Journal of International Translational Medicine最新文献_第10页

Diabetic Retinopathy Screening Programme: Attendance, Barriers and Enablers amongst Young People with Diabetes Mellitus Aged 12–26 Years 糖尿病视网膜病变筛检计划:12-26岁青少年糖尿病患者的出席率、障碍和促进因素

Journal of International Translational Medicine Pub Date : 2021-09-22 DOI: 10.3390/ijtm1030011

L. Cushley, K. Curran, Nicola B. Quinn, Aaron Bell, A. Muldrew, U. Graham, D. McCance, Qing Wen, T. Peto

{"title":"Diabetic Retinopathy Screening Programme: Attendance, Barriers and Enablers amongst Young People with Diabetes Mellitus Aged 12–26 Years","authors":"L. Cushley, K. Curran, Nicola B. Quinn, Aaron Bell, A. Muldrew, U. Graham, D. McCance, Qing Wen, T. Peto","doi":"10.3390/ijtm1030011","DOIUrl":"https://doi.org/10.3390/ijtm1030011","url":null,"abstract":"The study aim is to investigate characteristics, barriers and enablers for attendance at the Diabetic Eye Screening Programme Northern Ireland (DESPNI) among people with diabetes aged 12–26 years. A mixed-methods approach with retrospective analysis and prospective, questionnaire-based data collection was completed. Data were analysed using ordinal logistic regression. A questionnaire collected information on barriers and enablers to attending DESPNI. Age, diabetes duration, attendance at diabetes clinic and lower HbA1c values were significantly associated with better attendance. Those aged 12–15 were more likely to attend screening than 16–26 years, odds ratio (OR) 4.01. Subjects diagnosed less than 5 years were more likely to attend than those with longer diabetes duration (OR = 2.52, p =< 0.001). Subjects who attended diabetes clinics were more likely to attend screening (OR = 1.89, p =< 0.001) and have a lower HbA1c (OR = 1.46, p =< 0.001). Questionnaires revealed major barriers to attendance which included inconvenient appointment times, lack of access and poor communication. While many subjects were aware of the impact of diabetes on the eye, many had little understanding of screening. This study provides pivotal information on potential barriers and enablers for young people attending eye screening. We suggest modest changes such as convenient appointment times, clearer communication and one-stop clinics could improve attendance.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":"461 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82974992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Interleukin-6 Trans-Signaling Mediated Regulation of Paracellular Permeability in Human Retinal Endothelial Cells 白细胞介素-6反式信号介导的人视网膜内皮细胞旁通透性调控

Journal of International Translational Medicine Pub Date : 2021-09-16 DOI: 10.3390/ijtm1020010

J. Glass, Rebekah Robinson, T. Lee, Ashok Sharma, Shruti Sharma

{"title":"Interleukin-6 Trans-Signaling Mediated Regulation of Paracellular Permeability in Human Retinal Endothelial Cells","authors":"J. Glass, Rebekah Robinson, T. Lee, Ashok Sharma, Shruti Sharma","doi":"10.3390/ijtm1020010","DOIUrl":"https://doi.org/10.3390/ijtm1020010","url":null,"abstract":"Long-term hyperglycemia-mediated oxidative stress and inflammation lead to the blood-retinal barrier (BRB) dysfunction and increased vascular permeability associated with diabetic retinopathy (DR). Interleukin-6 (IL-6) is one of the primary mediators of retinal vascular inflammation. IL-6 signaling through its membrane-bound IL-6 receptor is known as classical signaling, and through a soluble IL-6 receptor (sIL-6R) is known as trans-signaling. Increasing evidence suggests that classical signaling is primarily anti-inflammatory, whereas trans-signaling induces the pro-inflammatory effects of IL-6. The purpose of this study was to compare the effects of these two pathways on paracellular permeability and expression of genes involved in inter-endothelial junctions in human retinal endothelial cells (HRECs). IL-6 trans-signaling activation caused significant disruption to paracellular integrity, with increased paracellular permeability, and was associated with significant changes in gene expression related to adherens, tight, and gap junctions. IL-6 classical signaling did not alter paracellular resistance in HRECs and had no distinct effects on gene expression. In conclusion, IL-6 trans-signaling, but not classical signaling, is a major mediator of the increased paracellular permeability characteristic of inner BRB breakdown in diabetic retinopathy. This study also identified potential inter-endothelial junction genes involved in the IL-6 trans-signaling mediated regulation of paracellular permeability in HRECs.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76368674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Crosstalk of Endothelial and Mesenchymal Stromal Cells under Tissue-Related O2 组织相关氧作用下内皮和间充质间质细胞的串扰

