Expression of RANK‐ligand in prostate cancer cell lines

The molecular mediators of bone remodelling, receptor activator of nuclear factor‐kappaB ligand (RANKL), receptor activator of nuclear factor‐kappaB (RANK) and osteoprotegerine (OPG), are believed to be involved in the cellular mechanisms by which tumours metastasize to bone. RANKL is a potent stimulator of osteoclastic bone resorption and is expressed in a variety of tumour cells. We have investigated if the membrane bound form of RANKL is expressed in prostate cancer cell lines, and whether this expression might be regulated by the presence of human osteoblasts. Three prostate cancer cell lines were co‐cultured with human osteoblast‐like cells (hOB) and RANKL expression on cell surface was measured by FACS. We found basal expression of RANKL on the cell surface, and in co‐culture with hOBs the number of cells expressing RANKL was increased between 2.5 and 4 times. These data suggest a signalling mechanism between bone cells and prostate cancer cells that might increase bone resorption and thereby promote bone metastases.     

白芍总苷对雷公藤多苷治疗狼疮性肾炎减毒增效作用的实验研究

目的 探讨白芍总苷(TGP)对雷公藤多苷(TG)治疗狼疮性肾炎(lupus nephritis,LN)小鼠的减毒增效作用.方法 取B6D2F1代杂交小鼠建立慢性移植物抗宿主病(cGVHD)LN小鼠模型,将成模小鼠随机分为3组,模型(LN)组、TG组、TG+TGP组,每组6只,另设正常对照组6只.TG组给予雷公藤多苷灌胃,剂量为30 mg·kg~(-1)·d~(-1);TG+TGP组给予雷公藤多苷及白芍总苷灌胃,剂量分别为30 mg·kg~(-1)·d~(-1)和200 mg·kg~(-1)·d~(-1),正常对照组和LN组分别给予等容量生理盐水灌胃,每日给药1次,各组给药方法及时间均相同,共计4周.实验结束时,观察并比较各组小鼠的24 h尿蛋白排泄率(UPE)、肝肾功能及肾脏病理改变.结果 与LN组相比,TG组、TG+TGP组小鼠的24 h UPE、尿素(BUN)、肌酐(SCr)显著降低(P＜0.05或P＜0.01),TG+TGP组显著低于TG组(P＜0.05或P＜0.01).与LN组相比,TG组小鼠的ALT、AST和MDA均显著增高(P＜0.01),SOD、GSH均显著降低(P＜0.05或P＜0.01).与TG组相比,TG+TGP组的ALT、AST、MDA均显著降低(P＜0.01),SOD、GSH均显著增高(P＜0.01).TG+TGP组对LN肾脏病理改变的改善作用显著优于TG组(P＜0.05或P＜0.01).结论 TGP对TG治疗LN具有减毒增效的作用.     

药用真菌新型(双向性)固体发酵工程对雷公藤解毒持效的初步研究

目的:探索对有毒中药雷公藤缓解毒性保持药效的新技术.方法:应用"约用真菌新型(双向性)固体发酵工程"(双向发酵)的原理和方法,以雷公藤为药性基质、多种药用真菌为发酵菌种,构成多组发酵组合,在一定条件下进行固体发酵,取得不同药性菌质,用所建"发酵组合三层优选法"进行发酵菌种优选,并对当选优秀发酵组合用"发酵过程成分、药效动态比较法"初步建立它的发酵工艺.结果:已筛选出具有解毒并保持免疫抑制作用的2种发酵真菌即灵芝、槐耳和适当的发酵工艺.结论:药用真菌双向性固体发酵工程可用于研究开发解毒持效的雷公藤菌质.     

