Anti-inflammatory and antiophidic effects of extract of Hymenaea eriogyne benth and structure-activity relationship prediction of the major markers in silico.

ETHNOPHARMACOLOGICAL RELEVANCE: Hymenaea eriogyne Benth (Fabaceae) is popularly known as "Jatobá". Despite its use in folk medicine to treat inflammatory disorders, there are no descriptions that show its anti-inflammatory potential. AIM OF THE STUDY: In this sense, this study aimed to evaluate the anti-inflammatory and antivenom action of bark and leaves extract of H. eriogyne. MATERIALS AND METHODS: The in vivo anti-inflammatory activity was conducted by carrageenan-induced paw edema and zymosan-induced air pouch models, evaluating the edematogenic effect, leukocyte migration, protein concentration, levels of pro-inflammatory cytokines, malondialdehyde (MDA) and myeloperoxidase (MPO) activity. The antivenom potential was investigated in vitro on the enzymatic action (proteolytic, phospholipase and hyaluronidase) of Bothrops brazili and B. leucurus venom, as well as in vivo on the paw edema model induced by B. leucurus. Furthermore, the influence of its markers (astilbin and rutin) on MPO activity was investigated in silico. For molecular docking, AutodockVina, Biovia Discovery Studio, and Chimera 1.16 software were used. RESULTS: The extracts and bark and leaves of H. eriogyne revealed a high anti-inflammatory effect, with a reduction in all inflammatory parameters evaluated. The bark extract showed superior results when compared to the leaf extract, suggesting the influence of the astilbin concentration, higher in the bark, on the anti-inflammatory action. In addition, only the H. eriogyne bark extract was able to reduce MDA, indicating an associated antioxidant effect. Regarding the in vitro antivenom action, the extracts (bark and leaves) revealed the ability to inhibit the proteolytic, phospholipase and hyaluronidase action of both bothropic venom, with a greater effect against B. leucurus venom. In vivo, extracts from the bark and leaves of H. eriogyne (50-200 mg/kg) showed antiedematogenic activity, reducing the release of MPO and pro-inflammatory cytokines, indicating the presence of bioactive components useful in controlling the inflammatory process induced by the venom. In the in silico assays, astilbin and rutin showed reversible interactions of 9 possible positions and orientations towards MPO, with affinities of -9.5 and -10.4 kcal/mol and interactions with Phe407, Gln91, His95 and Arg239, important active pockets of MPO. Rutin demonstrated more effective types of interactions with MPO. CONCLUSION: This approach reveals for the first time the anti-inflammatory action of H. eriogyne bark and leaf extracts in vivo, as well as its antiophidic potential. Moreover, the distinct effect of pharmacogens as antioxidant agents and distinct effect of astilbin and rutin under MPO sheds light on the different anti-inflammatory mechanisms of bioactive compounds present in H. eriogyne extracts, with high potential for the prospection of new pharmacological agents.

Structural and Functional Characterization of New Lipid Transfer Proteins with Chitin-Binding Properties: Insights from Protein Structure Prediction, Molecular Docking, and Antifungal Activity.

Faced with the emergence of multiresistant microorganisms that affect human health, microbial agents have become a serious global threat, affecting human health and plant crops. Antimicrobial peptides have attracted significant attention in research for the development of new microbial control agents. This work's goal was the structural characterization and analysis of antifungal activity of chitin-binding peptides from Capsicum baccatum and Capsicum frutescens seeds on the growth of Candida and Fusarium species. Proteins were initially submitted to extraction in phosphate buffer pH 5.4 and subjected to chitin column chromatography. Posteriorly, two fractions were obtained for each species, Cb-F1 and Cf-F1 and Cb-F2 and Cf-F2, respectively. The Cb-F1 (C. baccatum) and Cf-F1 (C. frutescens) fractions did not bind to the chitin column. The electrophoresis results obtained after chromatography showed two major protein bands between 3.4 and 14.2 kDa for Cb-F2. For Cf-F2, three major bands were identified between 6.5 and 14.2 kDa. One band from each species was subjected to mass spectrometry, and both bands showed similarity to nonspecific lipid transfer protein. Candida albicans and Candida tropicalis had their growth inhibited by Cb-F2. Cf-F2 inhibited the development of C. albicans but did not inhibit the growth of C. tropicalis. Both fractions were unable to inhibit the growth of Fusarium species. The toxicity of the fractions was tested in vivo on Galleria mellonella larvae, and both showed a low toxicity rate at high concentrations. As a result, the fractions have enormous promise for the creation of novel antifungal compounds.

Seeds of nonhost species as sources of toxic compounds for the cowpea weevil Callosobruchus maculatus (F.).

Cowpea weevil, Callosobruchus maculatus, is the primary pest of stored cowpea seeds. The management of this infestation currently relies on insecticides, resulting in environmental pollution and selection of insecticide-resistant pests. Consequently, research efforts are being devoted to identify natural insecticides as sustainable and environment friendly alternatives for the control of C. maculatus. In this study, we explore the toxic effects of the nonhost seeds Parkia multijuga, Copaifera langsdorffii, Ormosia arborea, Amburana cearensis, Lonchocarpus guilleminianus, Sapindus saponaria, and Myroxylon peruiferum, on the cowpea weevil C. maculatus. Notably, all nonhost seeds led to reductions between 60 and 100% in oviposition by C. maculatus females. Additionally, the larvae were unable to penetrate the nonhost seeds. Artificial seeds containing 0.05% to 10% of cotyledon flour were toxic to C. maculatus larvae. Approximately 40% of larvae that consumed seeds containing 0.05% of O. arborea failed to develop, in contrast to control larvae. Proteomic analysis of A. cearensis and O. arborea seeds identify revealed a total of 371 proteins. From those, 237 are present in both seeds, 91 were exclusive to O. arborea seeds, and 43 were specific to A. cearensis seeds. Some of these proteins are related to defense, such as proteins containing the cupin domain and 11S seed storage protein. The in silico docking of cupin domain-containing proteins and 11S storage protein with N-acetylglucosamine (NAG)4 showed negative values of affinity energy, indicating spontaneous binding. These results showed that nonhost seeds have natural insecticide compounds with potential to control C. maculatus infestation.

Immunosuppressants in women with repeated implantation failure in assisted reproductive techniques: a systematic review and meta-analysis

Abstract Objective To compare outcomes in patients with repeated implantation failure undergoing Intracytoplasmic Sperm Injection/In vitro fertilization (IVF/ICSI) plus immunosuppressants such as prednisolone, prednisone, or cyclosporine A versus the use of IVF/ICSI alone. Data source Databases were systematically searched in PubMed, Cochrane, and Embase databases in September 2023. Study Selection Randomized clinical trials and observational studies with the outcomes of interest were included. Data collect We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics. Data were analyzed using Review Manager 5.4.The main outcomes were live birth, miscarriage, implantation rate, clinical pregnancy, and biochemical pregnancy. Data synthesis Seven studies with 2,829 patients were included. Immunosuppressive treatments were used in 1,312 (46.37%). Cyclosporine A improved implantation rate (OR 1.48; 95% CI 1.01-2.18) and clinical pregnancy (1.89, 95% CI 1.14-3.14). Compared to non-immunosuppressive treatment, prednisolone and prednisone did not improve live birth (OR 1.13, 95% CI 0.88-1.46) and miscarriage (OR 1.49, 95% CI 1.07-2.09). Prednisolone showed no significant effect in patients undergoing IVF/ICSI, clinical pregnancy (OR 1.34; 95% CI 0.76-2.36), or implantation rate (OR 1.36; 95% CI 0.76-2.42). Conclusion Cyclosporine A may promote implantation and clinical pregnancy rates. However, given the limited sample size, it is important to approach these findings with caution. Our results indicate that prednisolone and prednisone do not have any beneficial effects on clinical outcomes of IVF/ICSI patients with repeated implantation failure. PROSPERO CRD42023449655

A review of the pathophysiology and the role of ion channels on bronchial asthma.

Asthma is one of the main non-communicable chronic diseases and affects a huge portion of the population. It is a multifactorial disease, classified into several phenotypes, being the allergic the most frequent. The pathophysiological mechanism of asthma involves a Th2-type immune response, with high concentrations of allergen-specific immunoglobulin E, eosinophilia, hyperreactivity and airway remodeling. These mechanisms are orchestrated by intracellular signaling from effector cells, such as lymphocytes and eosinophils. Ion channels play a fundamental role in maintaining the inflammatory response on asthma. In particular, transient receptor potential (TRP), stock-operated Ca2+ channels (SOCs), Ca2+-activated K+ channels (IKCa and BKCa), calcium-activated chloride channel (TMEM16A), cystic fibrosis transmembrane conductance regulator (CFTR), piezo-type mechanosensitive ion channel component 1 (PIEZO1) and purinergic P2X receptor (P2X). The recognition of the participation of these channels in the pathological process of asthma is important, as they become pharmacological targets for the discovery of new drugs and/or pharmacological tools that effectively help the pharmacotherapeutic follow-up of this disease, as well as the more specific mechanisms involved in worsening asthma.

Temperature effect in the inhibition of PLA2 activity of Bothrops brazili venom by Rosmarinic and Chlorogenic acids, experimental and computational approaches.

Myotoxicity caused by snakebite envenoming emerges as one of the main problems of ophidic accidents as it is not well neutralized by the current serum therapy. A promising alternative is to search for efficient small molecule inhibitors that can act against multiple venom components. Phospholipase A2 (PLA2) is frequently found in snake venom and is usually associated with myotoxicity. Thus it represents an excellent target for the search of new treatments. This work reports the effect of temperature in the inhibition of catalytic properties of PLA2 from Bothrops brazili venom by Rosmarinic (RSM) and Chlorogenic (CHL) acids through experimental and computational approaches. Three temperatures were evaluated (25, 37 and 50 °C). In the experimental section, enzymatic assays showed that RSM is a better inhibitor in all three temperatures. At 50 °C, the inhibition efficiency decayed significantly for both acids. Docking studies revealed that both ligands bind to the hydrophobic channel of the protein dimer where the phospholipid binds in the catalytic process, interacting with several functional residues. In this context, RSM presents better interaction energies due to stronger interactions with chain B of the dimer. Molecular dynamics simulations showed that RSM can establish selective interactions with ARG112B of PLA2, which is located next to residues of the putative Membrane Disruption Site in PLA2-like structures. The affinity of RSM and CHL acids towards PLA2 is mainly driven by electrostatic interactions, especially salt bridge interactions established with residues ARG33B (for CHL) and ARG112B (RSM) and hydrogen bonds with residue ASP89A. The inability of CHL to establish a stable interaction with ARG112B was identified as the reason for its lower inhibition efficiency compared to RSM at the three temperatures. Furthermore, extensive structural analysis was performed to explain the lower inhibition efficiency at 50 °C for both ligands. The analysis performed in this work provides important information for the future design of new inhibitors.Communicated by Ramaswamy H. Sarma.

