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1.
Free Radic Biol Med ; 210: 258-270, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38042221

RESUMEN

One of the major pathological processes in cataracts has been identified as ferroptosis. However, studies on the iron metabolism mechanism in lens epithelial cells (LECs) and the methods of effectively alleviating ferroptosis in LECs are scarce. Along these lines, we found that in the ultraviolet radiation b (UVB) induced cataract model in vitro and in vivo, the ferritin of LECs is over-degraded by lysosomes, resulting in the occurrence of iron homeostasis disorder. Glycine can affect the ferritin degradation through the proton-coupled amino acid transporter (PAT1) on the lysosome membrane, further upregulating the content of nuclear factor erythrocyte 2 related factor 2 (Nrf2) to reduce the damage of LECs from two aspects of regulating iron homeostasis and alleviating oxidative stress. By co-staining, we further demonstrate that there is a more sensitive poly-(rC)-binding protein 2 (PCBP2) transportation of iron ions in LECs after UVB irradiation. Additionally, this study illustrated the increased expression of nuclear receptor coactivator 4 (NCOA4) in NRF2-KO mice, indicating that Nrf2 may affect ferritin degradation by decreasing the expression of NCOA4. Collectively, glycine can effectively regulate cellular iron homeostasis by synergistically affecting the lysosome-dependent ferritin degradation and PCBP2-mediated ferrous ion transportation, ultimately delaying the development of cataracts.


Asunto(s)
Catarata , Ferritinas , Ratones , Animales , Ferritinas/metabolismo , Glicina/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Rayos Ultravioleta , Hierro/metabolismo , Células Epiteliales/metabolismo , Catarata/metabolismo , Homeostasis/fisiología , Lisosomas/metabolismo
2.
Environ Res ; 243: 117804, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38042519

RESUMEN

Limiting the negative impact of climate change on nature and humans is one of the most pressing issues of the 21st century. Meanwhile, people in modern society spend most of the day indoors. It is therefore surprising that comparatively little attention has been paid to indoor human exposure in relation to climate change. Heat action plans have now been designed in many regions to protect people from thermal stress in their private homes and in public buildings. However, in order to be able to plan effectively for the future, reliable information is required about the long-term effects of climate change on indoor air quality and climate. The Indoor Air Quality Climate Change (IAQCC) model is an expediant tool for estimating the influence of climate change on indoor air quality. The model follows a holistic approach in which building physics, emissions, chemical reactions, mold growth and exposure are combined with the fundamental parameters of temperature and humidity. The features of the model have already been presented in an earlier publication, and it is now used for the expected climatic conditions in Central Europe, taking into account various shared socioeconomic pathway (SSP) scenarios up to the year 2100. For the test house examined in this study, the concentrations of pollutants in the indoor air will continue to rise. At the same time, the risk of mold growth also increases (the mold index rose from 0 to 4 in the worst case for very sensitive material). The biggest problem, however, is protection against heat and humidity. Massive structural improvements are needed here, including insulation, ventilation, and direct sun protection. Otherwise, the occupants will be exposed to increasing thermal discomfort, which can also lead to severe heat stress indoors.


Asunto(s)
Contaminación del Aire Interior , Contaminación del Aire , Humanos , Cambio Climático , Contaminación del Aire Interior/análisis , Humedad , Ventilación
3.
Invest Ophthalmol Vis Sci ; 64(7): 21, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37310354

