The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to ...The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (M展开更多
Diabetic nephropathy(DN) is the leading cause of end-stage renal failure worldwide. Besides, diabetic nephropathy is associated with cardiovascular disease, and increases mortality of diabetic patients. Several factor...Diabetic nephropathy(DN) is the leading cause of end-stage renal failure worldwide. Besides, diabetic nephropathy is associated with cardiovascular disease, and increases mortality of diabetic patients. Several factors are involved in the pathophysiology of DN, including metabolic and hemodynamic alterations, oxidative stress, and activation of the renin-angiotensin system. In recent years, new pathways involved in the development and progression of diabetic kidney disease have been elucidated; accumulated data have emphasized the critical role of inflammation in the pathogenesis of diabetic nephropathy. Expression of cell adhesion molecules, growth factors, chemokines and pro-inflammatory cytokines are increased in the renal tissues of diabetic patients, and serum and urinary levels of cytokines and cell adhesion molecules, correlated with albuminuria. In this paper we review the role of inflammation in the development of diabetic nephropathy, discussing some of the major inflammatory cytokines involved in the pathogenesis of diabetic nephropathy, including the role of adipokines, and take part in other mediators of inflammation, as adhesion molecules.展开更多
Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global pu...Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound Tem preparation, Chinese materia medica, and active components on I/R-induced cerebral imicrocirculatory disturbances, brain injury and neuron damage. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. Alt rights reserved.展开更多
Background： Acute coronary syndrome （ACS） is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability a...Background： Acute coronary syndrome （ACS） is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1（ICAM-1 ）, chitinase-3-like protein I （YKL-40）, and lipoprotein-associated phospholipase A2 （Lp-PLA2） in patients with ACS and its clinical significance. Methods： A total of 120 patients with coronary heart disease （CHD） were categorized into 2 groups： 69 with ACS and 51 with stable angina pectoris （SAP）： 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score 〈26 （n = 36）, moderate CHD group with its Gensini score being 26-54 （n = 48） and severe CHD group with its Gensini score 〉54 （n = 36）. Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed. Results： The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group （all P 〈 0.05）： and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group （P 〉 0.05）.The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group （all P 〉 0.05）. The levels of seru展开更多
AIM: To demonstrate the relationship between H-ras oncogene and hepatocellular carcinoma (HCC) metastasis. METHODS: Activated H-ras oncogene was transfected into SMMC 7721, a cell line derived from human HCC, by calci...AIM: To demonstrate the relationship between H-ras oncogene and hepatocellular carcinoma (HCC) metastasis. METHODS: Activated H-ras oncogene was transfected into SMMC 7721, a cell line derived from human HCC, by calcium phosphate transfection method. Some metastasis-related parameters were detected in vitro, including adhesion assay, migration assay, expression of collagenase IV(c IV ase) and epidermal growth factor receptor (EGFR). RESULTS: The abilities of H-ras-transfected cell clones in adhesion to laminin (LN) or fibronectin (FN), migration, c IV ase secretion increased markedly, and the expression of EGFR elevated moderately. More importantly, these alterations were consistent positively with the expression of p21, the protein product of H-ras oncogene. CONCLUSION: H-ras oncogene could induce the metastatic phenotype of HCC cell in vitro to raise its metastatic potential.展开更多
