Multitarget anti-parasitic activities of isoquinoline alkaloids isolated from Hippeastrum aulicum (Amaryllidaceae).

BACKGROUND: Chagas disease and leishmaniasis affect a significant portion of the Latin American population and still lack efficient treatments. In this context, natural products emerge as promising compounds for developing more effective therapies, aiming to mitigate side effects and drug resistance. Notably, species from the Amaryllidaceae family emerge as potential reservoirs of antiparasitic agents due to the presence of diverse biologically active alkaloids. PURPOSE: To assess the anti-Trypanosoma cruzi and anti-Leishmania infantum activity of five isolated alkaloids from Hippeastrum aulicum Herb. (Amaryllidaceae) against different life stages of the parasites using in silico and in vitro assays. Furthermore, molecular docking was employed to evaluate the interaction of the most active alkaloids. METHODS: Five natural isoquinoline alkaloids isolated in suitable quantities for in vitro testing underwent preliminary in silico analysis to predict their potential efficacy against Trypanosoma cruzi (amastigote and trypomastigote forms) and Leishmania infantum (amastigote and promastigote forms). The in vitro antiparasitic activity and mammalian cytotoxicity were investigated with a subsequent comparison of both analysis (in silico and in vitro) findings. Additionally, this study employed the molecular docking technique, utilizing cruzain (T. cruzi) and sterol 14α-demethylase (CYP51, L. infantum) as crucial biological targets for parasite survival, specifically focusing on compounds that exhibited promising activities against both parasites. RESULTS: Through computational techniques, it was identified that the alkaloids haemanthamine (1) and lycorine (8) were the most active against T. cruzi (amastigote and trypomastigote) and L. infantum (amastigote and promastigote), while also revealing unprecedented activity of alkaloid 7­methoxy-O-methyllycorenine (6). The in vitro analysis confirmed the in silico tests, in which compound 1 presented the best activities against the promastigote and amastigote forms of L. infantum with half-maximal inhibitory concentration (IC50) 0.6 µM and 1.78 µM, respectively. Compound 8 exhibited significant activity against the amastigote form of T. cruzi (IC50 7.70 µM), and compound 6 demonstrated activity against the trypomastigote forms of T. cruzi and amastigote of L. infantum, with IC50 values of 89.55 and 86.12 µM, respectively. Molecular docking analyses indicated that alkaloids 1 and 8 exhibited superior interaction energies compared to the inhibitors. CONCLUSION: The hitherto unreported potential of compound 6 against T. cruzi trypomastigotes and L. infantum amastigotes is now brought to the forefront. Furthermore, the acquired dataset signifies that the isolated alkaloids 1 and 8 from H. aulicum might serve as prototypes for subsequent structural refinements aimed at the exploration of novel leads against both T. cruzi and L. infantum parasites.

First Description of Marinoquinoline Derivatives' Activity against Toxoplasma gondii.

Toxoplasmosis is a globally prevalent zoonotic disease with significant clinical implications, including neurotoxoplasmosis, a leading cause of cerebral lesions in AIDS patients. The current pharmacological treatments for toxoplasmosis face clinical limitations, necessitating the urgent development of new therapeutics. Natural sources have yielded diverse bioactive compounds, serving as the foundation for clinically used derivatives. The exploration of marine bacteria-derived natural products has led to marinoquinolines, which feature a pyrroloquinoline core and demonstrate in vitro and in vivo anti-Plasmodium activity. This study investigates the in vitro anti-Toxoplasma gondii potential of six marinoquinoline derivatives. Additionally, it conducts absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions, and evaluates the in vivo efficacy of one selected compound. The compounds displayed half-maximal effective concentration (EC50) values between 1.31 and 3.78 µM and half-maximal cytotoxic concentration (CC50) values ranging from 4.16 to 30.51 µM, resulting in selectivity indices (SI) from 3.18 to 20.85. MQ-1 exhibiting the highest in vitro SI, significantly reduced tachyzoite numbers in the peritoneum of RH-infected Swiss mice when it was orally administered at 12.5 mg/kg/day for eight consecutive days. Also, MQ-1 significantly reduced the cerebral parasite burden in chronically ME49 infected C57BL/6 mice when it was orally administered at 25 mg/kg/day for 10 consecutive days. These findings underscore the promising anti-T. gondii activity of marinoquinolines and their potential as novel therapeutic agents against this disease.

Natural Phenolic Compounds with Antithrombotic and Antiplatelet Effects: A Drug-likeness Approach.

