Research progress of histidine-based tumor-targeting drug delivery systems / 药学学报

As a basic amino acid, histidine has a pKa close to the acidity of the tumor microenvironment, thus the charge and solubility of histidine are able to vary as the pH changes. Under a neutral environment, histidine is not charged and exhibits hydrophobic properties, while it can be protonated and becomes hydrophilic when exposed to mildly acidic pH, such as tumor microenvironment. Therefore, histidine is widely used in the design of drug delivery systems to target the mildly acidic pH of tumor microenvironment. This article reviews the recent progresses of histidine-based tumor-targeting drug delivery systems, and summarizes the principles on promoting internalization and tuning drug release by taking advantage of histidine. Finally, we point out the common issues on histidine application and illustrate its future prospects.

An Investigation on the Molecular Characteristics and Intracellular Growth Ability among Environmental and Clinical Isolates of Legionella pneumophila in Sichuan Province, China / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the molecular characteristics and intracellular growth ability of Legionella pneumophila (L. pneumophila) strains from 1989 to 2016 in Sichuan Province, China.@*METHODS@#Seventy-nine isolates of L. pneumophila were collected from environmental and clinical sources, including cooling towers, hot springs, bath water, fountains, and patients, and identified with 16S rRNA gene analysis and serum agglutination assay. The isolates were then typed by Sequence-Based Typing (SBT), and Genotyping of forty-two LP1 strains were analyzed by means of multiple-locus VNTR analysis with 8 loci (MLVA-8). All strains were further analyzed for two virulence genes: Legionella vir homologue (lvh) and repeats in structural toxin (rtxA). The intracellular growth ability of 33 selected isolates was determined by examining their interaction with J774 cells.@*RESULTS@#All isolates were identified to L. pneumophila including 11 serogroups, among which the main serogroup were LP1, accounting for 54.43%. Thirty-three different sequence types (STs) from five main clonal groups and five singletons were identified, along with 8 different MLVA patterns. Both the lvh and rtxA loci were found in all 79 strains. Thirty isolates showed high intracellular growth ability in J774 cells.@*CONCLUSION@#L. pneumophila is a potential threat to public health, and effective control and prevention strategies are urgently needed.

Inhibitory effect of Biejiajianwan pills on tumor growth and proliferating cell nuclear antigen expression in mice bearing H22 cell-induced tumor / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the anti-tumor effect of Biejiajianwan pills and explore its mechanism.</p><p><b>METHODS</b>Mice bearing neoplasm induced by H22 cell inoculation were randomized into 4 groups, namely the negative control group, positive control group (with cyclophosphamide treatment), and high- and low-dose Biejiajianwan pill group. The tumor-bearing mice received corresponding treatments for 15 consecutive days, after which their thymuses and spleens were isolated and weighed to calculate the thymus and spleen indices. The tumor mass was also weighed and the tumor inhibition rate calculated. Immunohistochemistry was performed to evaluate the expression intensity of proliferating cell nuclear antigen (PCNA) in the tumor tissue.</p><p><b>RESULTS</b>The pills significantly inhibited the growth of the implanted tumor and reduced the expression of PCNA in the tumor.</p><p><b>CONCLUSION</b>One of the possible mechanisms of the anti-tumor effects of Biejiajian pills might be associated with the inhibition of PCNA expression in the tumor.</p>

In vivo and in vitro anti-tumor effect of Sanjie Kangliu Decoction / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the anti-tumor effect of Sanjie Kangliu (swelling-dispersing) Decoction in vivo and in vitro.</p><p><b>METHODS</b>The mice bearing tumors (established by subcutaneous inoculation of SRS-82 cells) were fed with Sanjie Kangliu Decoction. The tumor was isolated and weighed to calculate the tumor inhibition rate, followed by morphological observation of the tumor cells under electron microscope. The DNA of the tumor cells was then extracted for agarose gel electrophoresis. In the in vitro experiment, cultured SRS-82 cells were treated with the serum of rats fed with Sanjie Kangliu Decoction, and the cell viability and apoptosis was examined by MTT assay and flow cytometry, respectively. Immunocytochemistry was employed to test the expression intensity of Bcl-2 protein of the rat serum-treated cells, and in situ hybridization performed to detect matrix metalloproteinase (MMP)-2 mRNA expression.</p><p><b>RESULTS</b>In the tumor-bearing mouse models, Sanjie Kangliu Decoction administration resulted in significant reduction of the tumor mass and apoptosis of the tumor cells as shown by typical apoptotic changes of the cell morphology and presence of DNA ladder in agarose gel electrophoresis. In comparison with the mice without the decoction treatment, the treated mice showed significantly lower tumor cell viability, higher cell apoptosis rate, and weaker Bcl-2 expression. The expression of MMP-2 mRNA showed no distinct difference between the groups.</p><p><b>CONCLUSION</b>Sanjie Kangliu Decoction has obvious anti-tumor effect both in vivo and in vitro possibly through the mechanism of inducing tumor cell apoptosis by reducing Bcl-2 expression without affecting the expression of MMP-2 mRNA.</p>