Synergistic interaction between melittin and chemotherapeutic agents and their possible mechanisms: an experimental research / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the effect of melittin and 5-Fu, DDP, and TXT on human gastric cancer cell line BGC-823 and to primarily explore their possible mechanisms.</p><p><b>METHODS</b>Median effect analysis was employed to determine the interaction between melittin and 5-Fu, DDP, TXT by analyzing the relationship between fraction affected (FA) and the combination index (CI) acquired from the dose-effect curve. Expressions of chemotherapeutic agent-associated genes of BGC-823 cells with or without treatment were measured by real-time fluorescent quantitative PCR.</p><p><b>RESULTS</b>(1) Both melittin and chemotherapeutic agents inhibited the growth of BGC-823. (2) For BGC-823 cells were acted by 5-Fu +melittin, when FA ranged between 0.35-0.75, CI was less than 1. For BGC-823 cells were acted by DDP + melittin, when FA ranged 0.55 or so, CI = 1; when Fa ranged below 0.55, CI was less than 1. For BGC-823 cells were acted by TXT + melittin, CI less than 1 could be seen in the whole interval. (3) After treatment suppressed were the expressions of chemotherapeutic agent-associated genes of BGC-823 cells such as thymidylate synthetase (TS), excision repair cross-complementing gene 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), beta-tubulin III (TUBB3), and microtubule-associated protein tau (MAPT).</p><p><b>CONCLUSIONS</b>Melittin had a synergistic effect on the cytotoxicity of chemotherapeutic agents. The possible mechanisms might be associated with down-regulating chemotherapeutic agent-associated genes.</p>

Mutation analysis and prenatal diagnosis of EXT1 gene mutations in Chinese patients with multiple osteochondromas / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Multiple osteochondromas (MO), an inherited autosomal dominant disorder, is characterized by the presence of multiple exostoses on the long bones. MO is caused by mutations in the EXT1 or EXT2 genes which encode glycosyltransferases implicated in heparin sulfate biosynthesis.</p><p><b>METHODS</b>In this study, efforts were made to identify the underlying disease-causing mutations in patients from two MO families in China.</p><p><b>RESULTS</b>Two novel EXT1 gene mutations were identified and no mutation was found in EXT2 gene. The mutation c.497T > A in exon 1 of the EXT1 gene was cosegregated with the disease phenotype in family 1 and formed a stop codon at amino acid site 166. The fetus of the proband was diagnosed negative. In family 2, the mutation c.1430-1431delCC in exon 6 of the EXT1 gene would cause frameshift and introduce a premature stop codon after the reading frame being open for 42 amino acids. The fetus of this family inherited this mutation from the father.</p><p><b>CONCLUSIONS</b>Mutation analysis of two MO families in this study demonstrates its further application in MO genetic counseling and prenatal diagnosis.</p>

Treatment of allergic airway inflammation and hyperresponsiveness by imiquimod modulating transcription factors T-bet and GATA-3 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Imiquimod is an imidazoquinoline, which class of compounds are known to have antiviral and antitumoural properties. In recent studies, it was shown that imiquimod modulates the T helper cell type Th1/Th2 response by inducing the production of Th1 cytokines like IFN-gamma, and by inhibiting the Th2 cytokines like interleukin (IL)-4. Several investigators have shown that T-bet and GATA-3 are master Th1 and Th2 regulatory transcription factors. This study investigated whether imiquimod treatment inhibited airway inflammation by modulating transcription factors T-bet and GATA-3.</p><p><b>METHODS</b>Thirty-six male SD rats were randomly divided into a control group, an asthmatic group, and an imiquimod group, which was exposed to an aerosol of 0.15% imiquimod. Twenty-four hours after the last ovalbumin (OVA) challenge, airway responsiveness was measured and changes in airway histology were observed. The concentrations of IL-4, IL-5 and IFN-gamma in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of IL-4, IL-5, IFN-gamma, T-bet and GATA-3 in lung and in CD4(+) T cells were determined by reverse transcription polymerase chain reaction (RT-PCR). The protein expressions of T-bet and GATA-3 were measured by Western blot.</p><p><b>RESULTS</b>It was demonstrated that imiquimod 1) attenuated OVA induced airway inflammation; 2) diminished the degree of airway hyperresponsiveness (AHR); 3) decreased the Th2 type cytokines and increased Th1 type cytokines mRNA and protein levels; 4) modulated the Th1/Th2 reaction by inhibiting GATA-3 production and increasing T-bet production.</p><p><b>CONCLUSION</b>Imiquimod treatment inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in committing T helper cells to a Th1 phenotype.</p>