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1.
Chem Commun (Camb) ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040106

RESUMO

We developed a novel enzyme-free amplified SERS immunoassay by combining silver nanoparticle (AgNP)-linked immunoreaction and SERS transduction for the detection of disease biomarkers. As a proof of concept, our method was successfully illustrated with the disease biomarker α-fetoprotein with the detection limit of 3.3 × 10-13 g mL-1 and a double-blind experiment consisting of tens of serum samples was performed to confirm its reliability.

2.
Gynecol Oncol ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32067813

RESUMO

OBJECTIVES: To develop a transcriptomic signature capable of predicting overall survival (OS) for uterine serous carcinoma (USC). METHODS: RNAseq data for 58 USC patients were obtained from TCGA. Expression of 73 candidate genes was measured for 67 Augusta University (AU) samples using NanoString technology. RESULTS: Analysis of the TCGA RNAseq data identified 73 genes that individually predict prognosis for USC patients and an elastic net model with all 73 genes (USC73) distinguishes a good OS group with low USC73 score from a poor OS group with high USC73 score (5-year OS = 83.3% and 13.3% respectively, HR = 40.1; p = 3 × 10-8). This finding was validated in the independent AU cohort (HR = 4.3; p = 0.0004). The poor prognosis group with high USC73 score consists of 37.9% and 32.8% of patients in the TCGA and AU cohort respectively. USC73 score and pathologic stage independently contribute to OS and together provide the best prognostic value. Early stage, low USC73 patients have the best prognosis (5-year OS = 85.1% in the combined dataset), while advanced stage, high USC73 patients have the worst prognosis (5-year OS = 6.4%, HR = 30.5, p = 1.2 × 10-12). Consistent with the observed poor survival, primary cell cultures from high USC73 patients had higher proliferation rate and cell cycle progression; and high USC73 patients had lower rates of complete response to standard therapy. CONCLUSIONS: The USC73 transcriptomic signature and stage independently predict OS of USC patients and the best prediction is achieved using USC73 and stage. USC73 may also serve as a therapeutic biomarker to guide patient care.

3.
J Anal Toxicol ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020177

RESUMO

MDMB-CHMINACA is a newly synthetic cannabinoid which scoped in NMS Lab, USA. Since there are currently no published data on MDMB-CHMINACA metabolism, we aimed to identify its biotransformation pathways and major metabolites. Liquid chromatography Q-Extractive HF Hybrid Quadrupole-Orbitrap mass spectrometry (LC-QE-HF-MS) using full scan positive ion mode and targeted MS/MS (ddms2) techniques with accurate mass measurement were employed to analyze the metabolic sites and pathways. An in vivo metabolic animal model of zebrafish was established to verify the metabolic pathways of MDMB-CHMINACA obtained from human liver microsomal experiment in vitro. The results showed that 29 metabolites were generated in the zebrafish animal model and human liver microsomes model. Biotransformations mainly occurred at the cyclohexylmethyl tail of the compound, minor reactions also occurred at the tert-butyl chain, and no reaction was analysised at the indazole ring. We recommend M1 group (MDMB-CHMINACA ester hydroxylation), and M2 group (MDMB-CHMINACA monohydroxylation) as the potential poisoning markers to document MDMB-CHMINACA intake in clinical and forensic cases. Additionally, this study provides preliminary information regarding the metabolism of MDMB-CHMINACA that will guide analytical standard manufacturers to better provide suitable references for further studies on newly encountered designer drugs.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 275-282, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027289

