Protection of Luteolin-7-<Emphasis Type="Italic">O</Emphasis>-Glucoside Against Doxorubicin-Induced Injury Through PTEN/Akt and ERK Pathway in H9c2 Cells

Luteolin-7-O-glucoside (LUTG) was isolated from the plants of Dracocephalum tanguticum Maxim. Previous research has showed that LUTG pretreatment had a significant protective effect against doxorubicin (DOX)-induced cardiotoxicity by reducing intracellular calcium overload and leakage of creatine kinase and lactate dehydrogenase. But the underlying mechanisms have not been completely elucidated. In the present study, we investigated the effects of LUTG on H9c2 cell morphology, viability, apoptosis, reactive oxygen species generation, and the mitochondrial transmembrane potentials. The expression of p-PTEN, p-Akt, p-ERK, p-mTOR, and p-GSK-3β were detected by Western blotting. Compared with DOX alone treatment group, the morphological injury and apoptosis of the cells in groups treated by DOX plus LUTG were alleviated, cell viability was increased, ROS generation was lowered remarkably, and mitochondrial depolarization was mitigated. In DOX group, the expression of p-PTEN was lower than normal group and the expression of p-Akt and p-ERK was higher than normal group. In the groups treated with LUTG (20 μM), the expression of p-PTEN was upregulated and the expression of p-Akt, p-ERK, p-mTOR, and p-GSK-3β was downregulated. These results indicated that the protective effects of LUTG against DOX-induced cardiotoxicity may be related to anti-apoptosis through PTEN/Akt and ERK pathway.     

Establishment of an I-SceI system and its application to introduce DNA double-strand break into human hepatoma cell line HepG2

OBJECTIVE: To construct a system of I-SceI and induce a site-specific DNA double-strand break (DSB) in the genome of HepG2 for using this system in future exploration of the potential mechanisms of HBV integration by DSB repair. METHODS: The eukaryotic expression plasmid pEGFP2 was constructed and transfected into human hepatoma cell line HepG2. The positive neomycin-resistant transfected cell clones were generated by G418 selection. Then the positive cells containing an 18-bp I-SceI endonuclease site were transfected transiently with pCMV(3NLS) I-SceI, an I-SceI expression plasmid. At 24 h post-transfection with pCMV (3NLS) I-SceI, gamma-H2AX, as an early cellular marker of DSB, was detected using immunocytochemistry and Western blot analysis. RESULTS: Restriction analysis and DNA sequencing verified that the plasmid pEGFP2 was successfully constructed. gamma-H2AX increased significantly in cells transfected with the I-SceI system. CONCLUSIONS: Genomic DSB can be induced into HepG2 by introducing an I-SceI system. The cell model could provide us with a practical tool for further study to see if DSB is a potential target for HBV integration.     

Combination of inhibition of thrombin and blockade of thromboxane A2 synthetase and receptors enhances thrombolysis and delays reocclusion in canine coronary arteries.

BACKGROUND. The efficacy of thrombolytic therapy in treating patients with acute myocardial infarction is limited by failure to achieve reperfusion in some patients, by the prolonged time required to achieve reperfusion, and by reocclusion of some coronary arteries. We designed this study to examine the effect of combined inhibition of thrombin and thromboxane synthesis and blockade of thromboxane A2 receptors in addition to tissue-type plasminogen activator (t-PA) on thrombolysis and reocclusion in an experimental canine model with coronary thrombosis. METHODS AND RESULTS. Blood flow velocity in the left anterior descending coronary artery (LAD) of 32 anesthetized mongrel dogs was monitored by a pulsed Doppler flow probe. Coronary thrombosis was induced by applying electrical stimulation to the LAD at the site where an external constrictor was used to narrow the artery. Three hours after the formation of occlusive thrombus, animals were randomly assigned to receive one of the following: 1) t-PA (80 micrograms/kg + 8 micrograms.kg-1.min-1 i.v.) and saline; 2) t-PA and hirulog, a hirudin-based synthetic peptide and specific thrombin inhibitor (2 mg/kg + 2 mg.kg-1.hr-1 i.v.); 3) t-PA and ridogrel, a combined thromboxane A2 synthetase inhibitor and receptor antagonist (5 mg/kg + 2.5 mg.kg-1.hr-1 i.v.); or 4) t-PA, hirulog, and ridogrel. Reperfusion developed in 14% (one of seven) of dogs treated with t-PA alone at an average of 86 +/- 4 minutes after treatment, in 78% (seven of nine) of dogs treated with t-PA plus hirulog at 53 +/- 11 minutes, in 13% (one of eight) of dogs treated with t-PA plus ridogrel at 85 +/- 5 minutes, and in 88% (seven of eight) of dogs treated with t-PA, hirulog, and ridogrel at 37 +/- 10 minutes (comparison of the frequency of and the time to reperfusion, both p < 0.01). Among the dogs with reestablished coronary blood flow, reocclusion developed in the one treated with t-PA alone at 36 minutes after reperfusion, in seven of the seven treated with t-PA plus hirulog at 66 +/- 15 minutes, and in two of the seven treated with t-PA, hirulog, and ridogrel at 151 +/- 21 minutes (comparison of the frequency of and time to reocclusion, both p < 0.05). Reocclusion was not detected in the one dog treated with t-PA and ridogrel or in the other five dogs treated with t-PA, hirulog, and ridogrel within 180 minutes after reperfusion. Hirulog prolonged and maintained activated clotting times at a level twice that of baseline values. Hirulog inhibited ex vivo platelet aggregation induced by thrombin, and ridogrel inhibited platelet aggregation induced by U46619, a thromboxane mimetic. CONCLUSIONS. Inhibition of thrombin in addition to treatment with t-PA enhances thrombolysis. A combination of inhibition of thrombin and thromboxane synthetase and blockade of thromboxane A2 receptor enhances thrombolysis and delays or may prevent reocclusion of the recanalized coronary arteries.     

