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1.
Front Med (Lausanne) ; 11: 1386979, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737759

RESUMEN

Primary vitreoretinal lymphoma (PVRL) is often associated with central nervous system involvement, contributing to a heightened mortality rate, thus imaging features that are characteristic enough to be potential biomarkers of PVRL are important, either in diagnosis or in assessment of disease activity. This report details the case of a 68-year-old male who presented with blurred vision in both eyes persisting for 2 months. Fundus examination demonstrated vitreous opacity and multiple subretinal yellow nodular lesions of varying sizes in the peripheral fundus of both eyes. Multiple vertical hyperreflective lesions in the neural retina of posterior pole, indistinct outer retina borders in the fovea, and hyperreflective lesions in the sub-retinal pigment epithelium (RPE) space of the peripheral retina were demonstrated on swept-source optical coherence tomography (SS-OCT) of the left eye. Hyperflow signals corresponding to the vertical hyperreflective lesions were detected on swept-source optical coherence tomography angiography (SS-OCTA) images of retinal deep capillary plexus (DCP) layer. Notably, the hyperflow signals, precisely located around retinal vessels from the nerve fiber layer to the outer plexiform layer, were postulated to stem from the dilation of infiltrated retinal vessels. Vitreous pathological results of the left eye confirmed the diagnosis of PVRL. Treatments with intravitreal methotrexate injections led to a marked improvement of best-corrected visual acuity (BCVA) and regression of the hyperflow microinfiltration lesions demonstrated on SS-OCTA. In conclusion, SS-OCTA effectively delineated the vertical hyperreflective lesions and corresponding hyperflow signals in the posterior pole macular region of a patient with PVRL. These lesions significantly diminished following intravitreal methotrexate injections. We speculated that the specific hyperflow signals on SS-OCTA could act as a potential biomarker of PVRL, and SS-OCTA holds promise in facilitating early diagnosis and monitoring therapeutic responses in PVRL cases.

2.
BMJ Open Ophthalmol ; 9(1)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38754892

RESUMEN

BACKGROUND/AIMS: Lipid profiles have been changed in numerous chronic conditions. The impact of uveitis on lipid metabolism remains unclear. METHODS: This is a cross-sectional study included 416 patients with non-infectious uveitis (NIU) and 416 healthy subjects. Standard techniques were used to measure total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDLc), low-density lipoprotein-cholesterol (LDLc) levels. Quantitative optical coherence tomography angiography (OCTA) parameters were obtained from 500 eyes in each group. Correlation analysis examined the relationship between lipid profile and OCTA parameters. RESULTS: Patients with NIU exhibited significantly elevated TC, TG and LDLc levels compared with controls (p=0.003; p<0.001; p<0.001, respectively). Subgroup analysis revealed that HDLc was significantly lower in Behçet's disease (p=0.024) compared with controls. Vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris and optic disk were significantly decreased in NIU eyes (p<0.05, respectively) compared with controls. HDLc exhibited a significant negative correlation with VDs in the whole and parafovea SCP (r=-0.489, p=0.008; r=-0.480, p=0.0026, respectively), while LDLc showed a significant positive correlation with VDs in the whole and parafovea DCP in NIU patients (r=0.576, p=0.032; r=0.267, p=0.034, respectively). CONCLUSIONS: The lipid profile is altered in NIU, and there are correlations between HDLc and LDLc levels and VD as measured by OCTA. Lipid profile analysis may offer valuable insights into evaluating vascular and metabolic aspects of NIU.


Asunto(s)
Angiografía con Fluoresceína , Lípidos , Tomografía de Coherencia Óptica , Uveítis , Humanos , Estudios Transversales , Masculino , Uveítis/diagnóstico por imagen , Uveítis/sangre , Femenino , Adulto , Angiografía con Fluoresceína/métodos , Lípidos/sangre , Persona de Mediana Edad , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Fondo de Ojo , Metabolismo de los Lípidos , Triglicéridos/sangre
3.
Brain Res ; 1833: 148868, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38519008

