Expression level of metastasis-associated protein 1 (MTA1) is closely related to tumor growth and metastasis in various cancers. Although increased expression level of MTA1 was observed in hepatocellular carcinoma (HCC), role of MTA1 complex containing histone deacetylase (HDAC) in hepatitis B virus (HBV)-associated hepatocarcinogenesis has not been studied. Here, we demonstrated that HBx strongly induced the expression of MTA1 and HDAC1 genes at transcription level. MTA1 and HDAC1/2 physically associated with hypoxia-inducible factor-1a (HIF-1a) in vivo in the presence of HBx, which was abolished by knockdown of MTA1 by short interfering RNA (siRNA). HBx induced deacetylation of the oxygen-dependent degradation domain of HIF-1a, which was accompanied with dissociation of prolyl hydroxylases and von Hippel-Lindau tumor suppressor from HIF-1a. These results indicate that HBx-induced deacetylation is important for proteasomal degradation of HIF-1a. Further, we observed that protein levels of MTA1 and HDAC1 were increased in the liver of HBxtransgenic mice. Also, there was a higher expression of HDAC1 in HCC than in the adjacent non-tumorous cirrhotic nodules in 10 out of 12 human HBV-associated HCC specimens. Together, our data indicate a positive cross talk between HBx and the MTA1/HDAC complex in stabilizing HIF-1a, which may play a critical role in angiogenesis and metastasis of HBV-associated HCC.
Melatonin, the major secretory product of the pineal gland, scavenges a variety of reactive oxygen and nitrogen species in vivo and in vitro, indicating that melatonin is a potent function as an antioxidant. The objective of this study was to investigate the effect of melatonin in the presence or absence of hydrogen peroxide (H(2)O(2)) on sperm characteristics (motility, viability, survival rate, membrane integrity, lipid peroxidation (LPO) and mitochondria activity) and also to examine the developmental rates to the blastocysts stage of porcine oocytes fertilized in vitro with semen treated with or without melatonin (100 nM) in the presence or absence of H(2)O(2) (250 μM). The sperm were treated with melatonin in the presence or absence of H(2)O(2) for 3, 6, 9 and 12 h at 37°C and then analysed for the sperm characteristics. The porcine embryos were produced by in vitro maturation and in vitro fertilization (IVM/IVF) using semen treated with or without melatonin (100 nM) in the presence or absence of H(2)O(2) (250 μM) for 6 h. The semen characteristics, including motility, viability, survival rate, membrane integrity and mitochondria activity, were higher in the groups that were treated with melatonin in comparison to other groups, irrespective of incubation periods. Malondialdehyde levels in control, melatonin and melatonin + H(2)O(2) groups were lower than H(2)O(2) only group. A positive correlation was shown among motility, viability, survival rate and membrane integrity, but a negative correlation was observed between LPO and the other evaluation methods. The developmental rates to blastocysts of IVM/IVF porcine oocytes fertilized by semen treated with melatonin were significantly increased compared with any other groups, with the cell number of blastocysts shown to have a similar trend to the developmental rates. These results demonstrate that melatonin can improve the semen characteristics during in vitro storage and support the developmental ability of IVM/IVF embryos in pigs.
Background and purpose: Activation of P2X receptors on macrophages is an important stimulus for cytokine release. This study seeks evidence for functional expression of P2X receptors in macrophages that had been only minimally activated. Experimental approach: Whole-cell recordings were made from macrophages isolated 2-6 h before by lavage from mouse peritoneum, without further experimental activation. ATP (1-1000 mM) elicited inward currents in all cells (holding potential À60 mV). The properties of this current were compared among cells from wild type, P2X 1 À/À and P2X 4 À/À mice. Key results: Immunoreactivity for P2X 1 and P2X 4 receptors was observed in wild type macrophages but was absent from the respective knock-out mice. In cells from wild type mice, ATP and abmethyleneATP (abmeATP) evoked inward currents rising in 10-30 ms and declining in 100-300 ms: these were blocked by pyridoxal-phosphate-6-azophenyl-2 0 ,4 0 -disulphonic acid (PPADS, 10 mM). ATP also elicited a second, smaller (B10% peak amplitude), more slowly decaying (1-3 s) at concentrations X10 mM: this was resistant to PPADS and prolonged by ivermectin. Macrophages from P2X 1 À/À mice responded to ATP (4100 mM) but not abmeATP: these small currents were prolonged by ivermectin. Macrophages from P2X 4 À/À mice responded to ATP and abmeATP as cells from wild type mice, except that ATP did not evoke the small, slowly decaying component: these currents were blocked by PPADS. Conclusion: Mouse peritoneal macrophages that are minimally activated demonstrate membrane currents in response to ATP and abmeATP that have the predominate features of P2X 1 receptors.
A relationship between radiological characteristics and molecular signatures in AO/AOAs was shown. It is believed that radiological characteristics have prognostic value as a surrogate marker for molecular characteristics.
The aim of the present study was to elucidate the fundamental mechanism of bovine oviduct epithelial cell (BOEC) co-culture on developmental capacity of bovine in vitro oocyte maturation/in vitro fertilization (IVM/IVF) embryos. We examined the effects of astaxanthin against nitric oxide-induced oxidative stress on cell viability by MTT assay, lipid peroxidation (LPO) by using thiobarbituric acid (TBA) reaction for malondialdehyde (MDA) and the expression of antioxidant genes (CuZnSOD, MnSOD and Catalase) or apoptosis genes (Bcl-2, Caspase-3 and Bax) by RT-PCR in BOEC. We also evaluated the developmental rates of bovine IVM/IVF embryos co-cultured with BOEC pre-treated with astaxanthin (500 μM) in the presence or absence of sodium nitroprusside (SNP, 1000 μM) for 24 h. Cell viability in BOEC treated with SNP (50-2000 μM) lowered, while astaxanthin addition (50-500 μM) increased it in a dose-dependent manner. Cell viability in astaxanthin plus SNP (1000 μM) gradually recovered according to the increase in astaxanthin additions (100-500 mM). The LPO in astaxanthin group (50-500 μM) gradually decreased in a dose dependent manner and among SNP or astaxanthin plus SNP group, SNP alone and astaxanthin (50 μM) plus SNP shown a significant increase than other groups (p < 0.05). Expression of apoptosis or antioxidant genes was detected by RT-PCR. Bcl-2 and antioxidant genes were detected in astaxanthin or astaxanthin plus SNP group, and Caspase-3 and Bax genes were only found in SNP group. When bovine IVM/IVF embryos were cultured for 6-7 days under co-culture system such as BOEC treated with astaxanthin in the presence or absence of SNP, the developmental ability to blastocysts in 500 μM astaxanthin group was the highest of all groups. These results suggest that astaxanthin has a antioxidative effect on cell viability and LPO of BOEC, and development of bovine IVM/IVF embryos due to the induction of antioxidant genes and suppression of apoptosis genes.
BACKGROUND AND PURPOSE: Subependymal enhancement and DWI have been reported to be useful MR imaging markers for identifying true progression. Our aim was to determine whether the subependymal enhancement pattern and ADC can differentiate true progression from pseudoprogression in patients with glioblastoma multiforme treated with concurrent chemoradiotherapy by using temozolomide.
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