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Interleukin-10 (IL-10) exerts complex effects on tumor growth, exhibiting both pro- and anti-tumor properties. Recent focus on the anti-inflammatory properties of IL-10 has highlighted its potential anti-tumor properties, particularly through the enhancement of CD8+ T cell activity. However, further research is needed to fully elucidate its other anti-tumor mechanisms. Our study investigates novel anti-tumor mechanisms of IL-10 in a murine mammary carcinoma model (4T1). We found that IL-10 overexpression in mouse 4T1 cells suppressed tumor growth in vivo. This suppression was accompanied by an increase in IFN-γ-secreting CD8+ T cells and a decrease in myeloid-derived suppressor cells (MDSCs) in tumor tissue. In vitro experiments showed that IL-10-rich tumor cell-derived supernatants inhibited myeloid cell differentiation into monocytic and granulocytic MDSCs while reducing MDSCs migration. In addition, IL-10 overexpression downregulated CXCL5 expression in 4T1 cells, resulting in decreased CXCR2+ MDSCs infiltration. Using RAG1-deficient mice and CXCL5 knockdown tumor models, we demonstrated that the anti-tumor effects of IL-10 depend on both CD8+ T cells and reduced MDSC infiltration. IL-10 attenuated the immunosuppressive tumor microenvironment by enhancing CD8+ T cell activity and inhibiting MDSCs infiltration. In human breast cancer, we observed a positive correlation between CXCL5 expression and MDSC infiltration. Our findings reveal a dual mechanism of IL-10-mediated tumor suppression: (1) direct enhancement of CD8+ T cell activity and (2) indirect reduction of immunosuppressive MDSCs through CXCL5 downregulation and inhibition of myeloid cell differentiation. This study provides new insights into the role of IL-10 in anti-tumor immunity and suggests potential strategies for breast cancer immunotherapy by modulating the IL-10-CXCL5-MDSCs axis.
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Flabby ridge remained a challenge in dental clinical practice to obtain an accurate impression for edentulous patients. During the traditional impression making process, the excessive and displaceable soft tissue are usually compressed. In this article, we presented an impression method by using a modified special stock tray, impression compound and polyvinyl siloxane impression materials.â¢the suitable stock tray was modified with holes about 5 mm diameter in the corresponding area to the crest of the flabby ridge.â¢the primary impression was made by position the modified tray with the softened compound impression on the edentulous ridge, avoiding the area of the flabby ridge.â¢the final accurate impression was obtained by using the light body polyvinyl siloxane impression material.
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OBJECTIVES: To evaluate the effects of background color, ceramic type and coping thickness on masking ability (ΔE) and translucency parameter (TP) of CAD/CAM lithium disilicate glass-ceramic/monolithic zirconia and, to determine the correlations between coping thickness, TP and ΔE. METHODS: A total of 120 ceramic specimens (2 mm, 1 mm and 0.5 mm thickness; n = 10) of four CAD/CAM ceramics: IPS e.max, IPS ZirCAD, Upcera Li CAD and Upcera TT CAD, were studied. Specimens were tested over nine fabricated backgrounds: A1, A2, A3.5, ND2 and ND7 shade resin-based composites, cobalt-chromium alloy (CC), medium precious alloy (MPA), black (B) and white (W). CIELab values (L*, a* and b*), color difference (ΔE) and translucency parameter (TP) were measured and calculated using a digital spectrophotometer (color i7, X-Rite, Pantone®). Data were analyzed using the Shapiro-Wilk test, one-way ANOVA, three-way ANOVA, independent t-tests and Tukey post-hoc tests (p < 0.05). RESULTS: 2 mm CAD/CAM ceramics showed ideal color matching (ΔE<2.6) over different backgrounds, except for CC, B and W backgrounds. Monolithic zirconia had lower ΔE values than lithium disilicate glass-ceramics. ΔE and TP values significantly reduced with the increased coping thickness (p < 0.05). Regardless of ceramic type and thickness, a strong TP-SD of ΔE correlation was observed. SIGNIFICANCE: CAD/CAM ceramic restoration color was significantly affected by background color, ceramic type and coping thickness. TP is a promising predictor for appropriate ceramic selection to receive an acceptable CAD/CAM ceramic restoration aesthetic.
