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1.
BMC Microbiol ; 24(1): 124, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622529

RESUMEN

BACKGROUND: Severe burns may alter the stability of the intestinal flora and affect the patient's recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association with phenotype can help to accurately assess the progression of the disease and identify potential microbiota markers. METHODS: We established mouse models of partial thickness deep III degree burns and collected faecal samples for 16 S rRNA amplification and high throughput sequencing at two time points in the acute phase for independent bioinformatic analysis. RESULTS: We analysed the sequencing results using alpha diversity, beta diversity and machine learning methods. At both time points, 4 and 6 h after burning, the Firmicutes phylum content decreased and the content of the Bacteroidetes phylum content increased, showing a significant decrease in the Firmicutes/Bacteroidetes ratio compared to the control group. Nine bacterial genera changed significantly during the acute phase and occupied the top six positions in the Random Forest significance ranking. Clustering results also clearly showed that there was a clear boundary between the communities of burned and control mice. Functional analyses showed that during the acute phase of burn, gut bacteria increased lipoic acid metabolism, seleno-compound metabolism, TCA cycling, and carbon fixation, while decreasing galactose metabolism and triglyceride metabolism. Based on the abundance characteristics of the six significantly different bacterial genera, both the XGboost and Random Forest models were able to discriminate between the burn and control groups with 100% accuracy, while both the Random Forest and Support Vector Machine models were able to classify samples from the 4-hour and 6-hour burn groups with 86.7% accuracy. CONCLUSIONS: Our study shows an increase in gut microbiota diversity in the acute phase of deep burn injury, rather than a decrease as is commonly believed. Severe burns result in a severe imbalance of the gut flora, with a decrease in probiotics and an increase in microorganisms that trigger inflammation and cognitive deficits, and multiple pathways of metabolism and substance synthesis are affected. Simple machine learning model testing suggests several bacterial genera as potential biomarkers of severe burn phenotypes.


Asunto(s)
Quemaduras , Microbioma Gastrointestinal , Microbiota , Humanos , Animales , Ratones , Bacterias/genética , Firmicutes/genética , ARN Ribosómico 16S/genética
2.
Psychosom Med ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38787544

RESUMEN

OBJECTIVE: Antibody response to vaccination is a powerful paradigm for studying the effects of chronic stress on immune function. In the present study, we used this paradigm to examine the interaction between caregiving (as a type of chronic stress) and sex on the antibody response to a single dose of a COVID-19 vaccination; recent research has called for examination of sex differences on health outcomes among family caregivers. A three-way interaction between caregiving, sex and psychological distress was also examined. METHODS: COVID-19 antibody data was extracted from 165 caregivers (98 females) and 386 non-caregivers (244 females) from the UK's Understanding Society COVID-19 study. Relevant socio-demographics, health and lifestyle, and distress variables were gathered as potential covariates. RESULTS: In a 2 x 2 ANOVA we found the interaction between caregiving and sex was significant; male caregivers had a lower antibody response to the vaccine compared to female caregivers F (1,547), =24.82, p < .001, η2 = .043. Following adjustment, male caregivers had the lowest antibody response relative to all other groups. The three-way interaction model, controlling for covariates was also significant, R2 = .013, p = .049; the conditional effects for the three-way interaction revealed that male caregivers, compared to the other groups had a lower antibody response at both low and medium levels of psychological distress. CONCLUSION: This study found evidence of a three-way interaction between caregiving, sex and distress on antibody response. Male caregivers had poorer antibody response to a single shot of the COVID-19 vaccination than female caregivers and male and female non-caregivers and this was evident at low and medium levels of distress. Our findings will be discussed in relation to the caregiver-and sex interactions during the pandemic.

3.
Ren Fail ; 46(1): 2355352, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38785291

RESUMEN

Background: Recent studies have shown that the baseline values of absolute aortic root diameter (ARD) and indexed diameter are associated with all-cause mortality and cardiovascular events in the general population, even in the absence of aneurysmal aortic disease. However, there is limited available data on the association between ARD and prognosis in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis (MHD). Accordingly, the purpose of this study is to investigate the predictive value of ARD for all-cause mortality and cardiovascular events in this specific population.Methods: ARD was measured by echocardiography at the level of the sinuses of Valsalva at end diastole and indexed to body surface area (BSA). The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiovascular events (MACE), including cardiovascular mortality, myocardial infarction and stroke. Cox proportional hazards models were conducted to evaluate the association between baseline ARD/BSA and clinical outcomes.Results: A total of 391 patients were included in this study. The primary endpoint occurred in 95 (24.3%) patients while the secondary endpoint occurred in 71 (18.2%) patients. Multivariate Cox regression analysis showed that ARD/BSA was an independent prognostic factor for all-cause mortality (HR, per 1-SD increase, 1.403; 95% CI, 1.118-1.761; p = 0.003) as well as MACE (HR, per 1-SD increase, 1.356; 95% CI, 1.037-1.772; p = 0.026).Conclusions: Our results show that ARD/BSA is predictive of all-cause mortality and MACE in MHD patients with ESRD and support the view that assessment of ARD/BSA may refine risk stratification and preventive strategies in this population.