BACKGROUND: Thrombosis is one of the major causes of morbidity and mortality in a wide range of vessel diseases. Several studies have been conducted to identify antithrombotic agents from medicinal plants, and phenolic compounds (PCs) have been shown to effectively inhibit plasma coagulation and platelet aggregation. OBJECTIVES: This study aimed to conduct a survey of the natural PCs with proven antithrombotic and antiplatelet activities, as well as to evaluate by computational modeling the physicochemical and toxicological properties of these compounds using drug-likeness approaches. METHODS: The data were collected from the scientific database: 'Web of Science', 'Scifinder', 'Pubmed', 'ScienceDirect' and 'Google Scholar', the different classes of PCs with antithrombotic or antiplatelet effects were used as keywords. These molecules were also evaluated for their Drug-Likeness properties and toxicity to verify their profile for being candidates for new antithrombotic drugs. RESULTS: In this review, it was possible to register 85 lignans, 73 flavonoids, 28 coumarins, 21 quinones, 23 phenolic acids, 8 xanthones and 8 simple phenols. Activity records for tannins were not found in the researched databases. Of these 246 compounds, 213 did not violate any of Lipinski's rules of five, of which 125 (59%) showed non-toxicity, being promising candidates for new potential antithrombotic drugs. CONCLUSION: This review arouses interest in the isolation of phenolic compounds that may allow a new approach for the prevention of both arterial and venous thrombosis, with the potential to become alternatives in the prevention and treatment of cardiovascular diseases.

Multitarget anti-parasitic activities of isoquinoline alkaloids isolated from Hippeastrum aulicum (Amaryllidaceae)

Background Chagas disease and leishmaniasis affect a significant portion of the Latin American population and still lack efficient treatments. In this context, natural products emerge as promising compounds for developing more effective therapies, aiming to mitigate side effects and drug resistance. Notably, species from the Amaryllidaceae family emerge as potential reservoirs of antiparasitic agents due to the presence of diverse biologically active alkaloids. Purpose To assess the anti-Trypanosoma cruzi and anti-Leishmania infantum activity of five isolated alkaloids from Hippeastrum aulicum Herb. (Amaryllidaceae) against different life stages of the parasites using in silico and in vitro assays. Furthermore, molecular docking was employed to evaluate the interaction of the most active alkaloids. Methods Five natural isoquinoline alkaloids isolated in suitable quantities for in vitro testing underwent preliminary in silico analysis to predict their potential efficacy against Trypanosoma cruzi (amastigote and trypomastigote forms) and Leishmania infantum (amastigote and promastigote forms). The in vitro antiparasitic activity and mammalian cytotoxicity were investigated with a subsequent comparison of both analysis (in silico and in vitro) findings. Additionally, this study employed the molecular docking technique, utilizing cruzain (T. cruzi) and sterol 14α-demethylase (CYP51, L. infantum) as crucial biological targets for parasite survival, specifically focusing on compounds that exhibited promising activities against both parasites. Results Through computational techniques, it was identified that the alkaloids haemanthamine (1) and lycorine (8) were the most active against T. cruzi (amastigote and trypomastigote) and L. infantum (amastigote and promastigote), while also revealing unprecedented activity of alkaloid 7‑methoxy-O-methyllycorenine (6). The in vitro analysis confirmed the in silico tests, in which compound 1 presented the best activities against the promastigote and amastigote forms of L. infantum with half-maximal inhibitory concentration (IC50) 0.6 µM and 1.78 µM, respectively. Compound 8 exhibited significant activity against the amastigote form of T. cruzi (IC50 7.70 µM), and compound 6 demonstrated activity against the trypomastigote forms of T. cruzi and amastigote of L. infantum, with IC50 values of 89.55 and 86.12 µM, respectively. Molecular docking analyses indicated that alkaloids 1 and 8 exhibited superior interaction energies compared to the inhibitors. Conclusion The hitherto unreported potential of compound 6 against T. cruzi trypomastigotes and L. infantum amastigotes is now brought to the forefront. Furthermore, the acquired dataset signifies that the isolated alkaloids 1 and 8 from H. aulicum might serve as prototypes for subsequent structural refinements aimed at the exploration of novel leads against both T. cruzi and L. infantum parasites.

Anti-Toxoplasma gondii screening of MMV pandemic response box and evaluation of RWJ-67657 efficacy in chronically infected mice.

