Latest ArticlesThis study was designed to investigate the impacts of particle shape of micelles on cell uptake and tumor imaging applications. We designed and synthesized an ultra-pH sensitive PEG-iPDPA diblock polymer, and prepared it into wormlike micelles and spherical micelles by thin-film dispersion method and modified solvent evaporation method, respectively. Firstly, the pH responsiveness of two kinds of micelles was investigated in vitro. Both forms of micelles responded to pH sensitively, and each of them could reach 100 times of ON/OFF fold after conjugated with BDP fluorescent probe. Moreover, the cellular uptake of two forms of micelles depended on the concentration and incubation time. However, the amount of cellular uptake of spherical micelles was much higher than that of the wormlike micelles, which proved that the shape of nanoparticles had a great influence on the cellular uptake. The results of in vivo imaging revealed that the spherical micelles had a better tumor accumulation as well as tumor imaging outcomes. Finally, the biosafety of micelles was tested by MTT assay and H & E staining, which indicated that none of the two kinds of micelles had obvious toxicity. Collectively, these results suggest that the spherical micelles could be a better carrier compared with wormlike micelles in terms of cellular uptake, tumor accumulation and tumor detection.
Mesoporous silica nanoparticles (MSNs) have been widely used as drug carriers in the diagnosis and treatment of diseases due to their specific characteristics, which include a large surface area, ordered mesoporous structures, easy surface modification and feasible sustained release action for encapsulated drugs. With the research development of MSNs, the biodegradability and removability of mesoporous silica nanomaterials have attracted considerable attention in the clinical application of the MSNs-based formulations. This paper was prepared to emphasize the preparation approaches of biodegradable mesoporous silica nanoparticles through the metal oxide doping method and the organic compound doping method. We discussed the biodegradable mechanism and process of such nanoparticles, and finally, provided an insightful and helpful review of the prospective application of the biodegradable mesoporous silica nanoparticles in medical field.
Hepatic fibrosis is an important pathological process in the development of liver cirrhosis and liver cancer from chronic liver damage. So far there is no effective chemical drug in clinic for treatment of hepatic fibrosis. Therefore, the research in anti-hepatic fibrosis drugs is a hot topic. For drugs currently under research and development, most of the mechanisms of action are related to inhibition of factors that could cause or deteriorate liver fibrosis, including activation and proliferation of hepatic stellate cells, inflammation, oxidative stress and production of extracellular matrix, et al. In this review, we briefly analyze targets and drugs related to the mechanisms mentioned above in order to provide a reference to the future research and development of anti-hepatic fibrosis drugs.
Jasmonic acid (JA) can promote the biosynthesis of artemisinin.To have an insight into the JA signaling in Artemisia annua, two new genes belonging to JAZ family, namely AaJAZ5 and AaJAZ6, were cloned from Artemisia annua, which might be the negative regulators involved in the JA signaling pathway.Bioinformatic analysis showed that AaJAZ5 and AaJAZ6 contained the conserved domains of ZIM and Jas specific to JAZ family.According to tissue profile analysis, AaJAZ5 had the highest expression level in leaf and AaJAZ6 had the highest expression level in root.The expression levels of both AaJAZ5 and AaJAZ6 were markedly elevated by methyl jasmonate and mechanical wounding.The BiFC results indicated that AaJAZ5, as well as AaJAZ6, physically interacted with AaMYC2.Importantly, only AaJAZ5 could interact with AaCOI1.The interaction assays given by BiFC suggested that AaJAZ5 might play a crucial role in JA signaling.This study facilitated the further analysis of the functional divergence of JAZ-family members and the understanding of molecular mechanism on JA signaling to regulate the artemisinin biosynthesis.
Tumor microenvironment (TME) is the internal environment of tumor. As a functional unit, the microenvironment determines the occurrence and development of tumors. Hypoxia, inflammation and immunosuppression are three major characteristics of TME. Hypoxia signals involve in multiple immunosuppressive pathway. There is communication among the gut microbiota, chronic inflammation and immunity. The three characteristics are associated with each other to form a complex network affecting the metastasis of the tumor. TME also influences the development of immunotherapy and efficacy of drugs in solid tumor. Therefore, it is important to identify the valuable biomarkers to predict disease progression, to elucidate the mechanistic networks in the microenvironment, to develop microenvironment targeting drugs and effective drug combination strategies to improve the drug efficacy. All of these have a profound clinical value.
