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1.
Invest Ophthalmol Vis Sci ; 60(6): 1845-1852, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042790

RESUMO

Purpose: Rose bengal (RB)-photosensitized protein crosslinking has been proposed for several applications in the eye. This study identifies oxygen-dependent and oxygen-independent mechanistic pathways in cornea for RB-photosensitized crosslinking to enhance its efficiency for ocular treatments. Methods: Rabbit corneas ex vivo were stained with 1 mM RB and irradiated at 532 nm. RB photobleaching, measured by spectrophotometry and linear tensile strength testing, were performed with and without oxygen present. The effects of sodium azide, D2O, arginine, and ascorbate were used to discriminate between mechanisms involving energy transfer (forming singlet oxygen) and electron transfer (forming radical ions). The influence of corneal depth on RB photobleaching was determined using inclined corneal incisions. Results: RB photobleaching was greater in the presence than the absence of oxygen, enhanced by D2O and partially inhibited by azide, indicating a singlet oxygen pathway. Photobleaching without oxygen was enhanced by arginine and ascorbate and accompanied by a shift in the absorption to shorter wavelengths, suggesting that electron transfer initiates RB photodecomposition. The RB-photosensitized tensile strength increase in air was enhanced by D2O and inhibited by azide. In an O2-free environment, arginine was required for an increase in tensile strength, which matched that attained by irradiation in air without arginine, suggesting an efficient electron transfer pathway. Rapid photobleaching was observed below 80 to 120 µm only when arginine was present. Conclusions: These results indicate that RB photosensitizes crosslinking in cornea by both singlet oxygen and electron transfer mechanisms and that adding enhancers may increase the efficiency of this treatment.


Assuntos
Colágeno/farmacologia , Córnea/metabolismo , Reagentes para Ligações Cruzadas/farmacologia , Luz , Fármacos Fotossensibilizantes/farmacologia , Rosa Bengala/farmacologia , Animais , Córnea/citologia , Córnea/efeitos dos fármacos , Corantes Fluorescentes/farmacologia , Modelos Animais , Coelhos , Espectrofotometria
2.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(5): 508-514, 2019 May 30.
Artigo em Chinês | MEDLINE | ID: mdl-31140412

RESUMO

OBJECTIVE: To investigate the effect of blocking pannexin-1 against acute kidney injury induced by cisplatin. METHODS: Twenty-six male C57BL/6 mice aged 6-8 weeks were randomly divided into control group, cisplatin model (Cis) group and cisplatin + carbenoxolone treatment group (Cis + CBX). In Cis group and Cis + CBX group, the mice were injected intraperitoneally with 20 mg/kg of cisplatin and with CBX (20 mg/kg) at 30 min before and 24 and 48 h after cisplatin inhjection, respectively. All the mice were sacrificed at 72 h after cisplatin injection, and plasma and kidney samples were collected for testing mRNA and protein expression levels of pannexin-1 in the renal tissue using RT-qPCR and Western blotting and for detecting plasma creatinine and BUN levels; the pathological changes in the renal tissues were observed using Periodic Acid-Schiff staining. The expression of kidney injury molecule 1 (KIM-1) was examined using immunohistochemistry and the mRNA expressions of KIM-1 and neutrophil gelatinase- related lipid transport protein (NGAL) were detected by RT-qPCR to evaluate the injuries of the renal tubules. The infiltration of F4/80-positive macrophages and CD4-positive T cells were observed by immunofluorescence. In the in vitro experiment, human proximal tubule epithelial cell line HK-2 was stimulated with 50 µmol/L cisplatin to establish a cell model of acute kidney injury, and the mRNA and protein expressions of pannexin-1 were detected by RT-qPCR and Western blotting at 4, 6, 12, 18 and 24 h after the stimulation. RESULTS: Compared with the control mice, the cisplatin-treated mice showed significantly up-regulated protein levels (P < 0.05) and mRNA levels (P < 0.005) of pannexin-1 in the kidney tissue. Cisplatin stimulation also caused significant increases in the protein levels (P < 0.005) and mRNA levels (P < 0.005) of pannexin-1 in cultured HK-2 cells. Compared with cisplatin-treated mice, the mice treated with both cisplatin and the pannexin-1 inhibitor CBX showed obviously lessened kidney pathologies and milder renal tubular injuries with significantly reduced plasma BUN and Scr levels (P < 0.01), expressions of KIM-1 and NGAL in the kidney (P < 0.05), and infiltration of F4/80-positive macrophages (P < 0.01) and CD4- positive T cells (P < 0.05) in the kidney tissues. CONCLUSIONS: In cisplatin induced acute kidney injury mice model, Pannexin-1 expression is up-regulated in the kidneys tissue, and blocking pannexin-1 alleviates the acute kidney injury via reducing renal inflammatory cell infiltration.


