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1.
J Am Chem Soc ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598684

RESUMO

Cross-coupling reactions represent an indispensable tool in chemical synthesis. An intriguing challenge in this field is to achieve selective cross-coupling between two precursors with similar reactivity or, to the limit, the identical molecules. Here we report an unexpected dehydrobrominative cross-coupling between 1,3,5-tris(2-bromophenyl)benzene molecules on silver surfaces. Using scanning tunneling microscopy, we examine the reaction process at the single-molecular level, quantify the selectivity of the dehydrobrominative cross-coupling, and reveal the modulation of selectivity by substrate lattice-related catalytic activity or molecular assembly effect. Theoretical calculations indicate that the dehydrobrominative cross-coupling proceeds via regioselective C-H bond activation of debrominated TBPB and subsequent highly selective C-C coupling of the radical-based intermediates. The reaction kinetics plays an important role in the selectivity for the cross-coupling. This work not only expands the toolbox for chemical synthesis but also provides important mechanistic insights into the selectivity of coupling reactions on the surface.

2.
Heliyon ; 10(8): e29817, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38681586

RESUMO

Background: RNA methylation is involved in major life processes. Angiogenesis is a normal phenomenon that occurs constantly in the bodies of all mammals, once it is aberrant or something goes wrong, it may lead to pathological changes. The bibliometric analysis could produce a comprehensive overview of RNA methylation during angiogenesis. Methods: The Web of Science Core Collection (WoSCC) database was used to screen publications about RNA methylation during angiogenesis from Jan 1, 2000 to Nov 24, 2022. Bibliometric and visualization analyses were conducted to understand publication trends by CiteSpace and VOSviewer. Results: In total, 382 publications from 2000 to 2022 were included in the bibliometric and visualization analyses. On the whole, the number of publications had exponential growth. China was the country and Sun Yat-Sen University was the university associated with the largest number of publications, although publications from the United Kingdom and Soochow University were currently having the strongest impact. Cancer was the most studied topic in this field, and N6-methyladenosine is the most studied RNA methylation type. Conclusion: There is a continuously increasing trend in publications related to RNA methylation and angiogenesis, which has attracted much attention, particularly since 2011. RNA methylation might be a promising target in the investigation of pathological angiogenesis and related disorders, which deserves further investigation.

3.
Heliyon ; 10(1): e23668, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192819

RESUMO

N6-methyladenosine (m6A) modification, as the most common modification method in eukaryotes, is widely involved in numerous physiological and pathological processes, such as embryonic development, malignancy, immune regulation, and premature aging. Under pathological conditions of ocular diseases, changes in m6A modification and its metabolism can be detected in aqueous and vitreous humor. At the same time, an increasing number of studies showed that m6A modification is involved in the normal development of eye structures and the occurrence and progress of many ophthalmic diseases, especially ocular neovascular diseases, such as diabetic retinopathy, age-related macular degeneration, and melanoma. In this review, we summarized the latest progress regarding m6A modification in ophthalmic diseases, changes in m6A modification-related enzymes in various pathological states and their upstream and downstream regulatory networks, provided new prospects for m6A modification in ophthalmic diseases and new ideas for clinical diagnosis and treatment.

4.
Anal Chem ; 95(50): 18504-18513, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38033201

RESUMO

Amino acids (AAs) in the d-form are involved in multiple pivotal neurological processes, although their l-enantiomers are most commonly found. Mass spectrometry-based analysis of low-abundance d-AAs has been hindered by challenging enantiomeric separation from l-AAs, low sensitivity for detection, and lack of suitable internal standards for accurate quantification. To address these critical gaps, N,N-dimethyl-l-leucine (l-DiLeu) tags are first validated as novel chiral derivatization reagents for chromatographic separation of 20 pairs of d/l-AAs, allowing the construction of a 4-plex isobaric labeling strategy for enantiomer-resolved quantification through single step tagging. Additionally, the creative design of N,N-dimethyl-d-leucine (d-DiLeu) reagents offers an alternative approach to generate analytically equivalent internal references of d-AAs using d-DiLeu-labeled l-AAs. By labeling cost-effective l-AA standards using paired d- and l-DiLeu, this approach not only enables absolute quantitation of both d-AAs and l-AAs from complex biological matrices with enhanced precision but also significantly boosts the combined signal intensities from all isobaric channels, greatly improving the detection and quantitation of low-abundance AAs, particularly d-AAs. We term this quantitative strategy CHRISTMAS, which stands for chiral pair isobaric labeling strategy for multiplexed absolute quantitation. Leveraging the ion mobility collision cross section (CCS) alignment, interferences from coeluting isomers/isobars are effectively filtered out to provide improved quantitative accuracy. From wild-type and Alzheimer's disease (AD) mouse brains, we successfully quantified 20 l-AAs and 5 d-AAs. The significant presence and differential trends of certain d-AAs compared to those of their l-counterparts provide valuable insights into the involvement of d-AAs in aging, AD progression, and neurodegeneration.


