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1.
EMBO J ; 42(16): e113258, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37409632

RESUMEN

Mitochondrial biogenesis is the process of generating new mitochondria to maintain cellular homeostasis. Here, we report that viruses exploit mitochondrial biogenesis to antagonize innate antiviral immunity. We found that nuclear respiratory factor-1 (NRF1), a vital transcriptional factor involved in nuclear-mitochondrial interactions, is essential for RNA (VSV) or DNA (HSV-1) virus-induced mitochondrial biogenesis. NRF1 deficiency resulted in enhanced innate immunity, a diminished viral load, and morbidity in mice. Mechanistically, the inhibition of NRF1-mediated mitochondrial biogenesis aggravated virus-induced mitochondrial damage, promoted the release of mitochondrial DNA (mtDNA), increased the production of mitochondrial reactive oxygen species (mtROS), and activated the innate immune response. Notably, virus-activated kinase TBK1 phosphorylated NRF1 at Ser318 and thereby triggered the inactivation of the NRF1-TFAM axis during HSV-1 infection. A knock-in (KI) strategy that mimicked TBK1-NRF1 signaling revealed that interrupting the TBK1-NRF1 connection ablated mtDNA release and thereby attenuated the HSV-1-induced innate antiviral response. Our study reveals a previously unidentified antiviral mechanism that utilizes a NRF1-mediated negative feedback loop to modulate mitochondrial biogenesis and antagonize innate immune response.


Asunto(s)
Antivirales , Biogénesis de Organelos , Animales , Ratones , ADN Mitocondrial/genética , Inmunidad Innata , Factor Nuclear 1 de Respiración/genética
2.
Genomics ; 115(4): 110644, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37279838

RESUMEN

Single-cell RNA sequencing (scRNA-seq) analysis have provided an unprecedented resolution for the studies on diabetic retinopathy (DR). However, the early changes in the retina in diabetes remain unclear. A total of 8 human and mouse scRNA-seq datasets, containing 276,402 cells were analyzed individually to comprehensively delineate the retinal cell atlas. The neural retinas were isolated from the type 2 diabetes (T2D) and control mice, and scRNA-seq analysis was conducted to evaluate the early effects of diabetes on the retina. Bipolar cell (BC) heterogeneity were identified. We found some stable BCs across multiple datasets, and explored their biological functions. A new RBC subtype (Car8_RBC) in the mouse retina was validated using the multi-color immunohistochemistry. AC149090.1 was significantly upregulated in the rod cells, ON cone BCs (CBCs), OFF CBCs, and RBCs in T2D mice. Additionally, the interneurons, especially BCs, were the most vulnerable cells to diabetes by integrating scRNA-seq and genome-wide association studies (GWAS) analyses. In conclusion, this study delineated a cross-species retinal cell atlas and uncovered the early pathological alterations in the retina of T2D mice.


Asunto(s)
Diabetes Mellitus Tipo 2 , Ratones , Animales , Humanos , Diabetes Mellitus Tipo 2/genética , Estudio de Asociación del Genoma Completo , Análisis de Expresión Génica de una Sola Célula , Retina , Células Fotorreceptoras Retinianas Conos/metabolismo , Análisis de la Célula Individual , Análisis de Secuencia de ARN , Proteínas del Tejido Nervioso/metabolismo , Biomarcadores de Tumor/metabolismo
3.
Sheng Li Xue Bao ; 76(4): 622-630, 2024 Aug 25.
Artículo en Zh | MEDLINE | ID: mdl-39192794

RESUMEN

Parkinson's disease (PD), a prevalent neurodegenerative condition, manifests predominantly through the degeneration of nigrostriatal dopaminergic (DA) pathways, culminating in a notable depletion of striatal dopamine. This pathophysiological process critically impairs the DA-mediated regulation of motor behaviors within the basal ganglia circuitry, particularly impacting various subtypes of striatal medium spiny neurons. Recent advancements in neuroscientific research have illuminated the pivotal role of D2-dopamine receptor expressing medium spiny neurons (D2-MSNs) plasticity in coordinating motor control in PD. Intriguingly, aerobic exercise emerges as a potent therapeutic intervention, capable of preventing or improving motor impairments. This ameliorative effect is mediated through the modulation of DA receptor activity and the consequent activation of downstream extracellular signal-regulated kinase (Erk) signaling pathway. This article meticulously reviewed the intricate regulatory mechanisms governing the structural and functional plasticity of striatal D2-MSNs in the context of PD. It particularly emphasized the transformative impact of aerobic exercise on motor deficits in PD, attributing this effect to the modulation of striatal D2-MSNs.


