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1.
Polymers (Basel) ; 13(23)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34883774

RESUMO

Cardiovascular Diseases (CVDs) such as atherosclerosis, where inflammation occurs in the blood vessel wall, are one of the major causes of death worldwide. Mesenchymal Stem Cells (MSCs)-based treatment coupled with nanoparticles is considered to be a potential and promising therapeutic strategy for vascular regeneration. Thus, angiogenesis enhanced by nanoparticles is of critical concern. In this study, Polyethylene Glycol (PEG) incorporated with 43.5 ppm of gold (Au) nanoparticles was prepared for the evaluation of biological effects through in vitro and in vivo assessments. The physicochemical properties of PEG and PEG-Au nanocomposites were first characterized by UV-Vis spectrophotometry (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), and Atomic Force Microscopy (AFMs). Furthermore, the reactive oxygen species scavenger ability as well as the hydrophilic property of the nanocomposites were also investigated. Afterwards, the biocompatibility and biological functions of the PEG-Au nanocomposites were evaluated through in vitro assays. The thin coating of PEG containing 43.5 ppm of Au nanoparticles induced the least platelet and monocyte activation. Additionally, the cell behavior of MSCs on PEG-Au 43.5 ppm coating demonstrated better cell proliferation, low ROS generation, and enhancement of cell migration, as well as protein expression of the endothelialization marker CD31, which is associated with angiogenesis capacity. Furthermore, anti-inflammatory and endothelial differentiation ability were both evaluated through in vivo assessments. The evidence demonstrated that PEG-Au 43.5 ppm implantation inhibited capsule formation and facilitated the expression of CD31 in rat models. TUNEL assay also indicated that PEG-Au nanocomposites would not induce significant cell apoptosis. The above results elucidate that the surface modification of PEG-Au nanomaterials may enable them to serve as efficient tools for vascular regeneration grafts.

2.
Cells ; 10(12)2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34943784

RESUMO

Tissue repair engineering supported by nanoparticles and stem cells has been demonstrated as being an efficient strategy for promoting the healing potential during the regeneration of damaged tissues. In the current study, we prepared various nanomaterials including pure Pul, pure Col, Pul-Col, Pul-Au, Pul-Col-Au, and Col-Au to investigate their physicochemical properties, biocompatibility, biological functions, differentiation capacities, and anti-inflammatory abilities through in vitro and in vivo assessments. The physicochemical properties were characterized by SEM, DLS assay, contact angle measurements, UV-Vis spectra, FTIR spectra, SERS, and XPS analysis. The biocompatibility results demonstrated Pul-Col-Au enhanced cell viability, promoted anti-oxidative ability for MSCs and HSFs, and inhibited monocyte and platelet activation. Pul-Col-Au also induced the lowest cell apoptosis and facilitated the MMP activities. Moreover, we evaluated the efficacy of Pul-Col-Au in the enhancement of neuronal differentiation capacities for MSCs. Our animal models elucidated better biocompatibility, as well as the promotion of endothelialization after implanting Pul-Col-Au for a period of one month. The above evidence indicates the excellent biocompatibility, enhancement of neuronal differentiation, and anti-inflammatory capacities, suggesting that the combination of pullulan, collagen, and Au nanoparticles can be potential nanocomposites for neuronal repair, as well as skin tissue regeneration in any further clinical treatments.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Glucanos/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Engenharia Tecidual , Células Cultivadas/efeitos dos fármacos , Glucanos/química , Ouro/química , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas Metálicas/química , Nanocompostos/química , Tecidos Suporte/química
3.
Cancers (Basel) ; 13(21)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34771481

