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1.
Clin Interv Aging ; 17: 653-664, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35520948

RESUMO

Objective: Type 2 diabetes mellitus (T2DM) and ischemic stroke, which are common diseases among older people, are closely related to cognitive impairment. This study aims to investigate the influencing factors of post-stroke cognitive impairment (PSCI) in patients with T2DM. Methods: We enrolled 161 patients with T2DM who experienced acute ischemic stroke and were hospitalized in the Department of Neurology, Jinan Central Hospital, Shandong, China. Cognitive function was evaluated with the Montreal Cognitive Assessment scale. According to the results, patients were divided into three groups-the cognitively normal group, mild cognitive impairment group, and severe cognitive impairment group. We analyzed general demographic data, laboratory information, imaging data, the results of neuropsychological evaluation, and clinical features as well as influencing factors of PSCI in these patients and established a prediction model. Results: The three groups of patients were significantly different in terms of age, education level, course of diabetes mellitus (DM), recurrent cerebral infarction (RCI), and other factors. RCI, course of DM, and glycated hemoglobin (HbA1c) were independent risk factors of PSCI in patients with T2DM, with odds ratio (95% confidence interval): 7.17 (2.09, 30.37), 5.39 (2.40, 14.59), and 3.89 (1.66, 10.04), respectively, whereas female, senior high school, serum albumin were protective factors: 0.28 (0.07, 0.95), 0.05 (0.01, 0.21), 0.20 (0.08, 0.42), respectively. Furthermore, we constructed a prediction model using sex, age, education level, RCI, DM course, HbA1c and serum albumin and obtained a receiver operating characteristic (ROC) curve. The area under the ROC curve is 0.966, suggesting the significant association of these influencing factors with PSCI in patients with T2DM. Conclusion: In this study, the occurrence of PSCI in patients with T2DM was related to RCI, course of DM, and HbA1c, among other factors. Attention to influencing factors is needed in these patients for early diagnosis and timely intervention of cognitive impairment.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Disfunção Cognitiva/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Feminino , Hemoglobinas Glicadas , Humanos , Albumina Sérica , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia
2.
Eur J Drug Metab Pharmacokinet ; 47(3): 431-440, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35146636

RESUMO

BACKGROUND AND OBJECTIVE: Strobilanthes crispus Blume sub-fraction (F3) has been reported to be cytotoxic against cancer cells and to cause murine mammary tumor regression. Potential utilization of F3 as an adjuvant in breast cancer treatment to alleviate chemotherapeutic drug resistance is currently hampered by potential cytochrome P450 (CYP)-mediated herb-drug interactions (HDIs). The current study assessed the inhibitory potency of F3 towards five CYP enzymes involved in tamoxifen metabolism. METHODS: Potential CYP inhibition by F3 was first determined using fluorescence assays, using known CYP inhibitors as reference. To further ascertain the inhibitory potency and mode of inhibition, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis of specific metabolites of a CYP probe substrate was conducted. RESULTS: The half-maximal inhibitory concentration (IC50) values indicate that F3 exhibited relatively weak inhibition on CYP2B6, CYP2C19, CYP2D6, and CYP3A4. Highest susceptibility to inhibition by F3 was observed for CYP2C9, where the IC50 value from fluorescence-based assay was 35-fold higher than control. Further analysis by HPLC-MS/MS revealed relatively weak mixed-type inhibition of F3 on CYP2C9, as indicated by IC50 and inhibition constant (KI) values. The risk of clinically significant CYP2C9 inhibition by F3 was then predicted based on the attained KI value and the presumed amount of F3 absorbed from S. crispus leaves following consumption. The calculated maximum plasma concentration to inhibition constant Cmax/KI) ratio suggests that F3 consumption could potentially result in clinically significant drug interactions with medications metabolized by CYP2C9. CONCLUSION: Taken together, the results revealed a low probability of inhibition by F3 on CYP enzymes involved in tamoxifen metabolism. However, further in vivo investigation is necessary for potential F3 interaction with CYP2C9. The utility of a preliminary in vitro approach in the assessment of potential HDI was demonstrated in this study.


