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1.
Nature ; 609(7929): 925-930, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36171386

RESUMO

The paradigmatic example of a topological phase of matter, the two-dimensional Chern insulator1-5, is characterized by a topological invariant consisting of a single integer, the scalar Chern number. Extending the Chern insulator phase from two to three dimensions requires generalization of the Chern number to a three-vector6,7, similar to the three-dimensional (3D) quantum Hall effect8-13. Such Chern vectors for 3D Chern insulators have never been explored experimentally. Here we use magnetically tunable 3D photonic crystals to achieve the experimental demonstration of Chern vectors and their topological surface states. We demonstrate Chern vector magnitudes of up to six, higher than all scalar Chern numbers previously realized in topological materials. The isofrequency contours formed by the topological surface states in the surface Brillouin zone form torus knots or links, whose characteristic integers are determined by the Chern vectors. We demonstrate a sample with surface states forming a (2, 2) torus link or Hopf link in the surface Brillouin zone, which is topologically distinct from the surface states of other 3D topological phases. These results establish the Chern vector as an intrinsic bulk topological invariant in 3D topological materials, with surface states possessing unique topological characteristics.

2.
J Neuroinflammation ; 21(1): 105, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649885

RESUMO

BACKGROUND: NADPH oxidase (NOX), a primary source of endothelial reactive oxygen species (ROS), is considered a key event in disrupting the integrity of the blood-retinal barrier. Abnormalities in neurovascular-coupled immune signaling herald the loss of ganglion cells in glaucoma. Persistent microglia-driven inflammation and cellular innate immune system dysregulation often lead to deteriorating retinal degeneration. However, the crosstalk between NOX and the retinal immune environment remains unresolved. Here, we investigate the interaction between oxidative stress and neuroinflammation in glaucoma by genetic defects of NOX2 or its regulation via gp91ds-tat. METHODS: Ex vivo cultures of retinal explants from wildtype C57BL/6J and Nox2 -/- mice were subjected to normal and high hydrostatic pressure (Pressure 60 mmHg) for 24 h. In vivo, high intraocular pressure (H-IOP) was induced in C57BL/6J mice for two weeks. Both Pressure 60 mmHg retinas and H-IOP mice were treated with either gp91ds-tat (a NOX2-specific inhibitor). Proteomic analysis was performed on control, H-IOP, and treatment with gp91ds-tat retinas to identify differentially expressed proteins (DEPs). The study also evaluated various glaucoma phenotypes, including IOP, retinal ganglion cell (RGC) functionality, and optic nerve (ON) degeneration. The superoxide (O2-) levels assay, blood-retinal barrier degradation, gliosis, neuroinflammation, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative PCR were performed in this study. RESULTS: We found that NOX2-specific deletion or activity inhibition effectively attenuated retinal oxidative stress, immune dysregulation, the internal blood-retinal barrier (iBRB) injury, neurovascular unit (NVU) dysfunction, RGC loss, and ON axonal degeneration following H-IOP. Mechanistically, we unveiled for the first time that NOX2-dependent ROS-driven pro-inflammatory signaling, where NOX2/ROS induces endothelium-derived endothelin-1 (ET-1) overexpression, which activates the ERK1/2 signaling pathway and mediates the shift of microglia activation to a pro-inflammatory M1 phenotype, thereby triggering a neuroinflammatory outburst. CONCLUSIONS: Collectively, we demonstrate for the first time that NOX2 deletion or gp91ds-tat inhibition attenuates iBRB injury and NVU dysfunction to rescue glaucomatous RGC loss and ON axon degeneration, which is associated with inhibition of the ET-1/ERK1/2-transduced shift of microglial cell activation toward a pro-inflammatory M1 phenotype, highlighting NOX2 as a potential target for novel neuroprotective therapies in glaucoma management.


