ABSTRACT
Blood-brain barrier (BBB) damage plays an important role in overall brain injury following acute ischemic stroke (AIS). We investigated the potential utility of serum occludin, a BBB damage biomarker, in predicting the severity of AIS, hemorrhagic transformation (HT) and patient prognosis. A total of 243 patients, suspected of suffering an AIS and admitted to the emergency room at Xuanwu Hospital between November 2018 to March 2019, were enrolled in this study. Serum occludin levels were measured by enzyme linked immunosorbent assay and clinical data were collected from each patient. Receiver operating characteristic curves (ROC) were used to analyze the relationship between serum occludin and AIS. Multiple logistic regression analysis was used to analyze the relationship between serum occludin and stroke prognosis. Serum occludin levels were significantly elevated in acute stroke cases compared with those with stroke-like symptoms (P<0.001). In the moderate and severe cerebral infarction (CI) groups, serum occludin levels were significantly higher than those in the mild CI group (P<0.001). Patients with HT had higher occludin levels than non-HT patients (P<0.05). In addition, serum occludin level of patients with poor prognosis was significantly higher than that of the patients with good prognosis for non-reperfusion therapy. The ROC curve showed that serum occludin could reasonably predict HT and poor prognosis. Moreover, serum occludin were independently associated with 90-day poor prognosis. These findings suggest that the serum occludin levels could be used to identify early acute stroke cases and may predict the severity of AIS and HT as well as the prognosis at 90 days.
ABSTRACT
Arsenic enhances the genotoxicity of other carcinogenic agents such as ultraviolet radiation and benzo[a]pyrene. Recent reports suggest that inhibition of DNA repair is an important aspect of arsenic cocarcinogenesis, and DNA repair proteins such as poly(ADP ribose) polymerase (PARP)-1 are direct molecular targets of arsenic. Although arsenic has been shown to generate reactive oxygen/nitrogen species (ROS/RNS), little is known about the role of arsenic-induced ROS/RNS in the mechanism underlying arsenic inhibition of DNA repair. We report herein that arsenite-generated ROS/RNS inhibits PARP-1 activity in cells. Cellular exposure to arsenite, as well as hydrogen peroxide and NONOate (nitric oxide donor), decreased PARP-1 zinc content, enzymatic activity, and PARP-1 DNA binding. Furthermore, the effects of arsenite on PARP-1 activity, DNA binding, and zinc content were partially reversed by the antioxidant ascorbic acid, catalase, and the NOS inhibitor, aminoguanidine. Most importantly, arsenite incubation with purified PARP-1 protein in vitro did not alter PARP-1 activity or DNA-binding ability, whereas hydrogen peroxide or NONOate retained PARP-1 inhibitory activity. These results strongly suggest that cellular generation of ROS/RNS plays an important role in arsenite inhibition of PARP-1 activity, leading to the loss of PARP-1 DNA-binding ability and enzymatic activity.
