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1.
Artigo em Inglês | MEDLINE | ID: mdl-32454162

RESUMO

Arecoline is a naturally occurring psychoactive alkaloid with partial agonism at nicotinic and muscarinic acetylcholine receptors. Arecoline consumption is widespread, making it the fourth (after alcohol, nicotine and caffeine) most used substance by humans. However, the mechanisms of acute and chronic action of arecoline in-vivo remain poorly understood. Animal models are a valuable tool for CNS disease modeling and drug screening. Complementing rodent studies, the zebrafish (Danio rerio) emerges as a promising novel model organism for neuroscience research. Here, we assessed the effects of acute and chronic arecoline on adult zebrafish behavior and physiology. Overall, acute and chronic arecoline treatments produced overt anxiolytic-like behavior (without affecting general locomotor activity and whole-body cortisol levels), with similar effects also caused by areca nut water extracts. Acute arecoline at 10 mg/L disrupted shoaling, increased social preference, elevated brain norepinephrine and serotonin levels and reduced serotonin turnover. Acute arecoline also upregulated early protooncogenes c-fos and c-jun in the brain, whereas chronic treatment with 1 mg/L elevated brain expression of microglia-specific biomarker genes egr2 and ym1 (thus, implicating microglial mechanisms in potential effects of long-term arecoline use). Finally, acute 2-h discontinuation of chronic arecoline treatment evoked withdrawal-like anxiogenic behavior in zebrafish. In general, these findings support high sensitivity of zebrafish screens to arecoline and related compounds, and reinforce the growing utility of zebrafish for probing molecular mechanisms of CNS drugs. Our study also suggests that novel anxiolytic drugs can eventually be developed based on arecoline-like molecules, whose integrative mechanisms of CNS action may involve monoaminergic and neuro-immune modulation.

2.
Brain Res Bull ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33027679

RESUMO

Neuroglia, including microglia and astrocytes, is a critical component of the central nervous system (CNS) that interacts with neurons to modulate their activity, development, metabolism and signaling. Thus, a better understanding of the role of neuroglia in the brain is critical. Complementing clinical and rodent data, the zebrafish (Danio rerio) is rapidly becoming an important model organism to probe the role of neuroglia in brain disorders. With high genetic and physiological similarity to humans, zebrafish possess some common (shared), as well as some specific molecular biomarkers and features of neuroglia development and functioning. Studying these common and zebrafish-specific aspects of neuroglia may generate important insights into key brain mechanisms, including neurodevelopmental, neurodegenerative, neuroregenerative and neurological deficits. Here, we discuss the biology of neuroglia in humans, rodents and fish, its role in various CNS processes, and further directions of translational research into the role of neuroglia in CNS disorders using zebrafish models.

3.
J Int Med Res ; 48(10): 300060520925666, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33100078

RESUMO

INTRODUCTION: Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is an autoimmune-mediated disease that is common in young female patients with ovarian teratomas. With appropriate immunotherapy, most patients achieve a good prognosis. Nevertheless, some patients may be refractory to first- and second-line immunotherapy, thus alternative treatments are required for these patients.Case presentation: We present a case of anti-NMDA receptor encephalitis with ovarian teratoma. After the prompt removal of the teratoma and intense immunotherapy was administered, including an intravenous methylprednisolone pulse, intravenous immunoglobin, plasmapheresis, immunoadsorption, intravenous cyclophosphamide, and rituximab, the patient's neurologic status did not improve. Bilateral salpingo-oophorectomy was then conducted, and intrathecal injection of methotrexate (MTX) and dexamethasone (DXM) was performed. The patient's neurological symptoms improved dramatically, and she achieved a good prognosis after 23 months. CONCLUSIONS: Intrathecal injection of MTX and DXM may be beneficial for treatment of refractory cases of anti-NMDA receptor encephalitis. Additional research is required to elucidate the mechanisms of intrathecal treatment with this therapy.