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Cerâmica , Estética Dentária , Ligas de Cromo , Desenho Assistido por ComputadorRESUMO
The molecular structure of sulfonated chitosan is similar to heparin, and it has been proved to have some heparin functions. Studies have shown that heparin and bone morphogenetic protein-2 (BMP-2) have synergistic effects, but heparin has limitations in clinical application. In this paper, the synergistic effect of 2-N,6-O-sulfonated chitosan (26SCS) and BMP-2 was studied. The preparation of 26SCS was explored and 26SCS was co-cultured with bone marrow mesenchymal stem cells (BMSCs) to study the effects of 26SCS on the proliferation, adhesion behavior and osteogenic differentiation of BMSCs. The synergistic mechanism of 26SCS and BMP-2 was explored by circular dichroism and isothermal calorimetric titration. The results showed that 26SCS affected the secondary structure of BMP-2 protein, mainly caused the significant change of antiparallel conformation in ß-fold, and then improved the biological activity of BMP-2 and showed a dose-dependent manner. 26SCS was expected to be a synergistic factor of BMP-2.
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Proteína Morfogenética Óssea 2/química , Proteína Morfogenética Óssea 2/metabolismo , Quitosana/química , Quitosana/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Heparina/química , Heparina/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Estrutura Secundária de Proteína/efeitos dos fármacos , Coelhos , Enxofre/químicaRESUMO
Developmental engineering strategy needs the biomimetic composites that can integrate the progenitor cells, biomaterial matrices and bioactive signals to mimic the natural bone healing process for faster healing and reconstruction of segmental bone defects. We prepared the gelatin-reduced graphene oxide (GOG) and constructed the composites that mimicked the procallus by combining the GOG with the photo-crosslinked gelatin hydrogel. The biological effects of the GOG-reinforced composites could induce the bi-differentiation of bone marrow stromal cells (BMSCs) for rapid bone repair. The proper ratio of GOG in the composites regulated the composites' mechanical properties to a suitable range for the adhesion and proliferation of BMSCs. Besides, the GOG-mediated bidirectional differentiation of BMSCs, including osteogenesis and angiogenesis, could be activated through Erk1/2 and AKT pathway. The methyl vanillate (MV) delivered by GOG also contributed to the bioactive signals of the biomimetic procallus through priming the osteogenesis of BMSCs. During the repair of the calvarial defect in vivo, the initial hypoxic condition due to GOG in the composites gradually transformed into a well-vasculature robust situation with the bi-differentiation of BMSCs, which mimicked the process of bone healing resulting in the rapid bone regeneration. As an inorganic constituent, GOG reinforced the organic photo-crosslinked gelatin hydrogel to form a double-phase biomimetic procallus, which provided the porous extracellular matrix microenvironment and bioactive signals for the bi-directional differentiation of BMSCs. These show a promised application of the bio-reduced graphene oxide in biomedicine with a developmental engineering strategy.
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Tissue engineering strategies to construct vascularized bone grafts are now attracting much attention. Strontium-hardystonite-Gahnite (Sr-HT-Gahnite) is a strong, highly porous, and biocompatible calcium silicate based bio-ceramic that contains strontium and zinc ions. Adipose derived stem cells (ASCs) have been demonstrated to have the ability in promoting osteogenesis and angiogenesis. In this study, the effects of Sr-HT-Gahnite on cell morphology, cell proliferation, and osteogenic differentiation of ASCs were systematically investigated. The cell proliferation, migration and angiogenic differentiation of human umbilical vein endothelial cell (HUVECs) were studied. Beta-tricalcium phosphate/hydroxyapatite (TCP/HA) bioceramic scaffolds were set as the control biomaterial. Both bio-ceramics exhibited no adverse influence on cell viability. The Sr-HT-Gahnite scaffolds promoted cell attachment and alkaline phosphatase (ALP) activity of ASCs. The Sr-HT-Gahnite dissolution products enhanced ALP activity, matrix mineralization, and angiogenic differentiation of ASCs. They could also improve cell proliferation, migration, and angiogenic differentiation of HUVECs. Levels of in vivo bone formation with Sr-HT Gahnite were significantly higher than that for TCP/HA. The combination of Sr-HT-Gahnite and ASCs promoted both osteogenesis and angiogenesis in vivo study, compared to Sr-HT-Gahnite and TCP/HA bio-ceramics when administered alone, suggesting Sr-HT-Gahnite can act as a carrier for ASCs for construction of vascularized tissue-engineered bone.
