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1.
J Control Release ; 369: 604-616, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38582337

RESUMEN

Corneal stromal fibrosis is a common cause of visual impairment resulting from corneal injury, inflammation and surgery. Therefore, there is an unmet need for inhibiting corneal stromal fibrosis. However, bioavailability of topical eye drops is very low due to the tear and corneal barriers. In situ delivery offers a unique alternative to improve efficacy and minimize systemic toxicity. Herein, a drug delivery platform based on thermoresponsive injectable hydrogel/nano-micelles composite with in situ drug-controlled release and long-acting features is developed to prevent corneal scarring and reduce corneal stromal fibrosis in lamellar keratoplasty. The in-situ gelation hydrogels enabled direct delivery of celastrol to the corneal stroma. In vivo evaluation with a rabbit anterior lamellar keratoplasty model showed that hydrogel/micelles platform could effectively inhibit corneal stromal fibrosis. This strategy achieves controlled and prolonged release of celastrol in the corneal stroma of rabbit. Following a single corneal interlamellar injection, celastrol effectively alleviated fibrosis via mTORC1 signal promoting autophagy and inhibiting TGF-ß1/Smad2/3 signaling pathway. Overall, this strategy demonstrates promise for the clinical application of celastrol in preventing corneal scarring and reducing corneal stromal fibrosis post-lamellar keratoplasty, highlighting the potential benefits of targeted drug delivery systems in ocular therapeutics.


Asunto(s)
Trasplante de Córnea , Hidrogeles , Triterpenos Pentacíclicos , Animales , Conejos , Triterpenos Pentacíclicos/administración & dosificación , Hidrogeles/administración & dosificación , Trasplante de Córnea/métodos , Cicatriz/prevención & control , Cicatriz/tratamiento farmacológico , Preparaciones de Acción Retardada , Fibrosis , Sistemas de Liberación de Medicamentos , Córnea/efectos de los fármacos , Córnea/metabolismo , Triterpenos/administración & dosificación , Liberación de Fármacos , Sustancia Propia/efectos de los fármacos , Humanos
2.
Sci Rep ; 14(1): 6937, 2024 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-38521828

RESUMEN

Keratoconus (KC) is a progressive degenerative disease that usually occurs bilaterally and is characterized by corneal thinning and apical protrusion of the cornea. Oxidative stress is an indicator of the accumulation of reactive oxygen species (ROS), and KC keratocytes exhibit increased ROS production compared with that of normal keratocytes. Therefore, oxidative stress in KC keratocytes may play a major role in the development and progression of KC. Here, we investigated the protective effect of sulforaphane (SF) antioxidants using a hydrogel-simulated model of the cell mechanical microenvironment of KC. The stiffness of the KC matrix microenvironment in vitro was 16.70 kPa and the stiffness of the normal matrix microenvironment was 34.88 kPa. Human keratocytes (HKs) were cultured for 24 h before observation or drug treatment with H2O2 in the presence or absence of SF. The levels of oxidative stress, nuclear factor E2-related factor 2 (Nrf-2) and antioxidant response element (ARE) were detected. The high-stress state of HKs in the mechanical microenvironment of KC cells compensates for the activation of the Nrf-2/ARE signaling pathway. H2O2 leads to increased oxidative stress and decreased levels of antioxidant proteins in KC. In summary, SF can reduce endogenous and exogenous oxidative stress and increase the antioxidant capacity of cells.