Uso de heparina versus citrato em cateter de hemodiálise: uma revisão sistemática / Use of heparin versus citrate in hemodialysis catheter: a systematic review / Uso de heparina versus citrato en catéter de hemodiálisis: una revisión sistemática

A heparina é a solução mais utilizada para selar cateteres de hemodiálise. Entretanto, seu uso está associado a complicações locais e sistêmicas. A solução de citrato surge como alternativa devido aos seus efeitos anticoagulantes. O objetivo desta revisão sistemática é avaliar o risco de infecção da corrente sanguínea relacionada ao cateter usando heparina em comparação com solução de bloqueio de citrato. Esta revisão sistemática seguiu o protocolo Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) e a estratégia Population, Intervention, Comparison, Outcome (PICO), bem como utilizou as bases de dados Medline, Lilacs e Scielo. Buscaram-se ensaios clínicos randomizados que comparassem heparina com citrato como solução de bloqueio associada à infecção de corrente sanguínea relacionada a cateter. Inicialmente, foram encontrados 1.204 artigos. Após a leitura de seus títulos e resumos, foram selecionados 33 estudos. Depois da aplicação dos critérios de exclusão, restaram quatro artigos. Destes, o desfecho primário foi infecção da corrente sanguínea relacionada ao cateter. Em Weijmer et al. houve redução no grupo citrato. Por outro lado, Barcellos et al. mostraram resultados opostos usando o modelo multivariado. Power et al. não identificaram diferença entre os grupos e Winnett et al. favoreceram o grupo citrato usando análise de subgrupo. Não foi possível determinar diferença entre o grupo citrato e heparina na redução da infecção da corrente sanguínea relacionada ao cateter. São necessários mais estudos utilizando uma população maior e solução padronizada de citrato ou heparina.

As the most used solution to seal hemodialysis catheters, heparin use is associated with local and systemic complications. Citrate solution emerges as an alternative due to its anticoagulant effects. This systematic review sought to evaluate the risk of catheter-related bloodstream infection using heparin compared to citrate lock solution. Based on the PRISMA protocol and PICO strategy, data were collected from the Medline, Lilacs and Scielo databases. The search strategy included randomized clinical trials that compared heparin versus citrate as lock solution associated with catheter-related bloodstream infection. Of the 1,204 articles identified, 33 were selected after reading tittles and abstract. After applying the exclusion criteria, four papers were included for review. Primary outcome was catheter-related bloodstream infection. Weijmer et al. observed a reduction in the citrate group. In turn, Barcellos et al. showed opposite results using a multivariate model. Power et al. found no difference between groups and Winnet et al. favored the citrate group using subgroup analysis. Results on the difference between citrate versus heparin in reducing catheter-related bloodstream infection were inconclusive. Further studies using a bigger population and standardized citrate or heparin solution are needed.

La heparina es muy utilizada para sellar catéteres de hemodiálisis. Sin embargo, su uso se asocia a complicaciones locales y sistémicas. La solución de citrato puede ser una alternativa por sus efectos anticoagulantes. El objetivo de esta revisión sistemática es evaluar el riesgo de infección del torrente sanguíneo relacionada con el catéter en el uso de heparina en comparación con la solución bloqueadora de citrato. Esta revisión sistemática siguió el protocolo PRISMA y la estrategia PICO, así como las bases de datos Medline, Lilacs y SciELO, para buscar ensayos clínicos aleatorizados que habían comparado la heparina versus citrato como solución bloqueadora asociada a la infección del torrente sanguíneo relacionada con el catéter. Inicialmente se encontraron 1.204 artículos. Realizada la lectura de sus títulos y resúmenes, se seleccionaron 33 textos. Después de aplicar los criterios de exclusión, quedaron cuatro artículos. De estos, el resultado primario fue la infección del torrente sanguíneo relacionada con el catéter. En Weijmer et al. hubo una reducción en el grupo de citrato. Por otro lado, Barcellos et al. mostró resultados opuestos utilizando el modelo multivariado. Power et al. no mostraron diferencias entre los grupos, y Winnet et al. favorecieron al grupo citrato mediante análisis de subgrupos. No fue posible determinar una diferencia entre el grupo de citrato y el de heparina en la reducción de la infección del torrente sanguíneo relacionada con el catéter. Se necesitan más estudios que utilicen una población mayor y una solución estandarizada de citrato o heparina.

Functional and morphologic dysfunctions in the airways of rats submitted to an experimental model of obesity-exacerbated asthma.