Asunto(s)
Cuerpo Estriado , Plasticidad Neuronal , Enfermedad de Parkinson , Receptores de Dopamina D2 , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/terapia , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/fisiología , Plasticidad Neuronal/fisiología , Humanos , Cuerpo Estriado/metabolismo , Cuerpo Estriado/fisiopatología , Animales , Ejercicio Físico/fisiología , Terapia por Ejercicio/métodos
4.
Int Ophthalmol ; 43(3): 779-793, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36056289

RESUMEN

PURPOSE: To investigate corneal sub-basal nerve morphology changes in primary Sjogren's syndrome (SS) dry eye (SSDE) patients and determine the association with disease severity at microstructural level. METHODS: Twenty-eight eyes of 17 SSDE and 82 eyes of 47 age- and sex-matched non-SS dry eye (NSSDE) patients were included. The Ocular Surface Disease Index questionnaire (OSDI), Schirmer's test (ST), tear meniscus height (TMH), non-invasive breakup time (NIBUT), meibomian gland (MG) morphology, and ocular staining score (OSS) were assessed. In vivo confocal microscopy was performed to observe corneal sub-basal nerve morphology (length, reflectivity, width, and tortuosity). Associations between clinical features and nerve parameters were analysed. RESULTS: SSDE patients more frequently had increased nerve reflectivity (151.12 ± 17.07 vs. 139.37 ± 14.31 grey value), width (4.45 ± 0.87 vs. 3.92 ± 0.81 µm), tortuosity (132.90 ± 8.04 vs. 129.50 ± 7.33 degree), and higher reflectivity, width, and total nerve grades than NSSDE individuals (all P < 0.05). Significant associations were found between nerve reflectivity/width and anti-SSA [OR = 1.139 (1.013-1.281)/1.802 (1.013-4.465)]/labial gland biopsy [OR = 1.046 (1.002-1.161)/1.616 (1.020-3.243)]. Higher nerve width was associated with increased OSDI [ß = 0.284 (0.187-0.455)], MG score [ß = 0.185 (0.109-0.300)] and OSS [ß = 0.163 (0.020-0.345)], but decreased NIBUT [ß = - 0.247 (- 0.548 ~ - 0.154)]. Higher nerve total grade was associated with increased OSDI [ß = 0.418 (0.157-0.793)] and OSS [ß = 0.287 (0.027-0.547)], but decreased ST [ß = - 0.410 (-0.857 ~ - 0.138)]. CONCLUSIONS: Corneal nerve morphology changes associated with clinical features in SS patients. These changes may facilitate severity evaluation and management of the disease.


Asunto(s)
Síndromes de Ojo Seco , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Lágrimas/química , Microscopía Confocal/métodos , Córnea/patología , Síndromes de Ojo Seco/etiología , Síndromes de Ojo Seco/complicaciones
5.
Exp Brain Res ; 240(6): 1713-1725, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35384454

RESUMEN

In Parkinson's disease (PD) state, with progressive loss of dopaminergic neurons in the substantia nigra, the striatal dopamine (DA) and glutamate (Glu) levels change, resulting in dysfunction of basal ganglia motor regulation. The PD patient presents motor dysfunction such as resting tremor, bradykinesia, and muscular rigidity. To investigate the mechanism of aerobic exercise to improve PD-related motor dysfunction, in the current study, 6-hydroxydopamine (6-OHDA) was used to induce the PD mice model, and the motor function of PD mice was comprehensively evaluated by open-field test, rotarod test, and gait test. The co-expression of prodynorphin (PDYN) and proenkephalin (PENK) with extracellular signal-regulated kinase (Erk1/2) and phosphorylation Erk1/2 (p-Erk1/2) were detected by double-labeling immunofluorescence. The results showed that a 4-week aerobic exercise intervention could effectively improve the motor dysfunction of PD mice. Moreover, it was found that the expressions of Erk1/2 and p-Erk1/2 in the dorsal striatum (Str) of PD mice were significantly increased, and the number of positive cells co-expressed by Erk1/2, p-Erk1/2, and PENK was significantly higher than PDYN. The above phenomenon was reversed by a 4-week aerobic exercise intervention. Therefore, this study suggests that the mechanism by which aerobic exercise improves PD-related motor dysfunction may be related to that the aerobic exercise intervention alleviates the activity of extracellular signal-regulated kinase/mitogen-activated protein kinases (Erk/MAPK) signaling pathway in striatal medium spiny neurons expressing D2-like receptors (D2-MSNs) of PD mice by regulating the striatal DA and Glu signaling.


