Objective： Survivin is one of the apoptosis inhibitor genes and is rarely expressed in adult tissues. However, survivin expression has been detected in various human cancers and correlations have been recognized betw...Objective： Survivin is one of the apoptosis inhibitor genes and is rarely expressed in adult tissues. However, survivin expression has been detected in various human cancers and correlations have been recognized between the level of expression of this gene in tumors and prognosis. In this study, we investigated the effect of Survivin-siRNA on the drug sensitivity of osteosarcoma cell line MG-63. Methods： Two siRNAs （Survivin-siRNA1, Survivin-siRNA2） specifically targeting Survivin gene were chemically synthesized and transfected into MG-63 ceils. The Survivin mRNA level was detected by reverse transcription-polymerase chain reaction （RT-PCR）. The survivin protein expression and cell apoptosis rate were analyzed by flow cytometry （FCM）. The 50% inhibition concentration （IC50） of cisplatin （DDP） and adriamycin （ADM） on MG-63 cells was determined by MTT method. Results： Two short siRNA targeting survivin down-regulated the transcription of survivin gene dramatically and elevated apoptosis rate. They increased the drug sensitivity of MG-63 cells to ADM by five-fold and to DDP by nine-fold. Conclusion： Validated Survivin specific siRNA can effectively inhibit Survivin expression in survivin-overexpressing osteosarcoma MG-63 cell line and enhance the drug sensitivity of MG-63 cell line to ADM and DDP. Short survivin-siRNA mediated gene silencing may be a useful therapeutic strategy for osteosarcoma. These results suggest that survivin might be helpful for diagnosis of osteosarcoma and survivin siRNA combined with adriamycin or cisplatin may be a feasible strategy to enhance the effects of chemotherapy in patients with osteosarcoma.展开更多
A thermo-responsive chitosan hydrogel system （TRCHS） was prepared by chitosan （ CS ） and β- glycerophosphate （ β- GP ） to deliver Adriamycin （ ADM ） locally for curing osteosarcoma. Release property was inv...A thermo-responsive chitosan hydrogel system （TRCHS） was prepared by chitosan （ CS ） and β- glycerophosphate （ β- GP ） to deliver Adriamycin （ ADM ） locally for curing osteosarcoma. Release property was investigated by release experiments in vitro and results show that it can be applied to local drug release because it is able to release drug at high concentration for 17 days. The treatment effect was studied by injecting intratumorally to osteosarcoma tumors （ CRL- 1427） implanted sabcutaneously on Specific Pathogen-free （SPF） mice. The statistical analytical results show that TRCHS delivering ADM is more efficacioas than saline intratumoral injection, which loads the same quantity of ADM , but is less poisonous. Based on the analysis above, this novel biodegradable polymer implant is an effective and safe vehicle for sustained local delivery of ADM, and is supposed to be applied in neoadjuvant chemotherapy for osteosarcoma.展开更多
Hydroxyapatite(HAP)porous microspheres with very high specific surface area and drug loading capacity,as well as excellent biocompatibility,have been widely used in tumour therapy.Mg^(2+)is considered to be a key fact...Hydroxyapatite(HAP)porous microspheres with very high specific surface area and drug loading capacity,as well as excellent biocompatibility,have been widely used in tumour therapy.Mg^(2+)is considered to be a key factor in bone regeneration,acting as an active agent to stimulate bone and cartilage formation,and is effective in accelerating cell migration and promoting angiogenesis,which is essential for bone tissue repair,anti-cancer,and anti-infection.In this study,abalone shells from a variety of sources were used as raw materials,and Mg^(2+)-doped abalone shell-derived mesoporous HAP microspheres(Mg-HAP)were prepared by hydrothermal