0000000000102034
AUTHOR
Alice Conigliaro
showing 51 related works from this author
Nanogel-antimiR-31 conjugates affect colon cancer cells behaviour
2017
Soft and flexible nanogels, produced by electron beam (e-beam) irradiation of poly(N-vinyl pyrrolidone) and acrylic acid, were evaluated as delivery devices of the inhibitor of miR-31, a small RNA molecule with an important role in colorectal cancer (CRC) progression. The nanogel carriers developed possess both carboxyl and primary amino groups; the former were activated to react with the primary amino group present in the purposely-functionalised AntimiR-31. Very high conjugation reaction yields were attained, as well as a remarkable colloidal and storage stability of the conjugates. The ability of these nanoconstructs to be internalized by cells and the specific interaction of conjugated …
LE VESCICOLE EXTRACELLULARI VEGETALI PER LO SVILUPPO DI NUOVI NUTRACEUTICI: STUDIO PRE-CLINICO E CLINICO DELLE PROPRIETÀ BIOLOGICHE DELLE VESCICOLE I…
2021
Razionale dello studio: Le vescicole extracellulari (EVs) sono strutture lipoproteiche rilasciate dalle cellule animali e vegetali, che veicolano sostanze bioattive tra cui lipidi, proteine, acidi nucleici e altri metaboliti, rendendole più stabili e biodisponibili. EVs isolate da semi, foglie e frutti di svariate specie vegetali presentano attività anti-tumorale, anti-infiammatoria ed anti-ossidante. Metodi e Risultati: Il nostro gruppo di ricerca si occupa da anni della caratterizzazione strutturale e funzionale delle EVs da succo di limone (LEVs). Le LEVs esercitano effetti antinfiammatori sia in vitro, su linee di macrofagi murini, che ex vivo, su linfociti T, attraverso l’inibizione de…
PO-162 Long non coding RNA H19 (IncH19) is required for the hypoxia mediated multiple myeloma progression
2018
ABSTRACT Introduction Multiple myeloma (MM) is a malignant disorder of post-germinal centre B cells, characterised by the clonal proliferation of malignant plasma cells within the bone marrow (BM). The hypoxic condition that develops in the BM niche during progression of MM, has been shown to play a major role in i) the dissemination of MM, ii) the proliferation of MM cells and iii) the induction of drug resistance finally determining a poor prognosis for MM patients. The molecular mechanisms driving hypoxic responses is the activation and nuclear translocation of the Hypoxia-inducible factor 1-alpha, (HIF1α) that, in turns, induce the expression of genes controlling angiogenesis, hypermeta…
Hypoxia-Induced miR-675-5p Supports β-Catenin Nuclear Localization by Regulating GSK3-β Activity in Colorectal Cancer Cell Lines
2020
The reduction of oxygen partial pressure in growing tumors triggers numerous survival strategies driven by the transcription factor complex HIF1 (Hypoxia Inducible Factor-1). Recent evidence revealed that HIF1 promotes rapid and effective phenotypic changes through the induction of non-coding RNAs, whose contribution has not yet been fully described. Here we investigated the role of the hypoxia-induced, long non-coding RNA H19 (lncH19) and its intragenic miRNA (miR-675-5p) into HIF1-Wnt crosstalk. During hypoxic stimulation, colorectal cancer cell lines up-regulated the levels of both the lncH19 and its intragenic miR-675-5p. Loss of expression experiments revealed that miR-675-5p inhibitio…
Mir-675-5p supports hypoxia-induced drug resistance in colorectal cancer cells.
2022
Abstract Background The uncontrolled proliferation of cancer cells determines hypoxic conditions within the neoplastic mass with consequent activation of specific molecular pathways that allow cells to survive despite oxygen deprivation. The same molecular pathways are often the cause of chemoresistance. This study aims to investigate the role of the hypoxia-induced miR-675-5p in 5-Fluorouracil (5-FU) resistance on colorectal cancer (CRC) cells. Methods CRC cell lines were treated with 5-Fu and incubated in normoxic or hypoxic conditions; cell viability has been evaluated by MTT assay. MiR-675-5p levels were analysed by RT-PCR and loss and gain expression of the miRNA has been obtained by t…
Mucoadhesive Polymeric Films to Enhance Barbaloin Penetration Into Buccal Mucosa: a Novel Approach to Chemoprevention.
