OBJECTIVE: To study the relationship between the radiotherapy resistance and autophagy. To provide a theoretiacal basis for drugs that regulate autophagy to improve radiotherapy sensitivity. METHOD: Flow cytometry (FCM) was performed to analyze the distribution of the cell cycle of CNE2 and CNE2/DDP cells under the action of X radiation. The expression of autopagy-specific gene Beclin1 and microtubule-associated protein light chain 3β (MAPLC3β) in CNE2 and CNE2/DDP cells was determined by real time PCR and Immumofluorescence staining. RESULT: CNE2/DDP and their parental CNE2 cells produced the G2-M phase arrest under the action of X radiation. With the radiation dose increasing,The cells which in the G2-M phase were more and more (P<0. 05). The G2-M phase arrest in CNE2/DDP cells was more obvious than in CNE2 cells (P<0. 05). The expression of Beclin1 and MAPLC3β in CNE2 and CNE2/DDP cells increased under the action of X radiation. What's more, the raise was more and more obvious with the increase of the irradiation dose(P<0. 05). The expression levels of Beclin1 and MAPLC3β in CNE2/DDP was lower than that in CNE2 cells (P<0. 05). CONCLUSION Autophagic cell death may be the one manner of death in nasopharyngeal carcinoma CNE2 and CNE2/DDP cells under the action of X radiation. The radiation resistance of CNE2/DDP cells may be related to the low expression of autophagy-related genes.
Apoptosis Regulatory Proteins ; genetics ; Autophagy ; Beclin-1 ; Carcinoma ; Cell Cycle ; Cell Line, Tumor ; radiation effects ; Dose-Response Relationship, Radiation ; Humans ; Membrane Proteins ; genetics ; Microtubule-Associated Proteins ; genetics ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; genetics ; Radiation Tolerance ; X-Rays

Objective: To study the recombinant epitope antigens of hepatitis C virus (HCV), in order to fulfil the requirements of recombinant immunoblot assay kit. Methods: An expressing vector pBVIL1 for expression of recombinant antigens in a fusion manner with IL-1β was constructed. A series of selected genes from the HCV antigens including the C, NS3, NS4 and NS5 were amplified from HCV gene-containing plasmids using PCR and the expression plasmids for these genes were constructed in pBVIL1, respectively. The activity of the purified recombinant antigens were tested against an identified HCV antibody positive and negative panel with ELISA. Results and Conclusions: All the cloned genes of chosen antigen epitopes were highly expressed in pBVIL1 in E.coli. The activity of the C and NS4 antigens were slightly higher than the RIBA3.0 antigens, while the activity of NS3 was slightly lower than the RIBA3.0 antigen. But the total evaluation for the panel was same as RIBA3.0. That means the cloned antigens were suitable for the use in RIBA test kit.

Objective To evaluate the efficacy and safety of Jinkui Shenqi Pills on hypertension through Meta-analysis and systematic review. Methods Articles about intervention of modified Jinkui Shenqi Pills in hypertensive clinical randomized controlled trials were retrieved from CNKI, Wanfang database, VIP, Cochrane Library, PubMed, and Embase. They were all searched from inception to June 2016. Cochrane system evaluation manual bias risk assessment method was used to evaluate the quality of the articles, and RevMan5.3 software was used for Meta-analysis. Results Nine articles involving 776 cases were included in the study. Meta-analysis showed that the total effective rate of modified Jinkui Shenqi Pills was better than that of conventional Western medicine treatment [OR=2.67, 95%CI (1.73, 4.11), P＜0.000 01], and combination therapy was superior to conventional Western medicine alone [OR=3.27, 95%CI (1.99, 5.39), P＜0.000 01]. However, the efficacy of modified Jinkui Shenqi Pills alone was equivalent to the conventional Western medicine alone [OR=1.16, 95%CI (0.43, 3.09), P=0.77). Conclusion Modified Jinkui Shenqi Pills can improve the clinical symptoms of the patients with hypertension, and combination treatment can improve the antihypertensive effect. However, the quality of the included research literature is too low, yet more large-scale, multi-center, high-quality clinical randomized controlled trials are needed to further verify.

