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1.
Biomed Chromatogr ; : e5235, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34553391

RESUMO

Dingkun Dan (DKD), a reputable traditional Chinese medicine formula, has been used to treat gynecological diseases and showed significant clinical effects since ancient times. However, the application and development of DKD are seriously hampered by the unclear active substances. Structural characterization of compounds absorbed in vivo and their corresponding metabolites is significant for clarifying the pharmacodynamic material basis. In this study, an integrated strategy using ultra-performance liquid chromatography, coupled with quadrupole time-of-flight mass spectrometry and UNIFI™ software, was used to identify prototypes and metabolites after oral administration of DKD in rats. As a result, a total of 261 compounds, including 140 prototypes and 121 metabolites, were tentatively characterized in rat plasma, urine, and feces. The metabolic pathways of prototypes have been studied to clarify their possible transformation process in vivo. Moreover, an in vitro metabolism study was applied for verifying the metabolites under simulating the metabolic environment in vivo. This first systematic metabolic study of DKD is important for elucidating the metabolites and metabolic pathways and could provide a scientific basis for explaining the integrative mechanism in further pharmacology study.

2.
Phytomedicine ; 79: 153330, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32932202

RESUMO

BACKGROUND: Compound Dan Zhi tablet (DZT) is a commonly used traditional Chinese medicine formula. It has been used for the treatment of ischemic stroke for many years in clinical. However, its pharmacological mechanism is unclear. PURPOSE: The aim of the current study was to understand the protective effects and underlying mechanisms of DZT on ischemic stroke. METHODS: Fifteen representative chemical markers in DZT were determined by ultra-performance liquid chromatography coupled with tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). The protective effect of DZT against ischemic stroke was studied in a rat model of middle cerebral artery occlusion (MCAO), and the mechanism was further explored through a combination of network pharmacology and experimental verification. RESULTS: Quantitative analysis showed that the contents of phenolic acids, furan sulfonic acids, tanshinones, flavonoids, saponins and phthalides in DZT were calculated as 7.47, 0.788, 0.627, 0.531 and 0.256 mg/g, respectively. Phenolic acids were the most abundant constituents. Orally administered DZT (1.701 g kg-1) significantly alleviated the infarct size and neurological scores in MCAO rats. The network analysis predicted that 53 absorbed active compounds in DZT-treated plasma targeted 189 proteins and 47 pathways. Ten pathways were associated with anti-platelet activity. In further experiments, DZT (0.4 and 0.8 mg mL-1) markedly inhibited in vitro prostaglandin G/H synthase 1 (PTGS1) activity. DZT (0.4 and 0.8 mg mL-1) significantly inhibited in vitro platelet aggregation in response to ADP or AA. DZT (113 and 226 mg kg-1, p.o.) also produced a marked inhibition of ADP- or AA-induced ex vivo platelet aggregation with a short duration of action. DZT decreased the level of thromboxane A2 (TXA2) in MCAO rats. In the carrageenan-induced tail thrombosis model and ADP-induced acute pulmonary thromboembolism mice model, DZT (113 and 226 mg kg-1, p.o.) prevented thrombus formation. Importantly, DZT (113 and 226 mg kg-1, p.o.) exhibited a low bleeding liability. CONCLUSION: DZT protected against cerebral ischemic injury. The inhibition of TXA2 level, platelet aggregation and thrombosis formation might involve in the protective mechanism.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , AVC Isquêmico/tratamento farmacológico , Ativação Plaquetária/efeitos dos fármacos , Trombose/tratamento farmacológico , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacocinética , Infarto da Artéria Cerebral Média/tratamento farmacológico , Masculino , Camundongos Endogâmicos ICR , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Embolia Pulmonar/tratamento farmacológico , Coelhos , Ratos Sprague-Dawley , Comprimidos , Trombose/induzido quimicamente , Tromboxano A2/metabolismo
3.
Biomed Chromatogr ; 34(10): e4914, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32515056

