Exercise inhibits the effects of smoke-induced COPD involving modulation of STAT3

Purpose . Evaluate the participation of STAT3 in the e ff ects of aerobic exercise (AE) in a model of smoke-induced COPD. Methods . C57Bl/6 male mice were divided into control, Exe, COPD, and COPD+Exe groups. Smoke were administered during 90 days. Treadmill aerobic training begun on day 61 until day 90. Pulmonary in fl ammation, systemic in fl ammation, the level of lung emphysema, and the airway remodeling were evaluated. Analysis of integral and phosphorylated expression of STAT3 by airway epithelial cells, peribronchial leukocytes, and parenchymal leukocytes was performed. Results . AE inhibited smoke-induced accumulation of total cells ( p <0 001 ), lymphocytes ( p <0 001 ), and neutrophils ( p <0 001 ) in BAL, as well as BAL levels of IL- 1 β ( p <0 001 ), CXCL1 ( p <0 001 ), IL-17 ( p <0 001 ), and TNF- α ( p <0 05 ), while increased the levels of IL-10 ( p <0 001 ). AE also inhibited smoke-induced increases in total leukocytes ( p <0 001 ), neutrophils ( p <0 05 ), lymphocytes ( p <0 001 ), and monocytes ( p <0 01 ) in blood, as well as serum levels of IL-1 β ( p <0 01 ), CXCL1 ( p <0 01 ), IL-17 ( p <0 05 ), and TNF- α ( p <0 01 ), while increased the levels of IL-10 ( p <0 001 ). AE reduced smoke-induced emphysema ( p <0 001 ) and collagen fi ber accumulation in the airways ( p <0 001 ). AE reduced smoke-induced STAT3 and phospho-STAT3 expression in airway epithelial cells ( p <0 001 ), peribronchial leukocytes ( p <0 001 ), and parenchymal leukocytes ( p <0 001 ). Conclusions .AE reduces smoke-induced COPD phenotype involving STAT3

Effects of enamel matrix derivative and transforming growth factor-β1 on human osteoblastic cells

<p>Abstract</p> <p>Background</p> <p>Extracellular matrix proteins are key factors that influence the regenerative capacity of tissues. The objective of the present study was to evaluate the effects of enamel matrix derivative (EMD), TGF-β1, and the combination of both factors (EMD+TGF-β1) on human osteoblastic cell cultures.</p> <p>Methods</p> <p>Cells were obtained from alveolar bone of three adult patients using enzymatic digestion. Effects of EMD, TGF-β1, or a combination of both were analyzed on cell proliferation, bone sialoprotein (BSP), osteopontin (OPN) and alkaline phosphatase (ALP) immunodetection, total protein synthesis, ALP activity and bone-like nodule formation.</p> <p>Results</p> <p>All treatments significantly increased cell proliferation compared to the control group at 24 h and 4 days. At day 7, EMD group showed higher cell proliferation compared to TGF-β1, EMD + TGF-β1 and the control group. OPN was detected in the majority of the cells for all groups, whereas fluorescence intensities for ALP labeling were greater in the control than in treated groups; BSP was not detected in all groups. All treatments decreased ALP levels at 7 and 14 days and bone-like nodule formation at 21 days compared to the control group.</p> <p>Conclusions</p> <p>The exposure of human osteoblastic cells to EMD, TGF-β1 and the combination of factors <it>in vitro </it>supports the development of a less differentiated phenotype, with enhanced proliferative activity and total cell number, and reduced ALP activity levels and matrix mineralization.</p

Leishmania donovani nucleoside hydrolase (NH36) Domains induce T-cell cytokine responses in human Visceral leishmaniasis

