RESUMO
Aiming at the fundamental understanding of solvent effects in amphiphilic polymer systems, we considered poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers in water mixed with an ionic liquid-ethylammonium nitrate (EAN), 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6), or 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF4)-and we investigated the hexagonal lyotropic liquid crystal structures by means of small-angle X-ray scattering (SAXS). At 50% polymer, the hexagonal structure (cylinders of self-assembled block copolymer) was maintained across the solvent mixing ratio. The effects of the ionic liquids were reflected in the characteristic length scales of the hexagonal structure and were interpreted in terms of the location of the ionic liquid in the self-assembled block copolymer domains. The protic ionic liquid EAN was evenly distributed within the aqueous domains and showed no affinity for the interface, whereas BMIMPF6 preferred to swell PEO and was located at the interface so as to reduce contact with water. BMIMBF4 was also interfacially active, but to a lesser extent.
RESUMO
BACKGROUND: Periodontitis is a chronic infection initiated by oral bacterial and their virulence factors, yet the severity of periodontitis is largely determined by the dysregulated host immuno-inflammatory response. Baicalein is a flavonoid extracted from Scutellaria baicalensis with promising anti-inflammatory properties. This study aims to clarify the anti-inflammatory and osteogenic effects of baicalein in periodontal ligament cells (PDLCs) treated with lipopolysaccharides (LPS). METHODS: Human PDLCs were incubated with baicalein (0-100 µM) for 2 h prior to LPS challenge for 24 h. MTT analysis was adopted to assess the cytoxicity of baicalein. The mRNA and protein expression of inflammatory and osteogenic markers were measured by real-time polymerase chain reaction (PCR), western blot and enzyme-linked immunosorbent assay (ELISA) as appropriate. Alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were performed to evaluate the osteogenic differentiation of PDLCs. The expression of Wnt/ß-catenin and mitogen-activated protein kinase (MAPK) signaling related proteins was assessed by western blot. RESULTS: MTT results showed that baicalein up to 100 µM had no cytotoxicity on PDLCs. Baicalein significantly attenuated the inflammatory factors induced by LPS, including interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), matrix metalloprotein-1 (MMP-1), MMP-2 and monocyte chemoattractant protein 1 (MCP-1) at both mRNA and protein level. Moreover, MAPK signaling (ERK, JNK and p38) was significantly inhibited by baicalein, which may account for the mitigated inflammatory response. Next, we found that baicalein effectively restored the osteogenic differentiation of LPS-treated PDLCs, as shown by the increased ALP and ARS staining. Accordingly, the protein and gene expression of osteogenic markers, namely runt-related transcription factor 2 (RUNX2), collagen-I, and osterix were markedly upregulated. Importantly, baicalein could function as the Wnt/ß-catenin signaling activator, which may lead to the increased osteoblastic differentiation of PDLCs. CONCLUSIONS: With the limitation of the study, we provide in vitro evidence that baicalein ameliorates inflammatory response and restores osteogenesis in PDLCs challenged with LPS, indicating its potential use as the host response modulator for the management of periodontitis.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Flavanonas/farmacologia , Osteogênese/efeitos dos fármacos , Ligamento Periodontal/efeitos dos fármacos , Periodontite/tratamento farmacológico , Scutellaria baicalensis/química , Fosfatase Alcalina/genética , Fosfatase Alcalina/imunologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/imunologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Lipopolissacarídeos/efeitos adversos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/imunologia , Ligamento Periodontal/citologia , Ligamento Periodontal/imunologia , Periodontite/genética , Periodontite/imunologia , Periodontite/fisiopatologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/genética , beta Catenina/imunologiaRESUMO
