolor. Exogenous introduction of AtPAP1 and ZmLc resulted in significant changes in pelargonidins, particularly pelargonidin-3-O-glucoside and pelargonidin-3-O-rutinoside in C. bicolor. Furthermore, 5 MYB-TFs, 9 structural genes, and 5 transporters were found to be closely associated with anthocyanin synthesis and transport in C. bicolor.DISCUSSION: In this study, a network regulatory model of AtPAP1 and ZmLc in the regulation of anthocyanin biosynthesis and transport in C. bicolor was proposed, which provides insights into the color formation mechanisms of C. bicolor, and lays a foundation for the precise regulation of anthocyanin metabolism and biosynthesis for economic plant pigment breeding.PMID:37416877 | PMC:PMC10320811 | DOI:10.3389/fpls.2023.1186816

Int J Biol Sci. 2023 Jun 14;19(10):3143-3158. doi: 10.7150/ijbs.84613. eCollection 2023.ABSTRACTSepsis-induced myocardial dysfunction (SIMD) is a prevalent and severe form of organ dysfunction with elusive underlying mechanisms and limited treatment options. In this study, the cecal ligation and puncture and lipopolysaccharide (LPS) were used to reproduce sepsis model in vitro and vivo. The level of voltage-dependent anion channel 2 (VDAC2) malonylation and myocardial malonyl-CoA were detected by mass spectrometry and LC-MS-based metabolomics. Role of VDAC2 malonylation on cardiomyocytes ferroptosis and treatment effect of mitochondrial targeting nano material TPP-AAV were observed. The results showed that VDAC2 lysine malonylation was significantly elevated after sepsis. In addition, the regulation of VDAC2 lysine 46 (K46) malonylation by K46E and K46Q mutation affected mitochondrial-related ferroptosis and myocardial injury. The molecular dynamic simulation and circular dichroism further demonstrated that VDAC2 malonylation altered the N-terminus structure of the VDAC2 channel, causing mitochondrial dysfunction, increasing mitochondrial ROS levels, and leading to ferroptosis. Malonyl-CoA was identified as the primary inducer of VDAC2 malonylation. Furthermore, the inhibition of malonyl-CoA using ND-630 or ACC2 knock-down significantly reduced the malonylation of VDAC2, decreased the occurrence of ferroptosis in cardiomyocytes, and alleviated SIMD. The study also found that the inhibition of VDAC2 malonylation by synthesizing mitochondria targeting nano material TPP-AAV could further alleviate ferroptosis and myocardial dysfunction following sepsis. In summary, our findings indicated that VDAC2 malonylation plays a crucial role in SIMD and that targeting VDAC2 malonylation could be a potential treatment strategy for SIMD.PMID:37416771 | PMC:PMC10321281 | DOI:10.7150/ijbs.84613

Int J Biol Sci. 2023 Jun 12;19(10):3077-3098. doi: 10.7150/ijbs.83392. eCollection 2023.ABSTRACTLooking for early diagnostic markers and therapeutic targets is the key to ensuring prompt treatment of myocardial ischemia (MI). Here, a novel biomarker xanthurenic acid (XA) was identified based on metabolomics and exhibited high sensitivity and specificity in the diagnosis of MI patients. Additionally, the elevation of XA was proved to induce myocardial injury in vivo by promoting myocardial apoptosis and ferroptosis. Combining metabolomics and transcriptional data further revealed that kynurenine 3-monooxygenase (KMO) profoundly increased in MI mice, and was closely associated with the elevation of XA. More importantly, pharmacological or heart-specific inhibition of KMO obviously suppressed the elevation of XA and profoundly ameliorated the OGD-induced cardiomyocytes injury and the ligation-induced MI injury. Mechanistically, KMO inhibition effectively restrained myocardial apoptosis and ferroptosis by modulating mitochondrial fission and fusion. In addition, virtual screening and experimental validation were adopted to identify ginsenoside Rb3 as a novel inhibitor of KMO and exhibited great cardioprotective effects by regulating mitochondrial dynamical balance. Taken together, targeting KMO may provide a new approach for the clinical treatment of MI through maintaining mitochondrial fusion and fission balance, and ginsenoside Rb3 showed great potential to be developed as a novel therapeutic drug targeting KMO.PMID:37416768 | PMC:PMC10321280 | DOI:10.7150/ijbs.83392