RESUMEN

Meningeal lymphatic vessels (MLVs) have crucial roles in removing metabolic waste and toxic proteins from the brain and transporting them to the periphery. Aged mice show impaired meningeal lymphatic function. Nevertheless, as the disease progresses, and significant pathological changes manifest in the brain, treating the condition becomes increasingly challenging. Therefore, investigating the alterations in the structure and function of MLVs in the early stages of aging is critical for preventing age-related central nervous system degenerative diseases. We detected the structure and function of MLVs in young, middle-aged, and aged mice. Middle-aged mice, compared with young and aged mice, showed enhanced meningeal lymphatic function along with MLV expansion and performed better in the Y maze test. Moreover, age-related changes in meningeal lymphatic function were closely associated with vascular endothelial growth factor-C (VEGF-C) expression in the brain cortex. Our data suggested that the cerebral cortex may serve as a target for VEGF-C supplementation to ameliorate meningeal lymphatic dysfunction, thus providing a new strategy for preventing age-related central nervous system diseases.


Asunto(s)
Envejecimiento , Vasos Linfáticos , Meninges , Factor C de Crecimiento Endotelial Vascular , Animales , Masculino , Ratones , Envejecimiento/fisiología , Envejecimiento/metabolismo , Corteza Cerebral/metabolismo , Vasos Linfáticos/metabolismo , Meninges/metabolismo , Ratones Endogámicos C57BL , Factor C de Crecimiento Endotelial Vascular/metabolismo
4.
Neuroimage ; 289: 120545, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38367652

RESUMEN

OBJECTIVE: Dual task (DT) is a commonly used paradigm indicative of executive functions. Brain activities during DT walking is usually measured by portable functional near infrared spectroscopy (fNIRS). Previous studies focused on cortical activation in prefrontal cortex and overlooked other brain regions such as sensorimotor cortices. This study is aimed at investigating the modulations of cortical activation and brain network efficiency in multiple brain regions from single to dual tasks with different complexities and their relationships with DT performance. METHODS: Forty-two healthy adults [12 males; mean age: 27.7 (SD=6.5) years] participated in this study. Participants performed behavioral tasks with portable fNIRS simultaneous recording. There were three parts of behavioral tasks: cognitive tasks while standing (serial subtraction of 3's and 7's), walking alone and DT (walk while subtraction, including serial subtraction of 3's and 7's). Cognitive cost, walking cost and cost sum (i.e., sum of cognitive and walking costs) were calculated for DT. Cortical activation, local and global network efficiency were calculated for each task. RESULTS: The cognitive cost was greater and the walking cost was less during DT with subtraction 3's compared with 7's (P's = 0.032 and 0.019, respectively). Cortical activation and network efficiency were differentially modulated among single and dual tasks (P's < 0.05). Prefrontal activation during DT was positively correlated with DT costs, while network efficiency was negatively correlated with DT costs (P's < 0.05). CONCLUSIONS: Our results revealed prefrontal over-activation and reduced network efficiency in individuals with poor DT performance. Our findings suggest that reduced network efficiency could be a possible mechanism contributing to poor DT performance, which is accompanied by compensatory prefrontal over-activation.


Asunto(s)
Corteza Prefrontal , Espectroscopía Infrarroja Corta , Adulto , Masculino , Humanos , Espectroscopía Infrarroja Corta/métodos , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiología , Función Ejecutiva/fisiología , Caminata/fisiología , Análisis y Desempeño de Tareas , Marcha
5.
J Exp Bot ; 75(1): 123-136, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37724960

RESUMEN

Lignin and cellulose are two essential elements of plant secondary cell walls that shape the mechanical characteristics of the culm to prevent lodging. However, how the regulation of the lignin and cellulose composition is combined to achieve optimal mechanical characteristics is unclear. Here, we show that increasing OsTCP19 expression in rice coordinately repressed lignin biosynthesis and promoted cellulose biosynthesis, resulting in enhanced lodging resistance. In contrast, repression of OsTCP19 coordinately promoted lignin biosynthesis and inhibited cellulose biosynthesis, leading to greater susceptibility to lodging. We found that OsTCP19 binds to the promoters of both MYB108 and MYB103L to increase their expression, with the former being responsible for repressing lignin biosynthesis and the latter for promoting cellulose biosynthesis. Moreover, up-regulation of OsTCP19 in fibers improved grain yield and lodging resistance. Thus, our results identify the OsTCP19-OsMYB108/OsMYB103L module as a key regulator of lignin and cellulose production in rice, and open up the possibility for precisely manipulating lignin-cellulose composition to improve culm mechanical properties for lodging resistance.