Toxoplasmosis is a significant public health concern with limited therapeutic options. The medicines for malaria venture (MMV) developed the pandemic response box (PRB) containing 400 drug-like molecules with broad pathogen activity. The aim of this work is to evaluate PRB compounds for their anti-Toxoplasma gondii activity and identify promising candidates for further evaluation. Screening identified 42 selective compounds with half effective concentration (EC50) ranging from 2.4 to 913.1 nm and half cytotoxic concentration (CC50) ranging from 6 µm to >50 µm. Selectivity index (SI) values (CC50/EC50) ranged from 11 to 17 708. Based on its in silico and in vitro profile and its commercial availability, RWJ-67657 was selected for further studies. Molecular docking analysis showed RWJ-67657 is predicted to bind to T. gondii p38 mitogen-activated protein kinase (TgMAPK). Oral administration of RWJ-67657 (20 mg kg day−1/10 days) significantly reduced parasite burden in chronically infected mice compared to mock-treated group (P < 0.01). These findings highlight the PRB as a promising source for anti-T. gondii compounds, with several showing favourable drug properties, including MMV1634492, MMV002731, MMV1634491, MMV1581551, MMV011565, MMV1581558, MMV1578577, MMV233495 and MMV1580482, firstly described here as anti-T. gondii agents. RWJ-67657 emerges as a valuable drug candidate for experimental chronic cerebral toxoplasmosis therapy.

Methyleugenol Has an Antidepressant Effect in a Neuroendocrine Model: In Silico and In Vivo Evidence.

Major depressive disorder is a severe mood disorder characterized by different emotions and feelings. This study investigated the antidepressant activity of the phenylpropanoid methyleugenol (ME) in adult female mice exposed to a stress model induced by dexamethasone. The animals were randomly divided into groups containing eight animals and were pre-administered with dexamethasone (64 µg/kg subcutaneously). After 165 and 180 min, they were treated with ME (25, 50 and 100 mg/kg intraperitoneally) or imipramine (10 mg/kg intraperitoneally) after 45 min and 30 min, respectively; they were then submitted to tests which were filmed. The videos were analyzed blindly. In the tail suspension test, ME (50 mg/kg) increased latency and reduced immobility time. In the splash test, ME (50 mg/kg) decreased grooming latency and increased grooming time. In the open field, there was no statistical difference for the ME groups regarding the number of crosses, and ME (50 mg/kg) increased the number of rearing and time spent in the center. Regarding in silico studies, ME interacted with dopaminergic D1 and α1 adrenergic pathway receptors and with tryptophan hydroxylase inhibitor. In the in vivo evaluation of the pathways of action, the antidepressant potential of ME (50 mg/kg) was reversed by SCH23390 (4 mg/kg intraperitoneally) dopaminergic D1 receptor, Prazosin (1 mg/kg intraperitoneally) α1 adrenergic receptor, and PCPA (4 mg/kg intraperitoneally) tryptophan hydroxylase inhibitor. Our findings indicate that ME did not alter with the locomotor activity of the animals and shows antidepressant activity in female mice with the participation of the D1, α1 and serotonergic systems.

The potential of Acmella oleracea as a nutraceutical source for the symptomatic treatment of Burning Mouth Syndrome.

This study analysed the phytochemical profile of Acmella oleracea extract and the molecular interactions of its main compounds with TRPV1 and CB2, target receptors in the Burning Mouth Syndrome (BMS) pathogenesis. The phytochemical profile of A. oleracea's floral buds extract treated with activated charcoal (TCEE) was analysed by High-Performance Liquid Chromatography (HPLC) coupled to Mass Spectrometry (LC-MS). The quantification of spilanthol was analysed by HPLC coupled to a Diode-Array Detector (HPLC-DAD). The phytochemical analysis revealed the presence of nine alkylamides and phenolic compounds. The TCEE showed a significant increase in spilanthol content compared to the crude extract (CEE), going from 28.33 mg/g to 117.96 mg/g. The molecular docking indicated a behaviour of the alkylamides as partial TRPV1 agonists and CB2 agonists and, for the first time, indicates the action of these compounds in the symptomatic management of BMS.

Repurposing the Medicines for Malaria Venture's COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice.

Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world's population and can cause severe congenital, neurological and ocular issues. Current treatment options are limited, and there are no human vaccines available to prevent transmission. Drug repurposing has been effective in identifying anti-T. gondii drugs. In this study, the screening of the COVID Box, a compilation of 160 compounds provided by the "Medicines for Malaria Venture" organization, was conducted to explore its potential for repurposing drugs to combat toxoplasmosis. The objective of the present work was to evaluate the compounds' ability to inhibit T. gondii tachyzoite growth, assess their cytotoxicity against human cells, examine their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, and investigate the potential of one candidate drug through an experimental chronic model of toxoplasmosis. Early screening identified 29 compounds that could inhibit T. gondii survival by over 80% while keeping human cell survival up to 50% at a concentration of 1 µM. The Half Effective Concentrations (EC50) of these compounds ranged from 0.04 to 0.92 µM, while the Half Cytotoxic Concentrations (CC50) ranged from 2.48 to over 50 µM. Almitrine was chosen for further evaluation due to its favorable characteristics, including anti-T. gondii activity at nanomolar concentrations, low cytotoxicity, and ADMET properties. Administering almitrine bismesylate (Vectarion®) orally at dose of 25 mg/kg/day for ten consecutive days resulted in a statistically significant (p < 0.001) reduction in parasite burden in the brains of mice chronically infected with T. gondii (ME49 strain). This was determined by quantifying the RNA of living parasites using real-time PCR. The presented results suggest that almitrine may be a promising drug candidate for additional experimental studies on toxoplasmosis and provide further evidence of the potential of the MMV collections as a valuable source of drugs to be repositioned for infectious diseases.

Auricular Vagal Neuromodulation and its Application in Patients with Heart Failure and Reduced Ejection Fraction. / Neuromodulação Vagal Auricular e sua Aplicabilidade em Pacientes com Insuficiência Cardíaca e Fração de Ejeção Reduzida.

BACKGROUND: The autonomic nervous system (ANS) imbalance in heart failure (HF) creates a vicious cycle, excess sympathetic activity, and decreased vagal activity contributing to the worsening of HF. Low-intensity transcutaneous electrical stimulation of the auricular branch of the vagus nerve (taVNS) is well tolerated and opens new therapeutic possibilities. OBJECTIVES: To hypothesize the applicability and benefit of taVNS in HF through intergroup comparison of echocardiography parameters, 6-minute walk test, Holter heart rate variability (SDNN and rMSSD), Minnesota quality of life questionnaire, and functional class by the New York Heart Association. In comparisons, p values <0.05 were considered significant. METHODS: Prospective, double-blind, randomized clinical study with sham methodology, unicentric. Forty-three patients were evaluated and divided into 2 groups: Group 1 received taVNS (frequencies 2/15 Hz), and Group 2 received sham. In comparisons, p values <0.05 were considered significant. RESULTS: In the post-intervention phase, it was observed that Group 1 had better rMSSD (31 x 21; p = 0.046) and achieved better SDNN (110 vs. 84, p = 0.033). When comparing intragroup parameters before and after the intervention, it was observed that all of them improved significantly in group 1, and there were no differences in group 2. CONCLUSION: taVNS is a safe to perform and easy intervention and suggests a probable benefit in HF by improving heart rate variability, which indicates better autonomic balance. New studies with more patients are needed to answer the questions raised by this study.

FUNDAMENTO: O desequilíbrio do sistema nervoso autônomo (SNA) na insuficiência cardíaca (IC) cria um ciclo vicioso, o excesso de atividade simpática e a diminuição da atividade vagal contribuindo para a piora da IC. A estimulação elétrica transcutânea de baixa intensidade do ramo auricular do nervo vago (taVNS) é bem tolerada e abre novas possibilidades terapêuticas. OBJETIVOS: Gerar hipótese da aplicabilidade e benefício da taVNS na IC através da comparação intergrupos de parâmetros ecocardiográficos, teste de caminhada de 6 min, variabilidade da frequência cardíaca pelo Holter (SDNN e rMSSD), questionário de qualidade de vida de Minnesota e classe funcional pela New York Heart Association. MÉTODOS: Estudo clínico prospectivo, duplo cego, randomizado com metodologia sham, unicêntrico. Avaliados 43 pacientes e alocados em 2 grupos: o Grupo 1 recebeu taVNS (frequências 2/15 Hz) e Grupo 2 recebeu sham. Nas comparações, valores de p<0,05 foram considerados significativos. RESULTADOS: Na fase pós-intervenção, observou-se que o Grupo 1 se manteve com melhor rMSSD (31 x 21; p = 0,046) e atingiu melhor SDNN (110 vs. 84, p = 0,033). Ao compararmos os parâmetros intragrupos, antes e após intervenção, observou-se que todos melhoraram significativamente no grupo 1 e não houve diferenças no grupo 2. CONCLUSÃO: A taVNS é uma intervenção segura, de fácil execução e que sugere provável benefício na IC pela melhora na variabilidade da frequência cardíaca, o que indica melhor equilíbrio autonômico. Novos estudos com maior número de pacientes são necessários para responder às questões levantadas por esse estudo.

