Guettarda viburnoides Cham. & Schltdl.: Neuroprotective Activities in Mice, Molecular Docking and Microchemical and Morphoanatomical Characteristics of Leaves and Stems.

BACKGROUND: Guettarda viburnoides Cham. & Schltdl., "veludinho do campo", is used in the Brazilian Amazon for its effects on the central nervous system (CNS) as a "brain tonic"; however, scientific evidence is needed to elucidate its ethnobotanical uses. OBJECTIVE: This study evaluated the neurobehavioural effects of an ethanolic extract of G. viburnoides (EEGV). Molecular docking, microchemical and morphoanatomical features of the species were investigated. METHODS: EEGV was investigated by UHPLC‒MS/MS and dereplication and molecular network were investigated using platforms available for natural product chemistry. For the in vivo assay, EEGV was administered to mice orally (3, 30 or 100 mg/kg). The effect of EEGV on spatial memory was measured using the Morris water maze test in mice with scopolamine-induced amnesia. The depression- and anxiety-like effects were assessed by forced swimming, tail suspension, marble burying and elevated plus maze tests. The AChE inhibition was evaluated in the brains of treated mice and molecular docking simulations were carried out with the main constituents. The leaves and stems of G. viburnoides were analysed via optical microscopy, scanning electron microscopy and energy dispersive X-ray spectroscopy. RESULTS: Secoxyloganin, grandifloroside, hyperin/or isoquercitrin, uncaric acid and ursolic acid were identified by UHPLC‒MS/MS. Molecular networking by three flavonoids, three triterpenes, two coumarins, two iridoids, and one phenolic acid. EEGV reversed these scopolamineinduced effects. In the forced swim and tail suspension test, EEGV (30 and 100 mg/kg) significantly reduced the immobility time. EEGV significantly reduced the number of buried marbles, while in the elevated plus maze test, no changes were observed compared to the Sco group. AChE activity was altered in the hippocampus. Studies of the molecular coupling of iridoid glycosides (grandifloroside and secoxyloganin) and flavonoid hyperin with AChE revealed significant interactions, corroborating the activity indicated by the inhibition assay. CONCLUSIONS: These results might be in accordance with medicinal use for neuroprotetor effects and important microchemical and micromorphological data that support the identification and quality control of G. viburnoides.

Clinical and imaging research in the diagnosis of anorectal melanoma with surgical outcome: a case report and literature review

Objective: This study aims to report the case of a 69-year-old female patient with a diagnosis of anorectal melanoma (AM) established by immunohistochemistry. Methods: Clinical case report, a descriptive and qualitative study. Results: The patient had a nodular and ulcerative lesion in the anal region, the imaging exams revealed an expansive lesion that affected the rectum and the vaginal wall. The chosen course of treatment was initial surgical intervention, the surgery and postoperative course progressed without complications, and the anatomopathological examination confirmed the diagnosis of invasive malignant melanoma of the distal rectum of anorectal transition. The anatomopathological examination confirmed the diagnosis of invasive malignant melanoma located in the distal rectum of the anorectal transition. Immunohistochemistry analysis showed infiltrative melanoma with microsatellites, as well as peri and intratumoral lymphocytic infiltrate, angiolymphatic invasion, and perineural invasion. The surgical resection margins, ovaries, posterior vaginal wall, and parametrium showed no signs of neoplastic involvement. Following the surgery, the patient began immunotherapy, which she is still undergoing. Conclusions: The survival rate of AM can be improved through various diagnostic and therapeutic modalities. However, further exploration of this topic through clinical studies is necessary to enhance both diagnosis and treatment. (AU)

Geographical variation in the chemical composition, anti-inflammatory activity of the essential oil, micromorphology and histochemistry of Schinus terebinthifolia Raddi.

