Estrogen and beta-amyloid toxicity: role of integrin and PI3-K.

Beta-amyloid peptide (betaAP) induces apoptosis and down-regulation of alpha(1)beta(1) integrin in neuronal cells, indicating a relationship between betaAP neurotoxicity and modulation of integrin expression. Estrogen may play a role in protecting women from Alzheimer Disease (AD). It is here reported that both 17beta-estradiol (17betaE(2)) and its non-estrogenic stereoisomer 17alpha-estradiol (17alphaE(2)) rescue neuronal cells from betaAP-induced apoptosis.

The crystal structure of human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase in complex with 1,3-dihydroxyacetonephosphate suggests a regulatory link between NAD synthesis and glycolysis.

The enzyme alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) is a zinc-dependent amidohydrolase that participates in picolinic acid (PA), quinolinic acid (QA) and NAD homeostasis. Indeed, the enzyme stands at a branch point of the tryptophan to NAD pathway, and determines the final fate of the amino acid, i.e.

Tobacco smoke affects expression of peroxisome proliferator-activated receptor-gamma in monocyte/macrophages of patients with coronary heart disease.

Background And Purpose: Tobacco smoke represents a relevant risk factor for coronary heart disease (CHD). Although peroxisome proliferator-activated receptor (PPAR)gamma activation reduces inflammation and atherosclerosis, expression of PPARgamma in cells and its modulation by smoking are poorly investigated. We previously reported that monocyte/macrophages from healthy smokers exhibited an enhanced constitutive expression of PPARgamma.

Evaluation of Legionella pneumophila contamination in Italian hotel water systems by quantitative real-time PCR and culture methods.

Aims: This study was designed to define the extent of water contamination by Legionella pneumophila of certain Italian hotels and to compare quantitative real-time PCR with the conventional culture method.

Methods And Results: Nineteen Italian hotels of different sizes were investigated. In each hotel three hot water samples (boiler, room showers, recycling) and one cold water sample (inlet) were collected.

Calcipotriol induces apoptosis in psoriatic keratinocytes.

In recent years, vitamin D3 analogues have become one of the most widely prescribed topical treatments for mild or moderate chronic plaque psoriasis. These molecules are effective and safe, but their exact mechanism of action is not completely understood. In vitro studies have shown that D3 analogues decrease proliferation and induce differentiation of keratinocytes, and have strong immunomodulating effects, but there are no conclusive data about apoptosis.

DNA damage in A549 cells exposed to different extracts of PM(2.5) from industrial, urban and highway sites.

The aim of this research is to investigate the role played by the chemical fraction of PM(2.5) in the DNA damage induction in human lung cells (A549): in particular the effects of samples collected in urban, industrial and highway sites were compared. Organic and water-soluble extracts of PM(2.

Cellular and molecular pathways linking inflammation and cancer.

Several experimental and epidemiological evidence indicate that, irrespective of the trigger for the development (chronic infection/inflammation or genetic alteration), a "smouldering" inflammation is associated with the most of, if not all, tumours and supports their progression. Several evidence have highlighted that tumours promote a constant influx of myelomonocytic cells that express inflammatory mediators supporting pro-tumoral functions. Myelomonocytic cells are key orchestrators of cancer-related inflammation associated with proliferation and survival of malignant cells, subversion of adaptive immune response, angiogenesis, stroma remodelling and metastasis formation.

RNF168, a new RING finger, MIU-containing protein that modifies chromatin by ubiquitination of histones H2A and H2AX.

Background: Modulation of chromatin structure has emerged as a critical molecular device to control gene expression. Histones undergo different post-translational modifications that increase chromatin accessibility to a number of regulatory factors. Among them, histone ubiquitination appears relevant in nuclear processes that govern gene silencing, either by inhibiting or activating transcription, and maintain genome stability, acting as scaffold to properly organize the DNA damage response.

Estrogen receptor-beta affects the prognosis of human malignant mesothelioma.

Malignant pleural mesothelioma is an asbestos-related neoplasm with poor prognosis, refractory to current therapies, the incidence of which is expected to increase in the next decades. Female gender was identified as a positive prognostic factor among other clinical and biological prognostic markers for malignant mesothelioma, yet a role of estrogen receptors (ERs) has not been studied. Our goal was to investigate ERs expression in malignant mesothelioma and to assess whether their expression correlates with prognosis.

