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1.
Int J Nanomedicine ; 14: 5831-5848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534327

RESUMO

Purpose: In order to accelerate the tendon-bone healing processes and achieve the efficient osteointegration between the tendon graft and bone tunnel, we aim to design bioactive electrospun nanofiber membranes combined with tendon stem/progenitor cells (TSPCs) to promote osteogenic regeneration of the tendon and bone interface. Methods: In this study, nanofiber membranes of polycaprolactone (PCL), PCL/collagen I (COL-1) hybrid nanofiber membranes, poly(dopamine) (PDA)-coated PCL nanofiber membranes and PDA-coated PCL/COL-1 hybrid nanofiber membranes were successfully fabricated by electrospinning. The biochemical characteristics and nanofibrous morphology of the membranes, as well as the characterization of rat TSPCs, were defined in vitro. After co-culture with different types of electrospun nanofiber membranes in vitro, cell proliferation, viability, adhesion and osteogenic differentiation of TSPCs were evaluated at different time points. Results: Among all the membranes, the performance of the PCL/COL-1 (volume ratio: 2:1 v/v) group was superior in terms of its ability to support the adhesion, proliferation, and osteogenic differentiation of TSPCs. No benefit was found in this study to include PDA coating on cell adhesion, proliferation and osteogenic differentiation of TSPCs. Conclusion: The PCL/COL-1 hybrid electrospun nanofiber membranes are biocompatible, biomimetic, easily fabricated, and are capable of supporting cell adhesion, proliferation, and osteogenic differentiation of TSPCs. These bioactive electrospun nanofiber membranes may act as a suitable functional biomimetic scaffold in tendon-bone tissue engineering applications to enhance tendon-bone healing abilities.


Assuntos
Materiais Biocompatíveis/farmacologia , Osso e Ossos/fisiologia , Membranas Artificiais , Nanofibras/química , Células-Tronco/citologia , Tendões/citologia , Engenharia Tecidual/métodos , Animais , Osso e Ossos/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Nanofibras/ultraestrutura , Osteogênese , Ratos Sprague-Dawley , Células-Tronco/efeitos dos fármacos
2.
Int J Nanomedicine ; 14: 5697-5711, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413570

RESUMO

Purpose: Calcium (Ca) and magnesium (Mg) ions have been used as promising bioactive ions in the surface chemistry modification of titanium (Ti) bone implants to increase bone regeneration capacity. However, it is not clear which (Ca or Mg) plays the more important role in the early osteogenic differentiation of mesenchymal stem cells (MSCs) when applied to the surface of commercially available microstructured Ti implants. This study investigated the relative effect of these two ions on the early osteogenic functionality of primary mouse bone marrow MSCs in order to obtain insights into the surface design of Ti implants with enhanced early osteogenic capacity. Methods and results: Wet chemical treatment was performed to modify a microrough Ti implant surface using Ca or Mg ions. Both the Ca and Mg-incorporated surfaces accelerated early cellular events and the subsequent osteogenic differentiation of MSCs compared with an unmodified microrough Ti surface. Surface Mg modification exhibited a more potent osteoblast differentiation-promoting effect than the Ca modification. Surface Mg incorporation markedly inhibited the phosphorylation of ß-catenin. Conclusion: These results indicate that alteration of the surface chemistry of microstructured Ti implants by wet chemical treatment with Mg ions exerts a more effect on promoting the early osteogenic differentiation of MSCs than Ca ions by enhancing early cellular functions, including focal adhesion development and stabilization of intracellular ß-catenin.


Assuntos
Cálcio/farmacologia , Magnésio/farmacologia , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Próteses e Implantes , Titânio/farmacologia , Animais , Cátions Bivalentes/farmacologia , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Adesões Focais/efeitos dos fármacos , Íons , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/ultraestrutura , Camundongos , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Propriedades de Superfície , Água/química , Difração de Raios X , beta Catenina/metabolismo
3.
J Photochem Photobiol B ; 197: 111515, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31255939

