Dual‐function fluorescent probe for cancer imaging and therapy

To date, several fluorescent probes modified by a single targeting agent have been explored. However, studies on the preparation of dual‐function quantum dot (QD) fluorescent probes with dual‐targeting action and a therapeutic effect are rare. Here, a dual‐targeting CdTe/CdS QD fluorescent probe with a bovine serum albumin–glycyrrhetinic acid conjugate and arginine‐glycine‐aspartic acid was successfully prepared that could induce the apoptosis of liver cancer cells and showed enhanced targeting in in vitro cell imaging. Therefore, the as‐prepared fluorescent probe in this work is an efficient diagnostic tool for the simultaneous detection of liver cancer and breast cancer cells. Copyright © 2015 John Wiley & Sons, Ltd.     

Stage 2 Process Performance Qualification (PPQ): a Scientific Approach to Determine the Number of PPQ Batches

The approach documented in this article reviews data from earlier process validation lifecycle stages with a described statistical model to provide the “best estimate” on the number of process performance qualification (PPQ) batches that should generate sufficient information to make a scientific and risk-based decision on product robustness. This approach is based upon estimation of a statistical confidence from the current product knowledge (Stage 1), historical variability for similar products/processes (batch-to-batch), and label claim specifications such as strength. The analysis is to determine the confidence level with the measurements of the product quality attributes and to compare them with the specifications. The projected minimum number of PPQ batches required will vary depending on the product, process understanding, and attributes, which are critical input parameters for the current statistical model. This new approach considers the critical finished product CQAs (assay, dissolution, and content uniformity), primarily because assay/content uniformity and dissolution as well as strength are the components of the label claim. The key CQAs determine the number of PPQ batches. This approach will ensure that sufficient scientific data is generated to demonstrate process robustness as desired by the 2011 FDA guidance.     

Optimising Drug Solubilisation in Amorphous Polymer Dispersions: Rational Selection of Hot-melt Extrusion Processing Parameters

The aim of this article was to construct a T–ϕ phase diagram for a model drug (FD) and amorphous polymer (Eudragit® EPO) and to use this information to understand the impact of how temperature–composition coordinates influenced the final properties of the extrudate. Defining process boundaries and understanding drug solubility in polymeric carriers is of utmost importance and will help in the successful manufacture of new delivery platforms for BCS class II drugs. Physically mixed felodipine (FD)–Eudragit^® EPO (EPO) binary mixtures with pre-determined weight fractions were analysed using DSC to measure the endset of melting and glass transition temperature. Extrudates of 10 wt% FD–EPO were processed using temperatures (110°C, 126°C, 140°C and 150°C) selected from the temperature–composition (T–ϕ) phase diagrams and processing screw speed of 20, 100 and 200rpm. Extrudates were characterised using powder X-ray diffraction (PXRD), optical, polarised light and Raman microscopy. To ensure formation of a binary amorphous drug dispersion (ADD) at a specific composition, HME processing temperatures should at least be equal to, or exceed, the corresponding temperature value on the liquid–solid curve in a F–H T–ϕ phase diagram. If extruded between the spinodal and liquid–solid curve, the lack of thermodynamic forces to attain complete drug amorphisation may be compensated for through the use of an increased screw speed. Constructing F–H T–ϕ phase diagrams are valuable not only in the understanding drug–polymer miscibility behaviour but also in rationalising the selection of important processing parameters for HME to ensure miscibility of drug and polymer.KEY WORDS: DSC, Flory–Huggins theory, hot-melt extrusion, thermal processing     

High glucose concentration induces endothelial cell proliferation by regulating cyclin‐D2‐related miR‐98

