Background and AimsMesenchymal stromal cells (MSCs) were shown to have immunomodulatory activity and have been applied for treating immune-mediated disorders. We compared the homing and therapeutic action of cryopreserved subcutaneous adipose tissue (AT-MSCs) and bone marrow-derived mesenchymal stromal cells (BM-MSCs) in rats with trinitrobenzene sulfonic acid (TNBS)–induced colitis.MethodsAfter colonoscopic detection of inflammation AT-MSCs or BM-MSCs were injected intraperitoneally. Colonoscopic and histologic scores were obtained. Density of collagen fibres and apoptotic rates were evaluated. Cytokine levels were measured in supernatants of colon explants. For cell migration studies MSCs and skin fibroblasts were labelled with Tc-99m or CM-DiI and injected intraperitonealy or intravenously.ResultsIntraperitoneal injection of AT-MSCs or BM-MSCs reduced the endoscopic and histopathologic severity of colitis, the collagen deposition, and the epithelial apoptosis. Levels of TNF-α and interleukin-1β decreased, while VEGF and TGF-β did not change following cell-therapy. Scintigraphy showed that MSCs migrated towards the inflamed colon and the uptake increased from 0.5 to 24 h. Tc-99m-MSCs injected intravenously distributed into various organs, but not the colon. Cm-DiI-positive MSCs were detected throughout the colon wall 72 h after inoculation, predominantly in the submucosa and muscular layer of inflamed areas.ConclusionsIntraperitoneally injected cryopreserved MSCs home to and engraft into the inflamed colon and ameliorate TNBS-colitis.

In recent years, the functions of glial cells, namely, astrocytes and microglia, have gained prominence in several diseases of the central nervous system, especially in glioblastoma (GB), the most malignant primary brain tumor that leads to poor clinical outcomes. Studies showed that microglial cells or astrocytes play a critical role in promoting GB growth. Based on the recent findings, the complex network of the interaction between microglial/astrocytes cells and GB may constitute a potential therapeutic target to overcome tumor malignancy. In the present review, we summarize the most important mechanisms and functions of the molecular factors involved in the microglia or astrocytes–GB interactions, which is particularly the alterations that occur in the cell’s extracellular matrix and the cytoskeleton. We overview the cytokines, chemokines, neurotrophic, morphogenic, metabolic factors, and non-coding RNAs actions crucial to these interactions. We have also discussed the most recent studies regarding the mechanisms of transportation and communication between microglial/astrocytes – GB cells, namely through the ABC transporters or by extracellular vesicles. Lastly, we highlight the therapeutic challenges and improvements regarding the crosstalk between these glial cells and GB.

Prophylactic systemic P2X7-R blockade is effective in the prevention of experimental colitis, probably due to a systemic anti-inflammatory action, interfering with a stress-inflammation amplification loop mediated by P2X7-R.

RESUMODiversos aspectos da cirurgia experimental são ignorados pelos pesquisadores. Este artigo enfatiza padrões éticos, detalhes anatômicos e procedimentos anestésicos com o objetivo de auxiliar na escolha adequada de animais utilizados em laboratório para pesquisas em cirurgia e na educação médica.Descritores: Modelos animais. Cirurgia experimental. Ética. Anatomia. ABSTRACTSeveral aspects of experimental surgery are unknown by the researchers. This article emphasizes ethical standards, anatomical details and anesthetics procedures in order to allow and adequate choice on dealing with laboratory animals in surgical research and medical education.Key words: Animal models. Experimental surgery. Ethics. Anatomy. Introdução e contexto ético-profissionalA pesquisa cirúrgica em animais utilizados em laboratório tem se expandido nas últimas décadas, mormente em decorrência do melhor suporte anestésico, da sofisticação da infra-estrutura material para monitorização contínua peroperatória e de uma busca incessante por modelos que reproduzam condições mórbidas da espécie humana. Os focos principais destas pesquisas têm sido aprimorar o conhecimento acerca dos mecanismos fisiopatológicos de doenças, empreender ensaios terapêuticos com novos fármacos, estudar marcadores biológicos e avaliar novas técnicas com perspectivas de aplicabilidade na espécie humana. A diversidade de cenários que vinculam as necessidades humanas ao uso de animais fomentou, ao longo da história, reflexões éticas, bioéticas, filosóficas e religiosas direcionadas para pesquisa em animais vertebrados 1,2 . Aristóteles (384-322 a.C.), Galeno (131-201), Francis Bacon (1561-1626), William Harvey (1578-1657), Claude Bernard (1813-1878 representam alguns dos atores que se destacaram neste contexto.Todavia, somente por ocasião da segunda guerra mundial, em face das atrocidades cometidas nos campos de concentração, dentre as quais as cruéis experiências em anima nobile, ocorreu uma conscientização mundial para ações concretas capazes de preservar a vida humana 3 . Assim, o Código de Nurenberg (1947) determinou que a experimentação no homem

The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.

The anti-inflammatory effect of mammalian heparin analogues, named dermatan sulfate and heparin, isolated from the ascidian Styela plicata was accessed in a TNBS-induced colitis model in rats. Subcutaneous administration of the invertebrate compounds during a 7-day period drastically reduced inflammation as observed by the normalization of the macroscopic and histological characteristics of the colon. At the molecular level, a decrease in the production of TNF-␣, TGF-␤, and VEGF was observed, as well as a reduction of NF-B and MAPK kinase activation. At the cellular level, the heparin analogues attenuated lymphocyte and macrophage recruitment and epithelial cell apoptosis. A drastic reduction in collagen-mediated fibrosis was also observed. No hemorrhagic events were observed after glycan treatment. These results strongly indicate the potential therapeutic use of these compounds for the treatment of colonic inflammation with a lower risk of hemorrhage when compared with mammalian heparin.

During PSV, PEEP of 5 cmH2O, but not a PEEP of 2 cmH2O, reduced lung damage and inflammatory markers while maintaining epithelial cell integrity.

Variable ventilation improved lung function in both pulmonary acute respiratory distress syndrome and extrapulmonary acute respiratory distress syndrome. Variable ventilation led to more pronounced beneficial effects in biologic marker expressions in pulmonary acute respiratory distress syndrome compared with extrapulmonary acute respiratory distress syndrome but preserved E-cadherin in lung tissue only in extrapulmonary acute respiratory distress syndrome, thus suggesting lower damage to epithelial cells.