Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases

Physical exercise has beneficial effects on metabolic diseases, and a combined therapeutic regimen of regular exercise and pharmaceutical treatment is often recommended for their clinical management. However, the mechanisms by which exercise produces these beneficial effects are not fully understood. Myokines, a group of skeletal muscle (SkM) derived peptides may play an important part in this process. Myokines are produced, expressed and released by muscle fibers under contraction and exert both local and pleiotropic effects. Myokines such as IL-6, IL-10, and IL-1ra released during physical exercise mediate its health benefits. Just as exercise seems to promote the myokine response, physical inactivity seems to impair it, and could be a mechanism to explain the association between sedentary behavior and many chronic diseases. Myokines help configure the immune-metabolic factor interface and the health promoting effects of physical exercise through the release of humoral factors capable of interacting with other tissues, mainly adipose tissue (AT). AT itself secretes proinflammatory cytokines (adipokines) as a result of physical inactivity and it is well recognized that AT inflammation can lead to the development of metabolic diseases, such as type 2 diabetes mellitus (T2DM) and atherosclerosis. On the other hand, the browning phenotype of AT has been suggested to be one of the mechanisms through which physical exercise improves body composition in overweight/obese individuals. Although, many cytokines are involved in the crosstalk between SkM and AT, in respect of these effects, it is IL-6, IL-15, irisin, and myostatin which seem to have the decisive role in this “conversation” between AT and SkM. This review article proposes to bring together the latest “state of the art” knowledge regarding Myokines and muscle-adipose tissue crosstalk. Furthermore, it is intended to particularly focus on the immune-metabolic changes from AT directly mediated by myokines

Small-RNA characterization of Coffee Leaf Rust races having different virulence profiles

info:eu-repo/semantics/publishedVersio

Real-time MR tracking of AAV gene therapy with betagal-responsive MR probe in a murine model of GM1-gangliosidosis

Transformative results of adeno-associated virus (AAV) gene therapy in patients with spinal muscular atrophy and Leber\u27s congenital amaurosis led to approval of the first two AAV products in the United States to treat these diseases. These extraordinary results led to a dramatic increase in the number and type of AAV gene-therapy programs. However, the field lacks non-invasive means to assess levels and duration of therapeutic protein function in patients. Here, we describe a new magnetic resonance imaging (MRI) technology for real-time reporting of gene-therapy products in the living animal in the form of an MRI probe that is activated in the presence of therapeutic protein expression. For the first time, we show reliable tracking of enzyme expression after a now in-human clinical trial AAV gene therapy (ClinicalTrials.gov: NTC03952637) encoding lysosomal acid beta-galactosidase (betagal) using a self-immolative betagal-responsive MRI probe. MRI enhancement in AAV-treated enzyme-deficient mice (GLB-1(-/-)) correlates with betagal activity in central nervous system and peripheral organs after intracranial or intravenous AAV gene therapy, respectively. With \u3e 1,800 gene therapies in phase I/II clinical trials (ClinicalTrials.gov), development of a non-invasive method to track gene expression over time in patients is crucial to the future of the gene-therapy field

Cachexia-associated adipose tissue morphological rearrangement in gastrointestinal cancer patients

Background and aims: Cachexia is a syndrome characterized by marked involuntary loss of body weight. Recently, adipose tissue (AT) wasting has been shown to occur before the appearance of other classical cachexia markers. We investigated the composition and rearrangement of the extracellular matrix, adipocyte morphology and inflammation in the subcutaneous AT (scAT) pad of gastrointestinal cancer patients. Methods: surgical biopsies for scAT were obtained from gastrointestinal cancer patients, who were signed up into the following groups: cancer cachexia (CC, n = 11), weight‐stable cancer (WSC, n = 9) and weight‐stable control (non‐cancer) (control, n = 7). The stable weight groups were considered as those with no important weight change during the last year and body mass index <25 kg/m2. Subcutaneous AT fibrosis was quantified and characterized by quantitative PCR, histological analysis and immunohistochemistry. Results: the degree of fibrosis and the distribution and collagen types (I and III) were different in WSC and CC patients. CC patients showed more pronounced fibrosis in comparison with WSC. Infiltrating macrophages surrounding adipocytes and CD3 Ly were found in the fibrotic areas of scAT. Subcutaneous AT fibrotic areas demonstrated increased monocyte chemotactic protein 1 (MCP‐1) and Cluster of Differentiation (CD)68 gene expression in cancer patients. Conclusions: our data indicate architectural modification consisting of fibrosis and inflammatory cell infiltration in scAT as induced by cachexia in gastrointestinal cancer patients. The latter was characterized by the presence of macrophages and lymphocytes, more evident in the fibrotic areas. In addition, increased MCP‐1 and CD68 gene expression in scAT from cancer patients may indicate an important role of these markers in the early phases of cancer