Assuntos
Aminoácidos , Proteômica , Animais , Camundongos , Aminoácidos/análise , Proteômica/métodos , Leucina/química , Aminas , Cromatografia Líquida/métodos
5.
Anal Chem ; 95(48): 17637-17645, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-37982459

RESUMO

Glycans are vital biomolecules with diverse functions in biological processes. Mass spectrometry (MS) has become the most widely employed technology for glycomics studies. However, in the traditional data-dependent acquisition mode, only a subset of the abundant ions during MS1 scans are isolated and fragmented in subsequent MS2 events, which reduces reproducibility and prevents the measurement of low-abundance glycan species. Here, we reported a new method termed 6-plex mdSUGAR isobaric-labeling guide fingerprint embedding (MAGNI), to achieve multiplexed, quantitative, and targeted glycan analysis. The glycan peak signature was embedded by a triplicate-labeling strategy with a 6-plex mdSUGAR tag, and using ultrahigh-resolution mass spectrometers, the low-abundance glycans that carry the mass fingerprints can be recognized on the MS1 spectra through an in-house developed software tool, MAGNIFinder. These embedded unique fingerprints can guide the selection and fragmentation of targeted precursor ions and further provide rich information on glycan structures. Quantitative analysis of two standard glycoproteins demonstrated the accuracy and precision of MAGNI. Using this approach, we identified 304 N-glycans in two ovarian cancer cell lines. Among them, 65 unique N-glycans were found differentially expressed, which indicates a distinct glycosylation pattern for each cell line. Remarkably, 31 N-glycans can be quantified in only 1 × 103 cells, demonstrating the high sensitivity of our method. Taken together, our MAGNI method offers a useful tool for low-abundance N-glycan characterization and is capable of determining small quantitative differences in N-glycan profiling. Therefore, it will be beneficial to the field of glycobiology and will expand our understanding of glycosylation.


Assuntos
Glicômica , Espectrometria de Massas em Tandem , Feminino , Humanos , Espectrometria de Massas em Tandem/métodos , Glicômica/métodos , Reprodutibilidade dos Testes , Polissacarídeos/química , Íons
6.
Heliyon ; 9(7): e18228, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37539253

RESUMO

Background: Gene therapy is a treatment approach at the genetic level, which brings great advances in many diseases and develops rapidly in recent years. Currently, its mechanism of action is mainly through the replacement of missing or defective genes, or the reduction of harmful gene products. However, the application of gene therapy in ophthalmology remains limited. Methods: A total of 1143 articles and reviews published in the field of ocular gene therapies were found in the Web of Science Core Collection database and used for the bibliometric analysis. CiteSpace was mainly applied to the network analysis of countries, institutions, keywords, and dual-map overlay of journals. The visual analysis of authors, journals, and references was used by VOSviewer. The geographical distribution of publications was conducted by R language. Results: The annual publications are increasing in general. Currently, the USA and the UK are two main sources of publications in this field. Switzerland, Denmark, and Finland are the top 3 countries that establish the most cooperation and exchanges with other countries or regions. The most cited and co-cited journal in this field is Investigative Ophthalmology & Visual Science. Gene therapy studies for eye diseases are mainly focused on retinal dysfunctions by the analysis of references, keywords, and counting of original research, including Leber's congenital amaurosis and retinitis pigmentosa. Conclusion: This study used bibliometrics to analyze overall characteristics and put forward prospects for the future in the field of gene therapy in ophthalmology. Ocular diseases, especially hereditary retinal diseases, will be the major focus of gene therapy in the future.