RESUMO

An extraordinary arrangement of research is as yet going on in the area of orthopedic implants advancement to determine different issues being looked by the engineering today. In spite of a few detriments of the orthopedic metallic inserts, they keep on being utilized, essentially as a result of their unrivaled mechanical properties. We investigated the conceivable utilization of silicon carbide (SiC) as a nano-ceramic covering material of titanium (Ti)-based all out femoral substitution implants. The thought is to keep wear garbage arrangement from the delicate titanium exterior. Silicon carbide is a hard and firmly holding bio-ceramic surface substance, and in light of these physico-chemical properties, it isn't actually degradable, just like the case with apatite (HA). To improve cytocompatibility and osseous-integration, we deposited anodized titanium nanotubes (TiO2) inserts, by electrochemical deposition method (EDM), with silicon carbide (SiC) with apatite (SiC@HA). The deposition was affirmed by SEM, while phase composition properties were assessed by XRD. Calcium affidavit, osteocalcin creation, and articulation of bone genes were essentially higher in rodent osteoblast cell culture on SiC@HA-covered anodized titanium nanotubes than in cells cultured on uncoated anodized titanium nanotubes. Implantation into rodent femurs likewise demonstrated that the SiC@HA-covered substance had unrivaled osseous-integration movement in correlation with that of customary inserts, as evaluated by in vivo tomography and histology. Therefore, anodized titanium nanotubes covered with SiC@HA holds guarantee as an orthopedic implant substance.


Assuntos
Regeneração Óssea , Compostos Inorgânicos de Carbono/química , Materiais Revestidos Biocompatíveis/química , Durapatita/química , Nanopartículas/química , Compostos de Silício/química , Titânio/química , Animais , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Adesão Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/uso terapêutico , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Fraturas do Fêmur/terapia , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteocalcina/metabolismo , Próteses e Implantes , Ratos
4.
Life Sci ; 232: 116624, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276689

RESUMO

AIMS: Monocyte-endothelial adhesion is considered to be the primary initiator of inflammatory vascular diseases, such as atherosclerosis. Connexin 43 (Cx43) has been reported to play an important part in this process, however, the underlying mechanisms are not fully understood. Intravenous anesthetics, propofol is commonly used in the perioperative period and in the intensive care unit, and considered to have good anti-inflammatory and antioxidant effects. Thus, we speculate that propofol could influence monocyte-endothelial adhesion, and explore whether its possible mechanism is relative with Cx43 expression in U937 monocytes influencing cell adhesion of U937 monocytes to human umbilical vein endothelial cells (HUVEC). MAIN METHODS: Cx43-siRNAs or pc-DNA-Cx43 were used to alter Cx43 expression in U937 monocytes. Propofol was given as pretreatments to U937 monocytes. Then, cell adhesion, ZO-1, LFA-1, VLA-4, COX and MCP-1 were determined. PI3K/AKT/NF-κB signaling pathway was explored to clarify the possible mechanism. KEY FINDINGS: Alternation of Cx43 expression affects cell adhesion and adhesion molecules significantly, such as ZO-1, LFA-1, VLA-4, COX-2 and MCP-1, the mechanism of which is relative with Cx43 influencing the activation of PI3K/AKT/NF-κB signaling pathway. Preconditioning with propofol at its clinically relevant anesthesia concentration attenuates cell adhesion. Propofol not only decreases Cx43 expression in U937 monocytes, but also depresses the activation of PI3K/AKT/NF-κB signaling pathway. SIGNIFICANCE: Modulation Cx43 expression in U937 monocytes could affect cell adhesion via regulating the activation of PI3K/AKT/NF-κB signaling pathway. Propofol attenuates cell adhesion via inhibiting Cx43 and its downstream signaling pathway of PI3K/AKT/NF-κB.


Assuntos
Adesão Celular/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Propofol/farmacologia , Aterosclerose/metabolismo , Moléculas de Adesão Celular/metabolismo , Conexina 43/efeitos dos fármacos , Conexina 43/genética , Conexina 43/metabolismo , Endotélio Vascular/metabolismo , Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Monócitos/fisiologia , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Propofol/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células U937/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo
5.
Chemotherapy ; 64(1): 1-7, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31234166

RESUMO

Infections with herpes simplex virus type (HSV)-1 and HSV-2 are distributed worldwide. Although standard therapies with acyclovir and other synthetic drugs are available, the safety and efficacy of these drugs are limited due to the development of drug resistance and adverse side effects. The literature on essential oils and isolated compounds was reviewed regarding their antiviral activities against HSV-1 and HSV-2. The present overview aims to review experimental data and clinical trials focusing on the antiviral activity of selected essential oils and isolated oil components. HSV was found to be susceptible to many essential oils and their constituents. Whereas some essential oils and compounds exhibit direct virucidal activity or inhibit intracellular replication, many essential oils and compounds interact with HSV particles thereby inhibiting cell adsorption. Ayclovir-resistant HSV strains are also susceptible to essential oils since their mode of action is different from the synthetic drug. There are numerous publications on the antiherpetic activity of essential oils and their isolated active compounds. This field of research is still growing, and more clinical trials are required to explore the full potential of different essential oils for the topical treatment of herpetic infections.