synthesis as Mg^(2+)/icariin smart dual delivery system(ICA-Mg-HAP,IMHA).With increasing of Mg^(2+)doping,the surface morphology of HAP microspheres varied from collapsed macroporous to mesoporous to smooth and non-porous,which may be due to Mg^(2+)substitution or coordination in the HAP lattice.At 30%Mg^(2+)doping,the Mg-HAP microspheres showed a more homogeneous mesoporous morphology with a high specific surface area(186.06 m^(2)/g).The IMHA microspheres showed high drug loading(7.69%)and encapsulation rate(83.29%),sustained Mg^(2+)release for more than 27 days,sustained and stable release of icariin for 60 hours,and good responsiveness to pH(pH 6.4>pH 5.6).In addition,the IMHA delivery system stimulated the rapid proliferation of bone marrow mesenchymal stem cells and induced apoptosis in MG63 cells by blocking the G2 phase cycle of osteosarcoma cells and stimulating the high expression of apoptotic genes(Bcl-2,caspase-3,-8,-9).This suggests that the abalone shell-based IMHA may have potential applications in drug delivery and tumour therapy.展开更多
To explore the possibility of hydrogen sulfide (H 2S) as a messenger molecule in cardiovascular system, the authors discovered that H 2S (5×10 -5 -5×10 -4 mol·L -1 )exerted an effect on inhibiting endot...To explore the possibility of hydrogen sulfide (H 2S) as a messenger molecule in cardiovascular system, the authors discovered that H 2S (5×10 -5 -5×10 -4 mol·L -1 )exerted an effect on inhibiting endothelin 1 induced proliferation of cultured vascular smooth muscle cells (VSMCs) of rats in vitro . The 3H TdR incorporation decreased by 16.8%～37.4% in H 2S treated VSMCs as compared with the controls ( P <0.01). The inhibitory effect was found to be associated with reduced activity of MAPK. The authors also observed that endogenous H 2S levels markedly increased in vessels of rats with either endotoxic shock or septic shock [H 2S level (pmol·min -1 ·mg -1 ):tail artery (16.18±2.06) vs (8.12±0.55);mesenteric artery (10.17±1.11) vs (6.19 ±0.55);pulmonary artery(11.38±1.24) vs (5.27±0.51); aorta(6.21±0.48) vs (4.10± 0.28), P < 0.01 ]. The above findings suggested that H 2S might play an important role in the regulation of cardiovascular pathophysiologic events.展开更多
文摘Objective： Survivin is one of the apoptosis inhibitor genes and is rarely expressed in adult tissues. However, survivin expression has been detected in various human cancers and correlations have been recognized between the level of expression of this gene in tumors and prognosis. In this study, we investigated the effect of Survivin-siRNA on the drug sensitivity of osteosarcoma cell line MG-63. Methods： Two siRNAs （Survivin-siRNA1, Survivin-siRNA2） specifically targeting Survivin gene were chemically synthesized and transfected into MG-63 ceils. The Survivin mRNA level was detected by reverse transcription-polymerase chain reaction （RT-PCR）. The survivin protein expression and cell apoptosis rate were analyzed by flow cytometry （FCM）. The 50% inhibition concentration （IC50） of cisplatin （DDP） and adriamycin （ADM） on MG-63 cells was determined by MTT method. Results： Two short siRNA targeting survivin down-regulated the transcription of survivin gene dramatically and elevated apoptosis rate. They increased the drug sensitivity of MG-63 cells to ADM by five-fold and to DDP by nine-fold. Conclusion： Validated Survivin specific siRNA can effectively inhibit Survivin expression in survivin-overexpressing osteosarcoma MG-63 cell line and enhance the drug sensitivity of MG-63 cell line to ADM and DDP. Short survivin-siRNA mediated gene silencing may be a useful therapeutic strategy for osteosarcoma. These results suggest that survivin might be helpful for diagnosis of osteosarcoma and survivin siRNA combined with adriamycin or cisplatin may be a feasible strategy to enhance the effects of chemotherapy in patients with osteosarcoma.