BACKGROUND:Experimental and clinical observations show that proinflammatory cytokines and oxidative stress are involved in the development of local and particularly systemic complications in acute pancreatitis (AP) pa...BACKGROUND:Experimental and clinical observations show that proinflammatory cytokines and oxidative stress are involved in the development of local and particularly systemic complications in acute pancreatitis (AP) patients. There are often pulmonary complications in such patients. The mechanisms through which lung injury is induced in AP are not fully clear. METHODS:In order to assess the role of activated neutrophils, pro- and anti-inflammatory cytokines and adhesion molecules at the onset and development of respiratory complications and respiratory failure, we measured the serum levels of pro-inflammatory (IL-1β, IL-6, IL-8, IL-18, TNF-α) and anti-inflammatory (IL-1ra, IL-10) cytokines in 51 AP patients who had been diagnosed with pancreatitis-associated lung injury with and without the development of organ dysfunction. RESULTS:When admitted to the hospital, severe AP patients had increased concentrations of IL-1β, IL-6, IL-8, IL-18, and TNF-α. The concentration of IL-18 alone was considerably increased in the patients who later developed respiratory failure. The onset of acute respiratory distress syndrome in the AP patients was accompanied by an increase in the level of anti-inflammatory cytokines, especially IL-10. It was noted that in severe lung injury, myeloperoxidase activity in the blood increased significantly, but still reflected the processes taking place in the lung parenchyma. Increase in the concentrations of adhesion molecules preceded the development of pulmonary infiltration with respiratory failure symptoms, which provoked endothelial dysfunction and determined the capillary surface permeability for neutrophils and monocytes.CONCLUSIONS:In the pathogenesis of respiratory complications in AP cytokines, chemokines and adhesion molecules, in particular IL-1β, IL-6, IL-8, IL-18, TNF-α, ICAM-1, and E-selectin play major roles. At IL-18 concentrations >650 pg/ml, AP patients are likely to develop pulmonary dysfunction (sensitivity 58%, specificity 100%, LR-positive >58) which allows us to use展开更多
Objective:To investigate the change of the hs-CRP,sVC AM-1,NT-proBNP levels of the patients with pregnancy-induced hypertension(PIH) syndrome.Methods:A total of 200 patients with PIH were divided into mild,moderate an...Objective:To investigate the change of the hs-CRP,sVC AM-1,NT-proBNP levels of the patients with pregnancy-induced hypertension(PIH) syndrome.Methods:A total of 200 patients with PIH were divided into mild,moderate and severe group,and 50 healthy pregnancy patients served as the control group.The serum sVCAM-1 levels were detected by enzyme-linked immunosorbent assay,hs-CRP were detected by immunity transmission turbidity,and NT-proBNP levels were determined by the colloidal gold method.Patients were treated with magnesium sulfate and nifudipine and the contrastive analysis was performed before and after treatment.And the pathological changes in placental of PIH patients were delected by hematoxylin-eosin staining at the same time.Results:The hs-CRP,sVCAM-l,NT-proBNP levels of patients in the mild, moderate and severe PHI group were significantly higher than that in the control group(P<0.05). The hs-CKP,sVCAM-l,NT-proBNP levels in the severe group were significantly higher than the mild group and the moderate group,the difference was statistically significant(P<0.05).The hsCRP,sVCAM-l,NT-proBNP of the moderate group were significantly higher than the mild group(P<0.05).There was a positive correlation between hs-CRP,sVCAM-1,NT-proBNP expression levels and the degree of the PIH.The expression of hs-CRP,sVCAM-1,NT-proBNP levels of the moderate and the severe group were significantly decreased(P<0.05).The number of placental villi and interstitial blood vessel in the moderate and severe PIH group were significantly less than the control group(P<0.05).Conclusions:The increased levels of serum hs-CRP,sVCAM-1, NT-proBNP may be involved in the process of vascular endothelial cell injury of the PIH,and the hs-CRP,sVCAM-1,NT-proBNP can be used as the auxiliary index for diagnosis of PIH and determination of PIH severity.展开更多
Objective： Intrauterine adhesion （IUA） is a major health problem that causes infertility, menstrual irregularities, and recurrent pregnancy losses in women. Unfortunately, treatments for IUA are limited, and there ...Objective： Intrauterine adhesion （IUA） is a major health problem that causes infertility, menstrual irregularities, and recurrent pregnancy losses in women. Unfortunately, treatments for IUA are limited, and there are currently no effective strategies for preventing IUA recurrence. In this review, we introduced the role of Hippo signaling in the normal endometrium and IUA and described the mechanisms by which the Hippo pathway integrates with the Wnt and transforming growth factor-β （TGF-β） signaling pathways to form an intricate network governing the development of fibrosis. Data Sources： Original research articles in English that were published until July 2017 were collected from the PubMed database. Study Selection： Literature search was conducted using the search terms ＂endometrial fibrosis OR fibrosis AND or OR intrauterine adhesion OR Asherman syndrome OR IUA,＂ ＂Hippo AND or OR Hippo/TAZ,＂ ＂TGF-β,＂ and ＂Wnt.