In vivo real-time imaging of gemcitabine-leaded growth inhibition in the orthotopic transplantation model of human pancreatic tumor

AbstractHuman xenograft mouse models, which have been used in cancer research for over a century, provided significant advances for our understanding of this multifaceted family of diseases. Orthotopic transplantation tumor models are emerging as the preference for cancer research due to the increasing clinical relevance over subcutaneous mouse models. In this study, a stable luciferase-expressed Capan-2 cell line was constructed and the expression of luciferase was tested. The results showed that the luminorescence intensity of Capan-2Luc cells was associated with the number of cells and the minimal detectable cell population was 600cells/well. We established an orthotopic transplantation model of pancreatic cancer using Capan-2Luc cell line in athymic mice and investigated the inhibitory effects of gemcitabine (Gem) in vitro and in vivo. Optical imaging system was applied to evaluate the tumor growth of orthotopic transplantation model in vivo. The results suggested that the orthotopic transplantation model of pancreatic cancer was well established and the luminorescence intensity of Gem-treated group was markedly lower than that of control group with an inhibitory rate of 56.8% (P<0.001). Our orthotopic transplantation model of pancreatic cancer and real-time imaging observation method established in this study could be an ideal model and a useful tool for therapeutic approaches for pancreatic cancers

Studies on Anti-Depressant Activity of Four Flavonoids Isolated from Apocynum venetum Linn (Apocynaceae) Leaf in Mice

Purpose: To investigate the anti-depressant activity of kaempferol, quercetin, kaempferol-3-O-β-Dglucose and quercetin-3-O-β-D-glucose isolated from Apocynum venetum Linn. (Apocynaceae) leaf and their mechanisms of action.Methods: The four flavonoids were isolated from Apocynum venetum leaf by chromatography. Mice were divided into vehicle, fluoxetine, kaempferol, quercetin, kaempferol-3-O-β-D-glucose and quercetin- 3-O-β-D-glucose groups (n = 10). Forced swimming (FST), tail suspension (TST) and locomotor activity (LAT) tests were used to evaluate the effects of the four flavonoids (0.35 mM/kg) on immobility time, monoamine neurotransmitters, viz, norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5- HT), as well as on the metabolite (5-HIAA) in mice brain and central nervous system (CNS) with the aid of video camera, HPLC-ECD and activity-monitoring system.Results: The four flavonoids significantly (p &lt; 0.05) reduced mice immobility time (72.58 - 90.24; 52.58 - 70.24 s), 5-HIAA levels (940.8 - 1244.7; 880.8 - 1164.1 ng/g) and 5-HIAA/5-HT ratio (1.77 - 4.76; 1.83 - 4.16), but increased NE, DA and 5-HT levels (238.7 - 405.7, 308.4 - 528.1, 261.4 - 531.9; 243.9 - 423.6, 296.7 - 534.9, 279.8 - 481.4 ng/g) in FST and TST, compared with control group (146.18, 126.18 s; 1363.4, 1240.9 ng/g; 7.43, 6.16; 138.4, 235.4, 183.4 and 143.7, 218.6, 201.4 ng/g). The effects of the four flavonoids on the above indices were significant (p &lt; 0.05) and positively related to their polarity. They had no CNS-stimulating effects in LAT.Conclusion: The anti-depressant activities of the four flavonoids are positively related to their polarity, and the mechanisms may be due to increased NE, DA and 5-HT and reduced 5-HT metabolism.Keywords: Kaempferol, Quercetin, Forced swimming test, Tail suspension test, Locomotor activity test, Neurotransmitter

Hierarchical Nanotube-Constructed Porous TiO₂-B Spheres for High Performance Lithium Ion Batteries

Hierarchically structured porous TiO(2)-B spheres have been synthesized via a hydrothermal process using amorphous titania/oleylamine composites as a self-sacrificing template. The TiO(2)-B spheres are constructed by interconnected nanotubes and possess a high specific surface area of 295 m(2) g(-1). When evaluated as an anode material in lithium-half cells, the as-obtained TiO(2)-B material exhibits high and reversible lithium storage capacity of 270 mA h g(-1) at 1 C (340 mA g(-1)), excellent rate capability of 221 mA h g(-1) at 10 C, and long cycle life with over 70% capacity retention after 1000 cycles at 10 C. The superior electrochemical performance of TiO(2)-B material strongly correlates to the synergetic superiorities with a combination of TiO(2)-B polymorph, hierarchically porous structure, interconnected nanotubes and spherical morphology. Post-mortem structural analyses reveal some discrete cubic LiTiO(2) nanodots formed on the outer surfaces of TiO(2)-B nanotubes, which might account for the slight capacity loss upon prolonged electrochemical cycling

Engineering 3D bicontinuous hierarchically macro-mesoporous LiFePO₄/C nanocomposite for lithium storage with high rate capability and long cycle stability

A highly crystalline three dimensional (3D) bicontinuous hierarchically macro-mesoporous LiFePO(4)/C nanocomposite constructed by nanoparticles in the range of 50~100 nm via a rapid microwave assisted solvothermal process followed by carbon coating have been synthesized as cathode material for high performance lithium-ion batteries. The abundant 3D macropores allow better penetration of electrolyte to promote Li(+) diffusion, the mesopores provide more electrochemical reaction sites and the carbon layers outside LiFePO(4) nanoparticles increase the electrical conductivity, thus ultimately facilitating reverse reaction of Fe(3+) to Fe(2+) and alleviating electrode polarization. In addition, the particle size in nanoscale can provide short diffusion lengths for the Li(+) intercalation-deintercalation. As a result, the 3D macro-mesoporous nanosized LiFePO(4)/C electrode exhibits excellent rate capability (129.1 mA h/g at 2 C; 110.9 mA h/g at 10 C) and cycling stability (87.2% capacity retention at 2 C after 1000 cycles, 76.3% at 5 C after 500 cycles and 87.8% at 10 C after 500 cycles, respectively), which are much better than many reported LiFePO(4)/C structures. Our demonstration here offers the opportunity to develop nanoscaled hierarchically porous LiFePO(4)/C structures for high performance lithium-ion batteries through microwave assisted solvothermal method