RESUMO

Dingkun Dan (DKD), a famous traditional Chinese medicine, has been widely used in the treatment of irregular menstruation, leucorrhea abnormality, and postpartum gynecological diseases since Qing dynasty (1739). It comprises 30 flavors of Chinese medicinal materials, which results in its complex chemical composition. In this study, an integrative method was developed to rapidly characterize the chemical components of DKD using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry combined with the UNIFI™ software. A total of 234 compounds, including 47 triterpenoid saponins, 55 flavonoids, and 38 alkaloids, were identified. Of them, 170 compounds were characterized initially and 61 compounds were identified unambiguously using reference standards. Under the same analysis conditions, 43 prototypical components, which were tentatively assigned as triterpenoid saponins, flavonoids, alkaloids, terpenoids, phenylpropanoids, and others, were absorbed in rat by serum pharmacochemistry analysis. DKD exhibited diverse pharmacological activities through the combined effect of these components. This study was the first systematic study of chemical components in vitro originating from 30 medicinal materials and prototypes in vivo of DKD, which could provide scientific evidence for explaining its therapeutic effect.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas/métodos , Administração Oral , Alcaloides/análise , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Flavonoides/análise , Medicina Tradicional Chinesa , Ratos , Ratos Sprague-Dawley , Saponinas/análise , Triterpenos/análise
4.
J Pharm Biomed Anal ; 184: 113197, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32120187

RESUMO

Untargeted mass spectrometry analysis is one of the most challenging and meaningful steps in the rapid structural elucidation of the highly complex and diverse constituents of traditional Chinese medicine. Specifically, it is a laborious and time-consuming way to identify unknown compounds. Herein, a workflow was proposed to expedite the annotations of the chemical structures in Pheretima aspergillum (E. Perrier) (Di-Long, DL). First, ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) was performed to obtain the untargeted mass spectral data. Then, the spectral data were uploaded to the Global Natural Products Social Molecular Networking (GNPS) platform to create a network and extract the Mass2Motifs (co-occurring fragments and neutral losses) using unsupervised substructure annotation topic modeling (MS2LDA). Finally, a structural analysis was performed using the proposed workflow of MS2LDA in combination with mass spectral molecular networking and in silico fragmentation prediction. As a result, a total of 124 compounds from DL were effectively characterized, of which 89 (7 furan sulfonic acids, 57 phospholipids and 25 carboxamides) were identified as potentially new compounds from DL. The results presented in this article significantly improve the understanding of the chemical composition of DL and provide a solid scientific basis for the future study of the quality control, underlying pharmacology and mechanism of DL. Moreover, the proposed workflow was used for the first time to accelerate the annotations of unknown molecules from TCM. Furthermore, this workflow will increase the efficiency of characterizing the 'unknown knowns' and elucidation of the 'unknown unknowns' from TCM, which are crucial steps of discovering the natural product drugs in TCM.


Assuntos
Fatores Biológicos/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Simulação por Computador , Medicina Tradicional Chinesa/métodos , Controle de Qualidade , Fluxo de Trabalho
5.
Curr Pharm Des ; 25(43): 4606-4612, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31657676

