AIM:Receptor tyrosine kinase (RTK) activation is critical for growth factor-mediated cell proliferation. The present study was designed to determine the effect of the tyrphostin AG1295 and AG1296, a selective blocker of PDGF βand αRTK,on proliferative vitreoretinopathy (PVR) development.METHODS:Rabbit conjunctival fibroblasts (RCF) cells were cultured.The effects of AG1295, AG1296,PDGF-AA and PDGF-BB on RCF proliferation are evaluated by MTT assay.Homologous rabbit conjunctival fibroblasts were injected intravitreally to make animal PVR model, followed by injection of 100μmol/L of AG1295 or AG1296 respectively. The presence of tractional retinal detachment (TRD) was assessed to evaluate the effect of AG1295 and AG1296 in vivo .Electroretinography and histologic studies were performed after intravitreal injection of AG1295 into untreated eyes to evaluate toxicity. RESULTS: Both AG1295 and AG1296 (10μmol/L) significantly inhibited rabbit conjunctival fibroblast cell growth stimulated by PDGF-AA or -BB in vitro.Development of TRD was significantly reduced (P<0.05) with 100 μmol/L of AG1295 or AG1296 in vivo, but the effect of AG1295 only present till day 14. Inhibitive effect of AG1296 is longer than that of AG1295.No significant histologic or retinal functional damage was found in both drug-treated groups. CONCLUSION: PDGF αand βreceptor specific inhibitor AG1296 and AG1295 attenuated PVR without significant side effects in rabbits, and AG1296 was better than AG1295. The much longer and stronger therapeutic effect from PDGFαreceptor inhibitor indicated that PDGF α receptor is more important in the development of PVR, and inhibition of this pathway could be a useful treatment alternative to prevent PVR.

Une new flavonoids named as notabilisin K (1), together with four known compounds, morusin (2), mulberrofuran A (3), neocyclomorusin (4) and mornigrol F (5) are separated from 95% ethanol extracts of the twigs of Morus notabilis. Compounds 2-5 are separated from this plant for the first time. Notabilisin I, notabilisin J exhibits certain effect against cells of HCT-116, HepG2 and A2780 with IC50 values ranging from 1.47 μmol x L(-1) to 5.46 μmol x L(-1). Morusin exhibits strong effect against five kinds of human cancer cells (BGC823, A2780, HCT-116, HepG2 and NCI-H1650) with IC50 values ranging from 0.74 μmol x L(-1) to 1.58 μmol x L(-1).
Antineoplastic Agents, Phytogenic ; chemistry ; Benzofurans ; chemistry ; Flavonoids ; chemistry ; Hep G2 Cells ; Humans ; Inhibitory Concentration 50 ; Morus ; chemistry ; Plant Extracts ; chemistry ; Terpenes ; chemistry

A new steroidal ester, beta-rosaterol palmitate (1) along with ten known compounds, uvaol(2), 3-epi-ursolic acid (3), 2alpha, 3beta, 24-trihydroxyolean-12-en-28-oic acid (4), 2alpha, 3alpha, 24-trihydroxyurs-12-en-28-oic acid (5), 2alpha, 3alpha, 24-trihydroxyolean-12-en-28-oic acid (6), 2alpha, 3alpha, 24-trihydroxyolean-12-en-28-oic acid-28-O-beta-D-glucopyranosyl ester (7), (Z)-9-hexadecenoic acid (8), octacosyl alcohol (9), beta-sitosterol (10) and beta-daucosterol (11), has been isolated from the stems and leaves of Vitex trifolia. Their structures were elucidated using a combination of 1D and 2D NMR techniques (COSY, HMQC, and HMBC)and HR-ESI-MS analyses. Compounds 2-7 were isolated from this plant for the first time.
Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization ; Vitex ; chemistry

OBJECTIVETo explore the scavenging action of tenuigenin (TEN) on intracerebral amyloid β protein (Aβ) aggregation and the abnormal phosphorylated tau protein and its mechanism in Alzheimer's disease (AD) rats' brain.