Assuntos
Lesão Renal Aguda , Cisplatino , Conexinas , Reagentes para Ligações Cruzadas , Proteínas do Tecido Nervoso , Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/metabolismo , Animais , Cisplatino/farmacologia , Conexinas/efeitos dos fármacos , Conexinas/metabolismo , Reagentes para Ligações Cruzadas/farmacologia , Humanos , Rim , Túbulos Renais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Distribuição Aleatória
3.
Graefes Arch Clin Exp Ophthalmol ; 257(7): 1443-1452, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31041523

RESUMO

PURPOSE: To evaluate the efficacy of corneal cross-linking (CXL) as adjuvant therapy for the treatment of fungal ulcerative keratitis. METHODS: Forty-one patients with fungal ulcerative keratitis were recruited and assigned into two randomized controlled groups. These groups were treated with CXL combined with antifungal medications (CXL-M) or antifungal medications alone (M). The ulcers were assessed by slit-lamp biomicroscopy, slit-lamp images, in vivo confocal microscopy (IVCM), and anterior segment optical coherence tomography (AS-OCT). The patients were followed up before surgery/first visit (FV), 1 day after surgery, 1 and 2 weeks, and 1, 2, 3, 4, 5, and 6 months after surgery/FV. RESULTS: In the cured patients, the area of corneal ulcers, the duration of ulcer healing, the time to non-observed fungal hyphae by IVCM, the number of antifungal medications, the frequency of administered medications, and the maximum ulcer depth decreased significantly after CXL (all P < 0.05) compared with the M group. There were no significant differences in either corneal thickness or epithelial thickness of ulcers after healing between 5 and 6 months after surgery in the CXL-M group, while these were increased significantly at 6 months compared with 5 months after FV in the M group (both P < 0.05). CONCLUSIONS: In our study, CXL accelerated healing of the fungal ulcers, shortened the treatment duration, and minimized the need for medications and surgery. It appears that CXL is an effective procedure and adjuvant therapy for managing fungal keratitis.


Assuntos
Antifúngicos/farmacologia , Córnea/patologia , Úlcera da Córnea/tratamento farmacológico , Reagentes para Ligações Cruzadas/farmacologia , Infecções Oculares Fúngicas/tratamento farmacológico , Fotoquimioterapia/métodos , Riboflavina/farmacologia , Córnea/microbiologia , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/microbiologia , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/microbiologia , Feminino , Seguimentos , Fungos/isolamento & purificação , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/farmacologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Raios Ultravioleta
4.
Graefes Arch Clin Exp Ophthalmol ; 257(7): 1435-1442, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31065848

RESUMO

PURPOSE: To investigate the safety of blue light scleral cross-linking (SXL) by evaluating changes in biological parameters in the retina and choroid in the eyes of rhesus macaques (Macaca mulatta). METHODS: Fifteen 3-year-old macaques (30 eyes) were randomly divided into three groups (n = 5). SXL was performed via riboflavin (0.5%) and blue light (460 nm) at the location of the equatorial sclera. Right eyes served as experimental eyes, and left eyes as control eyes. One quadrant of each right eye was irradiated in group A, two quadrants of each right eye and one quadrant of each left eye were irradiated in group B, and two quadrants of each right eye were irradiated in group C. Optical coherence tomography, optical coherence tomography angiography, and flash electroretinography (f-ERG) examinations were performed at baseline and 1 week, 1 month, 3 months, and 6 months after SXL. Additionally, retinal tissue alterations were detected via transmission electron microscopy at 1 week postoperatively. RESULTS: There were no significant differences between experimental eyes and control eyes in retinal thickness, vessel density of retinal superficial capillary plexus, and choroid thickness in any of the groups at any of the time points investigated (p > 0.05). Significant reductions in f-ERG parameters were detected 1 week postoperatively in the experimental eyes of groups A and C (p < 0.05), but they gradually recovered, and there was no significant difference 1 month postoperatively (p > 0.05). Ultrastructural changes were evident in the retinal layers of SXL eyes. In group B, there were no significant differences between the right and left eyes at any of the follow-up time points investigated. CONCLUSIONS: Blue light SXL can cause transient retina damage. The f-ERG parameters reductions and retinal ultrastructural changes were found at early stage, even though there were not significant changes in retinal thickness, vessel density of retinal superficial capillary plexus, and choroid thickness after blue light SXL. The long-term intraocular safety of the blue light SXL technique should be investigated further.