Asunto(s)
Enfermedad de Parkinson Secundaria , Condicionamiento Físico Animal , Transducción de Señal , Animales , Cuerpo Estriado/metabolismo , Modelos Animales de Enfermedad , Dopamina/farmacología , Neuronas Dopaminérgicas/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ratones , Oxidopamina , Enfermedad de Parkinson Secundaria/metabolismo , Enfermedad de Parkinson Secundaria/terapia
6.
Graefes Arch Clin Exp Ophthalmol ; 259(2): 547-555, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32902756

RESUMEN

PURPOSE: To establish a more sensitive diagnostic tool for traumatic optic neuropathy (TON), we explored the diagnostic efficacy of isolated-check visual evoked potential (ic-VEP) for TON in orbital fracture and compared ic-VEP with pattern-reversal visual evoked potential (P-VEP) testing. METHODS: This was a prospective single-center study. A total of 137 eyes from 131 patients diagnosed between December 2016 and October 2019 with orbital fractures were included in the study. Injury history, best-corrected visual acuity (BCVA), visual field, computed tomography (CT), P-VEP, and ic-VEP data were collected. Parameters of ic-VEP (signal-to-noise ratio [SNR]) and P-VEP (peak latency and amplitude of P100) were compared and diagnostic accuracy was analyzed. RESULTS: TON was associated with worse BCVA than non-TON (median 0.52 versus 0.10 logMAR, P < 0.001). SNRs were negatively associated with the P100 peak latency while positively associated with the P100 amplitude. The sensitivity of ic-VEP for TON (79.6%) was higher than that of P-VEP (61.2%, P = 0.049), although this difference was not statistically significant after Bonferroni correction. Using ic-VEP and P-VEP together could increase sensitivity (87.8%). Maximum areas under curve were obtained using the SNR criteria of 1.3, 1.47, and 1.54 at 8%, 16%, and 32% depth of modulation, respectively. CONCLUSION: ic-VEP was more sensitive than P-VEP in diagnosing TON, and a combination of the two examination tests was recommended. The use of ic-VEP as the new diagnostic standard technique for TON should be considered.


Asunto(s)
Traumatismos del Nervio Óptico , Fracturas Orbitales , Potenciales Evocados Visuales , Humanos , Traumatismos del Nervio Óptico/diagnóstico , Traumatismos del Nervio Óptico/etiología , Estudios Prospectivos , Agudeza Visual
7.
Exp Eye Res ; 201: 108279, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32991882

RESUMEN

We aimed to investigate the associations among lens epithelium telomere length (LETL), cataract types, and systemic pro-senescence factors in patients with age-related cataract. In this prospective study, the general demographic factors, body mass index, smoking history, depression, hypertension, diabetes, various psychological measures, and uncorrected distant visual acuity of patients with age-related cataract were recorded. Lens Opacities Classification System III (LOCS III) scores and lens density measured by Scheimpflug imaging were used to evaluate the cataracts. LETL was measured by real-time polymerase chain reaction. Correlations among these parameters were analyzed. The LOCS III nuclear opalescence (NO) score was associated with age (ß = 0.053, P < 0.001) and Patient Health Questionnaire-9 score (ß = -0.042, P = 0.004). Smoking was identified as a risk factor affecting LOCS III NO score (odds ratio = 1.546, 95% confidence interval, 1.128-2.119), but not the LOCS III cortical or posterior subcapsular scores. LETLs showed a weak association with systemic factors and LOCS III scores, and a significantly moderate correlation with the average objective lens densities of different regions measured by Scheimpflug imaging (r values ranged from -0.278 to -0.523, P < 0.05). However, there was no correlation between the LETLs and the maximum lens densities. The groups with a relatively low lens density had longer LETLs. In Conclusion, being an age-related disease, cortical cataract was also associated with "aging of the lens epithelium." Notably, lens epithelium activity rarely showed systemic effects. Thus, future studies should emphasize the importance of the telomeric system in cataractous process and aging.


