Enhancing the antischistosomal activity of carvacryl acetate using nanoemulsion.

Aim: To formulate a carvacryl acetate nanoemulsion (CANE) and test its antischistosomal activity. Materials & methods: CANE was prepared and tested in vitro on Schistosoma mansoni adult worms and both human and animal cell lines. Next, CANE was administered orally to mice infected with either a prepatent infection or a patent infection of S. mansoni. Results: CANE was stable during 90 days of analysis. CANE showed in vitro anthelmintic activity, and no cytotoxic effects were observed. In vivo, CANE was more effective than the free compounds in reducing worm burden and egg production. Treatment with CANE was more effective for prepatent infections than praziquantel. Conclusion: CANE improves antiparasitic properties and may be a promising delivery system for schistosomiasis treatment.

Antileishmanial Activity of Cinnamic Acid Derivatives against Leishmania infantum.

Leishmania infantum is the etiological agent of visceral leishmaniasis (VL) in South America, the Mediterranean basin, and West and Central Asia. The most affected country, Brazil, reported 4297 VL cases in 2017. L. infantum is transmitted by female phlebotomine sand flies during successive blood meals. There are no validated vaccines to prevent the infection and the treatment relies on drugs that often present severe side effects, which justify the efforts to find new antileishmanial drugs. Cinnamic acid derivatives have shown several pharmacological activities, including antiparasitic action. Therefore, in the present study, the biological evaluation of cinnamic acid and thirty-four derivatives against L. infantum is reported. The compounds were prepared by several synthesis methods and characterized by spectroscopic techniques and high-resolution mass spectrometry. The results revealed that compound 32 (N-(4-isopropylbenzyl)cinnamamide) was the most potent antileishmanial agent (IC50 = 33.71 µM) with the highest selectivity index (SI > 42.46), followed by compound 15 (piperonyl cinnamate) with an IC50 = 42.80 µM and SI > 32.86. Compound 32 was slightly less potent and nineteen times more selective for the parasite than amphotericin B (MIC = 3.14 uM; SI = 2.24). In the molecular docking study, the most likely target for the compound in L. infantum was aspartyl aminopeptidase, followed by aldehyde dehydrogenase, mitochondrial. The data obtained show the antileishmanial potential of this class of compounds and may be used in the search for new drug candidates against Leishmania species.

Synthetic Cinnamides and Cinnamates: Antimicrobial Activity, Mechanism of Action, and In Silico Study.

The severity of infectious diseases associated with the resistance of microorganisms to drugs highlights the importance of investigating bioactive compounds with antimicrobial potential. Therefore, nineteen synthetic cinnamides and cinnamates having a cinnamoyl nucleus were prepared and submitted for the evaluation of antimicrobial activity against pathogenic fungi and bacteria in this study. To determine the minimum inhibitory concentration (MIC) of the compounds, possible mechanisms of antifungal action, and synergistic effects, microdilution testing in broth was used. The structures of the synthesized products were characterized with FTIR spectroscopy, 1 H-NMR, 13 C-NMR, and HRMS. Derivative 6 presented the best antifungal profile, suggesting that the presence of the butyl substituent potentiates its biological response (MIC = 626.62 µM), followed by compound 4 (672.83 µM) and compound 3 (726.36 µM). All three compounds were fungicidal, with MFC/MIC ≤ 4. For mechanism of action, compounds 4 and 6 directly interacted with the ergosterol present in the fungal plasmatic membrane and with the cell wall. Compound 18 presented the best antibacterial profile (MIC = 458.15 µM), followed by compound 9 (550.96 µM) and compound 6 (626.62 µM), which suggested that the presence of an isopropyl group is important for antibacterial activity. The compounds were bactericidal, with MBC/MIC ≤ 4. Association tests were performed using the Checkerboard method to evaluate potential synergistic effects with nystatin (fungi) and amoxicillin (bacteria). Derivatives 6 and 18 presented additive effects. Molecular docking simulations suggested that the most likely targets of compound 6 in C. albicans were caHOS2 and caRPD3, while the most likely target of compound 18 in S. aureus was saFABH. Our results suggest that these compounds could be used as prototypes to obtain new antimicrobial drugs.

