Reversing multidrug resistance by intracellular delivery of Pluronic P85 unimers

Pluronics have been demonstrated as excellent multidrug resistance (MDR) reversal agent in the form of unimers rather than micelles. However, the effective intracellular delivery of Pluronic^® unimers to MDR cancer cells still remains a big challenge. To address this issue, a mixed micellar system based mainly on the pH-sensitive copolymer of poly (l-histidine)-poly (d,l-lactide)-polyethyleneglycol-poly (d,l-lactide)-poly (l-histidine) (PHis-PLA-PEG-PLA-PHis) and Pluronic^® F127, some of which was conjugated with folate, was constructed to intracellularly deliver the unimers of Pluronic^® P85 to MDR cells. The folate-mediated endosomal pH-sensitive mixed micelles (pH_endoSM-P85/f) were prepared by a thin-film hydration method, by which Pluronic^® P85 unimers and doxorubicin (DOX) were incoporated into the mixed micelles. The incorporation of Pluronic^® P85 unimers was investigated by the surface tension test. The results indicated that the Pluronic^® P85 unimers probably first inserted into the binary mixed micelles and then formed a triple-component mixed micelles with Pluronic^® F127 and PHis-PLA-PEG-PLA-PHis as the loading content increased. Further analyzed with flow cytometry, confocal laser scanning microscopy (CLSM) and MTT assay, the micelles with inserted Pluronic^® P85 unimers demonstrated much more cellular uptake and higher cytotoxicity against MDR cells than the triple-component mixed micelles and plain Pluronic^® micelles. The enhanced MDR reversal effect was attributed to the successful intracellular delivery of Pluronic^® P85 unimers to the MDR cells, which was confirmed by the subcellular colocalization of Pluronic^® P85 unimers with mitochondria, the decreased ATP energy and mitochondrial membrane potential (MP) in the MCF-7/ADR cells. The pH_endoSM-P85/f/DOX also demonstrated more dramatic antitumor efficiency and remarkable reduction of ATP energy in the MDR cells in tumors than the control formulations. The intracellular delivery of Pluronic^® P85 unimers to the MDR cells based on the targeted and endosomal pH triggerd release mixed micelles has been demonstrated as a promising approach to reverse MDR.     

新型动力化前路方形区钛板螺钉系统在不同置钉方法下固定髋臼骨折的有限元比较

目的 采用三维有限元分析法研究新型动力化前路方形区钛板螺钉系统(DAPSQ)固定髋臼高位双柱骨折的生物力学特点,并比较其在不同方形区螺钉置钉方法 下的生物力学稳定性.方法 应用1例成年男性志愿者骨盆CT图像构建左侧髋臼高位双柱骨折的全骨盆有限元模型,并采用新型动力化前路方形区钛板螺钉系统固定.分别构建DAPSQ联合单方形区螺钉(A组)、双方形区螺钉(B组)、三方形区螺钉(C组)和四方形区螺钉(D组)固定模型,施加600 N垂直载荷或8N/m扭矩,模拟骨盆站位、坐位、站位+健侧旋转和站位+患侧旋转,比较各组内固定方法 下骨折线平均位移和内固定应力分布情况.结果 在站位、坐位、健侧旋转和患侧旋转4种工况下,方形区骨折线路径上各节点平均位移表现为A组>B组>C组>D组,组间比较显示D组位移显著低于A组和B组(P<0.05),C组和D组比较差异无统计学意义(P>0.05).应力分析结果 显示,站位和坐位下D组应力主要集中在钛板螺钉结合处,以近端第1枚方形区螺钉承担应力最大.结论 新型动力化前路方形区钛板螺钉系统固定髋臼高位双柱骨折的生物力学性能可靠,推荐在方形区应至少置入3或4枚螺钉进行固定,且靠近坐骨大切迹的方形区螺钉为关键钉.     

整体切削的聚醚醚酮可摘局部义齿即刻修复1例

聚醚醚酮(PEEK)是一种具有良好的力学性能和生物安全性的新型高分子化合物,近年来逐渐应用于口腔修复、种植、正畸等领域。目前,PEEK在可摘局部义齿中的应用已有临床报道,但整体切削的PEEK可摘局部义齿还未见相关临床报道。本病例应用全程数字化设计和PEEK材料,整体切削制作了集支架、人工牙和基托为一体的可摘局部义齿,对1例83岁上下颌牙列缺损的患者进行了即刻修复治疗,并进行了3~6个月的随访,患者对修复效果满意。     

