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Objective To analyze the differences in the incidence of malignant tumors among urban and rural residents in Shenyang from 2013 to 2018. Methods From 2013 to 2018, the incidence data of malignant tumors of residents with household registration from national cancer surveillance sites in Shenyang urban area and rural Kangping and Faku counties were extracted. Crude incidence rate, age-standardized rate (standardized rate by Chinese population, standardized rate by world population), age specific incidence rate, cumulative incidence rate (0-74 years old), and truncated incidence rate (35-64 years old) were respectively calculated. SPSS23.0 software was used to carry out chi square test for the incidence of disease in urban and rural areas and in different age groups. Joinpoint 3.5.3 software was used to analyze the incidence trend in urban and rural areas. Results From 2013 to 2018, the age-standardized rate of cancer incidence by Chinese population（2000）and the cumulative rate of 0-74 years old in urban residents of Shenyang City were 199.85/105 and 22.21%, respectively, which were higher than those in rural residents, 172.84/105 and 19.85%, respectively. The incidence rate of cancer in males and females in urban area was higher than that in rural areas (χ2=262.47，χ2=103.83, P<0.05). The incidence rates in urban males and females and in rural females all showed an increasing trend in the past 6 years (APC=3.06%, APC=4.03%，APC=3.28% , P<0.05). The top five malignant tumors of urban males were lung cancer, colorectal cancer, liver cancer, gastric cancer and bladder cancer, while the top five malignant tumors of rural males were lung cancer, esophageal cancer, liver cancer, gastric cancer and colorectal cancer, respectively. The top five malignant tumors of urban women were breast cancer, lung cancer, colorectal cancer, thyroid cancer and cervical cancer, while the malignant tumors of rural women were lung cancer, breast cancer, colorectal cancer, cervical cancer and liver cancer, respectively. Conclusion From 2013 to 2018, the incidence of malignant tumor in urban residents in Shenyang is higher than that in rural areas. The incidence rates of urban males and females and rural females have showed an upward trend year by year in the past 6 years. There is a large difference in the order of tumor incidence between urban and rural men and women.
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The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.
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Objective To investigate the effects and probable mechanism ofShenfu injection on the oxidaitve damage of H2O2-induced PC12 cells.Methods PC12 cells were cultured and exposed to 100μmol/L H2O2 for 1 h to establish the oxidative damage model. The protective effect ofShenfu injection was observed by the cell survival rate measured by colorimetric MTT assay, and the leakage rate of lactic dehydrogense (LDH). Western blot methods were used to detect the expression of NF-κB signaling pathway.Results Compared with the model group,Shenfu injection at 5, 10, 20 ml/L could improve the PC12 cells survival rate (83.11% ± 2.59 %, 87.99% ± 0.59%, 85.26% ± 1.07%vs. 73.82% ± 1.82%;P<0.01 orP<0.05), decrease the LDH leakage rate (32.75% ± 4.10%, 28.52% ± 1.14%, 35.79% ± 1.62%vs. 64.34% ± 3.18%;P<0.01 or P<0.05). Western blot results showed thatShenfu injection could protect the PC12 cells from oxidaitve damage by suppressing the p-p65/p65 (1.30 ± 0.10, 1.17 ± 0.06, 1.37 ± 0.15 vs. 1.70 ± 0.10;P<0.01 orP<0.05), p-IκBα/IκBα (1.07 ± 0.12, 1.00 ± 0.10, 1.03 ± 0.06 vs. 1.17 ± 0.06; P<0.01 orP<0.05).ConclusionShenfu injection has a obvious antioxidant effect on PC12 cells in vitro.
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@#Cognitive function is an important part of non-motor function of the cerebellum. The cerebellum is involved in cognition and has a variety of cognitive functions, including working memory function, language function, spatial cognitive function (spatial processing and spatial memory), and temporal cognitive function (time perception and time processing), etc. This article reviewed recent advances in these aspects of cognitive function of the cerebellum.