Assuntos
Barreira Hematorretiniana , Pressão Intraocular , Camundongos Endogâmicos C57BL , NADPH Oxidase 2 , Doenças Neuroinflamatórias , Animais , NADPH Oxidase 2/metabolismo , NADPH Oxidase 2/genética , Camundongos , Barreira Hematorretiniana/patologia , Barreira Hematorretiniana/metabolismo , Pressão Intraocular/fisiologia , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Camundongos Knockout , Proliferação de Células/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Neuroglia/metabolismo , Neuroglia/patologia , Hipertensão Ocular/patologia , Hipertensão Ocular/metabolismo , Glaucoma/patologia , Glaucoma/metabolismo , Estresse Oxidativo/fisiologia
3.
Opt Lett ; 49(11): 3138-3141, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824347

RESUMO

Visible light communication (VLC) technology with rich spectrum resources is thought of as an essential component in the future ubiquitous communication networks. Accurately monitoring its transmission impairments is important for improving the stability of high-speed communication networks. Existing research on intelligently monitoring the signal-to-noise ratio (SNR) performance of VLC focuses primarily on the application of neural networks but neglects the physical nature of communication systems. In this work, we propose an intelligent SNR estimation scheme for VLC systems, which is based on the symmetry of constellation diagrams with classical deep learning frameworks. In order to increase the accuracy of the SNR estimation scheme, we introduce two data augmentation methods (DA): point normalization and quadrant normalization. The results of extensive simulations demonstrate that the proposed point normalization method is capable of improving accuracy by about 5, 10, 14, and 26%, respectively, for 16-, 64-, 256-, and 1024-quadrature amplitude modulation compared with the same network frameworks without DA. The effect of accuracy improvement can be further superimposed with traditional DA methods. Additionally, the extensive number of constellation points (e.g., 32, 64, 128, 256, 512, 1024, and 2048) on the accuracy of SNR estimation is also investigated.

4.
Phys Rev Lett ; 132(15): 156602, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38682981

RESUMO

Photonic Chern insulators are known for their topological chiral edge states (CESs), whose absolute existence is determined by the bulk band topology, but concrete dispersion can be engineered to exhibit various properties. For example, the previous theory suggested that the edge dispersion can wind many times around the Brillouin zone to slow down light, which can potentially overcome fundamental limitations in conventional slow-light devices: narrow bandwidth and keen sensitivity to fabrication imperfection. Here, we report the first experimental demonstration of this idea, achieved by coupling CESs with resonance-induced nearly flat bands. We show that the backscattering-immune hybridized CESs are significantly slowed down over a relatively broad bandwidth. Our work thus paves an avenue to broadband topological slow-light devices.

5.
Phys Rev Lett ; 132(11): 113802, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38563911

RESUMO

Quantum Hall systems host chiral edge states extending along the one-dimensional boundary of any two-dimensional sample. In solid state materials, the edge states serve as perfectly robust transport channels that produce a quantized Hall conductance; due to their chirality, and the topological protection by the Chern number of the bulk band structure, they cannot be spatially localized by defects or disorder. Here, we show experimentally that the chiral edge states of a lossy quantum Hall system can be localized. In a gyromagnetic photonic crystal exhibiting the quantum Hall topological phase, an appropriately structured loss configuration imparts the edge states' complex energy spectrum with a feature known as point-gap winding. This intrinsically non-Hermitian topological invariant is distinct from the Chern number invariant of the bulk (which remains intact) and induces mode localization via the "non-Hermitian skin effect." The interplay of the two topological phenomena-the Chern number and point-gap winding-gives rise to a non-Hermitian generalization of the paradigmatic Chern-type bulk-boundary correspondence principle. Compared to previous realizations of the non-Hermitian skin effect, the skin modes in this system have superior robustness against local defects and disorders.

6.
Opt Express ; 31(9): 13875-13887, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37157263

RESUMO

Self-assembled photonic structures have greatly expanded the paradigm of optical materials due to their ease of access, the richness of results offered and the strong interaction with light. Among them, photonic heterostructure shows unprecedent advances in exploring novel optical responses that only can be realized by interfaces or multiple components. In this work, we realize visible and infrared dual-band anti-counterfeiting using metamaterial (MM) - photonic crystal (PhC) heterostructures for the first time. Sedimentation of TiO2 nanoparticles in horizontal mode and polystyrene (PS) microspheres in vertical mode self-assembles a van der Waals interface, connecting TiO2 MM to PS PhC. Difference of characteristic length scales between two components support photonic bandgap engineering in the visible band, and creates a concrete interface at mid-infrared to prevent interference. Consequently, the encoded TiO2 MM is hidden by structurally colored PS PhC and visualized either by adding refractive index matching liquid or by thermal imaging. The well-defined compatibility of optical modes and facility in interface treatments further paves the way for multifunctional photonic heterostructures.

