Molecular approaches for structural characterization of a new potassium channel blocker from Tityus stigmurus venom: cDNA cloning, homology modeling, dynamic simulations and docking

AbstractPotassium channels are involved in the maintenance of resting membrane potential, control of cardiac and neuronal excitability, neurotransmitters release, muscle contractility and hormone secretion. The Tityus stigmurus scorpion is widely distributed in Northeastern Brazil and known to cause severe human envenomations, inducing pain, hypoesthesia, edema, erythema, paresthesia, headaches and vomiting. Most potassium channel blocking peptides that have been purified from scorpion venoms contain 30–40 amino acids with three or four disulfide bridges. These peptides belong to α-KTx subfamily. On the other hand, the β-KTx subfamily is poorly characterized, though it is very representative in some scorpion venoms. A transcriptomic approach of T. stigmurus scorpions developed by our group revealed the repertoire of possible molecules present in the venom, including many toxins of the β-KTx subfamily. One of the ESTs found, named TSTI0003C has a cDNA sequence of 538bp codifying a mature protein with 47 amino acid residues, corresponding to 5299Da. This β-KTx peptide is a new member of the BmTXKβ-related toxins, and was here named TstKMK. The three-dimensional structure of this potassium channel toxin of the T. stigmurus scorpion was obtained by computational modeling and refined by molecular dynamic simulations. Furthermore, we have made docking simulations using a Shaker kV-1.2 potassium channel from rats as receptor model and proposed which amino acid residues and interactions could be involved in its blockade

Structural characterization of a novel peptide with antimicrobial activity from the venom gland of the scorpion Tityus stigmurus: Stigmurin

AbstractA new antimicrobial peptide, herein named Stigmurin, was selected based on a transcriptomic analysis of the Brazilian yellow scorpion Tityus stigmurus venom gland, an underexplored source for toxic peptides with possible biotechnological applications. Stigmurin was investigated in silico, by circular dichroism (CD) spectroscopy, and in vitro. The CD spectra suggested that this peptide interacts with membranes, changing its conformation in the presence of an amphipathic environment, with predominance of random coil and beta-sheet structures. Stigmurin exhibited antibacterial and antifungal activity, with minimal inhibitory concentrations ranging from 8.7 to 69.5μM. It was also showed that Stigmurin is toxic against SiHa and Vero E6 cell lines. The results suggest that Stigmurin can be considered a potential anti-infective drug

Molecular characterization of Cratylia argentea accessions and its phylogenetic relationship with other legumes

O objetivo deste trabalho foi realizar a caracterização molecular de 11 acessos de Cratylia argentea, com base no sequenciamento da região ITS (ITS1/5,8S/ITS2), bem como o estabelecimento de suas relações filogenéticas com outras leguminosas. As relações filogenéticas dessa espécie com outras 15 leguminosas foram estabelecidas com o uso de sequência do gene que codifica a subunidade 18S do rRNA (rDNA 18S). A amplificação do DNA da região ITS/5,8S dos 11 acessos revelou uma única banda de aproximadamente 650 pb. Sequências ITS/5,8S foram obtidas de todos os acessos analisados e depois alinhadas com a região ITS/5,8S da leguminosa Galactia striata. O tamanho das sequências ITS/5,8S dos acessos de C. argentea variou de 565 a 615 pb. Os conteúdos médios de G + C nas regiões ITS1 e ITS2 variaram entre 46 e 47%. O alinhamento múltiplo das seqüências ITS/5,8S dos acessos de C. argentea com Galactia striata revelou a presença de deleções e inserções. Os acessos de C. argentea constituíram um único clado politômico. A análise filogenética de C. argentea demonstrou que essa espécie está incluída no clado das Diocleinae verdadeiras e que os gêneros Calopogonium e Pachyrhizus estão fora desse clado.The objective of this work was to molecularly characterize 11 Cratylia argentea accessions, ITS (ITS1/5.8S/ITS2) region as well to establish its phylogenetic relationship using a gene sequence that codes the subunit 18S of the rRNA (rDNA 18S). DNA amplification of the ITS/5.8S region of these 11 accessions revealed an amplicon with around 650 bp. ITS/5.8S sequences were obtained from all accessions analysed, and then aligned with the region ITS/5.8S of Galactia striata legume. The size of ITS/5.8S region ranged from 565 to 615 bp. Average G + C contents in the ITS1 and ITS2 regions ranged between 46 and 47%. The multiple sequence alignment between the ITS sequences from C. argentea accessions and Galactia striata revealed the presence of deletions and insertions. C. argentea accessions formed a unique politomic clade. Cratylia argentea phylogenetic analysis demonstrated that this species is placed into the true Diocleinae Clade, and that Calopogonium and Pachyrhizus are not included in subtribe Diocleinae

