A comparative proteomic study identified LRPPRC and MCM7 as putative actors in imatinib mesylate cross-resistance in Lucena cell line

<p>Abstract</p> <p>Background</p> <p>Although chronic myeloid leukemia (CML) treatment has improved since the introduction of imatinib mesylate (IM), cases of resistance have been reported. This resistance has been associated with the emergence of multidrug resistance (MDR) phenotype, as a BCR-ABL independent mechanism. The classic pathway studied in MDR promotion is ATP-binding cassette (ABC) family transporters expression, but other mechanisms that drive drug resistance are largely unknown. To better understand IM therapy relapse due to the rise of MDR, we compared the proteomic profiles of K562 and Lucena (K562/VCR) cells.</p> <p>Results</p> <p>The use of 2-DE coupled with a MS approach resulted in the identification of 36 differentially expressed proteins. Differential mRNA levels of <it>leucine-rich PPR motif-containing (LRPPRC) protein, minichromosome maintenance complex component 7 (MCM7) </it>and <it>ATP-binding cassette sub-family B (MDR/TAP) member 1 (ABCB1) </it>were capable of defining samples from CML patients as responsive or resistant to therapy.</p> <p>Conclusions</p> <p>Through the data presented in this work, we show the relevance of MDR to IM therapy. In addition, our proteomic approach identified candidate actors involved in resistance, which could lead to additional information on BCR-ABL-independent molecular mechanisms.</p

Targeting hodgkin and reed–sternberg cells with an inhibitor of heat-shock protein 90: Molecular pathways of response and potential mechanisms of resistance

Classical Hodgkin lymphoma (cHL) cells overexpress heat-shock protein 90 (HSP90), an important intracellular signaling hub regulating cell survival, which is emerging as a promising therapeutic target. Here, we report the antitumor effect of celastrol, an anti-inflammatory compound and a recognized HSP90 inhibitor, in Hodgkin and Reed-Sternberg cell lines. Two disparate responses were recorded. In KM-H2 cells, celastrol inhibited cell proliferation, induced G0/G1 arrest, and triggered apoptosis through the activation of caspase-3/7. Conversely, L428 cells exhibited resistance to the compound. A proteomic screening identified a total of 262 differentially expressed proteins in sensitive KM-H2 cells and revealed that celastrol’s toxicity involved the suppression of the MAPK/ERK (extracellular signal regulated kinase/mitogen activated protein kinase) pathway. The apoptotic effects were preceded by a decrease in RAS (proto-oncogene protein Ras), p-ERK1/2 (phospho-extracellular signal-regulated Kinase-1/2), and c-Fos (proto-oncogene protein c-Fos) protein levels, as validated by immunoblot analysis. The L428 resistant cells exhibited a marked induction of HSP27 mRNA and protein after celastrol treatment. Our results provide the first evidence that celastrol has antitumor effects in cHL cells through the suppression of the MAPK/ERK pathway. Resistance to celastrol has rarely been described, and our results suggest that in cHL it may be mediated by the upregulation of HSP27. The antitumor properties of celastrol against cHL and whether the disparate responses observed in vitro have clinical correlates deserve further research.Fil: Segges, Priscilla. Instituto Nacional de Câncer; BrasilFil: Corrêa, Stephany. Instituto Nacional de Câncer; BrasilFil: Du Rocher, Bárbara. Fundación Oswaldo Cruz; Brasil. Instituto Nacional de Câncer; BrasilFil: Vera Lozada, Gabriela. Instituto Nacional de Câncer; BrasilFil: Krsticevic, Flavia Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; ArgentinaFil: Arce, Debora Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones en Ciencias Agrarias de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias. Instituto de Investigaciones en Ciencias Agrarias de Rosario; ArgentinaFil: Sternberg, Cinthya. Universidade Federal do Rio de Janeiro; BrasilFil: Abdelhay, Eliana. Instituto Nacional de Câncer; BrasilFil: Hassan, Rocio. Instituto Nacional de Câncer; Brasi

Fatores nutricionais associados à depressão: Nutritional factors associated with depression

As mudanças nos padrões de alimentação das últimas décadas implicaram em alterações fisiológicas potencialmente significativas, inclusive em relação a alterações psicológicas, como no caso da depressão. Desta forma, o objetivo deste estudo foi identificar na literatura a relação dos fatores nutricionais e a depressão. Para tanto, realizou-se um estudo bibliográfico descritivo do tipo revisão integrativa e abordagem qualitativa. A busca foi realizada nas bases de dados SCIELO, PUBMED e MEDLINE no período de março a maio de 2020 e foram analisados artigos completos, disponíveis gratuitamente que abordassem os fatores da dieta correlacionados com a nutrição e depressão, escritos em inglês e português. Verificou-se uma relação entre a depressão e os padrões alimentares, considerando o estilo de vida dos indivíduos na atualidade, fatores socioeconômicos, instalação de doenças crônicas não transmissíveis, sexo. A ingestão de bebidas e alimentos ricos em gorduras saturadas e trans, componentes processados ​​e açucarados, assim como de alta índice energético influenciam negativamente na manifestação da depressão. Em contraponto, uma alimentação saudável, rica em alimentos in natura e minimamente processados possui função antioxidante no corpo; alimentos à base de frutas, legumes e grãos integrais fornecem um efeito anti-inflamatório, refletindo maior felicidade, motivação, maior satisfação com a vida e maior bem-estar socioemocional. Assim, é necessário manter uma boa alimentação, pois irá atuar como prevenção da doença e promover uma melhor qualidade de vida, ademais, deve evitar alimentos ricos em gordura trans e açúcar para não prejudicar a conexão que há entre o cérebro e intestino.&nbsp

