1,721,012 research outputs found

    Next Generation of Brain Cancer Nanomedicines to Overcome the Blood–Brain Barrier (BBB):Insights on Transcytosis, Perivascular Tumor Growth, and BBB Models

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    Brain cancers, particularly malignant gliomas such as glioblastoma, are highly invasive and characterized by elevated complexity, heterogeneity, and high infiltration ability. Therefore, they pose a significant challenge to conventional treatments due to the limited drug permeability of the blood–brain barrier (BBB), the involvement of numerous acquired and intrinsic drug resistance mechanisms in metastatic brain tumors, and the high sensitivity of surrounding healthy tissues. Despite recent advances in diagnosis and treatment, their prognosis remains poor, with their median overall survival rarely exceeding 12 months. To overcome these limitations, different nanomedicine-based therapeutic approaches have recently been proposed, aiming to provide more effective and safer drug delivery for targeting brain cancers. However, most reported nanomedicines to date have failed to meet the high expectations in the clinic. This fact can be attributed to limited understanding of brain tumor biology and lack of knowledge about bio-nanoparticle interactions, among other factors. This review discusses recent progress in brain cancer nanomedicines, with a particular focus in understanding intracellular sorting mechanisms, perivascular tumor growth, and the design of advanced BBB models. It also highlights how an improved understanding of brain tumor biology can pave the way for designing safer and more effective nanomedicines for brain cancer treatment.</p

    Silica Replicas Derived from Mammalian Cells as an Innovative Approach to Physically Direct Cell Lineage Decisions of Mesenchymal Stem Cells

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    By means of a “live-cell” template strategy, silica replicas displaying the same morphology and topography of the mammalian cells used as templates are fabricated. The replicas are used as substrates to direct the differentiation of mesenchymal stem cells (MSCs) to predefined cell lineages. Upregulation of specific genes shows how the silica replica-based substrates have the ability to induce the molecular characteristics of the mature cell types from which they have been derived from. Thus, MSCs cultured in the presence of silica replicas of human osteoblasts (HObs) differentiate into HObs-like cells, as shown by the upregulation of specific osteogenic genes. Likewise, when MSCs are incubated with silica replicas derived from human chondrocytes, an enhanced expression of chondrogenic markers is observed. Importantly, the effects of the silica replicas are cell type-specific since the incubation of MSCs with HObs silica replicas does not result in upregulation of chondrogenic markers and vice versa. What is more, for both cases, the differentiation rate is enhanced when the silica replicas are used in combination with growth factors, suggesting a potential synergistic effect. These results demonstrate the potential of this innovative method as an efficient and cheap approach with the potential to eliminate, or at least reduce, the use of biochemically soluble compounds in stem cells research.</p

    Recent and prominent examples of nano- and microarchitectures as hemoglobin-based oxygen carriers

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    Blood transfusions, which usually consist in the administration of isolated red blood cells (RBCs), are crucial in traumatic injuries, pre-surgical conditions and anemias. Although RBCs transfusion from donors is a safe procedure, donor RBCs can only be stored for a maximum of 42 days under refrigerated conditions and, therefore, stockpiles of RBCs for use in acute disasters do not exist. With a worldwide shortage of donor blood that is expected to increase over time, the creation of oxygen-carriers with long storage life and compatibility without typing and cross-matching, persists as one of the foremost important challenges in biomedicine. However, research has so far failed to produce FDA approved RBCs substitutes (RBCSs) for human usage. As such, due to unacceptable toxicities, the first generation of oxygen-carriers has been withdrawn from the market. Being hemoglobin (Hb) themain component of RBCs, a lot of effort is being devoted in assembling semi-synthetic RBCS utilizing Hb as the oxygen-carrier component, the so-called Hb-based oxygen carriers (HBOCs). However, a native RBC also contains a multi-enzyme system to prevent the conversion of Hb into non-functional methemoglobin (metHb). Thus, the challenge for the fabrication of next-generation HBOCs relies in creating a system that takes advantage of the excellent oxygen-carrying capabilities of Hb, while preserving the redox environment of native RBCs that prevents or reverts the conversion of Hb into metHb. In this review, we feature the most recent advances in the assembly of the new generation of HBOCs with emphasis in two main approaches: the chemical modification of Hb either by cross-linking strategies or by conjugation to other polymers, and the Hb encapsulation strategies, usually in the form of lipidic or polymeric capsules. The applications of the aforementioned HBOCs as blood substitutes or for oxygen-delivery in tissue engineering are highlighted, followed by a discussion of successes, challenges and future trends in this field

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Therapeutic Applications of Multifunctional Nanozymes

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    Nanozymes, which are functional nanomaterials with enzyme-like characteristics, have emerged as a highly-stable and low-cost alternative to natural enzymes. Apart from overcoming the limitations of natural enzymes (e.g., high cost, low stability or complex production), nanozymes are also equipped with the unique intrinsic properties of nanomaterials such as magnetism, luminiscence or near infrared absorbance. Therefore, the development of nanozymes exhibiting additional functions to their catalytic activity has opened up new opportunities and applications within the biomedical field. To highlight the progress in the field, this review summarizes the novel applications of multifunctional nanozymes in various biomedical-related fields ranging from cancer diagnosis, cancer and antibacterial therapy to regenerative medicine. Future challenges and perspectives that may advance nanozyme research are also discussed at the end of the review

    Topography: A Biophysical Approach to Direct the Fate of Mesenchymal Stem Cells in Tissue Engineering Applications

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    Tissue engineering is a promising strategy to treat tissue and organ loss or damage caused by injury or disease. During the past two decades, mesenchymal stem cells (MSCs) have attracted a tremendous amount of interest in tissue engineering due to their multipotency and self-renewal ability. MSCs are also the most multipotent stem cells in the human adult body. However, the application of MSCs in tissue engineering is relatively limited because it is difficult to guide their differentiation toward a specific cell lineage by using traditional biochemical factors. Besides biochemical factors, the differentiation of MSCs also influenced by biophysical cues. To this end, much effort has been devoted to directing the cell lineage decisions of MSCs through adjusting the biophysical properties of biomaterials. The surface topography of the biomaterial-based scaffold can modulate the proliferation and differentiation of MSCs. Presently, the development of micro- and nano-fabrication techniques has made it possible to control the surface topography of the scaffold precisely. In this review, we highlight and discuss how the main topographical features (i.e., roughness, patterns, and porosity) are an efficient approach to control the fate of MSCs and the application of topography in tissue engineering

    Stepping stones to the future of haemoglobin-based blood products: clinical, preclinical and innovative examples

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    There is an enormous demand for blood transfusions in daily clinical practices since blood products, especially red blood cells (RBCs), can significantly improve survival. However, donor-derived RBCs have important limitations as a result of their insufficient availability, the need for typing and cross-matching, short shelf-life or risk of pathogenic contamination. Thus, as a result of the unique oxygen-transport ability of hemoglobin (Hb), Hb-based oxygen carriers (HBOCs) have attracted a lot of attention for the development of RBC surrogates able to provide tissue oxygenation. Here, we highlight the progress in the development of HBOCs, focusing on different examples that have undergone exhaustive pre-clinical and clinical evaluation. In addition, we also provide a comprehensive review of very recent and innovative examples to aid in the development of the next generation of blood substitutes
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