7.
Int J Mol Sci ; 24(17)2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37686017

RESUMO

Glaucoma is a leading cause of irreversible blindness worldwide. While intraocular pressure (IOP) presents a major risk factor, the underlying pathophysiology still remains largely unclear. The correlation between vascular abnormalities and glaucoma has been deliberated for decades. Evidence for a role played by vascular factors in the pathogenesis of glaucomatous neurodegeneration has already been postulated. In addition, the fact that glaucoma causes both structural and functional changes to retinal blood vessels has been described. This review aims to investigate the published evidence concerning the relationship between vascular abnormalities and glaucoma, and to provide an overview of the "chicken or egg" dilemma in glaucoma. In this study, several biomarkers of glaucoma progression from a vascular perspective, including endothelin-1 (ET-1), nitric oxide, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs), were identified and subsequently assessed for their potential as pharmacological intervention targets.


Assuntos
Glaucoma , Fator A de Crescimento do Endotélio Vascular , Humanos , Glaucoma/etiologia , Pressão Intraocular , Cegueira , Endotelina-1
8.
Exp Eye Res ; 213: 108853, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34800481

RESUMO

PURPOSE: The roles of vascular dysfunction and chronic stress have been extensively discussed in the pathophysiology of glaucoma. Our aim was to test whether chronic stress causes retinal vascular dysfunction and therewith induces retinal ganglion cells (RGCs) loss. METHODS: Twelve mice underwent chronic social defeat (CSD) stress, while 12 mice received control treatment only. Intraocular pressure (IOP) was measured with a rebound tonometer. Blood plasma corticosterone concentration and adrenal gland weight were used to assess stress levels. Brn-3a staining in retinas and PPD staining in optic nerve cross sections were conducted to assess the survival of RGCs and axons respectively. The ET-1 and α-SMA levels were determined in retina. Retinal vascular autoregulation, functional response to various vasoactive agents and vascular mechanics were measured using video microscopy. RESULTS: No significant difference in IOP levels was observed during and after CSD between CSD mice and controls. CSD stress caused hypercortisolemia 2 days post-CSD. However, increased corticosterone levels went back to normal 8 months after CSD. CSD-exposed mice developed adrenal hyperplasia 3 days post-CSD, which was normalized by 8 months. RGC and axon survival were similar between CSD mice and controls. However, CSD stress caused irreversible, impaired autoregulation and vascular dysfunction of retinal arterioles in CSD mice. In addition, impaired maximal dilator capacity of retinal arterioles was observed 8 months post-CSD rather than 3 days post-CSD. Remarkably, ET-1 levels were increased 3 days post-CSD while α-SMA levels were decreased 8 months post-CSD. CONCLUSIONS: We found that CSD stress does not cause IOP elevation, nor loss of RGCs and their axons. However, it strikingly causes irreversible impaired autoregulation and endothelial function in murine retinal arterioles. In addition, CSD changed vascular mechanics on a long-term basis. Increased ET-1 levels and loss of pericytes in retina vessels may involve in this process.


Assuntos
Artéria Retiniana/fisiopatologia , Doenças Retinianas/fisiopatologia , Células Ganglionares da Retina/patologia , Derrota Social , Estresse Psicológico/fisiopatologia , Actinas/metabolismo , Hiperplasia Suprarrenal Congênita/fisiopatologia , Animais , Sobrevivência Celular , Doença Crônica , Corticosterona/sangue , Modelos Animais de Doenças , Transtorno 46,XY do Desenvolvimento Sexual/fisiopatologia , Endotelina-1/metabolismo , Pressão Intraocular/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hipertensão Ocular/fisiopatologia , Nervo Óptico/fisiopatologia , Artéria Retiniana/metabolismo , Doenças Retinianas/metabolismo , Células Ganglionares da Retina/metabolismo , Estresse Psicológico/metabolismo , Tonometria Ocular , Fator de Transcrição Brn-3A/metabolismo , Gravação em Vídeo
9.
Int J Med Sci ; 18(1): 270-275, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390795

