Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nanotechnology ; 33(13)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34933287

RESUMO

Flexible conductive thin films have recently become a research area of focus in both academia and industry. In this study, a method of preparing nanofiber conductive films by centrifugal spinning is proposed. Polyurethane (PU) nanofiber films were prepared by centrifugal spinning as the flexible substrate film, and carbon nanotubes (CNTs) were used as the conducting medium, to obtain CNTs/PU nanofiber conductive films with good conductivity and elasticity. The effects of different CNT concentrations on the properties of the nanofiber films were investigated. It was found that the conductivity of the nanofiber conductive films was optimal when an impregnation concentration of 9% CNTs was used in the stretching process. Cyclic tensile resistance tests showed that the nanofiber conductive films have good durability and repeatability. Physical and structural property analysis of the CNT/PU conductive films indicate that the adsorption of the CNTs on the PU surface was successful and the CNTs were evenly dispersed on the surface of the matrix. Moreover, the CNTs improved the thermal stability of the PU membrane. The CNT/PU conductive films were pasted onto a human finger joint, wrist joint, and Adam's apple to test the detection of movement. The results showed that finger bending, wrist bending, and laryngeal prominence movement all caused a change in resistance of the conductive film, with an approximately linear curve. The results indicate that the CNT/PU nanofiber conductive film developed in this study can be used to test the motion of human joints.

2.
Front Pharmacol ; 12: 749169, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912218

RESUMO

Objective: A robust, quick, and reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the quantification of erdafitinib in beagle dog plasma was developed and validated to evaluate the changes of posaconazole and isavuconazole on the pharmacokinetics of erdafitinib in beagle dogs, respectively. Methods: This experiment adopted a three-period self-control experimental design. In the first period (group A), erdafitinib was orally administered to six beagle dogs at a dose of 4 mg/kg. In the second period (group B), the same six beagle dogs were orally given posaconazole at a dose of 7 mg/kg, and after 30 min, erdafitinib was orally given. In the third period (group C), isavuconazole at a dose of 7 mg/kg was given orally, and then, erdafitinib was orally given. At the different time points after erdafitinib was given in the three periods, the blood samples were collected. The concentration of erdafitinib was detected by the developed UPLC-MS/MS method. DAS 2.0 was used to calculate the pharmacokinetic parameters of erdafitinib. Results: Erdafitinib had a good linear relationship in the range of 1-500 ng/ml, and the lower limit of quantification was 1 ng/ml. The precision, accuracy, extraction recovery, matrix effect, and stability meet the requirements of the guiding principles. After erdafitinib was combined with posaconazole, the Cmax and AUC0→t of erdafitinib increased by 27.19% and 47.62%, respectively, and the t1/2 was prolonged to 6.33 h. After erdafitinib was combined with isavuconazole, the Cmax and AUC0→t of erdafitinib increased by 23.13% and 54.46%, respectively, and the t1/2 was prolonged to 6.31 h. Conclusion: A robust and reliable UPLC-MS/MS method was fully optimized and developed to detect the plasma concentration of erdafitinib in beagle dogs. Posaconazole and isaconazole could inhibit the metabolism of erdafitinib in beagle dogs and increase the plasma exposure of erdafitinib.

3.
Bioorg Chem ; 115: 105172, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34303898

RESUMO

Two series of tetrahydrocarbazole derivatives have been designed and synthesized based on ZG02, a promising candidate developed in our previous studies. The newly prepared compounds were screened for glucose consumption activity in HepG2 cell lines. Aza-tetrahydrocarbazole compound 12b showed the most potent hypoglycemic activity with a 45% increase in glucose consumption when compared to the solvent control, which had approximately 1.2-fold higher activity than the positive control compounds (metformin and ZG02). An investigation of the potential mechanism indicated that 12b may exhibit hypoglycemic activity via activation of the AMPK pathway. Metabolic stability assays revealed that 12b showed good stability profiles in both artificial gastrointestinal fluids and blood plasma from SD rats. An oral glucose tolerance test (OGTT) was performed and the results further confirmed that 12b was a potent hypoglycemic agent.

