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1.
Environ Res ; 231(Pt 1): 116116, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37182831

ABSTRACT

Autoimmune eye diseases (AEDs), a collection of autoimmune inflammatory ocular conditions resulting from the dysregulation of immune system at the ocular level, can target both intraocular and periorbital structures leading to severe visual deficit and blindness globally. The roles of air pollution and meteorological factors in the initiation and progression of AEDs have been increasingly attractive, among which the systemic and local mechanisms are both involved in. Exposure to excessive air pollution and extreme meteorological conditions including PM2.5/PM0.1, environmental tobacco smoke, insufficient sunshine, and high temperature, etc., can disturb Th17/Treg balance, regulate macrophage polarization, activate neutrophils, induce systemic inflammation and oxidative stress, decrease retinal blood flow, promote tissue fibrosis, activate sympathetic nervous system, adversely affect nutrients synthetization, as well as induce heat stress, therefore may together deteriorate AEDs. The crosstalk among inflammation, oxidative stress and dysregulated immune system appeared to be prominent. In the present review, we will concern and summarize the potential mechanisms underlying linkages of air pollution and meteorological factors to ocular autoimmune and inflammatory responses. Moreover, we concentrate on the specific roles of air pollutants and meteorological factors in several major AEDs including uveitis, Graves' ophthalmopathy (GO), ocular allergic disease (OAD), glaucoma, diabetic retinopathy (DR), etc.


Subject(s)
Air Pollutants , Air Pollution , Autoimmune Diseases , Eye Diseases , Humans , Air Pollution/adverse effects , Air Pollutants/toxicity , Air Pollutants/analysis , Meteorological Concepts , Autoimmune Diseases/chemically induced , Autoimmune Diseases/epidemiology , Inflammation/chemically induced , Inflammation/epidemiology , Particulate Matter/toxicity , China
2.
Zootaxa ; 5091(3): 455-466, 2022 Jan 14.
Article in English | MEDLINE | ID: mdl-35391237

ABSTRACT

Three new species of Megastylus Schidte, 1838 (Ichneumonidae, Orthocentrinae), M. (Dicolus) mentouense Sheng Li, sp. nov. collected from Mentougou, Beijing, M. (D.) flavicornis Sheng Li, sp. nov. from Shennongjia National Natural Reserve, Hubei and M. (Megastylus) yindianense Sheng Li, sp. nov. from Minquan, Henan, are described and illustrated. A taxonomic key to the species of Megastylus known from China and the Oriental Region is provided.


Subject(s)
Hymenoptera , Animals , China
3.
Front Genet ; 13: 823517, 2022.
Article in English | MEDLINE | ID: mdl-35368656

ABSTRACT

Macrophage polarization is a process that macrophages exert different functions according to surrounding micro-environment. Macrophages commonly exist in two distinct subsets: classically activated M1 macrophages and alternatively activated M2 macrophages. Circular RNAs (circRNAs) are a novel class of non-coding RNAs generated by back-splicing. Thousands of circRNAs were identified in different cells and tissues. Recent studies have revealed that circRNAs play a crucial role in regulating transcriptional and post-transcriptional gene expression. However, the effects and roles of circRNAs in macrophage polarization have not been well elucidated. Here, circRNAs expression profiles were determined in human THP-1 macrophages incubated in conditions causing activation toward M1 (interferon-γ + LPS) or M2 (interleukin-4) phenotypes. Overall, 9,720 circular RNA were detected from RNA sequencing data. Compared with M2 macrophages, a total of 140 circRNAs were aberrantly expressed in M1 macrophages, including 71 up-regulated circRNAs and 69 down-regulated circRNAs. Quantitative real-time PCR (qRT-PCR) results were generally consistent with the selected differentially expressed circRNAs. Gene Ontology (GO) and KEGG pathway analyses were used to predict biological functions and potential mechanisms of the host linear transcripts of these up-regulated and down-regulated circRNAs. Furthermore, we found that the expression level of circRNA-RNF19B (circRNF19B) in M1 macrophages was significantly higher than that in THP-1 macrophages and M2 macrophages. circRNF19B expression was increased when M2 converted to M1 whereas decreased when M1 converted to M2. Knockdown of circRNF19B following the activation of THP-1 cells using interferon-γ + LPS diminished the expression of M1 macrophages markers and elevated the expression of M2 macrophages markers. In conclusion, these data suggest the involvement of altered circRNAs expression patterns in macrophages exposure to different activating conditions. Circular RNAs may play important roles in regulating macrophage polarization.