Assuntos
Corioide/patologia , Colágeno/farmacologia , Reagentes para Ligações Cruzadas/farmacologia , Miopia/tratamento farmacológico , Fotoquimioterapia/métodos , Retina/patologia , Riboflavina/farmacologia , Animais , Modelos Animais de Doenças , Eletrorretinografia , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Luz , Macaca mulatta , Miopia/diagnóstico , Miopia/fisiopatologia , Fármacos Fotossensibilizantes/farmacologia , Esclera , Tomografia de Coerência Óptica , Resultado do Tratamento
5.
Carbohydr Polym ; 213: 70-78, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30879691

RESUMO

A novel ß-cyclodextrin-based nanosponge (CDNS) was proposed as curcumin (CUR) delivery system improving pharmacokinetics and anticancer activity of CUR. The effect of molar ratio of Epiclon (EPI) as cross-linker and ß-cyclodextrin (ßCD) on the porosity, surface area, swelling ratio, CUR solubility and loading capacity, rate of drug release and selective toxicity of the CDNSs was fully investigated. The high degree of cross-linking led to the formation of mesoporous CDNS having high specific surface area and high loading capacity. All CUR-free CDNSs showed no toxicity against MCF 10A and 4T1 cells as normal and cancerous cells, respectively. While CDNSs-CUR exhibited selective toxicity against cancerous cells. In sum, high CUR aqueous solubility, significant loading and controllable release of the CUR, outstanding and selective toxicity against cancerous cells make CDNS8-CUR (EPI/ßCD = 8) as promising candidate for further study in the cancer therapy.


Assuntos
Reagentes para Ligações Cruzadas/farmacologia , Curcumina/toxicidade , Nanopartículas/química , beta-Ciclodextrinas/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Reagentes para Ligações Cruzadas/administração & dosagem , Reagentes para Ligações Cruzadas/química , Curcumina/administração & dosagem , Curcumina/química , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Humanos , Camundongos , Estrutura Molecular , Tamanho da Partícula , Solubilidade , Relação Estrutura-Atividade , Propriedades de Superfície , Termodinâmica , beta-Ciclodextrinas/química
6.
Cornea ; 38(6): 780-790, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30882538

RESUMO

PURPOSE: There has been a recent explosion in the variety of techniques used to accomplish corneal cross-linking (CXL) for the treatment of ectatic corneal diseases. To understand the success or failure of various techniques, we review the physicochemical basis of corneal CXL and re-evaluate the current principles and long-standing conventional wisdom in the light of recent, compelling, and sometimes contradictory research. METHODS: Two clinicians and a medicinal chemist developed a list of current key topics, controversies, and questions in the field of corneal CXL based on information from current literature, medical conferences, and discussions with international practitioners of CXL. RESULTS: Standard corneal CXL with removal of the corneal epithelium is a safe and efficacious procedure for the treatment of corneal ectasias. However, the necessity of epithelium removal is painful for patients, involves risk and requires significant recovery time. Attempts to move to transepithelial corneal CXL have been hindered by the lack of a coherent understanding of the physicochemistry of corneal CXL. Misconceptions about the applicability of the Bunsen-Roscoe law of reciprocity and the Lambert-Beer law in CXL hamper the ability to predict the effect of ultraviolet A energy during CXL. Improved understanding of CXL may also expand the treatment group for corneal ectasia to those with thinner corneas. Finally, it is essential to understand the role of oxygen in successful CXL. CONCLUSIONS: Improved understanding of the complex interactions of riboflavin, ultraviolet A energy and oxygen in corneal CXL may provide a successful route to transepithelial corneal CXL.


