Antitumor Efficacy of Colon‐Specific HPMA Copolymer/9‐Aminocamptothecin Conjugates in Mice Bearing Human‐Colon Carcinoma Xenografts

The antitumor activity of a colon‐specific N‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymer – 9‐aminocamptothecin (9‐AC) conjugate (P‐9‐AC) was assessed in orthotopic and subcutaneous animal (HT29 xenograft) tumor models. P‐9‐AC treatment of mice bearing orthotopic colon tumors, with a dose of 3 mg/kg of 9‐AC equivalent every other day for 6 weeks, resulted in regression of tumors in 9 of 10 mice. A lower dose of P‐9‐AC (1.25 mg/kg of 9‐AC equivalent) every other day for 8 weeks inhibited subcutaneous tumor growth in all mice. No liver metastases were observed. Colon‐specific release of 9‐AC from polymer conjugates enhanced antitumor activity and minimized the systemic toxicity.

     

Hemostatic Efficacy of Biological Self‐Assembling Peptide Nanofibers in a Rat Kidney Model

We evaluated the hemostatic efficacy of a biological self‐assembling peptide RADA16‐I in a rat kidney injury model. Adult male rats were randomized into five groups: sham operation (no renal excision), no hemostatic agent (control), commercially available gelatin sponge (Gelfoam), 1% RADA16‐I, and 2% RADA16‐I. After left partial nephrectomy, the anesthetized animal was anticoagulated using 300 IU · kg^?1 heparin, and the topical hemostatic agent was applied to the injury. Blood loss and mean arterial pressure (MAP) were recorded. As was the case for Gelfoam, 2% RADA16‐I produced marked hemostasis versus controls (p < 0.01). Blood loss with 1% and 2% RADA16‐I was significantly less than controls. The decline in MAP during surgery was less with 2% versus 1% RADA16‐I. RADA16‐I also resulted in less histological tissue responses than Gelfoam. These data suggest that RADA16‐I can stop hemorrhage, with only minimal tissue responses, in experimental renal injury.

     

基于“成分-药效”关联分析的六味地黄丸质量控制方法

本文以中药复方制剂六味地黄丸为研究示例,分别进行六味地黄丸药效成分明确化鉴别、典型药理模型的药效实验、成分与药效的关联分析,共鉴别出六味地黄丸中16个成分.通过成分与药效的关联性分析,得出4个与典型药理模型药效相关的成分.建立了指标性成分的含量测定方法学,通过"成分与药效"的关联性分析所得出指标性成分的含量测定方法,可实现对中药复方制剂六味地黄丸的质量控制.     

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研究了无汞等离子体平板荧光光源的气压、气隙、气体组成、光源结构及荧光粉加工对光源发光效率的影响。通过优化,光源的发光效率显著提高。实验结果表明,在450Torr、纯氙气、气体间隙0.7mm、前板玻璃厚为2.8mm,在前板采用60%浓度荧光粉图案印刷获得约20μm厚荧光粉层时,尺寸130mm×90mm的等离子体平板光源的发光效率和亮度超过40lm•w-1、11000cd•m-2,光通量超过500lm。通过优化,获得了较高的亮度和较高的发光效率,讨论了各影响因素引起光源发光效率变化的原因。     

Polyanhydride modified unsaturated polyesters as injectable drug carriers: Synthesis and antitumor efficacy in Sarcoma-180 mice bearing tumor

New polyanhydride modified unsaturated polyesters, poly(dodecanedioic acid-tetradecanedioic acid) [P(DDDA-TA)] modified poly(fumaric acid-glycol) [P(FA-GLY)] copolymers, were prepared by melt polycondensation with corresponding polyanhydride and unsaturated polyester synthesized beforehand. The polyanhydride was characterized by FT-IR, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA), the liquid poly(fumaric acid-glycol) [P(FA-GLY)] and polyanhydride modified unsaturated polyesters were characterized by FT-IR, gel permeation chromatography (GPC) and viscosity of the polymers was measured with a Ubbelohde viscometer. In vitro studies showed that some of the copolymers are degradable in phosphate buffer at 37 °C and have properly drug release rate as drug carriers. The biocompatibility of P(DDDA-TA)-P(FA-GLY) copolymers under mice skin was also evaluated; macroscopic observation and microscopic analysis demonstrated that the copolymer is biocompatible and well tolerated in vivo. Antitumor efficacy of P(DDDA-TA) [molar ratio M_DDDA:M_TA = 1.0:1.0, 20% weight ratio in polyanhydride modified unsaturated polyester]-P(FA-GLY) [molar ratio M_FA:M_GLY = 1.0:1.1] containing 5% adriamycin hydrochloride (ADM) in Sarcoma-180 mice bearing tumor exhibited increased volume doubling time (VDT) (21 ± 1.5 days) compared to plain subcutaneous injection of adriamycin hydrochloride (ADM) (7 ± 1.0 days), and the antitumor efficacy of injected preparation of P(DDDA-TA)-P(FA-GLY)-ADM inside tumor twice intervene 16 days exhibited an especially increased cytotoxic effect as revealed by increased volume doubling time (VDT) (32 ± 2.5 days). The studies suggested that P(DDDA-TA)-P(FA-GLY) copolymers as an effective and injectable carrier of antineoplastic drug like adriamycin hydrochloride have a very good foreground in treatment of noumenon tumor.     

