The unperturbed dimension and temperature character of poly(dibenzyl itaconate)s (PDBzI) are studied by a revised rotational isomeric state (RIS) method. The improved formulas of the mean-square radius of gyration, de...The unperturbed dimension and temperature character of poly(dibenzyl itaconate)s (PDBzI) are studied by a revised rotational isomeric state (RIS) method. The improved formulas of the mean-square radius of gyration, deduced by the pseudo-stereochemical equilibrium approach, may be used to investigate the configurational-conformational properties of atactic polymers with large side groups [poly(itaconates) for instance]. The calculated results showed that poly(itaconates) have larger dimension of the molecule than other vinyl polymers. Comparison of the dimension between considering and without considering side groups showed that the effect of large side groups on the unperturbed dimension for short-chain polymers is more obvious than that of long-chain polymers and, if the dimension of side groups increases, the effect also increases. The dimension differences of PDBzI between short-chain and long-chain polymers are investigated by the relation of characteristic ratios and temperature coefficients with temperature. Moreover, the dependence between the temperature coefficients and the tacticity of chains shows that the temperature characters of the isotactic, syndiotactic and atactic PDBzI chains have remarkable difference.展开更多
AIM:To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line,BxPC-3.METHODS:RNAi was ...AIM:To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line,BxPC-3.METHODS:RNAi was performed using the vector (pGPU6)-based small interference RNA (siRNA) plasmid gene silence system to specifically knock down MMP-2 expression in pancreatic cancer cell line,BxPC-3. Four groups of different specific target sequence in coding region of MMP-2 and one non-specific sequence were chosen to construct four experimental siRNA plasmids of pGPU6-1,pGPU6-2,pGPU6-3 and pGPU6-4,and one negative control siRNA plasmid of pGPU6 (-). MMP-2 expression was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) and flow cytometry,respectively. The abilities of adhesion and invasion were detected by cell adhesion assay and cell invasion assay using Transwell chambers.RESULTS:The expression of MMP-2 was inhibited and the inhibitory effects of different sequence varied. pGPU6-1 group had the most efficient inhibitory effect,followed by pGPU6-2 and pGPU6-3 groups.Invasiveness and adhesion were more significantly reduced in pGPU6-1,pGPU6-2 and pGPU6-3 groups as compared with pGPU6 (-) and blank control groups. However,no difference concerning cell proliferation and apoptosis was observed after transfection between experiment groups and control groups.CONCLUSION:RNAi against MMP-2 successfully inhibited the mRNA and protein expression of MMP-2 in the pancreatic cancer cell line,BxPC-3,leading to a potent suppression of tumor cell adhesion and invasion without affecting cell proliferation and apoptosis. These findings suggest that the RNAi approach towards MMP-2 may be an effective therapeutic strategy for the clinical management of pancreatic tumor.展开更多
Pure red cell aplasia (PRCA) is a rare hematological disorder which is characterized by severe anemia,reticulocytopenia and almost complete absence of erythroid precursors in bone marrow.The pathophysiology of PRCA ma...Pure red cell aplasia (PRCA) is a rare hematological disorder which is characterized by severe anemia,reticulocytopenia and almost complete absence of erythroid precursors in bone marrow.The pathophysiology of PRCA may be congenital or acquired.To our knowledge,there is only one case report in the English literature of PRCA after pegylated interferon combination therapy for chronic hepatitis C.We report a second case of PRCA after pegylated interferon combination treatment for chronic hepatitis C.The diagnosis of PRCA was confirmed by the typical findings of bone marrow biopsy.The possible etiologies of our case are also discussed in this paper.展开更多