METHODSAβ1-40 was injected into the right CA1 region hippocampus to establish the AD model. Successfully modeled rats were divided into the model group, the low, middle, high TEN group. Rats were administered with TEN (18.5, 37.0, 74.0 mg/kg) by gastrogavage. Besides, a sham-operation group was set up. Expression levels of Aβ1-40 and Tau p-Ser262 were detected by immunohistochemistry. Expression levels of ubiquitin (Ub) and Ub-protein ligase E3 were measured by Western blotting.The content of 26S proteasome was detected by ELISA.

RESULTSImmunohistochemical results showed that the number of Aβ and Tau p-Ser262 positively reacted neurons significantly increased in model group, when compared with the sham-operation group (P < 0.01). Results of Western blot showed expression levels of ubiquitinated protein were up-regulated and those of Ub-protein ligase E3 were down-regulated in the model group (P < 0.01). ELISA results showed that the content of 26S proteasome significantly decreased in AD rats' brain (P < 0.01). Compared with the model group, expression levels of Aβ1-40, Tau p-Ser262, and Ub significantly decreased; expression levels of Ub-protein ligase E3 apparently increased; the content of 26S proteasome significantly increased in each TEN treatment group (P < 0.05, P < 0.01). Best effect was shown in 37.0 mg/kg and 74.0 mg/kg TEN groups.

CONCLUSIONSUb proteasome pathway (UPP) participated in the occurrence of AD. TEN could obviously reduce intracere- bral Aβ1-40 accumulation and abnormal tau phosphorylation.

Alzheimer Disease ; metabolism ; Amyloid beta-Peptides ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Hippocampus ; metabolism ; Neurons ; metabolism ; Phosphorylation ; Proteasome Endopeptidase Complex ; metabolism ; Rats ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitins

BACKGROUND: Intrapulmonary vascular abnormalities result in the right-to-left shunting and severe hypoxemia in liver transplantation candidates. Currently, a convenient, sensitive and effective method is absent to screen the intrapulmonary vascular dilatations.OBJECTIVE: To evaluate the role of contrast-enhanced echocardiography on clinical diagnosis of intrapulmonary shunting in liver transplantation candidates.DESIGN, TIME AND SETTING: The experiment, prospective controlled observation based on cases, was performed at the Hepatology Unit of the 458 Hospital of PLA (Guangzhou, Guangdong, China) from February 2004 to February 2006.PARTICIPANTS: Twenty-four consecutive liver transplantation candidates were recruited from the Hepatology Unit of the 458Hospital of PLA.METHODS: Routine examination was conducted under the condition without any regimen of vascular dilatation drugs.Contrast-enhanced echocardiography was applied to detect the prevalence of right-to-left shunting in the patients with end-stage liver disease. The microvesicle of the left ventricle in patients was qualitatively assessed by a score from 1+ to 3+. Accordingly, all patients were divided into two groups: intrapulmonary shunting and non-intrapulmonary shunting.MAIN OUTCOME MEASURES: The prevalence of right-to-left shunting and clinical characteristics of liver transplantation candidates were determined.RESULTS: Ten (41.7%) of 24 patients with positive contrast-enhanced echocardiography were proved to develop the intrapulmonary right-to-left shunting, including 6 for l+ and 4 for 2+ by left ventricle abnormality, which emerged after 6-10 cardiac cycles of right ventricle abnormality. There were no significant differences in age, gender, arterial blood gas analysis and liver function tests between the two groups (P > 0.05). Echocardiography results demonstrated that, the upper digestive tract hemorrhage,spleen thickness that indicated portal hypertension, pulmonary artery systolic pressure and Tei index were significandy higher in the patients of intrapulmonary shunting than in those of non-intrapulmonary shunting (P<0.05-0.01 ).CONCLUSION: Intrapulmonary vascular dilatation occurs frequently in liver transplantation candidates associated with intrapulmonary shunting but without hypoxemia. Contrast-enhanced echocardiography is a sensitive and non-invasive method for the early diagnosis of intrapulmonary vascular dilatation. The pathogenic cause is portal hypertension. Tel index can be used as an important parameter for evaluating right ventricular function in patients of intrapulmonary vascular dilatation.

