Backgroud and Objective Proline-rich tyrosine kinase2(Pyk2) is a Ca~(2+) sensitive,non-receptor tyrosine protein kinase.Previous reports showed Pyk2 involved in development of left ventrieular hypertrophy. The present paper aimed to study the effects of valsartan on ventricular hypertrophy and its effect on the expression of Pyk2 in myocardium in renovascular hypertensive rats(RHR).Methods Two-kidney and one-clip(2K1C) renal hypertensive model was established in Sprague-Dawley rats by chronic partial occlusion of left renal artery,and ran- domized to receive valsartan (30 mg/kg?d) or without treatment for 4 or 8 weeks.Left ventricular mass to body mass ratio was measured.Pyk2 protein expression and phosphorylation was detected by Western blotting.Results Blood pressure,left ventricular mass to body mass ratio,Pyk2 activity in myocardium of RHR were increased gradu- ally.Valsartan reduced BP and prevent myocardial hypertrophy(P

Angiopoietin-1 ; chemistry ; physiology ; Angiopoietin-2 ; chemistry ; physiology ; Angiopoietins ; physiology ; Animals ; Cardiovascular Diseases ; therapy ; Embryonic and Fetal Development ; Humans ; Neoplasms ; blood supply ; Receptor, TIE-2 ; chemistry ; physiology ; Signal Transduction

OBJECTIVE To investigate the inhibitory effect of eight lignan compounds of Fructus Schisandrae chinensis in vitro on carboxylesterase 2 (CES2) and to estimate the herb-drug interaction (HDI) risks of strong CES2 inhibitors selected from the above compounds. METHODS Fluorescein diacetate (FD) was employed as a specific fluorescent probe of CES2. The residual activity of CES2 was detected in human liver microsomes after the intervention with deoxyschizandrin, schisanhenol, schisantherin E, schisandrol A, schisandrol B, gomisin J, gomisin G, and gomisin O at 37℃ for 10 min, respectively. 1% DMSO served as control. Residual activity of CES2 was assessed with metabolite production of FD detected by fluorescent intensity, combined with IC50 values of the above compounds to predict HDI risks between lignans and CES2-metabolizing drugs. RESULTS Compared with control group, the activity of CES2 was significantly inhibited by deoxyschizandrin and schisanhenol (P<0.01), with IC50 values of 8.06 μmol · L- 1 and 8.91 μmol · L- 1, respectively. The other six lignans compounds exhibited mild inhibitory effect on CES2. HDI risk prediction of deoxyschizandrin or schisanhenol indicated that exposure of CES2-metabolizing drugs might increase 11.24 and 0.40 times, respectively. CONCLUSION Deoxyschizandrin and schisanhenol exhibit strong inhibitory effects against CES2 in vitro so that potential HDI risks should be taken into account during administration of drugs containing Fructus Schisandrae chinensis.

Metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1) is a well-established oncogenic long non-coding RNA, the higher expression of which is strongly correlated with cancer events such as tumorigenesis, progression, metastasis, drug resistance, and treatment outcome in solid cancers. Recently, a series of studies has highlighted its potential role in hematological malignancies in terms of these events. Similar to solid cancers, MALAT1 can regulate various target genes via sponging and epigenetic mechanisms, but the miRNAs sponged by MALAT1 differ from those identified in solid cancers. In this review, we systematically describe the role and underlying mechanisms of MALAT1 in multiple types of hematological malignancies, including regulation of cell proliferation, metastasis, stress response, and glycolysis. Clinically, MALAT1 expression is related to poor treatment outcome and drug resistance, therefore exhibiting potential prognostic value in multiple myeloma, lymphoma, and leukemia. Finally, we discuss the evaluation of MALAT1 as a novel therapeutic target against cancer in preclinical studies.

AIMTo assess the parameters of cardiac structure and function of male Balb/c mice by the echocardiography.

METHODSA total of 27 male Balb/c mice (from five to seven week old) were examined with a 13-MHz transthoracic linear-array transducer, hearts were removed from mice anesthetized with Nembutal, and the left ventricular (LV) mass were weighed.

RESULTSComplete 2-dimensional echocardiography for cardiac structure and function were obtained. Hemodynamic parameters were recorded. A correlation existed between LV weight (x) and echocardiographic LV mass (y) with the 2D) guided M-mode method: y = 1.15x + 3.26, (r = 0.80).

CONCLUSIONEchocardiography appears to be a promising approach for noninvasively assessing LV mass and function in mice.

Animals ; Echocardiography ; Heart ; physiology ; Heart Ventricles ; diagnostic imaging ; Male ; Mice ; Mice, Inbred BALB C ; Ventricular Function, Left

OBJECTIVETo study the possible role of JNK1, Raf-1 and Livin in the carcinogenesis of sporadic colorectal tubular adenoma.