Assuntos
Interações Ervas-Drogas , Microssomos Hepáticos , Animais , Citocromo P-450 CYP2C9/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Camundongos , Microssomos Hepáticos/metabolismo , Tamoxifeno/metabolismo , Tamoxifeno/farmacologia , Espectrometria de Massas em Tandem
3.
Small Methods ; 5(7): e2100505, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34927987

RESUMO

Design and development of cost-effective electrocatalysts with high efficiency and stability for scalable and sustainable hydrogen production through water splitting is still challenging. Herein, with the aid of divinyl functionalized ionic liquids, uniformly distributed Ru nanoparticles (NPs) on nitrogen-doped carbon frameworks are obtained via an in situ confined polymerization strategy. Attributed to the unique lamellar structure and confinement effect of carbon supports, the optimized homo-PIL-Ru/C-600 (with Ru 10 wt%) catalyst exhibits superior catalytic efficiency for the hydrogen evolution reaction with the overpotential of only 16 mV at a current density of 10 mA cm-2 and the corresponding Tafel slope of only 42 mV dec-1 . Moreover, the performance can be well reserved even after 10 000 cycles, demonstrating excellent stability and promising potentials for industrial application. This work not only provides a facile approach for the preparation of highly efficient Ru-based catalysts, but also guides the synthesis of other highly dispersed metallic NPs for special applications.

4.
Shanghai Kou Qiang Yi Xue ; 30(2): 135-139, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-34109350

RESUMO

PURPOSE: To compare the accuracy of implant placement between modified and traditional immediate implant placement in mandibular molar regions. METHODS: Twenty-four patients were selected for immediate implantation in the molar area including 24 implantation sites. Preoperative cone-beam CT(CBCT) was conducted and then digital software Simplant 18.0 was used to design the ideal three-dimensional position of the implants. In the experimental group, the implant socket was prepared first according to reference of the remaining natural teeth, then the implant was implanted after minimally invasive extraction. Twelve patients in the control group underwent immediate implantation by traditional immediate implant procedures. Minimally invasive extraction, then socket preparation, and final implanting were performed. All patients underwent CBCT after surgery. Implant sites designed prior to surgery and actual implant sites differences between modified and traditional immediate implant placement were measured by Simplant 18.0 and compared with SPSS 17.0 software package. RESULTS: In the experimental group and control group, the measured average deviation were as follows, the angle was (4.492±0.912)° and (7.255±1.307)°, respectively; The horizontal error of the implant shoulder was (0.379±0.083) mm and (1.229±0.270) mm, respectively; The measuring horizontal error of the implant apex was (1.263±0.267) mm and (2.183±0.264) mm, respectively; The calculative horizontal error of the implant apex was (1.324±0.203) mm and (2.709±0.383) mm, respectively; Depth error of the implant apex was (0.663±0.123) mm and (1.533±0.155) mm, respectively, which were significantly lower than those of the control group. CONCLUSIONS: Compared with the traditional method, modified immediate implantation can improve the accuracy of implantation in mandibular molars.


Assuntos
Implantes Dentários , Boca Edêntula , Cirurgia Assistida por Computador , Tomografia Computadorizada de Feixe Cônico , Implantação Dentária Endóssea , Humanos , Dente Molar/diagnóstico por imagem
5.
Cell Cycle ; 18(16): 1868-1881, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31204565

RESUMO

MicroRNAs (miRNAs) have emerged as key mediators of posttranscriptional gene silencing in both pathogenic and pathological aspects of ischemic stroke biology. Therefore, the purpose of present study was to explore the effect of microRNA-199b-3p (miR-199b-3p) on the cerebral microvascular endothelial cells (CMECs) in middle cerebral artery occlusion-reperfusion (MCAO-R) mice by regulating MAPK/ERK/EGR1 axis. Mice were used to establish MCAO-R models and to measure the expression of miR-199b-3p and the MAPK/ERK/EGR1 axis-related genes. CMECs were extracted from the MCAO-R mice. A series of mimic or inhibitor for miR-199b-3p, or U0126 (an inhibitor for the MAPK/ERK/EGR1 axis) were introduced to treat these CMECs. The levels of miR-199b-3p and MAPK/ERK/EGR1 axis-related genes in tissues and cells were detected. The effects miR-199b-3p on the process of CMECs, including cell viability, cell cycle and cell apoptosis were evaluated. miR-199b-3p expressed poorly in the brain tissues after MCAO-R, along with activated MAPK/ERK/EGR1 axis and increased CMECs apoptosis. CMECs transfected with miR-199b-3p mimics and U0126 manifested with increased cell viability, more cells arrested at the S stage, and inhibited apoptosis of CMECs. In conclusion, these key results demonstrated up-regulated miR-199b-3p could protect mice against ischemic stroke by inhibiting the apoptosis of CMECs through blockade of MAPK/ERK/EGR1 axis.


