PKA对跨膜型和分泌TNF—α胞毒效应的影响

目的：研究ＰＫＡ对跨膜型ＴＮＦα（ｍＴＮＦ－α）杀瘤效应的影响。方法：用ＴＮＦ生物活性检测方法在体外观察ＰＫＡ激活剂和抑制剂对一型ＴＮＦ－α杀伤不同肿瘤细胞的影响。结果：ＰＫＡ激活剂Ｆｏｒｓｋｏｌｉｎ（１０μｍｏｌ／Ｌ）和抑制剂Ｈ８（１５μｍｏｌ／Ｌ）可分别增强和抑制ｓＴＮＦ－α对其第三靶细胞的胞毒活性,对其余４株耐受细胞却无逆转使用,而且对ｍＴＮＦ－α的胞毒效应无任何影响。此外,ＰＫＡ活性增强,     

Preparation and Characterization of Novel Temperature Sensitive Poly(N‐isopropylacrylamide‐co‐acryloyl beta‐cyclodextrin) Hydrogels with Fast Shrinking Kinetics

Summary: Novel temperature sensitive poly(N‐isopropylacrylamide‐co‐acryloyl beta‐cyclodextrin) (P(NIPA‐co‐A‐CD)) hydrogels with fast shrinking rates were prepared by radical polymerization of NIPA, A‐CD and crosslinker in a mixture of water/1,4‐dioxane as solvent. Because the mixed solvent was a poor solvent for the copolymers, phase separation occurred during the polymerization, which resulted in a heterogeneous, porous structure of the hydrogels. In contrast to the normal PNIPA hydrogel and the homo P(NIPA‐co‐A‐CD) gel prepared in water, the P(NIPA‐co‐A‐CD) hydrogels synthesized in water/1,4‐dioxane as solvent exhibited higher swelling ratios at the temperature below the lower critical solution temperature (LCST) and shrunk rapidly to equilibrium within shorter time when the temperature was increased above LCST. Increasing the acryloyl beta‐cyclodextrin content in the gels led to a slight decrease of the swelling ratio at lower temperature and had no marked influence on the shrinking kinetics. The gels prepared in water/1,4‐dioxane, at different v/v ratios of 1.0/0.2, 0.8/0.4 and 0.6/0.6, showed similar properties.

SEM photos of the heterogeneous P(NIPA‐co‐A‐CD) hydrogel prepared in water/1,4‐dioxane.     

青春期糖尿病雄鼠血清和性腺血管紧张素转换酶活性变化

４０日龄雄性Ｗｉｓｔａｒ大鼠２１只，分为对照（Ｃ）组，腹腔内注射赋形剂和糖尿病（Ｄ）组，腹腔内注射链脲菌素（ｓｔｒｅｐｔｏｚｏｔｏｃｉｎ，ＳＴＺ），５５ｍｇ／ｋｇ体重，观察６０天。结果表明，Ｄ组大鼠的睾丸、附睾、附睾尾重量显著低于Ｃ组（Ｐ＜０．０１）；Ｄ组附睾尾精子计数显著少于Ｃ组（Ｐ＜０．００１）。ＡＣＥ活性测定结果表明，Ｄ组睾丸和附睾尾组织ＡＣＥ活性显著低于Ｃ组（Ｐ＜０．０５），而血清ＡＣＥ显著高于Ｃ组（Ｐ＜０．０１），相关检验显示，附睾重量，附睾尾精子计数与附睾尾ＡＣＥ水平呈显著正相关（Ｐ＜０．０１），与血清ＡＣＥ呈显著负相关（Ｐ＜０．０５，Ｐ＜０．０１）。     

Analysis of fMRI data by blind separation of data in a tiny spatial domain into independent temporal component

Independent Component Analysis (ICA) is a promising tool for the analysis of functional magnetic resonance imaging (fMRI) time series. In these studies, mostly assumed is a spatially independent component map of fMRI data (spatial ICA). In this paper, we assume that the temporal courses of the signal and noises are independent within a Tiny spatial domain (temporal ICA). Then with fast-ICA algorithm, spatially neighboring fMRI data were blindly separated into several temporal courses and were preassumed to be formed by a signal time course and several noise time courses where the signal has the largest correlation coefficient with the reference signal. The final functional imaging was completed for the signals obtained from each voxel. Simulations showed that compared with the spatial ICA method, the new temporal ICA method is more effective than the spatial ICA in detecting weak signal in a fMRI dataset. As background noise, the simulations include simulated Gaussian noise and fMRI data without stimulation. Finally, vivo fMRI tests showed that the excited areas evoked by a visual stimuli are mainly in the region of the primary visual cortex and that evoked by auditory stimuli are mainly in the region of the primary temporal cortex.     