ETHNOPHARMACOLOGICAL RELEVANCE: Schinus terebinthifolia Raddi (Anacardiaceae) is rich in essential oil, distinguished by a predominance of monoterpenes and sesquiterpenes, it being widely used in traditional medicine for the treatment of inflammations. AIM OF STUDY: This study's objective was to investigate the chemical composition of the essential oil of S. terebinthifolia (EOST) collected in six states of Brazil, evaluate its anti-inflammatory effects in mice, and analyze the histochemistry and micromorphology of leaves and stems. MATERIALS AND METHODS: Aerial parts of S. terebinthifolia were collected in six states of Brazil, and the essential oil was extracted by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). The histochemistry and micromorphology of leaves and stems were performed using standard reagents, light and field emission scanning electron microscopy, beyond energy-dispersive X-ray spectroscopy. The EOST were evaluated for anti-inflammatory activity and hyperalgesia using the carrageenan-induced paw edema methodology. RESULTS: The EOST showed variation across the six states in its yield (0.40%-0.86%) and chemical composition: hydrocarbon monoterpenes (28.76%-47.73%), sesquiterpenes, (31.43%-41.76%), oxygenated monoterpenes (14.31%-19.57%), and oxygenated sesquiterpenes (4.87%-14.38%). Both α-pinene and limonene were predominant constituents of essential in five regions, except for one state where α-phellandrene and limonene were the dominant components. A comprehensive description of the leaf and stem micromorphology and histochemistry was performed. In the in vivo testing, all EOST samples exerted antiedematogenic and anti-hyperalgesic effects, when tested in a carrageenan-induced paw inflammation (mechanical and thermal hyperalgesia) model with oral doses of 30 mg/kg. CONCLUSION: Our results indicate that the EOST samples collected in six Brazilian states differed in their chemical composition but not their anti-inflammatory and antihyperalgesic effects, which was correlated with the synergistic effect of its components, collaborating the etnhopharmacologycal use of this plant due to its an anti-inflammatory effect. Also, micromorphology and histochemistry of leaves and stems presented in this study provide anatomical and microchemical information, which aids species identification.

Zika Virus Envelope Protein Domain III Produced in K. phaffii Has the Potential for Diagnostic Applications.

Zika virus (ZIKV) represents a global human health threat and it is related to severe diseases such as congenital Zika syndrome (CZS) and Guillain-Barré syndrome (GBS). There is no vaccine available nor specific antiviral treatment, so developing sensitive, specific, and low-cost diagnostic tests is necessary. Thus, the objective of this work was to produce the Zika virus envelope protein domain III (ZIKV-EDIII) in Komagataella phaffii KM71H and evaluate its potential for diagnostic applications. After the K. phaffii had been transformed with the pPICZαA-ZIKV-EDIII vector, an SDS-PAGE and Western Blot were performed to characterize the recombinant protein and an ELISA to evaluate the antigenic potential. The results show that ZIKV-EDIII was produced in the expected size, with a good purity grade and yield of 2.58 mg/L. The receiver operating characteristic (ROC) curve showed 90% sensitivity and 87.5% specificity for IgM, and 93.33% sensitivity and 82.76% specificity for IgG. The ZIKV-EDIII protein was efficiently produced in K. phaffi, and it has the potential for diagnostic applications.

Synthesis, Characterization, Antiproliferative Activity of Galloyl Derivatives and Investigation of Cytotoxic Properties in HepG2/C3A Cells.

BACKGROUND: Appropriate substituents in the galloyl group could lead to significant biological properties. OBJECTIVES: Novel galloyl-substituted compounds bearing 2-substituted-1, 3, 4-oxadiazol-5-yl, 5- substituted-1,2,4-triazol-3-yl, and carboxamide groups were synthesized and evaluated for their antiproliferative activity. Additionally, galloyl hydrazide (2) was evaluated by performing cytotoxicity, membrane integrity, cell cycle, and apoptosis assays in HepG2/C3A cells. METHODS: General procedure was used for the synthesis of galloyl-substituted (3-9, 11) and characterized by their spectroscopic data (1H and 13C NMR). The antiproliferative activity of all novel galloyl derivatives was evaluated against nine human tumors and one nontumoral cell line. Three response parameters (GI50, TGI, and LC50) were calculated. The cytotoxicity test was performed for the resazurin assay. The membrane integrity, cell cycle, and apoptosis assays were performed by flow cytometry. RESULTS: The substitution of the methoxy group of the galloyl ring system for a carboxamide group (3, 4, 5, and 6) produced compounds with moderate antitumoral activity, particularly 6, against six human cancer cell lines, K-562, PC-3, NCI-ADR/RES, OVCAR, 786-0 and NCI-H460, with GI50 values ≤ 9.45 µg/mL. Triazole derivatives 7 and 8 exhibited higher antitumoral activity toward OVCAR, MCF-7 and leukemia K-562 cell lines, exhibiting GI50 values less than 10 µg/mL. Compound 11 displayed significant activity against PC-3 (GI50 = 4.31 µg/mL), OVCAR (GI50 = 8.84 µg/mL) and K-562 (GI50 = 8.80 µg/mL) cell lines. Galloyl hydrazide (2) had cytotoxic activity in HepG2/C3A cells (IC50 = 153.7 µg/mL). In membrane permeability, cell count, cell cycle, and apoptosis assays, as determined using the IC50 of compound (2) in HepG2/C3A cells, increased membrane permeability, decreased cell count, altered cell cycle, and initial apoptosis was observed compared to the control group. CONCLUSION: Thus, our results showed for the first time the synthesis, antiproliferative activity, and cytotoxicity of galloyl-substituted compounds. Galloyl-substitution does not have a very strong synergistic effect in the inhibition of cancer cell proliferation compared with galloyl hydrazide (2). Compound 2 demonstrated promising activity in HepG2/C3A hepatocarcinoma cells.

