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Data from hippocampal slices that were directly exposed to AA, or from animals that received the acid by intracerebroventricular infusion, contribute to understanding its neuroprotective effect.Extracellular RNAs (exRNAs) are present in all biofluids and incorporate many types of RNAs including miRNA. To enhance their stability outside of the cell, exRNAs are bound within ribonucleoprotein complexes or packaged into extracellular vesicles (EVs). The blood-brain barrier (BBB) is a dynamic interface between the systemic circulation and the CNS and is responsible for maintaining a stable extracellular environment for CNS cells. The intent of this study was to determine if EVs and their contents are transferred from the peripheral circulation to the CNS under conditions of an impaired BBB. The BBB of mice was disrupted by unilateral intracarotid artery infusion with hyperosmolar mannitol solution. To validate barrier opening, the uptake clearance of [13C12]-sucrose in the left forebrain (i.e. the ipsilateral, mannitol injected hemisphere) was quantified and revealed a 14-fold increase in the mannitol perfused hemisphere compared to sham treated mice. EVs were isolated from the extracellular spaces of the left forebrain following gentle tissue lysis and differential ultracentrifugation. EVs were confirmed using nanotracking analysis, electron microscopy and western blotting. qRT-PCR showed that the erythrocyte-enriched miR-451a in brain tissue EVs increased with mannitol treatment by 24-fold. Small RNA sequencing performed on the EVs isolated from the sham and mannitol treated mice showed that miR-9-5p was the most abundant miRNA contained within the brain EVs. qRT-PCR analysis of plasma EVs did not produce a statistically significant difference in the expression of the CNS-enriched miR-9-5p or miR-9-3p, suggesting that transfer of CNS EVs to the peripheral circulation did not occur under the conditions of our experiment. We demonstrate that EVs containing miR-451a, a highly abundant miRNA present within erythrocytes and erythrocyte EVs, are enhanced in the CNS upon BBB disruption.RNA metabolism involves complex and regulated processes, some of which include transcription, intracellular transport, translation, and degradation. The involvement of RNA binding proteins in these processes remains mostly uncharacterized regarding brain functions, especially cognition. In this study, we report that knockdown of hnRNPM in the CA1 hippocampal region of the mouse brain leads to learning and memory impairment. This finding is further supported, by the reduction of pre- and post-synaptic protein levels synaptophysin and PSD95. Notably, loss of hnRNPM affects the physiological spine in vivo by impairing the morphology of the dendritic spines. Additionally, our study demonstrates that hnRNPM directly binds to the 3'UTR of synaptophysin and PSD95 mRNAs, resulting in the stabilization of these mRNAs. Together, these findings present novel insight into the regulatory role of hnRNPM in neuronal structure and function.
Current evidence suggests that Brugada syndrome (BrS), far from being a purely electrical condition, is associated with subtle mechanical abnormalities primarily affecting the right ventricle (RV). We aimed to characterize RV function in BrS and investigate the echocardiographic profile of patients with arrhythmic events, with a special focus on parameters of RV dyssynchrony using speckle-tracking echocardiography (STE).
An echocardiogram was performed in 71 BrS patients and 25 healthy controls. STE was performed to assess regional and global RV mechanics, including RV outflow tract shortening (RVOTS). RVOT contraction time was considered to calculate the modified RV mechanical dispersion (RVMD
). Arrhythmic events were prospectively evaluated in the BrS cohort.
Compared to controls, BrS patients showed subtle contractile abnormalities, including impaired RV longitudinal strain, higher RV index of myocardial performance (RIMP) and lower RVOTS. BrS patients also exhibited a greater contraction delay betssment of the arrhythmic risk in BrS.
To evaluate the performance of a single‑lead, 14-day continuous electrocardiogram (ECG) patch for the detection of arrhythmias compared to conventional 24-h monitoring.
This prospective clinical trial enrolled patients suspected of arrhythmias but not diagnosed by 12‑lead ECGs. Each patient underwent a 24-h Holter and 14-day ECG patch simultaneously. Seven types of arrhythmias were classified supraventricular tachycardia (SVT, repetitive atrial beats >4 beats), irregular SVT without P wave (>4 beats), AF/AFL (irregular SVT without P wave ≥30 s), pause ≥3 s, atrioventricular block (AVB; Mobitz type II, third-degree, two to one or high degree AVB), ventricular tachycardia (VT), and polymorphic VT.
A total of 158 patients were recruited (mean wear time12.3 ± 3.2 days). The overall arrhythmia detection rate was higher with 14-day ECG patches (59.5%) compared to 24-h Holter (19.0%, P < 0.001). Up to 87.2% of arrhythmias recorded with 14-day ECG patches were not associated with symptoms. The 14-day ECG patch was associated with higher detection rates compared to the 24-h Holter in patients with SVT (52.5% versus 15.8%, P < 0.001), irregular SVT without P wave (12.7% versus 4.4%, P = 0.002), AF/AFL (9.5% versus 3.8%, P = 0.042), and critical arrhythmias (pause ≥3 s, AVB, VT, polymorphic VT) (16.5% versus 2.5%, P < 0.001). The 14-day ECG patch detected more than 2 types of arrhythmias in 5.1% of patients. No serious adverse events in patients wearing the 14-day ECG patch were reported.
