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1.
BMC Cancer ; 21(1): 83, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472598

RESUMO

BACKGROUND: Non-invasive diagnosis of IDH1 mutation for gliomas has great clinical significance, and PET has natural advantage to detect metabolism, as IDH mutated gliomas share lower glucose consumption. METHODS: Clinical data of patients with gliomas and 18F-FDG PET were retrospectively reviewed. Receiver operating characteristic curve (ROC) analysis was conducted, and standard uptake value (SUV) was estimated in combination with grades or IDH1 mutation. The glucose consumption was investigated with U251 cells expressing wild-type or mutated IDH1 by glucose assay. Quantification of glucose was determined by HPLC in clinical tissues. Meanwhile, bioinformatics and western blot were applied to analyze the expression level of metabolic enzymes (e.g. HK1, PKM2, PC) in gliomas. RESULTS: Seventy-one glioma cases were enrolled, including 30 carrying IDH1 mutation. The sensitivity and specificity dependent on SUVmax (3.85) predicting IDH1 mutation reached 73.2 and 86.7%, respectively. The sensitivity and specificity of differentiating grades by SUVmax (3.1) were 92.3 and 64.4%, respectively. Glucose consumption of U251 IDH1 mutant cells (0.209 ± 0.0472 mg/ml) was obviously lower than IDH1wild-type cells (0.978 ± 0.0773 mg/ml, P = 0.0001) and astrocyte controls (0.335 ± 0.0592 mg/ml, P = 0.0451). Meanwhile, the glucose quantity in IDH1mutant glioma samples were significantly lower than those in IDH1 wild-type tissues (1.033 ± 1.19608 vs 6.361 ± 4.3909 mg/g, P = 0.0051). Silico analysis and western blot confirmed that HK1 and PKM2 in IDH1 wild-type gliomas were significantly higher than in IDH1 mutant group, while PC was significantly higher in IDH1 mutant gliomas. CONCLUSION: SUVmax on PET can predict IDH1 mutation with adequate sensitivity and specificity, as is supported by reduced glucose consumption in IDH1 mutant gliomas.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Glucose/metabolismo , Isocitrato Desidrogenase/genética , Mutação , Tomografia por Emissão de Pósitrons/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Estudos de Casos e Controles , Fluordesoxiglucose F18/metabolismo , Seguimentos , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/metabolismo , Humanos , Prognóstico , Curva ROC , Compostos Radiofarmacêuticos/metabolismo , Células Tumorais Cultivadas
2.
Int J Ophthalmol ; 12(11): 1708-1713, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31741858

RESUMO

AIM: To compare the anti-inflammatory effects of intense pulsed light (IPL) with tobramycin/dexamethasone plus warm compress through clinical signs and cytokines in tears. METHODS: Eighty-two patients with dry eye disease (DED) associated meibomian gland dysfunction (MGD) were divided into two groups. Group A was treated with IPL, and Group B was treated with tobramycin/dexamethasone plus warm compress. Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), corneal fluorescein staining (CFS), meibomian gland expressibility (MGE), meibum quality, gland dropout and tear cytokine levels were evaluated before treatment, 1wk and 1mo after treatment. RESULTS: TBUT in Group A was higher (P=0.035), and MGE score was lower than Group B at 1mo (P=0.001). The changes of interleukin (IL)-17A and IL-1ß levels in tears were lower in Group A compared with that in Group B at 1wk after treatment (P=0.05, P=0.005). CONCLUSION: Treatment with IPL can improve TBUT and MGE and downregulate levels of IL-17A and IL-1ß in tears of patients with DED associated MGD better than treatment with tobramycin/dexamethasone plus warm compress in one-month treatment period.

