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1.
J Infect Dis ; 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37711050

RESUMO

Developing new adjuvants that can effectively induce both humoral and cellular immune responses while broadening the immune response is of great value. In this study, we aimed to develop GM-CSF- or IL-18-expressing single-stranded RNA (ssRNA) adjuvants based on the encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES) and tested their efficacy in combination with ovalbumin (OVA) or inactivated influenza vaccines. Notably, cytokine-expressing RNA adjuvants increased the expression of antigen-presenting cell activation markers. Specifically, GM-CSF-expressing RNA adjuvants increased CD4+T cell responses, while IL-18-expressing RNA adjuvants increased CD8+T cell responses in mice when combined with OVA. In addition, cytokine-expressing RNA adjuvants increased the frequency of polyclonal T cells in combination with the influenza vaccine and reduced the clinical illness scores and weight loss of mice after viral challenge. Collectively, our results suggest that cytokine-expressing RNA adjuvants can be applied to protein-based or inactivated vaccines to increase their efficacy.

2.
J Med Virol ; 95(12): e29309, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38100632

RESUMO

The E6 and E7 proteins of specific subtypes of human papillomavirus (HPV), including HPV 16 and 18, are highly associated with cervical cancer as they modulate cell cycle regulation. The aim of this study was to investigate the potential antitumor effects of a messenger RNA-HPV therapeutic vaccine (mHTV) containing nononcogenic E6 and E7 proteins. To achieve this, C57BL/6j mice were injected with the vaccine via both intramuscular and subcutaneous routes, and the resulting effects were evaluated. mHTV immunization markedly induced robust T cell-mediated immune responses and significantly suppressed tumor growth in both subcutaneous and orthotopic tumor-implanted mouse model, with a significant infiltration of immune cells into tumor tissues. Tumor retransplantation at day 62 postprimary vaccination completely halted progression in all mHTV-treated mice. Furthermore, tumor expansion was significantly reduced upon TC-1 transplantation 160 days after the last immunization. Immunization of rhesus monkeys with mHTV elicited promising immune responses. The immunogenicity of mHTV in nonhuman primates provides strong evidence for clinical application against HPV-related cancers in humans. All data suggest that mHTV can be used as both a therapeutic and prophylactic vaccine.


Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Animais , Camundongos , Papillomavirus Humano , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/prevenção & controle , RNA Mensageiro/genética , Proteínas E7 de Papillomavirus/genética , Camundongos Endogâmicos C57BL , Vacinação/métodos , Imunização , Neoplasias do Colo do Útero/prevenção & controle
3.
Opt Express ; 31(2): 2049-2060, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36785227

RESUMO

We proposed inverse-designed nanophotonic waveguide devices which have the desired optical responses in the wide band of 1450-1650 nm. The proposed devices have an ultra-compact size of just 1.5 µm × 3.0 µm and are designed on a silicon-on-insulator (SOI) waveguide platform. Individual nano-pixels with dimensions of 150 nm × 150 nm were made of either silicon or silicon dioxide, and the materials for the 200 total cells were determined using a trained deep neural network. While training the two networks, the hyperparameter optimization method was applied to make the training process efficient. We then fabricated the proposed devices using a CMOS-compatible fabrication process, and experimentally verified the fabricated device performance.

4.
Opt Express ; 31(6): 9935-9944, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37157557

RESUMO

Precise imaging in three-dimension (3D) is an essential technique for solid-state light detection and ranging (LiDAR). Among various solid-state LiDAR technologies, silicon (Si) optical phased array (OPA)-based LiDAR has the significant advantage of robust 3D imaging due to its high scanning speed, low power consumption, and compactness. Numerous techniques employing a Si OPA have utilized two-dimensional arrays or wavelength tuning for longitudinal scanning but the operation of those systems is restricted by additional requirements. Here, we demonstrate high-accuracy 3D imaging using a Si OPA with a tunable radiator. As we adapted a time-of-flight approach for distance measurement, we have developed an optical pulse modulator that allows a ranging accuracy of less than 2 cm. The implemented Si OPA is composed of an input grating coupler, multimode interferometers, electro-optic p-i-n phase shifters, and thermo-optic n-i-n tunable radiators. With this system, it is possible to attain a wide beam steering range of 45° in a transversal angle with a 0.7° divergence angle, and 10° in a longitudinal angle with a 0.6° divergence angle can be achieved using Si OPA. The character toy model was successfully imaged in three dimensions with a range resolution of 2 cm using the Si OPA. The further improvement of each component of the Si OPA will allow even more accurate 3D imaging over a longer distance.