4.
Cancer Sci ; 111(5): 1567-1581, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32133742

RESUMO

The histone demethylase lysine-specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in PC cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream effector of the USP1-KDM4A/androgen receptor axis in driving PC cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression was observed in most prostate tumors and inhibition of USP1 promotes PC cells response to therapeutic agent enzalutamide. Our studies propose USP1 could be an anticancer therapeutic target in PC.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Histona Desmetilases com o Domínio Jumonji/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Proteases Específicas de Ubiquitina/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Benzamidas , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Inibidores Enzimáticos/farmacologia , Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Masculino , Camundongos , Camundongos Mutantes , Nitrilas , PTEN Fosfo-Hidrolase/deficiência , Feniltioidantoína/análogos & derivados , Feniltioidantoína/farmacologia , Feniltioidantoína/uso terapêutico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ligação Proteica/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/genética , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo , Ubiquitinação/efeitos dos fármacos
5.
Mol Cancer Res ; 18(5): 698-708, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32019811

RESUMO

The histone demethylase JMJD1A plays a key functional role in spermatogenesis, sex determination, stem cell renewal, and cancer via removing mono- and di-methyl groups from H3K9 to epigenetically control gene expression. However, its role in prostate cancer progression remains unclear. Here, we found JMJD1A was significantly elevated in prostate cancer tissue compared with matched normal tissue. Ectopic JMJD1A expression in prostate cancer cells promoted proliferation, migration, and invasion in vitro, and tumorigenesis in vivo; JMJD1A knockdown exhibited the opposite effects. Mechanically, we revealed that JMJD1A directly interacted with the Snail gene promoter and regulated its transcriptional activity, promoting prostate cancer progression both in vitro and in vivo. Furthermore, we found that JMJD1A transcriptionally activated Snail expression via H3K9me1 and H3K9me2 demethylation at its special promoter region. In summary, our studies reveal JMJD1A plays an important role in regulating proliferation and progression of prostate cancer cells though Snail, and thus highlight JMJD1A as potential therapeutic target for advanced prostate cancer. IMPLICATIONS: Our studies identify that JMJD1A promotes the proliferation and progression of prostate cancer cells through enabling Snail transcriptional activation, and thus highlight JMJD1A as potential therapeutic target for advanced prostate cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Histona Desmetilases com o Domínio Jumonji/metabolismo , Neoplasias da Próstata/patologia , Fatores de Transcrição da Família Snail/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Feminino , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Fatores de Transcrição da Família Snail/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Neural Regen Res ; 14(9): 1635-1642, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31089064

RESUMO

The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson's disease. However, the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear. To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex, a model of Parkinson's disease was established by injecting 8 µg 6-hydroxydopamine into the substantia nigra compacta of rats. After 1 or 3 weeks, 0.3 µg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain. At 3 or 5 weeks after the initial injury, neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically. The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining. Results demonstrated that after injury, the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats. Compared with normal medial prefrontal cortical neurons, at 3 and 5 weeks after substantia nigra compacta injury, the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge, with an increased discharge interval. The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge, but the discharge interval was only higher at 3 weeks. At 3 weeks after the combined lesions, the discharge frequency, discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex. These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex. The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefrontal cortex neurons after substantia nigra compacta injury. All experimental procedures were approved by the Institutional Animal Care and Use Committee of Xi'an Jiaotong University, China (approval No. XJTULAC2017-067) on August 26, 2017.

7.
C R Biol ; 341(3): 152-159, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29477283

RESUMO

Polygala tenuifolia Willd. is an important protected species used in traditional Chinese medicine. In the present study, amplified fragment length polymorphism (AFLP) markers were employed to characterize the genetic diversity in wild and cultivated P. tenuifolia populations. Twelve primer combinations of AFLP produced 310 unambiguous and repetitious bands. Among these bands, 261 (84.2%) were polymorphic. The genetic diversity was high at the species level: percentage of polymorphic loci (PPL)=84.2%, Nei's gene diversity (h)=0.3296 and Shannon's information index (I)=0.4822. Between the two populations, the genetic differentiation of 0.1250 was low and the gene flow was relatively high, at 3.4989. The wild population (PPL=81.9%, h=0.3154, I=0.4635) showed a higher genetic diversity level than the cultivated population (PPL=63.9%, h=0.2507, I=0.3688). The results suggest that the major factors threatening the persistence of P. tenuifolia resources are ecological and human factors rather than genetic. These results will assist with the design of conservation and management programs, such as in natural habitat conservation, setting the excavation time interval for resource regeneration and the substitution of cultivated for wild plants.


