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1.
Nanotechnology ; 31(27): 275707, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32235049

RESUMO

In this work, to maximize the unique attributes of reduced graphene oxide (RGO) for excellent microwave absorption, the ultralight RGO aerogels with improved dispersion and interface polarization performance were fabricated via a facile cation-assisted hydrothermal treatment process. The prepared RGO/paraffin composite exhibits excellent microwave absorption (MA) performance in a wideband frequency range of 8.0 ∼ 18.0 GHz with an ultralow absorbent content of 0.5 wt.%. Such performance is comparable with most previously reported results on RGO-based composites but required much higher absorbent content. The mechanisms for the enhancement of polarization relaxation loss and conductive loss were investigated in detail. This study provides a promising and facile method for preparing RGO-based excellent microwave absorption materials with ultra-low filler content, which is significant for designing efficient MA absorbers.

2.
CNS Neurol Disord Drug Targets ; 19(1): 66-82, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31957620

RESUMO

BACKGROUND: Brain-Derived Neurotrophic Factor (BDNF) plays critical roles during development of the central and peripheral nervous systems, as well as in neuronal survival after injury. Although proBDNF induces neuronal apoptosis after injury in vivo, whether it can also act as a death factor in vitro and in vivo under physiological conditions and after nerve injury, as well as its mechanism of inducing apoptosis, is still unclear. OBJECTIVE: In this study, we investigated the mechanisms by which proBDNF causes apoptosis in sensory neurons and Satellite Glial Cells (SGCs) in Dorsal Root Ganglia (DRG) After Sciatic Nerve Transection (SNT). METHODS: SGCs cultures were prepared and a scratch model was established to analyze the role of proBDNF in sensory neurons and SGCs in DRG following SNT. Following treatment with proBDNF antiserum, TUNEL and immunohistochemistry staining were used to detect the expression of Glial Fibrillary Acidic Protein (GFAP) and Calcitonin Gene-Related Peptide (CGRP) in DRG tissue; immunocytochemistry and Cell Counting Kit-8 (CCK8) assay were used to detect GFAP expression and cell viability of SGCs, respectively. RT-qPCR, western blot, and ELISA were used to measure mRNA and protein levels, respectively, of key factors in BDNF-TrkB, proBDNF-p75NTR/sortilin, and apoptosis signaling pathways. RESULTS: proBDNF induced mitochondrial apoptosis of SGCs and neurons by modulating BDNF-TrkB and proBDNF-p75NTR/sortilin signaling pathways. In addition, neuroprotection was achieved by inhibiting the biological activity of endogenous proBDNF protein by injection of anti-proBDNF serum. Furthermore, the anti-proBDNF serum inhibited the activation of SGCs and promoted their proliferation. CONCLUSION: proBDNF induced apoptosis in SGCs and sensory neurons in DRG following SNT. The proBDNF signaling pathway is a potential novel therapeutic target for reducing sensory neuron and SGCs loss following peripheral nerve injury.

3.
J Viral Hepat ; 27(3): 224-232, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31954089

RESUMO

Covalently closed circular DNA (cccDNA), which is stably present in the nucleus of hepatocytes, is an important indicator for evaluating antiviral efficacy. Since cccDNA quantification requires an invasive procedure, serum biological markers that can effectively reflect the transcriptional activity of intrahepatic virus and the efficacy of treatment are required. Here, from the aspects of virus and host, we outline the focus of clinical research of HBV in recent years, including HBV RNA, empty virus, hepatitis B core-related antigen and changes in the immune response. We briefly discuss their significance in predicting disease activity and monitoring treatment response in chronic hepatitis B. On this basis, some issues worthy of attention in laboratory diagnosis are proposed.

