631 research outputs found

    Pathophysiological role and therapeutic potential of extracellular vesicles in cancer

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    Extracellular vesicles (EVs) are nanosized lipid bilayer vesicles that are endogenously generated through various biogenesis pathways within most cellular entities. Subsequently, they are released into the extracellular milieu to facilitate intercellular communication. They are composed of diverse bioactive molecules with important roles in physiological and pathological states. Over the past few decades, the therapeutic potential of EVs has garnered significant interest in the drug delivery field. However, deepened understanding of EV biology and further technological advances are needed to bridge the gap between research and clinical translation. In this thesis, we address these challenges and investigate EVs as novel biomedical agents. EVs are crucial components of physiological processes and disease development. Sensitive visualisation techniques are needed to better understand their function as therapeutic agents. In paper I, a bioluminescent labelling system was developed to track EVs in vitro and in vivo. The system uses genetic modifications to enable the encapsulation of sensitive luciferase-variants in EVs. The system was used in vivo to enable highly sensitive detection of EV distribution pattern. Exogenously administered EVs were found to rapidly distribute within different organs, with a preference for the spleen, lung, and liver. In addition to endogenously engineered EVs for in vivo tracking, exogenously engineered EVs can be utilised as promising drug delivery platforms. However, cargo loading is often insufficient, requiring improved EV loading approaches. In paper II, we developed an optimised cargo loading method using electroporation. An optimised protocol was designed to load EVs with doxorubicin, which increased cargo loading, EV recovery, and drug potency by 190-fold over free doxorubicin. Owing to their potential to cross biological barriers, transport bioactive cargo, and targetability, EVs can be exploited as delivery vehicles for targeting of therapeutics. EVs were used as delivery vectors in paper III by coating their surfaces with an Fc domain-specific antibodybinding moiety. These Fc-EVs were then decorated with various IgG antibodies and targeted to cells of interest. In vitro and in vivo antibody targeting studies showed the broad potential of this technology for cancer therapy. The platform efficiently targeted EVs to cancer cells, including HER2 and PD-L1 positive cells. As proof of concept, Fc-EVs with PD-L1 antibody accumulate in tumour tissue and, when loaded with doxorubicin, reduce tumour burden, and increase survival in melanoma-bearing mice. Despite significant EV engineering advances, we have a limited understanding of the biology of tumour-derived extracellular vesicles (tEVs). In paper IV, we investigated the role of in vitrogenerated melanoma-derived EVs as indirect communicators in tumour-induced haematopoiesis dysregulation. The tEVs, which contain high levels of angiogenic factors like VEGF, osteopontin, and tissue factor, were found to cause splenomegaly, extramedullary haematopoiesis, expansion of splenic immature erythroid progenitors, reduced bone marrow cellularity, medullary expansion of granulocytic myeloid suppressor cells, and anaemia in syngeneic mice. These findings suggest that tEVs dysregulate haematopoiesis during the immune escape phase of cancer immunoediting, making them potential targets for overcoming immune evasion and restoring normal haematopoiesis. To summarise, the tools generated in this thesis, including the ability to detect EVs in vivo, effective cargo loading, display antibody binding moieties on EV surfaces for targeting, and understanding the pathophysiological role of tEVs, contribute to the advancement of EVs for biomedical purposes, and clinical translation down the line

    Effects of municipal smoke-free ordinances on secondhand smoke exposure in the Republic of Korea

