Coupled Modeling of Lipid Deposition, Inflammatory Response and Intraplaque Angiogenesis in Atherosclerotic Plaque.

We propose a multiphysical mathematical model by fully coupling lipid deposition, monocytes/macrophages recruitment and angiogenesis to investigate the pathophysiological responses of an atherosclerotic plaque to the dynamic changes in the microenvironment. The time evolutions of cellular (endothelial cells, macrophages, smooth muscle cells, etc.) and acellular components (low density lipoprotein, proinflammatory cytokines, extravascular plasma concentration, etc.

Mathematical modeling of atherosclerotic plaque destabilization: Role of neovascularization and intraplaque hemorrhage.

Observational studies have identified angiogenesis from the adventitial vasa vasorum and intraplaque hemorrhage (IPH) as critical factors in atherosclerotic plaque progression and destabilization. Here we propose a mathematical model incorporating intraplaque neovascularization and hemodynamic calculation with plaque destabilization for the quantitative evaluation of the role of neoangiogenesis and IPH in the vulnerable atherosclerotic plaque formation. An angiogenic microvasculature is generated by two-dimensional nine-point discretization of endothelial cell proliferation and migration from the vasa vasorum.

A novel role of angiopoietin-like-3 associated with podocyte injury.

Background: Angiopoietin-like-3 (ANGPTL3) expression is increased in glomerular podocytes of nephrotic syndrome. We hypothesize whether ANGPTL3 plays an important role in podocyte injury and promoting proteinuria.

Methods: Angptl3(+/+) and Angptl3(-/-) female mice on B6;129S5 gene background were injected with adriamycin by tail vein at the dose of 25 mg/Kg to produce nephropathy.

[Expression of neonatal Fc receptor on human nephritis and rat nephritis models].

Objective: To study the expression of neonatal Fc receptor in podocytes in human nephritis and immune-induced rat nephritis models: anti-Thy1.1 nephritis and Heymann nephritis.

Methods: Thirty-nine cases of renal biopsies were enrolled from September 2009 to February 2010, including 8 cases of minimal change disease, 4 cases of focal segmental glomerulosclerosis, 9 cases of membranous nephropathy, 12 cases of IgA nephropathy and 6 cases of lupus nephritis.

[FAK/c-Src signaling pathway mediates the expression of cell surface HSP90 in cultured human prostate cancer cells and its association with their invasive capability].

Objective: To investigate the expression of heat shock protein 90 (HSP90) on the cell surface of highly invasive human prostate cancer cells PC3 and its possible molecular mechanisms of its effect on cell invasion through analyzing FAK/Src signaling pathway.

Methods: The expression of cell surface HSP90 on PC3 cells was studied by immunofluorescence staining and surface biotinylation assay respectively. A specific HSP90 antibody was used to inhibit the cell surface HSP90.

Cell surface heat shock protein 90 modulates prostate cancer cell adhesion and invasion through the integrin-β1/focal adhesion kinase/c-Src signaling pathway.

Heat shock protein (Hsp) 90 is a molecular chaperone that maintains the active conformation and function of numerous client oncoproteins in cancer cells. Hsp90 has also been detected on the plasma membrane of cells, and its expression has been suggested to correlate with metastatic potential. We studied the PC3 cell line, which is a highly invasive human prostate cancer cell line, and confirmed that Hsp90 is present on the cell surface of PC3 cells.

[Electron microscopic examination on 50 cases of prostatic needle biopsies].

Objective: To study the differences in ultrastructural findings between prostatic carcinoma and benign prostatic hypertrophy, and the various ultrastructural features seen in moderately to poorly differentiated prostatic carcinoma.

Methods: Utrasound-guided needle biopsies were carried out in 50 clinically suspicious cases of prostatic carcinoma. For each case, one additional core was sampled from the most suspicious area, fixed in glutaraldehyde and examined under electron microscopy.

Role of cross-talk between the Smad2 and MAPK pathways in TGF-beta1-induced collagen IV expression in mesangial cells.

