Palmitic acid-induced microRNA-143-5p expression promotes the epithelial-mesenchymal transition of retinal pigment epithelium via negatively regulating JDP2.

BACKGROUND: The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is the most crucial step in the etiopathogenesis of proliferative vitreoretinopathy. This study aimed to investigate the role of miR-143-5p in the EMT of RPE cells induced by palmitic acid (PA). METHODS: ARPE-19 cells were treated with PA to induce EMT, followed by E-cadherin and α-smooth muscle actin (α-SMA) expression and the microRNA expression profile analyses. Subsequently, miR-143-5p mimics/inhibitors, and plasmids expressing its predicted target gene c-JUN-dimerization protein 2 (JDP2), were transfected in ARPE-19 cells using lipofectamine 3000, and followed by PA treatment. Their impacts on EMT were explored using wound healing and Western blot assays. Additionally, miR-143-5p mimics and JDP2-expressing plasmid were co-transfected into ARPE-19 cells and treated with PA to explore whether PA induced EMT of ARPE-19 cells via the miR-143-5p/JDP2 axis. RESULTS: PA decreased E-cadherin expression and increased those of α-SMA and miR-143-5p. Inhibiting miR-143-5p suppressed the migration of ARPE-19 cells and altered the expressions of E-cadherin and α-SMA. However, additional PA treatment attenuated these alterations. JDP2 was a target of miR-143-5p. Overexpression of JDP2 inhibited the EMT of ARPE-19 cells, resulting in α-SMA downregulation and E-cadherin upregulation, which were reversed by additional PA treatment via inhibiting JDP2 expression. Overexpression of miR-143-5p reversed the effect of JDP2 on the EMT of ARPE-19 cells and additional PA treatment markedly enhanced the effect of miR-143-5p mimics. CONCLUSION: PA promotes EMT of ARPE-19 cells via regulating the miR-143-5p/JDP2 axis, and these findings provide significant insights into the potential targeting of this axis to treat proliferative vitreoretinopathy.

Sulfiredoxin-1 protects retinal ganglion cells from high glucose-induced oxidative stress and inflammatory injury by potentiating Nrf2 signaling via the Akt/GSK-3ß pathway.

Sulfiredoxin-1 (Srxn1) has been acknowledged as a remarkable pro-survival factor in the protection of cells against stress-induced damage. The persistent exposure of retinal ganglion cells (RGCs) to high glucose (HG) in diabetes induces cellular damage, which contributes to the onset of diabetic retinopathy, a severe complication of diabetes. So far, little is known about the role of Srxn1 in regulating HG-induced injury of RGCs. The goals of this work were to evaluate the possible relevance of Srxn1 in the modulation of HG-induced apoptosis, oxidative stress and inflammation of RGCs in vitro. Our data showed that HG exposure caused a marked decrease in Srxn1 expression in RGCs. The up-regulation of Srxn1 markedly decreased HG-evoked apoptosis, reactive oxygen species (ROS) generation and pro-inflammatory cytokine release in RGCs. On the contrary, the depletion of Srxn1 rendered RGCs more susceptible to HG-induced injury. Further data demonstrated that Srnx1 enhanced the activation of nuclear factor erythroid-2 (E2)-related factor 2 (Nrf2) signaling in HG-exposed RGCs associated with up-regulating the phosphorylation of Akt and glucogen synthase kinase-3ß (GSK-3ß). Notably, the inhibition of Akt abolished Srnx1-overexpression-mediated Nrf2 activation, while GSK-3ß inhibition reversed Srnx1-depletion-mediated inactivation of Nrf2. In addition, Nrf2 inhibition partially abrogated Srnx1-mediated protective effects against HG-induced injury of RGCs. In summary, these data demonstrate that the overexpression of Srxn1 protects RGCs from the HG-induced injury of RGCs by enhancing Nrf2 signaling via modulation of Akt/GSK-3ß axis. Our work highlights that the Srxn1-mediated Akt/GSK-3ß/Nrf2 axis may exert a possible role in regulating RGC injury of diabetic retinopathy.

Adaptive Resilient Event-Triggered Control Design of Autonomous Vehicles With an Iterative Single Critic Learning Framework.

