Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response.

It has recently been reported that phycocyanin, a biliprotein found in the blue-green microalgae Spirulina, exerts anti-inflammatory effects in some animal models of inflammation. Taking into account these findings, we decided to elucidate whether phycocyanin might exert also inhibitory effects in the induced allergic inflammatory response and on histamine release from isolated rat mast cells. In in vivo experiments, phycocyanin (100, 200 and 300mg/kg post-orally (p.o.)) was administered 1 h before the challenge with 1 microg of ovalbumin (OA) in the ear of mice previously sensitized with OA. One hour later, myeloperoxidase activity and ear edema were assessed. Phycocyanin significantly reduced both parameters. In separate experiments, phycocyanin (100 and 200 mg/kg p.o.) also reduced the blue spot area induced by intradermal injections of histamine, and the histamine releaser compound 48/80 in rat skin. In concordance with the former results, phycocyanin also significantly reduced histamine release induced by compound 48/80 from isolated peritoneal rat mast cells. The inhibitory effects of phycocyanin were dose dependent. Taken together, our results suggest that inhibition of allergic inflammatory response by phycocyanin is mediated, at least in part, by inhibition of histamine release from mast cells

Estoc: New approach warrants long-term support to the oceanic observational program

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A model based on the quantification of complement C4c, CYFRA 21-1 and CRP exhibits high specificity for the early diagnosis of lung cancer

Lung cancer screening detects early-stage cancers, but also a large number of benign nodules. Molecular markers can help in the lung cancer screening process by refining inclusion criteria or guiding the management of indeterminate pulmonary nodules. In this study, we developed a diagnostic model based on the quantification in plasma of complement-derived fragment C4c, cytokeratin fragment 21-1 (CYFRA 21-1) and C-reactive protein (CRP). The model was first validated in two independent cohorts, and showed a good diagnostic performance across a range of lung tumor types, emphasizing its high specificity and positive predictive value. We next tested its utility in two clinically relevant contexts: assessment of lung cancer risk and nodule malignancy. The scores derived from the model were associated with a significantly higher risk of having lung cancer in asymptomatic individuals enrolled in a computed tomography (CT)-screening program (OR = 1.89; 95% CI = 1.20–2.97). Our model also served to discriminate between benign and malignant pulmonary nodules (AUC: 0.86; 95% CI = 0.80–0.92) with very good specificity (92%). Moreover, the model performed better in combination with clinical factors, and may be used to reclassify patients with intermediate-risk indeterminate pulmonary nodules into patients who require a more aggressive work-up. In conclusion, we propose a new diagnostic biomarker panel that may dictate which incidental or screening-detected pulmonary nodules require a more active work-up

Theory of low frequency magnetoelectric coupling in magnetostrictive-piezoelectric bilayers

A theoretical model is presented for low-frequency magnetoelectric (ME) effects in bilayers of magnetostrictive and piezoelectric phases. A novel approach, the introduction of an interface coupling parameter k, is proposed for the consideration of actual boundary conditions at the interface. An averaging method is used to estimate effective material parameters. Expressions for ME voltage coefficients are obtained by solving elastostatic and electrostatic equations. We consider both unclamped and rigidly clamped bilayers and three different field orientations of importance: (i) longitudinal fields in which the poling field, bias field and ac fields are all parallel to each other and perpendicular to the sample plane; (ii) transverse fields for magnetic fields parallel to each other and perpendicular to electric fields, and (iii) in-plane longitudinal fields for all the fields parallel to each other and to the sample plane. The theory predicts a giant ME coupling for bilayers with cobalt ferrite (CFO), nickel ferrite (NFO), or lanthanum strontium manganite (LSMO) for the magnetostrictive phase and barium titanate (BTO) or lead zirconate titanate (PZT) for the piezoelectric phase.Comment: To be published in Physical Review B, August 1, 200

YES1 drives lung cancer growth and progression and predicts sensitivity to dasatinib