RESUMO

OBJECTIVE: To investigate the effect of prostaglandin E2 recoptor 4 antagonist (EP4A) on the self-renewal ability of human CD34+ cells and its mechamism. METHODS: The peripheral blood hematopoietic stem cell of 20 healthy donors received the G-CSF-mobilization were collected, then the human CD34+ cells were sorted out by MACS microbead kit. The human CD34+ cells were treated with DMSO (control group), EP4A (EP4A group) and EP4A+EP4A antagonist (EP4A+EP4A group) for 72 hours. The differential genes and pathways related with CD34+ cell stemness were detected by Thermogram and Pathway enrichment analysis. and then the expression levels of protein and gene (ß-catenin, Nanog, Oct4, Sox2, Stat3, AKT, P38) were detected by qRT-PCR and Western blot respectively. RESULTS: EP4A could elevate the mRNA and protein expression of ß-catenin, Nanog, Oct4, Sox2, in comparison with control group, however, mRNA and protein expression of STAT3, AKT, P38 were not changed. When human CD34+ cell were cultured with EP4A+XAV939 it was found that the mRNA and protein expression of ß-catenin was downregulated, moreover the mRNA and protein expression of Nanog, Oct4, Sox2 were reduced. CONCLUSION: EP4A can upregulate stemness factors-ß-catenin, Nanog, Oct4 and Sox2 in human CD34+ cell in vitro, but not STAT3, AKT and P38.

6.
Int Ophthalmol ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31925656

RESUMO

BACKGROUND: Nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF) are well-known neurotrophic factors and widely used in the clinical treatment for its promotion effect on peripheral nerve regeneration. And they were also recommended for the acute paralytic strabismus treatment. However, whether the NGF and CNTF have protective effect for the extraocular muscles of acute paralytic strabismus patients is still poorly understood. PURPOSE: In this study, we want to evaluate the biological function of NGF and CNTF on the extraocular muscle cells and reveale the regulation mechanism behind it. METHODS: Firstly, the relative expression of ngf and cntf was assessed by quantitative real-time RT-PCR. Then, the influence of NGF and CNTF on the extraocular muscle cell proliferation was determined by CCK-8. The inflammatory response in muscle cells after NGF and CNTF treatment was evaluated by ELISA and ROS detection. In addition to this, the up-stream regulation of the ngf and cntf expression was also studied. The TargetScan was used for the predication of potential miRNAs targeting with ngf and cntf 30-UTR, which is soon confirmed by luciferase activity assay. RESULTS: all the results in this research indicated that NGF and CNTF could promote the muscle cell proliferation and inhibit the inflammatory levels, then exert protective effect on the muscle cell function. RESULTS: All the results in this research indicated that NGF and CNTF could promote the muscle cell proliferation and inhibit the inflammatory levels, then exert protective effect on the muscle cell function. CONCLUSION: It was conceivable that let 7-5p was the up-stream regulator of ngf and cntf, and let 7-5p might serve as a potential molecular target for acute paralytic strabismus treatment.

7.
Fish Shellfish Immunol ; 98: 122-129, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31917320

RESUMO

Caspase 3 plays an important role in apoptotic pathways and contributes to maintaining the homeostasis of the immune system in organisms. The structure, functions, and characteristics of caspase 3 have been extensively investigated in many species, but the research is scarce when it comes to bivalves, particularly oysters. In this study, we identified and cloned a previously unknown caspase 3 gene, named ChCas 3, in C. hongkongensis. The full-length cDNA of ChCas 3 was 1562 bp and included a 175 bp 5'-untranslated region (UTR), a 141 bp 3'-UTR and a 1245 bp open reading frame (ORF) that encoded a polypeptide of 415 amino acids. Similar to caspase 3 in other species, ChCas 3 has a pro-domain, a conserved cysteine active site, a large p20 subunit and a small p10 subunit. Our findings demonstrated the expression of ChCas 3 in all the eight tissues via tissue-specific expression assays with the highest expression in haemocytes. ChCas 3 was confirmed to be expressed throughout the larval development stages, and fluorescence from pEGFP-N1-ChCas 3 was found to be distributed throughout the entire HEK293T cell. In addition, the relative expression of ChCas 3 significantly enhanced in hemocytes post bacterial stimulation, and overexpression of ChCas 3 led to upregulation of the transcriptional activity of NF-κB and p53 reporter genes in HEK293T cells, which indicated that it was involved in innate immune responses. Finally, the apoptosis rate of the haemocytes declined considerably compared with that of the control group after the expression of ChCas 3 was successfully silenced by dsRNA, corroborating its sentinel role in apoptosis. This study provides comprehensive underpinning evidences, affirming caspase 3 crucial role against bacterial infection and apoptosis in C. hongkongensis.

