Estradiol induces apoptosis via activation of miRNA-23a and p53: implication for gender difference in liver cancer development

published_or_final_versio

Effect of nucleos(t)ide analogues therapy on HBsAg, intrahepatic HBV DNA and covalently closed circular DNA levels

BACKGROUND: We aimed to study 1) the effects of 1-year nucleos(t)ide analogue (NA) therapy on HBsAg and covalently closed circular DNA (cccDNA) levels; and 2) the possible use of HBsAg reduction as a marker for cccDNA reduction. METHODS: We recruited 124 NA-treated patients with ...postprin

Serum levels of IL-33 and soluble ST2 and their association with disease activity in systemic lupus erythematosus

BACKGROUND: IL-33 has recently been found to be the specific ligand of ST2, an IL-1 receptor family member that is selectively expressed on Th2 cells and mediates Th2 response. This study aimed to measure serum levels of soluble form of ST2 (sST2) and IL-33 in patients with systemic lupus erythematosus (SLE) and to examine its association with disease activity. METHODS: Seventy SLE patients were evaluated for disease activity determined by SLE disease activity index (SLEDAI), serological features (anti-dsDNA antibody, C3 and C4) and 57 patients were evaluated longitudinally on a second occasion. IL-33 and sST2 were measured by sandwich ELISA in the 127 SLE serum samples and compared to 28 age- and sex-matched healthy controls. RESULTS: Serum sST2 level was significantly higher in SLE patients with active disease (0.51+0.18 ng/mL) compared to those with inactive disease (0.42+0.08 ng/mL) [P=0.006] and to normal controls (0.36+0.13 ng/mL) [P<0.001]. sST2 level correlated significantly and positively with SLEDAI, level of anti-dsDNA antibody and prednisolone dosage and negatively with C3 and remained significantly predictive of active disease after adjustment for prednisolone use in logistic regression analysis (odds ratio=4.6, P=0.01). sST2 level was sensitive to change in disease activity in longitudinal evaluation and not influenced by age, gender, and renal function. Elevated serum IL-33 was comparable in frequency (4.3% vs 7.1%, P=0.62) and levels (P=0.53) between SLE patients and controls. CONCLUSION: Elevated serum sST2 level in SLE patients was found to correlate with disease activity and was sensitive to change, suggesting a potential role as surrogate marker of disease activity.published_or_final_versionThe 15th Medical Research Conference (15th MRC), Department of Medicine, University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16 n. 1, suppl. 1, p. 46, abstract no. 7

Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1

Identification of Hepatitis B Virus DNA Polymerase Sequences to Predict Virological Response to Entecavir Therapy

Poster Presentations: Emerging / Infectious DiseasesConference Theme: Translating Health Research into Policy and Practice for Health of the Populationpublished_or_final_versio

Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281–1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50 μ m. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung