Potential of the Blue Calm® food supplement in the treatment of alcohol withdrawal-induced anxiety in adult zebrafish (Danio rerio).

Alcohol use disorder (AUD) is characterized by a set of behavioral, cognitive, nutritional, and physiological phenomena derived from the uncontrolled use of alcoholic beverages. There are cases in which AUD is associated with anxiety disorder, and when untreated, it requires careful pharmacotherapy. Blue Calm® (BC) is a food supplement indicated to aid restorative sleep, which has traces of medicinal plant extracts, as well as myo-inositol, magnesium bisglycinate, taurine, and L-tryptophan as its main chemical constituents. In this context, this study aimed to evaluate the potential of the BC in the treatment alcohol withdrawal-induced anxiety in adult zebrafish (aZF). Initially, BC was submitted to antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl radical. Subsequently, the aZF (n = 6/group) were treated with BC (0.1 or 1 or 10 mg/mL; 20 µL; p.o.), and the sedative effect and acute toxicity (96 h) were evaluated. Then, the anxiolytic-like effect and the possible GABAergic mechanism were analyzed through the Light & Dark Test. Finally, BC action was evaluated for treating alcohol withdrawal-induced anxiety in aZF. Molecular docking was performed to evaluate the interaction of the major chemical constituents of BC with the GABAA receptor. BC showed antioxidant potential, a sedative effect, was not toxic, and all doses of BC had an anxiolytic-like effect and showed potential for the treatment of alcohol withdrawal-induced anxiety in aZF. In addition to the anxiolytic action, the main chemical constituents of BC were confirmed in the molecular docking, thus suggesting that BC is an anxiolytic that modulates the GABAergic system and has pharmacological potential for the treatment of alcohol withdrawal-induced anxiety.

Codium isthmocladum lectin 1 (CiL-1): Interaction with N-glycans explains antinociceptive and anti-inflammatory activities in adult zebrafish (Danio rerio).

Inflammation and oxidative stress are processes associated with different human diseases. They are treated using drugs that have several side effects. Seaweed are sources of potentially relevant natural compounds for use as treatment of these disorders. Lectins are able to reversibly interact with complex carbohydrates and modulate cell membrane glycosylated receptors through this interaction. This study aimed to determine the antinociceptive and anti-inflammatory potential of CiL-1 in adult zebrafish by modulation of TRPA1 through lectin-glycan binding. Possible neuromodulation by TRPA1 channel was also evaluated by camphor pretreatment. CiL-1 was efficacious at all tested doses, revealing anti-nociceptive and anti-inflammatory effects in adult zebrafish. This galactose-binding lectin was also able to reduce the content of ROS in brain and liver. In silico analyses showed CiL-1 interactions with both ligands tested. LacNac2 presents the most favorable binding energy with the protein. The interaction occurs at 4 subsites as an extended conformation at the site. LacNac2-Sia had a less favorable curved-shape interaction energy. Based on the predictions made for the oligosaccharides, a tetra-antenate putative glycan was schematically constructed, illustrating an interaction between TRPA1 N-glycan and CiL-1. This binding seems to be related to CiL-1 anti-inflammatory activity as result of receptor modulation.

Morphological, Ultrastructural, and Immunocytochemical Characterization and Assessment of Puma (Puma concolor Linnaeus, 1771) Cell Lines After Extended Culture and Cryopreservation.

Cell lines are valuable tools to safeguard genetic material from species threatened with extinction that is mainly due to human action. In this scenario, the puma constitutes a species whose population is being rapidly reduced in the ecosystems it inhabits. For the first time, we characterized puma skin-derived cell lines and assessed these cells after extended culture (experiment 1) and cryopreservation (experiment 2). Initially, we identified and characterized four dermal fibroblast lines using morphology, ultrastructure, and immunofluorescence assays. Moreover, we evaluated the effects of culture time (1st, 3rd, and 10th passages) and cryopreservation on their morphology, ultrastructure, viability, metabolism, proliferative activity, reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), and apoptosis. The cells showed a typical spindle-shaped morphology with centrally located oval nuclei. The cells were identified as fibroblasts by staining for vimentin. In vitro culture after the 1st, 3rd, and 10th passages did not alter most of the evaluated parameters. Cells in the 3rd and 10th passages showed a reduction in ROS levels (p < 0.05). The ultrastructure revealed morphological damage in the prolongments, and nuclei of cells derived from the 3rd and 10th passages. Moreover, cryopreservation resulted in a reduction in ΔΨm compared with that of noncryopreserved cells, suggesting that the optimization of cryopreservation methods for puma fibroblasts is essential. In conclusion, we found that viable fibroblasts could be obtained from puma skin, with slight changes after the 10th passage in in vitro culture and cryopreservation. This is the first report on the development of cell lines derived from pumas.

Antinociceptive, anti-inflammatory and hypoglycemic activities of the ethanolic Turnera subulata Sm. flower extract in adult zebrafish (Danio rerio).

Turnera subulata Sm. belongs to the family Turneraceae and is found in Brazil. The present study evaluated the antinociceptive, anti-inflammatory, and hypoglycemic potential of T. subulata flower extract (EtFloTsu) in zebrafish (Danio rerio). The total phenol and flavonoid contents of EtFloTsu were determined and identified using the Folin Ciocalteu reagent and aluminum chloride (AlCl3), respectively. The constituents of the extract were identified by HPLC-DAD, and the in vitro antioxidant activity (DPPH) was determined, toxicity in brine shrimp, and acute toxicity of 96 h in adult zebrafish. In addition, adult zebrafish (n = 6/fish) were treated orally with EtFloTsu (4, 20, or 40 mg/kg; vo) and subjected to formalin-induced nociception tests (with its possible mechanism of action with camphor), carrageenan-induced inflammation, and D-glucose-induced hyperglycemia (111 mM). Oxidative stress in the liver and brain tissues was assessed. EtFloTsu showed high levels of phenolic and flavonoid compounds with antioxidant activity. The phytochemicals chlorogenic acid, luteolin-7-o-glucoside, vitexin, and apigenin-7-o-glucoside were also identified in EtFloTsu. The synergism between these constituents was possibly responsible for the antinociceptive (via TRPA1), anti-inflammatory, and hypoglycemic effects of EtFloTsu in adult zebrafish, without causing toxicity in animals. Therefore, T. subulata flowers have therapeutic agents that could treat pain, inflammation, diabetes, and related complications.Communicated by Ramaswamy H. Sarma.

Lesão transfixante de carótida por espinha de peixe - relato de caso / Carotid artery perforation by fish bone - a case report

Abstract Accidental fish bone ingestion is a common complaint at emergency departments. The majority of cases have a benign course. However, serious complications such as esophagus perforation, cervical vessel injury and cervical abscess can occur in 7.4% of cases. Mortality rates can be as high as 50% when mediastinitis occurs. We report a case of an esophageal perforation caused by a fish bone with a lesion to the right common carotid artery after 20 days of evolution. Surgical exploration occurred with corrections of the lesion in the right common carotid and esophagus. Early identification of this kind of injury is paramount to prevent potentially fatal complications.

Abstract Accidental fish bone ingestion is a common complaint at emergency departments. The majority of cases have a benign course. However, serious complications such as esophagus perforation, cervical vessel injury and cervical abscess can occur in 7.4% of cases. Mortality rates can be as high as 50% when mediastinitis occurs. We report a case of an esophageal perforation caused by a fish bone with a lesion to the right common carotid artery after 20 days of evolution. Surgical exploration occurred with corrections of the lesion in the right common carotid and esophagus. Early identification of this kind of injury is paramount to prevent potentially fatal complications.

Hypolipidemic and reduced nitrergic effects of p-hydroxycinnamic diesters extracted from Copernicia prunifera in mice challenged by a high-fat diet.