The obesity-exacerbated asthma phenotype is characterized by more severe asthma symptoms and glucocorticoid resistance. The aim of this study was to standardize an obesity-exacerbated asthma model by a high glycemic level index (HGLI) diet and ovalbumin (OVA) sensitization and challenges in Wistar rats. Animals were divided into groups: control (Ctrl), obese (Ob), asthmatic (Asth), obese asthmatic (Ob + Asth) and obese asthmatic treated with dexamethasone (Ob + Asth + Dexa), and in vivo and in vitro functional and morphological parameters were measured. After HGLI consumption, there was an increase in body weight, fasting blood glucose, abdominal circumferences, body mass index and adiposity index. Respiratory function showed a reduction in pulmonary tidal volume and ventilation. In isolated tracheas, carbachol showed an increase in contractile efficacy in the Ob, Ob + Asth and Ob + Asth + Dexa, but mostly on Ob + Asth. Histological analysis of lungs showed peribronchovascular inflammation and smooth muscle hypertrophy and extracellular remodeling on Ob + Asth and Ob + Asth + Dexa. An obesity-exacerbated asthma model was successfully established. Therefore, this model allows further molecular investigations and the search for new therapies for the treatment and relief of symptoms of patients with obesity-induced resistant asthma.

Deleterious effects of Schinus terebinthifolius Raddi seed flour on cowpea weevil, Callosobruchus maculatus (F.), larval development.

Schinus terebinthifolius, Raddi, has been extensively studied due to its anti-inflammatory and antibiotic properties. S. terebinthifolius was also toxic to some insects, however little has been explored about the nature of its insecticide compounds or the toxicity of this plant to insect species. In this work, we investigate the toxicity of S. terebinthifolius seed flour against the insect C. maculatus. S. terebinthifolius seed flour interfered with the post hatch development of the C. maculatus larvae, decreasing larval survival, mass and length. Using DEAE-cellulose chromatography, five protein fractions were isolated, a non-retained fraction (NRF) and four retained fractions, eluted with 0.25, 0.5, 0.7 and 1.0 M NaCl. Proteins with varying molecular masses were observed in all fractions. The majority protein bands were identified by mass spectrometry analysis and among the main identified proteins are 11S globulins (such glycinin), lipoxygenase, chitinases, 7S globulins (vicilins, canavalin and ß conglycinin), annexin, catalase and sucrose binding protein. All DEAE-protein fractions were toxic to the insect, interfering with the post hatch larval development and survival. Decreases greater than 90% were observed in the larval mass and length at 20 days after oviposition (DAO) for larvae raised on diet containing 0.5% of some fractions. Alterations in the level of proteins, glucose and in the activity of the enzymes lipases and cysteine proteases were also detected in these larvae. Our results show that seeds of S. terebinthifolius have an arsenal of toxic proteins with potential for the control of the insect C. maculatus.

Antidiarrheal Effect of Zornia brasiliensis Vogel (Leguminosae) on Mice Involves Adrenergic Pathway Activation.

Several secondary metabolites have been isolated from Zornia brasiliensis (Leguminosae), mainly flavonoids. These compounds are known for many pharmacological actions, such as antispasmodic and antidiarrheal. Therefore, we evaluated the antidiarrheal effect of the ethanolic extract obtained from Zornia brasiliensis aerial parts (ZB-EtOHAP), as well as its underlying mechanisms. Castor-oil-induced diarrhea, fluid accumulation, and intestinal transit (normal and castor oil induced) were performed to assess the antidiarrheal, antisecretory, and antipropulsive activities of the extract. The involvement of opioid and adrenergic pathways was also investigated. ZB-EtOHAP inhibited, in a dose-dependent manner, both total defecation frequency and the number of watery stools. The extract showed no effect on fluid accumulation or normal intestinal transit. On the other hand, when the animals were pretreated with castor oil, the extract decreased the distance traveled by the marker in the small intestine. Investigation of the involvement of opioid and adrenergic systems showed that the pharmacological potency of the extract did not change in the presence of naloxone, but it was reduced in the presence of yohimbine. The data indicate that Zornia brasiliensis has an antidiarrheal effect due to inhibition of the intestinal motility through adrenergic pathway activation.

Uncovering the Role of Oxidative Imbalance in the Development and Progression of Bronchial Asthma.

Asthma is a chronic inflammatory disease of the airways related to epithelial damage, bronchial hyperresponsiveness to contractile agents, tissue remodeling, and luminal narrowing. Currently, there are many data about the pathophysiology of asthma; however, a new aspect has emerged related to the influence of reactive oxygen and nitrogen species (ROS and RNS) on the origin of this disease. Several studies have shown that an imbalance between the production of ROS and RNS and the antioxidant enzymatic and nonenzymatic systems plays an important role in the pathogenesis of this disease. Considering this aspect, this study is aimed at gathering data from the scientific literature on the role of oxidative distress in the development of inflammatory airway and lung diseases, especially bronchial asthma. For that, articles related to these themes were selected from scientific databases, including human and animal studies. The main findings of this work showed that the respiratory system works as a highly propitious place for the formation of ROS and RNS, especially superoxide anion, hydrogen peroxide, and peroxynitrite, and the epithelial damage is reflected in an important loss of antioxidant defenses that, in turn, culminates in an imbalance and formation of inflammatory and contractile mediators, such as isoprostanes, changes in the activity of protein kinases, and activation of cell proliferation signalling pathways, such as the MAP kinase pathway. Thus, the oxidative imbalance appears as a promising path for future investigations as a therapeutic target for the treatment of asthmatic patients, especially those resistant to currently available therapies.

The resistance of the cowpea cv. BRS Xiquexique to infestation by cowpea weevil is related to the presence of toxic chitin-binding proteins.

