0000000000265283

AUTHOR

Raimondo Stefania

Two distinct extracellular RNA signatures released by a single cell type identified by microarray and next-generation sequencing

ABSTRACT Cells secrete extracellular RNA (exRNA) to their surrounding environment and exRNA has been found in many body fluids such as blood, breast milk and cerebrospinal fluid. However, there are conflicting results regarding the nature of exRNA. Here, we have separated 2 distinct exRNA profiles released by mast cells, here termed high-density (HD) and low-density (LD) exRNA. The exRNA in both fractions was characterized by microarray and next-generation sequencing. Both exRNA fractions contained mRNA and miRNA, and the mRNAs in the LD exRNA correlated closely with the cellular mRNA, whereas the HD mRNA did not. Furthermore, the HD exRNA was enriched in lincRNA, antisense RNA, vault RNA, …

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LEMON-DERIVED EXTRACELLULAR VESICLES EXERT ANTI-INFLAMMATORY EFFECTS BY INHIBITING THE ERK/NF-KB PATHWAY

nflammation can be the leading cause of several diseases, including cancer, diabetes, and ulcerative colitis; however, the existing anti-inflammatory drugs cause side effects. For these reasons, it is necessary to find new supportive therapeutic agents. In recent years, plant-derived extracellular vesicles (PDEVs) are gaining increasing interest in the scientific community as they have been found to possess a variety of biological properties; among those, the anti-inflammatory effects have been described by different groups that evaluated the effects of PDEVs in in vitro and in vivo models. We successfully isolated and characterized extracellular vesicles from Citrus limon juice (LEVs) and …

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Nobiletin and xanthohumol sensitize colorectal cancer stem cells to standard chemotherapy

Simple Summary Colorectal cancer stem cells (CR-CSCs) play a pivotal role in the therapy resistance and relapse of CRC patients. Herein we demonstrate that new treatment approaches comprising polymethoxyflavones and prenylflavonoids extracted from Citrus sinensis and Humulus lupulus, respectively, hamper the viability of CR-CSCs as well as synergizing with 5-fluorouracil and oxaliplatin (FOX)-based chemotherapy. Extract fractions containing Nobiletin and Xanthohumol, in combination with chemotherapy, decreased stemness properties of CR-CSCs and restrained the outgrowth of chemoresistant metastatic CR-CSCs. These data pinpoint Nobiletin and Xanthohumol as efficacious anti-cancer compounds in…

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The gene expression profile of cumulus cells reveals altered pathways in patients with endometriosis

PURPOSE: The objective of this experimental study was to compare the global gene expression profile of CC of mature oocytes in 18 patients with severe endometriosis and CC in 18 control patients affected by a severe male factor. METHODS: For each group, the CC were pooled, RNA was extracted and a microarray performed. For validating the microarray, a quantitative real-time PCR was performed in the CC of an independent set of patients with endometriosis (n = 5) and controls (n = 7). RESULTS: 595 differentially expressed genes (320 down-regulated, 275 up-regulated, p < 0.05, fold change ≥1.5) were identified. The most significant changes were observed in genes involved in the chemokine signal…

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Anti-inflammatory properties of lemon-derived extracellular vesicles are achieved through the inhibition of ERK/NF-κB signalling pathways

Chronic inflammation is associated with the occurrence of several diseases. However, the side effects of anti-inflammatory drugs prompt the identification of new therapeutic strategies. Plant-derived extracellular vesicles (PDEVs) are gaining increasing interest in the scientific community for their biological properties. We isolated PDEVs from the juice of Citrus limon L. (LEVs) and characterized their flavonoid, limonoid and lipid contents through reversed-phase high-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (RP-HPLC-ESI-Q-TOF-MS). To investigate whether LEVs have a protective role on the inflammatory process, murine a…

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Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an Interleukin 8-dependent survival of leukemia cells

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the Bcr-Abl oncoprotein with constitutive tyrosine kinase activity. Exosomes are nanovesicles released by cancer cells that are involved in cell-to-cell communication thus potentially affecting cancer progression. It is well known that bone marrow stromal microenvironment contributes to disease progression through the establishment of a bi-directional crosstalk with cancer cells. Our hypothesis is that exosomes could have a functional role in this crosstalk. Interleukin-8 (IL 8) is a proinflammatory chemokine that activates multiple signalling pathways downstream of two receptors (CXCR1 and CXCR2). We demon…

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Preliminary Results of CitraVes™ Effects on Low Density Lipoprotein Cholesterol and Waist Circumference in Healthy Subjects after 12 Weeks: A Pilot Open-Label Study

Appropriate monitoring and control of modifiable risk factors, such as the level of low-density lipoprotein cholesterol (LDL-C) and other types of dyslipidemia, have an important role in the prevention of cardiovascular diseases (CVD). Recently, various nutraceuticals with lipid-lowering effects have gained attention. In addition to the plant-derived bioactive compounds, recent studies suggested that plant cells are able to release small lipoproteic structures named extracellular vesicles (EVs). The interaction between EVs and mammalian cells could lead to beneficial effects through anti-inflammatory and antioxidant activities. The present study aimed to assess the safety of the new patente…

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Exosomes: Nanocarriers of Biological Messages

Cell-cell communication is crucial to maintain homeostasis in multicellular organism. Cells communicate each other by direct contact or by releasing factors that, soluble or packaged in membrane vesicles, can reach different regions of the organism. To date numerous studies highlighted the existence of several types of extracellular vesicles that, differing for dimension, origin and contents, play a role in physiological and/or pathological processes. Among extracellular vesicles, exosomes are emerging as efficient players to modulate target cells phenotype and as new non-invasive diagnostic and prognostic tools in multiple diseases. They, in fact, strictly reflect the type and functional s…

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Emerging insights on the biological impact of extracellular vesicle-associated ncRNAs in multiple Myeloma

Increasing evidence indicates that extracellular vesicles (EVs) released from both tumor cells and the cells of the bone marrow microenvironment contribute to the pathobiology of multiple myeloma (MM). Recent studies on the mechanisms by which EVs exert their biological activity have indicated that the non-coding RNA (ncRNA) cargo is key in mediating their effect on MM development and progression. In this review, we will first discuss the role of EV-associated ncRNAs in different aspects of MM pathobiology, including proliferation, angiogenesis, bone disease development, and drug resistance. Finally, since ncRNAs carried by MM vesicles have also emerged as a promising tool for early diagnos…

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