Asunto(s)
Lignina , Oryza , Lignina/metabolismo , Oryza/metabolismo , Celulosa/metabolismo , Metabolismo de los Hidratos de Carbono , Pared Celular/metabolismo
6.
Plant Sci ; 337: 111890, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37813192

RESUMEN

Lignin is a complex polymer that provides structural support and defense to plants. It is synthesized in the secondary cell walls of specialized cells. Through regulates its stability, LTF1 acts as a switch to control lignin biosynthesis in Populus, a dicot plant. However, how lignin biosynthesis is regulated in rice, a monocot plant, remains unclear. By employing genetic, cellular, and chemical approaches, we discovered that LTF1L1, a rice homolog of LTF1, regulates lignin biosynthesis through a distinct mechanism from Populus LTF1. Knockout of LTF1L1 increased lignin synthesis in the sclerenchyma cells of rice stems, while overexpression of LTF1L1 decreased it. LTF1L1 is phosphorylated by OsMPK6 at Ser169, which did not affect its stability but impaired its ability to repress the expression of lignin biosynthesis genes. This was supported by the non-phosphorylated mutant of LTF1L1 (LTF1L1S169A), which displayed a stronger repressive effect on lignin biosynthesis in both rice and Populus. Our findings reveal that LTF1L1 acts as a negative regulator of lignin biosynthesis via a distinct mechanism from that of LTF1 in Populus and highlight the evolutionary diversity in the regulation of lignin biosynthesis in plants.

7.
Quant Imaging Med Surg ; 13(4): 2634-2646, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37064402

RESUMEN

Background: The American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) used with ultrasonography cannot guide the individual management of solid breast tumors, but preoperative core biopsy categories (CBCs) can. We aimed to use machine learning to analyze clinical and ultrasonic features for predicting CBCs and to aid in the development of a new ultrasound (US) imaging reporting system for solid tumors of the breast. Methods: This retrospective study included women with solid breast tumors who underwent US-guided core needle biopsy from March 1, 2019, to December 31, 2019. All patients were randomly assigned to a training or validation cohort (7:3 ratio). CBC was predicted using 5 machine learning models: random forest (RF), support vector machine (SVM), k-nearest-neighbor (KNN), multilayer perceptron (MLP), and ridge regression (RR). In the validation cohort, the area under the curve (AUC) and accuracy were ascertained for every algorithm. Based on AUC values, the optimal algorithm was determined, and the features' importance was depicted. Results: A total of 1,082 female patients were included (age range, 12-96 years; mean age ± standard deviation, 42.22±13.37 years). The proportion of the 4 CBCs was 4% (44/1,185) for the B1 group, 60% (714/1,185) for the B2 group, 5% (57/1,185) for the B3 group, and 31% (370/1,185) for the B5 group. In the validation cohort, AUCs of the optimal algorithm constructed RF were 0.78, 0.88, 0.64, and 0.92 for B1, B2, B3, and B5, respectively, with an accuracy of 0.82. Conclusions: Machine learning could strongly predict CBC, particularly in B2 and B5 categories of solid breast tumors, with RF being the optimal machine learning model.

8.
Ocul Immunol Inflamm ; : 1-12, 2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37023410

RESUMEN

PURPOSE: Diabetic retinopathy (DR) has become a major cause of blindness with increased prevalence of diabetic mellitus. Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) plays a part in pathological neovascularization. This study aimed to investigate the role of CEACAM1 in the progression of DR. METHODS: Aqueous and vitreous samples were collected from proliferative or non-proliferative DR and the control group. Multiplex fluorescent bead-based immunoassays were used to detect the levels of Cytokines. Expression of CEACAM1, VEGF, VEGF receptor 2 (VEGFR2) and hypoxia-induced factor-1α (HIF-1α) were detected in human retinal microvascular endothelial cells (HRECs). RESULTS: CEACAM1 and VEGF levels were significantly upregulated in PDR group and positively correlated with PDR progression. Expression CEACAM1 and VEGFR2 were increased in HRECs under hypoxic conditions. The HIF-1α/VEGFA/VEGFR2 pathway was blocked by CEACAM1 siRNA in vitro. CONCLUSIONS: CEACAM1 might play a role in the pathology of PDR. CEACAM1 might be a therapeutic target for retinal neovasculariztion.