Kaurane-Type Diterpenoids as Potential Inhibitors of Dihydrofolate Reductase-Thymidylate Synthase in New World Leishmania Species.

The bifunctional enzyme Dihydrofolate reductase-thymidylate synthase (DHFR-TS) plays a crucial role in the survival of the Leishmania parasite, as folates are essential cofactors for purine and pyrimidine nucleotide biosynthesis. However, DHFR inhibitors are largely ineffective in controlling trypanosomatid infections, largely due to the presence of Pteridine reductase 1 (PTR1). Therefore, the search for structures with dual inhibitory activity against PTR1/DHFR-TS is crucial in the development of new anti-Leishmania chemotherapies. In this research, using the Leishmania major DHFR-TS recombinant protein, enzymatic inhibitory assays were performed on four kauranes and two derivatives that had been previously tested against LmPTR1. The structure 302 (6.3 µM) and its derivative 302a (4.5 µM) showed the lowest IC50 values among the evaluated molecules. To evaluate the mechanism of action of these structures, molecular docking calculations and molecular dynamics simulations were performed using a DHFR-TS hybrid model. Results showed that hydrogen bond interactions are critical for the inhibitory activity against LmDHFR-TS, as well as the presence of the p-hydroxyl group of the phenylpropanoid moiety of 302a. Finally, additional computational studies were performed on DHFR-TS structures from Leishmania species that cause cutaneous and mucocutaneous leishmaniasis in the New World (L. braziliensis, L. panamensis, and L. amazonensis) to explore the targeting potential of these kauranes in these species. It was demonstrated that structures 302 and 302a are multi-Leishmania species compounds with dual DHFR-TS/PTR1 inhibitory activity.

Selene-Ethylenelacticamides and N-Aryl-Propanamides as Broad-Spectrum Leishmanicidal Agents.

The World Health Organization classifies Leishmania as one of the 17 "neglected diseases" that burden tropical and sub-tropical climate regions with over half a million diagnosed cases each year. Despite this, currently available anti-leishmania drugs have high toxicity and the potential to be made obsolete by parasite drug resistance. We chose to analyze organoselenides for leishmanicidal potential given the reduced toxicity inherent to selenium and the displayed biological activity of organoselenides against Leishmania. Thus, the biological activities of 77 selenoesters and their N-aryl-propanamide derivatives were predicted using robust in silico models of Leishmania infantum, Leishmania amazonensis, Leishmania major, and Leishmania (Viannia) braziliensis. The models identified 28 compounds with >60% probability of demonstrating leishmanicidal activity against L. infantum, and likewise, 26 for L. amazonesis, 25 for L. braziliensis, and 23 for L. major. The in silico prediction of ADMET properties suggests high rates of oral absorption and good bioavailability for these compounds. In the in silico toxicity evaluation, only seven compounds showed signs of toxicity in up to one or two parameters. The methodology was corroborated with the ensuing experimental validation, which evaluated the inhibition of the Promastigote form of the Leishmania species under study. The activity of the molecules was determined by the IC50 value (µM); IC50 values < 20 µM indicated better inhibition profiles. Sixteen compounds were synthesized and tested for their activity. Eight molecules presented IC50 values < 20 µM for at least one of the Leishmania species under study, with compound NC34 presenting the strongest parasite inhibition profile. Furthermore, the methodology used was effective, as many of the compounds with the highest probability of activity were confirmed by the in vitro tests performed.

Four diterpenes identified in silico were isolated from Hyptidinae and demonstrated in vitro activity against Mycobacterium tuberculosis.

Plants of Hyptidinae subtribe (Lamiaceae - family), as Mesosphaerum sidifolium, are a source of bioactive molecules. In the search for new drug candidates, we perform chemical characterization of diterpenes isolated from the aerial parts of M. sidifolium was carried out with uni- and bidimensional NMR spectral data, and evaluate in silico through the construction of a predictive model followed by in vitro testing Mycobacterium tuberculosis and Mycobacterium smegmatis. Resulted in the isolation of four components: Pomiferin D (1), Salviol (2), Pomiferin E (3) and 2α-hydroxysugiol (4), as well as two phenolic compounds, rosmarinic and caffeic acids. In silico model identified 48 diterpenes likely to have biological activity against M. tuberculosis. The diterpenes isolated were tested in vitro against M. tuberculosis demonstrating MIC = 125 µM for 4 and 1, while 2 and 3 -MIC = 250 µM. These compounds did not show biological activity at these concentrations for M. smegmatis.