Asunto(s)
Ecocardiografía , Fallo Renal Crónico , Diálisis Renal , Humanos , Masculino , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Femenino , Persona de Mediana Edad , Pronóstico , Anciano , Aorta/diagnóstico por imagen , Aorta/patología , Estudios Retrospectivos , Modelos de Riesgos Proporcionales , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/etiología , Factores de Riesgo
4.
Phys Chem Chem Phys ; 24(41): 25287-25297, 2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36226481

RESUMEN

Direct Z-scheme water-splitting is a promising route to enhancing the photocatalytic performance due to the effective separation of photogenerated carriers while simultaneously preserving the strong oxidation activity of holes and reduction activity of electrons. In this work, the MoSSe/XY2 (X = Hf, Zr; S, Se) heterostructures (HSs) with different contacts are proposed for Z-scheme photocatalytic water-spitting by first principles calculation. The separation of photogenerated carriers for HfSe2/SMoSe and ZrSe2/SMoSe HSs is limited by the type-I band alignment, while the hydrogen production ability of HfSe2/SeMoS and ZrSe2/SeMoS HSs is limited by the lower conduction band edge positions relative to the water reduction potential. The HfS2/SMoSe, HfS2/SeMoS, ZrS2/SMoSe, and ZrS2/SeMoS HSs are direct Z-scheme water-splitting photocatalysts with the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) occurring at the Hf(Zr)S2 layer and MoSSe layer, respectively. More excitingly, the S (or Se) vacancies effectively lower the HER overpotentials. Besides, the solar-to-hydrogen efficiencies are 6.1%, 5.9%, 6.4%, and 6.3% for HfS2/SMoSe, HfS2/SeMoS, ZrS2/SMoSe, and ZrS2/SeMoS HSs, respectively. This work paves the way for designing highly efficient overall water-splitting photocatalysts using 2D materials.

5.
Biochem Biophys Res Commun ; 548: 27-34, 2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33631670

RESUMEN

Degenerative retinal diseases, including age-related macular degeneration, are serious diseases that may lead to irreversible retinal neuron damage and permanent vision impairment. There are currently no effective treatments for these diseases due to our incomplete understanding of the underlying pathological mechanisms. Ferroptosis, a newly identified iron-dependent mode of cell death, is implicated in various diseases. However, it is unknown whether ferroptosis is involved in light-induced retinal degeneration. In this study, we found that light exposure significantly reduced the viability of photoreceptor cells in vitro and induced pro-ferroptotic changes, including iron accumulation, mitochondrial shrinkage, glutathione depletion, increased malondialdehyde (MDA), and decreased protein expression of SLC7A11 and GPX4. The effects of light exposure on ferroptosis were attenuated by ferrostatin-1. Consistently, the results of in vivo studies demonstrated that ferrostatin-1 protected against light-induced ferroptosis. And it exerted therapeutic effects by inhibiting neuroinflammation and prevented the effects of light exposure on the structure and function of the retina. The findings reveal an important role of ferroptosis in the pathogenesis of light-induced retinal degeneration and suggest that ferroptosis may be a novel treatment target for preventing retinal degeneration.


Asunto(s)
Ciclohexilaminas/uso terapéutico , Ferroptosis/efectos de los fármacos , Luz , Fármacos Neuroprotectores/uso terapéutico , Fenilendiaminas/uso terapéutico , Retina/patología , Degeneración Retiniana/tratamiento farmacológico , Animales , Línea Celular , Ciclohexilaminas/farmacología , Masculino , Fármacos Neuroprotectores/farmacología , Fenilendiaminas/farmacología , Ratas Sprague-Dawley , Retina/efectos de los fármacos , Retina/ultraestructura , Degeneración Retiniana/patología
6.
Retina ; 41(1): 199-207, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32251241