4.
Analyst ; 146(22): 6815-6821, 2021 Nov 08.
Article in English | MEDLINE | ID: mdl-34643194

ABSTRACT

Solid-state nanochannels have attracted considerable attention for their similar ion transport properties to biological ion channels. The construction of porous ion channels with good stability at the submicro/micrometer scale is very beneficial to develop large-area ion channel devices. In this manuscript, based on in-situ thermal crosslinking of a small organic molecule containing triphenylamine and styrene groups, we construct a heterogeneous membrane with asymmetrical charge and wettability on cylindrical anodic aluminum oxide (AAO) channels (D ≈ 319 nm). This heterogeneous membrane has typical ion current rectification characteristics with a high rectification ratio of 36.9 and good stability. This work provides an effective strategy for the construction of submicrochannel heterogeneous membranes and also broadens the application range of bionic ion channels.


Subject(s)
Proton-Motive Force , Ion Transport , Porosity , Wettability
5.
Adv Sci (Weinh) ; 8(9): 2003410, 2021 05.
Article in English | MEDLINE | ID: mdl-33977048

ABSTRACT

Atherosclerosis is a chronic inflammatory disease that can cause acute cardiovascular events. Activation of the NOD-like receptor family, pyrin domain containing protein 3 (NLRP3) inflammasome enhances atherogenesis, which links lipid metabolism to sterile inflammation. This study examines the impact of an endogenous metabolite, namely ketone body 3-hydroxybutyrate (3-HB), on a mouse model of atherosclerosis. It is found that daily oral administration of 3-HB can significantly ameliorate atherosclerosis. Mechanistically, 3-HB is found to reduce the M1 macrophage proportion and promote cholesterol efflux by acting on macrophages through its receptor G-protein-coupled receptor 109a (Gpr109a). 3-HB-Gpr109a signaling promotes extracellular calcium (Ca2+) influx. The elevation of intracellular Ca2+ level reduces the release of Ca2+ from the endothelium reticulum (ER) to mitochondria, thus inhibits ER stress triggered by ER Ca2+ store depletion. As NLRP3 inflammasome can be activated by ER stress, 3-HB can inhibit the activation of NLRP3 inflammasome, which triggers the increase of M1 macrophage proportion and the inhibition of cholesterol efflux. It is concluded that daily nutritional supplementation of 3-HB attenuates atherosclerosis in mice.


Subject(s)
3-Hydroxybutyric Acid/therapeutic use , Atherosclerosis/drug therapy , Receptors, G-Protein-Coupled/drug effects , Animals , Calcium/metabolism , Disease Models, Animal , Ketone Bodies/therapeutic use , Mice , Signal Transduction/drug effects
6.
Mol Ther ; 29(7): 2268-2280, 2021 07 07.
Article in English | MEDLINE | ID: mdl-33647458

ABSTRACT

Myopia has become a global public health problem due to high prevalence. Although the etiological factors of myopia have been gradually recognized, the underlying mechanism remains largely elusive. Choroidal vascular dysfunction is recognized as a critical vision-threatening complication in myopia. Circular RNAs (circRNAs) are shown as the critical regulators in many biological processes and human diseases. In this study, we investigated the role of circRNAs in choroidal vascular dysfunction in myopia. The level of circFoxO1 was significantly upregulated in myopic choroid. circFoxO1 silencing suppressed choroidal endothelial cell viability, proliferation, migration, and tube formation in vitro and alleviated choroidal vascular dysfunction in vivo and ex vivo. circFoxO1 silencing retarded the progression of myopia as shown by reduced extracellular matrix remodeling and improved refractive error and axial elongation. Mechanistically, circFoxO1 acted as the sponge of miR-145 to sequester and inhibit miR-145 activity, thereby inducing VEGFA or ANGPT2 expression. miR-145 could mimic the effects of circFoxO1 silencing on choroidal endothelial phenotypes. Collectively, intervention of choroidal vascular dysfunction via regulating circFoxO1 level is a potential strategy for the prevention and management of myopia.


Subject(s)
Choroid/drug effects , Endothelium, Vascular/drug effects , Forkhead Box Protein O1/genetics , Gene Expression Regulation , Myopia/prevention & control , RNA, Circular/administration & dosage , Angiopoietin-2/genetics , Angiopoietin-2/metabolism , Animals , Apoptosis , Cell Movement , Cell Proliferation , Cells, Cultured , Choroid/metabolism , Choroid/pathology , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Humans , Male , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , Myopia/etiology , Myopia/pathology , RNA, Circular/antagonists & inhibitors , RNA, Circular/genetics , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism
7.
J Food Biochem ; 44(8): e13248, 2020 08.
Article in English | MEDLINE | ID: mdl-32557695