Transforming growth factor beta1 (TGF-beta1) can promote sclerosis in many kidney diseases by enhancing the synthesis of collagens. However, the mechanisms of down-stream intracellular signal transduction in TGF-beta1-induced collagen synthesis is not fully understood. The purpose of this study was to further investigate the mechanisms and the cross-talk between the MAPK and Smad2 pathways.

Regulation of intracellular decorin via proteasome degradation in rat mesangial cells.

Decorin (DCN) is a member of small leucine-rich proteoglycan family that neutralizes the bioactivity of transforming growth factor-beta1 (TGF-β1). It has been proven to be a promising anti-fibrotic agent to treat glomerulonephritis. But the underlining mechanism for regulating and degrading intracellular DCN is still not fully understood.

[Apoptosis inducing factor mediates cisplatin-induced apoptosis of renal tubular epithelial cells].

Objective: To investigate the involvement of apoptosis inducing factor (AIF) in caspase-independent pathway mediating apoptosis of cultured renal tubular epithelial cells induced by cisplatin (CP).

Methods: Western Blot analysis and real-time PCR were performed to detect cytosol AIF (cAIF), nuclear AIF (nAIF) and AIF mRNA expression in cultured renal epithelial cells (HK-2) treated with cisplatin (CP) at various concentrations (0 - 200 micromol/L) and time courses (0 - 12 h). Immunofluorescence analysis was used to detect the AIF protein distribution in HK-2 cells.

Expression of USP2-69 in mesangial cells in vivo and in vitro.

Ubiquitin-specific protease 2 (USP2) is a member of a family of de-ubiquitinating enzymes. It may play an important role in the regulation of cell growth and differentiation. It is known that expression of the isoform USP2-69 kD is high in kidney tissue, but its role remains unclear.

UCH-L1 expression of podocytes in diseased glomeruli and in vitro.

Ubiquitin C-terminal hydrolase-L1 (UCH-L1), an important member of de-ubiquitination enzyme families involved in the ubiquitin-proteasome pathway, is expressed mainly in neural and reproductive systems as well as in some tumours. Recently, expression of UCH-L1 has been discovered in parietal epithelial cells of Bowman's capsules and some tubular epithelia in the kidney. However, whether UCH-L1 is expressed in the capillary tufts of the glomeruli has not yet become clear.

[Pro-apoptotic effect of decorin on rat mesangial cells in vitro].

Objective: To investigate the effects of over-expression of decorin (DCN) gene on apoptosis of cultured rat mesangial cells (MsC).

Methods: PcDNA3.1A-DCN plasmid was transfected into cultured rat MsC by the induction of liposome and positive clones were selected by treating the cells with G418.

Overexpression of decorin induces apoptosis and cell growth arrest in cultured rat mesangial cells in vitro.

Background: Decorin (DCN) is a small leucine-rich proteoglycan that plays an important role in the regulation of intercellular contact, cell migration and proliferation. DCN suppresses cell growth and induces apoptosis in various tumour cells. The aim of this study was to investigate whether overexpression of DCN could induce apoptosis and cell growth arrest in mesangial cells (MsCs) in vitro.

[Clinicopathologic analysis of 34 patients with microscopic polyangitis].

Objective: To study the clinicopathologic features of microscopic polyangitis (MPA), and to compare the differences in anti-neutrophil cytoplasmic autoantibody (ANCA)-positive and ANCA-negative patients, as well as in ANCA-positive cases with or without glomerular immunoglobulin deposition.

Methods: Thirty-four biopsy-proven cases of MPA were retrieved from the archival files of the Department during the past 7 years. The clinicopathologic characteristics between ANCA-positive and negative patients, as well as between ANCA-positive cases with and without glomerular immunoglobulin deposition, were compared.

Detection of UCH-L1 expression by pre-embedding immunoelectron microscopy with colloidal gold labeling in diseased glomeruli.