Efficacy of Single- and Multi-Site Fungicides Against Neopestalotiopsis spp. of Strawberry.

Recently, the Florida strawberry industry faced unprecedented outbreaks of an emerging disease caused by the fungus Neopestalotipsis spp. Currently, there are no fungicides labeled to control this disease in the United States and the efficacy of single- and multisite fungicides is unknown. Therefore, this study aimed to determine the in vitro sensitivity of Neopestalotiopsis spp. isolates to fungicides with different modes of action and to evaluate the efficacy of these products on detached fruit and in the field. In preliminary in vitro tests, 30 commercially available fungicides were screened using discriminatory doses. The effective concentration that inhibited mycelial growth by 50% was determined for the most effective single-site fungicides. Four field experiments were conducted during the 2019-20, 2020-21, and 2021-22 seasons to determine product efficacy in managing the disease. The single-site fungicides fludioxonil, fluazinam, and sterol demethylation inhibitors, and the multisite fungicides captan, thiram, and chlorothalonil were the most effective in inhibiting pathogen growth and suppressing disease development. Conversely, products in Fungicide Resistance Action Committee (FRAC) groups 1 (methyl benzimidazole carbamate) and 7 (succinate-dehydrogenase inhibitors), except for benzovindiflupyr, were not effective against Neopestalotiopsis spp. Resistance to fungicides from FRAC group 11 (e.g., azoxystrobin) was confirmed by the presence of the G143A mutation in the cytochrome b gene together with inoculation tests and field trials. Our results provide information to support or discourage the registration of fungicides to manage Neopestalotiopsis fruit rot and leaf spot in strawberry production.

Nanoemulsion Improves the Anti-Inflammatory Effect of Intraperitoneal and Oral Administration of Carvacryl Acetate.

Carvacryl acetate (CA) is a monoterpene obtained from carvacrol, which exhibits anti-inflammatory activity. However, its low solubility in aqueous media limits its application and bioavailability. Herein, we aimed to develop a carvacryl acetate nanoemulsion (CANE) and assess its anti-inflammatory potential in preclinical trials. The optimized nanoemulsion was produced by ultrasound, and stability parameters were characterized for 90 days using dynamic light scattering after hydrophilic-lipophilic balance (HLB) assessment. To evaluate anti-inflammatory activity, a complete Freund's adjuvant-induced inflammation model was established. Paw edema was measured, and local interleukin (IL)-1ß levels were quantified using ELISA. Toxicity was assessed based on behavioral changes and biochemical assays. The optimized nanoemulsion contained 3% CA, 9% surfactants (HLB 9), and 88% water and exhibited good stability over 90 days, with no signs of toxicity. The release study revealed that CANE followed zero-order kinetics. Dose-response curves for CA were generated for intraperitoneal and oral administration, demonstrating anti-inflammatory effects by both routes; however, efficacy was lower when administered orally. Furthermore, CANE showed improved anti-inflammatory activity when compared with free oil, particularly when administered orally. Moreover, daily treatment with CANE did not induce behavioral or biochemical alterations. Overall, these findings indicate that nanoemulsification can enhance the anti-inflammatory properties of CA by oral administration.

Sintomatologia de ansiedade em profissionais do serviço de atendimento móvel de urgência / Sintomatología de la ansiedad en los profesionales del servicio de atención móvil de urgencias / Anxiety symptomatology in professionals of the mobile emergency care service

Objetivo: Rastrear sintomas de ansiedade em profissionais do Serviço de Atendimento Móvel de Urgência (SAMU). Método: Estudo exploratório, descritivo e transversal, de abordagem quantitativa, realizado em SAMU localizado no interior do Piauí, entre abril e junho de 2021, através de questionário on-line. O instrumento classificou os participantes em: ansiedade mínima; ansiedade leve; ansiedade moderada; e ansiedade grave. Para análise estatística utilizou-se o teste de razão de verossimilhança, pois, a razão esperada foi menor que 5 nas variáveis analisadas, sendo considerado o nível de significância de 5% (p<0,05). Resultados: Participaram do estudo 14 profissionais assistenciais. Entre os sintomas indagados, houve prevalência de: "incapacidade de relaxar" (35,7%), "medo que o pior aconteça" (35,6%), "palpitação ou aceleração do coração" (28,6%) e "sensação de calor" (28,5%). Conclusão: A maioria dos emergencistas foi classificada com ansiedade mínima, contudo, a baixa adesão de participantes dificultou uma análise mais consistente da sintomatologia de ansiedade nesses profissionais.(AU)

Objective: To screen anxiety symptoms in Mobile Emergency Care Service (SAMU) professionals. Method: Exploratory, descriptive and cross-sectional study, with quantitative approach, conducted in SAMU located in the interior of Piauí, between April and June 2021, through an online questionnaire. The instrument classified participants into: minimal anxiety; mild anxiety; moderate anxiety; and severe anxiety. For statistical analysis we used the likelihood ratio test, because the expected ratio was less than 5 in the variables analyzed, being considered the significance level of 5% (p<0.05). Results: Fourteen caregivers participated in the study. Among the symptoms inquired, there was a prevalence of: "inability to relax" (35.7%), "fear that the worst will happen" (35.6%), "palpitation or acceleration of the heart" (28.6%) and "feeling hot" (28.5%). Conclusion: Most emergency responders were classified with minimal anxiety, however, the low adherence of participants hindered a more consistent analysis of anxiety symptomatology in these professionals (AU)

Objetivo: Identificar los síntomas de ansiedad entre los profesionales del Servicio de Atención Móvil de Urgencias (SAMU). Método: Estudio exploratorio, descriptivo y transversal, con enfoque cuantitativo, realizado en un SAMU ubicado en el interior de Piauí, entre abril y junio de 2021, a través de un cuestionario online. El instrumento clasificó a los participantes en: ansiedad mínima, ansiedad leve, ansiedad moderada y ansiedad grave. Para el análisis estadístico se utilizó la prueba de la razón de verosimilitud, ya que la razón esperada era inferior a 5 en las variables analizadas, considerándose el nivel de significación del 5% (p<0,05). Resultados: Catorce cuidadores participaron en el estudio. Entre los síntomas indagados, hubo una prevalencia de: "incapacidad para relajarse" (35,7%), "miedo a que ocurra lo peor" (35,6%), "palpitaciones o aceleración del corazón" (28,6%) y "sensación de calor" (28,5%). Conclusión: La mayoría de los socorristas fueron clasificados con ansiedad mínima, sin embargo, la baja adherencia de los participantes impidió un análisis más consistente de la sintomatología de ansiedad en estos profesionales (AU)

In silico, in vitro, and in vivo investigation of antioxidant potential and toxicity of ethyl ferulate.