Journal of International Translational Medicine Pub Date : 2021-09-07 DOI: 10.3390/ijtm1020009

O. Zhidkova, E. Andreeva, M. Ezdakova, L. Buravkova

{"title":"Crosstalk of Endothelial and Mesenchymal Stromal Cells under Tissue-Related O2","authors":"O. Zhidkova, E. Andreeva, M. Ezdakova, L. Buravkova","doi":"10.3390/ijtm1020009","DOIUrl":"https://doi.org/10.3390/ijtm1020009","url":null,"abstract":"Mesenchymal stromal cells (MSCs) are considered a valuable tool for cell therapy. After systemic administration, the outcome of MSCs and endothelial cells (ECs) interactions strongly depend on the local microenvironment and tissue O2 levels in particular. In vitro analysis of EC effects on MSC regenerative potential in co-culture was performed after short-term interaction at “physiological” hypoxia (5% O2) and acute hypoxic stress (0.1% O2). At 5% O2, MSCs retained stromal phenotype and CFU-f numbers, osteogenic RUNX2 was upregulated. A shift in the expression of adhesion molecules, and an increase in transcription/synthesis of IL-6, IL-8 contributed to facilitation of directed migration of MSCs. In the presence of MSCs, manifestations of oxidative stress in ECs were attenuated, and a decrease in adhesion of PBMCs to TNF-α-activated ECs was observed. Under 0.1% O2, reciprocal effects of ECs and MSCs were similar to those at 5% O2. Meanwhile, upregulation of RUNX2 was canceled, IL-6 decreased, and IL-8 significantly increased. “Protective” effects of MSCs on TNF-α-ECs were less pronounced, manifested as NOS3 downregulation and intracellular NO elevation. Therefore, interaction with ECs at “physiological” hypoxia enhanced pro-regenerative capacities of MSCs including migration and anti-inflammatory modulation of ECs. Under acute hypoxic stress, the stimulating effects of ECs on MSCs and the “protective” potential of MSCs towards TNF-α-ECs were attenuated.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85848906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Regional Differences in Gene Expression of Proliferating Human Choroidal Endothelial Cells 增殖的人脉络膜内皮细胞基因表达的区域差异

Journal of International Translational Medicine Pub Date : 2021-09-01 DOI: 10.3390/IJTM1020007

A. Browning, E. Halligan, E. Stewart, Daniel Swan, S. Cockell, W. Amoaku

{"title":"Regional Differences in Gene Expression of Proliferating Human Choroidal Endothelial Cells","authors":"A. Browning, E. Halligan, E. Stewart, Daniel Swan, S. Cockell, W. Amoaku","doi":"10.3390/IJTM1020007","DOIUrl":"https://doi.org/10.3390/IJTM1020007","url":null,"abstract":"Choroidal diseases including inflammation and neovascularization seem to have predilection for different vascular beds. In order to improve our understanding of human macular choroidal angiogenic diseases, we investigate the differences in gene expression between matched human macular and peripheral inner choroidal endothelial cells (CEC) and matched human macular inner and outer CEC. The gene expression profiles of matched, unpassaged human macular and peripheral inner CEC and matched human unpassaged macular inner and outer CEC were conducted using Affymetrix GeneChip arrays. Selected differences in gene expression were validated by real-time-PCR and immunohistochemistry. No differences in probeset expression were demonstrated between inner CECs compared with peripheral inner CECs. In comparison, there was a difference of 1.6% of probesets when matched, unpassaged proliferating human macular inner CEC and macular outer CEC from the same donors were compared. Macular inner CECs demonstrated up-regulation of probesets involved in nervous system development, growth factors, PLVAP, and collagen XVI, while macular outer CECs demonstrated up-regulation of probesets involved in immune function and intracellular signalling. There was a marked homogeneity of human macular and peripheral inner CECs. This suggests that gene expression differences in inner CECs are not responsible for the site specific selectivity of choroidal neovascularisation. Variability was noted, however, in the gene expression of matched macular inner and outer CECs. This could be explained by the differences in the roles and microenvironments of the inner and outer choroid.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75297842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HGF and VEGF-A and Their Receptors Show Expression and Angiogenic Effects on Human Choroidal Endothelial Cells: Implications for Treatments of Neovascular Age-Related Macular Degeneration HGF和VEGF-A及其受体在人脉络膜内皮细胞中的表达和血管生成作用:对新生血管性年龄相关性黄斑变性治疗的意义

Journal of International Translational Medicine Pub Date : 2021-06-16 DOI: 10.3390/IJTM1010006