ABSTRACT

Crude pea (Pisum sativum L.) polysaccharides (CPPs) were extracted under ultrasound assistance, and CPP yield was highest to 6.27381%, which optimized using response surface methodology. Enzymatic method was more effective in deproteinization than Trichloroacetic acid and Sevag method, when considering the polysaccharide retention value as well as the protein clearance. Three-phase partitioning deproteinization indicated that the combination of the enzyme and Sevag method was more effective than their single use. Pea polysaccharide fractions were obtained by diethylaminoethyl-52 cellulose (W-DE-PP, N-DE-PP1, and N-DE-PP2) and Sephadex G-100 size-exclusion chromatography (W-DE-GPP, N1-DE-GPPa, and N1-DE-GPPb) in that order. Polysaccharide fractions W-DE-GPP and N1-DE-GPPa were showed a smooth surface with many cavities by Scanning electron microscopy (SEM) in 1,000 folds. All polysaccharides, characterized by high-performance liquid chromatography (HPLC), were composed of rhamnose, arabinose, galactose, glucose, and mannose, with the highest concentrations of galactose and glucose. Compared with different purification levels, N-DE-GPP showed the strongest activity against 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) free radicals and the highest ferric reducing antioxidant power, which were similar to the results of W-DE-GPP. Therefore, W-DE-GPP and N-DE-GPP may be promising natural sources of antioxidants. PRACTICAL APPLICATIONS: Recently, numerous studies on the extraction, purification, characteristics, and bioactivities of polysaccharides have been conducted. We mainly focused on the functional compounds of legumes. Comprehensive studies on pea polysaccharides are limited. Therefore, in the present study, extraction of CPPs was performed to optimize conditions using response surface methodology. Polysaccharide fractions were obtained from different purification levels and were chemically characterized using HPLC and SEM. Antioxidant activities of polysaccharides with different purification levels were determined. All the conventional methods, described in previous studies, were applied in the study. Furthermore, we analyzed and compared the characteristics of polysaccharides at different purification levels. We believe that our results would likely supplement the fundamental studies on pea polysaccharides.


Subject(s)
Pisum sativum , Polysaccharides , Antioxidants , Galactose , Plant Extracts
8.
J Clin Invest ; 130(7): 3833-3847, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32343678

ABSTRACT

Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Vascular pericyte degeneration is the predominant clinical manifestation of DR, yet the mechanism governing pericyte degeneration is poorly understood. Circular RNAs (circRNAs) play important roles in multiple biological processes and disease progression. Here, we investigated the role of circRNA in pericyte biology and diabetes-induced retinal vascular dysfunction. cZNF532 expression was upregulated in pericytes under diabetic stress, in the retinal vessels of a diabetic murine model, and in the vitreous humor of diabetic patients. cZNF532 silencing reduced the viability, proliferation, and differentiation of pericytes and suppressed the recruitment of pericytes toward endothelial cells in vitro. cZNF532 regulated pericyte biology by acting as a miR-29a-3p sponge and inducing increased expression of NG2, LOXL2, and CDK2. Knockdown of cZNF532 or overexpression of miR-29a-3p aggravated streptozotocin-induced retinal pericyte degeneration and vascular dysfunction. By contrast, overexpression of cZNF532 or inhibition of miR-29a-3p ameliorated human diabetic vitreous-induced retinal pericyte degeneration and vascular dysfunction. Collectively, these data identify a circRNA-mediated mechanism that coordinates pericyte biology and vascular homeostasis in DR. Induction of cZNF532 or antagonism of miR-29a-3p is an exploitable therapeutic approach for the treatment of DR.


Subject(s)
Diabetic Retinopathy/metabolism , Pericytes/metabolism , RNA, Circular/metabolism , Retinal Vessels/metabolism , Animals , Cell Line , Diabetic Retinopathy/genetics , Diabetic Retinopathy/pathology , Eye Proteins/genetics , Eye Proteins/metabolism , Humans , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Pericytes/pathology , RNA, Circular/genetics , Retinal Vessels/pathology
9.
Theranostics ; 10(7): 3293-3307, 2020.
Article in English | MEDLINE | ID: mdl-32194869

