激光近形制造钛合金试件力学性能的初步研究

目的 比较激光近形制造技术和铸造技术制作的钛合金试件的材料性能,探索激光快速成形此新工艺在口腔修复领域中的应用.方法 以-200～325目气雾化法制备的球形钛合金粉末为原料,应用激光近形制造技术制作钛合金试件,测试其在拉伸试验中的抗拉强度、屈服强度,三点弯曲试验中的弯曲弹性模量、抗弯强度,以及维氏显微硬度,并与铸造技术制作的钛合金试件进行对比;观察两种不同加工方法制作的钛合金试件的组织结构,以及拉伸断口的微观形貌特征.结果 激光近形制造技术制作钛合金试件,成形速度快,成形件无缺陷,其抗拉强度、屈服强度、弯曲弹性模量、抗弯强度、维氏显微硬度分别为(1 056.92±61.69)N/mm2、(62.65±61.91)N/mm2、(133 722.62±3 618.18)MPa、(2 313.42±129.16)MPa、376.24±14.88.激光近形制造试件的抗拉强度、屈服强度显著高于铸造钛合金试件.金相显微镜显示激光近形制造钛合金试件的组织为针状细枝晶的微晶结构,拉伸断口呈现均匀细致的韧窝形貌,发生韧性断裂.结论 激光近形制造技术可以满足口腔修复的加工要求,但需要进一步研究其成形性能及提高精度.     

Modeling therapy resistance in genetically engineered mouse cancer models

Resistance to anti-cancer drugs is a major obstacle in successful treatment of cancer. Multidrug resistance is not only observed with clinically established chemotherapeutics, but also with novel targeted therapies. Although a range of drug resistance mechanisms have been identified up till now, for most drugs it is still controversial which mechanisms are responsible for resistance and therapy failure in patients. Hence, the development of strategies to circumvent drug resistance is often unfocused. Since several years genetically engineered mouse models have been generated which develop tumors that closely resemble cancer in humans. We argue that such models can be used to investigate relevant in vivo mechanisms of resistance. This includes the analysis of intrinsic and acquired resistance, and the characterization of residual cells which survive the treatment. In such model systems different drugs and therapy combinations can be optimized prior to clinical trials.     

Influence of insulin-like growth factor-I (IGF-I) on nerve autografts and tissue-engineered nerve grafts

To overcome the problems of limited donor nerves for nerve reconstruction, we established nerve grafts made from cultured Schwann cells and basal lamina from acellular muscle and used them to bridge a 2-cm defect of the rat sciatic nerve. Due to their basal lamina and to viable Schwann cells, these grafts allow regeneration that is comparable to autologous nerve grafts. In order to enhance regeneration, insulin-like growth factor (IGF-I) was locally applied via osmotic pumps. Autologous nerve grafts with and without IGF-I served as controls. Muscle weight ratio was significantly increased in the autograft group treated with IGF-I compared to the group with no treatment; no effect was evident in the tissue-engineered grafts. Autografts with IGF-I application revealed a significantly increased axon count and an improved g-ratio as indicator for "maturity" of axons compared to autografts without IGF-I. IGF-I application to the engineered grafts resulted in a decreased axon count compared to grafts without IGF-I. The g-ratio, however, revealed no significant difference between the groups. Local administration of IGF-I improves axonal regeneration in regular nerve grafts, but not in tissue-engineered grafts. Seemingly, in these grafts the interactive feedback mechanisms of neuron, glial cell, and extracellular matrix are not established, and IGF-I cannot exert its action as a pleiotrophic signal.     

Advances in molecular carcinogenesis: current and future use of mouse models to screen and validate molecularly targeted anticancer drugs

Survival of patients with advanced solid tumors has not significantly improved over the past 30 years. Although molecularly targeted anticancer drugs offer promise, few drugs make it through the end of the Food and Drug Administration approval process. Animal models that more closely resemble human carcinogenesis may bridge the gap between preclinical success and benefits for patients. We discuss pros and cons of several mouse models, including genetically engineered mice that each represent different aspects of human cancer, and the screening of targeted drugs in these models.     

