To investigate the anticancer effects of ring C in 18β-glycyrrhetinic acid (GA), a series of GA derivatives featured with 9(11)-ene moiety in ring C were designed and synthesized. The structures were confirmed by IR, LC-MS and 1H NMR. Their inhibitory effects towards human prostate cancer PC-3 and leukemia HL-60 cell lines were determined. Most of the derivatives displayed stronger antiproliferative activities than GA. Particularly, compound 14 showed promising anticancer activity with the GI50 values of 4.48 µmol · L(-1) and 1.2 µmol · L(-1) against PC-3 and HL-60 cells respectively, which is worth further study.
Antineoplastic Agents ; chemistry ; pharmacology ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; drug effects ; Drug Design ; Glycyrrhetinic Acid ; analogs & derivatives ; chemistry ; HL-60 Cells ; drug effects ; Humans ; Male ; Prostatic Neoplasms ; pathology

OBJECTIVETo study the molecular mechanism of curcumin in human esophageal carcinoma cell line (EC109).

METHODSEC109 cells were cultivated in vitro. When 80%-90% confluence was reached, they were treated with curcumin in different concentrations (15-120 µmol/L). The effects on cell proliferation were examined by CCK-8 colorimetry. The ultrastructure of EC109 cells were detected with transmission electron microscope(TEM). The cells apoptosis was observed with laser confocal microscope(LCM) by AnnexinV-FITC/PI double staining. The proteins level of PTEN, AKT, GSK3β and Caspase 3 were tested by flow cytometry(FCM) .

RESULTSCCK-8 test showed that curcumin could inhibit the proliferation of EC109 cells in a time- and concentration-dependent manner. TEM and LCM examinations indicated that curcumin could make EC109 cells apoptosis. The data of FCM showed that curcumin could increase the expression of PTEN, GSK3β and Caspase 3, decreased the expression of AKT.

CONCLUSIONThe effects of curcumin on inhibiting proliferation and promoting apoptosis of EC109 cells were related with increased expression of PTEN and inhibition of PI3K/AKT signaling pathway.

Apoptosis ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Curcumin ; pharmacology ; Esophageal Neoplasms ; metabolism ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; PTEN Phosphohydrolase ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction

Background The underlying mechanism of choroidal neovascularization(CNV) is multifactorial and complex.Focal adhesion kinase(FAK) plays a crucial role in controlling essential cellular processes and influencing distinct steps of the angiogenic response.But to our knowledge,seldom study on the effect of FAK on CNV formation has been reported previously.Objective In this study,the effect of several CNV risk factors on the expression of FAK in cultured retinal pigment epithelium(RPE) cells was investigated to illuminate effect of FAK on CNV.Methods Human RPE cells were isolated from donor eyes and exposed to H2O2,swallow of outer segment of photoreceptors(POS) and extracellular matrix(ECM) separately with the treating as follows:RPE cells were co-cultured with 10,20,50 and 100μmol/L H2O2 for 20 days;POS(1×106/ml) were co-cultivated with RPE cells for 20 days(setting control group,POS group,hypoxia group with 200μmol/L CoCl2,and POS+hyoxia group);RPE cells were cultured on the plates coated with 100mg/L fibronectin(FN),laminin(LN) or collagen typeⅠfor 30minutes or 1 hour.The expression of FAK and pFAK in RPE cells were examined by Western blot analysis.Results FAK was highly expressed in the 20μmol/L and 50μmol/L H2O2 groups compared with control group(P＜0.01);while he expression level of pFAK was reduced after treated with H2O2 in comparison with the control group(P＜0.01).After cultured with POS for 20 days,the undigested lysosome could be observed in RPE cells.The expressions of FAK and pFAK in RPE cells were not significantly changed between control group and POS groups(P＞0.05),but those in hypoxia group were significantly up-regulated in comparison with control group(P＜0.01).Compared with the hypoxia group,the expression amount of pFAK was elevated in POS+hyoxia group(P＜0.01).In comparison with control group,the increased pFAK expression was seen in FN,LN and collagen typeⅠtreating for 1-hour groups(P＜0.05,P＜0.01).Conclusion FAK pathway participates in several CNV-initiated signaling,such as H2O2,POS and ECM,in cultured RPE cells.It is reasonable to believe that FAK potentially plays an important role in CNV-dependent disorder.