3.
Medicine (Baltimore) ; 97(5): e9758, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29384861

RESUMO

INTRODUCTION: Spontaneous cerebrospinal fluid leakage is usually caused by developmental abnormalities and is rare, accounting for approximately 5% of the cases of cerebrospinal fluid (CSF) leakage. To the best of our knowledge, clival dysplasia-caused CSF rhinorrhea has never been reported in the neurosurgical field. CONCLUSION: Spontaneous cerebrospinal fluid rhinorrhea is often treated by surgery, and a transsphenoidal approach repair is the main surgical method used, offering the advantages of less trauma, fewer complications, rapid postoperative recovery, and low recurrence rate.


Assuntos
Rinorreia de Líquido Cefalorraquidiano/diagnóstico por imagem , Rinorreia de Líquido Cefalorraquidiano/cirurgia , Fossa Craniana Posterior/diagnóstico por imagem , Idoso , Rinorreia de Líquido Cefalorraquidiano/etiologia , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino
4.
Sensors (Basel) ; 17(5)2017 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-28448431

RESUMO

This paper investigates a two-dimensional angle of arrival (2D AOA) estimation algorithm for the electromagnetic vector sensor (EMVS) array based on Type-2 block component decomposition (BCD) tensor modeling. Such a tensor decomposition method can take full advantage of the multidimensional structural information of electromagnetic signals to accomplish blind estimation for array parameters with higher resolution. However, existing tensor decomposition methods encounter many restrictions in applications of the EMVS array, such as the strict requirement for uniqueness conditions of decomposition, the inability to handle partially-polarized signals, etc. To solve these problems, this paper investigates tensor modeling for partially-polarized signals of an L-shaped EMVS array. The 2D AOA estimation algorithm based on rank- ( L 1 , L 2 , · ) BCD is developed, and the uniqueness condition of decomposition is analyzed. By means of the estimated steering matrix, the proposed algorithm can automatically achieve angle pair-matching. Numerical experiments demonstrate that the present algorithm has the advantages of both accuracy and robustness of parameter estimation. Even under the conditions of lower SNR, small angular separation and limited snapshots, the proposed algorithm still possesses better performance than subspace methods and the canonical polyadic decomposition (CPD) method.

5.
Biomed Res Int ; 2017: 6132436, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28255556

RESUMO

As a pathological condition, epilepsy is caused by abnormal neuronal discharge in brain which will temporarily disrupt the cerebral functions. Epilepsy is a chronic disease which occurs in all ages and would seriously affect patients' personal lives. Thus, it is highly required to develop effective medicines or instruments to treat the disease. Identifying epilepsy-related genes is essential in order to understand and treat the disease because the corresponding proteins encoded by the epilepsy-related genes are candidates of the potential drug targets. In this study, a pioneering computational workflow was proposed to predict novel epilepsy-related genes using the random walk with restart (RWR) algorithm. As reported in the literature RWR algorithm often produces a number of false positive genes, and in this study a permutation test and functional association tests were implemented to filter the genes identified by RWR algorithm, which greatly reduce the number of suspected genes and result in only thirty-three novel epilepsy genes. Finally, these novel genes were analyzed based upon some recently published literatures. Our findings implicate that all novel genes were closely related to epilepsy. It is believed that the proposed workflow can also be applied to identify genes related to other diseases and deepen our understanding of the mechanisms of these diseases.


Assuntos
Epilepsia/genética , Estudos de Associação Genética/métodos , Algoritmos , Bases de Dados Genéticas , Humanos
6.
PLoS One ; 10(6): e0129474, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26058041

RESUMO

Cancer is a serious disease responsible for many deaths every year in both developed and developing countries. One reason is that the mechanisms underlying most types of cancer are still mysterious, creating a great block for the design of effective treatments. In this study, we attempted to clarify the mechanism underlying esophageal cancer by searching for novel genes and chemicals. To this end, we constructed a hybrid network containing both proteins and chemicals, and generalized an existing computational method previously used to identify disease genes to identify new candidate genes and chemicals simultaneously. Based on jackknife test, our generalized method outperforms or at least performs at the same level as those obtained by a widely used method--the Random Walk with Restart (RWR). The analysis results of the final obtained genes and chemicals demonstrated that they highly shared gene ontology (GO) terms and KEGG pathways with direct and indirect associations with esophageal cancer. In addition, we also discussed the likelihood of selected candidate genes and chemicals being novel genes and chemicals related to esophageal cancer.


