Search results for "Wester"

Evaluation of the Role of Candida albicans Agglutinin-Like Sequence (Als) Proteins in Human Oral Epithelial Cell Interactions

2012

The fungus C. albicans uses adhesins to interact with human epithelial surfaces in the processes of colonization and pathogenesis. The C. albicans ALS (agglutinin-like sequence) gene family encodes eight large cell-surface glycoproteins (Als1-Als7 and Als9) that have adhesive function. This study utilized C. albicans Δals mutant strains to investigate the role of the Als family in oral epithelial cell adhesion and damage, cytokine induction and activation of a MAPK-based (MKP1/c-Fos) signaling pathway that discriminates between yeast and hyphae. Of the eight Δals mutants tested, only the Δals3 strain showed significant reductions in oral epithelial cell adhesion and damage, and cytokine pro…

P38 MAP Kinase Signaling Is Required for the Conversion of CD4+CD25− T Cells into iTreg

2008

CD4+CD25+ regulatory T cells (Treg) are important mediators of immune tolerance. A subset of Treg can be generated in the periphery by TGF-beta dependent conversion of conventional CD4+CD25− T cells into induced Treg (iTreg). In chronic viral infection or malignancy, such induced iTreg, which limit the depletion of aberrant or infected cells, may be of pathogenic relevance. To identify potential targets for therapeutic intervention, we investigated the TGF-beta signaling in Treg. In contrast to conventional CD4+ T cells, Treg exhibited marked activation of the p38 MAP kinase pathway. Inhibition of p38 MAP kinase activity prevented the TGF-beta-dependent conversion of CD4+CD25− T cells into …

Evaluation of acyl coenzyme A oxidase (Aox) isozyme function in the n- alkane-assimilating yeast Yarrowia lipolytica

1999

ABSTRACT We have identified five acyl coenzyme A (CoA) oxidase isozymes (Aox1 through Aox5) in the n -alkane-assimilating yeast Yarrowia lipolytica , encoded by the POX1 through POX5 genes. The physiological function of these oxidases has been investigated by gene disruption. Single, double, triple, and quadruple disruptants were constructed. Global Aox activity was determined as a function of time after induction and of substrate chain length. Single null mutations did not affect growth but affected the chain length preference of acyl-CoA oxidase activity, as evidenced by a chain length specificity for Aox2 and Aox3. Aox2 was shown to be a long-chain acyl-CoA oxidase and Aox3 was found to …

3-Deazaneplanocin A (DZNep), an Inhibitor of the Histone Methyltransferase EZH2, Induces Apoptosis and Reduces Cell Migration in Chondrosarcoma Cells

2014

Objective Growing evidences indicate that the histone methyltransferase EZH2 (enhancer of zeste homolog 2) may be an appropriate therapeutic target in some tumors. Indeed, a high expression of EZH2 is correlated with poor prognosis and metastasis in many cancers. In addition, 3-Deazaneplanocin A (DZNep), an S-adenosyl-L homocysteine hydrolase inhibitor which induces EZH2 protein depletion, leads to cell death in several cancers and tumors. The aim of this study was to determine whether an epigenetic therapy targeting EZH2 with DZNep may be also efficient to treat chondrosarcomas. Methods EZH2 expression was determined by immunohistochemistry and western-blot. Chondrosarcoma cell line CH2879…

Novel combination of celecoxib and proteasome inhibitor MG132 provides synergistic antiproliferative and proapoptotic effects in human liver tumor ce…

2010

Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Celecoxib (Celebrex®) exhibits antitumor effects in human HCC cells, and its mechanism of action is mediated either by its ability to inhibit cyclooxygenase 2 (COX-2) or by a number of various other COX-2 independent effects. Proteasome inhibitors (PIs) can exert cell growth inhibitory and apoptotic effects in different tumor cell types, including HCC cells. The present study examined the interaction between celecoxib and the PI MG132 in two human liver tumor cell lines HepG2 and HA22T/VGH. Our data showed that each inhibitor reduced proliferation and induced apoptosis in a dose-dependen…

2016

AbstractUnderstanding the dynamics of zoonotic pathogens in their reservoir host populations is a prerequisite for predicting and preventing human disease epidemics. The human infection risk of Puumala hantavirus (PUUV) is highest in northern Europe, where populations of the rodent host (bank vole, Myodes glareolus) undergo cyclic fluctuations. We conducted a 7-year capture-mark-recapture study to monitor seasonal and multiannual patterns of the PUUV infection rate in bank vole populations exhibiting a 3-year density cycle. Infected bank voles were most abundant in mid-winter months during years of increasing or peak host density. Prevalence of PUUV infection in bank voles exhibited a regul…

The nucleotide excision repair protein XPC is essential for bulky DNA adducts to promote interleukin-6 expression via the activation of p38-SAPK

2016

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants, and many are potent carcinogens. Benzo[a]pyrene (B[a]P), one of the best-studied PAHs, is metabolized ultimately to the genotoxin anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE). BPDE triggers stress responses linked to gene expression, cell death and survival. So far, the underlying mechanisms that initiate these signal transduction cascades are unknown. Here we show that BPDE-induced DNA damage is recognized by DNA damage sensor proteins to induce activation of the stress-activated protein kinase (SAPK) p38. Surprisingly, the classical DNA damage response, which involves the kinases ATM and ATR, is not involved in p38-SA…

Serine/threonine-kinase 33 (Stk33) – Component of the neuroendocrine network?

2016

The present study was conducted to investigate the expression of serine/threonine-kinase 33 (Stk33) in neuronal structures of the central nervous system in rat and hamster as well as the presence of the protein in the brain of higher mammals, using a polyclonal antibody on cryosections of fixed brains. We found a distinct immunostaining pattern that included intense fluorescence of the ependymal lining of cerebral ventricles, and of hypothalamic tanycytes and their processes. We further observed intense staining of magnocellular neurons in the hypothalamic paraventricular, supraoptic and accessory neurosecretory nuclei, in particular the circular nuclei, and less intense stained neurons in …

Haem Biosynthesis and Antioxidant Enzymes in Circulating Cells of Acute Intermittent Porphyria Patients

2016

The aims of the present study were to explore the expression pattern of haem biosynthesis enzymes in circulating cells of patients affected by two types of porphyria (acute intermittent, AIP, and variegate porphyria, VP), together with the antioxidant enzyme pattern in AIP in order to identify a possible situation of oxidative stress. Sixteen and twelve patients affected by AIP and VP, respectively, were analysed with the same numbers of healthy matched controls. Erythrocytes, neutrophils and peripheral blood mononuclear cells (PBMCs) were purified from blood, and RNA and proteins were extracted for quantitative real time PCR (qRT-PCR) and Western-blot analysis, respectively. Porhobilinogen…

Human case of Fasciola gigantica-like infection, review of human fascioliasis reports in Nepal, and epidemiological analysis within the South Central…

2018

Abstract The diagnosis of a 22 year-old male patient from Kerabari, Morang District, Nepal led to the review of human fascioliasis cases and analysis of the epidemiological situation in that country not included in the WHO fascioliasis map. Symptom onset one month before egg detection and normal levels of ALT and AST did not agree with the 3–4-month migratory period of fascioliasis. A shorter acute phase may happen when the main biliary duct is reached by the migratory juveniles directly from the intestinal lumen. The causal agent was ascribed to F. gigantica-like worms after considering adult fluke morphology, altitude of the patient’s infection area, fasciolid characteristics in the neigh…