2018
Nowadays, chemoprevention by administering natural supplements is considered an attractive strategy to reverse, suppress, or prevent the evolution of premalignant oral lesions. In particular, Barbaloin exhibits anti-proliferative, anti-inflammatory, and anti-cancer properties, and it results useful in multi-therapy with classic chemotherapeutics. Therefore, in this work, mucoadhesive buccal films, as locoregional drug delivery system able to provide a targeted and efficient therapeutic delivery of Barbaloin, are proposed. Thus, Aloin extract-loaded Eudragit (R) RL100 or Eudragit (R) RS100-based buccal films were designed in order to obtain an easily self-administrable formulation capable of…
How miR-31-5p and miR-33a-5p Regulates SP1/CX43 Expression in Osteoarthritis Disease: Preliminary Insights
2021
Osteoarthritis (OA) is a degenerative bone disease that involved micro and macro-environment of joints. To date, there are no radical curative treatments for OA and novel therapies are mandatory. Recent evidence suggests the role of miRNAs in OA progression. In our previous studies, we demonstrated the role of miR-31-5p and miR-33a families in different bone regeneration signaling. Here, we investigated the role of miR-31-5p and miR-33a-5p in OA progression. A different expression of miR-31-5p and miR-33a-5p into osteoblasts and chondrocytes isolated from joint tissues of OA patients classified in based on different Kellgren and Lawrence (KL) grading was highlighted
Convergence of Wnt signaling on the HNF4alpha-driven transcription in controlling liver zonation.
2009
Background & Aims: In each hepatocyte, the specific repertoire of gene expression is influenced by its exact location along the portocentrovenular axis of the hepatic lobule and provides a reason for the liver functions compartmentalization defined "metabolic zonation." So far, few molecular players controlling genetic programs of periportal (PP) and perivenular (PV) hepatocytes have been identified; the elucidation of zonation mechanisms remains a challenge for experimental hepatology. Recently, a key role in induction and maintenance of the hepatocyte heterogeneity has been ascribed to Wnt/β-catenin pathway. We sought to clarify how this wide-ranging stimulus integrates with hepatocyte s…
Extracellular Vesicle microRNAs Contribute to the Osteogenic Inhibition of Mesenchymal Stem Cells in Multiple Myeloma
2020
Osteolytic bone disease is the major complication associated with the progression of multiple myeloma (MM). Recently, extracellular vesicles (EVs) have emerged as mediators of MM-associated bone disease by inhibiting the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Here, we investigated a correlation between the EV-mediated osteogenic inhibition and MM vesicle content, focusing on miRNAs. By the use of a MicroRNA Card, we identified a pool of miRNAs, highly expressed in EVs, from MM cell line (MM1.S EVs), expression of which was confirmed in EVs from bone marrow (BM) plasma of patients affected by smoldering myeloma (SMM) and MM. Notably,we found that miR-129-5p, whic…
Altered insulin pathway compromises mitochondrial function and quality control both in in vitro and in vivo model systems.
2021
Abstract Altered insulin signaling and insulin resistance are considered the link between Alzheimer's disease (AD) and metabolic syndrome. Here, by using an in vitro and an in vivo model, we investigated the relationship between these disorders focusing on neuronal mitochondrial dysfunction and mitophagy. In vitro Aβ insult induced the opening of mitochondrial permeability transition pore (mPTP), mitochondrial membrane potential (ΔΨm) loss, and apoptosis while insulin addition ameliorated these dysfunctions. The same alterations were detected in a 16 weeks of age mouse model of diet-induced obesity and insulin resistance. In addition, we detected an increase of fission related proteins and …
Biological Properties of a Citral-Enriched Fraction of Citrus limon Essential Oil
2020
Lemon essential oil (LEO) is a well-known flavoring agent with versatile biological activities. In the present study, we have isolated and characterized four citral-enriched fractions of winter LEO. We reported that in murine and human macrophages the pre-treatment with a mix of these fractions (Cfr-LEO) reduces the expression of the pro-inflammatory cytokines TNF-&alpha
Isolation and characterization of a murine resident liver stem cell.
