首页 > 最新文献

Journal of International Translational Medicine最新文献

英文 中文
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
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
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.
该研究的目的是调查12-26岁糖尿病患者参加北爱尔兰糖尿病眼筛查项目(DESPNI)的特点、障碍和促进因素。采用回顾性分析和前瞻性、基于问卷的数据收集的混合方法。数据分析采用有序逻辑回归。一份问卷收集了参加DESPNI的障碍和促进因素的信息。年龄、糖尿病病程、糖尿病门诊就诊和较低的HbA1c值与较好的出勤率显著相关。12-15岁的人比16-26岁的人更有可能参加筛查,优势比(OR) 4.01。诊断时间少于5年的受试者比糖尿病病程较长的受试者更有可能参加治疗(OR = 2.52, p =< 0.001)。参加糖尿病诊所的受试者更有可能参加筛查(OR = 1.89, p =< 0.001),并且HbA1c较低(OR = 1.46, p =< 0.001)。问卷调查显示,就诊的主要障碍包括预约时间不方便、缺乏通道和沟通不畅。虽然许多受试者意识到糖尿病对眼睛的影响,但许多人对筛查知之甚少。这项研究为年轻人参加眼科筛查提供了潜在障碍和促进因素的关键信息。我们建议适当的改变,如方便的预约时间,更清晰的沟通和一站式诊所可以提高出勤率。
{"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
Pub Date : 2021-09-16 DOI: 10.3390/ijtm1020010
J. Glass, Rebekah Robinson, T. Lee, Ashok Sharma, Shruti Sharma
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.
长期高血糖介导的氧化应激和炎症导致血视网膜屏障(BRB)功能障碍和血管通透性增加,与糖尿病视网膜病变(DR)相关。白细胞介素-6 (IL-6)是视网膜血管炎症的主要介质之一。IL-6通过其膜结合IL-6受体的信号被称为经典信号,通过可溶性IL-6受体(sIL-6R)的信号被称为反式信号。越来越多的证据表明,经典信号主要是抗炎的,而反式信号则诱导IL-6的促炎作用。本研究的目的是比较这两种通路对人视网膜内皮细胞(HRECs)细胞旁通透性和内皮间连接相关基因表达的影响。IL-6反式信号激活对细胞旁完整性造成显著破坏,增加细胞旁通透性,并与粘附、紧密和间隙连接相关基因表达的显著变化相关。IL-6经典信号没有改变HRECs的细胞旁耐药,对基因表达也没有明显影响。总之,IL-6反式信号,而非经典信号,是糖尿病视网膜病变内BRB分解的细胞旁通透性增加特征的主要介质。本研究还发现了参与白细胞介素-6反式信号介导的HRECs细胞旁通透性调节的潜在内皮间连接基因。
{"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
Pub Date : 2021-09-07 DOI: 10.3390/ijtm1020009
O. Zhidkova, E. Andreeva, M. Ezdakova, L. Buravkova
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.
间充质基质细胞(MSCs)被认为是一种有价值的细胞治疗工具。在系统给药后,MSCs和内皮细胞(ECs)相互作用的结果强烈依赖于局部微环境和组织O2水平。在“生理”缺氧(5% O2)和急性缺氧应激(0.1% O2)短期相互作用后,体外分析EC对共培养MSC再生潜能的影响。在5% O2下,MSCs保留基质表型和CFU-f数量,成骨RUNX2上调。粘附分子表达的改变和IL-6、IL-8转录/合成的增加有助于促进间充质干细胞的定向迁移。在MSCs的存在下,内皮细胞的氧化应激表现减弱,PBMCs对TNF-α-活化的内皮细胞的粘附减少。在0.1% O2条件下,内皮细胞和间充质干细胞的相互作用与5% O2条件下相似。同时,RUNX2上调被取消,IL-6降低,IL-8显著升高。MSCs对TNF-α-ECs的“保护”作用不明显,表现为NOS3下调和细胞内NO升高。因此,在“生理性”缺氧条件下,与内皮细胞的相互作用增强了MSCs的促再生能力,包括内皮细胞的迁移和抗炎调节。急性缺氧应激下,ECs对MSCs的刺激作用和MSCs对TNF-α-ECs的“保护”潜力减弱。
{"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
Pub Date : 2021-09-01 DOI: 10.3390/IJTM1020007
A. Browning, E. Halligan, E. Stewart, Daniel Swan, S. Cockell, W. Amoaku
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.