Asunto(s)
Isotiocianatos , Queratocono , Sulfóxidos , Humanos , Queratocono/tratamiento farmacológico , Queratocono/metabolismo , Antioxidantes/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Elementos de Respuesta Antioxidante , Peróxido de Hidrógeno/metabolismo , Córnea/metabolismo
3.
Ann Med ; 56(1): 2313680, 2024 12.
Artículo en Inglés | MEDLINE | ID: mdl-38335557

RESUMEN

PURPOSE: To evaluate the role of M2 macrophages in subconjunctival fibrosis after silicone implantation (SI) and investigate the underlying mechanisms. MATERIALS AND METHODS: A model of subconjunctival fibrosis was established by SI surgery in rabbit eyes. M2 distribution and collagen deposition were evaluated by histopathology. The effects of M2 cells on the migration (using wound-scratch assay) and activation (by immunofluorescence and western blotting) of human Tenon's fibroblasts (HTFs) were investigated. RESULTS: There were more M2 macrophages (CD68+/CD206+ cells) occurring in tissue samples around silicone implant at 2 weeks postoperatively. Dense collagen deposition was observed at 8 weeks after SI. In vitro experiment showed M2 expressed high level of CD206 and transforming growth factor-ß1 (TGF-ß1). The M2-conditioned medium promoted HTFs migration and the synthesis of collagen I and fibronectin. Meanwhile, M2-conditioned medium increased the protein levels of TGF-ß1, TGF-ßR II, p-Smad2/3, yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ). Verteporfin, a YAP inhibitor, suppressedTGF-ß1/Smad2/3-YAP/TAZ pathway and attenuated M2-induced extracellular matrix deposition by HTFs. CONCLUSIONS: TGF-ß1/Smad2/3-YAP/TAZ signalling may be involved in M2-induced fibrotic activities in HTFs. M2 plays a key role in promoting subconjunctival fibrosis and can serve as an attractive target for anti-fibrotic therapeutics.


Asunto(s)
Macrófagos , Factor de Crecimiento Transformador beta1 , Animales , Humanos , Conejos , Colágeno , Medios de Cultivo Condicionados , Fibrosis , Macrófagos/metabolismo , Siliconas , Factor de Crecimiento Transformador beta1/metabolismo , Proteínas Señalizadoras YAP/metabolismo , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ/metabolismo
4.
ACS Infect Dis ; 9(10): 2005-2015, 2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37788827

RESUMEN

The eyelid-related disease of blepharitis remains a tricky ocular disorder and affects patient compliance. However, there is no available and effective treatment, making it extremely challenging. Herein, an antibacterial system based on antibiotic delivery was developed and applied in a blepharitis model induced by bacteria. The antibacterial tests against Staphylococcus aureus both in vitro and in vivo demonstrated that the system shows a favorable bactericidal effect. Then, histological evaluation indicated that the system shows both antibacterial and anti-inflammatory effects. This facile design provided an effective ocular infection management, which displays a promising prospect while addressing other complex ocular disorders.


Asunto(s)
Antibacterianos , Blefaritis , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Blefaritis/tratamiento farmacológico , Blefaritis/microbiología , Bacterias , Staphylococcus aureus , Resultado del Tratamiento
5.
Heliyon ; 9(8): e18853, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37600383

RESUMEN

Purpose: To report a novel technique to facilitate amniotic membrane transplantation (AMT) for acute stage Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Design: Laboratory investigation and retrospective, single-center case series. Methods: The polylactic acid (PLA) amniotic fornical ring (AFR) have been successfully manufactured by three-dimensional (3D) printing technology for AMT. This study retrospectively analyzed the medical records of 5 SJS/TEN patients at the acute stage between 2019 and 2023. Patients were surgically treated with AFR or sutured amniotic membrane transplant (SAMT). Epidemiology, best-corrected visual acuity (BCVA), acute ocular severity score, operative duration, epithelial healing time, amniotic dissolution and follow-up time were evaluated. Results: Of all five patients, three patients (6 eyes) received AFR/AMT (Group A), and 2 patients (4 eyes) received SAMT (Group B). There were no significant differences between two groups in the mean preoperative days and vision changes. The mean operation duration was 11.7 ± 3.8 mins in group A. Compared with the SAMT (48.8 ± 5.3 mins), the operation duration was reduced by 76.02%. The mean times for epithelial healing were 32.5 ± 29.2 days in group A and 12.0 ± 0.0 days in group B. In addition, there were no significant side effects of 3D-printed sterile AFR on the eyes. Conclusions: 3D-printed PLA scaffolds could be used as an AFR device for acute SJS/TEN. In addition, personalized 3D-printed AFR is superior to conventional SAMT in operation duration.