HIV-1 reverse transcriptase (RT) plays an important role in HIV-1 life cycle. At present, the listed NRTIs and NNRTIs targeting the RT showed high efficiency as clinical first-line drugs. However, the rapid emergence of multidrug-resistant viruses and significant cumulative drug toxicities compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, there is an urgent demand for new types of RT inhibitors with novel mechanism of action to address this challenge. In recent years, additional inhibitors with novel mechanism of action have been reported, including nucleic acid competitive inhibitors, reverse transcriptase-directed mutagenesis inhibitors, primers/templates-competitive reverse transcriptase inhibitors, polymerase-RNase H inhibitors, reverse transcription initiation process inhibitors, peptide inhibitors etc., which have brought new hope to the development of novel anti-HIV drugs. This article focuses on the development of these inhibitors.
The study was designed to explore the influence of high-fat diet on the metabolism profile of feces and intestinal contents of golden hamster to provide new information for the mechanism of drug action. Twelve golden hamsters fed with high-fat diet and twelve golden hamsters fed with normal diet were used as model group and control group, respectively. Serum samples were collected from the normal group and the model group at 2 weeks, 4 weeks and 8 weeks after the induction of high-fat diet. Serum biochemical parameters were measured in the control and model groups. The levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) levels in model group were higher than the control group. After 8 weeks, the feces and intestine contents were taken. The intestine was divided into four sections:jejunum, ileum, cecum and colon. The changes of endogenous metabolites in intestinal contents were analyzed by 1H NMR based metabolomics combined with multivariate statistical analysis to find the significant differences in metabolites. The metabolic profiles of hyperlipidemia model group and control group were significantly distinguished by the othorgonal partial least squares-discriminate analysis, (OPLS-DA). Compared with the control group, the endogenous metabolites in feces such as amino acids, fatty acids, tricarboxylic acid cycle intermediates and nucleotides related to intestinal microflora were changed significantly (P < 0.05), and the amino acid metabolites, protein spoilage products and choline metabolites in intestinal contents had significant changes (P < 0.05). The data suggest that the intestinal microflora plays an important role in the development of hyperlipidemia in golden hamsters from the molecular level of metabolites. This result provides useful information for the clinical treatment of hyperlipidemia and development of hyperlipidemia drug.
Fluorinated compounds, which now make up 20%-25% of all marketed chemical drugs, are playing significant role and showing great potential in medicinal chemistry. Fluorine substitution is always utilized to change the physicochemical properties of the compounds to improve the ADME/T properties. In addition, fluorine substitution leads to improvement of the ligand binding affinity. With respect to molecular level, organofluorine can form various intermolecular interactions with the target proteins, e.g., hydrogen bond, halogen bond, C-F…π interaction, polar interaction and so on. These interactions display unique properties or nature due to the specificity of fluorine atom, which are at the center of attention. This paper reviews the related research background, followed by the research progress of hydrogen bond, halogen bond, C-F…π interaction, polar interaction and some other interactions involved organofluorine.
Primary hepatocellular carcinoma as the main pathological type of liver cancer is one of the common malignant tumors in our country. Liver cancer stem cells (LCSCs) have the characteristics of multidrug resistance, anti-radiotherapy and high tumorigenicity in addition to the characteristics of stem cells, namely, self-renewal, multi-directional differentiation and unlimited proliferation. Based on the above features, relapse and metastasis often occur after the patients being treated with conventional methods, which results in poor prognosis. Effective treatment targeting LCSCs has the potential to cure hepatocellular carcinoma (HCC) completely. This article reviews the common biomarkers used in identification of LCSCs and development of stem cell-targeted therapy for HCC.
Berberine is one of the most studied original natural drugs in China in recent years. It is a new lipid-lowering drug with completely different mechanism from statins, which has been used in the multi-center clinical trials. However, berberine is poorly absorbed in the intestinal tract after oral administration leading a significant pharmacokinetic characteristic of low blood concentration (1%) and bioavailability (< 5%). That is to say, it is difficult to explain the therapeutical effect in vivo by the current pharmacokinetic results. In fact, this phenomenon also exists in a number of clinically effective natural drugs. This review introduces the pharmacokinetic characteristic of berberine by focusing on the gut microbiota to mediate the metabolic process of berberine in vivo. Meanwhile, taking berberine as an example, we emphasized the important role of intestinal bacteria on the pharmacokinetic study on the oral chemical drugs, and put forward a new research mode of drug PK-PD mediated by the gut microbiota.
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