Heliyon. 2023 Jun 24;9(6):e17612. doi: 10.1016/j.heliyon.2023.e17612. eCollection 2023 Jun.ABSTRACTBACKGROUND: Tribulus terrestris L. (TT) is one of the most common Chinese herbs and distributes in various regions in China. TT was first documented to treat breast cancer in Shen-Nong-Ben-Cao-Jing. However, the pharmacological activities of TT extract on liver cancer have not been reported. In this study, we investigated its anti-liver cancer activity and underlying mechanism.METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases were used to obtain the active ingredients and the targets of TT. Genecards database was employed to acquire TT targets in liver cancer. Furthermore, Venny 2.1, Cytoscape 3.8.2, DAVID 6.8 software were utilized to analyze the relationship between TT and liver cancer. In vivo experiment: The animal model of liver cancer was established by injection of H22 cells into Balb/c mice. After five days, drugs were intragastrically administered to the mice daily for 10 days. Body weight, tumor size and tumor weight were recorded. Tumor inhibitory rate was calculated. Protein levels were examined by Western blotting. Pathological changes of liver cancer tissues were evaluated by HE and Tunel staining. Metabolomics study: LC-MS was used to analyze different metabolites between model and TTM groups.RESULTS: 12 active ingredients of TT, 127 targets of active ingredients, 17,378 targets of liver cancer, and 125 overlapping genes were obtained. And then, 118 items of GO biological processes (BP), 54 items of GO molecular function (MF), 35 items of GO cellular component (CC) and 128 pathways of KEGG were gotten (P < 0.05). Moreover, 47 differential metabolites were affirmed and 66 pathways of KEGG (P < 0.05) were obtained. In addition, after TT and sorafenib treatment, tumor size was markedly reduced, respectively, compared with model group. Tumor weight was significantly decreased and tumor inhibitory rate was more than 44% in TTM group. After TT treatment, many adipocytes, cracks between tumor cells and apoptosis were found. The levels of pro-Cathepsin B, Cathepsin B, Bax, Bax/Bcl2, Caspase3 and Caspase7 were markedly increased, but the level of Bcl2 was significantly reduced after TT treatment.CONCLUSION: TT has a broad range of effects on various signaling pathways and biological processes, including the regulation of apoptosis. It exhibits antitumor activity in an animal model of liver cancer and activates the apoptotic pathway by decreasing Sph level. This study provides valuable information regarding the potential use of TT extract in the treatment of liver cancer and highlights the importance of investigating the underlying molecular mechanisms of traditional medicines for the development of new therapeutic drugs in liver cancer.PMID:37416661 | PMC:PMC10320314 | DOI:10.1016/j.heliyon.2023.e17612

iScience. 2023 Jun 8;26(7):107082. doi: 10.1016/j.isci.2023.107082. eCollection 2023 Jul 21.ABSTRACTThe pinewood nematode Bursaphelenchus xylophilus is an invasive and destructive pathogen in forestry. Serratia marcescens AHPC29 was previously found to have nematicidal activity on B. xylophilus. The effect of AHPC29 growth temperature on B. xylophilus inhibition is unknown. Here we show that AHPC29 cultured at 15°C or 25°C, but not 37°C, inhibited B. xylophilus reproduction. Metabolomic analysis found 31 up-regulated metabolites as potential effective substances in this temperature-related difference, with five of them were tested to be effective in inhibiting B. xylophilus reproduction. Among the five metabolites, salsolinol was further verified in bacterial cultures with effective inhibition concentrations. This study found the inhibition of S. marcescens AHPC29 on B. xylophilus reproduction was temperature regulated and the differently expressed metabolites salsolinol played roles in this temperature-regulated effect, which implies the capability of S. marcescens and its metabolites as promising new agents for the management of B. xylophilus.PMID:37416473 | PMC:PMC10320214 | DOI:10.1016/j.isci.2023.107082

iScience. 2023 Jun 14;26(7):107111. doi: 10.1016/j.isci.2023.107111. eCollection 2023 Jul 21.ABSTRACTThe toxicity of insecticides used in the field decreases gradually to sublethal concentrations over time. Therefore, it is necessary to study sublethal effects of pesticides for controlling population explosion. Panonychus citri is a global pest which control is based on insecticides. This study explores the stress responses of spirobudiclofen on the P. citri. Spirobudiclofen significantly inhibited survival and reproduction of P. citri, and the effects aggravated as concentration increased. The transcriptomes and metabolomes of spirobudiclofen-treated and control were compared to characterize spirobudiclofen molecular mechanism. Transcriptomics indicated stress induced by spirobudiclofen stimulated immune defense, antioxidative system, cuticle formation, and lipid metabolism, as deduced from RNA-seq analysis. Meanwhile, our study found that tolerance metabolism in P. citri was regulated by promoting the metabolism of glycerophospholipids, glycine, serine, and threonine. The results of this study can provide a basis for exploring the adaptation strategies of P. citri to spirobudiclofen stress.PMID:37416453 | PMC:PMC10320506 | DOI:10.1016/j.isci.2023.107111