RESUMEN

Purpose: The purpose of this study was to investigate the role of lncRNA H19 in epithelial-mesenchymal transition (EMT) and its molecular mechanism in fibrotic cataracts. Methods: TGF-ß2-induced EMT was induced in human lens epithelial cell line (HLECs) and rat lens explants to mimic posterior capsular opacification (PCO) in vitro and in vivo. Anterior subcapsular cataract (ASC) was induced in C57BL/6J mice. The long noncoding RNA (lncRNA) H19 (H19) expression was detected by RT-qPCR. Whole-mount staining of lens anterior capsule was used to detect α-SMA and vimentin. Lentiviruses carrying shRNA or H19 vector were transfected in HLECs to knockdown or overexpress H19. Cell migration and proliferation were characterized by EdU, Transwell, and scratch assay. EMT level was detected by Western blotting and immunofluorescence. The rAAV2 carrying mouse H19 shRNA was injected into ASC model mouse anterior chambers as a gene therapy to determine its therapeutic potential. Results: PCO and ASC models were built successfully. We found H19 upregulation in PCO and ASC models in vivo and in vitro. Overexpression of H19 by lentivirus transfection increased cell migration, proliferation, and EMT. In addition, H19 knockdown by lentivirus suppressed cell migration, proliferation, and EMT levels in HLECs. Moreover, transfection of rAAV2 H19 shRNA alleviated fibrotic area in ASC mouse lens anterior capsules. Conclusions: Excessive H19 participates in lens fibrosis. Overexpression of H19 increases, whereas knockdown of H19 ameliorates HLECs migration, proliferation, and EMT. These results demonstrate H19 might be a potential target for fibrotic cataracts.


Asunto(s)
Catarata , ARN Largo no Codificante , Animales , Humanos , Ratones , Ratas , Catarata/genética , Catarata/patología , Células Epiteliales/metabolismo , Lentivirus , Ratones Endogámicos C57BL , ARN Largo no Codificante/genética , ARN Interferente Pequeño , Fibrosis/genética , Fibrosis/patología , Transición Epitelial-Mesenquimal/genética
4.
Front Med (Lausanne) ; 10: 1089613, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37305131

RESUMEN

Introduction: The efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear. Methods: 3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer's tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment. Results: Based on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs. Discussion: The use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019).

5.
Free Radic Biol Med ; 204: 161-176, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37156294

RESUMEN

Oxidative stress-induced lens epithelial cells (LECs) death plays a pivotal role in age-related cataract (ARC) with severe visual impairment, in which ferroptosis is gradually receiving numerous attention resulting from lipid peroxide accumulation and reactive oxygen species (ROS) overproduction. However, the essential pathogenic factors and the targeted medical strategies still remain skeptical and indistinct. In this work, by transmission electron microscopy (TEM) analysis, the major pathological courses in the LECs of ARC patients have been identified as ferroptosis, which was manifested with remarkable mitochondrial alterations, and similar results were found in aged mice (24-month-old). Furthermore, the primary pathological processes in the NaIO3-induced mice and HLE-B3 cell model have also been verified to be ferroptosis with an irreplaceable function of Nrf2, proved by the increased sensitivity to ferroptosis when Nrf2 was blocked in Nrf2-KO mice and si-Nrf2-treated HLE-B3 cells. Importantly, it has been found that an increased expression of GSK-3ß was indicated in low-Nrf2-expressed tissues and cells. Subsequently, the contributions of abnormal GSK-3ß expression to NaIO3-induced mice and HLE-B3 cell model were further evaluated, inhibition of GSK-3ß utilizing SB216763 significantly alleviated LECs ferroptosis with less iron accumulation and ROS generation, as well as reversed expression alterations of ferroptosis markers, including GPX4, SLC7A11, SLC40A1, FTH1 and TfR1, in vitro and in vivo. Collectively, our findings conclude that targeting GSK-3ß/Nrf2 balance might be a promising therapeutic strategy to mitigate LECs ferroptosis and thus probably delay the pathogenesis and development of ARC.


Asunto(s)
Catarata , Ferroptosis , Animales , Ratones , Antioxidantes/farmacología , Antioxidantes/metabolismo , Catarata/genética , Catarata/metabolismo , Células Epiteliales/metabolismo , Ferroptosis/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo
6.
Front Nutr ; 10: 1130032, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37139451