Assuntos
Neoplasias Esofágicas/genética , Proteínas/genética , Algoritmos , Biologia Computacional/métodos , Bases de Dados Genéticas , Ontologia Genética , Humanos
7.
Biomed Res Int ; 2015: 964795, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25874234

RESUMO

Thyroid cancer is a typical endocrine malignancy. In the past three decades, the continued growth of its incidence has made it urgent to design effective treatments to treat this disease. To this end, it is necessary to uncover the mechanism underlying this disease. Identification of thyroid cancer-related genes and chemicals is helpful to understand the mechanism of thyroid cancer. In this study, we generalized some previous methods to discover both disease genes and chemicals. The method was based on shortest path algorithm and applied to discover novel thyroid cancer-related genes and chemicals. The analysis of the final obtained genes and chemicals suggests that some of them are crucial to the formation and development of thyroid cancer. It is indicated that the proposed method is effective for the discovery of novel disease genes and chemicals.


Assuntos
Bases de Dados Genéticas , Ligantes , Neoplasias da Glândula Tireoide/genética , Algoritmos , Descoberta de Drogas , Humanos , Mapas de Interação de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia
8.
Hepatogastroenterology ; 61(134): 1801-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25436382

RESUMO

OBJECTIVE: To study the safety and survival outcome of surgical management for elderly gastric cancer patients. Methods: Patients proven of gastric cancer who aged ≥80 years during November 2002 to July 2011 were retrospectively analyzed. The detailed information of patients' characteristics and surgical management was retrieved. Follow-up of overall survival status was performed to analyze the surgical effectiveness. RESULTS: Totally, 92 (48 in surgery and 44 in non-surgery group) out of 187 eligible patients recorded adequate information and analyzed finally. There were 34 patients undergone radical gastrectomy, 6 palliative gastrectomy, 1 gastrojejunostomy and 7 exploratory laparotomy. Median follow-up durations were 25 (9-111) and 28 (8-114) months in surgery and non-surgery groups, respectively (p=0.797). Clinical-pathological T stage and node status were comparable. Clinical-pathological distal metastasis status was 15 and 26 M1 cases for surgery and nonsurgery, respectively (p=0.006). Incidence of postoperative complications and hospital mortality were 25.0% and 2.1%, respectively. The 2-year survival rates of M0 subgroups were 35.7% and 0% for surgery and nonesurgery, respectively (HR=3.98, p=0.022). CONCLUSIONS: The safety of surgery for well-selected ≥ 80-year elderly gastric cancer patients was potentially acceptable and the patients of early or locally advanced diseases could obtain survival benefits by surgery.


Assuntos
Gastrectomia , Derivação Gástrica , Neoplasias Gástricas/cirurgia , Fatores Etários , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Derivação Gástrica/efeitos adversos , Derivação Gástrica/mortalidade , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/mortalidade , Fatores de Tempo , Resultado do Tratamento
9.
Biomed Res Int ; 2014: 891945, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25050377

RESUMO

Glioma, as the most common and lethal intracranial tumor, is a serious disease that causes many deaths every year. Good comprehension of the mechanism underlying this disease is very helpful to design effective treatments. However, up to now, the knowledge of this disease is still limited. It is an important step to understand the mechanism underlying this disease by uncovering its related genes. In this study, a graphic method was proposed to identify novel glioma related genes based on known glioma related genes. A weighted graph was constructed according to the protein-protein interaction information retrieved from STRING and the well-known shortest path algorithm was employed to discover novel genes. The following analysis suggests that some of them are related to the biological process of glioma, proving that our method was effective in identifying novel glioma related genes. We hope that the proposed method would be applied to study other diseases and provide useful information to medical workers, thereby designing effective treatments of different diseases.