8.
Emerg Microbes Infect ; 9(1): 246-255, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31996093

RESUMO

Human coronavirus NL63 (HCoV-NL63) is primarily associated with common cold in children, elderly and immunocompromised individuals. Outbreaks caused by HCoV-NL63 are rare. Here we report a cluster of HCoV-NL63 cases with severe lower respiratory tract infection that arose in Guangzhou, China, in 2018. Twenty-three hospitalized children were confirmed to be HCoV-NL63 positive, and most of whom were hospitalized with severe pneumonia or acute bronchitis. Whole genomes of HCoV-NL63 were obtained using next-generation sequencing. Phylogenetic and single amino acid polymorphism analyses showed that this outbreak was associated with two subgenotypes (C3 and B) of HCoV-NL63. Half of patients were identified to be related to a new subgenotype C3. One unique amino acid mutation at I507 L in spike protein receptor binding domain (RBD) was detected, which segregated this subgenotype C3 from other known subgenotypes. Pseudotyped virus bearing the I507 L mutation in RBD showed enhanced entry into host cells as compared to the prototype virus. This study proved that HCoV-NL63 was undergoing continuous mutation and has the potential to cause severe lower respiratory disease in humans.

9.
Dev Comp Immunol ; 106: 103596, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31877328

RESUMO

Phagocytosis is an evolutionarily conserved immune response, whose efficiency is fundamentally coupled with opsonization of extracellular microbes. How marine mollusks cells recognize and selectively capture pathogens during phagocytosis to clear them is not completely understood. In this study, we observed that plasma is extremely effective for oyster hemocyte phagocytosis, so we investigated candidate proteins among plasma proteins with binding affinity for Vibrio parahaemolyticus in Pacific oyster (Crassostrea gigas) by subjecting them to mass spectroscopy analysis for protein identification and characterization, and address the complex regulatory network to engulf invaders. There were 620 identified proteins potentially associated with bacteria binding and phagocytosis which could be quantified. Our results showed that C1q and lectins identified in Pacific oyster plasma held binding ability to bacteria, clearly suggesting their potent to be opsonins. The dominant expressed plasma protein p1-CgC1q (Complement component 1q)-like protein was identified and its opsonic role was confirmed in this study. The cell surface receptor Cgintegrin interacts directly with p1-CgC1q to mediate phagocytosis. We further confirmed that the interaction between C1q and integrin not rely on the typical recognition site RGD but on the RGE. Evidence exist revealed that p1-CgC1q could coat bacteria via the endotoxin LPS (lipopolysaccharide) and subsequently bind the receptor integrin to significantly enhance hemocytic phagocytosis and bacteria clearance. This study has thus furnished clear evidence for the importance of plasma proteins in mollusk, shedding light on the humoral immunity and an underappreciated strategy in marine host-pathogen interactions.

10.
Dev Comp Immunol ; 103: 103501, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31634519

RESUMO

Tumor necrosis factor receptor-associated factor 6 (TRAF6), an E3 ubiquitin ligase, participates in both innate and adaptive immunity and regulates the apoptotic process. In this study, we observed that an ortholog of TRAF6 could inhibit the activity of p53 and suppress the apoptotic process in the Hong Kong oyster, Crassostrea hongkongensis. To investigate the possible molecular mechanism of the ChTRAF6-induced antiapoptotic effect, a GST pull-down screening assay was conducted, and ChPellino was found to physically interact with ChTRAF6. In addition, the interaction between them was confirmed by Co-immunoprecipitation. Furthermore, western blotting revealed that the phosphorylation level of ChPellino was decreased after the RNAi of ChTRAF6, demonstrating that ChTRAF6 may be an upstream regulator of Pellino activation. Furthermore, the apoptosis level of hemocytes increased after ChPellino knockdown, and ChPellino overexpression suppressed ChTRAF6-dependent p53 activation. Taken together, these results indicate that ChPellino plays a critical role in suppressing ChTRAF6-dependent anti-apoptosis in the hemocytes of Crassostrea hongkongensis.