＂ Related original research articles were included in the comprehensive analysis. Results： Endometrial fibrosis is recognized as a key pathological event in the development of IUA, which is characterized by epithelial/fibroblast-myofibroblast transition. Myofibroblasts play crucial roles in the pathogenesis of fibrous scarring, and myofibroblast differentiation can be triggered by multiple signaling pathways. H ippo signaling is a critical regulator of the epithelial/fibroblast-myofibroblast transition and α-smooth muscle actin, which exhibits a specific spatiotemporal expression in the endometrium. Conclusions： Hippo signaling plays a critical role in fibrous diseases and participates in cross talks with Wnt and TGF-β signaling. Our findings not only contributed to knowledge on the pathogenesis of endometrial fibrosis, but can also serve as a useful resource for developing specific molecular inhibitors for IUA treatment and prevention.展开更多
Cancer metastasis is the major cause of cancer morbidity and mortality, and accounts for about 90% of cancer deaths. Although cancer survival rate has been signi fi cantly improved over the years, the improvement is p...Cancer metastasis is the major cause of cancer morbidity and mortality, and accounts for about 90% of cancer deaths. Although cancer survival rate has been signi fi cantly improved over the years, the improvement is primarily due to early diagnosis and cancer growth inhibition. Limited progress has been made in the treatment of cancer metastasis due to various factors. Current treatments for cancer metastasis are mainly chemotherapy and radiotherapy, though the new generation anti-cancer drugs(predominantly neutralizing antibodies for growth factors and small molecule kinase inhibitors) do have the effects on cancer metastasis in addition to their effects on cancer growth. Cancer metastasis begins with detachment of metastatic cells from the primary tumor, travel of the cells to different sites through blood/lymphatic vessels, settlement and growth of the cells at a distal site. During the process, metastatic cells go through detachment, migration, invasion and adhesion. These four essential, metastatic steps are inter-related and affected by multi-biochemical events and parameters. Additionally, it is known that tumor microenvironment(such as extracellular matrix structure,growth factors, chemokines, matrix metalloproteinases) plays a signi fi cant role in cancer metastasis. The biochemical events and parameters involved in the metastatic process and tumor microenvironment have been targeted or can be potential targets for metastasis prevention and inhibition. This review provides an overview of these metastasis essential steps, related biochemical factors, and targets for intervention.展开更多
文摘The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (M
文摘Diabetic nephropathy(DN) is the leading cause of end-stage renal failure worldwide. Besides, diabetic nephropathy is associated with cardiovascular disease, and increases mortality of diabetic patients. Several factors are involved in the pathophysiology of DN, including metabolic and hemodynamic alterations, oxidative stress, and activation of the renin-angiotensin system. In recent years, new pathways involved in the development and progression of diabetic kidney disease have been elucidated; accumulated data have emphasized the critical role of inflammation in the pathogenesis of diabetic nephropathy. Expression of cell adhesion molecules, growth factors, chemokines and pro-inflammatory cytokines are increased in the renal tissues of diabetic patients, and serum and urinary levels of cytokines and cell adhesion molecules, correlated with albuminuria. In this paper we review the role of inflammation in the development of diabetic nephropathy, discussing some of the major inflammatory cytokines involved in the pathogenesis of diabetic nephropathy, including the role of adipokines, and take part in other mediators of inflammation, as adhesion molecules.
文摘Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound Tem preparation, Chinese materia medica, and active components on I/R-induced cerebral imicrocirculatory disturbances, brain injury and neuron damage. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. Alt rights reserved.