Assuntos
Herpes Simples/tratamento farmacológico , Óleos Voláteis/uso terapêutico , Antivirais/química , Antivirais/farmacologia , Antivirais/uso terapêutico , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Humanos , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Simplexvirus/efeitos dos fármacos , Simplexvirus/fisiologia
6.
Int J Nanomedicine ; 14: 3669-3678, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190818

RESUMO

Background: Electrospun gelatin/polycaprolactone (Gt/PCL) nanofibrous scaffolds loaded with graphene are novel nanomaterials with the uniquely strong property of electrical conductivity, which have been widely investigated for their potential applications in cardiovascular tissue engineering, including in bypass tracts for atrioventricular block. Purpose: Electrospun Gt/PCL/graphene nanofibrous mats were successfully produced. Scanning electron micrography showed that the fibers with graphene were smooth and homogeneous. In vitro, to determine the biocompatibility of the scaffolds, hybrid scaffolds with different fractions of graphene were seeded with neonatal rat ventricular myocytes. In vivo, Gt/PCL scaffolds with different concentrations of graphene were implanted into rats for 4, 8 and 12 weeks. Results: CCK-8 assays and histopathological staining (including DAPI, cTNT, and CX43) indicated that cells grew and survived well on the hybrid scaffolds if the mass fraction of graphene was lower than 0.5%. After implanting into rats for 4, 8 or 12 weeks, there was no gathering of inflammatory cells around the nanomaterials according to the HE staining results. Conclusion: The results indicate that Gt/PCL nanofibrous scaffolds loaded with graphene have favorable electrical conductivity and biological properties and may be suitable scaffolds for use in the treatment of atrioventricular block. These findings alleviate safety concerns and provide novel insights into the potential applications of Gt/PCL loaded with graphene, offering a solid foundation for comprehensive in vivo studies.


Assuntos
Gelatina/toxicidade , Grafite/toxicidade , Nanofibras/toxicidade , Poliésteres/toxicidade , Engenharia Tecidual , Tecidos Suporte/química , Testes de Toxicidade , Animais , Apoptose/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Processamento de Imagem Assistida por Computador , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos , Suínos
7.
Mem Inst Oswaldo Cruz ; 114: e190088, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31188952

RESUMO

BACKGROUND: Despite treatment with effective antimalarial drugs, the mortality rate is still high in severe cases of the disease, highlighting the need to find adjunct therapies that can inhibit the adhesion of Plasmodium falciparum-infected erythrocytes (Pf-iEs). OBJECTIVES: In this context, we evaluated a new heparan sulfate (HS) from Nodipecten nodosus for antimalarial activity and inhibition of P. falciparum cytoadhesion and rosetting. METHODS: Parasite inhibition was measured by SYBR green using a cytometer. HS was assessed in rosetting and cytoadhesion assays under static and flow conditions using Chinese hamster ovary (CHO) and human lymphatic endothelial cell (HLEC) cells expressing intercellular adhesion molecule-1 (ICAM1) and chondroitin sulfate A (CSA), respectively. FINDINGS: This HS inhibited merozoite invasion similar to heparin. Moreover, mollusk HS decreased cytoadherence of P. falciparum to CSA and ICAM-1 on the surface of endothelial cells under static and flow conditions. In addition, this glycan efficiently disrupted rosettes. CONCLUSIONS: These findings support a potential use for mollusk HS as adjunct therapy for severe malaria.