Pioglitazone Treatment Increases Survival and Prevents Body Weight Loss in Tumor-Bearing Animals: Possible Anti-Cachectic Effect

Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. the former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ) was proposed to exhibit anticancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. for greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2x10(7)) of Walker 256 tumor cells. the animals were randomly assigned to two experimental groups: TC (tumor + saline-control) and TP5 (tumor + PGZ/5 mg). Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT) depots were collected on days 7 and 14 and stored at -80oC (5 to 7 animals per day/group). the PGZ treatment showed an increase in the survival average of 27.3%(P<0.01) when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p<0.01) on day 14 and 26 compared with the TC group. the treatment also reduced the final tumor mass (53.4%, p<0.05) and anorexia compared with the TC group during late-stage cachexia. the retroperitoneal AT (RPAT) mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-gamma, adiponectin, LPL and C/EBP-alpha from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT) was entirely re-established due to PGZ treatment. Taken together, the results demonstrate beneficial effects of PGZ treatment at both the early and final stages of cachexia.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Mogi das Cruzes, Integrated Grp Biotechnol, Lab Adipose Tissue Biol, Mogi Das Cruzes, BrazilUniv São Paulo, Inst Biomed Sci, Canc Metab Res Grp, São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Physiol Lab, São Paulo, BrazilUniv Estadual Maringa, Dept Physiol Sci, Maringa, Parana, BrazilUniversidade Federal de São Paulo, Dept Biomed Engn, Sao Jose Dos Campos, BrazilBoston Sch Med, Dept Biochem, Boston, MA USAUniversidade Federal de São Paulo, Dept Biomed Engn, Sao Jose Dos Campos, BrazilFAPESP: 2010/51078-1FAPESP: 2008/54091-9FAPESP: 2012/51094-1Web of Scienc

Manual de boas práticas de produção vitivinícola (BPPV)