RESUMEN

PURPOSE: To describe the multimodal imaging characteristics of flat irregular pigment epithelial detachment (FIPED) in patients with chronic central serous chorioretinopathy and determine the risk factors for vascularized FIPED and to explore the activity of vascularized FIPED before and after half-dose photodynamic therapy. METHODS: Multimodal imaging data of 185 eyes of 155 consecutive patients with chronic central serous chorioretinopathy included spectral domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography. Optical coherence tomography angiography was available for 56 eyes. Flat irregular PED was classified into two types based on indocyanine green angiography or optical coherence tomography angiography findings: avascular FIPED and vascularized FIPED. RESULTS: The avascular FIPED and vascularized FIPED were detected in 127 (68.6%) and 42 (22.7%) eyes, respectively. Age (P = 0.001), visual acuity (P = 0.048), subfoveal choroidal thickness (P = 0.032), height (P < 0.001) and width (P < 0.001) of FIPED, choriocapillary thickness (P = 0.015), and maximum vessel diameter (P = 0.009) beneath the FIPED were significantly different between avascular and vascularized FIPEDs. Old age was an independent risk factor for vascularized FIPED. On optical coherence tomography angiography, all vascularized FIPEDs manifested the pattern of mature choroidal neovascularization (CNV). After half-dose photodynamic therapy, vascularized FIPED remained stable without the reaccumulation of subretinal fluid at the last follow-up. CONCLUSION: In chronic central serous chorioretinopathy, vascularized FIPED was closely associated with Type I CNV. Old age was an independent risk factor for vascularized FIPED. Vascularized FIPED is suggested as "quiescent" CNV, and half-dose photodynamic therapy may be recommended as the first-line therapy in chronic central serous chorioretinopathy complicated with quiescent CNV, except when the activity of CNV becomes evident.


Asunto(s)
Coriorretinopatía Serosa Central/tratamiento farmacológico , Neovascularización Coroidal/tratamiento farmacológico , Angiografía con Fluoresceína/métodos , Fotoquimioterapia/métodos , Desprendimiento de Retina/tratamiento farmacológico , Epitelio Pigmentado de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Adulto , Anciano , Coriorretinopatía Serosa Central/complicaciones , Coriorretinopatía Serosa Central/diagnóstico , Coroides/patología , Neovascularización Coroidal/complicaciones , Neovascularización Coroidal/diagnóstico , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/etiología , Estudios Retrospectivos , Agudeza Visual
7.
Future Gener Comput Syst ; 115: 531-541, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33041408

RESUMEN

The development of cyberspace offers unprecedentedly convenient access to online communication, thus inducing malicious individuals to subtly manipulate user opinions for benefits. Such malicious manipulations usually target those influential and susceptible users to mislead and control public opinion, posing a bunch of threats to public security. Therefore, an intelligent and efficient searching strategy for targeted users is one prominent and critical approach to defend malicious manipulations. However, the major body of current studies either provide solutions under ideal scenarios or offer inefficient solutions without guaranteed performance. As a result, this work adopts the combination of unsupervised learning and heuristic search to discover susceptible and key users for defense. We first propose a greedy algorithm fully considering the susceptibilities of different users, then adopt unsupervised learning and utilize the community property to design an accelerated algorithm. Moreover, the approximation guarantees of both greedy and community-based algorithms are systematically analyzed for some practical circumstances. Extensive experiments on real-world datasets demonstrate that our algorithms significantly outperform the state-of-the-art algorithm.

8.
BMC Plant Biol ; 20(1): 204, 2020 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-32393175

RESUMEN

BACKGROUND: Frequent freeze-thaw phenomena, together with widely used deicing salt and intense acid precipitation, often occur in northeastern China, causing damage to various aspects of plants, such as the permeability of biological membranes, osmotic adjustment, and photosystems. Aiming to explore the resistance of alfalfa to freezing-thawing (F), acid precipitation (A) and deicing salt (D), this study used Medicago sativa cv. Dongmu-70 as the experimental material, and the contents of malondialdehyde (MDA), soluble protein, soluble sugars, proline and chlorophyll were evaluated. RESULTS: As the temperature decreased, the MDA content in the seedlings of the group under combined stress (A-D-F) increased and was significantly higher than that of group F (by 69.48 ~ 136.40%). Compared with those in the control (CK) group, osmotic substances such as soluble sugars and proline in the treatment groups were higher, while the soluble protein content was lower. The chlorophyll contents in the seedlings of the treatment groups were lower than those of the CK group; however, the chlorophyll content displayed a non-significant change during the free-thaw cycle. CONCLUSION: Injury to the permeability of the biological membranes and photosystems of alfalfa results from stress. Moreover, alfalfa maintains osmotic balance by adaptively increasing the potential of osmotic substances such as soluble sugars and proline. Furthermore, the influence of stress from freezing-thawing and deicing salt is highly substantial, but the combined stresses of acid precipitation with the two factors mentioned above had little effect on the plants.


