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Browsing by Subject "Extracellular vesicles"
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Item Call for papers: Exploiting extracellular vesicles as therapeutic agents(Elsevier, 2022) Frederickson, Robert M.; Ritter, Thomas; Morris, Kevin; Kortylewski, Marcin; Nasr, Maha; Herzog, Roland W.; Pediatrics, School of MedicineItem Cardioprotection vs. regeneration: the case of extracellular vesicle-derived microRNAs(Springer, 2021-03-19) Wollert, Kai C.; Field, Loren J.; Pediatrics, School of MedicineItem Cholangiocarcinoma: novel therapeutic targets(Taylor & Francis, 2020-04) Sato, Keisaku; Glaser, Shannon; Alvaro, Domenico; Meng, Fanyin; Francis, Heather; Alpini, Gianfranco; Medicine, School of MedicineIntroduction: Cholangiocarcinoma (CCA) is a liver cancer derived from the biliary tree with a less than 30% five-year survival rate. Early diagnosis of CCA is challenging and treatment options are limited. Some CCA patients have genetic mutations and several therapeutic drugs or antibodies have been introduced to target abnormally expressed proteins. However, CCA is heterogeneous and patients often present with drug resistance which is attributed to multiple mutations or other factors. Novel approaches and methodologies for CCA treatments are in demand.Area covered: This review summarizes current approaches for CCA treatments leading to the development of novel therapeutic drugs or tools for human CCA patients. A literature search was conducted in PubMed utilizing the combination of the searched term 'cholangiocarcinoma' with other keywords such as 'miRNA', 'FGFR', 'immunotherapy' or 'microenvironment'. Papers published within 2015-2019 were obtained for reading.Expert opinion: Preclinical studies have demonstrated promising therapeutic approaches that target various cells or pathways. Recent studies have revealed that hepatic cells coordinate to promote CCA tumor progression in the tumor microenvironment, which may be a new therapeutic target. Although further studies are required, novel therapeutic tools such as extracellular vesicles could be utilized to manage CCA and its microenvironment.Item Data-Independent Acquisition Phosphoproteomics of Urinary Extracellular Vesicles Enables Renal Cell Carcinoma Grade Differentiation(Elsevier, 2023) Hadisurya, Marco; Lee, Zheng-Chi; Luo, Zhuojun; Zhang, Guiyuan; Ding, Yajie; Zhang, Hao; Iliuk, Anton B.; Pili, Roberto; Boris, Ronald S.; Tao, W. Andy; Urology, School of MedicineTranslating the research capability and knowledge in cancer signaling into clinical settings has been slow and ineffective. Recently, extracellular vesicles (EVs) have emerged as a promising source for developing disease phosphoprotein markers to monitor disease status. This study focuses on the development of a robust data-independent acquisition (DIA) using mass spectrometry to profile urinary EV phosphoproteomics for renal cell cancer (RCC) grades differentiation. We examined gas-phase fractionated library, direct DIA (library-free), forbidden zones, and several different windowing schemes. After the development of a DIA mass spectrometry method for EV phosphoproteomics, we applied the strategy to identify and quantify urinary EV phosphoproteomes from 57 individuals representing low-grade clear cell RCC, high-grade clear cell RCC, chronic kidney disease, and healthy control individuals. Urinary EVs were efficiently isolated by functional magnetic beads, and EV phosphopeptides were subsequently enriched by PolyMAC. We quantified 2584 unique phosphosites and observed that multiple prominent cancer-related pathways, such as ErbB signaling, renal cell carcinoma, and regulation of actin cytoskeleton, were only upregulated in high-grade clear cell RCC. These results show that EV phosphoproteome analysis utilizing our optimized procedure of EV isolation, phosphopeptide enrichment, and DIA method provides a powerful tool for future clinical applications.Item Dysbiosis in gastrointestinal pathophysiology: Role of the gut microbiome in Gulf War Illness(Wiley, 2023) Slevin, Elise; Koyama, Sachiko; Harrison, Kelly; Wan, Ying; Klaunig, James E.; Wu, Chaodong; Shetty, Ashok K.; Meng, Fanyin; Medicine, School of MedicineGulf War Illness (GWI) has been reported in 25%-35% of veterans returned from the Gulf war. Symptoms of GWI are varied and include both neurological and gastrointestinal symptoms as well as chronic fatigue. Development of GWI has been associated with chemical exposure particularly with exposure to pyridostigmine bromide (PB) and permethrin. Recent studies have found that the pathology of GWI is connected to changes in the gut microbiota, that is the gut dysbiosis. In studies using animal models, the exposure to PB and permethrin resulted in similar changes in the gut microbiome as these found in GW veterans with GWI. Studies using animal models have also shown that phytochemicals like curcumin are beneficial in reducing the symptoms and that the extracellular vesicles (EV) released from gut bacteria and from the intestinal epithelium can both promote diseases and suppress diseases through the intercellular communication mechanisms. The intestinal epithelium cells produce EVs and these EVs of intestinal epithelium origin are found to suppress inflammatory bowel disease severity, suggesting the benefits of utilizing EV in treatments. On the contrary, EV from the plasma of septic mice enhanced the level of proinflammatory cytokines in vitro and neutrophils and macrophages in vivo, suggesting differences in the EV depending on the types of cells they were originated and/or influences of environmental changes. These studies suggest that targeting the EV that specifically have positive influences may become a new therapeutic strategy in the treatment of veterans with GWI.Item Editorial: Role of extracellular vesicles (EVs) in pathogenesis, diagnosis, therapeutic delivery, treatment and theranostic applications in cancer(Frontiers Media, 2023-09-15) Shahbazi, Reza; Kalishwaralal, Kalimuthu; Paul, Manash K.; Anto, Ruby John; Medicine, School of MedicineItem Extracellular vesicles in β