The incidence and mortality of hepatocellular carcinoma(HCC) have fallen dramatically in China and elsewhere over the past several decades. Nonetheless, HCC remains a major public health issue as one of the most commo...The incidence and mortality of hepatocellular carcinoma(HCC) have fallen dramatically in China and elsewhere over the past several decades. Nonetheless, HCC remains a major public health issue as one of the most common malignant tumors worldwide and one of the leading causes of death caused by cancer in China. Hepatocarcinogenesis is a very complex biological process associated with many environmental risk factors and factors in heredity, including abnormal activation of cellular and molecular signaling pathways such as Wnt/β-catenin, hedgehog, MAPK, AKT, and ERK signaling pathways, and the balance between the activation and inactivation of the proto-oncogenes and anti-oncogenes, and the differentiation of liver cancer stem cells. Molecule-targeted therapy, a new approach for the treatment of liver cancer, blocks the growth of cancer cells by interfering with the molecules required for carcinogenesis and tumor growth, making it both specific and selective. However, there is no one drug completely designed for liver cancer, and further development in the research of liver cancer targeted drugs is now almost stagnant. The purpose of this review is to discuss recent advances in our understanding of the molecular mechanisms underlying the development of HCC and in the development of novel strategies for cancer therapeutics.展开更多
In the present study, we investigated the dynamic expression of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway related factors in the process of in vitro hippocampal neural stem/progenitor cell differ...In the present study, we investigated the dynamic expression of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway related factors in the process of in vitro hippocampal neural stem/progenitor cell differentiation from embryonic Sprague-Dawley rats or embryonic Kunming species mice, using fluorescent quantitative reverse transcription-PCR and western blot analyses. Results demonstrated that the dynamic expression of fibroblast growth factor 8 was similar to fibroblast growth factor receptor 1 expression but not to other fibroblast growth factor receptors. Enzyme-linked immunosorbent assay demonstrated that fibroblast growth factor 8 and Sonic Hedgehog signaling pathway protein factors were secreted by neural cells into the intercellular niche. Our experimental findings indicate that fibroblast growth factor 8 and Sonic Hedgehog expression may be related to the differentiation of neural stem/progenitor cells.展开更多
Cardiac hypertrophy is the heart＇s response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress. Traditionally, it has been considered a beneficial mechanism; however, sustained...Cardiac hypertrophy is the heart＇s response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress. Traditionally, it has been considered a beneficial mechanism; however, sustained hypertrophy has been associated with a significant increase in the risk of cardiovascular disease and mortality. Delineating intracellular signaling pathways involved in the different aspects of cardiac hypertrophy will permit future improvements in potential targets for therapeutic intervention. Generally, there are two types of cardiac hypertrophies, adaptive hypertrophy, including eutrophy （normal growth） and physiological hypertrophy （growth induced by conditioning）, and maladaptive hypertrophy, physical including pathologic or reactive hypertrophy （growth induced by pathologic stimuli） and hypertrophic growth caused by genetic mutations affecting sarcomeric or cytoskeletal proteins. Accumulating observations from animal models and human patients have identified a number of intracellular signaling pathways that characterized as important transducers of the hypertrophic response, including calcineurin/nuclear factor of activated Tcells, phosphoinositide 3-kinases/Akt （PI3Ks/Akt）, G protein-coupled receptors, small G proteins, MAPK, PKCs, Gp130/STAT3, Na＋/H＋ exchanger, peroxisome proliferator-activated receptors, myocyte enhancer factor 2/histone deacetylases, and many others. Furthermore, recent evidence suggests that adaptive cardiac hypertrophy is regulated in large part by the growth hormone/insulin-like growth factors axis via signaling through the PI3K/Akt pathway. In contrast, pathological or reactive hypertrophy is triggered by autocrine and paracrine neurohormonal factors released during biomechanical stress that signal through the Gq/phosphorlipase C pathway, leading to an increase in cytosolic calcium and activation of PKC.展开更多