Asunto(s)
Medicago sativa/fisiología , Plantones/fisiología , Estrés Fisiológico , Lluvia Ácida/efectos adversos , Clorofila/metabolismo , Congelación , Malondialdehído/metabolismo , Proteínas de Plantas/metabolismo , Prolina/metabolismo , Azúcares/metabolismo
9.
Mol Vis ; 26: 64-75, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32165827

RESUMEN

Purpose: Excessive angiogenesis, also known as neovascularization, has considerable pathophysiologic roles in several retinal diseases, including retinopathy of prematurity, diabetic retinopathy, and exudative age-related macular degeneration. Accumulated evidence has revealed that miRNAs play important roles in endothelial cell dysfunction and angiogenesis. However, the role of microRNA-29b-3p (miR-29b-3p) in retinal angiogenesis is still unclear. Therefore, we investigated whether and how miR-29b-3p affects the function of retinal microvascular endothelial cells (RMECs). Methods: The overexpression and inhibition of miR-29b-3p were achieved by transfecting rat RMECs with an miR-29b-3p mimic and inhibitor, respectively. The proliferation, migration, and angiogenesis of RMECs were evaluated using a Cell Counting Kit-8 assay, Ki67 staining, western blotting (of proliferating cell nuclear antigen, cyclin A2, cyclin D1, and cyclin E1), wound healing test, and tube formation assay. The expression levels of vascular endothelial growth factor A (VEGFA) and platelet-derived growth factor B (PDGFB) were examined with quantitative real-time PCR and western blotting, respectively. Results: Overexpression of miR-29b-3p statistically significantly inhibited the function of RMECs in cell proliferation and angiogenesis, while inhibition of miR-29b-3p increased the proliferative and angiogenic activities of RMECs. Moreover, VEGFA and PDGFB, as the targets of miR-29b-3p, were statistically significantly downregulated by the miR-29b mimic, whereas the miR-29b-3p inhibitor had the opposite effects. Conclusions: miR-29b-3p negatively regulates RMEC proliferation and angiogenesis, at least partly by targeting VEGFA and PDGFB. These data may provide a potential therapeutic strategy for treating ocular neovascular diseases.


Asunto(s)
Proliferación Celular/genética , Células Endoteliales/metabolismo , MicroARNs/metabolismo , Neovascularización Patológica/metabolismo , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Retina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Supervivencia Celular/genética , Células Cultivadas , Regulación hacia Abajo , MicroARNs/genética , Neovascularización Patológica/genética , Factor de Crecimiento Derivado de Plaquetas/genética , Ratas , Transfección , Regulación hacia Arriba , Cicatrización de Heridas/genética
10.
Toxicol Appl Pharmacol ; 403: 115131, 2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32687838

RESUMEN

Baicalin (BA) inhibits hepatitis B virus (HBV) RNAs production and reduces levels of the related hepatocyte nuclear factors (HNFs), although the underlying mechanism is unclear. In this study, we investigated the specific pathway by which BA regulates HBV transcription through the HBV-related HNFs. Following transfection of HepG2 cells with pHBV1.2, we observed that BA inhibited the production of HBV RNAs and viral proteins in a time- and dose-dependent manner. These effects were consistent with the downregulation of HNF1α, which was abolished by HNF1α-shRNA. The shRNA of HNF4α, the upstream gene of HNF1α, also remarkedly reduced HNF1α expression and impaired the anti-HBV efficacy of BA, indicating that this function of BA depended on HNF4α/HNF1α axis. Furthermore, chromatin immunoprecipitation assay showed that BA significantly reduced HNF4α-HNF1α transactivation activity. The similar effects of BA were observed in entecavir (ETV)-resistant HBVrtM204V/rtLl80M transfected HepG2 cells. Thus, we proposed a mechanism for the anti-HBV activity of BA in an HNF4α-HNF1α-dependent manner, which impaired HNF4α and HNF1α transactivation, and effectively inhibited HBV transcription and viral replication.