Assuntos
Algoritmos , Neoplasias Encefálicas/genética , Genes Neoplásicos , Estudos de Associação Genética/métodos , Glioma/genética , Ontologia Genética , Humanos , Transdução de Sinais/genética
10.
Biomed Res Int ; 2013: 132724, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24350241

RESUMO

Most drugs have beneficial as well as adverse effects and exert their biological functions by adjusting and altering the functions of their target proteins. Thus, knowledge of drugs target proteins is essential for the improvement of therapeutic effects and mitigation of undesirable side effects. In the study, we proposed a novel prediction method based on drug/compound ontology information extracted from ChEBI to identify drugs target groups from which the kind of functions of a drug may be deduced. By collecting data in KEGG, a benchmark dataset consisting of 876 drugs, categorized into four target groups, was constructed. To evaluate the method more thoroughly, the benchmark dataset was divided into a training dataset and an independent test dataset. It is observed by jackknife test that the overall prediction accuracy on the training dataset was 83.12%, while it was 87.50% on the test dataset-the predictor exhibited an excellent generalization. The good performance of the method indicates that the ontology information of the drugs contains rich information about their target groups, and the study may become an inspiration to solve the problems of this sort and bridge the gap between ChEBI ontology and drugs target groups.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Ontologias Biológicas , Bases de Dados Factuais , Proteínas/metabolismo
11.
PLoS One ; 8(6): e66678, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23805260

RESUMO

Most of pyruvoyl-dependent proteins observed in prokaryotes and eukaryotes are critical regulatory enzymes, which are primary targets of inhibitors for anti-cancer and anti-parasitic therapy. These proteins undergo an autocatalytic, intramolecular self-cleavage reaction in which a covalently bound pyruvoyl group is generated on a conserved serine residue. Traditional detections of the modified serine sites are performed by experimental approaches, which are often labor-intensive and time-consuming. In this study, we initiated in an attempt for the computational predictions of such serine sites with Feature Selection based on a Random Forest. Since only a small number of experimentally verified pyruvoyl-modified proteins are collected in the protein database at its current version, we only used a small dataset in this study. After removing proteins with sequence identities >60%, a non-redundant dataset was generated and was used, which contained only 46 proteins, with one pyruvoyl serine site for each protein. Several types of features were considered in our method including PSSM conservation scores, disorders, secondary structures, solvent accessibilities, amino acid factors and amino acid occurrence frequencies. As a result, a pretty good performance was achieved in our dataset. The best 100.00% accuracy and 1.0000 MCC value were obtained from the training dataset, and 93.75% accuracy and 0.8441 MCC value from the testing dataset. The optimal feature set contained 9 features. Analysis of the optimal feature set indicated the important roles of some specific features in determining the pyruvoyl-group-serine sites, which were consistent with several results of earlier experimental studies. These selected features may shed some light on the in-depth understanding of the mechanism of the post-translational self-maturation process, providing guidelines for experimental validation. Future work should be made as more pyruvoyl-modified proteins are found and the method should be evaluated on larger datasets. At last, the predicting software can be downloaded from http://www.nkbiox.com/sub/pyrupred/index.html.


Assuntos
Biologia Computacional/métodos , Proteínas/metabolismo , Serina/metabolismo , Algoritmos , Área Sob a Curva , Bases de Dados de Proteínas , Curva ROC
12.
Chin Med J (Engl) ; 126(10): 1930-3, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23673112

RESUMO

BACKGROUND: Stomach cancer is among the most commonly occurring malignancies worldwide. It would be beneficial to develop a urine-based assay whereby patients with undiagnosed stomach cancer could be screened and their cancer detected in the earliest stages. METHODS: A urinary metabonomics method based on ultra-performance liquid chromatography combined with quadruple time-of-flight mass spectrometry was used to analyze urine samples from patients with stomach cancer and healthy controls. RESULTS: Statistical analysis revealed a clear separation of patients and healthy controls using the aforementioned methodology. Some significantly changed metabolites were identified. CONCLUSIONS: Use of the metabonomics method in patients with stomach cancer could effectively detect distinct changes in urinary metabolites and had the capacity to detect cancer; therefore, it may be a valuable tool in earlier diagnosis. Furthermore, the detection and identification of altered metabolites in the current study may help elucidate possible mechanisms involved in stomach cancer.