11.
Mol Cancer Ther ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694888

RESUMO

Malignant pleural mesothelioma (MPM) is an aggressive cancer with dismal prognosis, largely due to poor response rates to and rapid relapse after first-line pemetrexed (MTA)/cisplatin chemotherapy. A better understanding of the molecular mechanisms underlying chemotherapy sensitivity and duration represents a significant but still unmet clinical need. In this study, we reported on a kinome CRISPR/Cas9 knockout screen that identified several G2-M checkpoint kinases, including WEE1, whose loss of function sensitizes MPM cells to standard chemotherapy. We further showed that deregulation of the G2-M checkpoint contributes to chemotherapy resistance, and that WEE1 inhibition synergizes with cisplatin/MTA, leading to enhanced MPM cell death in vitro and potent anti-tumor effects in vivo. Mechanistically, WEE1 blockage overrides chemotherapy-induced G2-M cell cycle arrest and promotes premature mitotic entry, which causes DNA damage accumulation and ultimately apoptosis. Our results suggest a new therapeutic combination for MPM, and support the application of CRISPR/Cas9-based functional genomics in identifying novel therapeutic targets to potentiate existing cancer therapies.

12.
Cancers (Basel) ; 11(10)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597321

RESUMO

Malignant pleural mesothelioma (MPM) is a lethal cancer with limited treatment options. No targeted therapy has emerged yet. Here, we performed an integrated molecular characterization of patient tumors in the TCGA dataset, and discovered that endoplasmic reticulum (ER) stress and the adaptive unfolded protein response (UPR) signaling are characteristically deregulated in MPM. Consequently, pharmacological perturbation of ER stress/UPR axis by HA15, an agent that induces persistent proteotoxic stress in the ER, selectively suppresses the viability of MPM cells including those refractory to standard chemotherapy. Mechanically, HA15 augments the already high basal level of ER stress in MPM cells, embarks pro-apoptotic malfunctional UPR and autophagy, which eventually induces cell death in MPM. Importantly, HA15 exerts anti-MPM effectiveness in a mouse model of patient-derived xenografts (PDX) without eliciting overt toxicity when compared to chemotherapy. Our results revealed that programs orchestrating ER stress/UPR signaling represent therapeutic vulnerabilities in MPM and validate HA15 as a promising agent to treat patients with MPM, naïve or resistant to chemotherapy.

13.
Eur J Clin Microbiol Infect Dis ; 38(12): 2355-2364, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31489496

RESUMO

To investigate the features of paramyxovirus respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (HMPV) infection and determine the effect of meteorological conditions in Guangzhou, a subtropical region of southern China. We collected 11,398 respiratory samples from hospitalized pediatric patients with acute respiratory illness between July 2009 and June 2016 in Guangzhou. The samples were tested simultaneously for 18 respiratory pathogens using real-time PCR. Local meteorological data were also collected for correlation analysis. Of 11,398 patients tested, 5606 (49.2%) patients tested positive for one or more pathogens; RSV, PIV, and HMPV were the first, sixth, and ninth most frequently detected pathogens, in 1690 (14.8%), 502 (4.4%), and 321 (2.8%) patients, respectively. A total 17.9% (4605/5606) of patients with positive results had coinfection with other pathogens. Significant differences were found in the prevalence of RSV, PIV, and HMPV among all age groups (p < 0.001). RSV and HMPV had similar seasonal patterns, with two prevalence peaks every year. PIV appeared alternatively with RSV and HMPV. Multiple linear regression models were established for RSV, PIV, and HMPV prevalence and meteorological factors (p < 0.05). RSV and PIV incidence was negatively correlated with monthly mean relative humidity; RSV and HMPV incidence was negatively correlated with sunshine duration; PIV incidence was positively correlated with mean temperature. We described the features of paramyxovirus infection in a subtropical region of China and highlighted the correlation with meteorological factors. These findings will assist public health authorities and clinicians in improving strategies for controlling paramyxovirus infection.

14.
Adv Mater ; 31(39): e1902469, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31402525

RESUMO

Cells transport mass dynamically, crossing cell membranes to maintain metabolism and systemic homeostasis, through which biomolecules are also delivered to cells for gene editing, cell reprograming, therapy, and other purposes. Quantifying the translocation kinetics is fundamentally and clinically essential, but remains limited by fluorescence-based technologies, which are semi-quantitative and only provide kinetics information at cellular level or in discrete time. Herein, a real-time method of quantifying cell internalization kinetics is reported using functionalized firefly-luciferase nanocapsules as the probe. This quantitative assay will facilitate the rational design of delivery vectors and enable high-throughput screening of peptides and other functional molecules, constituting an effective tool for broad applications, including drug development and cancer therapy.