Espiritualidade e qualidade de vida relacionada à saúde de mulheres com câncer de mama / Espiritualidad y calidad de vida relacionada con la salud de mujeres con cáncer de mama / Spirituality and health-related quality of life of women with breast cancer

Objetivos: avaliar a associação do enfrentamento religioso-espiritual com a qualidade de vida relacionada à saúde de mulheres com câncer de mama em tratamento oncológico. Método: pesquisa transversal, exploratória, quantitativa, descritiva e analítica, desenvolvida nos meses de março a outubro de 2020, em hospital oncológico. Foram utilizados três instrumentos de avaliação (Caracterização Sociodemográfica e Clínica, Functional Assessment of Cancer Therapy-Breast plus Arm Morbidity e Escala Coping Religioso-Espiritual) e realizadas análises descritivas e estatísticas. Resultados: amostra composta de 39 mulheres, maioria adulta (79,5%), casada/união estável (48,7%), submetida à mastectomia junto com a linfadenectomia (53,8%), católica (53,8%), dentre as quais 94% acreditavam que espiritualidade/religiosidade ajudava no enfrentamento do câncer. Houve correlação positiva entre o domínio Bem-estar social/familiar de qualidade de vida relacionada à saúde com níveis de enfrentamento religioso-espiritual positivo e total. Conclusão: espiritualidade/religiosidade e qualidade de vida relacionada à saúde influenciaram positivamente à mulher durante tratamento oncológico, havendo maior utilização dessas estratégias.

Objetivos: avaliar a associação do enfrentamento religioso-espiritual com a qualidade de vida relacionada à saúde de mulheres com câncer de mama em tratamento oncológico. Método: pesquisa transversal, exploratória, quantitativa, descritiva e analítica, desenvolvida nos meses de março a outubro de 2020, em hospital oncológico. Foram utilizados três instrumentos de avaliação (Caracterização Sociodemográfica e Clínica, Functional Assessment of Cancer Therapy-Breast plus Arm Morbidity e Escala Coping Religioso-Espiritual) e realizadas análises descritivas e estatísticas. Resultados: amostra composta de 39 mulheres, maioria adulta (79,5%), casada/união estável (48,7%), submetida à mastectomia junto com a linfadenectomia (53,8%), católica (53,8%), dentre as quais 94% acreditavam que espiritualidade/religiosidade ajudava no enfrentamento do câncer. Houve correlação positiva entre o domínio Bem-estar social/familiar de qualidade de vida relacionada à saúde com níveis de enfrentamento religioso-espiritual positivo e total. Conclusão: espiritualidade/religiosidade e qualidade de vida relacionada à saúde influenciaram positivamente à mulher durante tratamento oncológico, havendo maior utilização dessas estratégias.

Objective: to evaluate the association of religious-spiritual coping with the health-related quality of life of women with breast cancer undergoing cancer treatment. Method: cross-sectional, exploratory, quantitative, descriptive and analytical research, conducted from March to October 2020, in an oncological hospital. Three assessment instruments were used (Sociodemographic and Clinical Characterization, Functional Assessment of Cancer Therapy-Breast plus Arm Morbidity and Religious-Spiritual Coping Scale), descriptive and statistical analyzes were performed. Results: sample size composed of 39 women, mostly adults (79.5%), married/stable union (48.7%), submitted to mastectomy along with lymphadenectomy (53.8%), Catholic (53.8%), among which 94% believed that spirituality/religiosity helped in coping with cancer. There was a positive correlation between the domain Social/family well-being and health-related quality of life with levels of positive and total religious-spiritual coping. Conclusion: Spirituality/religiosity and health-related quality of life positively influenced women during cancer treatment, with greater use of these strategies.

Neuromodulação Vagal Auricular e sua Aplicabilidade em Pacientes com Insuficiência Cardíaca e Fração de Ejeção Reduzida / Auricular Vagal Neuromodulation and its Application in Patients with Heart Failure and Reduced Ejection Fraction