Assuntos
Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Metabolômica/métodos , Neoplasias Gástricas/urina , Adulto , Humanos
13.
Biomed Res Int ; 2013: 287019, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23586028

RESUMO

Colorectal cancer is generally categorized into the following four stages according to its development or serious degree: Dukes A, B, C, and D. Since different stage of colorectal cancer actually corresponds to different activated region of the network, the transition of different network states may reflect its pathological changes. In view of this, we compared the gene expressions among the colorectal cancer patients in the aforementioned four stages and obtained the early and late stage biomarkers, respectively. Subsequently, the two kinds of biomarkers were both mapped onto the protein interaction network. If an early biomarker and a late biomarker were close in the network and also if their expression levels were correlated in the Dukes B and C patients, then a signal propagation path from the early stage biomarker to the late one was identified. Many transition genes in the signal propagation paths were involved with the signal transduction, cell communication, and cellular process regulation. Some transition hubs were known as colorectal cancer genes. The findings reported here may provide useful insights for revealing the mechanism of colorectal cancer progression at the cellular systems biology level.


Assuntos
Transformação Celular Neoplásica/genética , Neoplasias Colorretais/genética , Mapas de Interação de Proteínas/genética , Transdução de Sinais/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Estadiamento de Neoplasias
14.
Med Oncol ; 30(1): 437, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23292837

RESUMO

The purpose of this study was to analyze ß-catenin and matrix metalloproteinase-2 (MMP-2) expression in non-small cell lung cancer (NSCLC) and to investigate the association between their expression and clinicopathologic characteristics of NSCLC patients. Immunohistochemistry was performed to examine ß-catenin and MMP-2 protein expression in 39 resected NSCLC samples and 8 adjacent normal lung tissues. Statistical analysis with SPSS13.0 software was performed to investigate the association between ß-catenin and MMP-2 expression and clinicopathologic features of the patients. Expression of cytosolic ß-catenin in NSCLC tissue was significantly higher than that in normal tissues (P < 0.001). In addition, cytosolic protein expression of ß-catenin in lung squamous cell carcinoma was significantly elevated compared to that in lung adenocarcinoma (P = 0.02). However, cell membrane protein expression of ß-catenin in squamous cell carcinoma was lower than that in adenocarcinoma (P = 0.041). Cytosolic MMP-2 protein expression in NSCLC samples was significantly higher than that in normal tissues (P = 0.002). MMP-2 expression in N (1-2) NSCLC patients was significantly increased relative to N (0) patients (P = 0.019). However, statistical analysis showed no correlation between ß-catenin and MMP-2 expression in NSCLC samples. Collectively, our results show that cytosolic protein expression of ß-catenin in NSCLC samples is increased relative to normal lung tissues. Also, expression of ß-catenin is significantly elevated in squamous cell carcinoma compared to that in lung adenocarcinoma subtypes. Additionally, MMP-2 expression in N (1-2) NSCLC tissues is higher than that in N (0) lung tissue. There is no correlation between ß-catenin and MMP-2 expression in NSCLC, and our study suggests that evaluation of ß-catenin and MMP-2 expression may have potential in diagnosis and progression in patients with NSCLC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Metaloproteinase 2 da Matriz/biossíntese , beta Catenina/biossíntese , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Masculino , Metaloproteinase 2 da Matriz/análise , Pessoa de Meia-Idade , beta Catenina/análise
15.
Mol Biosyst ; 9(1): 61-9, 2013 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-23117653

