This article reviews the literatures dealing with the lingualized occlusion of complete denture including the origin,development and research.Lingualized occlusion is a valuable concept because many advantages of anat...This article reviews the literatures dealing with the lingualized occlusion of complete denture including the origin,development and research.Lingualized occlusion is a valuable concept because many advantages of anatomic and nonanatomic occlusions are retained,satisfactory occlusion is easily obtained,balanced occlusion can be accomplished.展开更多
It is necessary to investigate the characteristics of Mesenchymal stem cells(MSCs)derived exosomes,and especially their application in tissue regeneration.Previous studies have shown that inflammatory stimulation enha...It is necessary to investigate the characteristics of Mesenchymal stem cells(MSCs)derived exosomes,and especially their application in tissue regeneration.Previous studies have shown that inflammatory stimulation enhanced the secretion of MSC-derived exosomes with stronger anti-inflammatory protein,cytokine profiles,and functional RNA via altering COX2/PGE2 pathway.Recently,accumulating evidence has also revealed that biophysical cues(especially biomechanical cues)in cell microenvironment have significant effects not only on cells but also on their exosomes.It has been reported that applying bi-axial strain to MSCs induces formation of a stiffer cytoskeleton through mTORC2 signaling,which biases against adipogenic differentiation and toward osteoblastogenesis.At the same time,For example,dimensionality,composition and stiffness of the extracellular matrix(ECM)has been proved to affect the size and composition of exosomes secreted by cancer cells.However,the effects of biomechanical cues in the three-dimensional(3D)microenvironment on stem cell-derived exosomes remains to be unveiled.Therefore,it is important to understand the roles of 3D cell mechanical microenvironment in regulating the characteristics of stem cell-derived exosomes and develop more efficient approaches to enhance their functions.This study aimed to explore the changes in characteristics of exosomes secreted by MSCs in periodontium in response to the matrix strain in 3D.Periodontal ligament stem cells(PDLSCs)were cultured in a 3D strain microenvironment engineered with microscale magnetically stretched collagen hydrogels.The morphology,particle distribution,marker protein expression of PDLSC-derived exosomes were analyzed.Then the pro-osteogenic property of exosomes was evaluated by assessing cell viability,proliferation,migration and osteogenic differentiation of target cells,for instance human bone marrow mesenchymal stem cells(hBMSCs).Detailed characterizations revealed that PDLSC-derived exosomes in the 3D strain mi-croenvironment were with similar morphology,particle distribution and surface markers.Notably,Exosomes secreted by PDLSCs in strain microenvironment were more endocytosed by hBMSCs and were more potent in improving proliferation and migration of hBMSCs,comparing with PDLSCs in non-strain environment.Alizarin red staining and molecular biology experiments confirmed that treatment of exosomes secreted by PDLSCs under mechanical stimulation led to a significant increase in osteogenic differentiation of hBMSCs in vitro.Meanwhile,in vivo study also indicated that PDLSC-derived exosomes obtained from the 3D strain microenvironment could obviously promote new bone formation.Our findings revealed that mechanical cues profoundly affected the characteristics of PDLSC-derived exosomes,especially for their bio-activity,providing a foundation for using the 3D mechanical microenvironment to enhance the osteo-inductive functions of stem cell-derived exosomes in cell-free therapy for bone regeneration.展开更多
Mesenchymal intricate stem cells(MSCs)represent a versatile population of multipotent progenitor cells with remarkable capacity for selfrenewal and differentiation[1].The fate commitment of MSCs is orchestrated by a c...Mesenchymal intricate stem cells(MSCs)represent a versatile population of multipotent progenitor cells with remarkable capacity for selfrenewal and differentiation[1].The fate commitment of MSCs is orchestrated by a complex interplay of intrinsic and extrinsic factors,encompassing signaling pathways,transcriptional regulators,epigenetic modifiers,and microenvironmental cues[2-5].展开更多
OBJECTIVE The aim of the study was to characterize the pharmacokinetics(PK) and pharmacodynamics(PD) profile of cisatracurium in 0-2 years and 2-5 years old children patients with cheilopalatognathus,to find if there ...OBJECTIVE The aim of the study was to characterize the pharmacokinetics(PK) and pharmacodynamics(PD) profile of cisatracurium in 0-2 years and 2-5 years old children patients with cheilopalatognathus,to find if there are some connections between the different muscle relaxation action and different PK procedure.METHODS 14 children patients were divided into two groups,≤2 years and 2-5 years group,venous samples were taken before injection of a 0.15 mg·kg-1 dose of cisatracurium and then at 2,5,10,30,60,90,and 120 min.Cisatracurium plasma concentrations were determined by ultra-performance liquid chromatography/electrospray ionization/triple quadrupole tandem mass spectrometer system(UPLC/MS/MS).The degree of neuromuscular block was measured by train of four(TOF) testing.An indirect PK-PD link model with a sigmoid E max model was established using Win Nonlin software.The model were applied to PK and PD data analysis,respectively.RESULTS The TOF monitor parameters showed