Acute pancreatitis(AP)is a devastating disease characterized by an inflammatory disorder of the pancreas.P-selectin glycoprotein ligand-1(PSGL-1)plays a crucial role in the initial steps of the adhesive at process to ...Acute pancreatitis(AP)is a devastating disease characterized by an inflammatory disorder of the pancreas.P-selectin glycoprotein ligand-1(PSGL-1)plays a crucial role in the initial steps of the adhesive at process to inflammatory sites,blockade of PSGL-1 might confer potent anti-inflammatory effects.In this study,we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1,RH001-6 and RH001-22,which were screened from immunized rhesus macaques.We found that RH001-6,can effectively block the binding of P-selectin to PSGL-1,and abolish the adhesion of leukocytes to endothelial cells in vitro.In vivo,we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and L-arginine induced AP models.We also evaluated the safety profile after RH001-6 treatment in mice,and verified that RH001-6 did not cause any significant pathological damages in vivo.Taken together,we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity,named RH001-6,which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP.Therefore,RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases,such as AP.展开更多
This study investigated the biomechanical micro-motion associated with the application of acetabular reinforcement ring with hook （Ganz ring） for the correction of segmental acetabular rim defects, by finite element...This study investigated the biomechanical micro-motion associated with the application of acetabular reinforcement ring with hook （Ganz ring） for the correction of segmental acetabular rim defects, by finite element analysis. The objective was to determine whether the Ganz ring is suitable for correcting segmental acetabular rim defects at different regions during total hip arthroplasty revision as well as the number of screws required to fix the Ganz ring. A finite element model of the hip joint was generated to simulate and evaluate the insertion and fixation of the Ganz ring and acetabular cup in the context of segmental rim defects in the anterior column, superior portion, and posterior column. Micro-motion was the greatest in the posterior column defect and the least in the anterior column defect. However, the peak stress distribution on the remaining portion of the acetabular rim was the highest in the superior portion defect, following the pos- terior column defect and anterior column defect. Increasing the number of fixations of the Ganz ring did not decrease the micro-motion. We found that the Ganz ring effectively provided biomechanical stability during the reconstruction of the segmental rim defect as long as the screws fixed the Ganz ring well to the host bone.展开更多
CORYNE（CRN） plays important roles in stem cell division and differentiation of shoot apical meristem （SAM） in Arabidopsis thaliana.The cytoplasmic kinase domain of CRN has been cloned and expressed in Escherichia ...CORYNE（CRN） plays important roles in stem cell division and differentiation of shoot apical meristem （SAM） in Arabidopsis thaliana.The cytoplasmic kinase domain of CRN has been cloned and expressed in Escherichia coli,and further purified by two consecutive steps of affinity chromatography.By using this purified CRN as a ligand,a 12-mer random-peptide library was used to determine the specific amino acid sequences binding with the recombinant CRN molecule.After four rounds of biopanning,positive phage clones were isolated and sequenced,and further tested by enzyme linked immunosorbent assay for their binding ability and specificity.Two positive clones that specifically bind to the intracellular protein kinase domain of CRN have been identified.Alignment of these peptides and the kinase-associated protein phosphatase（KAPP） shows high similarity,indicating that KAPP might interact with the cytoplasmic kinase domain of CRN and negatively regulate the CLV signal.Our current study would be helpful to better understand the CLV3 signal pathway.展开更多
基金supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CAMS,2021-I2M1-072,China)National Natural Science Foundation of China (82161138027 and 81970358)。
文摘Acute pancreatitis(AP)is a devastating disease characterized by an inflammatory disorder of the pancreas.P-selectin glycoprotein ligand-1(PSGL-1)plays a crucial role in the initial steps of the adhesive at process to inflammatory sites,blockade of PSGL-1 might confer potent anti-inflammatory effects.In this study,we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1,RH001-6 and RH001-22,which were screened from immunized rhesus macaques.We found that RH001-6,can effectively block the binding of P-selectin to PSGL-1,and abolish the adhesion of leukocytes to endothelial cells in vitro.In vivo,we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and L-arginine induced AP models.We also evaluated the safety profile after RH001-6 treatment in mice,and verified that RH001-6 did not cause any significant pathological damages in vivo.Taken together,we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity,named RH001-6,which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP.Therefore,RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases,such as AP.
文摘This study investigated the biomechanical micro-motion associated with the application of acetabular reinforcement ring with hook （Ganz ring） for the correction of segmental acetabular rim defects, by finite element analysis. The objective was to determine whether the Ganz ring is suitable for correcting segmental acetabular rim defects at different regions during total hip arthroplasty revision as well as the number of screws required to fix the Ganz ring. A finite element model of the hip joint was generated to simulate and evaluate the insertion and fixation of the Ganz ring and acetabular cup in the context of segmental rim defects in the anterior column, superior portion, and posterior column. Micro-motion was the greatest in the posterior column defect and the least in the anterior column defect. However, the peak stress distribution on the remaining portion of the acetabular rim was the highest in the superior portion defect, following the pos- terior column defect and anterior column defect. Increasing the number of fixations of the Ganz ring did not decrease the micro-motion. We found that the Ganz ring effectively provided biomechanical stability during the reconstruction of the segmental rim defect as long as the screws fixed the Ganz ring well to the host bone.
文摘CORYNE（CRN） plays important roles in stem cell division and differentiation of shoot apical meristem （SAM） in Arabidopsis thaliana.The cytoplasmic kinase domain of CRN has been cloned and expressed in Escherichia coli,and further purified by two consecutive steps of affinity chromatography.By using this purified CRN as a ligand,a 12-mer random-peptide library was used to determine the specific amino acid sequences binding with the recombinant CRN molecule.After four rounds of biopanning,positive phage clones were isolated and sequenced,and further tested by enzyme linked immunosorbent assay for their binding ability and specificity.Two positive clones that specifically bind to the intracellular protein kinase domain of CRN have been identified.Alignment of these peptides and the kinase-associated protein phosphatase（KAPP） shows high similarity,indicating that KAPP might interact with the cytoplasmic kinase domain of CRN and negatively regulate the CLV signal.Our current study would be helpful to better understand the CLV3 signal pathway.