Assuntos
Apoptose/genética , Isquemia Encefálica/metabolismo , Cérebro/patologia , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Células Endoteliais/metabolismo , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Acidente Vascular Cerebral/metabolismo , Animais , Sobrevivência Celular/genética , Modelos Animais de Doenças , Regulação para Baixo/genética , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Pontos de Checagem da Fase S do Ciclo Celular/genética , Regulação para Cima/genética
6.
J Cell Biochem ; 120(1): 368-379, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30246455

RESUMO

Traumatic brain injury (TBI), an acute degenerative pathology of the central nervous system, is a leading cause of death and disability. As the glial scar is a mechanical barrier to nerve regeneration, inhibitory molecules in the forming scar and methods to overcome them have suggested molecular modification strategies to allow neuronal growth and functional regeneration. Herein, we aim to investigate the effects of aquaporin-4 (AQP4) gene silencing on the glial scar formation after TBI by establishing rat models. After modeling, TBI rats were transfected with AQP4 small hairpin RNA [shRNA] (AQP4 gene silencing by lentiviral vector-delivered shRNA) and empty vectors, respectively. Neurological functions of the rats were evaluated after TBI. The hematoxylin and eosin staining was conducted to observe histomorphological changes in rat brain tissues. The messenger RNA (mRNA) and protein expressions of glial fibrillary acidic protein (GFAP), vimentin, fibronectin, laminin, and AQP4 were measured by reverse transcription-quantitative polymerase chain reaction and Western blot analysis. The ratio of positive expression area was calculated, and the glial scar was observed by immunohistochemistry. At the 7th, 14th, and 28th days after TBI, TBI rats treated with AQP4 shRNA showed improved neurological function and lessened histomorphological changes. AQP4 gene silencing mediated by lentivirus decreased the mRNA and protein expressions of GFAP, vimentin, fibronectin, and laminin, the number of positive cells, the ratio of positive expression area, and the glial scar. Our study demonstrates that lentivirus-mediated AQP4 gene silencing could inhibit the formation of glial scar after TBI, which is beneficial to the recovery of neurological function.


Assuntos
Aquaporina 4/genética , Lesões Encefálicas Traumáticas/terapia , Cicatriz/terapia , Inativação Gênica , Neuroglia/metabolismo , Animais , Aquaporina 4/metabolismo , Lesões Encefálicas Traumáticas/patologia , Cicatriz/genética , Cicatriz/metabolismo , Modelos Animais de Doenças , Fibronectinas/genética , Fibronectinas/metabolismo , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Laminina/genética , Laminina/metabolismo , Lentivirus , Masculino , Exame Neurológico , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Transfecção , Vimentina/genética , Vimentina/metabolismo
7.
Chinese Journal of Urology ; (12): 889-894, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-824603

RESUMO

Objective A predictive model of WHO/ISUP grading of renal clear cell carcinoma was constructed based on CT radiomics.Methods The clinical data of 104 patients with ccRCC confirmed by operation or biopsy from March 2014 to December 2018 in the Mfiliated Hospital of Shaanxi University of Traditional Chinese Medicine were retrospectively analyzed.There were 70 males and 34 females,and the age was 61.2 ± 11.7 years.The patients were randomly divided into development cohort (73 cases) and validation cohort (31 cases) by stratified sampling according to 7∶3 ratio.According to the WHO/ISUP pathological grading criteria of renal cancer in 2016,Ⅰ and Ⅱ were defined as low-grade group,Ⅲ and Ⅳ were defined as high-grade group.The radiomics features of ccRCC were calculated in cortical phase images of CT enhanced scanning.LASSO regression was used to reduce the radiomics feature dimensionality in the training group,and to establish radiomics risk scores.The binary logistic regression was used to build the prediction model,which was used in the validation group.Bootstrap method was used to validate the model of training and validation group.AUC,sensitivity and specificity were calculated respectively.Hosmer-Lemeshow goodness-of-fit test was used to evaluate model calibration degree.Results After dimensionality reduction,the radiomics risk score of ccRCC was established.The low and high-level risk scores of the training group were-2.49 ± 1.73 and 1.23 ± 2.17,with significant difference (t =-7.785,P < 0.01).The binary logistic regression multivariate analysis showed that the radiomics risk score was an independent risk factor in identifying low or high-grade ccRCC with odds ratio of (OR =3.576,95% CI 1.964 ~ 6.513).The predictive model was Y =1/[1 + exp(-Z)],Z =1.274 × radiomics risk score + 0.072.The AUC of radiomics risk score in training group was 0.940 (95% CI 0.883-0.998) with 95.5% sensitivity and 88.2% specificity after internal verification by Bootstrap method,and good Hosmer-Lemeshow goodness-of-fit test (x2 =4.463,P > 0.05).The low and high-level risk scores of the Validation group were-2.27 ± 2.02 and 0.82 ± 2.08,with significant difference (t =-3.832,P < 0.01).The AUC in validation group was 0.859(95% CI 0.723-0.995) with 77.8% sensitivity and 81.8% specificity,and with good Hosmer-Lemeshow goodness-of-fit test (x2 =14.554,P =0.068) as well.Conclusions The prediction model based on CT radiomics has high accuracy in predicting high or low grade of ccRCC.