RESUMEN

Objective: Glaucoma has currently become the second leading cause of blindness in the world. Serum vitamin B12 level has been found to be involved in the development and progression of glaucoma. We performed the present study to confirm this association. Methods: This cross-sectional study included 594 participants aged 40 years and older in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008. Retinal imaging was performed using the Ophthalmic Digital Imaging system (Retinography) to assess the retina for the presence of features of glaucomatous lesions. Logistic regression models were used to assess the association between dietary vitamin intake and glaucoma. Results: After screening, 594 subjects were finally included. Among all vitamin intakes, we observed significant differences between the two groups for vitamin B12 intake (5.93 vs. 4.77 mg, p = 0.033). According to the logistic regression results, the intake of vitamin B12 was significantly positively associated with glaucoma (model 1: OR = 1.078, 95% CI = 1.019-1.141; model 2: OR = 1.092, 95% CI = 1.031-1.158; model 3: OR = 1.092, 95% CI = 1.029-1.158). After performing a quantile regression, we observed a significant positive association between vitamin B12 intake and incident glaucoma in the fourth quartile (model 1: OR = 1.133, 95% CI = 1.060-1.210; model 2: OR = 1.141, 95% CI = 1.072-1.215; model 3: OR = 1.146, 95% CI = 1.071-1.226). Conclusions: Therefore, the above results, high-dose intake of vitamin B12 may promote the development of glaucoma.

7.
Front Nutr ; 10: 1042893, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36776608

RESUMEN

Introduction: Cataract is one of the leading causes of blindness and visual impairment, about 16 million people around the world. Trace elements play an important role in a variety of the processes in human body. This study aimed to investigate the association between daily dietary intake of trace elements and age-related cataract incidence based on data from the National Health and Nutrition Examination Survey (NHANES) 2001-2008. Methods: Iron, zinc, copper, and selenium were conducted in this study among subjects aged 50 years and older for African Americans and 55 and older in US adults. Multivariate logistic regression analysis was used in different models to investigate the association of trace elements intake and cataract. Results: After screening, 7,525 subjects were ultimately included in this study. A significant negative association was found between selenium intake and cataract incidence in adjusted models using multivariate logistic regression analysis (model 1: OR = 0.998, 95% CI = 0.997-1.000; model 2: OR = 0.997, 95% CI = 0.995-1.000; and model 3: OR = 0.998, 95% CI = 0.995-1.000). After dividing selenium intake into quintiles, significant negative associations between selenium intake and cataract were observed in the first quintile of model 3, the fourth and fifth quintiles of all models. In subgroup analyses adjusted for age and sex, a significant negative association was observed only in women aged 65-74 years. Discussion: Our study points out that maintaining daily dietary selenium intake at higher levels is helpful for cataract prevention, and that increasing daily dietary selenium intake in American women aged 65-74 years may contribute to the prevention of age-related cataract. The intakes of iron, zinc, copper may not be associated with age-related cataract.

8.
Bull Math Biol ; 85(4): 28, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-36853371

RESUMEN

Hosts can activate a defensive response to clear the parasite once being infected. To explore how host survival and fecundity are affected by host-parasite coevolution for chronic parasitic diseases, in this paper, we proposed an age-structured epidemic model with infection age, in which the parasite transmission rate and parasite-induced mortality rate are structured by the infection age. By use of critical function analysis method, we obtained the existence of the host immune evolutionary singular strategy which is a continuous singular strategy (CSS). Assume that parasite-induced mortality begins at infection age [Formula: see text] and is constant v thereafter. We got that the value of the CSS, [Formula: see text], monotonically decreases with respect to infection age [Formula: see text] (see Case (I)), while it is non-monotone if the constant v positively depends on the immune trait c (see Case (II)). This non-monotonicity is verified by numerical simulations and implies that the direction of immune evolution depends on the initial value of immune trait. Besides that, we adopted two special forms of the parasite transmission rate to study the parasite's virulence evolution, by maximizing the basic reproduction ratio [Formula: see text]. The values of the convergence stable parasite's virulence evolutionary singular strategies [Formula: see text] and [Formula: see text] increase monotonically with respect to time lag L (i.e., the time lag between the onset of transmission and mortality). At the singular strategy [Formula: see text] and [Formula: see text], we further obtained the expressions of the case mortalities [Formula: see text] and how they are affected by the time lag L. Finally, we only presented some preliminary results about host and parasite coevolution dynamics, including a general condition under which the coevolutionary singular strategy [Formula: see text] is evolutionarily stable.