Asunto(s)
Envejecimiento , Catarata/genética , Epitelio/patología , Núcleo del Cristalino/patología , Telómero/patología , Agudeza Visual , Anciano , Catarata/patología , Femenino , Humanos , Masculino , Estudios Prospectivos
8.
Int Ophthalmol ; 40(7): 1831-1839, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32249376

RESUMEN

PURPOSE: To evaluate the relationship between cataract types and subjective visual function among patients with age-related cataract. METHODS: This was a prospective, multicenter, 831 Chinese patient-based, cross-sectional study. Patients were administered the Visual Function Index-14 (VF-14) and the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) to evaluate their subjective visual function. Lens Opacities Classification System III (LOCS III) was used to evaluate the type of cataract. Relationships among these parameters were analyzed. RESULTS: LOCS III cortical (C) and posterior subcapsular scores are negatively associated with VF-14 (r = - 0.188, P < 0.01; r = - 0.146, P < 0.01) and total score of NEI-VFQ-25 (r = - 0.223, P < 0.01; r = - 0.160, P < 0.01), respectively; LOCS III nuclear opalescence (NO) score is positively associated with VF-14 (r = 0.087, P < 0.05) and total score of NEI-VFQ-25 (r = 0.097, P < 0.05). In multiple linear regression, a decrease in the LOCS III C score is a significant predictor for improvement of the total score of NEI-VFQ-25 (ß = - 1.286, P < 0.05). In contrast, an increase in LOCS III NO score is a significant predictor for improvement of VF-14 (ß = 3.826, P < 0.01) and total score of NEI-VFQ-25 (ß = 4.618, P < 0.01). Patients with LOCS III C score ≤ 2 have higher VF-14 (49.38 versus 43.74, P < 0.01), total (80.73 versus 71.58, P < 0.01) and subscale scores of NEI-VFQ-25 than patients with LOCS III C score > 2. CONCLUSION: Cortical cataract has adverse effects on subjective visual function, while mild-to-moderate nuclear cataract has positive effects. Furthermore, "LOCS III C score > 2" can be a potential cutoff as a reference for cataract surgery without self-assessing questionnaires.


Asunto(s)
Catarata , National Eye Institute (U.S.) , Factores de Edad , Anciano , Catarata/diagnóstico , Estudios Transversales , Femenino , Humanos , Masculino , Estudios Prospectivos , Calidad de Vida , Encuestas y Cuestionarios , Estados Unidos , Agudeza Visual
9.
Brain Res Bull ; 209: 110906, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38395109

RESUMEN

OBJECTIVE: To investigate the role of the striatal extracellular signal-regulated kinase (Erk1/2) and its phosphorylation (p-Erk1/2) in aerobic training to alleviate the development of the L-DOPA induced dyskinesia (LID) in PD mice. METHODS: Forty-eight male C57BL/6 N mice were randomly divided into the 6-OHDA surgery group (6-OHDA, n=42) and the sham surgery group (Sham, n=6). A two-point injection of 6-OHDA into the right striatum was used to establish a lateralized injury PD model. PD mice were randomly divided into a PD control group (PD, n=13) and a PD exercise group (PDE, n=16), this is followed by 4 weeks of L-DOPA treatment, and PDE mice received concurrent running table training (18 m/min, 40 min/day, 5 times/week). AIM scores were performed weekly, and mice were assessed for motor function after 4 weeks using the rotarod, open field, and gait tests. Immunohistochemistry was used to test nigrostriatal TH expression, Western blot was used to determine Erk1/2 and p-Erk1/2 protein expression, and immunofluorescence double-labeling technique was used to detect Erk1/2 and p-Erk1/2 co-expression with prodynorphin (PDYN). RESULTS: (1) All AIM scores of PD and PDE mice increased significantly (P < 0.05) with the prolongation of L-DOPA treatment. Compared with PD, all AIM scores were significantly lower in PDE mice (P < 0.05). (2) After 4 weeks, the motor function of PD mice was significantly reduced compared with Sham (P < 0.05 or P < 0.01); compared with PD, the motor function of PDE mice was significantly increased (P < 0.05). (3) Compared with Sham, the expression of Erk1/2 protein, the number of positive cells of Erk1/2 and p-Erk1/2 and the number of positive cells co-expressed with PDYN were significantly increased in PD mice (P < 0.05); compared with PD, Erk1/2 protein expression was significantly decreased in PDE mice (P < 0.05), and the number of Erk1/2 and p-Erk1/2 positive cells was significantly reduced (P < 0.05). CONCLUSION: 4 weeks of aerobic exercise can effectively alleviate the development of L-DOPA-induced dyskinesia and improve motor function in PD mice. The related mechanism may be related to the inhibition of striatal Erk/MAPK signaling pathway overactivation by aerobic exercise, but this change did not occur selectively in D1-MSNs.