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@#Objective To observe the effects of electroacupuncture on learning and memory, and discuss the therapeutic mechanism. Methods 45 Sprague-Dawley rats were randomly divided into sham group (n=15), model group (n=15) and electroacupuncture group (n= 15). The latter 2 groups were modeled with middle cerebral artery occlusion for 1.5 h and reperfusion. The rats of electroacupuncture group received electroacupuncture at Shenting (DU24) and Baihui (DU20) for 7 days. Learning and memory ability was tested with Morris water maze. Neurologic impairment was assessed with Longa's score. Their hippocampus were observed under HE staining and the level of brain-derived neurotrophic factor (BDNF) and p75 neurotrophin receptor (p75NTR) protein were determined with Western blotting. Results Compared with the model group, the latency of water maze decreased and the times crossing the platform increased in electroacupuncture group (P<0.05), while the Longa's score significantly reduced (P<0.05), and the lesion of nerve cells were alleviated, with the decrease of p75NTR and increase of BDNF in the ischemic hippocampus (P<0.01). Conclusion Electroacupuncture can improve the learning and memory of cerebral ischemia-reperfusion rats, which may relate with up-regulating BDNF and down-regulating p75NTR in hippocampus.
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Objective To observe the effects of electroacupuncture on learning and memory, and discuss the therapeutic mechanism. Methods 45 Sprague-Dawley rats were randomly divided into sham group (n=15), model group (n=15) and electroacupuncture group (n=15). The latter 2 groups were modeled with middle cerebral artery occlusion for 1.5 h and reperfusion. The rats of electroacupuncture group received electroacupuncture at Shenting (DU24) and Baihui (DU20) for 7 days. Learning and memory ability was tested with Morris water maze. Neurologic impairment was assessed with Longa's score. Their hippocampus were observed under HE staining and the level of brain-derived neurotrophic factor (BDNF) and p75 neurotrophin receptor (p75NTR) protein were determined with Western blotting. Results Compared with the model group, the latency of water maze decreased and the times crossing the platform increased in electroacupuncture group (P<0.05), while the Longa's score significantly reduced (P<0.05), and the lesion of nerve cells were alleviated, with the decrease of p75NTR and increase of BDNF in the ischemic hippocampus (P<0.01). Conclusion Electroacupuncture can improve the learning and mem-ory of cerebral ischemia-reperfusion rats, which may relate with up-regulating BDNF and down-regulating p75NTR in hippocampus.
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Aim To investigate the effect of indirubin derivative PHⅡ-7 and TRAIL on proliferation in breast cancer cell MCF-7 and its MDR counterpart MCF-7/ADR and the mechanism.Methods Growth inhibition rate was examined respectively by MTT assay under treatment with TRAIL or PHⅡ-7 or in combination. Cell apoptosis and ROS production were examined by flow cytometry.The change of TRAIL receptors(DR4/DR5 )in mRNA was analysed by realtime PCR.Re-sults IC50 of PHⅡ-7 on MCF-7 and MCF-7/ADR was (4.49 ±1.55 ),(3.44 ±0.90 )μmol · L-1 respec-tively;MDA-MB-231 was TRAIL sensitive cell line, and apparently TRAIL induced apoptosis in MDA-MB-23 1 .Low concentration of PHⅡ-7 in combination with TRAIL could augment TRAIL-induced cytotoxic effect including apoptosis while TRAIL or PHⅡ-7 treatment alone had limited cytotoxity to those cells.Besides, PHⅡ-7 at this concentration had little toxicity to hu-man peripheral blood mononuclear cells even if in com-bination with TRAIL.PHⅡ-7 generated ROS produc-tion inside MCF-7 and MCF-7/ADR cells and up-regu-lated DR4/DR5 expression concentration dependently. Once upon ROS scavenger NAC involved,the effect of TRAIL receptors up-regualtion by expression was abro-gated.Conclusions PHⅡ-7 at low concentration could improve the sensitivities of breast cancer cell MCF-7 and MCF-7/ADR to TRAIL,the mechanism of which may be the ability of ROS production by PHⅡ-7 help up-regulated TRAIL receptor DR4,DR5 .Our re-search set a solid foundation for PHⅡ-7 in combination with TRAIL in future clinical application.
