Peroxisome proliferator-activated receptor γ ligand-induced growth inhibition of human hepatocellular carcinoma

Peroxisome proliferator-activated receptor γ (PPARγ) ligands have been implicated in the growth inhibition and differentiation of certain human cancers with diverse tissue origin. In this study, expression of PPARγ in human hepatocellular carcinoma (HCC) and the effect of PPARγ ligands on HCC cells were investigated in vitro using Hep G2, HuH-7, KYN-1 and KYN-2 cell lines. All cell lines were found to express functionally active PPARγ and a marked growth inhibition was induced by thiazolidinedione ligands troglitazone, and pioglitazone as well as with its natural ligand 15-deoxy-Δ12,14-prostaglandin J 2. The growth inhibitory effect was associated with a dose-dependent inhibition of DNA synthesis, cell cycle progression and α fetoprotein expression. © 2001 Cancer Research Campaign http://www.bjcancer.co

Disparities in risks of malaria associated with climatic variability among women, children and elderly in the Chittagong hill tracts of Bangladesh

Malaria occurrence in the Chittagong Hill Tracts in Bangladesh varies by season and year, but this pattern is not well characterized. The role of environmental conditions on the occurrence of this vector-borne parasitic disease in the region is not fully understood. We extracted information on malaria patients recorded in the Upazila (sub-district) Health Complex patient registers of Rajasthali in Rangamati district of Bangladesh from February 2000 to November 2009. Weather data for the study area and period were obtained from the Bangladesh Meteorological Department. Non-linear and delayed effects of meteorological drivers, including temperature, relative humidity, and rainfall on the incidence of malaria, were investigated. We observed significant positive association between temperature and rainfall and malaria occurrence, revealing two peaks at 19 °C (logarithms of relative risks (logRR) = 4.3, 95% CI: 1.1–7.5) and 24.5 °C (logRR = 4.7, 95% CI: 1.8–7.6) for temperature and at 86 mm (logRR = 19.5, 95% CI: 11.7–27.3) and 284 mm (logRR = 17.6, 95% CI: 9.9–25.2) for rainfall. In sub-group analysis, women were at a much higher risk of developing malaria at increased temperatures. People over 50 years and children under 15 years were more susceptible to malaria at increased rainfall. The observed associations have policy implications. Further research is needed to expand these findings and direct resources to the vulnerable populations for malaria prevention and control in the Chittagong Hill Tracts of Bangladesh and the region with similar setting

Development and Function of Invariant Natural Killer T Cells Producing TH2- and TH17-Cytokines

Four distinct subsets of invariant natural killer T (NKT) cells are shown to differentiate in the thymus, then migrate to peripheral tissues where they retain their phenotypic and functional characteristics

Estimating the subsolar magnetopause position from soft X-ray images using a low-pass image filter

The Lunar Environment heliospheric X-ray Imager (LEXI) and Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) missions will image the Earth’s dayside magnetopause and cusps in soft X-rays after their respective launches in the near future, to specify global magnetic reconnection modes for varying solar wind conditions. To support the success of these scientific missions, it is critical to develop techniques that extract the magnetopause locations from the observed soft X-ray images. In this research, we introduce a new geometric equation that calculates the subsolar magnetopause position (\begin{document}${R}_{\mathrm{s}}$\end{document}) from a satellite position, the look direction of the instrument, and the angle at which the X-ray emission is maximized. Two assumptions are used in this method: (1) The look direction where soft X-ray emissions are maximized lies tangent to the magnetopause, and (2) the magnetopause surface near the subsolar point is almost spherical and thus \begin{document}${R}_{\mathrm{s}}$\end{document} is nearly equal to the radius of the magnetopause curvature. We create synthetic soft X-ray images by using the Open Geospace General Circulation Model (OpenGGCM) global magnetohydrodynamic model, the galactic background, the instrument point spread function, and Poisson noise. We then apply the fast Fourier transform and Gaussian low-pass filters to the synthetic images to remove noise and obtain accurate look angles for the soft X-ray peaks. From the filtered images, we calculate \begin{document}${R}_{\mathrm{s}}$\end{document} and its accuracy for different LEXI locations, look directions, and solar wind densities by using the OpenGGCM subsolar magnetopause location as ground truth. Our method estimates \begin{document}${R}_{\mathrm{s}}$\end{document} with an accuracy of \begin{document}${10\;\mathrm{c}\mathrm{m}}^{-3}$\end{document}. The accuracy improves for greater solar wind densities and during southward interplanetary magnetic fields. The method captures the magnetopause motion during southward interplanetary magnetic field turnings. Consequently, the technique will enable quantitative analysis of the magnetopause motion and help reveal the dayside reconnection modes for dynamic solar wind conditions. This technique will support the LEXI and SMILE missions in achieving their scientific objectives