甲氨蝶呤/层状双金属氢氧化物的性能调控及细胞生物实验研究

在乙醇-水混合体系中,以氨水为沉淀剂共沉淀合成了甲氨蝶呤/层状双金属氢氧化物（MTX/LDH）纳米复合物,采用控制水热处理时间的方式来调控其性能。利用X-射线衍射（XRD）、透射电镜（TEM）和红外光谱（FT-IR）等表征手段,对其结构及形貌进行了表征。研究表明：MTX分子以单层倾斜或垂直方式插入LDH层间,随着水热处理时间的不同,MTX在层间的倾斜角度发生了变化;水热处理时间对产物的结晶度、粒径和层间排列方式都有影响,当水热处理时间为12h时,得到的MTX/LDH纳米复合物的结晶度最高,单分散性最好。在磷酸缓冲液中考察了MTX/LDH纳米复合物的缓释性能,结果表明样品均呈现出良好的缓释性能,释放速率先快后慢。重点考察了这几种MTX/LDH纳米复合物作用于肺癌细胞A549的细胞生物实验,研究表明这几种复合物对肺癌细胞A549都具有良好的抑制作用,其效果与纳米复合物的单分散性和粒径有密切的关系,单分散性越好,粒径分布越均匀,对A₅₄₉癌细胞的抑制效果越好。     

健骨胶囊功效成分矿物质钙和蛋白质的分析

对健骨胶囊中的功效成分矿物质钙和蛋白质进行了测定。方法简单、快速、准确度高。方法的使用为健骨胶囊中主要功效成分的分析测试及其质量标准的建立,胶囊的营养学、功效学研究,具有重要意义。     

Testing behavior of the reversed hazard rate

The concept of reversed hazard rate of a random life is defined as the ratio between the life probability density to its distribution function. This concept plays a role in analyzing censored data and is applicable in such areas as Forensic Sciences. In this investigation, we address the question of testing the reversed hazard rate where the null is that the reversed hazard rate is an assigned function while the alternative is that it is decreasing but not equal to the null function. Two approaches are discussed: one is based on the empirical distribution function while the other is based on the celebrated kernel methods. The limiting distributions of the test statistics are given and its asymptotic Pittman efficiencies are evaluated for well-known alternatives when the null distribution is exponential. Some other related problems are also addressed.     

A Rationally Designed Bimetallic Platinum (II)-Ferrocene Antitumor Agent Induces Non-Apoptotic Cell Death and Exerts in Vivo Efficacy

Despite phenomenal clinical success, the efficacy of platinum anticancer drugs is often compromised due to inherent and acquired drug resistant phenotypes in cancers. To circumvent this issue, we designed two heterobimetallic platinum (II)-ferrocene hybrids that display multi-pronged anticancer action. In cancer cells, our best compound, 2 , platinates DNA, produces reactive oxygen species, and has nucleus, mitochondria, and endoplasmic reticulum as potential targets. The multi-modal mechanism of action of these hybrid agents lead to non-apoptotic cell death induction which enables circumventing apoptosis resistance and significant improvement in platinum cross resistance profile. Finally, in addition to describing detail mechanistic insights, we also assessed its stability in plasma and demonstrate anticancer efficacy in an in vivo A2780 xenograft model. Strikingly, compared to oxaliplatin, our compound displays better tolerability, safety profile and efficacy in vivo.     

Oral Supplementation with Hydrolyzed Fish Cartilage Improves the Morphological and Structural Characteristics of the Skin: A Double-Blind,Placebo-Controlled Clinical Study

Collagen and its peptides are natural ingredients used in food supplements and nutricosmetics with the claim of providing benefits for skin health and beauty. In this context, the aim of the present study was to evaluate the clinical efficacy of oral supplementation with hydrolyzed fish cartilage for the improvement of chronological and photoaging-induced skin changes. A total of 46 healthy females aged 45 to 59 years were enrolled and divided into two groups: G1—placebo and G2—oral treatment with hydrolyzed fish cartilage. Measurements of skin wrinkles, dermis echogenicity and thickness, and morphological and structural characteristics of the skin were performed in the nasolabial region of the face before and after a 90-day period of treatment using high-resolution imaging, ultrasound, and reflectance confocal microscopy image analyses. A significant reduction in wrinkles and an increase of dermis echogenicity were observed after a 90-day period of treatment with hydrolyzed fish cartilage compared to the placebo and baseline values. In addition, reflectance confocal microscopy (RCM) image analysis showed improved collagen morphology and reduced elastosis after treatment with hydrolyzed fish cartilage. The present study showed the clinical benefits for the skin obtained with oral supplementation with a low dose of collagen peptides from hydrolyzed fish cartilage.