Avaliação in silico de derivados naftoquinônicos frente à NSP9 do SARS-COV-2 / In silico evaluation of naphtoquinonic derivatives against SARS-COV-2 NSP9

O SARS-CoV-2 é o agente etiológico da COVID-19, que representa uma emergência de saúde global. A proteína Nsp9 Replicase é crítica para a maquinaria de RNA replicase e parece desempenhar um papel fundamental na transcrição do genoma do RNA do SARS-CoV-2. Dessa forma, essa proteína não estrutural pode ser um alvo potencial para a pesquisa de fármacos capazes de inibir a progressão viral. Em vista das poucas opções terapêuticas disponíveis para essa doença, buscou-se planejar, por meio de triagem virtual, derivados naftoquinônicos com potencial de inibição da Nsp9 Replicase e que apresentassem perfil físico-químicos ideais para candidatos a fármacos. Foram planejados 6 derivados, onde apenas 2 (D5 e D6) obtiveram um perfil de complementariedade com a enzima Nsp9. Quanto ao perfil físico-químico, D5 atendem à Regrado dos 5 Lipinski. Adicionalmente, as etapas para a sua síntese são simples e de custo acessível, tornando viável sua produção para testes in vitro e in vivo. Sendo assim, estre trabalho traz uma proposta de nova molécula de fácil obtenção e características farmacocinéticas apropriadas e que apresenta potencial de inibição de uma importante proteína de SARS-CoV-2, responsável por um dos maiores problemas de saúde pública da era moderna

Caracterização química dos extratos in natura das folhas de Arrabidaea chica Verlot e avaliação do potencial regenerativo através de testes in vitro e in vivo em fibroblastos : Chemical characterization of in natura extracts from the leaves of Arrabidaea chica Verlot and evaluation of the regenerative potential through in vitro and in vivo tests in fibroblasts

A biodiversidade da flora brasileira é bastante vasta e representa um imenso potencial de utilização econômica pela indústria farmacêutica e cosmética. Dentre as espécies vegetais catalogadas no Brasil, a Arrabidaea chica Verlot, pertencente à família Bignoniaceae, conhecida popularmente pelos nomes de pariri, cipó-pau ou crajiru, encontra-se listada na Relação Nacional de Plantas Medicinais de Interesse ao SUS (RENISUS) para estudo e viabilidade como cicatrizante e tratamento de ulcerações diabéticas. Este trabalho avaliou os extratos de folhas de Arrabidaea chica para fins de identificação de compostos ativos e demonstrou que o extrato foi capaz de reduzir as lesões na pele 13% em apenas dois dias de aplicação tópico, além de demonstrar mediante ensaio in vitro de indução de crescimento de fibroblastos. Com a caracterização química dos extratos, observou-se a possível presença de compostos do grupo de flavonoides e antocianinas como quercetina e 3-desoxiantocianidina, respectivamente. Nenhuma das amostras apresentou citotoxicidade nas concentrações testadas, assim como não teve diferença significativa na quantidade de células nos diferentes tratamentos no ensaio de proliferação celular

Dysregulation of Transcription Factor Networks Unveils Different Pathways in Human Papillomavirus 16-Positive Squamous Cell Carcinoma and Adenocarcinoma of the Uterine Cervix

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are the most common histological types of cervical cancer (CC). The worse prognosis of ADC cases highlights the need for better molecular characterization regarding differences between these CC types. RNA-Seq analysis of seven SCC and three ADC human papillomavirus 16-positive samples and the comparison with public data from non-tumoral human papillomavirus-negative cervical tissue samples revealed pathways exclusive to each histological type, such as the epithelial maintenance in SCC and the maturity-onset diabetes of the young (MODY) pathway in ADC. The transcriptional regulatory network analysis of cervical SCC samples unveiled a set of six transcription factor (TF) genes with the potential to positively regulate long non-coding RNA genes DSG1-AS1, CALML3-AS1, IGFL2-AS1, and TINCR. Additional analysis revealed a set of MODY TFs regulated in the sequence predicted to be repressed bymiR-96-5p ormiR-28-3p in ADC. These microRNAs were previously described to target LINC02381, which was predicted to be positively regulated by two MODY TFs upregulated in cervical ADC. Therefore, we hypothesize LINC02381might act by decreasing the levels ofmiR-96-5p andmiR-28-3p, promoting the MODY activation in cervical ADC. The novel TF networks here described should be explored for the development of more efficient diagnostic tools