cell biology: Role of lipids in vesicle biogenesis, cargo, and intercellular signaling(Elsevier, 2022) Aguirre, Rebecca S.; Kulkarni, Abhishek; Becker, Matthew W.; Lei, Xiaoyong; Sarkar, Soumyadeep; Ramanadham, Sasanka; Phelps, Edward A.; Nakayasu, Ernesto S.; Sims, Emily K.; Mirmira, Raghavendra G.; Pediatrics, School of MedicineBackground: Type 1 diabetes (T1D) is a complex autoimmune disorder whose pathogenesis involves an intricate interplay between β cells of the pancreatic islet, other islet cells, and cells of the immune system. Direct intercellular communication within the islet occurs via cell surface proteins and indirect intercellular communication has traditionally been seen as occurring via secreted proteins (e.g., endocrine hormones and cytokines). However, recent literature suggests that extracellular vesicles (EVs) secreted by β cells constitute an additional and biologically important mechanism for transmitting signals to within the islet. Scope of review: This review summarizes the general mechanisms of EV formation, with a particular focus on how lipids and lipid signaling pathways influence their formation and cargo. We review the implications of EV release from β cells for T1D pathogenesis, how EVs and their cargo might be leveraged as biomarkers of this process, and how EVs might be engineered as a therapeutic candidate to counter T1D outcomes. Major conclusions: Islet β cells have been viewed as initiators and propagators of the cellular circuit giving rise to autoimmunity in T1D. In this context, emerging literature suggests that EVs may represent a conduit for communication that holds more comprehensive messaging about the β cells from which they arise. As the field of EV biology advances, it opens the possibility that intervening with EV formation and cargo loading could be a novel disease-modifying approach in T1D.Item Human extracellular microvesicles from renal tubules reverse kidney ischemia-reperfusion injury in rats(PLOS, 2018-08-27) Dominguez II, James M.; Dominguez, Jesus H.; Xie, Danhui; Kelly, Katherine J.; Medicine, School of MedicineHypoxic acute kidney injury, a major unresolved problem, initiates, or aggravates, renal functional and structural decline. There is no treatment for hypoxic acute renal injury and its sequelae. We tested the hypothesis that human kidney tubular cells, or their extracellular vesicles (exosomes), prevent renal injury when infused intravenously 24 hours after 50 minutes of bilateral renal ischemia in Nude rats. Cells and their exosomes were from harvested human kidneys declined for transplantation. Injections of either cells or exosomes, given after 24 and 48 hours of reperfusion, preserved renal function and structure in both treatment groups. However, exosomes were superior to cells; and maintained renal vascular and epithelial networks, prevented renal oxidant stress, and apoptosis; and restrained activation of pro-inflammatory and pro-fibrogenic pathways. Exosomes worked in 24 hours, consistent with functional rather than regenerative activity. Comprehensive proteomic analysis identified 6152 renal proteins from all cellular compartments; and 628 were altered by ischemia at all cell levels, while 377 were significantly improved by exosome infusions. We conclude that renal damage from severe ischemia was broad, and human renal exosomes prevented most protein alterations. Thus, exosomes seem to acutely correct a critical and consequential abnormality during reperfusion. In their absence, renal structure and cells transition to a chronic state of fibrosis and extensive renal cell loss.Item Intercellular Communication between Hepatic Cells in Liver Diseases(MDPI, 2019-05-02) Sato, Keisaku; Kennedy, Lindsey; Liangpunsakul, Suthat; Kusumanchi, Praveen; Yang, Zhihong; Meng, Fanyin; Glaser, Shannon; Francis, Heather; Alpini, Gianfranco; Medicine, School of MedicineLiver diseases are perpetuated by the orchestration of hepatocytes and other hepatic non-parenchymal cells. These cells communicate and regulate with each other by secreting mediators such as peptides, hormones, and cytokines. Extracellular vesicles (EVs), small particles secreted from cells, contain proteins, DNAs, and RNAs as cargos. EVs have attracted recent research interests since they can communicate information from donor cells to recipient cells thereby regulating physiological events via delivering of specific cargo mediators. Previous studies have demonstrated that liver cells secrete elevated numbers of EVs during diseased conditions, and those EVs are internalized into other liver cells inducing disease-related reactions such as inflammation, angiogenesis, and fibrogenesis. Reactions in recipient cells are caused by proteins and RNAs carried in disease-derived EVs. This review summarizes cell-to-cell communication especially via EVs in the pathogenesis of liver diseases and their potential as a novel therapeutic target.Item microRNAs and connexins in bone: interaction and mechanisms of delivery(Springer, 2017-06) Plotkin, Lilian I.; Pacheco-Costa, Rafael; Davis, Hannah M.; Anatomy and Cell Biology, School of MedicinePURPOSE OF REVIEW: To describe the current knowledge on the cross-talk between connexins and microRNAs (miRs) in bone cells. RECENT FINDINGS: Connexins play a crucial role on bone development and maintenance, and disruptions in their abundance or localization can affect how bone perceives and responds to mechanical, hormonal, and pharmacological stimuli. Connexin expression can be modified by miRs, which modulate connexin mRNA and protein levels. Recently, different manners by which miRs and connexins can interact in bone have been identified, including mechanisms that mediate miR exchange between cells in direct contact through gap junctions, or between distant cells via extracellular vesicles (EVs). SUMMARY: We bring to light the relationship between miRs and connexins in bone tissue, with special focus on regulatory effects of miRs and connexins on gene expression, as well as the mechanisms that mediate miR exchange between cells in direct contact through gap junctions, or between distant cells via EVs.