Objective To study the neuroprotective effect of fucoidan against 6-OHDA-induced damage on MN9D cell line and preliminarily explore its mechanism.Methods The MN9D cells were treated with different concentrations of 6-OHDA(12.5,25,50,100 and 200 μmol/L)for 24 h and with 50 μmol/L 6-OHDA for different time courses(6,12,24 and 48 h)as well.Based on the above experiment,the best concentration(50 μmol/L)of 6-OHDA and time course(24 h)were selected and the damaged model of MN9D cell line was induced accordingly.The MN9D cells were pretreated with 0.01,0.1 and 1.0 mg/mL fucoidan for 1 h,and then co-treated with 50 μmol/L 6-OHDA for 24 h.The viability of MN9D cells was detected by MTT assay;the LDH leakage was detected by bioassay;the level of intracellular xidative stress was observed by 2',7'-dichlorodihydrofluorescein diacetate assay.Results MTT metabolic value decreased following the increase of 6-OHDA concentration or the extension of processing time.Treatment with 50 μmol/L 6-OHDA for 24 h induced a significant decrease of MTT metabolic rate and an increase of LDH leakage rate in the MN9D cells.Pretreatment with 0.1 and 1.0 mg/mL fucoidan inhibited the death of 6-OHDA-induced cells,increased the MTT metabolic value and decreased the LDH leakage.Cell morphological changes were consistent with the biochemical experiments.Treatment with 50 μmol/L 6-OHDA for 8 h could significantly increased the generation of reactive oxygen species induced by 6-OHDA,while pretreatment with 1.0 mg/mL fucoidan for 1 h showed antagonism on that.Conclusion Fucoidan can protect MN9D cells from the death induced by 6-OHDA and the underlying mechanism may be involved in the antioxidant capacity of fucoidan.

OBJECTIVETo evaluate whether or not administration of folic acid and resveratrol have preventive effects on cleft palate formation as well as the comparison of the two drugs' s effects.

METHODSPregnant mice were randomly divided into 9 groups, with 8 mice in each group. The TCDD group mice were dosed with TCDD 28 microg/kg body weight on gestation day 10 (GD 10) animals in folic acid group were respectively dosed with folic acid 15, 10, 5 mg/kg and TCDD 28 microg/kg; resveratrol treated mice were divided into 3 groups: resveratrol 50 mg/kg were orally administered for 6 consecutive days, from gestational day GD 8 to GD13 in resveratrol (GD8-13 ) group; resveratrol 50 mg/kg were orally administered for 6 consecutive days, from gestational day GD 8 to GD13, followed hy an oral administered with TCDD on GD10 in resveratrol (GD8-13) + TCDD group; resveratrol 50mg/kg and TCDD 28 microg/kg were used by gavage administration at GD10 in resveratrol (GD10) + TCDD group. Control mice were treated with the same volume of water for 6 consecutive days from GD8 to GD13 and were given a single dose of corn oil on GD10. The pregnant mice weight and embryos, the number of live, cleft palate, dead and resorption fetal mice were recorded on GD 17.5. The coronal sections of the fetal mice heads were prepared at GD 17.5 and observed by microscopy.

RESULTSTotal frequency of clefts was 92.86% in TCDD group, 84.00% (15 mg), 73.08% (10 mg), 84.00% (5 mg) in folic acid + TCDD groups, 0% in resveratrol (GD10) group, 74.51% (GD10), 57.78% (GD8-13) in resveratrol + TCDD groups. The frequency of cleft was 0% in the control group. Compared with the control and the TCDD groups, there were significant differences in the number of live, dead and resorption fetal mice in TCCD + resveratrol (GD8-13) group (P < 0.05). No significant differences in embryonic weight, live fetuses weight, the number of live, dead and resorption fetal mice were found in the other groups (P > 0.05).

CONCLUSIONTest dose of folic acid and resveratrol both had certain antagonistic effect on cleft palate in mice induced by TCDD, with folic acid 10 mg/kg, resveratrol 50 mg/kg GD8-13 doses having stronger antagonistic action. Effects of both the two drugs have no significant difference, but resveratrol (50 mg/kg, GD8-13) significantly affects the fetal mice's growth and development under TCDD exposure in utero.

