Ovarian cancer has one of the highest mortalities in malignancies in women, but little is known of its tumour progression properties and there is still no effective molecule that can monitor its growth or therapeutic responses. MSLN (mesothelin), a secreted protein that is overexpressed in ovarian cancer tissues with a poor clinical outcome, has been previously identified to activate PI3K (phosphoinositide 3-kinase)/Akt signalling and inhibit paclitaxel-induced apoptosis. The present study investigates the correlation between MSLN and MMP (matrix metalloproteinase)-7 in the progression of ovarian cancer, and the mechanism of MSLN in enhancing ovarian cancer invasion. The expression of MSLN correlated well with MMP-7 expression in human ovarian cancer tissues. Overexpressing MSLN or ovarian cancer cells treated with MSLN showed enhanced migration and invasion of cancer cells through the induction of MMP-7. MSLN regulated the expression of MMP-7 through the ERK (extracellular-signal-regulated kinase) 1/2, Akt and JNK (c-Jun N-terminal kinase) pathways. The expression of MMP-7 and the migrating ability of MSLN-treated ovarian cancer cells were suppressed by ERK1/2- or JNK-specific inhibitors, or a decoy AP-1 (activator protein 1) oligonucleotide in in vitro experiments, whereas in vivo animal experiments also demonstrated that mice treated with MAPK (mitogen-activated protein kinase)/ERK- or JNK-specific inhibitors could decrease intratumour MMP-7 expression, delay tumour growth and extend the survival of the mice. In conclusion, MSLN enhances ovarian cancer invasion by MMP-7 expression through the MAPK/ERK and JNK signal transduction pathways. Blocking the MSLN-related pathway could be a potential strategy for inhibiting the growth of ovarian cancer. 相似文献
Hepatitis E virus (HEV) is one of the major pathogens that cause acute viral hepatitis. The human (genotypes 1 and 2) and zoonotic (genotypes 3 and 4) groups of HEV present different epidemiology and clinical features. In this study, we developed a classification method for rapidly classifying HEV into human or zoonotic groups that combines a general antigen test with a zoonotic group-specific antigen test. Evaluation of serial samples from HEV-infected rhesus monkeys indicated that HEV antigen-positive samples can be classified using the antigen-based classification method. The antigen-based classification method was evaluated further on 55 genotyped samples from acute hepatitis E patients, including 9 human and 46 zoonotic groups. The novel method was completely consistent with the sequencing results: 9/9 for the human groups (100%, 95% confidence interval [CI] 66.4–100%) and 46/46 for the zoonotic groups (100%, 95% CI 92.3–100%). This method was also successfully used for the clustering of some samples that could not be clustered by sequencing. Compared with the sequencing-based method, this method is less time-consuming, less expensive, and less technically complex and is therefore ideal for large numbers of samples. In conclusion, this study provides a convenient and sensitive method for classifying different groups of HEV, and it has potentially important public health applications, especially in underdeveloped areas that cannot afford the high cost of nucleic acid testing.
A series of novel Ligustrazine derivatives was designed, synthesized, and assayed for their protective effects on damaged ECV-304 cells and antiplatelet aggregation activities. The results showed that most Ligustrazine derivatives exhibited lower EC(50) values for protective effects on the ECV-304 cells damaged by hydrogen peroxide in comparison with Ligustrazine. And some Ligustrazine derivatives presented better antiplatelet aggregation activities than Ligustrazine. The derivatives containing the bisphenylmethyl pharmacophore (7a-c) exhibited highest potency. Compound 7a displayed most potential protective effects on the ECV-304 cells damaged by hydrogen peroxide, and compound 7c was found to be the most active antiplatelet aggregation agent. Structure-activity relationships were briefly discussed. 相似文献
A series of new sulfonyl pyrrolidine derivatives was designed, synthesized, and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and aminopeptidase N (AP-N). The results showed that these pyrrolidine derivatives exhibited highly selective inhibition against MMP-2 as compared with AP-N. The compounds 4c, 4j, 5a, and 5b were equally or more potent MMP-2 inhibitors than the positive control LY52. The FlexX docking was done to explain the reason for the different potency between MMP-2 and AP-N. Structure-activity relationships were also briefly discussed. 相似文献
Journal of Plant Growth Regulation - The apple (Malus domestica Borkh.) has a relatively long sapling stage which prevents fruit breeding. The understanding of the flowering system is important to... 相似文献
In this study, we evaluated the ability of 8.8 mT static magnetic fields (SMF) to enhance the in vitro action of a chemotherapeutic agent, paclitaxel, against K562 human leukemia cells. We analyzed the cell proliferation, cell cycle distribution, DNA damage and alteration of cell surface and cell organelle ultrastructure after K562 cells were exposed to paclitaxel in the presence or absence of 8.8 mT SMF. The results showed that in the presence of SMF, the efficient concentration of paclitaxel on K562 cells was decreased from 50 to 10 ng/ml. Cell cycle analysis indicated that K562 cells treated with SMF plus paclitaxel were arrested at the G2 phase, which was mainly induced by paclitaxel. Through comet assay, we found that the cell cycle arrest effect of paclitaxel with or without SMF on K562 cells was correlated with DNA damage. The results of atomic force microscopy and transmission electron microscopy observation showed that the cell ultrastructure was altered in the group treated with the combination of SMF and paclitaxel, holes and protuberances were observed, and vacuoles in cytoplasm were augmented. Our data indicated that the potency of the combination of SMF and paclitaxel was greater than that of SMF or paclitaxel alone on K562 cells, and these effects were correlated with DNA damage induced by SMF and paclitaxel. Therefore, the alteration of cell membrane permeability may be one important mechanism underlying the effects of SMF and paclitaxel on K562 cells. 相似文献