HIRUDINELLA VENTRICOSA (TREMATODA) PARASITANDO MAKAIRA NIGRICANSYACANTHOCYBIUM SOLANDRI DE LA REGIÓN NEOTROPICAL, BRASIL

In January 2002, were caught 11 Makaira nigricansLacepède, 1802 (Istiophoridae) and two Acanthocybium solandri(Cuvier, 1832) (Scombridae) off Cabo Frio municipality, Rio de Janeiro State, Brazil. We collected digenetic trematodes from the stomach of some of these fishes. We studied these trematodes with optical and scanning electron microscopy and identified them as Hirudinella ventricosa(Pallas, 1774) Baird, 1835. This is the first report of this species in A. solandriin the Brazilian coast, and in M. nigricansin South America.En enero del 2002, fueron capturados 11 Makaira nigricansLacepède, 1802 y dos Acanthocybium solandri(Cuvier, 1832) en la costa del municipio de Cabo Frio, Rio de Janeiro, Brasil. Del estómago de algunos de estos peces fueron colectados trematodos digenéticos. Después del análisis macroscópico y microscópico de la morfología y la morfometría de las estructuras externas e internas de los helmintos, mediante estereoscópio, microscopio de campo claro, de cortes histológicos coloreados con hematoxilina-eosina, y microscopio electrónico de barrido, los especímenes fueron identificados como pertenecientes a la especie Hirudinella ventricosa(Pallas, 1774) Baird, 1835. Este es el primer reporte de esta especie en A. solandri en la costa brasileña, y en M.nigricansen América del Sur

Whipworm infection promotes bacterial invasion, intestinal microbiota imbalance, and cellular immunomodulation

Infections with Trichuris trichiura are among the most common causes of intestinal parasitism in children worldwide, and the diagnosis is based on microscopic egg identification in the chronic phase of the infection. During parasitism, the adult worm of the trichurid nematode maintains its anterior region inserted in the intestinal mucosa, which causes serious damage and which may open access for gut microorganisms through the intestinal tissue. The immune-regulatory processes taking place during the evolution of the chronic infection are still not completely understood. By use of the Swiss Webster outbred mouse model, mice were infected with 200 eggs, and tolerance to the establishment of a chronic Trichuris muris infection was induced by the administration of a short pulse of dexamethasone during nematode early larval development. The infected mice presented weight loss, anemia, an imbalance of the microbiota, and intense immunological cell infiltration in the large intestine. It was found that mice have a mixed Th1/Th2/Th17 response, with differences being found among the different anatomical locations. After 45 days of infection, the parasitism induced changes in the microbiota composition and bacterial invasion of the large intestine epithelium. In addition, we describe that the excretory-secretory products from the nematode have anti-inflammatory effects on mouse macrophages cultured in vitro, suggesting that T. muris may modulate the immune response at the site of insertion of the worm inside mouse tissue. The data presented in this study suggest that the host immune state at 45 days postinfection with T. muris during the chronic phase of infection is the result of factors derived from the worm as well as alterations to the microbiota and bacterial invasion. Taken together, these results provide new information about the parasite-host-microbiota relationship and open new treatment possibilities.Fil: Schachter, Julieta. Universidade Federal do Rio de Janeiro; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: De Oliveira, Dayane Alvarinho. Universidade do Estado de Rio do Janeiro; BrasilFil: Da Silva, Camila Marques. Universidade Federal do Rio de Janeiro; BrasilFil: De Barros Alencar, Alba Cristina Miranda. Hospital Universitario Antonio Pedro; BrasilFil: Duarte, Michelle. Universidade Federal do Rio de Janeiro; BrasilFil: Müller Pereira da Silva, Matheus. Universidade Federal do Rio de Janeiro; BrasilFil: De Paula Rosa Ignácio, Ana Claudia. Universidade do Estado de Rio do Janeiro; BrasilFil: Lopes Torres, Eduardo José. Universidade do Estado de Rio do Janeiro; Brasi