Assuntos
Colágeno/metabolismo , Córnea , Doenças da Córnea/tratamento farmacológico , Reagentes para Ligações Cruzadas/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Riboflavina/farmacologia , Raios Ultravioleta , Córnea/efeitos dos fármacos , Córnea/efeitos da radiação , Epitélio Anterior/efeitos dos fármacos , Epitélio Anterior/efeitos da radiação , Humanos
8.
Carbohydr Polym ; 212: 403-411, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30832874

RESUMO

Developing biomaterials based on the natural biomacromolecule silk sericin from Bombyx mori cocoon is of great interest for biomedical application. Dialdehyde carboxymethyl cellulose (DCMC) is derived from periodate oxidation of carboxy- methyl cellulose. Here, we developed a novel strategy of cross-linking of sericin with DCMC via the Schiff's base reaction. Fourier transform infrared spectroscopy and scanning electron microscopy indicated the formation of Schiff's base via the blending of sericin and DCMC. The mechanical properties tests suggested the covalent cross-linking effectively enhanced the tensile strength of sericin. The swelling test and water contact angle indicated the DCMC/SS film had excellent hydrophilicity, swellability. Additionally, we demonstrated the DCMC/SS film had excellent blood compatibility, cytocompatibility and promoting cell proliferation activity by the hemolysis ratio analysis, cell adhesion, cells viability and proliferation assays. The prepared DCMC/SS film has shown great promise in biomedical applications such as wound dressing, artificial skin and tissue engineering.


Assuntos
Carboximetilcelulose Sódica/síntese química , Celulose/análogos & derivados , Reagentes para Ligações Cruzadas/síntese química , Sericinas/síntese química , Seda/síntese química , Animais , Bandagens , Bombyx , Carboximetilcelulose Sódica/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Celulose/síntese química , Celulose/farmacologia , Reagentes para Ligações Cruzadas/farmacologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/farmacologia , Camundongos , Células NIH 3T3 , Sericinas/farmacologia , Seda/farmacologia , Engenharia Tecidual/tendências
9.
Nat Commun ; 10(1): 186, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30643139

RESUMO

Tetrathiomolybdate (TM) is used in the clinic for the treatment of Wilson's disease by targeting the cellular copper efflux protein ATP7B (WLN). Interestingly, both TM and WLN are associated with the efficacy of cisplatin, a widely used anticancer drug. Herein, we show that TM induces dimerization of the metal-binding domain of ATP7B (WLN4) through a unique sulfur-bridged Mo2S6O2 cluster. TM expels copper ions from Cu-WLN4 and forms a copper-free dimer. The binding of Mo to cysteine residues of WLN4 inhibits platination of the protein. Reaction with multi-domain proteins indicates that TM can also connect two domains in the same molecule, forming Mo-bridged intramolecular crosslinks. These results provide structural and chemical insight into the mechanism of action of TM against ATPase, and reveal the molecular mechanism by which TM attenuates the cisplatin resistance mediated by copper efflux proteins.


Assuntos
Antineoplásicos/farmacologia , Quelantes/farmacologia , Cisplatino/farmacologia , ATPases Transportadoras de Cobre/metabolismo , Molibdênio/farmacologia , Antineoplásicos/uso terapêutico , Quelantes/uso terapêutico , Cisplatino/uso terapêutico , Cobre/metabolismo , ATPases Transportadoras de Cobre/antagonistas & inibidores , ATPases Transportadoras de Cobre/química , Reagentes para Ligações Cruzadas/química , Reagentes para Ligações Cruzadas/farmacologia , Reagentes para Ligações Cruzadas/uso terapêutico , Cristalografia por Raios X , Cisteína/química , Cisteína/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Molibdênio/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Platina/metabolismo , Domínios e Motivos de Interação entre Proteínas/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Estrutura Secundária de Proteína
10.
J Fr Ophtalmol ; 42(2): 166-169, 2019 Feb.
Artigo em Francês | MEDLINE | ID: mdl-30679128

RESUMO

Cross-linking (CXL) is a technique whose design aims to achieve a specific goal: to harden the corneal tissue of eyes with a progressive form of keratoconus. Other indications are being investigated, such as treatment of infectious keratitis and prevention of corneal ectasia post corneal ablative refractive surgery. Hardening the cornea means changing its biomechanical properties. The existence of true corneal hardening after CXL would inevitably result in an increase in measured intraocular pressure (IOP). This would have a considerable impact in the screening and follow-up of glaucoma patients who have undergone cross-linking because of the central role of IOP measurement in glaucomatous pathology.


