Latest ArticlesThis study was designed to explore the mechanism of Coix seed oil (Coix) impact on the drug resistance, bioluminescence imaging (BLI) and the efflux of D-luciferin potassium salt, the substrate of ABC transporters, in doxorubicin-resistant breast cancer cells. Multidrug resistance (MDR) gene and protein expression were analyzed in the cells by q-PCR and Western blot. First, in order to investigate the effect of the efflux function by ABC protein, a cell line with overexpressed luciferase was established in MCF-7 cell line. BLI was used to monitor the efflux kinetics of D-luciferin potassium salt before and after Coix treament. The results showed that the efflux of D-fluorescein potassium from MCF-7/DOXFluc was lessened when pretreated with Coix, which means that Coix may decrease the efflux of other chemotherapies using ABC transporters. Both of the results of q-PCR and Western blot showed that gene and protein expression of ABC transporters such as ABCG2, ABCC1 and ABCB1 were down-regulated by Coix treatment. The efficacy of Coix reversing MDR was verified with the chemotherapy medication doxorubicin (DOX). MTT assay showed that Coix increased the inhibitory effect of DOX on proliferation of MCF-7/DOX, and the optimal combination of ratio was 25 times that of DOX. The results suggest that Coix may reverse MDR of the substrate of ABC transporters from two aspects, one is to cut down the ABC protein efflux function, and the other is to decrease the quantity of ABC gene and protein expression.
The key of gene therapy is to deliver the functional gene to the target tissue in the body. The safe and efficient gene carrier is particularly important in the targeted delivery. Multifunctional envelope-type nano device (MEND), based on concept "Programmed packaging", is a new type of gene carrier system, with high encapsulation efficiency, favourable stability, high transfection efficiency, easy preparation, etc. MEND is designed to control intracellular trafficking as well as the tissue distribution of encapsulated compounds such as nucleic acids/proteins/peptides, permitting them to function at the appropriate location. In this paper, research progresses in MEND are reviewed in accordance with three types of payloads:the small interfering RNA (siRNA), DNA and proteins/peptides in recent years.
The study was designed to test the estrogen-like effects about allantoin. The activity of the allantoin was investigated by mouse uterine weight gain test and MCF-7 cell proliferation assay. The levels of E2, FSH and LH were also measured. ICI182, 780, MPP, THC and G15 antagonnist assay and Western blot were adopted to explore the mechanism of allantoin. Allantoin increased the uterus index of premature female mice, the levels of E2 and FSH, and the expression of ERα and GPR30, compared with the control group. Allantoin also promoted the proliferation of MCF-7 cells. Co-incubation of MCF-7 cells with estrogen receptor blockers, ICI182, 780, MPP and G15 abolished the inductive effect of the proliferation. These results suggest that allantoin has estrogenic activities, which are mainly mediated by ERα, GPR30.
Vancomycin has been widely prescribed as the first-line antibiotic in the treatment of methicillin-resistant Staphylococcus aureus and other serious Gram-positive infections. Due to its large pharmacokinetic (PK) variability and narrow therapeutic range, it requires optimization of dosage to achieve target exposure. In this study, SmartDose, a decision support system for individualization of vancomycin dosage is developed using the maximum a posterior Bayesian estimation (MAPB) by the open-source language R combined with the population PK characteristics of vancomycin in Chinese patients. It provides initial design and adjustment of dose regimens based on the therapeutic drug monitoring (TDM) results, as well as a user-defined module to facilitate optimal vancomycin therapy. SmartDose has a high computational reliability, which is validated by NONMEM, the golden standard PK software. Meanwhile, SmartDose is established as a web-based application and its operational flexibility makes it an efficient tool for vancomycin dose optimization in routine clinical settings.
Severe acute pancreatitis (SAP) is characterized by both local and systemic inflammatory responses. This study was designed to develop a site-specific delivery strategy for SAP therapy using celastrol (CLT). First, murine RAW264.7 cells were used as a model of macrophage cell line, cell membranes were obtained by emptying intracellular contents via hypotonic lysing, mechanical membrane disruption, and differential centrifugation. Poly(ethylene glycol) methyl ether-block-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs) were then prepared by sonication. With the collected membrane materials, macrophage membrane coated PEG-PLGA NPs (RNPs) were then prepared by extrusion through a 400 nm polycarbonate membrane. Biodistribution study in rats with SAP showed RNPs selectively accumulated in the inflamed pancreatic tissues. Compared with CLT loaded NPs, CLT loaded RNPs were proven to effectively attenuate local pancreatic inflammation and systemic inflammation in rats with SAP.