5.
BMC Ophthalmol ; 23(1): 343, 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37537533

RESUMO

BACKGROUND: To evaluate the efficacy of 1% and 2% rebamipide clear solution in the treatment of dry eye disease (DED). METHODS: Two hundred twenty patients with DED were randomly assigned to one of three groups: the 1% rebamipide, 2% rebamipide, or placebo (eye drops containing the same ingredients, except for the active components). Each eye drop was instilled four times daily for 12 weeks. Changes in tear film break-up time (TBUT), corneal and conjunctival staining score, Schirmer 1 test, and the Ocular Surface Disease Index (OSDI) from baseline to 12-week visit between the study groups were compared for efficacy assessment. RESULTS: The mean age of study patients was 43.8±14.2 years. The 1% and 2% rebamipide groups showed greater improvement in TBUT (1.99±1.87 and 2.02±2.21 s) at 12 weeks from baseline than the placebo group (1.25±2.93 s). The 2% rebamipide group showed greater improvement in the corneal staining score (- 3.15±2.00) at 12 weeks from baseline than the placebo group (- 2.85±1.80). The 1% and 2% rebamipide groups showed improvement in Schirmer 1 test (1.27±3.86 and 1.50±4.14 mm) at 12 weeks of treatment, but not the placebo group (0.55±2.99 mm). Both the rebamipide groups and the placebo group showed significantly improved OSDI after treatment for 12 weeks; however, there was no significant difference among the three groups. CONCLUSIONS: 1% and 2% rebamipide clear solutions are an effective therapeutic option for improving TBUT and tear volume, and stabilizing the corneal staining score in DED.


Assuntos
Síndromes do Olho Seco , Quinolonas , Humanos , Adulto , Pessoa de Meia-Idade , Síndromes do Olho Seco/tratamento farmacológico , Quinolonas/uso terapêutico , Soluções Oftálmicas , Alanina/uso terapêutico , Lágrimas
6.
Int J Mol Sci ; 24(3)2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36768200

RESUMO

Skeletal muscle atrophy occurs when protein degradation exceeds protein synthesis and is associated with increased circulating glucocorticoid levels. Salvia plebeia R.Br. (SPR) has been used as herbal remedy for a variety of inflammatory diseases and has various biological actions such as antioxidant and anti-inflammatory activities. However, there are no reports on the effects of SPR and its bioactive components on muscle atrophy. Herein, we investigated the anti-atrophic effect of SPR and rosmarinic acid (RosA), a major compound of SPR, on dexamethasone (DEX)-induced skeletal muscle atrophy in C2C12 myotubes. Myotubes were treated with 10 µM DEX in the presence or absence of SPR or RosA at different concentrations for 24 h and subjected to immunocytochemistry, western blot, and measurements of ROS and ATP levels. SPR and RosA increased viability and inhibited protein degradation in DEX-treated C2C12 myotubes. In addition, RosA promoted the Akt/p70S6K/mTOR pathway and reduced ROS production, and apoptosis. Furthermore, the treatment of RosA significantly recovered SOD activity, autophagy activity, mitochondrial contents, and APT levels in DEX-treated myotubes. These findings suggest that SPR and RosA may provide protective effects against DEX-induced muscle atrophy and have promising potential as a nutraceutical remedy for the treatment of muscle weakness and atrophy.


Assuntos
Dexametasona , Fibras Musculares Esqueléticas , Humanos , Dexametasona/efeitos adversos , Dexametasona/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Fibras Musculares Esqueléticas/metabolismo , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Músculo Esquelético/metabolismo , Ácido Rosmarínico
7.
Int J Mol Sci ; 24(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37446091

