43 research outputs found
Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity
Background: T-cell tolerance of allergic cutaneous contact
sensitivity (CS) induced in mice by high doses of reactive hapten
is mediated by suppressor cells that release antigen-specific
suppressive nanovesicles.
Objective: We sought to determine the mechanism or
mechanisms of immune suppression mediated by the
nanovesicles.
Methods: T-cell tolerance was induced by means of intravenous
injection of hapten conjugated to self-antigens of syngeneic
erythrocytes and subsequent contact immunization with the same
hapten. Lymph node and spleen cells from tolerized or control
donors were harvested and cultured to produce a supernatant
containing suppressive nanovesicles that were isolated from the
tolerized mice for testing in active and adoptive cell-transfer
models of CS.
Results: Tolerance was shown due to exosome-like nanovesicles
in the supernatants of CD81 suppressor T cells that were not
regulatory T cells. Antigen specificity of the suppressive
nanovesicles was conferred by a surface coat of antibody light
chains or possibly whole antibody, allowing targeted delivery of
selected inhibitory microRNA (miRNA)–150 to CS effector T
cells. Nanovesicles also inhibited CS in actively sensitized mice
after systemic injection at the peak of the responses. The role of
antibody and miRNA-150 was established by tolerizing either
panimmunoglobulin-deficient JH2/2 or miRNA-1502/2 mice
that produced nonsuppressive nanovesicles. These nanovesicles
could be made suppressive by adding antigen-specific antibody
light chains or miRNA-150, respectively.
Conclusions: This is the first example of T-cell regulation
through systemic transit of exosome-like nanovesicles delivering
a chosen inhibitory miRNA to target effector T cells in an
antigen-specific manner by a surface coating of antibody light
chains
The impact of formative testing on study behaviour and study performance of (bio)medical students: a smartphone application intervention study.
BACKGROUND: Formative testing can increase knowledge retention but students often underuse available opportunities. Applying modern technology to make the formative tests more attractive for students could enhance the implementation of formative testing as a learning tool. This study aimed to determine whether formative testing using an internet-based application ("app") can positively affect study behaviour as well as study performance of (bio)medical students. METHODS: A formative testing app "Physiomics, to the next level" was introduced during a 4-week course to a large cohort (n = 461) of Dutch first year (bio)medical students of the Radboud University. The app invited students to complete 7 formative tests throughout the course. Each module was available for 3-4 days to stimulate the students to distribute their study activities throughout the 4-week course. RESULTS: 72% of the students used the app during the course. Study time significantly increased in intensive users (p < 0.001), while no changes were observed in moderate (p = 0.07) and non-users (p = 0.25). App-users obtained significantly higher grades during the final exam of the course (p < 0.05). Non-users more frequently failed their final exam (34%, OR 3.6, 95% CI: 2.0-6.4) compared to moderate users (19%) and intensive users (12%). Students with an average grade <6.5 during previous courses benefitted most from the app, as intensive (5.8 ± 0.9 / 36%) and moderate users (5.8 ± 0.9 / 33%) obtained higher grades and failed their exam less frequently compared to non-users (5.2 ± 1.1 / 61%). The app was also well appreciated by students; students scored the app with a grade of 7.3 ± 1.0 out of 10 and 59% of the students indicated that they would like the app to be implemented in future courses. CONCLUSIONS: A smartphone-based application of formative testing is an effective and attractive intervention to stimulate study behaviour and improve study performance in (bio) medical students
Effects of typical and atypical antipsychotic drugs on gene expression profiles in the liver of schizophrenia subjects