9.
New Phytol ; 238(5): 1972-1985, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36922397

RESUMEN

In trees, secondary xylem development is essential for the growth of perennial stem increments. Many signals regulate the process of development, but our knowledge of the molecular components involved in signal transduction is still limited. In this study, we identified Attenuation of Secondary Xylem (ASX) knockouts by screening genome-editing knockouts of xylem-expressed receptor-like kinases (RLKs) in Populus. The ASX role in secondary xylem development in Populus was discovered using biochemical, cellular, and genomic analyses. The ASX knockout plants had abnormal secondary stem growth but had little effect on shoot apical primary growth. ASX and SOMATIC EMBRYOGENESIS RECEPTOR KINASE (SERK)2/4 were co-precipitated in developing xylem. Through their interaction, ASX is phosphorylated by SERK. Transcriptome analysis of developing xylem revealed that ASX deficiency inhibited the transcriptional activity of genes involved in xylem differentiation and secondary cell wall formation. By forming a complex, ASX and SERK may function as a signaling module for signal transduction required in the regulation of secondary xylem development in trees. This study shows that ASX, which encodes a RLKs, is required for secondary xylem development and sheds light on regulatory signals found in tree stem secondary growth.


Asunto(s)
Populus , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Xilema/fisiología , Perfilación de la Expresión Génica , Diferenciación Celular/genética , Regulación de la Expresión Génica de las Plantas
10.
Clin Immunol ; 246: 109210, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36528252

RESUMEN

Uveitis with complex pathogenesis is a kind of eye emergency involving refractory and blinding inflammation. Dysregulation of TANK binding kinase 1 (TBK1), which plays an important role in innate immunity, often leads to inflammatory diseases in various organs. However, the role of TBK1 in uveitis remains elusive. In this study, we identified that the mRNA expression level of TBK1 and its phosphorylation level were significantly increased in peripheral blood mononuclear cells (PBMCs) of patients with uveitis. Consistent with this, the expression of Tbk1 was elevated in the ocular tissues of uveitis rats and primary peritoneal macrophages while its phosphorylation levels, which present activation forms, were upregulated as well, accompanied by an increase in the level of nuclear factor-κB (NF-κB) and proinflammatory cytokines. In addition, inhibition of TBK1 may effectively reduce the inflammatory response of uveitis rats by blocking NF-κB entry into the nucleus and impeding the initiation of NLRP3 inflammasome- and caspase-1-mediated pyroptosis pathways.


Asunto(s)
FN-kappa B , Uveítis , Animales , Ratas , Inflamasomas/metabolismo , Inflamación/metabolismo , Leucocitos Mononucleares/metabolismo , FN-kappa B/metabolismo , Transducción de Señal , Uveítis/genética
11.
Front Genet ; 13: 972501, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36186469

RESUMEN

Hereditary transthyretin (ATTRv) amyloidosis is a rare disease caused by transthyretin gene (TTR) mutation. We identified that the p.G103R mutation of the TTR gene in a Han Chinese family was associated with vitreous hemorrhage. The proband was a 48-year-old woman who had progressive visual impairment in both eyes for 12 years. A Glass wool-like posterior vitreous cortex attached to the posterior retinal surface of both eyes was found using ocular coherence tomography. Visual acuity improved after the first vitrectomy. Two years later, the patient underwent two more vitrectomies because of vitreous opacity recrudescence. Four years later, she presented with vitreous hemorrhage in the right eye. The vitreous fluids acquired during the vitrectomy showed increased vascular endothelial growth factor, basic fibroblast growth factor, interleukin-6, interleukin-10, vascular cell adhesion molecule, and interleukin-8. Mutation sequencing revealed a heterozygous mutation in nucleotide c.307G > C (p.G103R) in exon 3 of the TTR gene in the proband (IV-13), her daughter (IV-9), and her fourth sister (III-11). To our knowledge, this is the first case of ATTRv amyloidosis caused by a p.G103R mutation of the TTR gene associated with vitreous hemorrhage in China.