15.
Nat Biomed Eng ; 3(9): 706-716, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31384008

RESUMO

Approximately 15-40% of all cancers develop metastases in the central nervous system (CNS), yet few therapeutic options exist to treat them. Cancer therapies based on monoclonal antibodies are widely successful, yet have limited efficacy against CNS metastases, owing to the low levels of the drug reaching the tumour site. Here, we show that the encapsulation of rituximab within a crosslinked zwitterionic polymer layer leads to the sustained release of rituximab as the crosslinkers are gradually hydrolysed, enhancing the CNS levels of the antibody by approximately tenfold with respect to the administration of naked rituximab. When the nanocapsules were functionalized with CXCL13-the ligand for the chemokine receptor CXCR5, which is frequently found on B-cell lymphoma-a single dose led to improved control of CXCR5-expressing metastases in a murine xenograft model of non-Hodgkin lymphoma, and eliminated lymphoma in a xenografted humanized bone marrow-liver-thymus mouse model. Encapsulation and molecular targeting of therapeutic antibodies could become an option for the treatment of cancers with CNS metastases.

16.
Oncogenesis ; 8(9): 45, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431614

RESUMO

Drug resistance and tumor heterogeneity are formidable challenges in cancer medicine, which is particularly relevant for KRAS-mutant cancers, the epitome of malignant tumors recalcitrant to targeted therapy efforts and first-line chemotherapy. In this study, we delineate that KRAS-mutant lung cancer cells resistant to pemetrexed (MTA) and anti-MEK drug trametinib acquire an exquisite dependency on endoplasmic reticulum (ER) stress signaling, rendering resistant cancer cells selectively susceptible to blockage of HSP90, the receptor tyrosine kinase AXL, the eukaryotic translation initiation factor 4E (eIF4E), and the unfolded protein response (UPR). Mechanistically, acquisition of drug resistance enables KRAS-mutant lung cancer cells to bypass canonical KRAS effectors but entail hyperactive AXL/eIF4E, increased protein turnover in the ER, and adaptive activation of an ER stress-relief UPR survival pathway whose integrity is maintained by HSP90. Notably, the unique dependency and sensitivity induced by drug resistance are applicable to KRAS-mutant lung cancer cells undergoing de novo intratumor heterogeneity. In line with these findings, HSP90 inhibitors synergistically enhance antitumor effects of MTA and trametinib, validating a rational combination strategy to treat KRAS-mutant lung cancer. Collectively, these results uncover collateral vulnerabilities co-occurring with drug resistance and tumor heterogeneity, informing novel therapeutic avenues for KRAS-mutant lung cancer.

17.
Nucl Med Biol ; 72-73: 62-69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31330414

RESUMO

PURPOSE: A novel radiolabeled probe 1­(17­[18F]fluoro­3,6,9,12,15­pentaoxaheptadecyl­1H­1,2,3­triazole testosterone ([18F]FPTT) was synthesized and evaluated for PET imaging of progesterone receptor (PR)-positive breast cancer. METHODS: The ethinyl group of ethisterone, a PR targeting pharmacophore, was coupled with azide modified PEG-OTs by click chemistry to obtain the labeling precursor. The final [18F]FPTT was synthesized by a one-step nucleophilic substitution reaction with 18F. The in vitro stabilities of [18F]FPTT in saline or rat serum were determined after 2 h incubation. Then the in vitro cell binding, ex vivo biodistribution and in vivo imaging of [18F]FPTT were further investigated to evaluate the PR targeting ability and feasibility for the diagnosis of PR-positive breast cancer with PET imaging. RESULTS: [18F]FPTT was obtained in high decay-corrected radiochemical yield (78 ±â€¯9%) at the end of synthesis. It had high radiochemical purity (>98%) after HPLC purification and good in vitro stability. The molar activity of [18F]FPTT was calculated as 17 GBq/µmol. The microPET imaging of [18F]FPTT in tumor-bearing mice showed much higher tumor uptake in PR-positive MCF-7 tumor (3.9 ±â€¯0.20%ID/g) than that of PR-negative MDA-MB-231 tumor (1.3 ±â€¯0.08%ID/g). The high MCF-7 tumor uptake could be specifically inhibited by blocking with ethisterone (1.3 ±â€¯0.11%ID/g) or [19F]FPTT (2.20 ±â€¯0.17%ID/g), respectively. The biodistribution in estrogen-primed female SD rats of [18F]FPTT showed high uterus and ovary uptakes (8.31 ±â€¯1.74%ID/g and 3.79 ±â€¯0.82%ID/g at 1 h post-injection). The specific uptakes of uterus and ovary in normal rats were 3.52 ±â€¯0.29%ID/g and 3.22 ±â€¯0.50%ID/g respectively and could be inhibited by co-injecting of ethisterone. CONCLUSION: A novel [18F]FPTT probe based on ethisterone modification could be a potential diagnostic agent for PR-positive breast cancer.