Objective To search for the changes of T cells subpopulations and immunoglobulin and their relation-ship in children patients with simple nephrotic syndrome. Design Case-control research. Patients aud Participants 39 patients with simple nephrotic syndrome were divided into two groups:the incipient group and relapse group (6 cases were determined at the incipient and relapse time) .Thereare 28 patients in incipient group, 19 males and 9 females, at the age of 2 to 10 years old. There are20 patients in relapse group, 12 males and 8 females, at the age of 3 to 13 years old. There are 35health children in control group, 21 males and 14 females, 2～13 years old. Interventions T cells subpopulations were determined by indirect immunofluorescence of OKT linesmonoclonal antibodies. The serum IgG was determined by routine simple agar immunodiffusion tests. Results and Conclusions The CD_3~+ and CD_4~+ cells are of no change in the children patients withsimple nephrotic syndrome, and the CD_8~+ and CD_(10)~+ cells are obviously increased, the Values of CD_4~+/CD_8~+ are obviously lower than those in the control qroup, there are no difference between the incipientand relapse groups. The levels of serum IgG were decreased in the 85.3% children patients, IgM were inc-reased in 29.4% of that. The values of CD_4~+/CD_8~+ have positive correlation and negative correlationwith the levels of serum IgG and IgM respectively.

OBJECTIVETo investigate the inhibition effect of curcumin on the proliferation of the human esophageal carcinoma cell line Ec109 and its impact on PEN/PI3K/Akt signaling pathway.

METHODSEsophageal carcinoma Ec109 cells were cultured in vitro conventionally and were treated with curcumin at different concentrations. The cell proliferation level was examined by MIT colorimetry, the ultrastructure of curcumin-treated Ec109 cells were detected with transmission electron microscope (TEM) and cell apoptosis was observed by FCM with AnnexinV-FITC/PI double staining. The protein levels of PTEN, Akt, GSK3P and Caspase 3 of curcumin-treated Ec109 cells were detected by Western blot.

RESULTSMTT test showed that curcumin could inhibit the proliferation of Ec109 cells in a time and concentration-dependent manner. TEM examination indicated that curcumin could induce Ec109 cell apoptosis. FCM detection showed that Ec109 cell apoptotic rate increased significantly with the increase of drug concentration. On the other hand, curcumin could promote the expression of PTEN, GSK3beta and Caspase 3 yet reduce the expression of Akt.

CONCLUSIONCurcumin could obviously up-regulate the expression of PTEN, GSK3beta and Caspase 3, surpress PI3K/Akt signaling pathway and hence inhibit the proliferation of Ec109 cells.

Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Curcumin ; pharmacology ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Oncogene Protein v-akt ; metabolism ; PTEN Phosphohydrolase ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Signal Transduction ; drug effects

AIM: To explore the relationship between the expression of caspase-2 and caspase-3 and the apoptosis in retinal ischemia/reperfusion (I/R) injury of rats, as well as the therapeutic effects of brain derived neurotrophic factor (BDNF)on the ischemic and reperfused retina.METHODS: This experiment was conducted at the laboratory of Affiliated Hospital of Qingdao University Medical College from February 2007 to July 2007. The models of retinal ischemia/reperfusion injury were made by transiently elevating intraocular pressure. A total of 28 rats were divided into Normal and Operative Groups. Operative group was divided into six subgroups. In each subgroup there were four rats. The left eyes of rats were used for I/R and the right eyes were used for intravitreal injection of brain-derived neurotrophic factor (BDNF) as treatment group. After reperfusion we divided our subgroups according to the reperfusion time as 1, 6, 12, 24, 48, 72 hours. The retinal ganglion cell number was counted by using optic microscope(BX-51,Olympus). Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) method, and the expression of caspase-2,caspase-3 was studied by enzyme linked immunosorbent assay (ELISA) and strept avidin-biotin complex (SABC)immunohistochemistry.RESULTS: No positive apoptotic cells were observed in the normal rats' retinae, but there were a significant number of positive apoptosis cells in 6-24 hours after transient ischemia followed by a decrease at 48 hours. The number of apoptotic cells reached a maximum at 24 hours after ischemia .The expression of caspase-2 gradually increased as early as at 6 hours, reached a peak at 24 hours, then decreased between 48 and 72 hours. Similarly, caspase-3 has the same rule with caspsae-2 in the time courses of expression in retinal tissues.BDNF administered before reperfusion inhibited the expression of apoptosis and ameliorated the retinal tissue damage. It also decreased caspase-2 and caspase-3 expression in ischemic/reperfused retina.CONCLUSION: Retinal ischemia-reperfusion can induce apoptosis of cells in the retina. BDNF rescues retinal ganglion cells (RGCs) from retinal ischemia/reperfusion injury through down-regulation of cell apoptosis and caspase-2 and caspase-3 expression. BDNF have a neuroprotective effect on retina.