Taurolidine and oxidative stress: a rationale for local treatment of mesothelioma.

Malignant mesothelioma is an asbestos-related, aggressive tumour, resistant to most anticancer therapies. Akt is a key mediator of mesothelioma cell survival and chemoresistance. This study aimed to clarify the mechanism by which taurolidine (TN), a known synthetic compound with antimicrobial and antineoplastic properties, leads to mesothelioma cell death.

Application of semipermeable membrane device (SPMD) to assess air genotoxicity in an occupational environment.

Semipermeable membrane device (SPMD) is a passive sampler that sequesters lipophilic contaminants, mimicking the bioconcentration in the fatty tissue of organisms. This study was designed to assess the use of SPMD and biological tests (Comet assay and Ames test) for air monitoring. For this purpose an occupational environment with expected polycyclic aromatic hydrocarbons (PAHs) contamination (coke plant) was selected for a case study.

Curiosity to kill the KAT (kynurenine aminotransferase): structural insights into brain kynurenic acid synthesis.

Kynurenine aminotransferases are pyridoxal-5'-phosphate-dependent enzymes, which catalyze the synthesis of kynurenic acid, a highly neuroactive metabolite whose impairment is associated with a number of severe brain disorders. Crystallographic studies of these enzymes from different organisms, including humans, have revealed distinctive structural traits of type I and type II kynurenine aminotransferases. A striking difference concerns domain swapping of the N-terminal regions, which play equivalent key functional roles in both an unswapped and swapped structure in type I and type II isozymes.

Adult dorsal root ganglia sensory neurons express the early neuronal fate marker doublecortin.

It has been widely accepted that doublecortin (DCX) may represent a neuronal fate marker transiently expressed by immature neurons during development of the central and peripheral nervous tissue and in neurogenic areas of the adult brain. Previous work described the presence of DCX in the developing dorsal root ganglia (DRG), structures of the peripheral nervous system originating from the neural crest, but no information is available on its expression in adulthood. To this purpose, we have performed an immunohistochemical and biochemical analysis for DCX expression in DRG from adult male mice and rats.

Purification and biochemical characterization of a recombinant Anopheles gambiae tryptophan 2,3-dioxygenase expressed in Escherichia coli.

In the malaria vector Anopheles gambiae, tryptophan 2,3-dioxygenase (TDO) is the only enzyme able to initiate l-tryptophan degradation through the kynurenine pathway. TDO converts l-tryptophan to N-formylkynurenine by catalyzing the heme-dependent oxidative opening of the substrate indole ring. Despite the central role exerted by kynurenines in the physiology of living organisms, only a few insect TDOs have been subjected to biochemical characterization in vitro.

Microbiological and chemical characterization of a typical Italian cheese: Robiola di Roccaverano.

Robiola di Roccaverano is a traditional Italian goat's milk cheese carrying a Protected Designation of Origin (PDO). The present work studied both cheese microflora and cheese physicochemical characteristics to obtain a more accurate description of this PDO product. Multivariate statistical analysis (PCA) was performed to evaluate the influence of cheesemaking (artisanal and industrial), ripening time, and season of production on cheese characteristics.

Ultrasonography for the monitoring of subcutaneous damage in Mycobacterium ulcerans infection (Buruli ulcer).

We used ultrasonography to evaluate the nature and the extent of subcutaneous damage provoked by Mycobacterium ulcerans (M. ulcerans) and to investigate the possible involvement of the tributary lymph nodes during the various stages of progression of Buruli ulcer. Nineteen patients affected by M.

Use of highly sensitive sublethal stress responses in the social amoeba Dictyostelium discoideum for an assessment of freshwater quality.

In this work, the sensitivity of a battery of tests on the social amoeba Dictyostelium discoideum has been assessed within a freshwater toxicity study. The results obtained from the evaluation of survival and replication rate of D. discoideum were compared to those derived with a series of widely used tests for freshwater toxicity assessment, i.

A novel activity for substance P: stimulation of peroxisome proliferator-activated receptor-gamma protein expression in human monocytes and macrophages.