Background The protective effects of magnesium sulfate against ischemia-reperfusion injury of the small intestine in Sprague-Dawley （SD） rats have been confirmed in our previous research. However, its exact mechanis...Background The protective effects of magnesium sulfate against ischemia-reperfusion injury of the small intestine in Sprague-Dawley （SD） rats have been confirmed in our previous research. However, its exact mechanism is unclear. This study was to evaluate the role of PI3K/Akt signal pathway in the protective effect of magnesium sulfate against ischemia-reperfusion injury of the small intestine in SD rats. Methods Rat model of intestinal ischemia-reperfusion injury was used. The SD rats were divided into four groups randomly： sham operation group, ischemia-reperfusion group, magnesium sulfate group and magnesium sulfate plus LY294002 （an inhibitor of PI3K） group. The pathological changes of intestinal mucosa were examined; the activity of diamine oxidase （DAO） in plasma, the plasma contents of malondialdehyde （MDA）, and apoptosis rate of the intestinal mucosal cells were determined and compared. The expression of p-Akt was detected by Western blotting. Results There were more evident pathological changes of the intestinal mucosa （higher Chiu＇s score, P 〈0.05）, enhanced DAO activity （P 〈0.05）, elevated contents of MDA （P 〈0.05）, higher apoptosis rate （P 〈0.05）, and lower level of p-Akt （P 〈0.05） in the ischemia-reperfusion group compared with the sham operation group. There were less evident pathological changes of the intestinal mucosa （lower Chiu＇s score, P 〈0.05）, lower DAO activity （P 〈0.05）, lower contents of MDA （P 〈0.05）, and lower apoptosis rate （P 〈0.05）, but higher level of p-Akt （P 〈0.05） irL the magnesium sulfate group compared with the ischemia-reperfusion group. There were more evident pathological changes of the intes,inal mucosa （higher Chiu＇s score, P 〈0.05）, higher contents of MDA （P 〈0.05）, higher DAO activity （P 〈0.05） and higher apoptosis rate （P 〈0.05）, and lower level of p-Akt （P 〈0.05） in the magnesium sulfate plus LY294002 group compared with the magnesium sulfate group. Conclusions Activation of PI3K/Akt signal pathway results in the reduction of cell apoptosis, which likely accounts for the protective effect of magnesium sulfate against intestinal ischemia-reperfusion injury.展开更多
The histamine receptor antagonists in the treatment of allergic disease have limitations.The treatments of Chinese herbs have some curative effects on allergic skin lesions.Present research indicates that the mitogen-...The histamine receptor antagonists in the treatment of allergic disease have limitations.The treatments of Chinese herbs have some curative effects on allergic skin lesions.Present research indicates that the mitogen-activated protein kinase（MAPK）signaling pathway might be equally important in allergic reactions.It was found that the inhibition of MAPK signaling pathways might relieve allergy symptoms,and some herbs can inhibit the MAPK pathway,which yields anti-allergy effects.Chinese medicines（CMs）have immense potential in the development of treatments for allergic disease.展开更多
文摘The incidence and mortality of hepatocellular carcinoma(HCC) have fallen dramatically in China and elsewhere over the past several decades. Nonetheless, HCC remains a major public health issue as one of the most common malignant tumors worldwide and one of the leading causes of death caused by cancer in China. Hepatocarcinogenesis is a very complex biological process associated with many environmental risk factors and factors in heredity, including abnormal activation of cellular and molecular signaling pathways such as Wnt/β-catenin, hedgehog, MAPK, AKT, and ERK signaling pathways, and the balance between the activation and inactivation of the proto-oncogenes and anti-oncogenes, and the differentiation of liver cancer stem cells. Molecule-targeted therapy, a new approach for the treatment of liver cancer, blocks the growth of cancer cells by interfering with the molecules required for carcinogenesis and tumor growth, making it both specific and selective. However, there is no one drug completely designed for liver cancer, and further development in the research of liver cancer targeted drugs is now almost stagnant. The purpose of this review is to discuss recent advances in our understanding of the molecular mechanisms underlying the development of HCC and in the development of novel strategies for cancer therapeutics.
基金supported by the National Natural Science Foundation of China,No.81070614the Key Project of the Natural Science Foundation of Hubei Province of China,No.2008CDA044the Natural Science Foundation of Hubei University of Medicine,No.2011QDZR-2
文摘In the present study, we investigated the dynamic expression of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway related factors in the process of in vitro hippocampal neural stem/progenitor cell differentiation from embryonic Sprague-Dawley rats or embryonic Kunming species mice, using fluorescent quantitative reverse transcription-PCR and western blot analyses. Results demonstrated that the dynamic expression of fibroblast growth factor 8 was similar to fibroblast growth factor receptor 1 expression but not to other fibroblast growth factor receptors. Enzyme-linked immunosorbent assay demonstrated that fibroblast growth factor 8 and Sonic Hedgehog signaling pathway protein factors were secreted by neural cells into the intercellular niche. Our experimental findings indicate that fibroblast growth factor 8 and Sonic Hedgehog expression may be related to the differentiation of neural stem/progenitor cells.
