In the last decades, the treatment of primary and secondary bone tumors has faced a slow-down in its development, being mainly based on chemotherapy, radiotherapy, and surgical interventions. However, these conventional therapeutic strategies present a series of disadvantages (e.g., multidrug resistance, tumor recurrence, severe side effects, formation of large bone defects), which limit their application and efficacy. In recent years, these procedures were combined with several adjuvant therapies, with different degrees of success. To overcome the drawbacks of current therapies and improve treatment outcomes, other strategies started being investigated, like carrier-mediated drug delivery, bone substitutes for repairing bone defects, and multifunctional scaffolds with bone tissue regeneration and antitumor properties. Thus, this paper aims to present the types of bone tumors and their current treatment approaches, further focusing on the recent advances in new therapeutic alternatives.
Summary. Background: Chronic venous insufficiency (CVI) results when the veins in the legs no longer pump blood back to the heart effectively. Microparticles (MPs) are small membrane vesicles released by several circulating and vascular cells upon activation or apoptosis. Objectives: The purpose of this study was to assess the subpopulations of circulating endothelial (EMPs) and platelet microparticles (PMPs) in CVI, and to disclose their contribution in mediating dysfunction of human peripheral venules. Patients and methods: Human peripheral venules were explanted during leg surgery on patients with CVI and on control subjects (C); concurrently, blood samples were collected and circulating MPs isolated. The techniques used were: flow cytometry, fluorescence and electron microscopy, myograph technique and western-blotting technique. Results: The results showed that compared with controls, patients with CVI had: (i) a marked elevation of circulating EMPs and PMPs; (ii) a structural modification of the venous wall consisting of activation of endothelial and smooth muscle cells, an abundance of intermediary filaments and synthesis of hyperplasic-multilayered basal lamina; (iii) a significantly altered reactivity of the venous wall, closely associated with EMPs and PMPs adherence; (iv) altered contractile response to noradrenaline, acetylcholine, 5-hydroxytryptamine and KCl, and an impeded relaxation in response to sodium nitroprusside; and (iv) a substantially increased protein expression of tissue factor (TF) and of P-Selectin both in the venular vascular wall and on the surface of EMPs and PMPs. Conclusions: The findings indicate that CVI is accompanied by an enhanced release of EMPs and PMPs that contribute to altered dysfunctional response of the venous wall.
Bone tissue engineering is a complex domain that requires further investigation and benefits from data obtained over past decades. The models are increasing in complexity as they reveal new data from co-culturing and microfluidics applications. The in vitro models now focus on the 3D medium co-culturing of osteoblasts, osteoclasts, and osteocytes utilizing collagen for separation; this type of research allows for controlled medium and in-depth data analysis. Oxidative stress takes a toll on the domain, being beneficial as well as destructive. Reactive oxygen species (ROS) are molecules that influence the differentiation of osteoclasts, but over time their increasing presence can affect patients and aid the appearance of diseases such as osteoporosis. Oxidative stress can be limited by using antioxidants such as vitamin K and N‑acetyl cysteine (NAC). Scaffolds and biocompatible coatings such as hydroxyapatite and bioactive glass are required to isolate the implant, protect the zone from the metallic, ionic exchange, and enhance the bone regeneration by mimicking the composition and structure of the body, thus enhancing cell proliferation. The materials can be further functionalized with growth factors that create a better response and higher chances of success for clinical use. This review highlights the vast majority of newly obtained information regarding bone tissue engineering, such as new co-culturing models, implant coatings, scaffolds, biomolecules, and the techniques utilized to obtain them.
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