Assuntos
Variação Genética , Polygala/genética , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados/métodos , China , Fluxo Gênico , Filogenia , Polimorfismo Genético
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(6): 756-62, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-27320874

RESUMO

OBJECTIVE: To investigate the activity of pyramidal neurons in the medial prefrontal cortex (mPFC) of normal and 6-OHDA-lesioned rats and the responses of the neurons to 5-hydroxytryptamine-7 (5-HT(7)) receptor stimulation. METHODS: The changes in spontaneous firing of the pyramidal neurons in the mPFC in response to 5-HT(7) receptor stimulation were observed by extracellular recording in normal and 6-OHDA-lesioned rats. RESULTS: Both systemic and local administration of 5-HT(7) receptor agonist AS 19 resulted in 3 response patterns (excitation, inhibition and no change) of the pyramidal neurons in the mPFC of normal and 6-OHDA-lesioned rats. In normal rats, the predominant response of the pyramidal neurons to AS 19 stimulation was excitatory, and the inhibitory effect of systemically administered AS 19 was reversed by GABAA receptor antagonist picrotoxinin. In the lesioned rats, systemic administration of AS 19 also increased the mean firing rate of the pyramidal neurons, but the cumulative dose for producing excitation was higher than that in normal rats. Systemic administration of AS 19 produced an inhibitory effect in the lesioned rats, which was partially reversed by picrotoxinin. Local administration of AS 19 at the same dose did not change the ?ring rate of the neurons in the lesioned rats. CONCLUSION: The activity of mPFC pyramidal neurons is directly or indirectly regulated by 5-HT7 receptor, and degeneration of the nigrostriatal pathway leads to decreased response of these neurons to AS 19.


Assuntos
Doença de Parkinson/metabolismo , Córtex Pré-Frontal/citologia , Células Piramidais/efeitos dos fármacos , Receptores de Serotonina/metabolismo , Agonistas do Receptor de Serotonina/farmacologia , Potenciais de Ação , Animais , Oxidopamina , Ratos
9.
Sheng Li Xue Bao ; 67(5): 479-86, 2015 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-26490065

RESUMO

The present study was aimed to explore the effect of sodium nitrite on cytoskeletal protein phosphorylation and spatial learning and memory in rats. Rats were served with drinking water containing sodium nitrite (100 mg/kg) for 60 days, then, the ability of spatial learning and memory of the rats was measured by Morris water maze. Phosphorylation level of tau and neurofilament, and the expression of protein phosphatase 2A (PP2A) catalytic subunit in the hippocampus were detected by immunohistochemistry and Western blot. In comparison with the rats served with normal tap water, the rats served with sodium nitrite water showed significantly longer latency to find the hidden platform in Morris water maze (P < 0.05), elevated phosphorylation level of tau and neurofilament, and decreased expression of PP2A catalytic subunit (P < 0.05). These results indicated that administration of sodium nitrite could impair the spatial learning and memory of the rats, and the hyperphosphorylation of cytoskeletal proteins and the down-regulation of PP2A might be underlying mechanisms for the impairment.


Assuntos
Proteínas do Citoesqueleto/metabolismo , Memória/efeitos dos fármacos , Nitrito de Sódio/farmacologia , Aprendizagem Espacial/efeitos dos fármacos , Animais , Regulação para Baixo , Hipocampo/metabolismo , Aprendizagem em Labirinto , Proteínas de Neurofilamentos/metabolismo , Fosforilação , Proteína Fosfatase 2/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas tau/metabolismo
10.
Sheng Li Xue Bao ; 66(6): 667-74, 2014 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-25516515

RESUMO

The present study is aimed to investigated the firing activity of pyramidal neurons and interneurons in the medial prefrontal cortex (mPFC) in rats with bilateral intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) by using in vivo extracellular recording. The results showed that the injection of 5,7-DHT reduced the 5-hydroxytryptamine (5-HT) levels in the mPFC and dorsal raphe nucleus in the rats. The firing rate of mPFC pyramidal neurons in rats with 5,7-DHT injection was significantly higher than that of normal rats, and the firing pattern of these neurons also changed significantly towards a more burst-firing, while the injection decreased the firing rate of mPFC interneurons and changed the firing pattern of the interneurons towards a more irregular. These results indicate that the lesions of the serotonergic neurons lead to the changes in the firing activity of mPFC pyramidal neurons and interneurons, suggesting that serotonergic system plays an important role in the regulation of the neuronal activity in the mPFC.


