Association of Life's essential 8 score with the risk of all-cause mortality and cardio-cerebrovascular mortality in patients with stroke.

BACKGROUND: A higher Life's Essential 8 (LE8)-based cardiovascular health (CVH) has been reported to be associated with a lower risk of both all-cause mortality and cardio-cerebrovascular diseases (CCVDs) related mortality in adults in the United States. At the same time, multiple studies have shown a significant negative association of CVH with the risk of stroke and CCVDs. Since no research has investigated the applicability of the LE8 in stroke patients, this study aimed to explore the association of LE8 with all-cause mortality and cardio-cerebrovascular mortality in stroke patients. METHODS: Data of patients were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2007-2018 in this retrospective cohort study. Weighted univariate and multivariate COX regression analyses were utilized to investigate the associations of LE8 with all-cause mortality and cardio-cerebrovascular mortality. We further explored these relationships in subgroups of age, gender, body mass index (BMI), cancer, congestive heart failure (CHF), and coronary heart disease (CHD). The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among the eligible patients, 278 died from all-cause and 89 (8.38%) of them died due to CCVDs. After adjusting for covariates, patients with LE8 score ≥ 58.75 seemed to have both lower risk of all-cause mortality (HR = 0.46, 95%CI: 0.31-0.69) and cardio-cerebrovascular mortality (HR = 0.51, 95%CI: 0.26-0.98), comparing to those with LE8 score < 48.123. Higher LE8 scores were associated with lower risk of all-cause mortality in patients aged < 65 years old, without cancer, and whatever the gender, BMI, CHF or CHD conditions (all P < 0.05). The relationships between high LE8 scores and low cardio-cerebrovascular mortality risk were only found in age < 65 years old and non-cancer subgroups (all P < 0.05). CONCLUSION: A higher LE8 score was associated with lower risk of both all-cause mortality and cardio-cerebrovascular mortality in patients with stroke, which may provide some reference for risk management and prognosis improvement in stoke. However, more evidences are needed to verify this beneficial role of high LE8 score in stroke prognosis.

Smurf2-Mediated Ubiquitination of FOXO4 Regulates Oxygen-glucose Deprivation/Reperfusion-induced Pyroptosis of Cortical Neurons.

BACKGROUND: Smad ubiquitination regulatory factor 2 (Smurf2) has been observed to alleviate ischemia-reperfusion injury. This study sought to explore the molecular mechanism of Smurf2-mediated forkhead box O4 (FOXO4) ubiquitination in oxygen-glucose deprivation/ reperfusion (OGD/R)-induced pyroptosis of cortical neurons. METHODS: Human cortical neurons (HCN-2) were subjected to OGD/R to establish a cell model of cerebral stroke. Smurf2, FOXO4, and doublecortin domain containing 2 (DCDC2) expressions were determined by RT-qPCR and Western blot. LDH release, pyroptosis-related proteins NLRP3, GSDMD-N, and cleaved-caspase-3, as well as inflammatory factors IL-1ß and IL-18, were assessed by LDH assay kit, Western blot, and ELISA. The ubiquitination level of FOXO4 was determined by ubiquitination assay. The bindings of Smurf2 to FOXO4 and FOXO4 to DCDC2 were testified by Co-IP, ChIP, and dual-luciferase assays. Rescue experiments were designed to validate the role of FOXO4/DCDC2 in the pyroptosis of HCN-2 cells. RESULTS: Smurf2 was weakly expressed, while FOXO4 and DCDC2 were prominently expressed in OGD/R-treated HCN-2 cells. Smurf2 overexpression promoted LDH release, reduced NLRP3, GSDMD-N, and cleaved-caspase-3 proteins, and decreased IL-1ß and IL-18 concentrations. Sumrf2 improved the ubiquitination level of FOXO4 to downregulate its protein level. FOXO4 is bound to the DCDC2 promoter to facilitate its transcription. Overexpression of FOXO4 or DCDC2 reversed the inhibition of Smurf2 overexpression on pyroptosis of OGD/Rtreated HCN-2 cells. CONCLUSION: Smurf2 overexpression facilitated the ubiquitination of FOXO4 to reduce its protein level, thereby suppressing DCDC2 transcription and restricting OGD/R-induced pyroptosis of cortical neurons.

Multimodal neuroimaging with optically pumped magnetometers: A simultaneous MEG-EEG-fNIRS acquisition system.