Assuntos
Heparitina Sulfato/farmacologia , Merozoítos/efeitos dos fármacos , Moluscos/química , Plasmodium falciparum/efeitos dos fármacos , Animais , Adesão Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Proteínas de Protozoários/efeitos dos fármacos , Reprodutibilidade dos Testes , Fatores de Tempo
8.
Int J Nanomedicine ; 14: 3831-3843, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213804

RESUMO

Purpose: On the basis of reasonable superposition of various surface treatment methods, alkali-treated titanium with nanonetwork structures (TNS) was coated with mussel adhesive protein (MAP) and named TNS-MAP. The aims were to optimize the biological properties of TNS, endue it with new properties, and enhance its utility in clinical dental applications. Methods: TNS disks were coated with MAP and the product surface was characterized. Its osteogenic properties were determined by evaluating its effects on cell adhesion, cell proliferation, the expression of osteogenesis-related genes, and in vivo experiments. Results: The treated materials showed excellent hydrophilicity, good surface roughness, and advantages of both TNS and MAP. TNS-MAP significantly promoted initial cell attachment especially after 15 mins and 30 mins. At every time point, cell adhesion and proliferation, the detection rate of osteogenesis-related markers in the extracellular matrix, and the expression of osteogenesis-related genes were markedly superior on TNS-MAP than the control. The in vivo experiments revealed that TNS-MAP promoted new bone growth around the implants and the bone-implant interface. Conclusion: We verified through in vitro and in vivo experiments that we successfully created an effective TNS-MAP composite implant with excellent biocompatibility and advantages of both its TNS and MAP parent materials. Therefore, the new biocomposite implant material TNS-MAP may potentially serve in practical dentistry and orthopedics.


Assuntos
Álcalis/química , Materiais Revestidos Biocompatíveis/farmacologia , Nanopartículas/química , Osseointegração/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Proteínas/farmacologia , Titânio/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Interface Osso-Implante/diagnóstico por imagem , Interface Osso-Implante/patologia , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Microtomografia por Raio-X
9.
Int J Nanomedicine ; 14: 3929-3941, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213809

RESUMO

Introduction: Hierarchical nanofibrous scaffolds are emerging as a promising bone repair material due to their high cell adhesion activity and nutrient permeability. However, the existing method for hierarchical nanofibrous scaffolds fabrication is complicated and not perfectly suitable for further biomedical application in view of both structure and function. In this study, we constructed a hierarchical nanofibrous poly (l-lactic acid)/poly(ε-caprolactone) (PLLA/PCL) scaffold and further evaluated its bone healing ability. Methods: The hierarchical PLLA/PCL nanofibrous scaffold (PLLA/PCL) was prepared by one-pot TIPS and then rapidly mineralized at room temperature by an electrochemical deposition technique. After electrode-positioning at 2 V for 2 hrs, a scaffold coated with hydroxyapatite (M-PLLA/PCL) could be obtained. Results: The pore size of the M-PLLA/PCL scaffold was hierarchically distributed so as to match the biophysical structure for osteoblast growth. The M-PLLA/PCL scaffold showed better cell proliferation and osteogenesis activity compared to the PLLA/PCL scaffold. Further in vivo bone repair studies indicated that the M-PLLA/PCL scaffold could accelerate defect healing in 12 weeks. Conclusion: The results of this study implied that the as-prepared hydroxyapatite coated hierarchical PLLA/PCL nanofibrous scaffolds could be developed as a promising material for efficient bone tissue repair after carefully tuning the TIPS and electrodeposition parameters.


Assuntos
Regeneração Óssea/fisiologia , Galvanoplastia/métodos , Minerais/química , Nanofibras/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Tecidos Suporte/química , Fosfatase Alcalina/metabolismo , Animais , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Eletricidade , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/ultraestrutura , Osteogênese/efeitos dos fármacos , Porosidade , Ratos Sprague-Dawley , Crânio/diagnóstico por imagem , Crânio/efeitos dos fármacos , Crânio/patologia , Fatores de Tempo , Engenharia Tecidual/métodos , Microtomografia por Raio-X
10.
J Photochem Photobiol B ; 196: 111508, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31152936

