Overexpression of angiotensin converting enzyme 2 inhibits inflammatory response of atherosclerotic plaques in hypercholesterolemic rabbits / 中华心血管病杂志

<p><b>OBJECTIVE</b>Angiotensin converting enzyme 2 (ACE2) efficiently hydrolyses the potent vasoconstrictor angiotensin II to vasodilative angiotensin (1-7). We hypothesized that ACE2 overexpression may inhibit inflammation response in atherosclerotic plaque by degrading Ang II into Ang-(1-7).</p><p><b>METHODS</b>Atherosclerosis (AS) plaques were induced in the abdominal aorta of 38 rabbits by endothelial injury and atherogenic diet for 3 months. Rabbits were then underwent injection of a recombinant adenovirus (2.5 x 10(9) pfu/ml) carrying a murine ACE2 gene (Ad-ACE2) through a catheter into the abdominal aortic segments rich in plaques (n = 19) or injection of a control vector Ad-EGFP (n = 19). One month later, all rabbits were sacrificed and plaques from aortic segments were analyzed.</p><p><b>RESULTS</b>ACE2 expression in aortic tissues of the Ad-ACE2 group were confirmed by immunohistochemistry. Macrophage infiltration (13.6% +/- 4.2% vs. 23.6% +/- 6.9%, P < 0.01) and MCP-1 expression (13.2% +/- 0.4% vs. 25.0% +/- 7.4%, P < 0.01) were significantly reduced in Ad-ACE2 group compared to Ad-EGFP group.</p><p><b>CONCLUSIONS</b>Overexpression of ACE2 inhibited atherosclerotic plaque inflammation response in hypercholesterolemic rabbits.</p>

Loss expression of active fragile sites genes associated with the severity of breast epithelial abnormalities / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>WWOX and FHIT are two candidate tumor suppressor genes located in active fragile sites, the damage of which has been associated with the development of breast cancer. The association of the expression of these genes and the development of breast cancer has not been fully explored. We evaluated mRNA and protein expression of WWOX and FHIT in breast tissue with normal histological appearances, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive cancer to see if a progressive decline in expression was present.</p><p><b>METHODS</b>Reverse transcription-polymerase chain reaction and Western blotting were used to evaluate the specimens for mRNA and protein expression, including 28 specimens with normal tissue, 28 specimens with atypical ductal hyperplasia, 33 specimens with ductal carcinoma in situ, and 51 specimens with invasive ductal carcinoma.</p><p><b>RESULTS</b>Compared with in situ and invasive cancer specimens, both normal and atypical hyperplasia specimens had greater rates of detectable mRNA (WWOX rate ratio = 2.95, 95% CI 1.24 - 7.08; FHIT rate ratio = 4.58, 95% CI 1.82 - 11.81) and Western blotting detectable protein (WWOX rate ratio = 4.12, 95% CI 1.63 - 10.73; FHIT rate ratio = 3.76, 95% CI 1.44 - 10.06). For both proteins, differences between normal and atypical hyperplasia specimens and between in situ and invasive carcinoma specimens were explainable by chance (P > 0.05 for each analysis). Within each histological category, differences among fractions of specimens showed that FHIT and WWOX mRNA and protein expression were explainable by chance (P > 0.05 for each analysis).</p><p><b>CONCLUSION</b>Expression of FHIT and WWOX decreases along with breast tissue progress from a normal histological appearance to atypical ductal hyperplasia, in situ cancer, and the final invasive cancer.</p>

Two novel mutations of GLA gene in Chinese patients with Fabry disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the disease-causing GLA gene mutations in Chinese patients with Fabry disease and the correlation between the genotype and phenotype.</p><p><b>METHODS</b>DNA from 2 Chinese patients with Fabry disease and their relatives were collected. The seven exons and nonjunctional regions of GLA gene were amplified with polymerase chain reaction and the products were sequenced. The correlation between the genotype and phenotype was analyzed.</p><p><b>RESULTS</b>Two mutations, G1168A and G1170A, located in 5' untranslated regions (5'UTR) were identified in the two probands and the two mutations were absent in normal controls. Three patients with the same genotype were found in the pedigree with G1168A mutation and there was no gene mutation carrier in the pedigree with G1170A mutation. Symptoms of the disease are less in female patients than that in male patients.</p><p><b>CONCLUSION</b>GLA gene mutation in 5'UTR may also be involved in the disease process of patients with Fabry disease and the phenotype is partly affected by gender.</p>

PPARgamma1 overexpression on caveolin-1 expression of Raw264.7 cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of PPARgamma1 gene overexpression on caveolin-1 mRNA and protein expressions in a murine macrophage cell line Raw264.7.</p><p><b>METHODS</b>Replication-deficient recombinant adenovirus expression vector of PPARgamma1 was constructed using the AdEasy system. Raw264.7 cells were randomly treated as follows: P group (PPARgamma1 gene overexpression), T group (Troglitazone 40 micromol/L in DMSO), PT group (PPARgamma1 gene overexpression and Troglitazone) and control group. Changes of PPARgamma1 and caveolin-1 at mRNA and protein levels were investigated.</p><p><b>RESULTS</b>Caveolin-1 expression can be detected by RT-PCR in Raw264.7, by immunocytochemistry method in cell and nuclear membrane but not by immunoblotting at protein level. Caveolin-1 expression at mRNA and protein levels in Raw264.7 were significantly higher in P, T and PT groups compared to control group and the expression was also significantly higher in PT group than that in P group and T group (P < 0.05). PPARgamma expression was significantly increased in PT group and P group where remained unchanged in T group compared to control group.</p><p><b>CONCLUSION</b>PPARgamma1 overexpression can upregulate caveolin-1 expression in macrophages. Troglitazone upregulated caveolin-1 expression in the absence of increased PPARgamma1 expressions at mRNA and protein levels.</p>

The negative regulatory effect of IFN-gamma on cognitive function of human natural killer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the regulatory effect of IFN-gamma on recognition of target cells by human natural killer (NK) cells.</p><p><b>METHODS</b>The cytotoxic activity of human NK cell lines (NK92, NKL) was detected by MTT method. Expression of NK cell receptors (NKG2D, NKG2A/B, KIR2DL1 and KIR2DS1) and MICA on target cells (the ligand of NKG2D) was measured by RT-PCR.</p><p><b>RESULTS</b>Both NK92 and NKL cells exerted higher cytotoxicity to tumor cells with MICA expression, while tumors without MICA expression could resist NK cell lysis. IFN-gamma (> 1000 U/ml) inhibited NK lysis of tumor cells with MICA expression through down-regulating the expression of NKG2D, but up-regulating the expression of NKG2A/B and KIR2DL1.</p><p><b>CONCLUSION</b>IFN-gamma has a negative effect on activation and cytotoxicity of human NK cells by altering the balance between the expression of activating and inhibitory receptors on NK cells in favor of inhibition. This may serve to limit NK cell over-activation in vivo.</p>

Inhibitory effect of breast cancer metastasis suppressor I gene on metastasis of human ovarian cancer cell in vitro and in vivo / 中华妇产科杂志

0.05).The ultramicrostructure of cells detected by electron microscope showed that GJIC function in transfected group was higher than that in the other two groups.While in migration assay,the numbers of cells in lower chamber passing through the membrane in transfected group,blank control group and negative control group were 112?23,306?49 and 322?91, respectively;with significant differences among 3 groups(P