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Tecido Adiposo/citologia , Materiais Biocompatíveis/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Crânio/anormalidades , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Materiais Biocompatíveis/química , Regeneração Óssea , Compostos de Cálcio/química , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cerâmica/química , Modelos Animais de Doenças , Células Endoteliais da Veia Umbilical Humana , Humanos , Ratos , Silicatos/química , Crânio/efeitos dos fármacos , Transplante de Células-Tronco , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Estrôncio/química , Engenharia TecidualRESUMO
Thermal oxidation, which serves as a low-cost, effective and relatively simple/facile method, was used to modify a micro-structured titanium surface in ambient atmosphere at 450 °C for different time periods to improve in vitro and in vivo bioactivity. The surface morphology, crystallinity of the surface layers, chemical composition and chemical states were evaluated by field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Cell behaviours including cell adhesion, attachment, proliferation, and osteogenic differentiation were observed in vitro study. The ability of the titanium surface to promote osseointegration was evaluated in an in vivo animal model. Surface thermal oxidation on titanium implants maintained the microstructure and, thus, both slightly changed the nanoscale structure of titanium and enhanced the crystallinity of the titanium surface layer. Cells cultured on the three oxidized titanium surfaces grew well and exhibited better osteogenic activity than did the control samples. The in vivo bone-implant contact also showed enhanced osseointegration after several hours of oxidization. This heat-treated titanium enhanced the osteogenic differentiation activity of rBMMSCs and improved osseointegration in vivo, suggesting that surface thermal oxidation could potentially be used in clinical applications to improve bone-implant integration.
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Interface Osso-Implante , Osseointegração/fisiologia , Osteogênese/fisiologia , Titânio/química , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Osseointegração/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Oxirredução , Espectroscopia Fotoeletrônica , Coelhos , Ratos Sprague-Dawley , Propriedades de Superfície , Temperatura , Titânio/farmacologia , Difração de Raios XRESUMO
BACKGROUND: The presence of insufficient bone volume remains a major clinical problem for dental implant placement to restore oral function. Tissue engineering provides a promising approach for inducing bone regeneration and enhancing osseointegration in dental implants. PURPOSE: The tissue-engineered bone consisting of recombinant human platelet-derived growth factor (rhPDGF-BB), bone marrow stem cells (BMSCs), and beta-tricalcium phosphate (ß-TCP) particles was validated for the first time in a preclinical large animal canine model in terms of its ability to promote new bone formation around the implants, as well as osseointegration between the tissue-engineered bone and dental implants. MATERIALS AND METHODS: Proliferation and osteogenic differentiation of canine BMSCs treated with rhPDGF-BB were evaluated with an MTT, alkaline phosphatase (ALP) activity, Alizarin Red staining, and real-time quantitative PCR (RT-qPCR) analysis of osteogenic genes. The therapeutic potential of tissue-engineered bone consisting of rhPDGF-BB/BMSCs/ß-TCP in bone repair was evaluated in mesial-implant defects of immediate postextraction implants in the canine mandible. RESULTS: rhPDGF-BB treatment significantly increased proliferation and osteogenic differentiation of canine BMSCs. Furthermore, the tissue-engineered bone consisting of rhPDGF-BB/BMSCs/ß-TCP significantly enhanced bone formation and osseointegration. CONCLUSION: This study provides important evidence that supports the potential application of rhPDGF-BB/BMSCs/ß-TCP tissue-engineered bone in immediate implantation for oral function restoration.