2008
Increasing evidence provides support that mammalian liver contains stem/progenitor cells, but their molecular phenotype, embryological derivation, biology and their role in liver cell turnover and regeneration remain to be further clarified. In this study, we report the isolation, characterization and reproducible establishment in line of a resident liver stem cell (RLSC) with immunophenotype and differentiative potentiality distinct from other previously described liver precursor/stem cells. RLSCs, derived from fetal and neonatal murine livers as well as from immortalized hepatocytic MMH lines and established in lines, are Sca+, CD34-, CD45-, alpha-fetoprotein+ and albumin-. This molecular…
Long Non Coding RNA H19: A New Player in Hypoxia-Induced Multiple Myeloma Cell Dissemination
2019
The long non-coding RNA H19 (lncH19) is broadly transcribed in the first stage of development and silenced in most cells of an adult organism
MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation
2019
Mesenchymal stromal cells (hMSCs) display a pleiotropic function in bone regeneration. The signaling involved in osteoblast commitment is still not completely understood, and that determines the failure of current therapies being used. In our recent studies, we identified two miRNAs as regulators of hMSCs osteoblast differentiation driving hypoxia signaling and cytoskeletal reorganization. Other signalings involved in this process are epithelial to mesenchymal transition (EMT) and epidermal growth factor receptor (EGFR) signalings through the regulation of Yes-associated protein (YAP)/PDZ-binding motif (TAZ) expression. In the current study, we investigated the role of miR-33a family as a (…
An epistatic mini-circuitry between the transcription factors Snail and HNF4α controls liver stem cell and hepatocyte features exhorting opposite reg…
2011
Preservation of the epithelial state involves the stable repression of epithelial-to-mesenchymal transition program, whereas maintenance of the stem compartment requires the inhibition of differentiation processes. A simple and direct molecular mini-circuitry between master elements of these biological processes might provide the best device to keep balanced such complex phenomena. In this work, we show that in hepatic stem cell Snail, a transcriptional repressor of the hepatocyte differentiation master gene HNF4α, directly represses the expression of the epithelial microRNAs (miRs)-200c and-34a, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4α, p…
TGFβ-induced EMT requires focal adhesion kinase (FAK) signaling
2007
The epithelial-to-mesenchymal transition (EMT) is a crucial process, occurring both during development and tumor progression, by which an epithelial cell undergoes a conversion to a mesenchymal phenotype, dissociates from initial contacts and migrates to secondary sites. We recently reported that in hepatocytes the multifunctional cytokine TGFβ induces a full EMT characterized by (i) Snail induction, (ii) E-cadherin delocalization and down-regulation, (iii) down-regulation of the hepatocyte transcriptional factor HNF4α and (iv) up-regulation of mesenchymal and invasiveness markers. In particular, we showed that Snail directly causes the transcriptional down-regulation of E-cadherin and HN…
Evidence for a common progenitor of epithelial and mesenchymal components of the liver
2013
Tissues of the adult organism maintain the homeostasis and respond to injury by means of progenitor/stem cell compartments capable to give rise to appropriate progeny. In organs composed by histotypes of different embryological origins (e.g. The liver), the tissue turnover may in theory involve different stem/precursor cells able to respond coordinately to physiological or pathological stimuli. In the liver, a progenitor cell compartment, giving rise to hepatocytes and cholangiocytes, can be activated by chronic injury inhibiting hepatocyte proliferation. The precursor compartment guaranteeing turnover of hepatic stellate cells (HSCs) (perisinusoidal cells implicated with the origin of the …