A Brazilian cohort of patients with immuno-mediated chronic inflammatory diseases infected by SARS-CoV-2 (ReumaCoV-Brasil Registry) : protocol for a prospective, observational study

Background: Patients with immune-mediated rheumatic diseases (IMRD) are at increased risk of infections, including significant morbidity and high mortality. Considering the potential for unfavorable outcomes of SARS-CoV-2 infection in patients with IMRD, several questions were raised regarding the impact of COVID-19 at the start of the pandemic. Objective: This paper presents the protocol of a study that aims to prospectively evaluate patients with IMRD and a confirmed COVID-19 diagnosis (using criteria provided by the Brazilian Ministry of Health). Methods: The study comprised a prospective, observational cohort (patients with IMRD and COVID-19) and a comparison group (patients with only IMRD), with a follow-up time of 6 months to evaluate differences in health outcomes. The primary outcomes will be changes in IMRD disease activity after SARS-CoV-2 infection at 4 time points: (1) at baseline, (2) within 4-6 weeks after infection, (3) at 3 months after the second assessment (±15 days), and (4) at 6 months (±15 days). The secondary outcomes will be the progression rate to moderate or severe forms of COVID-19, need for intensive care unit admission and mechanical ventilation, death, and therapeutic changes related to IMRD. Two outcomes—pulmonary and thromboembolic events in patients with both IMRD and SARS-CoV-2 infection—are of particular interest and will be monitored with close attention (clinical, laboratory, and function tests as well as imaging). Results: Recruitment opened in May 2020, with 1300 participants recruited from 43 sites as of November 2020. Patient recruitment will conclude by the end of December 2020, with follow-up occurring until April 2021. Data analysis is scheduled to start after all inclusion data have been collected, with an aim to publish a peer-reviewed paper in December 2020. Conclusions: We believe this study will provide clinically relevant data on the general impact of COVID-19 on patients with IMRD

Revisiting hydroxychloroquine and chloroquine for patients with chronic immunity-mediated inflammatory rheumatic diseases

Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs

Erythrina velutina Willd. alkaloids: Piecing biosynthesis together from transcriptome analysis and metabolite profiling of seeds and leaves

Introduction: Natural products of pharmaceutical interest often do not reach the drug market due to the associated low yields and difficult extraction. Knowledge of biosynthetic pathways is a key element in the development of biotechnological strategies for plant specialized metabolite production. The scarce studies regarding non-model plants impair advances in this field. Erythrina spp. are mainly used as central nervous system depressants in folk medicine and are important sources of bioactive tetracyclic benzylisoquinoline alkaloids, which can act on several pathology-related biological targets. Objective: Herein the purpose is to employ combined transcriptome and metabolome analyses (seeds and leaves) of a non-model medicinal Fabaceae species grown in its unique arid natural habitat. The study tries to propose a putative biosynthetic pathway for the bioactive alkaloids by using an omic integrated approach. Methods: The Next Generation Sequencing-based transcriptome (de novo RNA sequencing) was carried out in a Illumina NextSeq 500 platform. Regarding the targeted metabolite profiling, Nuclear Magnetic Resonance and the High-Performance Liquid Chromatography coupled to a micrOTOF-QII, High Resolution Mass Spectrometer, were used. Results: This detailed macro and micromolecular approach applied to seeds and leaves of E. velutina revealed 42 alkaloids by metabolome tools. Based on the combined evidence, 24 gene candidates were put together in a putative pathway leading to the singular alkaloid diversity of this species. Conclusion: These results contribute by indicating potential biotechnological targets Erythrina alkaloids biosynthesis as well as to improve molecular databases with omic data from a non-model medicinal plant. Furthermore, they reveal an interesting chemical diversity in Erythrina velutina harvested in Caatinga. Last, but not least, this data may also contribute to tap Brazilian biodiversity in a rational and sustainable fashion, promoting adequate public policies for preservation and protection of sensitive areas within the Caatinga

Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in Schistosoma mansoni

Treatment and control of schistosomiasis still rely on only one effective drug, praziquantel (PZQ) and, due to mass treatment, the increasing risk of selecting for schistosome strains that are resistant to PZQ has alerted investigators to the urgent need to develop novel therapeutic strategies. The histone-modifying enzymes (HMEs) represent promising targets for the development of epigenetic drugs against Schistosoma mansoni. In the present study, we targeted the S. mansoni lysine-specific demethylase 1 (SmLSD1), a transcriptional corepressor, using a novel and selective synthetic inhibitor, MC3935, which was used to treat schistosomula and adult worms in vitro. By using cell viability assays and optical and electron microscopy, we showed that treatment with MC3935 affected parasite motility, egg-laying, tegument, and cellular organelle structures, culminating in the death of schistosomula and adult worms. In silico molecular modeling and docking analysis suggested that MC3935 binds to the catalytic pocket of SmLSD1. Western blot analysis revealed that MC3935 inhibited SmLSD1 demethylation activity of H3K4me1/2. Knockdown of SmLSD1 by RNAi recapitulated MC3935 phenotypes in adult worms. RNA-Seq analysis of MC3935-treated parasites revealed significant differences in gene expression related to critical biological processes. Collectively, our findings show that SmLSD1 is a promising drug target for the treatment of schistosomiasis and strongly support the further development and in vivo testing of selective schistosome LSD1 inhibitors

Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

<p>Abstract</p> <p>Background</p> <p>Several association studies have shown that -844 G/A and <it>HindIII </it>C/G <it>PAI-1 </it>polymorphisms are related with increase of PAI-1 levels, obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia, which are components of metabolic syndrome. The aim of this study was to analyze the allele and genotype frequencies of these polymorphisms in <it>PAI-1 </it>gene and its association with metabolic syndrome and its components in a sample of Mexican mestizo children.</p> <p>Methods</p> <p>This study included 100 children with an age range between 6-11 years divided in two groups: a) 48 children diagnosed with metabolic syndrome and b) 52 children metabolically healthy without any clinical and biochemical alteration. Metabolic syndrome was defined as the presence of three or more of the following criteria: fasting glucose levels ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, HDL-cholesterol < 40 mg/dL, obesity BMI ≥ 95^thpercentile, systolic blood pressure (SBP) and diastolic blood pressure (DBP) ≥ 95^thpercentile and insulin resistance HOMA-IR ≥ 2.4. The -844 G/A and <it>HindIII </it>C/G <it>PAI-1 </it>polymorphisms were analyzed by PCR-RFLP.</p> <p>Results</p> <p>For the -844 G/A polymorphism, the G/A genotype (OR = 2.79; 95% CI, 1.11-7.08; <it>p </it>= 0.015) and the A allele (OR = 2.2; 95% CI, 1.10-4.43; <it>p </it>= 0.015) were associated with metabolic syndrome. The -844 G/A and A/A genotypes were associated with increase in plasma triglycerides levels (OR = 2.6; 95% CI, 1.16 to 6.04; <it>p </it>= 0.02), decrease in plasma HDL-cholesterol levels (OR = 2.4; 95% CI, 1.06 to 5.42; <it>p </it>= 0.03) and obesity (OR = 2.6; 95% CI, 1.17-5.92; <it>p </it>= 0.01). The C/G and G/G genotypes of the <it>HindIII </it>C/G polymorphism contributed to a significant increase in plasma total cholesterol levels (179 vs. 165 mg/dL; <it>p </it>= 0.02) in comparison with C/C genotype.</p> <p>Conclusions</p> <p>The -844 G/A <it>PAI-1 </it>polymorphism is related with the risk of developing metabolic syndrome, obesity and atherogenic dyslipidemia, and the <it>HindIII </it>C/G <it>PAI-1 </it>polymorphism was associated with the increase of total cholesterol levels in Mexican children.</p

Erratum to: The study of cardiovascular risk in adolescents – ERICA: rationale, design and sample characteristics of a national survey examining cardiovascular risk factor profile in Brazilian adolescents

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