Asunto(s)
Flavonoides/farmacología , Virus de la Hepatitis B/metabolismo , Factor Nuclear 1-alfa del Hepatocito/metabolismo , Factor Nuclear 4 del Hepatocito/metabolismo , Transcripción Genética/efectos de los fármacos , Animales , Antiinfecciosos/farmacología , Simulación por Computador , Bases de Datos Genéticas , Regulación hacia Abajo , Regulación de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Virus de la Hepatitis B/genética , Factor Nuclear 1-alfa del Hepatocito/genética , Factor Nuclear 4 del Hepatocito/genética , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Plásmidos
11.
Nanotechnology ; 31(48): 485701, 2020 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-32931462

RESUMEN

The electronic structures of two dimensional (2D) CdS/ZnO heterostructure (CdZnHT) consisting of CdS singlelayer (SL) and ZnO SL are explored based on hybrid density functional calculation. The negative interface formation energies suggest the formation of CdZnHT is exothermic. The bandgap of CdZnHT is favorable for absorbing visible light, and the decent band edge position makes it thermodynamically feasible for spontaneous generation of oxygen and hydrogen. The formed electric field across the interface induced by charge transfer will reduce photogenerated carrier recombination and promote carrier migration. Particularly, CdZnHT is a type-II heterostructure. Oxygen generation takes place at ZnO layer and hydrogen production occurs at CdS layer, which will also promote the effective separation and migration of phogogenerated carriers and enhance photocatalytic performance. These findings suggest that 2D CdZnHTs are possible candidates as water-splitting photocatalysts.

12.
Graefes Arch Clin Exp Ophthalmol ; 258(8): 1697-1707, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32350652

RESUMEN

PURPOSE: To describe optical coherence tomography angiography (OCTA) and other multimodal imaging features of multiple evanescent white dot syndrome (MEWDS). METHODS: The retinal and choriocapillary vascular density of MEWDS patients were measured by OCTA (OptoVue Inc.) in the acute and recovery phases. And other multimodal imaging data were also retrospectively reviewed. RESULTS: Sixteen patients with a mean age of 26.5 ± 6.99 years were included. Three patients were complicated with choroidal neovascularization (CNV). The mean baseline logMAR BCVA of the affected eyes was 0.52 ± 0.36 (Snellen equivalent 20/50). OCTA revealed significant reductions in vascular densities of deep capillary plexus (45.72 ± 3.70%, P = 0.0007), and choriocapillaris (46.08 ± 3.22%, P < 0.0001) of the affected eyes compared with the contralateral eyes (50.23 ± 4.06% and 52.28 ± 4.19%, respectively) in the acute phase. During the recovery phases, vascular densities of deep capillary plexus (49.50 ± 3.15%, P < 0.0001) and choriocapillaris (53.67 ± 2.58%, P < 0.0001) increased significantly in the affected eyes while those of the superficial capillary plexus remained stable. SD-OCT revealed an increase of the subfoveal choroidal thickness and disruption of the outer retinal layer, including ellipsoid zone discontinuities and the accumulation of hyperreflective material, corresponding to the hypofluorescent spots and dots on ICGA, respectively. BCVA increased to normal values after recovery, together with restoration of the structural morphology and choroidal thickness on SD-OCT, except in eyes with CNV. CONCLUSION: The inner retinal layer and choroid can be secondarily transiently compromised in MEWDS. MEWDS complicated with CNV is associated with worse visual outcomes.


Asunto(s)
Coroides/irrigación sanguínea , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodos , Síndromes de Puntos Blancos/diagnóstico , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Fondo de Ojo , Humanos , Masculino , Densidad Microvascular , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto Joven
13.
BMC Ophthalmol ; 20(1): 476, 2020 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-33276763

RESUMEN

BACKGROUND: To report undescribed characteristics of patients with bilateral diffuse uveal melanocytic proliferation (BDUMP) on ultrasound biomicroscopy (UBM) and high-frequency B-scan ultrasonography. CASE PRESENTATION: Two of four participants presented with worsening bilateral vision after previously diagnosed primary pulmonary or ovarian carcinoma. The other two patients were diagnosed with lung carcinoma after presentation with BDUMP. All patients had ciliary body nevi-like lesion in combination with iris or ciliary body cysts, and uveal thickening on UBM. Focally elevated choroidal nevi-like lesion and exudative retinal detachment with choroidal thickening were detected with B-scan ultrasonography. CONCLUSIONS: Our case series demonstrates the uveal characteristics of patients with BDUMP based on high-frequency B-scan ultrasonography and UBM. Ultrasonographic findings are crucial in the diagnosis of BDUMP because it is occult in nature.