The cowpea weevil (Callosobruchus maculatus) is the main pest that attacks cowpea (Vigna unguiculata) seeds during storage, causing nutritional and economic losses in the cowpea crop. Thus, studies aiming to identify resistant cowpea cultivars have been developed. Chitin-binding proteins (CBP), such vicilins and chitinases, have been detected in seeds and related with the toxicity to insects. In this work, we investigated the presence of chitin-binding proteins in the partially resistant cowpea cv. BRS Xiquexique and evaluated their toxicity towards cowpea weevil. The CBP fraction was isolated by chitin affinity chromatography. CBP fraction showed, through 15% SDS PAGE, protein bands with varying molecular masses, mainly below 55 kDa. Proteins present in CBP fraction were identified by Western blotting and mass spectrometry analysis, as vicilins and chitinases. CBP fraction, at 5%, was able to interfere with the development of cowpea weevil, decreasing larval mass and length. A CBV (chitin-binding vicilin) fraction isolated from CBP fraction was toxic, at 2.0%, to C. maculatus, decreasing larval mass and length in 64.3% and 33.23%, respectively. These results suggest that chitin binding proteins, such vicilins and chitinases, may be related to the resistance of cowpea cv. BRS Xiquexique to the infestation by C. maculatus.

Investigation of ethnomedicinal use of Commiphora leptophloeos (Mart.) J. B. Gillett (Burseraceae) in treatment of diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Commiphora leptophloeos (Mart.) J.B. Gillett, popularly known as "imburana", "imburana-de-cheiro" or "imburana-de-espinho", has been used in folk medicine for the treatment of gastrointestinal diseases, such as diarrhea. The indian tribes "Kairir-Shokó and shokó use the bark to treat diarrhea. However, there is no scientific evidence to justify the therapeutic use of this species. AIM OF THE STUDY: To investigate the ethnomedicinal use of Commiphora leptophloeos, with respect to the antimicrobial, antisecretory, antimotility and antispasmodic activities of the crude ethanolic extract obtained from its leaves (CL-EtOHL) and the mechanism underlying this action in rodents. MATERIAL AND METHODS: In the evaluation of antibacterial and antifungal activities was determined the minimum inhibitory concentration (MIC) of the extract, against different strains of bacteria and fungi. All experimental protocols were approved by the Animal Ethics Committee of the Federal University of Paraíba (045/2016). In addition, behavioral screening and acute toxicity assessment of CL-EtOHL were performed in female mice (n = 6). In the investigation of antidiarrheal activity (n = 6), frequency of defecation and number of liquid stools, were classified during 4 h, and intestinal fluid and transit were measured. In addition, the antispasmodic effect on rat ileum (n = 5) was also investigated. RESULTS: The ethanolic extract is rich in flavonoids and the main were identified as C-glycosylated flavonoids (isoorientin, orientin, and vitexin). In the evaluation of antimicrobial and antifungal activity, the extract showed moderate efficacy only against the tested strains of Candida krusei ATCC-6258, Candida parapsilosis ATCC-22019 and Candida glabrata ATCC-90030. The extract had no toxic effect until 2000 mg/kg. In castor oil-induced diarrhea, CL-EtOHL inhibited, in a dose-dependent manner, both total defecation frequency (ED50 = 380.4 ± 145.4 mg/kg) and the number of watery stools (ED50 = 151.2 ± 76.3 mg/kg). The extract showed no effect on fluid accumulation or normal intestinal transit. On the other hand, when the animals were pretreated with castor oil, the extract decreased the distance traveled by the activated charcoal (ED50 = 177.0 ± 50.3 mg/kg). In the investigation of antispasmodic effect, CL-EtOHL antagonized the contractions induced by KCl 30 mM (IC50 = 208.2 ± 25.9 µg/mL) and CCh 10-6 M (IC50 = 95. ± 22.0 µg/mL). To verify the participation of muscarinic receptors in this effect, cumulative carbachol curves were performed in the absence and presence of the extract, and a non-competitive pseudo-irreversible antagonism of these receptors was observed. CONCLUSION: The data indicate that ethanol extract obtained from the leaves of Commiphora leptophloeos has an antidiarrheal effect due to inhibition of the intestinal motility and antispasmodic effect, through the antagonism of muscarinic receptors. In addition, we suggest that flavonoids isolated from CL-EtOHL may be responsible for antidiarrheal activity of this extract. This explains its ethnomedicinal use in the treatment of diarrhea.

Knowledge of basic attention professionals about prevention and early detection of breast cancer in the state of Goiás

The role of Basic Health Care (BHC) professionals is essential in the primary and secondary prevention of breast cancer. The aim of this study was to characterize BHC professionals in the Health Regions of a federative unit and to assess their knowledge about breast cancer. This was a prospective study carried out with BHC professionals from the state of Goiás. Phase 1 ­ Preparation of material and training of the team. Phase 2 ­ Agreement of actions between executing team and coordination of health regions. Phase 3 ­ Presentation of project at the collegiate meeting. Phase 4 ­ Qualification of BHC professionals with different learning methods and application of questionnaires, evaluating the contribution of the action. A total of 1,133 professionals were included; mean age was 36.3 years, and they were predominantly women (87.6%), working as community health agents (59.2%) and at public service (76.3%). Only 53.8% of professionals identified the female sex as a risk factor for breast cancer, while 90% identified family history as an important factor for the development of the disease. Important changes in physical examination that can occur in patients with the disease, such as skin retraction, skin bulging and nipple injury, were mentioned as a risk factor only by 35.3%, 31.3% and 39.7%, respectively. BHC professionals who participated in the project had less than ten years of professional experience and significant restrictions of knowledge about primary and secondary prevention of breast cancer. They still experience difficulties in accessing mammography and specialized care.