Asunto(s)
Parásitos , Animales , Virulencia , Conceptos Matemáticos , Modelos Biológicos , Número Básico de Reproducción
9.
Heliyon ; 8(10): e11074, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36303931

RESUMEN

Background: Suspected aerosol-generating dental instruments may cause risks for operators by transmitting pathogens, such as the SARS-CoV-2 virus. The aim of our study was to measure aerosol generation in various dental procedures in clinical settings. Methods: The study population comprised of 84 patients who underwent 253 different dental procedures measured with Optical Particle Sizer in a dental office setting. Aerosol particles from 0.3 to 10 µm in diameter were measured. Dental procedures included oral examinations (N = 52), restorative procedures with air turbine handpiece (N = 8), high-speed (N = 6) and low-speed (N = 30) handpieces, ultrasonic scaling (N = 31), periodontal treatment using hand instruments (N = 60), endodontic treatment (N = 12), intraoral radiographs (N = 24), and dental local anesthesia (N = 31). Results: Air turbine handpieces significantly elevated <1 µm particle median (p = 0.013) and maximum (p = 0.016) aerosol number concentrations as well as aerosol particle mass concentrations (p = 0.046 and p = 0.006) compared to the background aerosol levels preceding the operation. Low-speed dental handpieces elevated >5 µm median (p = 0.023), maximum (p = 0.013) particle number concentrations,> 5 µm particle mass concentrations (p = 0.021) and maximum total particle mass concentrations (p = 0.022). High-speed dental handpieces elevated aerosol concentration levels compared to the levels produced during oral examination. Conclusions: Air turbine handpieces produced the highest levels of <1 µm aerosols and total particle number concentrations when compared to the other commonly used instruments. In addition, high- and low-speed dental handpieces and ultrasonic scalers elevated the aerosol concentration levels compared to the aerosol levels measured during oral examination. These aerosol-generating procedures, involving air turbine, high- and low-speed handpiece, and ultrasonic scaler, should be performed with caution. Clinical significance: Aerosol generating dental instruments, especially air turbine, should be used with adequate precautions (rubber dam, high-volume evacuation, FFP-respirators), because aerosols can cause a potential risk for operators and substitution of air turbine for high-speed dental handpiece in poor epidemic situations should be considered to reduce the risk of aerosol transmission.

10.
Medicine (Baltimore) ; 101(30): e29961, 2022 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-35905284

RESUMEN

INTRODUCTION: The present study was conducted to determine the association of transforming growth factor-beta (TGF-ß) gene polymorphism and myopia. METHOD: Four hundred twelve articles were identified, of which 11 articles with 5213 participants in 4 countries were included in the final analysis. Review Manager software (RevMan, version 5.4) was used for data analysis. RESULT: Odds ratio (OR) value of TGF-ß1 rs1800469 is 1.33 (95% confidence interval [CI] = 1.15-1.54) in the allelic model; in the dominant model is 1.76 (95% CI = 1.16-2.67); in homozygous model is 5.98 (95% CI = 4.31-8.06). OR value of TGF-ß1 rs4803455 is 0.62 (95% CI = 0.43-0.88) in recessive model. TGF-ß2 is not associated with myopia. Relevant study on TGF-ß3 is scarce. CONCLUSION: Our systematic review and meta-analysis found that TGF-ß1 rs4803455 and rs1800469 were correlated with myopia.


Asunto(s)
Miopía , Factor de Crecimiento Transformador beta1/uso terapéutico , Alelos , Predisposición Genética a la Enfermedad , Humanos , Miopía/genética , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Factor de Crecimiento Transformador beta1/genética
11.
Indoor Air ; 32(6): e13039, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35762234

RESUMEN

The IPCC 2021 report predicts rising global temperatures and more frequent extreme weather events in the future, which will have different effects on the regional climate and concentrations of ambient air pollutants. Consequently, changes in heat and mass transfer between the inside and outside of buildings will also have an increasing impact on indoor air quality. It is therefore surprising that indoor spaces and occupant well-being still play a subordinate role in the studies of climate change. To increase awareness for this topic, the Indoor Air Quality Climate Change (IAQCC) model system was developed, which allows short and long-term predictions of the indoor climate with respect to outdoor conditions. The IAQCC is a holistic model that combines different scenarios in the form of submodels: building physics, indoor emissions, chemical-physical reaction and transformation, mold growth, and indoor exposure. IAQCC allows simulation of indoor gas and particle concentrations with outdoor influences, indoor materials and activity emissions, particle deposition and coagulation, gas reactions, and SVOC partitioning. These key processes are fundamentally linked to temperature and relative humidity. With the aid of the building physics model, the indoor temperature and humidity, and pollutant transport in building zones can be simulated. The exposure model refers to the calculated concentrations and provides evaluations of indoor thermal comfort and exposure to gaseous, particulate, and microbial pollutants.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Cambio Climático , Humedad , Temperatura
12.
J Control Release ; 345: 625-645, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35321827