RESUMO

Rationale: To identify whether the initial chest computed tomography (CT) findings of patients with coronavirus disease 2019 (COVID-19) are helpful for predicting the clinical outcome. Methods: A total of 224 patients with laboratory-confirmed COVID-19 who underwent chest CT examination within the first day of admission were enrolled. CT findings, including the pattern and distribution of opacities, the number of lung lobes involved and the chest CT scores of lung involvement, were assessed. Independent predictors of adverse clinical outcomes were determined by multivariate regression analysis. Adverse outcome were defined as the need for mechanical ventilation or death. Results: Of 224 patients, 74 (33%) had adverse outcomes and 150 (67%) had good outcomes. There were higher frequencies of more than four lung zones involved (73% vs 32%), both central and peripheral distribution (57% vs 42%), consolidation (27% vs 17%), and air bronchogram (24% vs 13%) and higher initial chest CT scores (8.6±3.4 vs 5.4±2.1) (P < 0.05 for all) in the patients with poor outcomes. Multivariate analysis demonstrated that more than four lung zones (odds ratio [OR] 3.93; 95% confidence interval [CI]: 1.44 to 12.89), age above 65 (OR 3.65; 95% CI: 1.11 to 10.59), the presence of comorbidity (OR 5.21; 95% CI: 1.64 to 19.22) and dyspnea on admission (OR 3.19; 95% CI: 1.35 to 8.46) were independent predictors of poor outcome. Conclusions: Involvement of more than four lung zones and a higher CT score on the initial chest CT were significantly associated with adverse clinical outcome. Initial chest CT findings may be helpful for predicting clinical outcome in patients with COVID-19.


Assuntos
COVID-19/diagnóstico por imagem , Radiografia Torácica , Tomografia Computadorizada por Raios X , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
10.
Antioxidants (Basel) ; 11(10)2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36290587

RESUMO

Research has been conducted into vascular abnormalities in the pathogenesis of glaucoma, but conclusions remain controversial. Our aim was to test the hypothesis that retinal endothelial dysfunction induced by elevated intraocular pressure (IOP) persists after IOP normalization, further triggering retinal ganglion cell (RGC) loss. High intraocular pressure (HP) was induced in mice by episcleral vein occlusion (EVO). Retinal vascular function was measured via video microscopy in vitro. The IOP, RGC and their axons survival, levels of oxidative stress and inflammation as well as vascular pericytes coverage, were determined. EVO caused HP for two weeks, which returned to baseline afterwards. Mice with HP exhibited endothelial dysfunction in retinal arterioles, reduced density of RGC and their axons, and loss of pericytes in retinal arterioles. Notably, these values were similar to those of mice with recovered IOP (RP). Levels of oxidative stress and inflammation were increased in HP mice but went back to normal in the RP mice. Our data demonstrate that HP induces persistent endothelial dysfunction in retinal arterioles, which persists one month after RP. Oxidative stress, inflammation, and loss of pericytes appear to be involved in triggering vascular functional deficits. Our data also suggest that retinal endothelial dysfunction does not affect RGC and their axon survival.

11.
PLoS One ; 16(1): e0245430, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33444389

RESUMO

Reducing the water content of oily sludge is essential for the disposal of it. Despite conditioning and solid-liquid separation, the water content of oily sludge generally exceeds 65%. A large amount of this water exists in the form of emulsified and bound water, reducing the efficiency of water removal during the natural semi-drying process of oily sludge. To shorten the time required for natural semi-drying, this study applied an orthogonal test to screen an oily sludge modified material (OSM). The effect and mechanism of OSM on the natural semi-drying of oily sludge were studied using a thermal gravimetric analyzer (TGA), scanning electron microscope (SEM), surface tension measurement, and microscopic observations. The results show that when the ambient temperature exceeded 10°C, the OSM increased in mass by 8-10%, and the time required for the natural semi-drying of oily sludge was shortened from 15 days to less than 5 days. OSM can rupture the emulsion, reduce the surface tension, convert the emulsion and bound water in the oily sludge into free water, and accelerate the rate of water migration, diffusion, and natural evaporation from the inside of the oily sludge to the surface and air. The research results show that changing the form of water can speed up the drying of oily sludge, creating positive economic benefits in the process of oily sludge reduction and recycling.


