Convolutamydine A and synthetic analogues have antinociceptive properties in mice

AbstractConvolutamydine A, an oxindole that originated from a marine bryozoan, has several biological effects. In this study, we aimed to investigate the antinociceptive effects of convolutamydine A and two new synthetic analogues.Convolutamydine A and the two analogues were given orally to assess their ability to induce antinociceptive effects. Formalin-induced licking response, acetic acid-induced contortions, and hot plate models were used to characterize the effects of convolutamydine A and its analogues.Convolutamydine A (4,6-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole), compound 1 (3-(2-oxopropyl)-3-hydroxy-2-oxindole), and compound 2 (5-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole) caused peripheral antinociceptive and anti-inflammatory effects in the acetic acid-induced contortions and the formalin-induced licking models. Supraspinal effects were also observed in the hot plate model and were similar to those obtained with morphine. The peripheral effects were not mediated by the cholinergic or opioid systems. The antinociceptive effects of convolutamydine A seem to be mediated by all three systems (cholinergic, opioid, and nitric oxide systems), and the mechanism of action of compounds 1 and 2 involved cholinergic and nitric oxide-mediated mechanisms. Convolutamydine A and its analogues (compounds 1 and 2) showed good antinociceptive ability after systemic administration in acute pain models. The antinociceptive action mediated by cholinergic, opioid, and nitric oxide systems could explain why convolutamydine A, compound 1, and compound 2 retained their antinociceptive effects. The doses used were similar to the doses of morphine and were much lower than that of acetylsalicylic acid, the classical analgesic and anti-inflammatory drug.In conclusion, convolutamydine A and the two analogues demonstrated antinociceptive effects comparable to morphine's effects

Toward Light-Controlled Supramolecular Peptide Dimerization

The selective photodeprotection of the NVoc-modified FGG tripeptide yields the transformation of its 1:1 receptor−ligand complex with cucurbit[8]uril into a homoternary FGG2@CB8 assembly. The resulting lightinduced dimerization of the model peptide provides a tool for the implementation of stimuli-responsive supramolecular chemistry in biologically relevant contexts.The work was supported by the Associate Laboratory for Green ChemistryLAQV (UIDB/50006/2020) and by the Applied Molecular Biosciences UnitUCIBIO (UIDB/ 04378/2020), both financed by FCT. FCT/MCTES is also acknowledged for supporting the National Portuguese NMR Network (ROTEIRO/0031/2013-PINFRA/22161/2016, cofinanced by FEDER through COMPETE 2020, POCI, PORL, and FCT through PIDDAC) and for the grants PTDC/QUICOL/32351/2017, PTDC/QUI-QFI/30951/2017, and CEECIND/00466/2017 (N.B.). U.P. thanks the Spanish Ministry of Science, Innovation, and Universities (CTQ2017-89832-P). We are grateful to Dr. J.P. Da Silva for the mass spectrometry data (equipment financed by CRESC Algarve 2020 and COMPETE 2020; project EMBRC.PT ALG-01-0145-FEDER022121). Funding for open access charge: Universidad de Huelva / CBU

Production of Cu/Diamond composites for first-wall heat sinks

Due to their suitable thermal conductivity and strength copper-based materials have been considered appropriate heat sinks for first wall panels in nuclear fusion devices. However, increased thermal conductivity and mechanical strength are demanded and the concept of property tailoring involved in the design of metal matrix composites advocates for the potential of nanodiamond dispersions in copper. Copper-nanodiamond composite materials can be produced by mechanical alloying followed by a consolidation operation. Yet, this powder metallurgy route poses several challenges: nanodiamond presents intrinsically difficult bonding with copper; contamination by milling media must be closely monitored; and full densification and microstructural homogeneity should be obtained with consolidation. The present line of work is aimed at an optimization of the processing conditions of Cu-nanodiamond composites. The challenges mentioned above have been addressed, respectively, by incorporating chromium in the matrix to form a stable carbide interlayer binding the two components; by assessing the contamination originating from the milling operation through particle-induced X-ray emission spectroscopy; and by comparing the densification obtained by spark plasma sintering with hot-extrusion data from previous studies

Blocking Zika virus vertical transmission.

