Effect of hypoxia inducible factor-1α on thermotolerance against hyperthemia induced cardiomyocytes apoptosis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the expression changes and effects of hypoxia inducible factor-1α (HIF-1α) on non-lethal high temperature induced thermotolerance and its role on thermotolerance protection.</p><p><b>METHODS</b>H9c2 cardiomyocytes were cultured and pretreated with the HIF-1α inhibitor YC-1, the cells were then subjected to normal temperature (37 °C), thermotolerance induction (40 °C, 3 h), or hyperthermia (43 °C, 2 h). The cells were divided into 8 groups (n = 3 each): normal temperature control group; thermotolerance group; thermotolerance/hyperthermia group; hyperthermia group; DMSO+normal temperature group; YC-1+thermotolerance group; YC-1+thermotolerance/hyperthermia group; YC-1+hyperthermia group. Cell apoptotic rate was assessed by flow cytometry. Western blot was used to detect the expression of HIF-1α and caspase-3.</p><p><b>RESULTS</b>Flow cytometry results showed that apoptosis rate was similar between control group and thermotolerance group, between DMSO+normal temperature group and YC-1+thermotolerance group, between YC-1+thermotolerance/hyperthermia group and YC-1+hyperthermia group, but was significantly higher in hyperthermia group [(17.35 ± 1.07)%] than in control group [(7.52 ± 1.55)%, P < 0.01] which was partly reduced in thermotolerance/hyperthermia group [(12.58 ± 1.97)%, P < 0.01 vs. thermotolerance group]. Cell apoptosis rate of YC-1+thermotolerance/hyperthermia group (23.75 ± 1.92)% was significantly higher than that of thermotolerance/hyperthermia group [(12.58 ± 1.97)%, P < 0.01], and in YC-1+hyperthermia group [(24.89 ± 1.83)%] than in hyperthermia group [(17.35 ± 1.07)%, P < 0.01]. HIF-1α expression was obviously upregulated in thermotolerance cells compared with control cells, in thermotolerance/hyperthermia cells than in hyperthermia cells, in YC-1+thermotolerance group, YC-1+thermotolerance/hyperthermia group and YC-1+hyperthermia group than in DMSO group (all P < 0.05). Caspase-3 expression was similar between control group and thermotolerance group, but was significantly lower in thermotolerance/hyperthermia group than in hyperthermia group (P < 0.05), significantly higher in YC-1+thermotolerance group, YC-1+thermotolerance/hyperthermia group and YC-1+hyperthermia group than in DMSO group (all P < 0.05) and significantly higher in YC-1+thermotolerance/hyperthermia group than in thermotolerance/hyperthermia group (P < 0.01) and in YC-1+hyperthermia group than in hyperthermia group (P < 0.01).</p><p><b>CONCLUSION</b>Non-lethal high temperature induced thermotolerance can reduce heat stress-induced cardiomyocytes apoptosis rate via upregulating the expression of HIF-1α and inhibiting caspase-3 signalling pathways.</p>

Bone marrow stromal cells transfected with ciliary neurotrophic factor gene ameliorates the symptoms and inflammation in C57BL/6 mice with experimental allergic encephalomyelitis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the anti-inflammatory effect of bone marrow stromal cells (MSCs) transfected with recombinant adenovirus-mediated ciliary neurotrophic factor (CNTF) gene in C57BL/6 mice with experimental allergic encephalomyelitis (EAE).</p><p><b>METHODS</b>An adenovirus vector containing CNTF gene Ad-CNTF-IRES-GFP was constructed and transfected in the MSCs (MSC-CNTF). After examination of CNTF expression, the transfected cells were transplanted in C57BL/6 mice with MOG 35-55-induced EAE, which were monitored for the changes in the symptoms scores. The levels of tumor necrosis factor-alpha (TNF-alpha), inteferon-gamma (IFN-gamma), interleukin-12P35 (IL-12P35), and IL-10 in the peripheral blood of the mice were detected, and the number of MSC-CNTF cells in the spleen and spinal cord was counted. CD3+ T cell infiltration and TNF-alpha and IFN-gamma expressions in the lesions were also observed after the cell transplantation.</p><p><b>RESULTS</b>CNTF gene transfection resulted in significantly increased CNTF expression in the MSCs. The mice receiving MSC-CNTF transplantation exhibited significantly improved symptoms with shortened disease course and lessened disease severity. The cell transplantation also resulted in significantly decreased peripheral blood TNF-alpha levels, ameliorated CD3+T cell infiltrations and lowered TNF-alpha expression in the lesions, while the levels of IFN-gamma underwent no significant changes.</p><p><b>CONCLUSION</b>Transplantation of CNTF gene-transfected MSCs results in decreased peripheral blood TNF-alpha and IFN-gamma levels and reduced inflammatory cells, CD3-positive cells and TNF-alpha expression in the lesion of EAE, therefore providing better effect than MSCs in relieving the symptoms of EAE in mice.</p>