18.
J Am Chem Soc ; 141(24): 9500-9503, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31179694

RESUMO

Although π-π interactions have been studied for several decades, the quantification of the strength of π-π interactions in a macromolecule remains a big challenge. Herein, we utilize single-molecule atomic force microscopy and steered molecular dynamics simulations to study the π-π interactions in polystyrene (PS). It is found that in high vacuum, the single-chain mechanics of PS differs largely from that of polyethylene (PE). Accordingly, the strength of intrachain π-π interactions in PS is estimated to be 0.7 kcal/(mol stack), which is much lower than that in a small-molecule system (benzene dimer, 2-3 kcal/(mol stack)). Further study shows that in high vacuum, there are two types of π-π stacking in the single PS chain, i.e., the every-other-moiety (E) type and the adjacent-moiety (A) type. Upon force stretching, a transition from E-type to A-type π-π stacking can be observed.

19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(3): 407-413, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31232543

RESUMO

Tree shrew is a novel and high-quality experimental animal model. In this study, the real-time polymerase chain reaction methods were established to detect infection-related cytokines interleukin-6 (IL-6), IL-8, IL-10, IL-17A, interferon-γ (IFN-γ) and housekeeping gene glyceraldehyde-phosphate dehydrogenase ( GAPDH) of tree shrew. The results indicated that the establised methods had good specificity. The high point of the linear range of these reagents reached 1 × 10 10 copies, and the low points ranged from 10 copies (IL-6, IL-17A), 100 copies (IL-10, GAPDH) to 1 000 copies (IL-8, IFN-γ). In this interval, the linear correlation coefficient R 2 of each reagent was greater than 0.99. The lowest detectable values of IL-6, IL-8, IL-10, IL-17A, IFN-γ and GAPDH were 8, 8, 4, 8, 128 and 4 copies, respectively. The results showed that the established detection methods had good specificity, sensitivity and wide linear range. The methods were suitable for detection of multiple concentration range samples, and could be used for the subsequent studies of tree shrew cytokines.


Assuntos
Citocinas/análise , Reação em Cadeia da Polimerase em Tempo Real , Musaranhos , Animais
20.
Front Chem ; 7: 240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31041306

RESUMO

In this study, the metabolic profiles of a new illicit drug AMB-FUBINACA were investigated using both human liver microsome and zebrafish models. Liquid chromatography Q Extractive HF Hybrid Quadrupole-Orbitrap mass spectrometry (LC-QE-HF-MS) was employed to analyze the metabolic sites and pathways. AMB-FUBINACA was added to the in vitro liver microsome incubation model to simulate the metabolic processes in human body. The results showed that a total of 17 metabolites were generated in the human liver microsome model; the main metabolic pathways of the phase I metabolism included ester hydrolysis, methylation, ester hydrolysis combined with decarboxylation, hydroxylation, ester hydrolysis combined with indazole ring hydroxylation, etc. while glucuronidation served as the main metabolic pathway of the phase II metabolism. The zebrafish system produced a similar result with 16 of the same 17 metabolites identified. The phase I metabolites M3.1 (ester hydrolysis), M1.2 (alkyl chain hydrolysis) and the phase II metabolite M3.2 (M3.1 glucuronide) were recommended to be the potential poisoning markers.

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