Resumo Fundamento O desequilíbrio do sistema nervoso autônomo (SNA) na insuficiência cardíaca (IC) cria um ciclo vicioso, o excesso de atividade simpática e a diminuição da atividade vagal contribuindo para a piora da IC. A estimulação elétrica transcutânea de baixa intensidade do ramo auricular do nervo vago (taVNS) é bem tolerada e abre novas possibilidades terapêuticas. Objetivos Gerar hipótese da aplicabilidade e benefício da taVNS na IC através da comparação intergrupos de parâmetros ecocardiográficos, teste de caminhada de 6 min, variabilidade da frequência cardíaca pelo Holter (SDNN e rMSSD), questionário de qualidade de vida de Minnesota e classe funcional pela New York Heart Association. Métodos Estudo clínico prospectivo, duplo cego, randomizado com metodologia sham, unicêntrico. Avaliados 43 pacientes e alocados em 2 grupos: o Grupo 1 recebeu taVNS (frequências 2/15 Hz) e Grupo 2 recebeu sham. Nas comparações, valores de p<0,05 foram considerados significativos. Resultados Na fase pós-intervenção, observou-se que o Grupo 1 se manteve com melhor rMSSD (31 x 21; p = 0,046) e atingiu melhor SDNN (110 vs. 84, p = 0,033). Ao compararmos os parâmetros intragrupos, antes e após intervenção, observou-se que todos melhoraram significativamente no grupo 1 e não houve diferenças no grupo 2. Conclusão A taVNS é uma intervenção segura, de fácil execução e que sugere provável benefício na IC pela melhora na variabilidade da frequência cardíaca, o que indica melhor equilíbrio autonômico. Novos estudos com maior número de pacientes são necessários para responder às questões levantadas por esse estudo.

Abstract Background The autonomic nervous system (ANS) imbalance in heart failure (HF) creates a vicious cycle, excess sympathetic activity, and decreased vagal activity contributing to the worsening of HF. Low-intensity transcutaneous electrical stimulation of the auricular branch of the vagus nerve (taVNS) is well tolerated and opens new therapeutic possibilities. Objectives To hypothesize the applicability and benefit of taVNS in HF through intergroup comparison of echocardiography parameters, 6-minute walk test, Holter heart rate variability (SDNN and rMSSD), Minnesota quality of life questionnaire, and functional class by the New York Heart Association. In comparisons, p values <0.05 were considered significant. Methods Prospective, double-blind, randomized clinical study with sham methodology, unicentric. Forty-three patients were evaluated and divided into 2 groups: Group 1 received taVNS (frequencies 2/15 Hz), and Group 2 received sham. In comparisons, p values <0.05 were considered significant. Results In the post-intervention phase, it was observed that Group 1 had better rMSSD (31 x 21; p = 0.046) and achieved better SDNN (110 vs. 84, p = 0.033). When comparing intragroup parameters before and after the intervention, it was observed that all of them improved significantly in group 1, and there were no differences in group 2. Conclusion taVNS is a safe to perform and easy intervention and suggests a probable benefit in HF by improving heart rate variability, which indicates better autonomic balance. New studies with more patients are needed to answer the questions raised by this study.

Communication of the Diagnosis of Spinal Muscular Atrophy in the Views of Patients and Family Members, a Qualitative Analysis.

INTRODUCTION: Communicating the diagnosis of a genetic and neurodegenerative disease, such as spinal muscular atrophy (SMA), requires a transmission centered on the patient and/or the family caregiver, ensuring autonomy to those involved and strengthening the doctor-patient relationship. OBJECTIVE: Analyzing the communication of the SMA diagnosis from the perspective of patients and family members. METHODS: This qualitative study was developed through semi-structured interviews, via teleconsultation. The analysis was developed by systematically condensing the answers and synthesizing them into four thematic axes (clarification of the diagnosis, communication of the prognosis, affective memory related to the event, and advice to physicians). RESULTS AND DISCUSSION: Twenty-nine patients with SMA and 28 family caregivers of people with this condition, from all regions of Brazil, reported that individualized, clear, honest, and welcoming communication, emphasizing positive aspects, in the presence of family members and with the possibility of continuous monitoring, was important to meeting their communication needs. A lack of empathy, monitoring and guidance, and estimating life expectancy resulted in negative experiences. CONCLUSIONS: The communication needs of patients and family members described during the clarification of the diagnosis and prognosis of SMA predominantly involve empathic factors related to the attitude of the attending physician throughout the evolution of the disease. Future research evaluating other neurodegenerative diseases and the development of research protocols are important to improving communication between physicians, patients, and family members.

Review on Compounds Isolated from Eriocaulaceae Family and Evaluation of Biological Activities by Machine Learning.