This article investigates the adaptive resilient event-triggered control for rear-wheel-drive autonomous (RWDA) vehicles based on an iterative single critic learning framework, which can effectively balance the frequency/changes in adjusting the vehicle's control during the running process. According to the kinematic equation of RWDA vehicles and the desired trajectory, the tracking error system during the autonomous driving process is first built, where the denial-of-service (DoS) attacking signals are injected into the networked communication and transmission. Combining the event-triggered sampling mechanism and iterative single critic learning framework, a new event-triggered condition is developed for the adaptive resilient control algorithm, and the novel utility function design is considered for driving the autonomous vehicle, where the control input can be guaranteed into an applicable saturated bound. Finally, we apply the new adaptive resilient control scheme to a case of driving the RWDA vehicles, and the simulation results illustrate the effectiveness and practicality successfully.

Higher serum level of myoglobin could predict more severity and poor outcome for patients with sepsis.

BACKGROUND: There have been sporadic case reports published focusing on myoglobin and sepsis. However, there are no systematic studies evaluating the correlation between myoglobin level and sepsis. This study investigated the correlation between the serum myoglobin level and the severity of septic patients. Next, we assessed the predictive value of the serum myoglobin level for the prognosis of septic patients. METHODS: Seventy septic patients were included and subdivided into the following 3 groups: sepsis group, severe sepsis group, and septic shock group. We collected blood samples at 0, 6, 12, 18, and 24hours after admission. The serum levels of myoglobin, C-reactive protein, and procalcitonin were analyzed. We also evaluated the levels of malondialdehyde, which is a biomarker for oxidative stress. RESULTS: The data indicate that the myoglobin level increased gradually within 24hours after admission. The median myoglobin levels of the sepsis, severe sepsis, and septic shock groups were 635.7, 903.6, and 1094.8µg/L, respectively (P<.05). The elevated myoglobin level was positively correlated with Sequential Organ Failure Assessment score, C-reactive protein, and procalcitonin level in septic patients. The increased myoglobin level was also associated with the mortality of septic patients. The Kaplan-Meier survival curves indicated that patients with high myoglobin levels had an elevated mortality rate. Moreover, an elevated myoglobin level indicated more oxidative stress. CONCLUSIONS: The myoglobin level can be detected in the early stage of sepsis and may serve as a potential biomarker for evaluating sepsis severity and further prognosis.

Clinical evaluation of circulating microRNA-25 level change in sepsis and its potential relationship with oxidative stress.

OBJECTIVE: To investigated the circulating microRNA expression profile in sepsis and its clinical evaluation. METHODS: 70 patients with sepsis and 30 patients with SIRS were selected and their blood samples were collected. Using liquid bead array with 3 statistical analysis approaches analyzed the circulating microRNA expression profiles, for confirming the data of liquid bead array, qRT-PCR was performed. The prognostic value of the changed microRNA in sepsis was determined and compared with CRP and PCT by analyzing the receiver operating characteristic (ROC) curves. To reveal whether the selected microRNAs could predict the outcome of patients, 28 d survival rate were calculated using Kaplan-Meier curves. Furthermore, the level of malondialdehyde (MDA), activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in plasma were detected and the relationship with the changed microRNA was determined. RESULTS: By integrating data from liquid bead array, we ultimately identified 6 microRNAs that were consistently changed in both of 3 statistical analysis approaches, however, only the change of microRNA-25 was significant according to the qPCR's result. The area under ROC curve showed that the clinical accuracy of microRNA-25 for sepsis diagnosis was better than CRP and PCT (AUG=0.806, 0.676 and 0.726, P<0.05).The decrease in level of microRNA-25 was correlated with the severity of sepsis, SOFA score, CRP and PCT level, meanwhile, microRNA-25 level can be used for predicting the prognosis of patients, the patients with microRNA-25 level ≤0.492 had a lower 28 d survival rate. Moreover, Decreased microRNA-25 level was related to the level of oxidative stress indicators in sepsis patients. CONCLUSIONS: MicroRNA-25 can be used as a biomarker for the diagnosis and assessment of sepsis. Meanwhile, microRNA-25 level may be associated with oxidative stress in patients with sepsis, and it is expected to become a target for anti-oxidation therapy.