RESUMO

Gold nanoparticles (AuNPs) were fabricated with biocompatible collagen (Col) and then conjugated with berberine (BB), denoted as Au-Col-BB, to investigate the endocytic mechanisms in Her-2 breast cancer cell line and in bovine aortic endothelial cells (BAEC). Owing to the superior biocompatibility, tunable physicochemical properties, and potential functionalization with biomolecules, AuNPs have been well studied as carriers of biomolecules for diseases and cancer therapeutics. Composites of AuNPs with biopolymer, such as fibronectin or Col, have been revealed to increase cell proliferation, migration, and differentiation. BB is a natural compound with impressive health benefits, such as lowering blood sugar and reducing weight. In addition, BB can inhibit cell proliferation by modulating cell cycle progress and autophagy, and induce cell apoptosis in vivo and in vitro. In the current research, BB was conjugated on the Col-AuNP composite ("Au-Col"). The UV-Visible spectroscopy and infrared spectroscopy confirmed the conjugation of BB on Au-Col. The particle size of the Au-Col-BB conjugate was about 227 nm, determined by dynamic light scattering. Furthermore, Au-Col-BB was less cytotoxic to BAEC vs. Her-2 cell line in terms of MTT assay and cell cycle behavior. Au-Col-BB, compared to Au-Col, showed greater cell uptake capacity and potential cellular transportation by BAEC and Her-2 using the fluorescence-conjugated Au-Col-BB. In addition, the clathrin-mediated endocytosis and cell autophagy seemed to be the favorite endocytic mechanism for the internalization of Au-Col-BB by BAEC and Her-2. Au-Col-BB significantly inhibited cell migration in Her-2, but not in BAEC. Moreover, apoptotic cascade proteins, such as Bax and p21, were expressed in Her-2 after the treatment of Au-Col-BB. The tumor suppression was examined in a model of xenograft mice treated with Au-Col-BB nanovehicles. Results demonstrated that the tumor weight was remarkably reduced by the treatment of Au-Col-BB. Altogether, the promising findings of Au-Col-BB nanocarrier on Her-2 breast cancer cell line suggest that Au-Col-BB may be a good candidate of anticancer drug for the treatment of human breast cancer.

4.
Biomedicines ; 9(11)2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34829861

RESUMO

In this study, polyethylene glycol (PEG) with hydroxyapatite (HA), with the incorporation of physical gold nanoparticles (AuNPs), was created and equipped through a surface coating technique in order to form PEG-HA-AuNP nanocomposites. The surface morphology and chemical composition were characterized using scanning electron microscopy (SEM), atomic force microscopy (AFM), UV-Vis spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and contact angle assessment. The effects of PEG-HA-AuNP nanocomposites on the biocompatibility and biological activity of MC3T3-E1 osteoblast cells, endothelial cells (EC), macrophages (RAW 264.7), and human mesenchymal stem cells (MSCs), as well as the guiding of osteogenic differentiation, were estimated through the use of an in vitro assay. Moreover, the anti-inflammatory, biocompatibility, and endothelialization capacities were further assessed through in vivo evaluation. The PEG-HA-AuNP nanocomposites showed superior biological properties and biocompatibility capacity for cell behavior in both MC3T3-E1 cells and MSCs. These biological events surrounding the cells could be associated with the activation of adhesion, proliferation, migration, and differentiation processes on the PEG-HA-AuNP nanocomposites. Indeed, the induction of the osteogenic differentiation of MSCs by PEG-HA-AuNP nanocomposites and enhanced mineralization activity were also evidenced in this study. Moreover, from the in vivo assay, we further found that PEG-HA-AuNP nanocomposites not only facilitate the anti-immune response, as well as reducing CD86 expression, but also facilitate the endothelialization ability, as well as promoting CD31 expression, when implanted into rats subcutaneously for a period of 1 month. The current research illustrates the potential of PEG-HA-AuNP nanocomposites when used in combination with MSCs for the regeneration of bone tissue, with their nanotopography being employed as an applicable surface modification approach for the fabrication of biomaterials.