Eriocaulaceae is a pantropical family whose main center of biodiversity is in Brazil. In general, the family has about 1200 species, in which phytochemical and biological studies have shown a variety of structures and activities. The aim of this research is to compile the compounds isolated in the Eriocaulaceae family and carry out a computational study on their biological targets. The bibliographic research was carried out on six databases. Tables were built and organized according to the chemical class. In addition, a summary of the methods of isolating the compounds was also made. In the computational study were used ChEMBL platform, DRAGON 7.0, and the KNIME 4.4.0 software. Two hundred and twenty-two different compounds have been isolated in sixty-eight species, divided mainly into flavonoids and naphthopyranones, and minor compounds. The ligand-based virtual screening found promising molecules and molecules with multitarget potential, such as xanthones 194, 196, 200 and saponin 202, with xanthone 194 as the most promising. Several compounds with biological activities were isolated in the family, but the chemical profiles of many species are still unknown. The selected structures are a starting point for further studies to develop new antiparasitic and antiviral compounds based on natural products.

Communicating the Spinal Muscular Atrophy diagnosis to children and the principle of autonomy.

INTRODUCTION: The trinomial relationship between physicians/children/guardians is essential in the process of communicating a disease and its prognosis. OBJECTIVE: Analyzing the exercise of autonomy by this trinomial relationship in communicating the diagnosis of spinal muscular atrophy (SMA).   METHODOLOGY: Caregivers of SMA patients answered a questionnaire containing a structured interview and the Event Impact Scale - Revised. RESULTS: The sample comprised 50 volunteers, 94% of whom were female caregivers. Psychological trauma was predominantly reported when caregivers communicated the diagnosis to children. 22% have a high risk of post-traumatic stress, relating the feeling of unpreparedness in communicating this to the child. CONCLUSIONS: It was identified that the failure in communication is the main factor for negative repercussions on the autonomy of children and their guardians, with self-reported psychological trauma, besides the high risk for post-traumatic stress syndrome.

EMPATIA: A Guide for Communicating the Diagnosis of Neuromuscular Diseases.

INTRODUCTION: Neuromuscular diseases comprise a heterogeneous group of genetic syndromes that lead to progressive muscle weakness, resulting in functional limitation. There is a gap in the literature regarding the communication of the diagnosis of such diseases, compromising the autonomy of patients and families, besides causing stress on the assistant physician. OBJECTIVES: Developing a guide to reduce communication barriers in the diagnosis of neuromuscular diseases. METHODOLOGY: Systematic review, after searching the descriptors ("Muscular Diseases" OR "Neuromuscular Diseases") AND ("Truth Disclosure" OR "Bad news communication" OR "Breaking bad News") in the Pubmed, Bireme, and Scopus websites, and these results were analyzed through narrative textual synthesis. RESULTS: 16 articles were submitted to the final analysis, giving rise to seven steps to support the communication process. These are Empathy, Message, Prognosis, Reception, Time, Individualization, and Autonomy. DISCUSSION AND CONCLUSION: The empathic transmission of the message and the prognosis must accommodate the feelings of the interlocutors with different information needs. In this way, communication planning optimizes the time and individualizes each context, respecting the autonomy of those involved. EMPATIA reflects the bioethical and interdisciplinary analysis of the literature and comes to fill the gap related to the communication of bad news in neuromuscular diseases.

MolPredictX: Online Biological Activity Predictions by Machine Learning Models.

Here we report the development of MolPredictX, an innovate and freely accessible web interface for biological activity predictions of query molecules. MolPredictX utilizes in-house QSAR models to provide 27 qualitative predictions (active or inactive), and quantitative probabilities for bioactivity against parasitic (Trypanosoma and Leishmania), viral (Dengue, Sars-CoV and Hepatitis C), pathogenic yeast (Candida albicans), bacterial (Salmonella enterica and Escherichia coli), and Alzheimer disease enzymes. In this article, we introduce the methodology and usability of this webtool, highlighting its potential role in the development of new drugs against a variety of diseases. MolPredictX is undergoing continuous development and is freely available at https://www.molpredictx.ufpb.br/.

Natural Products from Annonaceae as Potential Antichagasic Agents.

Chagas disease, a neglected tropical disease, is endemic in 21 Latin American countries and particularly prevalent in Brazil. Chagas disease has drawn more attention in recent years due to its expansion into non-endemic areas. The aim of this work was to computationally identify and experimentally validate the natural products from an Annonaceae family as antichagasic agents. Through the ligand-based virtual screening, we identified 57 molecules with potential activity against the epimastigote form of T. cruzi. Then, 16 molecules were analyzed in the in vitro study, of which, six molecules displayed previously unknown antiepimastigote activity. We also evaluated these six molecules for trypanocidal activity. We observed that all six molecules have potential activity against the amastigote form, but no molecules were active against the trypomastigote form. 13-Epicupressic acid seems to be the most promising, as it was predicted as an active compound in the in silico study against the amastigote form of T. cruzi, in addition to having in vitro activity against the epimastigote form.