Nursing Care Approach Towards an Alcoholic Patient Bearing the Wernicke-Korsakoff Syndrome: Case Study / Cuidados de Enfermagem a um Paciente Alcoolista Portador Da Síndrome de Wernicke-Korsakoff: Estudo de Caso

Introdução: A síndrome de Wernicke-Korsakoff (SWK) é uma das mais graves consequências do abuso de álcool. O impacto cognitivo da patologia é derivado da neurotoxicidade alcóolica e deficiência de tiamina, podendo progredir para estupor, coma e morte. Objetivo: Realizar um estudo de caso de paciente alcoolista portador de SWK e construir um plano de assistência de enfermagem. Métodos: Estudo de caso com abordagem qualitativa. O estudo foi realizado no Hospital Universitário Oswaldo Cruz (HUOC), em Recife, Brasil, fevereiro a março de 2016. Resultados: Identificamos 14 diagnósticos de enfermagem: confusão crônica/memória prejudicada/processos do pensamento perturbados/ comunicação verbal prejudicada; deambulação prejudicada/risco de quedas; déficit no autocuidado; nutrição desequilibrada menor que as necessidades/fadiga; volume excessivo de líquido/integridade tissular prejudicada; risco de sangramento; integridade da pele prejudicada; perfusão tissular ineficaz. Conclusão: A enfermagem tem especial importância na execução das ações de educação em saúde e tratamento de alcoolistas prevenindo as complicações da doença

Reduction of SARS-CoV-2 viral load in saliva after rinsing with mouthwashes containing cetylpyridinium chloride: a randomized clinical study

Background Symptomatic patients with COVID-19 typically have a high SARS-CoV-2 viral load in their saliva. Procedures to reduce the viral load in their oral cavity are important for mitigating the viral transmission. Methods This randomized clinical trial investigated the impact of two mouthwashes (0.075% cetylpyridinium chloride plus 0.28% zinc lactate (CPC+Zn) (n = 32), and 0.075% cetylpyridinium chloride (CPC) (n = 31)) on the viral load of SARS-CoV-2 in saliva when compared to the distilled water negative control (n = 32). Saliva was collected before (T0) and after (5 min, T1; 30 min, T2; and 60 min, T3) the intervention. Viral load in saliva was measured by qRT-PCR assays. The data in both groups was normalized for T0 and Negative Control, resulting in fold change values. Results CPC+Zn oral solution reduced the viral load in saliva by 6.34-fold at T1, 3.6-fold at T2 and 1.9-fold at T3. Rinsing with the CPC mouthwash reduced the viral load in saliva by 2.5-fold at T1, 1.9-fold at T2 and 2.0-fold at T3. Conclusion CPC+Zn mouthwash or with the CPC mouthwash reduced the viral load in saliva of COVID-19 patients immediately after rinsing. These reductions extended up to 60 min

Efeitos da fertilização potássica no crescimento inicial de Khaya senegalensis A. Juss no bioma Cerrado

In the present study, it was aimed to evaluate the initial growth of seedlings of African mahogany (Khaya senegalensis A. Juss.) composted with different doses of potassium. The experiment was conducted in a greenhouse, in plastic container with capacity for 7 dm³ and using soil as substrate classified as red-yellow Oxisols. The experimental design was completely randomized, with five treatments and five replications, totaling 25 experimental units. The treatments had consisted of five doses of K: 0; 40; 80; 120 and 160 mg dm-³, using the application of potassium chloride. To 150 days, were measured the height of the plant, the diameter of the collect and the mass of dry matter of leaf, stem, root and total dry matter mass. It was found that increasing potassium doses promoted increase in plant growth. The African mahogany presented low potassium requirement in the early stages of development for the edafoclimatic condition on the site of the experiment.No presente estudo, objetivou-se avaliar o crescimento inicial de mudas de mogno-africano (Khaya senegalensis A. Juss.) adubadas com diferentes doses de potássio. O experimento foi realizado em casa de vegetação, em recipiente de plástico com capacidade para 7 dm3 e utilizando como substrato o solo classificado como Latossolo Vermelho-Amarelo distrófico. O delineamento experimental utilizado foi inteiramente casualizado, com cinco tratamentos e cinco repetições, totalizando 25 unidades experimentais. Os tratamentos constituíram-se de cinco doses de K: 0; 40; 80; 120 e 160 mg dm-3, utilizando para aplicação o cloreto de potássio. Aos 150 dias, foram aferidos a altura da planta, o diâmetro do coleto e a massa de matéria seca de folhas, caule, raiz e massa de matéria seca total. Constatou-se que, as doses crescentes de potássio não promoveram aumento no crescimento das plantas. O mogno-africano apresentou baixa exigência em potássio nas fases iniciais de desenvolvimento para a condição edafoclimática no local do experimento

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

AVALIAÇÃO DE TECNOLOGIAS DE LEITOS FLUIDIZADOS A PARTIR DA ANÁLISE DOS PEDIDOS DE PATENTES

Diversos pesquisadores brasileiros e de outros países vem desenvolvendo trabalhos a respeito da utilização da tecnologia de leito fluidizado em experimentos científicos. Com isso o objetivo deste trabalho foi monitorar as informações contidas nos bancos de patentes do INPI, Espacenet e WIPO, objetivando contabilizar frequência de trabalhos por coleção (bases onde os trabalhos foram indexados), ano de publicação, país e CIP. Foram encontradas 203 patentes no INPI, 9 no Espacenet e 54474 no WIPO. O ano que ocorreram mais depositou foi o de 2010, e o pais que mais realizou depósitos foi o Estados Unidos. Espera-se que o desenvolvimento deste trabalho se torne um novo incentivo para os pesquisadores brasileiros, para desenvolver novos estudos direcionados as tecnologia de leito fluidizado