E. Stewart, C. Allen, Govindi J. Samaranayake, T. Stubington, Rukhsar Akhtar, M. J. Branch, W. Amoaku

{"title":"HGF and VEGF-A and Their Receptors Show Expression and Angiogenic Effects on Human Choroidal Endothelial Cells: Implications for Treatments of Neovascular Age-Related Macular Degeneration","authors":"E. Stewart, C. Allen, Govindi J. Samaranayake, T. Stubington, Rukhsar Akhtar, M. J. Branch, W. Amoaku","doi":"10.3390/IJTM1010006","DOIUrl":"https://doi.org/10.3390/IJTM1010006","url":null,"abstract":"Intraocular neovascularisation is associated with common blinding conditions including neovascular age-related macular degeneration (nAMD). Vascular endothelial growth factor (VEGF) is central in driving choroidal neovascularisation in this disease. Many clinical therapies target VEGF-A with intravitreal anti-VEGF drugs, which, however, have limited efficacy and require repeated, prolonged treatment. Other cytokines are known to be involved, including hepatocyte growth factor (HGF), which is shown to have a role in the early stages of nAMD. We investigated the effect of HGF and its co-operation with VEGF-A on human choroidal endothelial cells (CEC). The expression of HGF and related molecules in CEC was investigated using immunofluorescence, Western blotting and flow cytometry. In vitro assays for proliferation, tubule formation and migration were used to assess the potential role of HGF in neovascularisation. Primary human CEC expressed HGF, VEGF-A and their receptors MET and VEGF receptor 2 (VEGFR2). HGF increased CEC proliferation, tubule formation and migration; the increased proliferation and migration appeared to be additive with that achieved with VEGF-A. This study provides insight into growth factor co-operation in CEC signalling and indicates that simultaneous blockage of multiple growth factors or common downstream signalling pathways may provide a more sustained treatment response, enhancing treatments in nAMD.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72873950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Clusters, Assemblies and Aggregates of Tumor Cells in the Blood of Breast Cancer Patients; Composition, Mode of Action, Detection and Impact on Metastasis and Survival 乳腺癌患者血液中肿瘤细胞的聚集、聚集和聚集成分、作用方式、检测及对转移和生存的影响

Journal of International Translational Medicine Pub Date : 2021-06-04 DOI: 10.3390/IJTM1010005

U. Śmietanka, Malgorzata Szostakowska-Rodzos, S. Tabor, A. Fabisiewicz, Ewa A. Grzybowska

引用次数: 4

The Contribution of Endothelial-Mesenchymal Transition to Atherosclerosis 内皮-间质转化对动脉粥样硬化的贡献

Journal of International Translational Medicine Pub Date : 2021-05-31 DOI: 10.3390/IJTM1010004

Jinyu Zhang, S. C. Ogbu, P. Musich, D. Thewke, Zhiqiang Yao, Yongfa Jiang

{"title":"The Contribution of Endothelial-Mesenchymal Transition to Atherosclerosis","authors":"Jinyu Zhang, S. C. Ogbu, P. Musich, D. Thewke, Zhiqiang Yao, Yongfa Jiang","doi":"10.3390/IJTM1010004","DOIUrl":"https://doi.org/10.3390/IJTM1010004","url":null,"abstract":"Atherosclerosis is a chronic progressive condition in which the wall of the artery develops abnormalities and causes thickening of the blood vessels. The development of atherosclerosis is a complex process characterized by vascular inflammation and the growth of atherosclerotic plaques that eventually lead to compromised blood flow. The endothelial to mesenchymal transition (EndMT) is a phenomenon whereby endothelial cells lose their endothelial properties and acquire a mesenchymal phenotype similar to myofibroblast and smooth muscle cells. This process is considered a key contributor to the development and, importantly, the progression of atherosclerosis. Thus, therapeutically targeting the EndMT will provide a broad strategy to attenuate the development of atherosclerosis. Here, we review our current knowledge of EndMT in atherosclerosis including several key pathways such as hypoxia, TGF-β signaling, inflammation, and environmental factors during the development of atherosclerosis. In addition, we discuss several transgenic mouse models for studying atherosclerosis. Taken together, rapidly accelerating knowledge and continued studies promise further progress in preventing this common chronic disease.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76032846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Toll-Like Receptor Signalling Pathways Regulate Hypoxic Stress Induced Fibroblast Growth Factor but Not Vascular Endothelial Growth Factor-A in Human Microvascular Endothelial Cells toll样受体信号通路调节缺氧应激诱导的人微血管内皮细胞成纤维细胞生长因子而非血管内皮生长因子- a