Background And Purpose: Substance P (SP) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) play important roles in different inflammatory conditions and are both expressed in human monocytes and macrophages. However, it is not known whether or not they interact. This study was undertaken to evaluate the effects of SP on PPAR-gamma protein expression in monocytes and macrophages (MDMs: monocyte-derived macrophages) from healthy smokers and non-smokers.

Detection of biogenic amine producer bacteria in a typical Italian goat cheese.

The aim of this study was to research decarboxylating bacterial strains and biogenic amine content in a typical Italian goat cheese (Robiola di Roccaverano). The study was performed on fresh and ripened samples of goat cheese manufactured from industrial and artisanal producers. Sixty-seven bacterial strains isolated showed decarboxylating activity, and Enterococcus faecalis was the most widespread decarboxylating species in all artisanal and industrial products.

Imatinib mesylate enhances therapeutic effects of gemcitabine in human malignant mesothelioma xenografts.

Purpose: Platelet-derived growth factor receptor beta (PDGFRbeta), frequently activated in malignant mesothelioma, is a promising cancer therapeutic target. Imatinib mesylate (STI571; Glivec) is a selective inhibitor of tyrosine kinases as bcr-abl, c-kit, c-fms, and PDGFRbeta and enhances tumor drug uptake by reducing the interstitial fluid pressure. We previously showed that imatinib mesylate synergizes with gemcitabine and pemetrexed in PDGFRbeta-positive mesothelioma cells.

Crystal structure of human kynurenine aminotransferase II, a drug target for the treatment of schizophrenia.

Kynurenic acid is an endogenous neuroactive compound whose unbalancing is involved in the pathogenesis and progression of several neurological diseases. Kynurenic acid synthesis in the human brain is sustained by the catalytic activity of two kynurenine aminotransferases, hKAT I and hKAT II. A wealth of pharmacological data highlight hKAT II as a sensible target for the treatment of neuropathological conditions characterized by a kynurenic acid excess, such as schizophrenia and cognitive impairment.

Biosimilar drugs : concerns and opportunities.

Patents for biologic agents first marketed in the 1980s are now beginning to expire, opening the door for 'non-proprietary' versions of these agents to enter the market. However, there are fundamental differences between biologics and traditional pharmaceuticals that preclude the extrapolation of existing regulatory processes for traditional generic agents to these new biologic products. These include differences in dimensions (molecular weight), synthesis, purification, stability, and immunogenicity.

Minor polar compounds extra-virgin olive oil extract (MPC-OOE) inhibits NF-kappa B translocation in human monocyte/macrophages.

Epidemiological studies demonstrate that the Mediterranean diet, in which olive oil is the major source of fat, reduces the risk of coronary heart disease and cancer. It has been proposed that the beneficial effects of olive oil not only depend on oleic acid, but are also associated with minor polar compounds (MPC). A positive correlation between inflammation and cardiovascular diseases has long been described, monocyte/macrophages and NF-kappaB playing a pivotal role.

Diacylglycerol kinase-alpha mediates hepatocyte growth factor-induced epithelial cell scatter by regulating Rac activation and membrane ruffling.

Diacylglycerol kinases (Dgk) phosphorylate diacylglycerol (DG) to phosphatidic acid (PA), thus turning off and on, respectively, DG-mediated and PA-mediated signaling pathways. We previously showed that hepatocyte growth factor (HGF), vascular endothelial growth factor, and anaplastic lymphoma kinase activate Dgkalpha in endothelial and leukemia cells through a Src-mediated mechanism and that activation of Dgkalpha is required for chemotactic, proliferative, and angiogenic signaling in vitro. Here, we investigate the downstream events and signaling pathways regulated by Dgkalpha, leading to cell scatter and migration upon HGF treatment and v-Src expression in epithelial cells.

Quantification of PPAR-gamma protein in monocyte/macrophages from healthy smokers and non-smokers: a possible direct effect of nicotine.

Previous observations demonstrated that Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma), a key regulator of adipocyte differentiation, is expressed in a large variety of cells, including cells of the monocyte/macrophage lineage. This study was aimed to quantify both the constitutive and ligand-induced PPAR-gamma expression in monocytes and monocyte-derived macrophages (MDM) isolated from healthy smokers and non-smokers, and to evaluate the possible direct effect of nicotine. PPAR-gamma protein was detected by Western blot and quantification was performed by calculating the ratio between PPAR-gamma and beta-actin protein expression.