Modulation of blood redox status by the progression of induced apical periodontitis in rats

This study aimed to investigate if apical periodontitis in different periods changes systemic levels of the antioxidant and pro-oxidant parameters in Wistar rats. Twenty-four rats were randomly allocated into healthy animals, apical periodontitis at 14 days (AP14) and apical periodontitis at 28 days (AP28). The first mandibular molars were accessed in the AP groups, and the pulp chamber was exposed to the oral environment, inducing the apical lesion. After 14 and 28 days, the animals were anesthetized, euthanized, and hemimandibles were collected for micro-computed tomography (micro-CT) analysis to measure lesion volume, bone volume (BV), percent of bone to total tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular space (Tb.Sp). A histological examination of the remaining bone was also performed. Finally, blood samples were collected for oxidative biochemistry analysis, investigating glutathione (GSH), Trolox equivalent antioxidant capacity (TEAC), and lipid peroxidation (TBARS). The lesion volume was greater at 28 than at 14 days, as shown by micro-CT. AP14 and AP28 had decreased BV and Tb.Th, but only AP28 showed a reduction in BV/TV. Tb.N and Tb. Sp were increased in apical periodontitis at 28 days. In the histopathological analysis, AP14 had focal regions of moderate mononuclear inflammatory infiltrate, and AP28 had an intense inflammatory infiltrate with bacterial colonies. In the biochemical evaluation, GSH, TEAC, and TBARS were increased after 14 days. However, GSH returned to control levels, TEAC was similar to AP14, and TBARS increased significantly after 28 days. Therefore, the oxidative biochemistry response was modulated according to the progression of periapical damage. After 14 days, the organism could still react to the injury. However, at 28 days, the antioxidant response decreased, associated with an increase in TBAR

Remoção de Terceiro Molar Superior Localizado no Interior do Seio Maxilar: Relato de Caso/ Removal of an Upper Third Molar Located inside the Maxillary Sinus: Case Report

A remoção cirúrgica dos terceiros molares impactados é um dos procedimentos mais comuns realizados por cirurgiões bucomaxilofaciais e que algumas estruturas nobres como o nervo alveolar inferior ou o seio maxilar podem estar em intimo contato com os dentes inclusos e que necessita de um planejamento preciso e experiência do cirurgião para evitar maiores complicações. A presença de corpos estranhos nos seios paranasais é considerada rara pela literatura. Dentre os seios da face o seio maxilar é normalmente o mais acometido, estando a etiologia relacionada principalmente a iatrogenias e agressão física. O deslocamento de elementos dentários para o interior do seio maxilar tem como principal fator a iatrogenia decorrente do uso inadequado dos extratores, somados a fatores anatômicos como a proximidade do 3ºs molares superiores com esta estrutura. O presente trabalho busca relatar um caso clinico de tratamento de uma complicação cirúrgica de um terceiro molar deslocado para o interior do seio maxilar

A plumieridine-rich fraction from Allamanda polyantha inhibits chitinolytic activity and exhibits antifungal properties against Cryptococcus neoformans