Asunto(s)
Discinesia Inducida por Medicamentos , Ejercicio Físico , Enfermedad de Parkinson , Animales , Masculino , Ratones , Antiparkinsonianos/farmacología , Cuerpo Estriado/metabolismo , Modelos Animales de Enfermedad , Discinesia Inducida por Medicamentos/metabolismo , Levodopa , Sistema de Señalización de MAP Quinasas , Ratones Endogámicos C57BL , Oxidopamina/farmacología , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/metabolismo , Humanos
10.
J Photochem Photobiol B ; 255: 112908, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38663336

RESUMEN

The prevalence of Light-emitting diodes (LEDs) has exposed us to an excessive amount of blue light (BL) which causes various ophthalmic diseases. Previous studies have shown that conjunctiva is vulnerable to BL. In this study, we aimed to investigate the underlying mechanism of BL-induced injury in conjunctiva. We placed C57BL/6 mice and human conjunctival epithelial cell lines (HCECs) under BL (440 nm ± 15 nm, 0.2 mW/cm2) to establish a BL injury model in vivo and in vitro. Immunohistochemistry and MDA assay were used to identify lipid peroxidation (LPO) in vivo. HE staining was applied to detect morphological damage of conjunctival epithelium. DCFH-DA, C11-BODIPY 581/591, Calcein-AM, and FeRhoNox™-1 probes were performed to identify ferroptosis levels in vitro. Real-time qPCR and Western blotting techniques were employed to uncover signaling pathways of blue light-induced ferroptosis. Our findings demonstrated that BL affected tear film instability and induced conjunctival epithelium injury in vivo. Ferrostatin-1 significantly alleviated blue light-induced ferroptosis in vivo and in vitro. BL downregulates the levels of solute carrier family 7 member 11 (SLC7A11), Ferritin heavy chain (FTH1), and glutathione peroxidase (GPX4) by inhibiting the activation and translocation of the Signal transducer and activator of transcription 3 (STAT3) from inducing Fe2+ burst, ROS and LPO accumulation, ultimately resulting in ferroptosis. This study will offer new insight into BL-induced conjunctival injury and LED-induced dry eye.


Asunto(s)
Luz Azul , Conjuntiva , Ferroptosis , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Factor de Transcripción STAT3 , Animales , Humanos , Ratones , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Línea Celular , Conjuntiva/metabolismo , Conjuntiva/efectos de la radiación , Conjuntiva/patología , Ciclohexilaminas , Células Epiteliales/metabolismo , Células Epiteliales/efectos de la radiación , Células Epiteliales/patología , Epitelio/efectos de la radiación , Epitelio/metabolismo , Epitelio/patología , Ferroptosis/efectos de la radiación , Peroxidación de Lípido/efectos de la radiación , Ratones Endogámicos C57BL , Fenilendiaminas/farmacología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de la radiación , Factor de Transcripción STAT3/metabolismo
11.
Sci Rep ; 14(1): 12132, 2024 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802497

RESUMEN

The striatum plays a crucial role in providing input to the basal ganglia circuit and is implicated in the pathological process of Parkinson's disease (PD). Disruption of the dynamic equilibrium in the basal ganglia loop can be attributed to the abnormal functioning of the medium spiny neurons (MSNs) within the striatum, potentially acting as a trigger for PD. Exercise has been shown to mitigate striatal neuronal dysfunction through neuroprotective and neurorestorative effects and to improve behavioral deficits in PD model mice. In addition, this effect is offset by the activation of MSNs expressing dopamine D2 receptors (D2-MSNs). In the current study, we investigated the underlying neurobiological mechanisms of this effect. Our findings indicated that exercise reduces the power spectral density of the beta-band in the striatum and decreases the overall firing frequency of MSNs, particularly in the case of striatal D2-MSNs. These observations were consistent with the results of molecular biology experiments, which revealed that aerobic training specifically enhanced the expression of striatal dopamine D2 receptors (D2R). Taken together, our results suggest that aerobic training aimed at upregulating striatal D2R expression to inhibit the functional activity of D2-MSNs represents a potential therapeutic strategy for the amelioration of motor dysfunction in PD.


Asunto(s)
Cuerpo Estriado , Modelos Animales de Enfermedad , Enfermedad de Parkinson , Condicionamiento Físico Animal , Receptores de Dopamina D2 , Animales , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/genética , Cuerpo Estriado/metabolismo , Ratones , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/fisiopatología , Masculino , Neuronas/metabolismo , Ratones Endogámicos C57BL , Actividad Motora/fisiología , Neuronas Espinosas Medianas
12.
Invest Ophthalmol Vis Sci ; 64(12): 39, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37750741