Asunto(s)
Síndromes Paraneoplásicos Oculares , Enfermedades de la Úvea , Proliferación Celular , Cuerpo Ciliar/diagnóstico por imagen , Humanos , Melanocitos , Úvea , Enfermedades de la Úvea/diagnóstico por imagen
14.
Retina ; 39(8): 1613-1622, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29781975

RESUMEN

PURPOSE: To characterize novel BEST1 mutations and the phenotype-genotype correlations in vitelliform macular dystrophy in a Chinese population. METHODS: Seventeen individuals affected by vitelliform macular dystrophy underwent detailed ophthalmic examinations, including a best-corrected visual acuity test, slit-lamp biomicroscopy, fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and optical coherence tomography angiography. Next-generation sequencing was used to screen 790 genes frequently involved in common inherited nonsyndromic eye diseases in all participants. Sanger sequencing was used to identify possible disease-causing variants. RESULTS: The mean ± SD age of the patients was 44.20 ± 15.09 (range: 16-69) years. Seven novel BEST1 mutations were identified: six heterozygous missense (p.Thr307Asn, p.Ile295The, p.Leu75Pro, p.Thr2Ser, p.Ser79Tyr, and p.Val81Leu) and one frameshift (p.Glu115GlufsX120) mutation. Choroidal neovascularization was detected in two probands. One individual presented with subfoveal focal choroidal excavation. Arden ratios obtained by electrooculography were less than the 1.5 cutoff value in 7 patients. No mutations were identified in 2 patients, one of whom had a fundus appearance typical of vitelliform macular dystrophy and a decreased Arden ratio (1.2/1.2). CONCLUSION: Patients with the same heterozygous BEST1 mutations exhibited varying phenotypes. Our results have expanded the BEST1 mutation spectrum in a Chinese population with vitelliform macular dystrophy.


Asunto(s)
Pueblo Asiatico/genética , Bestrofinas/genética , Mutación Missense , Distrofia Macular Viteliforme/genética , Adolescente , Adulto , Anciano , China/epidemiología , Electrooculografía , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Estudios de Asociación Genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Linaje , Polimorfismo de Nucleótido Simple , Microscopía con Lámpara de Hendidura , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Distrofia Macular Viteliforme/patología , Adulto Joven
15.
Clin Exp Ophthalmol ; 47(5): 646-657, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30474307

RESUMEN

BACKGROUND: This study aimed to investigate the neuroprotective function of a synthesized glucocorticoid-induced leucine zipper peptide (GILZ-p) in a light-induced retinal degeneration model. METHODS: The GILZ98-134 peptide was synthesized and injected intravitreally into Sprague Dawley rats. Retinal injury was then induced in the rats by exposing their eyes to constant white light (5000 lux) for 24 h. The activation of retinal caspases-9/3 and the release of cytochrome c from the mitochondria to the cytosol were measured at 1, 3, 5 and 7 d after light injury. Photoreceptor apoptosis was evaluated with terminal-deoxynucleotidyl-transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) staining at 3 d after injury. Haematoxylin and eosin staining and electroretinography were used to observe the changes in the retinal morphology and function, respectively, at 7 and 14 d after light injury. RESULTS: The intravitreally injected synthesized GILZ-p successfully penetrated to the retina and significantly inhibited the activation of retinal caspase-3 and caspase-9 at 1, 3, 5 and 7 d after light injury, and reduced the number of TUNEL-positive photoreceptors at 3 d after light injury. GILZ-p pre-treatment also alleviated cytochrome c release and rescued mitochondria-mediated apoptosis after injury. Simultaneously, GILZ-p pre-treatment also mitigated the light-induced thinning of the outer nuclear layer and the loss of retinal function at 7 and 14 d after light injury, respectively. CONCLUSIONS: The synthesized GILZ-p prevented light-induced photoreceptor apoptosis and protected retinal function from degeneration, and is therefore a potential therapeutic option for degenerative retinal diseases.


Asunto(s)
Apoptosis/efectos de los fármacos , Luz/efectos adversos , Células Fotorreceptoras de Vertebrados/fisiología , Células Fotorreceptoras de Vertebrados/efectos de la radiación , Traumatismos Experimentales por Radiación/prevención & control , Degeneración Retiniana/prevención & control , Factores de Transcripción/farmacología , Animales , Western Blotting , Electrorretinografía , Células Ependimogliales/efectos de los fármacos , Etiquetado Corte-Fin in Situ , Inyecciones Intravítreas , Leucina Zippers , Masculino , Fragmentos de Péptidos/síntesis química , Traumatismos Experimentales por Radiación/etiología , Traumatismos Experimentales por Radiación/fisiopatología , Ratas , Ratas Sprague-Dawley , Degeneración Retiniana/etiología , Degeneración Retiniana/fisiopatología , Factores de Transcripción/síntesis química , Factores de Transcripción/fisiología
16.
Cell Physiol Biochem ; 46(1): 375-388, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29590655