7.
Heliyon ; 9(8): e18626, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37560684

RESUMO

Exosomes are extracellular vesicles that can be produced by most cells. Exosomes act as important intermediaries in intercellular communication, and participate in a variety of biological activities between cells. Non-coding RNAs (ncRNAs) usually refer to RNAs that do not encode proteins. Although ncRNAs have no protein-coding capacity, they are able to regulate gene expression at multiple levels. Angiogenesis is the formation of new blood vessels from pre-existing vessels, which is an important physiological process. However, abnormal angiogenesis could induce many diseases such as atherosclerosis, diabetic retinopathy and cancer. Many studies have shown that ncRNAs can stably exist in exosomes and play a wide range of physiological and pathological roles including regulation of angiogenesis. In brief, some specific ncRNAs can be enriched in exosomes secreted by cells and absorbed by recipient cells through the exosome pathway, thus activating relevant signaling pathways in target cells and playing a role in regulating angiogenesis. In this review, we describe the physiological and pathological functions of exosomal ncRNAs in angiogenesis, summarize their role in angiogenesis-related diseases, and illustrate potential clinical applications like novel drug therapy strategies and diagnostic markers in exosome research as inspiration for future investigations.

8.
Exp Eye Res ; 232: 109518, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37257714

RESUMO

The aim of the study is to reveal the expression profiling and clinical significance of peripheral blood mononuclear cell (PBMC) tRNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) of premature infants with treatment-requiring retinopathy of prematurity (ROP). Significantly altered tsRNAs and miRNAs were screened using small RNA sequencing. RT-qPCR was used to verify the altered RNAs identified by small RNA transcriptomics. The target genes, their enriched functions, and possibly involved signaling pathways were identified by bioinformatics analyses. According to the small RNA sequencing, 125 tsRNAs and 205 miRNAs were significantly altered in PBMCs obtained from infants with treatment-requiring ROP compared with the premature controls without retinopathy. We preliminarily validated the significant alterations of 6 tsRNAs and 9 miRNAs. The target genes for those tsRNAs were enriched for cellular macromolecule metabolic process, intracellular anatomical structure, transcription regulatory region nucleic acid binding, and Th17 cell differentiation; those of the altered miRNAs were enriched for the developmental process, cell junction, DNA-binding transcription activator activity, and FoxO signaling pathway. By verification with the extended sample size, we identified tsRNAs and miRNAs that could be potential biomarkers with clinical values. The study recognized the alterations and clinical significance of changed tsRNA/miRNA profiles in PBMCs from premature infants with ROP. These significantly altered tsRNAs and miRNAs might be useful as potential diagnostic biomarkers and molecular targets for treatment-requiring ROP.


Assuntos
MicroRNAs , Retinopatia da Prematuridade , Recém-Nascido , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Leucócitos Mononucleares/metabolismo , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/genética , Retinopatia da Prematuridade/metabolismo , Relevância Clínica , Biomarcadores/metabolismo
9.
Toxics ; 11(5)2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37235222

RESUMO

The embryonic zebrafish is a useful vertebrate model for assessing the effects of substances on growth and development. However, cross-laboratory developmental toxicity outcomes can vary and reported developmental defects in zebrafish may not be directly comparable between laboratories. To address these limitations for gaining broader adoption of the zebrafish model for toxicological screening, we established the Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) program to investigate how experimental protocol differences can influence chemical-mediated effects on developmental toxicity (i.e., mortality and the incidence of altered phenotypes). As part of SEAZIT, three laboratories were provided a common and blinded dataset (42 substances) to evaluate substance-mediated effects on developmental toxicity in the embryonic zebrafish model. To facilitate cross-laboratory comparisons, all the raw experimental data were collected, stored in a relational database, and analyzed with a uniform data analysis pipeline. Due to variances in laboratory-specific terminology for altered phenotypes, we utilized ontology terms available from the Ontology Lookup Service (OLS) for Zebrafish Phenotype to enable additional cross-laboratory comparisons. In this manuscript, we utilized data from the first phase of screening (dose range finding, DRF) to highlight the methodology associated with the development of the database and data analysis pipeline, as well as zebrafish phenotype ontology mapping.