RNA can catalyze and participate in many chemical and biochemical reactions. Non-coding RNAs (ncRNA) can regulate cellular transcription and translation reactions. We have demonstrated biochemically that RNA can als...RNA can catalyze and participate in many chemical and biochemical reactions. Non-coding RNAs (ncRNA) can regulate cellular transcription and translation reactions. We have demonstrated biochemically that RNA can also interfere with DNA polymerization via transforming DNA polymerase into deoxyribonucleoside triphosphate diphosphatase (dNTP-DPase). RNA, even with six nucleotides, can transform DNA polymerase into dNTP-DPase, and the dNTP-DPase activity causes the hydrolysis of dNTPs into dNMPs and pyrophosphate. Moreover, we have found that DNA polymerases from several families generally have similar RNA-dependent dNTP-DPase activity. We have also observed that in the presence of RNA, when the dNTP concentrations are relatively low, and that the dNTP-DPase activity can deplete dNTPs and interfere with DNA polymerization Thus, we have discovered for the first time that in the presence of RNA, DNA polymerase can behave as a diphosphatase and inhibit DNA synthesis when dNTP quantity is low. These in vitro observations might imply a plausible role of RNA in vivo, such as suppressing DNA synthesis during a resting phase (Go) of the cell cycle, when RNA quantity is high and dNTP quantity is low.展开更多
The covalent attachment of protein-resistant polymers to therapeutic proteins is a widely used method for extending their in vivo half-lives; however, the effect of molecular weight of polymer on the in vitro and in v...The covalent attachment of protein-resistant polymers to therapeutic proteins is a widely used method for extending their in vivo half-lives; however, the effect of molecular weight of polymer on the in vitro and in vivo functions of protein-polymer conjugates has not been well elucidated. Herein we report the effect of molecular weight of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) on the in vitro and in vivo properties of C-termi- nal interferon-alpha (IFN)-POEGMA conjugates. Increasing the molecular weight of POEGMA decreased the in vitro activity of IFN-ct but increased its thermal stability and in vivo pharmacokinetics. Intriguingly, the in vivo antitumor efficacy of IFN-a was increased by increasing the POEGMA molecular weight from ca. 20 to 60 kDa, but was not further increased by increasing the molecular weight of POEGMA from ca. 60 to 100 kDa due to the neutralization of the improved pharmacokinetics and the reduced in vitro activity. This finding offers a new viewpoint on the molecular size rationale for designing next-generation protein-polymer conjugates, which may benefit patients by reducing admin- istration frequency and adverse reactions, and improving therapeutic efficacy.展开更多
基金Project supported by the National Basic Research Program (973) of China (No. 10574109)the Zhejiang Provincial Science and Technology Department (No. 2005C24008)the Natural Science Foundation of Zhejiang Province (No. Y604064), China
文摘The unperturbed dimension and temperature character of poly(dibenzyl itaconate)s (PDBzI) are studied by a revised rotational isomeric state (RIS) method. The improved formulas of the mean-square radius of gyration, deduced by the pseudo-stereochemical equilibrium approach, may be used to investigate the configurational-conformational properties of atactic polymers with large side groups [poly(itaconates) for instance]. The calculated results showed that poly(itaconates) have larger dimension of the molecule than other vinyl polymers. Comparison of the dimension between considering and without considering side groups showed that the effect of large side groups on the unperturbed dimension for short-chain polymers is more obvious than that of long-chain polymers and, if the dimension of side groups increases, the effect also increases. The dimension differences of PDBzI between short-chain and long-chain polymers are investigated by the relation of characteristic ratios and temperature coefficients with temperature. Moreover, the dependence between the temperature coefficients and the tacticity of chains shows that the temperature characters of the isotactic, syndiotactic and atactic PDBzI chains have remarkable difference.