8.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(11): 3780-8, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30226716

RESUMO

This work mainly talks about serpentine mineral with the aim to explore the possible raw materials sources of ancient serpentine artifacts by trace element content analysis. The major and trace elements of serpentine samples from several typical deposits in China were nondestructively determined by external-beam proton-induced X-ray emission (PIXE). For comparison, trace element concentrations were destructively measured by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The results showed the trend of the trace element contents of serpentine jade obtained by the two methods have preferably coherence, which indicate that the nondestructive technique of PIXE can be applied to trace element analysis of serpentine. The relationship between trace element contents and serpentine formation mechanism was discussed. The difference of the trace elements contents in these serpentine minerals is obvious. It can be used to distinguish the different kinds of serpentine formed by different mechanisms. A low amount of Ni and almost no Cr and Co were found in type I serpentine group mineral, whereas significant amounts of Cr, Co and Ni were found in Type II serpentine group mineral. The chemical composition of 18 ancient serpentine artifacts were analyzed by PIXE, they were unearthed from 14 sites and tombs in provinces of Zhejing, Jiangsu, Henan, Anhui and Hubei and dated from Neolithic Age to the Warring States Period (4585 BC­231 BC). By comparing the trace element contents between ancient serpentine artifacts and two kinds of serpentine samples, the provenance of ancient serpentine artifacts were preliminarily inferred. It is beneficial to try to explore the possible raw material of ancient serpentine artifacts based on the relationship between the trace element contents and serpentine formation mechanism in this article.

9.
Drug Des Devel Ther ; 8: 1299-305, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25246771

RESUMO

OBJECTIVE: To investigate the clinical characteristics of seronegative hepatitis-associated aplastic anemia (AA) (SNHAA) and hepatitis B virus (HBV) infection complicating AA (HBVAA), and thereby compare the efficacy of immunosuppressive therapy (IST). METHODS: An analysis was conducted on the clinical data of ten patients with SNHAA out of 332 cases of AA from our center at AA diagnosis, and on the efficacy of IST. This was compared to 22 cases of HBVAA at AA onset as well as the associated IST outcomes. RESULTS: Nine patients with SNHAA developed severe aplastic anemia, with a median age of 18 years. After IST, six (60%) of the SNHAA patients achieved complete remission and two achieved partial remission. The patients with HBVAA had a total response rate of 82.3%. The disease recurred in two HBVAA patients. No statistically significant differences were observed in response rate, mortality, and recurrence rate between both groups. As compared with HBVAA, patients with SNHAA had a shorter interval from the acute episode of hepatitis to AA onset (4 months versus 92 months, P=0.00), a quicker response to IST (2.5 months versus 4.5 months, P=0.018), a lower proportion of bone marrow hematopoietic tissues (20.6% versus 23.6%, P=0.03), and lower white blood cell and absolute neutrophil count (0.8 × 10(9)/L versus 1.23 × 10(9)/L and 0.26 × 10(9)/L versus 0.58 × 10(9)/L, P=0.026 and P=0.0009, respectively). No significant liver damage or hepatitis B fulminant infection was observed in either group during the follow-up. CONCLUSION: The prevalence of SNHAA is 3.01%. SNHAA often presents as severe AA and responds to IST quickly. Neither hepatitis prior to AA nor AA complicating HBV infection have been shown to influence the early efficacy of IST and adverse events, and HBV may not be the causative agent of AA.