RESUMEN

OBJECTIVE: To perform a bibliometric analysis in the field of ocular drug delivery research to characterize the current international trends and to present visual representations of the past and emerging trends on ocular drug delivery research over the past decade. METHOD: In this cross-sectional study, a bibliometric analysis of data retrieved and extracted from the Web of Science Core Collection (WoSCC) database was performed to analyze evolution and theme trends on ocular drug delivery research from January 1, 2001, to December 31, 2020. A total of 4334 articles on ocular drug delivery were evaluated for specific characteristics, such as publication year, journals, authors, institutions, countries/regions, references, and keywords. Co-authorship analysis, co-occurrence analysis, co-citation analysis, and network visualization were constructed by VOSviewer. Some important subtopics identified by bibliometric characterization were further discussed and reviewed. RESULTS: From 2001 to 2020, the annual global publications increased by 746.15%, from 52 to 440. International Journal of Pharmaceutics published the most manuscripts (250 publications) and produced the highest citations (9509 citations), followed by Investigative Ophthalmology & Visual Science (202 publications) and Journal of Ocular Pharmacology and Therapeutics (136 publications). The United States (1289 publications, 31,512 citations), the University of Florida (82 publications, 2986 citations), and Chauhan, Anuj (52 publications, 2354 citations) were the most productive and impactful institution, country, and author respectively. The co-occurrence cluster analysis of the top 100 keywords form five clusters: (1) micro/nano ocular drug delivery systems; (2) the treatment of inflammation and posterior diseases; (3) macroscopic ocular drug delivery systems/devices; (4) the characteristics of drug delivery systems; (5) and the ocular drug delivery for glaucoma treatment. Diabetic macular edema, anti-VEGF, ranibizumab, bevacizumab, micelles and latanoprost, were the latest high-frequency keywords, indicating the emerging frontiers of ocular drug delivery. Further discussions into the subtopics were provided to assist researchers to determine the range of research topics and plan research direction. CONCLUSIONS: Over the last two decades there has been a progressive increase in the number of publications and citations on research related to ocular drug delivery across many countries, institutions, and authors. The present study sheds light on current trends, global collaboration patterns, basic knowledge, research hotspots, and emerging frontiers of ocular drug delivery. Novel solutions for ocular drug delivery and the treatment of inflammation and posterior diseases were the major themes over the last 20 years.


Asunto(s)
Retinopatía Diabética , Edema Macular , Bibliometría , Estudios Transversales , Sistemas de Liberación de Medicamentos , Humanos , Inflamación , Estados Unidos
13.
Transl Vis Sci Technol ; 11(3): 24, 2022 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-35315873

RESUMEN

Purpose: To compare the correlation between degree of lens opacity and the phacoemulsification energy parameter in patients with age-related cataract as determined by slit lamp, 25-MHz ultrasound biomicroscopy (UBM), and Scheimpflug imaging (Pentacam) and to evaluate the application of these three methods to measuring lens opacification. Methods: This observational study was conducted in 319 patients (381 eyes) with different types of age-related cataract. The average age of patients was 67.3 ± 11.4 years. The degree of lens opacity acquired by slit lamp, 25-MHz UBM, and Pentacam was determined by the Lens Opacity Classification System III (LOCSIII), pixel units calculated by ImageJ, and lens density, respectively. We primarily analyzed and compared the correlation between lens opacity and the cumulative dissipated energy (CDE) values of phacoemulsification. Results: Cortical, nuclear, and posterior subcapsular (PSC) cataracts were evaluated as follows: LOCSIII grades 3.31 ± 1.42, 3.29 ± 1.49, and 0.91 ± 0.83; pixel units 120.91 ± 22.8, 93.2 ± 15.9, and 99.7 ± 13.0; and lens density 51.8 ± 31.2, 21.2 ± 6.10, and 53.3 ± 35.3, respectively. The CDE values were 12.1 ± 12.4, 13.5 ± 9.11, and 3.93 ± 1.96. In cortical cataract, there was a linear correlation among LOCSIII, pixel units, and CDE value (r = 0.560, r = 0.832, and r = 0.582, respectively; both P < 0.05), but lens density had no correlation with other parameters. In nuclear cataract, there was a linear correlation among LOCSIII, lens density, and CDE value (r = 0.747, r = 0.865, and r = 0.906, respectively; both P < 0.05), but pixel units had no correlation with other parameters. In PSC, only pixel units and LOCSIII showed a correlation. Conclusions: The various imaging methods offered different advantages in terms of determining lens opacity, a feature related to types of age-related cataracts. Choosing the most suitable imaging method to evaluate lens opacification based on the type of age-related cataract is important for accurately predicting the phacoemulsification parameters for cataract surgery. Translational Relevance: Determining the appropriate phacoemulsification strategy depends on quantitative analysis of the degree of lens opacity to reduce intraoperative and postoperative complications and to obtain the optimal postoperative visual outcome.