Chemical Modifications of Vicilins Interfere with Chitin-Binding Affinity and Toxicity to Callosobruchus maculatus (Coleoptera: Chrysomelidae) Insect: A Combined In Vitro and In Silico Analysis.

Vicilins are related to cowpea seed resistance toward Callosobruchus maculatus due to their ability to bind to chitinous structures lining larval midgut. However, this binding mechanism is not fully understood. Here, we identified chitin binding sites and investigated how in vitro and in silico chemical modifications interfere with vicilin chitin binding and insect toxicity. In vitro assays showed that unmodified vicilin strongly binds to chitin matrices, mainly with acetylated chitin. Chemical modifications of specific amino acids (tryptophan, lysine, tyrosine), as well as glutaraldehyde cross-linking, decreased the evaluated parameters. In silico analyses identified at least one chitin binding site in vicilin monomer, the region between Arg208 and Lys216, which bears the sequence REGIRELMK and forms an α helix, exposed in the 3D structure. In silico modifications of Lys223 (acetylated at its terminal nitrogen) and Trp316 (iodinated to 7-iodine-L-tryptophan or oxidized to ß-oxy-indolylalanine) decreased vicilin chitin binding affinity. Glucose, sucrose, and N-acetylglucosamine also interfered with vicilin chitin binding affinity.

Antifungal activity of Copaíba resin oil in solution and nanoemulsion against Paracoccidioides spp.

Paracoccidioidomycosis (PCM) is a disease caused by fungi of the genus Paracoccidioides. The disease is responsible for high rates of premature deaths and socioeconomic repercussions. The limitations of antifungal agents against PCM have motivated the search for new compounds. In our ongoing exploration of Cerrado plants as potential sources of new antifungal agents, we selected Copaifera langsdorffii oil (Copaíba resin oil) in order to explore its bioactive potential and test a formulation to increase oil stability and solubilization employing Pluronic F-127 to obtain the nanoemulsion of the oil. We aim at testing both Copaíba resin oil and its nanoemulsion against four species of the Paracoccidioides genus. We performed cytotoxicity test in Balb/C3T3 cells, hemolytic activity and interaction of Copaíba resin oil and Copaíba resin oil nanoemulsion (CopaPlu) with the antifungal agents such as amphotericin B, co-trimoxazole, and itraconazole. Moreover, the Copaíba resin oil was analyzed by mass spectrometry to identify its chemical profile. Eventually, a new methodology to prepare the nanoemulsion is presented. The Copaíba resin oil and CopaPlu nanoemulsion inhibited Paracoccidioides sp. growth efficiently, and no cytotoxicity or hemolytic effect was observed at minimum inhibitory concentration (MIC). When combined with amphotericin B, Copaíba resin oil and its nanoemulsion showed an additive effect with reduction of MIC values. The Copaíba resin oil and CopaPlu nanoemulsion is a promising antifungal agent against Paracoccidioides.

Oceanapia magna Sponge Presents Dual Effect on the Gastrointestinal Motility of Rodents: In Vitro and In Vivo Assays.

Oceanapia magna Santos-Neto, Nascimento, Cavalcanti and Pinheiro sponges are distributed across tropical worldwide seas. Some studies of marine products have shown interesting activities in smooth muscle models. Hence, we assessed the effect of the ethanolic extract of Oceanapia magna. (OC-EtOH) on acute toxicity and gastrointestinal motility (in vitro and in vivo) in rodent models. On guinea pig ileum, OC-EtOH induced a concentration dependent contraction on basal tonus, which was not inhibited by atropine, but in the presence of pyrilamine or verapamil, the effect was antagonized. Contrastingly, on KCl- or histamine-induced contractions, OC-EtOH presented a transient contraction followed by a concentration-dependent relaxation. Moreover, OC-EtOH presented a relaxant profile on cumulative curves to CaCl2 and tonic contraction induced by S-(-)-BayK8644, through Cav blockade. The acute toxicity assay showed that OC-EtOH (2,000 mg/kg, p.o.) did not present any sign of toxicity in female mice. Additionally, OC-EtOH presented antidiarrheal effect in mice, increased the intestinal normal transit and reduced the castor oil-induced intestinal transit. Thus, OC-EtOH presented a dual effect on guinea pig ileum promoting contraction through activation of H1 and CaV, and relaxation through CaV blockade, besides the effect on upper gastrointestinal transit in mice, showing a potential medicinal use of this sponge in intestinal diseases such as diarrhea.

A New Mixed-Valence Mn(II)Mn(III) Compound With Catalase and Superoxide Dismutase Activities.