4.
Huan Jing Ke Xue ; 40(9): 3924-3934, 2019 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854854

RESUMO

Based on the concentrations of 21 inorganic elements in particulate matter with diameters less than 10 µm (PM10) in 2004, and PM2.5 in 2004 and 2013 of representative road dust in Beijing, the pollution characteristics and potential ecological risks of heavy metals in this dust were analyzed and discussed. The results showed that the six main elements in road dust in Beijing were Si, Ca, Al, Fe, Mg, and K, and the proportions of the total content of the six elements in PM10 in 2004, PM2.5 in 2004, and PM2.5 in 2013 accounted for 96.51%, 96.42%, and 96.53% of the total content of all elements tested, respectively. The elemental enrichment level and the pollution degree and the potential ecological risk of heavy metal in road dust in Beijing in 2004 were PM2.5>PM10. Se, a characteristic element of coal dust, was highly enriched in PM2.5 in 2004, and Cd was high in PM10 and PM2.5 in 2004 with enrichment factors of 1024.03, 68.15, and 871.55, respectively. Co, Zn, Ca, and Cu were significantly enriched in PM10 and PM2.5 in 2004 with enrichment factors of 12.93, 12.33, 8.30, and 8.07 in PM10 and 17.41, 21.80, 12.83, and 19.73 in PM2.5, respectively; Na and Si were not enriched in the road dust. The pollution load index (PLI) of heavy metals was 3.95 in PM10 and 7.71 in PM2.5 in 2004. Owing to the implementation of dust, motor vehicles, and combustion source control measures in Beijing and the relocation of the Shougang corporation, the elemental enrichment level, pollution degree, and potential ecological risk of heavy metals in road dust PM2.5 in 2013 were significantly lower than those in 2004. The enrichment factors of Cd and Se in PM2.5 in 2013 decreased to 98.47 and 0.95, respectively; those of Cu, Ca, and Zn decreased to 11.90, 8.84, and 8.20, respectively; and PLI decreased to 2.56. The results showed that the total potential ecological risk of heavy metals in road dust in Beijing was extremely strong. Heavy metal Cd was the most significant pollution factor and the main potential ecological risk source; its potential ecological risk index (RI) contribution to the total RI of heavy metals was more than 85%. In 2004, the pollution degree of heavy metals in road dust of main roads was significantly higher than that for other road types. The pollution degree of heavy metals in PM10 was main road > expressway entrance to Beijing > secondary main road > ring road; that for PM2.5 was main road > ring road > expressway entrance to Beijing > secondary main road. For PM2.5 in 2013, however, the order was expressway entrance to Beijing > main road > ring road > secondary main road. The pollution degree of heavy metals in road dust of secondary main roads was significantly lower than that for other road types. In 2013, for road dust PM2.5 in Beijing, the correlation of heavy metals Ti, Zn, V, Cr, Cu, Pb, and Ni was significant owing mainly to traffic-related emissions.


Assuntos
Poluentes Atmosféricos , Metais Pesados , Medição de Risco , Pequim , Poeira , Ecologia , Monitoramento Ambiental
5.
Cancer Chemother Pharmacol ; 84(6): 1279-1288, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549215

RESUMO

PURPOSE: Chemotherapy remains the primary treatment used to improve overall survival and quality of life for patients with gastric cancer (GC); however, multidrug resistance is a major reason underlying failure of chemotherapy. Drug resistance (DR) can arise because of molecular changes inhibiting drug-target interactions; for example, overexpression of drug efflux pumps, such as P-gp, mediated by the activation of AP-1. BATF2 is a suppressor of AP-1; therefore, this study aimed to determine how BATF2 interacts with AP-1to inhibit DR in GC cells. METHODS: Expression of BATF2 in drug-responsive and non-responsive GC tumor tissues was evaluated by quantitative PCR and western blotting. Further, expression levels of BATF2- and AP-1-related genes were confirmed in vincristine-resistant SGC7901/VCR cells treated with cisplatin or 5-fluorouracil. A BATF2 overexpression system was established in SGC7901/VCR cells, and then AP-1 also overexpressed in the cells with upregulated BATF2 levels. Further, an AP-1 knockdown system was generated in SGC7901/VCR cells. MTT and flow cytometry assays were performed in the BATF2/AP-1 overexpression system, to evaluate cell proliferation, cell cycle effects, and apoptosis, and the expression of various proteins was detected by western blotting in AP-1/BATF2 overexpression cells. Finally, the effects of BATF2 overexpression in an in vivo nude mouse GC model were evaluated. RESULTS: We found that BATF2 was overexpressed in tissues from patients with non-responsive GC and the VCR resistance cell line, SGC7901/VCR, while levels of c-Fos and c-Jun were reduced in the SGC7901/VCR cell line. BATF2 overexpression suppressed levels of AP-1 and P-gp. Further, our data demonstrate that cell proliferation is suppressed, and the cell cycle and apoptosis are induced in SGC7901/VCR cells overexpressing both AP-1 and BATF2. Overexpression of AP-1 restored levels of genes downstream of AP-1 in BATF2 overexpressing cells. Compared with controls, tumor growth of SGC7901/VCR cells in nude mice was suppressed in the BATF2 overexpression group. CONCLUSION: AP-1 down-regulation by BATF2 overexpression or AP-1 knockdown can inhibit DR in GC cells. These findings suggest that BATF2 inhibits DR in SGC7901/VCR GC cells by down-regulating AP-1 expression.