6.
Int J Biol Macromol ; 244: 125159, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37268068

RESUMEN

Persistent subconjunctival inflammation leads to subconjunctival fibrosis and eventual visual impairment. There is an unmet need for how to effectively inhibit subconjunctival inflammation. Herein, the effect of carboxymethyl chitosan (CMCS) on subconjunctival inflammation was investigated and the mechanism was involved. The evaluation of cytocompatibility demonstrated that CMCS had good biocompatibility. The in vitro results showed that CMCS inhibited secretions of pro-inflammatory cytokines (IL-6, TNF-α, IL-8 and IFN-γ) and chemokines (MCP-1), and downregulated TLR4/MyD88/NF-κB pathway in M1. The in vivo results displayed that CMCS alleviated conjunctival edema and congestion, and improved conjunctival epithelial reconstruction significantly. Both in vitro and in vivo results demonstrated that CMCS inhibited the infiltration of macrophages and reduced the expressions of iNOS, IL-6, IL-8 and TNF-α in the conjunctiva. Given that CMCS indicated the activities of inhibiting M1 polarization, NF-κB pathway, and subconjunctival inflammation, which may be employed as a potent treatment for subconjunctival inflammation.


Asunto(s)
Quitosano , FN-kappa B , Humanos , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Quitosano/farmacología , Quitosano/metabolismo , Interleucina-8/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Macrófagos , Lipopolisacáridos/farmacología
7.
Int J Bioprint ; 9(3): 713, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37273984

RESUMEN

In the present work, we used three-dimensional (3D) printing technology to make a polylactic acid (PLA) amniotic fornical ring (AFR) for ocular surface reconstruction. This work is a retrospective and interventional case series of patients with ocular surface diseases who underwent either personalized 3D-printed AFR-assisted amniotic membrane transplantation (AMT) or sutured AMT (SAMT). Patient epidemiology, treatment, operative duration, epithelial healing time, retention time, vision changes, morbidity, and costs were analyzed. Thirty-one patients (40 eyes) and 19 patients (22 eyes) were enrolled in the 3D-printed AFR group and the SAMT group, respectively. The clinical indications of AFR and SAMT were similar, such as corneal and/or conjunctival epithelial defects due to chemical burns, thermal burns, Stevens-Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN). The mean dissolution time was 15 ± 11 days in the AFR group, compared with 14 ± 7 days in the SAMT group. The percentage of healed corneal area was 90.91% (66.10%-100.00%) for AFR and 93.67% (60.23%-100.00%) for SAMT. The median time for corneal epithelial healing was 14 (7-75) days in the AFR group and 30 (14-55) days in the suture AMT group. There were no significant differences in the initial visual acuity, final visual acuity, or improvement in visual acuity between the two groups. The operation duration in the AFR group was significantly shorter than that in the SAMT group. Regarding the cost analysis, the average cost per eye in the AFR group was significantly lower than that in the SAMT group. Furthermore, 3D-printed and sterile AFR showed no obvious side effects on the eyes. Our results suggested that 3D-printed PLA scaffolds could be used as an AFR device for ocular surface disease. In addition, personalized 3D-printed AFR is superior to conventional AMT in operation duration and cost effectiveness, thereby reducing the financial burden on our health care system.