RESUMO

Cardiovascular malady (CVM) isn't just the essential driver of death in created western nations, yet additionally, its sickness load is expanding in China. Oxidative pressure initiated free radicals assume a basic job in cell forms involved in atherosclerosis and numerous other heart illnesses. Quercetin (QC) is cancer prevention agents medicate which is demonstrated that successfully secures against CVMs. Encapsulations of medications in polymeric materials are generally utilized in creating continued and controllable medication discharge, or to keep away from the debasement of non-discharged medications. In this present work, a novel arrangement of polymeric superparamagnetic nano-silica (SiN)@poly(lactic-co-glycolic acid) (PLGA) (SiN@PLGA) stacked with QC was created by means of lyophilization method so as to improve poor watery solvency and steadiness of the medication with the point of preventing atherosclerosis. The aftereffects of SEM investigation and the checking, TEM affirmed the manufacture of the circular nanocomposite, smooth surface, and thin size dispersion. The discharge profile of QC from the particles was explored by deciding the medication sum discharged at explicit interims for by iridescence. The data got from this investigation encourages the structure and manufacture of nanocomposite as conceivable conveyance frameworks for epitome, assurance and controlled arrival of the flavonoid QC which is expecting to secure against CVMs.


Assuntos
Nanocompostos/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Quercetina/química , Dióxido de Silício/química , Animais , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Camundongos , Miocárdio/metabolismo , Miocárdio/patologia , Nanocompostos/toxicidade , Quercetina/metabolismo , Quercetina/uso terapêutico
11.
Cell Physiol Biochem ; 53(1): 87-100, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31204440

RESUMO

BACKGROUND/AIMS: Different components of the tumor microenvironment can be either tumor-promoting or tumor-suppressive agents depending on factors which are not fully understood. Fibulins are components of the extracellular matrix from different tissues and constitute a clear example of this dual function. In fact, fibulins may either support tumor growth or abolish progression of malignant cells depending on the crosstalk between tumor cells and their surrounding stroma through mechanisms that remain to be elucidated. Among all fibulins, fibulin-5 contains a particular structural hallmark which consists in the presence of a RGD motif within its architecture. Previous reports have highlighted the importance of the interaction of this motif with integrins, and not only in normal functions but also in a tumor context. METHODS: Site-Directed Mutagenesis technique was employed to introduce the change RGD to RGE (RGD-to-RGE) within Fbln5 cDNA sequence. Cell proliferation was measured using the MTT assay or by counting Ki-67 positive cell nuclei. Cell adhesion was analysed using culture plates coated with different extracellular matrix components. Cell invasion was evaluated using 24-well Matrigel-coated invasion chambers, and mammosphere formation was monitored using ultralow attachment culture plates. BALB/c mice were employed to induce subcutaneous tumors. RESULTS: The RGD-to-RGE change alters the capacity of breast cancer cells to adhere to different extracellular matrix proteins as well as to αvß3 and α5ß1 integrins, and promotes protumor effects using different cell-based assays. Moreover, 4T1 cells, a mouse breast cancer cell line model, shows an increased capacity to generate tumors when exogenously expresses fibulin-5 with a RGD-to-RGE change, and such capacity is similar to that shown for 4T1 cells with an interfered Fbln5 gene. CONCLUSION: These data highlight the importance of the RGD motif of fibulin-5 to induce antitumor effects and provide new insights into the involvement of fibulins in tumor processes.


Assuntos
Adesão Celular/efeitos dos fármacos , Proteínas da Matriz Extracelular/farmacologia , Oligopeptídeos/metabolismo , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Proteínas da Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/uso terapêutico , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mutagênese Sítio-Dirigida , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Oligopeptídeos/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Transplante Homólogo , Vimentina/metabolismo
12.
Chem Commun (Camb) ; 55(49): 7001-7004, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31155630

RESUMO

Chiral polyoxometalates (POMs) were deposited onto the inner surface of an ordered cavernous film to construct POM-based chiral interfaces, which exhibit a significantly different chiral influence on the adhesion and proliferation of Escherichia coli (E. coli) cells tuned by protein adsorption. Anti-fouling was also shown for the racemic surface.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Escherichia coli/citologia , Escherichia coli/efeitos dos fármacos , Compostos de Tungstênio/farmacologia , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Imagem Óptica , Propriedades de Superfície
13.
Int J Nanomedicine ; 14: 3331-3343, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123401