Longitudinal analysis of antibody responses to the Pfizer BNT162b2 vaccine in Patients Undergoing Maintenance Hemodialysis

BackgroundHemodialyzed patients are at higher risk for COVID-19 and were prioritized in the Portuguese vaccination campaign MethodsWe performed a prospective, longitudinal, cohort analysis of 143 patients on hemodialysis and 143 age-matched controls along BTN162b2 vaccination. ELISA quantified anti-full-length Spike IgG, IgM and IgA levels prior to the first vaccine dose (t0); 3 weeks later (second dose, t1); and 3 weeks later (t2); 127 patients were re-evaluated140 (t3) and 180 days (t4) after the first dose. ResultsSeroconversion at t1 was remarkably low in patients, with positivity for anti-spike IgG, IgM and IgA antibodies of 29.4%, 12% and 41%, respectively, increasing to 90.9% (IgG) and 83.9% (IgA) in t2, (IgM remained unchanged). Below 70 years of age anti-spike IgG levels at t1 were significantly lower compared to age-matched controls and showed a profile similar to older individuals. Immunosuppression was associated with lower antibody responses (p=0.005 at t1; p=0.008 at t2). Previous unresponsiveness to hepatitis B vaccination (75/129, 58% of patients negative for anti-HBs antibodies) did not correlate with humoral unresponsiveness to BTN162b2. Anti-spike IgG, IgM and IgA positivity and antibody levels significantly decay at t3, with IgG levels showing further waning at t4. ConclusionsThe large majority of hemodialyzed patients showed IgG seroconversion upon BNT162b2 mRNA vaccination, albeit a sizable proportion of patients presented poor responses. Follow-up of antibody responses 180 days post vaccination unveiled significant decay of anti-spike antibodies and warrant close monitoring of COVID-19 infection and further studies on reinforced vaccination schedules in patients undergoing maintenance hemodialysis.

Variation in essential oil components and anti-inflammatory activity of Allophylus edulis leaves collected in central-western Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: An infusion obtained from the leaves of "chal-chal" (Allophylus edulis Radlk.) is used for popular treatment of intestinal disorders and as an anti-inflammatory throat treatment. Because of the anti-inflammatory medicinal folk use, a previous work reported scientific research confirming the anti-inflammatory activity of A. edulis essential oil collected in Dourados, MS, Brazil, in March 2015. AIM OF THE STUDY: The aim of this study was to evaluate the variation in the chemical profile of the essential oil of A. edulis plants collected in Dourados (EOAE-D) and Bonito (EOAE-B), two cities in Mato Grosso do Sul State, Brazil. Additionally, we evaluated the anti-inflammatory effects of the essential oil, as well as that of the major compounds (caryophyllene oxide and α-zingiberene), in experimental in vivo models of inflammation in mice. MATERIALS AND METHODS: Leaves were collected from plants at both sites in July 2018. The composition of the essential oil (EOAE-D and EOAE-B) was determined by GC/MS, and major compounds (caryophyllene oxide and α-zingiberene) were isolated and identified by chromatographic methods and NMR spectroscopy. Anti-inflammatory capacities were assessed using two classical models of inflammatory models, carrageenan- and CFA-induced paw inflammation (mechanical and thermal hyperalgesia). RESULTS: Both EOAE-D and EOAE-B showed sesquiterpenes as a major constituent, namely, caryophyllene oxide (29.5%) and α-zingiberene (45.0%), respectively. In tests, EOAE, caryophyllene oxide and α-zingiberene-induced antiedematogenic and antihyperalgesic effects were found in the different utilized models. CONCLUSIONS: The results indicate that samples from the two cities differed in chemical composition but not in their anti-inflammatory and antihyperalgesic effects. This finding corroborates the use of A. edulis as a medicinal plant and indicates its potential in the therapy of inflammatory conditions.