Dyslipidemia is a chronic non-transmissible condition that has increased due to an unhealthy lifestyle. Statins have been used as the standard treatment to control hyperlipidemia. However, side effects and high costs may be associated with its prolonged treatment, so plants derivatives have been an attractive therapy to overcome these problems. Among the compounds extracted from plants, the p-hydroxycinnamic diesters (HCE), present in carnauba wax (CW), have been found with good pharmacological properties. Therefore, this study aimed to evaluate the potential anti-hypercholesterolemic and possible toxicological effects of HCE in C57BL/6J mice under a high-fat (HF) diet. Male C57BL/6J mice were fed during 60 days under the HF diet and therefore were either treated with HCE (200 and 400 mg/kg) or simvastatin (20 mg/kg) or received saline (controls) by gavage for 30 days under the same diet. HCE treatment was able to reduce serum total cholesterol and LDL levels. Besides, this compound increased liver X receptor (LXR) and but not significantly affected IL-1ß and TNF-α liver mRNA transcription activity. In conclusion, HCE treatment was found safe and may attenuate the deleterious effects of dyslipidemia due to chronic feeding with western diets.

Effects of somatic tissue cryopreservation on puma (Puma concolor L, 1771) tissue integrity and cell preservation after in vitro culture.

Somatic resource banks play a crucial role in the conservation of genetic diversity, allowing for the preservation of biological samples from different populations. Puma somatic cells can be recovered from these banks and used in assisted techniques toward enhancing their multiplication and conservation. In response to the population reduction of this ecologically importance species, we aimed to evaluate the capacity of cryopreservation of somatic tissues on the maintenance of the integrity and quality of the cells recovered after culture, with the aim of establishing a somatic tissue bank that will allow for the safeguarding of a wide genetic sampling of pumas. Cryopreservation increased the thickness of the corneum layer in the tissues, and the number of perinuclear halos and empty gaps. Nevertheless, cryopreservation was able to maintain normal fibroblast patterns, even showing an increase in the percentage of collagen fibers. Cryopreservation maintained the proliferative potential of the tissues and the parameters evaluated during in vitro culture, mainly regarding the viability, proliferative activity, and apoptosis levels. Nevertheless, cells from cryopreserved tissues showed decreased metabolism and mitochondrial membrane potential when compared to cells from non-cryopreserved tissues. In summary, we demonstrated for the first time that puma somatic tissues subjected to cryopreservation are viable and maintain tissue integrity, featuring minimal changes after warming. Although viable somatic cells are obtained from these tissues, they undergo alterations in their metabolism and mitochondrial membrane potential. Improvements in the conservation conditions of somatic samples are needed to increase the quality of somatic tissue banks in this species.

Prevalence of COVID-19 in children, adolescents and adults in remote education situations in the city of Fortaleza, Brazil.

OBJECTIVES: A retrospective study was conducted to identify the prevalence of COVID-19 through serology and RT-PCR in children, adolescents and adults. A database of the COVID-19 Tracking Program in school children was used. METHODS: The data comprised sociodemographic and clinical variables, results of serological tests (IgM and IgG), and real-time-polymerase chain reaction (RT-PCR) results of IgM-positive individuals. The statistical analysis was performed with a 5% significance level. RESULTS: Among 423 children, 107 (25.3%) exhibited seroprevalence with IgG, IgM or IgG/IgM; among 854 adolescents, 250 (29.2%) had positive serology; and among 282 adults, 59 (20.9%) were positive. The frequency of positivity on RT-PCR for SARS-CoV-2 was 3.5%, 3.6% and 6.0% in children, adolescents and adults, respectively. Children had a lower incidence of symptoms than adolescents (p = 0.001) and adults (p = 0.003); the most frequent were fever, ageusia, anosmia, headache, dry cough, sore throat, muscle pain, runny nose, dyspnoea, and diarrhoea. CONCLUSIONS: The prevalence rate for all groups was 26.7% in serology and 4.04% in RT-PCR. Children had lower rates of IgM and fewer symptoms compared with adolescents and adults. The data suggest the potential for transmissibility in all age groups.

Orally hypoglycemic activity of an insulin mimetic glycoprotein isolated from Cnidoscolus quercifolius Pohl. (Euphorbiaceae) seeds, Cq-IMP.