MiR675-5p Acts on HIF-1α to Sustain Hypoxic Responses: A New Therapeutic Strategy for Glioma
2016
Hypoxia is a common feature in solid tumours. In glioma, it is considered the major driving force for tumour angiogenesis and correlates with enhanced resistance to conventional therapies, increased invasiveness and a poor prognosis for patients. Here we describe, for the first time, that miR675-5p, embedded in hypoxia-induced long non-coding RNA H19, plays a mandatory role in establishing a hypoxic response and in promoting hypoxia-mediated angiogenesis. We demonstrated, in vitro and in vivo, that miR675-5p over expression in normoxia is sufficient to induce a hypoxic moreover, miR675-5p depletion in low oxygen conditions, drastically abolishes hypoxic responses including angiogenesis. In …
The stable repression of mesenchymal program is required for hepatocyte identity: A novel role for hepatocyte nuclear factor 4α
2011
The concept that cellular terminal differentiation is stably maintained once development is complete has been questioned by numerous observations showing that differentiated epithelium may undergo an epithelial-to-mesenchymal transition (EMT) program. EMT and the reverse process, mesenchymal-to-epithelial transition (MET), are typical events of development, tissue repair, and tumor progression. In this study, we aimed to clarify the molecular mechanisms underlying these phenotypic conversions in hepatocytes. Hepatocyte nuclear factor 4α (HNF4α) was overexpressed in different hepatocyte cell lines and the resulting gene expression profile was determined by real-time quantitative polymerase…
Data on the effects of low iron diet on serum lipid profile in HCV transgenic mouse model
2017
Here, we presented new original data on the effects of iron depletion on the circulating lipid profile in B6HCV mice, a murine model of HCV-related dyslipidemia. Male adult B6HCV mice were subjected to non-invasive iron depletion by low iron diet. Serum iron concentration was assessed for evaluating the effects of the dietary iron depletion. Concentrations of circulating triglycerides, total cholesterol, Low Density Lipoproteins (LDLs), High Density Lipoproteins (HDLs) were analyzed and reported by using stacked line charts. The present data indicated that low serum iron concentration is associated to i) lower serum triglycerides concentrations and ii) increased circulating LDLs. The presen…
Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic ir…
2014
Hepatitis C virus (HCV)-induced iron overload has been shown to promote liver fibrosis, steatosis, and hepatocellular carcinoma. The zonal-restricted histological distribution of pathological iron deposits has hampered the attempt to perform large-scale in vivo molecular investigations on the comorbidity between iron and HCV. Diagnostic and prognostic markers are not yet available to assess iron overload-induced liver fibrogenesis and progression in HCV infections. Here, by means of Spike-in SILAC proteomic approach, we first unveiled a specific membrane protein expression signature of HCV cell cultures in the presence of iron overload. Computational analysis of proteomic dataset highlighte…
MiR-675-5p supports hypoxia induced epithelial to mesenchymal transition in colon cancer cells
2017
// Viviana Costa 1, * , Alessia Lo Dico 2, * , Aroldo Rizzo 3 , Francesca Rajata 3 , Marco Tripodi 4, 5 , Riccardo Alessandro 6, 7, * , Alice Conigliaro 4, * 1 Innovative Technological Platforms for Tissue Engineering, Theranostic and Oncology, Rizzoli Orthopedic Institute, Palermo, Italy 2 Department of Pathophysiology and Transplantation, Universita degli Studi di Milano, Milano, Italy 3 Unita Operativa di Anatomia Patologica, Azienda Ospedaliera Ospedali Riuniti “Villa Sofia-Cervello”, Palermo, Italy 4 Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza University of Rome, Rome, Italy 5 National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy 6 Dipartimen…
Hepatic progenitors for liver disease: current position
2010
Alice Conigliaro1, David A Brenner2, Tatiana Kisseleva21University “La Sapienza”, Dipartimento di Biotecnologie Cellulari ed Ematologia Policlinico Umberto I, V Clinica Medica, Rome, Italy; 2Department of Medicine, University of California, San Diego, La Jolla, CA, USAAbstract: Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangi…
Developing liver spheroids for elucidating the role of colorectal cancer-derived smallextracellular vesicles in the pre-metastatic niche formation
2022
Introduction: Colorectal cancer (CRC) is the third most common tumor in the world frequently associated with liver metastasiscausing unfavorable prognosis. A recent study performed in our laboratory has demonstrated that CRC small extracellular vesi-cles (SEVs) induce an epithelial to mesenchymal transition (EMT) of hepatocytes (heps) driving them to actively participate inthe pre-metastatic niche formation, probably contributing to form a liver fibrotic microenvironment. Since 2D cell cultures par-tially reflect the structural complexity of the in vivo microenvironment to give more power to our functional model, we switchedto use hepatocyte spheroids (HeSPHs), which can give us more proper…
Development of a Multifunctional Bioerodible Nanocomposite Containing Metronidazole and Curcumin to Apply on L-PRF Clot to Promote Tissue Regeneratio…
2020
Teeth extractions are often followed by alveolar bone reabsorption, although an adequate level of bone is required for reliable rehabilitations by dental implants. Leukocyte and platelet-rich fibrin (L-PRF) has been widely applied in regenerative procedures and with antibiotic and antioxidant agents could play an essential role in hard and soft tissue healing. In this work, a nanocomposite (Sponge-C-MTR) consisting of a hyaluronate-based sponge loaded with metronidazole (MTR) and nanostructured lipid carriers containing curcumin (CUR-NLC) was designed to be wrapped in the L-PRF&trade
CD90+ liver cancer cells modulate endothelial cell phenotype through the release of exosomes containing H19 lncRNA
2015
Background CD90+ liver cancer cells have been described as cancer stem-cell-like (CSC), displaying aggressive and metastatic phenotype. Using two different in vitro models, already described as CD90+ liver cancer stem cells, our aim was to study their interaction with endothelial cells mediated by the release of exosomes. Methods Exosomes were isolated and characterized from both liver CD90+ cells and hepatoma cell lines. Endothelial cells were treated with exosomes, as well as transfected with a plasmid containing the full length sequence of the long non-coding RNA (lncRNA) H19. Molecular and functional analyses were done to characterize the endothelial phenotype after treatments. Results …
Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs
2018
Abstract Bone microenvironment provides growth and survival signals essential for osteosarcoma (OS) initiation and progression. OS cells regulate communications inside tumor microenvironment through different ways and, among all, tumor-derived exosomes support cancer progression and metastasis. To define the contribution of OS-derived exosomes inside the microenvironment, we investigated the effects induced in bone remodeling mechanism and tumor angiogenesis. We demonstrated that exosomes promoted osteoclasts differentiation and bone resorption activity. Furthermore, exosomes potentiated tube formation of endothelial cells and increased angiogenic markers expression. We therefore investigat…
Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4…
2021
Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), a…
Hepatocyte-targeted fluorescent nanoparticles based on a polyaspartamide for potential theranostic applications
2015