4.
Sci Rep ; 10(1): 17432, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060705

RESUMO

Lung cancer is the leading cause of cancer death worldwide. The Xuanwei-Fuyuan (XF) region of Yunnan, China has a high incidence of lung cancer from coal-related pollution. Effort to raise public awareness screening for lung cancer has been ongoing. We retrospectively analyzed overall survival (OS) of lung cancer patients of a tertiary cancer center in Yunnan to investigate screening and regional residential status as predictive factors. Consecutive cases of newly diagnosed lung cancer were reviewed. The lung cancer cases diagnosed by screening were more likely to be early-staged and treated by surgery than those diagnosed not by screening. In patients diagnosed not by screening, XF residential status was a significant predictor of improved OS. Frailty model detected significant heterogeneity associated with region of residence in unscreened patients. Potential biases associated with screening were examined by Monte Carlo simulations and sensitivity analyses. Focused effort in cancer screening and increased public awareness of pollution-related lung cancer in XF might have led to early diagnosis and improved OS, and increased investment in health care resources in high risk areas may have produced additional unobserved factors that underlay the association of XF residential status with improved OS in patients diagnosed not by screening.

5.
Medicine (Baltimore) ; 99(39): e22406, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991468

RESUMO

Giant cell arteritis (GCA) is the most common vasculitis in elderly, with ischemic and constitutional symptoms caused by vascular involvement and systemic inflammation. Early initiation of therapy results in prompt remission, while patients may still experience flares or severe complications during glucocorticoid tapering. This study was to identify the characteristics of Chinese GCA patients with different prognosis.Ninety-one patients diagnosed with GCA in Peking Union Medical College Hospital in the last 20 years were followed up. Those who were lost to follow up or were followed up for less than 1 year were excluded. According to the prognosis, patients were divided into the group of favourable prognosis (patients who sustained disease remission for over 1 year) and unfavorable prognosis (patients who had relapses or severe complications). Clinical data at disease onset and after treatment were collected and analysed between the 2 groups.Thirty-seven patients with favourable prognosis and 40 patients with unfavourable prognosis were admitted into the study. Fever as an onset symptom was less common in favourable group (P=.016). As for presentations of GCA, fever, tenderness and abnormal pulsation of temporal artery and jaw claudication were less frequently observed in patients with favourable prognosis (P=.029, .049, .043, respectively). At onset, medium-size arteries were affected more in unfavorable prognosis group (P = .048), and involvement of branches below the aortic arch were more common in favorable prognosis group (P = .034). Erythrocyte sedimentation rate in group of favourable prognosis were significantly lower after treatment (P = .041). Compared with healthy subjects, GCA patients had increased monocytes and decreased lymphocytes at disease onset (P < .01). Monocyte counts were higher in patients with favourable prognosis at disease onset (P = .043), while no significant differences were seen between the 2 groups after treatment. Lymphocyte counts were lower in patients with unfavourable prognosis (P = .014) after treatment.Complete blood count may reflect the disease status of GCA. Little change in monocyte during treatment and lower lymphocytes after treatment may serve as potential predictors of unfavourable clinical prognosis.


Assuntos
Arterite de Células Gigantes/sangue , Idoso , Contagem de Células Sanguíneas , Feminino , Arterite de Células Gigantes/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
6.
J Ethnopharmacol ; : 113383, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32918992

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Although Traditional Chinese Medicine (TCM) has a millennia-long history of treating human brain disorders, its complex multi-target mechanisms of action remain poorly understood. Animal models are widely used to probe the effects of various TCMs on brain and behavior. The zebrafish (Danio rerio) has recently emerged as a novel vertebrate model for neuroscience research, and is increasingly used for CNS drug screening and development. AIM OF THE STUDY: As zebrafish models are only beginning to be applied to studying TCM, we aim to provide a systematic review about the TCM effects using zebrafish models. MATERIALS AND METHODS: A comprehensive search of published literature was conducted using biomedical databases (Web of Science, Pubmed, Sciencedirect, Google Scholar and China National Knowledge Internet, CNKI), with key search words zebrafish, brain, Traditional Chinese Medicine, herbs, CNS, behavior. RESULTS: We recognize the growing use of zebrafish for studying TCM, as well as outline the existing model limitations, problems and challenges, as well as future directions of research in this field. CONCLUSIONS: We demonstrate the growing value of zebrafish models for studying TCM, aiming to improve our understanding of TCM' therapeutic mechanisms and potential in treating brain disorders.

7.
Chem Commun (Camb) ; 56(83): 12558-12561, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32940265

RESUMO

A novel genotoxicity sensor was developed based on the base repair process associated with the electrochemiluminescence (ECL) detection of abasic sites in a double-stranded DNA monolayer. This is the first time that an ECL sensor with the ability to identify the removed nucleobases in a DNA duplex has been studied. The successful detection of abasic sites created by DNA glycosylase indicates its further applications for examining some other specific types of DNA damage.

