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We report an electrochemical intramolecular [3 + 2] cyclization of alkynyl enaminones in a user-friendly undivided cell under constant current conditions without an oxidant and catalyst, and indeno[1,2-c]pyrrole derivatives could be obtained in good to excellent yields. Notably, preliminary substituent-controlled selective transformation is also achieved under electrocatalysis alone, and indeno[1,2-c]pyrrole (R4 ≠ H) or indanone derivatives (R4 = H) could be prepared directly under electrocatalysis without adding a base and heating process.
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Indanos , Pirróis , Catálise , Ciclização , Indanos/química , Pirróis/químicaRESUMO
A methylenation-cyclization reaction, employing cyclic enaminones with primary aromatic amines and two molecules of CO2, furnishing fused-tetrahydropyrimidines, is discussed. In this Cs2CO3 and ZnI2 catalyzed one-pot two-step procedure, two molecules of CO2 were selectively converted to methylene groups. The multi-component reaction might proceed through the formation of bis(silyl)acetal which was followed by condensation and further aza-Diels-Alder reaction. Hydroquinazoline, hydrocyclopenta[d]pyrimidine and hydroindeno[1,2-d]pyrimidine derivatives could be prepared with CO2 as the C1 source, effectively.
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By condensing M and TFP under solvothermal conditions, a new porous organic polymer POPM-TFP was obtained. The electrode modified with triazine containing POPM-TFP exhibits well-defined rapid redox processes and showed a high specific capacitance of 130.5 F g-1 at 2 A g-1, suggesting well electrochemical performance.
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INTRODUCTION: Bone tissue has an intrinsic ability to repair and regenerate itself through a continuous remodelling cycle of resorption of old or damaged bone and deposition of new. However, significant morbidity and mortality arise when bone cannot heal itself. Effective bone regeneration strategy can improve the current clinical therapies of many orthopaedic disorders. Cell activity stimulation, growth factors, and appropriate mechanical conditions are essential components of clinical treatment. However, growth factors tend to degrade over time in the human body. Gene therapy offers an alternative method to cure bone defects, with the advent of exciting new delivery capabilities via gene vectors. Gene vectors accurately deliver regenerative molecules to the lesion site. Additionally, gene therapy provides a highly efficient treatment option with a lower effective concentration. Compared with viral gene vectors, non-viral gene vectors have proven to be more potent due to their safety, non-immunogenicity, and ease of manufacture. CONCLUSION: Thus, in this paper, we review the application and progress of non-viral gene vector therapy in bone regeneration.
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Doenças Ósseas/terapia , Regeneração Óssea , Terapia Genética/métodos , Vetores Genéticos/genética , Animais , Doenças Ósseas/genética , Doenças Ósseas/fisiopatologia , Osso e Ossos/citologia , Osso e Ossos/fisiologia , Técnicas de Transferência de Genes , Humanos , Engenharia Tecidual/métodosRESUMO
Burn wounds are associated with a series of risks, such as infection and pathologic scar tissue formation, which significantly delay wound healing and lead to complications. In this study, we successfully fabricated a dextran-hyaluronic acid (Dex-HA) hydrogel enriched with sanguinarine (SA) incorporated into gelatin microspheres (GMs), which had high porosity, good swelling ratio, enhanced NIH-3T3 fibroblast cell proliferation, and sustained SA release profile. The in vitro degradation results indicate that the SA/GMs/Dex-HA hydrogel can be degraded. The in vitro antibacterial tests showed that the SA/GMs/Dex-HA hydrogel can inhibit methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). We evaluated the wound-healing effects and antibacterial properties of SA/GMs/Dex-HA hydrogels in a rat full-thickness burn infection model. The hematoxylin-eosin (H&E) and Masson's trichrome staining results of the SA/GMs/Dex-HA hydrogel showed that it improved re-epithelialization and enhanced extracellular matrix remodeling, and immunohistochemistry results showed that the expression of TGF-ß1 and TNF-α was decreased, while the TGF-ß3 expression was increased. Our findings suggest that the SA/GMs/Dex-HA hydrogel provides a potential way for infected burn treatment with high-quality and efficient scar inhibition.