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Regeneração Óssea , Fosfatos de Cálcio , Implantes Dentários , Fator de Crescimento Derivado de Plaquetas , Células-Tronco , Animais , Cães , Humanos , Mandíbula , Osseointegração , OsteogêneseRESUMO
Platelet-derived growth factor-BB (PDGF-BB) plays important roles in regenerating damaged tissue. In this study we investigated the effects of a tissue-engineered bone combined with recombinant human PDGF-BB (rhPDGF-BB), bone marrow stem cells (BMSCs) and ß-tricalcium phosphate (ß-TCP) to repair critical-size calvarial bone defects in rat. Proliferation and osteogenic differentiation of BMSCs treated with different concentration rhPDGF-BB (0, 10, and 50 ng/ml) was evaluated by MTT, alkaline phosphatase (ALP) activity, alizarin red staining and real-time quantitative PCR (RT-qPCR) analysis of osteogenic gene. BMSCs were then combined with rhPDGF-BB-loaded ß-TCP and transplanted into 5 mm calvarial bone defects. The new bone formation and mineralization was evaluated by micro-computerized tomography (Micro-CT) and histological analysis at week 8 after operation. It was observed that the proliferation of BMSCs treated with rhPDGF-BB was enhanced with a time- and dose- dependent manner. There were increased ALP activity, mineralized deposition and elevated mRNA levels of osteogenic gene for BMSCs treated with rhPDGF-BB, particularly in the 50 ng/ml group. Histological analysis showed new bone formation and mineralization in the rhPDGF-BB/BMSCs/ß-TCP group was significantly higher than BMSCs/ß-TCP, rhPDGF-BB/ß-TCP, and ß-TCP alone group (P < 0.05). In conclusion, rhPDGF-BB/BMSCs/ß-TCP is a promising tissue-engineered bone for craniofacial bone regeneration.
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Osso e Ossos/efeitos dos fármacos , Fosfatos de Cálcio , Células-Tronco Hematopoéticas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-sis/farmacologia , Cicatrização/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Sequência de Bases , Becaplermina , Osso e Ossos/patologia , Células Cultivadas , Primers do DNA , Corantes Fluorescentes , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/enzimologia , Humanos , Masculino , Ratos , Ratos Endogâmicos F344 , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Recombinantes/farmacologia , Tomografia Computadorizada por Raios XRESUMO
There is an increased use of nanophase titanium dioxide (TiO(2)) in bone implants and scaffolds. However, nano-debris is generated at the bone-biomaterial interface. Therefore, TiO(2) nanoparticles (NPs) of many sizes were investigated for cytotoxic effects on murine MC3T3-E1 preosteoblasts. These TiO(2) NPs induced a time- and dose-dependent decrease in cell viability. There was a significant increase in lactate dehydrogenase (LDH) release, apoptosis and mitochondrial membrane permeability following short-term exposure of the cells to TiO(2) NPs. These NPs also increased granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) gene expression. Compared with the 32 nm TiO(2) NPs, 5 nm TiO(2) NPs were more toxic, induced more apoptosis, increased mitochondrial membrane permeability and stimulated more GM-CSF expression at a high concentration (≥100 µg/ml). The results implied that the differential toxicity was associated with variations in size, so more attention should be given to the toxicity of small NPs for the design of future materials for implantation.
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Nanopartículas Metálicas , Osteoblastos/efeitos dos fármacos , Titânio/toxicidade , Células 3T3 , Animais , Apoptose/efeitos dos fármacos , Sequência de Bases , Permeabilidade da Membrana Celular/efeitos dos fármacos , Primers do DNA , Citometria de Fluxo , L-Lactato Desidrogenase/metabolismo , Camundongos , Microscopia Eletrônica de Transmissão , Mitocôndrias/efeitos dos fármacos , Osteoblastos/citologia , Osteoblastos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Polyethyleneimine (PEI) was used to create active groups on the poly (lactide-co-glycolide)/nano-hydroxyapatite (PLGA/NHA) surface and Arg-Gly-Asp (RGD) was grafted on the active groups and novel PLGA/NHA 2-D membranes and 3D scaffolds modified with RGD were obtained. X-ray photoelectron spectrum (XPS) results show that sulfur displays only on the modified surface. The RGD-modified PLGA/NHA materials also have much lower static water contact angle and much higher water-absorption ability, which shows that after chemical treatment, the modified materials show better hydrophilic properties. Atomic force microscope (AFM) shows that after surface modification, the surface morphology of PLGA is greatly changed. All these results indicate that RGD peptide has successfully grafted on the surface of PLGA. Rabbit bone marrow stromal cells (MSCs) were seeded in the 2D membranes and 3D scaffolds materials. The influences of the RGD on the cell attachment, growth and differentiation, and proliferation on the different materials were studied. The modified scaffolds were implanted into rabbits to observe preliminary application in regeneration of mandibular defect. The PLGA/NHA-RGD presents better results in bone regeneration in rabbit mandibular defect.