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    ObjectiveTo reduce premature deaths due to secondhand smoke (SHS) exposure among non-smokers, the Republic of Korea (ROK) adopted changes to the National Health Promotion Act, which allowed local governments to enact municipal ordinances to strengthen their authority to designate smoke-free areas and levy penalty fines. In this study, we examined national trends in SHS exposure after the introduction of these municipal ordinances at the city level in 2010.MethodsWe used interrupted time series analysis to assess whether the trends of SHS exposure in the workplace and at home, and the primary cigarette smoking rate changed following the policy adjustment in the national legislation in ROK. Population-standardized data for selected variables were retrieved from a nationally representative survey dataset and used to study the policy action’s effectiveness.ResultsFollowing the change in the legislation, SHS exposure in the workplace reversed course from an increasing (18% per year) trend prior to the introduction of these smoke-free ordinances to a decreasing (−10% per year) trend after adoption and enforcement of these laws (β2 = 0.18, p-value = 0.07; β3 = −0.10, p-value = 0.02). SHS exposure at home (β2 = 0.10, p-value = 0.09; β3 = −0.03, p-value = 0.14) and the primary cigarette smoking rate (β2 = 0.03, p-value = 0.10; β3 = 0.008, p-value = 0.15) showed no significant changes in the sampled period. Although analyses stratified by sex showed that the allowance of municipal ordinances resulted in reduced SHS exposure in the workplace for both males and females, they did not affect the primary cigarette smoking rate as much, especially among females.ConclusionStrengthening the role of local governments by giving them the authority to enact and enforce penalties on SHS exposure violation helped ROK to reduce SHS exposure in the workplace. However, smoking behaviors and related activities seemed to shift to less restrictive areas such as on the streets and in apartment hallways, negating some of the effects due to these ordinances. Future studies should investigate how smoke-free policies beyond public places can further reduce the SHS exposure in ROK

    Modern meat: the next generation of meat from cells

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    Modern Meat is the first textbook on cultivated meat, with contributions from over 100 experts within the cultivated meat community. The Sections of Modern Meat comprise 5 broad categories of cultivated meat: Context, Impact, Science, Society, and World. The 19 chapters of Modern Meat, spread across these 5 sections, provide detailed entries on cultivated meat. They extensively tour a range of topics including the impact of cultivated meat on humans and animals, the bioprocess of cultivated meat production, how cultivated meat may become a food option in Space and on Mars, and how cultivated meat may impact the economy, culture, and tradition of Asia

    Biomaterials for Bone Tissue Engineering 2020

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    This book presents recent advances in the field of bone tissue engineering, including molecular insights, innovative biomaterials with regenerative properties (e.g., osteoinduction and osteoconduction), and physical stimuli to enhance bone regeneration

    International consensus statement on allergy and rhinology: Allergic rhinitis – 2023

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    Background In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. Methods ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. Results ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment

    2023- The Twenty-seventh Annual Symposium of Student Scholars

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    The full program book from the Twenty-seventh Annual Symposium of Student Scholars, held on April 18-21, 2023. Includes abstracts from the presentations and posters.https://digitalcommons.kennesaw.edu/sssprograms/1027/thumbnail.jp

    Orvosképzés 2023

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    Propaedeutics of Internal Diseases

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    УЧЕБНЫЕ ПОСОБИЯДИАГНОСТИКАПИЩЕВАРИТЕЛЬНОЙ СИСТЕМЫ БОЛЕЗНИ /ДИАГНОСТИКАМОЧЕПОЛОВЫЕ БОЛЕЗНИ /ДИАГНОСТИКАГЕМАТОЛОГИЧЕСКИЕ БОЛЕЗНИ /ДИАГНОСТИКАДИАГНОСТИЧЕСКИЕ МЕТОДЫ ЭНДОКРИННЫЕДИАГНОСТИЧЕСКИЕ МЕТОДЫ ПИЩЕВАРИТЕЛЬНЫЕКОСТНО-МЫШЕЧНОЙ СИСТЕМЫ БОЛЕЗНИ /ДИАГНОСТИКАТЕРАПИЯ (ДИСЦИПЛИНА)DISEASES OF THE ENDOCRINE GLANDSDISEASES OF THE MUSCULOSKELETAL SYSTEMDISEASES OF THE BLOODDISEASES OF THE URINARY TRACTDISEASES OF THE DIGESTIVE SYSTEMINTERNAL DISEASESPROPAEDEUTICS OF INTERNAL DISEASESINTERNAL MEDICINEИНОСТРАННЫЕ СТУДЕНТЫСодержит следующие разделы: обследование пациентов с заболеваниями органов систем пищеварения, мочевыделения, крови, желез внутренней секреции и опорно-двигательного аппарата. Для студентов 2 и 3 курсов, изучающих пропедевтику внутренних болезней на английском языке. It contains the following sections: examination of patients with diseases of the digestive system, urinary tract, blood, endocrine glands and musculoskeletal system

    Proceedings of 14th international symposium Modern trends in livestock production

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