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Versican is a chondroitin sulfate proteoglycan (CSPG), which deposits in perineurium as a physical barrier and prevents the growth of axons out of the fascial boundary. Several studies have indicated that the chondroitin sulfate (CS) chains on versican have several possible functions beyond the physical barrier, including the ability to stabilize versican core protein in the extracellular matrix. As chondroitin sulfate synthase 1 (Chsy1) is a crucial enzyme for CS elongation, we hypothesized that in vivo knockdown of Chsy1 at peripheral nerve lesion site may decrease CS and versican accumulation, and result in accelerating neurite regeneration. In the present study, end-to-side neurorrhaphy (ESN) in Wistar rats was used as an in vivo model of peripheral nerve injury to evaluate nerve regeneration after surgical intervention. The distribution and expression of versican and Chsy1 in regenerating axons after ESN was studied using confocal microscopy and western blotting. Chsy1 was silenced at the nerve lesion (surgical) site using in vivo siRNA transfection. The results indicated that Chsy1 was successfully silenced in nerve tissue, and its downregulation was associated with functional recovery of compound muscle action potential. Silencing of Chsy1 also decreased the accumulation of versican core protein, suggesting that transient treating of Chsy1-siRNA may be an alternative and an effective strategy to promote injured peripheral nerve regeneration.
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Sulfatos de Condroitina , Versicanas , Ratos , Animais , Versicanas/genética , Sulfatos de Condroitina/farmacologia , Ratos Wistar , Axônios/metabolismo , Regeneração Nervosa , RNA Interferente Pequeno/farmacologiaRESUMO
Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium iodate (NaIO3) has been reported to induce AMD-like retinal pathology in mice. We established a mouse model for AMD to evaluate the effects of quercetin on NaIO3-induced retinal apoptosis, and to investigate the pertinent underlying mechanisms. Our in vitro results indicated that quercetin protected human retinal pigment epithelium (ARPE-19) cells from NaIO3-induced apoptosis by inhibiting reactive oxygen species production and loss of mitochondrial membrane potential as detected by Annexin V-FITC/PI flow cytometry. We also evaluated the relative expression of proteins in the apoptosis pathway. Quercetin downregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP and upregulated the expression of Bcl-2 through reduced PI3K and pAKT expressions. Furthermore, our in vivo results indicated that quercetin improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer, whereas the expression of caspase-3 was inhibited. Taken together, these results demonstrate that quercetin could protect retinal pigment epithelium and the retina from NaIO3-induced cell apoptosis via reactive oxygen species-mediated mitochondrial dysfunction, involving the PI3K/AKT signaling pathway. This suggests that quercetin has the potential to prevent and delay AMD and other retinal diseases involving NaIO3-mediated apoptosis.
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Degeneração Macular/tratamento farmacológico , Quercetina/farmacologia , Retina/efeitos dos fármacos , Doenças Retinianas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Apoptose/genética , Caspase 3/genética , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Iodatos/toxicidade , Degeneração Macular/genética , Degeneração Macular/patologia , Mitocôndrias/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/genética , Espécies Reativas de Oxigênio/metabolismo , Retina/patologia , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/genética , Doenças Retinianas/patologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/crescimento & desenvolvimento , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/genéticaRESUMO