Assuntos
Óleos/química , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Água/química , Dessecação , Emulsões/química
12.
Int J Ophthalmol ; 14(4): 497-503, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33875938

RESUMO

AIM: To explore the effect of the Andrographis paniculata (A. paniculata) polysaccharide on the proliferation and apoptosis of human retinoblastoma (RB) Y79 cells and its mechanism. METHODS: The refined A. paniculata polysaccharide was obtained using techniques such as water extraction, ethanol precipitation, and decompression concentration. The inhibition effect of the A. paniculata polysaccharide on the proliferation of Y79 cells was detected by cell proliferation assay. Flow cytometry was used for the detection of cell apoptosis rate and cycle change. Real-time qunatitative polymerase chain reaction (RT qPCR)and Western blotting were used to detect the expression of cell apoptosis signal pathway-related factors (caspase-3, caspase-8, and caspase-9) and cell cycle signal pathway-related factors (CDK1 and cyclinB1) at the transcriptional and translational levels. RESULTS: Infrared and ultraviolet spectrum scanning showed that the extracted drug was a polysaccharide with high purity. After being treated with different concentrations of A. paniculata polysaccharide for different periods of time, the Y79 cells showed different degrees of proliferation inhibition. Flow cytometric observations showed that the cell apoptosis rate and the proportion of cells blocked in the G2/M phase were significantly increased after A. paniculata polysaccharide treatment. Further analysis revealed that the mRNA and protein expression of caspase-3, caspase-8, and caspase-9 in the A. paniculata polysaccharide treatment groups increased significantly compared with that in the control groups, while the expression of CDK1 and cyclinB1 decreased significantly. CONCLUSION: The A. paniculata polysaccharide could inhibit the proliferation and induce apoptosis of Y79 cells. Its possible mechanism is via the upregulation of caspase-3, caspase-8, and caspase-9 expression in the cell apoptotic signaling pathway and the downregulation of CDK1 and cyclinB1 expression in the cell cycle signaling pathway.

13.
Curr Med Res Opin ; 36(11): 1747-1752, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32986475

RESUMO

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has high morbidity and mortality, and spreads rapidly in the community to result in a large number of infection cases. This study aimed to compare clinical features in adult patients with coronavirus disease 2019 (COVID-19) pneumonia to those in adult patients with community-acquired pneumonia (CAP). METHODS: Clinical presentations, laboratory findings, imaging features, complications, treatment and outcomes were compared between patients with COVID-19 pneumonia and patients with CAP. The study group of patients with COVID-19 pneumonia consisted of 120 patients. One hundred and thirty-four patients with CAP were enrolled for comparison. RESULTS: Patients with COVID-19 pneumonia had lower levels of abnormal laboratory parameters (white blood cell count, lymphocyte count, procalcitonin level, erythrocyte sedimentation rate and C-reactive protein level) and more extensive radiographic involvement. More severe respiratory compromise resulted in a higher rate of intensive care unit admission, acute respiratory distress syndrome (ARDS) and mechanical ventilation (36% vs 15%, 34% vs 15% and 32% vs 12%, respectively; all p < .05). The 30 day mortality was more than twice as high in patients with COVID-19 pneumonia (12% versus 5%; p = .063), despite not reaching a statistically significant difference. CONCLUSIONS: Lower levels of abnormal laboratory parameters, more extensive radiographic involvement, more severe respiratory compromise, and higher rates of ICU admission, ARDS and mechanical ventilation are key characteristics that distinguish patients with COVID-19-associated pneumonia from patients with CAP.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Adulto , Idoso , COVID-19 , Estudos de Casos e Controles , China/epidemiologia , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/terapia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Prognóstico , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença
14.
Immun Inflamm Dis ; 8(4): 584-594, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32857453

RESUMO

BACKGROUND: Detailed descriptions of the patterns of disease progression of deceased coronavirus disease 2019 (COVID-19) patients have not been well explored. OBJECTIVES: This study sought to explore disease progression patterns and risk factors associated with mortality of deceased patients with COVID-19. MATERIALS AND METHODS: Epidemiological, clinical, laboratory, and imaging data (from 15 January to 26 March 2020) of laboratory-confirmed COVID-19 patients were collected retrospectively from two hospitals, Hubei province, China. Disease progression patterns of patients were analyzed based on laboratory data, radiological findings, and Sequential Organ Failure Assessment (SOFA) score. Risk factors associated with death were analyzed. RESULTS: A total of 792 patients were enrolled in this study, of whom 68 died and 724 survived. Complications during hospitalization, such as sepsis, severe acute respiratory distress syndrome, acute cardiac injury, and acute kidney injury, were markedly more frequent in deceased patients than in surviving patients. Deceased patients presented progressive deterioration pattern in laboratory variables, chest computed tomography evaluation, and SOFA score, while surviving patients presented initial deterioration to peak level involvement followed by improvement pattern over time. Days 10 to 14 after illness onset was a critical stage of disease course. Older age, number of preexisting comorbidities ≥2, and SOFA score were independently associated with death for COVID-19. CONCLUSIONS: Multiorgan dysfunction was common in deceased COVID-19 patients. Deceased patients presented progressive deterioration pattern, while surviving patients presented a relatively stable pattern during disease progression. Older age, number of preexisting comorbidities ≥2, and SOFA score were independent risk factors for death for COVID-19.