Assuntos
Córnea/efeitos dos fármacos , Reagentes para Ligações Cruzadas/farmacologia , Pressão Intraocular/efeitos dos fármacos , Ceratocone/tratamento farmacológico , Adolescente , Adulto , Fenômenos Biomecânicos/efeitos dos fármacos , Córnea/diagnóstico por imagem , Córnea/fisiologia , Topografia da Córnea , Reagentes para Ligações Cruzadas/uso terapêutico , Feminino , Seguimentos , Glaucoma/diagnóstico , Glaucoma/tratamento farmacológico , Glaucoma/fisiopatologia , Humanos , Ceratocone/diagnóstico , Ceratocone/fisiopatologia , Masculino , Tonometria Ocular , Adulto Jovem
11.
Indian J Ophthalmol ; 67(1): 8-15, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30574883

RESUMO

Corneal cross-linking (CXL), introduced by Wollensak et al. in 2003, is a minimally invasive procedure to halt the progression of keratoconus. Conventional CXL is recommended in eyes with corneal thickness of at least 400 microns after de-epithelialization to prevent endothelial toxicity. However, most of the keratoconic corneas requiring CXL may not fulfill this preoperative inclusion criterion. Moderate-to-advanced cases are often found to have a pachymetry less than this threshold. There are various modifications to the conventional method to circumvent this issue of CXL thin corneas while avoiding the possible complications. This review is an update on the modifications of conventional CXL for thin corneas.


Assuntos
Colágeno/farmacologia , Córnea/diagnóstico por imagem , Reagentes para Ligações Cruzadas/farmacologia , Ceratocone/tratamento farmacológico , Fotoquimioterapia/métodos , Riboflavina/uso terapêutico , Córnea/efeitos dos fármacos , Paquimetria Corneana , Humanos , Ceratocone/diagnóstico , Fármacos Fotossensibilizantes/uso terapêutico , Raios Ultravioleta
12.
Int J Biol Macromol ; 126: 221-228, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30590143

RESUMO

Salecan, a water-soluble extracellular ß-glucan, is considered as an attractive alternative for hydrogel preparation due to its good physicochemical and biological properties. Herein, a novel cryogel was prepared by cryopolymerization of salecan and acryloyloxyethyltrimethyl ammonium chloride using triallyl cyanurate (TAC) as a crosslinker. FT-IR spectroscopy and XRD analysis confirmed the structure of cryogels. The addition of more hydrophilic salecan inside the cryogels significantly increased their water uptake. More importantly, the compressive and storage moduli were significantly improved by the introduction of TAC as crosslinker, probably due to the multiplication of potential crosslinking points when TAC was used in the polymerization process and subsequent the formation of a stiffer polymer network. In vitro cytotoxicity assay confirmed the non-cytotoxic nature of the cryogels. They were biocompatible and supported adhesion, proliferation and viability of L929 and 3 T3-L1 cells as shown by cell proliferation and Live/Dead assay. Altogether, this work opens a door to the design and development of mechanically strong salecan-based cryogel for cell adhesion and proliferation, and further soft tissue engineering application.


Assuntos
Reagentes para Ligações Cruzadas/farmacologia , Criogéis/química , Fibroblastos/citologia , Polissacarídeos/farmacologia , Triazinas/farmacologia , Células 3T3-L1 , Animais , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Força Compressiva , Módulo de Elasticidade , Fibroblastos/efeitos dos fármacos , Cinética , Camundongos , Polissacarídeos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente , Termogravimetria , Triazinas/química , Difração de Raios X , beta-Glucanas/química
13.
Int J Nanomedicine ; 13: 4473-4492, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30122921

RESUMO

Introduction: In search for cross-linkers with multifunctional characteristics, the present work investigated the utility of quaternary ammonium organosilane (QOS) as a potential cross-linker for electrospun collagen nanofibers. We hypothesized that the quaternary ammonium ions improve the electrospinnability by reducing the surface tension and confer antimicrobial properties, while the formation of siloxane after alkaline hydrolysis could cross-link collagen and stimulate cell proliferation. Materials and methods: QOS collagen nanofibers were electrospun by incorporating various concentrations of QOS (0.1%-10% w/w) and were cross-linked in situ after exposure to ammonium carbonate. The QOS cross-linked scaffolds were characterized and their biological properties were evaluated in terms of their biocompatibility, cellular adhesion and metabolic activity for primary human dermal fibroblasts and human fetal osteoblasts. Results and discussion: The study revealed that 1) QOS cross-linking increased the flexibility of otherwise rigid collagen nanofibers and improved the thermal stability; 2) QOS cross-linked mats displayed potent antibacterial activity and 3) the biocompatibility of the composite mats depended on the amount of QOS present in dope solution - at low QOS concentrations (0.1% w/w), the mats promoted mammalian cell proliferation and growth, whereas at higher QOS concentrations, cytotoxic effect was observed. Conclusion: This study demonstrates that QOS cross-linked mats possess anti-infective properties and confer niches for cellular growth and proliferation, thus offering a useful approach, which is important for hard and soft tissue engineering and regenerative medicine.