RESUMEN

BACKGROUND/AIMS: Lipocalin 2 (LCN2), an important mediator of a variety of cellular processes, is involved in regulating the inflammatory response, but its roles in different inflammatory diseases are controversial. Because the role of LCN2 in ocular inflammation has been unclear until now, we explored the function of LCN2 in lipopolysaccharide (LPS)-induced ocular inflammation in vivo and in vitro. METHODS: Endotoxin-induced uveitis (EIU) was induced in male Sprague Dawley rats by the intravitreal injection of LPS. The expression and location of LCN2 in the retina were detected with western blotting and immunohistochemistry, respectively. We determined the clinical scores for anterior inflammation, quantified the infiltrated inflammatory cells, and measured the pro-inflammatory factors to determine the anti-inflammatory effects of LCN2 in EIU eyes. Cultured primary rat Müller cells were stimulated with LPS and the expression and secretion of LCN2 were measured with real-time PCR, western blotting, and an ELISA. After Müller cells were cotreated with LPS and LCN2 or PBS, the expression and secretion of TNF-α, IL-6, and MCP-1 were examined with realtime PCR, western blotting, and ELISAs. Western blotting and immunofluorescence were used to detect the phosphorylation and cellular distribution of nuclear factor kappaB (NF-κB) subunit p65. RESULTS: In EIU, the expression of LCN2 was significantly upregulated in the retina, especially in the outer nuclear layer (mainly composed of Müller cells). LPS stimulation of cultured Müller cells also markedly elevated LCN2 expression. Intravitreal injection of LCN2 significantly reduced the clinical scores, inflammatory infiltration, and protein leakage in EIU, which correlated with the reduced levels of proinflammatory factors in the aqueous humor and retina. LCN2 treatment also reduced the expression and secretion of TNF-α, IL-6, and MCP-1 in LPS-stimulated Müller cells. LCN2 inhibited the inflammatory response by inhibiting the phosphorylation and translocation of NF-κB p65. CONCLUSIONS: LCN2 protects against ocular inflammation, at least in part, by negatively regulating the activation of the NF-κB signaling pathway. LCN2 may be a promising anti-inflammatory therapy for ocular diseases, such as uveitis.


Asunto(s)
Lipocalina 2/metabolismo , FN-kappa B/metabolismo , Animales , Células Cultivadas , Quimiocina CCL2/análisis , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Células Ependimogliales/citología , Células Ependimogliales/efectos de los fármacos , Células Ependimogliales/metabolismo , Inmunohistoquímica , Interleucina-6/análisis , Interleucina-6/genética , Interleucina-6/metabolismo , Lipocalina 2/farmacología , Lipopolisacáridos/toxicidad , Masculino , Ratas , Ratas Sprague-Dawley , Retina/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Uveítis/etiología , Uveítis/metabolismo
17.
BMC Ophthalmol ; 18(1): 79, 2018 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-29558906

RESUMEN

BACKGROUND: Epiretinal membranes (ERMs), secondary to retinal cell proliferation on the retinal surface, usually affect patients over 50 years of age but occur rarely in children. Here we report the case of a 4-year-old patient with a unilateral sub-inner limiting membrane (sub-ILM) membrane mimicking epiretinal membrane with notable ultrastructural features indicating its possible origin from old sub-ILM hemorrhage. CASE PRESENTATION: A 4-year-old boy was admitted with the complaint of poor vision in his right eye, which had been detected at school vision screening performed 6 months earlier. Fundal examination showed a feather-shaped white membrane in the macula of the right eye, and optical coherence tomography (OCT) revealed a thickened retina with a hyper-reflective band on the retinal nerve fiber layer. We suspected epiretinal membrane in the right eye, and pars plana vitrectomy with membrane peeling was performed to improve the patient's vision. Surprisingly, the membrane was found intraoperatively to be located beneath the intact ILM; it was lifted carefully from the underlying retina as it was strongly adhered to a retinal artery of the superotemporal arcade. Postoperative scanning electron microscopy showed that the membrane consisted of hemosiderin, collagenous fibre and fibrinoid deposits. At follow-up visits, fundal examination and OCT revealed improvement in the retinal structure with disappearance of the hyper-reflective band and reduced retinal thickness. The patient's visual acuity in the right eye was stable at 20/100 at 1 year post operation. CONCLUSIONS: The white membrane presented here was found to lie between the intact ILM and the rest of the retina, adhering firmly to the superotemporal vessel arch. Given the ultrastructural findings of the membrane and the medical history, we speculate that the sub-ILM membrane probably developed secondary to a sub-ILM hemorrhage.