脉络膜疾病包括炎症和新生血管似乎偏爱不同的血管床。为了提高我们对人类黄斑脉络膜血管生成性疾病的认识,我们研究了匹配的人类黄斑与外周内脉络膜内皮细胞(CEC)和匹配的人类黄斑内外内皮细胞(CEC)的基因表达差异。采用Affymetrix基因芯片对匹配的、未传代的人黄斑和外周内CEC以及匹配的人非传代黄斑内、外CEC进行基因表达谱分析。通过实时荧光定量pcr和免疫组织化学方法验证基因表达差异。与外周内cec相比,内cec之间的问题集表达没有差异。相比之下,当匹配时,来自同一供体的未传代增殖的人类黄斑内CEC和黄斑外CEC比较,差异为1.6%。黄斑内CECs表达与神经系统发育、生长因子、PLVAP和胶原XVI相关的基因表达上调,黄斑外CECs表达与免疫功能和细胞内信号传导相关的基因表达上调。人类黄斑和周围的内CECs有明显的同质性。这表明,内部CECs的基因表达差异不是脉络膜新生血管形成的位点特异性选择性的原因。然而,在匹配的黄斑内、外cec的基因表达中,存在可变性。这可以通过内外脉络膜的作用和微环境的差异来解释。
{"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
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
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.
眼内新生血管与常见致盲疾病相关,包括新生血管性年龄相关性黄斑变性(nAMD)。血管内皮生长因子(VEGF)是驱动脉络膜新生血管在本病的中心。许多临床治疗通过玻璃体内抗vegf药物靶向VEGF-A,然而,这些药物的疗效有限,需要反复、长时间的治疗。已知其他细胞因子也参与其中,包括肝细胞生长因子(HGF),它被证明在nAMD的早期阶段发挥作用。我们研究了HGF及其与VEGF-A的协同作用对人脉络膜内皮细胞(CEC)的影响。采用免疫荧光、Western blotting和流式细胞术检测HGF及相关分子在CEC中的表达。增殖、小管形成和迁移的体外实验被用来评估HGF在新生血管中的潜在作用。原代人CEC表达HGF、VEGF- a及其受体MET和VEGF受体2 (VEGFR2)。HGF促进CEC增殖、小管形成和迁移;增殖和迁移的增加似乎与VEGF-A实现的增加是相加的。该研究深入了解了生长因子在CEC信号传导中的合作,并表明同时阻断多种生长因子或常见的下游信号通路可能提供更持续的治疗反应,从而增强对nAMD的治疗。
{"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
Pub Date : 2021-06-04 DOI: 10.3390/IJTM1010005
U. Śmietanka, Malgorzata Szostakowska-Rodzos, S. Tabor, A. Fabisiewicz, Ewa A. Grzybowska
Circulating tumor cells (CTCs) are gaining momentum as a diagnostic tool and therapeutic target. CTC clusters are more metastatic, but harder to study and characterize, because they are rare and the methods of isolation are mostly focused on single CTCs. This review highlights the recent advances to our understanding of tumor cell clusters with the emphasis on their composition, origin, biology, methods of detection, and impact on metastasis and survival. New approaches to therapy, based on cluster characteristics are also described.