Assuntos
Anemia Aplástica/complicações , Anemia Aplástica/tratamento farmacológico , Antivirais/uso terapêutico , Ciclosporina/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/complicações , Imunossupressores/uso terapêutico , Adolescente , Adulto , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/farmacologia , Criança , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Ciclosporina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Humanos , Imunoglobulinas/imunologia , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Adulto Jovem
10.
Drug Des Devel Ther ; 7: 767-70, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23976844

RESUMO

A 41-year-old male had suffered from gradual hearing loss in his right ear for 2 years. Head computed tomography and magnetic resonance imaging scans showed a neoplasm in the cerebellopontine angle region, which was confirmed by the diagnosis of acoustic neurilemmoma by pathological findings after surgery. Following surgery, he routinely received valproic acid (VPA) to prevent seizures. However, the patient presented with hypofibrinogenemia and cerebral hemorrhage after taking VPA for 12 days. The hypofibrinogenemia recurred when VPA was re-administered. After withdrawal of VPA, his fibrinogen concentration rose to normal within several days. As far as we are aware, this is the first case of cerebral hemorrhage due to VPA to have been reported. Herein, as well as reporting on this case, a mini review of the relevant literature is also presented.


Assuntos
Afibrinogenemia/induzido quimicamente , Anticonvulsivantes/efeitos adversos , Hemorragia Cerebral/induzido quimicamente , Ácido Valproico/efeitos adversos , Adulto , Anticonvulsivantes/uso terapêutico , Humanos , Masculino , Convulsões/prevenção & controle , Fatores de Tempo , Ácido Valproico/uso terapêutico
11.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(9): 2305-10, 2012 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-23240384

RESUMO

The coloration mechanism of Xiuyan Jade was studied with the chemical composition, valance and coordination states of transition metal ions. The result of inductively-coupled plasma atom emission spectrometer (ICP-AES) indicated that there are little other transition metal elements except for iron and manganese. Electron paramagnetic resonance (EPR) revealed that Fe3+ ions locate at both octahedral sites and tetrahedral sites. Optical absorption spectrum (OAS) showed the presence of Fe2+ and Fe3+ ions. Moreover, depending on the results of OAS, Fe2+ ions determine the green color of Xiuyan Jade, while the coexistence of Fe3+ and Fe2+ ions introduces the yellow color of Xiuyan Jade. The chromaticity coordinate was calculated according to diffuse reflectance spectrum. The result demonstrated that chromaticity coordinates can be used to quantitatively distinguish Xiuyan Jade with similar color, which can provide a scientific reference for the evaluation of the value of Xiuyan Jade.

12.
Asian Pac J Cancer Prev ; 13(9): 4777-81, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23167419

RESUMO

OBJECTIVE: To investigate the relationship between the efficacy and safety of different doses of thalidomide (Thal) plus dexamethasone (Dex) as the initial therapy in elderly patients with newly diagnosed multiple myeloma (MM). METHODS: Clinical data of 28 elderly patients with newly diagnosed MM who underwent the TD regimen as the initial therapy were analyzed retrospectively. The patients were divided into two groups according to the maximal sustained dose of Thal: lower dose (group A) and higher dose (group B). The overall response rate (ORR), progression free survival (PFS), overall survival (OS), and adverse events (AES) were compared between the two groups. RESULTS: A total of 28 patients were followed up with a median of 18 months. The ORR was 60.1%. The median response time and PFS were 2.0 and 17.0 months, respectively. The mean sustained dose of Thal in group B was significantly higher than group A (292.9 mg v 180.4 mg, P=0.01). There was no significantly difference in ORR (57.1% v 64.3%, P=1.00) and PFS (9.63months v 17.66 months, P=0.73) between groups A and B. During the follow up, only five patients died (<40%) and, therefore, median OS values were not available. It is estimated, however, that the mean survival time in the two groups was 35.6 and 33.4 months (P>0.05), respectively. All of the patients tolerated the treatment well. The incidence of AES in patients with a grading above 3 in group B was significantly higher than in group A (P=0.033). CONCLUSIONS: The TD regimen results in a high response rate and manageable AES as the initial therapy in elderly patients with MM. TD should be considered as the front line regimen for the treatment of elderly patients with MM in areas with financial constraints. The clinical response can be achieved at a low dose Thal with minimal toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Talidomida/administração & dosagem , Resultado do Tratamento
13.
PLoS One ; 7(8): e42490, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22905138