12.
Front Nutr ; 9: 890277, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35669071

RESUMEN

The essential fatty acids (EFA), n3 alpha-linolenic acid (ALA), and n6 linoleic acid (LA) are of benefit in diabetes mellitus, but their mechanisms of action are unknown. We, therefore, examined the effects of EFAs on the metabolism, gut microbiota, and inflammatory and retinal histopathology indices in streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) animals, and we assessed the levels of vitreal lipoxin A4 (LXA4)-derived from LA-in subjects with diabetic retinopathy (DR). STZ-induced T1DM rats received LA or ALA 100 µg/day intraperitoneally on alternate days for 21 days, and their blood glucose; lipid profile; plasma, hepatic, and retinal fatty acid profiles (by gas chromatography); retinal histology; activities of hepatic and retinal desaturases; and inflammatory markers (by qRT-PCR) were evaluated. Gut microbiota composition was assayed by 16S rDNA sequencing technology of the fecal samples, and their short-chain fatty acids and bile acids were assayed by gas chromatography, liquid chromatography coupled with tandem mass spectrometry, respectively. The human vitreal fatty acid profiles of subjects with proliferative DR and LXA4 levels were measured. LA and ALA significantly improved the plasma glucose and lipid levels; increased the abundance of Ruminococcaceae (the ALA-treated group), Alloprevotella, Prevotellaceae_Ga6A1_group, Ruminococcaceae_UCG_010, and Ruminococcus_1 (the LA-treated group) bacteria; enhanced acetate and butyrate levels; and augmented fecal and hepatic concentrations of cholic acid, chenodeoxycholic acid, and tauro ursodeoxycholic acid in ALA- and LA-treated animals. Significant STZ-induced decreases in plasma LA, gamma-linolenic acid, arachidonic acid, and ALA levels reverted to near normal, following LA and ALA treatments. Significant changes in the expression of desaturases; COX-2, 5-LOX, and 12-LOX enzymes; and cytokines in T1DM were reverted to near normal by EFAs. DR subjects also had low retinal LXA4 levels. The results of the present study show that ALA and LA are of significant benefit in reversing metabolism, gut microbiota, and inflammatory and retinal index changes seen in T1DM, suggesting that EFAs are of benefit in diabetes mellitus.

14.
Ocul Immunol Inflamm ; 30(5): 1092-1098, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33793358

RESUMEN

PURPOSE: to explore the aqueous cytokine profiles in nAMD patients before and after conbercept therapy. METHODS: aqueous levels of 17 cytokines were detected in 20 treatment-naïve nAMD eyes and 20 age- and sex-matched age-related cataract (ARC) eyes. All of the nAMD patients received three intravitreal injections of conbercept. The central macular thickness (CMT) and maximum retinal thickness-3 mm (MRT-3 mm) were measured by SD-OCT. Fundus fluorescein angiography (FA) was used to measure the greatest linear diameter (GLD). RESULTS: Aqueous endoglin, endostatin, FGF-α, HGF, and thrombospondin-2 levels were significantly higher in the nAMD group than those in the ARC group, whether before or after two conbercept injections. In the nAMD group, baseline thrombospondin-2 was positively correlated with GLD. Baseline FGF-α, thrombospondin-2, and VEGF-A were positively correlated with MRT-3 mm. After two conbercept injections, endostatin levels were positively correlated with VEGF-A. CONCLUSIONS: Endoglin, endostatin, FGF-α, HGF, and thrombospondin-2 may participate in the pathogenesis of nAMD.


Asunto(s)
Humor Acuoso , Degeneración Macular Húmeda , Inhibidores de la Angiogénesis/uso terapéutico , Citocinas , Endoglina , Endostatinas , Factor de Crecimiento de Hepatocito , Humanos , Inyecciones Intravítreas , Ranibizumab , Trombospondinas , Factor A de Crecimiento Endotelial Vascular , Degeneración Macular Húmeda/tratamiento farmacológico
15.
Front Oncol ; 11: 724656, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34926246

