Pappaspate8022

RESULTS Pharmacological inhibition of p90RSK by FMK or inhibition of p90RSK with adenoviral vector encoding a dominant negative form of p90RSK suppressed TGF-β1-induced ECM accumulation and EMT in lung epithelial cells and fibroblasts. Interestingly, FMK significantly inhibited TGF-β1-induced Smad3 nuclear translocation and smad binding element-dependent transcriptional activity, but not Smad3 phosphorylation. Furthermore, in a mouse model of bleomycin-induced lung fibrosis, FMK ameliorated pulmonary fibrosis. CONCLUSION These findings indicate that p90RSK plays critical roles in pulmonary fibrosis, which suggests it be viewed as a novel therapeutic target for the treatment of lung fibrosis. © Copyright by the Author(s). Published by Cell Physiol Biochem Press.Graphene quantum dots (GQDs) are known as emerging sub-10 nm nanoparticles (NPs), which are in fact few-layered pieces of graphene, capable of emitting blue fluorescence, when exposed to 360 nm UV light. Understanding the details of the interaction between GQDs and lipase can serve as a critical step for improving the biological outcome of GQD-derived drug-delivery and diagnosis systems. The interaction occurs in the form of surface adsorption, which can subsequently influence the physicochemical properties of both the NP and the protein. Hence, a systematic approach was taken here to optimize the GQDs' synthesis conditions in order to achieve the highest possible quantum yield (QY). Furthermore, to understands the influence of the interaction of GQDs and lipase, on both the activity of lipase and the emission intensity of GQDs, various incubation conditions were tested to achieve optimized conditions over central composite design algorithm by Design-Expert®, using response surface methodology. The results show that the GQDs fabricated by thermal decomposition of citric acid at 160°C, with a heating duration of 55 min, obtain almost three times higher QY than the highest values reported previously. The best enzymatic activity after the formation of the hard corona, as well as the highest fluorescent emission, were achieved at GQD-to-enzyme ratios within the rage of 23-25%, at temperatures between 41 and 42°C, for 6-8 min. In the aforementioned condition, the enzyme retains 91-95% of its activity and the NP preserves about 80-82% of its fluorescence intensity after incubation. © 2020 Wiley Periodicals, Inc.Congenital heart disease (CHD) is common, costly, and critical. Approximately half of all infant deaths due to congenital anomalies are associated with CHD or neural tube defects. As infant mortality improves due to better infection control and peripartum care, congenital anomalies are becoming a key driver of pediatric survival and health. Improving CHD prevention and care globally will play a significant role toward key goals such as United Nation's sustainable development goals (SDGs) of good health and well-being (SDG 3) and reduced inequalities (SDG 10). This review addresses two questions how can we reinterpret and reframe available data on CHD to spur action in prevention and care? How can we re-engineer how we currently track CHD in populations to efficiently generate new data to assess successes and detect gaps in prevention and care? Answering these questions requires understanding the causal chain of disease, from cause to CHD occurrence to health outcomes. This perspective provides a logical basis for two innovations. First, develop a data-driven message that reframes epidemiologic and clinical data in terms of incentives for action, evidence for change, and strategies for population-wide impact. Second, through partnerships between clinical and public health systems, implement an integrated "triple surveillance," which, in the same population, concurrently tracks the three elements of the causal chain-causes, disease occurrence, health outcomes. By streamlining activities and minimizing operational waste, such systems can have a vital role in improving prevention and care on a population level, including in many low and middle-income countries. © 2020 Wiley Periodicals, Inc.BACKGROUND Falls and fall-related injuries along with fear of falling (FoF) seem to restrict activities of daily living (ADL), resulting in physical dependence. However, it is still unclear how falls and related injuries or FoF by themselves explain general and specific ADL dependence. OBJECTIVES To investigate the relationships between falls and related injuries, FoF and physical dependence on ADL in community-dwelling older adults, controlling for age, gender, physical activity and physical fitness as confounders. METHODS This cross-sectional descriptive study assessed 588 community-dwelling older adults. Falls and fall-related injuries, ADL dependence on basic, instrumental and advanced activities, FoF, demographic characteristics and health conditions were assessed through a questionnaire. Physical activity was measured through the International Physical Activity Questionnaire. Physical fitness was assessed by the Senior Fitness Test and the Fullerton Advanced Balance Scale. Body composition was measured ccurate clinical evaluations and develop more successful interventions to prevent further dependence. © 2020 John Wiley & Sons Ltd.Autism research is heavily skewed toward western high-income countries. Culturally appropriate screening and diagnostic instruments for autism are lacking in most low- and middle-income settings where the majority of the global autism population lives. To date, a clear overview of the possible cultural and contextual factors that may affect the process of identifying and diagnosing individuals with autism spectrum disorders (ASD) is missing. Epigenetic inhibitor cost This study aims to outline these factors by proposing a conceptual framework. A multidisciplinary review approach was applied to inform the development of the conceptual framework, combining a systematic review of the relevant autism research literature with a wider literature search spanning key texts in global mental health, cultural psychiatry, cross-cultural psychology, and intellectual disability research. The resulting conceptual framework considers the identification, help-seeking, and diagnostic process at four interrelated levels (a) the expression; (b) recognition; (c) interpretation; and (d) reporting of autism symptoms, and describes the cultural and contextual factors associated with each of these levels, including cultural norms of typical and atypical behavior, culture-specific approaches to parenting, mental health literacy, cultural beliefs, attitudes and stigma, as well as the affordability, availability, accessibility, and acceptability of services.