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.

Diacylglycerol kinase is required for HGF-induced invasiveness and anchorage-independent growth of MDA-MB-231 breast cancer cells.

Background: Estrogen receptor (ER)-negative breast cancers have a worse prognosis than ER-positive cancers, being more aggressive and overexposed to stimuli leading to their progression. Hepatocyte growth factor (HGF) has been associated with proliferation, migration and invasion of tumor cells, and several tumors, including those of breast cancer, produce HGF and overexpress its receptor. Diacylglycerol kinases (Dgks), which phosphorylate diacylglycerol to phosphatidic acid, are key regulators of cell signaling.

Erionite and asbestos differently cause transformation of human mesothelial cells.

Malignant mesothelioma (MM) is an aggressive tumor associated with environmental or occupational exposure to asbestos fibers. Erionite is a fibrous zeolite, morphologically similar to asbestos and it is assumed to be even more carcinogenic. Onset and progression of MM has been suggested as the result of the cooperation between asbestos and other cofactors, such as SV40 virus infection.

Proteomic characterization of copper stress response in Cannabis sativa roots.

Cannabis sativa is an annual herb with very high biomass and capability to absorb and accumulate heavy metals in roots and shoots; it is therefore a good candidate for phytoremediation of soils contaminated with metals. Copper is an essential micronutrient for all living organisms, it participates as an important redox component in cellular electron transport chains; but is extremely toxic to plants at high concentrations. The aim of this work was to investigate copper effects on the root proteome of C.

Preliminary data suggestive of a novel translational approach to mesothelioma treatment: imatinib mesylate with gemcitabine or pemetrexed.

Background: Malignant mesothelioma is a cancer which is refractory to current treatments. Imatinib mesylate is a selective inhibitor of tyrosine kinases such as bcr-abl, c-Kit, c-Fms and platelet derived growth factor receptor beta (PDGFRbeta). PDGFRbeta is often overexpressed in mesothelioma cells and is a therapeutic target for imatinib in some solid tumours.

Geldanamycins trigger a novel Ron degradative pathway, hampering oncogenic signaling.

Ron, the tyrosine kinase receptor for macrophage-stimulating protein is responsible for proliferation and migration of cells from different tissues. Ron can acquire oncogenic potential by single point mutations in the kinase domain, and dysregulated Ron signaling has been involved in the development of different human cancers. We have previously shown that ligand-activated Ron recruits the negative regulator c-Cbl, which mediates its ubiquitylation and degradation.

Macrophage-stimulating protein differently affects human alveolar macrophages from smoker and non-smoker patients: evaluation of respiratory burst, cytokine release and NF-kappaB pathway.

Macrophage activation is a key feature of inflammatory reactions occurring during bacterial infections, immune responses and tissue injury. We previously demonstrated that human macrophages of different origin express the tyrosine kinase receptor recepteur d'origine nantaise, the human receptor for MSP (RON) and produce superoxide anion (O(2)(-)) when challenged with macrophage-stimulating protein (MSP), the endogenous ligand for RON. This study was aimed to evaluate the role of MSP in alveolar macrophages (AM) isolated from healthy volunteers and patients with interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis), either smokers or non-smokers, by evaluating the respiratory burst, cytokine release and nuclear factor-kappa B (NF-kappaB) activation.

Cardiovascular dysautonomia as a cause of falls in Parkinson's disease.

Parkinson's disease (PD) patients have a ninefold increased risk of recurring falls compared to healthy controls. The risk of falling due to cardiovascular dysautonomia (CVD) is not quantifiable. But, CVD is an integral part of the disease and at least 20% of PD patients suffer from orthostatic hypotension, an expression of CVD.

Role of ghrelin in the regulation of appetite in children.

Ghrelin, the new recently discovered hormone, is a 28 amino-acid acylated peptide predominantly produced by the stomach characterized by a strong GH-releasing activity mediated by the hypothalamic-pituitary GH secretagogues (GHSs) receptors. Ghrelin and GHSs, acting on central and peripheral receptors, exert other actions such as stimulation of ACTH and prolactin secretion, influence on insulin secretion and glucose metabolism, orexigenic effect and modulatory activity on the neuroendocrine and metabolic response to starvation, influence on exocrine gastro-entero-pancreatic functions, cardiovascular activities and modulation of cell proliferation and apoptosis. The wide spectrum of ghrelin action requires further studies to provide critical information on the role of ghrelin and the potential perspectives of its analogues in the clinical practice.

Oral glucose load inhibits circulating ghrelin levels to the same extent in normal and obese children.

Objective: The presence of both the GH secretagogue (GHS) receptor and ghrelin in the pancreas indicates an involvement of this hormone in glucose metabolism. Ghrelin secretion is increased by fasting and energy restriction, decreased by food intake, glucose load, insulin and somatostatin in normal adults; however, food intake is not able to inhibit circulating ghrelin levels in children, suggesting that the profile of ghrelin secretion in children is different from that in adults. Moreover, how ghrelin secretion is regulated in childhood as a function of fat mass is still unclear.

Ghrelin: a new hormone with endocrine and non-endocrine activities.

Ghrelin, the new and recently discovered hormone, is a 28 amino-acid acylated peptide predominantly produced by the stomach, characterized by a strong GH-releasing activity mediated by the hypothalamic-pituitary GH Secretagogues (GHSs) receptors. Ghrelin and GHSs, acting on central and peripheral receptors, exert other actions such as: stimulation of ACTH and prolactin secretion; influence insulin secretion and glucose metabolism; have an orexigenic effect and modulatory activity on the neuroendocrine and metabolic response to starvation; influencing exocrine gastro-entero-pancreatic functions; influencing cardiovascular activities and modulation of cell proliferation and apoptosis. With the discovery of ghrelin and the characterization of these GH-independent biological activities, we have to pay more attention to these molecules as candidate drugs for the treatment of pathophysiological conditions including those unrelated to GH secretion disorders.

