Objective:Lymphatic endothelial cell(LEC)proliferation is essential for lymphangiogenesis.Hypoxia induces lymphangiogenesis,but it directly inhibits LEC proliferation and the underlying mechanisms have not been fully ...Objective:Lymphatic endothelial cell(LEC)proliferation is essential for lymphangiogenesis.Hypoxia induces lymphangiogenesis,but it directly inhibits LEC proliferation and the underlying mechanisms have not been fully understood.The aim of this study was to investigate the role of carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1)in hypoxia-repressed LEC proliferation.Methods:Human dermal lymphatic endothelial cells(HDLECs)were cultured under normoxic or hypoxic conditions,and cell proliferation was determined using MTT or CCK-8 assays.CEACAM1 expression was silenced by siRNA transfection.Activation of mitogen-activated protein kinases(MAPKs)was examined by Western blotting and blocked by specific inhibitors.Results:Under hypoxia,HDLECs proliferation was suppressed and CEACAM1 expression was downregulated.Silence of CEACAM1 in normoxia inhibited HDLECs proliferation and did not further decrease proliferation in HDLECs in response to hypoxia,suggesting that CEACAM1 may mediate hypoxia-induced inhibition of HDLECs proliferation.In addition,silence of CEACAM1 increased phosphorylation of MAPK molecules:extracellular signal-regulated kinase(ERK),p38 MAPK and Jun N-terminal kinase(JNK)in HDLECs.However,only inhibition of the JNK pathway rescued the reduction of HDLEC proliferation induced by CEACAM1 silence.Conclusion:Our results suggested that hypoxia downregulates CEACAM1 expression by activation of the JNK pathway,leading to inhibition of HDLEC proliferation.These findings may help to understand the mechanisms of LEC-specific response to hypoxia and develop novel therapies for pathological lymphangiogenesis.展开更多
The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peri...The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A m RNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration.展开更多
This study determined the levels of serum soluble intercellular adhesion molecule-1 （sI-CAM-l） and soluble vascular cell adhesion molecular-1 （sVCAM-1） in patients with different types of Keshan disease （KD）, ex...This study determined the levels of serum soluble intercellular adhesion molecule-1 （sI-CAM-l） and soluble vascular cell adhesion molecular-1 （sVCAM-1） in patients with different types of Keshan disease （KD）, examined the relationship between Coxsackie B virus-specific IgM antibody （CBV-IgM） and slCAM-1 or sVCAM-1 in KD patients, and investigated the role of these adhesion molecules in the pathogenesis of KD and their clinical implications. The levels of serum slCAM-1, sVCAM-1 and CBV-IgM were measured by using enzyme-linked immunosorbent assay in 22 patients with chronic Keshan disease （CKD）, 27 with latent Keshan disease （LKD） and 28 healthy controis. The subjects in different groups were adjusted for sex and age. Echocardiography was adopted to determine left ventricular ejection fraction （LVEF） in 22 patients with CKD. The results showed that CKD patients had significantly higher levels of slCAM-1 and sVCAM-1 than LKD patients and healthy controls （P〈0.01 for all）. And there was significant difference in the levels of the 2 adhesion molecules between LKD patients and healthy controls （P〈0.05）. A negative correlation was found between LVEF and slCAM-1 or sVCAM-1 in CKD patients. The percentage of CBV-specific IgM positive individuals in KD patients was significantly higher than that of healthy controls. In CVB-specific IgM positive patients, the levels of serum slCAM-1 and sVCAM-1 were significantly greater than those in CBV-specific IgM negative counterpart. It was concluded that the increase in the levels of slCAM-1 and sVCAM-1 suggests the progression of inflammation in KD. slCAM-1 and sVCAM-1 can promote the development of myocardial pathology and lead to poor myocardial function. The increased serum slCAM-1 and sVCAM-1 in KD patients may be related to CBV infection.展开更多