RESUMO

The cornea, with its delicate structure, is vulnerable to damage from physical, chemical, and genetic factors. Corneal transplantation, including penetrating and lamellar keratoplasties, can restore the functions of the cornea in cases of severe damage. However, the process of corneal transplantation presents considerable obstacles, including a shortage of available donors, the risk of severe graft rejection, and potentially life-threatening complications. Over the past few decades, mesenchymal stem cell (MSC) therapy has become a novel alternative approach to corneal regeneration. Numerous studies have demonstrated the potential of MSCs to differentiate into different corneal cell types, such as keratocytes, epithelial cells, and endothelial cells. MSCs are considered a suitable candidate for corneal regeneration because of their promising therapeutic perspective and beneficial properties. MSCs compromise unique immunomodulation, anti-angiogenesis, and anti-inflammatory properties and secrete various growth factors, thus promoting corneal reconstruction. These effects in corneal engineering are mediated by MSCs differentiating into different lineages and paracrine action via exosomes. Early studies have proven the roles of MSC-derived exosomes in corneal regeneration by reducing inflammation, inhibiting neovascularization, and angiogenesis, and by promoting cell proliferation. This review highlights the contribution of MSCs and MSC-derived exosomes, their current usage status to overcome corneal disease, and their potential to restore different corneal layers as novel therapeutic agents. It also discusses feasible future possibilities, applications, challenges, and opportunities for future research in this field.


Assuntos
Doenças da Córnea , Exossomos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Exossomos/metabolismo , Células Endoteliais , Doenças da Córnea/terapia , Doenças da Córnea/metabolismo , Córnea , Células-Tronco Mesenquimais/metabolismo
8.
Cleft Palate Craniofac J ; 60(10): 1326-1330, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35473400

RESUMO

Patau syndrome (trisomy 13) is a severe disorder associated with multiple systemic defects. Patau syndrome is commonly associated with ocular abnormalities but rarely associated with congenital glaucoma. To obtain a better surgical view, palatoplasty requires neck extension during surgery. The intraocular pressure (IOP) of patients with Patau syndrome can increase owing to the neck extension position while undergoing palatoplasty, particularly in those with congenital glaucoma. Here, we describe a case with increased IOP measured using a rebound tonometer during palatoplasty in a pediatric patient with Patau syndrome and congenital glaucoma. This case shows that it may be important to reduce the degree of neck extension and shorten the operation time to minimize any increase in the IOP during palatoplasty in pediatric patients with Patau syndrome accompanied by congenital glaucoma.


Assuntos
Fissura Palatina , Glaucoma , Humanos , Criança , Pressão Intraocular , Síndrome da Trissomia do Cromossomo 13 , Tonometria Ocular , Glaucoma/cirurgia , Glaucoma/congênito , Fissura Palatina/cirurgia
9.
Int Ophthalmol ; 43(1): 73-82, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35794405

RESUMO

PURPOSE: We investigated the subjective and objective outcome after intense pulsed light (IPL) treatment and meibomian gland expression on the upper and lower eyelids compared with those after IPL treatment on the lower eyelid alone in patients with moderate-to-severe meibomian gland dysfunction (MGD). METHODS: Patients who underwent four IPL treatment sessions with meibomian gland expression were divided into upper and lower treatment group and conventional treatment group treated with lower eyelid alone. All patients underwent an ophthalmologic examination and answered a symptom questionnaire before the first treatment and 1 month after the last treatment. An ophthalmologic examination included tear break-up time (TBUT), fluorescein staining score, Schirmer's test, matrix metalloproteinase-9 (MMP-9), meibum grade, color, consistency, and lid margin telangiectasia. Additionally, visual acuity and adverse effects were checked on every visit. RESULTS: Of 115 patients, 75 in the upper and lower treatment group and 40 in the conventional treatment group were included. TBUT, fluorescein staining score, subjective symptom, and meibum grade were significantly improved in both groups. Additionally, meibum color and consistency of upper and lower eyelids significantly decreased post-treatment in both groups. The lid margin telangiectasia of the upper and lower eyelids significantly decreased post-treatment in the upper and lower treatment group. MMP-9 positivity and grading scores significantly decreased post-treatment in both groups, and no severe adverse effects occurred during the follow-up period. CONCLUSION: Additional IPL treatment on the upper eyelid using a protective device was proven safe and provided an additive improvement in treating moderate-to-severe MGD.