O Manual de Boas Práticas de Produção Vitivinícola (BPPV) surge no âmbito do Projecto 762 “EnoSafe – Segurança e controlo de qualidade de vinhos: implementação de técnicas rápidas para monitorização e rastreabilidade microbiológica” fi nanciado pelo do Programa AGRO – Medida 8.1., e tem por objectivo sistematizar um conjunto de procedimentos que devem ser aplicados em toda a fi leira vitivinícola. Este Manual resulta de uma extensa consulta de documentos idênticos existentes em vários países, bem como da experiência do grupo de trabalho afecto ao projecto, tomando como princípios a legislação comunitária. Encontrase estruturado como uma lista de verifi cação, tendo cada empresa que adaptar a implementação destes procedimentos à realidade da sua organização. Cada indústria tem as suas próprias necessidades e considerações no que respeita à segurança alimentar. As empresas do sector dos vinhos estão, desde 1 de Janeiro de 2006, abrangidas pelo disposto no Regulamento (CE) nº 852/2004 de 29 de Abril de 2004, que enumera os requisitos a cumprir no que se refere a pessoal, instalações, meios de transporte, equipamentos, abastecimento de água e tratamento de resíduos. No entanto, existem alguns princípios universais aplicados tanto à indústria vitivinícola como a qualquer outra indústria alimentar, pelo que se revela imprescindível a compilação dos princípios mais relevantes das boas práticas de fabrico neste sector. O Manual de BPPV deve ser encarado como um exercício generalista que contempla uma ampla descrição de boas práticas de conduta para a vinha e para o vinho. A sua aplicação requer um esforço acrescido aos profi ssionais do sector que passa pela defi nição de procedimentos e instruções de trabalho adicionais conducentes a uma politica de qualidade. A adopção das BPPV facilitará o desenvolvimento e a introdução dos programas de controlo de qualidade ISO 9000, ou programas de controlo de qualidade total (total quality management, TQM) e de segurança alimentar, como por exemplo o HACCP (hazard analysis control critical point/ análise dos pontos críticos de controlo). O presente documento sugere normas de boas práticas do processo produtivo, mas não indica de forma detalhada como estas devem ser implementadas e controladas. O Manual de BPPV é um pilar importante de qualquer sistema de qualidade e parte integrante de um programa de segurança alimentar, consequentemente as indicações apresentadas não substituem uma análise de HACCP, nem um sistema da qualidade, e não garantem a segurança de um produto no momento do seu consumo. Com a existência do Manual de BPPV, a empresa pode informar os seus colaboradores com maior facilidade quais as práticas aceitáveis/ inaceitáveis e divulgar dados sobre a mesma, com o objectivo de garantir o compromisso e o apoio dos colaboradores a todos os níveis de gestão. Algumas empresas facultam aos seus fornecedores cópias das suas BPPV e exigem o seu cumprimento, outras usam-nas como argumento de venda e para demonstrar aos clientes os princípios e práticas com as quais operam. A adopção destes procedimentos conduz à melhoria do processo produtivo ao nível da segurança e da higiene, à redução de riscos e de exposição a perigos, aumentando a segurança dos produtos para consumo humano. O vinho tem as suas particularidades, pois apresenta um risco mínimo comparado com outros alimentos, o que implica que as medidas descritas não sejam tão rígidas como as estabelecidas para outros produtos alimentares. As Boas Práticas de Produção Vitivinícola (BPPV) constituem um conjunto de princípios, genericamente aceites, e que devem ser aplicados em toda a fi leira vitivinícola. Representam igualmente, uma orientação para profi ssionais que exercem funções na indústria dos vinhos, os quais devem colocar a sua própria experiência na aplicação das práticas descritas. Com este trabalho pretende-se realçar as regras básicas que devem ser seguidas na vinha e nas adegas de forma a assegurar a qualidade fi nal dos produtos obtidos.Ministério de Agricultura. Instituto Nacional de Investigação Agrária e das Pescas (INIAP) – Programa Agro, Medida 8, Acção 8.1.Projecto ENOSAFE – Segurança e controlo de qualidade de vinhos: implementação de técnicas rápidas para monitorização e rastreabilidade microbiológic

Setting performance indicators for coastal marine protected areas: An expert-based methodology

Marine Protected Areas (MPAs) require effective indicators to assess their performance, in compliance with the goals of relevant national and international commitments. Achieving and prioritizing shortlists of multidisciplinary indicators demands a significant effort from specialists to depict the multiple conservation and socioeconomic interests, and the large complexity of natural systems. The present paper describes a structured expert-based methodology (process and outputs) to co-define a list of multidisciplinary MPA performance indicators. This work was promoted by the management authority of coastal MPAs in mainland Portugal to gather a consensual and feasible list of indicators that would guide the design of a future national monitoring program. Hence, Portuguese coastal MPAs served as a case study to develop such a process between 2019 and 2020. In the end, participants (1) agreed on a shortlist of prioritized indicators (i.e., environmental, governance, and socioeconomic indicators) and (2) defined minimum monitoring frequencies for the indicators in this list, compatible with the potential replicability of the associated survey methods. The present approach recommends that management plans incorporate monitoring procedures and survey methods, with a validated list of indicators and associated monitoring periodicity, agreed among researchers, MPA managers and governance experts. The proposed methodology, and the lessons learned from it, can support future processes aiming to define and prioritize MPA performance indicatorsFundação para a Ciência e Tecnologia - FCT, European Maritime and Fisheries Fund (EMFF)info:eu-repo/semantics/publishedVersio