10.
J Proteome Res ; 22(5): 1483-1491, 2023 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-37014956

RESUMO

A major challenge in reducing the death rate of colorectal cancer is to screen patients using low-invasive testing. A blood test shows a high compliance rate with reduced invasiveness. In this work, a multiplex isobaric tag labeling strategy coupled with mass spectrometry is adopted to relatively quantify primary and secondary amine-containing metabolites in serum for the discovery of metabolite level changes of colorectal cancer. Serum samples from patients at different risk statuses and colorectal cancer growth statuses are studied. Metabolite identification is based on accurate mass matching and/or retention time of labeled metabolite standards. We quantify 40 metabolites across all the serum samples, including 18 metabolites validated with standards. We find significantly decreased levels of threonine and asparagine in the patients with growing adenomas or high-risk adenomas (p < 0.05). Glutamine levels decrease in patients with adenomas of unknown growth status or high-risk adenomas. In contrast, arginine levels are elevated in patients with low-risk adenoma. Receiver operating characteristic analysis shows high sensitivity and specificity of these metabolites for detecting growing adenomas. Based on these results, we conclude that a few metabolites identified here might contribute to distinguishing colorectal patients with growing adenomas from normal individuals and patients with unknown growth status of adenomas.


Assuntos
Adenoma , Neoplasias Colorretais , Humanos , Espectrometria de Massas , Curva ROC , Aminas/análise , Adenoma/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo
11.
Int J Med Sci ; 20(2): 254-261, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36794165

RESUMO

Ischemia-induced pathological neovascularization in the retina is a leading cause of blindness in various age groups. The purpose of the current study was to identify the involvement of circular RNAs (circRNAs) methylated by N6-methyladenosine (m6A), and predict their potential roles in oxygen-induced retinopathy (OIR) in mice. Methylation assessment via microarray analysis indicated that 88 circRNAs were differentially modified by m6A methylation, including 56 hyper-methylated circRNAs and 32 hypo-methylated circRNAs. Gene ontology enrichment analysis predicted that the enriched host genes of the hyper-methylated circRNAs were involved in cellular process, cellular anatomical entity, and protein binding. Host genes of the hypo-methylated circRNAs were enriched in the regulation of cellular biosynthetic process, the nucleus, and binding. According to the Kyoto Encyclopedia of Genes and Genomes analysis, those host genes were involved in the pathways of selenocompound metabolism, salivary secretion, and lysine degradation. MeRIP-qPCR verified significant alterations in m6A methylation levels of mmu_circRNA_33363, mmu_circRNA_002816, and mmu_circRNA_009692. In conclusion, the study revealed the m6A modification alterations in OIR retinas, and the findings above shed light on the potential roles of m6A methylation in circRNA regulatory functions in the pathogenesis of ischemia-induced pathological retinal neovascularization.


Assuntos
RNA Circular , Neovascularização Retiniana , Animais , Camundongos , RNA Circular/genética , RNA Circular/metabolismo , RNA/genética , RNA/metabolismo , Neovascularização Retiniana/genética , Perfilação da Expressão Gênica , Isquemia/complicações , Isquemia/genética
12.
Pharmaceutics ; 14(12)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36559245

RESUMO

Diabetic retinopathy (DR) is a major cause of blindness worldwide and may be non-proliferative (NPDR) or proliferative (PDR). To Investig.gate the metabolomic and lipidomic characteristics of plasma in DR patients, plasma samples were collected from patients with type 2 diabetes mellitus (DR group) with PDR (n = 27), NPDR (n = 18), or no retinopathy (controls, n = 21). Levels of 54 and 41 metabolites were significantly altered in the plasma of DR patients under positive and negative ion modes, respectively. By subgroup analysis, 74 and 29 significantly changed plasma metabolites were detected in PDR patients compared with NPDR patients under positive and negative ion modes, respectively. KEGG analysis indicated that pathways such as biosynthesis of amino acids and neuroactive ligand-receptor interaction were among the most enriched pathways in altered metabolites in the DR group and PDR subgroup. Moreover, a total of 26 and 41 lipids were significantly changed in the DR group and the PDR subgroup, respectively. The panel using the 29-item index could discriminate effectively between diabetic patients with and without retinopathy, and the panel of 22 items showed effective discrimination between PDR and NPDR. These results provide a basis for further research into the therapeutic targets associated with these metabolite and lipid alterations.