Assuntos
Injúria Renal Aguda/epidemiologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/mortalidade , Insuficiência Cardíaca/epidemiologia , Pneumonia Viral/mortalidade , Injúria Renal Aguda/etiologia , Adulto , Fatores Etários , Idoso , Betacoronavirus/isolamento & purificação , COVID-19 , China/epidemiologia , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Progressão da Doença , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , SARS-CoV-2 , Tomografia Computadorizada por Raios X
15.
Oxid Med Cell Longev ; 2019: 9736047, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31976030

RESUMO

OBJECTIVE: Glaucoma is a leading cause of severe visual impairment and blindness. Although high intraocular pressure (IOP) is an established risk factor for the disease, the role of abnormal ocular vessel function in the pathophysiology of glaucoma gains more and more attention. We tested the hypothesis that elevated intraocular pressure (IOP) causes vascular dysfunction in the retina. METHODS: High IOP was induced in one group of mice by unilateral cauterization of three episcleral veins. The other group received sham surgery only. Two weeks later, retinal vascular preparations were studied by video microscopy in vitro. Reactive oxygen species (ROS) levels and expression of hypoxia markers and of prooxidant and antioxidant redox genes as well as of inflammatory cytokines were determined. RESULTS: Strikingly, responses of retinal arterioles to stepwise elevation of perfusion pressure were impaired in the high-IOP group. Moreover, vasodilation responses to the endothelium-dependent vasodilator, acetylcholine, were markedly reduced in mice with elevated IOP, while no differences were seen in response to the endothelium-independent nitric oxide donor, sodium nitroprusside. Remarkably, ROS levels were increased in the retinal ganglion cell layer including blood vessels. Expression of the NADPH oxidase isoform, NOX2, and of the inflammatory cytokine, TNF-α, was increased at the mRNA level in retinal explants. Expression of NOX2, but not of the hypoxic markers, HIF-1α and VEGF-A, was increased in the retinal ganglion cell layer and in retinal blood vessels at the protein level. CONCLUSION: Our data provide first-time evidence that IOP elevation impairs autoregulation and induces endothelial dysfunction in mouse retinal arterioles. Oxidative stress and inflammation, but not hypoxia, appear to be involved in this process.


Assuntos
Arteríolas/fisiopatologia , Pressão Intraocular/fisiologia , Retina/fisiopatologia , Animais , Arteríolas/patologia , Pressão Sanguínea , Citocinas/genética , Citocinas/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Camundongos Endogâmicos C57BL , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo , Oxirredução , Perfusão , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Retina/patologia , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Oncol Lett ; 11(1): 75-80, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26870170

RESUMO

Transcription factors encoded by HOX genes are vital in the determination of cell fate and identity during embryonic development. In certain malignancies, HOX genes also behave as oncogenes. The present study demonstrated suppression of the invasive tendency of glioblastoma multiforme U-118 and U-138 cells by the introduction of the antisense fragments of HOXA6 and B13 genes using electroporation. The invasion index indicated 79 and 72% reductions in the invasive ability of antisense HOXA6 and B13, respectively. No significant differences in the invasive index of the parental and mock cells of each HOX gene were observed (invasive index, 0.75-0.91; P=0.05). A reduction in invasion tendency was also observed following betulinic acid (BA) treatment: The results from the matrigel assay analysis clearly demonstrated a significant inhibition in the invasive behaviour of U-118 and U-138 cell lines from day 15 following BA treatment, with a maximum effect on day 30. The invasion index demonstrated 62 and 65% reductions in invasion ability in the U-118 and U-138 cell lines, respectively. The suppression of HOXC6 and B13 expression by the introduction of the corresponding antisense fragments in addition to BA reduced invasion tendency in U-118 and U-138 cell lines. The mechanism underlying the association between the HOX gene and invasive behavior in glioma cells is yet to be understood. However, the anti-invasive behavior of BA may aid understanding of the mechanism in future studies.

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