8.
Invest Ophthalmol Vis Sci ; 64(3): 9, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36867128

RESUMEN

Purpose: The purpose of this study was to investigate the effect of celastrol (CEL) on corneal stromal fibrosis after Descemet stripping endothelial keratoplasty (DSEK) and its associated mechanism. Methods: Rabbit corneal fibroblasts (RCFs) were isolated, cultured, and identified. A CEL-loaded positive nanomedicine (CPNM) was developed to enhance corneal penetration. CCK-8 and scratch assays were performed to evaluate cytotoxicity and the effects of CEL on the migration of RCFs. The RCFs were activated by TGF-ß1 with or without CEL treatment, and then the protein expression levels of TGFßRII, Smad2/3, YAP, TAZ, TEAD1, α-SMA, TGF-ß1, FN, and COLI were assessed by immunofluorescence or Western blotting (WB). An in vivo DSEK model was established in New Zealand White rabbits. The corneas were stained using H&E, YAP, TAZ, TGF-ß1, Smad2/3, TGFßRII, Masson, and COLI. H&E staining of the eyeball was performed to assess the tissue toxicity of CEL at 8 weeks after DSEK. Results: In vitro CEL treatment inhibited the proliferation and migration of RCFs induced by TGF-ß1. Immunofluorescence and WB showed that CEL significantly inhibited the protein expression of TGF-ß1, Smad2/3, YAP, TAZ, TEAD1, α-SMA, TGF-ßRII, FN, and COL1 induced by TGF-ß1 in RCFs. In the rabbit DSEK model, CEL significantly reduced the levels of YAP, TAZ, TGF-ß1, Smad2/3, TGFßRII, and collagen. No obvious tissue toxicity was observed in the CPNM group. Conclusions: CEL effectively inhibited corneal stromal fibrosis after DSEK. The TGF-ß1/Smad2/3-YAP/TAZ pathway may be involved in the mechanism by which CEL alleviates corneal fibrosis. The CPNM is a safe and effective treatment strategy for corneal stromal fibrosis after DSEK.


Asunto(s)
Enfermedades de la Córnea , Queratoplastia Endotelial de la Lámina Limitante Posterior , Animales , Conejos , Factor de Crecimiento Transformador beta1 , Sustancia Propia , Córnea
9.
Nanomedicine (Lond) ; 17(20): 1449-1461, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-36205091

RESUMEN

Aim: To formulate an injectable thermosensitive micelle-hydrogel hybrid system loaded with celastrol (celastrol-loaded micelle hydrogel: CMG) to prevent posterior capsule opacification (PCO). Materials & methods: Celastrol-loaded micelles were embedded in a thermosensitive hydrogel matrix to enable controlled on-demand celastrol delivery into the residual capsule. The efficacy and mechanisms of the system for eliminating PCO were evaluated in rabbits. Results: Celastrol-loaded micelles inhibited the migration and proliferation of lens epithelial cells induced by TGF-ß1. Celastrol prevents epithelial-mesenchymal transition in lens epithelial cells induced by TGF-ß1 through the TGF-ß1/Smad2/3/TEAD1 signaling pathway. In vivo efficiency evaluations showed that CMG demonstrated an excellent inhibitory effect on PCO in rabbits and had no obvious tissue toxicity. Conclusion: Injectable CMG may represent a promising ophthalmic platform for preventing PCO. This versatile injectable micelle-hydrogel hybrid represents a clinically relevant platform to achieve localized therapy and controlled release of drugs in other disease therapies.


Asunto(s)
Opacificación Capsular , Animales , Conejos , Opacificación Capsular/tratamiento farmacológico , Opacificación Capsular/prevención & control , Opacificación Capsular/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Micelas , Hidrogeles/farmacología , Nanomedicina , Transición Epitelial-Mesenquimal , Células Epiteliales/metabolismo
10.
Contrast Media Mol Imaging ; 2022: 9198626, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35845730