PURPOSE: In normal tension glaucoma (NTG), factors other than elevated intraocular pressure are likely to have a role in the pathogenesis of optic neuropathy. Recent studies of glaucoma or retinal ganglion cells (RGCs) reveal that the cytokine interleukin-6 (IL-6) is linked to the pathogenesis of glaucoma and may regulate RGC survival or death. The IL-6 (-174) G allele has also been shown to increase the IL-6 protein. We hypothesized that the IL-6 (-174) polymorphism may be a predisposing genetic factor affecting the severity of glaucoma. The aim of the present study was to evaluate the IL-6 polymorphism and serum IL-6 levels as a potential risk factor related to the severity of NTG. METHODS: A total of 256 subjects with NTG in the Chinese population were enrolled. The patients were genotyped for the IL-6 (-174) C/G polymorphism. Genomic DNA was amplified by a polymerase chain reaction, followed by the enzymatic restriction fragment length polymorphism technique. Serum IL-6 levels were measured by ELISA. Patient age at diagnosis, cup/disc (C/D) ratio, rim area (RA), retinal nerve fiber layer (RNFL) thickness, and visual field (VF) were analyzed. The associations between genotypes of IL-6 (-174) C/G and the clinical parameters were calculated using a logistic regression. RESULTS: The IL-6 (-174) GC genotype in NTG patients was significantly associated with a smaller C/D ratio (p = 0.04), larger RA (p = 0.04), and thicker RNFL (p = 0.05) compared with IL-6 (-174) GG patients. The allele frequency of IL-6 (-174) C was significantly higher in the NTG patients at an early-moderate stage than at an advanced stage according to the C/D ratio (OR 0.55; 95% CI 0.31-0.99). Pattern standard deviation of VF was borderline lower in IL-6 (-174) GC patients (p = 0.06), and serum IL-6 levels were borderline higher in advanced stages than in early-moderate stages (7.66 ± 3.22 vs. 4.46 ± 3.83 pg/mL; p = 0.06). CONCLUSION: The IL-6 (-174) GC genotype is associated with a smaller C/D ratio, larger RA, and thicker RNFL compared with IL-6 (-174) GG in NTG patients. We found that the IL-6 (-174) G/C polymorphism and serum IL-6 levels may be associated with the severity of NTG.
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DNA/genética , Interleucina-6/genética , Pressão Intraocular , Glaucoma de Baixa Tensão/genética , Disco Óptico/diagnóstico por imagem , Polimorfismo Genético , Ensaio de Imunoadsorção Enzimática , Seguimentos , Frequência do Gene , Genótipo , Humanos , Interleucina-6/sangue , Glaucoma de Baixa Tensão/sangue , Glaucoma de Baixa Tensão/diagnóstico , Reação em Cadeia da Polimerase , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia de Coerência ÓpticaRESUMO
Caspofungin exhibits potent antifungal activities against Candida and Aspergillus species. The elimination rate and retinal toxicity of caspofungin were determined in this study to assess its pharmacokinetics and safety in the treatment of fungal endophthalmitis. Intravitreal injections of 50 µg/0.1 ml of caspofungin were administered to rabbits. Levels of caspofungin in the vitreous and aqueous humors were determined using high-performance liquid chromatography (HPLC) at selected time intervals (10 min and 1, 2, 4, 8, 16, 24, and 48 h), and the half-lives were calculated. Eyes were intravitreally injected with caspofungin to obtain concentrations of 10 µg/ml, 50 µg/ml, 100 µg/ml, and 200 µg/ml. Electroretinograms were recorded 4 weeks after injections, and the injected eyes were examined histologically. The concentrations of intravitreal caspofungin at various time points exhibited an exponential decay with a half-life of 6.28 h. The mean vitreous concentration was 6.06 ± 1.76 µg/ml 1 h after intravitreal injection, and this declined to 0.47 ± 0.15 µg/ml at 24 h. The mean aqueous concentration showed undetectable levels at all time points. There were no statistical differences in scotopic a-wave and b-wave responses between control eyes and caspofungin-injected eyes. No focal necrosis or other abnormality in retinal histology was observed. Intravitreal caspofungin injection may be considered to be an alternative treatment for fungal endophthalmitis based on its antifungal activity, lower retinal toxicity, and lower elimination rate in the vitreous. More clinical data are needed to determine its potential role as primary therapy for fungal endophthalmitis.