METHODSImmunohistochemical staining was used to detect the expression of JNK1, Raf-1 and Livin proteins in 65 sporadic colorectal tubular adenomas with dysplasia of varying degrees and 22 colorectal tubular adenoma with cancerous area.

RESULTSIn normal colorectal mucosa, colorectal tubular adenoma with dysplasia and colorectal tubular adenoma with cancerous area, the positive rate of JNK1, Raf-1 and Livin expression was increased gradually. The positive expression of JNK1, Raf-1 and Livin was all significantly higher in the cases of colorectal tubular adenoma with dysplasia or with cancerous area than that in normal colorectal mucosa (P < 0.05), and the positive expression of JNK1, Raf-1 and Livin was significantly higher in colorectal tubular adenoma with cancerous area than that in colorectal tubular adenoma with dysplasia of different degrees (P < 0.05). In the cases of colorectal tubular adenoma with dysplasia of varying degrees, the positive expression of Raf-1 was increased along with the increasing dysplasia degree of colorectal tubular adenoma (P < 0.05). Coexpression of JNK1, Raf-1 and Livin increased gradually in the carcinogenesis of sporadic colorectal tubular adenoma, while positive correlation was found among the expressions of JNK1, Raf-1 and Livin.

CONCLUSIONJNK1, Raf-1 and Livin may be involved in the carcinogenesis of sporadic colorectal tubular adenoma.

Adaptor Proteins, Signal Transducing ; metabolism ; Adenoma ; metabolism ; pathology ; Adult ; Carcinoma ; metabolism ; pathology ; Cell Transformation, Neoplastic ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Intestinal Mucosa ; metabolism ; pathology ; Male ; Mitogen-Activated Protein Kinase 8 ; metabolism ; Neoplasm Proteins ; metabolism ; Precancerous Conditions ; metabolism ; pathology ; Proto-Oncogene Proteins c-raf ; metabolism

OBJECTIVETo evaluate prognostic factors in patients with stage IB-IIA of cervical carcinoma treated by surgery.

METHODSBetween December 1992 and December 2001, 111 patients with stage IB-IIA cervical cancer surgically treated were analyzed. Median age 40 years. According to 1994 FIGO Staging System: IB 80 (IB1 40, IB2 40) and IIA 31. There were 93 cases of squamous cell carcinoma (83.5%), 17 cases of adenocarcinoma (15.3%) and one case of small cell carcinoma. All patients were treated by radical hysterectomy and pelvic lymphadenectomy, 74 patients had preoperative adjuvant radiotherapy, 24 patients had postoperative adjuvant treatment. Kaplan-Meier method was used to evaluate the survival, the related prognostic factors were assessed by Cox regression and chi(2) test.

RESULTSThe overall 5-year survival rate was 85.9%, being 89.1%, 90.7% and 78.4% for stage IB1, IB2 and IIA, respectively. Univariate analysis showed that tumor size (hazards ratio [HR] = 1.479, P = 0.152), tumor type (HR = 1.440, P = 0.264), clinical stage (HR = 1.380, P = 0.354), adjuvant treatment (HR = 1.210, P = 0.450), lymph node metastasis (HR = 1.432, P = 0.540), endocervical involvement (HR = 2.244, P = 0.036), depth of myometrial invasion (HR = 3.295, P = 0.06) and multiple sexual partners during pregnancy (HR = 10.172, P = 0.000) were of prognostic significance. The latter two were the most important factors indicative of poor prognosis.

CONCLUSIONThe depth of myometrial invasion and multi-partners combined with pregnancy are closely related to the prognosis while the pre- and/or postoperative adjuvant therapy should be considered for stage IB-IIA cervical cancer with deep myometrial invasion and in pregnant patients with multiple sexual partners.

Adenocarcinoma ; pathology ; surgery ; Adolescent ; Adult ; Aged ; Carcinoma, Squamous Cell ; pathology ; surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Hysterectomy ; Lymph Node Excision ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Pregnancy ; Pregnancy Complications, Neoplastic ; pathology ; surgery ; Prognosis ; Radiotherapy, Adjuvant ; Survival Rate ; Tumor Burden ; Uterine Cervical Neoplasms ; pathology ; surgery

BACKGROUNDThe self-consciousness and practicality of preferentially prescribed essential medicines (EMs) are not high enough in county hospitals. The purposes of this study were to use the information-motivation-behavioral skills (IMB) model to identify the predictors of essential medicines prescribing behavior (EMPB) among doctors and to examine the association between demographic variables, IMB, and EMPB.

METHODSA cross-sectional study was carried out to assess predictive relationships among demographic variables and IMB model variables using an anonymous questionnaire administered in nine county hospitals of Anhui province. A structural equation model was constructed for the IMB model to test the instruments using analysis of moment structures 17.0.

