The Experts below are selected from a list of 141 Experts worldwide ranked by ideXlab platform
Ming-xia Wang - One of the best experts on this subject based on the ideXlab platform.
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Sonic hedgehog signalling pathway regulates apoptosis through Smo Protein in human umbilical vein endothelial cells
Rheumatology (Oxford England), 2014Co-Authors: Shangling Zhu, Weixiang Peng, Ming-xia Wang, Minqi Luo, Zhi-ying Feng, Xiaoxue Feng, Fang Liu, J. HuangAbstract:OBJECTIVE The aim of this study was to investigate the expression of Smoothened Protein (Smo), a sonic hedgehog (Shh) signalling component, in synovium of RA and its role in the survival and apoptosis of endothelial cells. METHODS The expression of Smo pxrotein in RA synovial tissue was examined by immunohistochemistry. Real-time PCR and western blotting techniques were employed to measure the expression of Shh signalling components in EA.hy926 endothelial cells exposed to TNF-α in the presence or absence of cyclopamine (a Smo-specific antagonist). Lastly, the effect of cyclopamine and Smo small interfering RNA on apoptosis induced by TNF-α and actinomycin D (ActD) was determined. RESULTS We found that Smo was highly expressed in synovial tissues of RA, especially in endothelial cells, compared with the trauma group. TNF-α significantly increased the expression of Shh signalling components in EA.hy926 endothelial cells, while cyclopamine decreased the expression of Shh signalling components. EA.hy926 endothelial cells treated with various concentrations of cyclopamine (2-8 μmol/l) showed a significant decrease in cell viability and cell survival rate, and an increase in the rate of cell apoptosis compared with endothelial cells treated with TNF-α and ActD (P < 0.05). EA.hy926 endothelial cells transfected with Smo-siRNA also showed a lower cell survival rate and higher apoptotic rate, compared with cells in the control group (P < 0.05). CONCLUSION The Shh signalling pathway plays a role in regulating endothelial cell apoptosis in a Smo-dependent manner.
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AB0107 Sonic hedgehog promotes survival and apoptosis resistance through Smoothened Protein in human umbilical vein endothelial cell
Annals of the Rheumatic Diseases, 2013Co-Authors: Shangling Zhu, J. Huang, Weixiang Peng, Ming-xia WangAbstract:Background Rheumatoid arthritis (RA) is characterized by chronic synovitis and pannus formation, leading to destruction of cartilage and bone. Sonic Hedgehog (Shh) signaling pathway plays significant role in regulating the morphogenesis during development and promotes angiogenesis in tumor. Earlier studies showed that endothelial cell apoptosis may play a major regulatory role in neovascularization. Objectives We investigated the expression level of Smoothened(Smo) in endothelial cells in synovial tissue from patients with RA and analyzed the expression of Shh signaling pathway components(Shh, Ptch1, Smo and Gli1) in human umbilical vein endothelial cell line (EA.hy926 cell) and examined the effect of Smo Protein on endothelial cell survival and apoptosis. Methods The expression of Shh signaling pathway component Smo in synovial tissues from 4 RA patients and 4 patients with traumatic or meniscal injury was examined by immunohistochemistry assay. EA.hy926 cells were used as the model of human umbilical vein endothelial cells. Shh, Ptch1, Smo, Gli1 mRNA expression levels in EA.hy926 cells exposed to TNFα with or without specific Shh signaling pathway inhibitor(Cyclopamine) were detected by Real time-PCR, and the Protein expression levels were measured by Western blot analysis.EA.hy926 cells were treated with different concentrations of Cyclopamine or transfected with the small interfering RNA (siRNA) specifically targeting Smo gene before exposure to TNFα and actinomycinD (ActD). The cell survival rate was detected by CCK-8 assay and the cell apoptotic rate was examined by flow cytometry. Results Smo was highly expressed in synovial tissue in RA, especially in endothelial cells than that in control group. TNFα significantly increased the mRNA and Protein expression of Shh signaling pathway components in EA.hy926 cells, while the expression was decreased in the presence of TNFα and Cyclopamine. EA.hy926 cells treated with Cyclopamine or transfected with Smo-siRNA showed a significant decrease in cell viability, with decreased cell survival rates and increased apoptotic rates, compared with those of the control group. Conclusions Shh signaling pathway may play a role in the regulatory of apoptosis in endothelial cells in RA synovium and promote angiogenesis. References Gravallese EM. Bone destruction in arthritis. Ann Rheum Dis. 2002. 61 Suppl 2: ii84-6. Dimmeler S, Zeiher AM. Endothelial cell apoptosis in angiogenesis and vessel regression. Circ Res. 2000. 87(6): 434-9. Varjosalo M, Taipale J. Hedgehog: functions and mechanisms. Genes Dev. 2008. 22(18): 2454-72. Disclosure of Interest None Declared
Farzaneh Fakhari - One of the best experts on this subject based on the ideXlab platform.
