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Colorectal Cancer (CRC) is the third most frequent type of cancer worldwide. In the past few years, studies have revealed a protective effect of metformin (MET-an anti-hyperglycemic drug, used to treat type 2 diabetes), against CRC. The protective effect of MET has been associated with AMPK activation (and mTOR inhibition), resulting in suppressed protein synthesis, and reduced cell proliferation in malignant transformed cells. To elucidate new mechanisms for the protective effect of metformin, we evaluated the oxidative stress and inflammatory process modulation, since these processes are strictly involved in colorectal carcinogenesis. The present study evaluated the protective effect of MET in a CRC model induced by 1,2-dimethylhydrazine (DMH) in Balb/c female mice. The simultaneous/continuous treatment (administration of MET and DMH simultaneously), revealed protective activity of MET, preventing the formation of aberrant crypt foci (ACF) in 71.4% at distal colon sections, and was able to restore basal labeling of apoptosis. Treatment with MET also reduced the inflammatory process induced by DMH, resulting in of the reduction of oxidative stress and nitric oxide related parameters. © 2016 Wiley Periodicals, Inc.

TGF-β1 and oxidative stress are involved in cancer progression, but in melanoma, their role is still controversial. Our aim was to correlate plasma TGF-β1 levels and systemic oxidative stress biomarkers in patients with melanoma, with or without disease metastasis, to understand their participation in melanoma progression. Thirty patients were recruited for melanoma surveillance, together with 30 healthy volunteers. Patients were divided into two groups: Non-metastasis, comprising patients with tumor removal and no metastatic episode for 3 years; and Metastasis, comprising patients with a metastatic episode. The plasmatic cytokines TGF-β1, IL-1 β, and TNF-α were analyzed by ELISA. For oxidative stress, the following assays were performed: malondialdehyde (MDA), advanced oxidation protein products (AOPP) levels, total radical-trapping antioxidant parameter (TRAP) and thiol in plasma, and lipid peroxidation, SOD and catalase activity and GSH in erythrocytes. Patients with a metastatic episode had less circulating TGF-β1 and increased TRAP, thiol, AOPP and lipid peroxidation levels. MDA was increased in both melanoma groups, while catalase, GSH, and IL-1β was decreased in Non-metastasis patients. Significant negative correlations were observed between TGF-β1 levels and systemic MDA, and TGF-β1 levels and systemic AOPP, while a positive correlation was observed between TGF-β1 levels and erythrocyte GSH. Lower levels of TGF-β1 were related to increased oxidative stress in Metastasis patients, reinforcing new evidence that in melanoma TGF-β1 acts as a tumor suppressor, inhibiting tumor relapse. These findings provide new knowledge concerning this cancer pathophysiology, extending the possibilities of investigating new therapies based on this evidence.

O gengibre (Zingiber officinale Roscoe) vem sendo utilizado tanto na medicina natural tradicional quanto contemporânea, sendo descritos mais de 115 componentes do gengibre fresco e seco. Dentre esses componentes, os compostos fenólicos, gingerol e o shoagol, têm sido amplamente estudados apresentando diferentes propriedades destas moléculas como efeito antipirético, analgésico, inibidor da angiogênese, atividades imunomoduladoras, entre outras. Esta revisão tem como objetivo apresentar os componentes do gengibre assim como o seu efeito antagônico sobre o lipopolissacarídeo (LPS), propriedade anti-inflamatória e possível via de sinalização envolvida. O efeito do gengibre sobre o LPS consiste na inibição da produção de Interleucina 12 (IL -12), resultando em menor ativação de macrófagos induzidos pelo LPS; diminuição na expressão de moléculas co-estimulatórias e expressão de MHC classe II e diminuição de Interleucina 2 (IL-2), suprimindo a ativação e proliferação de células T CD4+. A propriedade anti-inflamatória do composto está relacionada com a capacidade de modular o linfócito T, de forma a inibir a eosinofilia, reduzir a quantidade de mastócitos, inibir a liberação de IL-4 e reduzir a resposta Th2. Além disso, pode ocorrer inibição da translocação da subunidade p65 para o núcleo e inibição da fosforilação do complexo IkB-α, culminando com a diminuição dos níveis de COX-2. Através deste estudo, podemos concluir que componentes do gengibre podem atuar antagonicamente sobre o efeito de ativação do LPS em macrófagos, conduzindo um efeito imunomodulador e anti-inflamatório, no qual a possível via de sinalização afetada seja do NFkB com envolvimento das MAPquinases. Palavras-Chave: Zingiber officinale Roscoe. Gingerol. Shogaol. Inflamação AbstractGinger (Zingiber officinale Roscoe) has been used in both traditional and contemporary natural medicine, with over 115 described components of fresh and dried ginger. Among these components, the phenolic compounds: gingerol and shoagol have been broadly studied and these molecules have different properties, such as antipyretic, analgesic, angiogenesis inhibitor, immunomodulatory activities, among others. This review aims to present the components of ginger as well as its antagonistic effect on LPS, anti -inflammatory property and possible signaling pathway involved. The effect of ginger on lipopolysaccharide (LPS) consists in inhibiting the production of interleukin 12 (IL-12), resulting in reduced activation of macrophages induced by LPS; decreased expression of co-stimulatory molecules and MHC class II expression and reduced IL-2, impairing the activation and proliferation of CD4 + T cells. The anti-inflammatory property of the compound is associated with the ability to modulate T lymphocyte, in order to inhibit eosinophilia, reducing the amount of mast cells and inhibit the release