RESUMEN

The study investigates the diagnostic efficacy of ultrasound combined with the molybdenum target mode in breast cancer staging and the relationship between blood flow parameters and the expression of insulin-like growth factor 1 (IGF-1) and factor 2 (IGF-2) and prognosis. A total of 96 patients admitted to hospital from January 2020 to January 2021 are included in the breast cancer group, and 58 patients admitted to our hospital during the same period are included in the control group, who are diagnosed with benign breast lesions. All patients receive clinicopathological diagnosis, ultrasound detection, and X-ray molybdenum detection. Ultrasound detection, molybdenum target detection, ultrasound combined with the molybdenum target detection mode, and clinicopathological diagnosis results are compared. B-ultrasound combined with the molybdenum target detection mode has high efficiency in diagnosing breast cancer and differentiating pathological stages. Besides, blood flow parameters of patients are closely related to IGF-1 and IGF-2, and IGF-1 and IGF-2 expressions are closely related to the prognosis of patients. Subsequent diagnosis of the disease degree of breast cancer patients can be carried out by ultrasound combined with the molybdenum target detection mode. In addition, the expression of IGF-1 and IGF-2 in patients can be monitored to improve the clinical diagnosis and treatment plan to improve the prognosis of patients, which has a high clinical application value and is worth promoting.


Asunto(s)
Neoplasias de la Mama , Factor I del Crecimiento Similar a la Insulina , Neoplasias de la Mama/patología , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/uso terapéutico , Factor II del Crecimiento Similar a la Insulina/uso terapéutico , Molibdeno/uso terapéutico , Estadificación de Neoplasias , Pronóstico
11.
J Healthc Eng ; 2022: 9937051, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35222901

RESUMEN

Abdominal B-ultrasound images of intrauterine pregnancy tissue residues were analyzed to discuss their diagnostic value. With the rapid development of computer technology and medical imaging technology, doctors are also faced with more and more medical image diagnosis tasks, and computer-aided diagnosis systems are especially important in order to reduce the work pressure of doctors. In recent years, deep learning has made rapid development and achieved great breakthroughs in various fields. In medical-aided diagnostic systems, deep learning has greatly improved the diagnostic efficiency, but there are no mature research results for abdominal B-ultrasound image recognition of intrauterine pregnancy tissue residues. Therefore, the study of liver ultrasound image classification based on deep learning has important practical application value. In this paper, we propose to give a CNN model optimization method based on grid search. Compared with the conventional CNN model design, this method saves time and effort by eliminating the need to manually adjust parameters based on experience and has an accuracy of more than 92% in classifying abdominal B-ultrasound images of intrauterine pregnancy tissue residues. The diagnosis of intrauterine pregnancy tissue residues by abdominal B-ultrasound can effectively improve the diagnosis and provide important reference for patients to receive treatment, which has high diagnostic value.


Asunto(s)
Macrodatos , Procesamiento de Imagen Asistido por Computador , Diagnóstico por Computador/métodos , Femenino , Humanos , Neuroimagen , Embarazo , Ultrasonografía
13.
Carbohydr Polym ; 275: 118762, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34742450

RESUMEN

Fungal keratitis remains a serious infectious ocular disease, and the traditional administration of eye drops is limited by ocular intrinsic barriers and drug shortages. Herein, we fabricated a chitosan-based dual-functional platform for ocular topical delivery of econazole. The platform can prolong the residence time on the ocular surface due to its strong interaction with the mucin layer by physical adhesion and covalent bonding, and also open corneal epithelial tight junctions for being positively charged, thereby enhancing corneal penetration of drug. Using these strategies, dosing concentration was reduced from 0.3 wt% to 0.1 wt%, dosing frequency was reduced from once-an-hour to twice-daily, in vitro and in vivo antifungal therapeutic effects were achieved and patient compliance could be improved. Given its high structural adaptability, many other ocular anterior segment-related diseases would benefit from this platform.


Asunto(s)
Antifúngicos/farmacología , Materiales Biocompatibles/farmacología , Quitosano/farmacología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Queratitis/tratamiento farmacológico , Soluciones Oftálmicas/farmacología , Administración Oftálmica , Animales , Antifúngicos/administración & dosificación , Antifúngicos/química , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/química , Conformación de Carbohidratos , Quitosano/administración & dosificación , Quitosano/química , Sistemas de Liberación de Medicamentos , Infecciones Fúngicas del Ojo/microbiología , Femenino , Fusarium/efectos de los fármacos , Humanos , Queratitis/microbiología , Ratones , Ratones Endogámicos C57BL , Pruebas de Sensibilidad Microbiana , Soluciones Oftálmicas/administración & dosificación , Soluciones Oftálmicas/química
14.
J Mater Chem B ; 9(41): 8694-8707, 2021 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-34622266

