miRNA-137-5p improves spatial memory and cognition in Alzheimer's mice by targeting ubiquitin-specific peptidase 30.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder causing progressive dementia. Research suggests that microRNAs (miRNAs) could serve as biomarkers and therapeutic targets for AD. Reduced levels of miR-137 have been observed in the brains of AD patients, but its specific role and downstream mechanisms remain unclear. This study sought to examine the therapeutic potential of miR-137-5p agomir in alleviating cognitive dysfunction induced in AD models and explore its potential mechanisms. METHODS: This study utilized bioinformatic analysis and a dual-luciferase reporter assay to investigate the relationship between miR-137-5p and ubiquitin-specific peptidase 30 (USP30). In vitro experiments were conducted using SH-SY5Y cells to assess the impact of miR-137-5p on Aß1-42 neurotoxicity. In vivo experiments on AD mice evaluated the effects of miR-137-5p on cognition, Aß1-42 deposition, Tau hyperphosphorylation, and neuronal apoptosis, as well as its influence on USP30 levels. RESULTS: It was discovered that miR-137-5p mimics efficiently counteract Aß1-42 neurotoxicity in SH-SY5Y cells, a protective effect that is negated by USP30 overexpression. In vivo experiments demonstrated that miR-137-5p enhances the cognition and mobility of AD mice, significantly reducing Aß1-42 deposition, Tau hyperphosphorylation, and neuronal apoptosis within the hippocampus and cortex regions. Mechanistically, miR-137-5p significantly suppresses USP30 levels in mice, though USP30 overexpression partially buffers against miR-137-5p-induced AD symptom improvement. CONCLUSION: Our study proposes that miR-137-5p, by instigating the downregulation of USP30, has the potential to act as a novel and promising therapeutic target for AD.

Ferrocene-reduced graphene oxide-polyoxometalates based ternary nanocomposites as electrochemical detection for acetaminophen.

Developing a convenient and accurate method for the determination of acetaminophen (APAP) content is very vital, and ferrocene (Fc) based nanocomposites coupled with polyoxometalates (POMs) as electrochemical sensor is a promising approach to address the issues. Herein, a new ternary nanocomposite of Fc based carbon nanomaterials (Fc-rGO) with PMo12 (Fc-rGO/PMo12, rGFP-n) was successfully fabricated, and the electrochemical activities and APAP detection of rGFP-n as electro-active materials were systematically investigated, and results of the differential pulse voltammetry (DPV) and electro-active surface area (0.0332 cm2) show that rGFP-1 is an excellent electrochemical sensor for APAP, and the proportion of Fc in rGFP-n can affect the charge transfer between APAP and rGFP. Under the optimal experimental conditions, rGFP-1 can be used to detect APAP with the limit of detection (LOD) of 13.27 nM (S/N = 3), the sensitivity of 36.81µA⋅µM-1cm-2, and the detection range from 1×10-6 to 1×10-3M, meeting the lowest plasma concentration of APAP (1.3 mM).

Synthesis of POMOFs with 8-fold helix and its composite with carboxyl functionalized SWCNTs for the voltammetric determination of dopamine.

Although many satisfactory studies have been developed for biomolecule detection, the complexity of biofluids still poses a major challenge to improve the performance of nanomaterials as electrochemical sensors. Herein, unprecedented polyoxometalate-based metal-organic frameworks (POMOFs) with 8-fold meso-helical feature, [Ag5(trz)4]2[PMo12O40] (PAZ), were synthesized and explored as electrochemical sensors to detect dopamine (DA). To improve the conductivity of PAZ and the binding ability with single-walled carbon nanotubes (SWCNTs), the nanocomposite of carboxyl functionalized SWCNTs (SWCNTs-COOH) with nano-PAZ (NPAZ), NPAZ@SWCNTs-COOH, was fabricated, and transmission electron microscopy (TEM) shows that NPAZ can interact stably and uniformly with SWCNTs-COOH, owing to more defect sites on the surface of SWCNTs-COOH. The electrochemical result of NPAZ@SWCNTs-COOH/GCE towards detecting DA shows that the linear range was from 0.05 to 100 µM with a detection limit (LOD) of 8.6 nM (S/N = 3). A new electrochemical biosensing platform by combining 8-fold helical POMOFs with SWCNTs-COOH was developed for enhancing detection of dopamine for the first time, exhibiting the lowest detection limit to date.

Implementation of regional Acute Stroke Care Map increases thrombolysis rates for acute ischaemic stroke in Chinese urban area in only 3 months.