RESUMEN

Purpose: Wet AMD (wAMD) is associated with cellular senescence. However, senescent cell-targeted therapies for wAMD have rarely been comprehensively studied. This study aimed to explore the therapeutic effects of senolytic agents on choroidal neovascularization (CNV). Methods: RNA sequencing datasets were obtained from the Gene Expression Omnibus database and used to explore the association between senescence and wAMD. We explored the effects of senescent adult RPE cell line-19 cells on the proliferation, migration, invasion, and tube formation of human umbilical vein endothelial cells. A laser-induced CNV animal model was used to study wAMD. We studied a senescent cell elimination therapy for CNV progression using two types of senolytics and a transgenic method. Results: Cells in the retinal pigment epithelium-choroid of the CNV model were enriched in senescence, inflammation, and angiogenesis gene sets. AP20187 was used to specifically eliminate senescent cells and proven to alleviate CNV progression in INK-ATTAC transgenic mice. Senescent adult RPE cell line-1 cells produced elevated levels of senescence-associated secretory phenotypes, including VEGFs; they also demonstrated increased proliferation, migration, invasion, and tube formation in human umbilical vein endothelial cells. The number of senescent cells increased in the laser-induced CNV rat model, and intravitreal injections of dasatinib with quercetin reduced the expression of p16 in CNV and alleviated neovascularization. Conclusions: Senescent RPE cells can accelerate pathological neovascularization; thus, senescent cell-targeting therapy has great clinical potential for wAMD.


Asunto(s)
Neovascularización Coroidal , Quercetina , Adulto , Humanos , Ratones , Animales , Ratas , Dasatinib/farmacología , Quercetina/farmacología , Quercetina/uso terapéutico , Epitelio Pigmentado de la Retina , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/genética , Senescencia Celular , Coroides , Células Endoteliales de la Vena Umbilical Humana , Metildopa
13.
Int J Ophthalmol ; 15(10): 1591-1597, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36262855

RESUMEN

AIM: To explore the changes in lens thickness and density with age. METHODS: A Chinese population-based retrospective study was performed. A total of 497 individuals (490 right eyes and 495 left eyes), ranging from 3 to 69 years old were included. Lens images obtained from IOL Master 700 were used to measure lens thickness and density. Piecewise regression model was chosen to illustrate the relationship of lens thickness and density with age. RESULTS: The proportion of people aged 3-18, 19-40, over 40 was 38.6%, 50.9% and 10.5% respectively. The whole lens thickness decreased with age during the first 7 years of life, kept stable from 8 to 16 years old, and then increased at the rate of about 27 µm per year. The thickness of the lens cortex and nucleus tended to decrease first and then increase with age, which was dependent on age stages. The whole lens density also decreased with age until 7 years old. The increasing rate of lens density was different in different age groups. The whole lens density increased rapidly from 7 to 22 years old and slowed down after 22 years old. Similarly, the changing tendency of lens cortical and nuclear density differed in different age phases. CONCLUSION: Both lens thickness and density are significantly associated with age, whereas they do not change linearly with age. Moreover, it is necessary to increase the population over 40 years old and conduct further research.

14.
J Colloid Interface Sci ; 624: 650-669, 2022 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-35691230

RESUMEN

Designing efficient nanohybrid electrocatalysts with advanced structure is of great essential for energy conversion devices. Herein, a multi-dimensional hierarchical strategy is proposed to design melamine sponge-derived sulfur and nitrogen co-doped tetrapod carbon (SNTC) supported cobalt-nickel telluride (CoTe2/SNTC, NiTe2/SNTC, and CoNiTe2/SNTC) 1D/3D and 0D/3D nanohybrids for boosting hydrogen evolution reaction (HER) and triiodide reduction reaction (IRR). Among these, the CoNiTe2/SNTC 0D/3D hybrid exhibited superior catalytic activities and excellent electrochemical stability. In alkaline HER, the CoNiTe2/SNTC catalyst had a low Tafel slope of 72 mV dec-1, which was comparable to that of Pt/C (49 mV dec-1). CoNiTe2/SNTC served as counter electrode catalyst in photovoltaics and obtained a power conversion efficiency (PCE) of 8.11%, which is higher than that of Pt (7.25%). This investigation provides a novel approach for designing highly efficient nanohybrid catalysts in advanced energy devices.