RESUMO

BACKGROUND: The human ether-a-go-go-related gene (hERG) potassium channel is the rapidly activating component of cardiac delayed rectifier potassium current (IKr), which is a crucial determinant of cardiac repolarization. The reduction of hERG current is commonly believed to cause Long QT Syndrome (LQTs). Probucol, a cholesterol-lowering drug, induces LQTs by inhibiting the expression of the hERG channel. Unfortunately, there is currently no effective therapeutic method to rescue probucol-induced LQTs. METHODS: Patch-clamp recording techniques were used to detect the action potential duration (APD) and current of hERG. Western blot was performed to measure the expression levels of proteins. RESULTS: In this study, we demonstrated that 1 µM matrine and oxymatrine could rescue the hERG current and hERG surface expression inhibited by probucol. In addition, matrine and oxymatrine significantly shortened the prolonged action potential duration induced by probucol in neonatal cardiac myocytes. We proposed a novel mechanism underlying the probucol induced decrease in the expression of transcription factor Specificity protein 1 (Sp1), which is an established transactivator of the hERG gene. We also demonstrated that matrine and oxymatrine were able to upregulate Sp1 expression which may be one of the possible mechanisms by which matrine and oxymatrine rescued probucol-induced hERG channel deficiency. CONCLUSION: Our current results demonstrate that matrine and oxymatrine could rescue probucol-induced hERG deficiency in vitro, which may lead to potentially effective therapeutic drugs for treating acquired LQT2 by probucol in the future.


Assuntos
Alcaloides/farmacologia , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Miócitos Cardíacos/efeitos dos fármacos , Probucol/efeitos adversos , Quinolizinas/farmacologia , Animais , Linhagem Celular , Humanos , Técnicas de Patch-Clamp , Ratos Sprague-Dawley
6.
Ann Palliat Med ; 8(4): 469-475, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31594375

RESUMO

BACKGROUND: This study aimed to investigate the effects of dexmedetomidine on the post-operative recovery and mental status in patients receiving robotic-assisted thoracic surgery (RATS). METHODS: One hundred patients who received selective RATS under general anesthesia were recruited and assigned into control group (C) and dexmedetomidine group (D). The anesthesia induction and maintenance were consistent between groups. Midazolam, sufentanil, propofol and rocuronium were intravenously injected for anesthesia induction, followed by mechanical ventilation after endotracheal intubation. Sevoflurane inhalation at a minimum alveolar concentration (MAC) of 0.5 was administered, propofol and remifentanil were intravenously injected to maintain the bispectral index (BIS) at 40-60, and rocuronium was intravenously injected once every 30 min. In the D group, dexmedetomidine was intravenously injected after endotracheal intubation, and then it was injected before the end of surgery. In the C group, normal saline of equal volume was injected. The hemodynamic parameters, blood loss, urine volume, time of surgery, time of anesthesia, total dose of propofol, time of thoracic tube indwelling, hospital stay and pulmonary complications were recorded; blood gas analysis was performed after extubation; the QoR-15 and mini-mental state examination (MMSE) questionnaires were employed for the assessment of mental status at 1 and 3 days after surgery. RESULTS: The mean arterial pressure (MAP), heart rate (HR) and brain oxygenation were similar between groups at different time points (P>0.05). There were no significant differences in the operation time, time of anesthesia and intra-operative urine volume between groups. As compared to the C group, the blood loss and dose of propofol reduced significantly (P<0.05). After extubation, the respiratory frequency reduced and PaO2 increased markedly (P<0.05). After surgery, the time of thoracic tube indwelling and hospital stay reduced dramatically in the D group as compared to the C group (P<0.05). The QoR-15 score and MMSE score in the D group were markedly higher than in the C group (P<0.05). CONCLUSIONS: Dexmedetomidine can improve the post-operative recovery and mental status after RATS.


Assuntos
Dexmedetomidina/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Transtornos Mentais/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Robóticos/reabilitação , Procedimentos Cirúrgicos Torácicos/reabilitação , Adjuvantes Anestésicos , Adulto , Idoso , Feminino , Nível de Saúde , Humanos , Masculino , Midazolam , Pessoa de Meia-Idade , Propofol , Respiração Artificial/estatística & dados numéricos , Rocurônio , Sufentanil , Adulto Jovem
7.
Chin Med J (Engl) ; 131(20): 2461-2473, 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30334531

