HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth

n addition to genetic changes, post-transcriptional events strongly contribute to the progression of malignant tumors. The RNA-binding protein HuR (ELAVL1) is able to bind and stabilize a large group of target mRNAs, which contain AU-rich elements (ARE) in their 3′-untranslated region. We found HuR to be upregulated in malignant melanoma in vitro and in vivo, significantly correlating with progression in vivo. Additionally, we could show that miR-194-5p can regulate HuR expression level. HuR knockdown in melanoma cells led to the suppression of proliferation and the induction of cellular senescence. Interestingly, HuR overexpression was sufficient to inhibit senescence in BRAFV600E-expressing melanocytes and to force their growth. Here, MITF (Microphthalmia-associated transcription factor), a key player in suppressing senescence and an ARE containing transcript, is positively regulated by HuR. Our results show for the first time that the overexpression of HuR is an important part of the regulatory pathway in the development of malignant melanoma and functions as a switch to overcome oncogene-induced senescence and to support melanoma formation. These newly defined alterations may provide possibilities for innovative therapeutic approaches

Obesity and Fatty Liver Are 'Grease' for the Machinery of Hepatic Fibrosis

Nonalcoholic fatty liver disease (NAFLD) starts with hepatic steatosis, which can progress with inflammation to nonalcoholic steatohepatitis, and a subset of patients develop progressive fibrosis and ultimately cirrhosis. In the majority of cases, NAFLD is associated with (components of) the metabolic syndrome. Obesity, diabetes and hepatic steatosis are also independent risk factors for hepatic fibrosis in different chronic liver diseases. However, the question is whether it is actually nonalcoholic steatohepatitis and not ‘simple’ steatosis that promotes fibrosis progression based on hepatocellular injury. In this review, the concept will be put forward that (1) hepatic steatosis per se is profibrogenic, and (2) that in NAFLD development and progression of hepatic fibrosis is not simply determined by (the degree of) hepatic inflammation. In addition to the liver, this view is expanded to other organs affected by the metabolic syndrome, which affects hepatic injury and fibrosis also via extrahepatic pathophysiological alterations. In conclusion, fatty liver and the metabolic syndrome, respectively, have to be recognized as significant lubricants of hepatic fibrosis, and simple hepatic steatosis cannot be considered as benign

Vietnams human resources quality

В наше время, в условиях быстро и всесторонне развивающейся в различных областях общественной жизни научно- технической революции, значение человеческих ресурсов не вызывает сомнений. Они становятся факторами, играющими решающую роль в социально-экономическом развитии стран. Качество человеческих ресурсов является одним из ключевых элементов производительности труда и национальной конкурентоспособности, что подтверждает актуальность данного исследования. Целью работы является изучение существующей ситуации в области качества человеческих ресурсов Вьетнама и определение путей ее совершенствования. Во время проведения исследования использованы следующие методы: сравнительный и ретроспективный анализ, описательный, научно-фактологический с применением общенаучных методов познания. Результаты исследования. Проведенный анализ настоящего положения в области качества человеческих ресурсов Вьетнама позволяет сделать вывод о том, что все еще существует большой разрыв в условиях экономического развития и качества человеческих ресурсов между Вьетнамом и другими странами мира, даже в рамках стран АСЕАН. Поэтому, совершенствование качества человеческих ресурсов становится настоятельным и требует системного подхода. Оно должно начинаться в раннем детстве с улучшения вопросов физического развития людей и продолжаться во взрослом состоянии путем совершенствования системы образования и обучения. Это важная задача, на решении которой правительство Вьетнама должно сфокусироваться путем разработки долгосрочной политики повышения качества человеческих ресурсов страны.Nowadays, under the conditions of rapidly and comprehensively developed in various fields of social life scientific and technological revolution, the importance of human resources has been clearly confirmed. They become the factors which play a decisive role in social and economic development of countries. The quality of human resources is one of the key elements to make up labor productivity and national competitiveness that confirms the relevance of the research. The main aim of the paper is to investigate the real situation of Vietnam's human resources quality and to determine the ways of improving it. The methods used during the investigation are the following: comparative and retrospective analysis, descriptive research method, scientific factual method, with applience of the common scientific methods of research. The results. The analysis of the real situation in Vietnam's human resources quality leads to the conclusion that there is still a big gap between Vietnam and other countries in the world and even within the ASEAN region in terms of economic development and human resources quality. Thus, the improvement of the human resources quality is becoming imperative and requires an approach with system synchronization. It should start right from the im proved physical quality of human resources in early childhood to improve the quality of education and training in adulthood to solve this problem. This is the job that Vietnam government should focus on solving the problem through long-term specific policies to improve the quality of human resources of the country

Tumor Cells Develop Defined Cellular Phenotypes After 3D-Bioprinting in Different Bioinks

Malignant melanoma is often used as a model tumor for the establishment of novel therapies. It is known that two-dimensional (2D) culture methods are not sufficient to elucidate the various processes during cancer development and progression. Therefore, it is of major interest to establish defined biofabricated three-dimensional (3D) models, which help to decipher complex cellular interactions. To get an impression of their printability and subsequent behavior, we printed fluorescently labeled melanoma cell lines with Matrigel and two different types of commercially available bioinks, without or with modification (RGD (Arginine-Glycine-Aspartate)-sequence/laminin-mixture) for increased cell-matrix communication. In general, we demonstrated the printability of melanoma cells in all tested biomaterials and survival of the printed cells throughout 14 days of cultivation. Melanoma cell lines revealed specific differential behavior in the respective inks. Whereas in Matrigel, the cells were able to spread, proliferate and form dense networks throughout the construct, the cells showed no proliferation at all in alginate-based bioink. In gelatin methacrylate-based bioink, the cells proliferated in clusters. Surprisingly, the modifications of the bioinks with RGD or the laminin blend did not affect the analyzed cellular behavior. Our results underline the importance of precisely adapting extracellular matrices to individual requirements of specific 3D bioprinting applications

Verification of Conjugate Heat Transfer Models in a Closed Volume with Radiative Heat Source

The results of verification of mathematical model of convective-conductive heat transfer in a closed volume with a thermally conductive enclosing structures are presented. Experiments were carried out to determine the temperature of floor premises in the working conditions of radiant heating systems. Comparison of mathematical modelling of temperature fields and experiments showed their good agreement. It is concluded that the mathematical model of conjugate heat transfers in the air cavity with a heat-conducting and heat-retaining walls correspond to the real process of formation of temperature fields in premises with gas infrared heaters system