Two new diarylheptane derivatives were isolated from Rhizoma Zingiberis by Diaion HP-20, MCI Gel CHP-20, ODS, silica gel column and reverse phase semi-prepared high performance liquid chromatography. Their structures were elucidated by spectrum technology (MS, UV, IR, NMR), which were identified as 3-keto-5R-ethoxy-1-(3-methoxy-4-hydroxyphenyl)-7-(3, 4-dihydroxyphenyl)heptane (1) and 3-keto-5R-ethoxy-1-(3-methoxy-4-hydroxyphenyl)-7-(3-methoxy-4, 5-dihydroxyphenyl)heptane (2). Compounds 1 and 2 are new compounds.
Follow-on drug approach is to follow-up and make-up of the innovation of pioneering drugs. Since the millennium new molecular entities (NME) have experienced ample optimization, and the patents have claimed in wide ranges, as well as the drug administration requires NME being superior or non-inferior to the existing drugs of the same class. These situations have made the space of follow-on drug innovation narrow and smaller than before. The follow-on drug approach can be concisely differentiated into two aspects:one is to start from the chemistry of small molecules, which are performed with a niche-targeting manipulation to optimize the safety, efficacy and (or) convenience for dose superior to the existing drugs; another proceeds with the macromolecule targets. Based on the knowledge of the mechanism of action or of target mutation, active compounds are constructed through complementary binding or by the reaction mechanism. In this article successful examples are briefly described to illustrate the features of follow-on drug approach.
Ginsenoside Rg1 is one of the main active components of ginseng with various pharmacological activities including anti-inflammatory, anti-oxidation, anti-aging, anti-tumor and anti-apoptosis. Ginsenoside Rg1 plays a protective role in multiple tissues and organs, which shows the multiple targeting properties of the pharmacological effects. Recently, a number of studies have demonstrated that ginsenoside Rg1 has a protective role in the liver due to its multiple pharmacological effects. In chemical liver injury models, or in other liver injury models, ginsenoside Rg1 can alleviate liver necrosis induced by oxidative stress and inflam-mation. This article provides a review of the recent studies on the efficacy of ginsenoside Rg1 in the treatment of various liver damage and the molecular mechanism.
This study was carried out to investigate the pharmacokinetics/bioequivalence of levornidazole disodium phosphate by using stable isotope labeled drug, evaluated the pharmacokinetic profile and confirmed the prodrug characteristics of levornidazole disodium phosphate in monkey. Levornidazole (Drug A) and stable isotope 15N labeled levornidazole disodium phosphate (Drug B) were mixed with equal mole amount (experiment Ⅰ); stable isotope 15N labeled levornidazole disodium phosphate (Drug B) and levornidazole disodium phosphate (Drug C) were mixed with equal mole amount, respectively. After giving the mixed drugs to the monkey, the concentration of 15N-levornidazole disodium phosphate, levornidazole disodium phosphate, 15N-levornidazole and levornidazole in plasma samples of pre-dosing and 24 h after administration were analyzed by a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. Pharmacokinetic calculations were performed through non-compartmental analysis using WinNonlin software. Two-sided 90% confidence intervals (CI) were used to evaluate the bioequivalence of two drugs. The results showed that levornidazole disodium phosphate was metabolized to levornidazole rapidly after administration, the body exposure were increased with the dosage. The method of bioequivalence used in this study was different from the traditional two periods, crossover design. By using the method of this study, the effects of administration period, intra-individual variability, and sequence of administration on bioequivalence were avoided. The results of this study had successfully supported the pharmacokinetic and bioequivalence study of this drug in human using the same approach.
As a new generation of anti-tumor drugs, taxanes has a good clinical efficacy in the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, head and neck cancer. However, low bioavailability of oral administration from low water solubility and low permeability significantly limited the development of their oral applications. Currently, the marketed preparations were non-oral drug preparations, and the injection contained a large number of surfactants (cremophor EL or Tween 80) and organic solvents (ethanol), which could result in fluid retention, hypersensitivity and other side effects, as well as poor compliance. Oral preparation will be an ideal form for development of taxanes medicines. According to the research by our and other groups in recent years, we investigate the technical strategies enhancing the water solubility and absorptive permeability to improve their oral bioavailability. Among them, we emphasize the application prospects of crystallography technology, and provide a theoretical basis to guide future research in the development of oral preparations for taxanes.
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