RESUMO

Background: Fine particulate matter (PM2.5) exacerbates airway inflammation and hyperreactivity in patients with asthma, but the mechanism remains unclear. The aim of this study was to observe the effects of prolonged exposure to high concentrations of PM2.5on the pathology and airway hyperresponsiveness (AHR) of BALB/c mice undergoing sensitization and challenge with ovalbumin (OVA) and to observe the effects of apoptosis and T-cell immunoglobulin and mucin domain 1 (TIM-1) in this process. Methods: Forty female BALB/c mice were divided into four groups: control group, OVA group, OVA/PM group, and PM group (n = 10 in each group). Mice in the control group were exposed to filtered clean air. Mice in the OVA group were sensitized and challenged with OVA. Mice in the OVA/PM group were sensitized and challenged as in the OVA group and then exposed to PM2.5for 4 h per day and 5 days per week for a total of 8 weeks using a nose-only "PM2.5online enrichment system" in The Second Hospital of Hebei Medical University. Mice in the PM group were exposed to the PM2.5 online enrichment system only. AHR was detected. Bronchoalveolar lavage fluid (BALF) was collected for cell classification. The levels of interleukin-4 (IL-4), IL-5, and IL-33 in BALF were measured using enzyme-linked immunosorbent assay. Changes in histological structures were examined by light microscopy, and changes in ultramicrostructures were detected by electron microscopy. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay in the lung tissues. Western blotting and immunohistochemistry were utilized to analyze the expression of Bcl-2, Bax, and TIM-1 in the lungs. Results: The results showed that AHR in the OVA/PM group was significantly more severe than that in the OVA and PM groups (P < 0.05). AHR in the PM group was also considerably more severe than that in the control group (P < 0.05). The BALF of OVA/PM group (28.00 ± 6.08 vs. 12.33 ± 4.51, t = 4.631, P = 0.002) and PM group (29.00 ± 3.00 vs. 12.33 ± 4.51, t = 4.927, P = 0.001) had more lymphocytes than the BALF of the control group. The number of neutrophils in the BALF of the OVA/PM group (6.67 ± 1.53 vs. 3.33 ± 1.53, t = 2.886, P = 0.020) and PM group (6.67 ± 1.53 vs. 3.33 ± 1.53, t = 2.886, P = 0.020) was much higher than those in the BALF of OVA group (P < 0.05). TUNEL assays showed that the number of apoptotic cells in the OVA/PM group was significantly higher than that in the OVA group (Tunel immunohistochemical scores [IHS%], 1.20 ± 0.18 vs. 0.51 ± 0.03, t = 8.094, P < 0.001) and PM group (Tunel IHS%, 1.20 ± 0.18 vs. 0.51 ± 0.09, t = 8.094, P < 0.001), and that the number of apoptotic cells in the PM group was significantly higher than that in the control group (Tunel IHS%, 0.51 ± 0.09 vs. 0.26 ± 0.03, t = 2.894, P = 0.020). The concentrations of IL-4 (77.44 ± 11.19 vs. 48.02 ± 10.02 pg/ml, t = 4.595, P = 0.002) and IL-5 (15.65 ± 1.19 vs. 12.35 ± 0.95 pg/ml, t = 3.806, P = 0.005) and the Bax/Bcl-2 ratio (1.51 ± 0.18 vs. 0.48 ± 0.10, t = 9.654, P < 0.001) and TIM-1/ß-actin ratio (0.78 ± 0.11 vs. 0.40 ± 0.06, t = 6.818, P < 0.001) in the OVA/PM group were increased compared to those in the OVA group. The concentrations of IL-4 (77.44 ± 11.19 vs. 41.47 ± 3.40 pg/ml, t = 5.617, P = 0.001) and IL-5 (15.65 ± 1.19 vs. 10.99 ± 1.40 pg/ml, t = 5.374, P = 0.001) and the Bax/Bcl-2 ratio (1.51 ± 0.18 vs. 0.97 ± 0.16, t = 5.000, P = 0.001) and TIM-1/ß-actin ratio (0.78 ± 0.11 vs. 0.31 ± 0.06, t = 8.545, P < 0.001) in the OVA/PM group were increased compared to those in the PM group. The concentration of IL-4 (41.47 ± 3.40 vs. 25.46 ± 2.98 pg/ml, t = 2.501, P = 0.037) and the Bax/Bcl-2 ratio (0.97 ± 0.16 vs. 0.18 ± 0.03, t = 7.439, P < 0.001) and TIM-1/ß-actin ratio (0.31 ± 0.06 vs. 0.02 ± 0.01, t = 5.109, P = 0.001) in the PM group were also higher than those in the control group. Conclusions: Exacerbated AHR associated with allergic asthma caused by PM2.5is related to increased apoptosis and TIM-1 activation. These data might provide insights into therapeutic targets for the treatment of acute exacerbations of asthma induced by PM2.5.


