Retinol encapsulated into amorphous Ca2+ polyphosphate nanospheres acts synergistically in MC3T3-E1 cells

Both the quality and quantity of collagen, the major structural component of the skin, decrease in aging skin. We succeeded to encapsulate retinol into amorphous inorganic polyphosphate (polyP) nanoparticles together with calcium ions (“aCa-polyP-NP”), under formation of amorphous Ca-polyP/retinol nanospheres (“retinol/aCa-polyP-NS”). The globular nanospheres are not cytotoxic, show an almost uniform size of ≈45 nm and have a retinol content of around 25%. Both components of those nanospheres, retinol and the aCa-polyP-NP, if administered together, caused a strong increase in proliferation of mouse calvaria MC3T3 cells. The expressions of collagen types I, II and III genes, but not the expression of collagen type V gene, were significantly enhanced if retinol is added together with aCa-polyP-NP. This synergistic effect was especially pronounced for the expression of the collagen type III gene. We propose that the synergistic effect of the retinol/aCa-polyP-NS on cell growth and collagen type III expression is induced via two routes, first through cellular uptake of the 45 nm nanospheres by clathrin-mediated endocytosis and second through extracellular disintegration of the nanospheres resulting in the release of retinol which is then taken up into the cells after binding to the retinal binding protein receptor.     

Combination of Protoporphyrin IX-mediated Sonodynamic Treatment with Doxorubicin Synergistically Induced Apoptotic Cell Death of a Multidrug-Resistant Leukemia K562/DOX Cell Line

The main objective of this study was to evaluate the efficacy of administration of doxorubicin (DOX) in combination with protoporphyrin IX (PpIX)-assisted low-level therapeutic ultrasound (US) in K562/DOX cells as a potential strategy in cancer therapy. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine the cytotoxicity of different treatments. Apoptosis was analyzed using annexin V-PE/7-amino-actinomycin D staining. Changes in DNA fragmentation, intracellular reactive oxygen species production, cellular membrane permeability, P-glycoprotein expression and DOX uptake were analyzed with flow cytometry. Under optimal conditions, PpIX-US significantly aggravated DOX-induced K562/DOX cell death, compared with either monotherapy. Synergistic potentiation of DNA damage, generation of reactive oxygen species and P-glycoprotein inhibition were observed. Plasma membrane integrity changed slightly after US exposure, and DOX uptake was notably improved after PpIX-US exposure. The results indicate that PpIX-US could increase the susceptibility of tumors to antineoplastic drugs, suggesting a clinical potential method for sonodynamic therapy-mediated tumor chemotherapy.     

Influence of humic substances on the toxic effects of cadmium and SDBS to the green alga Scenedesmus obliquus

The joint toxicity of chemicals mixture in the aquatic environment was still not well clear. To clarify the joint toxicity of the mixtures of metals and organic pollutants, as well as the influence of dissolved organic matter (DOM) in field water-body on their toxic effects, we conducted the toxicity tests with cadmium (Cd) and sodium dodecyl benzene sulfonate (SDBS) on Scenedesmus obliquus (S. obliquus) with or without the presence of fulvic acid (FA), a typical of DOM. Our results showed Cd was more toxic to S. obliquus than SDBS, and the effects of fulvic acid on SDBS were greater than Cd. The joint toxicity of Cd and SDBS expressed a synergistic effect on S. obliquus, which was observed to be increased with the presence of FA. Our results gave an example for the joint toxicity investigations of organics and metals, aiding to understanding the toxicity of pollutant mixtures in field water bodies containing DOM.     

Hydroxyapatite nanorods loaded with parathyroid hormone (PTH) synergistically enhance the net formative effect of PTH anabolic therapy

Parathyroid hormone (PTH) has been a major contributor to the anabolic therapy for osteoporosis, but its delivery to bone without losing activity and avoiding adverse local effects remain a challenge. Being the natural component of bone, use of hydroxyapatite for this purpose brings a major breakthrough in synergistic anabolism. This study focuses on synthesis, characterization and evaluation of in vitro and in vivo efficacy of PTH (1-34) adsorbed hydroxyapatite nanocarrier for synergistic enhancement in the anabolic activity of PTH for bone regeneration. The negative zeta potential of this nanocarrier facilitated its affinity to the Ca²⁺ rich bone tissue and solubilization at low pH enhanced specific delivery of PTH to the resorption pits in osteoporotic bone. In this process, PTH retained its anabolic effect and at the same time an increase in bone mineral content indicated enhancement of the net formative effect of the PTH anabolic therapy.     