Background Loss of carcinoembryonic antigen-related cell adhesion molecule 1 （CEACAM1） expression is an adverse prognostic factor in hepatocellular carcinoma （HCC）. The purpose of this study was to investigate the...Background Loss of carcinoembryonic antigen-related cell adhesion molecule 1 （CEACAM1） expression is an adverse prognostic factor in hepatocellular carcinoma （HCC）. The purpose of this study was to investigate the expression of CEACAM1 and its effect on relapse-free survival （RFS） following liver transplantation （LT） for HCC. Methods Expression of CEACAM1 was immunohistochemically detected in HCC specimens from 48 patients. The relationship between CEACAM1 expression and clinicopathologic variables, as well as tumor recurrence, was further analyzed. Results Of the 48 HCC specimens, membranous CEACAM1 expression was detected in 25 specimens and cytoplasmic CEACAM1 expression was detected in 19 specimens. Four specimens had loss of CEACAM1 expression. Loss of membranous CEACAM1 expression was significantly associated with tumor size, tumor number, and serum （z-fetoprotein levels （all P 〈0.05）. Patients with loss of membranous CEACAM1 had significantly poorer RFS than patients with membranous expression, determined via Kaplan-Meier analysis （P=0.027）. Multivariate analysis revealed that loss of membranous CEACAM1 expression might be an independent prognostic factor of RFS for HCC patients after liver transplantation （P=0.037）. Conclusion Loss of membranous CEACAM1 expression in HCC was closely associated with aggressive tumor biology and might be a relapsing biomarker of HCC treated with LT.展开更多
Objective:To investigate the frequency and function of Tim-3^(+)CD8^(+)T cells in the third trimester of normal pregnancies(NPs)and preeclamptic(PE)pregnancies.Methods:T-cell immunoglobulin mucin-3(Tim-3)expression le...Objective:To investigate the frequency and function of Tim-3^(+)CD8^(+)T cells in the third trimester of normal pregnancies(NPs)and preeclamptic(PE)pregnancies.Methods:T-cell immunoglobulin mucin-3(Tim-3)expression levels of CD8^(+)T cells in the decidua,peripheral blood,and umbilical cord blood obtained from women showing NPs and PE pregnancies were analyzed using flow cytometry.Decidual CD8^(+)T cells were cultured in the presence of recombinant human carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1)protein and/or Tim-3-specific neutralizing antibodies for analyzing CD107a and intracellular cytokine expression.The placental CEACAM1 protein expression was analyzed using immunohistochemistry.Results:Tim-3^(+)CD8^(+)T cells were more abundant in the decidua than in the peripheral blood.Tim-3 expression in the decidual CD8^(+)T cells was significantly lower in PE patients.Decidual Tim-3^(+)CD8^(+)T cells from PE patients expressed higher levels of CD107a and the Th1-type cytokine IFN-γ,but lower levels of the Th2-type cytokine IL-4.CEACAM1 altered the CD107a,IFN-γ,and IL-4 levels;this was reversed by anti-Tim-3 antibodies.The CEACAM1 protein levels were lower in the placental tissues of women with PE pregnancies than in those of women with NPs.Conclusions:Abnormal CEACAM1/Tim-3 regulation may participate in the development of PE,accompanied by disturbed Th2 cell predominance and higher cytotoxicity of decidual CD8^(+)T cells.展开更多
AIM: To provide further insight into the characterization of mucosa-associated Escherichia coli (E. coli) isolated from the colonic mucosa of cancer patients.
Objective To determine whether the antiatherogenic effect of L arginin e is due to an inhibition of vascular cell adhesion molecule 1 (VCAM 1) expres sion in the aortae of hypercholesterolemic rats. Methods T...Objective To determine whether the antiatherogenic effect of L arginin e is due to an inhibition of vascular cell adhesion molecule 1 (VCAM 1) expres sion in the aortae of hypercholesterolemic rats. Methods Twenty four male Wistar rats were randomized into three gr oups : Group NC with normal diet (NC, n=8), Group CC with 4% cholesterol and 1% choli c acid diet (CC, n=8), Group AC with 4% cholesterol and 1% cholic acid diet supp lemented with 3% L arginine HCl in the drinking water (AC, n=8). Eight weeks la ter, the blood samples were collected for biochemical studies, and the aortae we re harvested for RT PCR and immunohistochemical studies.Results The results showed that dietary L arginine supplementation red uced expression of VCAM 1 in protein level and mRNA level. Conclusion Inhibitory effect of dietary supplementation of L argin ine on VCAM 1 expression may be one of the mechanisms of its antiatherosclerosis.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81873473 and No.91939110)Academic Promotion Program of Shandong First Medical University(No.2019QL014)Shandong Taishan Scholarship(Ju Liu).