RESUMEN

Dental plaque biofilms are believed to be one of the principal virulence factors in periodontitis resulting in tooth loss. Traditional mouthwashes are limited due to the continuous flow of saliva and poor drug penetration ability in the biofilm. Herein, we fabricated an antibiotic delivery platform based on natural polysaccharides (chitosan and cyclodextrin) as a novel mouthwash for the topical cavity delivery of minocycline. The penetration and residence mechanisms demonstrate that the platform can prolong the residence time up to 12 h on biofilms. Furthermore, sustained release can enhance the penetration of drugs into biofilms. In vitro antibiofilm experimental results indicated that the mouthwash effectively kills bacteria and eradicate biofilms. Effective treatment in vivo was confirmed by the significantly reduced dental plaque and alleviated inflammation observed in a rat periodontitis model. In summary, this novel platform can improve antibiofilm efficiency and prevent drugs from being washed away by saliva, which may provide benefits for many oral infectious diseases.


Asunto(s)
Antibacterianos/farmacología , Quitosano/farmacología , Ciclodextrinas/farmacología , Antisépticos Bucales/farmacología , Periodontitis/tratamiento farmacológico , Porphyromonas gingivalis/efectos de los fármacos , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Biopelículas/efectos de los fármacos , Quitosano/síntesis química , Quitosano/química , Ciclodextrinas/síntesis química , Ciclodextrinas/química , Placa Dental/tratamiento farmacológico , Placa Dental/microbiología , Placa Dental/patología , Masculino , Pruebas de Sensibilidad Microbiana , Antisépticos Bucales/síntesis química , Antisépticos Bucales/química , Periodontitis/microbiología , Periodontitis/patología , Ratas , Ratas Sprague-Dawley
15.
ACS Appl Mater Interfaces ; 13(41): 49369-49379, 2021 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-34636236

RESUMEN

Biomimetic scaffolds with transparent, biocompatible, and in situ-forming properties are highly desirable for corneal tissue engineering, which can deeply fill corneal stromal defects with irregular shapes and support tissue regeneration. We here engineer a novel class of corneal scaffolds from oligoethylene glycol (OEG)-based dendronized chitosans (DCs), whose aqueous solutions show intriguing sol-gel transitions triggered by physiological temperature, resulting in highly transparent hydrogels. Gelling points of these hydrogels can be easily tuned, and furthermore, their mechanical strengths can be significantly enhanced when injected into PBS at 37 °C instead of pure water. In vitro tests indicate that these DC hydrogels exhibit excellent biocompatibility and can promote proliferation and migration of keratocyte. When applied in the rabbit eyes with corneal stromal defects, in situ formed DC hydrogels play a positive effect for new tissue regeneration. Overall, this thermo-gelling DCs possess appealing features as corneal tissue substitutes with their excellent biocompatibility and unprecedented thermoresponsiveness.


Asunto(s)
Materiales Biomiméticos/química , Quitosano/análogos & derivados , Córnea/metabolismo , Dendrímeros/química , Andamios del Tejido/química , Animales , Materiales Biomiméticos/toxicidad , Movimiento Celular/efectos de los fármacos , Quitosano/toxicidad , Córnea/citología , Córnea/cirugía , Dendrímeros/toxicidad , Inflamación/metabolismo , Queratectomía , Polietilenglicoles/química , Polietilenglicoles/toxicidad , Conejos , Células del Estroma/efectos de los fármacos , Ingeniería de Tejidos/métodos , Cicatrización de Heridas/efectos de los fármacos
16.
J Nanobiotechnology ; 19(1): 341, 2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34702273

