Using the plants of Brazilian Cerrado for wound healing : from traditional use to scientific approach

Ethnopharmacological relevance The Brazilian Cerrado is a biome with a remarkable diversity of plant species, many of which are used mainly by local communities as a source of treatment to several pathologic processes, especially for the treatment of wounds. However, no systematic review exists focusing on the plants used in this respect and on the appropriate pharmacological investigations that substantiate the actions that are reported. This study revisits the traditional use of medicinal plants from the Brazilian Cerrado in the treatment of wounds and the pharmacological characteristics of the reported plant species. Methodology For the present article, previous studies on plants of the Brazilian Cerrado used for wound healing carried out between 1996 and 2018 were researched on various academic databases (PubMed, Elsevier, Springer, Lilacs, Google Escolar, and Scielo). Results A total of 33 studies were carried out on 29 plant species distributed into 18 families, mainly Fabaceae or Leguminosae (9), Bignoniaceae (2), Asteraceae (2), Euphorbiaceae (2). Considering the great diversity of Cerrado plants, only a small number of wound healing studies were carried out between 1996 and 2018. It was observed that there is a large gap between experimentation assay and traditional use. There are only few connections between the form of use by the population and the experiments conducted in the laboratory. We found that only about 12% of these studies considered to use the methodologies, or at least in parts, to obtain extracts such as those used in folk medicine. Approximately 37% of the experiments were performed using the bark as well as the same ratio for leaves, 6% using the fruits, and 9% using the seeds, roots or flowers. In several studies, there are reports of chemical constituents such as flavonoids and tannins, followed by steroid terpenes, saponins, and fatty acids, and alkaloids. However, approximately 35% of the studies did not supply information about compounds present in the preparation or the effect which could be attributed to these agents in respect to wound healing. Regarding treatment, most of the studies employed a topical treatment, though intraperitoneal and oral treatment were also described using either topical, oil-based formulations, but also gel- or saline-based formulations. Conclusions Although, there has been an increase in knowledge about the biological actions of plants from Cerrado biome, the scientific basis for the traditional use of these local medicinal plants in wound healing does not provide sufficient information on the efficacy of the treatment, the molecular mechanisms, or, in particular, the effective doses used and the drug interactions. Thus, focused research investigating these hypotheses from traditional knowledge is necessary to prove the evidence of the potential pharmacological action

Análise da presença de benzodiazepínicos no ambiente aquático e o possível cenário de impacto ambiental / Analysis of the presence of benzodiazepines in the aquatic environment and the possible environmental impact scenario

Os benzodiazepínicos são fármacos psicotrópicos amplamente utilizados, que podem atingir o meio aquático por diversas vias e persistirem nestes ambientes como micropoluentes, devido aos processos de tratamento de água e esgoto convencionais não removerem os mesmos em sua totalidade. Dessa forma, foi realizada uma revisão narrativa com o objetivo de avaliar estudos que retratem a presença de benzodiazepínicos em ambientes aquáticos e suas respectivas concentrações, além de analisar os possíveis impactos negativos ao meio ambiente. Foram realizadas buscas de artigos, em quatro bases de dados: PubMed, Science Direct, SciELO e Google Acadêmico, utilizando os descritores “Sewage”, “Benzodiazepine”, “Effluents” e “Wastewater”, juntamente com o operador booleano “AND”. 34 artigos foram incluídos nesta revisão, sendo três realizados no Brasil e 31 em outros países. Foi observado que 32/34 artigos relataram a presença de benzodiazepínicos no ambiente aquático, sendo os mais frequentes o diazepam, oxazepam e lorazepam, e os encontrados em maiores concentraçoes o bromazepam, oxazepam e lorazepam. Dois estudos abordaram também alguns efeitos tóxicos decorrentes da presença de benzodiazepínicos no ambiente aquático, tais como citotoxicidade em leveduras e diatomáceas, bioacumulação e alterações comportamentais em peixes. A presença destes fármacos no ambiente aquático é preocupante, uma vez que os benzodiazepínicos podem causar danos não só aos organismos aquáticos, mas também à saúde pública. Portanto, a presente revisão coloca em foco a presença de benzodiazepínicos no ambiente aquático e seus efeitos nocivos, sendo necessários mais estudos de toxicidade e o desenvolvimento de novas tecnologias para resolução desta problemática.