5.
Cells ; 10(11)2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34831077

RESUMO

A nanocomposite composed of polyethylene glycol (PEG) incorporated with various concentrations (~17.4, ~43.5, ~174 ppm) of gold nanoparticles (Au) was created to investigate its biocompatibility and biological performance in vitro and in vivo. First, surface topography and chemical composition was determined through UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), free radical scavenging ability, and water contact angle measurement. Additionally, the diameters of the PEG-Au nanocomposites were also evaluated through dynamic light scattering (DLS) assay. According to the results, PEG containing 43.5 ppm of Au demonstrated superior biocompatibility and biological properties for mesenchymal stem cells (MSCs), as well as superior osteogenic differentiation, adipocyte differentiation, and, particularly, neuronal differentiation. Indeed, PEG-Au 43.5 ppm induced better cell adhesion, proliferation and migration in MSCs. The higher expression of the SDF-1α/CXCR4 axis may be associated with MMPs activation and may have also promoted the differentiation capacity of MSCs. Moreover, it also prevented MSCs from apoptosis and inhibited macrophage and platelet activation, as well as reactive oxygen species (ROS) generation. Furthermore, the anti-inflammatory, biocompatibility, and endothelialization capacity of PEG-Au was measured in a rat model. After implanting the nanocomposites into rats subcutaneously for 4 weeks, PEG-Au 43.5 ppm was able to enhance the anti-immune response through inhibiting CD86 expression (M1 polarization), while also reducing leukocyte infiltration (CD45). Moreover, PEG-Au 43.5 ppm facilitated CD31 expression and anti-fibrosis ability. Above all, the PEG-Au nanocomposite was evidenced to strengthen the differentiation of MSCs into various cells, including fat, vessel, and bone tissue and, particularly, nerve cells. This research has elucidated that PEG combined with the appropriate amount of Au nanoparticles could become a potential biomaterial able to cooperate with MSCs for tissue regeneration engineering.

6.
Int J Mol Sci ; 22(19)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34638579

RESUMO

Parkinson's disease (PD) is a degenerative disease that can cause motor, cognitive, and behavioral disorders. The treatment strategies being developed are based on the typical pathologic features of PD, including the death of dopaminergic (DA) neurons in the substantia nigra of the midbrain and the accumulation of α-synuclein in neurons. Peiminine (PMN) is an extract of Fritillaria thunbergii Miq that has antioxidant and anti-neuroinflammatory effects. We used Caenorhabditis elegans and SH-SY5Y cell models of PD to evaluate the neuroprotective potential of PMN and address its corresponding mechanism of action. We found that pretreatment with PMN reduced reactive oxygen species production and DA neuron degeneration caused by exposure to 6-hydroxydopamine (6-OHDA), and therefore significantly improved the DA-mediated food-sensing behavior of 6-OHDA-exposed worms and prolonged their lifespan. PMN also diminished the accumulation of α-synuclein in transgenic worms and transfected cells. In our study of the mechanism of action, we found that PMN lessened ARTS-mediated degradation of X-linked inhibitor of apoptosis (XIAP) by enhancing the expression of PINK1/parkin. This led to reduced 6-OHDA-induced apoptosis, enhanced activity of the ubiquitin-proteasome system, and increased autophagy, which diminished the accumulation of α-synuclein. The use of small interfering RNA to down-regulate parkin reversed the benefits of PMN in the PD models. Our findings suggest PMN as a candidate compound worthy of further evaluation for the treatment of PD.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Cevanas/farmacologia , Doença de Parkinson/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , alfa-Sinucleína/metabolismo , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/metabolismo , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Degeneração Neural/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Substância Negra/metabolismo , Ubiquitina/metabolismo
7.
J Chin Med Assoc ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34643620

RESUMO

BACKGROUND: Nanoparticles (NPs) have wide potential applications in biolabeling, bioimaging, and cell tracking. Development of dual functional nanoparticles increases the versatility. METHODS: we combined the fluorescent property of nano-epoxy (N-Epo) and the magnetic characteristic of FePt to fabricate the FePt-decorated N-Epo (N-Epo-FePt). The size in diameter of N-Epo-FePt (177.38 ±39.25 nm) was bigger than N-Epo (2.28 ±1.01 nm), both could be absorbed into mesenchymal stem cells (MSCs) via clathrin-mediated endocytosis and have multiple fluorescent properties (blue, green, and red). RESULTS: N-Epo-FePt prevented N-Epo-induced platelet activation, CD68+-macrophage differentiation in blood, and intracellular ROS generation in MSCs. The induction of apoptosis and the inhibitory effects of N-Epo-FePt on cell migration, MMP-9 activity, and secretion of SDF-1α were less than that of N-Epo in MSCs. CONCLUSION: N-Epo-FePt was more biocompatible without altering biological performance than N-Epo in MSCs. These results suggest that N-Epo-FePt nanoparticle can be used for fluorescence labeling of MSCs and is potential to apply to bioimaging and cell tracking of MSCs in vivo by magnetic resonance imaging (MRI) or computed tomography (CT).