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Antifúngicos/farmacocinética , Equinocandinas/farmacocinética , Endoftalmite/tratamento farmacológico , Infecções Oculares Fúngicas/tratamento farmacológico , Retina/efeitos dos fármacos , Animais , Antifúngicos/farmacologia , Humor Aquoso/efeitos dos fármacos , Humor Aquoso/microbiologia , Caspofungina , Adaptação à Escuridão , Equinocandinas/farmacologia , Eletrorretinografia , Endoftalmite/microbiologia , Endoftalmite/patologia , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/patologia , Meia-Vida , Injeções Intravítreas , Lipopeptídeos , Coelhos , Retina/microbiologia , Retina/patologia , Corpo Vítreo/efeitos dos fármacos , Corpo Vítreo/microbiologia , Corpo Vítreo/patologiaRESUMO
PURPOSE: To examine the safety and efficacy of soft multifocal contact lenses on slowing the rate of myopia progression. METHODS: A prospective, randomized, double-masked clinical trial was conducted including 115 children (55 boys and 60 girls) aged 8 to 15 years. Children were assigned to wear one of two daily disposable soft contact lens designs; a multifocal design (Pegavision) or a dual-focus design (MiSight, Coopervision) in both eyes for at least 8 h per day for one year. All contact lenses were replaced on a daily basis. Measurements were obtained using a logMAR vision meter, including objective refraction, handheld retinoscopy, high (96 %) and low (12 %) contrast sensitivity, and distance and near visual acuity. Axial length was measured every 6 months. RESULTS: After one year, the spherical equivalent refractive error and axial length of the experimental group (Pegavision) increased by -0.50 ± 0.48 D and 0.24 ± 0.16 mm, respectively, in the right eye and -0.47 ± 0.37 D and 0.23 ± 0.16 mm, respectively, in the left eye. The spherical equivalent refractive error and axial length of the control group (MiSight) increased by -0.48 ± 0.47 D and 0.22 ± 0.13 mm, respectively, in the right eye and by -0.50 ± 0.44 D and 0.23 ± 0.14 mm, respectively, in the left eye, with no significant differences observed between the two lens types. CONCLUSIONS: The one-year results from this clinical trial show that the multifocal soft contact lenses used in the experimental group have a similar myopia control efficacy with respect to spherical equivalent refraction and axial length elongation as a commercially available dual focus soft contact lens design.
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Identification of an early biomarker and effective testing device to differentiate dry eye disease secondary to autoimmune disease (Sjögren's syndrome dry eye disease) from non-Sjögren's dry eye disease are prerequisites for appropriate treatment. We aimed to demonstrate the capacity of a new photo-detection device to evaluate tear lactoferrin levels as a tool for differentiating systemic conditions associated with dry eye disease. Patients with non-Sjögren's and Sjögren's syndrome dry eye disease (n = 54 and n = 52, respectively) and controls (n = 11) were enrolled. All participants completed the Ocular Surface Disease Index questionnaire. Tear collection was performed with Schirmer test, and tear break-up time was examined using a slit lamp. Tear lactoferrin was evaluated using our newly developed photo-detection device. The average lactoferrin concentration was significantly lower in samples from patients with non-Sjögren's dry eye disease (0.337 ± 0.227 mg/mL, n = 54) and Sjögren's syndrome dry eye disease (0.087 ± 0.010 mg/mL, n = 52) than in control samples (1.272 ± 0.54 mg/mL, n = 11) (p < 0.0001). Further, lactoferrin levels were lower in patients with Sjögren's syndrome dry eye disease than in those with non-Sjögren's dry eye disease (p < 0.001). Our cost-effective, antibody-free, highly sensitive photo-detection device for evaluating tear lactoferrin levels can assist ophthalmologists in differentiating different types of dry eye diseases.