Assuntos
5,7-Di-Hidroxitriptamina/farmacologia , Interneurônios/efeitos dos fármacos , Córtex Pré-Frontal/citologia , Células Piramidais/efeitos dos fármacos , Potenciais de Ação , Animais , Núcleo Dorsal da Rafe/citologia , Injeções Intraventriculares , Ratos , Serotonina/metabolismo
11.
J Agric Food Chem ; 60(25): 6399-407, 2012 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-22670709

RESUMO

Prostate cancer is one of the leading causes of cancer death in men in Western countries. Epidemiological studies have linked the consumption of fruits and vegetables to a reduced risk of prostate cancer, and small fruits are particularly rich sources of many active phytochemical stilbenes, such as pterostilbene. As a constituent of small fruits such as grapes, berries, and their products, pterostilbene is under intense investigation as a cancer chemopreventive agent. Using the p53 wild type LNCaP and p53 null PC3 cells, we found that treatment with pterostilbene resulted in dose-dependent inhibition of cellular proliferation, which suggested that the interaction of pterostilbene with the p53 might not fully explain its inhibitory effect on proliferation. In this study, we found that pterostilbene activated AMPK in both p53 positive and negative human prostate cancer cells. Pterostilbene-activated AMPK decreased the activity and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). Interestingly, the resolution between apoptosis and growth arrest following AMPK activation is greatly influenced by p53 status. In p53 positive LNCaP cells, pterostilbene blocked the progression of cell cycle at G1 phase by inducing p53 expression and further up-regulating p21 expression. However, pterostilbene induced apoptosis in p53 negative PC3 cells. Our results suggest that pterostilbene may be a functional chemopreventive agent and that dietary exposure to pterostilbene would be helpful for antiprostate cancer activity.


Assuntos
Ciclo Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Neoplasias da Próstata/fisiopatologia , Proteínas Quinases/metabolismo , Estilbenos/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/enzimologia , Proteínas Quinases/genética , Proteína Supressora de Tumor p53/genética
12.
Mol Divers ; 16(2): 415-21, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22528272

RESUMO

A series of benzopyrano[3,4-b](N-arylsulfonyl) indole derivatives and benzopyrano[4,3-b](N-arylsulfonyl) indole derivatives were synthesized from 2- or 3-methylindole via intermolecular S( N )2 reaction and subsequent intramolecular palladium-catalyzed aryl-aryl coupling reaction for the first time. It was suggested that, besides using the Fischer cyclization, benzopyrano[4,3-b]indoles and benzopyrano[3,4-b]indoles could also be prepared via intermolecular S( N )2 reaction and sequential intramolecular palladium-catalyzed coupling reaction.


Assuntos
Indóis/síntese química , Paládio/química , Catálise , Ciclização , Indóis/química , Estrutura Molecular
13.
Hepatology ; 56(4): 1331-41, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22505225

RESUMO

UNLABELLED: At least some cancer stem cells (CSCs) display intrinsic drug resistance that may thwart eradication of a malignancy by chemotherapy. We explored the genesis of such resistance by studying mouse models of liver cancer driven by either MYC or the combination of oncogenic forms of activation of v-akt murine thymoma viral oncogene homolog (AKT) and NRAS. A common manifestation of chemoresistance in CSCs is efflux of the DNA-binding dye Hoechst 33342. We found that only the MYC-driven tumors contained a subset of cells that efflux Hoechst 33342. This "side population" (SP) was enriched for CSCs when compared to non-SP tumor cells and exhibited markers of hepatic progenitor cells. The SP cells could differentiate into non-SP tumor cells, with coordinate loss of chemoresistance, progenitor markers, and the enrichment for CSCs. In contrast, non-SP cells did not give rise to SP cells. Exclusion of Hoechst 33342 is mediated by ATP binding cassette drug transporter proteins that also contribute to chemoresistance in cancer. We found that the multidrug resistance gene 1 (MDR1) transporter was responsible for the efflux of Hoechst from SP cells in our MYC-driven model. Accordingly, SP cells and their tumor-initiating subset were more resistant than non-SP cells to chemotherapeutics that are effluxed by MDR1. CONCLUSION: The oncogenotype of a tumor can promote a specific mechanism of chemoresistance that can contribute to the survival of hepatic CSCs. Under circumstances that promote differentiation of CSCs into more mature tumor cells, the chemoresistance can be quickly lost. Elucidation of the mechanisms that govern chemoresistance in these mouse models may illuminate the genesis of chemoresistance in human liver cancer.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Diferenciação Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Células-Tronco Neoplásicas/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Western Blotting , Diferenciação Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Citometria de Fluxo , Humanos , Hidrocortisona/análogos & derivados , Hidrocortisona/farmacologia , Imuno-Histoquímica , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Células-Tronco Neoplásicas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Transplante Homólogo
14.
Chin J Physiol ; 54(5): 303-9, 2011 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-22135908