6.
Virol Sin ; 34(6): 729, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31270662

RESUMO

In Fig. 2B, labels were misnamed in the original article. MVC label and MVC + OMT label were opposite. Now the correct Fig. 2 has been provided below.

7.
Cell Rep ; 28(2): 554-566.e4, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31291588

RESUMO

G-protein-coupled receptors (GPCRs) constitute the largest superfamily of cell surface signaling proteins. However, the molecular mechanisms underlying their cell surface delivery after synthesis remain poorly understood. Here, we screen the TBC domain-containing proteins, putative Rab GTPase-activating proteins (GAPs), in the intracellular trafficking of GPCRs and identify several TBC proteins that activity-dependently regulate the anterograde transport, en route from the endoplasmic reticulum to the Golgi or from the Golgi to the cell surface, of several prototypic GPCR members without affecting other plasma membrane proteins. We also show that TBC1D6 functions as a GAP for Rab26, physically associates with Rab26, and attenuates Rab26 interaction with GPCRs. Furthermore, both overexpression and depletion of TBC1D6 inhibit the post-Golgi traffic of GPCRs. These data demonstrate important roles of the TBC proteins in forward trafficking of nascent GPCRs and reveal regulatory mechanisms of GPCR targeting to the functional destination.

8.
Chem Commun (Camb) ; 55(41): 5805-5808, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31041958

RESUMO

Reported is a confined lattice plane electrochemical exfoliation method that exploits the electrochemical reaction of face (basal) or side (edge) planes of highly oriented pyrolytic graphite (HOPG) while other planes are blocked using wax, based on the anisotropy of HOPG for efficient and effective fabrication of graphene nanodots with uniform size distribution.

9.
In Vitro Cell Dev Biol Anim ; 55(6): 445-452, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31140101

RESUMO

Gastric cancer (GC) is a commonly occurring neoplasm worldwide. The occurrence of multidrug resistance (MDR) in GC cells is the main obstacle to effective GC chemotherapy. The aim of the present study was to reveal the functional role and the underlying mechanisms of basic leucine zipper ATF-like transcription factor 2 (BATF2), a novel tumor suppressor, on MDR in GC cells. Here, we first found that SGC7901/VCR and SGC7901/ADR cells had higher drug resistance than SGC7901 cells using methylthiazol tetrazolium (MTT) and flow cytometry analysis. Moreover, MDR-related proteins and Wnt/ß-catenin pathway markers were all upregulated in SGC7901/VCR cells compared to SGC7901 cells by quantitative reverse transcription-PCR (qRT-PCR) and western blot analyses. Subsequently, we observed BATF2 was downregulated in SGC7901/VCR cells and BATF2 overexpression significantly induced cell cycle G0/G1 phase arrest and apoptosis. Furthermore, overexpression of BATF2 could suppress Wnt/ß-catenin signaling and increase drug susceptibility by downregulating Wnt/ß-catenin pathway markers. In addition, knockdown of ß-catenin imitated the effects of BATF2 overexpression on drug susceptibility. Importantly, enhancing the Wnt/ß-catenin pathway could reverse the inhibitory effects of BATF2 on MDR. In conclusion, BATF2 was downregulated in MDR GC cells and overexpression of BATF2 could reverse the MDR of GC cells by inactivating the Wnt/ß-catenin pathway.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Resistencia a Medicamentos Antineoplásicos/fisiologia , Neoplasias Gástricas/tratamento farmacológico , Proteínas Supressoras de Tumor/genética , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Vincristina/farmacologia
10.
Biomed Pharmacother ; 111: 1066-1073, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30841420