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Síndromes do Olho Seco , Lactoferrina , Síndrome de Sjogren , Lágrimas , Lactoferrina/análise , Lactoferrina/metabolismo , Humanos , Lágrimas/química , Lágrimas/metabolismo , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/metabolismo , Feminino , Pessoa de Meia-Idade , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/metabolismo , Masculino , Adulto , Biomarcadores/análise , Diagnóstico Diferencial , Idoso , FluorescênciaRESUMO
Exosomes are membranous structures measuring between 40-120 nm that are secreted by various cells of the human body into the body fluid system. Exosomes contain proteins, mRNA, miRNA, and signaling molecules, and physiologically they assist in the intercellular transport of proteins and RNA molecules. In this study, we used an immunoaffinity filter paper platform combined with scanning electron microscopy and microfluidic systems to detect the size of exosomes within the aqueous humor. Eight aqueous humor samples showed three distinct sizes of exosomes that were significantly different on scanning electron microscopy(P < 0.01). We further used nanoparticle tracking analysis to assess the size distribution of exosomes within the aqueous humor. We found significantly different distributions of exosomes between patients with three different ocular diseases and patients with normal cataracts as controls. An obvious peak of exomeres(size around 35 nm)was found in the patients with central retinal vein occlusion and vitreous hemorrhage. Flare-ups of large exosomes(size 90-120 nm)were found in the patients with the inflammatory ocular disease pars planitis. No obvious peaks in exomeres or large exosomes were found in the control group. There was a high association between the distribution of exosomes and the pathogenesis of ocular diseases. After intravitreal anti-vascular endothelial growth factor treatment, the aqueous humor from the patients with neovascular diseases showed a significant reduction in exosomes in nanoparticle tracking analysis. These findings suggest that at least three distinct sizes of exosomes exist in the aqueous humor:(1)exomeres:<35 nm;(2)small exosomes:60-80 nm; and (3)large exosomes:90-120 nm. Different sizes of exosomes may have different implications in normal or diseased eyes.
Three different sized exosomes were identified in aqueous humor.The distribution of exosome size was significantly different between the patients with inflammatory and neovascularization retinal diseases.After intravitreal anti-vascular endothelial growth factor treatment, the aqueous humor from patients with neovascular diseases showed a significant reduction in exosomes in nanoparticle tracking analysis.
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Catarata , Exossomos , MicroRNAs , Doenças Retinianas , Humanos , Exossomos/genética , Doenças Retinianas/genética , Doenças Retinianas/metabolismo , MicroRNAs/metabolismo , Humor Aquoso/metabolismo , Catarata/genética , Catarata/metabolismoRESUMO
AIMS: Evidence showed that SGLT2 inhibitors have greater protective effects against retinal diseases compared to other hypoglycemic agents. Thus, we explore the association between SGLT2 inhibitor usage and macular degeneration (MD) in Taiwanese patients with diabetes. METHODS: The National Health Insurance (NHI) program's claim data are released as the National Health Insurance Research Database (NHIRD). This database covers more than 99% of the residents in Taiwan. We included data on patients who were newly diagnosed with type 2 diabetes mellitus (ICD-9-CM: 250, exclude 250.1x; ICD-10-CM: E11), with an age at diagnosis of over 20 years as our study population. Patients who received (sodium-glucose cotransporter 2 inhibitor) SGLT2i (ATC code: A10BK) over 90 days in 2016-2019 were defined as the SGLT2i cohort. Conversely, patients who did never received SGLT2i were defined as the non-SGLT2i cohort. The exclusion criteria were having MD before the index date, receiving SGLT2i within 1-89 days, and missing data on sex, age, or days of SGLT2i usage. Two cohorts were matched by 1:1 propensity score matching, which was based on age, sex, payroll bracket grade, urbanization, comorbidities, and medications. RESULTS: Compared to non-SGLT2i cohort, patients who received SGLT2i had a significantly lower risk of MD (adjusted hazard ratio = 0.70, 95%CI = 0.66-0.75). CONCLUSIONS: We found that SGLT2is has a strong protective effect against MD in patients with diabetes. SGLT2is may have benefits beyond glycemic control in patients with DR. However, additional clinical and experimental studies are required.