BACKGROUND: Periodontal pathogenic bacteria promote the destruction of periodontal tissues and cause loosening and loss of teeth in adults. However, complete removal of periodontal pathogenic bacteria, at both the bottom of the periodontal pocket and the root bifurcation area, remains challenging. In this work, we explored a synergistic antibiotic and photothermal treatment, which is considered an alternative strategy for highly efficient periodontal antibacterial therapy. METHODS: Mesoporous silica (MSNs) on the surface of Au nanobipyramids (Au NBPs) were designed to achieve the sustained release of the drug and photothermal antibacterials. The mesoporous silica-coated Au NBPs (Au NBPs@SiO2) were mixed with gelatin methacrylate (GelMA-Au NBPs@SiO2). Au NBPs@SiO2 and GelMA-Au NBPs@SiO2 hybrid hydrogels were characterized, and the drug content and photothermal properties in terms of the release profile, bacterial inhibition, and cell growth were investigated. RESULTS: The GelMA-Au NBPs@SiO2 hybrid hydrogels showed controllable minocycline delivery, and the drug release rates increased under 808 nm near-infrared (NIR) light irradiation. The hydrogels also exhibited excellent antibacterial properties, and the antibacterial efficacy of the antibiotic and photothermal treatment was as high as 90% and 66.7% against Porphyromonas gingivalis (P. gingivalis), respectively. Moreover, regardless of NIR irradiation, cell viability was over 80% and the concentration of Au NBPs@SiO2 in the hybrid hydrogels was as high as 100 µg/mL. CONCLUSION: We designed a new near-infrared light (NIR)-activated hybrid hydrogel that offers both sustained release of antibacterial drugs and photothermal treatment. Such sustained release pattern yields the potential to rapidly eliminate periodontal pathogens in the periodontal pocket, and the photothermal treatment maintains low bacterial retention after the drug treatment.
Assuntos
Antibacterianos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Porphyromonas gingivalis/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacocinética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Liberação Controlada de Fármacos , Ouro/química , Hidrogéis/farmacocinética , Hidrogéis/efeitos da radiação , Lasers , Metacrilatos/química , Camundongos , Minociclina/química , Minociclina/farmacocinética , Minociclina/farmacologia , Nanoestruturas/química , Doenças Periodontais/tratamento farmacológico , Doenças Periodontais/microbiologia , Fototerapia/métodos , Dióxido de Silício/químicaRESUMO
BACKGROUND AND OBJECTIVE: Bone remodeling during orthodontic treatment is achieved by the osteogenesis of human periodontal ligament cells (PDLCs) subjected to mechanical loadings. Transcriptional co-activator with PDZ-binding motif (TAZ) mediates bone remodeling in response to extracellular mechanical signals. This study aims to investigate the role of TAZ in osteogenesis of PDLCs under tensile strain. MATERIALS AND METHODS: A uniaxial cyclic tensile stress (CTS) at 12% elongation and 6 cycles/min (5 s on and 5 s off) was applied to PDLCs. The osteogenic differentiation was determined by the protein and gene expressions of osteogenic markers using qRT-PCR and Western blot, respectively, and further by alkaline phosphatase (ALP) activity and Alizarin Red S staining. The interaction of TAZ with core-binding factor α1 (Cbfα1) was examined by co-immunoprecipitation. The immunofluorescence histochemistry was used to examine the nucleus aggregation of TAZ and the reorganization of actin filaments. Moreover, small interfering RNA-targeting TAZ (TAZsiRNA) was used for TAZ inhibition and Y-27632 was employed for Ras homologue-associated coiled-coil protein kinase (ROCK) signaling blockage. RESULTS: CTS clearly stimulated the nucleus accumulation of TAZ and its interaction with Cbfα1. CTS-induced osteogenesis in PDLCs was significantly abrogated by the infection with TAZsiRNA, as shown by the decreased stained nodules and protein expressions of Cbfα1, collagen type I, osterix, and osteocalcin, along with the inhibition of ß-catenin signaling. Moreover, ROCK inhibition by Y-27632 hindered TAZ nucleus aggregation and its binding with Cbfα1, which subsequently lead to the decreased osteoblastic differentiation of PDLCs. CONCLUSIONS: Taken together, we propose that TAZ nucleus localization and its interaction with Cbfα1 are essential for the CTS-induced osteogenic differentiation in PDLCs. And such TAZ activation by CTS could be mediated by ROCK signaling, indicating the pivot role of ROCK-TAZ pathway for PDLCs differentiation.