Assuntos
Síndromes do Olho Seco , Disfunção da Glândula Tarsal , Humanos , Disfunção da Glândula Tarsal/terapia , Metaloproteinase 9 da Matriz , Glândulas Tarsais , Fototerapia , Lágrimas , Fluoresceínas , Síndromes do Olho Seco/terapia
10.
Opt Lett ; 47(19): 4857-4860, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36181135

RESUMO

We demonstrate beam steering using a passive silica optical phased array (OPA) with wavelength tuning. In this OPA, a constant path difference is built up to assign sequential phase delays with a wavelength variation in arrayed waveguide channels for the beam steering. From as-fabricated 1 × 101 passive silica OPA chips, we successfully achieved beam forming with a transversal divergence angle of 0.57° at a 1548.3-nm wavelength and also beam steering of 15.4° by wavelength tuning of 30.7 nm. Combining a cylindrical lens in front of the end-fire radiators, the longitudinal divergence angle could be reduced from 13.0° to 0.42°. The side-mode suppression ratio of the beam was 10.3 dB at the center position. Through simulation, we analyzed the effects of the phase errors on the beam quality, due to the effective index fluctuation of the waveguide channels, and provided an allowable error range to attain beam forming from the passive OPA.

11.
Opt Lett ; 47(5): 1165, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35230317

RESUMO

This publisher's note contains a correction to Opt. Lett. 47, 714 (2022).

12.
Opt Lett ; 47(3): 714-717, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35103715

RESUMO

We developed an inter-chip optical link using direct optical wire (DOW) bonding by open-to-air polymerization. An arch-shaped wire was drawn from a tip in a similar way to a metal wire, but the wire was formed from a polymer solution that solidified in the air during wiring. The DOW bonding was examined for silicon photonic chips where grating couplers are integrated for input/output coupling. Cone-shaped studs were formed at the ends of the wire, and their geometry was optimized using finite-difference time-domain simulation to give a mode conversion function. Although the polymer wire had a multimode scale of 7 µm, the wire bonding between the grating couplers showed a relatively low insertion loss of 5.8 dB at a wavelength of 1590 nm compared to a conventional connection using single-mode fiber blocks. It also showed a larger wavelength tolerance within the range of ∼1520-1590 nm. DOW bonding between a grating coupler and a single-mode fiber were also examined to verify the feasibility of out-of-plane connection with edge-coupling devices. The grating-to-fiber wire link also exhibited a large wavelength tolerance.

13.
BMC Cancer ; 22(1): 1041, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36199130

RESUMO

BACKGROUND: Adjuvant therapies such as radiation therapy, chemotherapy, and immunotherapy are usually given after cancer surgery to improve the survival of cancer patients. However, despite advances in several adjuvant therapies, they are still limited in the prevention of recurrences. METHODS: We evaluated the immunological effects of RNA-based adjuvants in a murine melanoma model. Single-stranded RNA (ssRNA) were constructed based on the cricket paralysis virus (CrPV) internal ribosome entry site (IRES). Populations of immune cells in bone marrow cells and lymph node cells following immunization with CrPVIRES-ssRNA were determined using flow cytometry. Activated cytokine levels were measured using ELISA and ELISpot. The tumor protection efficacy of CrPVIRES-ssRNA was analyzed based on any reduction in tumor size or weight, and overall survival. RESULTS: CrPVIRES-ssRNA treatment stimulated antigen-presenting cells in the drain lymph nodes associated with activated antigen-specific dendritic cells. Next, we evaluated the expression of CD40, CD86, and XCR1, showing that immunization with CrPVIRES-ssRNA enhanced antigen presentation by CD8a+ conventional dendritic cell 1 (cDC1), as well as activated antigen-specific CD8 T cells. In addition, CrPVIRES-ssRNA treatment markedly increased the frequency of antigen-specific CD8 T cells and interferon-gamma (IFN-γ) producing cells, which promoted immune responses and reduced tumor burden in melanoma-bearing mice. CONCLUSIONS: This study provides evidence that the CrPVIRES-ssRNA adjuvant has potential for use in therapeutic cancer vaccines. Moreover, CrPVIRES-ssRNA possesses protective effects on various cancer cell models.


Assuntos
Vacinas Anticâncer , Melanoma , Adjuvantes Imunológicos , Animais , Vacinas Anticâncer/uso terapêutico , Imunoterapia , Interferon gama/genética , Sítios Internos de Entrada Ribossomal , Melanoma/genética , Melanoma/terapia , Camundongos , RNA Viral/genética
14.
Microbiol Immunol ; 66(11): 529-537, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35979884