Synergetic action of atorvastatin and fluconazole against fluconazole-resistant Candida albicans in vitro and in a murine model for intra-abdominal Candidiasis / Ação sinérgica da atorvastatina e fluconazol contra Candida albicans resistente ao fluconazol in vitro e em um modelo murino contra Candidíase intra-abdominal

Introduction: Candida albicans is the most common causative agent of Intra-abdominal Candidiasis (IAC) and it is resistant to most antifungal drugs currently available. Here we investigated atorvastatin in vitro and in vivo antifungal activities against a fluconazole-resistant C. albicans strain as a potential repurposed drug. The following tests were carried out: antifungal susceptibility tests to determine minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), determination of time-kill curve, biofilm assays, Candida albicans yeast-hyphae transition inhibition assay, murine model of Intra-abdominal candidiasis, survival curve, fungal load quantification, histopathology analysis, quantification of TNF-α and IL-17 cytokines, quantification of N-acetyl-β-D-glucosaminidase. In vitro assays showed the synergetic action of atorvastatin and fluconazole against C. albicans growth and biofilm maturation while the time-kill curve assay revealed their fungicidal effect after 24 h of treatment. When yeast-to-hyphae transition was assessed, the synergetic effect of atorvastatin and fluconazole reduced C. albicans filamentation significantly. In vivo tests showed that one of the most noticeable signs of IAC is the intense systemic inflammation. However, our survival curve test showed that despite being ill, animals exhibited little to no clinical signs of systemic inflammation when treatment included a combination of atorvastatin and fluconazole. Altogether, these findings suggest that atorvastatin could be feasibly used in the treatment fluconazole-resistant C. albicans strains, showing that drug repurposing is an important strategy when considering the limited number of antifungal drugs available for treatment in addition to financial hardship experienced in research and development of new antifungal drugs.

Immunohistochemical, morphological and histometrical analyses of follicular development in Astyanax bimaculatus (Teleostei: Characidae) exposed to an organochlorine insecticide

Thiodan® is an organochlorine insecticide used in agriculture that can reach aquatic ecosystems where it can affect fish reproduction. This research aimed to evaluate follicular development and the expression of integrin β1, collagen type IV and caspase 3 by morphological, histometrical and immunohistochemical analyses of Astyanax bimaculatus exposed to Thiodan®. Treatments included three sublethal concentrations of Thiodan® (1.15, 2.30, and 5.60 μg L−1) for 96 h and a control without the insecticide. Mature females with ovaries in advanced follicular development were chosen for study (average weight: 11.52 ± 2.0 g; average total length: 9.12 ± 0.64 cm). The follicles of A. bimaculatus exhibited normal morphology, while the diameters of secondary follicles showed an increase (P< 0.05) in all concentrations when compared to the control group; a characteristic of follicles undergoing the initial stages of intoxication. Immunohistochemical analysis revealed secondary follicles with greater expression of integrin β1 and collagen type IV in cytoplasm of follicular cells than in the primary follicles in all treatments and in the control. Immunolocalization of caspase 3 was detected in follicular cells during secondary development in all tested concentrations of Thiodan® and the control. These analyses demonstrate positive immunolocalization throughout the course of follicular development, even in fish exposed to varying concentrations of Thiodan® for 96 h, demonstrating that follicular cells retain their physiological integrity

<b>Length-weight relationship and reproductive activity of the <i>Leporinus piau</i> Fowler, 1941 captured in a small deactivated hydropower plant</b> - doi: 10.4025/actascibiolsci.v35i3.17675

Reproductive activity of ‘piau gordura’ <em>Leporinus piau</em> was studied using biometric, macroscopic and microscopic analysis. A total of 74 specimens of <em>L. piau</em> were collected quarterly from January to December 2005 in a small deactivated  hydropower plant located at Jorge Pequeno Stream and preserved in a fixative solution until analysis. The alterations after fixation were evaluated. The stages of gonadal maturation were determined by histology and gonadosomatic index (GSI). The females and males in the spawning capable and regressing stage were registered from October to December. <em>L. piau</em> is total spawning and the HSI (hepatossomatic index), SRI (stomach repletion index) and CFI (coelomic fat index) of females and males did not showed a statistical difference. However they were numerically different between the stages of maturation. For both sexes, the smallest specimens captured during the reproductive activity have measured around 8.3 cm in total standard. The length-weight relationship observed for the parameter ‘b’ was 3.01 and the parameter ‘a’ was 0.02. This study demonstrates the importance of Jorge Pequeno Stream in the reproductive activity of migratory fish in the upper São Francisco river.<br /> <p class="akeyword"> </p><p> </p

WIN55,212-2 induces caspase-independent apoptosis on human glioblastoma cells by regulating HSP70, p53 and Cathepsin D

Despite the standard approaches to treat the highly aggressive and invasive glioblastoma (GBM), it remains incurable. In this sense, cannabinoids highlight as a promising tool, because this tumor overexpresses CB1 and/or CB2 receptors and being, therefore, can be susceptible to cannabinoids treatment. Thus, this work investigated the action of the cannabinoid agonist WIN55-212-2 on GBM cell lines and non-malignant cell lines, in vitro and in vivo. WIN was selectively cytotoxic to GBM cells. These presented blebbing and nuclear alterations in addition to cell shrinkage and chromatin condensation. WIN also significantly inhibited the migration of GAMG and U251 cells. Finally, the data also showed that the antitumor effects of WIN are exerted, at least to some extent, by the expression of p53 and increased cathepsin D in addition to the decreased expression of HSP70.This data can indicate caspase-independent cell death mechanism. In addition, WIN decreased tumoral perimeter as well as caused a reduction the blood vessels in this area, without causing lysis, hemorrhage or blood clotting. So, the findings herein presented reinforce the usefulness of cannabinoids as a candidate for further evaluation in treatment in glioblastoma treatment.Minas Gerais State Research Foundation (FAPEMIG) and NationalCouncil for Scientific and Technological Development (CNPq) bothfrom Brazil, provided thefinancial support to this stud

Spermatogonial stem cell markers and niche in equids.