The genus Cnidoscolus (Euphorbiaceae) is widely distributed in tropical areas. In the Northeast of Brazil, the species C. quercifolius is endemic and has been used in traditional medicine. In this study, a novel protein was isolated from C. quercifolius seeds and characterized by its molecular weight, primary structure, isoelectric point (pI), and carbohydrate content. The hypoglycemic activity of this protein was investigated by in vitro assay with the RIN-5F glucose-responsive cell line and in vivo test using alloxan-induced diabetic mice models. In addition, safe use of the protein was also investigated by cytotoxicity, hemagglutinating, and immunogenicity assays. The protein which was named Cq-IMP (Cnidoscolus quercifolius - Insulin Mimetic Protein) showed a single 11.18 KDa glycopolypeptide chain (16.4% of carbohydrates, m/m), pI of 8.0 and N-terminal sequence (TKDPELKQcKKQQKKqQQYDDDDKK) with similarity around 46-62% to sucrose binding protein-like and vicilin-like protein that was confirmed by mass spectrometry tryptic peptides analysis. Besides that, Cq-IMP presented anti-insulin antibody cross-reactivity as hypoglycemic activity in both in vitro and in vivo models. Additionally, it did not present any toxicity by methods tested. In conclusion, Cq-IMP is an insulin-mimetic protein, with a potent hypoglycemic activity and no toxicity showing great potential for therapeutic applications and drug development.

Clinical and pathological features of thrombotic microangiopathy influencing long-term kidney transplant outcomes.

INTRODUCTION: Thrombotic microangiopathy (TMA) in post-transplant setting has heterogeneous clinical manifestations. METHODS: We retrospectively studied data of 89 patients with post-transplant TMA, which was characterized by thrombi in at least one glomerulus and/or arteriole. Systemic TMA was defined by thrombocytopenia and microangiopathic anemia and early onset TMA, when occurred less than 90 days post transplant. RESULTS: The cumulative incidence was 0.93%. The majority of the recipients were young (mean age 39 years), female (52%) and Caucasian (48%) with primary kidney disease of unknown etiology (37%). Early TMA occurred in 51% of the patients and systemic TMA, in 25%. Underlying precipitating factors were: infection (54%), acute rejection (34%), calcineurin inhibitor toxicity (13%) and pregnancy (3%). 18% of the patients had several triggers. Glomerular TMA was observed in 50% of the biopsies and endothelial cell activation, in 61%. The 1-year patient survival was 97% and corresponding graft survival, 66%. Allograft survival was inferior when acute antibody mediated rejection (ABMR) occurred (with 41%; without 70%, p = 0.01), however no differences were determined by hemolysis, time of onset, thrombi location or endothelial cell activation. CONCLUSIONS: Our results suggest that post-transplant TMA is a rare but severe condition, regardless of its clinical and histological presentation, mainly when associated to ABMR.

Functional Characterization and Pharmacological Evaluation of a Novel GLA Missense Mutation Found in a Severely Affected Fabry Disease Family.

BACKGROUND: Fabry disease (FD) is a rare X-linked storage disorder resulting from the deficient activity of the lysosomal hydrolase α-galactosidase A (α-Gal A). Here we describe a 23-year-old man with FD possessing a novel mutation in the GLA gene, the evaluation of his family, and the functional characterization of the novel variant. METHODS: Two generations of a family were screened for FD by clinical symptoms and low enzymatic activity. This step was followed by DNA sequencing that showed a novel GLA missense mutation. To confirm the pathogenicity potential of the mutation, we employed site-directed polymerase chain reaction mutagenesis. GLA wild-type and mutant plasmids were transfected into mammalian cells; RNA and proteins were extracted for expression and analysis of enzymatic activity. RESULTS: The patient presents the variant p.Asn34Asp in the GLA and had several manifestations of FD since adolescence. The investigation of the deficiency of α-Gal A was initiated due to stage 4 of chronic kidney disease. All family members carrying the novel mutation presented early symptoms, including index case's mother, who received a renal transplant when she was 35 years old. In silico and in vitro analysis confirmed the pathogenic potential of the mutation p.Asn34Asp showing that the enzyme had only 4% of residual activity due to protein misfolding. The ability of the pharmacological chaperone 1-deoxygalactonojirimycin to recover the mutant was confirmed, producing 37.5% of residual activity. CONCLUSION: In this work, we present a novel missense mutation in GLA that leads to the production of a catalytically competent α-Gal A, which is degraded before its delivery to the lysosome, promoting severe manifestations of FD, with a very similar disease course in affected men and women.