RESUMO

Following the development of various types of vaccines, the use of adjuvants to boost vaccine efficacy has become a focus of research. Aluminum hydroxide (alum), the most commonly used adjuvant, induces a certain immune response and ensures safety in human trials. However, alum mainly induces only a Th2 response; its Th1 response is weak. Thus, we previously developed a single-stranded ribose nucleic acid (ssRNA) adjuvant that induces a Th1 response through toll-like receptors. Here, we explored whether 10-valent human papilloma virus (HPV)-like particle (VLP) vaccine formulated with ssRNA adjuvant and alum helped to enhance immune response and maintained memory response. The mice were immunized intramuscularly twice at 2 week intervals and were inoculated 4 days after the second boost (after about 1 year). The antibody response and T cell activation were measured by Elispot, ELISA using harvested serum and splenocytes. The 10-valent HPV VLP vaccine formulated with ssRNA adjuvant and alum increased the antigen-specific immune response more than alum used alone. It increased each type-specific IgG1/IgG2a titer, and antigen-specific IFN-γ cells. Furthermore, the ssRNA adjuvant with alum induced memory response. In memory response, each type-specific IgG1/IgG2c, IFN-γ, and IL-6 cytokine, and neutralizing antibodies were increased by the ssRNA adjuvant with alum. Overall, the ssRNA adjuvant with alum induced memory responses and balanced Th1/Th2 responses. The ssRNA adjuvant and alum may help to enhance prophylactic vaccine efficacy.


Assuntos
Alphapapillomavirus , Papiloma , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Vacinas de Partículas Semelhantes a Vírus , Humanos , Camundongos , Animais , Papillomaviridae , Infecções por Papillomavirus/prevenção & controle , Adjuvantes Imunológicos/farmacologia , Imunoglobulina G , RNA , Camundongos Endogâmicos BALB C
15.
Graefes Arch Clin Exp Ophthalmol ; 260(3): 885-891, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34625847

RESUMO

PURPOSE: To compare the anti-inflammatory activity of preoperatively applied eyedrops, as determined by cytokine concentrations in aqueous humor collected during surgery in patients undergoing femtosecond laser-assisted cataract surgery. METHODS: A total of 120 patients undergoing femtosecond laser-assisted cataract surgery were randomly assigned to four groups of 30 patients each. Groups were administered 0.1% fluorometholone eyedrops, 0.45% ketorolac tromethamine eyedrops, both 0.1% fluorometholone and 0.45% ketorolac tromethamine eyedrops, or no eyedrops. Eyedrops were instilled 1 h, 20 min, and just before surgery. After anterior capsulotomy and nuclear fragmentation using a femtosecond laser, 0.1 cc aqueous humor was obtained using a needle and syringe. Cytokine and prostaglandin E2 (PGE2) concentrations were quantitatively determined. RESULTS: The 120 patients included 59 men and 61 women, of mean age 65.02 years. The mean interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations after treatment did not differ significantly in the four groups. The average interleukin-8 (IL-8) concentrations were significantly lower in the fluorometholone (4.80 pg/mL), ketorolac tromethamine (4.84 pg/mL), and fluorometholone + ketorolac tromethamine (4.68 pg/mL) groups than in the control group (6.83 pg/mL). Furthermore, the average PGE2 concentrations were significantly lower in the ketorolac tromethamine (270.04 pg/mL) and fluorometholone + ketorolac tromethamine (239.00 pg/mL) groups, but not in the fluorometholone (393.16 pg/mL) group, than in the control group (472.36 pg/mL). CONCLUSION: Preoperative fluorometholone instillation reduced IL-8, and ketorolac tromethamine instillation reduced IL-8 and PGE2, in aqueous humor of patients undergoing femtosecond laser surgery, with the combination of both eyedrops being more effective than either alone. TRIAL REGISTRATION: KCT0005717.


Assuntos
Humor Aquoso , Catarata , Idoso , Anti-Inflamatórios não Esteroides , Citocinas , Feminino , Humanos , Lasers , Masculino , Soluções Oftálmicas
16.
Lasers Med Sci ; 37(7): 2907-2915, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35476305