Development of immunoprotection against visceral leishmaniasis (VL) focused on the identification of antigens capable of inducing a Th1 immune response. Alternatively, antigens targeting the CD8 and T-regulatory responses are also relevant in VL pathogenesis and worthy of being included in a preventive human vaccine. We assessed in active and cured patients and VL asymptomatic subjects the clinical signs and cytokine responses to the Leishmania donovani nucleoside hydrolase NH36 antigen and its N-(F1), central (F2) and C-terminal (F3) domains. As markers of VL resistance, the F2 induced the highest levels of IFN-gamma, IL-1 beta, and TNF-a and, together with F1, the strongest secretion of IL-17, IL-6, and IL-10 in DTH+ and cured subjects. F2 also promoted the highest frequencies of CD3(+)CD4(+)IL-2(+)TNF-alpha-IFN-gamma(-), CD3(+)CD4(+)IL-2(+)TNF-alpha+IFN-gamma(-), CD3(+)CD4(+)IL-2(+)TNF-alpha-IFN-gamma(+), and CD3(+)CD4(+)IL-2(+)TNF-alpha+IFN-gamma(+) T cells in cured and asymptomatic subjects. Consistent with this, the IFN-gamma increase was correlated with decreased spleen (R = -0.428, P = 0.05) and liver sizes (R = -0.428, P = 0.05) and with increased hematocrit counts (R = 0.532, P = 0.015) in response to F1 domain, and with increased hematocrit (R = 0.512, P 0.02) and hemoglobin counts (R = 0.434, P = 0.05) in response to F2. Additionally, IL-17 increases were associated with decreased spleen and liver sizes in response to F1 (R = -0.595, P = 0.005) and F2 (R = -0.462, P = 0.04). Conversely, F1 and F3 increased the CD3(+)CD8(+)IL-2(+)TNF-alpha-IFN-gamma(-), CD3(+)CD8(+)IL-2(+)TNF-alpha+IFN-gamma(-), and CD3(+)CD8(+)IL-2(+)TNF-alpha+IFN-gamma(+) T cell frequencies of VL patients correlated with increased spleen and liver sizes and decreased hemoglobin and hematocrit values. Therefore, cure and acquired resistance to VL correlate with the CD4(+)-Th1 and Th-17 T-cell responses to F2 and F1 domains. Clinical VL outcomes, by contrast, correlate with CD8(+) T-cell responses against F3 and F1, potentially involved in control of the early infection. The in silico-predicted NH36 epitopes are conserved and bind to many HL-DR and HLA and B allotypes. No human vaccine against Leishmania is available thus far. In this investigation, we identified the NH36 domains and epitopes that induce CD4(+) and CD8(+) T cell responses, which could be used to potentiate a human universal T-epitope vaccine against leishmaniasis.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ)Fundacao Carlos Chagas de Amparo a Pesquisa do Estado de Rio de Janeiro (FAPERJ)Coordenacao de Aperfeicoamento de Pessoal de Nivel SuperiorCNPQ-Fundacao de Apoio a Pesquisa e a Inovacao Tecnologica do Estado de Sergipe-PRONEXFAPITEC CNPq (PRONEX)VII PN I+D+IFEDER FundsUniv Fed Sergipe HU UFS, Dept Med, Univ Hosp, Mol Biol Lab, Aracaju, Sergipe, BrazilUniv Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Dept Microbiol Geral, Lab Biol Bioquim Leishmania, Rio De Janeiro, RJ, BrazilPontificia Univ Catolica Rio de Janeiro, Lab Biometrol, Programa Posgrad Metrol, Rio De Janeiro, RJ, BrazilInst Salud Carlos III, WHO Collaborating Ctr Leishmaniasis, Ctr Nacl Microbiol, Madrid, Comunidad De Ma, SpainInst Oswaldo Cruz, Lab Imunoparasitol, Rio De Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Inst Microbiologia Paulo de Goes, Dept Imunol, Lab Imunol Integrada, Rio De Janeiro, RJ, BrazilUniv Sao Paulo, Fac Med, Inst Invest Imunol, Sao Paulo, BrazilUniv Fed Sao Paulo UNIFESP, Dept Microbiol Imunol & Parasitol, Lab Vacinas Expt, Sao Paulo, SP, BrazilUniv Fed Rio de Janeiro, Fac Med, Lab Imunohematol, Hosp Univ Clementino Fraga Filho, Rio De Janeiro, RJ, BrazilUniv Fed Sergipe HU UFS, Dept Morfol, Aracaju, Sergipe, BrazilUniv Fed Sao Paulo UNIFESP, Dept Microbiol Imunol & Parasitol, Lab Vacinas Expt, Sao Paulo, SP, BrazilCNPq: 300639/2003-1CNPq: 310977/2014-2CNPq: 310797/2015-2CNPq: 404400/2012-4FAPERJ: E-26-201.583/2014FAPERJ: E-26-102957/2011FAPERJ: E-26/111.682/2013FAPERJ: E-26/102415/2010FAPERJ: E-26/201747/2015CAPES: 23038.005304/2011-0CNPQ-PRONEX: 12/2009FAPITEC CNPq (PRONEX): 019.203.02712/2009-8FEDER Funds: RICET RD12/0018/0003Web of Scienc

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu