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1.
Mixed lineage leukemia 1(MLL1)是组蛋白甲基转移酶SET家族的成员之一。MLL1与WDR5、RbBP5、Ash2L和DPY-30组成MLL1甲基转移酶复合物调控组蛋白H3的第4位赖氨酸的甲基化水平,对造血系统的发育和血细胞的更新至关重要。部分白血病患者体内存在因MLL1基因易位而产生的致癌蛋白——MLL1融合蛋白,MLL1融合蛋白在发挥其致癌作用时需要功能完整的MLL1酶复合物,故靶向MLL1-WDR5的蛋白-蛋白相互作用成为治疗MLL1融合型白血病的潜在策略。本文对MLL1-WDR5蛋白-蛋白相互作用的生物学机制、结构信息以及抑制剂进行了系统的总结,并结合已报道数据对该领域进行了展望,以期为后续研究提供参考。 相似文献
2.
淫羊藿是一种常用的中药材,淫羊藿苷是从淫羊藿中提取的一种黄酮类化合物,也是淫羊藿中最主要的活性物质。研究发现,淫羊藿苷具有促进成骨细胞的生成和活化、调节免疫、抗衰老和抗炎等多种功能。临床上淫羊藿(苷)用于治疗生殖系统、骨关节系统、呼吸系统、神经系统、心血管系统和免疫系统等多种疾病。淫羊藿(苷)对男性生殖系统的作用及机制主要包括具有雄性激素样作用,促进睾内睾酮的合成和分泌。淫羊藿(苷)通过改善精子发生的微环境、增强睾丸抗氧化作用促进精子生成,增加精子密度,改善精子活力,减缓生殖衰退。此外,淫羊藿(苷)可促进阴茎勃起,治疗勃起功能障碍及早泄。 相似文献
3.
《Journal of pharmaceutical sciences》2023,112(8):2212-2222
For supersaturating formulations of BCS-II compounds, which by definition have high intestinal permeability, a closed USP apparatus does not provide the necessary absorptive conditions during dissolution. To address this, an artificial gut simulator (AGS) has been constructed consisting of a 2.5 mL donor compartment in which a hollow fiber-based absorption module is suspended. Drug from donor diffuses across the hollow fiber membrane to be absorbed by the continuously flowing intraluminal receiver fluid. The membrane surface area and intraluminal fluid flow rate are tuned to obtain the physiologically observed absorption rate constant for a weakly basic, poorly water-soluble model compound, ketoconazole (KTZ). Supersaturated solutions of KTZ were generated in the donor in pH 6.5 phosphate buffer by the pH-shift method in the absence (closed system, control) and presence (open system, biorelevant) of an optimally or suboptimally tuned absorption module. Drug concentrations in the donor and intraluminal fluids were determined by in-line UV spectroscopy. The presence of an absorptive sink reduced the supersaturated solution's crystallization propensity, more so in the case of the optimally tuned AGS. This study demonstrates the significance of simulating absorption of drug at a physiological rate during dissolution studies, especially to predict the performance of formulations of BCS-II drugs. 相似文献
4.
长三角一体化上升并发展为国家战略后,国内鲜有探讨长三角地区生物医药产业一体化协同发展的研究,长三角作为我国生物医药产业的重要地区,已初步形成产业集群的发展模式。本研究基于专利及基金项目合作的产学研模式,利用社会网络分析方法(SNA)对长三角地区生物医药产业中专利和国家自然科学基金重大项目合作进行分析研究。研究表明,长三角地区生物医药领域的产学研合作还处于发展阶段,一体化程度也有待提高;高校及科研院所更倾向于与企业合作开展发明专利,与高校合作开展基金项目研究。长三角地区三省一市间的生物医药产业发展也存在一定差距,建议长三角地区采取产学研深度融合模式,相关龙头科研机构建立开放式创新平台,医药类高校借助学科优势培养创新型人才,采取“揭榜挂帅”等方式进行关键核心技术攻关。 相似文献
5.
《Journal of pharmaceutical sciences》2023,112(8):2249-2259
A serious challenge in transdermal iontophoresis (IP) delivery of insulin (INS) is the low permeability of the drug across the skin. In this paper, we introduced deep eutectic solvent (DESs) as novel chemical penetration enhancers (CPEs) for transdermal IP of INS across rat skin, both in vitro and in vivo. Three different DESs based on choline chloride (ChCl), namely, ChCl/UR (ChCl and urea), ChCl/GLY (ChCl and glycerol), and ChCl/EG (ChCl and ethylene glycol) in the 1:2 molar ratios have been prepared. To evaluate the capability of studied DESs as CPEs for IP delivery of INS, the rat skin sample was treated with each DES. The effects of different experimental parameters (current density, formulation pH, INS concentration, NaCl concentration, and treatment time) on the in vitro transdermal iontophoretic delivery of INS were investigated. The in vitro permeation studies exhibited that INS was easily delivered employing ChCl/EG, and ChCl/GLY treatments, compared with ChCl/UR: the cumulative amount of permeated INS at the end of the experiment (Q24h) was found to be 131.0, 89.4, and 29.6 µg cm−2 in the presence of ChCl/EG, ChCl/GLY, and ChCl/UR, respectively. The differences in Q24h values of INS are due to the different capabilities of the studied DESs to treat the epidermis layer of skin. In vivo experiments revealed that the blood glucose level in diabetic rats could be decreased using ChCl/EG, and ChCl/GLY as novel CPEs in the IP delivery of INS. The presented work will open new doors towards searching for novel CPEs in the development of transdermal IP of INS. 相似文献
6.