RESUMO

Activation of metabotropic glutamate receptor 5 (mGluRs) in the subthalamic nucleus (STN) results in burst-firing activity of STN neurons, which is similar to that observed in Parkinson's disease (PD). We examined the effects of chronic and systemic treatment with 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective mGluR5 antagonist, in firing activity of STN neurons in partially lesioned rats by 6-hydroxydopamine (6-OHDA). In 6-OHDA-lesioned rats treated with vehicle, injection of 6-OHDA (4 microg) into the medial forebrain bundle produced a partial lesion causing 36% loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc). The 6-OHDA lesion in vehicle-treated rats showed an increasing firing rate and a more irregular firing pattern of STN neurons. Whereas chronic, systemic treatment of MPEP (3 mg/kg/day, 14 days) produced neuroprotecive effects on the TH-ir neurons and normalized the hyperactive firing activity of STN neurons in 6-OHDA partially lesioned rats. These data demonstrate that partial lesion of the nigrostriatal pathway increases firing activity of STN neurons in the rat, and chronic, systemic MPEP treatment has the neuroprotective effect and reverses the abnormal firing activity of STN neurons, suggesting that MPEP has an important implication for the treatment of PD.


Assuntos
Antagonistas de Aminoácidos Excitatórios/farmacologia , Oxidopamina/farmacologia , Piridinas/farmacologia , Receptores de Ácido Caínico/antagonistas & inibidores , Núcleo Subtalâmico/efeitos dos fármacos , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Ácido Caínico/análise , Receptores de Ácido Caínico/genética , Núcleo Subtalâmico/fisiologia , Tirosina 3-Mono-Oxigenase/análise
15.
Brain Res Bull ; 85(6): 329-38, 2011 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-21624440

RESUMO

Although increasing evidence indicates that psychiatric symptoms are crucial characteristic of the early stage of Parkinson's disease (PD) and precede motor impairments, the neuronal firing activity of the basolateral nucleus of the amygdala (BLA) in the psychiatric symptom of PD and the involved mechanism are still unclear. In the present study, we examined the changes in emotional and cognitive tests not focused on motor fluency and firing activity of projection neurons in the BLA rats with 6-hydroxydopamine (6-OHDA) injected bilaterally into dorsal striatum, and the effects of apomorphine and the medial prefrontal cortex (mPFC) on these changes. Injection of 6-OHDA (10.5 µg) into the dorsal striatum produced 18-22% and 26-30% loss of tyrosine hydroxylase immunoreactive neurons in the ventral tegmental area and substantia nigra pars compacta of rats, respectively. The striatal lesions induced anxiety-like responses in the rats but did not result in depressive-like behavior or cognitive impairments. In the lesioned rats, the firing rate of BLA projection neurons decreased significantly compared with sham-operated rats, and the firing pattern of BLA projection neurons was not changed. No significant differences were observed either in behaviors or firing activity of BLA projection neurons by further ibotenic acid lesions of the mPFC in the lesioned rats. Systemic administration of cumulative apomorphine (10-160 µg/kg) inhibited the firing rate of BLA projection neurons in sham-operated, 6-OHDA-lesioned and combined 6-OHDA- and mPFC-lesioned rats, but the latter needed more apomorphine stimulation. These data suggest that the anxiety in early stage of PD is possibly related to the decrease in firing activity of BLA projection neurons, which may be regulated by the activation of dopamine receptor in the mPFC.


