OBJECTIVE To explore the effect and potential mechanism of 717 Jiedu decoction in ameliorating local tissue injury induced by Gloydius brevicaudus venom via regulating macrophage phenotype transformation.METHODS Rat blank-serum and drug-containing serum were prepared by intragastric administration of normal saline， tail-vein injection of anti- G. brevicaudus venom serum （0.6 mL per rat）， and intragastric administration of 717 Jiedu decoction at doses of 0.495， 0.99 and 1.98 g/kg （calculated as crude drug）. M0-type macrophages derived from human leukemia monocytic THP-1 cells induced and differentiated by PMA were divided into normal control group， model group， positive control group， and low-， medium- and high-concentration 717 Jiedu decoction drug-containing serum groups. Except for the normal control group， all other groups were treated with 10 μg/mL G. brevicaudus venom working solution and 10% blank or drug-containing serum. After the cultivation period， the cellular ultrastructural changes in each group were observed； the proportions of M1- and M2-type macrophages， as well as the mRNA and protein expression of macrophage phenotype transformation and hypoxia-inducible factor-1α （HIF-1α） were detected.RESULTS Compared with the normal control group， cells in the model group presented ultrastructural injuries including mitochondrial swelling， cristae rupture and cytoplasmic vacuolization. The proportion of M1-type macrophages and the mRNA and protein expression levels of related phenotype transformation markers [inducible nitric oxide synthase， tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β] and HIF-1α were significantly increased （ P ＜0.05），whereas the proportion of M2-type macrophages and the mRNA and protein expression levels of related phenotype transformation markers （arginase-1， IL-10， mannose receptor C type 1 and chitinase-3-like protein 1） were significantly decreased （ P ＜0.05）. Compared with the model group， cellular ultrastructural injuries were obviously alleviated， and the above-mentioned indexes were significantly reversed in the high-concentration 717 Jiedu decoction drug-containing serum group （ P ＜0.05）.CONCLUSIONS717 Jiedu decoction can exert anti-inflammatory and tissue-repairing effects by regulating the balance of M1-， M2-type macrophages phenotype transformation and repairing cellular ultrastructural damage. Its mechanism may be related to inhibiting the excessive activation of the HIF-1α pathway.

OBJECTIVETo study genome-wide gene expression changes in gastric cancer cells after iodine-125 ¹²⁵(I) particle irradiation.

METHODS¹²⁵I particles were used to irradiate three gastric cancer cell lines of various differentiation levels:high (BGC-823) , medium (AGS) and low (NCI-N87) .Whole-genome gene expression was investigated with microarray. The gene expression in iodine-125 irradiated and untreated cancer cells was compared, and the genes with transcript levels altered for at least 2 folds (P < 0.05) were selected. The change in gene expression levels was verified by using quantitative real-time (qRT) -PCR.

RESULTSThe three gastric cancer cell lines received the same dose rate of ¹²⁵I particle irradiation. Cluster analysis showed that the Gene Ontology (GO) categories did not change in the three cell lines, but changes in gene expression levels were evident for many genes. After ¹²⁵I particle irradiate NCI-N87 cells, 895 genes were up-regulated, 786 genes were down-regulated; AGS was irradiated by ¹²⁵I seed, there were 124 genes upregulated, 161 genes were down-regulated; BGC-823 cells were treated by ¹²⁵I seed irradiation, 2 412 genes upregulated, 3 243 downregulated genes. After ionizing radiation can cause very complex transcriptional regulation changes, KEGG pathway analysis shows that these differentially expressed genes overlap in a particular cell pathway. Four genes, TRAF3IP2-AS1, SDC1, RABL2B and NOM, were found having at least 2-fold difference in expression (P < 0.05) , and the gene expression alteration was confirmed by qRT-PCR.

CONCLUSIONS¹²⁵I particle irradiation caused gene expression changes in gastric cancer cells. The expressions of TRAF3IP2-AS1, SDC1, RABL2B and NOM are altered significantly in all three cell lines studied, indicating that these genes may play an important role in the ¹²⁵I seed treatment of gastric cancer. These genes could be potential targets for developing anti-cancer drugs in the future.

Cell Line, Tumor ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; radiation effects ; Humans ; Iodine Radioisotopes ; adverse effects ; Stomach Neoplasms ; metabolism ; pathology

Objective To explore the effectiveness of 125I seed implantation for gastric cancer and to determine whether the therapy could increase the survival rate.Methods Seventy-six gastric cancer patients in stage Ⅱ or Ⅲ were involved and randomly divided into treatment group (n =42) and control group (n =34)by simple random sampling method.The patients in the control group underwent D2 or D3 surgery and the patients in treatment group underwent D2 or D3 surgery plus interstitial implantation of 125I seeds.All patients signed the informed consents.Treatment results were evaluated as CR,PR,NC and PD.CR and PR were considered as effective and the effective rate was calculated.All patients were followed up and the three-or five-year survival rate was calculated,the complications were examined.x2 test was used to compare the significant difference between the two groups.Results The total effective rate in control group was 50.00％ (17/34),lower than that of treatment group (73.81％,31/42; x2 =4.578,P＜0.05).In the treatment group,the three-year and five-year survival rates were 61.90％(26/42) and 42.86％(18/42) respectively,and the corresponding rates in the control group were 11.76％(4/34) and 0(0/34) respectively (x2=19.771,19.094,both P＜0.001).Both of the two groups had few severe side effects.Conclusion Radical surgery plus 1~Iseed implantation is effective and safe for the treatment of stage Ⅱ or Ⅲ gastric cancer and can further improvelong-term survival.