A multi-stimuli responsive gold nanocage–hyaluronic platform for targeted photothermal and chemotherapy

Noninvasive and pinpointed intracellular drug release that responds to multiple stimulus is still a formidable challenge for cancer therapy. Herein, we reported a multi-stimuli responsive platform based on drug loaded gold nanocages @ hyaluronic acid (AuNCs-HA) for pinpointed intracellular drug release. These well-prepared nanohybrids could specifically recognize cancer cells via HA-CD44 interactions and be efficiently endocytosed by receptor-mediated process. Subsequently, the coated HA molecules could be degraded in lysosomes, resulting in the release of encapsulated drug. In addition, by taking advantage of the excellent photothermal properties, the AuNCs could accelerate the release of encapsulated drug and induce a higher therapeutic efficacy upon near-infrared (NIR) irradiation. In vitro results confirmed that the encapsulated drug could only be pinpointedly released in intracellular environments, which permitted high therapeutic efficacy against cancer cells and minimized the side effects. Importantly, as compared to that of the two therapies independently, a complete inhibition of tumor growth treated with the combination of chemotherapy and photothermal therapy was observed in vivo. Taken together, our present study provides new insights into developing pinpointed, multi-stimuli responsive intracellular drug release systems for synergistic cancer therapy.     

针药结合治疗糖尿病胃轻瘫研究进展

糖尿病胃轻瘫(DGP)是糖尿病患者中发病率较高的慢性胃肠道并发症,其发病原因及机制十分复杂,目前临床尚无针对性的治疗方案,其治疗一直为临床所重视。目前研究表明,针药结合较单纯用药及单纯针灸具有明显优势,但大多属于临床小样本观察,机制尚不明确。     

基于管理协同理论的国内外医疗机构上下联动工作机制分析

连续性医疗服务的提供需要分级诊疗制度的实施, “上下联动”是实现分级诊疗的重要途径.通过文献研究并结合管理协同理论,对国内外医疗机构上下联动的协同机会识别、沟通交流、要素整合、序参量选择、信息反馈5大工作机制进行分析.研究认为,落实机构功能定位是各级医疗机构上下联动的基础;标准化、安全化的信息建设及监督反馈机制的建立有...     

荞麦花叶提取物对S180荷瘤小鼠化疗的减毒增效作用

目的研究荞麦花叶提取物(extraction of buckwheat flower and leaf,EBFL)对环磷酰胺(CTX)化疗S180荷瘤小鼠的减毒和增效作用。方法建立小鼠S180实体瘤模型;大、小剂量治疗组分别ig荞麦花叶提取物20,40 mg/kg,连续给药14 d,测定荷瘤小鼠的生存期和化疗药物CTX的毒副作用,以及荞麦花叶提取物对CTX的减毒和增效作用。同时检测荞麦花叶提取物对淋巴细胞增殖、IL-2水平等免疫系统功能的影响。结果 EBFL对肿瘤抑制作用不明显但可使荷瘤小鼠生存率明显增高。与CTX伍用可发挥协同作用,提高荷瘤小鼠生存质量,体质量、白细胞计数、免疫器官指数,与CTX阳性对照组比较均显示显著差异(P<0.05或P<0.01)。结论荞麦花叶提取物可提高机体免疫力,延长生存期,同时减轻CTX的毒性。     

Normalized EMG to normalized torque relationship of vastus intermedius muscle during isometric knee extension

The purpose of the present study was to investigate the electromyography (EMG) to torque relationship of the vastus intermedius (VI) muscle. Thirteen healthy men performed maximal voluntary contraction (MVC) and submaximal contraction during isometric knee extension at 10% of the MVC to 90% of the MVC at intervals of 10% of the MVC level. Surface EMG was detected from four muscle components of the QF muscle group, i.e., VI, vastus lateralis (VL), vastus medialis, and rectus femoris (RF) muscles. Normalized muscle activation in the VI muscle was significantly lower than in the VL muscle at a lower torque level (20 and 40% of MVC) and significantly lower compared to the RF muscle at a higher torque level (from 60 to 90% of MVC). These results suggest that neuromuscular activation in the VI muscle is not consistent with the other components of QF muscle group during submaximal knee extension contractions.     

Stability enhanced polyelectrolyte-coated gold nanorod-photosensitizer complexes for high/low power density photodynamic therapy

Photodynamic therapy (PDT) is a promising treatment modality for cancer and other malignant diseases, however safety and efficacy improvements are required before it reaches its full potential and wider clinical use. Herein, we investigated a highly efficient and safe photodynamic therapy procedure by developing a high/low power density photodynamic therapy mode (high/low PDT mode) using methoxypoly(ethylene glycol) thiol (mPEG-SH) modified gold nanorod (GNR)-AlPcS4 photosensitizer complexes. mPEG-SH conjugated to the surface of simple polyelectrolyte-coated GNRs was verified using Fourier transform infrared spectroscopy; this improved stability, reduced cytotoxicity, and increased the encapsulation and loading efficiency of the nanoparticle dispersions. The GNR-photosensitizer complexes were exposed to the high/low PDT mode (high light dose = 80 mW/cm² for 0.5 min; low light dose = 25 mW/cm² for 1.5 min), and a high PDT efficacy leads to approximately 90% tumor cell killing. Due to synergistic plasmonic photothermal properties of the complexes, the high/low PDT mode demonstrated improved efficacy over using single wavelength continuous laser irradiation. Additionally, no significant loss in viability was observed in cells exposed to free AlPcS4 photosensitizer under the same irradiation conditions. Consequently, free AlPcS4 released from GNRs prior to cellular entry did not contribute to cytotoxicity of normal cells or impose limitations on the use of the high power density laser. This high/low PDT mode may effectively lead to a safer and more efficient photodynamic therapy for superficial tumors.