Asunto(s)
Cobalto , Níquel , Carbono , Hidrógeno , Nitrógeno , Azufre , Triazinas
15.
Transl Pediatr ; 11(3): 368-374, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35378965

RESUMEN

Background: Neuroblastoma with opsoclonus-myoclonus syndrome (OMS-NB) is a rare disease in children. Few studies of long-term outcome of children with OMS-NB were conducted. This study aimed to review the rate of recovery of neurological symptoms and the long-term neurological outcomes of children with OMS-NB. Methods: This study retrospectively assessed 14 children with OMS-NB diagnosed at Peking University First Hospital from May 2011 to November 2019. Demographic data, neurological symptoms, oncological status and treatments were retrospectively reviewed from the records. Neurological sequelae were recorded by clinical and remote follow-up. Results: During the acute stage, myoclonus and ataxia were observed in all children while opsoclonus was observed in 10/14 children. The median durations of neurological symptoms were 15 months (range, 5-48 months). Approximately 93% (13/14) children revealed neurological sequelae. Significant correlations were as follows: motor retardation with female gender (P<0.001) and residual tumors (P<0.05); language impairment with non-adrenal-gland-located tumors (P<0.05). There were no obvious factors that had a statistical relationship with cognitive disorder or behavioral changes. Conclusions: Children with OMS-NB have favorable outcomes in terms of neurological symptoms. Neurological sequelae occurred in almost all children. Children with different features tend to reveal different sequalae. Features of female gender and residual tumors tend to reveal motor retardation while that of non-adrenal-gland-located tumors tend to reveal language impairment.

16.
J Funct Biomater ; 14(1)2022 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-36662053

RESUMEN

Senescent cells accumulate in aged organisms and promote the progression of age-related diseases including cataracts. Therefore, we aimed to study the therapeutic effects of senescence-targeting drugs on cataracts. In this study, a 28-day D-galactose-induced cataract rat model was used. The opacity index, a grading based on slit-lamp observations, was used to assess lens cloudiness. Furthermore, the average lens density (ALD), lens density standard deviation (LDSD), and maximum lens density (MLD) obtained from Scheimpflug images were used to assess lens transparency. Immunohistochemical stainings for p16 and γH2AX were used as hallmarks of senescence. We treated rat cataract models with the senolytic drug combination dasatinib plus quercetin (D+Q) and senescence-associated secretory phenotype (SASP) inhibitors. In comparison to control lenses, D-galactose-induced cataract lenses showed a higher opacity index, ALD, LDSD, and MLD values, as well as accumulation of senescent lens epithelial cells (LECs). After D+Q treatment, ALD, LDSD, and MLD values on day 21 were significantly lower than those of vehicle-treated model rats. The expression levels of p16 and γH2AX were also reduced after D+Q administration. In addition, the SASP inhibitor rapamycin decreased the opacity index, ALD, LDSD, and MLD values on day 21. In conclusion, D+Q alleviated D-galactose-induced cataract progression by reducing the senescent LEC burden in the early stage of cataract.

17.
J Colloid Interface Sci ; 625: 800-816, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35772208

RESUMEN

The design and exploration of high-efficiency and low-cost electrode catalysts are of great significance to the development of novel energy conversion technologies. In this work, metal and nonmetal heteroatoms co-doped biphasic tungsten-based chalcogenide heterostructured catalyst (Co-WS2/P-WO2.9) with rich defects is successfully synthesized by a vulcanization technique. The electrocatalytic performance of WS2/WO3 in the hydrogen evolution reaction (HER) and triiodide reduction reaction is significantly enhanced by modifying and optimizing its electronic structure through a defect engineering strategy. As an electrocatalyst for HER, the optimized Co-WS2/P-WO2.9 exhibits a low overpotential at 10 mA cm-2 of 146 and 120 mV with small Tafel slopes of 86 and 74 mV dec-1 in alkaline and acidic electrolyte, respectively. In addition, a Co-WS2/P-WO2.9 assembled solar cell yields a short circuit current density of 15.85 mA cm-2, an open-circuit voltage of 0.74 V, a fill factor of 0.66, and a competitive power conversion efficiency (7.83%), which is comparable or higher than conventional Pt-based solar cell (16.02 mA cm-2, 0.70 V, 0.63, 7.14%). The formation of a heterostructure in Co-WS2/P-WO2.9 leads to the presence of a built-in electric field in the interfacial region between Co-WS2 and P-WO2.9, which leads to an increased open-circuit voltage from 0.70 V for Pt to 0.74 V for Co-WS2/P-WO2.9. This work can provide a technical support for developing high-performance heterostructured catalysts, which open up a way for improving catalytic performance of heterostructured catalysts in the field of electrocatalysis.

