Comparative Study of Regulatory T Cell Function of Human CD25+CD4+ T Cells from Thymocytes, Cord Blood, and Adult Peripheral Blood

CD25+CD4+ regulatory T cells suppress T cell activation and regulate multiple immune reactions in in vitro and in vivo studies. To define the regulatory function of human CD25+CD4+ T cells at various stages of maturity, we investigated in detail the functional differences of CD25+CD4+ T cells from thymocytes, cord blood (CB), and adult peripheral blood (APB). CB CD25+CD4+ T cells displayed low-FOXP3 protein expression level and had no suppressive activity. In contrast, CD25+CD4+ T cells from thymocytes or APB expressed high expression level of FOXP3 protein associated with significant suppressive activity. Although CB CD25+CD4+ T cells exhibited no suppressive activity, striking suppressive activity was observed following expansion in culture associated with increased FOXP3 expression and a shift from the CD45RA+ to the CD45RA− phenotype. These functional differences in CD25+CD4+ T cells from Thy, CB, and APB hence suggest a pathway of maturation for Treg in the peripheral immune system

Energy-loss Function for Lead

We study the energy-loss function for lead in the framework of the time-dependent density functional theory, using the full-potential linearized augmented plane-wave plus local orbitals method. The ab initio calculations are performed in the adiabatic local density approximation. The comparison between the obtained energy-loss function for zero momentum transfer with those from reflection electron energy loss spectroscopy measurements and from first-principles calculations shows good agreement

Spatiotemporal analysis of historical records (2001-2012) on dengue fever in Vietnam and development of a statistical model for forecasting risk

Background: Dengue fever is the most widespread infectious disease of humans transmitted by Aedes mosquitoes. It is the leading cause of hospitalization and death in children in the Southeast Asia and western Pacific regions. We analyzed surveillance records from health centers in Vietnam collected between 2001–2012 to determine seasonal trends, develop risk maps and an incidence forecasting model. Methods: The data were analyzed using a hierarchical spatial Bayesian model that approximates its posterior parameter distributions using the integrated Laplace approximation algorithm (INLA). Meteorological, altitude and land cover (LC) data were used as predictors. The data were grouped by province (n = 63) and month (n = 144) and divided into training (2001–2009) and validation (2010–2012) sets. Thirteen meteorological variables, 7 land cover data and altitude were considered as predictors. Only significant predictors were kept in the final multivariable model. Eleven dummy variables representing month were also fitted to account for seasonal effects. Spatial and temporal effects were accounted for using Besag-York-Mollie (BYM) and autoregressive (1) models. Their levels of significance were analyzed using deviance information criterion (DIC). The model was validated based on the Theil’s coefficient which compared predicted and observed incidence estimated using the validation data. Dengue incidence predictions for 2010–2012 were also used to generate risk maps. Results: The mean monthly dengue incidence during the period was 6.94 cases (SD 14.49) per 100,000 people. Analyses on the temporal trends of the disease showed regular seasonal epidemics that were interrupted every 3 years (specifically in July 2004, July 2007 and September 2010) by major fluctuations in incidence. Monthly mean minimum temperature, rainfall, area under urban settlement/build-up areas and altitude were significant in the final model. Minimum temperature and rainfall had non-linear effects and lagging them by two months provided a better fitting model compared to using unlagged variables. Forecasts for the validation period closely mirrored the observed data and accurately captured the troughs and peaks of dengue incidence trajectories. A favorable Theil’s coefficient of inequality of 0.22 was generated. Conclusions: The study identified temperature, rainfall, altitude and area under urban settlement as being significant predictors of dengue incidence. The statistical model fitted the data well based on Theil’s coefficient of inequality, and risk maps generated from its predictions identified most of the high-risk provinces throughout the country

Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines

<p>Abstract</p> <p>Background</p> <p>CD26 (dipeptidyl peptidase IV, DPPIV) is a 110 kDa surface glycoprotein expressed in most normal tissues, and is a potential novel therapeutic target for selected cancers. Our work evaluates the mechanism involved in confluence-dependent CD26 expression in colon cancer.</p> <p>Methods</p> <p>Colon adenocarcinoma cells were grown to confluence, and expression of CD26 and transcription factors implicated in its regulation was confirmed by immunofluorescence and Western blotting. Real-time PCR was also performed to evaluate CD26 upregulation at the transcriptional level. The influence of c-Myc on CD26 expression during different growth conditions was further evaluated following transient transfection of a c-Myc-expressing plasmid and a c-Myc specific siRNA.</p> <p>Results</p> <p>We found that the colon cancer cell lines HCT-116 and HCT-15 exhibited a confluence-dependent increase in CD26 mRNA and protein, associated with decreased expression of c-Myc, increased USF-1 and Cdx 2 levels, and unchanged HNF-1α expression. Meanwhile, ectopic expression of c-Myc in both cell lines led to decreased CD26 expression. In contrast, transfection of a siRNA targeted to Cdx2 resulted in decreased CD26 level. Importantly, culturing of cells in serum-depleted media, but not acidic conditions, upregulated CD26. While HIF-1α level also increased when cells were cultured in serum-depleted media, its expression was required but not sufficient for CD26 upregulation.</p> <p>Conclusions</p> <p>CD26 mRNA and protein levels increase in a confluence-dependent manner in colon carcinoma cell lines, with c-Myc acting as a repressor and Cdx2 acting as an enhancer of CD26 expression. The enhanced expression of CD26 in serum-depleted media and a requirement for HIF-1α suggest a role for nutrients or growth factors in the regulation of CD26 protein expression.</p