8.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502171

RESUMO

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its biological function and biocompatibility in Wharton's jelly-derived mesenchymal stem cells (MSCs) and rat models was investigated. The surface morphology as well as chemical composition for pure FN and the FN-AgNP nanocomposites incorporating various amounts of AgNP were firstly characterized by atomic force microscopy (AFM), UV-Visible spectroscopy (UV-Vis), and Fourier-transform infrared spectroscopy (FTIR). Among the nanocomposites, FN-AgNP with 30.2 ppm silver nanoparticles demonstrated the best biocompatibility as assessed through intracellular ROS production, proliferation of MSCs, and monocytes activation. The expression levels of pro-inflammatory cytokines, TNF-α, IL-1ß, and IL-6, were also examined. FN-AgNP 30.2 ppm significantly inhibited pro-inflammatory cytokine expression compared to other materials, indicating superior performance of anti-immune response. Mechanistically, FN-AgNP 30.2 ppm significantly induced greater expression of vascular endothelial growth factor (VEGF) and stromal-cell derived factor-1 alpha (SDF-1α) and promoted the migration of MSCs through matrix metalloproteinase (MMP) signaling pathway. Besides, in vitro and in vivo studies indicated that FN-AgNP 30.2 ppm stimulated greater protein expressions of CD31 and von Willebrand Factor (vWF) as well as facilitated better endothelialization capacity than other materials. Furthermore, the histological tissue examination revealed the lowest capsule formation and collagen deposition in rat subcutaneous implantation of FN-AgNP 30.2 ppm. In conclusion, FN-AgNP nanocomposites may facilitate the migration and proliferation of MSCs, induce endothelial cell differentiation, and attenuate immune response. These finding also suggests that FN-AgNP may be a potential anti-inflammatory surface modification strategy for vascular biomaterials.


Assuntos
Anti-Inflamatórios/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Fibronectinas/administração & dosagem , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Nanopartículas Metálicas , Prata , Animais , Proliferação de Células , Células Cultivadas , Citoesqueleto , Células Endoteliais/metabolismo , Imuno-Histoquímica , Metaloproteinases da Matriz/metabolismo , Células-Tronco Mesenquimais/citologia , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula , Ratos , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
9.
Nanomaterials (Basel) ; 11(8)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34443877

RESUMO

Graphene-based nanocomposites such as graphene oxide (GO) and nanoparticle-decorated graphene with demonstrated excellent physicochemical properties have worthwhile applications in biomedicine and bioengineering such as tissue engineering. In this study, we fabricated gold nanoparticle-decorated GO (GO-Au) nanocomposites and characterized their physicochemical properties using UV-Vis absorption spectra, FTIR spectra, contact angle analyses, and free radical scavenging potential. Moreover, we investigated the potent applications of GO-Au nanocomposites on directing mesenchymal stem cells (MSCs) for tissue regeneration. We compared the efficacy of as-prepared GO-derived nanocomposites including GO, GO-Au, and GO-Au (×2) on the biocompatibility of MSCs, immune cell identification, anti-inflammatory effects, differentiation capacity, as well as animal immune compatibility. Our results showed that Au-deposited GO nanocomposites, especially GO-Au (×2), significantly exhibited increased cell viability of MSCs, had good anti-oxidative ability, sponged the immune response toward monocyte-macrophage transition, as well as inhibited the activity of platelets. Moreover, we also validated the superior efficacy of Au-deposited GO nanocomposites on the enhancement of cell motility and various MSCs-derived cell types of differentiation including neuron cells, adipocytes, osteocytes, and endothelial cells. Additionally, the lower induction of fibrotic formation, reduced M1 macrophage polarization, and higher induction of M2 macrophage, as well as promotion of the endothelialization, were also found in the Au-deposited GO nanocomposites implanted animal model. These results suggest that the Au-deposited GO nanocomposites have excellent immune compatibility and anti-inflammatory effects in vivo and in vitro. Altogether, our findings indicate that Au-decorated GO nanocomposites, especially GO-Au (×2), can be a potent nanocarrier for tissue engineering and an effective clinical strategy for anti-inflammation.

