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Purpose@#Isocitrate dehydrogenase 1 (IDH1) mutations are the most common genetic abnormalities in low-grade gliomas and secondary glioblastomas. Glioma patients with these mutations had better clinical outcomes. However, the effect of IDH1 mutation on drug sensitivity is still under debate. @*Materials and Methods@#IDH1-R132H mutant cells were established by lentivirus. IDH1-R132H protein expression was confirmed by western blot. The expression of ataxia telangiectasia mutated (ATM) signaling pathway and apoptosis-related proteins were detected by immunofluorescence and western blot. Temozolomide (TMZ) induced cell apoptosis was detected by flow cytometry. Tumor cell proliferation was detected by Cell Counting Kit-8. In vivo nude mice were used to confirm the in vitro roles of IDH1 mutation. @*Results@#We established glioma cell lines that expressed IDH1-R132H mutation stably. We found that TMZ inhibited glioma cells proliferation more significantly in IDH1 mutant cells compared to wild type. The IC50 of TMZ in IDH1-R132H mutant group was less than half that of wild-type group (p < 0.01). TMZ significantly induced more DNA damage (quantification of γH2AX expression in IDH1 mutation vs. wild type, p < 0.05) and apoptosis (quantification of AnnexinV+propidium iodide–cells in IDH1 mutation versus wild type, p < 0.01) in IDH1 mutant gliomas compared to wild-type gliomas. The ATM-associated DNA repair signal was impaired in IDH1 mutant cells. Inhibiting the ATM/checkpoint kinase 2DNA repair pathway further sensitized IDH1 mutant glioma cells to chemotherapy. We found that IDH1 mutation significantly inhibited tumor growth in vivo (the tumor size was analyzed statistically, p < 0.05). Moreover, we confirmed that gliomas with IDH1 mutation were more sensitive to TMZ in vivo compared to wild type significantly and the results were consistent with the in vitro experiment. @*Conclusion@#These results provide evidence that combination of TMZ and ATM inhibitor enhances the antitumor effect in IDH1 mutant gliomas.
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Purpose@#Isocitrate dehydrogenase 1 (IDH1) mutations are the most common genetic abnormalities in low-grade gliomas and secondary glioblastomas. Glioma patients with these mutations had better clinical outcomes. However, the effect of IDH1 mutation on drug sensitivity is still under debate. @*Materials and Methods@#IDH1-R132H mutant cells were established by lentivirus. IDH1-R132H protein expression was confirmed by western blot. The expression of ataxia telangiectasia mutated (ATM) signaling pathway and apoptosis-related proteins were detected by immunofluorescence and western blot. Temozolomide (TMZ) induced cell apoptosis was detected by flow cytometry. Tumor cell proliferation was detected by Cell Counting Kit-8. In vivo nude mice were used to confirm the in vitro roles of IDH1 mutation. @*Results@#We established glioma cell lines that expressed IDH1-R132H mutation stably. We found that TMZ inhibited glioma cells proliferation more significantly in IDH1 mutant cells compared to wild type. The IC50 of TMZ in IDH1-R132H mutant group was less than half that of wild-type group (p < 0.01). TMZ significantly induced more DNA damage (quantification of γH2AX expression in IDH1 mutation vs. wild type, p < 0.05) and apoptosis (quantification of AnnexinV+propidium iodide–cells in IDH1 mutation versus wild type, p < 0.01) in IDH1 mutant gliomas compared to wild-type gliomas. The ATM-associated DNA repair signal was impaired in IDH1 mutant cells. Inhibiting the ATM/checkpoint kinase 2DNA repair pathway further sensitized IDH1 mutant glioma cells to chemotherapy. We found that IDH1 mutation significantly inhibited tumor growth in vivo (the tumor size was analyzed statistically, p < 0.05). Moreover, we confirmed that gliomas with IDH1 mutation were more sensitive to TMZ in vivo compared to wild type significantly and the results were consistent with the in vitro experiment. @*Conclusion@#These results provide evidence that combination of TMZ and ATM inhibitor enhances the antitumor effect in IDH1 mutant gliomas.
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BACKGROUND: Porosity has been proven to improve the stability of orthopedic implants, and the architecture of pores is considered as a significant factor to improve the osseointegration of implants. OBJECTIVE: To introduce the research advance in porous architecture. METHODS: WOS database was searched for the articles addressing the porous structure of the implants published from January 2000 to April 2016 using the keywords of scaffold, pore size, porosity, osteogenesis. The literatures were screened according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION: (1) The stability of traditional implants cannot meet the requirements in some specific circumstances, while the implants with porosity can improve the stability due to its osteogenesis ability. (2) Porous structure is a hotspot, and the osseointegration of porous implants in vivo is explored through series of in vitro and in vivo experiments. (3) It has been shown that higher porosity, proper pore size, microporous morphology and microstructure of the pore wall may contribute to the growth and differentiation of bone tissue under enough mechanical support. (4) However, most studies on the porous implants are still on the in vivo and animal experimental stage, and its promoting effects on the osteogenesis and bone in-growth are needed to be investigated in depth.