Role of membrane sterol and redox system in the anti-candida activity reported for Mo-CBP2, a protein from Moringa oleifera seeds.

Plant proteins are emerging as an alternative to conventional treatments against candidiasis. The aim of this study was to better understand the mechanism of action of Mo-CBP2 against Candida spp, evaluating redox system activity, lipid peroxidation, DNA degradation, cytochrome c release, medium acidification, and membrane interaction. Anti-candida activity of Mo-CBP2 decreased in the presence of ergosterol, which was not observed with antioxidant agents. C. albicans treated with Mo-CBP2 also had catalase and peroxidase activities inhibited, while superoxide dismutase was increased. Mo-CBP2 increased the lipid peroxidation, but it did not alter the ergosterol profile in live cells. External medium acidification was strongly inhibited, and cytochrome c release and DNA degradation were detected. Mo-CBP2 interacts with cell membrane constituents, changes redox system enzymes in C. albicans and causes lipid peroxidation by ROS overproduction. DNA degradation and cytochrome c release suggest apoptotic or DNAse activity. Lipid peroxidation and H+-ATPases inhibition may induce the process of apoptosis. Finally, Mo-CBP2 did not have a cytotoxic effect in mammalian Vero cells. This study highlights the biotechnological potential of Mo-CBP2 as a promising molecule with low toxicity and potent activity. Further studies should be performed to better understand its mode of action and toxicity.

Ferramenta referencial para elaboração de valores em ortodontia / Reference tool for preparing values in orthodontics

Com a difícil missão de estabelecer valores adequados dos serviços prestados na odontologia, e em frente a uma carência de informações específicas na literatura de classe a cerca deste assunto, o objetivo deste trabalho foi o desenvolvimento de uma ferramenta referencial para elaboração de valores, útil e simplificada na forma de um web aplicativo, a fim de guiar uma correta precificação, com a Ortodontia como especialidade eleita da pesquisa. Os materiais e métodos utilizados para o desenvolvimento deste estudo abordam variáveis direta e indiretamente influenciadoras do processo de formação dos preços, colocados estrategicamente dentro de um programa de dados criados em parceria com a Diretoria Técnica de Informática (DTI) da Universidade Estadual Paulista "Júlio de Mesquita Filho" (UNESP). Como resultado a apresentação da FREVO (Ferramenta Referencial para Elaboração de Valores em Ortodontia) para facilitar na prática a formação dos honorários, de forma adaptável ao perfil de cada profissional, cliente e tipo de consultório, com a sugestão final de valores a serem praticados na área, que possam ser justificados com mais clareza, em frente a uma grande divergência de preços sem transparência, na prestação dos serviços oferecidos e realizados pelos cirurgiões dentistas. Conclui se que há uma enorme carência de dados na literatura odontológica sobre este assunto tão pertinente e necessário para a saúde financeira de qualquer negócio e que a utilização de aplicativos como a "FREVO" facilita a problemática de precificação(AU)

The thesis has researched and developed a reference framework, called FREVO (Ferramenta Referencial para Elaboração de Valores em Ortodontia), which is a web-based toolkit to guide the cost-effective pricing for Orthodontics. Currently, there is a lack of dental literature and adequate orthodontic pricing reference values when performing dentistry services. The materials and methods used for the development of this study address variables directly and indirectly influencing the price formation process. This data program was created in partnership with the Technical Directorate of Informatics (TDI) of the Universidade Estadual Paulista "Júlio de Mesquita Filho "(UNESP). The FREVO toolkit helps estimate the orthodontic pricing reference value, which can be customizable and adaptable to the profile of each professional, client and type of dental office. It provides dental service transparency and the right recommendation of pricing values to be practiced by the dentists, given the vast discrepancy and lack of data available in the market. In conclusion, FREVO is therefore, a relevant toolkit to be used by any dentist professional in their day-to-day dental business to estimate the right orthodontics service pricing(AU)

Gender and alcohol consumption among young people: evaluation and validation of the conformity to Masculine Norms Inventory. / Gênero e consumo de álcool entre jovens: avaliação e validação do Inventário de Conformidade com Normas Masculinas.