Abnormalities, Drug-Induced ; prevention & control ; Animals ; Cleft Palate ; chemically induced ; prevention & control ; Female ; Fetus ; Folic Acid ; administration & dosage ; pharmacology ; Humans ; Mice ; Mice, Inbred C57BL ; Polychlorinated Dibenzodioxins ; antagonists & inhibitors ; Pregnancy ; Random Allocation ; Stilbenes ; administration & dosage ; pharmacology ; Teratogens

Fucoidan is a natural polysaccharide extracted from brown seaweeds, with a wide variety of biological features, especially the anti-inflammatory and anti-oxidative effects. Studies indicated that the anti-inflammatory effect of fucoidan related to its capacity to interact with the selectin or scavenger receptor on the cell membrane. Fucoidan can also inhibit the synthesis and release of reactive oxygen species (ROS), as well as promote its clearance, showing the anti-oxidative activity.
Animals ; Anti-Inflammatory Agents ; isolation & purification ; metabolism ; pharmacology ; Antioxidants ; isolation & purification ; pharmacology ; Polysaccharides ; isolation & purification ; metabolism ; pharmacology ; Reactive Oxygen Species ; metabolism ; Receptors, Scavenger ; metabolism ; Seaweed ; chemistry ; Selectins ; metabolism

Objective To investigate the efficacy of micro?surgery for the treatment of medulla oblongata cavernomas. Methods A retrospective analysis was conducted on the clinical data of 21 patients with cavernous hemangioma who received micro?surgical treatment. Of the 21 patients, 13 were men and 8 women,aged 22 to 63 years. The preoperative Karnofsky performance status(KPS)score was 76.5 ± 10.2. The main clinical manifestations included sensory disorder and difficulty swallowing etc. According to the location of the lesions ,the posterior transchoroidal fissure approach was employed for 16 patients;far?lateral approach,5 patients. Electrophysiological monitoring and nervous system navigation were supple?mentarily adopted in both types of surgery. Further ,KPS scoring was conducted to evaluate the patients 'quality of life. Results The medulla cav?ernous hemangioma was excised in all cases. For 17 patients with primary neurological disorders ,their symptoms were alleviated or resolved;4 pa?tients had severe symptoms and 8 presented with new clinical symptoms. A follow?up visit was conducted 8 to 97 months post?surgery(average 47.6 months). All patients were found capable of caring for themselves in daily life and performing simple or normal learning and working activities without recurrence or bleeding. The mean postoperative KPS score was 83.7 ± 15.5. Conclusion Patients with medulla cavernous hemangioma bleeding or severe symptoms should actively seek surgical treatment. Repeated bleeding is the absolute indication for surgery. Surgical skills ,elec?trophysiological monitoring,and nervous system navigation can reduce nervous system damage and protect the brainstem. The patient's quality of life is expected to significantly improve after surgery.

BACKGROUNDBevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, has shown promising activity in recurrent malignant gliomas. We reported the treatment response for the combination of bevacizumab and chemotherapy in a series of six patients with recurrent malignant glioma and investigated the molecular alterations in cancer pathways using the surgical biopsies from these patients.

METHODSStandard therapy with primary resection followed by adjuvant chemoradiotherapy had failed in all patients. Bevacizumab was administered at a dose of 10 mg/kg every 2 weeks. Concomitantly, four patients received temozolomide (50 mgxm(-2)xd(-1)), one patient irinotecan (125 mg/m(2) every 2 weeks) and one patient topotecan (1.2 mgxm(-2)xd(-1)). Response to therapy was mainly determined by magnetic resonance imaging. The expression of Ras, phosphorylated mitogen activated protein kinase (p-MAPK), phosphorylated AKT (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) were semiquantitatively assessed by immunohistochemistry using surgical biopsies before the initial treatment.

