The Modulatory Effect of 15d-PGJ2 in Dendritic Cells

The PPAR-γ ligands, in special 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), negatively regulate the cells of innate and adaptative immune system and present excellent results in different models of inflammatory diseases. These findings support the notion that PPAR-γ ligands may be used as therapeutic agents in different diseases. Although PPAR-γ is expressed in different cells and tissues including dendritic cells (DC), few studies have evaluated the effects of these ligands on DCs. Thus, in this study we evaluated the effect of 15d-PGJ2 on DC surface molecule expression, including MHC-II, CD80, and CD86. In addition, we quantified cytokine production in the presence of 15d-PGJ2 or rosiglitazone. Expression of the surface molecules was measured by flow cytometry and cytokines production was measured by ELISA in supernatant of BMDC cultures. The results suggest that 15d-PGJ2 reduced the expression of costimulatory molecules (CD80 and CD86), without altering MCH-class II expression. Furthermore the natural PPAR-γ agonist significantly reduced levels of proinflammatory cytokines (IL-12, IFN-γ, and TNF-α) and appears to also reduce IL-1β levels. Rosiglitazone reduced the expression of these cytokines albeit to a lesser extent. These data suggest the idea that 15d-PGJ2 could be a therapeutic strategy in diseases where DCs play a crucial role, due to its ability to reduce costimulatory molecules expression and modulate the inflammatory environment

Antitumor potential of lipid nanoformulations with natural antioxidants

ABSTRACT: Quercetin (QUE), tannic acid (TA) and ascorbic acid (AA) are among the antioxidants that have demonstrated efficacy in the treatment and prevention of cancer, cardiovascular and neurodegenerative diseases. However, the optimal method of administering these compounds for therapeutic purposes is not well understood, especially when considering their differences in size and solubility. In this context, nanoencapsulation rises as a promising strategy, since this technology could protect active ingredients and maximize their absorption. In this study, the aforementioned antioxidants were encapsulated in a lipid mixture with the objective of developing nontoxic and effective materials for antitumor therapy. The results demonstrated that the compounds were satisfactorily encapsulated in Large Unilamellar Vesicles (LUVs) composed of phosphatidylcholine (PC) and phosphatidylglycerol (PG). The formulations exhibited good homogeneity in average size as well as stability, as investigated by dynamic light scattering and zeta potential measurements. The encapsulation efficiency was as follows: QUE (78.76%) > TA (61.93%) > AA (47.13%). The Korsmeyer-Peppas model was employed to analyze the release kinetics, illustrating that the delivery of antioxidants follows Fick's law. Biological tests using bioactive-loaded LUVs demonstrated that the encapsulation of these antioxidants resulted in low-toxicity formulations. Quercetin-loaded LUVs (QUE-LUVs) stood out among the formulations studied, as tumor cell viability was significantly reduced after treatment with QUE-LUVs when compared to untreated cells. Furthermore, QUE-LUVs exhibited a differential cytotoxic effect between tumor cells and non-tumor cells, suggesting potential applications in anticancer therapy. Aligned with the demand for innovative treatments as well as drug delivery methods that show less toxicity and adverse effects, the approach developed in the present study resulted in formulations with significant potential and versatility, and could serve as a potential mixed lipid-based delivery system in tumor management using antioxidant therapy

Progressive multifocal leukoencephalopathy triggered by COVID-19 in a previously asymptomatic person living with undiagnosed HIV infection

This report presents the case of a 47-year-old male patient who worked as a mathematics teacher and experienced the sudden onset of disorientation, aphasia, and acalculia during an online class. The current study reveals the first documented case of HIV and progressive multifocal leukoencephalopathy with the detection of SARS-CoV-2 and human polyomavirus 2 (previously known as John Cunningham virus) in the cerebrospinal fluid. Furthermore, serum analysis revealed elevated concentrations of interleukin (IL)-6, IL-17, and IL-8, which are potential factors known to reduce the expression of tight junctions and adhesion molecules in the extracellular matrix, thereby affecting the permeability of the blood-brain barrier. Finally, the study discusses whether SARS-CoV-2 triggers or exacerbates progressive multifocal leukoencephalopathy

Development of Ag-ZnO/AgO Nanocomposites Effectives for Leishmania braziliensis Treatment

Tegumentary leishmaniasis (TL) is caused by parasites of the genus Leishmania. Leishmania braziliensis (L.b) is one of the most clinically relevant pathogens that affects the skin and mucosa, causing single or multiple disfiguring and life-threatening injuries. Even so, the few treatment options for patients have significant toxicity, high dropout rates, high cost, and the emergence of resistant strains, which implies the need for studies to promote new and better treatments to combat the disease. Zinc oxide nanocrystals are microbicidal and immunomodulatory agents. Here, we develop new Ag-ZnO/xAgO nanocomposites (NCPs) with three different percentages of silver oxide (AgO) nanocrystals (x = 49%, 65%, and 68%) that could act as an option for tegumentary leishmaniasis treatment. Our findings showed that 65% and 68% of AgO inhibit the extra and intracellular replication of L.b. and present a high selectivity index. Ag-ZnO/65%AgO NCPs modulate activation, expression of surface receptors, and cytokine production by human peripheral blood mononuclear cells toward a proinflammatory phenotype. These results point to new Ag-ZnO/AgO nanocomposites as a promising option for L. braziliensis treatment