that cisatracurium works very quickly,the onset time were(2.64±0.93) min and(2.59 ± 0.90) min for ≤2 years and 2-5 years group respectively.Young children ≤2 years have longer muscle blocking duration time(62.5 ± 6.01 min vs 53.86 ± 12.18 min) and slower recovery index(32.14±7.10 min and 27.43±10.63 min) than those children in group of 2-5 years.More children ≤2 years have postoperative complication than that in 2-5 children.PK parameters showed that there were no statistical differences in blood concentration and pharmacokinetic parameters.While the concentration of cisatracurium in muscle site calculated by using PK/PD model were higher and longer for ≤2 year children than that of 2-5 year children.This means that cisatracurium could stay at high concentration for a longer time in younger children' muscle tissue.CONCLUSION As a result young children tend to have postoperative complications related to slower muscle recovery action and increased concentration in skeletal muscle.So more careful observation and monitor are needed for younger children,our study could be of use in clinical practice for the administration of cisatracurium to children patients.展开更多
Objective:Drug-loaded mucoadhesive silk fibroin(SF)microneedle patch can overcome the limitations of low bioavailability and significant pain associated with traditional treatment methods,such as topical application o...Objective:Drug-loaded mucoadhesive silk fibroin(SF)microneedle patch can overcome the limitations of low bioavailability and significant pain associated with traditional treatment methods,such as topical application or injection of triamcinolone for oral submucous fibrosis(OSF).However,these systems release the drug too quickly,failing to meet the clinical requirements.This study aims to construct a mucoadhesive SF microneedle patch pre-assembled with silk fibroin nanospheres(SFN)and explore its ability to sustain the release of triamcinolone in the treatment of OSF.Methods:SFN was pre-assembled via precipitation reaction and characterized by scanning electron microscope(SEM)for the morphology.The particle size andζ-potential were measured by dynamic light scattering(DLS).Triamcinolone was loaded onto SFN using a diffusional post-loading method.The effective loading of triamcinolone was confirmed using Fourier-transform infrared spectroscopy(FTIR).The concentration of unloaded triamcinolone was quantified by high-performance liquid chromatography.Drug encapsulation efficiency and loading capacity of SFN were then calculated to determine the optimal amount of drug loading.The SFN suspension was pre-mixed with SF solution to prepare the microneedle under-layer.The microneedle morphology was observed by SEM.Compression mechanical tests were performed to evaluate the fracture force of microneedles at different nanosphere contents(5%,10%,and 20%),determining the optimal pre-mixing ratio.Ex-vivo mouse oral mucosa permeation studies were performed to ascertain the insertion depth of the microneedles via histological sections.The adhesive top layer was synthesized using SF and tannic acid,with FTIR confirming its successful synthesis.Its viscoelasticity was characterized by a rheometer,and differential scanning calorimetry analyzed thermal properties.Tensile tests evaluated the interfacial bonding strength between the adhesive layer and microneedle base to ensure no detachment during use.Adhesion to wet oral mucosal tissues was tested and compared to commercial oral patches.Under the optimized conditions,the double-layered mucoadhesive microneedle patch with pre-assembled nanospheres was prepared.Its cell compatibility was evaluated by cell counting kit-8(CCK-8),live/dead staining,and phalloidin staining after co culturing with fibroblasts.The drug release experiment was conducted to demonstrate its sustained release efficacy.Results:SFN(mean diameter 46.25 nm)was successfully prepared.The maximum drug encapsulation efficiency was(63.88±1.09)%(corresponding loading capacity of SFN was(27.41±3.06)%when the weight ratio of triamcinolone/SFN was 0.5.The corporation of SFN did not affect microneedle morphology.The mechanical properties of microneedles decreased with increasing nanosphere amount.Only the fracture force of the group with 5%SFN[(0.07±0.01)N/needle]exceeded the minimum force required for mucosal penetration,thus selected as the optimal pre-mixing ratio.Histological sections confirmed that the SFN microneedles could penetrate the epithelial layer and deliver drugs to OSF affected areas.Adhesion strength between the microneedle base and top layer was(94.8±6.89)kPa,confirming strong bonding with no detachment during use.The wet adhesive strength of the double-layered mucoadhesive microneedle patch[(41.28±7.43)kPa]was significantly enhanced compared to commercial oral patches(4.5 kPa,P<0.01).CCK-8 and live/dead staining results confirmed no significant cytotoxicity.Drug release experiment showed the double-layered mucoadhesive microneedle patch with pre-assembled SFN enabled sustained release time of triamcinolone from 4 days to 14 days.Conclusion:Pre-assembling nanospheres in mucoadhesive SF microneedle patches can extend triamcinolone release time,meeting clinical requirements for sustained drug delivery.展开更多
文摘This article reviews the literatures dealing with the lingualized occlusion of complete denture including the origin,development and research.Lingualized occlusion is a valuable concept because many advantages of anatomic and nonanatomic occlusions are retained,satisfactory occlusion is easily obtained,balanced occlusion can be accomplished.