Thysanoptera dermatitis.

Thysanoptera dermatitis is caused by the bite of small (1-2 mm) insects (generally thrips). Thrips usually feed on the juices of vegetables but if they reach human skin they can suck the epidermal lymph after biting. The cutaneous lesions formed are small pink and itchy papules localized mainly on the trunk and the arms.

SV40-dependent AKT activity drives mesothelial cell transformation after asbestos exposure.

Human malignant mesothelioma is an aggressive cancer generally associated with exposure to asbestos, although SV40 virus has been involved as a possible cofactor by a number of studies. Asbestos fibers induce cytotoxicity in human mesothelial cells (HMC), although cell survival activated by key signaling pathways may promote transformation. We and others previously reported that SV40 large T antigen induces autocrine loops in HMC and malignant mesothelioma cells, leading to activation of growth factor receptors.

School-based prevention for illicit drugs' use.

Background: Drug addiction is a chronic, relapsing disease. Primary interventions should be aimed to reduce first use, or prevent the transition from experimental use to addiction. School is the appropriate setting for preventive interventions.

Expression of functional NK1 receptors in human alveolar macrophages: superoxide anion production, cytokine release and involvement of NF-kappaB pathway.

1 Substance P (SP) is deeply involved in lung pathophysiology and plays a key role in the modulation of inflammatory-immune processes. We previously demonstrated that SP activates guinea-pig alveolar macrophages (AMs) and human monocytes, but a careful examination of its effects on human AMs is still scarce. 2 This study was undertaken to establish the role of SP in human AM isolated from healthy smokers and non-smokers, by evaluating the presence of tachykinin NK(1) receptors (NK-1R) and SP's ability to induce superoxide anion (O(2)(-)) production and cytokine release, as well as activation of the nuclear factor-kappaB (NF-kappaB) pathway.

Cellular and molecular facets of keratinocyte reepithelization during wound healing.

Cutaneous wound healing is a highly coordinated physiological process that rapidly and efficiently restores skin integrity. Reepithelization is a crucial step during wound healing, which involves migration and proliferation of keratinocytes to cover the denuded dermal surface. Recent advances in wound biology clarified the molecular pathways governing keratinocyte reepithelization at wound sites.

Anti-inflammatory drugs and tumor necrosis factor-alpha production from monocytes: role of transcription factor NF-kappa B and implication for rheumatoid arthritis therapy.

Inhibition of tumor necrosis factor-alpha (TNF-alpha) represents a relevant target in rheumatoid arthritis therapy. Besides inhibiting cyclooxygenase, anti-inflammatory drugs can affect the activation of transcription factors. We investigated the ability of dexamethasone, indomethacin, and rofecoxib to modulate nuclear factor-kappaB (NF-kappaB) activation and TNF-alpha release from human monocytes challenged with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA).

The structure of Rigidoporus lignosus Laccase containing a full complement of copper ions, reveals an asymmetrical arrangement for the T3 copper pair.

Laccase is a multicopper blue oxidase that couples the four-electron reduction of oxygen with the oxidation of a broad range of organic substrates, including phenols and arylamines. The enzyme is the object of intense biotechnological research, due to its employment in bioremediation of soils and water as well as in other biotechnological applications. We report here the cDNA and protein sequences, the post-translational modifications, the crystallization and X-ray structure determination of a laccase from the white-rot fungus Rigidoporus lignosus.

Involvement of beta(1) integrin in betaAP-induced apoptosis in human neuroblastoma cells.

Integrin-mediated cell adhesion is required for cell survival and differentiation. Recently, integrins have been proposed as a target for beta-amyloid peptide (betaAP) neurotoxicity. We report here that treatment with betaAP (1-42) or with the active betaAP fragment (25-35) induced a great deal of apoptosis in SK-N-BE and SH-SY5Y cell lines.

Centripetal approach to the facial nerve in parotid surgery: personal experience.

There is particular interest in parotid surgery on account of the close relationship between the gland and the extrapetrous facial nerve. The seventh cranial nerve is generally located by means of an anterograde or proximal surgical identification technique aimed at identifying the facial nerve at its point of exit from the stylomastoid canal. There are very few reports in the literature on retrograde or centripetal identification techniques, which may be adapted to the morphology of the neoformation limiting surgical access, in order to isolate the nerve from its peripheral rami.

Protein phosphatase 1 binds to phospho-Ser-1394 of the macrophage-stimulating protein receptor.

The tyrosine kinase Ron, receptor for MSP (macrophage-stimulating protein), displays several serine residues of unknown functions. Using [(32)P]H(3)PO(4) metabolic labelling, we found that Ron is serine-phosphorylated and dephosphorylated in vitro by PP1 (protein phosphatase 1). PP1 associates with Ron obtained from cells of different origins.

The MSP receptor regulates alpha6beta4 and alpha3beta1 integrins via 14-3-3 proteins in keratinocyte migration.

Growth factors, integrins, and the extracellular matrix (ECM) are known to play key roles in epidermal wound healing, although the interplay between these proteins is not fully understood. We show that growth factor macrophage stimulating protein (MSP)- and its receptor Ron-mediated PI3K activation in keratinocytes induces phosphorylation of both Ron and alpha6beta4 integrin at specific 14-3-3 binding sites. Consequently, a Ron/alpha6beta4 complex formed via 14-3-3 binding displaces alpha6beta4 from its location at hemidesmosomes (structures supporting cell adhesion) and relocalizes it to lamellipodia.