Anti-inflammatory Activity of Methanolic Extract and an Alkaloid from Palicourea crocea (Sw.) Roem and Schult.

Palicourea crocea (Sw.) Roem. and Schult., "douradinha," are used by treat inflammation (edema). Croceaine A (PC-1) was isolated from P. crocea (MEPC) leaves and studied for its antioxidant and anti-inflammatory activity, as well as concentrations of constituents and acute toxicity. The phenols and polyphenolics compounds and HPLC/DAD were determined. The antioxidant activity were evaluated for DPPH, ABTS, and MDA. MEPC (300, 100, and 300 mg/kg) and PC-1 (10 and 30 mg/kg) were tested for anti-inflammatory effects in paw edema, pleurisy, cold sensitivity, and mechanical hyperalgesia. Acute toxicity is also described. MEPC contained high concentrations of phenolic and flavonoid compounds (≤ 800.35 mg/g), as well as caffeic acid, ferulic acid, rutin, and quercetin, revealed by HPLC-DAD analysis. MEPC displayed antioxidant activity against ABTS radicals (IC50 = 68.5 µg/mL) and MDA (74%). MEPC and alkaloid PC-1 demonstrated an anti-edematogenic effect in Cg-induced paw edema in 2 and 4 h, and also significantly reduced mechanical hyperalgesia, cold response to acetone in mice, at 3 and 4 h after injection, as well as leukocyte migrationin the pleurisy model. No toxicity was detected by MEPC. For the first time, P. crocea was evaluated for its antioxidant, systemic anti-inflammatory, and anti-hyperalgesic activities.

Contact lenses as drug controlled release systems: a narrative review / As lentes de contacto como sistema de libertação controlada de fármacos: uma revisão narrativa

ABSTRACT Topically applied therapy is the most common way to treat ocular diseases, however given the anatomical and physiological constraints of the eye, frequent dosing is required with possible repercussions in terms of patient compliance. Beyond refractive error correction, contact lenses (CLs) have, in the last few decades emerged as a potential ophthalmic drug controlled release system (DCRS). Extensive research is underway to understand how to best modify CLs to increase residence time and bioavailability of drugs within therapeutic levels on the ocular surface.These devices may simultaneously correct ametropia and have a role in managing ophthalmic disorders that can hinder CL wear such as dry eye, glaucoma, ocular allergy and cornea infection and injury. In this narrative review the authors explain how the ocular surface structures determine drug diffusion in the eye and summarize the strategies to enhance drug residence time and bioavailability. They synthesize findings and clinical applications of drug soaked CLs as DCRS combined with delivery diffusion barriers, incorporation of functional monomers, ion related controlled release, molecular imprinting, nanoparticles and layering. The authors draw conclusions about the impact of these novel ophthalmic agents delivery systems in improving drug transport in the target tissue and patient compliance, in reducing systemic absorption and undesired side effects, and discuss future perspectives.

RESUMO A forma mais frequente de aplicação terapêutica em oftalmologia consiste na instilação de gotas oculares, mas dadas as limitações anatómicas e fisiológicas do olho, é necessária dosagem frequente com possível repercussão na adesão do paciente à terapêutica. Nas últimas décadas, as lentes de contacto (CLs) têm surgido como um potencial sistema de libertação controlada de fármacos na superfície ocular (DCRS) para correção do erro refrativo. Está em curso uma extensa investigação para entender a melhor forma de modificar as CLs, de modo a aumentar o tempo de residência e a biodisponibilidade do medicamento na superfície ocular dentro de níveis terapêuticos. Ao corrigirem a ametropia, estes dispositivos poderão simultaneamente desempenhar um papel na gestão de perturbações oftalmológicas, tais como a síndrome do olho seco, glaucoma, alergia ocular e infecção corneana, que podem comprometer o porte seguro e confortável das CLs. Nesta revisão narrativa, os autores explicam como as estruturas da superfície ocular determinam a difusão de fármacos no olho e sintetizam as estratégias para aumentar a permanência e biodisponibilidade dos mesmos. Em seguida, apresentam os resultados e as aplicações clínicas das CLs embebidas em fármacos, como DCRS, através da incorporação de barreiras de difusão, de monómeros funcionais, da liberação controlada por iões, da impressão molecular, de nanopartículas e pelo processo camada sobre camada. Os autores concluem avaliando o impacto destes novos sistemas de entrega de agentes farmacológicos ao melhorar o seu transporte no tecido alvo, reduzindo a sua absorção sistémica e os seus efeitos colaterais indesejáveis, e discutem perspectivas futuras.