RESUMO

Identification of catalytic residues plays a key role in understanding how enzymes work. Although numerous computational methods have been developed to predict catalytic residues and active sites, the prediction accuracy remains relatively low with high false positives. In this work, we developed a novel predictor based on the Random Forest algorithm (RF) aided by the maximum relevance minimum redundancy (mRMR) method and incremental feature selection (IFS). We incorporated features of physicochemical/biochemical properties, sequence conservation, residual disorder, secondary structure and solvent accessibility to predict active sites of enzymes and achieved an overall accuracy of 0.885687 and MCC of 0.689226 on an independent test dataset. Feature analysis showed that every category of the features except disorder contributed to the identification of active sites. It was also shown via the site-specific feature analysis that the features derived from the active site itself contributed most to the active site determination. Our prediction method may become a useful tool for identifying the active sites and the key features identified by the paper may provide valuable insights into the mechanism of catalysis.


Assuntos
Biologia Computacional/métodos , Enzimas/química , Enzimas/metabolismo , Modelos Químicos , Domínio Catalítico , Fenômenos Químicos , Sequência Conservada , Bases de Dados de Proteínas , Árvores de Decisões , Estrutura Secundária de Proteína , Análise de Sequência de Proteína , Relação Estrutura-Atividade , Máquina de Vetores de Suporte
16.
PLoS One ; 7(9): e45944, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23029334

RESUMO

Metabolic pathway analysis, one of the most important fields in biochemistry, is pivotal to understanding the maintenance and modulation of the functions of an organism. Good comprehension of metabolic pathways is critical to understanding the mechanisms of some fundamental biological processes. Given a small molecule or an enzyme, how may one identify the metabolic pathways in which it may participate? Answering such a question is a first important step in understanding a metabolic pathway system. By utilizing the information provided by chemical-chemical interactions, chemical-protein interactions, and protein-protein interactions, a novel method was proposed by which to allocate small molecules and enzymes to 11 major classes of metabolic pathways. A benchmark dataset consisting of 3,348 small molecules and 654 enzymes of yeast was constructed to test the method. It was observed that the first order prediction accuracy evaluated by the jackknife test was 79.56% in identifying the small molecules and enzymes in a benchmark dataset. Our method may become a useful vehicle in predicting the metabolic pathways of small molecules and enzymes, providing a basis for some further analysis of the pathway systems.


Assuntos
Redes e Vias Metabólicas , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Algoritmos , Bases de Dados Factuais , Metabolômica , Modelos Biológicos , Mapeamento de Interação de Proteínas
17.
Int J Mol Med ; 26(4): 541-7, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20818494

RESUMO

Statins have recently come under evaluation for the treatment of pulmonary arterial hypertension (PAH). The aim of this study was to examine the effects of atorvastatin on the clinical manifestations and expression of p38, p27 and Jab1 using a rat PAH model. Ninety-six male Wistar rats were divided into control (receiving no surgical treatment), vehicle and treatment groups, among which the last two groups underwent left pneumonectomy and were then treated with monocrotaline (MCT, 60 mg/kg). Both control and vehicle groups subsequently received saline, and the treatment group received atorvastatin (20 mg/kg) by stomach catheter. Rats were sacrificed, and mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured. The expression of p38, p27, and Jab1 was evaluated by immunohistochemistry and Western blotting. At 28 days, mPAP and RVHI and expression levels of Jab1 and p38 in the vehicle group were significantly higher than those in the treatment and control groups. However, the expression of p27 was lowest in the vehicle group among the three groups. Atorvastatin reduced PAP and RVHI in the rat PAH model, decreased expression of p38 and Jab1 but increased expression of p27.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Antígeno Nuclear de Célula em Proliferação/genética , Proteínas/genética , Pirróis/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Animais , Atorvastatina , Complexo do Signalossomo COP9 , Ácidos Heptanoicos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/patologia , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Monocrotalina , Pneumonectomia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Pirróis/farmacologia , Ratos , Ratos Wistar
18.
Chin Med J (Engl) ; 122(13): 1558-63, 2009 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-19719948