ABSTRACT

Rationale: Choroidal neovascularization (CNV) is a major cause of severe vision loss and occurs in many ocular diseases, especially neovascular age-related macular degeneration (nAMD). Circular RNAs (circRNAs) are emerging as a new class of endogenous noncoding RNAs, which have been implicated in the regulation of endothelial cell dysfunction in diabetes mellitus and cancer. In this study, we aimed to determine the role of circRNA-ZBTB44 (cZBTB44) in the pathogenesis of CNV. Methods: Quantitative polymerase chain reaction was conducted to detect cZBTB44 expression pattern during CNV development. Isolectin B4 staining, hematoxylin and eosin (HE) staining, and choroidal sprouting assay ex vivo were conducted to evaluate the role of cZBTB44 in the development of CNV. Endothelial cell proliferation, migration and tube formation assays were conducted to determine the role of cZBTB44 in angiogenic effect in vitro. Bioinformatics analysis, RNA immunoprecipitation assay, luciferase assay, and in vitro studies were conducted to investigate the mechanism of cZBTB44-mediated CNV development. Results: cZBTB44 expression was significantly up-regulated in a laser-induced CNV mouse model in vivo and in endothelial cells upon hypoxia stress in vitro. cZBTB44 silencing retarded CNV development, while overexpression of cZBTB44 showed the opposite effects. The role of cZBTB44 in CNV development was confirmed in choroidal sprouting assay ex vivo. cZBTB44 silencing reduced endothelial cell viability, proliferation, migration and tube formation in vitro. cZBTB44 acted as miR-578 sponge to sequester and inhibit miR-578 activity, which led to increased expression of vascular endothelial growth factor A (VEGFA) and vascular cell adhesion molecule-1 (VCAM1). Overexpression of miR-578 mimicked cZBTB44 silencing-mediated anti-angiogenic effects in vivo and in vitro. Furthermore, dysregulated cZBTB44 expression was detected in the clinical samples of nAMD patients. Conclusions: This study provided novel insights into the molecular pathogenesis of CNV. The cZBTB44-miR-578-VEGFA/VCAM1 axis might be a potential source of novel therapeutic targets for neovascularization-related diseases.


Subject(s)
Choroidal Neovascularization/genetics , RNA, Circular/metabolism , 3' Untranslated Regions , Animals , Cell Hypoxia , Choroid/cytology , Disease Models, Animal , Endothelial Cells/drug effects , Genetic Vectors , Lasers , Macaca mulatta , Mice , Mice, Inbred C57BL , RNA, Circular/biosynthesis , RNA, Circular/genetics , RNA, Small Interfering/genetics , Retina/cytology , Staining and Labeling , Up-Regulation , Vascular Cell Adhesion Molecule-1/genetics , Vascular Endothelial Growth Factor A/genetics
10.
Lab Chip ; 19(14): 2383-2393, 2019 07 21.
Article in English | MEDLINE | ID: mdl-31187104

ABSTRACT

The root system of plants is a major component of their bodies in terms of both function and bulk. The investigation of root system development is greatly assisted by microfluidic devices, which improve the spatial and temporal resolution of observations without destroying tissue. In the present study, a multi-chamber petaloid root-growth chip was developed for studying the development and physiology of root systems that have thin branching structures (i.e., fibrous root systems). The petaloid root-growth chip includes a central seed germination chamber and five root-growth chambers for observing the development of fibrous roots. The proposed device was applied for investigating the root system development of Oryza sativa. The phenotype and growth kinetics of O. sativa root systems grown in the proposed device were compared with those obtained during growth in a conventional conical flask with agar-based medium, and the results indicated that cultivation in the miniaturized device did not delay root system growth in the early stage (≤2 weeks). In addition, the transparent device enabled the non-destructive observation of the developmental and microstructural characteristics of the roots, such as the root caps, root border cells, and root hairs. Moreover, the ability to control the microenvironment in each of the five root-growth chambers individually facilitated the investigation of specific adaptations in the fibrous root growth of single O. sativa seedlings to different drought stresses. Accordingly, five polyethylene glycol (PEG)6000-induced drought stress conditions were established in the five root-growth chambers to investigate the root development of a single O. sativa seedling in the central germination chamber. In situ observations demonstrated that the different PEG6000-induced conditions affected the root growth responses and root microstructural adaptations of the single seedlings in each root-growth chamber. Therefore, the petaloid root-growth microfluidic chip can eliminate the effects of variations in different plant seeds to reveal the responses of plants to different environmental conditions more objectively while concurrently allowing for non-destructive observations at very high spatial and temporal resolution.


Subject(s)
Culture Techniques/instrumentation , Lab-On-A-Chip Devices , Oryza/growth & development , Plant Roots/growth & development , Droughts , Germination , Oryza/physiology , Plant Roots/physiology , Seeds/growth & development , Stress, Physiological
11.
Theranostics ; 9(4): 1170-1180, 2019.
Article in English | MEDLINE | ID: mdl-30867823

