Objective Drug resistance is a major problem for the successful chemotherapeutic treatment and prognosis of cervi -cal cancer .The article investigated the role of Twist on cisplatin resistance of Hela cervical cancer cells in hypoxia microenvironment and its possible mechanism to provide an experimental basis to improve the therapeutic efficacy for cervical cancer . Methods Hela Cells were divided into two groups, normal oxygen group A (no CoCl2) and hypoxia group A (addition of 150μmol/L CoCl2 medium).6 hours later, different degrees(10-3, 10-4, 10-5, 10-6, 10-7 mol/L) of cisplatin (10 -3 , 10 -4 , 10 -5 , 10 -6 , 10 -7 mol/L) were added into two groups .24 hours later , MTT were added to measure IC 50 and growth inhibition ratio .CoCl2 were used to mimic hypoxia environ-ment.The working concentration and the treatment duration of Cispla-tin was optimized by MTT method.The expressions of Twist and MDR1 in normal oxygen group , cisplatin group , hypoxic group B and hypoxic cisplatin group B were determined by immunofluores-cence and western blot . Results The IC50 values were 10 -5.3 mol/L and 10 -4.5 mol/L of cisplatin respectively in normal oxygen group and hypoxia group, and there was significantly difference between them (P<0.05).The optimized working concentration and work time of cisplatin was 10 -5 mol/L and 24 h.Compare to the normal oxygen group (13.08 ±2.39, 29.57 ±12.80), the expres-sions of Twist (20.81 ±2.07, 24.25 ±4.51, 33.14 ±4.24) and MDR1 (35.26 ±8.41, 60.13 ±22.32, 76.00 ±9.96) was signifi-cantly higher than those in other three groups and which were the highest in hypoxic cisplatin group (P<0.05).There were significant positive correlations among them in hypoxic group and hypoxic cisplatin group (r =0.686,P <0.05;r =0.546,P <0.05). Conclusion The hypoxia microenvironment may be related to the cisplatin resistance of Hela cervical cancer cells .The possible mechanism is hypoxia activates Twist and upregulates MDR 1 expression , resulting in cisplatin resistance of Hela cells .

Nucleic acid aptamer is an oligonucleotide generated by the systematic evolution of ligands by exponential enrichment (SELEX)process from oligonucleotide library.Nucleic acid aptamer can bind to various targets with high specificity and can recognize or inhibit the biological activity of targeting molecular. Glioma-specific aptamers are developed by either targeting the glioma cells or known biomarkers,which can be coupled with nanoparticles,drugs or molecular probes,and can be applied in the imaging,targeted therapy and drug delivery of glioma.

Objective:To explore the effect of regular aerobic exercise on oxidative stress, inflammatory reaction and apoptosis with a rat model of colitis.Methods:Forty-five C57BL/6 mice were randomly divided into a control group, a model group and a model exercise group, each of 15. Colitis was induced in the rats of the model and model exercise groups through administration of 3.5% sodium dextran sulfate. The control group and the model group were kept quiet in their cages, while the model exercise group performed voluntary wheel running for 8 weeks after the successful modelling. Any histopathological changes in the colon tissue were observed after hematoxylin and eosin staining. Oxidative stress, inflammatory reaction and apoptosis were measured from colon tissue homogenates.Results:Compared with the control group, the average expression of the tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and prostaglandin E2 (PGE2) as well as levels of reactive oxygen species (ROS), malondialdehyde (MDA) and nitric oxide (NO) and inducible nitric oxide synthase (iNOS) and Caspase-3 activity and the protein expression of cyclooxygenase 2 (COX2), nuclear factor kappa B (NF-κB) p65, apoptosis inducing factor (AIF), cytochrome c (Cyt C) and Bax had all increased significantly in the other two groups, while the levels of IL-10 and glutathione (GSH), the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the protein expression of Bcl-2 protein had decreased significantly in the model group. Compared with the model group, the average content of TNF-α, IL-1 β, IL-6, PGE2, ROS, MDA and NO, the activity of iNOS and Caspase-3 and the protein expression of COX2, NF-κB p65, AIF, CytC and Bax had decreased significantly, while that of IL-10 and GSH, the activity of SOD and GPx and the protein expression of Bcl-2 protein had increased significantly in the model exercise group.Conclusion:Regular aerobic exercise has a protective effect against colitis through improving oxidative stress, inflammation and apoptosis, at least in rats.

