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Objectives: To determine the inflammatory profile of CRSwNP in Brazil and characterize the subgroups of CRSwNP patients in this population through cluster analysis. Study Design: Multicenter cross‐sectional study involving 15 centers representing different regions of Brazil. Subjects and Methods: Clinical data of 166 patients and 80 controls, aged 18 to 70 years old, number of surgeries for CRS, history of asthma and aspirin sensitivity, and Lund‐Mackay scores on CT scans. During nasal endoscopy, we obtained the Lund‐Kennedy scores and collected 2 samples of nasal polyps: one for eosinophil and neutrophil tissue counts and one to quantify different cytokines. Results: 79.6% of our patients had 10 or more eosinophils/HPF. CRSwNP groups exhibited significantly lower concentrations of TNF‐alpha and significantly higher concentrations of IFN‐gamma, CCL11/Eotaxin, CCL24/Eotaxin‐2/MPIF‐2, and CCL26/Eotaxin‐3 versus the control group (Kruskal‐Wallis test). Comparison between CRSwNP groups (≥10 vs <10 eosinophils/HPF) showed no difference in cytokine concentration (Mann‐Whitney test). Hierarchical clustering and PCA according to cytokine concentrations revealed 2 main Clusters, with a significantly higher concentration of all cytokines in Cluster 1 (n = 35) than in Cluster 2 (n = 121), except IL‐6 and IL‐33 (Mann‐Whitney test). According to ROC curve analysis the best cut‐off to differentiate the 2 clusters was 43 eosinophils/HPF. The group with ≥43 presented a higher prevalence of men and a higher Lund‐Mackay score (Mann‐Whitney test). Conclusions: CRSwNP patients in Brazil present mixed inflammation, with 2 distinct groups (high and low inflammatory pattern) that can be distinguished by tissue eosinophilia of ≥43 eosinophils/HPF cut‐off in nasal polyps. [ABSTRACT FROM AUTHOR]

Oxidative stress role on metformin process of dacarbazine (DTIC) inducing resistance of B16F10 melanoma murine cells are investigated. To induce resistance to DTIC, murine melanoma cells were exposed to increasing concentrations of dacarabazine (DTIC‐res group). Metformin was administered before and during the induction of resistance to DTIC (MET‐DTIC). The oxidative stress parameters of the DTIC‐res group showed increased levels of malondialdehyde (MDA), thiol, and reduced nuclear p53, 8‐hydroxy‐2ʹ‐deoxyguanosine (8‐OH‐DG), nuclear factor kappa B (NF‐ĸB), and Nrf2. In presence of metformin in the resistant induction process to DTIC, (MET‐DTIC) cells had increased antioxidant thiols, MDA, nuclear p53, 8‐OH‐DG, Nrf2, and reducing NF‐ĸB, weakening the DTIC‐resistant phenotype. The exclusive administration of metformin (MET group) also induced the cellular resistance to DTIC. The MET group presented high levels of total thiols, MDA, and reduced percentage of nuclear p53. It also presented reduced nuclear 8‐OH‐DG, NF‐ĸB, and Nrf2 when compared with the control. Oxidative stress and the studied biomarkers seem to be part of the alterations evidenced in DTIC‐resistant B16F10 cells. In addition, metformin administration is able to play a dual role according to the experimental protocol, preventing or inducing a DTIC‐resistant phenotype. These findings should help future research with the aim of investigating DTIC resistance in melanoma. [ABSTRACT FROM AUTHOR]

High doses of metformin induces oxidative stress (OS) and transforming growth factor β1 (TGF-β1) in breast cancer cells, which was associated with increased cancer stem cell population, local invasion, liver metastasis and treatment resistance. Considering the impact of TGF- β1 and OS in breast cancer and the interrelation between these two pathways, the objective of this work was to investigate the effects of consecutive metformin treatments, at a non-cytotoxic dosage, in TGF- β1 targets in MCF-7 and MDA-MB-231 cells. Cells were exposed to 6 μM of metformin for seven consecutive passages. Samples were collected to immunocytochemistry (evaluation of p53, Nf-кB, NRF2 and TGF-β1), biochemical (determination of lipoperoxidation, total thiols and nitric oxide/peroxynitrite levels) and molecular biology analyzes (microarray and Real-time quantitative array PCR). Microarray analysis confirmed alterations in genes related to OS and TGF-β1. Treatment interfered in several TGF-β1 target-genes. Metformin upregulated genes involved in OS generation and apoptosis, and downregulated genes associated with metastasis and epithelial mesenchymal transition in MCF-7 cells. In MDA-MB-231 cells, metformin downregulated genes involved with cell invasion, viability and proliferation. The results shows that even a non-cytotoxic dosage of metformin can promote a less aggressive profile of gene expression in breast cancer cells., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Introduction: We sought to verify whether isoflavin-beta (Iso-β), a mixture of isoflavones with antioxidant properties, could prevent thyrotoxicosis-induced loss of muscle mass and the participation of oxidative stress (OS) in the mechanisms of this prevention., Methods: Two experimental periods of thyrotoxicosis induction were used in Wistar rats: 3 and 5 days to assess Iso-β effects before and after thyrotoxicosis-induced muscle wasting. After euthanasia, peritoneal fat and gastrocnemius muscle were collected, weighed, and muscle OS was assessed., Results: Iso-β prevented the loss of gastrocnemius mass in thyrotoxic rats through the prevention of muscle OS generation during thyrotoxicosis, increasing muscle total antioxidant capacity and decreasing mitochondrial cytochrome c oxidase activity, lipid peroxidation, and protein carbonyl content., Conclusion: Iso-β decreased oxidative modification of proteins, which is known to exert a major role during proteolysis induction and is present in thyrotoxic myopathy, highlighting the potential action of Iso-β in this complication of the disease. Muscle Nerve 56: 975-981, 2017., (© 2016 Wiley Periodicals, Inc.)