Abstract: Objective　To analyze the emergency response and long-term intervention effects after the detection of infectious snails epidemic by loop-mediated isothermal amplification (LAMP) assays in Hannan District, Wuhan City, and to explore the application of LAMP in early surveillance and early-warning of schistosomiasis transmission. Methods Snails picked up by the risk monitoring system in Hannan District were examined by anatomical microscopy and LAMP technology to identify the schistosomiasis infection. Emergency response and intensive intervention were initiated in the environment where positive snails appeared, and the long-term effects were evaluated. Results In May 2018, the infectious snails were detected by LAMP technology in Hannan District, and the positive snails were located in Zhujiacha, Dongzhuang Village, Obstacles and weeds were removed and buried by machine in Zhujiacha. 12 700 m2 of snails were killed by drugs, and the mortality rate of snails was more than 80%; no new seropositive persons were found in the emergency examination within 500 m of the positive snail sites. 506 people were examined in Dong Zhuang Village at the end of the year, and 30 positive IHA cases were detected with a blood positive rate of 5.93%, no positive fecal test was found, and all positive blood test patients took preventive medication. The monitoring results of sentinel rats and wild feces were all negative. Health education was carried out, 7 warning signs were deployed and refreshed, and 500 publicity brochures were distributed. After nearly three years of intensified intervention and monitoring in the villages where the positive environment is located, and the density of snails on the stubborn snail has dropped from 0.094/frame to 0.027/frame, and the positive rate of blood test in Dongzhuang Village has steadily dropped from 5.93% to 3.74%. Conclusions The infected snails missed by microscopy were detected by LAMP in Hannan District, which created conditions for the rapid emergency treatment of environment and elimination of positive snail and improved the sensitivity of the surveillance and early warning system in transmission-interrupted areas.

OBJECTIVETo evaluate the academic level and influence of National Journal of Andrology through statistical analysis for the fund sponsored articles.

METHODSUtilizing the information from China Hospital Knowledge Database (CHKD), and adopting bibliometrics methods, we carried on statistical analysis for the fund sponsored articles published on National Journal of Andrology dated from Mar. 2000 to Jun. 2005.

RESULTSNine hundred and fourty-two articles were screened, of which 204 (21.7%) were fund sponsored, and the proportion of the articles supported by various funds, including the funds from national key projects, presented an increasing tendency every year. The authors were distributed among 30 provinces and 6 oversea countries with an average age 37.4 years old, of whom 37.7% got doctor's degree and 38.7% masters degree. The articles involved clinical research were at 28.9%, and basic study and applied study were at 71.1%, respectively.

CONCLUSIONThe articles supported by various funds in National Journal of Andrology have taken a high percentage, so the journal achieves a fine academic level and social influence.

Andrology ; statistics & numerical data ; Bibliometrics ; China ; Periodicals as Topic ; statistics & numerical data ; Research Support as Topic

500 pmol/L were greater than those in any group.Conclusion Serum MMP-2 can be involved in left ventricular remodeling of HF,and measuring its concentration is helpful to judge the severity and prognosis of HF.

Objective To evaluate the genotoxicity of a magnesium alloy coated with β-tricalcium phosphate(β-TCP).Methods Four groups were designed.In the first group,AZ31B magnesium alloy surface was coated with β-TCP using chemical bath deposition,and in the second group magnesium alloy was tested.The other two groups were negative control(pure titanium)and positive control groups(0.5 mg/L bleomycin).Single cell gel electrophoresis was adopted to investigate genotoxicity of the alloy samples in different groups,and 60 cells from each group were analysed.Tail moment and tail DNA percentage were used as reliable indicators to show DNA damage in lymphocytes induced by every testing sample.Student-Newman-Keuls(SNK)test wag used to compare results from 4 groups.Results There were no significant differences in tail moment and tail DNA percentage between magnesium alloy group[(0.52±0.12),(6.82±1.81)%]and magnesium alloy coated with β-TCP group[(0.51±0.12),(6.89±1.93)%,P＞0.05].Tail moment and tail DNA percentage in negative group were(0.47±0.14)and(6.29±1.64)%,and tail moment and tail DNA percentage in positive group were(5.17±1.23)and(22.09±4.51)%.Conclusions No significant increase was found in DNA damage in lymphocytes induced by magnesium alloy coated with β-TCP.