8.
Chem Commun (Camb) ; 56(78): 11629-11632, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32870209

RESUMO

We report a new strongly birefringent material, [Al(H2O)6](IO3)2(NO3) (AINO). Based on a detailed analysis, we concluded that its enhanced birefringence (0.253 at 546 nm) predominantly resulted from a synergy of the effects of its (NO3)- and (IO3)- functional motifs, combined with an equally important and indispensable optimal arrangement of these two groups in the structure. This work has provided insight for discovering new birefringent materials.

9.
Zhongguo Zhong Yao Za Zhi ; 45(16): 3915-3921, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893589

RESUMO

This study aimed to investigate the effect and possible mechanism of Bidens pilosa decoction on non-alcoholic fatty liver disease(NAFLD) induced by high fat and high glucose in mice. Bald/c mice were randomly divided into normal group, model group, metformin(200 mg·kg~(-1)) treatment group, Bidens pilosa decoction(10 g·kg~(-1)) treatment group, metformin and B. pilosa decoction(100 mg·kg~(-1)+5 g·kg~(-1)) treatment group. Except for the normal group, mice in the other four groups were fed with high-fat and high-glucose diet for 8 weeks to establish the non-alcoholic fatty liver model. After 4 weeks of treatment, blood was collected from the eyeballs, the mice were sacrificed, and relevant indicators were detected. The results showed that compared with the model group, blood lipid and blood glucose levels of each treatment group were significantly lower(P<0.05); HE staining results showed that liver pathological damage in each treatment group was significantly improved; oil red O staining results showed fat distribution in each treatment group significantly reduced(P<0.01); immunohistochemical staining showed that glucose regulated the protein expression of protein 78(GRP78) in liver tissues of each treatment group was also significantly reduced(P<0.01); Western blot results showed that endoplasmic reticulum stress signal pathway-related factors GRP78, phosphorylated-protein kinase R-like ER kinase(p-PERK), eukaryotic translation-initiation factor 2α(eIF2α), activating transcription factor 4(ATF4), C/EBP homologous protein(Chop), inositol requiring 1α(IRE1α), and cleaved-cysteinyl aspartate specific proteinase 12(cleaved-caspase-12) were significantly reduced(P<0.01). The results of the combined drug treatment group were better than those of the single drug treatment group. These results showed that B. pilosa decoction had the effect in improving non-alcoholic fatty liver, and its mechanism may be related to the down-regulation of the expression of endoplasmic reticulum stress(ERS)-related factors, and the reduction of the apoptosis of hepatocytes caused by ERS and the down-regulation of blood lipid and blood glucose levels.


Assuntos
Bidens , Hepatopatia Gordurosa não Alcoólica , Animais , Apoptose , Estresse do Retículo Endoplasmático , Endorribonucleases , Glucose , Camundongos , Proteínas Serina-Treonina Quinases
10.
Anal Chim Acta ; 1132: 74-82, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-32980113

RESUMO

Bile acids (BAs), as crucial endogenous metabolites, are closely related to cholestasis, metabolic disorders, and cancer. To better understand their function and disease pathogenesis, global profiling of BAs is necessary. Here, multidimensional data mining was developed for the discovery and identification of potentially unknown BAs in cholestasis rats. Based on an in-house theoretical BA database and using a newly established liquid chromatography-tandem high-resolution mass spectrometry (LC-HRMS/MS) method, four-dimensional (4D) data including the retention times (RT), abundances, HRMS, and HRMS/MS spectra were acquired and elucidated. And 491 BAs were totally profiled. Then, the relationships between RT with different conjugation types, different positions and configurations of hydroxyl/ketone groups as well as fragmentation rules of hydroxyl, ortho-hydroxyl, ketone, and conjugated groups of BAs were summarized to assist BA identification for the first time. Finally, 292 BAs were assigned with molecular formulas, 201 of which were putatively identified by integrating the 4D data, applying structure-driven relative retention time rules, and a comparison with synthetic BAs. The estimated concentrations of 201 BAs, including 93 reported and 108 newly identified BAs, were quantified by using surrogate standards with similar structure. Among 201 BAs, 38 BAs were detected in both humans and rats for the first time. Our strategy has expanded the scope of BAs and provides a way to identify a class of metabolites. Compared to normal rats, the significantly increased sulfated and glucuronide conjugated BAs in urine and feces from experimentally cholestatic rats may reveal a way to diagnose intrahepatic cholestasis.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32924279

