MicroRNA-370-3p inhibits cell proliferation and induces chronic myelogenous leukaemia cell apoptosis by suppressing PDLIM1/Wnt/ß-catenin signaling.

Growing evidence has suggested that microRNA-370-3p (miR-370-3p) is downregulated and acts as a suppressor in several cancers. However, the role of miR-370-3p in chronic myeloid leukemia (CML) remains unknown. Here, the expression level and molecular mechanism of miR-370-3p in CML were investigated. Firstly, the expression of miR-370-3p has markedly decreased in the peripheral blood mononuclear cells (PBMCs) of patients with CML and in cell lines. Moreover, miR-370-3p in CML cells upregulated and downregulated proliferation and apoptosis, respectively. Notably, miR-370-3p directly targeted the 3'-untranslated region of PDZ and LIM domain protein 1 (PDLIM1). A negative correlation was observed between the levels of miR-370-3p and PDLIM1 in the PBMCs of patients with CML and healthy volunteers. PDLIM1 was shown to have an oncogenic role in CML cells by promoting proliferation and suppressing apoptosis. Finally, the miR-370-3p-PDLIM1-Wnt/ß-catenin signaling axis was indicated to play an important role in CML progression.

The oncogenic role of androgen receptors in promoting the growth of oral squamous cell carcinoma cells.

OBJECTIVES: The aims of this study were to examine the expression of androgen receptors (AR) in oral squamous cell carcinoma (OSCC) cells and tumors and to determine the role of AR in regulating OSCC cell growth. MATERIALS AND METHODS: Four OSCC cell lines were used for analyzing AR expression and transcriptional activity. The effects of AR knockdown on the growth and tumorigenicity of OSCC cells were examined. A series of 11 benign, 22 premalignant, and 21 malignant lesions of the oral cavity were used for analyzing AR expression. RESULTS: OSCC cells expressed AR proteins with differential activities. Stimulation of AR by dihydrotestosterone in OSCC cells caused an increase in cyclin D1 expression and promoted cell growth, whereas treatment with bicalutamide led to decreased cyclin D1 expression and inhibited cell growth. Knockdown of AR expression in OSCC cells resulted in decreased proliferation, increased apoptosis, and inhibited tumorigenicity. Results from immunohistochemical studies showed that AR immunoreactivity was found in 27% (3/11) of benign lesions, while 68% (15/22) of premalignant and 67% (14/21) of malignant lesions showed positive AR staining. CONCLUSION: Our data suggest that OSCC cells express functional AR proteins which are critical for promoting cell growth and causing malignant disease.

[The mechanism of macrophage apoptosis induced by lipopolysaccharide in mice].

Apoptosis is a major form of cell death, characterized morphologically by chromatin condensation and biochemically by endonuclease cleavage of DNA into oligonucleosomal fragments. We investigated apoptosis mechanism of peritoneal macrophage(M phi) induced by peritoneal injection of lipopolysaccharide(LPS) in mice. The results showed that: LPS induced the apoptosis of peritoneal M phi and concomitant decrease of phagocytosis(vs control group, P < 0.01), the concentration of NO2-/No3- in the peritoneal lavage fluid significantly increased after LPS injection; AG(inhibitor of iNOS) and PDTC(inhibitor of reactive oxygen species) prevented the apoptosis of M phi and reduced the concentration of NO2-/NO3- in the peritoneal lavage fluid. In vitro experiment, we found that AG and PDTC inhibited the apoptosis of M phi induced by IFN(100 U.ml-1) + LPS (10 micrograms.ml-1) by using DNA gel electrophoresis analysis. These evidences support that NO and active oxygen species may be involved in the apoptosis process of peritoneal M phi induced by LPS in mice.

Heat shock pretreatment prevents hydrogen peroxide injury of pulmonary endothelial cells and macrophages in culture.

The purpose of the present study was to determine whether heat shock pretreatment would protect pulmonary endothelial cells and alveolar macrophages against hydrogen peroxide (H2O2)-induced injury. The bovine pulmonary artery endothelial cells (BPAECs) heat-shocked (42 degrees C for 2 h) prior to exposure to H2O2 (1 mmol/L for 45 min) showed significant decrease in H2O2-mediated increment of release of lactate dehydrogenase and production of thiobarbituric acid-reactive substances, and obvious alleviation in H2O2-induced decrease in activities of catalase and superoxide dismutase. Heat-shocked (42 degrees C for 2 h) rat pulmonary alveolar macrophages (PAMs) also obtained acquired resistance to injury by subsequent exposure of 1, 2, or 3 mmol/L H2O2 for 45 min. Simultaneously with this acquired oxidative resistance, Northern blot analysis showed that heat-shocked BPAECs and PAMs, contained an increased level of mRNA coding for the inducible form of heat shock protein 70 (HSP70), and Western blot analysis indicated that there were increased expression of HSP70. Inhibition of protein synthesis by cycloheximide (25 micrograms/mL) and inhibition of RNA synthesis by actinomycin D (5 micrograms/mL) prevented the cytoprotection against H2O2. These results are consistent with the hypothesis that heat shock pretreatment would protect pulmonary endothelial cells and alveolar macrophages against H2O2-induced injury, and possibly that HSPs play a role in this cytoprotection.