The purpose of this report was to study the use of pre-embedding immunoelectron microscopy technique with gold and horseradish peroxidase (HRP) labeling in detecting the expression of ubiquitin C-terminal hydrolase 1 (UCH-L1) of podocytes in glomerulonephritis. The specimens of human IgA nephropathy and lupus nephritis were fixed with paraformaldehyde and lysine-HCl buffer, labeled by colloidal gold or HRP, embedded with epoxy resin, and examined under the transmission electron microscope. The high density of gold particles or peroxidase reaction products (DAB) combined with UCH-L1 was obvious in cytoplasm and processes of podocytes.

[Effect of interferon-gamma on transforming growth factor beta/Smad signal pathway and expression of matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinase-2 in cultured rat mesangial cells].

Objective: To study the effect of interferon-gamma (IFN-gamma) on the proliferation of mesangial cells (MsC) and transforming growth factor (TGF)-beta/Smad signal pathway, the mRNA and protein expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase-2 (TIMP-2), and to provide an experimental basis for IFN-gamma treatment of renal fibrosis.

Methods: Cultured MsC were treated with IFN-gamma at different concentrations and the proliferation of MsC was examined by MTT. Protein and RNA samples were extracted from MsC at 0, 0.

[Changes of fibronectin and type IV collagen expression in cultured rat mesangial cells transfected with connective tissue growth factor expression vector].

Objective: To study the role of connective tissue growth factor (CTGF) in the development of glomerulosclerosis by experimental alteration of fibronectin (FN) and Type IV collagen (Col IV) expression in cultured rat mesangial cells (MsC).

Methods: CTGF expression vector was transfected into MsC by Lipofectimine method. Protein and mRNA expression levels of CTGF, FN and Col IV were studied by Western blot and reverse transcription-polymerase chain reaction (RT-PCR) respectively.

[Protective effect of amifostine on cisplatin-induced nephrotoxicity and its mechanism].

Objective: To investigate the sites and pattern of renal toxicity in rats treated with cisplatin and the protective effect of amifostine, and to understand whether Fas/FasL system is involved in cisplatin-induced nephrotoxicity.

Methods: Forty-eight Sprague-Dawley rats were randomly divided into 3 groups: control group (0.9% saline solution), cisplatin group (6 mg/kg) and amifostine group (cisplatin 6 mg/kg + amifostine 200 mg/kg).

[Changes of fibronectin and type IV collagen expression in cultured rat mesangial cells transfected with Smad 2 vector].

Objective: To study the changes of fibronectin (FN) and type IV collagen (ColIV) expression in cultured rat mesangial cells (MsC) transfected with Smad 2 vector and to investigate the molecular mechanism of glomerular extracellular matrix accumulation in glomerulosclerosis via transforming growth factor-beta (TGF-beta)/Smad signal pathway.

Methods: Smad 2 vector was transfected into MsC by calcium phosphate. Western blot analysis was used to detect Smad 2 protein.

Ex vivo transfer of the decorin gene into rat glomerulus via a mesangial cell vector suppressed extracellular matrix accumulation in experimental glomerulonephritis.

The activation of transforming growth factor-beta (TGF-beta) is known to be one of the major causes of glomerulosclerosis. Decorin (DCN) is a natural inhibitor of TGF. The purpose of this study was to assess the feasibility of transferring the DCN gene to antithymocyte serum (ATS) glomerulonephritis glomeruli via a mesangial cell vector to treat glomerulonephritis fibrosis.

Significance of MMP-2 and TIMP-2 mRNA expressions on glomerular cells in the development of glomerulosclerosis.

Objective: To study the expressions of MMP-2 and TIMP-2 mRNA on cultured rat mesangial cells (MsC) and in human diseased glomeruli, and to explore their significance in the development of glomerulosclerosis.

Methods: The expressions of MMP-2, TIMP-2, and Col IV mRNA on cultured rat MsC stimulated by IL-1 or/and TGF-beta1 were investigated through Northern blot analysis. The levels of MMP-2 and TIMP-2 mRNA expressions and immunoreactivity of PCNA and Col IV in human diseased glomeruli from renal biopsies of lupus nephritis (LN) patients were examined by in situ hybridization and immunohistochemistry, respectively.