Gender role social norms influence behaviors and affirm identities and belonging to particular groups. Dominant norms will continue to exist even if they change according to ethical, social and cultural norms. This study validated for the Brazilian reality the Conformity to Masculine Norms Inventory (CMNI-29) and searched for evidence of its applicability to specific factors of the consumption of alcoholic beverages of young university students. We collected data from 341 men in the age group 19-25 years living in the states of Minas Gerais and São Paulo. Participants completed the CMNI-29 and questions regarding their alcohol consumption. Even with adaptations to fit the context, the inventory was deemed valid. In general, reliability data were satisfactory and convergent and discriminant validity was achieved for all realms of masculinity. The CMNI-29 proved to be a useful measure to understand the multiple realms of masculinity in behavior. In addition, we found evidence of influence of norms on the frequency of alcohol consumption. The use of the scale broadens the scope of gender research in the country and enables search of its effect with other variables and health behaviors that affect this population.

Normas sociais de papel de gênero influenciam comportamentos e afirmam identidades e pertencimento a determinados grupos. Mesmo que alterem-se conforme padrões éticos, sociais e culturais, vão existir normativas dominantes. Este estudo validou para a realidade brasileira o Inventário de Conformidade com Normas Masculinas (CMNI-29) e buscou indícios da sua aplicabilidade a fatores específicos do consumo de bebidas alcoólicas de jovens universitários. Foram coletados dados de 341 homens, entre 19 e 25 anos, residentes em Minas Gerais e São Paulo. Os participantes completaram o CMNI-29 e perguntas sobre seu consumo de álcool. Mesmo com as adaptações realizadas para a adequação ao contexto, o inventário foi considerado válido. De maneira geral, os dados de confiabilidade se mostraram satisfatórios e atingiu-se validade convergente e discriminante para todas as dimensões da masculinidade. O CMNI-29 mostrou-se uma medida útil para compreender as múltiplas dimensões da masculinidade no comportamento. Além disso, indícios de influência das normas sobre a frequência de consumo de álcool foram encontrados. O uso da escala amplia o escopo de pesquisa de gênero no país, e possibilita a busca de seu efeito com outras variáveis e comportamentos de saúde que atingem esta população.

Gênero e consumo de álcool entre jovens: avaliação e validação do Inventário de Conformidade com Normas Masculinas / Gender and alcohol consumption among young people: evaluation and validation of the conformity to Masculine Norms Inventory

Resumo Normas sociais de papel de gênero influenciam comportamentos e afirmam identidades e pertencimento a determinados grupos. Mesmo que alterem-se conforme padrões éticos, sociais e culturais, vão existir normativas dominantes. Este estudo validou para a realidade brasileira o Inventário de Conformidade com Normas Masculinas (CMNI-29) e buscou indícios da sua aplicabilidade a fatores específicos do consumo de bebidas alcoólicas de jovens universitários. Foram coletados dados de 341 homens, entre 19 e 25 anos, residentes em Minas Gerais e São Paulo. Os participantes completaram o CMNI-29 e perguntas sobre seu consumo de álcool. Mesmo com as adaptações realizadas para a adequação ao contexto, o inventário foi considerado válido. De maneira geral, os dados de confiabilidade se mostraram satisfatórios e atingiu-se validade convergente e discriminante para todas as dimensões da masculinidade. O CMNI-29 mostrou-se uma medida útil para compreender as múltiplas dimensões da masculinidade no comportamento. Além disso, indícios de influência das normas sobre a frequência de consumo de álcool foram encontrados. O uso da escala amplia o escopo de pesquisa de gênero no país, e possibilita a busca de seu efeito com outras variáveis e comportamentos de saúde que atingem esta população.