The synthesis, X-ray molecular structure, physico-chemical characterization and dual antioxidant activity (catalase and superoxide dismutase) of a new polymeric mixed valence Mn(III)Mn(II) complex, containing the ligand H2BPClNOL (N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)[(3-chloro)(2-hydroxy)] propylamine) is described. The monomeric unit is composed of a dinuclear Mn(II)Mn(III) moiety, [Mn(III)(µ-HBPClNOL)(µ-BPClNOL)Mn(II)(Cl)](ClO4)·2H2O, 1, in which the Mn ions are connected by two different bridging groups provided by two molecules of the ligand H2BPClNOL, a phenoxide and an alkoxide group. In the solid state, this mixed valence dinuclear unit is connected to its neighbors through chloro bridges. Magnetic measurements indicated the presence of ferromagnetic [J = +0.076(13) cm-1] and antiferromagnetic [J = -5.224(13) cm-1] interactions. The compound promotes O 2 • - dismutation in aqueous solution (IC50 = 0.370 µmol dm-3, k cat = 3.6x106 M-1 s-1). EPR studies revealed that a high-valent Mn(III)-O-Mn(IV) species is involved in the superoxide dismutation catalytic cycle. Complex 1 shows catalase activity only in the presence of a base, e.g., piperazine or triethylamine. Kinetic studies were carried out in the presence of piperazine and employing two different methods, resulting in k cat values of 0.58 ± 0.03 s-1 (detection of O2 production employing a Clark electrode) and 2.59 ± 0.12 s-1 (H2O2 consuption recorded via UV-Vis). EPR and ESI-(+)-MS studies indicate that piperazine induces the oxidation of 1, resulting in the formation of the catalytically active Mn(III)-O-Mn(IV) species.

Avaliação da atividade antibacteriana e moduladora dos extratos metanólico e hexânico da folha de Allium cepa / Evaluation of the Antibacterial and Modulating Activity of Methanolic and Hexanic Extracts of the Allium Cepa / Evaluación de la actividad antibacteriana y moduladora de los extractos metanol y hexano de la hoja de Allium cepa

Introdução: A resistência bacteriana tem crescido significativamente nos últimos tempos, tornando-se imprescindível a busca por novos alvos terapêuticos. Nesse contexto, compostos bioativos presentes em algumas plantas medicinais podem apresentar várias atividades biológicas, como ação antimicrobiana. Allium cepa conhecida popularmente como cebola é utilizada de maneira etnofarmacológica há muito tempo para o tratamento de diversas enfermidades: tuberculose, diabetes, hipertensão, reumatismo e assim por diante. Objetivo: O principal objetivo deste trabalho foi avaliar a atividade antimicrobiana e modulatória dos extratos metanólico e hexânicoda das folhas A. cepa frente às cepas de bactérias padrões e multirresistentes. Materiais e métodos: Pelos métodos e microdiluição e modulação com antibióticos. Resultados: Os resultados deste estudo demonstraram uma variação no CMI (Concentração Inibitória Mínima) de 128 a ≥ 1024 μg/mL dos extratos metanólico de A. cepa (EMAC) e hexânico de A. cepa (EHAC). Na modulação com os aminoglicosídeos (amicacina e gentamicina) observaram-se efeitos sinérgicos e antagônicos dos extratos EHAC e EMAC frente às cepas Escherichia coli e Staphylococcus aureus de linhagem multirresistente. Novas pesquisas são necessárias para uma possível utilização das plantas medicinais combinadas com os antimicrobianos frente às linhagens patogênicas. Conclusão: Através desses resultados sugere-se que os produtos naturais representam fontes promissoras no combate à resistência bacteriana.

Introduction: Bacterial resistance has grown significantly in recent years, making the search for new antibiotics imperative. Bioactive compounds in some medicinal plants may exhibit various biological activities as antimicrobial activity. Allium cepa, popularly known as onion, is ethnopharmacologically used for treating various diseases, such as tuberculosis, diabetes, hypertension and rheumatism; it is also considered a powerful bactericide. Objective: The main objective of this study was to evaluate the antimicrobial and modulating activity of methanol and hexane extracts of A. cepa against the strains of multiresistant bacteria. Materials and methods: Microdilution and modulation of antibiotics. Results: The results showed a variation in the MIC (Minimum Inhibitory Concentration) from 128 to ≥ 1024μg / mL between A. cepa methanol (EMAC) and A. cepa hexane (EHAC) extracts. Modulation with aminoglycosides (gentamicin and amikacin) have proved to have antagonistic effects of the extracts sinérgicose EHAC and EMAC against strains of multiresistant Escherichia coli and Staphylococcus aureus. Further research is needed related to the use of medicinal plants combined with antimicrobials against pathogenic strains. Conclusion: Through these results it can be inferred that natural products could constitute a promising source for combating bacterial resistance.