Loss of p53 gene and amplification of HER-2 oncogene in primary hepatocellular carcinoma and their clinical significance / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the deletion of p53 gene and amplification of HER-2 oncogene at chromosome 17 in primary hepatocellular carcinoma (HCC) and the clinical significance.</p><p><b>METHODS</b>Interphase dual fluorescence in situ hybridization (FISH) was applied to detect the ratio of the number of p53 gene copy or HER-2 oncogene copy to that of chromosome 17 copy, to determine the p53 gene deletion and HER-2 oncogene amplification in nuclei prepared from 42 surgical specimens of HCC. Statistical analysis for their clinical significance was performed.</p><p><b>RESULTS</b>Loss of p53 gene and amplification of HER-2 oncogene were detected in 27 (64.3%) and 9 (21.4%) of the 42 HCC respectively including 4 cases with low and 5 with high copy amplification. Six (14.3%) of 42 HCC showed simultaneously p53 gene deletion and HER-2 oncogene amplification. 61.9% (26/42) of HCC were polysomy 17, which correlated positively with p53 gene deletion (chi(2) = 12.286, P < 0.001). No close correlation between p53 gene loss and HER-2 oncogene amplification was found (chi(2) = 0.00, P = 1.00). Loss of p53 gene was related to the serum alpha-fetoprotein (AFP) level and the tumor size (P < 0.05). The postoperative 2-year survival rate (18.5%) of HCC patients with p53 gene deletion was significantly lower than postoperative 2-year survival rate (60.0%) of those without p53 gene loss (chi(2) = 7.467, P = 0.006). Meanwhile, HER-2 oncogene amplification showed a tendency of correlation with the tumor size (chi(2) = 2.973, P = 0.085), and the postoperative 2-year survival rate (0/9) of HCC patients with HER-2 oncogene amplification was significantly lower than those (42.4%) without HER-2 oncogene amplification (chi(2) = 3.977, P = 0.046).</p><p><b>CONCLUSION</b>There were a high frequency of p53 gene deletion and a low frequency of HER-2 oncogene amplification in primary HCC, which might be involved in initiation and development of a subset of primary HCC.</p>

Effect of hejie decoction on T-cell receptor V beta 7 gene expression in patients of chronic hepatitis B / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the therapeutic effect of Hejie Decoction (HJD) in treating chronic hepatitis B and its relationship with T-cell receptor V beta 7 (TCRV beta 7) gene expression.</p><p><b>METHODS</b>Forty-five patients of chronic hepatitis B were randomly divided into two groups. The 30 patients in the treated group were treated by HJD, and the 15 patients in the control group were treated by conventional western medicine. The therapeutic effect and changes of TCRV beta 7 gene expression after treatment were observed.</p><p><b>RESULTS</b>After 6 months treatment, the ALT level in the two groups were obviously decreased (P < 0.01). No significant difference was shown in comparison of the total effective rate between the two groups but it did show in comparison of markedly effective rate between them. TCRV beta 7 expression was detected in 5 patients of the treated group, and HBV-DNA and HBeAg in the 5 patients were all negatively converted. While in the control group, no one had TCRV beta 7 expression detected, either no one with negative conversion of HBV-DNA and HBeAg. TCRV beta 7 could not be detected in all the patients whose HBV-DNA and HBeAg hasn't negatively converted, though their liver function could be normalized.</p><p><b>CONCLUSION</b>HJD might have the effect of regulation on TCRV beta 7 expression, it possibly is the important way for HBV replication inhibition and virucidal action of HJD.</p>