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Polyethylene glycol (PEG) at various molecular weights (MWs) has been regarded as a wonder molecule in biomedical applications. For instance, PEG serves as a unique moiety for pegylation of "biobetter" drug development, PEG provides controlled-release and preserved activity of biologics, and PEG modified surface works as an antibiofouling surface. The primary characteristics of PEG molecules used in relevant applications have been attributed mainly to the hydration behavior in aqueous solutions. However, the effects on the solvation of solutes in solution caused by presenting PEG molecules as a cosolvent, as well as the thermodynamics aspect of the hydration behavior of PEG in solution, have not been well documented. The solvation behavior of solutes, such as protein, with PEG as a cosolvent, indicates the success of PEG applications, such as biofouling and controlled release. In this investigation, we examined the effects of a buffer solution containing PEG molecules on the solution behavior of solute and the interactions between solid surfaces with solutes. We adapted the study by selecting a lysozyme as a solute in a buffer solution with either ammonium sulfate (kosmotrope) or sodium chloride (chaotrope) and anionic resin (SP-Sepharose) as solid surfaces. The experiments primarily involved binding equilibrium measurements and thermodynamics analysis. The results revealed that, in both saline buffers, adding PEG increases the binding affinity between the lysozyme and the resin, similar to kosmotropic salt in the examined salt concentrations. The thermodynamics analyses involving microcalorimetric measurements show that the bindings are mainly driven by enthalpy, indicating that electrostatic interaction was the primary binding force under these experimental conditions. The variations of the enthalpy and entropy of the binding thermodynamics when adding PEG to different salt types in the buffer solution showed opposite behavior, and the results support the concept of kosmotrope-like behavior of PEG. The equilibrium and thermodynamics data demonstrate that PEG has a kosmotrope-like hydration behavior, and the extent of kosmotrope-like behavior depends on the molecular weight of PEG with the outcomes of various molecular weights of PEG being added to the binding solution. The results of this study provide essential knowledge for PEG as an additive (or cosolvent) in various research applications.
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Polietilenoglicóis/química , Termodinâmica , Calorimetria , Muramidase/química , Muramidase/metabolismo , Água/químicaRESUMO
Purpose: To identify the characteristic corneal biomechanical properties of osteogenesis imperfecta (OI), and to compare the corneal biomechanical properties between OI and keratoconus. Methods: We included 46 eyes of 23 patients with OI, 188 eyes of 99 keratoconus patients, and 174 eyes of 92 normal controls to compare corneal biomechanical parameters between OI corneas, keratoconus, and normal controls by using Corneal Visualization Scheimpflug Technology (Corvis ST). Results: Patients with OI had significantly higher Corvis biomechanical index (CBI) (P < 0.001), higher tomographic and biomechanical index (TBI) (P = 0.040), lower Corvis Biomechanical Factor (CBiF) (P = 0.034), and lower stiffness parameter at first applanation (SP-A1) (P < 0.001) compared with normal controls. In contrast, OI group showed lower CBI (P < 0.001), lower TBI (P < 0.001), higher CBiF (P < 0.001), and higher SP-A1 (P = 0.020) than keratoconus group. Notably, the stress-strain index (SSI) was not significantly different between the OI and normal controls (P = 1.000), whereas keratoconus showed the lowest SSI compared with OI group (P = 0.025) and normal controls (P < 0.001). Conclusions: Although the corneal structures of OI patients are less stable and easier to deform as compared to those of the control group, there is no significant difference in material stiffness observed between the OI and normal controls. In contrast, the corneas of keratoconus showed not only lower structural stability and higher deformability but also lower material stiffness compared with those of OI cornea and normal controls. Translational Relevance: The biomechanical alterations are different between OI corneas and keratoconus.