Assuntos
Anti-Infecciosos/farmacologia , Colágeno/farmacologia , Reagentes para Ligações Cruzadas/farmacologia , Nanofibras/química , Compostos de Organossilício/farmacologia , Compostos de Amônio Quaternário/farmacologia , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Área Sob a Curva , Bovinos , Forma Celular/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/ultraestrutura , Humanos , Nanofibras/ultraestrutura , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Tamanho da Partícula , Espectroscopia Fotoeletrônica , Espectroscopia de Infravermelho com Transformada de Fourier , Estresse Mecânico , Temperatura Ambiente , Molhabilidade
14.
Carbohydr Polym ; 197: 292-304, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30007617

RESUMO

Hydrogels are widely used as debriding agents on account of providing a moist environment for wound healing, however the lack of mechanical strength, angiogenesis and antibacterial property limits their applications. In this study, we synthesized novel divalent ion cross-liking hydrogels (copper, zinc, strontium and calcium) and compared the mechanical performance, swelling ratio, antibacterial properties and biocompatibility in vitro and vivo. Thereinto, among the four divalent ions cross-linked hydrogels, copper ion crosslinking exhibited the maximum breaking strength, while strontium and zinc ion cross-linked hydrogels exhibited an excellent mechanical strength. In addition, the swelling ratio and pore size of no-ion cross-linked hydrogels was larger than ion cross-kinked hydrogels. In vitro, the improvements on wound healing after hydrogel application were evaluated by histological and molecular assays by detecting VEGF and TGF-ß expression. In vitro and in vivo study results showed that zinc cross-kinked hydrogel had a spectrum of antibacterial activities, cell viability, mechanical strength and the ability of wound closure by promoting fibroblasts migration, vascularization, collagen deposition and the formation of granulation tissue.


Assuntos
Antibacterianos/farmacologia , Reagentes para Ligações Cruzadas/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Resinas Acrílicas/química , Resinas Acrílicas/farmacologia , Alginatos/química , Alginatos/farmacologia , Antibacterianos/química , Sobrevivência Celular/efeitos dos fármacos , Reagentes para Ligações Cruzadas/química , Ácido Glucurônico/química , Ácido Glucurônico/farmacologia , Ácidos Hexurônicos/química , Ácidos Hexurônicos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Estresse Mecânico
15.
Biomater Sci ; 6(8): 2197-2208, 2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-30003209

RESUMO

Electrospun collagen nanofibers are effective for wound healing; however, many problems, such as the tedious preparation process, weak strength and poor structure integration, limit further applications. In this study, recombinant human collagen (RHC) peptides and a simple one-step crosslinking strategy were used to prepare RHC/chitosan nanofibers. With the nonpathogenic, water-soluble RHC and a mild electrospinning solvent, in situ crosslinked nanofibers (S-CN) not only simplified the preparation procedure but also maintained a more integrated morphology. Compared with the immersed crosslinked nanofibers (I-CN), S-CN showed better performance in moisture retention, degradation and mechanical strength tests. In vitro cell proliferation, morphology and RT-PCR studies confirmed that fibroblasts presented better activities on nanofibers crosslinked in situ. Importantly, after treating with the nanofibers, rapid epidermidalization and angiogenesis were observed in an SD rat scalding model. All these data suggest that electrospun RHC/chitosan nanofibers crosslinked in situ are an ideal candidate that can be used for wound healing applications.


Assuntos
Quitosana/farmacologia , Colágeno/farmacologia , Reagentes para Ligações Cruzadas/farmacologia , Nanofibras/química , Peptídeos/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Colágeno/química , Reagentes para Ligações Cruzadas/química , Modelos Animais de Doenças , Técnicas Eletroquímicas , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Masculino , Camundongos , Células NIH 3T3 , Tamanho da Partícula , Peptídeos/química , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/química
16.
Colloids Surf B Biointerfaces ; 170: 152-162, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29902729