13.
Front Immunol ; 13: 953812, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081509

RESUMO

Purpose: This study aims to reveal the altered expression profiles of circular RNAs (circRNAs) in the peripheral blood mononuclear cells (PBMCs) of patients with retinopathy of prematurity (ROP), and to identify potential biomarkers for ROP diagnosis. Methods: Differentially expressed circRNAs in PBMCs of five infants with ROP and five controls were identified using microarray analysis. Twelve altered circRNAs were validated using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Bioinformatic analyses were conducted to predict the circRNA/miRNA interactions, competing endogenous RNA (ceRNA) network, related biological functions, and signaling pathways. Four selected circRNAs in PBMCs were verified using RT-qPCR in another cohort, including 24 infants with ROP and 23 premature controls, and receiver operating characteristic (ROC) curves were used to estimate their potential as diagnostic biomarkers of ROP. Results: A total of 54 and 143 circRNAs were significantly up- and down-regulated, respectively, in the PBMCs of patients with ROP compared with controls. Twelve of the significantly altered circRNAs were preliminarily validated by RT-qPCR, which confirmed the reliability of the microarray analysis. The circRNA/miRNA interactions and ceRNA network were displayed according to the altered circRNAs. Three circRNAs (hsa_circRNA_061346, hsa_circRNA_092369, and hsa_circRNA_103554) were identified as potential diagnostic biomarkers for ROP with certain clinical values. Conclusions: CircRNAs were significantly altered in PBMCs of treatment-requiring ROP patients. CircRNAs may be used as potential biomarkers and possible therapeutic targets for ROP.


Assuntos
Leucócitos Mononucleares , MicroRNAs , RNA Circular , Retinopatia da Prematuridade , Biomarcadores , Humanos , Recém-Nascido , Leucócitos Mononucleares/metabolismo , MicroRNAs/genética , RNA Circular/genética , Reprodutibilidade dos Testes , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/genética , Retinopatia da Prematuridade/metabolismo
14.
Anal Chem ; 94(34): 11773-11782, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35960654

RESUMO

Intact glycopeptide analysis has been of great interest because it can elucidate glycosylation site information and glycan structural composition at the same time. However, mass spectrometry (MS)-based glycoproteomic analysis is hindered by the low abundance and poor ionization efficiency of glycopeptides. Relatively large amounts of starting materials are needed for the enrichment, which makes the identification and quantification of intact glycopeptides from samples with limited quantity more challenging. To overcome these limitations, we developed an improved isobaric labeling strategy with an additional boosting channel to enhance N,N-dimethyl leucine (DiLeu) tagging-based quantitative glycoproteomic analysis, termed as Boost-DiLeu. With the integration of a one-tube sample processing workflow and high-pH fractionation, 3514 quantifiable N-glycopeptides were identified from 30 µg HeLa cell tryptic digests with reliable quantification performance. Furthermore, this strategy was applied to human cerebrospinal fluid (CSF) samples to differentiate N-glycosylation profiles between Alzheimer's disease (AD) patients and non-AD donors. The results revealed processes and pathways affected by dysregulated N-glycosylation in AD, including platelet degranulation, cell adhesion, and extracellular matrix, which highlighted the involvement of N-glycosylation aberrations in AD pathogenesis. Moreover, weighted gene coexpression network analysis (WGCNA) showed nine modules of glycopeptides, two of which were associated with the AD phenotype. Our results demonstrated the feasibility of using this strategy for in-depth glycoproteomic analysis of size-limited clinical samples. Taken together, we developed and optimized a strategy for the enhanced comprehensive quantitative intact glycopeptide analysis with DiLeu labeling, showing significant promise for identifying novel therapeutic targets or biomarkers in biological systems with a limited sample quantity.


Assuntos
Glicopeptídeos , Glicopeptídeos/análise , Células HeLa , Humanos , Leucina/análogos & derivados , Leucina/química , Espectrometria de Massas
15.
Front Endocrinol (Lausanne) ; 13: 913370, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35903272