RESUMO

Background and methods: A Cu-doped composite scaffold of nano calcium-deficient hydroxyapatite (n-CDHA)/multi(amino acid) copolymer (MAC) was prepared. The structure, porosity, morphology and compressive strength of the scaffolds were characterized, the in vitro degradability in phosphate-buffered solution (PBS) and cell responses to the scaffolds were investigated, and in vivo stimulation of bone formation were analyzed. Results: The scaffolds showed the compressive strength of approximately 12 MPa and total porosity of about 81%. Weight loss of the composite scaffolds was 63% after 16-week immersion in PBS. Cu release in scaffolds showed a marked dependence on the initial amount in the scaffolds over time. Cu-doped n-CDHA/MAC scaffolds with the content of Cu 0.5% and 1% in mass ratio showed better cell responses to proliferation and differentiation of rat bone marrow stromal cells (rBMSCs) than that with no Cu. After 12-week implantation in rabbits, 1% Cu-doped n-CDHA/MAC showed better ability of angiogenesis and osteogenesis compared to 0% Cu-doped n-CDHA/MAC. Conclusion: The 1% Cu-doped n-CDHA/MAC composite scaffold showed good capacity of angiogenesis and osteogenesis, and the Cu showed positive effects on cell growth and osteogenesis. And it has potential to be used as bone regeneration scaffolds.


Assuntos
Aminoácidos/farmacologia , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/fisiologia , Cobre/farmacologia , Durapatita/farmacologia , Nanopartículas/química , Polímeros/química , Tecidos Suporte/química , Fosfatase Alcalina/metabolismo , Animais , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Força Compressiva , Implantes Experimentais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/ultraestrutura , Osteogênese/efeitos dos fármacos , Porosidade , Coelhos , Ratos , Microtomografia por Raio-X
14.
Gut ; 68(9): 1688-1700, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31127023

RESUMO

Intestinal immune cell trafficking has been identified as a central event in the pathogenesis of inflammatory bowel diseases (IBD). Intensive research on different aspects of the immune mechanisms controlling and controlled by T cell trafficking and retention has led to the approval of the anti-α4ß7 antibody vedolizumab, the ongoing development of a number of further anti-trafficking agents (ATAs) such as the anti-ß7 antibody etrolizumab or the anti-MAdCAM-1 antibody ontamalimab and the identification of potential future targets like G-protein coupled receptor 15. However, several aspects of the biology of immune cell trafficking and regarding the mechanism of action of ATAs are still unclear, for example, which impact these compounds have on the trafficking of non-lymphocyte populations like monocytes and how precisely these therapies differ with regard to their effect on immune cell subpopulations. This review will summarise recent advances of basic science in the field of intestinal immune cell trafficking and discuss these findings with regard to different pharmacological approaches from a translational perspective.


Assuntos
Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/imunologia , Linfócitos T/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Adesão Celular/efeitos dos fármacos , Adesão Celular/imunologia , Quimiotaxia de Leucócito/efeitos dos fármacos , Quimiotaxia de Leucócito/imunologia , Fármacos Gastrointestinais/farmacologia , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal/imunologia , Terapia de Alvo Molecular/métodos , Natalizumab/farmacologia , Natalizumab/uso terapêutico , Oligonucleotídeos Fosforotioatos/farmacologia , Oligonucleotídeos Fosforotioatos/uso terapêutico
15.
Biomed Res Int ; 2019: 3638469, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31058187

RESUMO

Eosinophil asthma is characterized by the infiltration of eosinophils to the bronchial epithelium. The toxic cationic protein released by eosinophils, mainly major basic protein (MBP), is one of the most important causative factors of epithelium damage. Poly-L-Arginine (PLA) is a kind of synthetic cationic polypeptides, which is widely used to mimic the effects of MBP on epithelial cells in vitro. However, little is known about the changes of differentially expressed genes (DEGs) and transcriptome profiles in cationic protein stimulated epithelial cells. In this study, we compared the expression of DEGs and transcriptome profiles between PLA-treated airway epithelial cells NCI-H292 and control. The results showed that there were a total of 230 DEGs, of which 86 were upregulated and 144 were downregulated. These DEGs were further analyzed using gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results showed that the upregulated DEGs were involved in cholesterol synthesis, protein binding, and composition of cellular membranes, mainly enriched in metabolic and biosynthesis pathways. While downregulated DEGs were implicated in cell adhesion, extracellular matrix (ECM) composition and cytoskeleton and were enriched in ECM pathway. In conclusion, our research provided the mechanism of the cationic polypeptides acting on the airway epithelial cells on the basis of transcriptomic profile, and this could be regarded as important indications in unveiling the pathologic role of natural cationic proteins in the damage to epithelial cells of asthmatics.