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Células da Medula Óssea/citologia , Regeneração Óssea/efeitos dos fármacos , Durapatita/farmacologia , Ácido Láctico/farmacologia , Mandíbula/patologia , Nanoestruturas/química , Oligopeptídeos/farmacologia , Ácido Poliglicólico/farmacologia , Absorção/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Materiais Biocompatíveis/farmacologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/ultraestrutura , Adesão Celular/efeitos dos fármacos , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Células Cultivadas , Proteínas Imobilizadas/farmacologia , Mandíbula/diagnóstico por imagem , Mandíbula/efeitos dos fármacos , Microscopia de Força Atômica , Espectroscopia Fotoeletrônica , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Radiografia , Células Estromais/citologia , Células Estromais/efeitos dos fármacos , Células Estromais/ultraestrutura , Fatores de Tempo , Alicerces Teciduais/química , ÁguaRESUMO
PURPOSE: The aim of this prospective randomized controlled trial is to evaluate the clinical effect of glass fiber-reinforced post core applied in the restoration of premolar or molar residual crown and root. METHODS: 195 residual crown and root of posterior teeth from 100 patients, aged from 18 to 60 years, were included in the study. Among 195 teeth, 95 teeth in the experimental group were restored with glass fiber-reinforced post core, while the other 100 teeth in the control group were restored with metal cast post core. All the teeth were then restored with porcelain fused metal crown. The esthetical property, function, and survival rate of the prostheses were observed. The data was analyzed with SPSS13.0 software package for X(2) test. RESULTS: The prostheses were followed up in this clinical study for a period of up to 36 months. In the experimental group, there were a total of 90 teeth with excellent chewing function, no complaint of discomfort, no debounding, no gingivitis or periapical periodontitis. The success rate of the experimental group was 94.74%, while that of the control group was 85.00%. The difference of the success rate between two groups was statistically significant(P<0.05). CONCLUSION: Glass fiber-reinforced post core can be used as an ideal restoration material for the premolar or molar residual crown and root.
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Coroas , Técnica para Retentor Intrarradicular , Adolescente , Adulto , Dente Pré-Molar , Porcelana Dentária , Vidro , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Coroa do Dente , Adulto JovemRESUMO
PURPOSE: The purpose of this study is to evaluate immediate autologous bone graft combined with secondary dental implant to repair traumatogenic defect and lost teeth. METHODS: 16 patients with labial anterior maxillary alveolar bone defect, caused by trauma for various reasons were selected as the experimental group. The suitable size autologous skull plates or chin bone plates were harvested and transplanted to the bone defect site and fixed with titanium screw immediately after the wound was completely cleaned, and then the gingiva and mucosa were sutured adequately. 42 ITI SLA implants were implanted 12 weeks after bone graft surgery. Porcelain fused metal crowns were made 12 weeks after implantation. Meanwhile, a total of 22 patients with 50 ITI SLA implants which were routinely implanted in anterior maxillary alveolar bone without bone graft surgery were selected as the control group. Resonance frequency analysis(RFA) was taken at 0,4,12,52 weeks after implant surgery in both groups to get implant stability quotient(ISQ) values. Student's t test was used to calculate P values for ISQ with SPSS13.0 software package. RESULTS: The soft tissue wound of 16 patients healed 7-9 days after trauma. The alveolar arch returned normal, the alveolar ridge was with adequate height and width. The contour and function of dentures restored 12 weeks after implantation. No significant difference in ISQ values was found between the two groups at 0,4,12,52 weeks after implant surgery(P>0.05). CONCLUSIONS: The course of treatment is shortened, the times of surgery are reduced, and the repair effect is satisfied by immediate autologous bone graft and secondary dental implantation for upper anterior labial alveolar bone defect and teeth loss caused by trauma.