ABSTRACT

Retinal pigment epithelial (RPE) degeneration is potentially involved in the pathogenesis of several retinal degenerative diseases. mTORC1 signaling is shown as a crucial regulator of many biological processes and disease progression. In this study, we aimed at investigating the role of mTORC1 signaling in RPE degeneration. Methods: Western blots were conducted to detect mTORC1 expression pattern during RPE degeneration. Cre-loxP system was used to generate RPE-specific mTORC1 activation mice. Fundus, immunofluorescence staining, transmission electron microscopy, and targeted metabolomic analysis were conducted to determine the effects of mTORC1 activation on RPE degeneration in vivo. Electroretinography, spectral-domain optical coherence tomography, and histological experiments were conducted to determine the effects of mTORC1 activation on choroidal and retinal function in vivo. Results: RPE-specific activation of mTORC1 led to RPE degeneration as shown by the loss of RPE-specific marker, compromised cell junction integrity, and intracellular accumulation of lipid droplets. RPE degeneration further led to abnormal choroidal and retinal function. The inhibition of mTORC1 signaling with rapamycin could partially reverse RPE degeneration. Targeted metabolomics analysis further revealed that mTORC1 activation affected the metabolism of purine, carboxylic acid, and niacin in RPE. Conclusion: This study revealed that abnormal activation of mTORC1 signaling leads to RPE degeneration, which could provide a promising target for the treatment of RPE dysfunction-related diseases.


Subject(s)
Mechanistic Target of Rapamycin Complex 1/metabolism , Retinal Degeneration/physiopathology , Retinal Pigment Epithelium/pathology , Signal Transduction , Animals , Blotting, Western , Cells, Cultured , Disease Models, Animal , Electroretinography , Gene Expression Profiling , Histocytochemistry , Humans , Metabolome , Mice , Microscopy, Electron, Transmission , Microscopy, Fluorescence , Tomography, Optical Coherence
12.
Proc Natl Acad Sci U S A ; 116(15): 7455-7464, 2019 04 09.
Article in English | MEDLINE | ID: mdl-30914462

ABSTRACT

The crosstalk between vascular pericytes and endothelial cells (ECs) is critical for microvascular stabilization and remodeling; however, the crosstalk is often disrupted by diabetes, leading to severe and even lethal vascular damage. Circular RNAs are a class of endogenous RNAs that regulate several important physiological and pathological processes. Here we show that diabetes-related stress up-regulates cPWWP2A expression in pericytes but not in ECs. In vitro studies show that cPWWP2A directly regulates pericyte biology but indirectly regulates EC biology via exosomes carrying cPWWP2A. cPWWP2A acts as an endogenous miR-579 sponge to sequester and inhibit miR-579 activity, leading to increased expression of angiopoietin 1, occludin, and SIRT1. In vivo studies show that cPWWP2A overexpression or miR-579 inhibition alleviates diabetes mellitus-induced retinal vascular dysfunction. By contrast, inhibition of cPWWP2A-mediated signaling by silencing cPWWP2A or overexpressing miR-579 aggravates retinal vascular dysfunction. Collectively, this study unveils a mechanism by which pericytes and ECs communicate. Intervention of cPWWP2A or miR-579 expression may offer opportunities for treating diabetic microvascular complications.


Subject(s)
Cell Communication , Diabetic Retinopathy/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , MicroRNAs/biosynthesis , Pericytes/metabolism , Signal Transduction , Up-Regulation , Animals , Diabetic Retinopathy/pathology , Exosomes/metabolism , Exosomes/pathology , Human Umbilical Vein Endothelial Cells/pathology , Humans , Male , Mice , MicroRNAs/genetics , Pericytes/pathology , Retinal Vessels/metabolism , Retinal Vessels/pathology
13.
Theranostics ; 8(12): 3408-3415, 2018.
Article in English | MEDLINE | ID: mdl-29930739

ABSTRACT

Glaucoma is a major cause of visual impairment characterized by progressive retinal neurodegeneration. Circular RNAs are a class of endogenous noncoding RNAs that regulate gene expression in eukaryotes. In this study, we investigated the role of cZNF609 in retinal neurodegeneration induced by glaucoma. Methods: qRT-PCR and Sanger sequencing were conducted to detect cZNF609 expression pattern during retinal neurodegeneration. Immunofluorescence staining was conducted to detect the effect of cZNF609 silencing on retinal neurodegeneration in vivo. MTT assay, Ki67 staining, and PI staining were conducted to detect the effect of cZNF609 silencing on retinal glial cells and RGC function in vitro. Bioinformatics analysis, RNA pull-down assays, and in vitro studies were conducted to reveal the mechanism of cZNF609-mediated retinal neurodegeneration. Results: cZNF609 expression was significantly up-regulated during retinal neurodegeneration. cZNF609 silencing reduced retinal reactive gliosis and glial cell activation, and facilitated RGC survival in vivo. cZNF609 silencing directly regulated Müller cell function but indirectly regulated RGC function in vitro. cZNF609 acted as an endogenous miR-615 sponge to sequester and inhibit miR-615 activity, which led to increased METRN. METRN overexpression could partially rescue cZNF609 silencing-mediated inhibitory effects on retinal glial cell proliferation. Conclusion: Intervention of cZNF609 expression is a promising therapeutic strategy for retinal neurodegeneration.