植入型心律转复除颤器起搏电流导致室性心律失常一例

由植入型心律转复除颤器（ICD）起搏电流所引发的后除极而导致频发的室性期前收缩较为罕见。本文报告1例。     

Lymphoid crisis with T-cell phenotypes in a patient with Philadelphia chromosome negative chronic myeloid leukaemia

A case of Philadelphia (Ph1) chromosome negative chronic myeloid leukaemia (CML) developed lymphoid crisis. Immunological marker studies disclosed that the lymphoid cells were sheep erythrocyte-rosetting-, Leu-1+, Leu-5+, OKT-4+, OKT-8+, common ALL antigen-, HLA-DR-, cytoplasmic and surface immunoglobulin-, MAS 036C(antithymocyte)+ (after in vitro culture) and terminal deoxynucleotidyl transferase-, indicating T-cell phenotypes, probably of common thymocytes. Cytochemical staining also demonstrated immature T-cell characters: dot-positivity for acid phosphatase and beta-glucuronidase, and negative for acid alpha-naphthyl acetate esterase. All bone marrow metaphases exhibited normal karyotypes. Our observation suggests that the neoplastic features of a common stem cell for myeloid and lymphoid cell lines are very similar in Ph1 positive and negative CMLs, and that the stem cell can differentiate towards T-lineage.     

Endoscopic ultrasonography in rectal carcinoid tumors: contribution to selection of therapy

To assess the clinical value of endoscopic ultrasonography (EUS) in carcinoid tumors of the rectum, we studied endoscopic and EUS findings in five patients whose tumors were relatively small in size. Endoscopy revealed sessile or semi-pedunculated smooth elevations, with mucosa of normal appearance. The elevations ranged from 5 to 15 mm in diameter, and were yellowish to white in color. EUS failed to demonstrate a small tumor in two patients whereas in the remaining three patients, a homogeneously hypoechoic mass, which was restricted to the submucosal layer, was detected. All patients were treated by endoscopic excision or local resection of the tumor, which resulted in complete removal of the tumor. We believe that even though EUS is not efficacious in cases of very small carcinoid tumors of the rectum, it can provide clinically important information in choosing therapy.     

血清可溶性肿瘤坏死因子受体与胰岛素抵抗的关系

目的　了解血清可溶性肿瘤坏死因子受体 (STNFR) 1,2与胰岛素抵抗 (IR)的关系。方法　测定 43名男性和 41名绝经期前女性的STNFR1,2。以稳态模型 (HomaModel)公式评估IR。结果　肥胖男、女组STNFR1与非肥胖男、女组相近 ,而其STNFR2高于非肥胖男、女组 ,差异有显著性 (P <0 .0 5 )。所有男性STNFR1和STNFR2水平高于女性 (P <0 .0 1)。所有对象相关分析示STNFR2与臀腰比 (WHR)、空腹血糖、体重指数 (BMI)、HomaIR、空腹胰岛素正相关。STNFR1与上述指标无相关性。在男性中 ,STNFR2与瘦素正相关 (r =0 .34 ,P <0 .0 5 ) ,调整BMI、WHR影响后 ,STNFR2仍与瘦素正相关 (r=0 .30 ,P <0 .0 5 )。逐步回归分析示WHR和STNFR2对HomaIR的影响达 41.3%。结论　STNFR2与IR相关 ,在人类TNF系统对IR的影响可能主要通过TNFR2起作用。     

前列腺素E治疗病毒性肝炎的中文文献评价

1．资料与方法：以“前列腺素E(PGE)、前列地尔与病毒性肝炎”为检索词，计算机检索“中国生物医学文献数据库”，并手工检索全国会议论文汇编、中华传染病杂志、中华肝脏病杂志、临床肝胆病杂志、中国中西医结合杂志、中华内科杂志、中西医结合肝病杂志、中国药物杂志、中国新药杂志、中国临床药理学杂志以及所获文献的附属参考文献，检索年份为1979     

Function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome coronavirus

To identify the function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome (SARS) coronavirus (CoV), we analyzed the protein-protein interaction among HAb18G/CD147, cyclophilin A (CyPA), and SARS-CoV structural proteins by coimmunoprecipitation and surface plasmon resonance analysis. Although none of the SARS-CoV proteins was found to be directly bound to HAb18G/CD147, the nucleocapsid (N) protein of SARS-CoV was bound to CyPA, which interacted with HAb18G/CD147. Further research showed that HAb18G/CD147, a transmembrane molecule, was highly expressed on 293 cells and that CyPA was integrated with SARS-CoV. HAb18G/CD147-antagonistic peptide (AP)-9, an AP of HAb18G/CD147, had a high rate of binding to 293 cells and an inhibitory effect on SARS-CoV. These results show that HAb18G/CD147, mediated by CyPA bound to SARS-CoV N protein, plays a functional role in facilitating invasion of host cells by SARS-CoV. Our findings provide some evidence for the cytologic mechanism of invasion by SARS-CoV and provide a molecular basis for screening anti-SARS drugs.