Eosinopenia is a predictive factor for the severity of acute ischemic stroke.

Previous data have revealed an association between eosinopenia and mortality of acute ischemic stroke. However, the relationship of eosinopenia with infarct volume, infection rate, and poor outcome of acute ischemic stroke is still unknown. The retrospective study included 421 patients (273 males, 65%; mean age, 68.0 ± 13.0 years) with first acute ischemic stroke who were hospitalized in the Second Affiliated Hospital of Soochow University, China, from January 2017 to February 2018. Laboratory data, neuroimaging results, and modified Rankin Scale scores were collected. Patients were divided into four groups according to their eosinophil percentage level (< 0.4%, 0.4-1.1%, 1.1-2.3%, ≥ 2.3%). Spearman's correlation analysis showed that the percentage of eosinophils was negatively correlated with infarct volume (rs = -0.514, P < 0.001). Receiver operating characteristic analysis demonstrated that eosinopenia predicted a large infarct volume more accurately than neutrophilia; the area under curve was 0.906 and 0.876, respectively; a large infarct was considered as that with a diameter larger than 3 cm and involving more than two major arterial blood supply areas. Logistic regression analysis revealed that eosinophil percentage was an independent risk factor for acute ischemic stroke (P = 0.002). Moreover, eosinophil percentage was significantly associated with large infarct volume, high infection rate (pulmonary and urinary tract infections), and poor outcome (modified Rankin Scale score > 3) after adjusting for potential confounding factors (P-trend < 0.001). These findings suggest that eosinopenia has the potential to predict the severity of acute ischemic stroke. This study was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University, China (approval number: K10) on November 10, 2015.

Aspirin down Regulates Hepcidin by Inhibiting NF-κB and IL6/JAK2/STAT3 Pathways in BV-2 Microglial Cells Treated with Lipopolysaccharide.

Aspirin down regulates transferrin receptor 1 (TfR1) and up regulates ferroportin 1 (Fpn1) and ferritin expression in BV-2 microglial cells treated without lipopolysaccharides (LPS), as well as down regulates hepcidin and interleukin 6 (IL-6) in cells treated with LPS. However, the relevant mechanisms are unknown. Here, we investigate the effects of aspirin on expression of hepcidin and iron regulatory protein 1 (IRP1), phosphorylation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and P65 (nuclear factor-κB), and the production of nitric oxide (NO) in BV-2 microglial cells treated with and without LPS. We demonstrated that aspirin inhibited hepcidin mRNA as well as NO production in cells treated with LPS, but not in cells without LPS, suppresses IL-6, JAK2, STAT3, and P65 (nuclear factor-κB) phosphorylation and has no effect on IRP1 in cells treated with or without LPS. These findings provide evidence that aspirin down regulates hepcidin by inhibiting IL6/JAK2/STAT3 and P65 (nuclear factor-κB) pathways in the cells under inflammatory conditions, and imply that an aspirin-induced reduction in TfR1 and an increase in ferritin are not associated with IRP1 and NO.

Effects of cilostazol on the progression and regression of symptomatic intracranial artery stenosis: it reduces the risk of ischemic stroke.

OBJECTIVE: To assess the efficacy and safety of cilostazol on the progression and regression of symptomatic intracranial artery stenosis. DATA RETRIVAL: We searched the main databases for eligible trials including Medline (from 1966 to June 2014), Embase (from 1980 to June 2014), Cochrane Library (Issue 6, 2014), Chinese National Knowledge Infrastructure (from 1995 to June 2014), Current Controlled Trials (http://controlled-trials.com), Clinical Trials.gov (http://clinicaltrials.gov), and Chinese Clinical Trial Registry (http://www.chictr.org). All studies regarding prevention and treatment of symptomatic intracranial arterial stenosis by cilostazol were collected. The Mesh or text keywords were the English words: "cilostazol, phosphodiesterase 3 inhibitor, atherosclerosis, and ischemic stroke." No restrictions were put on publications or publication language. SELECTION CRITERIA: Grade A or B randomized controlled trials were selected according to the quality of evaluation criteria from the Cochrane Collaboration, in which cilostazol and aspirin were used to evaluate the effects of cilostazol in the treatment of patients with symptomatic intracranial artery stenosis. The quality of study methodology was evaluated based on criteria described in Cochrane Reviewer's Handbook 5.0.1. RevMan 5.2 software was used for data analysis. MAIN OUTCOME MEASURES: Clinical efficacy and safety of cilostazol in stopping progression and promoting regression of symptomatic intracranial artery stenosis were measured by magnetic resonance angiography and transcranial Doppler. RESULTS: Two randomized controlled trials with a total of 203 patients were included in this study. The results showed that while cilostazol was associated with a significantly reduced progression of intracranial artery stenosis (OR = 0.21, 95%CI: 0.09-0.47, P < 0.01), it had no beneficial effect on symptom regression (OR = 1.42, 95%CI: 0.80-2.51, P = 0.24). During the follow-up period, although some adverse effects developed, including headache, gastrointestinal disturbance, and dizziness, incidences of bleeding were lower than in aspirin-treated patients. CONCLUSION: Cilostazol may prevent the progression of symptomatic intracranial artery stenosis, which could reduce the incidence of ischemic stroke.

TDP-43 interaction with the intracellular domain of amyloid precursor protein induces p53-associated apoptosis.

TAR DNA-binding protein 43 (TDP-43), an essential pathological protein in both amyotrophic later sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), is expressed abnormally in Alzheimer's disease (AD). However, whether and how TDP-43 contributes the pathogenesis of AD remains unknown. We have shown here a colocalization between TDP-43 and the intracellular domain of APP (AICD) in the nucleus. Coimmunoprecipitation analysis showed an interaction between TDP-43 and AICD. Overexpression of TDP-43 in COS7 cells enhanced the transactivation of AICD in an APP-Gal4 luciferase reporter system. Real-time PCR analysis showed that cotransfection of TDP-43 and AICD in HEK293 cells increased P53 mRNA levels compared to either TDP-43-transfected or AICD-transfected cells. Moreover, cotransfection of TDP-43 and AICD in either N2a or COS7 cells showed increased numbers of apoptotic cells compared to either TDP-43-transfected or AICD-transfected cells, indicating that TDP-43 enhances AICD-mediated apoptosis in N2a or COS7 cells. Thus, TDP-43 may play a role in AD pathology through interaction with AICD.