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Protein ligand interaction study of signal transducer Smoothened Protein with different drugs molecular docking and qm mm calculations
RSC Advances, 2015Co-Authors: Hossein Farrokhpour, Vahid Pakatchian, Abdol-reza Hajipour, Fatemeh Abyar, Alireza Najafi Chermahini, Farzaneh FakhariAbstract:In this work, the interaction of signal transducer Smoothened (SMO) Protein, one of the main members of the Hedgehog (Hh) signaling pathway, with different ligands was studied. Seven hundred molecules, known as SMO ligands in literature, were selected for the docking screens. The site of the antitumor agent LY2940680, present in the X-ray crystal structure of the SMO Protein, was selected as the binding site to study the interaction of the selected ligands with the Protein. Docking screens only showed ten ligands that can be considered as favorable ligands based on their calculated free binding energies. The amino acid residues responsible for interacting with the ligands were identified. Quantum mechanics/molecular mechanics (QM/MM) calculations were also performed on the structure of the Protein interacting with the favorable ligands to obtain more accurate results for their electronic interaction energies. The contribution of the van der Waals (vdW) and electrostatic interaction in the calculated electronic interaction energy of each ligand were calculated by QM/MM calculations. In addition, the effect of the polarization of the wave function of ligand in the active site of the Protein on its electronic interaction with the Protein was also studied.
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Protein–ligand interaction study of signal transducer Smoothened Protein with different drugs: molecular docking and QM/MM calculations
RSC Advances, 2015Co-Authors: Hossein Farrokhpour, Vahid Pakatchian, Abdol-reza Hajipour, Fatemeh Abyar, Alireza Najafi Chermahini, Farzaneh FakhariAbstract:In this work, the interaction of signal transducer Smoothened (SMO) Protein, one of the main members of the Hedgehog (Hh) signaling pathway, with different ligands was studied. Seven hundred molecules, known as SMO ligands in literature, were selected for the docking screens. The site of the antitumor agent LY2940680, present in the X-ray crystal structure of the SMO Protein, was selected as the binding site to study the interaction of the selected ligands with the Protein. Docking screens only showed ten ligands that can be considered as favorable ligands based on their calculated free binding energies. The amino acid residues responsible for interacting with the ligands were identified. Quantum mechanics/molecular mechanics (QM/MM) calculations were also performed on the structure of the Protein interacting with the favorable ligands to obtain more accurate results for their electronic interaction energies. The contribution of the van der Waals (vdW) and electrostatic interaction in the calculated electronic interaction energy of each ligand were calculated by QM/MM calculations. In addition, the effect of the polarization of the wave function of ligand in the active site of the Protein on its electronic interaction with the Protein was also studied.
Shangling Zhu - One of the best experts on this subject based on the ideXlab platform.
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Sonic hedgehog signalling pathway regulates apoptosis through Smo Protein in human umbilical vein endothelial cells
Rheumatology (Oxford England), 2014Co-Authors: Shangling Zhu, Weixiang Peng, Ming-xia Wang, Minqi Luo, Zhi-ying Feng, Xiaoxue Feng, Fang Liu, J. HuangAbstract:OBJECTIVE The aim of this study was to investigate the expression of Smoothened Protein (Smo), a sonic hedgehog (Shh) signalling component, in synovium of RA and its role in the survival and apoptosis of endothelial cells. METHODS The expression of Smo pxrotein in RA synovial tissue was examined by immunohistochemistry. Real-time PCR and western blotting techniques were employed to measure the expression of Shh signalling components in EA.hy926 endothelial cells exposed to TNF-α in the presence or absence of cyclopamine (a Smo-specific antagonist). Lastly, the effect of cyclopamine and Smo small interfering RNA on apoptosis induced by TNF-α and actinomycin D (ActD) was determined. RESULTS We found that Smo was highly expressed in synovial tissues of RA, especially in endothelial cells, compared with the trauma group. TNF-α significantly increased the expression of Shh signalling components in EA.hy926 endothelial cells, while cyclopamine decreased the expression of Shh signalling components. EA.hy926 endothelial cells treated with various concentrations of cyclopamine (2-8 μmol/l) showed a significant decrease in cell viability and cell survival rate, and an increase in the rate of cell apoptosis compared with endothelial cells treated with TNF-α and ActD (P < 0.05). EA.hy926 endothelial cells transfected with Smo-siRNA also showed a lower cell survival rate and higher apoptotic rate, compared with cells in the control group (P < 0.05). CONCLUSION The Shh signalling pathway plays a role in regulating endothelial cell apoptosis in a Smo-dependent manner.