RESUMO

BACKGROUND: Precursor of nerve growth factor (proNGF) was previously considered biologically inactive; however, it has recently been identified as having important roles in the pathology of cancer development. AIM: This study aimed to explore the therapeutic effects of proNGF siRNA on the proliferation, invasion, and anoikis of pancreatic cancer cells and determine the functions of proNGF. METHODS: Pancreatic ductal adenocarcinoma (PDAC) and paired paracancerous tissue samples were collected from 60 patients for evaluation of proNGF expression by immunohistochemistry staining, qPCR, and western blotting. PDAC cell proliferation, migration, apoptosis, and anoikis following proNGF siRNA knockdown were investigated in two pancreatic cancer cell lines, Panc-1 and Bxpc-3, using BrdU incorporation assays, EdU staining, Ki-67 immunofluorescence (IF) staining, wound-healing assays, transwell invasion assays, and EthD-1 IF staining. Autophagy-related proteins were also measured by western blotting. RESULTS: Levels of proNGF protein were higher in pancreatic cancer tissues and cells lines than those in paracancerous tissues and normal pancreatic duct epithelial cells, respectively. In vitro, ProNGF knockdown by siRNA led to significantly reduced cell proliferation, remarkably inhibited wound-healing, and reduced the number of invaded PDAC cells in migration and transwell assays. Treatment with proNGF siRNA also downregulated ATG5 and Beclin 1 protein levels, increased those of P62, and increased EthD-1 staining in PDAC cells. CONCLUSION: ProNGF expression is elevated in PDAC tissues and cell lines, and proNGF siRNA can inhibit cell proliferation, migration, and invasion, and promote anoikis of pancreatic cancer cells, in which decreased proNGF may participate.


Assuntos
Anoikis/genética , Proliferação de Células/genética , Invasividade Neoplásica/genética , Fator de Crescimento Neural/genética , Neoplasias Pancreáticas/genética , RNA Interferente Pequeno/genética , Apoptose/genética , Carcinoma Ductal Pancreático/genética , Linhagem Celular , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia
11.
Virol Sin ; 34(1): 78-87, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30805776

RESUMO

Oxymatrine (OMT), as the main active component of Sophoraflavescens, exhibits a variety of pharmacological properties, including anti-oxidative, anti-inflammatory, anti-tumor, and anti-viral activities, and currently is extensively employed to treat viral hepatitis; however, its effects on parvovirus infection have yet to be reported. In the present study, we investigated the effects of OMT on cell viability, virus DNA replication, viral gene expression, cell cycle, and apoptosis in Walter Reed canine cells/3873D infected with minute virus of canines (MVC). OMT, at concentrations below 4 mmol/L(no cellular toxicity), was found to inhibit MVC DNA replication and reduce viral gene expression at both mRNA and protein levels, which was associated with the inhibition of cell cycle S-phase arrest in early-stage of MVC infection. Furthermore, OMT significantly increased cell viability, decreased MVC-infected cell apoptosis, and reduced the expression of activated caspase 3. Our results suggest that OMT has potential application in combating parvovirus infection.


Assuntos
Alcaloides/farmacologia , Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Bocavirus/efeitos dos fármacos , Bocavirus/genética , Quinolizinas/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Bocavirus/fisiologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Replicação do DNA , Cães , Expressão Gênica
12.
J Nanosci Nanotechnol ; 19(4): 2147-2153, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30486958

RESUMO

Cellulose/graphene oxide composite membranes (CGCMs) were prepared using a vacuum-filtration method. The CGCMs were then used as filters to remove organic pollutants from wastewater. It was found that the CGCM filters could efficiently and simultaneously achieve wastewater treatment and adsorbent separation. Their adsorption of Rhodamine B (RhB, an organic dye) varied with varying cellulose/graphene oxide mass ratios. The CGCM obtained at a cellulose/graphene oxide mass ratio of 8:1 exhibited the maximum removal efficiency for RhB. The maximum adsorption capacity of the CGCMs for RhB was found to be 86.4 mg/g. In addition, the CGCMs were easily regenerated and the regenerated CGCMs retained good abilities to remove contaminants, which could be significant for their application in wastewater treatment.