Journal of International Translational Medicine Pub Date : 2021-05-27 DOI: 10.3390/IJTM1010003

Rukhsar Akhtar, Husain Tahir, E. Stewart, R. Wei, Imran Mohammed, W. Amoaku

{"title":"Toll-Like Receptor Signalling Pathways Regulate Hypoxic Stress Induced Fibroblast Growth Factor but Not Vascular Endothelial Growth Factor-A in Human Microvascular Endothelial Cells","authors":"Rukhsar Akhtar, Husain Tahir, E. Stewart, R. Wei, Imran Mohammed, W. Amoaku","doi":"10.3390/IJTM1010003","DOIUrl":"https://doi.org/10.3390/IJTM1010003","url":null,"abstract":"Retinal diseases are the leading causes of irreversible blindness worldwide. The role of toll-like receptor (TLR) signalling mechanisms (MyD88 and TRIF) in the production of pro-angiogenic growth factors from human microvascular endothelial cells (HMEC-1) under hypoxic stress remains unexplored. HMEC-1 was incubated under normoxic (5% CO2 at 37 °C) and hypoxic (1% O2, 5% CO2, and 94% N2; at 37 °C) conditions for 2, 6, 24, and 48 h, respectively. For TLR pathway analysis, HMEC-1 was pre-treated with pharmacological inhibitors (Pepinh-MyD88 and Pepinh-TRIF) and subjected to normoxia and hypoxia conditions. Gene and protein expressions of vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor (FGF-2), hypoxia inducible factor 1-alpha (HIF1-α) were performed using quantitative polymerase chain reaction (qPCR), ELISA, and Western blot methodologies. Levels of TLR3 and TLR4 were analysed by flow cytometry. Under hypoxia, levels of VEGF-A and FGF-2 were elevated in a time-dependent fashion. Inhibition of MyD88 and TRIF signalling pathways decreased FGF-2 levels but failed to modulate the secretion of VEGF-A from HMEC-1. Blocking a known regulator, endothelin receptor (ETR), also had no effect on VEGF-A secretion from HMEC-1. Overall, this study provides the proof-of-concept to target TLR signalling pathways for the management of blinding retinal diseases.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":"68 1","pages":"25-38"},"PeriodicalIF":0.0,"publicationDate":"2021-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73415060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Development of Multilayer Mesenchymal Stem Cell Cell Sheets 多层间充质干细胞细胞片的发育

Journal of International Translational Medicine Pub Date : 2021-05-24 DOI: 10.3390/IJTM1010002

J. Ochiai, Y. Niihara, J. Oliva

引用次数: 0

Heparin–Avastin Complexes Show Enhanced VEGF Binding and Inhibition of VEGF-Mediated Cell Migration 肝素-阿瓦斯汀复合物增强VEGF结合并抑制VEGF介导的细胞迁移

Journal of International Translational Medicine Pub Date : 2021-01-01 DOI: 10.3390/ijtm1020008

Divyabharathy Tsiros, Casey E. Sheehy, M. Nugent

{"title":"Heparin–Avastin Complexes Show Enhanced VEGF Binding and Inhibition of VEGF-Mediated Cell Migration","authors":"Divyabharathy Tsiros, Casey E. Sheehy, M. Nugent","doi":"10.3390/ijtm1020008","DOIUrl":"https://doi.org/10.3390/ijtm1020008","url":null,"abstract":"Bevacizumab (known by the tradename Avastin) is an antibody that binds VEGF and blocks its binding to VEGF receptors on endothelial cells, and is used to treat cancers and other diseases associated with excessive vascular growth. Our previous findings showed enhanced VEGF binding to Avastin in the presence of heparin, indicating that colocalizing heparin with Avastin could enhance VEGF inhibitory activity. Thus, the aim of the present study was to determine if conjugating Avastin and heparin to one another would lead to enhanced anti-VEGF activity. Avastin was conjugated to either biotin or streptavidin, and biotin–heparin was used to bring the two molecules into close proximity via biotin–streptavidin binding. Radioligand binding assays with 125 I-VEGF and cell migration assays using human umbilical vein endothelial cells were used to evaluate the impact of heparin on Avastin binding and activity. We found that bringing Avastin and heparin together, either on a surface or through streptavidin conjugation of Avastin, led to increased VEGF binding compared to that with each molecule alone. The heparin-mediated increase in VEGF binding was also noted at acidic pH where Avastin showed decreased VEGF binding. Conditions where Avastin and heparin showed enhanced VEGF binding also showed reduced VEGF-induced migration of human umbilical vein endothelial cells. These findings suggest design principles for a modified Avastin-based inhibitor of angiogenesis.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84438540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1