Rationale: The characterization of new genetic alterations is essential to assign effective personalized therapies in non–small cell lung cancer (NSCLC). Furthermore, finding stratification biomarkers is essential for successful personalized therapies. Molecular alterations of YES1, a member of the SRC (proto-oncogene tyrosine-protein kinase Src) family kinases (SFKs), can be found in a significant subset of patients with lung cancer. Objectives: To evaluate YES1 (v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1) genetic alteration as a therapeutic target and predictive biomarker of response to dasatinib in NSCLC. Methods: Functional significance was evaluated by in vivo models of NSCLC and metastasis and patient-derived xenografts. The efficacy of pharmacological and genetic (CRISPR [clustered regularly interspaced short palindromic repeats]/Cas9 [CRISPR-associated protein 9]) YES1 abrogation was also evaluated. In vitro functional assays for signaling, survival, and invasion were also performed. The association between YES1 alterations and prognosis was evaluated in clinical samples. Measurements and Main Results: We demonstrated that YES1 is essential for NSCLC carcinogenesis. Furthermore, YES1 overexpression induced metastatic spread in preclinical in vivo models. YES1 genetic depletion by CRISPR/Cas9 technology significantly reduced tumor growth and metastasis. YES1 effects were mainly driven by mTOR (mammalian target of rapamycin) signaling. Interestingly, cell lines and patient-derived xenograft models with YES1 gene amplifications presented a high sensitivity to dasatinib, an SFK inhibitor, pointing out YES1 status as a stratification biomarker for dasatinib response. Moreover, high YES1 protein expression was an independent predictor for poor prognosis in patients with lung cancer. Conclusions: YES1 is a promising therapeutic target in lung cancer. Our results provide support for the clinical evaluation of dasatinib treatment in a selected subset of patients using YES1 status as predictive biomarker for therapy

Influence of C-phycocyanin on hepatocellular parameters related to liver oxidative stress and Kupffer cell functioning

Objectives: Kupffer cells, liver macrophages involved in immunomodulation, phagocytosis, and biochemical attack, can induce cytotoxicity and inflammation when their activity is exacerbated. The aim of this study was to evaluate the effects of C-phycocyanin on Kupffer cell functioning considering its antioxidant and anti-inflammatory properties. Materials and methods: Actions of C-phycocyanin on colloidal carbon phagocytosis, carbon-induced respiratory burst activity, and sinusoidal lactate dehydrogenase (LDH) release were studied in isolated perfused mouse liver. The influence of C-phycocyanin on tumor necrosis factor-α (TNF-α) and nitrite levels in serum and liver nitric oxide synthase (NOS) activity was assessed in rats subjected to thyroid hormone (T3) administration, a condition known to underlie hepatic oxidative stress comprising an increased Kupffer cell activity. Results: C-phycocyanin elicited a concentration-dependent inhibition of carbon phagocytosis and carbon-induced O2 u

Protective affects of lobenzarit against allyl alcohol-induced hepatoxicity in mice and rats.

The protective effects of lobenzarit disodium against the toxicity of allyl alcohol were investigated in vitro using isolated rat hepatocytes and in vivo using mice. In mice, at i.p. doses of 25, 50 and 100 mg/kg lobenzarit significantly decreased the activity of alanine amino transferase (ALT) in serum and the concentration of malondialdehyde (MDA) in liver homogenates, both of which were increased by allyl alcohol at a dose of 64 mg/kg. At concentrations of 0.2 and 0.3 mM, lobenzarit reduced the release of lactate dehydrogenase (LDH) and the levels of malondialdehyde (MDA) induced by 0.4 mM of allyl alcohol in isolated rat hepatocytes. However, lobenzarit did not increase the levels of reduced glutathione (GSH) depleted by allyl alcohol in any of the two experimental models. The protective effects of lobenzarit were dose- and concentration-dependent and they were most obvious when lobenzarit was administered 30 min before allyl alcohol. It is concluded that lobenzarit exerts the observed protective effects most likely by its antioxidant properties

Estoc: New approach warrants long-term support to the oceanic observational program

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