Abstract Here, the synthesis of a galactosylated amphiphilic copolymer bearing rhodamine (RhB) moieties and its use for the preparation of polymeric fluorescent nanoparticles for potential applications in therapy and diagnosis are described. To do this, firstly, a fluorescent derivative of α,β-poly( N -2-hydroxyethyl)- d , l -aspartamide (PHEA) was synthesized by chemical reaction with RhB, and with polylactic acid (PLA), to obtain PHEA-RhB-PLA. Then, the derivatization of PHEA-RhB-PLA with GAL-PEG-NH 2 allows obtaining PHEA-RhB-PLA-PEG-GAL copolymer, with derivatization degrees in -PLA and -PEG-GAL equal to 1.9 mol% and 4.5 mol%, respectively. Starting from this copolymer, liver-targeted f…
SENP1 activity sustains cancer stem cell in hypoxic HCC
2017
Hepatocellular carcinoma (HCC) represents the fifth most common cancer and the third leading cause of cancer mortality worldwide, with a minority of patients surviving at 5 years from diagnosis, despite treatment.1 HCC usually develops in conditions of chronic liver disease (CLD), mostly on the background of a cirrhotic liver, with liver transplantation at present being the only treatment strategy to cure both HCC and the specific CLD. All the other therapeutic strategies, because of the underlying liver cirrhosis, have to take into account, and may be limited in their feasibility, by the residual liver function of the individual patient, a critical parameter affecting the patient's prognos…
Exosome-Mediated Signaling in Epithelial to Mesenchymal Transition and Tumor Progression
2018
Growing evidence points to exosomes as key mediators of cell–cell communication, by transferring their specific cargo (e.g., proteins, lipids, DNA and RNA molecules) from producing to receiving cells. In cancer, the regulation of the exosome-mediated intercellular communication may be reshaped, inducing relevant changes in gene expression of recipient cells in addition to microenvironment alterations. Notably, exosomes may deliver signals able to induce the transdifferentiation process known as Epithelial-to-Mesenchymal Transition (EMT). In this review, we summarize recent findings on the role of exosomes in tumor progression and EMT, highlighting current knowledge on exosome-mediated inter…
Nobiletin and xanthohumol counteract the TNFα-mediated activation of endothelial cells through the inhibition of the NF-κB signaling pathway.
2022
Angiogenesis, a process characterized by the formation of new blood vessels from pre-existing ones, is a crucial step in tumor growth and dissemination. Given the ability of tumors to interfere with multiple or different molecular pathways to promote angiogenesis, there is an increasing need to therapeutically block tumor progression by targeting multiple antiangiogenic pathways. Natural polyphenols present health-protective properties, which are likely attributed to their ability to activate multiple pathways involved in inflammation, carcinogenesis, and angiogenesis. Recently, increased attention has been addressed to the ability of flavonoids, the most abundant polyphenols in the diet, t…
Exosome A Clinical Compendium - Chapter 1: Exosome basic mechanisms
2019
Cell-cell communication plays a key role in maintaining homeostasis in multicellular organism. Cells communicate each other not only via the canonical pathways (cytokines, neurotransmitters, direct contact, ECM-mediated interactions or hormones) but also releasing extracellular vesicles that can reach different regions of the organism acting as a new “endocrine signalling mechanism”. Among extracellular vesicles, exosomes are emerging as efficient players to modulate target cells phenotype through the delivery to compliant receiving cells of a multitude of molecules such as mRNAs, microRNAs, long non-coding RNAs, DNA, lipids, metabolites and proteins. A deeper understanding of their content…
Hypoxia‐induced non‐coding rnas controlling cell viability in cancer
2021
Hypoxia, a characteristic of the tumour microenvironment, plays a crucial role in cancer progression and therapeutic response. The hypoxia-inducible factors (HIF-1α, HIF-2α, and HIF-3α), are the master regulators in response to low oxygen partial pressure, modulating hypoxic gene expression and signalling transduction pathways. HIFs’ activation is sufficient to change the cell phenotype at multiple levels, by modulating several biological activities from metabolism to the cell cycle and providing the cell with new characteristics that make it more aggressive. In the past few decades, growing numbers of studies have revealed the importance of non-coding RNAs (ncRNAs) as molecular mediators i…