RESUMO

Purpose: We sought to reveal the expression profiles of transfer RNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) in the vitreous humor of patients with proliferative diabetic retinopathy (PDR). Methods: Vitreous humor samples were obtained from PDR patients and a control group for this study. Sequencing of small RNAs was conducted to assess the expression profiles of tsRNAs and miRNAs in both groups, which was followed by validation using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Bioinformatics analyses were conducted to predict the target genes and their potential biological functions and signaling pathways. Results: A total of 37 tsRNAs and 70 miRNAs with significant differences were screened out from the vitreous humor samples of PDR patients compared to controls. Following validation by RT-qPCR, the target genes of the validated tsRNAs and miRNAs were predicted, and Gene Ontology analysis indicated that the target genes of the tsRNAs were most enriched in the cellular macromolecule metabolic process, cytoplasm, and ion-binding, while those of the miRNAs were most abundant in the regulation of major metabolic process, cytoplasm, and protein-binding. In addition, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the target genes of said tsRNAs and miRNAs were most enriched in the adenosine monophosphate-activated protein kinase signaling pathway and Th17 cell differentiation, respectively. Conclusions: The present study identified altered tsRNAs and miRNAs in vitreous humor samples of PDR patients, which may play important roles in the pathogenesis of PDR and could be considered potential therapeutic targets in the treatment of PDR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , MicroRNAs , Diabetes Mellitus/patologia , Retinopatia Diabética/metabolismo , Ontologia Genética , Humanos , MicroRNAs/metabolismo , RNA de Transferência/metabolismo , Corpo Vítreo/metabolismo , Corpo Vítreo/patologia
16.
Invest Ophthalmol Vis Sci ; 63(8): 9, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35816041

RESUMO

Purpose: Retinal neovascularization is a major cause of blindness. This study aimed to investigate the effects of IL-19 and the underlying mechanisms in a mouse model of oxygen-induced retinopathy (OIR). Methods: C57BL/6J wild-type mice and IL-19 knockout (KO) mice were used to establish an OIR mouse model. Bone marrow-derived macrophages (BMDMs) with or without recombinant IL-19 (rIL-19) stimulation were injected intravitreally. Reverse transcription-quantitative polymerase chain reaction was used to determine the mRNA expressions. ELISA and western blotting were performed to assess the protein levels. Immunofluorescence staining was applied to assess retinal neovascularization. Human retinal endothelial cells (HRECs) stimulated with rIL-19 were cultured to evaluate the effects on cell proliferation and migration. Results: The level of IL-19 was significantly elevated at postnatal day 17 in OIR retinas. Both the avascular areas and pathological neovascular tufts were significantly increased in rIL-19-treated OIR retinas and suppressed in IL-19 KO retinas. IL-19 KO mice suppressed expression of ARG1, VEGFA, and pSTAT3. Moreover, BMDMs stimulated by rIL-19 enhanced that expression and suppressed the expression of inducible nitric oxide synthase (iNOS). The proliferation and migration of HRECs were significantly augmented by rIL-19. In addition, intravitreal injection of BMDMs stimulated by rIL-19 enhanced retinal neovascularization. Conclusions: These findings suggest that IL-19 enhances pathological neovascularization through a direct effect on microvascular endothelial cells and the promotion of M2 macrophage polarization. The inhibition of IL-19 may be a potential treatment for retinal neovascularization.


Assuntos
Doenças Retinianas , Neovascularização Retiniana , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Humanos , Interleucinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxigênio/metabolismo , Oxigênio/toxicidade , Doenças Retinianas/metabolismo , Neovascularização Retiniana/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Exp Eye Res ; 220: 109114, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35584758

RESUMO

Retinal neovascular diseases are major causes of blindness worldwide. As a common epitranscriptomic modification of eukaryotic RNAs, N6-methyladenosine (m6A) is associated with the pathogenesis of many diseases, including angiogenesis, through the regulation of RNA metabolism and functions. The aim of this study was to identify m6A modifications of mRNAs and long noncoding RNAs (lncRNAs) and determine their potential roles in retinal neovascularization. The transcriptome-wide m6A profiles of mRNAs and lncRNAs in the retinal tissues of mice with oxygen-induced retinopathy (OIR) and controls were identified by microarray analysis of immunoprecipitated methylated RNAs. The m6A methylation levels of mRNAs and lncRNAs identified in the microarray data were validated by MeRIP-qPCR. A total of 1321 mRNAs (151 hypermethylated and 1170 hypomethylated) and 192 lncRNAs (15 hypermethylated and 177 hypomethylated) were differentially methylated with the m6A modification in OIR and control mice. Gene ontology analysis showed that hypermethylated mRNAs were enriched in the regulation of multicellular organismal process, intracellular organelle, and protein binding, while hypomethylated mRNAs were enriched in cellular metabolic process, intracellular process, and binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that hypermethylated mRNAs were involved in dopaminergic synapses, glutamatergic synapse, and PI3K-Akt signaling pathway, while hypomethylated mRNAs were involved in autophagy, ubiquitin-mediated proteolysis, and spliceosome. Moreover, the altered levels of m6A methylation of ANGPT2, GNG12, ROBO4, and ENSMUST00000153785 were validated by MeRIP-qPCR. The results revealed an altered m6A epitranscriptome in OIR retinas. These methylated RNAs may act as novel modulators and targets in retinal neovascularization.