Collagen type II-induced arthritis (CIA) in Dark Agouti rats, a model of rheumatoid arthritis (RA), reproduces sexual dimorphism in the incidence and severity of the human disease. Th17 cells are central in the induction/propagation of autoimmune inflammation in CIA and RA. To assess mechanisms underlying this dimorphism in CIA rats, in lymph nodes draining inflamed joints and adjacent tissues (dLNs) from CIA rats of both sexes Th17/CD25+Foxp3+CD4+ T-regulatory cell (Treg) ratio, Th17 cell redifferentiation in functionally distinct subsets and Treg transdifferentiation into IL-17-producing cells (exTregs) were examined. In female rats (developing more severe CIA than their male counterparts) the higher frequency of all Th17 cells (reflecting partly their greater proliferation), followed by the higher frequency of highly pathogenic IFN-γ/GM-CSF-co-producing cells, but lower frequency of less pathogenic/immunoregulatory IL-10-producing cells among them was found. Additionally, compared with male rats, in female rats the lower frequency of Tregs was observed. Moreover, Tregs from female rats exhibited diminished proliferative and suppressive capacity (judging by PD-1 expression) and enhanced conversion into IL-17-producing cells. Given that TGF-β concentration was comparable in collagen-type II-stimulated dLN cell cultures from female and male rats, the shift in Th17/Treg ratio followed by augmented Th17 cell redifferentiation into IFN-γ/GM-CSF-co-producing cells and Treg transdifferentiation into IL-17-producing cells in female rats was associated with increased concentration of IL-6 in female rat dLN cell cultures, and the higher frequency of IL-1β- and IL-23-producing cells among their dLN cells. The lower frequency of IL-10-producing B cells, presumably B regulatory cells (Bregs) could also contribute to the shift in Th17/Treg ratio in female rat compared with male rat dLNs. Consistently, the lower expression of IL-35 (the cytokine promoting Treg expansion directly and indirectly, by favoring Breg expansion and conversion into IL-10/IL-35-producing cells) in female rat dLN cells was detected. Thus, the study identified putative cellular and molecular substrates of the sexual dimorphism in the immunopathogenesis and clinical outcome of CIA and suggested mechanisms to be targeted in females to improve control of Th17 response, and consequently clinical outcome of CIA, and possibly RA. 相似文献
7.
8.
丙型肝炎病毒(HCV)感染在慢性肾功能不全患者中较常见,尤其是在进行透析的患者中,HCV感染较普通患者的风险极大增加,同时还会导致肝细胞癌及肝硬化的发病率明显升高。近年来直接抗病毒药物(DAAs)在慢性丙型肝炎的治疗中取得了较好的疗效及安全性,本文通过总结DAAs在丙型肝炎合并透析患者中的应用进展,发现对于基因1~6型HCV合并透析患者,推荐使用G/P方案;由于索磷布韦(SOF)经肾脏代谢,在重度肾损害人群中的血药浓度较高,因此SOF组合方案并不推荐用于丙型肝炎合并透析患者的治疗。 相似文献
9.
10.
目的:为控制我国药品费用的不合理增长和促进医疗机构药学服务提供参考。方法:分析美国卫生系统药师协会制定的药品成本管理策略,对比我国医疗机构卫生现状,从而提出完善医疗机构药学工作,进行药品控费的建议。结果:美国药品成本管理策略建议医疗机构基于往年采购量(或金额)和使用量(或金额)开展药品预算管理;规范临床药师素质及临床药学服务质量的同时常态化开展交互治疗;成立药师参与临床治疗且获取医务人员支持的治疗小组;制定药品处方集并将成本较低、效果明显的药品纳入电子处方管理系统;建立药品使用替换制度,严格规范药品替换流程。结论:我国医疗机构可以开展药品预算研究来控制药品使用金额;通过提升临床药师技能来增强药师职业认知;加强药师医师沟通以明确两者职能分工;注重药师处方集制定并管控药品不合理使用;完善药品替换制度来规范药品使用管理。 相似文献