BACKGROUND: The rate of intravenous thrombolysis for acute ischaemic stroke remains low in China. We investigated whether the implementation of a citywide Acute Stroke Care Map (ASCaM) is associated with an improvement of acute stroke care quality in a Chinese urban area. METHODS: The ASCaM comprises 10 improvement strategies and has been implemented through a network consisting of 20 tertiary hospitals. We identified 7827 patients with ischaemic stroke admitted from April to October 2017, and 506 patients underwent thrombolysis were finally included for analysis. RESULTS: Compared with 'pre-ASCaM period', we observed an increased rate of administration of tissue plasminogen activator within 4.5 hours (65.4% vs 54.5%; adjusted OR, 1.724; 95% CI 1.21 to 2.45; p=0.003) during 'ASCaM period'. In multivariate analysis models, 'ASCaM period' was associated with a significant reduction in onset-to-door time (114.1±55.7 vs 135.7±58.4 min, p=0.0002) and onset-to-needle time (ONT) (169.2±58.1 vs 195.6±59.3 min, p<0.0001). Yet no change was found in door-to-needle time. Clinical outcomes such as symptomatic intracranial haemorrhage, favourable functional outcome (modified Rankin Scale ≤2) and in-hospital mortality remained unchanged. CONCLUSION: The implementation of ASCaM was significantly associated with increased rates of intravenous thrombolysis and shorter ONT. The ASCaM may, in proof-of-principle, serve as a model to reduce treatment delay and increase thrombolysis rates in Chinese urban areas and possibly other highly populated Asian regions.

Elevation of high-sensitivity cardiac troponin T at admission is associated with increased 3-month mortality in acute ischemic stroke patients treated with thrombolysis.

BACKGROUND: Elevated levels of cardiac troponin T (cTnT) have been associated with unfavorable outcomes in cardiac patients. However, no studies, to date, have discussed the prognostic value of high-sensitivity cTnT (hs-cTnT) in thrombolyzed patients with acute ischemic stroke (AIS). HYPOTHESIS: We hypothesized that elevated levels of hs-cTnT would be associated with poorer clinical outcomes in AIS patients treated with intravenous tissue-type plasminogen activator (IV tPA). METHODS: From January 2017 to February 2018, a total of 241 AIS patients treated with IV tPA within 4.5 hours of onset were recruited. On admission, patients were stratified into either normal or elevated hs-cTnT groups according to a cutoff value of 14 ng/L. Multivariable logistic regression analyses were conducted to identify determinants of hs-cTnT elevation and to detect whether elevated hs-cTnT was associated with disability and/or mortality. RESULTS: In multivariable regression analysis, older age (P < .001) and stroke etiology (P = .024) were significantly associated with elevated hs-cTnT levels. After adjusting for demographic and clinical characteristics, hs-cTnT elevation was still significantly associated with 14-day major disability (modified Rankin Scale (mRS) 3-5, model 1, P = .019, odds ratio [OR] 2.677; model 2, P = .015, OR 2.834), 14-day composite unfavorable outcome (mRS 3-6, model 1, P = .005, OR 3.525; model 2, P = .003, OR 3.976), 30-day mortality (P = .049, OR 4.545) and 90-day mortality (P = .049, OR 3.835). CONCLUSIONS: Elevation of hs-cTnT at admission is associated with an increased risk of 90-day mortality in AIS patients treated with IV tPA.

The small molecular CCR3 antagonist YM344031 attenuates neurodegenerative pathologies and improves learning and memory performance in a mouse model of Alzheimer's disease.

The chemokine C-C receptor 3 (CCR3) plays a role in the pathogenesis of Alzheimer's disease (AD). Based on our previous observations that deletion of CCR3 prevented neurodegenerative pathologies in amyloid precursor protein/presenilin 1 (APP/PS1) double-transgenic mice, we hypothesize that CCR3 antagonists may provide therapeutic benefits to AD. To this end, we examined the effect of the brain-penetrable CCR3 antagonist, YM344031, on AD-related pathologies in APP/PS1 double transgenic mice. Treatment of 10-month-old APP/PS1 double-transgenic mice with YM344031 (50 mg/kg, b.i.d.) for two months resulted in dramatic decreases in ß-amyloid deposition, tau hyperphosphorylation and synaptic loss in the forebrain, significant attenuation of microgliosis and astrogliosis, and marked improvement of spatial learning and memory performance compared with the vehicle-treated mice. These results support CCR3 antagonism as a potential therapeutic strategy for AD.

The critical interaction between valproate sodium and warfarin: case report and review.

BACKGROUND: Valproic acid (VPA) and warfarin are commonly prescribed for patients with epilepsy and concomitant atrial fibrillation (AF). When VPA and warfarin are prescribed together, clinically important interactions may occur. VPA may replace warfarin from the protein binding sites and result in an abnormally increased anticoagulation effect. This is commonly underrecognized. CASE PRESENTATION: In our case, we report a 78-year-old woman with a glioma who presented with status epilepticus. The patient was on warfarin to prevent cardiogenic embolism secondary to AF. Intravenous loading dose of VPA was administered, but international normalized ratio (INR) increased significantly to 8.26. Intravenous vitamin K1 was then given and the patient developed no overt bleeding during the hospitalization. CONCLUSION: By reviewing the literature and discussing the critical interaction between valproate sodium and warfarin, we conclude that intravenous VPA and the co-administrated warfarin may develop critical but underrecognized complications due to effects on the function of hepatic enzymes and displacement of protein binding sites.