Objective To investigate the effects and mechanism of hypoxia on the growth and invasion of human cervical cancer Hela cells. Methods Hypoxia microenvironment was mimicked by cobalt chloride (CoCl2), in which the growth of Hela cells were determined by MTT method, the migration ability was detected by scratch test, and the expressions of HIF-1αand Vimentin protein were measured by immunofluorescence. Results The growth of Hela cells treated with 150 μmol/L of CoCl2 for 6 h was promoted. The migration ability in hypoxia group at 48 h was significantly higher than that in ordinary oxygen group. The expressions of HIF-lαand Vimentin in Hela cells in hypoxia group were significantly higher than those in ordinary oxygen group. There was significantly positive correlation between the expressions of HIF-1α and Vimentin (P < 0.05). Conclusion Hypoxia could promote the expression of HIF-lα, which then could up-regulate the expression of Vimentin , and finally enhanced the ability of invasion and metastasis of Hela cells.

Objective To investigate effect of paclitaxel on expression of programmed death ligand-1 ( PD-L1 ) in the surface of cervical cancer TC-1 cells and its mechanism. Methods ①The cells were divided into two groups: paclitaxel group, paclitaxel combined with PKD blocker (G? 6976) group. There were 4 concentration gradient and 5 holes for each group, and each hole has its corresponding concentration of drugs. Influence of paclitaxel on TC-1 cell viability and effect of PKD blocker G? 6976 on IC50 value of paclitaxel were evaluated by MTT method.②The cells were divided into 0. 9% sodium chloride solution ( NS) group and paclitaxel group, There were 5 holes of each group. Effect of paclitaxel on PD-L1 expression on the surface of TC-1 cells were measured by immunohistochemistry.③The cells were divided into 4 groups:NS+DMSO group, G? 6976 group, paclitaxel group and paclitaxel+G? 6976 group. There were 5 holes for each group. Effect of paclitaxel and G? 6976 on PD-L1 expression on the surface of TC-1 cells were measured by immunohistochemistry. The expressions of PD-L1 on the surface of cells were measured by immunofluorescence treated with different drugs. Results The IC50 value of paclitaxel was 40 μg·mL-1 in paclitaxel group, and 38. 9 μg·mL-1 in paclitaxel combined with PKD blocker G? 6976 group, without significant difference between the two groups (P>0. 05). The expression of PD-L1 in the surface of TC-1 cells were significantly higher in paclitaxel group than in negative control group [(88. 48±13. 44)% vs. (39. 59±5. 99)%, P<0. 05]. The expression of PD-L1 in the surface of TC-1 cells was (79. 7%±4. 7)% after treatment with paclitaxel combined with PKD blocker G? 6976 for 24 h, and it was significantly lower than that in paclitaxel group [(96. 8±2. 5)%, P<0. 05]. Conclusion Paclitaxel promotes the expression of PD-L1 in the surface of TC-1 cells, which could be significantly inhibited by blocking PKD pathway. Paclitaxel may exert its effect through PKD pathway.

Objective To explore the anti-tumor effect and the influence of antitumor immunity of PD-L1/PD-1 blocked by PD-1 antibody combined with cisplatin. Methods Tumor models were established by injecting TC-1 cells into C57BL/6 mice, and the mice were divided into four groups (n = 4). The tumor growth curves and survival curves were drawn to observe the anti-tumor effect. The tumors were then removed; and the PD-L1 and CD8+ T cells were analyzed by immunohistochemical method. Results The anti-tumor effect was greater in the cisplatin group , PD-1 antibody group , and PD-1 antibody plus cisplatin group than in the control group (P < 0.05). Expression of PD-L1 in the tumor tissues was markedly increased in the cisplatin group and it was obviously decreased in the combination group (P < 0.05). CD8+ T cells decreased in the cisplatin group; and expression of CD8+ T cells was significantly increased the combination group (P < 0.05). Conclusion The anti-tumor effect and anti-tumor immunity of cisplatin are enhanced by blocking PD-L1/PD-1 pathway with PD-1 antibody.

