Methylseleninic acid inhibits human glioma growth in vitro and in vivo by triggering ROS-dependent oxidative damage and apoptosis.

Selenium-containing agents showed novel anticancer activity by triggering pro-oxidative mechanism. Studies confirmed that methylseleninic acid (MeSe) displayed broad-spectrum anti-tumor activity against kinds of human cancers. However, the anticancer effects and mechanism of MeSe against human glioma growth have not been explored yet. Herein, the present study showed that MeSeA dose-dependently inhibited U251 and U87 human glioma cells growth in vitro. Flow cytometry analysis indicated that MeSe induced significant U251 cells apoptosis with a dose-dependent manner, followed by the activation of caspase-7, caspase-9 and caspase-3. Immunofluorescence staining revealed that MeSe time-dependently caused reactive oxide species (ROS) accumulation and subsequently resulted in oxidative damage, as convinced by the increased phosphorylation level of Ser428-ATR, Ser1981-ATM, Ser15-p53 and Ser139-histone. ROS inhibition by glutathione (GSH) effectively attenuated MeSe-induced ROS generation, oxidative damage, caspase-3 activation and cytotoxicity, indicating that ROS was an upstream factor involved in MeSe-mediated anticancer mechanism in glioma. Importantly, MeSe administration in nude mice significantly inhibited glioma growth in vivo by inducing apoptosis through triggering oxidative damage. Taken together, our findings validated the possibility that MeSe as a selenium-containing can act as potential tumor chemotherapy agent for therapy of human glioma.

Association Between Hypoperfusion Intensity Ratio and Postthrombectomy Malignant Brain Edema for Acute Ischemic Stroke.

BACKGROUND: Malignant brain edema (MBE) is a life-threatening complication that can occur after mechanical thrombectomy (MT) for acute ischemic stroke. The hypoperfusion intensity ratio (HIR) reflects the tissue-level perfusion status within the ischemic territory. This study investigated the association between HIR and MBE occurrence after MT in patients with anterior circulation large artery occlusion. METHODS: We conducted a retrospective cohort study of patients who received MT at a comprehensive stroke center from February 2020 to June 2022. Using computed tomography perfusion, the HIR was derived from the ratio of tissue volume with a time to maximum (Tmax) > 10 s to that with a Tmax > 6 s. We dichotomized patients based on the occurrence of MBE following MT. The primary outcome, assessed using a multivariable logistic regression model, was the MBE occurrence post MT. The secondary outcome focused on favorable outcomes, defined as achieving a modified Rankin Scale score of 0-2 at 90 days. RESULTS: Of the 603 included patients, 90 (14.9%) developed MBE after MT. The median HIR exhibited a significantly higher value in the MBE group compared with the non-MBE group (0.5 vs. 0.3; P < 0.001). Multivariable logistic regression analysis indicated that a higher HIR (adjusted odds ratio [aOR] 8.98; 95% confidence interval [CI] 2.85-28.25; P < 0.001), baseline large infarction (Alberta Stroke Program Early Computed Tomography Score < 6; aOR 1.77; 95% CI 1.04-3.01; P = 0.035), internal carotid artery occlusion (aOR 1.80; 95% CI 1.07-3.01; P = 0.028), and unsuccessful recanalization (aOR 8.45; 95% CI 4.75-15.03; P < 0.001) were independently associated with MBE post MT. Among those with successful recanalization, a higher HIR (P = 0.017) and baseline large infarction (P = 0.032) remained as predictors of MBE occurrence. Furthermore, a higher HIR (P = 0.001) and the occurrence of MBE (P < 0.001) both correlated with reduced odds of achieving favorable outcomes. CONCLUSIONS: The presence of a higher HIR on pretreatment perfusion imaging serves as a robust predictor for MBE occurrence after MT, irrespective of successful recanalization.

Migraine and risk of rheumatoid arthritis: A systematic review and meta-analysis of observational studies.

Background: Exposure to Migraine may be one of the risk factors for the onset of rheumatoid arthritis (RA), while the relationship between the two is debatable. In this study, the connection between migraine and the risk of RA was investigated using a systematic review and meta-analysis of the pertinent literature. Methods: Up to July 2022, the PubMed, EMBASE, Web of Science (WOS), and scopus databases were employed to search for observational studies on the risk of RA in migraineurs. The effect sizes were pooled using a random-effects model or a fixed-effects model. Results: Out of 2345 records, 5 studies (3 case and control studies and 2 cohort studies) were identified and included in the meta-analysis. According to a pooled analysis, migraine sufferers had a higher chance of developing RA (pooled adjusted effect estimate: 1.94, 95% confidence interval: 1.74-2.17; p < 0.01). Conclusions: Migraine can be legitimately regarded as a risk factor for RA since this study demonstrated a relationship between migraine and RA. This conclusion should be treated with caution due to low power and precision. Rigorous design and larger sample sizes of studies are needed to verify the findings.