10.
J Chin Med Assoc ; 84(11): 1007-1018, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34320517

RESUMO

BACKGROUND: Chitosan (Chi) is a natural material which has been widely used in neural applications due to possessing better biocompatibility. In this research study, a novel of nanocomposites film based on Chi with hyaluronic acid (HA), combined with varying amounts of gold nanoparticles (AuNPs), was created resulting in pure Chi, Chi-HA, Chi-HA-AuNPs (25 ppm), and Chi-HA-AuNPs (50 ppm). METHODS: This study focused on evaluating their effects on mesenchymal stem cell (MSC) viability, colony formation, and biocompatibility. The surface morphology and chemical position were characterized through UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), SEM, and contact-angle assessment. RESULTS: When seeding MSCs on Chi-HA-AuNPs (50 ppm), the results showed high cell viability, biocompatibility, and the highest colony formation ability. Meanwhile, the evidence showed that Chi-HA-Au nanofilm was able to inhibit nestin and ß-tubulin expression of MSCs, as well as inhibit the ability of neurogenic differentiation. Furthermore, the results of matrix metalloproteinase 2/9 (MMP2/9) expression in MSCs were also significantly higher in the Chi-HA-AuNP (50 ppm) group, guiding with angiogenesis and wound healing abilities. In addition, in our rat model, both capsule thickness and collagen deposition were the lowest in Chi-HA-AuNPs (50 ppm). CONCLUSION: Thus, in view of the in vitro and in vivo results, Chi-HA-AuNPs (50 ppm) could not only maintain the greatest stemness properties and regulate the neurogenic differentiation ability of MSCs, but was able to also induce the least immune response. Herein, Chi-HA-Au 50 ppm nanofilm holds promise as a suitable material for nerve regeneration engineering.

11.
ACS Appl Mater Interfaces ; 12(40): 44393-44406, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32697572

RESUMO

Controlling the behavior of mesenchymal stem cells (MSCs) through topographic patterns is an effective approach for stem cell studies. We, herein, reported a facile method to create a dopamine (DA) pattern on poly(dimethylsiloxane) (PDMS). The topography of micropatterned DA was produced on PDMS after plasma treatment. The grid-topographic-patterned surface of PDMS-DA (PDMS-DA-P) was measured for adhesion force and Young's modulus by atomic force microscopy. The surface of PDMS-DA-P demonstrated less stiff and more elastic characteristics compared to either nonpatterned PDMS-DA or PDMS. The PDMS-DA-P evidently enhanced the differentiation of MSCs into various tissue cells, including nerve, vessel, bone, and fat. We further designed comprehensive experiments to investigate adhesion, proliferation, and differentiation of MSCs in response to PDMS-DA-P and showed that the DA-patterned surface had good biocompatibility and did not activate macrophages or platelets in vitro and had low foreign body reaction in vivo. Besides, it protected MSCs from apoptosis as well as excessive reactive oxygen species (ROS) generation. Particularly, the patterned surface enhanced the differentiation capacity of MSCs toward neural and endothelial cells. The stromal cell-derived factor-1α/CXantiCR4 pathway may be involved in mediating the self-recruitment and promoting the differentiation of MSCs. These findings support the potential application of PDMS-DA-P in either cell treatment or tissue repair.


Assuntos
Materiais Biocompatíveis/farmacologia , Dimetilpolisiloxanos/farmacologia , Dopamina/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/química , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Dimetilpolisiloxanos/química , Dopamina/química , Humanos , Células-Tronco Mesenquimais/metabolismo , Microscopia de Força Atômica , Estrutura Molecular , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície
12.
Int J Mol Sci ; 21(12)2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32585871