文摘Background： Acute coronary syndrome （ACS） is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1（ICAM-1 ）, chitinase-3-like protein I （YKL-40）, and lipoprotein-associated phospholipase A2 （Lp-PLA2） in patients with ACS and its clinical significance. Methods： A total of 120 patients with coronary heart disease （CHD） were categorized into 2 groups： 69 with ACS and 51 with stable angina pectoris （SAP）： 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score 〈26 （n = 36）, moderate CHD group with its Gensini score being 26-54 （n = 48） and severe CHD group with its Gensini score 〉54 （n = 36）. Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed. Results： The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group （all P 〈 0.05）： and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group （P 〉 0.05）.The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group （all P 〉 0.05）. The levels of seru
文摘AIM: To demonstrate the relationship between H-ras oncogene and hepatocellular carcinoma (HCC) metastasis. METHODS: Activated H-ras oncogene was transfected into SMMC 7721, a cell line derived from human HCC, by calcium phosphate transfection method. Some metastasis-related parameters were detected in vitro, including adhesion assay, migration assay, expression of collagenase IV(c IV ase) and epidermal growth factor receptor (EGFR). RESULTS: The abilities of H-ras-transfected cell clones in adhesion to laminin (LN) or fibronectin (FN), migration, c IV ase secretion increased markedly, and the expression of EGFR elevated moderately. More importantly, these alterations were consistent positively with the expression of p21, the protein product of H-ras oncogene. CONCLUSION: H-ras oncogene could induce the metastatic phenotype of HCC cell in vitro to raise its metastatic potential.
文摘BACKGROUND:Experimental and clinical observations show that proinflammatory cytokines and oxidative stress are involved in the development of local and particularly systemic complications in acute pancreatitis (AP) patients. There are often pulmonary complications in such patients. The mechanisms through which lung injury is induced in AP are not fully clear. METHODS:In order to assess the role of activated neutrophils, pro- and anti-inflammatory cytokines and adhesion molecules at the onset and development of respiratory complications and respiratory failure, we measured the serum levels of pro-inflammatory (IL-1β, IL-6, IL-8, IL-18, TNF-α) and anti-inflammatory (IL-1ra, IL-10) cytokines in 51 AP patients who had been diagnosed with pancreatitis-associated lung injury with and without the development of organ dysfunction. RESULTS:When admitted to the hospital, severe AP patients had increased concentrations of IL-1β, IL-6, IL-8, IL-18, and TNF-α. The concentration of IL-18 alone was considerably increased in the patients who later developed respiratory failure. The onset of acute respiratory distress syndrome in the AP patients was accompanied by an increase in the level of anti-inflammatory cytokines, especially IL-10. It was noted that in severe lung injury, myeloperoxidase activity in the blood increased significantly, but still reflected the processes taking place in the lung parenchyma. Increase in the concentrations of adhesion molecules preceded the development of pulmonary infiltration with respiratory failure symptoms, which provoked endothelial dysfunction and determined the capillary surface permeability for neutrophils and monocytes.CONCLUSIONS:In the pathogenesis of respiratory complications in AP cytokines, chemokines and adhesion molecules, in particular IL-1β, IL-6, IL-8, IL-18, TNF-α, ICAM-1, and E-selectin play major roles. At IL-18 concentrations >650 pg/ml, AP patients are likely to develop pulmonary dysfunction (sensitivity 58%, specificity 100%, LR-positive >58) which allows us to use
文摘Objective:To investigate the change of the hs-CRP,sVC AM-1,NT-proBNP levels of the patients with pregnancy-induced hypertension(PIH) syndrome.Methods:A total of 200 patients with PIH were divided into mild,moderate and severe group,and 50 healthy pregnancy patients served as the control group.The serum sVCAM-1 levels were detected by enzyme-linked immunosorbent assay,hs-CRP were detected by immunity transmission turbidity,and NT-proBNP levels were determined by the colloidal gold method.Patients were treated with magnesium sulfate and nifudipine and the contrastive analysis was performed before and after treatment.And the pathological changes in placental of PIH patients were delected by hematoxylin-eosin staining at the same time.Results:The hs-CRP,sVCAM-l,NT-proBNP levels of patients in the mild, moderate and severe PHI group were significantly higher than that in the control group(P<0.05). The hs-CKP,sVCAM-l,NT-proBNP levels in the severe group were significantly higher than the mild group and the moderate group,the difference was statistically significant(P<0.05).The hsCRP,sVCAM-l,NT-proBNP of the moderate group were significantly higher than the mild group(P<0.05).There was a positive correlation between hs-CRP,sVCAM-1,NT-proBNP expression levels and the degree of the PIH.The expression of hs-CRP,sVCAM-1,NT-proBNP levels of the moderate and the severe group were significantly decreased(P<0.05).The number of placental villi and interstitial blood vessel in the moderate and severe PIH group were significantly less than the control group(P<0.05).Conclusions:The increased levels of serum hs-CRP,sVCAM-1, NT-proBNP may be involved in the process of vascular endothelial cell injury of the PIH,and the hs-CRP,sVCAM-1,NT-proBNP can be used as the auxiliary index for diagnosis of PIH and determination of PIH severity.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 81601236 and No. 81471505）.