RESUMEN

Effectively promoting corneal allograft survival remains a challenge in corneal transplantation. The emerging therapeutic agents with high pharmacological activities and their appropriate administration routes provide attractive solutions. In the present study, a celastrol-loaded positive nanomedicine (CPNM) was developed to enhance corneal penetration and to promote corneal allograft survival. The in vitro, in vivo and ex vivo results demonstrated the good performance of CPNM prolonging the retention time on ocular surface and opening the tight junction in cornea, which resulted in enhanced corneal permeability of celastrol. Both in vitro and in vivo results demonstrated that celastrol inhibited the recruitment of M1 macrophage and the expression of TLR4 in corneal allografts through the TLR4/MyD88/NF-κB pathway, thereby significantly decreasing secretion of multiple pro-inflammatory cytokines to promote corneal allograft survival. This is the first celastrol-based topical instillation against corneal allograft rejection to provide treatment more potent than conventional eye drops for ocular anterior segment diseases.


Asunto(s)
Trasplante de Córnea , Supervivencia de Injerto/efectos de los fármacos , Nanomedicina/métodos , Triterpenos Pentacíclicos/farmacología , Animales , Citocinas/metabolismo , Femenino , Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Soluciones Oftálmicas/administración & dosificación , Soluciones Oftálmicas/farmacología , Triterpenos Pentacíclicos/administración & dosificación , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , Ratas Wistar
17.
Eur J Ophthalmol ; 31(6): 3518-3524, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34213382

RESUMEN

PURPOSE: To investigate the role of oxidative stress in keratocytes in the pathogenesis of keratoconus (KC) using the rabbit cornea as a model. METHODS: Immerse the rabbit cornea in collagenase type II solution at room temperature for 30 min in the KC group. The central cornea thickness (CCT), and mean keratometry (Km) were examined before and after the procedure. Reactive oxygen species (ROS), the nuclear translocation of nuclear factor E2-related factor 2 (NRF-2), the expression of heme oxygenase-1 (HO-1) protein, and nicotinamide adenine dinucleotide phosphate (NADPH) Oxidase (NOX) family members NOX-2 and NOX-4 protein levels were examined by immunohistochemistry analysis and Western Blot. The expression levels of HO-1, NOX-2, NOX-4, and NRF-2 mRNA were quantitatively detected by Real-time PCR. RESULTS: A significant increase in Km and a significant decrease in CCT were observed in the KC group compared with the control group after the surgery (both p < 0.001). Immunofluorescence staining showed the rabbit KC model induced a significant increase in ROS production (p < 0.001). The expression of HO-1, NOX-2, NOX-4, and NRF-2 proteins in the KC group were significantly higher than those in the control group (all p < 0.001). RT-PCR results showed the levels of HO-1, NOX-2, NOX-4, and NRF-2 mRNA in KC groups were all significantly increased compared with control groups (all p < 0.05). CONCLUSIONS: Oxidative stress and compensatory activation of antioxidant proteins suggest oxidative stress injury in corneal stromal cells plays an important role in the development of KC in a rabbit model.


Asunto(s)
Queratocono , Animales , Western Blotting , Córnea , Humanos , Estrés Oxidativo , Conejos , Células del Estroma
18.
Bioact Mater ; 6(11): 4053-4064, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33997492

RESUMEN

Effective osteogenesis remains a challenge in the treatment of bone defects. The emergence of artificial bone scaffolds provides an attractive solution. In this work, a new biomineralization strategy is proposed to facilitate osteogenesis through sustaining supply of nutrients including phosphorus (P), calcium (Ca), and silicon (Si). We developed black phosphorus (BP)-based, three-dimensional nanocomposite fibrous scaffolds via microfluidic technology to provide a wealth of essential ions for bone defect treatment. The fibrous scaffolds were fabricated from 3D poly (l-lactic acid) (PLLA) nanofibers (3D NFs), BP nanosheets, and hydroxyapatite (HA)-porous SiO2 nanoparticles. The 3D BP@HA NFs possess three advantages: i) stably connected pores allow the easy entrance of bone marrow-derived mesenchymal stem cells (BMSCs) into the interior of the 3D fibrous scaffolds for bone repair and osteogenesis; ii) plentiful nutrients in the NFs strongly improve osteogenic differentiation in the bone repair area; iii) the photothermal effect of fibrous scaffolds promotes the release of elements necessary for bone formation, thus achieving accelerated osteogenesis. Both in vitro and in vivo results demonstrated that the 3D BP@HA NFs, with the assistance of NIR laser, exhibited good performance in promoting bone regeneration. Furthermore, microfluidic technology makes it possible to obtain high-quality 3D BP@HA NFs with low costs, rapid processing, high throughput and mass production, greatly improving the prospects for clinical application. This is also the first BP-based bone scaffold platform that can self-supply Ca2+, which may be the blessedness for older patients with bone defects or patients with damaged bones as a result of calcium loss.

