Angiogenesis is a coordinated process tightly regulated by the balance between Delta-like-4 (DLL4) and Jagged-1 (JAG1) in endothelial cells. Here we show that galectin-3 (gal-3), a glycan-binding protein secreted by cancer cells under hypoxic conditions, triggers sprouting angiogenesis, assisted by hypoxic changes in the glycosylation status of endothelial cells that enhance binding to gal-3. Galectin-3′s proangiogenic functions were found to be predominantly dependent on the Notch ligand JAG1. Differential direct binding to JAG1 was shown by surface plasmon resonance assay. Upon binding to Notch ligands, gal-3 preferentially increased JAG1 protein half-life over DLL4 and preferentially activated JAG1/Notch-1 signaling in endothelial cells. JAG1 overexpression in Lewis lung carcinoma cells accelerated tumor growth in vivo, but this effect was prevented in Lgals3−/− mice. Our findings establish gal-3 as a molecular regulator of the JAG1/Notch-1 signaling pathway and have direct implications for the development of strategies aimed at controlling tumor angiogenesis.

Schistosomiasis affects approximately 240 million people in the world. Schistosoma mansoni eggs in the liver induce periportal fibrosis and hepatic failure driven by monocyte recruitment and macrophage activation, resulting in robust Th2 response. Here, we suggested a possible involvement of Galectin-3 (Gal-3), histone deacetylases (HDACs), and Hedgehog (Hh) signaling with macrophage activation during Th1/Th2 immune responses, fibrogranuloma reaction, and tissue repair during schistosomiasis. Gal-3 is highly expressed by liver macrophages (Kupffer cells) around Schistosoma eggs. HDACs and Hh regulate macrophage polarization and hepatic stellate cell activation during schistosomiasis-associated fibrogenesis. Previously, we demonstrated an abnormal extracellular matrix distribution in the liver that correlated with atypical monocyte–macrophage differentiation in S. mansoni-infected, Gal-3-deficient (Lgals3-/-) mice. New findings explored in this review focus on the chronic phase, when wild-type (Lgals3+/+) and Lgals3-/- mice were analyzed 90 days after cercariae infection. In Lgals3-/- infected mice, there was significant inflammatory infiltration with myeloid cells associated with egg destruction (hematoxylin and eosin staining), phagocytes (specifically Kupffer cells), numerically reduced and diffuse matrix extracellular deposition in fibrotic areas (Gomori trichrome staining), and severe disorganization of collagen fibers surrounding the S. mansoni eggs (reticulin staining). Granuloma-derived stromal cells (GR cells) of Lgals3-/- infected mice expressed lower levels of alpha smooth muscle actin (α-SMA) and eotaxin and higher levels of IL-4 than Lgals3+/+ mice (real-time PCR). The relevant participation of macrophages in these events led us to suggest distinct mechanisms of activation that culminate in defective fibrosis in the liver of Lgals3-/- infected mice. These aspects were discussed in this review, as well as the possible interference between Gal-3, HDACs, and Hh signaling during progressive liver fibrosis in S. mansoni-infected mice. Further studies focused on macrophage roles could elucidate these questions and clear the potential utility of these molecules as antifibrotic targets.

BackgroundThe adipocytolytic non-surgical esthetic procedures are indicated for the reduction of localized fat and are effective in reducing local adiposity through the ablation of adipocytes with fast and lasting results, besides causing local inflammation.ObjectiveThis study aimed to characterize the adipocytolytic procedures and correlate the phases of the inflammatory process with the results obtained from such procedures, in order to clarify the role of inflammation triggered by the adipocytolytic procedures and its relation with the lipolytic process, with a focus on body shaping.MethodsThis work is an integrative literature review that presents a total of 72 articles published between 1998 and 2015, derived from the PubMed database, in order to establish a relationship between clinical and basic science research, assuming an important role in medical practice based on evidence.ResultsThe results show that the adipocytolytic procedures are characterized by triggering inflammation arising from the disruption of adipocytes by interfering with the lipolytic signaling pathways in both acute and chronic phases of inflammation through the direct action of proinflammatory cytokines or catecholamines. Therefore, inflammation plays an important role in modulating the lipolytic process, influencing body shaping.ConclusionThe inflammatory process assists the adipolytic process in all stages of inflammation, contributing to the reduction of body contouring.

The use of cosmetic products is increasing around the world and a variety of chemical compounds used in the manufacture of these products grows at the same time. In this way, the risk of intoxication, allergic processes, prolonged chemical exposure, side effects and indiscriminate use are also increased. The present work aims to highlight the biological risks that cosmetics can pose to human health against the toxic substances used in its formulation. This work is an integrative literature review structured according to the methodology described by Whittemore, R. and Knafl, K., 2005. This work relates the main toxic chemical substances present in cosmetic products to the possible health complications reported in the scientific literature. Currently, the cosmetic industries have increased the use of compounds with preservative action, surfactant, fragrances, stains, etc. in the formulation of cosmetic products. Such substances potentiate the quality, property and shelf life of cosmetics, but on the other hand, many of these substances are toxic to the human body, presenting health risks ranging from a simple mild hypersensitivity reaction to an anaphylactic process or even a lethal intoxication. Thus, the indiscriminate use of cosmetics may present itself as an emerging issue of public health. In view of the above, this work seeks to encourage improvements in the search for new methodologies for quality control in the production and consumption of cosmetic products around the world.