循环肿瘤细胞(CTCs)作为一种诊断工具和治疗靶点正获得越来越大的发展势头。CTC集群转移性更强,但由于其罕见且分离方法主要集中在单个CTC上,因此更难研究和表征。本文综述了肿瘤细胞簇的组成、起源、生物学、检测方法以及对转移和生存的影响等方面的最新进展。新的治疗方法,基于集群特征也被描述。
{"title":"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","authors":"U. Śmietanka, Malgorzata Szostakowska-Rodzos, S. Tabor, A. Fabisiewicz, Ewa A. Grzybowska","doi":"10.3390/IJTM1010005","DOIUrl":"https://doi.org/10.3390/IJTM1010005","url":null,"abstract":"Circulating tumor cells (CTCs) are gaining momentum as a diagnostic tool and therapeutic target. CTC clusters are more metastatic, but harder to study and characterize, because they are rare and the methods of isolation are mostly focused on single CTCs. This review highlights the recent advances to our understanding of tumor cell clusters with the emphasis on their composition, origin, biology, methods of detection, and impact on metastasis and survival. New approaches to therapy, based on cluster characteristics are also described.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73579313","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
The Contribution of Endothelial-Mesenchymal Transition to Atherosclerosis 内皮-间质转化对动脉粥样硬化的贡献
Pub Date : 2021-05-31 DOI: 10.3390/IJTM1010004
Jinyu Zhang, S. C. Ogbu, P. Musich, D. Thewke, Zhiqiang Yao, Yongfa Jiang
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.
动脉粥样硬化是一种慢性进行性疾病,其中动脉壁发生异常并导致血管增厚。动脉粥样硬化的发展是一个复杂的过程,其特征是血管炎症和动脉粥样硬化斑块的生长,最终导致血流受损。内皮细胞向间充质转化(EndMT)是内皮细胞失去其内皮特性并获得与肌成纤维细胞和平滑肌细胞相似的间充质表型的一种现象。这一过程被认为是动脉粥样硬化发生和发展的关键因素。因此,以治疗为目标的EndMT将提供一种广泛的策略来减轻动脉粥样硬化的发展。在这里,我们回顾了我们目前对动脉粥样硬化中EndMT的了解,包括动脉粥样硬化发展过程中的几个关键途径,如缺氧、TGF-β信号、炎症和环境因素。此外,我们还讨论了几种用于研究动脉粥样硬化的转基因小鼠模型。总之,快速增长的知识和持续的研究有望在预防这一常见慢性疾病方面取得进一步进展。
{"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
Pub Date : 2021-05-27 DOI: 10.3390/IJTM1010003
Rukhsar Akhtar, Husain Tahir, E. Stewart, R. Wei, Imran Mohammed, W. Amoaku
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.
视网膜疾病是全世界不可逆转失明的主要原因。低氧应激下,toll样受体(TLR)信号机制(MyD88和TRIF)在人微血管内皮细胞(HMEC-1)生成促血管生成生长因子中的作用尚不清楚。HMEC-1在常氧(5% CO2, 37℃)和低氧(1% O2, 5% CO2, 94% N2)条件下孵育;在37°C)条件下分别发酵2、6、24和48小时。为了进行TLR通路分析,我们使用药物抑制剂(Pepinh-MyD88和Pepinh-TRIF)对HMEC-1进行预处理,并在常氧和缺氧条件下进行处理。采用定量聚合酶链反应(qPCR)、ELISA和Western blot方法检测血管内皮生长因子-a (VEGF-A)、成纤维细胞生长因子(FGF-2)、缺氧诱导因子1-α (HIF1-α)的基因和蛋白表达。流式细胞术检测TLR3和TLR4的表达水平。在缺氧条件下,VEGF-A和FGF-2水平呈时间依赖性升高。抑制MyD88和TRIF信号通路可降低FGF-2水平,但不能调节HMEC-1分泌VEGF-A。阻断已知的调节因子内皮素受体(ETR)对HMEC-1的VEGF-A分泌也没有影响。总的来说,这项研究为治疗致盲性视网膜疾病提供了靶向TLR信号通路的概念验证。
{"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
Pub Date : 2021-05-24 DOI: 10.3390/IJTM1010002
J. Ochiai, Y. Niihara, J. Oliva
Cell and gene therapies have been developing dramatically over the past decade. To face and adapt to the development of these new therapies, the Food and Drug Administration (FDA) wrote and updated new guidelines from 2016 and keep updating them. Mesenchymal stem cells (MSCs) are the most used cells for treatment, far ahead from the induced pluripotent stem cells (iPSCs), based on registered clinical trials at clinicaltrials.gov. They are widely used because of their differentiation capacity and their anti-inflammatory properties, but some controversies still require clear answers. Additional studies are needed to determine the dosage, the number, and the route of injections (location and transplantation method), and if allogenic MSCs are safe compared to autologous MSC injection, including their long-term effect. In this review, we summarize the research our company is conducting with the adipose stromal cells in engineering cell sheets and their potential application.