RESUMO

Studies on synthesis, physico-chemical and biological properties of novel biomimetic materials, potentially useful as injectable hydrogels are presented. These materials are in situ prepared chemically crosslinked collagen/chitosan/hyaluronic acid-based hydrogels exhibiting potential for tissue regeneration. Optimization of hydrogels involved testing the effect of various concentration of crosslinking agent (genipin) as well as different ratios of biopolymers used on their properties. The changes in the content of hyaluronic acid and in the genipin concentration used have been shown to be crucial. Employing the highest concentration of crosslinking agent studied (20 mM) the hydrogels of compact structure, characterized by good mechanical properties and prolonged degradation profile can be obtained. Changing the HA content in sol mixture the hydrogel of various wettability; more or less hydrophilic when compared to pure collagen/chitosan hydrogels can be fabricated. The in vitro cell culture study has shown that the surface of the prepared materials ensures suitable biocompatibility. These hydrogels can support the proliferation and adhesion of MG-63 cell line as it was demonstrated using Alamar Blue assay and SEM observations. It is believed that the collagen/chitosan/hyaluronic acid hydrogels crosslinked with genipin are particularly promising materials for bone regeneration procedures, especially attractive for regeneration of small bone losses. This is the first paper in the litearature presenting results of studies on that type of biopolymeric injectable hydrogels chemically crosslinked with genipin.


Assuntos
Quitosana/farmacologia , Colágeno/farmacologia , Ácido Hialurônico/farmacologia , Hidrogéis/farmacologia , Iridoides/farmacologia , Engenharia Tecidual , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/administração & dosagem , Quitosana/química , Colágeno/administração & dosagem , Colágeno/química , Reagentes para Ligações Cruzadas/administração & dosagem , Reagentes para Ligações Cruzadas/química , Reagentes para Ligações Cruzadas/farmacologia , Relação Dose-Resposta a Droga , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/química , Hidrogéis/administração & dosagem , Hidrogéis/química , Iridoides/administração & dosagem , Iridoides/química , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Relação Estrutura-Atividade , Propriedades de Superfície , Células Tumorais Cultivadas
17.
Colloids Surf B Biointerfaces ; 170: 373-381, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29940504

RESUMO

The high toxicity, poor stability, premature drug release, and lack of intracellular stimuli responsibility of current polymeric micelles still hinder them for potential clinical applications. To address these challenges, a novel type of multi-stimuli responsive, core cross-linked polypeptide hybrid micelles (CCMs) was developed for triggered anticancer drug delivery in tumor microenvironment. The CCMs was prepared via free radical copolymerization by using N,N'-methylene-bis-acylamide (BACy) as the cross-linking agent, 2,2-azobisisobutyronitrile (AIBN) as the initiator, where poly (γ-benzyl-L-glutamate) (PBLG) and N-isopropylacrylamide (NIPPAM) as comonomers. The doxorubicin (DOX) was then introduced into the CCMs by hydrazone bond to prepare the drug-incorporated core cross-linked micelles (CCMs-DOX). By the experimental results, the CCMs showed reduction responsibility due to the degradable disulfide bond in the polymer network. The hydrazone bond can be broken under acidic condition causing a controllable drug release for CCMs-DOX. Compared to only 7.7% DOX release under pH 7.4 at 37°C, a much higher DOX release rate up to 85.3% was observed under 10 mM GSH (pH 5.0, 42°C). In vitro cell assays showed that the blank CCMs showed almost no toxicity against HUVEC cells while the CCMS-DOX exhibited significant cancer cell killing effect. These experimental results suggested that the prepared multi-stimuli responsive polymeric micelles could serve as a smart and promising drug delivery candidate for anti-cancer therapy.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Reagentes para Ligações Cruzadas/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Micelas , Peptídeos/química , Temperatura Ambiente , Antibióticos Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Reagentes para Ligações Cruzadas/síntese química , Reagentes para Ligações Cruzadas/farmacologia , Doxorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Estrutura Molecular , Oxirredução , Tamanho da Partícula , Peptídeos/síntese química , Peptídeos/farmacologia , Propriedades de Superfície , Células Tumorais Cultivadas
18.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(4): 441-446, 2018 Apr 28.
Artigo em Chinês | MEDLINE | ID: mdl-29774883

RESUMO

OBJECTIVE: To compare the properties between decellularized rabbit carotid artery with different cross-linked technologies.
 Methods: The decellularized rabbit carotid arteries were randomly divided into a photo-oxidation group and a procyanidins group. One group was cross-linked with photo-oxidation and the other group was cross-linked with procyanidins. The in vitro or in vivo properties of the two groups were evaluated by testing heat-shrinking temperature, max tensile strength and the max elongation or by testing tissue structure, inflammatory reaction and calcification degree.
 Results: The heat-shrinking temperature, max tensile strength and the max elongation were similar in the two groups (P>0.05). The tissue structure and inflammatory reaction were also similar in the two groups. Although the result of Von-Kossa calcium salt stain was slightly different, the calcium content was lower in the procyanidins group than that in the photo-oxidation group (P<0.05).
 Conclusion: The grafts by two cross-linked technologies show excellent mechanical capability, lower immunogenicity, good biological stability and anti-calcification ability. The procyanidins group shows a better anti-calcification property than the photo-oxidation group.