Subject(s)
Glaucoma/pathology , Gliosis/pathology , MicroRNAs/metabolism , Neurodegenerative Diseases/pathology , Retina/pathology , Trans-Activators/genetics , Animals , Cell Proliferation , Ependymoglial Cells/physiology , Fluorescent Antibody Technique , Gene Expression Profiling , Intercellular Signaling Peptides and Proteins/metabolism , Nerve Tissue Proteins/metabolism , Neuroglia/physiology , RNA, Circular , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Sequence Analysis, DNA
14.
Cell Death Dis ; 9(5): 540, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29748605

ABSTRACT

Glaucoma is a neurodegenerative disease characterized by retinal ganglion cell (RGC) loss, optic disc excavation, and progressive visual field loss. Direct or indirect ameliorating retinal neurodegeneration is a promising therapeutic therapy for glaucoma. Circular RNAs (circRNAs) are a class of covalently closed circular RNA transcripts and have emerged as potential regulators in several neurodegenerative diseases. In this study, we show that cZRANB1 expression is significantly upregulated in retinal neurodegeneration induced by glaucoma. cZRANB1 knockdown decreases retinal reactive gliosis, glial cell activation, and facilitates RGC survival in vivo. cZRANB1 knockdown directly regulates Müller cell function and indirectly regulates RGC function in vitro. cZRANB1 acts as miRNA sponge to regulate Müller cell function through cZRANB1/miR-217/RUNX2 network. Intervention of cZRANB1 expression would become an effective strategy for treating retinal neurodegeneration.


Subject(s)
Glaucoma/metabolism , Neurodegenerative Diseases/metabolism , RNA/biosynthesis , Retina/metabolism , Up-Regulation , Animals , Cell Line , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Ependymoglial Cells/metabolism , Ependymoglial Cells/pathology , Glaucoma/genetics , Glaucoma/pathology , Glaucoma/therapy , Male , MicroRNAs/genetics , MicroRNAs/metabolism , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/pathology , Neurodegenerative Diseases/therapy , RNA/genetics , RNA, Circular , Rats , Rats, Sprague-Dawley , Retina/pathology
15.
Invest Ophthalmol Vis Sci ; 58(14): 6500-6509, 2017 12 01.
Article in English | MEDLINE | ID: mdl-29288268

ABSTRACT

Purpose: To reveal the expression profile and clinical significance of circular RNAs (circRNAs) in diabetic retinopathy (DR). Methods: Circular RNA microarrays were performed to identify DR-related circRNAs. Gene ontology (GO) enrichment and KEGG analysis was performed to determine the biologic modules and signaling pathway. TargetScan and miRana program was used to predict circRNA/miRNA interaction. Quantitative PCR assays were performed to detect circRNA expression pattern in clinical samples. Ki67 staining, Transwell, tube formation, and spheroid sprouting assays were performed to investigate the role and mechanism of circRNA in endothelial angiogenic function. Results: A total of 529 circRNAs were aberrantly expressed in diabetic retinas. The host genes of differentially expressed circRNAs were targeted to ATP binding (biologic process); extracellular exosome (cellular component); and intracellular signal transduction (molecular function). Circ_0005015 was verified to be upregulated in the plasma, vitreous sample, and fibrovascular membranes of DR patients. Circ_0005015 facilitated retinal endothelial angiogenic function via regulating endothelial cell proliferation, migration, and tube formation. Circ_0005015 acted as miR-519d-3p sponge to inhibit miR-519d-3p activity, leading to increased MMP-2, XIAP, and STAT3 expression. Conclusions: circRNAs are involved in DR pathogenesis, and thus serve as potential biomarkers of DR diagnosis.


Subject(s)
Diabetic Retinopathy/genetics , Gene Expression Regulation , RNA/genetics , Biomarkers/blood , Cell Movement , Cell Proliferation , Cells, Cultured , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Humans , RNA/biosynthesis , RNA, Circular , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/genetics
16.
Circulation ; 136(17): 1629-1642, 2017 Oct 24.
Article in English | MEDLINE | ID: mdl-28860123