Assuntos
Asma/induzido quimicamente , Asma/imunologia , Imunoglobulinas/metabolismo , Material Particulado/toxicidade , Linfócitos T/metabolismo , Animais , Apoptose/fisiologia , Asma/metabolismo , Líquido da Lavagem Broncoalveolar/imunologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C
8.
Shanghai Kou Qiang Yi Xue ; 25(2): 227-30, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27329891

RESUMO

PURPOSE: To evaluate the incidence of pain during intracanal medication before and after root canal instrumentation for therapeutic reference. METHODS: Three hundred and twenty four teeth were selected in this study, and the teeth received root canal therapy with crown-down technique using ProTaper rotary system, followed by calcium hydroxide intracanal medication. The degree of reported pain was recorded as 4 levels after treatment according to the Negm criteria. The incidence of endodontic interappointment emergencies (EIAE) at various recording times starting from root canal preparation was evaluated based on the results analyzed with MATLAB and SPSS19.0 software package. RESULTS: All patients reported of pain immediately after root canal therapy and calcium hydroxide intracanal medication, of which 1.54% were diagnosed as EIAE, the prevalence and degree of pain were increased. The prevalence of EIAE reached 25.62% one day after treatment, and decreased to 3.70% 3 days later. Most of the pain released without treatment; however, few patients experienced severe pain. The relationship between the EIAE percentage and time duration after treatment was fitted by using MATLAB as P(t)=100%×0.066t exp[-0.076t] (t: hour; RMSE=3.91). The patient started to report free of pain 6 hours after the treatment, 33.64% of the patients were painless 1 week after treatment, and 82.71% were painless 2 weeks later. There was significant difference between the pain level before and 2 weeks after treatment (P<0.01). CONCLUSIONS: During root canal preparation and intracanal medication, the prevalence and degree of pain were increased immediately after treatment, decreased 3 days later, and most of the pain was released 2 weeks after treatment.


Assuntos
Dor/epidemiologia , Preparo de Canal Radicular , Tratamento do Canal Radicular/estatística & dados numéricos , Hidróxido de Cálcio , Emergências , Humanos , Prevalência , Materiais Restauradores do Canal Radicular , Irrigantes do Canal Radicular
9.
Am J Transl Res ; 8(12): 5286-5297, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28078002

RESUMO

Recent studies have demonstrated that the crucial regulatory roles of long noncoding RNAs (lncRNAs) in tumorigenesis. Expression levels of several lncRNAs are abnormally up-regulated or down-regulated and play a primary role in colorectal cancer (CRC) cell tumorigenesis. However, the potential role and regulatory mechanisms of the novel human lncRNA, LINC00152, in CRC cells are poorly understood. Here, we found that LINC00152 expression was significantly decreased in CRC tissues and CRC cell lines, and this change was more frequent in patients with advanced stage (tumor-node-metastasisi (TNM) III and IV). Overexpression of LINC00152 (LINC000152over) resulted in decreased cell viability and increased apoptosis in CSC cell lines (HT-29 and SW480). Furthermore, decreased Ki-67 and B-cell lymphoma-2 (Bcl-2), and increased Fas, were observed in CSC cells. However, a change in Bax expression was undetected. Interestingly, microRNA (miR)-376c-3p down-regulated the expression of LINC00152 in CSC cells. Overexpression of miR-376c-3p (miR-376c-3pover) enhanced viability and limited apoptosis of CSC cells. In addition, miR-376c-3pover suppressed the effect of LINC00152over on the viability and apoptosis of CSC cells. Taken together, these data indicate that LINC00152 in CSC cells negatively regulated by miR-376c-3p, restricts cell viability and stimulates cell apoptosis, possibly by modulating the expression of Ki-67, Bcl-2, and Fas. MiR-376c-3p/LINC00152 plays an important role in the pathogenesis of CRC and may serve as a potential target for its diagnosis and treatment.