By submitting this manuscript, each author certifies that they have made a direct and substantial contribution to the work reported in the manuscript. In this manuscript the conception, design, investigation, acquisition of data and analysis, interpretation of data and writing of the article were conducted by author Camila Bomfim de Sá under the guidance of professors Margareth de Fátima Formiga Melo Diniz, Hilzeth de Luna Freire Pessôa and Caliandra Maria Bezerra Luna Lima, who also approved the final version of the manuscript. Professor Damião Pergentino de Sousa and his student Mayara Castro de Morais performed the production, synthesis and chemical characterization of ethyl ferulate (EF). Professor Abrahão Alves de Oliveira Filho assessed the in silico tests. PhD student Andressa Brito Lira participated in the critical review of the text for important intellectual content and assisted in the in vitro antioxidant activity and cytotoxicity tests. Kardilandia Mendes de Oliveira participated in acute oral toxicity tests evaluating the biochemical parameters. Students, Tafaela Dias and Cinthia Rodrigues Melo also assisted in the acute oral toxicity testing and preparing of slides for histopathological analysis. Pathologist Alexandre Rolim da Paz analyzed the histopathology results. EF, a phenolic compound of the large class of phenylpropanoids, is derived from ferulic acid and is produced both naturally and synthetically. Its principal pharmacological activities are: anti-inflammatory and antioxidant activity. This study aimed to investigate the in silico, in vitro and in vivo toxicity and antioxidant activity of EF. The in silico prediction showed more than 20 biological activities as well as good absorption at the biological membranes and no theoretical toxicity. However, EF presented high environmental toxicity. EF presented low hemolytic potential and exerted protective activity for the erythrocyte membrane for only blood type O. EF presented antioxidant activity against H2O2 at all concentrations and all blood types, but no effect against phenylhydrazine, being unable to prevent its oxidative effects. In the acute nonclinical toxicological trial, the treated animals presented behavioral changes (e.g., sedation). Feed intake was higher for the 2000 mg/kg group, but with no significant difference in weight change. The biochemical parameters presented no differences between treated and control animals, and the organs remained intact with no change. Thus, EF presents a low toxic profile and this study provides important information about the toxicity of this compound, suggesting future safe use.

Cytotoxic and Antifungal Amides Derived from Ferulic Acid: Molecular Docking and Mechanism of Action.

Amides derived from ferulic acid have a wide spectrum of pharmacological activities, including antitumor and antifungal activity. In the present study, a series of ten amides were obtained by coupling reactions using the reagents (benzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate (PyBOP) and N,N'-dicyclohexylcarbodiimide (DCC). All the compounds were identified on the basis of their IR, 1H- and 13C-NMR, HRMS data, and with yields ranging from 43.17% to 91.37%. The compounds were subjected to cytotoxic tests by the alamar blue technique and antifungal screening by the broth microdilution method to determine the minimum inhibitory concentration (MIC). The amides 10 and 11 displayed the best result in both biological evaluations, and compound 10 was the most potent and selective in HL-60 cancer cells, with no cytotoxicity on healthy cells. This amide had antifungal activity in all strains and had the lowest MIC against Candida albicans and Candida tropicalis. The possible mechanism of antifungal action occurs via the fungal cell wall. Molecular modeling suggested that compounds 10 and 11 interact with the enzymes GWT1 and GSC1, which are essential for the development of C. albicans. The findings of the present study demonstrated that compounds 10 and 11 may be used as a platform in drug development in the future.

Snakes of the Pernambuco Endemism Center, Brazil: diversity, natural history and conservation.

The Atlantic Forest is one of the largest and richest tropical rainforests on the planet, being one of the 25 world priorities for conservation. The Atlantic Forest portion located north of the São Francisco River corresponds to the Pernambuco Endemism Center (PEC). We describe the snake composition of the PEC, providing information about the diversity, natural history and geographical distribution of the species, based on records from five scientific collections and additional information from the literature. A total of 78 species of snakes distributed in eight families was registered in the Pernambuco Endemism Center. The Caatinga is the Brazilian biome that most shares species with the PEC, followed by Cerrado. On the other hand, seven species are considered endemic of this region. Most of the snake species in the PEC have been registered in forest (94.8%), followed by "Brejos Nordestinos" (46.1%), Tabuleiros (43.5%), Restingas (14.1%) and Mangroves (5.1%). The PEC snake fauna includes mainly terrestrial species (60.2%) and cryptozoic and/or fossorial species (21.7%), but also presents a high richness of semi-arboreal and arboreal species (29.5%). Vertebrates are the main food item consumed by the species (78% of species), among the main prey are mammals, lizards, and amphibians. Most species show a strictly nocturnal activity period (50%), followed by strictly diurnal (38%). The PEC is the most degraded and least known region of the Atlantic Forest, yet it has revealed a high richness of snake species, including seven endemic species. It is emphasized that regional conservation efforts need to be intensified, because few forests in the region are formally protected, and the majority consist of small and poorly protected fragments, which means that many species in the region may be in risk of extinction.