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Background and purpose:Breast cancer is one of the most common carcinoma among female patients with high mortalities. Drug-resistance is the major reason that leads to chemotherapy failure in clinical practice. MCF-7/ADR is a multi-drug resistant cell line that was established on the basis of breast cancer cell line MCF-7. This research aimed to investigate the anti-apoptotic effect of c-fos in resistant breast cancer cell MCF-7/ADR, and to compare with its sensitive counterpart MCF-7.Methods:Doxorubicin with various concentrations was used to treat MCF-7 as well as its MDR- counterpart MCF-7/ADR. The growth inhibitory rate of MCF-7 and MCF-7/ADR wasdetermined by MTT assay. Additionally, RT-PCR was used to test the expression of P-gp and c-fos mRNA in MCF-7 and MCF-7/ADR; The expression of c-fos mRNA was detected by RT-PCR after 3 μmol doxorubicin treatment;We further established cell lines that stably interfered with c-fos, named MCF-7/ADR/si-fos-8B, MCF-7/ADR/si-fos-3D. Flow cytometry and MTT assay were used to investigate the apoptosis rate and inhibitory rate in these above cells under the treatment of 5-FU, CDDP or γ-radiation. At last, RT-PCR and Western blot analysis were used to detect the expression of bax, bcl-2, puma, p53.Results:The expression of c-fos and P-gp (MDR-1) was up-regulated in MCF-7/ADR, compared with its sensitive counterpart MCF-7. Additionally, the resistant fold of MCF-7/ADR to doxorubicin was nearly 40; The expression of c-fos was gradually up-regulated after 3 μmol doxorubicin treatment; The sensitivity to drugs (5-FU and CDDP) was increased after c-fos interference while the apoptosis rate was also increased after 5-FU, CDDP and γ-radiation treatment. RT-PCR and Western blot analysis indicated that up-regulation ofbax,puma,p53 after c-fos interference while the expression of bcl-2 was down-regulated.Conclusion:c-fos may act as an anti-apoptotic protein in resistant breast cancer cell line MCF-7/ADR by regulating the expression of apoptosis related proteins, and may play a vital role in the formation of multi-drug resistance phenotype.
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Objective To identify multidrug resistance (MDR) associated cell surface antigen in hematologic neoplasia and to investigate the universality of membrane-relocated expression of this antigen in hematologic neoplasia.Methods The membrane antigen was isolated and precipitated by SDS-PAGE and co-immunoprecipitation (co-IP),then was identified by mass spectrum (MS).Specific siRNA was used to interfere with gene expression,laser confocal microsopy was used to validate the results involved in antigen information.FACS was performed to analyse relocated expression of the antigen in hematologic neoplasia.Results Co-IP and MS show that a nuclear factor PSF was the antigen of 5D12,a leukemia-MDR associated McAb,and this antigen could relocate on HL-60 cell membrane.A series of experiences further confirmed that PSF overexpressed on HL-60 cell membrane compared with HL-60/ADR.The binding percentages of 5D12 to many hematologic tumor cells were observed,HL-60 (78.56±0.76) ％,K562 (26.54±4.42) ％,Nomalwa (38.10±5.11) ％,U937 (64.03±7.96) ％,Jurkat (29.12±5.58) ％,Raji (74.92±3.41) ％,CEM (12.18±3.21) ％.Conclusion Nuclear protein,PSF relocalizes on cell surfaces in hematologic tumor cells and contributes to cell sensitivity.PSF is a potential target of MDR prediction in hematologic neoplasia.