The new murine hepatic 3A cell line responds to stress stimuli by activating an efficient Unfolded Protein Response (UPR)
2012
In the present study we have investigated the properties of a novel cell line (3A cells) obtained from the liver of 14.5. days post coitum (dpc) wild-type mouse embryo. 3A cells morphology was characterized by fluorescent localization of F-actin and β-catenin. The expression of specific genes and proteins essential to liver function in these cells was comparable or even more efficient then in the differentiated hepatocytic cell line MMH-D6. 3A cells also showed the capability to excrete molecules in extracellular spaces resembling functional bile canaliculi, glycogen storage activity and the ability to control retinol-binding protein 4 secretion in response to retinol deprivation. Their re…
SILAC labeling coupled to shotgun proteomics analysis of membrane proteins of liver stem/hepatocyte allows to candidate the inhibition of TGF-beta pa…
2014
Background: Despite extensive research on hepatic cells precursors and their differentiated states, much remains to be learned about the mechanism underlying the self-renewal and differentiation.Results: We apply the SILAC (stable isotope labeling by amino acids in cell culture) approach to quantitatively compare the membrane proteome of the resident liver stem cells (RLSCs) and their progeny spontaneously differentiated into epithelial/hepatocyte (RLSCdH). By means of nanoLC-MALDI-TOF/TOF approach, we identified and quantified 248 membrane proteins and 57 of them were found modulated during hepatocyte differentiation. Functional clustering of differentially expressed proteins by Ingenuity …
Exosome basic mechanisms
2020
Abstract Cell-cell communication plays a key role in maintaining homeostasis in multicellular organism. Cells communicate each other not only via the canonical pathways (cytokines, neurotransmitters, direct contact, ECM-mediated interactions or hormones) but also releasing extracellular vesicles that can reach different regions of the organism acting as a new “endocrine signalling mechanism”. Among extracellular vesicles, exosomes are emerging as efficient players to modulate target cells phenotype through the delivery to compliant receiving cells of a multitude of molecules such as mRNAs, microRNAs, long non-coding RNAs, DNA, lipids, metabolites and proteins. A deeper understanding of thei…
Rapamycin-Loaded Polymeric Nanoparticles as an Advanced Formulation for Macrophage Targeting in Atherosclerosis
2021
Recently, rapamycin (Rapa) represents a potential drug treatment to induce regression of atherosclerotic plaques
Anti-inflammatory properties of lemon-derived extracellular vesicles are achieved through the inhibition of ERK/NF-κB signalling pathways
2022
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…
miR-31-5p Is a LIPUS-Mechanosensitive MicroRNA that Targets HIF-1α Signaling and Cytoskeletal Proteins
2019
The roles of low-intensity pulsed ultrasound (LIPUS) and microRNAs (miRNAs) on hMSCs commitments have already been investigated
Molecular Mediators of RNA Loading into Extracellular Vesicles
2021
In the last decade, an increasing number of studies have demonstrated that non-coding RNA (ncRNAs) cooperate in the gene regulatory networks with other biomolecules, including coding RNAs, DNAs and proteins. Among them, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are involved in transcriptional and translation regulation at different levels. Intriguingly, ncRNAs can be packed in vesicles, released in the extracellular space, and finally internalized by receiving cells, thus affecting gene expression also at distance. This review focuses on the mechanisms through which the ncRNAs can be selectively packaged into extracellular vesicles (EVs).
