Background: Ischaemic stroke is a prevalent cause of mortality and morbidity worldwide. Despite several clinical trials, there is no effective treatment for motor and cognitive deficits induced by ...stroke, suggesting poorly understood pathology. Recent studies show a crucial role of microRNAs (miRNAs) in cellular adaptation to various stress conditions. MiRNAs can be trafficked in extracellular vesicles (EVs), providing a compelling mechanism for cell-to-cell communication. However, the effect of ischaemia on the release of EVs is largely unknown. This study was carried out to investigate whether vesicular miRNAs mediate cell-to-cell communication in ischaemic stroke. Methods: To screen for stroke-induced miRNA changes, small RNA sequencing was performed on brain tissue collected from healthy mice and after stroke surgery. Effects of cellular stress on the first stages of transcriptional regulation were obtained from nascent RNA sequencing (GRO-seq) performed on neurons exposed to glutamate. EVs were isolated by ultracentrifugation-based method from Neuro 2A (N2A) cell-conditioned medium from normal or ischaemia-related conditions. EV preparations were characterized by nanoparticle tracking analysis, electron microscopy and Western blot. RNAs from EVs and N2A cells were extracted, and miRNAs were analysed by qPCR. EVs were administered to microglial cells to analyse the effects of EVs on cytokine secretion. Results: The expression of miR-21-5p was upregulated in ischaemic brain tissue and N2A cells. Neuronal transcription of the miR-21 locus was increased after exposure to glutamate. N2A cell-derived EVs exhibited vesicular morphology and size distribution typical for exosomes, and EVs contained miR-21-5p. Administration of EVs from N2A cells altered microglial responses to lipopolysaccharide, suggesting immunomodulatory effects. Summary/Conclusion: Based on the current knowledge, we propose miR-21-5p as a promising candidate for further studies to investigate its functions in EVs and stroke-induced injury.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
232.
O3-01-08: APP processing in exosomes Hill, Andrew F; Sharples, Robyn; Vella, Laura J ...
Alzheimer's & dementia,
July 2008, Volume:
4, Issue:
4
Journal Article
Peer reviewed
Full text
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FZAB, GEOZS, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBJE, SBMB, UL, UM, UPUK
233.
Pontine hyperperfusion in sporadic hyperekplexia Vetrugno, Roberto; Mascalchi, Mario; Vella, Alessandra ...
Journal of neurology, neurosurgery and psychiatry,
09/2007, Volume:
78, Issue:
9
Journal Article
Peer reviewed
Open access
Objective: To explore with neuroimaging techniques the anatomical and functional correlates of sporadic hyperekplexia. Methods: Two elderly women with sporadic hyperekplexia underwent ...neurophysiological assessment, MRI of the brain and proton magnetic resonance spectroscopy (1H-MRS) of the brainstem and frontal lobes. Regional cerebral blood flow was investigated with single photon emission tomography (SPECT) during evoked startles and at rest. Results: Both patients showed excessively large and non-habituating startle responses. In both patients, MRI showed impingement of the brainstem by the vertebrobasilar artery, lack of frontal or brainstem abnormalities on 1H-MRS and hyperperfusion in the dorsal pons and cingulate cortex, and superior frontal gyrus at SPECT during evoked startles. Conclusions: In our patients with hyperekplexia, the vertebrobasilar arteries were found to impinge on the brainstem. Neurophysiological findings and neurofunctional imaging of evoked startles indicated a pontine origin of the movement disorder modulated by activation in cortical, especially frontal, areas. The neurofunctional correlates of evoked startles in human sporadic hyperekplexia are similar to those observed for the startle circuit in animals.
Penyakit Tidak Menular (PTM) adalah penyebab utama kematian di Indonesia, termasuk hipertensi, jantung, diabetes, stroke, dan kanker, dengan 73% kematian disebabkan oleh PTM. Faktor risiko PTM antara ...lain kurangnya aktivitas fisik, merokok, dan pola makan yang tidak sehat. Prevalensi PTM di Indonesia beragam, seperti hipertensi (25,8%) dan diabetes mellitus (8,5%). Di Daerah Istimewa Yogyakarta, terdapat estimasi 251.100 kasus hipertensi dan 83.568 kasus diabetes mellitus. Survei di Dukuh Wonosari menunjukkan sejumlah warga menderita hipertensi, diabetes melitus, kolesterol tinggi, obesitas, dan memerlukan rujukan ke fasilitas kesehatan. Penelitian ini bertujuan untuk mengukur tingkat pengetahuan masyarakat tentang penyakit tidak menular. Metode dalam penelitian ini menggunakan deskriptif observasional dengan pendekatan cross sectional berdasarkan tahapan community diagnosis. Sampel yang digunakan sebanyak 29 orang di Dukuh Wonosari, Kelurahan Bangunkerto, Kepanewon Turi, Kabupaten Sleman. Teknik pengambilan data melalui pengisian kuesioner pre-test dan post-test. Hasil kuesioner dikomparasikan dan diuji menggunakan Paired T Test. Hasil penelitian menujukkan bahwa nilai rata-rata pre-test sebesar 59,3 menjadi rata-rata post-test sebesar 68,62. Sehingga, keberhasilan dalam pengabdian masyarakat ini ditunjukkan melalui hasil kuesioner serta kesesuaian materi penyuluhan terhadap masalah yang sedang dihadapi masyarakat. Peran masyarakat Dukuh Wonosari sangat penting sebagai pelaksana screening, edukator, dan konselor.