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BACKGROUND:Titanium alloy, a commonly used bone biomaterial, holds good biocompatibility and proper mechanical properties, but without osteointegration ability. Surface bioactive coating of titanium alloy can overcome such problems. OBJECTIVE:To review the application progress of surface bioactive coating on titanium alloys, and to explore the mechanism underlying its osteogenic induction. METHODS:PubMed and CNKI databases were searched for literatures concerning surface bioactive coating on titanium alloys published from January 2000 to March 2016, using the keywords oftitanium, titanium alloys, coating, surface modification, bonein English and Chinese, respectively. Through preliminary analysis, 42 eligible articles were selected. RESULTS AND CONCLUSION:The surface modification method has undergone the transition from surface roughening, oxidation, acidification treatment to the most widely used biomimetic coating technology. The surface biomimetic coatings of titanium alloys mainly include hydroxyapatite, bioactive glass, zeolite, which have been developed from a single coating to the composite coatings and gradient coatings. What's more, the bioactive factor or/and metal ions in the coating can improve the osteointegration of surface coating. Surface modification for titanium alloys is a complex process, during which, both the osteogenesis ability and the bonding strength between the coating and its substrate cannot be ignored. Improving the fabrication method of existing coatings and exploring new materials of biomimetic coatings are critical to achieve a high-quality surface coating modification.
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In order to improve the comprehensive quality and innovation ability of undergraduates, we integrate the pharmacognosy, natural medicine chemistry, pharmaceutical chemistry, pharmaceutical analysis, pharmacy, pharmacology experiment module in accordance with the drug development program, to construct multidisciplinary innovative pharmaceutical experiment course. Besides, we carry out teaching with scientific research mode, scientific evaluation to assess the effects and making analysis to expose the prob-lems, which lay a solid foundation for establishment of the innovative pharmacy experiment in the future.
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BACKGROUND:Surface modification of titanium surface to improve its biological activity is the research hotspot. Strontium-doped coating is considered to be an effective approach to promote the implant osseointegration. OBJECTIVE:To introduce the research progress of strontium-modified biomedical titanium al oys.METHODS:Articles related to the medical titanium al oys modified with strontium published from January 2000 to April 2016 were retrieved from CNKI and PubMed databases. The keywords were“titanium (Ti), strontium (Sr), bone, osteogenic”in Chinese and English, respectively. RESULTS AND CONCLUSION:Titanium al oys have been widely used in bone implantation because of their good biocompatibility and similar elasticity modulus with human bones. However, pure titanium al oys have poor bioactivity which leads to weak bone-implant contact. Surface modification is a good approach to enhance implant osseointegration. Sr-doped surface treatment can promote new bone formation and osseointegration. Most of the studies about Sr-doped modification are ongoing at the extracorporeal and animal experiment stage;therefore, further investigation is required to seek rapid, stable, available, safe and effective methods.
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@#Recent advances in immunology and genetics have verified that the innate immune and adaptive immune responses that mediated by T cells, have been considered to play an important role in inducing inflammatory bowel disease. It’s difficult to cure the disease due to the complexity of the disease. However, the development and application of medicine, which target the immune response in the colon, attract great attention in recent years. In present, there are two types of targeting drugs in the intestinal immune systems: one of them targets the intestinal innate immune system, which includes targeting signal transduction, signal molecule and lymphocytes while the other targets adaptive immune system that includes inhibition of intenstinal T cell activation, differentiation and regulation of T cell cytokines and balance of T cell. This article mainly gives a comprehensive overview in four aspects, which include the intestinal innate immune response, adaptive immune response, drugs targeting in the intestinal innate and adaptive immune response. Furthermore, research directions are also pointed out in the review.
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Objective To study the test-retest reliability in quantitative measurement of proprioception using Tecnobody rehabilitation system.Methods Nine healthy volunteers [4 males,5 females,averaged age (22.8 ±0.68) years] participated in three consecutive measurements on both feet by using Tecnobody rehabilitation system for computerized proprioceptive assessment.Standard error of measurement(SEM),correlation coefficient and intraclass correlation coefficient(ICC) obtained from the three consecutive measurements were used to analyze the Timeused in each measuring session,and the average track error (ATE) of the measurements.ResultsSEM values of Time in left foot and right foot were 3.07 ～ 3.83 and 6.65 ～ 8.44 respectively.ATE values in left foot and right foot were 1.33 ～ 1.97 and 1.39 ～ 1.91 respectively.The Time and ATE correlation coefficients of left foot / right foot were 0.919/0.6 and 0.808/0.831,respectively.The Time ICC values were 0.893/0.639 for left foot / right foot,respectively ; and the ATE ICC values were 0.716/0.734 for left foot / right foot,respectively. Conclusion The Tecnobody rehabilitation system provided a fairly good reliability in both relative andabsolute values in quantitative evaluation of proprioception in the feet.These data in a larger amount may be useful for setting up variables and the standard values of the local population for reference in proprioceptive rehabilitation.