The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs. In vivo, SOF treatment post-infection (p.i.) decreased viral burden in an immunodeficient mouse model. Finally, we show for the first time that acute SOF treatment of pregnant dams p.i. was well-tolerated and prevented vertical transmission of the virus to the fetus. Taken together, our data confirmed SOF-mediated sparing of human neural cell types from ZIKV-mediated cell death in vitro and reduced viral burden in vivo in animal models of chronic infection and vertical transmission, strengthening the growing body of evidence for SOF anti-ZIKV activity

Walking Training Increases microRNA-126 Expression and Muscle Capillarization in Patients with Peripheral Artery Disease

Patients with peripheral artery disease (PAD) have reduced muscle capillary density. Walking training (WT) is recommended for PAD patients. The goal of the study was to verify whether WT promotes angiogenesis in PAD-affected muscle and to investigate the possible role of miRNA-126 and the vascular endothelium growth factor (VEGF) angiogenic pathways on this adaptation. Thirty-two men with PAD were randomly allocated to two groups: WT (n = 16, 2 sessions/week) and control (CO, n = 16). Maximal treadmill tests and gastrocnemius biopsies were performed at baseline and after 12 weeks. Histological and molecular analyses were performed by blinded researchers. Maximal walking capacity increased by 65% with WT. WT increased the gastrocnemius capillary-fiber ratio (WT = 109 ± 13 vs. 164 ± 21 and CO = 100 ± 8 vs. 106 ± 6%, p < 0.001). Muscular expression of miRNA-126 and VEGF increased with WT (WT = 101 ± 13 vs. 130 ± 5 and CO = 100 ± 14 vs. 77 ± 20%, p < 0.001; WT = 103 ± 28 vs. 153 ± 59 and CO = 100 ± 36 vs. 84 ± 41%, p = 0.001, respectively), while expression of PI3KR2 decreased (WT = 97 ± 23 vs. 75 ± 21 and CO = 100 ± 29 vs. 105 ± 39%, p = 0.021). WT promoted angiogenesis in the muscle affected by PAD, and miRNA-126 may have a role in this adaptation by inhibiting PI3KR2, enabling the progression of the VEGF signaling pathway

Relationship between depression and frailty in older adults: A systematic review and meta-analysis

Aim Depression and frailty are prevalent and burdensome in older age. However, the relationships between these entities are unclear and no quantitative meta-analysis exists. We conducted a systematic review and meta-analysis to investigate the associations between depression and frailty. Methods Two authors searched major electronic databases from inception until November-2016 for cross- sectional/longitudinal studies investigating depression and frailty. The strength of the reciprocal associations between frailty and depression was assessed through odds ratios (ORs) adjusted for potential confounders. Results From 2306 non duplicated hits, 24 studies were included. The overall prevalence of depression in 8023 people with frailty was 38.60% (95% CI 30.07 to 47.10, I2=94%). Those with frailty were at increased odds of having depression (OR adjusted for publication bias 4.42, 95%CI 2.66-7.35, k=11), also after adjusting for potential confounders (OR=2.64; 95%CI: 1.59-4.37, I2=55%, k=4). The prevalence of frailty in 2167 people with depression was 40.40% (95%CI 27.00-55.30, I2=97%). People with depression were at increased odds of having frailty (OR=4.07, 95%CI 1.93-8.55, k=8). The pooled OR for incident frailty, adjusted for a median of 7 confounders, was 3.72 (95%CI 1.95-7.08, I2=98%, k=4), whilst in two studies frailty increased the risk of incident depression with an OR=1.90 (95%CI 1.55-2.32, I2=0%). Conclusion This meta-analysis points to a reciprocal interaction between depression and frailty in older adults. Specifically, each condition is associated with an increased prevalence and incidence of the other, and may be a risk factor for the development of the other. However, further prospective investigations are warranted

Fluência de Leitura, Reconhecimento de Palavras e Compreensão Leitora em Alunos do 4º ao 9º Ano do Ensino Fundamental: Revisão Sistemática