在过去的十年里,细胞和基因疗法得到了巨大的发展。为了面对和适应这些新疗法的发展,美国食品和药物管理局(FDA)从2016年开始编写和更新新的指南,并不断更新。根据clinicaltrials.gov网站上注册的临床试验,间充质干细胞(MSCs)是治疗中使用最多的细胞,远远领先于诱导多能干细胞(iPSCs)。它们因其分化能力和抗炎作用而被广泛使用,但仍有一些争议需要明确的答案。需要进一步的研究来确定剂量、数量和注射途径(位置和移植方法),以及与自体间充质干细胞注射相比,同种异体间充质干细胞是否安全,包括它们的长期效果。本文就脂肪基质细胞在工程细胞片中的研究进展及其应用前景作一综述。
{"title":"Development of Multilayer Mesenchymal Stem Cell Cell Sheets","authors":"J. Ochiai, Y. Niihara, J. Oliva","doi":"10.3390/IJTM1010002","DOIUrl":"https://doi.org/10.3390/IJTM1010002","url":null,"abstract":"Cell and gene therapies have been developing dramatically over the past decade. To face and adapt to the development of these new therapies, the Food and Drug Administration (FDA) wrote and updated new guidelines from 2016 and keep updating them. Mesenchymal stem cells (MSCs) are the most used cells for treatment, far ahead from the induced pluripotent stem cells (iPSCs), based on registered clinical trials at clinicaltrials.gov. They are widely used because of their differentiation capacity and their anti-inflammatory properties, but some controversies still require clear answers. Additional studies are needed to determine the dosage, the number, and the route of injections (location and transplantation method), and if allogenic MSCs are safe compared to autologous MSC injection, including their long-term effect. In this review, we summarize the research our company is conducting with the adipose stromal cells in engineering cell sheets and their potential application.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81680293","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
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
Pub Date : 2021-01-01 DOI: 10.3390/ijtm1020008
Divyabharathy Tsiros, Casey E. Sheehy, M. Nugent
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.
贝伐单抗(以商品名Avastin闻名)是一种结合VEGF并阻断其与内皮细胞上VEGF受体结合的抗体,用于治疗与血管过度生长相关的癌症和其他疾病。我们之前的研究结果表明,在肝素存在的情况下,VEGF与阿瓦斯汀的结合增强,表明肝素与阿瓦斯汀共定位可以增强VEGF的抑制活性。因此,本研究的目的是确定阿瓦斯汀和肝素相互结合是否会导致抗vegf活性增强。阿瓦斯汀与生物素或链霉亲和素偶联,生物素-肝素通过生物素-链霉亲和素结合使这两个分子接近。采用125 I-VEGF放射配体结合试验和人脐静脉内皮细胞细胞迁移试验来评估肝素对阿瓦斯汀结合和活性的影响。我们发现,将阿瓦斯汀和肝素结合在一起,无论是在表面上还是通过阿瓦斯汀的链亲和素偶联,与单独使用每个分子相比,都会导致VEGF结合增加。在酸性pH下,肝素介导的VEGF结合增加也被注意到,阿瓦斯汀显示VEGF结合减少。在阿瓦斯汀和肝素显示VEGF结合增强的条件下,也显示VEGF诱导的人脐静脉内皮细胞迁移减少。这些发现提示了改良的阿瓦斯汀血管生成抑制剂的设计原则。
{"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
期刊
Journal of International Translational Medicine
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1