Preliminary Results of CitraVes™ Effects on Low Density Lipoprotein Cholesterol and Waist Circumference in Healthy Subjects after 12 Weeks: A Pilot O…
2021
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…
Exosomes: Nanocarriers of Biological Messages
2017
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…
Colorectal cancer-derived small extracellular vesicles induce TGFβ1-mediated epithelial to mesenchymal transition of hepatocytes
2023
Abstract Background Metastatic disease is the major cause of cancer-related deaths. Increasing evidence shows that primary tumor cells can promote metastasis by preparing the local microenvironment of distant organs, inducing the formation of the so-called “pre-metastatic niche”. In recent years, several studies have highlighted that among the tumor-derived molecular components active in pre-metastatic niche formation, small extracellular vesicles (sEVs) play a crucial role. Regarding liver metastasis, the ability of tumor-derived sEVs to affect the activities of non-parenchymal cells such as Kupffer cells and hepatic stellate cells is well described, while the effects on hepatocytes, the m…
Emerging insights on the biological impact of extracellular vesicle-associated ncRNAs in multiple Myeloma
2020
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…
Expression analysis of jagged genes in zebrafish embryos
2005
The interaction of transmembrane Delta and Jagged/Serrate ligands with Notch receptors on neighboring cells is critically involved in cell specification during development. In zebrafish, the early expression of delta but not of jagged genes has been investigated in some detail. We have analyzed the sequence and embryonic expression pattern of the three zebrafish genes jagged1a, jagged1b, and jagged2. These genes, whose transcripts are detectable by in situ hybridization from early somitogenesis, are widely and dynamically expressed in embryos. Coexpression is limited, however, to the notochord and lens (jagged1a and jagged1b) and to the otic vesicle and pronephros (jagged1b and jagged2). Co…
Extracellular Matrix Molecular Remodeling in Human Liver Fibrosis Evolution
2016
Chronic liver damage leads to pathological accumulation of ECM proteins (liver fibrosis). Comprehensive characterization of the human ECM molecular composition is essential for gaining insights into the mechanisms of liver disease. To date, studies of ECM remodeling in human liver diseases have been hampered by the unavailability of purified ECM. Here, we developed a decellularization method to purify ECM scaffolds from human liver tissues. Histological and electron microscopy analyses demonstrated that the ECM scaffolds, devoid of plasma and cellular components, preserved the three-dimensional ECM structure and zonal distribution of ECM components. This method has been then applied on 57 l…
Hypoxia-inducible factor 1Α may regulate the commitment of mesenchymal stromal cells toward angio-osteogenesis by mirna-675-5P
2017
Abstract Background aims During bone formation, angiogenesis and osteogenesis are regulated by hypoxia, which is able to induce blood vessel formation, as well as recruit and differentiate human mesenchymal stromal cells (hMSCs). The molecular mechanisms involved in HIF-1α response and hMSC differentiation during bone formation are still unclear. This study aimed to investigate the synergistic role of hypoxia and hypoxia-mimetic microRNA miR-675-5p in angiogenesis response and osteo-chondroblast commitment of hMSCs. Methods By using a suitable in vitro cell model of hMSCs (maintained in hypoxia or normoxia), the role of HIF-1α and miR-675-5p in angiogenesis and osteogenesis coupling was inv…
Human Haemato-Endothelial Precursors: Cord Blood CD34+ Cells Produce Haemogenic Endothelium
2012
Embryologic and genetic evidence suggest a common origin of haematopoietic and endothelial lineages. In the murine embryo, recent studies indicate the presence of haemogenic endothelium and of a common haemato-endothelial precursor, the haemangioblast. Conversely, so far, little evidence supports the presence of haemogenic endothelium and haemangioblasts in later stages of development. Our studies indicate that human cord blood haematopoietic progenitors (CD34+45+144-), triggered by murine hepatocyte conditioned medium, differentiate into adherent proliferating endothelial precursors (CD144+CD105+CD146+CD31+CD45-) capable of functioning as haemogenic endothelium. These cells, proven to give…
Additional file 1 of Mir-675-5p supports hypoxia-induced drug resistance in colorectal cancer cells
2022
Additional file 1.
Additional file 1: of CD90+ liver cancer cells modulate endothelial cell phenotype through the release of exosomes containing H19 lncRNA
2015
(a) Characterization of isolated exosomes. Left panel: DSL for exosomes released by SKHep Middle panel: Western blot forTsg101 and HSC70 in SkHep cells and their relative exosomes. Right panel: Confocal microscopy analysis on HUVECs treated for 1, 3 and 6 hours with 5 mg/ml of SKHep-derived exosomes. HUVECs were stained with phalloidin Alexa Fluor (green), nuclear counterstaining was performed using DAPI (blue), exosomes were labelled with PKH26 (red). (b) Target analysis. Real time-PCR analysis on HUVECs treated for 18 h with 5 mg/ml of SkHep-derived exosomes. Normalized for b-actin the DDct were indicated as fold of induction respect to control (untreated cells). *p<0.05. (c) Tubulogen…