RESUMEN

OBJECTIVES: Mucinous breast cancer (MBC), particularly pure MBC (pMBC), often tend to be confused with fibroadenoma (FA) due to their similar images and firm masses, so some MBC cases are misdiagnosed to be FA, which may cause poor prognosis. We analyzed the ultrasonic features and aimed to identify the ability of multilayer perceptron (MLP) to classify early MBC and its subtypes and FA. MATERIALS AND METHODS: The study consisted of 193 patients diagnosed with pMBC, mMBC, or FA. The area under curve (AUC) was calculated to assess the effectiveness of age and 10 ultrasound features in differentiating MBC from FA. We used the pairwise comparison to examine the differences among MBC subtypes (pure and mixed types) and FA. We utilized the MLP to differentiate MBC and its subtypes from FA. RESULTS: The nine features with AUCs over 0.5 were as follows: age, echo pattern, shape, orientation, margin, echo rim, vascularity distribution, vascularity grade, and tumor size. In subtype analysis, the significant differences were obtained in 10 variables (p-value range, 0.000-0.037) among pMBC, mMBC, and FA, except posterior feature. Through MLP, the AUCs of predicting MBC and FA were both 0.919; the AUCs of predicting pMBC, mMBC, and FA were 0.875, 0.767, and 0.927, respectively. CONCLUSION: Our study found that the MLP models based on ultrasonic characteristics and age can well distinguish MBC and its subtypes from FA. It may provide a critical insight into MBC preoperative clinical management.

16.
Front Public Health ; 9: 755163, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34805075

RESUMEN

The cognitive attitudes and behaviors of medical post-graduates may be influenced by the coronavirus disease 2019 (COVID-19) pandemic. A cross-sectional study was used from a questionnaire survey in hospitals affiliated with the Zhejiang University School of Medicine. Questionnaire was distributed online including demographic information, cognitive attitudes, and personal protective behaviors. Moreover, personal protective behaviors such as wearing protective equipment were compared between different academic major and gender, respectively. A total of 176 valid questionnaires were obtained. Of the medical post-graduates in this study, (1) 89.67% believed that the COVID-19 pandemic had an impact on their clinical internships, and 40.34% expressed concerns about their infection on inadequate personal protection; (2) 91.48% took personal protection in hospital and 86.36% enhanced personal hygiene; (3) There were no statistically differences in the personal protection by academic major and gender (p > 0.05). This study suggests that the COVID-19 pandemic had an impact on the medical post-graduates' clinical practice, and affected their cognitive attitudes and behaviors. As such, universities and hospitals should increase pandemic prevention training and investment, provide more psychological counseling to their medical post-graduates to reduce their psychological burden, and take measures to reduce the influence of the COVID-19 pandemic on their medical post-graduates' clinical practice.


Asunto(s)
COVID-19 , Pandemias , China/epidemiología , Cognición , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Humanos , Pandemias/prevención & control , SARS-CoV-2
17.
FASEB J ; 35(12): e22036, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34793603

RESUMEN

Therapeutic angiogenesis would be clinically valuable in situations such as peripheral vascular disease in diabetic patients and tissue reperfusion following ischemia or injury, but approaches using traditional isoforms of vascular endothelial growth factor-A (VEGF) have had little success. The isoform VEGF165 is both soluble and matrix-associated, but can cause pathologic vascular changes. Freely diffusible VEGF121 is not associated with pathologic angiogenesis, but its failure to remain in the vicinity of the targeted area presents therapeutic challenges. In this study, we evaluate the cellular effects of engineered VEGF variants that tether extracellular VEGF121 to the cell membrane with the goal of activating VEGF receptor 2 (VEGFR2) in a sustained, autologous fashion in endothelial cells. When expressed by primary human retinal endothelial cells (hRECs), the engineered, membrane-tethered variants eVEGF-38 and eVEGF-53 provide a lasting VEGF signal that induces cell proliferation and survival, increases endothelial permeability, promotes the formation of a cord/tube network, and stimulates the formation of elongated filopodia on the endothelial cells. The engineered VEGF variants activate VEGFR2, MAPK/ERK, and the Rho GTPase mediators CDC42 and ROCK, activities that are required for the formation of the elongated filopodia. The sustained, pro-angiogenic activities induced by eVEGF-38 and eVEGF-53 support the potential of engineered VEGF variants-overexpressing endothelial cells as a novel combination of gene and cell-based therapeutic strategy for stimulating endothelial cell-autologous therapeutic angiogenesis.