13.
Neural Regen Res ; 14(2): 339-345, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30531018

RESUMO

Satellite glial cells surround neurons within dorsal root ganglia. Previous studies have focused on single-cell suspensions of cultured neurons derived from rat dorsal root ganglia. At present, the primary culture method for satellite glial cells derived from rat dorsal root ganglia requires no digestion skill. Hence, the aim of the present study was to establish a novel primary culture method for satellite glial cells derived from dorsal root ganglia. Neonatal rat spine was collected and an incision made to expose the transverse protrusion and remove dorsal root ganglia. Dorsal root ganglia were freed from nerve fibers, connective tissue, and capsule membranes, then rinsed and transferred to 6-well plates, and cultured in a humidified 5% CO2 incubator at 37°C. After 3 days in culture, some cells had migrated from dorsal root ganglia. After subculture, cells were identified by immunofluorescence labeling for three satellite glial cell-specific markers: glutamine synthetase, glial fibrillary acidic protein, and S100ß. Cultured cells expressed glutamine synthetase, glial fibrillary acidic protein, and S100ß, suggesting they are satellite glial cells with a purity of > 95%. Thus, we have successfully established a novel primary culture method for obtaining high-purity satellite glial cells from rat dorsal root ganglia without digestion.

14.
CNS Neurol Disord Drug Targets ; 17(7): 547-556, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29992896

RESUMO

BACKGROUND & OBJECTIVE: Notoginsenoside R1 (NGR1) is one of the main effective components of Panax notoginseng. METHOD: Primary cortical neurons were harvested from neonatal rats and cultured to analyze the role of NGR1 in neuronal growth and the effects of NGR1 on the Wnt/ß-catenin signaling pathway. Following treatment with NGR1, immunocytochemistry was used to detect expression of Tuj1 and MAP2, and RT-qPCR was used to measure mRNA levels of key factors in the Wnt signaling pathway. RESULTS: Results showed that NGR1 promotes growth of cultured neurons and significantly upregulates mRNA levels of ß-catenin, Dishevelled, and Frizzled. To further confirm whether NGR1 promoted cortical neuron growth via the Wnt/ß-catenin signaling pathway, we knocked down ß- catenin mRNA by siRNA interference; following NGR1 treatment of ß-catenin-knockdown neurons, ß-catenin mRNA levels increased significantly. CONCLUSION: In conclusion, these results demonstrate that NGR1 promotes growth of cultured cortical neurons from the neonatal rat, possibly via the Wnt/ß-catenin signaling pathway.


Assuntos
Córtex Cerebral/citologia , Ginsenosídeos/farmacologia , Neurônios/efeitos dos fármacos , beta Catenina/metabolismo , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/genética , Animais , Animais Recém-Nascidos , Células Cultivadas , Relação Dose-Resposta a Droga , Embrião de Mamíferos , Ginsenosídeos/genética , Ginsenosídeos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/metabolismo , Técnicas de Patch-Clamp , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Transfecção , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/genética
15.
ACS Appl Mater Interfaces ; 9(39): 34456-34466, 2017 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-28901733

RESUMO

A novel electrochemical exfoliation mode was established to prepare graphene sheets efficiently with potential applications in transparent conductive films. The graphite electrode was coated with paraffin to keep the electrochemical exfoliation in confined space in the presence of concentrated sodium hydroxide as the electrolyte, yielding ∼100% low-defect (the D band to G band intensity ratio, ID/IG = 0.26) graphene sheets. Furthermore, ozone was first detected with ozone test strips, and the effect of ozone on the exfoliation of graphite foil and the microstructure of the as-prepared graphene sheets was investigated. Findings indicate that upon applying a low voltage (3 V) on the graphite foil partially coated with paraffin wax that the coating can prevent the insufficiently intercalated graphite sheets from prematurely peeling off from the graphite electrode thereby affording few-layer (<5 layers) holey graphene sheets in a yield of as much as 60%. Besides, the ozone generated during the electrochemical exfoliation process plays a crucial role in the exfoliation of graphite, and the amount of defect in the as-prepared graphene sheets is dependent on electrolytic potential and electrode distance. Moreover, the graphene-based transparent conductive films prepared by simple modified vacuum filtration exhibit an excellent transparency and a low sheet resistance after being treated with NH4NO3 and annealing (∼1.21 kΩ/□ at ∼72.4% transmittance).