RESULTSFive of the six patients had a radiographic response. Three were complete response, and two were partial response. Only one patient had progressive disease. The 6-month progession-free survival (PFS) was 33% and the median PFS was 15 weeks, with a range of 6 to more than 60 weeks. Of the three core pathways analyzed in this study, the Ras/MAPK and phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR pathways were more likely to be associated with the treatment response to bevacizumab. In two younger patients (ages < 50) with complete response, simultaneous overexpression of p-MAPK, p-AKT and p-mTOR might be the crucial feature.

CONCLUSIONSBevacizumab in combination with chemotherapeutic agents may be an effective strategy for patients with recurrent malignant glioma. Activated MAPK and AKT might be possible biomarkers for selecting suitable patients for this targeted therapy.

Adolescent ; Adult ; Angiogenesis Inhibitors ; therapeutic use ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents, Phytogenic ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; Bevacizumab ; Camptothecin ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Glioma ; drug therapy ; metabolism ; mortality ; pathology ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Young Adult

AIMTo study the effect of ginkgolide B from Ginkgo leave on action potential (AP), L-type calcium current (I(Ca) - L) and delayed rectifier potassium current (I(K)) in normal and ischemic guinea pig ventricular myocytes.

METHODSWith the standard microelectrode technique to record action potential and whole-cell variant patch-clamp technique to record calcium and potassium current.

RESULTS(1) Under normal condition, ginkgolide B shortened APD and had no effect on RP, AP and V(max). Ginkgolide B also increased I(K) in a concentration dependent manner and had no significant effect on I(Ca) - L (2) Under ischemia condition, it was observed that shortening of APD, APA, decrease V(max) and depolarization of RP was induced by ischemia, but ginkgolide B could attenuate above--mentioned changes. (3) Under ischemia condition, I(Ca) - L and I(K) were inhibited, perfusion with ischemia solution containing ginkgolide B could reverse the decrease of I(Ca) - L and I(K).

CONCLUSIONGinkgolide B had protective effect on ischemic myocardium to prevent ischemic arrhythmia.

Action Potentials ; drug effects ; Animals ; Calcium Channels, L-Type ; drug effects ; Delayed Rectifier Potassium Channels ; drug effects ; Ginkgolides ; pharmacology ; Guinea Pigs ; Heart Ventricles ; drug effects ; Lactones ; pharmacology ; Myocardial Ischemia ; metabolism ; Myocytes, Cardiac ; drug effects ; metabolism ; Patch-Clamp Techniques

OBJECTIVEThe study examined the changes of serum caspase-3 and IL-8 levels following selective head cooling with mild hypothermia (SHC) treatment in neonates with hypoxic-ischemic encephalopathy (HIE) in order to explore the mechanism of neuroprotection of SHC against HIE.

METHODSThirty-three neonates with moderate or severe HIE were randomly assigned to two groups: SHC treatment (n=16) and conventional treatment (n=17). Serum levels of caspase-3 and IL-18 were measured using ELISA before treatment and 24 hrs, 48 hrs, 72 hrs and 5 days after treatment.

RESULTSSerum caspase-3 levels in the SHC group decreased 24 and 48 hrs after treatment (3.8±1.9 and 2.6±1.2 ng/mL, respectively) compared with 6.1±2.3 ng/mL at 24 hrs and 7.2±3.1 ng/mL at 48 hrs in the conventional treatment group (P<0.05). Serum IL-18 levels in the SHC group decreased 24 hrs, 48 hrs and 72 hrs after treatment (119±30, 76±33 and 71±40 ng/mL, respectively) compared with those in the conventional treatment group (138±28 ng/mL at 24 hrs, 156±60 ng/mL at 48 hrs and 182±54 ng/mL at 72 hrs; P<0.01).

CONCLUSIONSSHC treatment can inhibit the release of caspase-3 and the expression of IL-18 in neonates with moderate or severe HIE. This may contribute to the neuroprotection of SHC against HIE.

Caspase 3 ; blood ; Female ; Humans ; Hypothermia, Induced ; Hypoxia-Ischemia, Brain ; blood ; therapy ; Infant, Newborn ; Interleukin-18 ; blood ; Male