The 14-day ECG patch outperformed 24-h Holter to detect overall, asymptomatic, critical and multiple arrhythmias. It is safe and has the potential to identify individuals with hidden arrhythmias, especially those with critical arrhythmias.
The 14-day ECG patch outperformed 24-h Holter to detect overall, asymptomatic, critical and multiple arrhythmias. It is safe and has the potential to identify individuals with hidden arrhythmias, especially those with critical arrhythmias.
LV asymmetric remodeling (LVAR) is a feature commonly found in AS patients and it is presumed to be mainly related to the severity of valve stenosis. The aim of this study was to determine the associated factors and impact on left ventricular (LV) systolic function of LVAR in patients with mild and moderate aortic valve stenosis (AS).
Clinical, Doppler-echocardiographic and computed-tomographic data of 155 AS patients with preserved LV ejection fraction (≥50%) prospectively recruited in the PROGRESSA study (NCT01679431) were analyzed. LVAR was defined as a septal wall thickness ≥ 13 mm and a ratio of septal/posterior wall thickness > 1.5. LV global longitudinal strain (LV-GLS) was available in 129 patients. Plasma levels of N-terminal natriuretic B-type peptides (Nt-proBNP) were also measured.
Mean age was 63 ± 15 years (70% men). LVAR was present in 21% (n = 33) of patients. A series of nested multivariate analysis revealed that age was the only factor associated with LVAR (all p ≤ 0.03). Additionalk of major adverse events and death. These findings provide support for closer clinical and echocardiographic surveillance of patients harboring this adverse LV remodeling feature.
LVAR was found in ~20% of patients with mild or moderate AS and was not related to the degree of AS severity or concomitant comorbidities, but rather to older age. LVAR was significantly associated with reduced LV longitudinal systolic function, increased Nt-proBNP levels, and higher risk of major adverse events and death. These findings provide support for closer clinical and echocardiographic surveillance of patients harboring this adverse LV remodeling feature.Ibervillea sonorae (Cucurbitaceae) is a medicinal plant utilized in Northwest Mexico against Diabetes and cancer. This natural product is taken orally, its presentation is capsules containing the plant's dried and powdered caudices. CX5461 There is no regulation or standardized dosage that allows reproducibility of its pharmacological effects. Cucurbitacins are the main group of compounds found in I. sonorae and are known for their antiproliferative activity in cancer cells. Cucurbitacin IIb (CIIb), one of the compounds present in I. sonorae, has demonstrated in experimental models with HeLa cervical cancer cells an apoptotic and anti-tumoral activity. The objective of this study is to obtain and standardize two phytopreparations of I. sonorae based on their CIIb content, evaluate their antiproliferative activity in cancer cell lines, and compare the results with those obtained with CIIb; expecting to find phytopreparations with anti-cancer potential. APCI-IT-MSn is utilized for the identification of cucurbitacins, FT-ICR-MS/MS for the quantification of CIIb, and the MTT assay for the evaluation of the antiproliferative activity. The CIIb content was 0.67% for Fito-Ison-EtOH and 1.84% for Fito-Ison-EtOAc. In both phytopreparations, six cucurbitacins have been identified, and a seventh one not previously identified. Phytopreparations were more effective against HeLa, with IC50 of 30.0 and 18.6 µg/mL for Fito-Ison-EtOH and Fito-Ison-EtOAc, respectively. This effect is lower than observed on CIIb in HeLa (5.8 µg/mL). There are no significant differences (p > 0.05) in the antiproliferative activity between Fito-Ison-EtOAc and CIIb in A549, LS180, and MDA-MB-231 cells. Phytopreparations of I. sonorae have potential for the development of anti-cancer products.Oxandrolone (OXA) used in clinical practice, however, its misuse is frequent, including by adolescents pursuing an aesthetic goal. However, the impacts of noxious doses on the cardiovascular system remain unknown.
To investigate cardiac effects of OXA in low (LD) and high (HD) doses.
Male Wistar prepubescent rats were separated into 3 experimental groups control (CON), LD, and HD. Only the CON group received the carrier (carboxymethylcellulose, 0.5%), while the LD and HD groups received, respectively, 2.5 and 37.5mg/kg/day of OXA via gavage for 4weeks. The hemodynamic parameters (+dP/dtmax, -dP/dtmin, and Tau) and cardiac autonomic tonus were assessed. Hearts were retrieved for histological analyses and oxidative stress evaluation. Expression levels of calcium-handling proteins were measured by western blot.
The OXA treatment changed neither the cardiac contractility nor the cardiac autonomic tonus. However, cardiac hypertrophy, collagen deposition, and increased angiotensin-converting enzyme (ACE) expression were observed in a dose-dependent way. Also, the p-phospholamban (p-PLB)/PLB ratio was observed to decrease and increase, respectively, in the LD and HD groups; the sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a)/PLB ratio being higher in both groups. OXA increased SOD1 expression and decreased catalase expression only in the LD group, and protein oxidation was increased in HD.
Both doses of OXA could promote pathological cardiac remodeling, probably via increased ACE, and these effects were exacerbated in the HD treatment, but cardiac contractility was not affected regardless of the dose.
Both doses of OXA could promote pathological cardiac remodeling, probably via increased ACE, and these effects were exacerbated in the HD treatment, but cardiac contractility was not affected regardless of the dose.
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