RESUMO

BACKGROUND: Local hypothermia induced by intravascular infusion of cold saline solution effectively reduces brain damage in stroke. We further determined the optimal temperature of local hypothermia in our study. METHODS: Seventy-eight adult male Sprague Dawley rats (260 - 300 g) were randomly divided into 3 groups: group A, ischemia/reperfusion without cold saline infusion (n = 26) (control group); group B, infusion with 20 degrees C saline before reperfusion (n = 26); group C: infusion with 10 degrees C saline before reperfusion (n = 26). In each group, we chose 15 rats for monitoring physical indexes and the temperature of the brain (cortex and striatum) and body (anus), measurement of brain infarction volume, assessment of neurological deficits and the survival rate of reperfusion at 48 hours. Another 8 rats from each group was chosen for examining brain edema, another 3 from each group for histological observation by electron microscopy (EM) and light microscopy (LM) at 48 hours after reperfusion. RESULTS: There was no significant difference among the 3 groups for physical indexes during the examination (F((2, 45)) = 0.577, P = 0.568; F((2, 45)) = 0.42, P = 0.78 for blood pressure and blood gas analysis, respectively). The brain temperature was significantly reduced in the group C compared to the other groups (F((2, 45)) = 37.074, P = 0.000; F((2, 45)) = 32.983, P = 0.000, for cortex and striatum temperature respectively), while the difference in rectal temperature between group A and B or C after reperfusion was not significant (F((2, 45)) = 0.17115, P = 0.637). And the brain infarct volume was significantly reduced in group C (from 40% +/- 10% in group A, 26% +/- 8% in group B, to 12% +/- 6% in group C, F((2, 45)) = 43.465, P = 0.000) with the neurological deficits improving in group C (chi(2) = 27.626, P = 0.000). The survival rate at 48 hours after 10 degrees C and 20 degrees C saline reperfusion was increased by 132.5% and 150%, respectively, as compared to the control group (chi(2) = 10.489, P = 0.005). The extent of the brain edema showed no significant difference (F((2, 21)) = 0.547, P = 0.587) after cold saline infusion compared to the control group. No obvious vascular injury was found by electron or light microscopy in either infusion group. CONCLUSIONS: Regional hypothermia with 10 degrees C cold saline infusion can significantly decrease the infarction volume, improve the neurological deficits, and 10 degrees C seems to be the optimal temperature in inducing a cerebral protection effect during stroke. This procedure could be adopted as a further treatment for acute stroke patients.


Assuntos
Hipotermia Induzida , Acidente Vascular Cerebral/terapia , Animais , Temperatura Corporal , Encéfalo/patologia , Infarto Cerebral/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia , Taxa de Sobrevida , Temperatura
19.
Zhonghua Jie He He Hu Xi Za Zhi ; 31(1): 37-41, 2008 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-18366905