Assuntos
RNA Longo não Codificante , Neovascularização Retiniana , Adenosina/análogos & derivados , Animais , Perfilação da Expressão Gênica/métodos , Camundongos , Oxigênio/toxicidade , Fosfatidilinositol 3-Quinases/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/genética , Neovascularização Retiniana/genética
18.
Front Psychol ; 13: 814869, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250745

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has fueled anti-Asian, especially anti-Chinese sentiments worldwide, which may negatively impact diasporic Chinese youths' adjustment and prosocial development. This study examined the association between compassion, discrimination and prosocial behaviors in diasporic Chinese youths during the COVID-19 pandemic. 360 participants participated and completed the multi-country, cross-sectional, web-based survey between April 22 and May 9, 2020, the escalating stage of the pandemic. This study found compassion as prosocial behaviors' proximal predictor, while discrimination independently predicted participation in volunteering, and could potentially enhance the association between compassion and charitable giving. These findings suggest that prosociality among young people is sensitive to social context, and that racial discrimination should be considered in future prosocial studies involving young members of ethnic and racial minorities.

19.
Front Med (Lausanne) ; 9: 840030, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35187013

RESUMO

Retinopathy of prematurity (ROP) is the main risk factor for vision-threatening disease in premature infants with low birth weight. An accumulating number of independent studies have focused on ROP pathogenesis and have demonstrated that laser photocoagulation therapy and/or anti-VEGF treatment are effective. However, early diagnosis of ROP is still critical. At present, the main method of ROP screening is based on binocular indirect ophthalmoscopy. However, the judgment of whether ROP occurs and whether treatment is necessary depends largely on ophthalmologists with a great deal of experience. Therefore, it is essential to develop a simple, accurate and effective diagnostic method. This review describes recent findings on novel biomarkers for the prediction, diagnosis and prognosis of ROP patients. The novel biomarkers were separated into the following categories: metabolites, cytokines and growth factors, non-coding RNAs, iconography, gut microbiota, oxidative stress biomarkers, and others. Biomarkers with high sensitivity and specificity are urgently needed for the clinical applications of ROP. In addition, using non-invasive or minimally invasive methods to obtain samples is also important. Our review provides an overview of potential biomarkers of ROP.

20.
J Hazard Mater ; 425: 128056, 2022 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-34986576

RESUMO

Occurrences of odor compounds in drinking water reservoirs are considered as a nuisance by the water industry. Through the high-frequency monitoring of Tianmuhu Reservoir, a drinking water source for a city with a population of 700,000, we found that odor compounds seasonal dynamics were significantly related to phytoplankton succession, which was controlled by hydrometeorological process. 2-Methylisoborneol (2-MIB) was significantly related to Aphanizomenon sp. (r = 0.51). When the surface water temperature exceeded 12 â„ƒ, 2-MIB concentration may exceed the odor threshold concentration. With the proliferation of Aphanizomenon sp. in spring, 2-MIB concentration reached 87.22 ng/L. After late spring heavy rain, 2-MIB concentration sharply decreased to 3.19 ng/L. As the temperature increased at the end of the rainy season, Aphanizomenon sp. biomass increased to 2.09 mg/L, and 2-MIB concentration increased to 40.16 ng/L. These results showed that the concentration of odor compounds in shallow layer varied greatly because odor compounds mainly originated from phytoplankton and were susceptible to short-term hydrometeorological processes. However, the concentrations of odor compounds in deep layer were relatively insensitive to short-term weather processes. This study will improve the understanding of seasonal changes in odor compounds at different depths, and provide useful information for reservoir managers to prevent odor problems.


Assuntos
Água Potável , Biomassa , China , Odorantes/análise , Fitoplâncton , Estações do Ano
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