Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,h...Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.展开更多
AIM:To explore the influencing factors of diabetes type 2 patients with mild non-proliferative diabetic retinopathy(NPDR)in the Kailuan area of Tangshan,Hebei Province,China.METHODS:In this non-interventional,retrospe...AIM:To explore the influencing factors of diabetes type 2 patients with mild non-proliferative diabetic retinopathy(NPDR)in the Kailuan area of Tangshan,Hebei Province,China.METHODS:In this non-interventional,retrospective study,683 patients with type 2 diabetes were included in the Kailuan Diabetic Retinopathy Study involving participants with diabetes in the community-based longitudinal Kailuan Study.Based on the undilated ultrawide field(200°;UWF)images and partial dilated digital fundus images,the diabetic retinopathy(DR)of the surveyed population was graded.Interobserver agreement was estimated by using Cohen’s Kappa statistics.The main outcome indicators included gender,age,weight,height,body mass index,blood pressure,circumferences of neck,waist and hip,current smoking,levels of fasting plasma glucose(FPG),hypersensitive C-reactive protein,creatinine,and cholesterol,etc.According to different lesions’locations of patients with mild NPDR,logistic regression models were used to estimate the odds ratios(ORs)and their 95%Cls of each risk factor.RESULTS:The study group of 683 patients included 570 males and 113 females.The mean age of the patients was62.18±9.41 y.Compared with dilated fundus examinations,there was fair agreement with the level of DR identified on UWF images in 63.91%of eyes(k=0.369,95%CI,0.00-0.00).Detected by UWF images,there were 98 patients with mild NPDR having peripheral retinal lesions,35 patients with mild NPDR having posterior lesions,44 patients with mild NPDR whose lesions were detected both in and out the standard two fields area,and 336 patients with non obvious DR.Parameters that conferred a statistically significant increased risks for mild NPDR with having peripheral retinal lesions were neck circumstance(OR,1.124;95%CI,1.044-1.211),and with posterior lesions were FPG(OR,1.052;95%CI,1.007-1.099).CONCLUSION:UWF is an effectiveness means of DR screening.Moreover,it is necessary to evaluate peripheral diabetic retinal lesions which can help to estimate the severity of DR.The phenomenon that nonuniform and inhomogeneous distribution of DR lesions has been found.And the influencing factors in mild NPDR are differing by different lesions’locations.展开更多
文摘Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.
文摘AIM:To explore the influencing factors of diabetes type 2 patients with mild non-proliferative diabetic retinopathy(NPDR)in the Kailuan area of Tangshan,Hebei Province,China.METHODS:In this non-interventional,retrospective study,683 patients with type 2 diabetes were included in the Kailuan Diabetic Retinopathy Study involving participants with diabetes in the community-based longitudinal Kailuan Study.Based on the undilated ultrawide field(200°;UWF)images and partial dilated digital fundus images,the diabetic retinopathy(DR)of the surveyed population was graded.Interobserver agreement was estimated by using Cohen’s Kappa statistics.The main outcome indicators included gender,age,weight,height,body mass index,blood pressure,circumferences of neck,waist and hip,current smoking,levels of fasting plasma glucose(FPG),hypersensitive C-reactive protein,creatinine,and cholesterol,etc.According to different lesions’locations of patients with mild NPDR,logistic regression models were used to estimate the odds ratios(ORs)and their 95%Cls of each risk factor.RESULTS:The study group of 683 patients included 570 males and 113 females.The mean age of the patients was62.18±9.41 y.Compared with dilated fundus examinations,there was fair agreement with the level of DR identified on UWF images in 63.91%of eyes(k=0.369,95%CI,0.00-0.00).Detected by UWF images,there were 98 patients with mild NPDR having peripheral retinal lesions,35 patients with mild NPDR having posterior lesions,44 patients with mild NPDR whose lesions were detected both in and out the standard two fields area,and 336 patients with non obvious DR.Parameters that conferred a statistically significant increased risks for mild NPDR with having peripheral retinal lesions were neck circumstance(OR,1.124;95%CI,1.044-1.211),and with posterior lesions were FPG(OR,1.052;95%CI,1.007-1.099).CONCLUSION:UWF is an effectiveness means of DR screening.Moreover,it is necessary to evaluate peripheral diabetic retinal lesions which can help to estimate the severity of DR.The phenomenon that nonuniform and inhomogeneous distribution of DR lesions has been found.And the influencing factors in mild NPDR are differing by different lesions’locations.