ABSTRACT

BACKGROUND: The vascular complications of diabetes mellitus are the major causes of morbidity and mortality among people with diabetes. Circular RNAs are a class of endogenous noncoding RNAs that regulate gene expression in eukaryotes. In this study, we investigated the role of circular RNA in retinal vascular dysfunction induced by diabetes mellitus. METHODS: Quantitative polymerase chain reactions, Sanger sequencing, and Northern blots were conducted to detect circular HIPK3 (circHIPK3) expression pattern on diabetes mellitus-related stresses. MTT (3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assays, EdU (5-ethynyl-2'-deoxyuridine) incorporation assays, Transwell migration assays, and Matrigel assays were conducted to detect the role of circHIPK3 in retinal endothelial cell function in vitro. Retinal trypsin digestion, vascular permeability assays, and ELISA assays were conducted to detect the role of circHIPK3 in retinal vascular dysfunction in vivo. Bioinformatics analysis, luciferase activity assays, RNA pull-down assays, and in vitro studies were conducted to reveal the mechanism of circHIPK3-mediated retinal vascular dysfunction. RESULTS: circHIPK3 expression was significantly upregulated in diabetic retinas and retinal endothelial cells following stressors related to diabetes mellitus. circHIPK3 silencing or overexpressing circHIPK3 changed retinal endothelial cell viability, proliferation, migration, and tube formation in vitro. circHIPK3 silencing in vivo alleviated retinal vascular dysfunction, as shown by decreased retinal acellular capillaries, vascular leakage, and inflammation. circHIPK3 acted as an endogenous miR-30a-3p sponge to sequester and inhibit miR-30a-3p activity, which led to increased vascular endothelial growth factor-C, FZD4, and WNT2 expression. Ectopic expression of miR-30a-3p mimicked the effect of circHIPK3 silencing on vascular endothelial phenotypes in vivo and in vitro. CONCLUSIONS: The circular RNA circHIPK3 plays a role in diabetic retinopathy by blocking miR-30a function, leading to increased endothelial proliferation and vascular dysfunction. These data suggest that circular RNA is a potential target to control diabetic proliferative retinopathy.


Subject(s)
Diabetes Mellitus, Experimental/metabolism , Diabetic Retinopathy/metabolism , Endothelial Cells/metabolism , RNA, Untranslated/metabolism , Retinal Vessels/metabolism , Animals , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Diabetic Retinopathy/genetics , Diabetic Retinopathy/pathology , Endothelial Cells/physiology , Frizzled Receptors/biosynthesis , Frizzled Receptors/genetics , Gene Expression Regulation , Male , Mice , MicroRNAs/biosynthesis , MicroRNAs/genetics , RNA, Untranslated/genetics , Retinal Vessels/pathology , Vascular Endothelial Growth Factor C/biosynthesis , Vascular Endothelial Growth Factor C/genetics , Wnt Proteins/biosynthesis , Wnt Proteins/genetics
17.
Ying Yong Sheng Tai Xue Bao ; 28(5): 1563-1570, 2017 May 18.
Article in Chinese | MEDLINE | ID: mdl-29745193

ABSTRACT

To investigate the influences of continuous decline of soil water content during different growth stages on the growth, development and yield of maize, artificial water control experiment with a rainout shelter were conducted, and the dynamic variations of several physiological and ecological indices of maize were analyzed, including plant height, leaf area index (LAI), photosynthesis characteristics, aboveground biomass, and yield. The experimental factors considered in this field experiment were the starting time and duration of water control. Rainfall was sheltered from jointing with duration of 20 (T1) and 27 days (T2) and from heading with duration of 20 (T3) and 27 days (T4) for each starting time. In total, there were 5 treatments in this field experiment, including the treatment of control check (CK). The results indicated that LAI was reduced by conti-nuous drought with leaves rolling, tresses and early aging of lower leaves, thus biomass accumulation and grain yield were reduced. At the end of each treatment of continuous drought, LAI was reduced to 74.9%, 68.2%, 60.5% and 48.3% of the CK LAI for the T1 to T4 treatments, respectively. After experiencing continuous water control, the maximum photosynthetic rate (Pn max) of leaf decreased gradually, with Pn max decreased to 23% of the CK Pn max for the treatment T1 and T3, and to less than 10% of the CK Pn max for the treatment T2 and T4 at the end of each treatment. Two weeks after re-watering, Pn max recovered to around 90% of the CK Pn max. Compared with CK, grain yield decreased by 18.5% and 24.0% for the T1 and T2 treatments, and by 46.1% and 45.8% for the T3 and T4 treatments, respectively. Continuous drought brought about more serious effects during heading period than during jointing period on aboveground biomass and yield components. The drought condition of soil could be represented by drought degree (D), which was linearly correlated with maize yield loss and could be used to predict the yield loss.


