Exploration of Risk Factors for Poor Prognosis of Non-Traumatic Non-Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a devastating neurological disease associated with high rates of mortality and disability. Aneurysms are the main cause of non-traumatic subarachnoid hemorrhages. However, non-traumatic non-aneurysmal subarachnoid hemorrhage (naSAH), another clinical type of SAH, has been poorly studied for its prognosis and risk factors. METHOD AND RESULT: We collected demographic and clinical variables for 126 naSAH and 89 aneurysmal subarachnoid hemorrhage (aSAH) patients, including age and gender; hospitalization days; hematological indicators; clinical score scales; past medical history; and personal history. We found that the monocytes in naSAH (0.50 ± 0.26) patients were lower than in aSAH patients (0.60 ± 0.27). The prevalence of diabetes in naSAH (30.2%) patients was higher than in aSAH (14.5%) patients. The naSAH patients were divided into good and poor outcome groups based on the modified Rankin Scale at the 90th day (90-day mRS) after discharge. A univariate analysis showed that there were significant differences in age, white blood cell count (WBC), monocyte count, D-dipolymer, neuron-specific enolase (NSE), random blood glucose (RBG), aspartate transaminase (AST), urea and free triiodothyronine (FT3) between the two groups. A logistic regression showed that aging and high level NSE were independent risk factors for a poor outcome. The predictive ability of age (area under curve (AUC) = 0.71) and NSE (AUC = 0.68) were analyzed by a receiver operating characteristic (ROC) curve. The results of the logistic regression suggested that age, D-dipolymer, NSE, RBG, urea and FT3 distinguished and predicted the prognosis of naSAH. The discriminant analysis of the above variables revealed that the discriminant accuracy was 80.20%. CONCLUSIONS: Compared with aSAHs, naSAHs are more likely to occur in patients with diabetes, and the level of monocytes is lower. Moreover, the prognosis of elderly patients with an naSAH is relatively poor, and the level of NSE in the course of the disease also reflects the prognosis. Multivariate comprehensive analysis is helpful to judge the prognosis of patients at a small cost.

Kaempferol Ameliorates Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Ferroptosis by Activating Nrf2/SLC7A11/GPX4 Axis.

Kaempferol has been shown to protect cells against cerebral ischemia/reperfusion injury through inhibition of apoptosis. In the present study, we sought to investigate whether ferroptosis is involved in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal injury and the effects of kaempferol on ferroptosis in OGD/R-treated neurons. Western blot, immunofluorescence, and transmission electron microscopy were used to analyze ferroptosis, whereas cell death was detected using lactate dehydrogenase (LDH) release. We found that OGD/R attenuated SLC7A11 and glutathione peroxidase 4 (GPX4) levels as well as decreased endogenous antioxidants including nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and superoxide dismutase (SOD) in neurons. Notably, OGD/R enhanced the accumulation of lipid peroxidation, leading to the induction of ferroptosis in neurons. However, kaempferol activated nuclear factor-E2-related factor 2 (Nrf2)/SLC7A11/GPX4 signaling, augmented antioxidant capacity, and suppressed the accumulation of lipid peroxidation in OGD/R-treated neurons. Furthermore, kaempferol significantly reversed OGD/R-induced ferroptosis. Nevertheless, inhibition of Nrf2 by ML385 blocked the protective effects of kaempferol on antioxidant capacity, lipid peroxidation, and ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be a significant cause of cell death associated with OGD/R. Kaempferol provides protection from OGD/R-induced ferroptosis partly by activating Nrf2/SLC7A11/GPX4 signaling pathway.

Titanium dioxide nanoparticle-induced dysfunction of cardiac hemodynamics is involved in cardiac inflammation in mice.

In the past two decades, titanium dioxide nanoparticles (TiO2 NPs) have been extensively used in medicine, food industry and other daily life, while their possible interactions with the their influence and human body on human health remain not well understood. Thus, the study was designed to examine whether long-term exposure to TiO2 NPs cause myocardial dysfunction which is involved in cardiac lesions and alter expression of genes and proteins involving inflammatory response in the mouse heart. The findings showed that intragastric feeding for nine consecutive months with TiO2 NPs resulted in titanium accumulation, infiltration of inflammatory cells and apoptosis of heart, reductions in net increases of body weight, cardiac indices of function (LV systolic pressure, maximal rate of pressure increase over time, maximal rate of pressure decrease over time and coronary flow), and increases in heart indices, cardiac indices of function (LV end-diastolic pressure and heart rate) in mice. TiO2 NPs also decreased ATP production in the hearts. Furthermore, TiO2 NPs increased expression of nuclear factor-κB, interleukin-lß and tumour necrosis factor-α, and reduced expression of anti-inflammatory cytokines including suppressor of cytokine signaling (SOCS) 1 and SOCS3 in the cardiac tissue. These results suggest that TiO2 NPs may modulate the cardiac function and expression of inflammatory cytokines. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2917-2927, 2016.