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AB0107 Sonic hedgehog promotes survival and apoptosis resistance through Smoothened Protein in human umbilical vein endothelial cell
Annals of the Rheumatic Diseases, 2013Co-Authors: Shangling Zhu, J. Huang, Weixiang Peng, Ming-xia WangAbstract:Background Rheumatoid arthritis (RA) is characterized by chronic synovitis and pannus formation, leading to destruction of cartilage and bone. Sonic Hedgehog (Shh) signaling pathway plays significant role in regulating the morphogenesis during development and promotes angiogenesis in tumor. Earlier studies showed that endothelial cell apoptosis may play a major regulatory role in neovascularization. Objectives We investigated the expression level of Smoothened(Smo) in endothelial cells in synovial tissue from patients with RA and analyzed the expression of Shh signaling pathway components(Shh, Ptch1, Smo and Gli1) in human umbilical vein endothelial cell line (EA.hy926 cell) and examined the effect of Smo Protein on endothelial cell survival and apoptosis. Methods The expression of Shh signaling pathway component Smo in synovial tissues from 4 RA patients and 4 patients with traumatic or meniscal injury was examined by immunohistochemistry assay. EA.hy926 cells were used as the model of human umbilical vein endothelial cells. Shh, Ptch1, Smo, Gli1 mRNA expression levels in EA.hy926 cells exposed to TNFα with or without specific Shh signaling pathway inhibitor(Cyclopamine) were detected by Real time-PCR, and the Protein expression levels were measured by Western blot analysis.EA.hy926 cells were treated with different concentrations of Cyclopamine or transfected with the small interfering RNA (siRNA) specifically targeting Smo gene before exposure to TNFα and actinomycinD (ActD). The cell survival rate was detected by CCK-8 assay and the cell apoptotic rate was examined by flow cytometry. Results Smo was highly expressed in synovial tissue in RA, especially in endothelial cells than that in control group. TNFα significantly increased the mRNA and Protein expression of Shh signaling pathway components in EA.hy926 cells, while the expression was decreased in the presence of TNFα and Cyclopamine. EA.hy926 cells treated with Cyclopamine or transfected with Smo-siRNA showed a significant decrease in cell viability, with decreased cell survival rates and increased apoptotic rates, compared with those of the control group. Conclusions Shh signaling pathway may play a role in the regulatory of apoptosis in endothelial cells in RA synovium and promote angiogenesis. References Gravallese EM. Bone destruction in arthritis. Ann Rheum Dis. 2002. 61 Suppl 2: ii84-6. Dimmeler S, Zeiher AM. Endothelial cell apoptosis in angiogenesis and vessel regression. Circ Res. 2000. 87(6): 434-9. Varjosalo M, Taipale J. Hedgehog: functions and mechanisms. Genes Dev. 2008. 22(18): 2454-72. Disclosure of Interest None Declared
Hossein Farrokhpour - One of the best experts on this subject based on the ideXlab platform.
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Protein ligand interaction study of signal transducer Smoothened Protein with different drugs molecular docking and qm mm calculations
RSC Advances, 2015Co-Authors: Hossein Farrokhpour, Vahid Pakatchian, Abdol-reza Hajipour, Fatemeh Abyar, Alireza Najafi Chermahini, Farzaneh FakhariAbstract:In this work, the interaction of signal transducer Smoothened (SMO) Protein, one of the main members of the Hedgehog (Hh) signaling pathway, with different ligands was studied. Seven hundred molecules, known as SMO ligands in literature, were selected for the docking screens. The site of the antitumor agent LY2940680, present in the X-ray crystal structure of the SMO Protein, was selected as the binding site to study the interaction of the selected ligands with the Protein. Docking screens only showed ten ligands that can be considered as favorable ligands based on their calculated free binding energies. The amino acid residues responsible for interacting with the ligands were identified. Quantum mechanics/molecular mechanics (QM/MM) calculations were also performed on the structure of the Protein interacting with the favorable ligands to obtain more accurate results for their electronic interaction energies. The contribution of the van der Waals (vdW) and electrostatic interaction in the calculated electronic interaction energy of each ligand were calculated by QM/MM calculations. In addition, the effect of the polarization of the wave function of ligand in the active site of the Protein on its electronic interaction with the Protein was also studied.