Subject(s)
Droughts , Zea mays , Biomass , Photosynthesis , Plant Leaves , Soil , Water
18.
Toxicol Appl Pharmacol ; 288(3): 349-58, 2015 Nov 01.
Article in English | MEDLINE | ID: mdl-26296503

ABSTRACT

Preconditioning against myocardial ischemia-reperfusion (I/R) injury can be suppressed in some pathological conditions. This study was designed to investigate whether morphine preconditioning (MPC) exerts cardioprotection in doxorubicin (DOX)-induced heart failure in rats and the mechanisms involved. Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), extracellular signal-regulated kinase (ERK) and glycogen synthase kinase (GSK)-3ß pathways were examined. Normal and DOX-induced failing rat hearts were subjected to I/R injury using a Langendorff perfusion system with or without MPC or ischemic preconditioning (IPC). The PI3K inhibitor (wortmannin) or ERK inhibitor (PD98059) was infused before MPC. In normal hearts, both MPC and IPC significantly reduced infarct size and the rise in lactate dehydrogenase (LDH) level caused by I/R injury. Pretreatment with wortmannin or PD98059 abrogated the protective effects of MPC and suppressed the phosphorylation of Akt, ERK and GSK-3ß. In failing rat hearts, however, MPC retained its cardioprotection while IPC did not. This protective effect was abolished by PD98059 but not wortmannin. MPC increased the level of p-ERK rather than p-Akt. The phosphorylation of GSK-3ß induced by MPC was reversed by PD98059 only. IPC did not elevate the expression of p-ERK, p-Akt and p-GSK-3ß in failing rat hearts. We conclude that MPC is cardioprotective in rats with DOX-induced heart failure while IPC is not. The effect of MPC appears to be mediated via the ERK/GSK-3ß pathway independent of PI3K/Akt.


Subject(s)
Cardiotonic Agents/pharmacology , Doxorubicin/adverse effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Glycogen Synthase Kinase 3/metabolism , Morphine/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Animals , Extracellular Signal-Regulated MAP Kinases/genetics , Glycogen Synthase Kinase 3/genetics , Glycogen Synthase Kinase 3 beta , Heart/drug effects , Ischemic Preconditioning, Myocardial , Male , Myocardial Reperfusion Injury/pathology , Phosphatidylinositol 3-Kinases/genetics , Phosphorylation , Proto-Oncogene Proteins c-akt/genetics , Rats , Rats, Sprague-Dawley , Signal Transduction
19.
Ying Yong Sheng Tai Xue Bao ; 26(1): 233-40, 2015 Jan.
Article in Chinese | MEDLINE | ID: mdl-25985675

ABSTRACT

Maize water suitability (MWS) model was developed at growth stage scale. Frequency and severity of drought were evaluated by combining MWS estimates and agricultural meteorological drought indexes. The MWS at each growth stage was calculated by using maize observational data and conventional meteorological data at 52 sites in Liaoning during the period from 1981 to 2010. Based on the climatic trend and abrupt change analysis, spatiotemporal dynamics of MWS were investigated. Meanwhile, occurrence of agricultural drought and its severity were also estimated. The results showed that the variation of MWS largely differed at different growth stages. Climatic abrupt change happened in 1994, 1996 and 1999 at the stages of emergence to seven leaves (II), jointing to tasseling (IV) and physiological maturity to maturity (VI). During the past 30 years, MWS showed an obvious increasing trend at the stages of sowing to emergence(I) , seven leaves to jointing(III), IV and tasseling to physiological maturity(V), while it showed a decreasing trend at the stages of II and VI, and that at VI stage was statistically significant. In addition, the climatic trend of MWS showed apparently spatial variability. The frequencies of drought at different severities varied with maize growth stages. Areas of high variability of MWS were located in the Northwest and South of Liaoning at the stages of I , II , III and VI, where were also the regions of high frequency of mid- and severe-drought. At the stages of IV and V, the frequency of drought was low and only light- and mid-drought occurred in few areas. In conclusion, the regional mean MWS could be capable to reasonably assess the agricultural drought in Liaoning at the regional scale.


Subject(s)
Agriculture , Droughts , Zea mays , China , Climate Change , Ecosystem , Models, Theoretical , Spatio-Temporal Analysis , Water
20.
Neurobiol Dis ; 74: 167-179, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25478814

ABSTRACT

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs.


Subject(s)
DNA Damage , DNA, Mitochondrial , Glaucoma/genetics , Glaucoma/physiopathology , Mutation , Retinal Ganglion Cells/physiology , Animals , Apoptosis/physiology , Axons/pathology , Axons/physiology , Cell Survival/genetics , Cell Survival/physiology , DNA Repair , Disease Models, Animal , Disease Progression , Glaucoma/pathology , Glutamic Acid/metabolism , Intraocular Pressure/genetics , Intraocular Pressure/physiology , Male , Mitochondria/genetics , Mitochondria/pathology , Mitochondria/physiology , Optic Nerve/pathology , Optic Nerve/physiopathology , Rats, Wistar , Retinal Ganglion Cells/pathology , Time Factors
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