Psidium guajava L. has extensive use in folk medicine. The aim of this study was to quantify the levels of phenolic, flavonoids, antioxidant activity, leathality assay and antibacterial and antitumoral activities of the extract of P. guajava. In the dry guava extract there were high levels of phenolics (766.08 ± 14.52 mg/g), flavonoids (118.90 ± 5.47 mg/g) and antioxidant activity (87.65%). The LD50 was 185.15 µg/ml. The MIC value was 250 µg/ml for Streptococcus mutans, Streptococcus mitis and Streptococcus oralis. IC50 of the extract tested in the HeLa, RKO and Wi cell lines was 15.6 ± 0.8 µg/ml, 21.2 ± 1.1 µg/ml and 68.9 ± 1.5 µg/ml, respectively. The results of all analyses allow us to conclude that the dry extract of guava leaves has promising activity to be applied topically in the oral cavity or in the development of antitumor formulation or even be used as a functional food.

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Paclitaxel (PTX) is a microtubule-stabilizing agent widely used to treat breast cancer. Nevertheless, the low solubility of the drug and the side effects of commercial formulations available limit its clinical use. In this way, our group recently described the preparation of PTX-loaded folate-coated long-circulating and pHsensitive liposomes (SpHL-folate-PTX). Therefore, a proof-ofconcept study was designed in order to demonstrate the feasibility of SpHL-folate-PTX against breast tumor cell line MDA-MB-231. Cellular uptake of the liposomes and PTX was evaluated. Apoptosis and cell cycle were analyzed by flow cytometry. In vivo antitumor activity was carried out in MDA-MB-231 tumor-bearing BALB/c nude mice. Cellular uptake assay showed a high cell delivery of PTX by SpHL-folate-PTX, which leads to superior cytotoxicity and activation of apoptosis pathways. The SpHL-folate-PTX treatment induces an expressive increase of cells in the G0/G1 phase compared to free PTX and SpHL-PTX (without folate). In vivo studies showed a significant reduction in the tumor growth and a lower uptake of a radiopharmaceutical in the scintigraphic images for the SpHL-folate-PTX group, suggesting its higher efficacy compared with free PTX and SpHL-PTX. Histomorphometric analyses demonstrated an increase in necrosis and inflammation areas in animals treated with SpHLfolate-PTX. A decrease in the proliferative cells and a higher percentage of apoptotic cells were observed by immunohistochemical analyses after the treatment with SpHL-folate-PTX. Therefore, the data confirmed the potential of SpHL-folate-PTX as an alternative antitumor therapy, especially for breast cancer.

BackgroundThere is substantial evidence that chronic renal and cardiovascular diseases are associated with coagulation disorders, endothelial dysfunction, inflammation and fibrosis. Angiotensin-Converting Enzyme Insertion/Deletion polymorphism (ACE I/D polymorphism) has also be linked to cardiovascular diseases. Therefore, this study aimed to compare plasma levels of ultrassensible C-reactive protein (usCRP), PAI-1, D-dimer and TGF-β1 in patients undergoing HD with different ACE I/D polymorphisms.MethodsThe study was performed in 138 patients at ESRD under hemodialysis therapy for more than six months. The patients were divided into three groups according to the genotype. Genomic DNA was extracted from blood cells (leukocytes). ACE I/D polymorphism was investigated by single polymerase chain reaction (PCR). Plasma levels of D-dimer, PAI-1 and TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA), and the determination of plasma levels of usCRP was performed by immunonephelometry. Data were analyzed by the software SigmaStat 2.03.ResultsClinical characteristics were similar in patients with these three ACE I/D polymorphisms, except for interdialytic weight gain. I allele could be associated with higher interdialytic weight gain (P = 0.017). Patients genotyped as DD and as ID had significantly higher levels of PAI-1 than those with II genotype. Other laboratory parameters did not significantly differ among the three subgroups (P = 0.033). Despite not reaching statistical significance, plasma levels of usCRP were higher in patients carrying the D allele.ConclusionACE I/D polymorphisms could be associated with changes in the regulation of sodium, fibrinolytic system, and possibly, inflammation. Our data showed that high levels of PAI-1 are detected when D allele is present, whereas greater interdialytic gain is associated with the presence of I allele. However, further studies with different experimental designs are necessary to elucidate the mechanisms involved in these associations.

Friedelan-3-one (1) and friedelane-3,16-dione (2) isolated from leaves and branches of Maytenus robusta Reissek were subjected to structural modifications via nucleophilic addition to the carbonyl group and Baeyer-Villiger oxidation in order to synthesize potential cytotoxic compounds. The oximes friedelane-3hydroxyimino (3) and 3-hydroxyiminofriedelan-16-one (4) together with the lactones friedelane-3,4-lactone (5) and 3,4-lactonefriedelan-16-one (6) were characterized by IR and NMR spectroscopic analyses. Compounds 4 and 6 are reported for the first time. Cytotoxic screening via MTT assay in human leukemia cell lines (THP-1 and K562) demonstrated no significant improvement of compounds 3-6 when compared to the starting materials. Only compounds 3 and 5 demonstrated an improvement against K562 cells. However, the same assay on ovarian and breast cancer cell lines (TOV-21G and MDA-MB-231) showed a reduction in the IC 50 for compounds 4-6, indicating that ring A modifications may enhance the biological potential.

ABSTRACT. Recent studies have shown an association between thrombosis and factor VII (FVII), tissue factor (TF), and angiotensinconverting enzyme (ACE). This suggests that individuals with FVII-402 G/A, FVII-401 G/T, TF+5466 A/G, and ACE-287 insertion/ deletion (I/D) polymorphisms present an increased risk of venous thrombosis, heart disease, and ischemic stroke compared with controls. In this study, we investigated the frequencies of these polymorphisms and their association with arterial and venous thrombosis. For the FVII-402 G/A polymorphism, there were 57.3% heterozygote (HT) genotypes and 8.3% homozygote (HM) genotypes in the patients, and 45.2% HT genotypes and 15.4% HM genotypes in the controls. For the FVII-401 G/T polymorphism, there were 37.5% HT genotypes and 3.1% HM genotypes in the patients, and 32.7% HT genotypes and 4.8% HM genotypes in the controls. The polymorphism TF+5466 A/G was not found in any of the samples analyzed. For the ACE-287 I/D polymorphism, there were 43 (40.6%) HT genotypes and 63 (59.4%) HM genotypes in the controls and 28 (45.2%) HT genotypes and 34 (54.8%) HM genotypes in the patients. No significant difference was observed by comparing patients and controls. In this study, no association was found between the presence of the evaluated polymorphisms and the occurrence of thrombotic events.