Human MDSCs derived from the bone marrow maintain their functional ability but have a reduced frequency of induction in the elderly compared to pediatric donors

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells developing from myeloid progenitors, which are enriched in pathological conditions such as cancer, and are known to inhibit the functions of effector T cells. During aging, several changes occur both at the adaptive and innate immune system level, in a process defined as immunoscenescence. In particular, the low-grade inflammation state observed in the elderly appears to affect hematopoiesis. We previously demonstrated that the combination of GM-CSF and G-CSF drives the in vitro generation of bone marrow-derived MDSCs (BM-MDSCs) from precursors present in human bone marrow aspirates of healthy donors, and that these cells are endowed with a strong immune suppressive ability, resembling that of cancer-associated MDSCs. In the present work we investigated BM-MDSCs induction and functional ability in a cohort of pediatric versus elderly donors. To this aim, we analyzed the differences in maturation stages and ability to suppress T cell proliferation. We found that the ex vivo distribution of myeloid progenitors is similar between pediatric and elderly individuals, whereas after cytokine treatment a significant reduction in the more immature compartment is observed in the elderly. Despite the decreased frequency, BM-MDSCs maintain their suppressive capacity in aged donors. Taken together, these results indicate that in vitro induction of MDSCs from the BM is reduced with aging and opens new hypotheses on the role of age-related processes in myelopoiesis

Immunosuppressive activity of tumor-infiltrating myeloid cells in patients with meningioma

Meningiomas WHO grade I and II are common intracranial tumors in adults that normally display a benign outcome, but are characterized by a great clinical heterogeneity and frequent recurrence of the disease. Although the presence of an immune cell infiltrate has been documented in these tumors, a clear phenotypical and functional characterization of the immune web is missing. Here, we performed an extensive immunophenotyping of peripheral blood and fresh tumor tissue at surgery by multiparametric flow cytometry in 34 meningioma patients, along with immunosuppressive activity of sorted cells of myeloid origin. Four subsets of myeloid cells, phenotypically corresponding to myeloid-derived suppressor cells (MDSCs) are detectable in the blood and in the tumor tissue of patients and three of them are significantly expanded in the blood of patients, but show no evidence of suppressive activity. At the tumor site, a large leukocyte infiltrate is present, predominantly constituted by CD33 myeloid cells, largely composed of macrophages endowed with suppressive activity and significantly expanded in grade II meningioma patients as compared to grade I

Reversible Monoacylglycerol Lipase Inhibitors: Discovery of a New Class of Benzylpiperidine Derivatives.

Monoacylglycerol lipase (MAGL) is the enzyme responsible for the metabolism of 2-arachidonoylglycerol in the brain and the hydrolysis of peripheral monoacylglycerols. Many studies demonstrated beneficial effects deriving from MAGL inhibition for neurodegenerative diseases, inflammatory pathologies, and cancer. MAGL expression is increased in invasive tumors, furnishing free fatty acids as pro-tumorigenic signals and for tumor cell growth. Here, a new class of benzylpiperidine-based MAGL inhibitors was synthesized, leading to the identification of 13, which showed potent reversible and selective MAGL inhibition. Associated with MAGL overexpression and the prognostic role in pancreatic cancer, derivative 13 showed antiproliferative activity and apoptosis induction, as well as the ability to reduce cell migration in primary pancreatic cancer cultures, and displayed a synergistic interaction with the chemotherapeutic drug gemcitabine. These results suggest that the class of benzylpiperidine-based MAGL inhibitors have potential as a new class of therapeutic agents and MAGL could play a role in pancreatic cancer

CARACTERIZAÇÃO DE LIPÍDIOS DE SEMENTES DE CANOLA NA REGIÃO DOS CAMPOS GERAIS, PARANÁ

Uma grande variedade de oleaginosas pode ser utilizada como matéria prima na produção de biodiesel, como soja, algodão e canola entre outras. A Canola (Brassica napus) é uma espécie de oleaginosa que apresenta alto teor de lipídios, sendo largamente utilizada para esse fim em alguns países da Europa. Este trabalho teve como objetivo caracterizar os lipídios de sementes de canola cultivada em Tibagi, região dos Campos Gerais, visando uso na produção de biodiesel. Foram utilizadas sementes colhidas em lavoura comercial da safra de inverno de 2013. O sistema de extração de óleo utilizado foi extração contínua por solvente.  As propriedades dos lipídios obtidos foram determinadas com relação à massa relativa de lipídios, massa específica e  estabilidade  oxidativa,  que  tiveram  média  de  370,4 g kg-1, 873 kg m-³, e 10,01 horas, respectivamente. A composição qualitativa de ácidos graxos foi avaliada pela Espectroscopia de Ressonância Magnética Nuclear de 1H. Pelas análises foi constatada a presença de ácidos Oleico (C18:1), Linoléico (C18:2) e Linolênico (C18:3)