16.
CNS Neurol Disord Drug Targets ; 16(7): 828-836, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28524001

RESUMO

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a crucial role in promoting survival and differentiation of neurons and neural stem cells (NSCs), but the downstream regulating mechanisms remain poorly understood. OBJECTIVE: We investigated whether BDNF exerts its effect by triggering the phosphoinositide 3-kinase (PI3K), protein kinase B, PKB (AKT), glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin signaling pathway in cultured neurons and NSCs derived from the rat embryonic spinal cord. METHOD: Immunocytochemistry was used to detect neuronal and NSCs characteristics. RT-PCR was used to detect PI3K/AKT/GSK3ß/ß-catenin pathway expression. RESULTS: Neurons and NSCs were successfully separated and cultured from Sprague-Dawley rat embryonic spinal cord and were respectively labeled using immunocytochemistry. Neuron-specific nuclear protein, neuronal class III ß-tubulin, and neurofilament expression were detected in neurons; nestin, glial fibrillary acidic protein, microtubule-associated protein 2 and chondroitin sulfate glycosaminoglycan expression were detected in the NSCs. BDNF promoted significant neuronal growth (number, soma size, and average neurite length), as well as NSCs proliferation and differentiation, but BDNF antibody decreased neuronal growth and NSCs proliferation and differentiation. RT-PCR was used to detect changes in BDNF signal pathway components, showing that BDNF upregulated tropomyosin receptor kinase B, phosphoinositide 3-kinase (PI3K), AKT and ß-catenin, but downregulated GSK-3ß in the neurons and NSCs. BDNF antibody downregulated BDNF, tropomyosin receptor kinase B, PI3K, AKT, ß-catenin and cellular-myelocytomatosis viral oncogene, but upregulated GSK- 3ß, in the neurons and NSCs. CONCLUSION: Our findings suggested that BDNF contributed to neuronal growth and proliferation and differentiation of NSCs in vitro by stimulating PI3K/AKT/GSK3ß/ß-catenin pathways.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/fisiologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Células-Tronco Neurais/enzimologia , Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Animais , Fator Neurotrófico Derivado do Encéfalo/antagonistas & inibidores , Divisão Celular , Células Cultivadas , Ratos , beta Catenina/metabolismo
17.
Am J Drug Alcohol Abuse ; 43(5): 602-608, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28032807

RESUMO

BACKGROUND: Alcohol abuse is a serious health problem worldwide that causes a variety of physical and mental disorders. Research has shown that the brain-derived neurotrophic factor (BDNF) plays an important role in alcohol addiction. The BDNF precursor (proBDNF) exhibits different actions than BDNF through separate receptors and pathways in the central nervous system. However, the effects of proBDNF and BDNF in alcohol addiction are not fully known. OBJECTIVES: The objective was to identify the expression patterns and effects of proBDNF and BDNF after chronic alcohol exposure. METHODS: A total of 40 male adult mice were studied. A mouse psychomotor sensitization (PS) model was established to explore the effects of BDNF and proBDNF treatment following chronic alcohol exposure. Reverse transcription PCR (RT-PCR) was performed to measure mRNA levels for BDNF, TrkB, P75NTR, and sortilin in the prefrontal cortex, hippocampus, and dorsal striatum of Kunming mice after chronic alcohol exposure. RESULTS: In Kunming mice, chronic alcohol exposure up-regulated BDNF and TrkB mRNA levels in the prefrontal cortex, but decreased sortilin and P75 mRNA levels in the dorsal striatum. No changes in mRNA levels were found in other measured brain regions in the alcohol and control groups. CONCLUSION: Chronic alcohol exposure induced the region-specific expression of BDNF and proBDNF and their respective receptors in the brain. These results suggest that BDNF and proBDNF signaling pathways may play major roles in alcohol preference and addiction.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corpo Estriado/efeitos dos fármacos , Etanol/administração & dosagem , Hipocampo/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Receptor trkB/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Corpo Estriado/metabolismo , Hipocampo/metabolismo , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo , Regulação para Cima
18.
Oncotarget ; 7(44): 71417-71428, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27659526

RESUMO

Prostate cancer is an androgen receptor (AR)-driven disease and post-translational modification of AR is critical for AR activation. We previously reported that Arrest-defective protein 1 (ARD1) is an oncoprotein in prostate cancer. It acetylates and activates AR to promote prostate tumorigenesis. However, the ARD1-targeted residue within AR and the mechanisms of the acetylation event in prostate tumorigenesis remained unknown. In this study, we show that ARD1 acetylates AR at lysine 618 (K618) in vitro and in vivo. An AR construct with the charged lysine substitution by arginine (AR-618R) reduces RNA Pol II binding, AR transcriptional activity, prostate cancer cell growth, and xenograft tumor formation due to attenuation of AR nuclear translocation, whereas, construct mimicking neutral polar substitution acetylation at K618 by glutamine (AR-618Q) enhanced these effects beyond that of the wild-type AR. Mechanistically, ARD1 forms a ternary complex with AR and HSP90 in vitro and in vivo. Expression of ARD1 increases levels of AR acetylation and AR-HSP90 dissociation in a dose dependent manner. Moreover, the AR acetylation defective K618R mutant is unable to dissociate from HSP90 while the HSP90-dissociated AR is acetylated following ligand exposure. This work identifies a new mechanism for ligand-induced AR-HSP90 dissociation and AR activation. Targeting ARD1-mediated AR acetylation may be a potent intervention for AR-dependent prostate cancer therapy.


Assuntos
Proteínas de Choque Térmico HSP90/química , Acetiltransferase N-Terminal A/fisiologia , Acetiltransferase N-Terminal E/fisiologia , Neoplasias da Próstata/etiologia , Processamento de Proteína Pós-Traducional , Receptores Androgênicos/metabolismo , Acetilação , Animais , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Humanos , Masculino , Camundongos , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/química
19.
Oncotarget ; 7(26): 39834-39845, 2016 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-27213581

RESUMO

ADP-ribosylation factor 1 (ARF1) is a crucial regulator in vesicle-mediated membrane trafficking and involved in the activation of signaling molecules. However, virtually nothing is known about its function in prostate cancer. Here we have demonstrated that ARF1 expression is significantly elevated in prostate cancer cells and human tissues and that the expression levels of ARF1 correlate with the activation of mitogen-activated protein kinases (MAPK) ERK1/2. Furthermore, we have shown that overexpression and knockdown of ARF1 produce opposing effects on prostate cancer cell proliferation, anchorage-independent growth and tumor growth in mouse xenograft models and that ARF1-mediated cell proliferation can be abolished by the Raf1 inhibitor GW5074 and the MEK inhibitors U0126 and PD98059. Moreover, inhibition of ARF1 activation achieved by mutating Thr48 abolishes ARF1's abilities to activate the ERK1/2 and to promote cell proliferation. These data demonstrate that the aberrant MAPK signaling in prostate cancer is, at least in part, under the control of ARF1 and that, similar to Ras, ARF1 is a critical regulator in prostate cancer progression. These data also suggest that ARF1 may represent a key molecular target for prostate cancer therapeutics and diagnosis.


Assuntos
Fator 1 de Ribosilação do ADP/metabolismo , Regulação Neoplásica da Expressão Gênica , Sistema de Sinalização das MAP Quinases , Neoplasias da Próstata/patologia , Animais , Butadienos/química , Carcinogênese , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Flavonoides/química , Humanos , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Camundongos SCID , Mutação , Nitrilos/química , Neoplasias da Próstata/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
Growth Factors ; 34(1-2): 19-32, 2016 02.
Artigo em Inglês | MEDLINE | ID: mdl-27144323

RESUMO

Brain-derived neurotrophic factor (BDNF) plays important roles in neural stem cell (NSC) growth. In this study, we investigated whether BDNF exerts its neurotrophic effects through the Wnt/ß-catenin signaling pathway in human embryonic spinal cord NSCs (hESC-NSCs) in vitro. We found an increase in hESC-NSC growth by BDNF overexpression. Furthermore, expression of Wnt1, Frizzled1 and Dsh was upregulated, whereas GSK-3ß expression was downregulated. In contrast, hESC-NSC growth was decreased by BDNF RNA interference. BDNF, Wnt1 and ß-catenin components were all downregulated, whereas GSK-3ß was upregulated. Next, we treated hESC-NSCs with 6-bromoindirubin-3'-oxime (BIO), a small molecule inhibitor of GSK-3ß. BIO reduced the effects of BDNF upregulation/downregulation on the cell number, soma size and differentiation, and suppressed the effect of BDNF modulation on the Wnt signaling pathway. Our findings suggest that BDNF promotes hESC-NSC growth in vitro through crosstalk with the Wnt/ß-catenin signaling pathway, and that this interaction may be mediated by GSK-3ß.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Proliferação de Células , Células-Tronco Embrionárias/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Células-Tronco Neurais/metabolismo , Via de Sinalização Wnt , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células Cultivadas , Células-Tronco Embrionárias/fisiologia , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Humanos , Células-Tronco Neurais/fisiologia , Regulação para Cima , beta Catenina/metabolismo
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