Artificial nano‐pin as a temporal molecular glue for the targeting of acidic tumor cells

Highly precise control of molecular structure for developing efficient anticancer drug delivery is challenging. Our method reported herein can satisfy the need for building novel hybrid molecule; this molecule serves as a built‐in transformer that changes its molecular configuration from a pin‐shaped arrangement to a dog bone‐shaped arrangement. This approach led to a significant increase in the efficiency of tumor inhibition. Copyright © 2014 John Wiley & Sons, Ltd.     

交变电场作用下骨表面温升的实验研究

骨具有力电性质,这一性质可促进骨组织生长。骨既是生理器官又是介电材料,在交变电场作用下,其表现行为可能有生理作用。为此,本文测量了骨悬臂梁试样在交变电场下的表面温升与顶端挠度。发现在电压70V,频率为10~70kHz的交流电场下,最大表面温升达到2~4℃,最大挠度变化为9.0~78.7μm;在频率10kHz,电压为70~175V的交流电场下,最大表面温升达到4~6℃,最大挠度变化为13.0~114.3μm。同时测量了两种经典介电材料有机玻璃和聚乙烯在交变电场下的温升与顶端挠度,最大温升低于0.5℃,但是挠度与骨试样相当,所以相对高温升是骨特有的性质。将交流电压有效值替换成相同幅值的直流电压时,最大温升也低于0.5℃,基本没有挠度变化,所以相对的高温升反映了骨的交流性质。分析后认为,骨在交变电场作用下的温升由胶原的介电损耗引起。实验数据显示,骨在交变电场下,表面温度变化与加载电压的平方成正比,且在实验加载的10~70kHz频段内,骨的介电常数随频率的变化明显。     

丝素纤维/硫酸钙抗感染骨材料的制备及性能

通过控制丝素蛋白自组装过程制备了溶液状态下的丝素纳米纤维（silk fibroin nanofibers,SFFs）,与硫酸钙、万古霉素（vancomycin,VCM）复合,制备了VCM/CS/SFFs抗菌骨材料。通过SEM、XRD、紫外分光光度计、万能力学试验机、抑菌圈、MTT等手段分别研究了复合材料的微观形貌与结构、药物释放、力学、抑菌及细胞相容性等性能。结果显示,与水作为固化液相比,随着SFFs溶液（0.017 5~2.1 mg·mL^-1）的加入,复合材料凝固时间可控,降解率逐渐降低,抗水性增强,韧性提高;同时随丝素纳米纤维含量的增加骨材料抗压强度表现为先增加后减小的趋势,一周内药物释放速率降低;材料同时具有抑菌作用;MTT实验结果显示,加入丝素纳米纤维后与纯的硫酸钙相比MC3T3细胞增殖明显。     

骨组织生长重建的力学生物学机制研究进展

生物力学已被证实是骨组织生长、重建及成形当中一个十分重要的因素. 骨组织的损 伤修复过程本质上是细胞的生物学过程和应力作用下的生长过程. 这虽然肯定了生物力学在 骨组织生长、重建过程中的重要地位, 但是, 人们对生物力学因素如何诱导骨生长、 重建的力学生物学机制仍不甚了解. 而骨组织工程需要更为科学完善的细胞生物学机制来研究和探 索骨组织的构建过程. 本文概述了国内外生物力学与骨组织生长重建的宏微观理论, 主要讨 论了骨组织结构及功能形成过程中的力学生物学相关问题.     

BMP-6 Loaded Polyelectrolyte Complex Nanoparticles Inducing Osteogenic Differentiation and Apoptosis of Malignant Plasma Cells for Local Treatment of Multiple Myeloma

In the malignant plasma cell disease multiple myeloma (MM), bone lesions and resulting fractures caused by MM cell (MMC) accumulation represent a major cause of morbidity and mortality. Despite recent advantages in systemic treatment, residual MMCs remain, especially in bone lesions. Therefore an interfacial delivery system for local treatment of MM and induced bone disease based on polyelectrolyte complex nanoparticles (PEC NP) loaded with bone morphogenetic protein 6 (BMP-6) inducing de-novo bone formation and MMC apoptosis is presented herein. BMP-6 loaded PEC NP are fabricated by defined mixing bio-related cationic and anionic polysaccharides and BMP-6 according to molar ratio of BMP-6/PEC-NP of 1/3. BMP-6/PEC NP bound to a model substrate releases 10% BMP-6 sustainably within two weeks as accessed by infrared spectroscopy. BMP-6 loaded PEC NP adheres to cell membranes of MMCs and MSCs and activated phosphorylation of Smad 1/5. Osteogenic differentiation (ALP-concentration) is enhanced in MSCs (p < 0.05). All patient samples (10/10) of MMCs show significant induction of apoptosis (median 84%, p < 0.05). Finally, BMP-6/PEC NP are successfully integrated in a commercial hyaluronic acid based hydrogel material revealing MMC death as principal proof for the local treatment of MM induced bone lesions.     