Assuntos
Artérias Carótidas/fisiologia , Animais , Calcinose/patologia , Artérias Carótidas/patologia , Artéria Carótida Primitiva/fisiologia , Reagentes para Ligações Cruzadas/farmacologia , Elasticidade , Temperatura Alta , Técnicas In Vitro , Oxirredução , Proantocianidinas/farmacologia , Coelhos , Distribuição Aleatória , Resistência à Tração
19.
Free Radic Res ; 52(7): 783-798, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29722278

RESUMO

Reactive oxygen and nitrogen species (ROS and RNS) generated by cold atmospheric-pressure plasma could damage genomic DNA, although the precise types of these DNA damage induced by plasma are poorly characterized. Understanding plasma-induced DNA damage will help to elucidate the biological effect of plasma and guide the application of plasma in ROS-based therapy. In this study, it was shown that ROS and RNS generated by physical plasma could efficiently induce DNA-protein crosslinks (DPCs) in bacteria, yeast, and human cells. An in vitro assay showed that plasma treatment resulted in the formation of covalent DPCs by activating proteins to crosslink with DNA. Mass spectrometry and hydroperoxide analysis detected oxidation products induced by plasma. DPC formation were alleviated by singlet oxygen scavenger, demonstrating the importance of singlet oxygen in this process. These results suggested the roles of DPC formation in DNA damage induced by plasma, which could improve the understanding of the biological effect of plasma and help to develop a new strategy in plasma-based therapy including infection and cancer therapy.


Assuntos
Pressão Atmosférica , Reagentes para Ligações Cruzadas/farmacologia , DNA/metabolismo , Gases em Plasma/farmacologia , Proteínas/química , Proteínas/metabolismo , DNA/química , Dano ao DNA/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Células HeLa , Humanos , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
20.
Adv Exp Med Biol ; 1059: 155-188, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29736573

RESUMO

Semi-interpenetrating polymer networks (semi-IPNs) and interpenetrating polymeric networks (IPNs) have emerged as innovative materials for biomedical and pharmaceutical applications. The interest in these structures is due to the possibility of combining the favorable properties of each polymeric component of the IPNs or semi-IPNs leading to a new system with properties that often differ from those of the two single components. In this respect, polysaccharides represent an opportunity in this field, combining a general biocompatibility and a good availability. Moreover, the functional groups along the polymer chains allow chemical derivatization, widening the possibilities in semi-IPNs and IPNs building up. At the same time, materials based on proteins are often used in this field, due to their similarity to the materials present in the human body. All these overall properties allow tailoring new materials, thus designing desired properties and preparing new hydrogels useful in the biomedical field. In the present chapter, we chose to describe systems prepared starting from the most important and studied hydrogel-forming polysaccharides: alginate, hyaluronic acid, chitosan, dextran, gellan, and scleroglucan. Besides, systems based on proteins, such as gelatin, collagen, and elastin, are also described. With this chapter, we aim describing the routes already traveled in this field, depicting the state of the art and hoping to raise interest in designing new promising strategies useful in biomedical and pharmaceutical applications.


Assuntos
Materiais Biocompatíveis/química , Biopolímeros/química , Hidrogéis/química , Materiais Biocompatíveis/uso terapêutico , Fenômenos Biomecânicos , Biopolímeros/uso terapêutico , Configuração de Carboidratos , Química Física , Colágeno/química , Colágeno/uso terapêutico , Reagentes para Ligações Cruzadas/farmacologia , Desenho de Drogas , Elastina/química , Elastina/uso terapêutico , Gelatina/química , Gelatina/uso terapêutico , Humanos , Hidrogéis/uso terapêutico , Concentração de Íons de Hidrogênio , Polissacarídeos/química , Polissacarídeos/uso terapêutico , Relação Estrutura-Atividade , Temperatura Ambiente , Tecidos Suporte
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