Myoblast sensitivity and fibroblast insensitivity to osteogenic conversion by BMP-2 correlates with the expression of Bmpr-1a

<p>Abstract</p> <p>Background</p> <p>Osteoblasts are considered to primarily arise from osseous progenitors within the periosteum or bone marrow. We have speculated that cells from local soft tissues may also take on an osteogenic phenotype. Myoblasts are known to adopt a bone gene program upon treatment with the osteogenic bone morphogenetic proteins (BMP-2,-4,-6,-7,-9), but their osteogenic capacity relative to other progenitor types is unclear. We further hypothesized that the sensitivity of cells to BMP-2 would correlate with BMP receptor expression.</p> <p>Methods</p> <p>We directly compared the BMP-2 sensitivity of myoblastic murine cell lines and primary cells with osteoprogenitors from osseous tissues and fibroblasts. Fibroblasts forced to undergo myogenic conversion by transduction with a MyoD-expressing lentiviral vector (LV-MyoD) were also examined. Outcome measures included alkaline phosphatase expression, matrix mineralization, and expression of osteogenic genes <it>(alkaline phosphatase, osteocalcin </it>and <it>bone morphogenetic protein receptor-1A) </it>as measured by quantitative PCR.</p> <p>Results</p> <p>BMP-2 induced a rapid and robust osteogenic response in myoblasts and osteoprogenitors, but not in fibroblasts. Myoblasts and osteoprogenitors grown in osteogenic media rapidly upregulated <it>Bmpr-1a </it>expression. Chronic BMP-2 treatment resulted in peak <it>Bmpr-1a </it>expression at day 6 before declining, suggestive of a negative feedback mechanism. In contrast, fibroblasts expressed low levels of <it>Bmpr-1a </it>that was only weakly up-regulated by BMP-2 treatment. Bioinformatics analysis confirmed the presence of myogenic responsive elements in the proximal promoter region of human and murine <it>BMPR-1A/Bmpr-1a</it>. Forced myogenic gene expression in fibroblasts was associated with a significant increase in <it>Bmpr-1a </it>expression and a synergistic increase in the osteogenic response to BMP-2.</p> <p>Conclusion</p> <p>These data demonstrate the osteogenic sensitivity of muscle progenitors and provide a mechanistic insight into the variable response of different cell lineages to BMP-2.</p

Effect of oral lactulose on clinical and immunohistochemical parameters in patients with inflammatory bowel disease: a pilot study

<p>Abstract</p> <p>Background</p> <p>The prebiotic potential of lactulose is well established and preclinical studies demonstrated a protective effect of lactulose in murine models of colitis. The aim of the present study was to investigate the clinical and histological efficacy of lactulose in patients with inflammatory bowel disease (IBD), for which probiotic therapy yielded promising results.</p> <p>Methods</p> <p>Patients were treated with standard medication alone or combined with 10 g lactulose daily as adjuvant therapy for 4 months. Clinical efficacy of treatment was assessed using clinical activity indices, a quality of life index (IBDQ), endoscopic scores, defecation frequency and monitoring corticosteroid medication. Orsomucoid, alpha1-antitrypsin and other laboratory parameters were determined. In addition, in some participants colonic biopsies were analyzed with haematoxylin-eosin staining or with antibodies against HLA-DR, CD68, IgA and CD3, and evaluated systematically. All measurements were performed both at enrolment and at the end of the trial.</p> <p>Results</p> <p>14 patients presenting ulcerative colitis (UC) and 17 patients presenting Crohn's disease (CD), most of them in a clinically active state, were enrolled in this pilot study. After 4 month no significant improvement of clinical activity index, endoscopic score or immunohistochemical parameters was observed in CD or UC patients receiving lactulose in comparison to the control group. However, significant improvement of quality of life was observed in UC patients receiving lactulose compared to the control group (p = 0.04).</p> <p>Conclusion</p> <p>The findings of the present pilot study indicate that oral lactulose has no beneficial effects in IBD patients in particular with regard to clinical activity, endoscopic score or immunohistochemical parameters. The importance of the beneficial effect of lactulose in UC patients regarding the quality of life needs further evaluation in larger controlled clinical trials.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN92101486</p