10.
Food Funct ; 6(5): 1643-51, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25892149

RESUMO

Ursolic acid (UA) is a natural pentacyclic triterpenoid compound, which is enriched with many herbs and plants, such as apple, cranberry and olive. UA performs multiple biological activities including anti-oxidation, anti-inflammation, anti-cancer and hepatoprotection. However, the exact mechanism underlying the hepatoprotective activity of UA remains unclear. In this study, the effects of UA on the development of nonalcoholic fatty liver disease (NAFLD) were investigated. In vivo, UA treatment (0.14%, w/w) significantly decreased the liver weight, serum levels of ALT/AST and hepatic steatosis in db/db mice (a type 2 diabetic mouse model). In vitro, UA treatment (10-30 µg ml(-1)) significantly decreased palmitic acid induced intracellular lipid accumulation in L02 cells. Our results suggested that the beneficial effects of UA on NAFLD may be due to its ability to increase lipid ß-oxidation and to inhibit the hepatic endoplasmic reticulum (ER) stress. Together, UA may be further considered as a natural compound for NAFLD treatment.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Triterpenos/administração & dosagem , Animais , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo
11.
Mol Med Rep ; 12(1): 470-4, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25739098

RESUMO

Colorectal cancer is one of the most commonly diagnosed types of cancer and is a leading cause of cancer-associated mortality worldwide. Short chain enoyl coenzyme A hydratase 1 (ECHS1) is an important gene involved in the mitochondrial fatty acid ß-oxidation pathway. In addition, ECHS1 has been implicated in a variety of cancers, including breast, prostate, colon and liver cancer. The aim of the present study was to examine the expression of ECHS1 in the human HCT-8 colorectal cancer cell line. The results showed that ECHS1 expression was significantly increased in poorly-differentiated cells compared with that in well-differentiated cells. In order to further investigate the functions of ECHS1 in colorectal cancer cells, a stably transfected HCT-8 cell line expressing small interfering (si)RNA targeting the ECHS1 gene was established. The expression of the ECHS1 siRNA was found to reduce ECHS1 protein levels in ECHS1-silenced cells by >40%. Cell proliferation and cell migration of the siECHS1 cells were characterized using Cell Counting Kit-8 and Transwell assays, respectively, the results of which showed that the constitutive knockdown of the ECSH1 gene in HCT-8 cells significantly inhibited cell proliferation and migration. Furthermore, decreased levels of Akt and glycogen synthase kinase (GSK)3ß phosphorylation were observed in ECHS1-silenced HCT-8 cells compared with that of parental or pU6 empty vector-transfected cells. In conclusion, the results of the present study suggested that ECHS1 may have an important role in colorectal cancer cell proliferation and migration via activation of Akt- and GSK3ß-associated signaling pathways.