Intravenous Injections of Human Mesenchymal Stromal Cells Modulated the Redox State in a Rat Model of Radiation Myelopathy

The main aim of the present study was to assess the antioxidative effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of radiation myelopathy. UC-MSCs were isolated from Wharton’s jelly (WJ) of umbilical cords. An irradiated cervical spinal cord rat model (C2-T2 segment) was generated using a 60Co irradiator to deliver 30 Gy of radiation. UC-MSCs were injected through the tail vein at 90 days, 97 days, 104 days, and 111 days after-irradiation. Histological damage was examined by cresyl violet/Nissl staining. The activities of two antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPX) in the spinal cord were measured by the biomedical assay. In addition, the levels of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) in the spinal cord were determined by ELISA methods. Multiple injections of UC-MSCs through the tail vein ameliorated neuronal damage in the spinal cord, increased the activities of the antioxidant enzymes CAT and GPX, and increased the levels of VEGF and Ang-2 in the spinal cord. Our results suggest that multiple injections of UC-MSCs via the tail vein in the rat model of radiation myelopathy could significantly improve the antioxidative microenvironment in vivo

Efficacy, Safety, and Immunogenicity of an Escherichia coliProduced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial

HPV是一种常见的生殖道感染病毒，高危型HPV持续性感染能够导致几乎所有的宫颈癌，其中HPV 16型和18型危害最大，可导致约70%的宫颈癌。预防性HPV疫苗有望减少甚至最终消灭由疫苗型别导致的宫颈癌，降低HPV相关的疾病负担。该研究是在全国4个中心5个现场的18-45岁健康女性中进行的多中心、随机、双盲、对照（戊肝疫苗）的三期临床试验，该研究结果证实我校自主研发的双价人乳头瘤病毒疫苗（大肠杆菌）具有良好的安全性、免疫原性和免疫持久性，可有效地预防HPV 16型和/或18型相关的宫颈高度癌前病变及持续性感染。 该论文报告了我校和厦门万泰沧海生物技术有限公司自主研发的双价人乳头瘤病毒疫苗（大肠杆菌）三期临床试验的期中分析结果。这是第一个进入临床试验并提交药品注册申请的国产人乳头瘤病毒疫苗（HPV疫苗），有望成为世界上第四个上市的HPV疫苗，受到世界卫生组织和盖茨基金会等国际组织的高度关注。 中国医学科学院肿瘤医院乔友林教授、我校吴婷教授、广西壮族自治区疾病预防控制中心李荣成主任医师、江苏省疾病预防控制中心胡月梅主任医师、北京大学人民医院魏丽惠教授、中国食品药品检定研究院李长贵研究员、中国医学科学院肿瘤医院陈汶教授为该论文的共同第一作者，我校张军教授、夏宁邵教授和中国医学科学院肿瘤医院乔友林教授为该论文的共同通讯作者。【Abstract】Background The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase 3 clinical trial was conducted to evaluate the efficacy, safety and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multi-centre, randomized, double-blind trial started on November 22, 2012, in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receiving 3 doses of the test or control (hepatitis E) vaccine at months 0, 1 and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received 3 doses of the vaccine. This report presents data from a pre-specified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval [CI] = 55.6% to 100.0%, 0/3306 in the vaccine group vs. 10/3296 in the control group) and 97.8% (95% CI = 87.1% to 99.9%, 1/3240 vs. 45/3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The Escherichia coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18 associated high-grade genital lesions and persistent infection in women.This work was supported by grants from the Chinese National High-tech R&D Program (863 program, 2012AA02A408), the Chinese National Major Scientific and Technological Special Project for “Significant New Drug Development” (2018ZX09308010 and 2012ZX09101316), the National Natural Science Foundation of China (81673240 and U1705283), the Fujian Provincial Major Scientific and Technological Project (2015YZ0002), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS, 2017-I2M-B&R-03, and 2016-I2M-1-019) and Xiamen Innovax. 该研究获得了国家高技术研究发展计划（863计划）、新药创制国家科技重大专项、国家自然科学基金、福建省科技重大专项、中国医学科学院医学与健康科技创新工程基金以及厦门万泰沧海生物技术有限公司的资助

Establishment of a New Cell Line from Lepidopteran Epidermis and Hormonal Regulation on the Genes

When an insect molts, old cuticle on the outside of the integument is shed by apolysis and a new cuticle is formed under the old one. This process is completed by the epidermal cells which are controlled by 20-hydroxyecdysone (20E) and juvenile hormone. To understand the molecular mechanisms of integument remolding and hormonal regulation on the gene expression, an epidermal cell line from the 5th instar larval integument of Helicoverpa armigera was established and named HaEpi. The cell line has been cultured continuously for 82 passages beginning on June 30, 2005 until now. Cell doubling time was 64 h. The chromosomes were granular and the chromosome mode was from 70 to 76. Collagenase I was used to detach the cells from the flask bottom. Non-self pathogen AcMNPV induced the cells to apoptosis. The cell line was proved to be an epidermal cell line based on its unique gene expression pattern. It responded to 20E and the non-steroidal ecdysone agonist RH-2485. Its gene expression could be knocked down using RNA interference. Various genes in the cell line were investigated based on their response to 20E. This new cell line represents a platform for investigating the 20E signaling transduction pathway, the immune response mechanism in lepidopteran epidermis and interactions of the genes