Norovirus ; chemistry ; Receptors, Virus ; physiology ; Viral Structural Proteins ; chemistry ; immunology ; Viral Vaccines ; immunology

Objective To study the biological characteristics of cypermethrin?resistance strain and?susceptible strain of Ae?des albopictus under different controlled temperatures in the laboratory. Methods The two strains were raised at three different temperatures 20 25℃and 28℃respectively and the biological characteristics of the two mosquito strains such as reproduc?tion development and life expectancy were observed and recorded in the laboratory. Results The life expectancy of both strains became shorter as the temperature raised and the resistant strain 69.37%± 0.01% 77.04%± 0.07% lived shorter than the susceptible strain 85.24%±0.03% 88.23%±0.05% in average. Under 25℃ the hatching rate of resistant strain decreased by 25.88% and the pupation rate decreased by 11.18%. In the three temperatures all the life expectancy expanded as the tem?perature went up the periods for the susceptible strain were 19.75±0.10 23.65±0.07 d and 25.08±0.08 d under 28 25℃and 20℃. While life expectancy for the resistant strain decreased to 17.21±0.09 20.95±0.09 22.58±0.10 d. Under the same tem?perature the development timing of the resistance strain was longer than that of the susceptible strain and the period was the longest under 28 ℃ 156.2 h 137.1 h . In the three temperatures all the development periods expanded as the temperature went up the susceptible and resistant larvae developed 137.1 d and 163.3 d 247.7 d and 156.2 d 182.3 d and 263.2 d under 28 25℃and 20℃. The differences show statistic significance P<0.05 . Conclusion The resistance of A. albopictus to cy?permethrin results in the decrease of adaptability to the environment change and the disadvantage of reproduction at different temperatures.

OBJECTIVETo observe the effects of qianggu electuary (QGE), a Chinese herbal preparation, on ovariectomy-induced osteoporotic rats.

METHODFemale Wistar rats were ovariectomized and administered QGE, calcium gluconate (CG) and longmu zhuanggu granules (LMZG) for 12 weeks. Bone mineral density (BMD), indexes of biomechanics and serum E2, Ca were detected in grouped rats including QGE, CG, LMZG and control groups.

RESULTQGE could significantly increase the BMD and maximum load, maximum stress YP-load of femora in the osteoporotic rats. The values of E2 in ovariectomized osteoporotic rats decreased, compared with those of control normal rats (P > 0.05), while in the QGE treated rats, the values of E2 increased.

CONCLUSIONQGE can increase the BMD and improve indexes of bone biomechanics in ovariectomized osteopotic rats, possibly due to its estrogen-like effect.

Animals ; Bone Density ; drug effects ; Calcium ; blood ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Estradiol ; blood ; Femur ; physiopathology ; Osteoporosis ; blood ; pathology ; physiopathology ; Ovariectomy ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Stress, Mechanical

This work was mainly studied the effects of the four alkaloids from Coptidis Rhizoma on the mouse peritoneal macrophages in vitro and preliminarily discussed the regulating mechanisms. The effect of alkaloids from Coptidis Rhizoma on the vitality of macrophages was measured by the MTT assay. The effect of alkaloids on the phagocytosis of macrophages was determined by neutral red trial and respiratory burst activity was tested by NBT. The expressions of respiratory-burst-associated genes influenced by alkaloids were detected by qRT-PCR. The conformation change of membrane protein in macrophages by the impact of alkaloids was studied by fluorospectro-photometer. Results showed that the four alkaloids from Coptidis Rhizoma could increase the phagocytosis of macrophages in different level and berberine had the best effect. Berberine, coptisine and palmatine had up-regulation effects on respiratory burst activity of mouse peritoneal macrophages stimulated by PMA and regulatory activity on the mRNA expression of PKC, p40phox or p47phox, whereas the epiberberine had no significant influence on respiratory burst. Moreover, alkaloids from Coptidis Rhizoma could change the conformation of membrane protein and the berberine showed the strongest activity. The results suggested that the four alkaloids from Coptidis Rhizoma might activate macrophages through changing the conformation of membrane protein of macrophages and then enhanced the phagocytosis and respiratory burst activity of macrophages. Furthermore, the regulatory mechanism of alkaloids on the respiratory burst activity of macrophages may be also related to the expression level of PKC, p40phox and p47phox.
Alkaloids ; pharmacology ; Animals ; Cells, Cultured ; Coptis ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gene Expression ; drug effects ; Macrophages, Peritoneal ; drug effects ; Mice ; Phosphoproteins ; genetics ; metabolism ; Protein Kinase C ; genetics ; metabolism ; Rhizome ; chemistry