RESUMO

This study aimed to evaluate the safety and efficacy of a low-level radiofrequency thermal treatment in an obstructive MGD rabbit model. Meibomian gland orifices of the central two-thirds of the upper and lower eyelid margins were coagulated twice at 2-week intervals using a 5-MHz high-frequency electrosurgical unit. Sixteen eyes of eight rabbits were treated with one session of radiofrequency thermal treatment (radiofrequency group) and eight eyes of four rabbits were followed up without treatment (control group). Lid margin abnormality and corneal staining scores, histologic examination of the eyelids and meibombian gland, and meibography imaging were evaluated just before and 4 weeks after meibomian gland orifice closure and 4 weeks after radiofrequency thermal treatment. Lid margin abnormality score improved significantly for the upper and lower eyelids after radiofrequency thermal treatment (P < 0.001 for both eyelids). Corneal staining score remained unchanged in the radiofrequency group; however, the control group saw an increase at final follow-up. There was a significant improvement to almost baseline levels in the mean area of secretory acini in the radiofrequency group (P = 0.004). Additionally, meibography indicated an improvement in meibomian gland loss rate in the radiofrequency group. Low-level radiofrequency thermal treatment heating the inner and outer eyelid surfaces is safe and effective to treat obstructive MGD in a rabbit animal model of MGD.


Assuntos
Doenças Palpebrais , Disfunção da Glândula Tarsal , Animais , Modelos Animais de Doenças , Doenças Palpebrais/diagnóstico , Doenças Palpebrais/patologia , Glândulas Tarsais/patologia , Coelhos
17.
Lasers Med Sci ; 37(4): 2185-2192, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35022869

RESUMO

Evaluate the improvement in clinical signs and symptoms in patients with moderate-to-severe meibomian gland dysfunction (MGD) treated with intense pulsed light (IPL) using an acne filter. A retrospective chart review of 70 eyes of 35 patients with moderate-to-severe MGD treated with IPL using the acne filter was performed. IPL treatment was administered using the acne filter four times at 2- to 3-week intervals to upper and lower eyelids. We evaluated tear break-up time (TBUT), matrix metalloproteinase (MMP)-9, Sjögren's International Clinical Collaborative Alliance (SICCA) staining score, and Oxford staining grade. We performed Schirmer's test I without topical anesthesia, slit-lamp microscopic examination of lid margin and meibomian gland, and patient's symptom score assessment and evaluated the incidence of adverse effects in the ocular and periocular areas at baseline and 30 days after the final treatment. Significant improvements (P < 0.001) were observed in TBUT, SICCA staining score, Oxford staining grade, quality of meibum, consistency of meibum, lid margin telangiectasia, MGD grade, and patient's symptom scores after acne filter IPL treatment. Furthermore, the positivity (100 to 71.43%, P = 0.002) and level (2.43 ± 0.98 to 1.14 ± 0.78, P < 0.001) of MMP-9 significantly decreased after treatment. However, there was no significant improvement in Schirmer's test I (P = 0.224). No systemic or regional adverse effects were observed in any patient. IPL treatment using the acne filter is an effective and safe therapeutic modality for treating moderate-to-severe MGD, especially for lid margin telangiectasia and MMP-9.


Assuntos
Acne Vulgar , Doenças Palpebrais , Disfunção da Glândula Tarsal , Telangiectasia , Acne Vulgar/complicações , Acne Vulgar/terapia , Doenças Palpebrais/terapia , Humanos , Metaloproteinase 9 da Matriz , Glândulas Tarsais , Estudos Retrospectivos , Telangiectasia/terapia
18.
Int J Mol Sci ; 23(23)2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36499735

RESUMO

Because of the limited differentiation capacity of human corneal endothelial cells (CECs), stem cells have emerged as a potential remedy for corneal endothelial dysfunction (CED). This study aimed to demonstrate the differentiation of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) into CECs and to investigate the efficacy of MSC-induced CEC injection into the anterior chamber in a rabbit model of CED. Human UC-MSCs were differentiated into CECs using medium containing glycogen synthase kinase 3ß inhibitor and two types of Rho-associated protein kinase inhibitors. In the MSC-induced CECs, CEC-specific proteins were identified through immunohistochemistry and changes in CEC-specific gene expressions over time were confirmed through quantitative RT-PCR. When MSC-induced CECs were injected into a rabbit model of CED, corneal opacity and neovascularization were improved compared with the non-transplanted control or MSC injection group. We also confirmed that MSC-induced CECs were well engrafted as evidenced by human mitochondrial DNA in the central cornea of an animal model. Therefore, we demonstrated the differentiation of UC-MSCs into CECs in vitro and demonstrated the clinical efficacy of MSC-induced CEC injection, providing in vivo evidence that MSC-induced CECs have potential as a treatment option for CED.