文摘Objective:Lymphatic endothelial cell(LEC)proliferation is essential for lymphangiogenesis.Hypoxia induces lymphangiogenesis,but it directly inhibits LEC proliferation and the underlying mechanisms have not been fully understood.The aim of this study was to investigate the role of carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1)in hypoxia-repressed LEC proliferation.Methods:Human dermal lymphatic endothelial cells(HDLECs)were cultured under normoxic or hypoxic conditions,and cell proliferation was determined using MTT or CCK-8 assays.CEACAM1 expression was silenced by siRNA transfection.Activation of mitogen-activated protein kinases(MAPKs)was examined by Western blotting and blocked by specific inhibitors.Results:Under hypoxia,HDLECs proliferation was suppressed and CEACAM1 expression was downregulated.Silence of CEACAM1 in normoxia inhibited HDLECs proliferation and did not further decrease proliferation in HDLECs in response to hypoxia,suggesting that CEACAM1 may mediate hypoxia-induced inhibition of HDLECs proliferation.In addition,silence of CEACAM1 increased phosphorylation of MAPK molecules:extracellular signal-regulated kinase(ERK),p38 MAPK and Jun N-terminal kinase(JNK)in HDLECs.However,only inhibition of the JNK pathway rescued the reduction of HDLEC proliferation induced by CEACAM1 silence.Conclusion:Our results suggested that hypoxia downregulates CEACAM1 expression by activation of the JNK pathway,leading to inhibition of HDLEC proliferation.These findings may help to understand the mechanisms of LEC-specific response to hypoxia and develop novel therapies for pathological lymphangiogenesis.
基金supported by the National Natural Science Foundation of China,No.81371389,31500927,31300942,81201017the Collegiate Natural Science Foundation of Jiangsu Province of China,No.13KJB180018the Natural Science Foundation of Nantong University of China,No.14ZY013
文摘The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A m RNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration.
文摘This study determined the levels of serum soluble intercellular adhesion molecule-1 （sI-CAM-l） and soluble vascular cell adhesion molecular-1 （sVCAM-1） in patients with different types of Keshan disease （KD）, examined the relationship between Coxsackie B virus-specific IgM antibody （CBV-IgM） and slCAM-1 or sVCAM-1 in KD patients, and investigated the role of these adhesion molecules in the pathogenesis of KD and their clinical implications. The levels of serum slCAM-1, sVCAM-1 and CBV-IgM were measured by using enzyme-linked immunosorbent assay in 22 patients with chronic Keshan disease （CKD）, 27 with latent Keshan disease （LKD） and 28 healthy controis. The subjects in different groups were adjusted for sex and age. Echocardiography was adopted to determine left ventricular ejection fraction （LVEF） in 22 patients with CKD. The results showed that CKD patients had significantly higher levels of slCAM-1 and sVCAM-1 than LKD patients and healthy controls （P〈0.01 for all）. And there was significant difference in the levels of the 2 adhesion molecules between LKD patients and healthy controls （P〈0.05）. A negative correlation was found between LVEF and slCAM-1 or sVCAM-1 in CKD patients. The percentage of CBV-specific IgM positive individuals in KD patients was significantly higher than that of healthy controls. In CVB-specific IgM positive patients, the levels of serum slCAM-1 and sVCAM-1 were significantly greater than those in CBV-specific IgM negative counterpart. It was concluded that the increase in the levels of slCAM-1 and sVCAM-1 suggests the progression of inflammation in KD. slCAM-1 and sVCAM-1 can promote the development of myocardial pathology and lead to poor myocardial function. The increased serum slCAM-1 and sVCAM-1 in KD patients may be related to CBV infection.