Trypanocidal Essential Oils: A Review.

Trypanosomiases are diseases caused by parasitic protozoan trypanosomes of the genus Trypanosoma. In humans, this includes Chagas disease and African trypanosomiasis. There are few therapeutic options, and there is low efficacy to clinical treatment. Therefore, the search for new drugs for the trypanosomiasis is urgent. This review describes studies of the trypanocidal properties of essential oils, an important group of natural products widely found in several tropical countries. Seventy-seven plants were selected from literature for the trypanocidal activity of their essential oils. The main chemical constituents and mechanisms of action are also discussed. In vitro and in vivo experimental data show the therapeutic potential of these natural products for the treatment of infections caused by species of Trypanosoma.

(-)-cis-Carveol, a Natural Compound, Improves ß-Amyloid-Peptide 1-42-Induced Memory Impairment and Oxidative Stress in the Rat Hippocampus.

Alzheimer's disease (AD) could be considered a multifactorial neurodegenerative disorder characterized by the accumulation of the ß-amyloid-peptide (Aß) within the brain leading to cognitive deficits, oxidative stress, and neuroinflammation. The present work was carried out to investigate the neuroprotective effect of (-)-cis-carveol (1% and 3%, for 21 days) against the ß-amyloid-peptide 1-42- (Aß1-42-) induced AD. Twenty-five rats were divided into five groups (n = 5/group): the first group-control (sham-operated); the second group-Aß1-42 (1 mM) that received donepezil treatment (5 mg/kg, as the positive reference drug in the Y-maze and the radial arm maze tests); the third group-Aß1-42 (1 mM); the fourth and fifth groups-Aß1-42 (1 mM) that received (-)-cis-carveol treatment groups (1% and 3%). The results of this study demonstrated that (-)-cis-carveol improved Aß1-42-induced memory deficits examined by using Y-maze and radial arm maze in vivo tests. Also, the biochemical analyses of the hippocampus homogenates showed that (-)-cis-carveol reduced hippocampal oxidative stress caused by Aß1-42. Our results suggested that the use of (-)-cis-carveol may be suitable for decreasing AD-related symptoms.

The Dual Antioxidant/Prooxidant Effect of Eugenol and Its Action in Cancer Development and Treatment.

The formation of reactive oxygen species (ROS) during metabolism is a normal process usually compensated for by the antioxidant defense system of an organism. However, ROS can cause oxidative damage and have been proposed to be the main cause of age-related clinical complications and diseases such as cancer. In recent decades, the relationship between diet and cancer has been more studied, especially with foods containing antioxidant compounds. Eugenol is a natural compound widely found in many aromatic plant species, spices and foods and is used in cosmetics and pharmaceutical products. Eugenol has a dual effect on oxidative stress, which can action as an antioxidant or prooxidant agent. In addition, it has anti-carcinogenic, cytotoxic and antitumor properties. Considering the importance of eugenol in the area of food and human health, in this review, we discuss the role of eugenol on redox status and its potential use in the treatment and prevention of cancer.

Safety and efficacy of the combination of T-DM1 with radiotherapy of the central nervous system in a patient with HER2-positive metastatic breast cancer: case study and review of the literature.

Approximately 35% of patients with confirmed HER2 breast cancer progress to metastases of the central nervous system (CNS). Total cerebral radiotherapy is considered as standard treatment for these cases; however, studies have shown that some chemotherapy drugs can be used during radiotherapy without significantly increasing its toxicity. In this article, we report the case of a patient with HER2-positive breast cancer who showed isolated progression of the illness in the CNS, which was observed during the treatment period using T-DM1 concomitantly with radiotherapy of the CNS without apparent toxicity of the combination and keeping the illness controlled. Through a review of the literature on the use of radiotherapy and chemotherapy with T-DM1 for the treatment of cerebral metastases in HER2-positive breast cancer, we describe the efficacy and tolerance of the concomitant application of these treatments.