文摘A thermo-responsive chitosan hydrogel system （TRCHS） was prepared by chitosan （ CS ） and β- glycerophosphate （ β- GP ） to deliver Adriamycin （ ADM ） locally for curing osteosarcoma. Release property was investigated by release experiments in vitro and results show that it can be applied to local drug release because it is able to release drug at high concentration for 17 days. The treatment effect was studied by injecting intratumorally to osteosarcoma tumors （ CRL- 1427） implanted sabcutaneously on Specific Pathogen-free （SPF） mice. The statistical analytical results show that TRCHS delivering ADM is more efficacioas than saline intratumoral injection, which loads the same quantity of ADM , but is less poisonous. Based on the analysis above, this novel biodegradable polymer implant is an effective and safe vehicle for sustained local delivery of ADM, and is supposed to be applied in neoadjuvant chemotherapy for osteosarcoma.
基金supported by Open Foundation of State Key Laboratory of Mineral Processing(No.BGRIMM-KJSKL-2023-23)Shandong Laboratory of Advanced Materials and Green Manufacturing(No.AMGM2021F02)+2 种基金Natural Science Foundation of Shandong Province(Nos.ZR2022QD057,ZR2023MC125)Open Project Fund for Hubei Key Laboratory of Oral and Maxillofacial Development and Regeneration(No.2021kqhm003)China Postdoctoral Science Foundation(Nos.2022M722434,2023T160492).
文摘Hydroxyapatite(HAP)porous microspheres with very high specific surface area and drug loading capacity,as well as excellent biocompatibility,have been widely used in tumour therapy.Mg^(2+)is considered to be a key factor in bone regeneration,acting as an active agent to stimulate bone and cartilage formation,and is effective in accelerating cell migration and promoting angiogenesis,which is essential for bone tissue repair,anti-cancer,and anti-infection.In this study,abalone shells from a variety of sources were used as raw materials,and Mg^(2+)-doped abalone shell-derived mesoporous HAP microspheres(Mg-HAP)were prepared by hydrothermal synthesis as Mg^(2+)/icariin smart dual delivery system(ICA-Mg-HAP,IMHA).With increasing of Mg^(2+)doping,the surface morphology of HAP microspheres varied from collapsed macroporous to mesoporous to smooth and non-porous,which may be due to Mg^(2+)substitution or coordination in the HAP lattice.At 30%Mg^(2+)doping,the Mg-HAP microspheres showed a more homogeneous mesoporous morphology with a high specific surface area(186.06 m^(2)/g).The IMHA microspheres showed high drug loading(7.69%)and encapsulation rate(83.29%),sustained Mg^(2+)release for more than 27 days,sustained and stable release of icariin for 60 hours,and good responsiveness to pH(pH 6.4>pH 5.6).In addition,the IMHA delivery system stimulated the rapid proliferation of bone marrow mesenchymal stem cells and induced apoptosis in MG63 cells by blocking the G2 phase cycle of osteosarcoma cells and stimulating the high expression of apoptotic genes(Bcl-2,caspase-3,-8,-9).This suggests that the abalone shell-based IMHA may have potential applications in drug delivery and tumour therapy.
文摘To explore the possibility of hydrogen sulfide (H 2S) as a messenger molecule in cardiovascular system, the authors discovered that H 2S (5×10 -5 -5×10 -4 mol·L -1 )exerted an effect on inhibiting endothelin 1 induced proliferation of cultured vascular smooth muscle cells (VSMCs) of rats in vitro . The 3H TdR incorporation decreased by 16.8%～37.4% in H 2S treated VSMCs as compared with the controls ( P <0.01). The inhibitory effect was found to be associated with reduced activity of MAPK. The authors also observed that endogenous H 2S levels markedly increased in vessels of rats with either endotoxic shock or septic shock [H 2S level (pmol·min -1 ·mg -1 ):tail artery (16.18±2.06) vs (8.12±0.55);mesenteric artery (10.17±1.11) vs (6.19 ±0.55);pulmonary artery(11.38±1.24) vs (5.27±0.51); aorta(6.21±0.48) vs (4.10± 0.28), P < 0.01 ]. The above findings suggested that H 2S might play an important role in the regulation of cardiovascular pathophysiologic events.