RESUMO

OBJECTIVE: To investigate the expressions of Urotensin II (UII) protein and mRNA and its receptor (UT) mRNA of medium and small pulmonary arteries of rats with chronic thromboembolic pulmonary hypertension. METHODS: The Wistar rats were injected thrombi through the jugular vein 2 times in 2 weeks and tranexamic acid was injected peritoneally once daily during the experiment to prevent thrombolysis. The mean pulmonary artery pressure (mPAP) was measured using right cardiac atheterzation. The expressions of UII protein in pulmonary arteries were studied by immunohischemistry with a polycolonal antibody. The expressions of UII mRNA and UT mRNA were detected by in situ hybridization using UII and UT oligonuclear probes. The changes of structures in pulmonary vessle were observed, including relative medial thickness of pulmonary artery (PAMT) and vessle wall area/total vessle area (WA/TA). RESULTS: The mPAP of the 4 weeks to the 12 weeks groups were (19.9 +/- 6.2) mm Hg (1 mm Hg = 0.133 kPa), (23.8 +/- 4.1) mm Hg and (27.4 +/- 5.4) mm Hg, higher than that of the control group (F = 13.75, P < 0.01, respectively). The PAMT of the 4 weeks to the 12 weeks groups were (42.6 +/- 11.16)%, (47.82 +/- 10.02)% and (53.79 +/- 10.41)%, and WA/TA of the 4 weeks to the 12 weeks groups were (22.75 +/- 6.79)%, (25.32 +/- 4.90)% and (27.05 +/- 7.71)%, both changed significantly as compared to the control group (F = 5.52 and 6.61, P < 0.01, respectively; P < 0.05 in 4 weeks group; P < 0.01 in 8 weeks and 12 weeks groups, respectively). The expressions of UIIprotein, UII mRNA and UT mRNA in the 4 weeks to the 12 weeks groups were obviously higher than the control group (F = 30.39, 30.78 and 14.49, P < 0.01, respectively), and their expressions were more marked in the small pulmonary arteries than in medium pulmonary arteries. The expressions of UIIprotein, UII mRNA and UT mRNA were positively correlated with mPAP and PAMT. The pulmonary vascular remodeling was time-dependently aggravated after embolism (r: 0.822, 0.866 and 0.846; 0.675, 0.712 and 0.756, P < 0.01, respectively). CONCLUSIONS: The expressions of UII protein, UII mRNA and UT mRNA of pulmonary arteries in the animal models were higher than those in the control group. These dynamic changes of UII mRNA, UIIprotein and UT mRNA may contribute to the development of pulmonary hypertension and vascular remodeling after pulmonary thromboembolism.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Artéria Pulmonar/metabolismo , Embolia Pulmonar/fisiopatologia , Receptores Acoplados a Proteínas G/biossíntese , Urotensinas/biossíntese , Animais , Pressão Sanguínea , Doença Crônica , Expressão Gênica , Imuno-Histoquímica , Hibridização In Situ , Masculino , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/genética , Urotensinas/genética
20.
Artigo em Chinês | MEDLINE | ID: mdl-15952566

RESUMO

OBJECTIVE: To study the cranial-cervical lymph return and pathway in rabbit in order to provide the experimental and theoretical basis for the study of intracranial metastasis of cervical tumor and extracranial metastasis of intracranial tumor. METHOD: The distribution and clearance of tracers were observed after microinjection of lymph developer labeled by 99mTc into cerebral cortex and deep cervical lymph nodes of rabbit. RESULTS: In the cerebral cortex microinjection with 99=Tc-labeled lymph developer group, the radioactivity were detected in Willis artery, deep cervical lymph nodes and venous blood. The radioactivity curve was the same in Willis artery and deep cervical lymph nodes. The peak in the artery blood was higher than that in venous blood. In the lymph nodes microinjection with 99mTc-labeled lymph developer cervical group, the radioactivity were detected in skull base dura mater, brain, cerebrospinal fluid and venous blood. The peak in skull base dura mater showed earlier than that in cerebrospinal fluid and brain. The peak in venous blood was the last, but the radioactivity in it was the highest. CONCLUSION: The cranial-cervical lymph return in rabbit is existent. Their pathway perhaps is Willis artery, skull base dura mater and cerebrospinal fluid circulation.


Assuntos
Linfonodos/metabolismo , Sistema Linfático/metabolismo , Animais , Linfa/diagnóstico por imagem , Linfa/metabolismo , Linfonodos/diagnóstico por imagem , Vasos Linfáticos/diagnóstico por imagem , Vasos Linfáticos/metabolismo , Linfocintigrafia , Masculino , Compostos de Organotecnécio , Coelhos
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