Introducción: la resistencia bacteriana ha crecido significativamente en los últimos años, por lo que es necesaria la búsqueda de nuevas dianas terapéuticas. En este contexto, los compuestos bioactivos presentes en algunas plantas medicinales pueden tener diversas actividades biológicas, tales como la acción antimicrobiana. Allium cepa, conocida como la cebolla, es utilizada, popularmente de forma etnofarmacológica para el tratamiento de diversas enfermedades tales como la tuberculosis, la diabetes, la hipertensión, el reumatismo y así sucesivamente. Objetivo: el objetivo de este estudio fue evaluar la actividad antimicrobiana y moduladora de extractos de metanol y hexano de Allium cepa frente a las cepas de bacterias y normas multirresistentes. Materiales y métodos: por los métodos microdilución y modulación con antibióticos. Resultados: los resultados mostraron una variación de MIC(concentración mínima inhibitoria) de 128 a ≥ 1024μg / mL dos extractos metanólicos A. cepa (EMAC) y hexano de A. cepa (EHAC). En la modulación con aminoglucósidos (amikacina y gentamicina), se observaron efectos sinérgicos y antagónicos de EHAC y EMAC, frente a las cepas de Escherichia coli y Staphylococcus aureus multirresistente. Se necesitan nuevas investigaciones para un posible uso de plantas medicinales combinadas con la cara antimicrobiana de las cepas patógenas. Conclusión: a partir de estos resultados, se sugiere que los productos naturales son fuentes prometedoras en la lucha contra la resistencia bacteriana.

AVALIAÇÃO DA ATIVIDADE ANTI-INFLAMATÓRIA TÓPICA E ANTIBACTERIANA DO EXTRATO METANÓLICO DAS FOLHAS DE Sideroxylon obtusifolium / Evaluation of the Topical Anti-inflammatory Activity and Antibacterial Activity of Methanol Extract in the Sideroxylon obtusifolium Leaves / Evaluación de la actividad antiedematogenic tópica y antibacteriana del extracto metanólico de hojas de Sideroxylon obtusifolium

Sideroxylon obtusifolium, conhecida como quixaba, é utilizada para diversos fins medicinais, dentre eles em casos de inflamações e infecções bacterianas, com isso, o estudo teve por objetivo investigar a atividade anti-inflamatória tópica e antibacteriana do extrato metanólico obtido das folhas de S. obtusifolium. A prospecção fitoquímica do extrato revelou a presença de diversas classes, entre eles: Fenóis; Taninos Pirogálicos, Flavonoides, Catequinas e alcaloides. Os polifenóis e flavonóides presentes neste extrato foram quantificados em 150,3 mg equivalentes de ácido gálico/g de extrato e 98,5 mg equivalentes de quercetina/g de extrato, respectivamente. Os resultados obtidos através dos testes de microdiluição e modulação mostraram potencial atividade antibacteriana quando associados a gentamicina e amicacina para cepas multirresistentes de Staphylococcus aureus. Para cepas de Escherichia coli, houve sinergismo frente ao antibiótico amicacina havendo antagonismo para gentamicina, o mesmo efeito foi observado para Pseudomonas aeruginosas em ambos antibióticos. Nos testes para inflamação aguda através dos modelos de edema de orelha induzido por óleo de cróton e fenol, o extrato apresentou um potente efeito antiedematogênico significativo (p < 0,05). Diante dos resultados, podem-se observar atividades biológicas de S. obtusifolium, o que condiz com seu uso na terapia popular.

Sideroxylon obtusifolium, known as "quixaba", is used for various medicinal purposes, including in cases of inflammation and bacterial infections, therefore, the study aimed to investigate the topical antibacterial and anti-inflammatory activity of the methanol extract obtained from the leaves of S. obtusifolium. The phytochemical screening of the extract revealed the presence of several classes, including Phenols; Tannins, Flavonoids, catechins and alkaloids. Polyphenols and flavonoids present in this extract were quantified in 150.3 mg of gallic acid equivalents / g extract and 98.5 mg of quercetin equivalents / g extract, respectively. The results obtained by the microdilution tests have shown potential and modulation antibacterial activity when associated gentamicin, and amikacin for multidrug-resistant strains of Staphylococcus aureus. For Escherichia coli, there was synergism for amikacin, gentamicin having antagonism, the same effect was observed for Pseudomonas aeruginosa on both antibiotics. In tests for acute models of inflammation by ear edema induced by croton oil, and phenol, the extract had a potent antiedematogenic significant effect (p < 0.05). Therefore, the results can be observed biological activities of S. obtusifolium, which is consistent with its use in popular therapy.

Sideroxylon obtusifolium conocida como quixaba, se utiliza para diversos fines medicinales, incluso en los casos de infecciones bacterianas y la inflamación, por lo tanto, este estudio tuvo como objetivo investigar la actividad antiinflamatoria tópica y antibacteriana del extracto de metanol obtenido de las hojas de S. obtusifolium. El tamizaje fitoquímico del extracto reveló la presencia de varias clases, incluyendo: fenoles; taninos pirogálicos, flavonoides, catequinas y alcaloides. Los polifenoles y flavonoides presentes en este extracto se cuantificaron en 150,3 mg de equivalentes de ácido/g de extracto gálico y 98,5 mg de extracto de quercetina equivalentes/g, respectivamente. Los resultados obtenidos por los ensayos de microdilución han mostrado actividad potencial y la modulación antibacteriana cuando se asocia gentamicina, amikacina y para las cepas resistentes a múltiples fármacos de Staphylococcus aureus. Para Escherichia coli, solo se obtuvo sinergismo con amikacina, y se observo antagonismo para gentamicina, este mismo efecto fue observado para Pseudomonas aeruginosa en ambos antibióticos. En las pruebas de modelos agudos de inflamación por edema de la oreja inducido por aceite de crotón, y el fenol, el extracto tuvo un efecto significativo antiedematogenic potente (p <0,05). Por lo tanto, los resultados muestran actividad biológica de S. obtusifolium, que es coherente con su uso en terapia popular.