基金financially supported by the Young Elite Scientist Sponsorship Program by CAST ( 2018QNRC001)the China Postdoctoral Science Foundation ( 2018M631172)
文摘It is necessary to investigate the characteristics of Mesenchymal stem cells(MSCs)derived exosomes,and especially their application in tissue regeneration.Previous studies have shown that inflammatory stimulation enhanced the secretion of MSC-derived exosomes with stronger anti-inflammatory protein,cytokine profiles,and functional RNA via altering COX2/PGE2 pathway.Recently,accumulating evidence has also revealed that biophysical cues(especially biomechanical cues)in cell microenvironment have significant effects not only on cells but also on their exosomes.It has been reported that applying bi-axial strain to MSCs induces formation of a stiffer cytoskeleton through mTORC2 signaling,which biases against adipogenic differentiation and toward osteoblastogenesis.At the same time,For example,dimensionality,composition and stiffness of the extracellular matrix(ECM)has been proved to affect the size and composition of exosomes secreted by cancer cells.However,the effects of biomechanical cues in the three-dimensional(3D)microenvironment on stem cell-derived exosomes remains to be unveiled.Therefore,it is important to understand the roles of 3D cell mechanical microenvironment in regulating the characteristics of stem cell-derived exosomes and develop more efficient approaches to enhance their functions.This study aimed to explore the changes in characteristics of exosomes secreted by MSCs in periodontium in response to the matrix strain in 3D.Periodontal ligament stem cells(PDLSCs)were cultured in a 3D strain microenvironment engineered with microscale magnetically stretched collagen hydrogels.The morphology,particle distribution,marker protein expression of PDLSC-derived exosomes were analyzed.Then the pro-osteogenic property of exosomes was evaluated by assessing cell viability,proliferation,migration and osteogenic differentiation of target cells,for instance human bone marrow mesenchymal stem cells(hBMSCs).Detailed characterizations revealed that PDLSC-derived exosomes in the 3D strain mi-croenvironment were with similar morphology,particle distribution and surface markers.Notably,Exosomes secreted by PDLSCs in strain microenvironment were more endocytosed by hBMSCs and were more potent in improving proliferation and migration of hBMSCs,comparing with PDLSCs in non-strain environment.Alizarin red staining and molecular biology experiments confirmed that treatment of exosomes secreted by PDLSCs under mechanical stimulation led to a significant increase in osteogenic differentiation of hBMSCs in vitro.Meanwhile,in vivo study also indicated that PDLSC-derived exosomes obtained from the 3D strain microenvironment could obviously promote new bone formation.Our findings revealed that mechanical cues profoundly affected the characteristics of PDLSC-derived exosomes,especially for their bio-activity,providing a foundation for using the 3D mechanical microenvironment to enhance the osteo-inductive functions of stem cell-derived exosomes in cell-free therapy for bone regeneration.
文摘Mesenchymal intricate stem cells(MSCs)represent a versatile population of multipotent progenitor cells with remarkable capacity for selfrenewal and differentiation[1].The fate commitment of MSCs is orchestrated by a complex interplay of intrinsic and extrinsic factors,encompassing signaling pathways,transcriptional regulators,epigenetic modifiers,and microenvironmental cues[2-5].
基金supported by Top Young Innovative Talents of Beijing(CIT&TCD201404174)Basic Clinical Cooperation Project of Capital Medical University(14JL79)
文摘OBJECTIVE The aim of the study was to characterize the pharmacokinetics(PK) and pharmacodynamics(PD) profile of cisatracurium in 0-2 years and 2-5 years old children patients with cheilopalatognathus,to find if there are some connections between the different muscle relaxation action and different PK procedure.METHODS 14 children patients were divided into two groups,≤2 years and 2-5 years group,venous samples were taken before injection of a 0.15 mg·kg-1 dose of cisatracurium and then at 2,5,10,30,60,90,and 120 min.Cisatracurium plasma concentrations were determined by ultra-performance liquid chromatography/electrospray ionization/triple quadrupole tandem mass spectrometer system(UPLC/MS/MS).The degree of neuromuscular block was measured by train of four(TOF) testing.An indirect PK-PD link model with a sigmoid E max model was established using Win Nonlin software.The model were applied to PK and PD data analysis,respectively.RESULTS The TOF monitor parameters showed that cisatracurium works very quickly,the onset time were(2.64±0.93) min and(2.59 ± 0.90) min for ≤2 years and 2-5 years group respectively.Young children ≤2 years have longer muscle blocking duration time(62.5 ± 6.01 min vs 53.86 ± 12.18 min) and slower recovery index(32.14±7.10 min and 27.43±10.63 min) than those children in group of 2-5 years.More children ≤2 years have postoperative complication than that in 2-5 children.PK parameters showed that there were no statistical differences in blood concentration and pharmacokinetic parameters.While the concentration of cisatracurium in muscle site calculated by using PK/PD model were higher and longer for ≤2 year children than that of 2-5 year children.This means that cisatracurium could stay at high concentration for a longer time in younger children' muscle tissue.CONCLUSION As a result young children tend to have postoperative complications related to slower muscle recovery action and increased concentration in skeletal muscle.So more careful observation and monitor are needed for younger children,our study could be of use in clinical practice for the administration of cisatracurium to children patients.