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Objective To construct a fusion protein that used for treatment of resistance and palindromia in leukemia and studied its biological activity. Methods IL-3 and LP gene fragments were amplified by PCR. After enzymatic digestion and T4 ligation, the fusion gene was cloned into expression vector pAYZ. The product was purified by exchange chromatography and anti-Etag affinity chromatography. IL3-G4SLP fusion protein was analyzed by SDS-PAGE and Western blot. Protein biological activity was detected by FACS. Results The fusion protein was expressed as soluble protein by E.Coli 16C9. The protein expression level was about 1 mg/L, its purity was over 95 %, and the expression level was about 1 mg/L. The fusion protein can combined specificely with CD123 on leukemia stem cells. Conclusion Fusion protein IL-3-G4S-LP can target on leukemia stem cells and maybe as a potential drug used for treatment of resistance and palindromia in leukemia.
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Objective:To prepare and characterize specific and discrepant mouse hybridoma antibodies on membrane of HL60 and HL60/ADR cell lines.Methods:BALB/c mice were immunized by subtractive immunization induced Cp(Cyclophosphamide).McAbs were prepared by hybridoma technique,screened and detected by FACS and LSCM.Results:51 candidates and discrepant antibodies were found,and one of them (5F6) was purified and identified.Conclusion:Combination of SI with discrepant screening method should facilitate the preparing and identifying discrepant McAbs for identifying antibodies that can distinguish the differences in proteins expressed in HL60 and HL60/ADR,which is a significative and potential method in the research and target therapy associated drug-resistance.
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OBJECTIVE:To establish a method for the determination of EPA and DHA in ray oil.METHODS:The determination was carried out on Diamonsil C18 column.The mobile phase consisted of acetonitrile-water(95 :5) with flow rate of 1.0 mL?min-1 and detection wavelength set at 220 nm.The column temperature was set at 25 ℃.RESULTS:The linear ranges were 1～4 ?g for EPA(r=0.999 1) and 2～8 ?g for DHA(r=0.999 4).The average recoveries were 99.23% for EPA(RSD=0.49%) and 99.30% for DHA(RSD=0.27%).CONCLUSION:The method is simple,rapid,accurate and reproducible for the detection of EPA and DHA in ray oil.
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Background and purpose:Multidrug resistance(MDR)is one of the major causes of progressive breast cancer chemotherapy failure.One of the major mechanisms of MDR is the overexpression of P-glycoprotein (P-gp).Therefore,the identification of novel agents which can inhibit the drug transporter function of P-gp or its expression is of utmost interest in cancer research.The aim of this study was to explore the antitumor and reversal effect of PHⅡ-7,natural products from traditional Chinese medicine(TCM).Methods:The cytotoxicity of PHⅡ7 alone and combined application of PHⅡ-7 and adriamycin(ADR)on breast cancer cells were determined using MTT assay.Annexin V–FITC/PI apoptosis detection kit was used to observe the apoptosis-inducing effect of PHⅡ-7 in MCF-7 and MCF-7/ADR cells.The effect of PHⅡ-7 on mdr1 mRNA was determined by reverse transcription PCR and real time PCR,flow cytometer was used to measure the intracellular ADR accumulation.Results:PHⅡ-7 alone inhibited cell growth of MCF-7 and MCF-7/ADR cells with the IC 50 (6.07?0.85),(5.51?1.22)?mol/L,respectively when combined with ADR,PHⅡ-7 enhanced the cytotoxicity of ADR toward MCF-7/ADR cells.In addition,PHⅡ-7 induced apoptosis both on MCF-7 and MCF-7/ADR cells;PHⅡ-7 reversed the drug resistance to ADR in MCF-7/ADR cells by inhibiting mdr1 mRNA transcription and increasing the intracellular ADR accumulation.Conclusion:PHⅡ-7 displayed significant anti-proliferative and apoptosis-inducing effect on sensitive and multidrug resistant breast cells in vitro.PHⅡ-7 reversed effectively MDR by blocking the drugs to be pumped out by inhibiting P-gp expression and function pathway.