文摘Background Loss of carcinoembryonic antigen-related cell adhesion molecule 1 （CEACAM1） expression is an adverse prognostic factor in hepatocellular carcinoma （HCC）. The purpose of this study was to investigate the expression of CEACAM1 and its effect on relapse-free survival （RFS） following liver transplantation （LT） for HCC. Methods Expression of CEACAM1 was immunohistochemically detected in HCC specimens from 48 patients. The relationship between CEACAM1 expression and clinicopathologic variables, as well as tumor recurrence, was further analyzed. Results Of the 48 HCC specimens, membranous CEACAM1 expression was detected in 25 specimens and cytoplasmic CEACAM1 expression was detected in 19 specimens. Four specimens had loss of CEACAM1 expression. Loss of membranous CEACAM1 expression was significantly associated with tumor size, tumor number, and serum （z-fetoprotein levels （all P 〈0.05）. Patients with loss of membranous CEACAM1 had significantly poorer RFS than patients with membranous expression, determined via Kaplan-Meier analysis （P=0.027）. Multivariate analysis revealed that loss of membranous CEACAM1 expression might be an independent prognostic factor of RFS for HCC patients after liver transplantation （P=0.037）. Conclusion Loss of membranous CEACAM1 expression in HCC was closely associated with aggressive tumor biology and might be a relapsing biomarker of HCC treated with LT.
基金National Natural Science Foundation of China(31700799,31970859,81601311,and 81630036)Shanghai Sailing Program(17YF1411600)+2 种基金Training Program for Young Talents of the Shanghai Health System(2018YQ07)Shanghai Chenguang Program(18CG09)Development Fund of Shanghai Talents(2018110)。
文摘Objective:To investigate the frequency and function of Tim-3^(+)CD8^(+)T cells in the third trimester of normal pregnancies(NPs)and preeclamptic(PE)pregnancies.Methods:T-cell immunoglobulin mucin-3(Tim-3)expression levels of CD8^(+)T cells in the decidua,peripheral blood,and umbilical cord blood obtained from women showing NPs and PE pregnancies were analyzed using flow cytometry.Decidual CD8^(+)T cells were cultured in the presence of recombinant human carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1)protein and/or Tim-3-specific neutralizing antibodies for analyzing CD107a and intracellular cytokine expression.The placental CEACAM1 protein expression was analyzed using immunohistochemistry.Results:Tim-3^(+)CD8^(+)T cells were more abundant in the decidua than in the peripheral blood.Tim-3 expression in the decidual CD8^(+)T cells was significantly lower in PE patients.Decidual Tim-3^(+)CD8^(+)T cells from PE patients expressed higher levels of CD107a and the Th1-type cytokine IFN-γ,but lower levels of the Th2-type cytokine IL-4.CEACAM1 altered the CD107a,IFN-γ,and IL-4 levels;this was reversed by anti-Tim-3 antibodies.The CEACAM1 protein levels were lower in the placental tissues of women with PE pregnancies than in those of women with NPs.Conclusions:Abnormal CEACAM1/Tim-3 regulation may participate in the development of PE,accompanied by disturbed Th2 cell predominance and higher cytotoxicity of decidual CD8^(+)T cells.
基金Supported by Ministère de l’Enseignement supérieur et de la Recherche,Inserm and Universitéd’Auvergne(UMR1071),INRA(USC-2018)Grants from the Association F.Aupetit(AFA)and Ligue contre le cancer
文摘AIM: To provide further insight into the characterization of mucosa-associated Escherichia coli (E. coli) isolated from the colonic mucosa of cancer patients.
文摘Objective To determine whether the antiatherogenic effect of L arginin e is due to an inhibition of vascular cell adhesion molecule 1 (VCAM 1) expres sion in the aortae of hypercholesterolemic rats. Methods Twenty four male Wistar rats were randomized into three gr oups : Group NC with normal diet (NC, n=8), Group CC with 4% cholesterol and 1% choli c acid diet (CC, n=8), Group AC with 4% cholesterol and 1% cholic acid diet supp lemented with 3% L arginine HCl in the drinking water (AC, n=8). Eight weeks la ter, the blood samples were collected for biochemical studies, and the aortae we re harvested for RT PCR and immunohistochemical studies.Results The results showed that dietary L arginine supplementation red uced expression of VCAM 1 in protein level and mRNA level. Conclusion Inhibitory effect of dietary supplementation of L argin ine on VCAM 1 expression may be one of the mechanisms of its antiatherosclerosis.