Assuntos
Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Enoil-CoA Hidratase/biossíntese , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Enoil-CoA Hidratase/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteína Oncogênica v-akt/genética , RNA Interferente Pequeno , Transdução de Sinais
12.
Epilepsia ; 54(9): e142-5, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23944193

RESUMO

Interleukin 17A (IL-17A) is implicated in the pathogenesis of several neuroimmunologic diseases. We aimed to evaluate the relationship between IL-17A and seizure severity in patients with epilepsy. Seventy patients with probable symptomatic epilepsy and 68 healthy controls were included. Interictal serum IL-17A and related cytokine (IL-23, IL-6, IL-1ß, interferon gamma (IFN-γ), and IL-10) levels were measured. The relationship between seizure severity and cytokine concentrations was assessed by Spearman correlation and multivariate linear regression test. IL-17A levels in the cerebrospinal fluid (CSF) were tested in 30 additional patients with epilepsy, either in the postictal or interictal period and 15 patients with idiopathic inflammatory demyelinating diseases (IIDDs). Interictal serum IL-17A levels were significantly elevated in patients with epilepsy compared to controls. IL-6, IFN-γ, and IL-1ß levels were also markedly elevated. Spearman correlation analysis revealed positive correlation between IL-17A, IL-6 levels and Veterans Administration Seizures Frequency and Severity Rating Scale score(VA score); IFN-γ, IL-10 levels, and National Hospital Seizure Severity Scale (NHS3) score. In addition, IL-17A levels correlated significantly with seizure frequency. Multivariate linear regression test showed that only IL-17A levels were independently positively correlated with VA scores (B = 0.288, p = 0.027). Postictal IL-17A levels in the CSF were significantly elevated compared to interictal patients and patients with IIDDs. Our results suggest that interictal IL-17A levels correlated highly with seizure severity.


Assuntos
Epilepsia/líquido cefalorraquidiano , Interleucina-17/líquido cefalorraquidiano , Adulto , Feminino , Humanos , Inflamação/líquido cefalorraquidiano , Interferon gama/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/líquido cefalorraquidiano , Índice de Gravidade de Doença , Regulação para Cima
13.
Sheng Li Xue Bao ; 64(6): 633-8, 2012 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-23258325

RESUMO

The influence of 3α-androstanediol (3α-diol) on twitch and electroencephalogram (EEG) of the epileptic rats induced by pentylenetetrazole (PTZ) has been observed in this experiment in order to comprehensively explore the role of 3α-diol on epileptic attack from the aspects of behavior and EEG. Thirty-two male Sprague-Dawley rats were evenly and randomly divided into 4 groups: the normal and supplied with oil epileptic (N+oil+PTZ) group, the normal and supplied with 3α-diol epileptic (N+3α-diol+PTZ) group, the gonadectomized and supplied with oil epileptic (GDX+oil+PTZ) group and the gonadectomized and supplied with 3α-diol epileptic (GDX+3α-diol+PTZ) group. The changes of the behavior and EEG of epileptic rats in every group were recorded and analyzed. The results of behavior observation showed that the latency to clonic seizure and tonic-clonic seizure was shortened and the number of tonic-clonic seizure was increased significantly in the GDX+oil+PTZ group in comparison with N+oil+PTZ group (P < 0.05); comparing GDX+3α-diol+PTZ group with GDX+oil+PTZ group, or N+3α-diol+PTZ group with N+oil+PTZ group, we found that the latency to clonic seizure and tonic-clonic seizure became prolonged significantly, and the number of clonic seizure and tonic-clonic seizure was decreased significantly (P < 0.05). The results of EEG showed that the latency to epileptic waves was cut and the number of epileptic waves was augmented significantly in the GDX+oil+PTZ group in comparison with N+oil+PTZ group (P < 0.05); comparing GDX+3α-diol+PTZ group with GDX+oil+PTZ group, or N+3α-diol+PTZ group with N+oil+PTZ group, we found that the latency to epileptic waves became lengthened significantly, the number of epileptic waves was reduced significantly and the percentage of change of TP (total power of spectrum) was lessened significantly (P < 0.05). These results indicate that 3α-diol has an antiepileptic activity in the gonadectomized and normal epileptic rats.