RESUMO

The movement disorder Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease, and is associated with aging, the environment, and genetic factors. The intracellular aggregation of α-synuclein and the loss of dopaminergic neurons in the substantia nigra pars compacta are the pathological hallmark of PD. At present, there is no successful treatment for PD. Maackiain (MK) is a flavonoid extracted from dried roots of Sophora flavescens Aiton. MK has emerged as a novel agent for PD treatment that acts by inhibiting monoamine oxidase B. In this study, we assessed the neuroprotective potential of MK in Caenorhabditis elegans and investigated possible mechanism of this neuroprotection in the human SH-SY5Y cell line. We found that MK significantly reduced dopaminergic neuron damage in 6-hydroxydopamine (6-OHDA)-exposed worms of the BZ555 strain, with corresponding improvements in food-sensing behavior and life-span. In transgenic worms of strain NL5901 treated with 0.25 mM MK, the accumulation of α-synuclein was diminished by 27% (p < 0.01) compared with that in untreated worms. Moreover, in worms and the SH-SY5Y cell line, we confirmed that the mechanism of MK-mediated protection against PD pathology may include blocking apoptosis, enhancing the ubiquitin-proteasome system, and augmenting autophagy by increasing PINK1/parkin expression. The use of small interfering RNA to downregulate parkin expression in vivo and in vitro could reverse the benefits of MK in PD models. MK may have considerable therapeutic applications in PD.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Neuroblastoma/tratamento farmacológico , Oxidopamina/toxicidade , Doença de Parkinson/tratamento farmacológico , Proteínas Quinases/metabolismo , Pterocarpanos/farmacologia , Ubiquitina-Proteína Ligases/metabolismo , alfa-Sinucleína/toxicidade , Adrenérgicos/toxicidade , Animais , Apoptose , Autofagia , Caenorhabditis elegans/crescimento & desenvolvimento , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Neuroblastoma/etiologia , Neuroblastoma/patologia , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , Proteínas Quinases/genética , Ubiquitina-Proteína Ligases/genética
13.
Curr Med Chem ; 27(10): 1634-1646, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30215329

RESUMO

Treatment of cardiovascular disease has achieved great success using artificial implants, particularly synthetic-polymer made grafts. However, thrombus formation and restenosis are the current clinical problems need to be conquered. New biomaterials, modifying the surface of synthetic vascular grafts, have been created to improve long-term patency for the better hemocompatibility. The vascular biomaterials can be fabricated from synthetic or natural polymers for vascular tissue engineering. Stem cells can be seeded by different techniques into tissue-engineered vascular grafts in vitro and implanted in vivo to repair the vascular tissues. To overcome the thrombogenesis and promote the endothelialization effect, vascular biomaterials employing nanotopography are more bio-mimic to the native tissue made and have been engineered by various approaches such as prepared as a simple surface coating on the vascular biomaterials. It has now become an important and interesting field to find novel approaches to better endothelization of vascular biomaterials. In this article, we focus to review the techniques with better potential improving endothelization and summarize for vascular biomaterial application. This review article will enable the development of biomaterials with a high degree of originality, innovative research on novel techniques for surface fabrication for vascular biomaterials application.


Assuntos
Engenharia Tecidual , Materiais Biocompatíveis , Prótese Vascular , Polímeros , Células-Tronco
14.
ACS Appl Bio Mater ; 2(3): 1017-1030, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35021392

RESUMO

A fluorescein isothiocyanate (FITC)-labeled, hyaluronic acid (HA)-coated nanogld (NP-FITC) was developed to carry plasmid or siRNA into mesenchymal stem cells (MSCs). NP-FITC was characterized by scanning electron microscopy (SEM), ultraviolet-visible (UV-vis) spectroscopy, and Fourier transform infrared (FTIR) spectrophotometry. Nontoxicity of NP-FITC in both normal cells and cancer cells was confirmed by the MTT assay. The cellular uptake of NP-FITC at different time points (30 min, 2 h, and 24 h) was verified using an immunofluorescence assay. The delivery efficiency of plasmid was tested on the delivery of superoxide dismutase-1 (SOD-1) plasmid, where the protein expression of SOD-1 was analyzed by Western blots. In addition, the delivery efficiency of siRNA was tested using CXCR4 siRNA. Besides, the siRNA delivery by NP-FITC was employed to elucidate the molecular mechanism associated with the effect of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1). The biological function of MSCs delivered with chemokine (C-X-C motif) receptor 4 (CXCR4) siRNA was examined using ELISA, gelatin zymography, and a migration assay. Finally, we evaluated the tissue distribution of NP-FITC after the direct injection in the retro orbital sinus of mice or after injection of NP-FITC internalized MSCs through the tail vein of mice. The data provided essential information for NP-FITC as a plasmid or siRNA carrier.