Asunto(s)
Extracción de Catarata , Catarata , Facoemulsificación , Anciano , Catarata/diagnóstico por imagen , Humanos , Persona de Mediana Edad , Facoemulsificación/efectos adversos , Facoemulsificación/métodos , Agudeza Visual
14.
EMBO Rep ; 23(4): e53691, 2022 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-35201651

RESUMEN

Uncovering the functions of genes in a complex biological process is fundamental for systems biology. However, currently there is no simple and reliable experimental tool available to conduct loss-of-function experiments for multiple genes in every possible combination in a single experiment, which is vital for parsing the interactive role of multiple genes in a given phenotype. In this study, we develop miR-AB, a new microRNA-based shRNA (shRNAmir) backbone for simplified, cost-effective, and error-proof production of shRNAmirs. After verification of its potent RNAi efficiency in vitro and in vivo, miR-AB was integrated into a viral toolkit containing multiple eukaryotic promoters to enable its application in diverse cell types. We further engineer eight fluorescent proteins emitting wavelengths across the entire visible spectrum into this toolkit and use it to set up a multicolor-barcoded multiplex RNAi assay where multiple genes are strongly and reliably silenced both individually and combinatorially at a single-cell level.


Asunto(s)
MicroARNs , Vectores Genéticos , MicroARNs/genética , MicroARNs/metabolismo , Regiones Promotoras Genéticas , Interferencia de ARN , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo
15.
Exp Cell Res ; 410(1): 112955, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34875217

RESUMEN

The retinal pigment epithelium cells (RPE) are sensitive to oxidative stimuli due to long-term exposure to various environmental stimuli. Thus, the oxidative injury of RPE cells caused by the imbalance of redox homeostasis is one of the main pathogenic factors of age-related macular degeneration (AMD). But the sophisticated mechanisms linking AMD to oxidative stress are not fully elucidated. Activation of Nrf2 signal pathway can protect RPE cells from oxidative damage. The present study investigated the regulating mechanism of miR-125b in Nrf2 cascade and evaluated its antioxidant capacity. The in vitro studies indicated that overexpression of miR-125b substantially inhibited Keap1 expression, enhanced Nrf2 expression and induced Nrf2 nuclear translocation. Importantly, functional studies demonstrated that forced expression of miR-125b could significantly elevate cell proliferation and superoxide dismutase (SOD) levels while reduce reactive oxygen species (ROS) overproduction and malondialdehyde (MDA) formation. Further studies showed that miR-125b had no effect when Nrf2 was silenced in ARPE-19 cells. Additionally, the results identified that Nrf2 silence induced ROS accumulation enhances HIF-1α protein expression, while miR-125b could offset this effect via promoting HIF-1α protein degradation. Subsequent in vivo studies demonstrated that sodium iodate induced outer retina thinner was reversed with exogenous supplementation of miR-125b, which was cancelled in Nrf2 knockout mice. In conclusion, this study illustrated that miR-125b can protect RPE from oxidative damage via targeting Nrf2/HIF-1α signal pathway and potentially may serve as a therapeutic agent of AMD.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Degeneración Macular/genética , MicroARNs/genética , Factor 2 Relacionado con NF-E2/genética , Regulación de la Expresión Génica/genética , Humanos , Degeneración Macular/metabolismo , Degeneración Macular/patología , Estrés Oxidativo/genética , Especies Reactivas de Oxígeno/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/patología , Transducción de Señal
16.
Curr Eye Res ; 47(4): 565-572, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34935556

