99mTc-转铁蛋白-DTPA-Gd核素/磁性双模态分子影像探针基于转铁蛋白受体表达水平的肿瘤成像

背景与目的：转铁蛋白（Holo-Transferrin，Tf）受体（transferrin receptor，TfR）广泛存在于恶性肿瘤细胞膜表面，并被认为是抗肿瘤治疗的靶点。本研究旨在探讨^99mTc-Tf-DTPA-Gd在体、无创性检测多种人源性肿瘤TfR表达情况的可行性。方法：制作10种人肿瘤细胞的BALB/c裸小鼠移植瘤模型；经荷瘤鼠尾静脉注射^99mTc-Tf-DTPA-Gd或Tf-DTPA-Gd 4 h后行单光子发射计算机断层摄影术（single-photon emission computed tomography，SPECT）/计算机断层摄影术（computed tomography，CT）或磁共振成像（magnetic resonance imaging，MRI）检查，勾画感兴趣区（region of interest，ROI），计算靶本比值即靶区/肌肉组织（target-to-muscle ratios，T/M）或相对信号增强值（relative signal enhancement，rSE）；显像结束后取肿瘤组织行H-E染色及免疫组织化学染色，采用H-score法评估10种肿瘤表达TfR水平。选用两样本t检验及Spearman分析数据。结果：10种移植瘤模型均可用于成像。注射双模态探针4 h后，有9种肿瘤摄取^99mTc-Tf-DTPA-Gd，其中胶质瘤细胞U87的T/M值最高，乳腺癌细胞MDA-MB-468也有较高的T/M值；而前列腺癌细胞PC-3肿瘤几乎不摄取，T/M值接近1，与MDA-MB-468 T/M值相比差异有统计学意义（t=6.919，P=0.002）。MRI显示，MDA-MB-468肿瘤强化明显，rSE达（154.88±8.71）%，而PC-3肿瘤为（111.31±3.46）%，差异有统计学意义（t=8.441，P=0.001）。PC-3肿瘤几乎不表达TfR，其余9种肿瘤均不同程度地表达TfR。TfR免疫组织化学检测结果与探针的T/M值呈明显的正相关（相关系数为r=0.915，P<0.001）。结论：^99mTc-Tf-DTPA-Gd可在体、无创性反映肿瘤表达TfR受体情况。     

Tf ligand-receptor-mediated exenatide-Zn2+ complex oral-delivery system for penetration enhancement of exenatide

Safe and effective oral delivery of peptide is a challenge. Here, we used exenatide and zinc ions (Zn²⁺) to form a complex to explore a meaningful oral-targeted drug-delivery system. Polyethylene glycol-poly(lactic acid-co-glycolic acid) (PEG-PLGA) was used to prepare nanoparticles (NPs) to escape the degradation caused by gastrointestinal enzymes. Transferrin (Tf) was used as a targeting group. PEG-PLGA-NPs and Tf-modified exenatide-Zn²⁺-loaded NPs (Tf-PEG-PLGA-NPs) were uniformly sized spheres according to transmission electron microscopy. The results of pharmacodynamic and pharmacokinetic investigations in vivo were consistent with in vitro studies using Caco-2 cells. Tf enhanced NPs transport in cell-uptake and transmembrane-transport experiments. Our results showed that the relative bioavailability of Tf-exenatide-Zn²⁺-NPs was higher than that of exenatide-Zn²⁺-NPs. The relative bioavailability of Tf-exenatide-Zn²⁺-NPs versus subcutaneous injection of exenatide was 6.45%. This was a preliminary exploration of the oral administration of exenatide, that data from which can be used for future investigations.     

Lipid based nanocarriers: a translational perspective

Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside.     

血液透析患者血清SF、TSAT水平与营养状况的相关性分析

目的分析维持性血液透析(MHD)患者血清铁蛋白(SF)、转铁蛋白饱和度(TSAT)水平与营养状况的关系。方法选取MHD患者92例(MHD组)和健康体检者50例(对照组),所有受试对象均完成营养状况评估[改良主观综合营养评估法(MQSGA)]、营养生化指标检测[血清白蛋白(Alb)、血红蛋白(Hb)],并行血清SF、TSAT测定。根据MQSGA评分将MHD组进一步分为重度营养不良亚组、轻中度营养不良亚组、营养正常亚组。结果相较于对照组,MHD组BMI、TSF、MAC、HGS及血清A1b、血清Hb均明显降低(P <0.05),MQSGA评分明显增高(P <0.05)。MHD组血清SF明显高于对照组(P <0.05), TSAT明显低于对照组(P <0.05)。MHD患者不同营养状况亚组血清SF、TSAT水平比较差异有统计学意义(P <0. 05),随着营养不良状况越严重,患者血清SF逐渐增高(P <0. 05),TSAT逐渐降低(P <0.05)。相关性分析显示,MHD患者MQSGA评分与血清SF水平呈正相关(r=0.468,P<0.05),与TSAT水平呈负相关(r=-0.394,P<0. 05)。结论 MHD患者血清SF明显增高,TSAT明显降低,血清SF、TSAT水平可能与MHD患者营养不良相关。     