Galectin-3 (Gal-3) is a β-galactoside binding protein that controls cell-cell and cell-extracellular matrix interactions. In lymphoid organs, gal-3 inhibits B cell differentiation by mechanisms poorly understood. The B cell development is dependent on tissue organization and stromal cell signaling, including IL-7 and Notch pathways. Here, we investigate possible mechanisms that gal-3 interferes during B lymphocyte differentiation in the bone marrow (BM) and spleen. The BM of gal-3-deficient mice (Lgals3−/− mice) was evidenced by elevated numbers of B220+CD19+c-Kit+IL-7R+ progenitor B cells. In parallel, CD45− bone marrow stromal cells expressed high levels of mRNA IL-7, Notch ligands (Jagged-1 and Delta-like 4), and transcription factors (Hes-1, Hey-1, Hey-2 and Hey-L). The spleen of Lgals3−/− mice was hallmarked by marginal zone disorganization, high number of IgM+IgD+ B cells and CD138+ plasma cells, overexpression of Notch ligands (Jagged-1, Delta-like 1 and Delta-like 4) by stromal cells and Hey-1. Morever, IgM+IgD+ B cells and B220+CD138+ CXCR4+ plasmablasts were significantly increased in the BM and blood of Lgals3−/− mice. For the first time, we demonstrated that gal-3 inhibits Notch signaling activation in lymphoid organs regulating earlier and terminal events of B cell differentiation.

BackgroundGalectin-3 is a multifunctional β-galactoside-binding lectin that once synthesized, is expressed in the nucleus, cytoplasm, cell surface and in the extracellular environment. Because of its unique structure, galectin-3 can oligomerize forming lattice upon binding to multivalent oligossacharides and influence several pathologic events such as tumorigenesis, invasion and metastasis.MethodsIn our study, balb/c Lgals3+/+ and Lgals3−/− female mice were inoculated in the fourth mammary fat pad with 4T1 breast cancer cell line. The primary tumor, inguinal lymph nodes and iliac bone marrow were evaluated 15, 21 and 28 days post-injection. The primary tumor growth was evaluated by measuring the external diameter, internal growth by ultrasound and weight of the excised tumor. The presence of cancer cells in the draining lymph nodes and iliac crest bone marrow were performed by immunohistochemistry, PCR and clonogenic metastatic assay.ResultsIn this study we demonstrated that the deletion of galectin-3 in the host affected drastically the in vivo growth rate of 4T1 tumors. The primary tumors in Lgals3−/− mice displayed a higher proliferative rate (p < 0,05), an increased necrotic area (p < 0,01) and new blood vessels with a wider lumen in comparison with tumors from Lgals3+/+ mice (P < 0,05). Moreover, we detected a higher number of 4T1-derived metastatic colonies in the lymph nodes and the bone marrow of Lgals3−/− mice (p < 0,05). Additionally, healthy Lgals3−/− control mice presented an altered spatial distribution of CXCL12 in the bone marrow, which may explain at least in part the initial colonization of this organ in Lgals3−/− injected with 4T1 cells.ConclusionsTaken together, our results demonstrate for the first time that the absence of galectin-3 in the host microenvironment favors the growth of the primary tumors, the metastatic spread to the inguinal lymph nodes and bone marrow colonization by metastatic 4T1 tumor cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2679-1) contains supplementary material, which is available to authorized users.

BackgroundDoxorubicin (Dox) is a chemotherapy drug with limited application due to cardiotoxicity that may progress to heart failure. This study aims to evaluate the role of cardiomyocytes derived from mouse embryonic stem cells (CM-mESCs) in the treatment of Dox-induced cardiomyopathy (DIC) in mice.MethodsThe mouse embryonic stem cell (mESC) line E14TG2A was characterized by karyotype analysis, gene expression using RT-PCR and immunofluorescence. Cells were transduced with luciferase 2 and submitted to cardiac differentiation. Total conditioned medium (TCM) from the CM-mESCs was collected for proteomic analysis. To establish DIC in CD1 mice, Dox (7.5 mg/kg) was administered once a week for 3 weeks, resulting in a cumulative Dox dose of 22.5 mg/kg. At the fourth week, a group of animals was injected intramyocardially with CM-mESCs (8 × 105 cells). Cells were tracked by a bioluminescence assay, and the body weight, echocardiogram, electrocardiogram and number of apoptotic cardiomyocytes were evaluated.ResultsmESCs exhibited a normal karyotype and expressed pluripotent markers. Proteomic analysis of TCM showed proteins related to the negative regulation of cell death. CM-mESCs presented ventricular action potential characteristics. Mice that received Dox developed heart failure and showed significant differences in body weight, ejection fraction (EF), end-systolic volume (ESV), stroke volume (SV), heart rate and QT and corrected QT (QTc) intervals when compared to the control group. After cell or placebo injection, the Dox + CM-mESC group showed significant increases in EF and SV when compared to the Dox + placebo group. Reduction in ESV and QT and QTc intervals in Dox + CM-mESC-treated mice was observed at 5 or 30 days after cell treatment. Cells were detected up to 11 days after injection. The Dox + CM-mESC group showed a significant reduction in the percentage of apoptotic cardiomyocytes in the hearts of mice when compared to the Dox + placebo group.ConclusionsCM-mESC transplantation improves cardiac function in mice with DIC.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0788-2) contains supplementary material, which is available to authorized users.

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