Cryptococcosis is a fungal infection caused mainly by the pathogenic yeasts Cryptococcus neoformans and Cryptococcus gattii. The infection initiates with the inhalation of propagules that are then deposited in the lungs. If not properly treated, cryptococci cells can disseminate and reach the central nervous system. The current recommended treatment for cryptococcosis employs a three-stage regimen, with the administration of amphotericin B, flucytosine and fluconazole. Although effective, these drugs are often unavailable worldwide, can lead to resistance development, and may display toxic effects on the patients. Thus, new drugs for cryptococcosis treatment are needed. Recently, an iridoid named plumieridine was found in Allamanda polyantha seed extract; it exhibited antifungal activity against C. neoformans with a MIC of 250 µg/mL. To address the mode of action of plumieridine, several in silico and in vitro experiments were performed. Through a ligand-based a virtual screening approach, chitinases were identified as potential targets. Confirmatory in vitro assays showed that C. neoformans cell-free supernatant incubated with plumieridine displayed reduced chitinase activity, while chitinolytic activity was not inhibited in the insoluble cell fraction. Additionally, confocal microscopy revealed changes in the distribution of chitooligomers in the cryptococcal cell wall, from a polarized to a diffuse cell pattern state. Remarkably, further assays have shown that plumieridine can also inhibit the chitinolytic activity from the supernatant and cell-free extracts of bacteria, insect and mouse-derived macrophage cells (J774.A1). Together, our results suggest that plumieridine can be a broad-spectrum chitinase inhibitor

Modulation of blood redox status by the progression of induced apical periodontitis in rats

This study aimed to investigate if apical periodontitis in different periods changes systemic levels of the antioxidant and pro-oxidant parameters in Wistar rats. Twenty-four rats were randomly allocated into healthy animals, apical periodontitis at 14 days (AP14) and apical periodontitis at 28 days (AP28). The first mandibular molars were accessed in the AP groups, and the pulp chamber was exposed to the oral environment, inducing the apical lesion. After 14 and 28 days, the animals were anesthetized, euthanized, and hemimandibles were collected for micro-computed tomography (micro-CT) analysis to measure lesion volume, bone volume (BV), percent of bone to total tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular space (Tb.Sp). A histological examination of the remaining bone was also performed. Finally, blood samples were collected for oxidative biochemistry analysis, investigating glutathione (GSH), Trolox equivalent antioxidant capacity (TEAC), and lipid peroxidation (TBARS). The lesion volume was greater at 28 than at 14 days, as shown by micro-CT. AP14 and AP28 had decreased BV and Tb.Th, but only AP28 showed a reduction in BV/TV. Tb.N and Tb. Sp were increased in apical periodontitis at 28 days. In the histopathological analysis, AP14 had focal regions of moderate mononuclear inflammatory infiltrate, and AP28 had an intense inflammatory infiltrate with bacterial colonies. In the biochemical evaluation, GSH, TEAC, and TBARS were increased after 14 days. However, GSH returned to control levels, TEAC was similar to AP14, and TBARS increased significantly after 28 days. Therefore, the oxidative biochemistry response was modulated according to the progression of periapical damage. After 14 days, the organism could still react to the injury. However, at 28 days, the antioxidant response decreased, associated with an increase in TBARS