19.
Eye Contact Lens ; 47(1): 38-44, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32282398

RESUMEN

OBJECTIVES: To evaluate clinical changes after intense pulsed light and meibomian gland expression (IPL/MGX) treatment in meibomian gland dysfunction (MGD) patients, and to identify ideal candidates, and the therapeutic window, for IPL/MGX. METHODS: This retrospective study reviewed the medical records of 44 MGD patients (44 eyes). The IPL/MGX treatment was applied on the eyelids three times at intervals of 4 weeks. Age, sex, relevant ocular history, Standard Patient Evaluation of Eye Dryness (SPEED), Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), corneal fluorescein staining score (CFSS), meiboscore, meibomian gland loss score (MGLS), meibomian glands yielding secretion score (MGYSS), meibomian glands yielding clear secretion (MGYCS), and meibomian glands yielding liquid secretion (MGYLS) were analyzed. RESULTS: Standard Patient Evaluation of Eye Dryness, OSDI, TBUT, CFSS, MGYSS, MGYLS, and MGYCS were significantly improved after three IPL/MGX treatments, but the meiboscore and MGLS remained unchanged. In patients who had better treatment outcomes (improvement in MGYSS >7), younger age (36.0, 22.5 vs. 53.0, 25.0 years; P=0.012), a longer TBUT (8.0, 4.5 vs. 6.0, 3.0 sec; P=0.010), better meiboscore (1.0, 0.5 vs. 2.0, 1.0; P=0.012), and less gland loss (19.8%, 20.3% vs. 41.1%, 30.2%; P=0.008) before IPL/MGX were noted. Sex, relevant ocular history, SPEED, OSDI, MGYSS, MGYLS, and MGYCS before IPL/MGX showed no significant differences between patients with an improvement in MGYSS >7 versus those with an improvement of ≤7. Meibomian glands yielding secretion score changes in patients who had a meiboscore of 0 to 1 and MGYSS of 0 before IPL/MGX (12.0, 10.0) were significantly higher than those who had a meiboscore of 2 to 3 and MGYSS of 0 (6.5, 9.3; P=0.031), or a meiboscore of 0 to 1 and MGYSS >0 (5.0, 11.5; P=0.041). CONCLUSIONS: Improved dry eye symptoms, TBUT, corneal staining, and meibomian gland secretion were observed in MGD patients after IPL/MGX. Patients in the early stages of MGD maybe benefited most from IPL/MGX treatment.


Asunto(s)
Síndromes de Ojo Seco , Tratamiento de Luz Pulsada Intensa , Disfunción de la Glándula de Meibomio , Síndromes de Ojo Seco/terapia , Humanos , Glándulas Tarsales , Pronóstico , Estudios Retrospectivos , Lágrimas , Resultado del Tratamiento
20.
J Org Chem ; 85(4): 2838-2845, 2020 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-31904235

RESUMEN

A rhodium(III)-catalyzed decarboxylative aminomethylation of glycine derivatives with indoles bearing a pyrimidine directing group was developed via C-H activation, exclusively affording the corresponding aminomethylated products with C3 selectivity. In this synthetic protocol, easily available and resourceful arylglycines were utilized as aminomethyl functional moieties.

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