<p>Abstract</p> <p>Background</p> <p>Although much progress has been made on antipsychotic drug development, precise mechanisms behind the action of typical and atypical antipsychotics are poorly understood.</p> <p>Methods</p> <p>We performed genome-wide expression profiling to study effects of typical antipsychotics and atypical antipsychotics in the postmortem liver of schizophrenia patients using microarrays (Affymetrix U133 plus2.0). We classified the subjects into typical antipsychotics (n = 24) or atypical antipsychotics (n = 26) based on their medication history, and compared gene expression profiles with unaffected controls (n = 34). We further analyzed individual antipsychotic effects on gene expression by sub-classifying the subjects into four major antipsychotic groups including haloperidol, phenothiazines, olanzapine and risperidone.</p> <p>Results</p> <p>Typical antipsychotics affected genes associated with nuclear protein, stress responses and phosphorylation, whereas atypical antipsychotics affected genes associated with golgi/endoplasmic reticulum and cytoplasm transport. Comparison between typical antipsychotics and atypical antipsychotics further identified genes associated with lipid metabolism and mitochondrial function. Analyses on individual antipsychotics revealed a set of genes (151 transcripts, FDR adjusted p < 0.05) that are differentially regulated by four antipsychotics, particularly by phenothiazines, in the liver of schizophrenia patients.</p> <p>Conclusion</p> <p>Typical antipsychotics and atypical antipsychotics affect different genes and biological function in the liver. Typical antipsychotic phenothiazines exert robust effects on gene expression in the liver that may lead to liver toxicity. The genes found in the current study may benefit antipsychotic drug development with better therapeutic and side effect profiles.</p
Stingless bee honey protects against lipopolysaccharide induced-chronic subclinical systemic inflammation and oxidative stress by modulating Nrf2, NF-κB and p38 MAPK
Background: Epidemiological and experimental studies have extensively indicated that chronic subclinical systemic inflammation (CSSI) and oxidative stress are risk factors for several chronic diseases, including cancer, arthritis, type 2 diabetes, and cardiovascular and neurodegenerative diseases. This study examined the protective effect of stingless bee honey (SBH) supplementation against lipopolysaccharide (LPS)-induced CSSI, pointing to the possible involvement of NF-κB, p38 MAPK and Nrf2 signaling. Methods: CSSI was induced in male Sprague Dawley rats by intraperitoneal injection of LPS three times per week for 28 days, and SBH (4.6 and 9.3 g/kg/day) was supplemented for 30 days. Results: LPS-induced rats showed significant leukocytosis, and elevated serum levels of CRP, TNF-α, IL-1β, IL-6, IL-8, MCP-1, malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), accompanied with diminished antioxidants. Treatment with SBH significantly ameliorated inflammatory markers, MDA and 8-OHdG, and enhanced antioxidants in LPS-induced rats. In addition, SBH decreased NF-κB p65 and p38 MAPK, and increased Nrf2 expression in the liver, kidney, heart and lung of LPS-induced rats. Furthermore, SBH prevented LPS-induced histological and functional alterations in the liver, kidney, heart and lung of rats. Conclusion: SBH has a substantial protective role against LPS-induced CSSI in rats mediated via amelioration of inflammation, oxidative stress and NF-κB, p38 MAPK and Nrf2 signaling
Bioassay-guided evaluation of Dioscorea villosa – an acute and subchronic toxicity, antinociceptive and anti-inflammatory approach
HPV and histological status of pelvic lymph node metastases in cervical cancer: a prospective study
Aims: The purpose of this prospective study was to describe the incidence and distribution pattern of human papillomavirus (HPV) DNA in intraoperative dissected lymph nodes and to relate this to the pathological confirmation of metastasis. Methods: Samples of primary cervical cancer lesions and dissected lymph nodes were obtained from women undergoing surgical treatment. The presence of HPV DNA was detected by the polymerase chain reaction. Results: Tissue from 79 tumours and 365 lymph nodes was analysed. Metastasis to the lymph nodes was found in 19 cases. Metastasis correlated with the volume of the primary lesion, the depth of cervical and vaginal invasion, and with invasion of the corpus. HPV DNA was found in 60 of the primary lesions and 31 of the lymph nodes. The presence of HPV DNA in the lymph nodes correlated with the volume of the primary lesion and vaginal invasion. Conclusions: The incidence of HPV DNA in lymph nodes is twice as high as that of histopathologically confirmed metastases. The risk of the presence of HPV DNA and histopathologically confirmed metastases in lymph nodes is related to certain features of the primary tumour