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Protein–ligand interaction study of signal transducer Smoothened Protein with different drugs: molecular docking and QM/MM calculations
RSC Advances, 2015Co-Authors: Hossein Farrokhpour, Vahid Pakatchian, Abdol-reza Hajipour, Fatemeh Abyar, Alireza Najafi Chermahini, Farzaneh FakhariAbstract:In this work, the interaction of signal transducer Smoothened (SMO) Protein, one of the main members of the Hedgehog (Hh) signaling pathway, with different ligands was studied. Seven hundred molecules, known as SMO ligands in literature, were selected for the docking screens. The site of the antitumor agent LY2940680, present in the X-ray crystal structure of the SMO Protein, was selected as the binding site to study the interaction of the selected ligands with the Protein. Docking screens only showed ten ligands that can be considered as favorable ligands based on their calculated free binding energies. The amino acid residues responsible for interacting with the ligands were identified. Quantum mechanics/molecular mechanics (QM/MM) calculations were also performed on the structure of the Protein interacting with the favorable ligands to obtain more accurate results for their electronic interaction energies. The contribution of the van der Waals (vdW) and electrostatic interaction in the calculated electronic interaction energy of each ligand were calculated by QM/MM calculations. In addition, the effect of the polarization of the wave function of ligand in the active site of the Protein on its electronic interaction with the Protein was also studied.
Yi Xin Zeng - One of the best experts on this subject based on the ideXlab platform.
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identification of cancer stem cell like side population cells in human nasopharyngeal carcinoma cell line
Cancer Research, 2007Co-Authors: Jing Wang, Liping Guo, Lizhen Chen, Yi Xin ZengAbstract:Side population (SP) cells have been isolated from several solid tumors. They lack distinct molecular markers for cancer stem cells (CSC) and increasing evidence suggests that they may play an important role in tumorigenesis and cancer therapy. However, there are no reports about the existence and function of SP cells in nasopharyngeal carcinoma (NPC) cells thus far. In this study, we scanned SP cells from five NPC cell lines and investigated stem cell characteristics, such as proliferation, self-renewal, and differentiation, using SP cells from the widely-used CNE-2 NPC cell line. We observed a strong tumorigenesis ability of SP cells following in vivo transplantation into nonobese diabetic/severe combined immunodeficient mice. Immunofluorescence revealed that cytokine 19 was highly expressed on SP cells. SP cells were found to be more resistant to chemotherapy and radiotherapy and this was related to the ATP-binding cassette half transporter member 2 of G family Protein and Smoothened Protein expression, respectively. Our results not only showed that SP cells in human NPC cell line CNE-2 had stem cell characteristics in vitro but also showed that they had a strong ability to form tumors in vivo. Importantly, we found the cell marker, cytokine 19, may serve as a potential molecular marker for further characterization of CSC. Taken together, our data shed light on tumorigenesis and therapeutic-resistant mechanisms, which are helpful for developing novel targets for effective clinical treatment of NPC. [Cancer Res 2007;67(8):3716–24]
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Identification of Cancer Stem Cell–Like Side Population Cells in Human Nasopharyngeal Carcinoma Cell Line
Cancer research, 2007Co-Authors: Jing Wang, Liping Guo, Lizhen Chen, Yi Xin ZengAbstract:Side population (SP) cells have been isolated from several solid tumors. They lack distinct molecular markers for cancer stem cells (CSC) and increasing evidence suggests that they may play an important role in tumorigenesis and cancer therapy. However, there are no reports about the existence and function of SP cells in nasopharyngeal carcinoma (NPC) cells thus far. In this study, we scanned SP cells from five NPC cell lines and investigated stem cell characteristics, such as proliferation, self-renewal, and differentiation, using SP cells from the widely-used CNE-2 NPC cell line. We observed a strong tumorigenesis ability of SP cells following in vivo transplantation into nonobese diabetic/severe combined immunodeficient mice. Immunofluorescence revealed that cytokine 19 was highly expressed on SP cells. SP cells were found to be more resistant to chemotherapy and radiotherapy and this was related to the ATP-binding cassette half transporter member 2 of G family Protein and Smoothened Protein expression, respectively. Our results not only showed that SP cells in human NPC cell line CNE-2 had stem cell characteristics in vitro but also showed that they had a strong ability to form tumors in vivo. Importantly, we found the cell marker, cytokine 19, may serve as a potential molecular marker for further characterization of CSC. Taken together, our data shed light on tumorigenesis and therapeutic-resistant mechanisms, which are helpful for developing novel targets for effective clinical treatment of NPC. [Cancer Res 2007;67(8):3716–24]