Objective To evaluate the clinical application of CT-guided localization with combination of methylene blue and a Hookwire system for small pulmonary nodules (SPNs) before video-assisted thoracoscopic resection.Methods CTguided localization the SPNs before resection in 56 patients and 60 nodules,then underwent video-assisted thoracic surgery (VATS) resection.Among 56 patients,19 males and 37 females,aged from 35 to 81 years,mean age was (61.1 ±8.9)years.Results SPNs diameter (6.80 ±4.12) mm,distance from the parietal pleura (15.38 ±4.63) mm.CT-guided localization success rate was 100％,positioning time (10.76 ± 8.17) min,8.9％ (5/56) had micro pneumothorax aftet positioning,7.1％ (4/56) occurrence of needle tract bleeding,no conservative treatment.VATS resection rate was 100％.The pathology of 60 lesions were shown:Bronchiolo-alveolar carcinoma(BAC) were 33 lesions(55.0％),BAC and adenocarcinoma were 11 lesions(18.3％),Atypicaladenomatous hyperplasia (AAH) were 7 lesions (11.8％),Inflammation were 4 lesions (6.7％),Harmatoma were 3 lesions(5.0％),Tuberculoses were 2 lesions(3.3％).Conclusion CT-guided localization with combination of methylene blue and a Hookwire system before video-assisted thoracoscopic resection is a promising technique for small solitary pulmonary nodules.It could play an important role in accurate localization of small pulmonary nodules,and it is a safe technique with clinical application.

Objective To compare the infectivity between laboratory adapted human inununodefi- ciency virus(HIV-1) and primary HIV-1 isolates for different mucosal epithelial cell lines. Methods Mu-cosal epithelial cells Caco-2, T-84, HeLa and lymphocyte MT-4 were infected with laboratory adapted HIV-1 SF33 and 2 primary HIV-1 isolates (02010561, 02010141). Culture supernatant and cells were collected respectively on 3-4 days interval after virus inoculation. The former was tested for HIV-1 antigen P24 level and viral load, and the latter was tested for total viral DNA and integrated viral DNA. Results All 3 virus strains could infect MT-4 cells and integrate into their genome. Only HIV-1 SF33 could infect Caco-2 cells but could not integrate into their genomic DNA. Both HIV-1 SF33 and 02010561 infected HeLa cells but only integration of HIV-1 SF33 was detected. All the 3 HIV-1 strains infected T-84 cells but only the integra-tion of HIV-1 SF33 and 02010141 was observed. Conclusion Although laboratory adapted and primary HIV-1 strains are able to infect human mucosal epithelial cell lines, transient or productive infection estab-lished in different mucosal epithelial cells is dependent on the character of cells and virus strains.

Antipsychotic Agents ; poisoning ; Clozapine ; blood ; poisoning ; Exchange Transfusion, Whole Blood ; methods ; Humans ; Infant, Newborn ; Male ; Treatment Outcome

The overexpression of doublecortin-like kinase 1 (DCLK1) is closely related to the occurrence and development of various malignant tumors. Discovery of novel anti-tumor agents targeting DCLK1 represents a hot spot in this field. So far, several DCLK1 small molecule inhibitors with excellent anti-tumor activity in vitro and in vivo have been designed and synthesized, which is expected to provide a new strategy for tumor therapy. This article reviews the research progress in the discovery, structure type, structural optimization, biological activity and mechanism of action of DCLK1 small molecule inhibitors, and provides research basis for the development of new anti-tumor small molecule inhibitors targeting DCLK1.

Objective Clutching internal fixtor(CIF)loose and the fixed part weakly heal up are often found in orthopedic clinic.In the present paper,biomechanics methods were used to try to explain and analyze these issues,providing a helpful suggestion for the application of CIF in clinic.Method Commerical finite element models(FEM)Program ANSYS was applied to set up the finite element models of orthopedic CIF and bone tissue to analyze and evaluate the biomechanical performances of the NiTi shape memory alloy CIF.Results There is an interaction force between embracing force of CIF and resistant force of bone tissue during the orthopedic clinical treatment.The embracing force along two semi-circular arms of CIF is increasing from the open position and reached the maximum value at the open symmetry position where the deformation of the bone occurred.Conclusion It is the key to choose the force loading position during the practical treatment,as the concentration force is the main force when there is an interactive force between the bone and the CIF.