Perillyl alcohol in Solid Lipid Nanoparticles (SLN-PA): Cytotoxicity and antitumor potential in sarcoma 180 mice model

Cancer is a group of diseases characterized by the uncontrolled growth of cells. These cells invade organs and tissues by extension or direct dissemination and can spread to other regions of the body. Nanomedicine offers many possibilities to prevent the spread of cancer tissue and help cure the disease. In this work, solid lipid nanoparticles (SLN) were used to encapsulate perillyl alcohol (PA), a volatile monoterpene with proven anticancer activity. Encapsulation of PA into SLN (SLN-PA) is expected to promote controlled release, increase PA bioavailability, and impair the volatility of the monoterpene. SLN-PA prepared by high-shear homogenization showed average particle diameter around 254 nm, polydispersity index ~ 0.35, zeta potential ~ -14.7 mV, and encapsulation efficiency 84.6%. Scanning electron microscope analysis revealed a decrease in crystallinity, suggesting the encapsulation of PA in the SLN, confirming the spherical shape and the loading of the monoterpene in the SLN. In vitro cytotoxicity assays against murine fibroblasts (L929) showed that SLN-PA in both treated doses did not induce any cytotoxicity on non-tumoral cells. In vivo antitumor effect of the SLN-PA was evaluated in sarcoma 180-transplanted mice. The in vivo results demonstrated a significant tumor inhibition rate of 51.76 and 54.49% via intraperitoneal application of SLN-PA at doses of 100 and 200 mg/kg/day (p < 0.05), respective when compared to the negative control (dimethyl sulfoxide). Adverse side effects of SLN-PA were not noticed in the liver, the kidney, or spleen tissue. The developed SLN-PA can be considered as a safe approach for site-specific antitumor effect in vivo, reinterpreting new nanoparticles- based cancer therapy.This work was supported by the Banco do Nordeste (grant FUNDECI/2016.0015), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (Fapitec) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Eliana B. Souto would like to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Herpetofauna of protected areas in the Caatinga II: Serra da Capivara National Park, Piauí, Brazil

We provide a list of amphibians, lizards, chelonians, and snakes collected during a 30-day expedition to the Serra da Capivara National Park, Piauí State, Brazil. Thirty-seven pitfall trap arrays composed of 4 buckets each, along with glue traps, funnel traps, and haphazard searches, were used to sample the herpetofaunal diversity. We recorded 17 species of lizards, 1 caecilian, 1 chelonian, 7 frogs, and 11 snakes. Rarefaction curves suggest that local biodiversity is still underestimated. An atypical drought during the period of study may have contributed to lower captures of certain groups, especially amphibians and snakes. The presence of water-dependent and forest-dependent species within local canyons (“Boqueirões”) suggests that these areas harbor faunas associated with relictual rainforest fragments and need to be better studied and managed accordinglyFil: Barbosa de Queiroga Calvacanti, Lucas. Universidade Federal Da Paraiba; BrasilFil: Borges Costa, Tais. Universidade Federal Da Paraiba; BrasilFil: Rinaldi Colli, Guarino. Universidade Do Brasilia; BrasilFil: Corrêa Costa, Gabriel. Universidade Federal Do Rio Grande Do Norte. Centro de Biociencias. Departamento de Boanica, Ecologia E Zoologia; BrasilFil: Rodrigues França, Frederico Gustavo. Universidade Federal Da Paraiba; BrasilFil: Oliveira Mesquita, Daniel. Universidade Federal Da Paraiba; BrasilFil: Silva Palmeira, Cristiane Nikely. Universidade Federal de Alagoas; BrasilFil: Pelegrin, Nicolas. Universidad Nacional de Cordoba. Facultad de Cs.exactas Fisicas y Naturales. Centro de Zoologia Aplicada; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Diversidad y Ecologia Animal; ArgentinaFil: Soares, Ana Hemínia Bello. Universidade Do Brasilia; BrasilFil: Tucker, Derek B.. University Brigham Young; Estados UnidosFil: Garda, Adrian Antonio. Universidade Federal do Rio Grande do Norte; Brasi

Silver nanoparticles-composing alginate/gelatine hydrogel improves wound healing in vivo