Assuntos
Potenciais de Ação/fisiologia , Tonsila do Cerebelo/fisiologia , Cognição/fisiologia , Corpo Estriado/anatomia & histologia , Emoções/fisiologia , Vias Neurais/patologia , Substância Negra/anatomia & histologia , Adrenérgicos/farmacologia , Tonsila do Cerebelo/anatomia & histologia , Tonsila do Cerebelo/patologia , Animais , Antiparkinsonianos/farmacologia , Apomorfina/farmacologia , Comportamento Animal/efeitos dos fármacos , Corpo Estriado/fisiologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Humanos , Ácido Ibotênico/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Testes Neuropsicológicos , Oxidopamina/farmacologia , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Ratos , Ratos Sprague-Dawley , Substância Negra/fisiologia
16.
Eur J Med Chem ; 46(5): 1919-25, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21388718

RESUMO

A series of new 5,6-dihydro-indolo[1,2-a]quinoxaline derivatives has been prepared in moderate to excellent yields from 2-(indol-1-yl)phenylamines with aromatic aldehydes by an efficient and economical iron-catalyzed Pictet-Spengler reaction. Meanwhile, as compared with hymexazol, a commercially available agricultural fungicide at the concentration of 50 µg/mL, some 5,6-dihydro-indolo[1,2-a]quinoxalines exhibited promising antifungal activities in vitro against the phytopathogenic fungi, and might be considered as novel promising lead candidates for further design and synthesis of agricultural fungicides.


Assuntos
Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Indóis/farmacologia , Quinoxalinas/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Desenho de Fármacos , Indóis/síntese química , Indóis/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Quinoxalinas/síntese química , Quinoxalinas/química , Estereoisomerismo
17.
Brain Res Bull ; 84(3): 215-23, 2011 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-21255635

RESUMO

Although 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective metabotropic glutamate receptor 5 antagonist, improves the motor symptoms of Parkinson's disease (PD), the effects of MPEP on the psychiatric symptom of PD and the mechanism involved are still unclear. In the present study, we examined the effects of MPEP in anxiolytic-like behavior and firing activity of projection neurons in the basolateral nucleus of the amygdala (BLA) in rats with 6-hydroxydopamine (6-OHDA) injected bilaterally into dorsal striatum. Rats were divided into three groups, sham-operated group, 6-OHDA lesion with vehicle treatment group and 6-OHDA lesion with MPEP treatment group. Injection of 6-OHDA (10.5 µg) into the dorsal striatum produced 31.5% loss of tyrosine hydroxylase immunoreactive (TH-ir) neurons in the SNpc. The 6-OHDA-lesioned rats showed anxiety behavior and the firing rate of BLA projection neurons decreased significantly compared with sham-operated rats, and no difference was found in the firing pattern of these neurons. Whereas chronic, systemic treatment of MPEP (3 mg/kg/day, i.p.; 14 days) attenuated loss of TH-ir neurons, produced anxiolytic-like effect and normalized the abnormal firing rate of projection neurons of the BLA in rats with the bilateral lesions. Systemic administration of cumulative apomorphine (10-160 µg/kg, i.v.) inhibited the firing rate of BLA projection neurons in sham-operated, 6-OHDA lesion with vehicle-treated and MPEP-treated rats, but the 6-OHDA lesion decreased the response of BLA projection neurons to apomorphine stimulation, while MPEP reversed the reactivity of these neurons. These data demonstrate that the partial lesion of the nigrostriatal pathway causes anxiety symptom and decreases firing rate of BLA projection neurons in the rat. Furthermore, chronic, systemic MPEP treatment has the neuroprotective and anxiolytic-like effects, and reverses the abnormal firing rate of BLA projection neurons, suggesting that MPEP has important implication for the treatment of PD.


Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Transtornos de Ansiedade/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/farmacologia , Neurônios/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Tonsila do Cerebelo/patologia , Tonsila do Cerebelo/fisiopatologia , Animais , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/fisiopatologia , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Masculino , Neurônios/patologia , Oxidopamina/toxicidade , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptor de Glutamato Metabotrópico 5 , Receptores de Glutamato Metabotrópico/fisiologia
18.
Eur J Med Chem ; 46(1): 364-9, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21093115

RESUMO

A series of novel indole[1,2-c]-1,2,4-benzotriazine derivatives were obtained by a modified Sandmeyer reaction in the presence of tert-butylnitrite (t-BuONO). As compared with hymexazol, a commercially available agricultural fungicide, at the concentration of 50 µg/mL, two indole[1,2-c]-1,2,4-benzotriazines, 5h and 5k, exhibited the more promising and pronounced antifungal activities in vitro against five phytopathogenic fungi. It clearly demonstrated that introduction of appropriate substituents on the indolyl ring of indole[1,2-c]-1,2,4-benzotriazine (5a) would lead to the more potent derivatives.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Plantas/microbiologia , Triazinas/química , Triazinas/farmacologia , Antifúngicos/síntese química , Triazinas/síntese química
19.
J Tradit Complement Med ; 1(1): 64-8, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24716107

RESUMO

Fatigue is a noticeable and highly prevalent symptom in tense, industriously, and economically affluent modern society. Therefore, new antifatigue agents to smooth the fatigue feature are an energetic topic. The total ethanol extract (ESI) of Saussurea involucrata Kar et Kir., known as Tian-Shan snow lotus, was evaluated for antifatigue activity in ICR mice with mice forced swimming test and the determination of the contents of blood lactic acid and serum urea nitrogen. ESI (0.05, 0.15, 0.25 g/kg) was administered orally to mice for 4 weeks. The average swimming times to exhaustion of the ESI-treated ICR mice (0.15, 0.25 g/kg) were prolonged by 132% and 180% (p<0.001) with a lessening of fatigue compared with that of the control group. Analysis of biochemical parameters showed that levels of serum urea nitrogen and blood lactic acid of experimental groups were also decreased significantly (p<0.001) compared with that of the control group. The antioxidant activity of ESI was investigated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging assay and the hydrogen peroxide-induced luminol chemiluminescence assay and the results indicated that ESI exerts DPPH scavenging ability and reducing power. These results provide scientific evidence that S. involucrata may have been potential as an antifatigue agent.

20.
J Agric Food Chem ; 58(6): 3356-65, 2010 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-20166659

RESUMO

Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of death of men in the United States. To date, no effective therapeutic treatment allows abrogation of the progression of prostate cancer to more invasive forms. In this study, we identified Saussurea involucrata Kar. et Kir., a rare traditional Chinese medicinal herb, as a potential agent for androgen-independent prostate cancer patients and investigated its biological mechanism as an antineoplastic agent. S. involucrata caused a concentration- and time-dependent inhibition of cell proliferation in human hormone-resistant prostate cancer PC-3 cells. Moreover, in vitro studies in a panel of several types of human cancer cell lines revealed that S. involucrata inhibited cell proliferation with high potency. To evaluate the bioactive compounds, we successively extracted the S. involucrata with fractions of methanol (SI-1), ethyl acetate (SI-2), n-butanol (SI-3), and water (SI-4). Among these extracts, SI-2 contains the most effective bioactivity. SI-2 treatment resulted in significant time-dependent growth inhibition together with G1 phase cell cycle arrest and apoptosis in PC3 cells. In addition, SI-2 treatment strongly induced p21WAF1/CIP and p27KIP1 expression, independent of the p53 pathway, and downregulated expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4). SI-2 treatment increased levels of Bax, cytochrome c, activated caspase-3, and active caspase-9 and decreased Bcl-2 expression level. One of the major targets for the therapy in prostate cancer can be epidermal growth factor receptor (EGFR). SI-2 markedly reduced phosphorylation of EGFR and inhibited activation of AKT and STAT3. Moreover, p.o. administration of SI-2 induced a dose-dependent inhibition of PC-3 tumor growth in vivo. In summary, our study identifies S. involucrata as an effective inhibitor of EGFR signaling in human hormone-resistant prostate cancer PC-3 cells. We suggest that S. involucrata could be developed as an agent for the management of EGFR-positive human cancers.


Assuntos
Regulação para Baixo , Medicamentos de Ervas Chinesas/farmacologia , Receptores ErbB/metabolismo , Hormônios/farmacologia , Extratos Vegetais/farmacologia , Neoplasias da Próstata/metabolismo , Saussurea/química , Transdução de Sinais/efeitos dos fármacos , Animais , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/fisiopatologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...