18.
Eur J Ophthalmol ; 31(5): NP53-NP56, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32498551

RESUMEN

BACKGROUND: Intraocular ossification is an uncommon calcium deposition process associated with trauma, chronic inflammation, tumor, and long-standing retinal detachment. This is the first reported extensive intraocular bone formation associated with silicone oil. CASE PRESENTATION: A 30-year-old Han Chinese man came to us with complaint of red, painful blind right eye. He had a history of ocular trauma, retinal detachment, and two failed retinal reattachment surgeries with silicone oil left in the eye. On examination, conjunctiva congestion, band keratopathy, silicone oil emulsification, and limbus neovascularization were found. B-scan ultrasound and computed tomography scanning demonstrated retinal detachment and calcification of the eyeball wall. Histopathological analysis indicated ossification overlying the choroid. Evisceration was finally operated to relieve the pain. CONCLUSION: The retention of silicone oil in the eye probably accelerates the ossification. Timely silicone oil removal and evisceration should be recommended if necessary for phthisis bulbi.


Asunto(s)
Lesiones Oculares , Desprendimiento de Retina , Adulto , Humanos , Masculino , Osteogénesis , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/etiología , Desprendimiento de Retina/cirugía , Aceites de Silicona/efectos adversos , Vitrectomía
19.
Front Med (Lausanne) ; 8: 759767, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34805225

RESUMEN

Purpose: To explore the associations between refractive errors and multiple eye health outcomes. Methods: This is an umbrella review based on systematic reviews with meta-analyses. In our study, refractive errors included myopia, hyperopia, astigmatism, and anisometropia. We reconducted the meta-analyses whose primary data were available in sufficient detail by random effect model. Heterogeneity was assessed by I 2. The main outcomes included myopic macular degeneration (MMD), retinal detachment (RD), cataract, open-angle glaucoma (OAG), strabismus, age-related macular degeneration (AMD), and diabetic retinopathy (DR). Results: Myopia was associated with increased risk of MMD (relative risk = 102.11, 95% CI 52.6-198.22), RD (3.45, 1.08-11.00), nuclear cataract (2.15, 1.53-3.03), posterior subcapsular (PSC) cataract (1.74, 1.41-2.15), OAG (1.95, 1.74-2.19), exotropia (5.23, 2.26-12.09), but decreased risk of DR (0.83, 0.66-1.04), and early AMD (0.80, 0.67-0.94). From mild-to-high myopia, the association strengthened for MMD, RD, nuclear cataract, PSC cataract, OAG, and DR. Hyperopia was associated with an increased risk of early AMD (1.09, 1.01-1.18) and esotropia (22.94, 10.20-51.62). Astigmatism and anisometropia were associated with increased risk of both exotropia and esotropia. Conclusions: Myopia, especially high myopia, demonstrated the highest risk for eye health outcomes, such as MMD, RD, OAG, nuclear and PSC cataracts, and exotropia. However, myopia was associated with a lower risk of early AMD and DR. Individuals with hyperopia are more likely to suffer early AMD and esotropia. Astigmatism and anisometropia predispose to strabismus. A lot of research studies on the mechanism of the associations are needed. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=239744; identifier: 239744.

20.
J Ophthalmol ; 2021: 1115076, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35003788

RESUMEN

PURPOSE: The purpose is to compare the outcomes of implantation of trifocal intraocular lenses (TIOLs) and extended depth of focus (EDOF) intraocular lenses (IOLs). METHODS: A comprehensive search of PubMed, Cochrane Library, EMBASE, and ClinicalTrial.gov was conducted in March 2020 to identify relevant studies. A meta-analysis of the results was performed. Patients implanted with EDOF IOLs or TIOLs in previous studies were included. The primary outcomes of the study were uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), and defocus curve. RESULTS: TIOLs and EDOF IOLs provided comparable binocular UDVA (MD = -0.01, 95% CI: -0.04, 0.03, logMAR). However, EDOF IOLs provided better UIVA (MD: -0.08, 95% CI: -0.14, -0.01, logMAR) and worse UNVA (MD: 0.10, 95% CI: 0.06, 0.14, logMAR) than TIOLs. Fewer patients achieved spectacle independence after implantation of EDOF IOLs (RR: 0.74, 95% CI: 0.63, 0.87) than after implantation of TIOLs, especially for near vision (RR = 0.82, 95% CI: 0.68, 0.99). There was no statistically significant difference in contrast sensitivity (CS) under photopic or mesopic conditions with both IOLs. Patient satisfaction after implantation of both IOLs was high. CONCLUSION: EDOF IOLs and TIOLs provide comparable distance vision. However, EDOF IOLs provide better intermediate vision and worse near vision than TIOLs. The advantages of EDOF IOLs over TIOLs in terms of CS, aberrations, and visual disturbance are not significant. Patients are satisfied with both types of IOLs.

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