1.5T磁共振1H-MRS鉴别良恶性胸腔积液的初步研究

目的：探讨磁共振波谱对良、恶性胸腔积液的鉴别诊断价值。方法收集行胸腔穿刺抽液的胸腔积液标本46例,其中原发病确诊为良性者20例（包括肺结核14例、肺炎6例）,原发病确诊为恶性者26例（包括原发性肺癌18例、乳腺癌5例、肝癌2例、胃癌1例）。对胸腔积液标本进行离心处理,然后利用1.5T磁共振对胸腔积液标本进行波谱采集,分析良恶性胸腔积液的波谱特征。结果胸腔积液的波谱图中主要的代谢峰有乳酸、胆碱、肌酸、肌醇及脂质等。主要代谢物波峰下面积比较：乳酸：结核性（5.19±1.31）、炎性（6.08±1.56）和恶性胸腔积液（2.40±0.43）的乳酸峰下面积差异有统计学意义（F=8.45,P<0.01）;胆碱：结核性（2.75±0.91）、炎性（3.27±1.21）和恶性胸腔积液（6.76±1.73）的胆碱峰下面积差异有统计学意义（F=2.98,P<0.01）;肌醇：结核性（2.71±1.19）、炎性（2.25±0.81）和恶性胸腔积液（5.83±2.08）的肌醇峰下面积差异有统计学意义（F=38.49,P<0.01）。结核性和炎性胸腔积液中乳酸（t=-1.04,P＞0.05）、胆碱（t=-0.58,P＞0.05）和肌醇（t=1.19,P＞0.05）波峰下面积差异无统计学意义。结论良、恶性胸腔积液具有不同的波谱特征,利用磁共振波谱对良、恶性胸腔积液进行鉴别具有一定的临床应用价值。     

Association between interluekin-17 gene polymorphisms and the risk of cervical cancer in a Chinese population

We conducted a study to analyze the association of three common SNPs of IL-17A rs2275913 and rs3748067 and IL-17F rs763780 gene polymorphisms with the risk of cervical cancer in a Chinese population. Our study included 352 cervical cancer patients and 352 controls between January 2013 and December 2014. Genotyping of IL-17A rs2275913 and rs3748067 and IL-17F rs763780 genes was performed by multiplex PCR assays using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). By χ² test, there was significantly difference in the genotype distribution of IL-17A rs2275913 between cervical cancer patients and control subjects (χ²=11.45, P=0.003). By conditional logistic regression analysis, we found that individuals with the GA and AA genotypes were associated with an increased risk of cervical cancer when compared with the GG genotype in codominant model, and the adjusted Ors (95% CI) were 1.57 (1.13-2.18) and 2.01 (1.15-3.49), respectively. In dominant model, we found that the GA+AA genotype of rs2275913 was correlated with a moderate increased risk of cervical cancer compared with the GG genotype (OR=1.64, 95% CI=1.20-2.24). We only found significant interaction between rs2275913 polymorphism and HPV-16 or 18 infection in the risk of cervical cancer (P for interaction <0.05). In conclusion, our study suggests that IL-17A rs2275913 polymorphism may affect the development of cervical cancer in codominant and dominant models, and this gene polymorphism has interaction with HPV-16 or 18 infection.     

Influence of different intensities of vibration on proliferation and differentiation of human periodontal ligament stem cells

Introduction

To understand the effects of low-magnitude, high-frequency (LMHF) mechanical vibration at different intensities on human periodontal ligament stem cell (hPDLSC) proliferation and osteogenic differentiation.

Material and methods

The effect of vibration on hPDLSC proliferation, osteogenic differentiation, tenogenic differentiation and cytoskeleton was assessed at the cellular, genetic and protein level.

Results

The PDLSC proliferation was decreased after different magnitudes of mechanical vibration; however, there were no obvious senescent cells in the experimental and the static control group. Expression of osteogenesis markers was increased. The expression of alkaline phosphatase (ALP) and osteocalcin (OCN) mRNA was up-regulated at 0.1 g, 0.3 g, 0.6 g and 0.9 g magnitude, with the peak at 0.3 g. The type I collagen (Col-I) level was increased after vibration exposure at 0.1 g, 0.3 g, and 0.6 g, peaking at 0.3 g. The expression levels of both mRNA and protein of Runx2 and osterix (OSX) significantly increased at a magnitude of 0.1 g to 0.9 g, reached a peak at 0.3 g and then decreased slowly. The scleraxis, tenogenic markers, and mRNA expression decreased at 0.05 g, 0.1 g, and 0.3 g, and significantly increased at 0.6 g and 0.9 g. Compared with the static group, the F-actin stress fibers of hPDLSCs became thicker and clearer following vibration.

Conclusions

The LMHF mechanical vibration promotes PDLSC osteogenic differentiation and implies the existence of a magnitude-dependent effect of vibration on determining PDLSC commitment to the osteoblast lineage. Changes in the cytoskeleton of hPDLSCs after vibration may be one of the mechanisms of the biological effects.     

An ultrasensitive chemiluminescent ELISA for determination of chloramphenicol in milk,milk powder,honey, eggs and chicken muscle

A competitive, direct, chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) for chloramphenicol (CAP) residues in milk, milk powder, honey, eggs and chicken muscle has been developed. The method gave a detection limit of 0.7 ng L^?1 and a linear range of 2.1–92.4 ng L^?1, with the IC₅₀ of 13.6 ng L^?1 under optimal conditions, dramatically better than any previously reported ELISA method for CAP detection. Spiked at levels of 5–60 ng L^?1 in different food samples, recoveries were in the range of 72.1–116.0%, with coefficient of variations of 4.2–20.2%. In a study of incurred residues, the chicken muscle samples diluted 5-, 10- and 20-fold, results obtained by CL-ELISA correlated well with those obtained by gas chromatography with microcell electron capture detector and traditional ELISA. The developed CL-ELISA method is, therefore, suitable for rapid screening trace CAP residues in food samples.