O processamento da leitura é resultado da interação de distintos processos cognitivos, como reconhecimento de palavras, compreensão oral e fluência. Há evidências sobre a importância da fluência para predizer a compreensão de leitura, mas ainda não é claro seu papel ao longo do desenvolvimento. Essa revisão sistemática analisou estudos nacionais e internacionais sobre a relação das habilidades de reconhecimento de palavras e fluência de leitura com a compreensão de leitura em alunos do 4º ao 9º ano. A revisão foi conduzida de acordo com a metodologia prisma e utilizou a base de dados PubMed, de 2000 a setembro de 2019. Foram incluídos artigos que respondiam à pergunta norteadora e atendiam à temática estabelecida pelos descritores e palavras-chave. Foram encontrados 992 artigos, dos quais 904 foram excluídos pelo título e resumo e 56 pela leitura do texto completo. Isto possibilitou a análise de 32 artigos. Os resultados sugerem que, diferentemente do reconhecimento de palavras, a habilidade de fluência de leitura tende a manter relação significativa com a compreensão de leitura no decorrer do segundo ciclo do Ensino Fundamental

Fluência de Leitura, Reconhecimento de Palavras e Compreensão Leitora em Alunos do 4º ao 9º Ano do Ensino Fundamental: Revisão Sistemática

Text processing results from the interaction of different cognitive processes, such as word recognition, listening comprehension, and fluency. There is evidence relating to the importance of fluency in predicting reading comprehension, but its role during the course of development is still uncertain. The present systematic review has analyzed national and international research on the relationship between word recognition skills and reading fluency with reading comprehension in students from the 4th to 9th grade. The review was conducted according to the PRISMA methodology and employed the PubMed database from 2000 to September 2019. The chosen papers answered the orienting question and corresponded to the topic established by the descriptors and keywords. We found 992 articles, of which 904 were excluded by reading the titles and abstracts and 56 by reading the full texts. It was possible to analyze 32 papers. The results suggest that, unlike word recognition, the ability to read fluently tends to uphold a significant relationship with reading comprehension during the second cycle of Elementary School.El procesamiento de la lectura es el resultado de la interacción de diferentes procesos cognitivos, como el reconocimiento de palabras, la comprensión oral y la fluidez. Existe evidencia sobre la importancia de la fluidez en la predicción de la comprensión lectora, pero a lo largo del desarrollo su papel no está claro. Esta revisión sistemática analizó estudios nacionales e internacionales sobre la relación entre las habilidades de reconocimiento de palabras y fluidez lectora con la comprensión lectora en estudiantes de 4° a 9° grado. La revisión se realizó de acuerdo con la metodología prisma y utilizó la base de datos  PubMed, desde el 2000 hasta septiembre de 2019. Fueron incluidos artículos que respondieron a la pregunta guía y cumplieron con la temática establecida por los descriptores y palabras clave. Se encontraron 992 artículos, de los cuales 904 fueron excluidos por título y resumen, y 56 por lectura de texto completo. Esto permitió el análisis de 32 artículos. Los resultados sugieren que, a diferencia del reconocimiento de palabras, la habilidad de fluidez lectora tiende a mantener una relación significativa con la comprensión lectora durante el segundo ciclo de la escuela primaria.O processamento da leitura é resultado da interação de distintos processos cognitivos, como reconhecimento de palavras, compreensão oral e fluência. Há evidências sobre a importância da fluência para predizer a compreensão de leitura, mas ainda não é claro seu papel ao longo do desenvolvimento. Essa revisão sistemática analisou estudos nacionais e internacionais sobre a relaçãodas habilidades de reconhecimento de palavrase fluência de leitura com a compreensão de leitura em alunos do 4º ao 9º ano. A revisão foi conduzida deacordo com a metodologia prisma e utilizou a basede dados PubMed, de 2000 a setembro de 2019. Foram incluídos artigos que respondiam à pergunta norteadora e atendiam à temática estabelecida pelos descritores e palavras-chave. Foram encontrados 992 artigos, dos quais 904 foram excluídos pelo título e resumo e 56 pela leitura do texto completo. Isto possibilitou a análise de 32 artigos. Os resultados sugerem que, diferentemente do reconhecimento de palavras, a habilidade de fluência de leitura tende a manter relação significativa com a compreensão de leitura no decorrer do segundo ciclo do Ensino Fundamental