Abstract Gender role social norms influence behaviors and affirm identities and belonging to particular groups. Dominant norms will continue to exist even if they change according to ethical, social and cultural norms. This study validated for the Brazilian reality the Conformity to Masculine Norms Inventory (CMNI-29) and searched for evidence of its applicability to specific factors of the consumption of alcoholic beverages of young university students. We collected data from 341 men in the age group 19-25 years living in the states of Minas Gerais and São Paulo. Participants completed the CMNI-29 and questions regarding their alcohol consumption. Even with adaptations to fit the context, the inventory was deemed valid. In general, reliability data were satisfactory and convergent and discriminant validity was achieved for all realms of masculinity. The CMNI-29 proved to be a useful measure to understand the multiple realms of masculinity in behavior. In addition, we found evidence of influence of norms on the frequency of alcohol consumption. The use of the scale broadens the scope of gender research in the country and enables search of its effect with other variables and health behaviors that affect this population.

Ethnobotanic, phytochemical uses and ethnopharmacological profile of genus Cnidoscolus spp. (Euphorbiaceae): A comprehensive overview.

The application of medicinal plants are the most important biotechnological alternative in the treatment of numerous diseases, especially in developing countries, such as Brazil. Among them, we specified some specimens of the genus Cnidoscolus used as phytotherapies, with healing properties, analgesic, anti-inflammatory, antibiotic and diuretic, anticancer, among others. Such effects are possibly associated with the presence of terpenoids, alkaloids, coumarins, flavonoids phenolic compounds, among others. Thus, the objective of this work was to evaluate in the literature the studies on the phytochemical, ethnopharmacological and biotechnological applications of this genus, from 1998 to 2017. Among the sixty-one studies reported in this review, ten species are popularly utilized to pharmacological and/or biotechnological applications. Cnidoscolus aconitifolius and Cnidoscolus chayamansa are the most cited species, which were also supported by either animal or cellular investigations indicating some beneficial pharmacological actions like antioxidant, anti-inflammatory and potential cytotoxic activity. The plant parts of this genus under study are important as sources for the isolation and identification of bioactive molecules with biotechnological applications, among the many diseases treated with this phytotherapy. Given these verdicts, ethnopharmacological approaches are significant systematic tools in the determination of plant species that exhibit medicinal and nutritional purposes. The results presented here should further stimulate the development of validation studies to ensure the safe and effective use of these plant species.

Antinociceptive activity of ethanolic extract of Azadirachta indica A. Juss (Neem, Meliaceae) fruit through opioid, glutamatergic and acid-sensitive ion pathways in adult zebrafish (Danio rerio).

Neem fruit (Azadirachta indica A. Juss.) are popularly used to treat infections, diarrhea, fever, bronchitis, skin diseases, infected burns and hypertension. Although the antinociceptive and anti-inflammatory potential of A. indica has already been investigated in experimental models of pain and inflammation in mice, the current research is the first to report the evaluation of the capacity of A. indica fruit ethanolic extract (EtFrNeem) in acute pain attenuation using the adult zebrafish (Danio rerio) as an alternative model to the use in rodents. EtFrNeem was submitted to antioxidant action, preliminary chemical prospecting, FT-IR and determination of phenol and flavonoid content tests. Subsequently, EtFrNeem was tested for acute nociception and abdominal inflammation, locomotor activity, and acute toxicity in adult zebrafish. Possible neuromodulation mechanisms were also evaluated. EtFrNeem showed low antioxidant activity, but was shown to be rich in flavonoids. EtFrNeem showed no anti-inflammatory action, did not alter the locomotor system, and it was not toxic. However, EtFrNeem significantly reduced the nociceptive behavior induced by formalin, glutamate and acidic saline, when compared to the control group. These effects of EtFrNeem were significantly similar to those of morphine, used as a positive control. The antinociceptive effect of EtFrNeem was inhibited by naloxone, ketamine and amiloride. EtFrNeem has the pharmacological potential for acute pain treatment and this effect is modulated by the opioid system, NMDA receptors and ASICs channels. These results lead us to studies of isolation and characterization of EtFrNeem bioactive principles, using adult zebrafish as an experimental model.