RESUMEN

PURPOSE: This study performs to evaluate the Hydrophobic and Hydrosmart 360°square-edge intraocular lens drug delivery of Aspirin using an in vitro lens capsular model. METHODS: Cell counting kit-8 assay was used to calculate 50% inhibiting concentration values in both SRA01/04 and HLE-B3 cells. Hoechst staining and transwell assay were used to detect cell proliferation and cell migration. The in vitro lens capsule model was established mainly with a special transwell-col and cell climbing sheet, in which an intraocular lens and the TGF-ß2 were added. The ultraviolet spectrophotometer was used to measure the drug concentrations released in vitro. Cell-exclusion zone assay was used to detect the cell migration in the in vitro capsular model. RESULTS: It shows that cell morphology and distribution of SRA01/04 in the in vitro lens capsular model were closer to those in vivo. The results revealed that there could be significant inhibiting effects on cell migration of the hydrosmart intraocular lens with a sustained drug release in vitro in 7 days, while the hydrophobic intraocular lens drug delivery of Aspirin was mainly performed only from day 1 to day 3. CONCLUSIONS: Results showed the developed hydrosmart intraocular lens could release Aspirin continuously in vitro to inhibit the cell migration of lens epithelial cells.


Asunto(s)
Opacificación Capsular , Cápsula del Cristalino , Cristalino , Lentes Intraoculares , Aspirina/farmacología , Opacificación Capsular/prevención & control , Movimiento Celular , Células Epiteliales , Humanos
17.
Int J Gen Med ; 14: 2183-2190, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34103973

RESUMEN

OBJECTIVE: The aim of the present study was to evaluate the stability of four different types of aspheric intraocular lenses (IOLs) after implantation. METHODS: This retrospective study included 124 eyes implanted with four different types of aspheric IOLs including a one-piece four-loop fixed hydrophilic acrylic IOL, a one-piece flat fixed acrylic IOL, a one-piece two-loop fixed acrylic IOL, and a three-piece two-loop fixed silicone IOL. IOL decentration, tilt, and ocular coma-like aberration (coma) at one-week, one-month, three-month, and one-year time points were evaluated postoperatively. RESULTS: IOL decentration, tilt, and coma in the AO, 36A, IQ, and KS-AiN implantation groups were statistically significantly different one week and one year postoperatively (p < 0.01). There were significant differences between each of the pairs of groups (p < 0.01), except for coma between the AO and 36A implantation groups one week postoperatively (p > 0.05). When comparing the different time points (ie, one week, one month, three months, and one year postoperatively), IOL decentration, tilt, and coma were significantly different in each group (p < 0.05). IOL decentration, tilt, and coma in each group increased over the period from one week to one year postoperatively. A positive linear correlation was observed between IOL decentration or tilt and coma one year postoperatively (p < 0.01). CONCLUSION: One-piece multi-point fixed acrylic IOLs demonstrate better stability when compared with three-piece two-point fixed silicone IOLs. IOL decentration, tilt, and coma increase gradually over time. Ocular coma-like aberrations are influenced by the stability of IOLs.

18.
Int J Ophthalmol ; 14(4): 589-599, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33875953

RESUMEN

AIM: To evaluate the global trends in and explore hotspots of high myopia (HM) research. METHODS: This bibliometric analysis was used to reveal the publication trends in HM research field based on the Web of Science Core Collection (WoSCC). VOSviewer version 1.6.13 software was used to analyze the data and construct a knowledge map including the yearly publication number, journals, countries, international collaborations, authors, research hotspots, and intellectual base in HM. RESULTS: The search engine found 3544 peer-reviewed publications on HM between 2010 and 2019, and the yearly research output substantially elevated over the past decade. China is the top publishing country, and Sun Yat-sen University was the most active academic institution. Jonas JB is the top publishing scientist, and Investigative Ophthalmology and Visual Science (IOVS) was the most productive journal. The highest cited references mainly focused on epidemiology and management. The keywords formed 6 clusters: 1) refractive surgery; 2) etiology and clinical characteristics; 3) the mechanism of eye growth; 4) management for myopic maculopathy; 5) vitrectomy surgical treatment; 6) myopia-associated glaucoma-like optic neuropathy. CONCLUSION: The evaluation of development trends based on the data extracted from WoSCC can provide valuable information and guidance for ophthalmologists and public health researchers to improve management procedures in HM field.