采用多元定时释药技术制备雷公藤胃漂浮缓释胶囊的研究

目的:采用多元定时释药技术制备雷公藤胃漂浮缓释制剂.方法:采用挤出滚圆法,以90%十八醇为助漂剂制得空白胃漂浮微丸.使用流化床包衣设备,制备载药胃漂浮微丸.再以低取代羟丙基纤维素作为内溶胀层材料,以乙基纤维素水分散体作为外控释层材料进行包衣制备胃漂浮定时释药包衣微丸.等量称取控释层包衣增重分别为0%,8%,12%,15%,22%的包衣微丸,混均装入硬胶囊中,即得雷公藤胃漂浮缓释胶囊.结果:当溶胀层处方及用量固定后,通过控制控释层的厚度,可使包衣微丸在预期的不同时间定时释药.将几种控释层增重不同的包衣微丸混合后制成雷公藤胃漂浮缓释胶囊,在溶出介质中,均立即起漂,包衣微丸8 h漂浮率大于80%,并于不同时间依次释药,从而在整体上呈现出一种缓释特征.结论:采用多元定时释药技术制备而成的雷公藤胃漂浮缓释胶囊具有良好的漂浮性能和缓释特性.     

Study on the Magnetocaloric Effect of Room Temperature Magnetic Refrigerant Material La0.5Pr0.5(Fe1−xCox)11.4Si1.6 and the Effect Arising from Co Doping on Its Curie Temperature

The arc-melting method was adopted to prepare the compound La_0.5Pr_0.5(Fe_1−xCo_x)_11.4Si_1.6 (x = 0, 0.02, 0.04, 0.06, 0.08), and the magnetocaloric effect of the compound was investigated. As indicated by the powder X-ray diffraction (XRD) results, after receiving 7-day high temperature annealing at 1373 K, all the compounds formed a single-phase cubic NaZn₁₃ crystal structure. As indicated by the magnetic measurement, the most significant magnetic entropy change |∆S_M(T)| of the sample decreased from 28.92 J/kg·K to 4.22 J/kg·K with the increase of the Co content under the 0–1.5 T magnetic field, while the Curie temperature T_C increased from 185 K to the room temperature 296 K, which indicated that this series of alloys are the room temperature magnetic refrigerant material with practical value. By using the ferromagnetic Curie temperature theory and analyzing the effect of Co doping on the exchange integral of these alloys, the mechanism that the Curie temperature of La_0.5Pr_0.5(Fe_1−xCo_x)_11.4Si_1.6 and La_0.8Ce_0.2(Fe_1−xCo_x)_11.4Si_1.6 increased with the increase in the Co content was reasonably explained. Accordingly, this paper can provide a theoretical reference for subsequent studies.     

雷公藤多甙抑制大鼠精子发生的研究

目的探讨雷公藤多甙对大鼠精子发生的抑制作用及其可能的信号通路。方法成年雄性大鼠给予雷公藤多甙(16 mg/kg)灌胃,每日1次,在2及6周检测血清睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)和可的松水平;光镜观察睾丸组织的形态学变化;原位末端标记法(TUNEL)观察睾丸生精细胞凋亡;免疫组织化学法观察凋亡通路相关蛋白Bax/Bcl-2的表达。结果给药组与对照组相比,性激素、肾上腺皮质激素均无显著变化(P均>0.05);给药2周后精子数下降和畸形率上升(P<0.05),给药4和6周精子数下降和畸形率升高更显著(P<0.001);组织学检查给药组大鼠生精小管内各级精母细胞和精子细胞数明显减少,生精细胞排列紊乱,原始精原细胞和支持细胞(Sertoli细胞)未见明显改变。与正常对照组相比,生精小管内生精细胞凋亡显著增加(2周P<0.05,4和6周P<0.001)。凋亡相关蛋白Bax表达明显上调,Bcl-2表达无显著差异。结论雷公藤对大鼠精子发生的抑制作用表现为增加生精细胞凋亡,导致精子计数下降,精子的畸形率升高。雷公藤多甙使睾丸Bax表达增加,与诱导生精细胞凋亡相关,可能是相关的信号通路之一。进一步研究雷公藤多甙作用的分子信号机制有助于今后降低剂量、减少毒副作用,探讨其作为一种安全的男性避孕药可能性。     

中药安全性事件的危险因素与防治对策

回顾马兜铃酸、雷公藤、八角莲、槟榔、仙灵骨葆胶囊、鱼腥草注射剂、双黄连注射剂等引发的中药安全性事件,旨在探讨影响中药安全性的危险因素,对中药毒性成分、生产工艺、储藏条件、体质差异、给药剂量、风险管控等方面存在的安全性问题进行探讨,提出加强源头控制以确保质量合格、探明配伍机制以增效减毒、提高生产标准以推进质量统一、完善法规政策以加强管控、健全安全性评价体系以确保质量达标等建议,以期为促进临床合理用药、减少中药安全性事件提供帮助。     

Activating NK‐cell receptors co‐stimulate CD4+CD28− T cells in patients with rheumatoid arthritis

Effector T‐cell responses can be modulated by competing positive or negative signals transduced by NK‐cell receptors (NKR). In the CD4⁺ T‐cell population, the expression of NKR is primarily found in the CD4⁺CD28⁻ T‐cell subset, also known as CD28^null T cells. These T cells are frequently found in rheumatoid arthritis (RA) and other inflammatory disorders, suggesting that signaling through NKR may play a role in the autoimmune reaction. Here we aimed to dissect the phenotype and function of NKR‐expressing CD4⁺CD28⁻ T cells in patients with RA. By analyzing a broad array of NKR on CD4⁺CD28⁻ T cells we found a significant expression of the co‐activating receptors 2B4 (CD244), DNAM‐1 (CD226), and CRACC. Pair‐wise ligations of 2B4 with DNAM‐1 and/or NKG2D lead to increased effector functions of primary CD4⁺CD28⁻ T cells to suboptimal levels of anti‐CD3 stimulation. Using multi‐parameter flow cytometry, we demonstrate that such co‐ligation led to an increased magnitude in overall responsiveness without changing qualitative aspects of the response. Altogether these results demonstrate a pattern of additive effects in NKR‐mediated functional modulation of CD4⁺CD28⁻ T cells in RA. This may have consequences for the inflammatory responses imposed by these cells, thus influencing disease manifestations.     

Ligation of the OX40 co‐stimulatory receptor reverses self‐Ag and tumor‐induced CD8 T‐cell anergy in vivo

Tumor‐specific CD8 T‐cell peripheral tolerance occurs through clonal deletion, suppression, and the induction of anergy and can limit the generation of anti‐tumor immunity. Several groups have demonstrated that prostate cancer can render tumor‐specific CD8 T cells anergic, suggesting reversing tumor‐induced anergy may greatly augment anti‐tumor immunity. Recent work has demonstrated that signaling through the OX40 (CD134) co‐stimulatory receptor, a member of the TNFR super‐family, can augment CD4 and CD8 T‐cell expansion, differentiation, and the generation of memory cells. However, whether OX40 ligation can reverse CD8 T‐cell anergy, and more specifically, tumor‐induced CD8 T‐cell anergy, remains unclear. In the current study, we demonstrate that OX40 ligation can reverse CD8 T‐cell anergy to a prostate‐specific self‐Ag in non‐tumor‐bearing hosts. Furthermore, OX40 engagement reversed tumor‐specific CD8 T‐cell anergy and restored the proliferative capacity of tumor‐reactive CD8 T cells, which attenuated tumor growth and enhanced the survival of tumor‐bearing hosts. These data demonstrate that OX40 ligation can rescue the function of anergic self‐ or tumor‐reactive CD8 T cells in vivo and suggests that OX40‐mediated therapy may provide a novel means of boosting anti‐tumor immunity by restoring the responsiveness of previously anergic tumor‐specific CD8 T cells.     

Simple Preparation of Novel Metal-Containing Mesoporous Starches

Metal-containing mesoporous starches have been synthesized using a simple and efficient microwave-assisted methodology followed by metal impregnation in the porous gel network. Final materials exhibited surface areas >60 m² g⁻¹, being essentially mesoporous with pore sizes in the 10–15 nm range with some developed inter-particular mesoporosity. These materials characterized by several techniques including XRD, SEM, TG/DTA and DRIFTs may find promising catalytic applications due to the presence of (hydr)oxides in their composition.