RESUMO

Plant cells can sense conserved molecular patterns through pattern recognition receptors (PRRs) and initiate pattern-triggered immunity (PTI). Details of the PTI signaling network are starting to be uncovered in Arabidopsis, but are still poorly understood in other species, including soybean (Glycine max). In this study, we perform a forward genetic screen for autoimmunity-related lesion mimic mutants (lmms) in soybean and identify two allelic mutants, which carry mutations in Glyma.13G054400, encoding a malectin-like receptor kinase (RK). The mutants exhibit enhanced resistance to both bacterial and oomycete pathogens, as well as elevated ROS production upon treatment with the bacterial pattern flg22. Overexpression of GmLMM1 gene in Nicotiana benthamiana severely suppresses flg22-triggered ROS production and oomycete pattern XEG1-induced cell death. We further show that GmLMM1 interacts with the flg22 receptor FLS2 and its co-receptor BAK1 to negatively regulate flg22-induced complex formation between them. Our study identifies an important component in PTI regulation and reveals that GmLMM1 acts as a molecular switch to control an appropriate immune activation, which may also be adapted to other PRR-mediated immune signaling in soybean.

12.
Psychopharmacology (Berl) ; 237(11): 3409-3416, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32757027

RESUMO

BACKGROUND: Previous studies have shown that patients with schizophrenia have higher smoking rates and worse cognitive function than healthy controls. However, there is no consistent conclusion about the relationship between smoking and cognitive impairment. OBJECTIVES: The main purpose of this study was to explore the effects of smoking on cognitive function by using MATRICS Cognitive Consensus Battery (MCCB) in Chinese male patients with schizophrenia. METHODS: There were 164 patients with chronic schizophrenia and 82 healthy controls. All subjects were interviewed about smoking status. The cognitive function was assessed by MCCB and Stroop tests. The Positive and Negative Syndrome Scale (PANSS) was used to assess the clinical symptoms of the patients. RESULTS: Compared with healthy controls, patients had lower MCCB scores in all of its domain scores (all p < 0.05). In the patients, the scores of spatial span test (42.3 ± 11.6), digital sequence test (42.9 ± 10.6), and Hopkins Verbal Learning Test (42.2 ± 10.1) were lower in smokers than those in nonsmokers (all p < 0.05, effect size: 0.28-0.45). Logistic regression analysis showed that the smoking status of the patients was correlated with digital sequence score (p < 0.05, OR = 1.072, 95%CI: 1.013-1.134). Multivariate regression analysis showed that the spatial span total score (ß = - 0.26, t = - 2.74, p < 0.001) was associated with the duration of smoking in patients with schizophrenia. CONCLUSIONS: Our findings show that smoking patients with chronic schizophrenia exhibit more severe cognitive impairment than nonsmoking patients, especially in working memory and executive function.

13.
Anal Chim Acta ; 1128: 193-202, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32825903

RESUMO

2,4,6-trinitrotoluene (TNT) sensing on surfaces and in solution is an important issue in sensor fabrication for homeland security and environmental protection. Herein, Play-Doh, a modeling material popular for kids, was proposed as a versatile sensor for on-site fluorescent (FL), visual FL (VFL), and colorimetric detection of TNT both on surfaces and in solution after being doped with -NH2 through a one-step approach. Play-Doh exhibits FL emission due to the main ingredient of flour. After -NH2 doping, amino-Play-Doh (APD) was utilized to construct a FL sensor based on FL resonance energy transfer and inner filter effect for TNT detection. The advantage of APD was that no additional fluorophore was needed compared with the traditional sensors for FL and VFL analysis. The orange complex visible to the naked eye was also recorded for smartphone-based colorimetric detection of TNT. In both cases, the APD demonstrated good analytical performance for TNT. Finally, APD was successfully utilized for TNT sensing on fingerprints, luggage, and in environmental water samples, respectively. Play-Doh might be a potential sensor for future on-site detection of TNT owing to the merits of being cost-effective and versatile.

14.
Nat Commun ; 11(1): 4028, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32788591

RESUMO

Changes in atmospheric CO2 concentration have played a central role in algal and plant adaptation and evolution. The commercially important red algal genus, Pyropia (Bangiales) appears to have responded to inorganic carbon (Ci) availability by evolving alternating heteromorphic generations that occupy distinct habitats. The leafy gametophyte inhabits the intertidal zone that undergoes frequent emersion, whereas the sporophyte conchocelis bores into mollusk shells. Here, we analyze a high-quality genome assembly of Pyropia yezoensis to elucidate the interplay between Ci availability and life cycle evolution. We find horizontal gene transfers from bacteria and expansion of gene families (e.g. carbonic anhydrase, anti-oxidative related genes), many of which show gametophyte-specific expression or significant up-regulation in gametophyte in response to dehydration. In conchocelis, the release of HCO3- from shell promoted by carbonic anhydrase provides a source of Ci. This hypothesis is supported by the incorporation of 13C isotope by conchocelis when co-cultured with 13C-labeled CaCO3.


