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Soluble receptor for advanced glycation end-products (sRAGE), which exerts cardioprotective effect through inhibiting cardiomyocyte apoptosis and autophagy during ischemia/reperfusion (I/R) injury, is also known to enhance angiogenesis in post-ischemic reperfusion injury-critical limb ischemia (PIRI-CLI) mice. However, whether sRAGE protects the heart from myocardial I/R injury via promoting angiogenesis remains unclear. Myocardial model of I/R injury was conducted by left anterior descending (LAD) ligation for 30 min and reperfusion for 2 weeks in C57BL/6 mice. And I/R injury in cardiac microvascular endothelial cells (CMECs) was duplicated by oxygen and glucose deprivation. The results showed that I/R-induced cardiac dysfunction, inflammation and myocardial fibrosis were all reversed by sRAGE. CD31 immunohistochemistry staining showed that sRAGE increased the density of vessels after I/R injury. The results from cultured CMECs showed that sRAGE inhibited apoptosis and increased proliferation, migration, angiogenesis after exposure to I/R. These effects were dependent on signal transducer and activator of transcription 3 (STAT3) pathway. Together, the present study demonstrated that activation of STAT3 contributed to the protective effects of sRAGE on myocardial I/R injury via promoting angiogenesis.PURPOSE The Working Group of the Gynecological Tumor Committee of the Japanese Radiation Oncology Study Group (JROSG) published recommendations for contouring high-risk clinical target volumes (HR-CTV) on CT for 3-dimentional image-guided brachytherapy for cervical cancer. The purpose of this study was to compare HR-CTV delineated on CT, referencing recommendations from JROSG, with HR-CTV delineated on MRI, referencing consensus guidelines from the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC ESTRO). MATERIAL AND METHODS Fourteen patients were evaluated. After the insertion of the CT/MR applicator into the patient, CT and MRI were performed. HR-CTVMR was delineated on MRI for clinical examination and HR-CTVCT was delineated on CT retrospectively referencing the MRI just before brachytherapy within a week. The volume and dosimetry of HR-CTV based on a 6&nbsp;Gy dose of the Manchester system were evaluated. RESULTS The median volumes of HR-CTVMR and HR-CTVCT were 24.4&nbsp;ml (range, 13.6-50.4&nbsp;ml) and 29.9&nbsp;ml (range, 13.2-49.2&nbsp;ml), respectively. Median D90 of HR-CTVMR and HR-CTVCT were 6.7&nbsp;Gy (range, 5.8-10.1&nbsp;Gy) and 6.8&nbsp;Gy (range, 5.1-10.4&nbsp;Gy), respectively. CONCLUSION Somewhat difference could be seen between HR-CTVMR and HR-CTVCT.In this study, 3D finite element analyses (FEA) are conducted to quantify the orthotropic elastic properties and investigate the load transfer mechanism of bone at the sub-lamellar level. Three finite element (FE) unit cells with periodic boundary conditions are presented to model a two-scale microstructure of bone including a mineralized collagen fibril (MCF), the extrafibrillar matrix (EFM) and the resulting fibril array (FAY) under arbitrary loading. The axial and transverse elastic properties of the FAY computed by FEA are calibrated with unique experimental results on ovine micro-samples showing a coherent fibril orientation. [https://www.selleckchem.com/products/az628.html AZ 628 mouse] They are then systematically compared with those calculated using analytical methods including the basic Voigt, Reuss and shear-lag models, the Mori-Tanaka scheme and the upper and lower bounds by Hashin and Shtrikman. The predicted axial strain ratios between the two-scales are discussed with respect to a recent small-angle X-ray scattering and wide-angle X-ray diffraction study. Beyond apparent elastic properties, the FE models provide stress distributions at both hierarchical levels, confirm the shear lag mechanisms within the MCF and between MCF and EFM and identify potential damage sites under arbitrary loading conditions. A comprehensive sensitivity analysis shows that mineral volume fraction in the fibril array is the dominant parameter on the axial and transverse elastic moduli, while the MCF volume fraction in FAY is the most sensitive variable for the ratio of axial versus transverse elastic modulus followed by the elastic moduli of hydroxyapatite and collagen. The FE model of the FAY developed and calibrated in the current study represents an anatomically realistic, experimentally validated and computationally efficient basis for investigating the apparent yield, post-yield and failure behaviors of lamellar bone in future research.Bone and soft tissue sarcomas are rare malignant tumors originated from mesenchymal tissues. They harbor more than 50 distinct subtypes and differ in pathological features and clinical courses. Despite the significant improvements in modern multi-modality treatment, the outcomes and overall survival rates remain poor for patients with advanced, refractory, metastatic, or relapsed diseases. The growth and metastasis of bone and soft tissue sarcoma largely depend on angiogenesis, and VEGF/VEGFR pathway is considered as the most prominent player in angiogenesis. Therefore, blockade of VEGF/VEGFR pathways is a promising therapeutic strategy to retard neovascularization. Several VEGFR inhibitors have been developed and revealed their favorable anti-neoplastic effects in various cancers, but such desirable anti-tumor effects are not obtained in advanced sarcomas because of multiple reasons, such as drug tolerance, short duration of response, and severe adverse effects. Fortunately, preclinical and clinical studies several difficulties should be tackled before full use of apatinib. In this review, we discuss the outstanding characteristics and main predicaments of apatinib as targeted therapy in advanced sarcomas.Chimeric antigen receptor (CAR) T cell therapy has come of age, offering a potentially curative option for patients who are refractory to standard anti-cancer treatments. The success of CAR T cell therapy in the setting of acute lymphoblastic leukemia and specific types of B cell lymphoma led to rapid regulatory approvals of CD19-directed CAR T cells, first in the United States and subsequently across the globe. Despite these major milestones in the field of immuno-oncology, growing experience with CAR T cells has also highlighted the major limitations of this strategy, namely challenges associated with manufacturing a bespoke patient-specific product, intrinsic immune cell defects leading to poor CAR T cell function as well as persistence, and/or tumor cell resistance resulting from loss or modulation of the targeted antigen. In addition, both on- and off-tumor immunotoxicities and the financial burden inherent in conventional cellular biomanufacturing often hamper the success of CAR T cell-based treatment approaches.