RESUMO

Hepatic stellate cells (HSCs) play a key role in the development of liver fibrosis caused by schistosomiasis. Chemokines were widely expressed and involved in cellular activation, proliferation and migration in inflammatory and infectious diseases. However, little is known about the expressions of chemokines on HSCs in the schistosoma infection. In addition, the roles of chemokines in pathogenesis of liver fibrosis are not totally clear. In our study, we used microarray to analyze the temporal gene expressions of primary HSCs isolated from mice with both acute and chronic schistosomiasis. Our microarray data showed that most of the chemokines expressed on HSCs were upregulated at 3 weeks post-infection (p.i) when the egg granulomatous response was not obviously evoked in the liver. However, some of them like CXCL9, CXCL10 and CXCL11 were subsequently decreased at 6 weeks p.i when the granulomatous response reached the peak. In the chronic stage, most of the differentially expressed chemokines maintained persistent high-abundances. Furthermore, several chemokines including CCR2, CCR5, CCR7, CXCR3, CXCR4, CCL2, CCL5, CCL21, CXCL9 and CXCL10 were expressed by HCSs and the abundances of them were changed following the praziquantel treatment in the chronic stage, indicating that chemokines were possibly necessary for the persistence of the chronic stage. In vitro experiments, hepatic non-parenchymal cells, primary HSCs and human HSCs line LX-2 were stimulated by chemokines. The results showed that CXCL9 and CXCL10, but not CXCL11 or CXCL4, significantly inhibited the gene expressions of Col1α1, Col3α1 and α-SMA, indicating the potential anti-fibrosis effect of CXCL9 and CXCL10 in schistosomiasis. More interestingly, soluble egg antigen (SEA) of Schistosoma japonicum was able to inhibit transcriptional expressions of some chemokines by LX-2 cells, suggesting that SEA was capable of regulating the expression pattern of chemokine family and modulating the hepatic immune microenvironment in schistosomiasis.


Assuntos
Quimiocina CXCL10/metabolismo , Quimiocina CXCL9/metabolismo , Quimiocinas/biossíntese , Regulação da Expressão Gênica , Células Estreladas do Fígado/metabolismo , Fígado/metabolismo , Schistosoma japonicum/imunologia , Esquistossomose/metabolismo , Animais , Quimiocina CXCL11/metabolismo , Quimiocinas/metabolismo , Feminino , Perfilação da Expressão Gênica , Genoma , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Fator Plaquetário 4/metabolismo , Praziquantel/farmacologia , Schistosoma japonicum/metabolismo
14.
Org Lett ; 14(5): 1210-3, 2012 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-22324403

RESUMO

A novel magnetically recoverable organic hydride compound was successfully constructed by using silica-coated magnetic nanoparticles as a support. An as-prepared magnetic organic hydride compound, BNAH (1-benzyl-1,4-dihydronicotinamide), showed efficient activity in the catalytic reduction of α,ß-epoxy ketones. After reaction, the magnetic nanoparticle-supported BNAH can be separated by simple magnetic separation which made the separation of the product easier.


Assuntos
Compostos de Epóxi/química , Compostos Férricos/química , Cetonas/química , Nanopartículas de Magnetita/química , NAD/análogos & derivados , Catálise , Hidrogenação , Nanopartículas de Magnetita/ultraestrutura , Microscopia Eletrônica de Transmissão , Estrutura Molecular , NAD/síntese química , NAD/ultraestrutura , Oxirredução
15.
PLoS One ; 6(5): e20247, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21629648

