Natural products represent a source of biologically active molecules that have an important role in drug discovery. The aromatic plant Blepharocalyx salicifolius has a diverse chemical constitution but the biological activities of its essential oils have not been thoroughly investigated. The aims of this paper were to evaluate in vitro cytotoxic, antifungal and antibacterial activities of an essential oil from leaves of B. salicifolius and to identify its main chemical constituents. The essential oil was extracted by steam distillation, chemical composition was determined by gas chromatography/mass spectrometry, and biological activities were performed by a microdilution broth method. The yield of essential oil was 0.86% (w/w), and the main constituents identified were bicyclogermacrene (17.50%), globulol (14.13%), viridiflorol (8.83%), γ-eudesmol (7.89%) and α-eudesmol (6.88%). The essential oil was cytotoxic against the MDA-MB-231 (46.60 μg·mL⁻¹) breast cancer cell line, being more selective for this cell type compared to the normal breast cell line MCF-10A (314.44 μg·mL⁻¹). Flow cytometry and cytotoxicity results showed that this oil does not act by inducing cell death, but rather by impairment of cellular metabolism specifically of the cancer cells. Furthermore, it presented antifungal activity against Paracoccidioides brasiliensis (156.25 μg·mL⁻¹) but was inactive against other fungi and bacteria. Essential oil from B. salicifolius showed promising biological activities and is therefore a source of molecules to be exploited in medicine or by the pharmaceutical industry.

Trypanosoma cruzi P21 is a protein secreted by the parasite that plays biological roles directly involved in the progression of Chagas disease. The recombinant protein (rP21) demonstrates biological properties, such as binding to CXCR4 receptors in macrophages, chemotactic activity of immune cells, and inhibiting angiogenesis. This study aimed to verify the effects of rP21 interaction with CXCR4 from non-tumoral cells (MCF-10A) and triple-negative breast cancer cells (MDA-MB-231). Our data showed that the MDA-MB-231 cells expressed higher levels of CXCR4 than did the non-tumor cell lines. Besides, cytotoxicity assays using different concentrations of rP21 showed that the recombinant protein was non-toxic and was able to bind to the cell membranes of both cell lineages. In addition, rP21 reduced the migration and invasion of MDA-MB-231 cells by the downregulation of MMP-9 gene expression. In addition, treatment with rP21 blocked the cell cycle, arresting it in the G1 phase, mainly in MDA-MB-231 cells. Finally, rP21 prevents the chemotaxis and proliferation induced by CXCL12. Our data showed that rP21 binds to the CXCR4 receptors in both cells, downregulates CXCR4 gene expression, and decreases the receptors in the cytoplasm of MDA-MB-231 cells, suggesting CXCR4 internalization. This internalization may explain the desensitization of the receptors in these cells. Thus, rP21 prevents migration, invasion, and progression in MDA-MB-231 cells.

Cell invasion by the intracellular protozoans requires interaction of proteins from both the host and the parasite. Many parasites establish chronic infections, showing they have the potential to escape the immune system; for example, Trypanosoma cruzi is an intracellular parasite that causes Chagas disease. Parasite internalization into host cell requires secreted and surface molecules, such as microvesicles. The release of microvesicles and other vesicles, such as exosomes, by different eukaryotic organisms was first observed in the late 20th century. The characterization and function of these vesicles have recently been the focus of several investigations. In this review, we discuss the release of microvesicles by T. cruzi. The molecular content of these vesicles is composed of several molecules that take place during parasite-host cell interaction and contribute to the parasite-driven mechanism of evasion from the host immune system. These new findings appear to have a profound impact on the comprehension of T. cruzi biology and highlight novel potential strategies for developing more efficient therapeutic approaches.

Klotho, a cellular anti‑senescence protein, is related to antitumor actions, growth regulation, proliferation and invasiveness in several types of tumor, including breast cancer. The present study aimed to analyze the serum levels of αKlotho in patients with breast cancer according to histopathological and immunohistochemical variables. A total of 74 patients and 60 healthy controls were recruited. Peripheral blood samples were collected and serum levels were assessed by sandwich ELISA. Clinical and diagnostic data were obtained from medical records and databases of the Clinical Hospital of the Federal University of Uberlândia (Uberlândia, Brazil). The results indicated no difference in the levels of αKlotho between patients and controls (P=0.068); however, the number of patients with breast cancer with undetectable αKlotho was high (n=52). Thus, the variables that were associated with the lowest survival rates were analyzed, relating them to undetectable αKlotho. Among cases of metastatic tumors or tumors with poor differentiation, positive lymph node status and triple‑negative status, patients with undetectable αKlotho predominated and had unfavorable overall survival. Due to the significant results obtained in triple‑negative patients, an in vitro analysis was performed to determine whether estrogen receptors (ERs) have a role in αKlotho production. Treatment of MCF‑7 cells with ER agonists, estradiol (E2) and diarylpropionitrile (DPN), resulted in increases in αKlotho expression and supernatant levels of both agonists, demonstrating a direct association between the ER and Klotho production; of note, the ERβ‑specific agonist DPN tripled αKlotho expression when compared to E2 (P=0.078). These data suggested that undetectable αKlotho in the serum of patients with breast cancer is related to unfavorable histopathological variables and poor prognosis and ERs possibly have an important role in maintaining adequate quantities of αKlotho.

Leishmaniasis causes alterations and lesions in the genital system, which leads to azoospermia and testicular atrophy in animals during the chronic phase of the infection. The aim of this study was to reveal the kinetics of Leishmania chagasi infection in the genital system of male golden hamsters (Mesocricetus auratus). Animals were intraperitoneally inoculated with amastigotes from L. chagasi. At different time points animals were euthanized and genital organs processed for histo-pathological, qPCR, cytokines and testosterone detection assays. Our results showed a high parasite load in testis, followed by an increase of pro-inflammatory cytokines IL1-β, TNF-α and IFN-γ, and testosterone. Subsequently, IL-4 expression was upregulated and basal parasite persistence in testis was observed using the experimental approach. Extracellular amastigotes migrated to the epididymis posing as a potential major factor of parasite persistence and venereal transmission of L. chagasi infection in hamsters.