Targeting pain mediators induced by injured nerve-derived COX2 and PGE2 to treat neuropathic pain.

INTRODUCTION: Neuropathic pain (NeP) is an intractable chronic pain condition which severely deteriorates the quality of life of 6% of the population. Caused by direct physical damage or diseases of the nervous system responsible for pain generation and transmission, NeP is manifested as spontaneous pain, hyperalgesia and allodynia. Its treatment is a challenging and unmet medical need. It is generally accepted that inflammatory mediators over-produced in injured nerves play a crucial role in the initiation and maintenance of NeP. AREAS COVERED: Among numerous inflammatory mediators, cyclooxygenase 2 (COX2) and its end product prostaglandin E2 (PGE2) are persistently up-regulated in infiltrating macrophages and Schwann cells in injured nerves and contribute to the development of NeP. In a NeP rat model and an ex vivo model of sensory ganglion explant culture, injured nerve-derived COX2 and PGE2 facilitate the synthesis of pain mediators including neuropeptides, ion channels, cytokines and neurotrophins in primary sensory neurons. EXPERT OPINION: Stimulating the synthesis of pain mediators in primary sensory neurons is a novel mechanism underlying the contribution of injured nerve-derived COX2 and PGE2 to the genesis of NeP. Targeting COX2/PGE2/EP signaling in injured nerves through local administration could open a novel therapeutic avenue to treat this debilitating disease.

Práticas educativas em nutrição na atenção básica em saúde: reflexões a partir de uma experiência popular em joão pessoa - paraíba / Educational practices in nutrition in primary care: Considerations from an experiemtn in popular extension in Joao Pessoa, Paraiba

O presente artigo se propõe a refletir sobre o processode construção de uma experiência de extensão populardesenvolvida pela Universidade Federal da Paraíba,destacando seus limites e possibilidades, no sentido decontribuir para a qualificação da formação dos profissionaisde saúde, especialmente do nutricionista, à luz dasnecessidades sócio-político-sanitárias contemporâneasimpostas pela realidade brasileira.O projeto de extensão?Práticas Integrais da Nutrição na Atenção Básica emSaúde? (PINAB), realizado no bairro do Cristo (JoãoPessoa-PB), é desenvolvido segundo o referencial teóricoda educação popular, com práticas de ação e reflexão daNutrição no campo da Saúde Coletiva e da SegurançaAlimentar e Nutricional. Possui cinco grupos operativos,cada um apoiando a organização e o exercício deatividades coletivas com gestantes, idosos, escolares,famílias beneficiárias pelo Programa Bolsa Família emobilização popular. Além disso, participam de visitasdomiciliares, aconselhamento dietético individual e dagestão compartilhada do próprio Projeto. Esta experiênciatem possibilitado aos extensionistas a percepçãodo trabalho em saúde como um ato pedagógico ético, decompromisso social e construção coletiva de cidadania.O desenvolvimento de suas ações tem possibilitado umaintervenção humanizada da nutrição no cotidiano da comunidade local, bem como da Escola Municipal Augustodos Anjos e da Unidade de Saúde da Família ?Vila Saúde?.Os extensionistas vêm construindo caminhos para umaatuação do nutricionista comprometida com a promoçãoda saúde na comunidade.

The article offers considerations of the process of buildingan experiment in extension activities for the disadvantagedby the Federal University of Paraiba (Brazil).It highlights its limitation and possibilities in the senseof contributing to the training of health professionals,especially nutritionists, given the current socio-politicalpublichealth needs imposed by Brazilian reality. Theproject ? Integrated practices in nutrition within primarycare (PINAB)? carried out in the Cristo neighborhoodof Joao Pessoa, Paraiba, was developed according to thetheoretical framework of Popular Education* with activitiesinvolving programs and reflection on nutrition inthe area of public health and Food and Nutrition Security.There were five active groups, each one undertaking theorganization and provision of group activities: for pregnantwomen, the elderly, school children, families enrolledin the government?s Family Scholarship Program, andcommunity mobilization. In addition it provided homevisits, individual dietetic counseling and the managementof the overall program. This experience helped extensionworkers to understand work in the health area as an actof pedagogic ethic, of social engagement and collectivecitizenship building. The development of these activitiesalso permitted a humanized intervention in nutrition inthe daily life of the communities such as in the PublicSchool Augusto dos Anjos and the Family Health Unitof Vila Saude. The trainees have been developing newpaths for the activities of nutritionists committed to thepromotion of health in the community.