15.
ACS Appl Mater Interfaces ; 10(23): 19436-19448, 2018 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-29775050

RESUMO

Nanomaterials with surface functionalized by different chemical groups can either provoke or attenuate the immune responses of the nanomaterials, which is critical to their biomedical efficacies. In this study, we demonstrate that synthetic waterborne polyurethane nanoparticles (PU NPs) can inhibit the macrophage polarization toward the M1 phenotype but not M2 phenotype. The surface-functionalized PU NPs decrease the secretion levels of proinflammatory cytokines (TNF-α and IL-1ß) for M1 macrophages. Specifically, PU NPs with carboxyl groups on the surface exhibit a greater extent of inhibition on M1 polarization than those with amine groups. These water-suspended PU NPs reduce the nuclear factor-κB (NF-κB) activation and suppress the subsequent NLR family pyrin domain containing 3 (NLRP3) inflammasome signals. Furthermore, the dried PU films assembled from PU NPs have a similar effect on macrophage polarization and present a smaller shifting foreign body reaction (FBR) in vivo than the conventional poly(l-lactic acid). Taken together, the biodegradable waterborne PU NPs demonstrate surface-dependent immunosuppressive properties and macrophage polarization effects. The findings suggest potential therapeutic applications of PU NPs in anti-inflammation and macrophage-related disorders and propose a mechanism for the low FBR observed for biodegradable PU materials.


Assuntos
Macrófagos , Inflamassomos , Nanopartículas , Fenótipo , Poliuretanos
16.
Nanomedicine ; 14(3): 699-711, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29325741

RESUMO

Vascularization of engineered tissues remains one of the key problems. Here, we described a novel approach to promote vascularization of engineered tissues using fibronectin (FN) incorporated gold nanoparticles (AuNP) coated onto catheters with mesenchymal stem cells (MSCs) for tissue engineering. We found that the FN-AuNP composite with 43.5 ppm of AuNP exhibited better biomechanical properties and thermal stability than pure FN. FN-AuNP composites promoted MSC proliferation and increased the biocompatibility. Mechanistically, vascular endothelial growth factor (VEGF) promoted MSC migration on FN-AuNP through the endothelial oxide synthase (eNOS)/metalloproteinase (MMP) signaling pathway. Vascular femoral artery tissues isolated from the implanted FN-AuNP-coated catheters with MSCs expressed substantial CD31 and alpha-smooth muscle actin (α-SMA), displayed higher antithrombotic activity, as well as better endothelialization ability than those coated with all other materials. These data suggested that the implantation of FN-AuNP-coated catheter with MSCs could be a novel strategy for vascular biomaterials applications.


Assuntos
Artéria Femoral/citologia , Fibronectinas/química , Ouro/química , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Nanopartículas Metálicas/administração & dosagem , Engenharia Tecidual/métodos , Cateteres , Adesão Celular , Diferenciação Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Artéria Femoral/fisiologia , Humanos , Teste de Materiais , Nanopartículas Metálicas/química , Regeneração , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização
17.
In Vivo ; 31(4): 585-590, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28652424

RESUMO

BACKGROUND/AIM: Metalloproteinases (MMPs) are a family of multifunctional proteins reported to be overexpressed in several types of cancers. However, the contribution of MMP8 genotype to oral cancer has not been elucidated. In this study, we focused on the contribution of polymorphisms in the promoter region of MMP-8 (C-799T) and two non-synonymous polymorphisms (Val436Ala and Lys460Thr) to Taiwanese oral cancer. MATERIALS AND METHODS: In this case-control study, MMP-8 genotype, was examined among 788 patients with oral cancer and 956 gender- and age-matched healthy controls regarding its potential to determine oral cancer risk. RESULTS: The distributions of MMP-8 C-799T, Val436Ala and Lys460Thr genotypes were not different between the oral cancer and non-cancer control groups. We also analyzed the allelic frequency distributions and no significant difference was found. As for gene-environment interaction analysis, there was an increased risk for smokers, alcohol drinkers or betel quid chewers with variant MMP-8 C-799T or Val436Ala genotypes. CONCLUSION: Our findings suggest that the polymorphisms at MMP-8 C-799T or Val436Ala may not play a major role in mediating personal risk of oral cancer; however, the detailed mechanisms require further investigation.