Asunto(s)
Proliferación Celular , Células Endoteliales/citología , Regulación de la Expresión Génica , Mutación , Neovascularización Fisiológica , Seudópodos/fisiología , Factor A de Crecimiento Endotelial Vascular/genética , Movimiento Celular , Células Endoteliales/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas , Retina/citología , Retina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Proteína de Unión al GTP cdc42/genética , Proteína de Unión al GTP cdc42/metabolismo , Quinasas Asociadas a rho/genética , Quinasas Asociadas a rho/metabolismo
18.
J Int Med Res ; 49(8): 3000605211032782, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34382463

RESUMEN

Sympathetic ophthalmia (SO) is a panuveitis that usually occurs after trauma to one eye. We describe two cases of SO occurring after 23-gauge vitrectomy. Case 1 involved a 66-year-old woman who underwent pars plana vitrectomy (PPV) for a rhegmatogenous retinal detachment. Two months later, she presented with decreased visual acuity (VA) and bilateral uveitis. Case 2 involved a 43-year-old woman who underwent a second PPV for recurrent retinal detachment. Two months later, she presented with bilateral panuveitis. Both patients were diagnosed with SO and were treated with methylprednisolone and cyclosporine. The first patient was further treated with a dexamethasone intravitreal implant (Ozurdex®) owing to the side effects of methylprednisolone. The VA and symptoms improved significantly after treatment in both patients. Bilateral granulomatous panuveitis following PPV should alert surgeons to consider SO. Appropriate interventions for SO can produce positive outcomes.


Asunto(s)
Oftalmía Simpática , Desprendimiento de Retina , Cirugía Vitreorretiniana , Adulto , Anciano , Ciclosporina , Femenino , Humanos , Oftalmía Simpática/tratamiento farmacológico , Oftalmía Simpática/etiología , Desprendimiento de Retina/cirugía , Estudios Retrospectivos , Vitrectomía
19.
J Zhejiang Univ Sci B ; 22(6): 504-511, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-34128373

RESUMEN

The prompt detection and proper evaluation of necrotic retinal region are especially important for the diagnosis and treatment of acute retinal necrosis (ARN). The potential application of artificial intelligence (AI) algorithms in these areas of clinical research has not been reported previously. The present study aims to create a computational algorithm for the automated detection and evaluation of retinal necrosis from retinal fundus photographs. A total of 149 wide-angle fundus photographs from 40 eyes of 32 ARN patients were collected, and the U-Net method was used to construct the AI algorithm. Thereby, a novel algorithm based on deep machine learning in detection and evaluation of retinal necrosis was constructed for the first time. This algorithm had an area under the receiver operating curve of 0.92, with 86% sensitivity and 88% specificity in the detection of retinal necrosis. For the purpose of retinal necrosis evaluation, necrotic areas calculated by the AI algorithm were significantly positively correlated with viral load in aqueous humor samples (R2=0.7444, P<0.0001) and therapeutic response of ARN (R2=0.999, P<0.0001). Therefore, our AI algorithm has a potential application in the clinical aided diagnosis of ARN, evaluation of ARN severity, and treatment response monitoring.


Asunto(s)
Algoritmos , Inteligencia Artificial , Síndrome de Necrosis Retiniana Aguda/diagnóstico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
20.
Exp Eye Res ; 205: 108506, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33609512

RESUMEN

Glaucoma is a neuropathic disease that causes optic nerve damage, loss of retinal ganglion cells (RGCs), and visual field defects. Most glaucoma patients have no early signs or symptoms. Conventional pharmacological glaucoma medications and surgeries that focus on lowering intraocular pressure are not sufficient; RGCs continue to die, and the patient's vision continues to decline. Recent evidence has demonstrated that neuroprotective approaches could be a promising strategy for protecting against glaucoma. In the case of glaucoma, neuroprotection aims to prevent or slow down disease progression by mitigating RGCs death and optic nerve degeneration. Notably, new pharmacologic medications such as antiglaucomatous agents, antibiotics, dietary supplementation, novel neuroprotective molecules, neurotrophic factors, translational methods such as gene therapy and cell therapy, and electrical stimulation-based physiotherapy are emerging to attenuate the death of RGCs, or to make RGCs resilient to attacks. Understanding the roles of these interventions in RGC protection may offer benefits over traditional pharmacological medications and surgeries. In this review, we summarize the recent neuroprotective strategy for glaucoma, both in clinical trials and in laboratory research.


Asunto(s)
Glaucoma/prevención & control , Fármacos Neuroprotectores/uso terapéutico , Enfermedades del Nervio Óptico/prevención & control , Células Ganglionares de la Retina/efectos de los fármacos , Animales , Tratamiento Basado en Trasplante de Células y Tejidos/tendencias , Terapia por Estimulación Eléctrica/tendencias , Terapia Genética/tendencias , Humanos , Presión Intraocular , Neuroprotección
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