Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 2Citation - Scopus: 2Osteoblasts-Derived Exosomes as Potential Novel Communicators in Particle-Induced Periprosthetic Osteolysis(Elsevier, 2024) de Souza, Wanderson; Gemini-Piperni, S.; Ruivo, Carolina; Bastos, Nuno; Almeida, Sofia; Lopes, Daniel; Ribeiro, Ana R.The inflammatory response to wear particles derived from hip prothesis is considered a hallmark of periprosthetic osteolysis, which can ultimately lead to the need for revision surgery. Exosomes (Exos) have been associated with various bone pathologies, and there is increasing recognition in the literature that they actively transport molecules throughout the body. The role of wear particles in osteoblast-derived Exos is unknown, and the potential contribution of Exos to osteoimmune communication and periprosthetic osteolysis niche is still in its infancy. Given this, we investigate how titanium dioxide nanoparticles (TiO2 NPs), similar in size and composition to prosthetic wear particles, affect Exos biogenesis. Two osteoblastic cell models commonly used to study the response of osteoblasts to wear particles were selected as a proof of concept. The contribution of Exos to periprosthetic osteolysis was assessed by functional assays in which primary human macrophages were stimulated with bone-derived Exos. We demonstrated that TiO2 NPs enter multivesicular bodies, the nascent of Exos, altering osteoblast-derived Exos secretion and molecular cargo. No significant differences were observed in Exos morphology and size. However, functional assays reveal that Exos cargo enriched in uPA stimulates macrophages to a mixed M1 and M2 phenotype, inducing the release of pro- and anti-inflammatory signals characteristic of periprosthetic osteolysis. In addition, we demonstrated the expression of uPA in exosomes derived from the urine of patients with osteolysis. These results suggest that uPA can be a potential biomarker of osteolysis. In the future, uPa may serve as a possible non-invasive biomarker to identify patients at risk for peri-implant osteolysis.Article Citation - WoS: 4Citation - Scopus: 4Colorimetric Assaying of Exosomal Metabolic Biomarkers(MDPI, 2023) Yan, Evelias; Goyal, Garima; Yıldız, Ümit Hakan; Boehm, Bernhard O.; Palaniappan, AlagappanExosomes released into the extracellular matrix have been reported to contain metabolic biomarkers of various diseases. These intraluminal vesicles are typically found in blood, urine, saliva, breast milk, cerebrospinal fluid, semen, amniotic fluid, and ascites. Analysis of exosomal content with specific profiles of DNA, microRNA, proteins, and lipids can mirror their cellular origin and physiological state. Therefore, exosomal cargos may reflect the physiological processes at cellular level and can potentially be used as biomarkers. Herein, we report an optical detection method for assaying exosomal biomarkers that supersedes the state-of-the-art time consuming and laborious assays such as ELISA and NTA. The proposed assay monitors the changes in optical properties of poly(3-(4-methyl-3'-thienyloxy) propyltriethylammonium bromide) upon interacting with aptamers/peptide nucleic acids in the presence or absence of target biomarkers. As a proof of concept, this study demonstrates facile assaying of microRNA, DNA, and advanced glycation end products in exosomes isolated from human plasma with detection levels of ~1.2, 0.04, and 0.35 fM/exosome, respectively. Thus, the obtained results illustrate that the proposed methodology is applicable for rapid and facile detection of generic exosomal biomarkers for facilitating diseases diagnosis.Article Citation - WoS: 9Citation - Scopus: 11Mir-Aculous New Avenues for Cancer Immunotherapy(Frontiers Media S.A., 2022) Tang, William W.; Bauer, Kaylyn M.; Barba, Cindy; Ekiz, Hüseyin Atakan; O’Connell, Ryan M.The rising toll of cancer globally necessitates ingenuity in early detection and therapy. In the last decade, the utilization of immune signatures and immune-based therapies has made significant progress in the clinic; however, clinical standards leave many current and future patients without options. Non-coding RNAs, specifically microRNAs, have been explored in pre-clinical contexts with tremendous success. MicroRNAs play indispensable roles in programming the interactions between immune and cancer cells, many of which are current or potential immunotherapy targets. MicroRNAs mechanistically control a network of target genes that can alter immune and cancer cell biology. These insights provide us with opportunities and tools that may complement and improve immunotherapies. In this review, we discuss immune and cancer cell–derived miRNAs that regulate cancer immunity and examine miRNAs as an integral part of cancer diagnosis, classification, and therapy.