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Antibacterianos/administração & dosagem , Benzofenantridinas/administração & dosagem , Dextranos/administração & dosagem , Ácido Hialurônico/administração & dosagem , Hidrogéis/administração & dosagem , Isoquinolinas/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Infecção dos Ferimentos/tratamento farmacológico , Animais , Antibacterianos/química , Benzofenantridinas/química , Queimaduras/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Dextranos/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Gelatina/administração & dosagem , Gelatina/química , Ácido Hialurônico/química , Hidrogéis/química , Isoquinolinas/química , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Camundongos , Células NIH 3T3 , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/patologia , Fator de Crescimento Transformador beta/imunologia , Fator de Necrose Tumoral alfa/imunologia , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/imunologia , Infecção dos Ferimentos/patologiaRESUMO
Drug/gene co-delivery carriers are a promising strategy for cancer treatment. Thus, herein, T7-conjugated redox-sensitive amphiphilic polyethylene glycol-polyethyleneimine-poly(caprolactone)-SS-poly(caprolactone)-polyethyleneimine-polyethylene glycol (PEG-PEI-PCL-SS-PCL-PEG) (PPPT) is designed to realize the co-delivery of pORF-hTRAIL and DOX efficiently into tumor cells. PPPT is synthesized via the ring opening polymerization (ROP) of ε-caprolactone followed by Michael addition polymerization and atom transfer radical polymerization (ATRP) of the maleic imide group of MAL-PEG-NHS. The PPPT micelles present a spherical or ellipsoidal geometry with a mean diameter of approximately 100-120 nm. Meanwhile, they also exhibit a redox-responsive drug release profile in vitro. The blood compatibility and complement activation tests reveal that the PPPT micelles do not induce blood hemolysis, blood clotting, or complement activation. The T7-modified co-delivery system shows a higher cellular uptake efficiency than the unmodified co-delivery system in human breast cancer MCF-7 cells and is accumulated in tumor more efficiently in vivo. These results suggest that the T7-targeted codelivery system of DOX and pORF-hTRAIL is a combined delivery platform that can significantly improve the treatment of breast cancer.
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Numerous biodegradable hydrogels for cartilage regeneration have been widely used in the field of tissue engineering. However, to non-invasively monitor hydrogel degradation and efficiently evaluate cartilage restoration in situ is still challenging. Methods: A ultrasmall superparamagnetic iron oxide (USPIO)-labeled cellulose nanocrystal (CNC)/silk fibroin (SF)-blended hydrogel system was developed to monitor hydrogel degradation during cartilage regeneration. The physicochemical characterization and biocompatibility of the hydrogel were evaluated in vitro. The in vivo hydrogel degradation and cartilage regeneration of different implants were assessed using multiparametric magnetic resonance imaging (MRI) and further confirmed by histological analysis in a rabbit cartilage defect model for 3 months. Results: USPIO-labeled hydrogels showed sufficient MR contrast enhancement and retained stability without loss of the relaxation rate. Neither the mechanical properties of the hydrogels nor the proliferation of bone-marrow mesenchymal stem cells (BMSCs) were affected by USPIO labeling in vitro. CNC/SF hydrogels with BMSCs degraded more quickly than the acellular hydrogels as reflected by the MR relaxation rate trends in vivo. The morphology of neocartilage was noninvasively visualized by the three-dimensional water-selective cartilage MRI scan sequence, and the cartilage repair was further demonstrated by macroscopic and histological observations. Conclusion: This USPIO-labeled CNC/SF hydrogel system provides a new perspective on image-guided tissue engineering for cartilage regeneration.
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Doenças das Cartilagens/terapia , Cartilagem/diagnóstico por imagem , Cartilagem/fisiologia , Hidrogel de Polietilenoglicol-Dimetacrilato/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Regeneração , Animais , Cartilagem/efeitos dos fármacos , Dextranos/efeitos adversos , Dextranos/análise , Modelos Animais de Doenças , Hidrólise , Nanopartículas de Magnetita/efeitos adversos , Nanopartículas de Magnetita/análise , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Nanopartículas/efeitos adversos , Nanopartículas/análise , Coelhos , Coloração e Rotulagem/métodosRESUMO
The objective of this study was to develop heparin-conjugated strontium-substituted hydroxyapatite/silk fibroin (Sr-nHAp/SF-Hep) scaffold loaded bone morphogenetic proteins-2 (BMP-2) with sustained release to improve bone regeneration. The average pore diameters and porosity of Sr-nHAp/SF scaffolds were respectively approximately 150 µm and 90%. The mechanical properties and thermostability of the Sr-nHAp/SF scaffolds were significantly stronger than those of the SF scaffold. The weight of composite scaffolds is higher than that of the SF scaffold in simulated body fluids. The Sr-nHAp/SF scaffold exhibited excellent biological function of bone marrow mesenchymal stem cell (BMSC) proliferation and adhesion. The expression of related osteogenic genes, including osteocalcin, osteopontion, and alkaline phosphatase activity was elevated by Sr-nHAp/SF-Hep-BMP-2 scaffold, which promoted the differentiation of BMSCs into osteoblasts. In vivo results showed that Sr-nHAp/SF-Hep-BMP-2 scaffolds enhanced bone mineral density and improved new bone regeneration, which was accomplished through microcomputed tomography (micro-CT) and histological and histochemical staining analysis. These results demonstrated Sr-nHAp/SF-Hep-BMP-2 scaffolds with favorable biocompatibility and good mechanical properties have great potential to repair bone defects.