Assuntos
Predisposição Genética para Doença , Metaloproteinase 8 da Matriz/genética , Neoplasias Bucais/genética , Adulto , Feminino , Interação Gene-Ambiente , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas
18.
In Vivo ; 31(4): 631-635, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28652430

RESUMO

BACKGROUND/AIM: Mounting evidence has suggested that polymorphisms in the promoters of matrix metalloproteinase (MMP) genes are associated with the risk of many types of cancer, but no study has ever explored these polymorphisms as biomarkers for renal cell cancer (RCC). Recently, it was suggested that serum MMP-7 levels have both diagnostic and prognostic potential for RCC. In this study, we focused on the contribution of two functional polymorphisms in the promoter region of MMP-7 (A-181G and C-153T) to RCC. MATERIALS AND METHODS: These two polymorphisms were genotyped in 92 patients with RCC and 580 controls by PRC-RFLP analysis. RESULTS: The results showed that there is no significant association of the RCC risk with the MMP-7 A-181G genotype, even after adjusted for the possible confounding factors. The MMP-7 C-153T polymorphism was not identified among the subjects investigated. CONCLUSION: Our findings suggest that the two MMP-7 polymorphisms A-181G and C-153T do not play a major role in determining personal susceptibility to RCC in Taiwan.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Predisposição Genética para Doença , Metaloproteinase 7 da Matriz/genética , Adulto , Idoso , Alelos , Carcinoma de Células Renais/patologia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Regiões Promotoras Genéticas , Taiwan
19.
Colloids Surf B Biointerfaces ; 155: 399-407, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28460302

RESUMO

The increasing prevalence of hospital-acquired infection and the evolution and increasing resistance of pathogens toward antibiotics can cause serious health problems and disease-related mortality. In this study, we introduce a simple process and inexpensive method to synthesize CuO nanoparticles and silver-functionalized copper oxide (Ag@CuO) nanocomposites as well as to validate their potential antibacterial efficiency against the following three common nosocomial infection-associated bacterial pathogens: E. coli, S. enterica and S. aureus. We show that Ag@CuO significantly disturbs pathogen growth and viability compared with CuO. Further, we find that Gram-positive S. aureus is susceptible to CuO-induced cell structure damage, while Ag@CuO can induce more extensive architectural destruction and ROS generation in both Gram-positive and Gram-negative bacterial pathogens. This study indicates that Ag@CuO nanoparticles can act as a disinfection system and can be used in antibacterial applications for the future prevention of nosocomial infection in medical and/or health institutions.


Assuntos
Cobre/química , Nanocompostos/química , Espécies Reativas de Oxigênio/metabolismo , Prata/química , Antibacterianos/química , Antibacterianos/farmacologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/prevenção & controle , Cobre/farmacologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Escherichia coli/ultraestrutura , Humanos , Viabilidade Microbiana/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanocompostos/toxicidade , Nanocompostos/ultraestrutura , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/metabolismo , Salmonella enterica/ultraestrutura , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismo , Staphylococcus aureus/ultraestrutura
20.
Cell Transplant ; 26(12): 1903-1918, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29390878

RESUMO

Parkinson's disease (PD) is the second most common degenerative disorder of the central nervous system in the elderly. It is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta, as well as by motor dysfunction. Although the causes of PD are not well understood, aggregation of α-synuclein (α-syn) in neurons contributes to this disease. Current therapeutics for PD provides satisfactory symptom relief but not a cure. Treatment strategies include attempts to identify new drugs that will prevent or arrest the progressive course of PD by correcting disease-specific pathogenic process. Betulin is derived from the bark of birch trees and possesses anticancer, antimicrobial, and anti-inflammatory properties. The aim of the present study was to evaluate the potential for betulin to ameliorate PD features in Caenorhabditis elegans ( C. elegans) models. We demonstrated that betulin diminished α-syn accumulation in the transgenic C. elegans model. Betulin also reduced 6-hydroxydopamine-induced dopaminergic neuron degeneration, reduced food-sensing behavioral abnormalities, and reversed life-span decreases in a pharmacological C. elegans model. Moreover, we found that the enhancement of proteasomes activity by promoting rpn1 expression and downregulation of the apoptosis pathway gene, egl-1, may be the molecular mechanism for betulin-mediated protection against PD pathology. Together, these findings support betulin as a possible treatment for PD and encourage further investigations of betulin as an antineurodegenerative agent.


Assuntos
Fármacos Neuroprotetores/uso terapêutico , Oxidopamina/farmacologia , Doença de Parkinson/tratamento farmacológico , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Degeneração Neural/tratamento farmacológico , Doença de Parkinson/patologia , Triterpenos
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