Cyclin D2 is involved in the pathology of vascular complications of type 2 diabetes mellitus (T2DM). This study investigated the role of cyclin‐D2‐regulated miRNAs in endothelial cell proliferation of T2DM. Results showed that higher glucose concentration (4.5 g/l) significantly promoted the proliferation of rat aortic endothelial cells (RAOECs), and significantly increased the expression of cyclin D2 and phosphorylation of retinoblastoma 1 (p‐RB1) in RAOECs compared with those under low glucose concentration. The cyclin D2‐3′ untranslated region is targeted by miR‐98, as demonstrated by miRNA analysis software. Western blot also confirmed that cyclin D2 and p‐RB1 expression was regulated by miR‐98. The results indicated that miR‐98 treatment can induce RAOEC apoptosis. The suppression of RAOEC growth by miR‐98 might be related to regulation of Bcl‐2, Bax and Caspase 9 expression. Furthermore, the expression levels of miR‐98 decreased in 4.5 g/l glucose‐treated cells compared with those treated by low glucose concentration. Similarly, the expression of miR‐98 significantly decreased in aortas of established streptozotocin (STZ)‐induced diabetic rat model compared with that in control rats; but cyclin D2 and p‐RB1 levels remarkably increased in aortas of STZ‐induced diabetic rats compared with those in healthy control rats. In conclusion, this study demonstrated that high glucose concentration induces cyclin D2 up‐regulation and miR‐98 down‐regulation in the RAOECs. By regulating cyclin D2, miR‐98 can inhibit human endothelial cell growth, thereby providing novel therapeutic targets for vascular complication of T2DM.     

Effects of exogenous spermidine on antioxidant system of tomato seedlings exposed to high temperature stress

The effects of foliar spraying with spermidine (Spd) on antioxidant system in tomato (Lycopersicon esculentum Mill.) seedlings were investigated under high temperature stress. The high temperature stress significantly inhibited plant growth and reduced chlorophyll (Chl) content. Application of exogenous 1 mM Spd alleviated the inhibition of growth induced by the high temperature stress. Malondialdehyde (MDA), hydrogen peroxide (H₂O₂) content and superoxide anion (O₂) generation rate were significantly increased by the high temperature stress, but Spd significantly reduced the accumulation of reactive oxygen species (ROS) and MDA content under the stress. The high temperature stress significantly decreased glutathione (GSH) content and activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR) and dehydroascorbate reductase (DHAR), but increased contents of dehydroascorbic acid (DHA), ascorbic acid (AsA), and oxidized glutathione (GSSG) in tomato leaves. However, Spd significantly increased the activities of antioxidant enzymes, levels of antioxidants and endogenous polyamines in tomato leaves under the high temperature stress. In addition, to varying degrees, Spd regulated expression of MnSOD, POD, APX2, APX6, GR, MDHAR, DHAR1, and DHAR2 genes in tomato leaves exposed to the high temperature stress. These results suggest that Spd could change endogenous polyamine levels and alleviate the damage by oxidative stress enhancing the non-enzymatic and enzymatic antioxidant system and the related gene expression.     

妊娠哺乳期乳腺癌患者的预后情况及其影响因素分析

目的:分析妊娠哺乳期乳腺癌患者的预后情况及其影响因素。方法:将2010年1月至2012年12月期间贵州省贵阳市妇幼保健院、贵州省医科大学和贵州省肿瘤医院收治的妊娠哺乳期乳腺癌患者60例作为研究组,选择同期收治的非妊娠哺乳期乳腺癌患者60例作为对照组,比较两组5年生存率和临床病理特征,并应用单因素和多因素Logistic回归分析患者预后的影响因素。结果:研究组5年生存率为61.67%(37/60),5年无病生存率为46.67%(28/60),均低于对照组的81.67%(49/60),73.33%(44/60)(P0.05)。研究组肿瘤最大直径、腋淋巴结转移率、TNM分期为III期的比例、雌激素受体阳性率、Ki67细胞阳性率≥20%的比例均高于对照组(P0.05),两组孕激素受体阳性率比较无统计学差异(P0.05)。单因素分析显示妊娠哺乳期乳腺癌患者总生存期与肿瘤最大直径、TNM分期、Ki67细胞阳性率≥20%的比例、腋淋巴结转移率有关(P0.05)。多因素Logistic回归分析显示,TNM分期为III期、Ki67细胞阳性率≥20%、腋淋巴结转移是影响妊娠哺乳期乳腺癌患者预后的独立危险因素(P0.05)。结论:妊娠哺乳期乳腺癌患者的预后较差,TNM分期为III期、Ki67细胞阳性率≥20%、腋淋巴结转移是影响患者预后的危险因素,对于临床防治具有重要的启示作用。