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Ceratocone , Osteogênese Imperfeita , Humanos , Ceratocone/diagnóstico , Osteogênese Imperfeita/diagnóstico por imagem , Topografia da Córnea/métodos , Fenômenos Biomecânicos , Córnea/diagnóstico por imagem , ColágenoRESUMO
Previous studies have indicated that NaIO3 induces intracellular reactive oxygen species (ROS) production and has been used as a model for age-related macular degeneration (AMD) due to the selective retinal pigment epithelium (RPE) cell damage it induces. Beta-mangostin (BM) is a xanthone-type natural compound isolated from Cratoxylum arborescens. The influence of BM on NaIO3-induced oxidative stress damage in ARPE-19 cells has not yet been elucidated. In this study, we investigated how BM protects ARPE-19 cells from NaIO3-induced ROS-mediated apoptosis. Our results revealed that BM notably improved cell viability and prevented ARPE-19 cell mitochondrial dysfunction mediated-apoptosis induced by NaIO3; it was mediated by significantly reduced NaIO3-upregulated ROS, cellular H2O2 production and improved downregulated glutathione and catalase activities. Furthermore, we found that BM could suppress the expression of Bax, cleaved PARP, and cleaved caspase-3 by decreasing phosphorylation of MEK/ERK and p53 expression in NaIO3-induced ARPE-19 cells. At the same time, we also used MEK inhibitors (PD98059) to confirm the above phenomenon. Moreover, our animal experiments revealed that BM prevented NaIO3 from causing retinal deformation; it led to thicker outer and inner nuclear layers and downregulated cleaved caspase-3 expression compared to the group receiving NaIO3 only. Collectively, these results suggest that BM can protect the RPE and retina from NaIO3-induced apoptosis through ROS-mediated mitochondrial dysfunction involving the MEK/ERK and p53 signaling pathways.
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Doenças Mitocondriais , Proteína Supressora de Tumor p53 , Animais , Espécies Reativas de Oxigênio/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Epitélio Pigmentado da Retina , Peróxido de Hidrogênio/metabolismo , Apoptose , Estresse Oxidativo , Transdução de Sinais , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: Tinnitus and uveitis have shared commonality in pathophysiology in terms of autoimmunity. However, no studies that have linked any association between the conditions of tinnitus and uveitis. METHODS: This is a retrospective study conducted from the Taiwan National Health Insurance database in order to investigate whether tinnitus patients are at increased risk of uveitis. Patients newly diagnosed with tinnitus between 2001 and 2014 were recruited and followed up until 2018. The endpoint of interest was a diagnosis of uveitis. RESULTS: A total of 31,034 tinnitus patients and 124,136 matched comparisons were analyzed. Tinnitus patients were found to have a significantly higher cumulative incidence for uveitis than those without the diagnosis of tinnitus with incidence rate of 1.68 (95% CI 1.55-1.82) per 10 000 person-months for tinnitus group and 1.48 (95% CI 1.42-1.54) per 10 000 person-months for non-tinnitus group. CONCLUSION: Tinnitus patients were found to have increased risk of developing uveitis.
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Peripheral nerve regeneration (PNR) following trauma requires the reconstruction of the extracellular matrix (ECM) and the proper stimulation of growth factors. Decellularised small intestine submucosa (SIS) has been extensively used as an ECM scaffold for tissue repair, but its potential to enhance the effects of exogenous growth factors on PNR is not well understood. In this study, we evaluated the effects of SIS implantation combined with glial cell-derived growth factor (GDNF) treatment on PNR in a rat neurorrhaphy model. We found that both SIS and regenerating nerve tissue expressed syndecan-3 (SDC3), one of major heparan sulphate proteoglycans in nerve tissue, and that SDC3 interacted with GDNF in the regenerating nerve tissue. Importantly, the SIS-GDNF combined treatment enhanced the recovery of neuromuscular function andß3-tubulin-positive axonal outgrowth, indicating an increase in the number of functioning motor axons connecting to the muscle after neurorrhaphy. Our findings suggest that the SIS membrane offers a new microenvironment for neural tissue and promotes neural regeneration based on SDC3-GDNF signalling, providing a potential therapeutic approach for PNR.