Spermatogonial stem cells (SSCs) are the foundation of spermatogenesis and are located in a highly dynamic microenvironment called "niche" that influences all aspects of stem cell function, including homing, self-renewal and differentiation. Several studies have recently identified specific proteins that regulate the fate of SSCs. These studies also aimed at identifying surface markers that would facilitate the isolation of these cells in different vertebrate species. The present study is the first to investigate SSC physiology and niche in stallions and to offer a comparative evaluation of undifferentiated type A spermatogonia (Aund) markers (GFRA1, PLZF and CSF1R) in three different domestic equid species (stallions, donkeys, and mules). Aund were first characterized according to their morphology and expression of the GFRA1 receptor. Our findings strongly suggest that in stallions these cells were preferentially located in the areas facing the interstitium, particularly those nearby blood vessels. This distribution is similar to what has been observed in other vertebrate species. In addition, all three Aund markers were expressed in the equid species evaluated in this study. These markers have been well characterized in other mammalian species, which suggests that the molecular mechanisms that maintain the niche and Aund/SSCs physiology are conserved among mammals. We hope that our findings will help future studies needing isolation and cryopreservation of equids SSCs. In addition, our data will be very useful for studies that aim at preserving the germplasm of valuable animals, and involve germ cell transplantation or xenografts of equids testis fragments/germ cells suspensions

Immunohistochemical Expression of Collagens in the Skin of Horses Treated with Leukocyte-Poor Platelet-Rich Plasma

This study evaluated the immunohistochemical expression of type I (COL I) and III (COL III) collagens during the healing process of skin treated with leukocyte-poor platelet-rich plasma (LP-PRP). Seven healthy gelding crossbred horses aged 16 to 17 years were used. Two rectangle-shaped wounds were created surgically in the right and left gluteal regions. Twelve hours after wound induction, 0.5 mL of the LP-PRP was administered in each edge of the wounds of one of the gluteal regions. The contralateral region was used as control (CG). Three samples were obtained: after wound induction (T0), 14 days (T1) of healing process, and after complete closure of the skin (T2). The normal skin (T0) showed strong staining for type III and I collagen in papillary and reticular dermis, respectively. In the scar of the treated group, COL III showed important (p<0.05) increase in immunoreaction in T2 compared with T1. The administration of a single dose of LP-PRP 12 h after induction of wound in horses does not influence formation of collagens I and III. However, the intense labeling for COL III suggests that the tissue was still weak during the macroscopic closure of the wound, demonstrating that healing was not completely finished

Tapirira guianensis is selectively cytotoxic, induces apoptosis to the glioblastoma and decreases tumor growth and angiogenesis in vivo

Glioblastoma is the most frequent primary malignant brain tumor without effective treatment, which makes this work extremely relevant. The study of the bioactive compounds from medicinal plants plays an important role in the discovery of new drugs.This research investigated the constituents of Tapirira guianensis and its antitumor potential (in vitro and in vivo) in glioblastoma. The T. guianensis extracts were characterized by mass spectrometry. The ethyl acetate partition (01ID) and its fractions 01ID-F2 and 01ID-F4 from T. guianensis showed potential antitumor treatment evidenced by selective cytotoxicity for GAMG with IC50 14.1 µg/mL, 83.07 µg/mL, 59.27 µg/mL and U251 with IC50 25.92 µg/mL, 37.3 µg/mL and 18.84 µg/mL. Fractions 01ID-F2 and 01ID-F4 were 10 times more selective when compared to TMZ and 01ID for the two evaluated cell lines. T. guianensis also reduced matrix metalloproteinases 2 - 01ID-F2 (21.84%), 01ID-F4 (29.6%) and 9 - 01ID-F4 (73.42%), ID-F4 (53.84%) activities, and induced apoptosis mainly through the extrinsic pathway. Furthermore, all treatments significantly reduced tumor size (01ID p < 0,01, 01ID-F2 p < 0,01 and 01ID-F4 p < 0,0001) and caused blood vessels to shrink in vivo. The present findings highlight that T. guianensis exhibits considerable antitumor potential in preclinical studies of glioblastoma. This ability may be related to the phenolic compounds and sesquiterpene derivatives identified in the extracts. This study deserves further in vivo research, followed by clinical investigation