Toxoplasma gondii is a protozoan that infects up to a third of the world’s population. This parasite can cause serious problems, especially if a woman is infected during pregnancy, when toxoplasmosis can cause miscarriage, or serious complications to the baby, or in an immunocompromised person, when the infection can possibly affect the patient’s eyes or brain. To identify potential drug candidates that could counter toxoplasmosis, we selected 13 compounds which were pre-screened in silico based on the proteome of T. gondii to be evaluated in vitro against the parasite in a cell-based assay. Among the selected compounds, three demonstrated in vitro anti-T. gondii activity in the nanomolar range (almitrine, bortezomib, and fludarabine), and ten compounds demonstrated anti-T. gondii activity in the micromolar range (digitoxin, digoxin, doxorubicin, fusidic acid, levofloxacin, lomefloxacin, mycophenolic acid, ribavirin, trimethoprim, and valproic acid). Almitrine demonstrated a Selectivity Index (provided by the ratio between the Half Cytotoxic Concentration against human foreskin fibroblasts and the Half Effective Concentration against T. gondii tachyzoites) that was higher than 47, whilst being considered a lead compound against T. gondii. Almitrine showed interactions with the Na+/K+ ATPase transporter for Homo sapiens and Mus musculus, indicating a possible mechanism of action of this compound.

Background: Oral cavity cancer is still an important public health problem throughout the world. Oral squamous cell carcinomas (OSCCs) can be quite aggressive and metastatic, with a low survival rate and poor prognosis. However, this is usually related to the clinical stage and histological grade, and molecular prognostic markers for clinical practice are yet to be defined. Heparanase (HPSE1) is an endoglycosidase associated with extracellular matrix remodeling, and although involved in several malignancies, the clinical implications of HPSE1 expression in OSCCs are still unknown.Methods: We sought to investigate HPSE1 expression in a series of primary OSCCs and further explore whether its overexpression plays a relevant role in OSCC tumorigenesis. mRNA and protein expression analyses were performed in OSCC tissue samples and cell lines. A loss-of-function strategy using shRNA and a gain-of-function strategy using an ORF vector targeting HPSE1 were employed to investigate the endogenous modulation of HPSE1 and its effects on proliferation, apoptosis, adhesion, epithelial–mesenchymal transition (EMT), angiogenesis, migration, and invasion of oral cancer in vitro.Results: We demonstrated that HPSE1 is frequently upregulated in OSCC samples and cell lines and is an unfavorable prognostic indicator of disease-specific survival when combined with advanced pT stages. Moreover, abrogation of HPSE1 in OSCC cells significantly promoted apoptosis and inhibited proliferation, migration, invasion, and epithelial–mesenchymal transition by significantly decreasing the expression of N-cadherin and vimentin. Furthermore, a conditioned medium of HPSE1-downregulated cells resulted in reduced vascular endothelial growth.Conclusion: Our results confirm the overexpression of HPSE1 in OSCCs, suggest that HPSE1 expression correlates with disease progression as it is associated with several important biological processes for oral tumorigenesis, and can be managed as a prognostic marker for patients with OSCC.

Background and aims:Diabetes affects the metabolism promoting damage in different tissues, including salivary glands. Current treatments, such as insulin, are ineffective to recovery of these tissues. In this aspect, the immunotherapy has been tested, but it can be inefficient as an agent for the control of damage caused by diabetes. The aim of this study to evaluate the association in anti-CD4 and anti-CD8 monoclonal antibody in the recovery of salivary glands of diabetic NOD mice. Material and methods: Fifteen spontaneously diabetic mice (NOD) were divided into three groups with 5 animals each: group I (Balb/C control mice), group II (untreated NOD mice), group III (NOD mice treated with CD4 and CD8 antibodies). The CD4 and CD8 antibodies (IMUNY, Rheabiotech Ltda, Brazil) were administered by intravenously injections (25 ug/days: 0, 7, 14, and 21). After treatment salivary glands samples were analyzed by immunofluorescence, microscopy, light microscopy and stereology. (ethical approval process: 304/11), Analysis of variance (ANOVA) and Kruskal-Wallis nonparametric test were used. Results: Elevated levels of glucose (mg/dl) were observed in untreated animals (group II) (605.25 ± 31.23, p≤0.05), whereas in treated animals (group III), were noted a decrease in these levels (464.77 ± 39.66, p≤0.05). Tissue restructure, characterized by cell volume recovery, also was observed in group III (nuclear volume of parotid glands: (109.91 ± 02.03, p≤0.05) and submandibular glands: (107.52 ± 02, p≤0.05) (cytoplasmic volume of parotid glands: (356.14 ± 26.34, p≤0.05) and submandibular glands: (331.22 ± 32.11, p≤0.05). Intense signaling (+++) of insulin receptors was observed in animals of group I. On the other hand, in group II was noted a reduction of these receptors (+). In treated animals (group III) were observed a recovery of the insulin receptors (+++). Conclusions: This treatment was effective in the recovery of salivary acinar cells, contributed also to homeostasis of body metabolism. Thus, this immunomodulation promoted a beneficial effect on the recovery of these tissues. key words: anti CD4 and CD8, immunotherapy, salivary glands, diabetes mellitus 157 25. Robinson CP. Elevated levels of cysteine protease activity in saliva and salivary glands of the nonobese diabetic (NOD) mouse model for Sjogren syndrome. Proc Natl Acad Sci 94 (11): 5767-71, 1997 26. Wildenberg ME, Van Helden-Meeuwsen CG, van de Merwe JP, Moreno C, Drexhage HA, Versnel MA. Lack of CCR5 on dendritic cells promotes a proinflammatory environment in submandibular glands of the NOD mouse. J Leukoc Biol 83(5): 1194-200, 2008 27. Markopoulos AK, Belazi M. Histopathological and immunohistochemical features of the labial salivary glands in children with type I diabetes. 29. Parish N, Cooke A. Characterisation of CD8 monoclonal antibody-induced protection from diabetes in NOD mice. Autoimmunity 38(8): 597-604, 2005 30. Yagi H, Matsumoto M, Kunimoto K, Kawaguchi J, Makino S, Harada M. Analysis of the roles of CD4+ and CD8+ T cells in autoimmune diabetes...