Assuntos
Células Epiteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Pulmão/metabolismo , Transcriptoma/genética , Cátions/farmacologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Colesterol/genética , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/genética , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/genética , Redes Reguladoras de Genes/genética , Humanos , Pulmão/efeitos dos fármacos , Peptídeos/farmacologia , Sequenciamento Completo do Exoma
16.
Int J Mol Sci ; 20(9)2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035668

RESUMO

Adhesion is a crucial characteristic of epithelial cells to form barriers to pathogens and toxic substances from the environment. Epithelial cells attach to each other using intercellular junctions on the lateral membrane, including tight and adherent junctions, as well as the Na+,K+-ATPase. Our group has shown that non-adherent chinese hamster ovary (CHO) cells transfected with the canine ß1 subunit become adhesive, and those homotypic interactions amongst ß1 subunits of the Na+,K+-ATPase occur between neighboring epithelial cells. Ouabain, a cardiotonic steroid, binds to the α subunit of the Na+,K+-ATPase, inhibits the pump activity and induces the detachment of epithelial cells when used at concentrations above 300 nM. At nanomolar non-inhibiting concentrations, ouabain affects the adhesive properties of epithelial cells by inducing the expression of cell adhesion molecules through the activation of signaling pathways associated with the α subunit. In this study, we investigated whether the adhesion between ß1 subunits was also affected by ouabain. We used CHO fibroblasts stably expressing the ß1 subunit of the Na+,K+-ATPase (CHO ß1), and studied the effect of ouabain on cell adhesion. Aggregation assays showed that ouabain increased the adhesion between CHO ß1 cells. Immunofluorescence and biotinylation assays showed that ouabain (50 nM) increases the expression of the ß1 subunit of the Na+,K+-ATPase at the cell membrane. We also examined the effect of ouabain on the activation of signaling pathways in CHO ß1 cells, and their subsequent effect on cell adhesion. We found that cSrc is activated by ouabain and, therefore, that it likely regulates the adhesive properties of CHO ß1 cells. Collectively, our findings suggest that the ß1 subunit adhesion is modulated by the expression levels of the Na+,K+-ATPase at the plasma membrane, which is regulated by ouabain.


Assuntos
Adesão Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Ouabaína/farmacologia , Subunidades Proteicas/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Células CHO , Membrana Celular/metabolismo , Cricetulus , Expressão Gênica , Ligação Proteica , Subunidades Proteicas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/química , ATPase Trocadora de Sódio-Potássio/genética , Quinases da Família src/metabolismo
17.
Molecules ; 24(9)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31071981

RESUMO

Atherosclerosis is the pathological basis of cardiovascular disease, whilst endothelial dysfunction (ED) plays a primary role in the occurrence and development of atherosclerosis. Simvastatin has been shown to possess significant anti-atherosclerosis activity. In this study, we evaluated the protective effect of simvastatin on endothelial cells under oxidative stress and elucidated its underlying mechanisms. Simvastatin was found to attenuate H2O2-induced human umbilical vein endothelial cells (HUVECs) dysfunction and inhibit the Wnt/ß-catenin pathway; however, when this pathway was activated by lithium chloride, endothelial dysfunction was clearly enhanced. Further investigation revealed that simvastatin did not alter the expression or phosphorylation of LRP6, but reduced intracellular cholesterol deposition and inhibited endoplasmic reticulum (ER) stress. Inducing ER stress with tunicamycin activated the Wnt/ß-catenin pathway, whereas reducing ER stress with 4-phenylbutyric acid inhibited it. We hypothesize that simvastatin does not affect transmembrane signal transduction in the Wnt/ß-catenin pathway, but inhibits ER stress by reducing intracellular cholesterol accumulation, which blocks intracellular signal transduction in the Wnt/ß-catenin pathway and ameliorates endothelial dysfunction.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/patologia , Peróxido de Hidrogênio/toxicidade , Sinvastatina/farmacologia , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colesterol/metabolismo , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Modelos Biológicos , Estresse Oxidativo/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos
18.
Carbohydr Polym ; 216: 86-96, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047085