J Healthc Eng. 2023 Jun 28;2023:9896064. doi: 10.1155/2023/9896064. eCollection 2023.ABSTRACT[This retracts the article DOI: 10.1155/2022/6480749.].PMID:37415900 | PMC:PMC10322247 | DOI:10.1155/2023/9896064

Forensic Sci Res. 2023 Apr 25;8(1):50-61. doi: 10.1093/fsr/owad007. eCollection 2023 Mar.ABSTRACTWound age estimation is one of the most challenging and indispensable issues for forensic pathologists. Although many methods based on physical findings and biochemical tests can be used to estimate wound age, an objective and reliable method for inferring the time interval after injury remains difficult. In the present study, endogenous metabolites of contused skeletal muscle were investigated to estimate the time interval after injury. Animal model of skeletal muscle injury was established using Sprague-Dawley rat, and the contused muscles were sampled at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 h postcontusion (n = 9). Then, the samples were analysed using ultraperformance liquid chromatography coupled with high-resolution mass spectrometry. A total of 43 differential metabolites in contused muscle were determined by metabolomics method. They were applied to construct a two-level tandem prediction model for wound age estimation based on multilayer perceptron algorithm. As a result, all muscle samples were eventually divided into the following subgroups: 4, 8, 12, 16-20, 24-32, 36-40, and 44-48 h. The tandem model exhibited a robust performance and achieved a prediction accuracy of 92.6%, which was much higher than that of the single model. In summary, the multilayer perceptron-multilayer perceptron tandem machine-learning model based on metabolomics data can be used as a novel strategy for wound age estimation in future forensic casework.KEY POINTS: The changes of metabolite profile were correlated with the time interval after injury in contused skeletal muscle.A panel of 43 endogenous metabolites screened by ultraperformance liquid chromatography coupled with high-resolution mass spectrometry could distinguish the wound ages.The multilayer perceptron (MLP) algorithm exhibited a robust performance in wound age estimation using metabolites.The combination of matabolomics and MLP-MLP tandem model could improve the accuracy of inferring the time interval after injury.PMID:37415796 | PMC:PMC10265958 | DOI:10.1093/fsr/owad007

J Sep Sci. 2023 Jul 6:e2300148. doi: 10.1002/jssc.202300148. Online ahead of print.ABSTRACTThe Yuquan capsules is a commonly used traditional Chinese Patent Medicine used for the treatment of diabetes mellitus. In this study, a high-throughput analytical method for identifying the chemical composition of Yuquan capsules was established for the first time by using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry. The data obtained were subjected to fragment analysis and this was combined with UNIFI processing of natural products. One-hundred sixteen compounds were characterized from Yuquan capsules. Twelve of the bioactive compounds were quantitatively analyzed by ultra-performance liquid chromatography-tandem triple quadrupole mass spectrometry. This study was undertaken to obtain a comprehensive chemical profile analysis as well as to evaluate the overall quality of Yuquan capsules. The results will provide a reference for the quality evaluation of different Yuquan preparations. In addition, the data will enable basic pharmacodynamic research into these extensively used capsules.PMID:37415310 | DOI:10.1002/jssc.202300148

J Gastroenterol Hepatol. 2023 Jul 6. doi: 10.1111/jgh.16279. Online ahead of print.ABSTRACTBACKGROUND AND AIM: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rising globally. NAFLD patients combined with cholestasis have more obvious liver fibrosis, impaired bile acid (BA), and fatty acid (FA) metabolism and severer liver injury; however, its therapeutic options are limited, and the underlying metabolic mechanisms are understood. Here, we aimed to investigate the effects of farnesoid X receptor (FXR) on BA and FA metabolism in NAFLD combined with cholestasis and related signaling pathways.METHODS: A mouse model of NAFLD combined with cholestasis was established by joint intervention with high-fat diet (HFD) and alpha-naphthylisothiocyanate. The effects of FXR on BA and FA metabolism were evaluated by serum biochemical analysis. Liver damage was identified by histopathology. The expression of nuclear hormone receptor, membrane receptor, FA transmembrane transporter, and BA transporter protein in mice were measured by western blot.RESULTS: NAFLD mice combined with cholestasis developed more severe cholestasis and dysregulated BA and FA metabolism. Meanwhile, the expression of FXR protein was decreased in NAFLD mice combined with cholestasis compared to the controls. Fxr-/- mice showed liver injury. HFD aggravated the liver injury with decreased BSEP expression, increased expression of NTCP, LXRα, SREBP-1c, FAS, ACC1, and CD36, and significantly increased BA and FA accumulation.CONCLUSION: All the results suggested that FXR plays a key role in both FA and BA metabolism in NAFLD combined with cholestasis and thus may be a potential target for the treatment of disorders of BA and FA metabolism in NAFLD combined with cholestasis.PMID:37415275 | DOI:10.1111/jgh.16279

