Matrix metalloproteinase gene polymorphisms and oral cancer

Since oral squamous cell carcinoma (OSCC) is the most prevalent malignant cancer in the oral cavity, several researches have been performed to study the role of important enzymes in this disease. Among them, the matrix metalloproteinases (MMPs) are highlighted, due to the fact that they are proteinases responsible to degrade many extra-cellular matrix components, making possible the invasion of neoplasic cells. Important tools in cancer prognosis have been utilized aiming to correlate high levels of MMPs and OSCC, such as immunohistochemical, zymographic and mRNA detection methods. However, these techniques are usually applied after cancer detection, characterizing a curative but not a preventive medicine. Trying to make interventions before the development of the disease and making possible the identification of people at high risk and, analysis of modifications in MMP genes has been a chance for modern medicine. Recently, polymorphisms in MMP genes have been related to different neoplasias, including OSCC. Despite investigation is beginning, MMP gene polymorphisms seems to have a promising future in oral cancer research and some of the present results have shown that there are MMP polymorphisms related to an increased risk for developing oral cancer. Key words:Oral cancer, polymorphism, matrix metalloproteinase.

Peptidome profiling of venom from the social wasp Polybia paulista

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Facing Hymenoptera venom allergy: from natural to recombinant allergens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ac2-26 mimetic peptide of annexin A1 inhibits local and systemic inflammatory processes induced by bothrops moojeni venom and the lys-49 phospholipase A2 in a rat model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Structural insights into substrate binding of brown spider venom class II phospholipases D

Phospholipases D (PLDs), the major dermonecrotic factors from brown spider venoms, trigger a range of biological reactions both in vitro and in vivo. Despite their clinical relevance in loxoscelism, structural data is restricted to the apo-form of these enzymes, which has been instrumental in understanding the functional differences between the class I and II spider PLDs. The crystal structures of the native class II PLD from Loxosceles intermedia complexed with myo-inositol 1-phosphate and the inactive mutant H12A complexed with fatty acids indicate the existence of a strong ligand-dependent conformation change of the highly conserved aromatic residues, Tyr 223 and Trp225 indicating their roles in substrate binding. These results provided insights into the structural determinants for substrate recognition and binding by class II PLDs.

Exenatide and sitagliptin decrease interleukin 1β, matrix metalloproteinase 9, and nitric oxide synthase 2 gene expression but does not reduce alveolar bone loss in rats with periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

L-Aminoacid oxidase from bothrops leucurus venom Induces nephrotoxicity via apoptosis and necrosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A new heterologous fibrin sealant as a scaffold to cartilage repair - experimental study and preliminary results

Autologous fibrin gel is commonly used as a scaffold for filling defects in articular cartilage. This biomaterial can also be used as a sealant to control small hemorrhages and is especially helpful in situations where tissue reparation capacity is limited. In particular, fibrin can act as a scaffold for various cell types because it can accommodate cell migration, differentiation, and proliferation. Despite knowledge of the advantages of this biomaterial and mastery of the techniques required for its application, the durability of several types of sealant at the site of injury remains questionable. Due to the importance of such data for evaluating the quality and efficiency of fibrin gel formulations on its use as a scaffold, this study sought to analyze the heterologous fibrin sealant developed from the venom of Crotalus durissus terrificus using studies in ovine experimental models. The fibrin gel developed from the venom of this snake was shown to act as a safe, stable, and durable scaffold for up to seven days, without causing adverse side effects. Fibrin gel produced from the venom of the Crotalus durissus terrificus snake possesses many clinical and surgical uses. It presents the potential to be used as a biomaterial to help repair skin lesions or control bleeding, and it may also be used as a scaffold when applied together with various cell types. The intralesional use of the fibrin gel from the venom of this snake may improve surgical and clinical treatments in addition to being inexpensive and adequately consistent, durable, and stable. The new heterologous fibrin sealant is a scaffold candidate to cartilage repair in this study.

Proteomic analysis of the rare Uracoan rattlesnake Crotalus vegrandis venom: evidence of a broad arsenal of toxins

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Immunohistochemical detection of metalloproteinase-9 (MMP-9), anti-oxidant like 1 protein (AOP-1) and synaptosomal-associated protein (SNAP-25) in the cerebella of dogs naturally infected with spontaneous canine distemper

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Study of visceral antinociceptive potential of bee Apis mellifera venom

Pain is one of the most common reasons for patients to seek medical care. Bee Apis mellifera venom (AMV) has traditionally been used to treat inflammatory diseases and the alleviation of pain. Herein, we aimed to investigate the visceral antinociceptive potential of A. mellifera bee venom and its possible mechanism of action. Acetic acid-induced writhing assay was used in mice to determine the degree of visceral antinociception. Visceral antinociceptive activity was expressed as the reduction in the number of abdominal constrictions. Mice received an intraperitoneal injection of acetic acid after administration of AMV (0.08 or 0.8 mg/kg; intraperitoneally (i.p.)). In mechanistic studies, separate experiments were realized to examine the role of α2-receptors, nitric oxide, calcium channels, K+ATP channel activation, TRPV1 and opioid receptors on the visceral antinociceptive effect of AMV (0.8 mg/kg), using appropriate antagonists, yohimbine (2 mg/kg), L-NG-Nitroarginine methyl ester (L-NAME, 10 mg/kg), verapamil (5 mg/kg), glibenclamide (5 mg/kg), ruthenium red (3 mg/kg) or naloxone (2 mg/kg). AMV presented visceral antinociceptive activity in both doses tested (0.08 and 0.8 mg/Kg). Visceral antinociceptive effect of AMV was resistant to all the antagonists used. Mice showed no significant alterations in locomotion frequency, indicating that the observed antinociception is not a consequence of motor abnormality. Although AMV efficient diminished the acetic acid-evoked pain-related behavior, its mechanism is unclear from this study and future studies are needed to verify how the venom exerts its antinociceptive action.