Multimodal neuroimaging plays an important role in neuroscience research. Integrated noninvasive neuroimaging modalities, such as magnetoencephalography (MEG), electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS), allow neural activity and related physiological processes in the brain to be precisely and comprehensively depicted, providing an effective and advanced platform to study brain function. Noncryogenic optically pumped magnetometer (OPM) MEG has high signal power due to its on-scalp sensor layout and enables more flexible configurations than traditional commercial superconducting MEG. Here, we integrate OPM-MEG with EEG and fNIRS to develop a multimodal neuroimaging system that can simultaneously measure brain electrophysiology and hemodynamics. We conducted a series of experiments to demonstrate the feasibility and robustness of our MEG-EEG-fNIRS acquisition system. The complementary neural and physiological signals simultaneously collected by our multimodal imaging system provide opportunities for a wide range of potential applications in neurovascular coupling, wearable neuroimaging, hyperscanning and brain-computer interfaces.

Expression of miRNA-214 in the sera of elderly patients with acute myocardial infarction and its effect on cardiomyocyte apoptosis.

The aim of the present study was to investigate the expression of microRNA (miRNA/miR)-214 in the sera of elderly patients with acute myocardial infarction (AMI) and the mechanism of how its expression affects cardiomyocyte apoptosis in these patients. The expression levels of miRNA-214 in elderly patients with AMI, unstable angina (UA) and healthy elderly subjects were detected by reverse transcription-quantitative polymerase chain reaction, and the correlation between the relative expressions of sera miRNA-214 and myocardial enzymes in elderly patients with AMI was examined by Pearson's analysis. Human cardiomyocyte (HCM) cell lines with a high expression miRNA-214 were established. The apoptotic rates of the different groups of cells were detected by flow cytometry and TUNEL assay. The expression of miRNA-214 target genes in the different groups of cells was detected by western blot assay. The relative expression levels of sera miR-214 in elderly AMI patients, UA patients and healthy subjects (as determined by physical examination) were 15.79±4.66, 4.60±2.51 and 2.07±0.99, respectively. The differences between each group were statistically significant (P<0.05). The relative expression of sera miRNA-214 in elderly AMI patients was positively correlated with sera aspartate aminotransferase (r=0.361, P=0.0174), lactate dehydrogenase (r=0.425, P=0.0045), creatine kinase-MB (r=0.835, P<0.001) and cardiac troponin (r=0.770, P<0.001). When compared with normal HCMs, the expressions of p53-upregulated modulator of apoptosis (PUMA), phosphatase and tensin homolog (PTEN), B-cell lymphoma-2-associated X protein (Bax) and caspase 7 proteins was decreased in HCMs overexpressing miRNA-214 following H2O2 induction, and the rate of apoptosis decreased by 63.64, 21.95, 46.67 and 50.05%, respectively. miRNA-214 was highly expressed in the sera of elderly patients with AMI, which may inhibit myocardial cell apoptosis by inhibiting the expression of miR-214 target genes including PUMA, PTEN, Bax and caspase 7.

miRNA-30-3p improves myocardial ischemia via the PTEN/PI3K/AKT signaling pathway.

The aim of this study was to explain the effect and mechanisms of miRNA-30-3p in myocardial ischemia-induced cell apoptosis in vitro and in vivo studies. In the cell experiment, the H9C2 cells were divided into the normal control (NC), and the model, miRNA, and miRNA + phosphatidylinositol 3-kinase (PI3K) inhibitor groups. The cell survival rates of the different groups were measured with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay kit; the lactate dehydrogenase (LDH), malondialdehyde (MDA) content, and superoxidedimutase (SOD) activity in the bathing medium were assayed for the evaluation of myocardial cell injury. The cell apoptosis rate of different groups was measured with flow cytometry analysis. The relative protein expressions of different cell groups were evaluated by Western blot analysis. In the vivo study, the Sprague-Dawley rats were divided into four groups: the NC group, the model group, miRNA group, and the (miRNA + PI3K inhibitor) group. The pathological observations, cell apoptosis, LDH, SOD, MDA, and relative protein expressions were evaluated with hematoxylin and eosin, enzyme-linked immunosorbent assay, terminal deoxynucleotide transferase dUTP nick-end labeling or immunohistochemical methods. The results show that miRNA-30-3p had the effect of improving cell apoptosis induced by myocardial ischemia in vitro and in vivo studies by the regulation of the PTEN/PI3K/AKT pathway.