Assuntos
Carbono/metabolismo , Genoma , Rodófitas/genética , Rodófitas/metabolismo , Movimentos da Água , Exoesqueleto/química , Animais , Antioxidantes/farmacologia , Composição de Bases/genética , Evolução Biológica , Carbonato de Cálcio/metabolismo , Anidrases Carbônicas/genética , Anidrases Carbônicas/metabolismo , Núcleo Celular/genética , Dosagem de Genes , Perfilação da Expressão Gênica , Transferência Genética Horizontal/genética , Moluscos , Fotossíntese/efeitos dos fármacos , Ploidias , Rodófitas/efeitos dos fármacos , Superóxido Dismutase/genética , Transcrição Genética/efeitos dos fármacos
15.
Biosci Rep ; 40(8)2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32766727

RESUMO

BACKGROUND: Papillary thyroid carcinoma (PTC) is one of the fastest-growing malignant tumor types of thyroid cancer. Therefore, identifying the interaction of genes in PTC is crucial for elucidating its pathogenesis and finding more specific molecular biomarkers. METHODS: Four pairs of PTC tissues and adjacent tissues were sequenced using RNA-Seq, and 3745 differentially expressed genes were screened (P<0.05, |logFC|>1). The enrichment analysis indicated that the vast majority of differentially expressed genes (DEGs) may play a positive role in the development of cancer. Then, the significant modules were analyzed using Cytoscape software in the protein-protein interaction network. Survival analysis, TNM analysis, and immune infiltration analysis of key genes were analyzed. And the expression of ADORA1, APOE, and LPAR5 genes were verified by qPCR in PTC compared with matching adjacent tissues. RESULTS: Twenty-five genes were identified as hub genes with nodes greater than 10. The expression of 25 genes were verified by the GEPIA database, and the overall survival and disease-free survival analyses were conducted with Kaplan-Meier plotter. We found only three genes were confirmed with our validation and were statistically significant in PTC, namely ADORA1, APOE, and LPAR5. Further analysis found that the mRNA levels and methylation degree of these three genes were significantly correlated with the TNM staging of PTC. And these three genes were related to PTC immune infiltration. Verification of the expression of these three genes by RT-qPCR and Western blot further confirmed the reliability of our results. CONCLUSION: Our study identified three genes that may play key regulatory roles in the development, metastasis, and immune infiltration of papillary thyroid carcinoma.

16.
Mikrochim Acta ; 187(9): 502, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32812088

RESUMO

A highly reproducible surface-enhanced Raman scattering (SERS) unsupported liquid-state platform (ULP) was developed for accurate quantitative determination of triazophos. Herein, citrate-reduced Ag NPs suspension was concentrated and placed in a stainless steel perforated template to form the SERS ULP. The relative standard deviation of the SERS measurements was less than 5% (n ≥ 10), and the R2 of the calibration curve was 0.994. The developed SERS ULP was applied for determination of triazophos in spiked agricultural products (rice, cabbage, and apple). Experiment results showed that the coefficient of variation ranged from 5.3 to 6.2% for intra-day and from 5.5 to 6.3% for inter-day (n = 3), which proved excellent SERS reproducibility. Moreover, the results were in good agreement with those from HPLC analysis. As a liquid-state SERS substrate, the highly reproducible ULP can perform precision quantitative analysis without surface modification of NPs, which is a significant improvement. This method provides a new perspective for quantitative SERS analysis of pesticide residues. Graphical abstract.