Roxithromycin Specifically Inhibits Development of Collagen Induced Arthritis and Production of Proinflammatory Cytokines by Human T Cells and Macrophages

ABSTRACT. Objective. Roxithromycin (RXM) is a macrolide antibiotic that is effective in treatment of chronic lower respiratory tract diseases including diffuse panbronchiolitis and bronchial asthma. Its mechanism of action apart from its antibacterial action remains unclear. To determine the mechanism of action of RXM, we evaluated the effect of RXM on T cell functions and the inflammatory responses in mice with collagen induced arthritis (CIA). Methods. T cell proliferation, cytokine production by T cells stimulated through CD28, CD26, or PMA with or without anti-CD3 Mab, cytokine production by macrophages stimulated with lipopolysaccharide, and transendothelial migration of T cells were analyzed in the presence or absence of various concentrations of RXM. We evaluated the effect of RXM treatment in collagen induced arthritis in mice. Results. RXM did not affect the production of Th1-type and Th2-type cytokines, whereas it specifically inhibited production of proinflammatory cytokines such as tumor necrosis factor-α and interleukin 6 (IL-6) by T cells and macrophages. RXM inhibited T cell migration. We found that RXM treatment of mice with CIA reduced the severity of arthritis and serum level of IL-6, as well as leukocyte migration into the affected joints and destruction of bones and cartilage. Conclusion. Our findings strongly suggest that RXM may be useful for the therapy of rheumatoid arthritis as well as other inflammatory diseases such as Crohn&apos;s disease. (J Rheumatol 2005; 32:1765-74

Interlaboratory comparison study of the Colony Forming Efficiency assay for assessing cytotoxicity of nanomaterials

Nanotechnology has gained importance in the past years as it provides opportunities for industrial growth and innovation. However, the increasing use of manufactured nanomaterials (NMs) in a number of commercial applications and consumer products raises also safety concerns and questions regarding potential unintended risks to humans and the environment. Since several years the European Commission’s Joint Research Centre (JRC) is putting effort in the development, optimisation and harmonisation of in vitro test methods suitable for screening and hazard assessment of NMs. Work is done in collaboration with international partners, in particular the Organisation for Economic Co-operation and Development (OECD). This report presents the results from an interlaboratory comparison study of the in vitro Colony Forming Efficiency (CFE) cytotoxicity assay performed in the frame of OECD's Working Party of Manufactured Nanomaterials (WPMN). Twelve laboratories from European Commission, France, Italy, Japan, Poland, Republic of Korea, South Africa and Switzerland participated in the study coordinated by JRC. The results show that the CFE assay is a suitable and robust in vitro method to assess cytotoxicity of NMs. The assay protocol is well defined and is easily and reliably transferable to other laboratories. The results obtained show good intra and interlaboratory reproducibility of the assay for both the positive control and the tested nanomaterials. In conclusion the CFE assay can be recommended as a building block of an in vitro testing battery for NMs toxicity assessment. It could be used as a first choice method to define dose-effect relationships for other in vitro assays.JRC.I.4-Nanobioscience

Prevalence and impacts of self-medication in a disadvantaged setting: the importance of multi-dimensional health interventions

BackgroundSelf-medication is recognized as an effective form of treatment and is increasingly encouraged to treat minor illnesses. However, misuse of self-medication leaves devastating impacts on human health and causes antimicrobial resistance. Using medication without a prescription among farmers could cause more severe effects on their health than non-farm workers since they suffer from several occupational hazards such as excessive exposure to pesticides.MethodsA cross-sectional study was conducted in 197 residents living in Moc Chau from August to September. A structured questionnaire and face-to-face were used to collecting data. The multivariate logistic model was applied to indicate associated factors with the self-medication.ResultsThe prevalence of self-medication among farmers was 67%. Pain relievers (66.7%) and antibiotics (32.5%) were the types of medicines that were the most commonly purchased and used without a medical prescription. Ethnics and health status also significantly affected the self-medication practice as well as the purchase and use of antibiotics. The distance to travel to a medical center and the dangerous or difficult travel, participants with arthritis or inpatient treatment had significantly associated with buying and using the medicine and antibiotics without the medical prescription of farmers.ConclusionOur research highlights a considerably high prevalence of self-medication among farmers residing in the mountainous area of Vietnam. Individual factors such as ethnics, health status, distance to health centers, and dangerous or difficult travel were found to be related to the SM practice as well as the purchase and use of antibiotics. From that, the current study suggests interventions. For instance, official guidelines are needed to raise awareness and minimize the disadvantages of self-medication; and digital health technologies should be applied to reduce the gap in healthcare service between mountainous and other areas of Vietnam

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. SHORT CONCLUSIONS: This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place