RESULTSA total of 732 participants completed the survey. The average age of the participants was 37.7 ± 8.9 years old (range: 22-67 years old). The correct rate of information was 90.64%. The average scores of the motivation and behavioral skills were 45.46 ± 7.34 (hundred mark system: 75.77) and 19.92 ± 3.44 (hundred mark system: 79.68), respectively. Approximately half (50.8%) of respondents reported that the proportion of EM prescription was below 60%. The final revised model indicated a good fit to the data (χ2 /df = 4.146, goodness of fit index = 0.948, comparative fit index = 0.938, root mean square error of approximation = 0.066). More work experience (β = 0.153, P < 0.001) and behavioral skills (β = 0.449, P < 0.001) predicted more EMPB. Higher income predicted less information (β = -0.197, P < 0.001) and motivation (β = -0.204, P < 0.001). Behavioral skills were positively predicted by information (β = 0.135, P < 0.001) and motivation (β = 0.742, P < 0.001).

CONCLUSIONThe present study predicted some factors of EMPB, and specified the relationships among the model variables. The utilization rate of EM was not high enough. Motivation and behavior skills were crucial factors affecting EMPB. The influence of demographic variables, such as income and work experience, on EMPB should be fully appreciated. Comprehensive intervention measures should be implemented from multiple perspectives.

Adult ; Aged ; China ; Cross-Sectional Studies ; Female ; Hospitals, County ; statistics & numerical data ; Humans ; Male ; Middle Aged ; Practice Patterns, Physicians' ; statistics & numerical data

OBJECTIVETo study the effect of human urotensin II (HU II) on secretion of adrenomedullin (ADM) from human vascular endothelial cells (HVEC) and its mechanism.

METHODSIn cultured HVEC, different concentrations of HUII were used to stimulate the ADM secretion from HVEC, and the inhibitors of different signal transduction pathway were used to investigate their effects on ADM secretion. The contents of ADM in medium were determined by radio immunoassay.

RESULTSHUII stimulated secretion of ADM from HVEC in a time-dependent and concentration-dependent manner. The contents of ADM in the experiment groups were changed compared with that in control group (P < 0.05). The increase of ADM could be inhibited by inhibitor of extracellular signal-regulated protein kinase (PD(98059)), inhibitor of P38 kinase (SB(202190)), inhibitor of calmodulin (W(7)) and inhibitor of Ca(2+) (nicardipine) (P < 0.05). The inhibition ratio in those groups was 68%, 78%, 24% and 25% respectively. But the inhibitor of Calcineurin (CaN) and inhibitor of protein kinase C (H(7)) had no influence on the secretion of ADM from HVEC (P > 0.05).

CONCLUSIONThe stimulated effect of HUII on the ADM secretion from HVEC may be mediated by Ca(2+), ERKs, CaM-PK and P38 signal transduction pathways.

Adrenomedullin ; metabolism ; Calcium ; metabolism ; Calcium Signaling ; Cells, Cultured ; Endothelial Cells ; secretion ; Humans ; Signal Transduction ; drug effects ; Urotensins ; pharmacology

OBJECTIVETo study the features of hypertension and vessel endothelium functional parameter in people living at the community level as well as the risk factors of hypertension. Differences of angiotensin II (Ang II ), prostacyclin (PGI2) and nitric oxide (NO) among normal group and three hypertension groups were also studied.

METHODSBy cluster sampling, 1134 adult Han people were selected from the residential communities. Medical history was documented and measurements of body height, body weight, waist circumference, hip circumference and blood pressure were performed. Serum NO levels were determined by cadmium reduction method while plasma Ang II and PGI2 concentration were determined by radioimmunoassay. SPSS 13.0 was used for data analysis.

RESULTSThe total ratio of hypertension from people living at the community was 44.5%, with the standardized prevalence of hypertension as 15.3%. With the increase of age, the prevalence of hypertension also increased. Overweight and obesity seemed to be independent risk factors for hypertension. History of smoking and drinking and gender did not enter the logistic equation for hypertension. The amount of plasma Ang II concentration of the three hypertension groups was significantly lower than that in the normal group while the lowest group appeared to from the one that hypertension was under control. The NO and PGI2 levels of the two groups whose hypertension had been known were significantly higher than in the normal group while the difference between the group whose hypertension had not been measured and the normal group was not found.

CONCLUSIONThe prevalence of hypertension had been increasing. Control of body weight seemed to be a useful way for prevention of hypertension. We assumed that the negative feedback regulation of renin-angiotonin-aldosterone system in hypertension patient still existed which called for the research on the mechanism of hypertension.

Adult ; Age Factors ; Aged ; Angiotensin II ; analysis ; Cluster Analysis ; Endothelium, Vascular ; physiology ; Epoprostenol ; analysis ; Female ; Humans ; Hypertension ; epidemiology ; Male ; Middle Aged ; Nitric Oxide ; analysis ; Obesity ; epidemiology ; Overweight ; epidemiology ; Prevalence ; Risk Factors