19.
Indoor Air ; 31(3): 818-831, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33247488

RESUMEN

More representative data on source-specific particle number emission rates and associated exposure in European households are needed. In this study, indoor and outdoor particle number size distributions (10-800 nm) were measured in 40 German households under real-use conditions in over 500 days. Particle number emission rates were derived for around 800 reported indoor source events. The highest emission rate was caused by burning candles (5.3 × 1013  h-1 ). Data were analyzed by the single-parameter approach (SPA) and the indoor aerosol dynamics model approach (IAM). Due to the consideration of particle deposition, coagulation, and time-dependent ventilation rates, the emission rates of the IAM approach were about twice as high as those of the SPA. Correction factors are proposed to convert the emission rates obtained from the SPA approach into more realistic values. Overall, indoor sources contributed ~ 56% of the daily-integrated particle number exposure in households under study. Burning candles and opening the window leads to seasonal differences in the contributions of indoor sources to residential exposure (70% and 40% in the cold and warm season, respectively). Application of the IAM approach allowed to attribute the contributions of outdoor particles to the penetration through building shell and entry through open windows (26% and 15%, respectively).


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Monitoreo del Ambiente , Material Particulado , Aerosoles , Composición Familiar , Humanos , Tamaño de la Partícula , Estaciones del Año , Ventilación
20.
Curr Eye Res ; 46(8): 1137-1147, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33327804

RESUMEN

MATERIALS AND METHODS: LECs were cultured and induced with TGF-ß2 (10 ng/mL). SiRNA against MALAT1 (Si-MALAT1) was transfected into LECs to knockdown the expression of MALAT1. To overexpress or knockdown miR-204-5p, miR-204-5p mimics (miR-204-5p mimics) and anti-miR-204-5p (miR-204-5p inhibitor) were transfected into LECs. We used RNA FISH to identify the location of MALAT1. RNA levels of MALAT1 and miR-204-5p were analyzed by RT-qPCR. Additionally, target protein levels of Smad4, epithelial differentiation and mesenchymal markers were analyzed with Western blot. We employed EdU Labeling to measured cell proliferation and performed Transwell Assay to analyze the cell migration. Dual-luciferase reporter assays in LECs were conducted to verify whether miRNA-204-5p was negatively regulated by MALAT1 and Smad4 was a direct target of miR-204-5p. RESULTS: The expression of MALAT1 was upregulated in PCO specimens. MALAT1 was overexpressed in TGF-ß2 induced LECs, and the knockdown of MALAT1 could attenuate TGF-ß2 induced EMT. Besides, the upregulation of MALAT1 was correlated with the downregulation of miR-204-5p and upregulation of Smad4. Importantly, MALAT1 was revealed to be located in the cytoplasm of LECs. Furthermore, luciferase reporter assays confirmed that MALAT1 could negatively regulate the expression of miR-204-5p and then regulate its direct target Smad4. Finally, the knockdown of MALAT1 could inhibit the EMT, proliferation, and migration of LECs; however, those can be reversed by anti-miR-204-5p. CONCLUSIONS: Our findings reveal that MALAT1 may regulate EMT, proliferation, and migration of LECs as a ceRNA by "sponging" miR-204-5p and targeting Smad4, and serve as a promising therapeutic target in preventing PCO.


Asunto(s)
Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Regulación de la Expresión Génica/fisiología , Cristalino/citología , MicroARNs/genética , ARN Largo no Codificante/genética , Proteína Smad4/genética , Western Blotting , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Células Cultivadas , Células Epiteliales/efectos de los fármacos , Vectores Genéticos , Humanos , Hibridación Fluorescente in Situ , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Transfección , Factor de Crecimiento Transformador beta2/farmacología
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