[A study on the relationship between drinking water with high arsenic content and incidence of malignant tumour in Heihe Village, western part of Huhehot, Inner Mongolia].

Since 1991, it has been repeatedly reported that endemic arsenism was noticed in the large areas in the middle and west parts of Inne Mongolian Autonomous Region. Heihe village is located in a geological area with rich natural arsenic. The inhabitants of the village have drunk the water with high arsenic content for a long time and many people have died of malignant tumours. A historical prospective method has been used in the study. The research has been carried out chronologically on the statistical relationship between drinking water with high arsenic content consumed by local inhabitants for 22 years and the mortality of malignant tumours. This study has confirmed that the accumulated mortality rate and the average mortality rate of Heihe villagers who had drunk the water with high arsenic content for a number of total 22 years (from January 1971 to January 1993) were 13 590/10(5) person-year and 642.01/10(5) person-year. In terms of the portion among all malignant tumour deaths, cancer for the lung takes the lead, followed by liver cancer and then bladder cancer. The risk of death of malignant tumours in the villagers who drink water with high arsenic content was 9.38 times to the risk in the inhabitants who do not drink water with high arsenic content.

Isolation of a strain of Hantaan virus from peritoneal exudate cells of a patient with hemorrhagic fever with renal syndrome.

A new strain of Hantaan virus (HTNV), GH716, was isolated from the peritoneal exudate cells (PEC) of a patient with severe hemorrhagic fever with renal syndrome (HFRS). The isolate was propagated in Vero E6 cells. At each passage the virus-infected cells were examined for HTNV with immunofluorescence technique using monoclonal antibodies (McAb) 25-1 and 84-1 against HTNV. From passage 5 on, fluorescent intensity tended to stabilize at (+++) and infectivity titer reached 10(5) TCID50/ml. Using 14 McAb to 76-118 and BI strains of HTNV, we found that strain GH716 was antigenically similar to strain 76-118 (Apodemus type) and different from strain R22 (Rattus type), suggesting that GH716 may fall into the Apodemus type of HTNV. This is the first isolation of an HTNV from human PEC collected on the tenth day of illness. The successful isolation of strain GH716 may provide an alternative source of obtaining HTNV during the later stages of HFRS.

Hemorrhagic fever with renal syndrome. Separation of human peripheral blood T and B cells and detection of viral antigen.

In this study, total blood lymphocytes were prepared from patients with hemorrhagic fever with renal syndrome (HFRS) by a density gradient on Ficoll-Hypaque. T and B cells were then purified by passing the total lymphocytes over a nylon wool column. The purities of total lymphocytes, T cells and B cells were 97.8 +/- 2.3%, 91.6 +/- 4.5% and 74.2 +/- 12.1%, respectively. Also, after modification of cell fixation and smear drying, the number of cells were increased and the time needed for slide preparation was shortened. Detection of viral antigen by immunofluorescence assay using monoclonal antibodies to Hantavirus (HTNV) showed that the total lymphocytes. T cells and B cells were infected by HTNV during the early stages of HFRS and no specific fluorescence was seen in the cells from the late diuretic phase to convalescent phase. The results suggest that virus replication in blood lymphocytes may partly contribute in the early stages to the impairment of cell immune response and in vivo spread of HTNV to its target sites.

Relevance of N-nitrosamines to esophageal cancer in China.

Studies on the relevance of the N-nitrosamines to esophageal cancer in China are reviewed. Esophageal cancer is a complex and multifactorial problem. Although a causal association between nitrosamines exposure and esophageal cancer in China has not yet been rigorously established, exposure of Lin-Xian subjects to nitrosamines either directly or as a result of their in vivo formation has been detected in our study. Several N-nitrosamines (NDMA, NDEA, NMBzA, NPyr, NPip, and NSAR) in gastric juice collected from Lin-Xian inhabitants have been detected. A correlation was found between the lesions of esophageal epithelium and the amount of nitrosamines present. In addition, the amounts of N-nitrosamino acids (N-nitrosoproline, N-nitrosothiazolidine 4-carboxylic acid, NSAR, and nitrates) excreted in 24-hr urine of subjects in Lin-Xian were significantly higher than those in Fan-Xian, indicating a higher exposure to N-nitroso compound and their precursors of the inhabitants in the high-risk area. The effect of nitrosamines on human esophagus has been investigated at the cellular levels. The amounts of O6-MedG in DNA of esophageal or stomach mucosa of patients from Lin-Xian were higher than that from Europe (Lyon and Essen). The presence of O6-MedG in the human fetal esophagus cultured with NMBzA was also detected. These findings indicate that the elevated levels of O6-MedG in esophageal DNA could be the result of a recent exposure to N-nitroso compounds or a genetically determined reduced cellular capacity for repair of O6-MedG from DNA. The hyperplasia was induced in the esophagus of human fetus that cultured with NMBzA for 2 weeks to 2 months. The intervention studies of esophageal cancer in Lin-Xian have been pursued. Intake of moderate doses of ascorbic acids by Lin-Xian subjects effectively reduced the urinary levels of N-nitrosamino acids to those found in un-dosed subjects in the low-risk area. If N-nitroso compounds are formed in vivo and are among the causative factors of esophageal cancer in Lin-Xian, ascorbic acid appears to be effective in lowering the body burden of these carcinogenic compounds. Thus, the plan of chemoprevention is carried out in Lin-Xian.