Assuntos
Células Endoteliais , Células-Tronco Mesenquimais , Animais , Humanos , Coelhos , Cordão Umbilical , Células-Tronco Mesenquimais/metabolismo , Endotélio Corneano , Diferenciação Celular/genética
19.
Int J Mol Sci ; 24(1)2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36614165

RESUMO

Corneal endothelial cells (CECs) do not proliferate or recover after illness or injury, resulting in decreased cell density and loss of pump/barrier function. Considering the shortage of donor cornea, it is vital to establish robust methods to generate CECs from induced pluripotent stem cells (iPSCs). We investigated the efficacy and safety of transplantation of iPSC-derived CECs into a corneal endothelial dysfunction (CED) rabbit model. iPSCs were generated from human fibroblasts. We characterized iPSCs by demonstrating the gene expression of the PSC markers OCT4, SOX2, TRA-1-60, and NANOG, teratoma formation, and differentiation into three germ layers. Differentiation of iPSCs into CECs was induced via neural crest cell (NCC) induction. CEC markers were detected using immunofluorescence and gene expression was analyzed using quantitative real-time PCR (qRT-PCR). After culturing iPSC-derived NCCs, we found the expression of zona occludens-1 (ZO-1) and Na+/K+ ATPase and a hexagonal morphology. ATP1A1, COL8A1, and AQP1 mRNA expression was higher in iPSC-derived CECs than in iPSCs and NCCs. We performed an injection of iPSC-derived CECs into the anterior chamber of a CED rabbit model and found improved levels of corneal transparency. We also found increased numbers of ZO-1- and ATP1A1-positive cells in rabbit corneas in the iPSC-derived CEC transplantation group. Usage of the coating material vitronectin (VTN) and fasudil resulted in good levels of CEC marker expression, demonstrated with Western blotting and immunocytochemistry. Combination of the VTN coating material and fasudil, instead of FNC mixture and Y27632, afforded the best results in terms of CEC differentiation's in vitro and in vivo efficacy. Successful transplantation of CEC-like cells into a CED animal model confirms the therapeutic efficacy of these cells, demonstrated by the restoration of corneal clarity. Our results suggest that iPSC-derived CECs can be a promising cellular resource for the treatment of CED.


Assuntos
Células-Tronco Pluripotentes Induzidas , Animais , Humanos , Coelhos , Endotélio Corneano , Células Endoteliais/metabolismo , Córnea , Diferenciação Celular , Células Cultivadas
20.
Exp Eye Res ; 202: 108319, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33080303

RESUMO

The purpose of this study was to investigate whether and how topical nerve growth factor (NGF) attenuates streptozotocin (STZ)-induced diabetic cataracts in vivo. Rats were randomly divided into three groups, including the normal control rat group, STZ-induced diabetic cataract rat group (DM group), and STZ-induced diabetic cataract rat group treated with 200 µg/mL recombinant rat ß-NGF (DM + NGF group). Cataract formation was evaluated by portable slit lamp biomicroscopy following pupil dilation at 8 weeks. The expression levels of NGF, aldose reductase (AR), and Na+/K+-ATPase in the lens epithelial cells (LECs) of the three groups were measured in the presence or absence of topical NGF. TUNEL-positive LECs were quantified to determine if hyperglycemia caused LEC apoptosis. At 8 weeks, the mean cataract score in the control group was significantly lower than that in DM and DM + NGF groups, and the score in the DM + NGF group was significantly lower than that in the DM group. At the equatorial zone and anterior central zone of lens, NGF and Na+/K+-ATPase expression levels were significantly decreased in the DM group; however, they were partially restored in the DM + NGF group. At the equatorial zone and anterior central zone of lens, AR expression and TUNEL-positive apoptotic LECs were significantly increased in the DM group compared with the control group, however, they were significantly decreased in the DM + NGF group. In conclusion, topical NGF could delay the progression of diabetic cataracts by attenuating polyol pathway activation and increasing Na+/K+-ATPase protein levels.


Assuntos
Catarata/prevenção & controle , Diabetes Mellitus Experimental/prevenção & controle , Fator de Crescimento Neural/uso terapêutico , ATPase Trocadora de Sódio-Potássio/metabolismo , Administração Oftálmica , Animais , Apoptose , Catarata/induzido quimicamente , Catarata/enzimologia , Catarata/patologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Experimental/patologia , Hiperglicemia/metabolismo , Marcação In Situ das Extremidades Cortadas , Masculino , Soluções Oftálmicas , Polímeros , Ratos , Ratos Sprague-Dawley , Estreptozocina/toxicidade , Regulação para Cima
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