基金Supported by Tiantan Hospital Scientific Project Grant Fund
文摘AIM:To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line,BxPC-3.METHODS:RNAi was performed using the vector (pGPU6)-based small interference RNA (siRNA) plasmid gene silence system to specifically knock down MMP-2 expression in pancreatic cancer cell line,BxPC-3. Four groups of different specific target sequence in coding region of MMP-2 and one non-specific sequence were chosen to construct four experimental siRNA plasmids of pGPU6-1,pGPU6-2,pGPU6-3 and pGPU6-4,and one negative control siRNA plasmid of pGPU6 (-). MMP-2 expression was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) and flow cytometry,respectively. The abilities of adhesion and invasion were detected by cell adhesion assay and cell invasion assay using Transwell chambers.RESULTS:The expression of MMP-2 was inhibited and the inhibitory effects of different sequence varied. pGPU6-1 group had the most efficient inhibitory effect,followed by pGPU6-2 and pGPU6-3 groups.Invasiveness and adhesion were more significantly reduced in pGPU6-1,pGPU6-2 and pGPU6-3 groups as compared with pGPU6 (-) and blank control groups. However,no difference concerning cell proliferation and apoptosis was observed after transfection between experiment groups and control groups.CONCLUSION:RNAi against MMP-2 successfully inhibited the mRNA and protein expression of MMP-2 in the pancreatic cancer cell line,BxPC-3,leading to a potent suppression of tumor cell adhesion and invasion without affecting cell proliferation and apoptosis. These findings suggest that the RNAi approach towards MMP-2 may be an effective therapeutic strategy for the clinical management of pancreatic tumor.
文摘Pure red cell aplasia (PRCA) is a rare hematological disorder which is characterized by severe anemia,reticulocytopenia and almost complete absence of erythroid precursors in bone marrow.The pathophysiology of PRCA may be congenital or acquired.To our knowledge,there is only one case report in the English literature of PRCA after pegylated interferon combination therapy for chronic hepatitis C.We report a second case of PRCA after pegylated interferon combination treatment for chronic hepatitis C.The diagnosis of PRCA was confirmed by the typical findings of bone marrow biopsy.The possible etiologies of our case are also discussed in this paper.
基金financially supported by the Georgia Cancer Coalition(GCC)Distinguished Cancer Clinicians and Scientists,USA NSF(IIP-1340153)and NIH(R01GM095881)
文摘RNA can catalyze and participate in many chemical and biochemical reactions. Non-coding RNAs (ncRNA) can regulate cellular transcription and translation reactions. We have demonstrated biochemically that RNA can also interfere with DNA polymerization via transforming DNA polymerase into deoxyribonucleoside triphosphate diphosphatase (dNTP-DPase). RNA, even with six nucleotides, can transform DNA polymerase into dNTP-DPase, and the dNTP-DPase activity causes the hydrolysis of dNTPs into dNMPs and pyrophosphate. Moreover, we have found that DNA polymerases from several families generally have similar RNA-dependent dNTP-DPase activity. We have also observed that in the presence of RNA, when the dNTP concentrations are relatively low, and that the dNTP-DPase activity can deplete dNTPs and interfere with DNA polymerization Thus, we have discovered for the first time that in the presence of RNA, DNA polymerase can behave as a diphosphatase and inhibit DNA synthesis when dNTP quantity is low. These in vitro observations might imply a plausible role of RNA in vivo, such as suppressing DNA synthesis during a resting phase (Go) of the cell cycle, when RNA quantity is high and dNTP quantity is low.
基金financially supported by Grants from the National Natural Science Foundation of China (21274043 and 21534006).
文摘The covalent attachment of protein-resistant polymers to therapeutic proteins is a widely used method for extending their in vivo half-lives; however, the effect of molecular weight of polymer on the in vitro and in vivo functions of protein-polymer conjugates has not been well elucidated. Herein we report the effect of molecular weight of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) on the in vitro and in vivo properties of C-termi- nal interferon-alpha (IFN)-POEGMA conjugates. Increasing the molecular weight of POEGMA decreased the in vitro activity of IFN-ct but increased its thermal stability and in vivo pharmacokinetics. Intriguingly, the in vivo antitumor efficacy of IFN-a was increased by increasing the POEGMA molecular weight from ca. 20 to 60 kDa, but was not further increased by increasing the molecular weight of POEGMA from ca. 60 to 100 kDa due to the neutralization of the improved pharmacokinetics and the reduced in vitro activity. This finding offers a new viewpoint on the molecular size rationale for designing next-generation protein-polymer conjugates, which may benefit patients by reducing admin- istration frequency and adverse reactions, and improving therapeutic efficacy.