PERFIL EPIDEMIOLÓGICO DOS TRANSTORNOS MENTAIS RELACIONADOS AO TRABALHO NO ESTADO DE GOIÁS ENTRE 2018 E 2023

The literature defines work-related psychological disorders as those resulting from diverse professional situations and with multifactorial causes, with historical records dating back to 1840, and although attention focused on this issue has increased after the SaRS-CoV-2 pandemic, exploration of this topic by science is still scarce. The present study aims to analyze work-related mental disorders, outlining the epidemiological profile of these conditions. This is an epidemiological, descriptive and cross-sectional study on the mental disorders of the working class in the state of Goiás in a period between 2018 and 2023. The data were collected from the SUS Information Technology Department (DATASUS) and analyzed using the R software version 4.2 .3. There was a prevalence of 115 reported female cases, 39 in white individuals and the most prevalent age group being between 35 and 49 years old, being more common in individuals studying higher education. A predominance of stress-related disorders was also observed, with 58 cases, followed by those linked to affective mood disorder, with 28 cases. Therefore, it is understood that work-related mental disorders are mainly related to stress, but also to long working hours, causing cases of psychosis and reducing the quality of life of individuals; which demonstrates the importance of mental health awareness initiatives.La literatura define los trastornos psicológicos relacionados con el trabajo como aquellos resultantes de situaciones profesionales diversas y con causas multifactoriales, con registros históricos que se remontan a 1840, y aunque la atención centrada en este tema ha aumentado después de la pandemia de SaRS-CoV-2, la exploración de este tema por la ciencia todavía es escasa. El presente estudio tiene como objetivo analizar los trastornos mentales relacionados con el trabajo, delineando el perfil epidemiológico de estas condiciones. Se trata de un estudio epidemiológico, descriptivo y transversal sobre los trastornos mentales de la clase trabajadora en el estado de Goiás en el período de 2018 a 2023. Los datos fueron recolectados del Departamento de Tecnología de la Información del SUS (DATASUS) y analizados mediante el método R versión de software 4.2 .3. Hubo una prevalencia de 115 casos reportados en el sexo femenino, 39 en personas de raza blanca y el grupo etario de mayor prevalencia fue el de 35 a 49 años, siendo más común en personas que cursan estudios de educación superior. También se observó predominio de los trastornos relacionados con el estrés, con 58 casos, seguidos de los vinculados al trastorno afectivo del estado de ánimo, con 28 casos. Por lo tanto, se entiende que los trastornos mentales relacionados con el trabajo están relacionados principalmente con el estrés, pero también con las largas jornadas laborales, provocando casos de psicosis y reduciendo la calidad de vida de las personas; lo que demuestra la importancia de las iniciativas de concientización sobre la salud mental.A literatura define transtornos psicológicos relacionados ao trabalho como aqueles resultantes de situações profissionais diversas e com causas multifatoriais, com registros históricos que datam desde 1840, e embora a atenção voltada para essa questão tenha aumentado após a pandemia pelo SaRS-CoV-2, a exploração dessa temática pela ciência ainda é escassa. O presente estudo tem como objetivo analisar os transtornos mentais relacionados ao trabalho, traçando o perfil epidemiológico dessas condições. Trata-se de um estudo epidemiológico, descritivo e transversal sobre os transtornos mentais da classe trabalhadora do estado de Goiás em um período entre 2018 e 2023. Os dados foram coletados do Departamento de Informática do SUS (DATASUS) e analisados no software R versão 4.2.3. Constatou-se uma prevalência de 115 casos notificados do sexo feminino, 39 em indivíduos da raça branca e a faixa etária mais  prevalente sendo entre 35 e 49 anos, sendo mais comum em indivíduos cursando o Ensino superior. Foi observado também um predomínio de transtornos relacionados ao estresse, com 58 casos, seguidos daqueles  ligados ao transtorno de humor afetivo, com 28 casos. Dessa forma, entende-se que os transtornos mentais ligados ao trabalho estão relacionados principalmente ao estresse, mas também, a jornadas de trabalhos prolongadas, acarretando casos de psicoses e reduzindo a qualidade de vida dos indivíduos; o que demonstra a importância de iniciativas de conscientização sobre saúde mental

Morinda citrifolia linn leaf extract possesses antioxidant activities and reduces nociceptive behavior and leukocyte migration

This is a copy of an article published in the Journal of Medicinal Food© 2011 - copyright Mary Ann Liebert, Inc.; Journal of Medicinal Food is available online at: http://online.liebertpub.comHerbal drugs have been used since ancient times to treat a wide range of diseases. Morinda citrifolia Linn (popularly known as ‘‘Noni’’) has been used in folk medicine by Polynesians for over 2,000 years. It is reported to have a broad range of therapeutic effects, including effects against headache, fever, arthritis, gingivitis, respiratory disorders, infections, tuberculosis, and diabetes. The aim of this study was to investigate the antioxidant, anti-inflammatory, antinociceptive, and antibacterial properties of the aqueous extract from M. citrifolia leaves (AEMC). Antioxidant activity was observed against lipid peroxidation, nitric oxide, and hydroxyl radicals. The antinociceptive effect of AEMC was observed in the acetic acid–induced writhing test at the higher dose. Moreover, AEMC significantly reduced the leukocyte migration in doses of 200 and 400 mg/kg and showed mild antibacterial activity. Together, the results suggest that properties of M. citrifolia leaf extract should be explored further in order to achieve newer tools for managing painful and inflammation conditions, including those related to oxidant states