RESUMO

BACKGROUND: Schistosomiasis is a parasitic disease infecting more than 200 million people in the world. Although chemotherapy targeting on killing schistosomes is one of the main strategies in the disease control, there are few effective ways of dealing with liver fibrosis caused by the parasite infection in the chronic and advanced stages of schistosomiasis. For this reason, new strategies and prospective drugs, which exert antifibrotic effects, are urgently required. METHODS AND FINDINGS: The antifibrotic effects of praziquantel were assessed in the murine models of schistosomiasis japonica. Murine fibrosis models were established by cutaneous infection with 14 ± 2 Schistosoma japonicum cercariae. Then, the mice of both chronic (8 weeks post-infection) and advanced (15 weeks post-infection) schistosomiasis were treated by gavage of praziquantel (250 mg/kg, once daily for 3 days) to eliminate worms, and followed by praziquantel anti-fibrosis treatment (300 mg/kg, twice daily for 30 days). The fibrosis-related parameters assessed were areas of collagen deposition, content of hydroxyproline and mRNA expressions of Col1α1, Col3α1, α-SMA, TGF-ß, MMP9, TIMP1, IL-4, IL-10, IL-13 and IFN-γ of liver. Spleen weight index, alanine aminotransferase activity and liver portal venous pressure were also measured. The results showed that anti-fibrosis treatment improved liver fibrosis, splenomegaly, hepatic function, as well as liver portal hypertension. In order to confirm the anti-fibrotic properties of praziquantel, we established a CCL(4)-induced model and revealed that CCL(4)-induced liver fibrosis was inhibited by PZQ treatment for 30 days. Furthermore, we analyzed the effects of praziquantel on mouse primary hepatic stellate cells (HSCs). It is indicated that mRNA expressions of Col1α1, Col3α1, α-SMA, TGF-ß, MMP9 and TIMP1 of HSCs were all inhibited after praziquantel anti-parasite treatments. CONCLUSIONS: The significant amelioration of hepatic fibrosis by praziquantel treatment validates it as a promising drug of anti-fibrosis and offers potential of a new chemotherapy for hepatic fibrosis resulting from schistosomiasis.


Assuntos
Anti-Helmínticos/uso terapêutico , Praziquantel/uso terapêutico , Schistosoma japonicum/patogenicidade , Esquistossomose Japônica/tratamento farmacológico , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Células Cultivadas , Feminino , Hidroxiprolina/metabolismo , Imuno-Histoquímica , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/etiologia , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase , Schistosoma japonicum/efeitos dos fármacos , Esquistossomose Japônica/complicações , Esquistossomose Japônica/metabolismo
16.
Ai Zheng ; 25(2): 175-8, 2006 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-16480581

RESUMO

BACKGROUND & OBJECTIVE: The mutation of von Hippel-Lindau (VHL) tumor suppressor gene is closely related with tumorigenesis of renal clear cell carcinoma (RCCC). Cyclin D1 gene plays an important role in progression of RCCC by stimulating cell proliferation. This study was to determine the mutation of VHL gene in RCCC, and explore its correlation to overexpression of Cyclin D1. METHODS: The specimens of RCCC and adjacent normal renal tissue from 50 patients were collected after surgery. Total RNA and genomic DNA were extracted from each sample. Variant exons in VHL gene were amplified by polymerase chain reaction (PCR) and sequenced, and DNA hypermethylation was detected by restriction analysis. Reverse transcription-PCR (RT-PCR) and Western blot were used to detect the expression of Cyclin D1. RESULTS: Of the 50 specimens, 42 (84.0%) had various VHL gene mutations, 12 (24.0%) had more than 1 kind of gene mutation. Of the 57 cases of exon mutation of VHL gene, 17 (29.8%) were located in exon 1, 26 (45.6%) in exon 2, and 14 (24.6%) in exon 3. The expression of Cyclin D1 in the 42 cases with VHL gene mutation was increased to 2-10 (3.91+/-1.54) times that of normal controls (P<0.01). Cyclin D1 expression in the other 8 cases was normal. CONCLUSION: There are variant mutations of VHL gene in RCCC, which may lead to overexpression of Cyclin D1.


Assuntos
Carcinoma de Células Renais/genética , Ciclina D1/biossíntese , Neoplasias Renais/genética , Mutação , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Carcinoma de Células Renais/metabolismo , Ciclina D1/genética , Éxons , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética
17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 31(6): 872-6, 2006 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-17213586