文摘Objective： Intrauterine adhesion （IUA） is a major health problem that causes infertility, menstrual irregularities, and recurrent pregnancy losses in women. Unfortunately, treatments for IUA are limited, and there are currently no effective strategies for preventing IUA recurrence. In this review, we introduced the role of Hippo signaling in the normal endometrium and IUA and described the mechanisms by which the Hippo pathway integrates with the Wnt and transforming growth factor-β （TGF-β） signaling pathways to form an intricate network governing the development of fibrosis. Data Sources： Original research articles in English that were published until July 2017 were collected from the PubMed database. Study Selection： Literature search was conducted using the search terms ＂endometrial fibrosis OR fibrosis AND or OR intrauterine adhesion OR Asherman syndrome OR IUA,＂ ＂Hippo AND or OR Hippo/TAZ,＂ ＂TGF-β,＂ and ＂Wnt.＂ Related original research articles were included in the comprehensive analysis. Results： Endometrial fibrosis is recognized as a key pathological event in the development of IUA, which is characterized by epithelial/fibroblast-myofibroblast transition. Myofibroblasts play crucial roles in the pathogenesis of fibrous scarring, and myofibroblast differentiation can be triggered by multiple signaling pathways. H ippo signaling is a critical regulator of the epithelial/fibroblast-myofibroblast transition and α-smooth muscle actin, which exhibits a specific spatiotemporal expression in the endometrium. Conclusions： Hippo signaling plays a critical role in fibrous diseases and participates in cross talks with Wnt and TGF-β signaling. Our findings not only contributed to knowledge on the pathogenesis of endometrial fibrosis, but can also serve as a useful resource for developing specific molecular inhibitors for IUA treatment and prevention.
文摘Cancer metastasis is the major cause of cancer morbidity and mortality, and accounts for about 90% of cancer deaths. Although cancer survival rate has been signi fi cantly improved over the years, the improvement is primarily due to early diagnosis and cancer growth inhibition. Limited progress has been made in the treatment of cancer metastasis due to various factors. Current treatments for cancer metastasis are mainly chemotherapy and radiotherapy, though the new generation anti-cancer drugs(predominantly neutralizing antibodies for growth factors and small molecule kinase inhibitors) do have the effects on cancer metastasis in addition to their effects on cancer growth. Cancer metastasis begins with detachment of metastatic cells from the primary tumor, travel of the cells to different sites through blood/lymphatic vessels, settlement and growth of the cells at a distal site. During the process, metastatic cells go through detachment, migration, invasion and adhesion. These four essential, metastatic steps are inter-related and affected by multi-biochemical events and parameters. Additionally, it is known that tumor microenvironment(such as extracellular matrix structure,growth factors, chemokines, matrix metalloproteinases) plays a signi fi cant role in cancer metastasis. The biochemical events and parameters involved in the metastatic process and tumor microenvironment have been targeted or can be potential targets for metastasis prevention and inhibition. This review provides an overview of these metastasis essential steps, related biochemical factors, and targets for intervention.