转铁蛋白受体1对淀粉样蛋白前体/早老素1转基因小鼠神经元的保护作用

目的 探讨转铁蛋白受体1(TfR1)在淀粉样蛋白前体（APP）/早老素1（PS1）转基因小鼠脑内异常表达情况及其对阿尔茨海默病（AD）神经元的保护作用。 方法 首先,利用免疫荧光及Western blotting技术检测出生后1月（P1M）至P12M各发育时间点,APP/PS1转基因小鼠与野生型小鼠大脑TfR1的表达情况;其次,取APP/PS1转基因与野生型新生小鼠原代海马神经元培养,培养12 d后利用TfR1 shRNA质粒干扰TfR1基因的表达,利用Western blotting技术检测干扰后细胞TfR1的表达变化;ELISA技术检测TfR1干扰前后细胞β-淀粉样蛋白(Aβ)_1-42的分泌量;利用微管相关蛋白2(MAP2)标记神经元突起,观察TfR1干扰前、后神经元突起的生长变化;最后,利用FM1-43染色观察由TfR1介导的轴质运输中囊泡的运输情况。 结果 在APP/PS1转基因小鼠生长发育过程中,随着年龄的增长TfR1的表达呈现先增加后减少的趋势,在P6M之后明显降低,且与对照组相比差异有显著性;TfR1 shRNA 干扰后可以使原代神经元细胞内TfR1基因沉默,使其突起明显变细、变长并影响囊泡的运输。与对照组相比,TfR1基因在APP/PS1转基因小鼠原代神经元中表达量减少,荧光减弱。 结论 APP、PS1基因突变可导致TfR1的表达下降;APP/PS1转基因小鼠原代神经元经TfR1 shRNA干扰Aβ_1-42分泌量增多,影响神经元突起的生长,使轴质运输速率减慢,囊泡的活动减缓,加重AD病情。故TfR1的表达可以对神经元起到保护作用。     

肝细胞癌转铁蛋白受体表达的免疫电镜研究

用转铁蛋白受体（ＴＦＲ）单抗ＯＫＴ５，以免疫电镜技术，对肝细胞癌（ＨＣＣ）ＴＦＲ的表达作亚细胞定位研究，结果表明，ＴＦＲ电镜下呈电子密度较高的颗粒状物质，肝癌细胞大量表达，正常肝细胞不表达或少量表达，肝癌细胞的ＴＦＲ分布在细胞，但更多地分布的胞浆，从而证实先前定位与定量的研究结果，并根据ＴＦＲ所在位置，就其在细胞的动态过程作了探讨。     

Fully automated analysis of Carbohydrate-Deficient Transferrin (CDT) by using a multicapillary electrophoresis system

BACKGROUND: The techniques universally believed as most reliable for determination of Carbohydrate-Deficient Transferrin (CDT) are HPLC and capillary electrophoresis (CE). Recently a reagent kit for CDT analysis to be used in a multicapillary electropherograph has been introduced. The present work was aimed at a validation of this new commercial system by application of the analytical chemistry parameters and by comparison with validated CE and HPLC methods. METHODS: One hundred forty serum samples were analyzed with multicapillary CE (Capillarys, Sebia, France) using kit reagents (CAPILLARYS CDT assay), with single capillary electropherograph (P/ACE MDQ, Beckman Coulter, USA) using an original method developed by our group and with HPLC, performed on a gradient HPLC (Shimadzu Europe, Germany), using column and reagents provided in kit (ClinRep, Recipe, Germany). RESULTS: The separation efficiency of the multicapillary system was about 15,000 theoretical plates/column. The resolution of the transferrin isoforms ranged from 1.23 to 1.67. The variation coefficient was < 10% in both intra-run and between run tests. The correlation of results of multicapillary CE with those obtained with single CE and HPLC was statistically significant. CONCLUSIONS: The multicapillary system shows high productivity with good analytical performances; however, a confirmation of positive results with an alternative method is required.     

血清铁蛋白水平与冠状动脉病变程度的相关性探讨

目的 现察血清铁、铁蛋白及转铁蛋白与冠状动脉狭窄的关系.探寻冠心痛的发病原因.方法 对315例冠心病患者行冠状动脉造影和血清铁、铁蛋白及转铁蛋白的测定,采用Gensini评分系统衡量冠状动脉造影结果 .按照Gensini评分的三分位间距将观察时象分为3组,应用方差分析研究铁代谢指标在3组中的分布情况,应用多因素回归分析研究Gensini评分与铁代谢指标的关系.结果 单因素方差分析显示.血清铁、血清铁蛋白及血清转铁蛋白/血清铁蛋白比值与Gensini评分肴相关性(相关系数分别为6.162、7.191和4.380,均P<0.05);多因素逐步线性回归分析显示,血清铁蛋白与冠状动脉狭窄程度的评分独立相关(其偏相关系数为0.240,P<0.01).结论 血清铁蛋白与冠状动脉狭窄独立相关.