摘要
Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidative stress pathways,such as POLDIP2,resulting in excessive reactive oxygen species(ROS)pro-duction and increased expression of vascular cell adhesion molecule-1(VCAM-1),hypoxia-inducible factor 1α(HIF-1α),and vascular endothelial growth factor(VEGF),causing microvascular dysfunction.Dihydromyricetin(DMY)is a natural flavonoid small molecule antioxidant.However,it exhibits poor solubility in physiological environments,has a short half-life in vivo,and has low oral bioavailability.In this study,we present,for the first time,the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles(Fe-DMY NCPs),formed by combining DMY with low-toxicity iron ions.In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endo-thelial cells by high glucose,scavenge excess ROS,and improve pathological features of DR,such as retinal vascular leakage and neovascularization.Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H2O2 signaling pathway and downregulate vital vascular function indicators such as VCAM-1,HIF-1α,and VEGF.These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent,with the potential as a novel multimeric drug for DR therapy.
摘要
<p><b>OBJECTIVE</b>To investigate the expression and prognosis significance of receptor interacting protein 2 (RIP2) in diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>The expression of RIP2 in DLBCL GCB and non-GCB type was detected by immunohistochemistry, at same time the expressions of BCL-2 and C-MYC were detected. Then, the role of RIP2 in development of DLBCL was analyzed by related clinical and pathological parameters.</p><p><b>RESULTS</b>The expression of RIP2 was related with middle-high risk group by IPI score, the An Arbor stage III+IV and intranodal lesions, and the differences were statistically significant (P<0.05). Besides, the single factor survival analysis suggested that GCB-type DLBCL showed a higher survival rate than that in non-GCB type(P<0.05). Patients with RIP2showed a lower survival rate as compared with patients with PIP2(P<0.05), among which the patients receiving R-CHOP had a higher survival rate than that of those receiving CHOP (P<0.01). The expression of RIP2 in DLBCL cell lines was higher than that in peripheral mononuclear cells of normal subjects (P<0.01) and expressed differently in DLBCL of GCB and non-GCB type (P<0.01).</p><p><b>CONCLUSION</b>The expression of RIP2 may relate with the poor prognosis and specific subtype of DLBCL.</p>
摘要
<p><b>OBJECTIVE</b>To detect the expression of miRNA-296-5p in diffuse large B cell lymphoma (DLBCL) cells and study the proliferation, migration and apoptosis of DLBCL cells after interfering the expression of miRNA-296-5p.</p><p><b>METHODS</b>The expression of miRNA-296-5p in DLBCL cells line DB cells was detected by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The possible roles of miRNA-296-5p in the biological and behavioral properties of DLBCL-DB cells were explored by transfection of miRNA-296-5p inhibitor for miRNA-296-5p knockdown, and detected by using CCK-8 method, Transwell method and Annexin V-FITC/PI.</p><p><b>RESULTS</b>miRNA-296-5p was highly expressed in DLBCL-DB cells, and the inhibition of miRNA-296-5p could induce suppression of cell proliferation and migration, but the cell apoptosis was not changed significantly.</p><p><b>CONCLUSION</b>The high expression of miRNA-296-5p may relate with the occurence and development of DLBCL, which may be a new therapeutic target for DLBCL.</p>