Polymer hydrogels have been suggested as dressing materials for the treatment of cutaneous wounds and tissue revitalization. In this work, we report the development of a hydrogel composed of natural polymers (sodium alginate and gelatin) and silver nanoparticles (AgNPs) with recognized antimicrobial activity for healing cutaneous lesions. For the development of the hydrogel, different ratios of sodium alginate and gelatin have been tested, while different concentrations of AgNO3 precursor (1.0, 2.0, and 4.0 mM) were assayed for the production of AgNPs. The obtained AgNPs exhibited a characteristic peak between 430450 nm in the ultraviolet-visible (UVVis) spectrum suggesting a spheroidal form, which was confirmed by Transmission Electron Microscopy (TEM). Fourier Transform Infra-red (FTIR) analysis suggested the formation of strong intermolecular interactions as hydrogen bonds and electrostatic attractions between polymers, showing bands at 2920, 2852, 1500, and 1640 cm1. Significant bactericidal activity was observed for the hydrogel, with a Minimum Inhibitory Concentration (MIC) of 0.50 µg/mL against Pseudomonas aeruginosa and 53.0 µg/mL against Staphylococcus aureus. AgNPs were shown to be non-cytotoxic against fibroblast cells. The in vivo studies in female Wister rats confirmed the capacity of the AgNP-loaded hydrogels to reduce the wound size compared to uncoated injuries promoting histological changes in the healing tissue over the time course of wound healing, as in earlier development and maturation of granulation tissue. The developed hydrogel with AgNPs has healing potential for clinical applications.This research received funding from the Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Sergipe (FAPITEC), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, #443238/2014-6, #470388/2014-5), and from the Portuguese Science and Technology Foundation (FCT) projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund).info:eu-repo/semantics/publishedVersio

Correction: Diniz et al. Silver Nanoparticles-Composing Alginate/Gelatine Hydrogel Improves Wound Healing In Vivo. Nanomaterials 2020, 10, 390

In the original publication, there was a mistake in Figure 6 as published [...]info:eu-repo/semantics/publishedVersio

CD4+ Th1 and Th17 responses and multifunctional CD8 T lymphocytes associated with cure or disease worsening in human visceral leishmaniasis

IntroductionIn VL, a proinflammatory phenotype is typically associated with enhanced phagocytosis and a Th1 mediated immune response resulting in infection control. In contrast, an anti-inflammatory phenotype, associated with a predominant regulatory response, typically enables intracellular multiplication of Leishmania parasites and disease progression.MethodsTo investigate the impact of chemotherapy on Th2 and Th17 immune responses in patients with visceral leishmaniasis (VL), we assessed all combinations of intracellular expression of IFN-γ, IL-10, IL-4 and IL-17 in the CD4+ and CD8+ T cell populations of peripheral blood mononuclear cell (PBMC) samples from patients, after antigenic stimulation with Leishmania lysate, throughout treatment and follow-up. As increases in spleen and liver sizes and decreases in hematocrit, hemogloblin, erythrocytes, monocytes, leukocytes and platelets levels are strongly related to the disease, we studied the correlations between the frequencies of T cells producing the afore mentioned cytokines, individually and in combination, and these variables, as markers of disease or cure.ResultsWe found that the frequency of IFN-γ-producingCD4+ T cells increased until the end of chemotherapy with Glucantime® or AmBisome ®, while IL-10, IL-4 and IL-17-producing CD4+ T cells peaked on day 7 following the start of treatment. Although the frequency of CD4+IL-17+ cells decreased during treatment an increase was observed after clinical cure. The frequency of CD4+ T cells producing only IFN-γ or IL-17 correlated with blood monocytes levels. Frequencies of double-producers of IFN-γ and IL-10 or IL-4 correlated positively with eosinophils and platelets levels. Together, this suggest that IFN-γ drives the immune response towards Th1 at cure. In contrast, and associated with disease or Th2 response, the frequency of CD4+ IL-10+ cells correlated positively with spleen sizes and negatively with circulating monocyte levels, while the frequency of CD4+ producing both IL-4 and IL-10 correlated negatively with platelets levels. The frequency of CD8+ single-producers of IFN-γ increased from day 21 to 90 while that of single-producers of IL-10 peaked on day 7, of IL-4 on day 30 and of IL-17, on day 180. IFN-γ expression in CD8+ single- and double-producers of cytokines was indicative of an immune response associated with cure. In contrast, frequencies of CD8+ double-producers of IL-4 and IL-10, IL-4 and IL-17 and IL-10 and IL-17 and producers of three and four cytokines, were associated with disease and were low after the cure. Frequencies of CD8+ T cells producing IFN-γ alone or with IL-17 were positively correlated with platelets levels. In contrast, as markers of disease: 1) frequencies of single producers of IL-10 correlated negatively with leukocytes levels, 2) frequencies of double producers of IL-4 and IL-10 correlated negatively with platelet, leukocyte, lymphocyte and circulating monocyte levels, 3) frequencies of triple-producers of IFN-γ, IL-4 and IL-10 correlated negatively with platelet, leukocyte and neutrophil levels and 4) frequencies of producers of IFN-γ, IL-4, IL-10 and IL-17 simultaneously correlated positively with spleen size, and negatively with leukocyte and neutrophil levels.DiscussionOur results confirmed that the clinical improvement of VL patients correlates with the decrease of an IL-4 and IL-10 CD4+Th2 response, the recovery of CD4+ Th1 and Th17 responses and the frequency of CD8+ single-producers of IFN-γ and double producers of IFN-γ and IL-17