Validation of the Body Concealment Scale for Scleroderma (BCSS): Replication in the Scleroderma Patient-centered Intervention Network (SPIN) Cohort

© 2016 Elsevier Ltd Body concealment is an important component of appearance distress for individuals with disfiguring conditions, including scleroderma. The objective was to replicate the validation study of the Body Concealment Scale for Scleroderma (BCSS) among 897 scleroderma patients. The factor structure of the BCSS was evaluated using confirmatory factor analysis and the Multiple-Indicator Multiple-Cause model examined differential item functioning of SWAP items for sex and age. Internal consistency reliability was assessed via Cronbach's alpha. Construct validity was assessed by comparing the BCSS with a measure of body image distress and measures of mental health and pain intensity. Results replicated the original validation study, where a bifactor model provided the best fit. The BCSS demonstrated strong internal consistency reliability and construct validity. Findings further support the BCSS as a valid measure of body concealment in scleroderma and provide new evidence that scores can be compared and combined across sexes and ages

Immunosuppressive activity of tumor-infiltrating myeloid cells in patients with meningioma

Meningiomas WHO grade I and II are common intracranial tumors in adults that normally display a benign outcome, but are characterized by a great clinical heterogeneity and frequent recurrence of the disease. Although the presence of an immune cell infiltrate has been documented in these tumors, a clear phenotypical and functional characterization of the immune web is missing. Here, we performed an extensive immunophenotyping of peripheral blood and fresh tumor tissue at surgery by multiparametric flow cytometry in 34 meningioma patients, along with immunosuppressive activity of sorted cells of myeloid origin. Four subsets of myeloid cells, phenotypically corresponding to myeloid-derived suppressor cells (MDSCs) are detectable in the blood and in the tumor tissue of patients and three of them are significantly expanded in the blood of patients, but show no evidence of suppressive activity. At the tumor site, a large leukocyte infiltrate is present, predominantly constituted by CD33+ myeloid cells, largely composed of macrophages endowed with suppressive activity and significantly expanded in grade II meningioma patients as compared to grade I

An Overview of Circulating Biomarkers in Neuroendocrine Neoplasms: A Clinical Guide

: Neuroendocrine neoplasms (NENs) are a heterogeneous group of diseases that are characterized by different behavior and clinical manifestations. The diagnosis and management of this group of tumors are challenging due to tumor complexity and lack of precise and widely validated biomarkers. Indeed, the current circulating mono-analyte biomarkers (such as chromogranin A) are ineffective in describing such complex tumors due to their poor sensitivity and specificity. In contrast, multi-analytical circulating biomarkers (including NETest) are emerging as more effective tools to determine the real-time profile of the disease, both in terms of accurate diagnosis and effective treatment. In this review, we will analyze the capabilities and limitations of different circulating biomarkers focusing on three relevant questions: (1) accurate and early diagnosis; (2) monitoring of disease progression and response to therapy; and (3) detection of early relapse

AVALIAÇÃO DA DECOMPOSIÇÃO TÉRMICA DE ESPÉCIES DE BAMBU POR TERMOGRAVIMETRIA

Rafaela Faber de Campos[1]Pedro Henrique Weirich Neto[2]Sandra Regina Masetto Antunes3Maria Elena Payret Arrúa4 RESUMOA biomassa sempre foi uma das fontes de energia mais utilizadas pelo homem, e como consequência, principalmente, dos problemas enfrentados pelo uso de combustíveis fosseis assume, novamente, grande importância.  Vários tipos de biomassa podem ser citados, como por exemplo, a madeira de árvores, entretanto nem sempre é a mais adequada para geração de energia. O bambu entre outras plantas apresenta estrutura ímpar e, se destaca pela produtividade, podendo-se tornar uma alternativa sustentável para a geração de energia. Neste trabalho foi investigada a estabilidade térmica, consequentemente, a degradação térmica de quatro espécies de bambu in natura e na forma de carvão utilizando a termogravimetria (TGA).  As espécies avaliadas foram Phyllostachys aurea A. C. Rivière (bambu dourado), Chusquea gracilis McClure & Smith (criciúma), Chusquea mimosa McClure & Smith (caratuva) e Merostachys multiramea Hackel (taquara lixa), presentes no centro-sul do estado do Paraná - Brasil. A análise dos resultados de termogravimetria indica que a decomposição destas espécies de bambu ocorre em 3 etapas. Estas etapas são associadas a perda de umidade (primeira), decomposição da hemicelulose e celulose (segunda) e decomposição da lignina (terceira). As espécies se diferenciam na temperatura de velocidade máxima de decomposição devido, provavelmente, às suas distintas composições.