Synthesis and drug release behavior of poly (trimethylene carbonate)-poly (ethylene glycol)-poly (trimethylene carbonate) nanoparticles

ABA-type triblock copolymers poly (trimethylene carbonate)-poly (ethylene glycol)-poly (trimethylene carbonate) were synthesized by ring-opening polymerization of trimethylene carbonate initiated by dihydroxyl poly (ethylene glycol). The critical micelle concentration of amphiphilic triblock copolymers in aqueous solution was determined by fluorescence spectroscopy using 9-chloromethyl anthracene as fluorescence probe. Core-shell-type nanoparticles were prepared by the dialysis technique. Transmission electron microscopy images showed that these nanoparticles were regularly spherical in shape. Micelle size determined by dynamic light scattering is 50-160 nm. Anticancer drug methotrexate (MTX) as model drug was loaded in the polymeric nanoparticles. X-ray powder diffraction spectra showed that model drugs were molecularly dispersed in the core. In vitro release behavior of MTX was investigated.     

山紫菀与紫菀镇咳祛痰作用的实验研究

本实验对山紫菀(蹄叶橐吾Ligularia fischeri Turcz.)作了镇咳、祛痰作用的研究,并与紫菀(Aster tataricus L.)在同等条件下进行了比较,它们的浓缩水煎剂均有明显的祛痰作用,而无明显的镇咳作用,二者之间无显著性差异。它们的挥发油乳剂及水煎剂也均未表现出明显的镇咳作用。紫菀挥发油毒性大于山紫菀。     

建立Duchenne型肌营养不良鼠的骨髓移植模型

【目的】建立Duchenne型肌营养不良鼠(mdx鼠)的骨髓移植模型,摸索有效的放疗剂量。【方法】用体外培养的不同数量的C57BL/6雄鼠的骨髓细胞、骨髓基质细胞、骨髓悬浮细胞,用不同方法移植给不同剂量放疗后的mdx鼠,观察受体鼠的存活率及存活时间,并对死亡鼠作GVHD(移植物抗宿主病)的病理学检测。【结果】16只mdx鼠移植前3d12Gyγ射线照射,在移植后7d内全部死亡,且注射细胞数较多者,存活时间相对较长;8只经6Gyγ射线照射的mdx鼠,移植后60d,存活4只,其中1例经腹腔注射骨髓细胞、1例肌肉局部注射骨髓细胞,移植后7d内死亡;而8Gyγ射线照射的14只mdx鼠,移植后60d10例存活,4例死亡。【结论】本实验条件下,移植前8Gyγ射线放疗较合理,在有效剂量放疗破坏受体骨髓造血系统后,静脉注射移植同种鼠的骨髓细胞、基质细胞、悬浮细胞,mdx鼠存活率较高,且移植细胞数量以1×10     

Anti-Interleukin-6 Therapy Decreases Hip Synovitis and Bone Resorption and Increases Bone Formation Following Ischemic Osteonecrosis of the Femoral Head

Legg-Calvé-Perthes disease (LCPD) is a juvenile form of ischemic femoral head osteonecrosis, which produces chronic hip synovitis, permanent femoral head deformity, and premature osteoarthritis. Currently, there is no medical therapy for LCPD. Interleukin-6 (IL-6) is significantly elevated in the synovial fluid of patients with LCPD. We hypothesize that IL-6 elevation promotes chronic hip synovitis and impairs bone healing after ischemic osteonecrosis. We set out to test if anti-IL-6 therapy using tocilizumab can decrease hip synovitis and improve bone healing in the piglet model of LCPD. Fourteen piglets were surgically induced with ischemic osteonecrosis and assigned to two groups: the no treatment group (n = 7) and the tocilizumab group (15 to 20 mg/kg, biweekly intravenous injection, n = 7). All animals were euthanized 8 weeks after the induction of osteonecrosis. Hip synovium and femoral heads were assessed for hip synovitis and bone healing using histology, micro-CT, and histomorphometry. The mean hip synovitis score and the number of synovial macrophages and vessels were significantly lower in the tocilizumab group compared with the no treatment group (p < .0001, p = .01, and p < .01, respectively). Micro-CT analysis of the femoral heads showed a significantly higher bone volume in the tocilizumab group compared with the no treatment group (p = .02). The histologic assessment revealed a significantly lower number of osteoclasts per bone surface (p < .001) in the tocilizumab group compared with the no treatment group. Moreover, fluorochrome labeling showed a significantly higher percent of mineralizing bone surface (p < .01), bone formation rate per bone surface (p < .01), and mineral apposition rate (p = .04) in the tocilizumab group. Taken together, tocilizumab therapy decreased hip synovitis and osteoclastic bone resorption and increased new bone formation after ischemic osteonecrosis. This study provides preclinical evidence that tocilizumab decreases synovitis and improves bone healing in a large animal model of LCPD. © 2020 American Society for Bone and Mineral Research (ASBMR).