Assuntos
Androstano-3,17-diol/análogos & derivados , Anticonvulsivantes/farmacologia , Epilepsia/tratamento farmacológico , Pentilenotetrazol/efeitos adversos , Convulsões/tratamento farmacológico , Androstano-3,17-diol/farmacologia , Animais , Eletroencefalografia , Epilepsia/induzido quimicamente , Masculino , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamente
14.
Seizure ; 20(10): 741-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21798770

RESUMO

PURPOSE: We sought to investigate the relationship between interictal personality changes and white matter abnormalities in epilepsy patients. METHODS: A total of 65 individuals with epilepsy and 40 demographically matched controls were evaluated by Eysenck Personality Questionnaire (EPQ) and diffusion tensor imaging (DTI) on 3T. Fractional anisotropy (FA) values of fibers were acquired. The relationship between EPQ scores, clinical variables and FA values was confirmed by Pearson correlation analysis and multiple linear regression analysis. RESULTS: Epilepsy patients had higher psychoticism scores (P score) and lower extraversion scores (E score) compared with controls. P scores were higher in patients with long duration (>10 years) and taking multiple antiepileptic drugs. No difference was found in E score according to all the clinical variables. Epilepsy patients showed significantly lower mean FA value compared with healthy controls in the bilateral uncinate fasciculus, cingulum bundle, arcuate fasciculus and forceps minor of the corpus callosum. Multivariate linear regression analysis revealed that duration of epilepsy and FA value of the right arcuate fasciculus was independent risk factors of psychoticism in epilepsy patients. CONCLUSIONS: Long disease duration and impairment of arcuate fasciculus integrity may predispose the development of psychoticism in patients with epilepsy. Our results provide important insights into the pathophysiological mechanisms underlying personality change in epilepsy.


Assuntos
Encéfalo/patologia , Epilepsia/patologia , Epilepsia/psicologia , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/patologia , Adulto , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Testes Neuropsicológicos , Inquéritos e Questionários
16.
World J Gastroenterol ; 11(21): 3217-21, 2005 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-15929170

RESUMO

AIM: To study the effect of IGF-1/IGF-1R and gastrin/CCK-BR on carcinogenesis and development of human gastric carcinoma and to explore its mechanism and provide a credible theoretical foundation for early diagnosis and molecular therapy of gastric carcinoma. METHODS: mRNA expression levels of IGF-1/IGF-1R and gastrin/CCK-BR were assessed by RT-PCR method in gastric cancer tissues, adjacent mucosa, and tumor-free tissues from 56 patients with gastric carcinoma and normal gastric mucosae from 56 healthy controls. Tissue specimens were obtained by biopsy and confirmed by histological evaluation. RESULTS: The mRNA levels of IGF-1/IGF-1R were increased in gastric cancer tissues compared with normal tissues from healthy controls and successively increased in tumor-free tissues, adjacent mucosa, and gastric cancer tissues. The mRNA levels of gastrin/CCK-BR were increased in gastric cancer tissues compared with normal tissues from healthy controls. There was a significant difference between gastric cancer tissues and adjacent mucosa and tumor-free tissues, but the mRNA levels of gastrin were not significantly increased in adjacent mucosa and gastric cancer tissues compared with tumor-free tissues. The mRNA levels of CCK-BR were increased in gastric cancer tissues and adjacent mucosa compared with tumor-free tissues, but not significantly increased in adjacent mucosa and gastric cancer tissues compared with gastric cancer tissues. CONCLUSION: Overexpression of IGF-1/IGF-1R and gastrin/CCK-BR promotes the disorderly proliferation of gastric mucosa epithelia and it is of great significance in the carcinogenesis and development of gastric carcinoma.


Assuntos
Gastrinas/genética , Fator de Crescimento Insulin-Like I/genética , Receptor de Colecistocinina B/genética , Receptor IGF Tipo 1/genética , Neoplasias Gástricas/genética , Regulação Neoplásica da Expressão Gênica , Humanos
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