基金supported by the National Key Research and Development Program(2022YFC2402900)the Key Research and Development Program of Hainan Province(ZDYF2024SHFZ128)the Science and Technology Innovation Program of Hunan Province(2022RC1213),China.
文摘Objective:Drug-loaded mucoadhesive silk fibroin(SF)microneedle patch can overcome the limitations of low bioavailability and significant pain associated with traditional treatment methods,such as topical application or injection of triamcinolone for oral submucous fibrosis(OSF).However,these systems release the drug too quickly,failing to meet the clinical requirements.This study aims to construct a mucoadhesive SF microneedle patch pre-assembled with silk fibroin nanospheres(SFN)and explore its ability to sustain the release of triamcinolone in the treatment of OSF.Methods:SFN was pre-assembled via precipitation reaction and characterized by scanning electron microscope(SEM)for the morphology.The particle size andζ-potential were measured by dynamic light scattering(DLS).Triamcinolone was loaded onto SFN using a diffusional post-loading method.The effective loading of triamcinolone was confirmed using Fourier-transform infrared spectroscopy(FTIR).The concentration of unloaded triamcinolone was quantified by high-performance liquid chromatography.Drug encapsulation efficiency and loading capacity of SFN were then calculated to determine the optimal amount of drug loading.The SFN suspension was pre-mixed with SF solution to prepare the microneedle under-layer.The microneedle morphology was observed by SEM.Compression mechanical tests were performed to evaluate the fracture force of microneedles at different nanosphere contents(5%,10%,and 20%),determining the optimal pre-mixing ratio.Ex-vivo mouse oral mucosa permeation studies were performed to ascertain the insertion depth of the microneedles via histological sections.The adhesive top layer was synthesized using SF and tannic acid,with FTIR confirming its successful synthesis.Its viscoelasticity was characterized by a rheometer,and differential scanning calorimetry analyzed thermal properties.Tensile tests evaluated the interfacial bonding strength between the adhesive layer and microneedle base to ensure no detachment during use.Adhesion to wet oral mucosal tissues was tested and compared to commercial oral patches.Under the optimized conditions,the double-layered mucoadhesive microneedle patch with pre-assembled nanospheres was prepared.Its cell compatibility was evaluated by cell counting kit-8(CCK-8),live/dead staining,and phalloidin staining after co culturing with fibroblasts.The drug release experiment was conducted to demonstrate its sustained release efficacy.Results:SFN(mean diameter 46.25 nm)was successfully prepared.The maximum drug encapsulation efficiency was(63.88±1.09)%(corresponding loading capacity of SFN was(27.41±3.06)%when the weight ratio of triamcinolone/SFN was 0.5.The corporation of SFN did not affect microneedle morphology.The mechanical properties of microneedles decreased with increasing nanosphere amount.Only the fracture force of the group with 5%SFN[(0.07±0.01)N/needle]exceeded the minimum force required for mucosal penetration,thus selected as the optimal pre-mixing ratio.Histological sections confirmed that the SFN microneedles could penetrate the epithelial layer and deliver drugs to OSF affected areas.Adhesion strength between the microneedle base and top layer was(94.8±6.89)kPa,confirming strong bonding with no detachment during use.The wet adhesive strength of the double-layered mucoadhesive microneedle patch[(41.28±7.43)kPa]was significantly enhanced compared to commercial oral patches(4.5 kPa,P<0.01).CCK-8 and live/dead staining results confirmed no significant cytotoxicity.Drug release experiment showed the double-layered mucoadhesive microneedle patch with pre-assembled SFN enabled sustained release time of triamcinolone from 4 days to 14 days.Conclusion:Pre-assembling nanospheres in mucoadhesive SF microneedle patches can extend triamcinolone release time,meeting clinical requirements for sustained drug delivery.