CONFORMATIONAL PREFERENCES ABOUT Cpy-S BONDS IN DI-2-PYRIDYL DISULFIDE

Abstract

The total energy, dipole moment and electron densities for each possible rotational conformation about the C_py-S bonds of di-2-pyridyl disulfide were evaluated by using the semi-quantitative CNDO/2 method. The conformations in which the pyridine rings are coplanar with the valency plane of the bonded sulfur atom (cis-cis, cis-trans and trans-trans) were predicted to be the most favored ones.

Results of the theoretical study, when compared to some experimental determinations such as dipole moment and variable temperature pmr spectra, provided evidence that easy interconversion between these conformations can occur.     

The N- and C-terminal domains of parathyroid hormone-related protein affect differently the osteogenic and adipogenic potential of human mesenchymal stem cells

Parathyroid hormone-related protein (PTHrP) is synthesized by diverse tissues, and its processing produces several fragments, each with apparently distinct autocrine and paracrine bioactivities. In bone, PTHrP appears to modulate bone formation in part through promoting osteoblast differentiation. The putative effect of PTH-like and PTH-unrelated fragments of PTHrP on human mesenchymal stem cell (MSCs) is not well known. Human MSCs were treated with PTHrP (1-36) or PTHrP (107-139) or both (each at 10 nM) in osteogenic or adipogenic medium, from the start or after 6 days of exposure to the corresponding medium, and the expression of several osteoblastogenic and adipogenic markers was analyzed. PTHrP (1-36) inhibited adipogenesis in MSCs and favoured the expression of osteogenic early markers. The opposite was observed with treatment of MSCs with PTHrP (107-139). Moreover, inhibition of the adipogenic differentiation by PTHrP (1-36) prevailed in the presence of PTHrP (107-139). The PTH/PTHrP type 1 receptor (PTH1R) gene expression was maximum in the earlier and later stages of osteogenesis and adipogenesis, respectively. While PTHrP (107-139) did not modify the PTH1R overexpression during adipogenesis, PTHrP (1-36) did inhibit it; an effect which was partially affected by PTHrP (7-34), a PTH1R antagonist, at 1 µM. These findings demonstrate that both PTHrP domains can exert varying effects on human MSCs differentiation. PTHrP (107-139) showed a tendency to favor adipogenesis, while PTHrP (1-36) induced a mild osteogenic effect in these cells, and inhibited their adipocytic commitment. This further supports the potential anabolic action of the latter peptide in humans.     

Aligned and molecularly oriented semihollow ultrafine polymer fiber yarns by a facile method

In this work, aligned and molecularly oriented bone‐like PLLA semihollow fiber yarns were manufactured continuously from an optimized homogeneous polymer‐solvent‐nonsolvent system [PLLA, CH₂Cl₂, and dimethyl formamide (DMF)] by a single capillary electrospinning via self‐bundling technique. Here, it should be emphasized that the self‐bundling electrospinning technique, a very facile electrospinning technique with a grounded needle (which is to induce the self‐bundling of polymer nanofibers at the beginning of electrospinning process), is used for the alignment and molecular orientation of the polymer fiber, and the take‐up speed of the rotating drum for the electrospun fiber yarn collection is very low (0.5 m/s). PLLA can be dissolved in DMF and CH₂Cl₂ mixed solvent with different ratios. By varying the ratios of mixed solvent system, PLLA electrospun semihollow fiber with the porous inner structure and compact shell wall could be formed, the thickness of the shell and the size of inner pores could be adjusted. The results of polarized FTIR and wide angle X‐ray diffraction investigations verified that as‐prepared PLLA semihollow fiber yarns were well‐aligned and molecularly oriented. Both the formation mechanism of semihollow fibers with core‐shell structure and the orientation mechanism of polymer chains within the polymer fibers were all discussed. The as‐prepared self‐bundling electrospun PLLA fiber yarns possessed enhanced mechanical performance compared with the corresponding conventional electrospun PLLA fibrous nonwoven membranes. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1118–1125, 2010     

Study of the circumstance influence on the elemental distribution in ancient animal bone using μ-XRF

Elemental analysis of archaeological bone plays an important role in the study of the dietary habits of ancient animals. The elemental characteristic of diagenetic skeletons depends on the surrounding circum-stance. The study of environmental influence on the elemental concentration of ancient bone is significant. In this paper, the diagenetic influence on archaeological skeletons is analyzed by microbeam X-ray fluorescence (μ-XRF). The results show that the enamel is an excellent barrier to the diagenesis and the element Sr in bone isn’t susceptible to contamination from the buried environment.