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Fator Neurotrófico Derivado de Linhagem de Célula Glial , Nervos Periféricos , Ratos , Animais , Sindecana-3 , Regeneração Nervosa , Intestino DelgadoAssuntos
Injúria Renal Aguda/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Bevacizumab/administração & dosagem , Humanos , Injeções Intravítreas , Masculino , Ranibizumab/administração & dosagemRESUMO
Long noncoding RNAs (lncRNAs) have been proven to play critical roles in diabetic retinopathy (DR). This study investigated whether the single nucleotide polymorphism (SNP) of long intergenic noncoding RNA 00673 (LINC00673) affects the clinical characteristics of diabetic retinopathy (DR). A total of three loci of LINC00673 SNPs (rs6501551, rs9914618, and rs11655237) were genotyped using TaqMan allelic discrimination in 276 and 454 individuals with and without DR, respectively. Our results revealed that LINC00673 SNP rs11655237 CT genotype (AOR: 1.592, 95% CI: 1.059-2.395, p = 0.026), CT + TT genotype (AOR: 1.255, 95% CI: 1.029-1.531, p = 0.025), and allele T (AOR: 1.185, 95% CI: 1.004-1.397, p = 0.044) yielded higher ratios in the non-proliferative diabetic retinopathy (NPDR) subgroup than in the non-DR group. Furthermore, the interval of diabetes mellitus (DM) was significantly shorter in the LINC00673 SNP rs11655237 CT + TT variant than that in the LINC00673 SNP rs11655237 wild type (10.44 ± 7.10 vs. 12.98 ± 8.34, p = 0.009). In conclusion, the LINC00673 SNP rs11655237 T allele is associated with a higher probability of NPDR development. Patients with the LINC00673 SNP rs11655237 CT + TT variant exhibited a short DM interval.
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The aim of this work was to appraise the potential associations of single nucleotide polymorphisms (SNPs) of long non-coding RNA growth arrest-specific 5 (GAS5) with diabetic retinopathy (DR) in a diabetes mellitus (DM) population. Two loci of the GAS5 SNPs (rs55829688 and rs145204276) were genotyped via TaqMan allelic discrimination in 449 non-DR patients and 273 DR subjects. The SNP rs145204276 Del/Del showed a significantly higher distribution in the DR group compared to the non-DR group (AOR: 2.487, 95% CI: 1.424-4.344, p = 0.001). During subgroup analyses, the non-proliferative diabetic retinopathy (NPDR) subgroup demonstrated a significantly higher ratio of the SNP rs145204276 Del/Del (AOR: 2.917, 95% CI: 1.574-5.406, p = 0.001) and Ins/Del + Del/Del (AOR: 1.242, 95% CI: 1.016-1.519, p = 0.034) compared to the non-DR population, while the proliferative diabetic retinopathy (PDR) subgroup did not reveal significant differences in either SNP rs145204276 or rs55829688 distributions compared to the non-DR group. Furthermore, patients with a GAS5 SNP rs145204276 Del/Del showed a significantly shorter DM duration than the wild type (Ins/Ins) (p = 0.021). In conclusion, our findings demonstrate that the GAS5 SNP rs145204276 Del/Del variant is associated with an increased susceptibility to DR in DM patients, particularly in those patients with NPDR.
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Diabetes Mellitus , Retinopatia Diabética , RNA Longo não Codificante , Retinopatia Diabética/genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética , RNA Longo não Codificante/genéticaRESUMO
ABSTRACT: Although uveitis can be an intraocular presentation of systemic lymphoma, it may be associated with direct lymphomatous infiltration and immune-mediated alterations. There have been no published studies describing the incidence of uveitis after systemic lymphoma. We conducted a nationwide cohort study to investigate the incidence of uveitis after systemic lymphoma diagnosis in Taiwan. Data were collected from the Taiwan National Health Insurance system and included patients newly diagnosed with systemic lymphoma between 2000 and 2017. We observed the risk of uveitis among study population since the index date until December 2017. The 1:8 of systemic lymphoma patient and paired comparison was identified by time distribution matching and individual paired with sex and age. Subsequent propensity score matching (PSM) was used to select the 1:1 of systemic lymphoma patient and paired comparison by greedy algorism with caliper of 0.05. The multiple Cox proportional hazard regression model was used to compare the developmental risk of uveitis (time-to-uveitis) between the systemic lymphoma and non-systemic lymphoma, while controlling for selected covariates. After time distribution matching, we selected 6846 patients with systemic lymphoma, and 54,768 comparisons. Among patients with systemic lymphoma groups, there were more men than women (52.94% vs 47.06%) and the mean age was 53.32â±â21.22âyears old. Systemic lymphoma incidence rates (per 10,000 person-months) of uveitis were 1.94 (95% confidence interval [CI], 1.60-2.35) in the systemic lymphoma cohort and 1.52 (95% CI, 1.42-1.63) in the non-systemic lymphoma cohort. Compared with the non-systemic lymphoma cohort, adjusted hazard ratio (aHR) of developing uveitis were 1.24 (95% CI, 1.00-1.52) in people with systemic lymphoma. But not significant in after PSM, aHR of developing uveitis were 1.17 (95% CI, 0.90-1.53). This 18-year nationwide population-based cohort study in Taiwan, showed that the risk of uveitis in patients' systemic lymphoma was not significantly higher than non-systemic lymphoma after PSM. In elderly and rheumatic patients with intraocular inflammation, it is important to first exclude uveitis masquerade syndrome, which could be a harbinger of intraocular involvement from systemic lymphoma. Further large-scale prospective clinical studies to investigate whether systemic lymphoma influences the incidence of uveitis are warranted.