文摘Cardiac hypertrophy is the heart＇s response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress. Traditionally, it has been considered a beneficial mechanism; however, sustained hypertrophy has been associated with a significant increase in the risk of cardiovascular disease and mortality. Delineating intracellular signaling pathways involved in the different aspects of cardiac hypertrophy will permit future improvements in potential targets for therapeutic intervention. Generally, there are two types of cardiac hypertrophies, adaptive hypertrophy, including eutrophy （normal growth） and physiological hypertrophy （growth induced by conditioning）, and maladaptive hypertrophy, physical including pathologic or reactive hypertrophy （growth induced by pathologic stimuli） and hypertrophic growth caused by genetic mutations affecting sarcomeric or cytoskeletal proteins. Accumulating observations from animal models and human patients have identified a number of intracellular signaling pathways that characterized as important transducers of the hypertrophic response, including calcineurin/nuclear factor of activated Tcells, phosphoinositide 3-kinases/Akt （PI3Ks/Akt）, G protein-coupled receptors, small G proteins, MAPK, PKCs, Gp130/STAT3, Na＋/H＋ exchanger, peroxisome proliferator-activated receptors, myocyte enhancer factor 2/histone deacetylases, and many others. Furthermore, recent evidence suggests that adaptive cardiac hypertrophy is regulated in large part by the growth hormone/insulin-like growth factors axis via signaling through the PI3K/Akt pathway. In contrast, pathological or reactive hypertrophy is triggered by autocrine and paracrine neurohormonal factors released during biomechanical stress that signal through the Gq/phosphorlipase C pathway, leading to an increase in cytosolic calcium and activation of PKC.
文摘Background The protective effects of magnesium sulfate against ischemia-reperfusion injury of the small intestine in Sprague-Dawley （SD） rats have been confirmed in our previous research. However, its exact mechanism is unclear. This study was to evaluate the role of PI3K/Akt signal pathway in the protective effect of magnesium sulfate against ischemia-reperfusion injury of the small intestine in SD rats. Methods Rat model of intestinal ischemia-reperfusion injury was used. The SD rats were divided into four groups randomly： sham operation group, ischemia-reperfusion group, magnesium sulfate group and magnesium sulfate plus LY294002 （an inhibitor of PI3K） group. The pathological changes of intestinal mucosa were examined; the activity of diamine oxidase （DAO） in plasma, the plasma contents of malondialdehyde （MDA）, and apoptosis rate of the intestinal mucosal cells were determined and compared. The expression of p-Akt was detected by Western blotting. Results There were more evident pathological changes of the intestinal mucosa （higher Chiu＇s score, P 〈0.05）, enhanced DAO activity （P 〈0.05）, elevated contents of MDA （P 〈0.05）, higher apoptosis rate （P 〈0.05）, and lower level of p-Akt （P 〈0.05） in the ischemia-reperfusion group compared with the sham operation group. There were less evident pathological changes of the intestinal mucosa （lower Chiu＇s score, P 〈0.05）, lower DAO activity （P 〈0.05）, lower contents of MDA （P 〈0.05）, and lower apoptosis rate （P 〈0.05）, but higher level of p-Akt （P 〈0.05） irL the magnesium sulfate group compared with the ischemia-reperfusion group. There were more evident pathological changes of the intes,inal mucosa （higher Chiu＇s score, P 〈0.05）, higher contents of MDA （P 〈0.05）, higher DAO activity （P 〈0.05） and higher apoptosis rate （P 〈0.05）, and lower level of p-Akt （P 〈0.05） in the magnesium sulfate plus LY294002 group compared with the magnesium sulfate group. Conclusions Activation of PI3K/Akt signal pathway results in the reduction of cell apoptosis, which likely accounts for the protective effect of magnesium sulfate against intestinal ischemia-reperfusion injury.
文摘The histamine receptor antagonists in the treatment of allergic disease have limitations.The treatments of Chinese herbs have some curative effects on allergic skin lesions.Present research indicates that the mitogen-activated protein kinase（MAPK）signaling pathway might be equally important in allergic reactions.It was found that the inhibition of MAPK signaling pathways might relieve allergy symptoms,and some herbs can inhibit the MAPK pathway,which yields anti-allergy effects.Chinese medicines（CMs）have immense potential in the development of treatments for allergic disease.
