RESUMEN
Disruptions in polyamine metabolism have been identified as contributing factors to various central nervous system disorders. Our laboratory has previously highlighted the crucial role of polyamine oxidation in retinal disease models, specifically noting elevated levels of spermine oxidase (SMOX) in inner retinal neurons. Our prior research demonstrated that inhibiting SMOX with MDL 72527 protected against vascular injury and microglial activation induced by hyperoxia in the retina. However, the effects of SMOX inhibition on retinal neovascularization and vascular permeability, along with the underlying molecular mechanisms of vascular protection, remain incompletely understood. In this study, we utilized the oxygen-induced retinopathy (OIR) model to explore the impact of SMOX inhibition on retinal neovascularization, vascular permeability, and the molecular mechanisms underlying MDL 72527-mediated vasoprotection in the OIR retina. Our findings indicate that inhibiting SMOX with MDL 72527 mitigated vaso-obliteration and neovascularization in the OIR retina. Additionally, it reduced OIR-induced vascular permeability and Claudin-5 expression, suppressed acrolein-conjugated protein levels, and downregulated P38/ERK1/2/STAT3 signaling. Furthermore, our results revealed that treatment with BSA-Acrolein conjugates significantly decreased the viability of human retinal endothelial cells (HRECs) and activated P38 signaling. These observations contribute valuable insights into the potential therapeutic benefits of SMOX inhibition by MDL 72527 in ischemic retinopathy.
RESUMEN
The pandemic, well-known as COVID-19, has been caused by the coronavirus SARS-CoV-2 and it has distinct characteristics from other coronavirus-related epidemics. This pandemic has been ravaging the whole world for more than a year now, and no drugs or vaccines have been found to eliminate this virus from the infected people effectively; only physical measures like social distancing, hand washing and face-mask wearing have been taken to reduce its spread and very recently Veklury (remdesivir) has been permitted by the USFDA to manage the critical patients. This disease can be asymptomatic, but when it is symptomatic, it presents with respiratory problems and cold- or flu-like symptoms, which can be diagnosed with a chest CT and confirmed with RT-PCR tests. In this review, the taxonomy and structure of SARS-CoV-2 and history, transmission, epidemiology, pathology, clinical features and impacts of the COVID-19 have been discussed. A summary of possible drug targets, attempted physical and chemical measures, as well as vaccine candidates, has also been provided. How this coronavirus is different from other coronaviruses, the obstacles in managing this disease and the possibility of a second wave have also been reviewed. This review represents a wide range of information regarding COVID-19 and intends to be used as a comprehensive overview in this regard.