Questão agrária e políticas públicas em Minas Gerais : conflitos sociais e alternativas populares

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Farmacologia clínica da doença de Parkinson: Clinical pharmacology of Parkinson's disease

As patologias neurodegenerativas cursam com depleção progressiva e irreversível dos neurônios existentes em regiões específicas do cérebro. A Doença de Parkinson (DP) é um protótipo, na qual o extravio neuronal do hipocampo e do córtex resulta em déficit de memória e disfunção cognitiva. O seguinte artigo objetivou descrever de modo narrativo as considerações clínicas da doença de Parkinson que justifiquem a ação farmacológica dos fármacos empregados em sua terapêutica. Atualmente, a intervenção farmacológica e a cirúrgica não são capazes de reverter o quadro clínico, mas evitam a progressão da morbimortalidade da DP. O tratamento é individual, baseado na reação específica, o quadro clínico, resposta farmacológica e aspectos socioeconômicos, ocupacionais e emocionais. A finalidade se baseia em perpetuar a autonomia e funcionalidade, o máximo de tempo possível. A escolha dos fármacos mais apropriados para cada paciente e o início do tratamento e o acompanhamento ao longo da evolução são etapas difíceis. Devido a cronicidade, o tratamento deve continuar por toda a vida, considerando que os fármacos e suas doses mudam com o tempo, o surgimento de efeitos adversos

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Production of Nutritious Flour from Residue Custard Apple (Annona squamosa L.) for the Development of New Products

Currently, the fruit processing industry generates a high volume of waste in fruits that have not reached a quality standard for consumption or by-products generated throughout the production process. To reduce this waste, mitigating measures, such as reuse in food formulations, have been proposed. In this work the custard apple bagasse flour (Annona squamosa L.) (CAB) was produced and incorporated into cookie formulations in different proportions (5 to 50%) evaluating its acceptability. The CAB flour was characterized by physicochemical analysis, proximate composition, mineral analysis, determination of the phenolic content, and antioxidant capacity. The results of the physicochemical and proximate characterizations show that the processed flour presents values and specifications suitable for food formulations. The mineral composition of the CAB flour responds to more than 20% of the daily intake of nutrients, highlighting the Cu, Fe, Mn, Zn, Ca, and Mg. The composition of phenolic compounds for CAB flour and cookies formulations presented values ranging from 200 to 658 mg GAE/100 g, similar to flour and formulations prepared of residues tropical fruit, while DPPH* inhibition showed a variation of 9.68–10.75%. Cookies made from the CAB flour showed high acceptability making the flour promising in the nutritional incorporation in food formulations

Intranasal instillation of distilled water, hypertonic saline and sodium bicarbonate promotes redox imbalance and acute lung inflammation in adult mice.

Bronchial obstruction, caused by retained secretions, is often treated by the administration of mucoactive agentes including distilled water, saline, hypertonic saline, and sodium bicarbonate. However, the inflammatory effect of these solutions on the lungs remains unclear. This study evaluated the instillation effects of different solutions on oxidative stress and lung inflammatory response in C57BL/6 mice. Fifty C57BL/6 mice were divided into 5 groups: control (CG); distilled water (DWG), hypertonic saline (HSG), saline (SG) and sodium bicarbonate (SBG). CG was exposed to ambient air while DWG, HSG, SG and SBG had 50 ?l of respective solutions administered intranasally for 5 consecutive days. Twenty-four hours after the last intranasal instillation, all animals were euthanized for subsequent analysis. All solutions promoted increased recruitment of inflammatory cells to the lung compared to controls. Superoxide dismutase activity was lower in HSG compared to all other groups; catalase activity was reduced in SG, while it increased in SBG and DWG compared to CG. Finally, there was na increase in the inflammatory markers TNF-?, CCL2 and IFN-? in DWG compared to CG, SG and HSG. In conclusions, the intranasal instillation of different solutions promotes redox imbalance and inflammation on lungs of adult mice