Phytopathology. 2023 Jul 6. doi: 10.1094/PHYTO-03-23-0105-R. Online ahead of print.ABSTRACTBlister blight infected with Exobasidium vexans is one of the most destructive foliar diseases that seriously affects the quality and yield of tea. This research was to investigate the metabolite changes of healthy and infected leaves on tea cultivar "Fuding Dabaicha", as well as further explore the potential antimicrobial substances against E. vexans infection. In total, 1166 compounds were identified in the whole stage of infection, among which 73 different common compounds were significantly accumulated involved in the important antimicrobial substances of flavonoids and phenolic acids, including kaempferol (3,5,7,4'-tetrahydroxyflavone), kaempferol-3-O-sophoroside-7-O-glucoside, phloretin, 2,4,6-trihydroxybenzoic acid, galloylprocyanidin B4, and procyanidin C1 3'-O-gallate, which indicated that these metabolites might positively dominate the resistance to E. vexans. Furthermore, the relevant biological pathways, such as "Flavone and flavonol biosynthesis", "Flavo-noid biosynthesis", and "Phenylpropane pathway", were more closely related to the resistance against E. vexans. Additionally, total flavonoids, phenolics, alkaloids and terpenoids contributing to antimicrobial and antioxidant capacity altered significantly in four different infection periods, especially the Leaf_S2 stage (the second stage of infection) in which the concentration accumulated the most. The leaves affected by E. vexans infection at the second stage had the relatively highest antioxidant activity. Accordingly, this study provided a theoretical support and comprehensive insights into the effects on the metabolite changes, tea quality components and antioxidant activity of blister blight caused by E. vexans.PMID:37414414 | DOI:10.1094/PHYTO-03-23-0105-R

Adv Drug Deliv Rev. 2023 Jul 4:114992. doi: 10.1016/j.addr.2023.114992. Online ahead of print.ABSTRACTNanotechnology has enabled the development of innovative therapeutics, diagnostics, and drug delivery systems. Nanoparticles (NPs) can influence gene expression, protein synthesis, cell cycle, metabolism, and other subcellular processes. Traditional methods are limited in characterizing these responses to NPs, whereas omics approaches can analyze whole sets of molecular entities that change upon exposure to NPs. This review discusses key omics approaches, namely transcriptomics, proteomics, metabolomics, lipidomics and multi-omics, applied to the assessment of biological responses to NPs. Fundamental concepts and the analytical tools used for each approach are presented, as well as good practices for omics experiments. Bioinformatics tools are essential to analyze, interpret and visualize large omics data, and to correlate observations in different molecular layers. The authors envision that conducting interdisciplinary multi-omics analyses in future nanomedicine studies will reveal integrated cell responses to NPs at different omics levels, and the incorporation of omics into the evaluation of targeted delivery, efficacy, and safety will improve the development of nanomedicine therapies.PMID:37414362 | DOI:10.1016/j.addr.2023.114992

Mol Cell Proteomics. 2023 Jul 4:100615. doi: 10.1016/j.mcpro.2023.100615. Online ahead of print.ABSTRACTThe asialoglycoprotein receptor (ASGPR) and the mannose receptor C-type 1 (MRC1) are well-known for their selective recognition and clearance of circulating glycoproteins. Terminal galactose and N-Acetylgalactosamine are recognized by ASGPR, while terminal mannose, fucose, and N-Acetylglucosamine are recognized by MRC1. The effects of ASGPR and MRC1 deficiency on the N-glycosylation of individual circulating proteins have been studied. However, the impact on the homeostasis of the major plasma glycoproteins is debated and their glycosylation has not been mapped with high molecular resolution in this context. Therefore, we evaluated the total plasma N-glycome and plasma proteome of ASGR1 and MRC1 deficient mice. ASGPR deficiency resulted in an increase in O-acetylation of sialic acids accompanied with higher levels of apolipoprotein D, haptoglobin and vitronectin. MRC1 deficiency decreased fucosylation without affecting the abundance of the major circulating glycoproteins. Our findings confirm that concentrations and N-glycosylation of the major plasma proteins are tightly controlled and further suggests that glycan-binding receptors have redundancy, allowing compensation for the loss of one major clearance receptor.PMID:37414249 | DOI:10.1016/j.mcpro.2023.100615