RESUMO

OBJECTIVE: To investigate the suppression of MDR1 and P-glycoprotein induced by small interfering RNA and the restoration of sensitivity to chemotherapeutic drugs in multidrug-resistant hepatocellular carcinoma cell line Bel7402/5-Fu. METHODS: MDR1j targeted small interfering RNA duplexes were introduced into multidrug-resistant hepatocellular carcinoma cell line Bel7402/5-Fu. The suppression of MDR1 and its gene product P-glycoprotein was examined by RT-PCR and Western blot. MTT assay was performed to measure the reverse effect of small interfering RNA based on the results of IC50. Cell apoptosis was assessed by flow cytometry after various cell lines were treated with chemotherapeutic drugs. RESULTS: The overexpression of MDR1 and P-glycoprotein was suppressed efficiently by the introduction of small interfering RNA, which caused sequence-specific gene silence. The level of MDR1 in the transfected Bel7402/5-Fu cells reduced to 22.55% and P-glycoprotein to 25.49% compared with those of the controls. The apoptosis rate of Bel7402/5-Fu cells increased significantly in the siRNA group during the chemotherapy (P<0.01). Their resistance to 5-Fu was reversed by 14.88 folds, which indicated the restoration of sensitivity to drugs. CONCLUSION: Small interfering RNA can inhibit MDR1 expression effective and reverse the multidrug resistance mediated by P-glycoprotein.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Resistencia a Medicamentos Antineoplásicos/genética , Interferência de RNA , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , RNA Interferente Pequeno/genética , Transfecção
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-813583

RESUMO

OBJECTIVE@#To investigate the suppression of MDR1 and P-glycoprotein induced by small interfering RNA and the restoration of sensitivity to chemotherapeutic drugs in multidrug-resistant hepatocellular carcinoma cell line Bel7402/5-Fu.@*METHODS@#MDR1j targeted small interfering RNA duplexes were introduced into multidrug-resistant hepatocellular carcinoma cell line Bel7402/5-Fu. The suppression of MDR1 and its gene product P-glycoprotein was examined by RT-PCR and Western blot. MTT assay was performed to measure the reverse effect of small interfering RNA based on the results of IC50. Cell apoptosis was assessed by flow cytometry after various cell lines were treated with chemotherapeutic drugs.@*RESULTS@#The overexpression of MDR1 and P-glycoprotein was suppressed efficiently by the introduction of small interfering RNA, which caused sequence-specific gene silence. The level of MDR1 in the transfected Bel7402/5-Fu cells reduced to 22.55% and P-glycoprotein to 25.49% compared with those of the controls. The apoptosis rate of Bel7402/5-Fu cells increased significantly in the siRNA group during the chemotherapy (P<0.01). Their resistance to 5-Fu was reversed by 14.88 folds, which indicated the restoration of sensitivity to drugs.@*CONCLUSION@#Small interfering RNA can inhibit MDR1 expression effective and reverse the multidrug resistance mediated by P-glycoprotein.


Assuntos
Humanos , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Genética , Metabolismo , Carcinoma Hepatocelular , Genética , Metabolismo , Patologia , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos , Genética , Resistencia a Medicamentos Antineoplásicos , Genética , Neoplasias Hepáticas , Genética , Metabolismo , Patologia , Interferência de RNA , RNA Interferente Pequeno , Genética , Transfecção
19.
Shanghai Kou Qiang Yi Xue ; 14(1): 14-7, 2005 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-15747006

RESUMO

PURPOSE: To evaluate the clinical value of X ray lateral cephalogram in the measurement of adenoids in children. METHODS: 45 cases (aged from 3 to 13 year old) with adenoid hypertrophy suspected clinically were examined with lateral cephalometric projections, of which 40 cases were examined with lateral nasopharyngeal projections at one time. Then the quality of films were appraisal and the adenoids were measured on the film. Student's X(2) test was used for statistics analysis. RESULTS: X ray lateral cephalogram can distinctly reveal the structure of nasopharynx. The method was simply and reproducible. The quality of the films were determined based on the conjunction between the base of the pterygoid plate and extracranial aspect of the occipital slope, with consideration of the mandibular margin and sphenoid saddle. The conjunction should be clearly demonstrated and the edges of the mandibular margin and sphenoid saddle should be sharp and well demarcated in qualified films. 45 cases were examined with lateral cephalometric projections, 34 cases had standard films, accounting for 76%. 40 cases were examined with lateral nasopharyngeal projections, 21 had standard films, accounting for 53%. The quality of X ray lateral cephalogram was significantly better than lateral nasopharyngeal projections (P<0.05). CONCLUSION: Compared with the routine lateral nasopharyngeal projection, lateral nasopharyngeal cephalogram has images of high quality, is better for showing the nasopharyngeal structures as well as measurement of the adenoids with parenchyma. It is the imaging method of choice for children with OSAHS.


Assuntos
Tonsila Faríngea/anatomia & histologia , Tonsila Faríngea/patologia , Cefalometria , Adolescente , Criança , Pré-Escolar , Humanos , Hipertrofia , Raios X
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