Background Diabetic retinopathy (DR) has become a worldwide concern because of the rising prevalence rate of diabetes mellitus (DM). Despite much energy has been committed to DR research, it remains a difficulty for diabetic patients all over the world. Since apoptosis of retinal microvascular pericytes (RMPs) is the early characteristic of DR, this study aimed to reveal the mechanism of Shuangdan Mingmu (SDMM) capsule, a Chinese patent medicine, on oxidative stress-induced apoptosis of pericytes implicated with poly (ADP-ribose) polymerase (PARP) / glyceraldehyde 3-phosphate dehydrogenase (GAPDH) pathway. Methods Network pharmacology approach was performed to predict biofunction of components of SDMM capsule dissolved in plasma on DR. Both PARP1 and GAPDH were found involved in the hub network of protein-protein interaction (PPI) of potential targets and were found to take part in many bioprocesses, including responding to the regulation of reactive oxygen species (ROS) metabolic process, apoptotic signaling pathway, and response to oxygen levels through enrichment analysis. Therefore, in vitro research was carried out to validate the prediction. Human RMPs cultured with media containing 0.5 mM hydrogen oxide (H2O2) for 4 h was performed as an oxidative-damage model. Different concentrations of SDMM capsule, PARP1 inhibitor, PARP1 activation, and GAPDH inhibitor were used to intervene the oxidative-damage model with N-Acetyl-L-cysteine (NAC) as a contrast. Flow cytometry was performed to determine the apoptosis rate of cells and the expression of ROS. Cell counting kit 8 (CCK8) was used to determine the activity of pericytes. Moreover, nitric oxide (NO) concentration of cells supernatant and expression of endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD), B cell lymphoma 2 (BCL2), vascular endothelial growth factor (VEGF), endothelin 1 (ET1), PARP1, and GAPDH were tested through RT-qPCR, western blot (WB), or immunocytochemistry (ICC). Results Overproduction of ROS, high apoptotic rate, and attenuated activity of pericytes were observed after cells were incubated with media containing 0.5 mM H2O2. Moreover, downregulation of SOD, NO, BCL2, and GAPDH, and upregulation of VEGFA, ET1, and PARP1 were discovered after cells were exposed to 0.5 mM H2O2 in this study, which could be improved by PARP1 inhibitor and SDMM capsule in a dose-dependent way, whereas worsened by PARP1 activation and GAPDH inhibitor. Conclusions SDMM capsule may attenuate oxidative stress-induced apoptosis of pericytes through downregulating PARP expression and upregulating GAPDH expression.

With the continuous enrichment of automobile functions and the complexity of automobile structure, the difficulty of automobile fault diagnosis is constantly increasing. The study of fault diagnosis methods with high real-time performance, accuracy, and predictability is of great significance to improve automobile safety performance and ensure driving safety. Since the convergence speed of the traditional BP neural network algorithm is slow and the accuracy is insufficient in the process of automobile engine fault diagnosis, this paper improves convergence speed of the algorithm by introducing the momentum term, and the weights and thresholds of the neural network are optimized by using GA selection, crossover, and genetic characteristics, to propose a genetic algorithm (GA) optimization BP neural network fault diagnosis method. The average absolute error of the traditional BP neural network algorithm is 0.5976, while the average absolute error of the improved BP neural network algorithm in this paper is 0.1027. The comparative simulation results show that the proposed improved algorithm is better than the traditional BP neural network algorithm in diagnosis precision, accuracy, and other key indicators.

Background Diabetic retinopathy (DR) is the main reason of visual impairment. Apigenin has anti-angiogenic effects in a variety of diseases. Our aim was to explore the role of apigenin in DR and the mechanism involved. Methods High glucose (HG) induced HRMEC to establish DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/AKT inhibitor LY294002. miR-140-5p, HDAC3 and PTEN were detected by qRT-PCR. Western blot measured HDAC3, PTEN and PI3K/AKT pathway related proteins expressions. Cell proliferation and migration were monitored by MTT, wound-healing assay and Transwell assay. Angiogenesis was detected by Tube formation assay. Results After HG treatment, miR-140-5p expression was repressed and miR-140-5p overexpression suppressed HG-induced HRMECs proliferation, migration and angiogenesis. Apigenin treatment significantly reversed the reduction in miR-140-5p level caused by HG treatment and repressed HG-induced HRMECs proliferation, migration and angiogenesis by elevating miR-140-5p. miR-140-5p targeted HDAC3, and overexpression of miR-140-5p could reverse the up-regulation of HDAC3 expression induced by HG treatment. HDAC3 could bind to the promoter region of PTEN and inhibit its expression, and then knocking down HDAC3 suppressed PI3K/AKT pathway via elevating PTEN level. In addition, apigenin inhibited angiogenesis in DR cell models by regulating miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Conclusions Apigenin inhibited angiogenesis of HG induced HRMECs by regulating miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Our study might provide new drugs and new targets for treating DR.

Background: Diabetic retinopathy (DR) is the main reason of visual impairment. Apigenin has anti-angiogenic effects in a variety of diseases. Our aim was to explore the role of apigenin in DR and the mechanism involved. Methods: High glucose (HG) induced HRMEC to establish DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/AKT inhibitor LY294002. miR-140-5p, HDAC3 and PTEN were detected by qRT-PCR. Western blot measured HDAC3, PTEN and PI3K/AKT pathway related proteins expressions. Cell proliferation and migration were monitored by MTT, wound-healing assay and Transwell assay. Angiogenesis was detected by Tube formation assay. Results: After HG treatment, miR-140-5p expression was repressed and miR-140-5p overexpression suppressed HG-induced HRMECs proliferation, migration and angiogenesis. Apigenin treatment significantly reversed the reduction in miR-140-5p level caused by HG treatment and repressed HG-induced HRMECs proliferation, migration and angiogenesis by elevating miR-140-5p. miR-140-5p targeted HDAC3, and overexpression of miR-140-5p could reverse the up-regulation of HDAC3 expression induced by HG treatment. HDAC3 could bind to the promoter region of PTEN and inhibit its expression, and then knocking down HDAC3 suppressed PI3K/AKT pathway via elevating PTEN level. In addition, apigenin inhibited angiogenesis in DR cell models by regulating miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Conclusions: Apigenin inhibited angiogenesis of HG induced HRMECs by regulating miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Our study might provide new drugs and new targets for treating DR.