IntroductionCombination therapy with BRAF and MEK inhibition is currently in clinical development for the treatment of BRAF mutated malignant melanoma. BRAF inhibitors are associated with enhanced ...antigen-specific T-lymphocyte recognition in vivo. Consequently BRAF inhibition has been proposed as pro-immunogenic and there has been considerable enthusiasm for combining BRAF inhibition with immunotherapy. MEK inhibitors inhibit ERK phosphorylation regardless of BRAF mutational status and have been reported to impair T-lymphocyte and dendritic cell function. In this study we investigate the effects on isolated T-lymphocytes and monocyte-derived dendritic cells (moDCs) of a MEK and BRAF inhibitor combination currently being evaluated in a randomized controlled clinical trial.Experimental designThe effects of a BRAF inhibitor and a MEK inhibitor, alone and in combination were studied on isolated normal T-lymphocyte and moDCs. Lymphocyte viability, together with functional assays including proliferation, cytokine production and antigen-specific expansion, were assessed. moDC phenotype in response to lipo-polysaccharide stimulation was evaluated by flow-cytometry, as were effects on antigen crosspresentation.ResultsBRAF inhibition did not have an impact on T-lymphocytes or moDCs, whereas MEK inhibition alone or in combination with BRAF inhibition suppressed T-lymphocyte proliferation, cytokine production and antigen-specific expansion. Similarly, moDC cross-presentation was suppressed in association with enhanced maturation following combined inhibition of MEK and BRAF. However no significant decrease in CD4+ or CD8+ T-lymphocyte viability was observed following kinase inhibition.ConclusionsMEK inhibition, alone or in combination with BRAF inhibition can suppress immune cell function and further studies in vivo will be required to evaluate the potential clinical impact of these findings.
Harlequin ichthyosis: a case study Murphy-Brown, Laura; Vella, Judith A; Lawlor-Klean, Phylls
Neonatal network,
05/2004, Volume:
23, Issue:
3
Journal Article
Peer reviewed
The most severe manifestation of congenital ichthyosis presents itself in the form known as harlequin ichthyosis. Harlequin ichthyosis is characterized by a profound thickening of the fetal skin. ...Affected infants are born with a thick "horny shell" of dense, waxy, platelike scales with deep, irregular fissures covering the body. Contraction of the extremities is seen, along with deformities of the ears, eyes, mouth, and digits. This "armor" limits movement and compromises the skin's barrier defense, leaving the newborn at risk for metabolic abnormalities and infection. A case study of our unit's experience is provided.
Limited data suggest that multiple sclerosis (MS) in Latin America (LA) could be less severe than in the rest of the world. The objective was to compare the course of MS between LA and other regions.
...Methods
Centers from 18 countries with >20 cases enrolled in the MSBase Registry participated. Patients with MS with a disease duration of >1 year and <30 years at time of EDSS measurement were evaluated. The MS Severity Score (MSSS) was used as a measure of disease progression. Comparisons among regions (North America, Europe, Australia and LA), hemispheres and countries were performed.
Results
A total of 9610 patients were included. Patients were from: Europe, 6290 (65.6%); North America, 1609 (16.7%); Australia, 1119 (11.6%); and LA, 592 (6.1%). The mean MSSS in patients from LA was 4.47 ± 2.8, 4.53 ± 2.8 in North America, 4.51 ± 2.8 in Europe and 4.49 ± 2.7 in Australia. Mean MSSS in the northern hemisphere was 4.51 ± 1.6 compared to 4.48 ± 1.9 in the southern hemisphere. No differences were found for MSSS among hemispheres (p = 0.68), regions (p = 0.96) or countries (p = 0.50).
Conclusions
Our analyses did not discover any difference in mean MSSS among patients from different regions, hemispheres or countries.
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