RESUMO

Water-activated shape memory bacterial cellulose/polyurethane nanocomposites were prepared by the immersion of bacterial cellulose (BC) wet membranes into waterborne polyurethane (WBPU) dispersions for different times. The high affinity between the hydrophilic BC and water stable polyurethane led to the coating and embedding of the BC membrane into the WBPU, facts that were confirmed by FTIR, SEM and mechanical testing of the nanocomposites. The mechanical performance of the nanocomposites resulted enhanced with respect to the neat WBPU, confirming the reinforcing effect of the BC membrane. An improvement of the shape fixity ability and faster recovery process with the presence of BC was observed. In 3 min, the nanocomposite with highest BC content recovered the 92.8 ± 6.3% of the original shape, while the neat WBPU only recovered the 33.4 ± 9.6%. The obtained results indicated that 5 min of impregnation time was enough to obtain nanocomposites with improved mechanical performance and fast shape recovery for potential biomedical applications. The present work provides an approach for developing environmentally friendly and biocompatible BC/polyurethane based materials with enhanced mechanical and shape memory properties.


Assuntos
Materiais Biocompatíveis/química , Celulose/química , Nanocompostos/química , Poliuretanos/química , Água/química , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/toxicidade , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Celulose/toxicidade , Módulo de Elasticidade , Fibroblastos/efeitos dos fármacos , Gluconacetobacter/química , Camundongos , Nanocompostos/toxicidade , Poliuretanos/toxicidade , Resistência à Tração , Temperatura de Transição
19.
Molecules ; 24(9)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035401

RESUMO

Osteogenic peptides have been reported as highly effective in directing mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo. Therefore, developing novel biomaterials for the controlled delivery of osteogenic peptides in scaffolds without lowering the peptide's biological activity is highly desirable. To repair a critical-sized bone defect to efficiently achieve personalized bone regeneration, a novel bioactive poly(lactic-co-glycolic acid) (PLGA)/ß-tricalcium phosphate (ß-TCP) composite scaffold, in which graphene oxide (GO) and bone morphogenetic protein (BMP)-2-like peptide were loaded in situ (PTG/P), was produced by an original cryogenic 3D printing method. The scaffolds were mechanically comparable to human cancellous bone and hierarchically porous. The incorporation of GO further improved the scaffold wettability and mechanical strength. The in situ loaded peptides retained a high level of biological activity for an extended time, and the loading of GO in the scaffold further tuned the peptide release so that it was more sustained. Our in vitro study showed that the PTG/P scaffold promoted rat bone marrow-derived mesenchymal stem cell ingrowth into the scaffold and enhanced osteogenic differentiation. Moreover, the in vivo study indicated that the novel PTG/P scaffold with sustained delivery of the peptide could significantly promote bone regeneration in a critical bone defect. Thus, the novel bioactive PTG/P scaffold with a customized shape, improved mechanical strength, sustainable peptide delivery, and excellent osteogenic ability has great potential in bone tissue regeneration.


Assuntos
Grafite , Osteogênese/efeitos dos fármacos , Óxidos , Peptídeos/química , Peptídeos/farmacologia , Engenharia Tecidual , Tecidos Suporte , Animais , Regeneração Óssea , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Emulsões , Grafite/química , Nanoestruturas/química , Óxidos/química , Impressão Tridimensional , Ratos , Análise Espectral
20.
Molecules ; 24(9)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31052167

RESUMO

Cyclooxygenase-2 (COX-2) as a rate-limiting metabolism enzyme of arachidonic acid has been found to be implicated in tumor occurrence, angiogenesis, metastasis as well as apoptosis inhibition, regarded as an attractive therapeutic target for cancer therapy. In our research, a series of dihydropyrazole derivatives containing benzo oxygen heterocycle and sulfonamide moieties were designed as highly potent and selective COX-2 inhibitors by computer-aided drug analysis of known COX-2 inhibitors. A total of 26 compounds were synthesized and evaluated COX-2 inhibition and pharmacological efficiency both in vitro and in vivo with multi-angle of view. Among them, compound 4b exhibited most excellent anti-proliferation activities against SW620 cells with IC50 of 0.86 ± 0.02 µM than Celecoxib (IC50 = 1.29 ± 0.04 µM). The results favored our rational design intention and provides compound 4b as an effective COX-2 inhibitor available for the development of colon tumor therapeutics.


Assuntos
Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Desenho de Drogas , Oxigênio/química , Pirazóis/química , Pirazóis/farmacologia , Sulfonamidas/química , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo , Inibidores de Ciclo-Oxigenase 2/síntese química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Camundongos , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Pirazóis/síntese química , Relação Quantitativa Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto
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