In Brazil, the state of São Paulo contains both preserved areas (Juréia-Itatins Ecological Station) and extremely impacted ones (Cubatão Municipality). This study evaluated the concentrations of five metals (Cu, Cd, Cr, Pb, and Hg) in two mangroves with different levels of anthropogenic impact and the apparent genotoxicity to Ucides cordatus. Water and sediment samples were obtained, and metal concentrations were determined with an atomic absorption spectrophotometer. The genotoxic impact was quantified based on the number of micronucleated cells per 1,000 analyzed (MN‰), using hemolymph slides stained with Giemsa. Metal concentrations in water were below the detection limit, except for lead, although no significant difference was observed between the areas (P > 0.05). Sediment from Cubatão had higher concentrations of Cd, Pb, Cr, and Cu than sediment from Juréia-Itatins (P < 0.05), but no significant differences in metal concentrations were detected among depth strata of the sediment (P > 0.05). Crabs from Cubatão had a 2.6 times higher mean frequency of micronucleated cells (5.2 ± 1.8 MN‰) than those from Juréia-Itatins (2.0 ± 1.0 MN‰; P < 0.0001). The more-polluted conditions found in the mangrove sediments of Cubatão were reflected in the micronucleus assay, demonstrating their genotoxic effect; however, genetic damage should be attributed to a synergistic effect with other kinds of pollutants previously recorded in different environments of Cubatão. U. cordatus proved to be an excellent bioindicator of mangrove pollution. This study established, for the first time, the normal frequency of MN‰ in a population of this species within an ecological station.

Very little is known about the immunomodulatory potential of secondary metabolites isolated from marine microorganisms. In the present study, we characterized pyrenocine A, which is produced by the marine-derived fungus Penicillium paxilli Ma(G)K and possesses anti-inflammatory activity. Pyrenocine A was able to suppress, both pretreatment and posttreatment, the LPS-induced activation of macrophages via the inhibition of nitrite production and the synthesis of inflammatory cytokines and PGE2. Pyrenocine A also exhibited anti-inflammatory effects on the expression of receptors directly related to cell migration (Mac-1) as well as costimulatory molecules involved in lymphocyte activation (B7.1). Nitrite production was inhibited by pyrenocine A in macrophages stimulated with CpG but not Poly I:C, suggesting that pyrenocine A acts through the MyD88-dependent intracellular signaling pathway. Moreover, pyrenocine A is also able to inhibit the expression of genes related to NFκB-mediated signal transduction on macrophages stimulated by LPS. Our results indicate that pyrenocine A has promissory anti-inflammatory properties and additional experiments are necessary to confirm this finding in vivo model.

Inflammation is part of an important mechanism triggered by the innate immune response that rapidly responds to invading microorganisms and tissue injury. One important elicitor of the inflammatory response is the Gram-negative bacteria component lipopolysaccharide (LPS), which induces the activation of innate immune response cells, the release of proinflammatory cytokines, such as interleukin 1 and tumor necrosis factor α(TNF-α), and the cellular generation of nitric oxide (NO) by the inducible nitric oxide synthase (iNOS). Although essential to the immune response, uncontrolled inflammatory responses can lead to pathological conditions, such as sepsis and rheumatoid arthritis. Therefore, identifying cellular targets for new anti-inflammatory treatments is crucial to improving therapeutic control of inflammation-related diseases. More recently, the translation factor eIF5A has been demonstrated to have a proinflammatory role in the release of cytokines and the production of NO. As eIF5A requires and essential and unique modification of a specific residue of lysine, changing it to hypusine, eIF5A is an interesting cellular target for anti-inflammatory treatment. The present study reviews the literature concerning the anti-inflammatory effects of inhibiting eIF5A function. We also present new data showing that the inhibition of eIF5A function by the small molecule GC7 significantly decreases TNF-α release without affecting TNF-α mRNA levels. We discuss the mechanisms by which eIF5A may interfere with TNF-α mRNA translation by binding to and regulating the function of ribosomes during protein synthesis.

The diagnosis of juvenile myelomonocytic leukaemia (JMML) is based on clinical, laboratory and molecular features but immunophenotyping [multiparametric flow cytometry (MFC)] has not been used routinely. In the present study, we describe the flow cytometric features at diagnosis with special attention to the distribution of monocytic subsets and the relation between MFC and molecular subgroups. MFC was performed with an eight-colour platform based on Euroflow. We studied 33 JMML cases. CD34 + /CD117 + /CD13 + cells >2% was found in 25 cases, and 51Á5% presented an aberrant expression of CD7. A decrease of CD34 + /CD19 + /CD10 + cells was seen in eight cases and in four they were absent. The granulocytic population had a decreased side scatter in 29 cases. Bone marrow monocytic precursors were increased in 28 patients, with a decrease in classical monocytes (median 80Á7%) and increase in CD16 + (intermediate and nonclassical). A more pronounced increase in myeloid CD34 + cells was seen in patients with Neurofibromatosis type 1 (NF1) and tyrosine-protein phosphatase non-receptor type 11 (PTPN11), with aberrant CD7 expression in four of six and 10/12 patients respectively. Thus, JMML shows an immunophenotypic profile similar to myelodysplastic syndromes, and a different monocyte subset distribution when compared with chronic MML. MFC proved to be an important diagnostic tool that can help in differential diagnosis with other clonal diseases with monocytosis.

Juvenile myelomonocytic leukaemia (JMML) is a rare clonal haematopoietic neoplasm from early childhood with characteristics of both myelodysplastic and myeloproliferative syndromes. It represents 3% of all haematologic malignancies in paediatric patients. [1][2][3] Most patients present mutation of genes of the Rat Sarcoma (RAS) pathway such as the genes tyrosine-protein phosphatase non-receptor type 11 (PTPN11), KRAS proto-oncogene, GTPase (KRAS), NRAS proto-oncogene, GTPase (NRAS), Casitas B-lineage lymphoma (CBL) and neurofibromin 1 (NF1). [4][5][6][7][8]