Methylene Blue Reduces Retinal Cell Inflammation, Apoptosis, and Oxidative Stress in a Rat Model of Diabetic Retinopathy via Sirtuin 1 Activation.

Objective: Diabetic retinopathy (DR), characterized by neuronal damage in the retina, is primarily driven by oxidative stress resulting from diabetes (DM). This study investigated the potential effects of methylene blue (MB) on streptozotocin (STZ)-induced DR. Methods: A rat model of DR was established via STZ injection, while a cell model was created using high-glucose (HG) exposure of human retinal microvascular endothelial cells. Evaluation of oxidative stress markers, pro-inflammatory cytokines, and pro-apoptotic proteins was performed based on their expression profiles in human retinal microvascular endothelial cells. Results: MB treatment significantly upregulated the expression of sirtuin 1 (SIRT1), which was found to be downregulated in the retinal tissues of STZ-treated rats and HG-exposed human retinal microvascular endothelial cells, as determined by polymerase chain reaction (PCR). Furthermore, MB therapy effectively suppressed STZ-induced oxidative stress, inflammation, and cell death. Consistent with the in vivo findings, MB activated the expression of SIRT1, thereby protecting HG-treated human retinal microvascular endothelial cells against oxidative stress, inflammation, and apoptosis. Conclusion: These results support the conclusion that MB mitigates DR by activating SIRT1, leading to a reduction of inflammation, apoptosis, and oxidative stress.

[Methylene blue reduces IL-1ß levels by enhancing ERK1/2 and AKT phosphorylation to improve diabetic retinopathy in rats].

Objective To investigate the neuroprotective effect of methylene blue on diabetic retinopathy in rats. Methods Thirty SD rats were randomly divided into blank, control and experimental groups. The control and experimental groups were induced with diabetes by streptozotocin (STZ) intraperitoneal injection. After 6 weeks of successful modeling, the experimental group received intravitreal injection of methylene blue at a dose of [0.2 mg/(kg.d)], while the control group received an equal amount of dimethyl sulfoxide (DMSO) intravitreal injection, both continuously injected for 7 days. ELISA was used to detect the levels of retinal superoxide dismutase (SOD), 8-iso-prostaglandin F2alpha (iPF2α) and interleukin-1ß (IL-1ß) in rats. Western blot analysis was used to detect the expression of retinal extracellular signal-regulated kinase 1/2 phosphorylation (p-ERK1/2) and phosphorylated protein kinase B (p-AKT), and PAS staining was used to detect retinal morphological changes. Results Compared with the blank group rats, the retinal SOD activity in the control and experimental group rats was significantly reduced. iPF2α, IL-1ß and p-ERK1/2 level increased, while p-AKT level decreased. Compared with the control group, the SOD activity of the experimental group rats increased. iPF2α and IL-1ß level went down, while p-ERK1/2 and p-AKT level went up significantly. The overall thickness of the retinal layer and the number of retinal ganglion cells were significantly reduced. Conclusion Methylene blue improves diabetic retinopathy in rats by reducing retinal oxidative stress and enhancing ERK1/2 and AKT phosphorylation.

The Effects of Boundary Conditions and Friction on the Helical Buckling of Coiled Tubing in an Inclined Wellbore.

Analytical buckling models are important for down-hole operations to ensure the structural integrity of the drill string. A literature survey shows that most published analytical buckling models do not address the effects of inclination angle, boundary conditions or friction. The objective of this paper is to study the effects of boundary conditions, friction and angular inclination on the helical buckling of coiled tubing in an inclined wellbore. In this paper, a new theoretical model is established to describe the buckling behavior of coiled tubing. The buckling equations are derived by applying the principles of virtual work and minimum potential energy. The proper solution for the post-buckling configuration is determined based on geometric and natural boundary conditions. The effects of angular inclination and boundary conditions on the helical buckling of coiled tubing are considered. Many significant conclusions are obtained from this study. When the dimensionless length of the coiled tubing is greater than 40, the effects of the boundary conditions can be ignored. The critical load required for helical buckling increases as the angle of inclination and the friction coefficient increase. The post-buckling behavior of coiled tubing in different configurations and for different axial loads is determined using the proposed analytical method. Practical examples are provided that illustrate the influence of the angular inclination on the axial force. The rate of change of the axial force decreases with increasing angular inclination. Moreover, the total axial friction also decreases with an increasing inclination angle. These results will help researchers to better understand helical buckling in coiled tubing. Using this knowledge, measures can be taken to prevent buckling in coiled tubing during down-hole operations.