Tumor reversion: correction of malignant behavior by microenvironmental cues

Cancer is characterized by unrestrained proliferation and loss of organization, a process that is intimately linked to, and controlled by, reciprocal signaling between the genetically altered tumor epithelium, the stroma, the components of the basement membrane and inflammatory mediators. Much work has been done to characterize the genetics of cancer cells. In this review, we describe the experiments that have been performed, which point to the significant role of the tissue microenvironment in the developmental regulation of normal and neoplastic cells. Using a variety of model systems, the works of a number of laboratories have converged on a hypothesis where the correction of 1 or 2 signaling defects can revert tumor cells to a normal phenotype, both in vivo and in culture, even when the tumor cells possess multiple genetic and epigenetic lesions. This paradigm has been successfully used to treat acute promyelocytic leukemia, and it remains the task of biomedical researchers to identify additional targets for the reversion of other human malignancies.     

蚕丝组织工程肌腱修复肌腱缺损的实验性研究

[目的]探讨用蚕丝与同种异体肌腱细胞联合培养植入体内,构建组织工程化肌腱的可行性。[方法]以罗曼鸡为实验对象分两组,术后第2、4、6、8周进行病理学检查、生物力学和拉伸度的测定。数据采用SPSS 13.0进行统计分析。[结果]细胞组在胶原的合成以及力学检测均明显优于非细胞组(P0.05)。[结论]本实验的结果说明蚕丝材料对肌腱细胞的吸附明显,降解缓慢,抗拉性能优越,构成组织工程化肌腱,可能会在肌腱缺损的治疗方面发挥出巨大潜能。     

Enzymatic synthesis of myricetin 3-O-galactoside through a whole-cell biocatalyst

Objective: Myricetin 3-O-galactoside is an active compound with pharmaceutical potential. The insufficient supply of this compound becomes a bottleneck in the druggability study of myricetin 3-O-galactoside. Thus, it is necessary to develop a biosynthetic process for myricetin 3-O-galactoside through metabolic engineering. Methods: Two genes OcSUS1 and OcUGE1 encoding sucrose synthase and UDP-glucose 4-epimerase were introduced into BL21(DE3) to reconstruct a UDP-D-galactose (UDP-Gal) biosynthetic pathway in Escherichia coli. The resultant chassis strain was able to produce UDP-Gal. Subsequently, a flavonol 3-O-galactosyltransferase DkFGT gene was transformed into the chassis strain producing UDP-Gal. An artificial pathway for myricetin 3-O-galactoside biosynthesis was thus constructed in E. coli. Results: The obtained engineered strain was demonstrated to be capable of producing myricetin 3-O-galactoside, reaching 29.7 mg/L. Conclusion: Biosynthesis of myricetin 3-O-galactoside through engineered E. coli could be achieved. This result lays the foundation for the large-scale preparation of myricetin 3-O-galactoside.     

Anti-tumor effect of the alphavirus-based virus-like particle vector expressing prostate-specific antigen in a HLA–DR transgenic mouse model of prostate cancer

The goal of this study was to determine if an alphavirus-based vaccine encoding human Prostate-Specific Antigen (PSA) could generate an effective anti-tumor immune response in a stringent mouse model of prostate cancer. DR2bxPSA F₁ male mice expressing human PSA and HLA-DRB1^*1501 transgenes were vaccinated with virus-like particle vector encoding PSA (VLPV–PSA) followed by the challenge with Transgenic Adenocarcinoma of Mouse Prostate cells engineered to express PSA (TRAMP–PSA). PSA-specific cellular and humoral immune responses were measured before and after tumor challenge. PSA and CD8 reactivity in the tumors was detected by immunohistochemistry. Tumor growth was compared in vaccinated and control groups. We found that VLPV–PSA could infect mouse dendritic cells in vitro and induce a robust PSA-specific immune response in vivo. A substantial proportion of splenic CD8 T cells (19.6 ± 7.4%) produced IFNγ in response to the immunodominant peptide PSA_65–73. In the blood of vaccinated mice, 18.4 ± 4.1% of CD8 T cells were PSA-specific as determined by the staining with H-2D^b/PSA_65–73 dextramers. VLPV–PSA vaccination also strongly stimulated production of IgG2a/b anti-PSA antibodies. Tumors in vaccinated mice showed low levels of PSA expression and significant CD8+ T cell infiltration. Tumor growth in VLPV–PSA vaccinated mice was significantly delayed at early time points (p = 0.002, Gehan–Breslow test). Our data suggest that TC-83-based VLPV–PSA vaccine can efficiently overcome immune tolerance to PSA, mediate rapid clearance of PSA-expressing tumor cells and delay tumor growth. The VLPV–PSA vaccine will undergo further testing for the immunotherapy of prostate cancer.