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Linfoma/complicações , Uveíte/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Linfoma/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Uveíte/etiologiaRESUMO
OBJECTIVES: Previous studies have demonstrated that patients with diabetic retinopathy (DR) have a higher prevalence of risk factors known to be associated with cardiovascular disease (CVD). We hypothesized that patients with more severe DR could have a higher relative risk of CVD. METHODS: To test this hypothesis, we used the National Health Insurance Research Database (NHIRD) to evaluate whether associations exist between DR and CVD. The data for this nationwide population-based retrospective cohort study were obtained from the NHIRD in Taiwan from 2001 to 2013. The assessed study outcome used was the incidence and other statistical analyses of CVD in patients with DR during a 13-year follow-up period. RESULTS: Our findings obtained from 2001 to 2013 suggest that the incidence rates of CVD are 2.026 times that of diabetes mellitus (DM) without DR (95% C.I. = 1.876-2.187) and 2.75 times that of DM with DR (95% C.I. = 2.487-3.04) compared with the Non-DM group. CONCLUSION: The relative risk of CVD in DR was greater than that in the Non-DM group for both men and women. Targeted monitoring of DM, especially the co-existence of diabetic retinopathy, is of utmost importance in the clinical care of the DM population.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Retinopatia Diabética , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Retinopatia Diabética/epidemiologia , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
Purpose: Subconjunctival hemorrhage (SCH) is usually a benign ocular disorder that causes painless, redness under the conjunctiva. However, since SCH and acute coronary syndrome (ACS) share many vascular risk factors, studies have suggested that these two disorders may be significantly associated with each other, and evaluate the concomitance of ACS in patients with SCH. Methods: This population-based cohort study, enrolled 35,260 Taiwanese patients, and used the Taiwan National Health Insurance Research Database to identify patients with ACS and SCH. Outcomes were compared between the with and without SCH groups. The study population was followed until the date of ACS onset, the date of withdrawal, death, or December 31st 2013, whichever came first. Results: Of the 85,925 patients identified with SCH between 1996 and 2013, 68,295 were excluded based on the study's exclusion criteria, and a total of 17,630 patients with SCH who were diagnosed by ophthalmologists between 2000 and 2012 were eligible for analysis. After 1:1 propensity score matching for 5-year age groups, gender, and the index year, the results showed that SCH was more common in the 40-59 age group (53.82%) and females (58.66%). As for the ACS-related risk factors, patients with diabetes mellitus (aHR = 1.58, 95% CI = [1.38, 1.81]), hypertension (aHR = 1.71, 95% CI = [1.49, 1.96]) and patients taking aspirin (aHR = 1.67, 95% CI = [1.47, 1.90]) had a notably higher risk of ACS. However, it was found that there were no significant differences in the occurrence of ACS between the non-SCH and SCH patients. Conclusion: This results of this study regarding the risk factors and epidemiology of SCH and ACS were in keeping with previously reported findings. However, the results revealed no significant association between SCH and ACS.