17.
ACS Sens ; 5(9): 2933-2939, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32799533

RESUMO

The advent of miniaturized, fiber-based, Raman spectrometers provides a clear path for the wide implementation of surface-enhanced Raman scattering (SERS) in analytical chemistry. For instance, miniaturized systems are especially useful in field applications due to their simplicity and low cost. However, traditional SERS substrates are generally developed and optimized using expensive Raman microscope systems equipped with high numerical aperture (NA) objective lenses. Here, we introduced a new type of SERS substrate with intrinsic Raman photon directing capability that compensates the relatively low signal collection power of fiber-based Raman spectrometers. The substrate was tested for the detection of buried 2,4-dinitrotoluene in simulated field conditions. A linear calibration curve (R2 = 0.98) for 2,4-dinitrotoluene spanning 3 orders of magnitude (from µg kg-1 to mg kg-1) was obtained with a limit of detection of 10 µg kg-1 within a total volume of 10 µL. This detection level is 2 orders of magnitude lower than that possible with the current state-of-the-art technologies, such as ion mobility spectrometry-mass spectrometry. The approach reported here demonstrated a high-performance detection of 2,4-dinitrotoluene in field conditions by a SERS platform optimized for miniaturized Raman systems that can be deployed for a routine inspection of landmine-contaminated sites and homeland security applications.

18.
Cancer Med ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32767662

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. Herein, we explored the underlying mechanism by which Propofol inhibited the development of HCC. METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out to detect the viability and proliferation. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to detect the expression of long noncoding RNA (lncRNA) H19, microRNA-520a-3p (miR-520a-3p), LIM domain kinase 1 (LIMK1), metastasis-associated markers (Snail, Twist, Vimentin and E-cadherin) and exosome markers (CD9 and CD81). Transmission electron microscopy (TEM) was used to observe the morphology and structure of exosomes. The apoptosis and metastasis were measured by flow cytometry and transwell assays. StarBase software was utilized to predict the targets of H19 and miR-520a-3p. Dual-luciferase reporter assay was performed to confirm the interaction between miR-520a-3p and H19 or LIMK1. Nude mice bearing tumors were used to validate the role of exosomal H19. RESULTS: The high expression of exosomal H19 accelerated the proliferation and motility while hampering the apoptosis of HCC cells. MiR-520a-3p could bind with H19. Exosomal H19 exacerbated HCC through sponging miR-520a-3p. The 3' untranslated region (3'UTR) of LIMK1 could bind to miR-520a-3p. MiR-520a-3p mimic transfection reversed the inhibitory effect of high expression of exosomal LIMK1 on the apoptosis of HCC cells and the promoting effects on the proliferation and metastasis of HCC cells. The mRNA and protein levels of LIMK1 were regulated by H19/miR-520a-3p signaling. The high level of exosomal H19 promoted the growth of HCC tumors in vivo. CONCLUSION: Circulating H19 promoted the proliferation, migration and invasion and inhibited the apoptosis of HCC cells treated with Propofol through upregulating LIMK1 via sponging miR-520a-3p.

20.
Cell Cycle ; 19(19): 2538-2552, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32857667

RESUMO

The involvement of propofol and circular RNAs (circRNAs) in lung cancer progression has been identified. However, the relationship between propofol and circRNAs as well as the underlying molecular mechanisms on lung cancer development remain unclear. Cell viability, migration and invasion were measured by cell counting kit-8 assay, 5-bromo-2-deoxyuridine (BrdU) and transwell assay. Glycolytic metabolism was calculated by measuring the glucose consumption, lactate production and extracellular acidification. Western blot was used to detect the protein of glucose transporter 1 (GLUT1), glycolysis enzymes, and forkhead box M1 (FOXM1). The expression of circRNA transcriptional adaptor 2A (circTADA2A), microRNA (miR)-455-3p and FOXM1 mRNA was detected by quantitative real-time polymerase chain reaction. The interaction between miR-455-3p and circTADA2A or FOXM1 was analyzed using the dual-luciferase reporter assay. Murine xenograft model was established to perform in vivo experiments. We found propofol treatment alleviated lung cancer cell proliferation, migration, invasion and aerobic glycolysis in vitro as well as inhibited tumor growth in vivo. Propofol decreased the level of circTADA2A and exerted anti-tumor effects by regulating circTADA2A. MiR-455-3p directly interacted with circTADA2A and FOXM1 in lung cancer cells, and circTADA2A could regulate FOXM1 expression by binding to miR-455-3p. Subsequently, rescue assay showed that propofol inhibited cell proliferation, migration, invasion and aerobic glycolysis by regulating circTADA2A/miR-455-3p/FOXM1 axis in lung cancer. Collectively, propofol suppressed cell carcinogenesis and aerobic glycolysis by regulating circTADA2A/miR-455-3p/FOXM1 axis in lung cancer, providing an effective clinical implication for propofol to prevent the development of lung cancer.

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