Asunto(s)
Membrana Epirretinal/patología , Retina/ultraestructura , Trastornos de la Visión/patología , Preescolar , Hemosiderina/análisis , Humanos , Masculino
18.
BMC Ophthalmol ; 18(1): 69, 2018 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-29506510

RESUMEN

BACKGROUND: To evaluate the structural changes associated with visual acuity (VA) in patients with idiopathic macular telangiectasia (MT) type 1 using multimodal imaging modalities. METHODS: A retrospective study of 14 patients with MT type 1 and of 10 eyes from 10 healthy individuals as age-matched controls was conducted. The medical records of patients who had undergone colour fundus photography, spectral domain optical coherence tomography (OCT), fluorescein angiography and OCT angiography were reviewed. Central macular thickness (CMT), the areas of macular oedema and ellipsoid zone (EZ) disruption, EZ length, disorganization of the retinal inner layers (DRIL) and external limiting membrane (ELM) disruption, as measured by spectral domain OCT; and vascular density and the foveal avascular zones (FAZ) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), as measured by OCT angiography, were assessed in MT type 1 eyes and correlated with VA. RESULTS: The mean baseline best-corrected VA of MT type 1 eyes was 0.45 ± 0.28. The mean CMT was 385.19 ± 75.21 µm in MT type 1 eyes and 252.43 ± 15.77 µm in contralateral eyes (Z = - 4.113, p < 0.001). The mean vessel density of the DCP was lower in MT type 1 eyes (47.25 ± 4.69%) than in contralateral eyes (53.93 ± 2.94%) and normal eyes (59.37 ± 2.50%) (Z = - 3.492, - 4.099; p < 0.001, < 0.001). The baseline logMAR VA was correlated with CMT (r = 0.682, p = 0.007), SCP density (r = - 0.652, p = 0.012), DCP density (r = - 0.700, p = 0.005), total area of EZ disruption (r = 0.649, p = 0.012); and total lengths of EZ (r = 0.681, p = 0.007), ELM (r = 0.699, p = 0.005) and DRIL (r = 0.707, p = 0.005) disruption in the 1-mm-diameter foveal region in MT type 1 eyes. CONCLUSIONS: Decreased DCP density and the presence of DRIL may be predictive biomarkers of VA in MT type 1. CMT, SCP density, total area of EZ disruption, and lengths of EZ and ELM disruption within the 1-mm-diameter central region were strongly associated with VA.


Asunto(s)
Angiografía por Tomografía Computarizada , Angiografía con Fluoresceína , Telangiectasia Retiniana/diagnóstico por imagen , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Adulto , Anciano , Biomarcadores , Femenino , Humanos , Edema Macular/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Imagen Multimodal , Telangiectasia Retiniana/fisiopatología , Vasos Retinianos/diagnóstico por imagen , Estudios Retrospectivos
20.
J Cardiovasc Pharmacol ; 64(1): 41-6, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24566464

RESUMEN

PURPOSE: The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is still unclear. We conducted a meta-analysis of randomized trials to assess the optimal duration of DAPT after DES implantation. METHODS: Articles were identified through a literature search of EMBASE, Pubmed, Europubmed, and the Cochrane Library until November 2013. Data were independently extracted by 2 reviewers. A random effect model was used to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs) of the clinical outcomes concerned. RESULTS: Three randomized controlled trials with zotarolimus- or everolimus-eluting stents and 6679 patients were included. There were no significant differences between short-term DAPT and standard-term DAPT in the comparison of incidences of cardiac death (OR, 0.84; 95% CI, 0.53-1.35; P = 0.48), myocardial infarction (OR, 1.21; 95% CI, 0.83-1.75; P = 0.32), stent thrombosis (OR, 1.30; 95% CI, 0.50-3.39; P = 0.59), and target vessel revascularization (OR, 1.16; 95% CI, 0.89-1.52; P = 0.26). Short-term DAPT did not increase the risk of all-cause death (OR, 0.86; 95% CI, 0.59-1.26; P = 0.44), cerebrovascular accidents (OR, 0.88; 95% CI, 0.421.81; P = 0.72), and major bleeding events (OR, 0.59; 95% CI, 0.30-1.15; P = 0.12). CONCLUSIONS: The results indicate that short-term DAPT do not increase the risk of cardiac death, myocardial infarction, stent thrombosis, target vessel revascularization, major bleeding, cerebrovascular accidents, and all-cause death at 12 months after implantation of DES compared with current standard-term DAPT. However, only 3 studies with second generation of DES are included in this meta-analysis. Further well-designed studies are still needed.


Asunto(s)
Stents Liberadores de Fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Quimioterapia Combinada , Everolimus , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Sirolimus/administración & dosificación , Sirolimus/análogos & derivados , Factores de Tiempo
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