Impactos da má qualidade do sono em profissionais da saúde em ambiente emergencial

This study aims to evaluate the impacts of poor sleep quality among healthcare professionals in emergency environments. Health services aimed at managing critical situations are often characterized by high pressure and stressful work environments. This is due to the severity of the conditions faced by patients, which may present an imminent risk of death or severe suffering. Professionals who work in these areas are particularly susceptible to occupational stress and health problems, due to the intrinsic demands of the role and adverse conditions, such as lack of human and material resources, work overload, inadequate environments, overcrowding and lack of recognition. by the administration. This is a narrative review of a critical and analytical nature, in research on the main concepts regarding CABG complications, in addition to the essential aspects of diagnosis and treatment. A review of articles was carried out in the Scientific Electronic Library Online (SciELO) and PubMed databases, with the following Health Sciences Descriptors (DeCS): Rest; Quality of life; Health. Work environments in emergency services are often associated with high levels of stress, resulting in a significant impact on the physical, mental and emotional well-being of professionals.Este estudio tiene como objetivo evaluar los impactos de la mala calidad del sueño entre los profesionales sanitarios en entornos de emergencia. Los servicios de salud destinados a gestionar situaciones críticas suelen caracterizarse por entornos laborales estresantes y de alta presión. Esto se debe a la gravedad de las condiciones que enfrentan los pacientes, que pueden presentar un riesgo inminente de muerte o sufrimiento severo. Los profesionales que actúan en estas áreas son particularmente susceptibles al estrés ocupacional y a problemas de salud, debido a las exigencias intrínsecas del rol y a condiciones adversas, como falta de recursos humanos y materiales, sobrecarga de trabajo, ambientes inadecuados, hacinamiento y falta de reconocimiento. por la administración. Se trata de una revisión narrativa, de carácter crítico y analítico, en la investigación sobre los principales conceptos sobre las complicaciones de la CABG, además de los aspectos esenciales del diagnóstico y tratamiento. Se realizó una revisión de artículos en las bases de datos Scientific Electronic Library Online (SciELO) y PubMed, con los siguientes Descriptores en Ciencias de la Salud (DeCS): Descanso; Calidad de vida; Salud. Los entornos laborales en los servicios de emergencia suelen estar asociados a altos niveles de estrés, lo que tiene como resultado un impacto significativo en el bienestar físico, mental y emocional de los profesionales.Este estudo tem como objetivo avaliar os impactos da má qualidade do sono entre os profissionais de saúde em ambientes emergenciais. Os serviços de saúde voltados para o manejo de situações críticas frequentemente são caracterizados por ambientes de trabalho de alta pressão e estresse. Isso ocorre devido à gravidade das condições enfrentadas pelos pacientes, que podem apresentar risco iminente de morte ou sofrimento severo. Os profissionais que atuam nessas áreas estão particularmente suscetíveis ao estresse ocupacional e a problemas de saúde, devido às demandas intrínsecas da função e às condições adversas, como a escassez de recursos humanos e materiais, sobrecarga de trabalho, ambientes inadequados, superlotação e falta de reconhecimento por parte da administração. trata-se de uma revisão narrativa de caráter crítico e analítico, na  pesquisa  sobre  os principais  conceitos  no  que tange às complicações da CRM, além dos aspectos essenciais de diagnóstico e tratamento. Foi  realizada  uma  revisão  de  artigos  nas  bases  de  dados   Scientific  Electronic  Library  Online (SciELO) e PubMed, com os seguintes Descritores em Ciências  da  Saúde  (DeCS): Descanso; Qualidade de vida; Saúde. Ambientes de trabalho em serviços de emergência estão frequentemente associados a elevados níveis de estresse, resultando em um impacto significativo no bem-estar físico, mental e emocional dos profissionais