The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model

2-Methoxyestradiol is one of the natural 17β-estradiol derivatives and a potential novel anticancer agent currently being under evaluation in advanced phases of clinical trials. However, the mechanism of anticancer action of 2-methoxyestradiol has not been yet fully established. In our previous studies we have demonstrated that 2-methoxyestradiol selectively induces the expression and nuclear translocation of neuronal nitric oxide synthase in osteosarcoma 143B cells. Heat shock proteins (Hsps) are factors involved in the regulation of expression and activity of nitric oxide synthases. Herein, we chose osteosarcoma cell lines differed in metastatic potential, metastatic 143B and highly metastatic MG63.2 cells, in order to further investigate the anticancer mechanism of 2-methoxyestradiol. The current study aimed to determine the role of major heat shock proteins, Hsp90 and Hsp70 in 2-methoxyestradiol-induced osteosarcoma cell death. We focused on the implication of Hsp90 and Hsp70 in control under expression of neuronal nitric oxide synthase, localization of the enzyme, and further generation of nitro-oxidative stress. To give the insight into the role of Hsp90 in regulation of anticancer efficacy of 2-methoxyestradiol, we used geldanamycin as a potent Hsp90 inhibitor. Herein, we evidenced that inhibition of Hsp90 controls the protein expression of 2-methoxyestradiol-induced neuronal nitric oxide synthase and inhibits enzyme nuclear translocation. We propose that decreased level of neuronal nitric oxide synthase protein after a combined treatment with 2-methoxyestradiol and geldanamycin is directly associated with the accompanying upregulation of Hsp70 and downregulation of Hsp90. This interaction resulted in abrogation of anticancer efficacy of 2-methoxyestradiol by geldanamycin

Engagement of Academic Libraries and Information Science Schools in Creating Curriculum for Sustainability: An Exploratory Study

In 2010, the Association for the Advancement of Sustainability in Higher Education released, “Sustainability curriculum in higher education: A call to action,” encouraging infusion of sustainability topics into universities\u27 teaching and research. Since then, academic programs and research related to social, economic, and environmental sustainability have enriched university curricula. An exploratory study was conducted to determine the position and engagements of academic libraries and information science schools in their contributions to scholarly sustainability activities and curricular initiatives. This article presents the results of the study which reveals a number of engagements by library professionals in the areas of sustainability, such as increasing open access to research, building sustainability-related collections and research guides, and incorporating sustainability content into information literacy. While academic libraries and information science schools are engaged in a broad spectrum of initiatives that support their institutions\u27 sustainability research and curricular functions, this study indicates that such activities require a more targeted approach

Improved Kansa RBF Method for the Solution of Nonlinear Boundary Value Problems

We apply the Kansa–radial basis function (RBF) collocation method to two-dimensional nonlinear boundary value problems. In it, the solution is approximated by a linear combination of RBFs and the governing equation and boundary conditions are satisfied in a collocation sense at interior and boundary points, respectively. The nonlinear system of equations resulting from the Kansa–RBF discretization for the unknown coefficients in the RBF approximation is solved by directly applying a standard nonlinear solver. In a natural way, the value of the shape parameter in the RBFs employed in the approximation may be included in the unknowns to be determined. The numerical results of several examples are presented and analyzed

Synovial membrane asks for independence

Synovial membrane is traditionally considered as a part of the joint capsule. It, however, differs from fibrous part of the capsule in development, structure, function, vascularisation, innervation and involvement in pathological processes. Moreover, in some areas, it even does not contact with the fibrous capsule. Thus, it appears that the synovial membrane should be considered as an independent organ and not as the lining of the joint capsule.

VEGF, VEGFR-1 and VEGFR-2 immunoreactivity in the porcine arteries of vascular subovarian plexus (VSP) during the estrous cycle.

Abstract: Vascular endothelial growth factor (VEGF) is an important angiogenic factor in the female reproductive tract. It binds to cell surface through ligand-stimulatable tyrosine kinase receptors, the most important being VEGFR-1 (flt-1) and VEGFR-2 (flk-1). The broad ligament of the uterus is a dynamic organ consisting of specialized complexes of blood vessels connected functionally to the uterus, oviduct and ovary. Endothelial cells form an inner coating of the vessel walls and thus they stay under the influence of various modulators circulating in blood including ovarian steriods involved in developmental changes in the female reproductive system. The aim of the present study was to immunolocalize VEGF and its two receptors: VEGFR-1 and VEGFR-2 in the broad ligament of the uterus in the area of vascular subovarian plexus during different phases of the estrous cycle in pig and to determine the correlation between immunoreactivity of the investigated factors and phases of the estrous cycle. The study was performed on cryostat sections of vascular subovarian plexus stained immunohistochemically by ABC method. Specific polyclonal antibodies: anti-VEGF, anti-VEGFR-1 and anti-VEGFR-2 were used. Data were subjected to one-way analysis of variance. Our study revealed the presence of VEGF and its receptors in endothelial and smooth muscle cells of VSP arteries. All agents displayed phase-related differences in immunoreactivity suggesting the modulatory effect of VEGF, VEGFR-1 and VEGFR-2 on the arteries of the VSP in the porcine broad ligament of the uterus

Formation of synovial joints and articular cartilage

Chondrocytes differentiate from mesenchymal progenitors and produce templates(anlagen) for the developing bones. Chondrocyte differentiation is controlled bySox transcription factors. Templates for the neighbour bones are subsequentlyseparated by conversion of differentiated chondrocytes into non-chondrogeniccells and emergence of interzone in which joints cavitation occurs. A central rolein initiating synovial joint formation plays Wnt-14/beta-catenin signalling pathway.Moreover, bone morphogenetic proteins and growth and differentiation factorsare expressed at the site of joint formation. Joint cavitation is associated withincreased hyaluronic acid synthesis. Hyaluronic acid facilitates tissue separationand creation of a functional joint cavity. According to the traditional view articularcartilage represents part of cartilage anlage that is not replaced by bone throughendochondral ossification. Recent studies indicate, however, that peri-joint mesenchymalcells take part in interzone formation and that these interzone cellssubsequently differentiate into articular chondrocytes and synovial cells. Thus,anlage chondrocytes have a transient character and disappear after cessation ofgrowth plate function while articular chondrocytes have stable and permanentphenotype and function throughout life

Cooperation between physicians and child patients and their parents in healt related matters. informing on a diagnosis

lekarz, choroba, pacjent, informacj