0000000000069127
AUTHOR
Marta Cristaldi
Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo chronic myelogenous Leukemia cell growth
Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents. In this study, we engineered HEK293T cells to express the exosomal protein Lamp2b, fused to a fragment of Interleukin 3 (IL3). The IL3 receptor (IL3-R) is overexpressed in CML…
Cigarette smoke promotes inflammasome‐independent activation of caspase‐1 and ‐4 leading to gasdermin D cleavage in human macrophages
Mechanisms and consequences of gasdermin D (GSDMD) activation in cigarette smoke (CS)-associated inflammation and lung disease are unknown. GSDMD is a downstream effector of caspase-1, -8, and -4. Upon cleavage, GSDMD generates pores into cell membranes. Different degrees of GSDMD activation are associated with a range of physiological outputs ranging from cell hyperactivation to pyroptosis. We have previously reported that in human monocyte-derived macrophages CS extract (CSE) inhibits the NLRP3 inflammasome and shifts the response to lipopolysaccharide (LPS) towards the TLR4-TRIF axis leading to activation of caspase-8, which, in turn, activates caspase-1. In the present work, we investig…
Salivary Biomarkers for Oral Squamous Cell Carcinoma Diagnosis and Follow-Up: Current Status and Perspectives.
Oral cancer is the sixth most common cancer type in the world, and 90% of it is represented by oral squamous cell carcinoma (OSCC). Despite progress in preventive and therapeutic strategies, delay in OSCC diagnosis remains one of the major causes of high morbidity and mortality; indeed the majority of OSCC has been lately identified in the advanced clinical stage (i.e., III or IV). Moreover, after primary treatment, recurrences and/or metastases are found in more than half of the patients (80% of cases within the first 2 years) and the 5-year survival rate is still lower than 50%, resulting in a serious issue for public health. Currently, histological investigation represents the “gold stan…
Growth and Osteogenic Differentiation of Discarded Gingiva-Derived Mesenchymal Stem Cells on a Commercial Scaffold
Background In periodontal patients with jawbone resorption, the autologous bone graft is considered a "gold standard" procedure for the placing of dental prosthesis; however, this procedure is a costly intervention and poses the risk of clinical complications. Thanks to the use of adult mesenchymal stem cells, smart biomaterials, and active biomolecules, regenerative medicine and bone tissue engineering represent a valid alternative to the traditional procedures. Aims In the past, mesenchymal stem cells isolated from periodontally compromised gingiva were considered a biological waste and discarded during surgical procedures. This study aims to test the osteoconductive activity of FISIOGRAF…
The phospholipase DDHD1 as a new target in colorectal cancer therapy
Background Our previous study demonstrates that Citrus-limon derived nanovesicles are able to decrease colon cancer cell viability, and that this effect is associated with the downregulation of the intracellular phospholipase DDHD domain-containing protein 1 (DDHD1). While few studies are currently available on the contribution of DDHD1 in neurological disorders, there is no information on its role in cancer. This study investigates the role of DDHD1 in colon cancer. Methods DDHD1 siRNAs and an overexpression vector were transfected into colorectal cancer and normal cells to downregulate or upregulate DDHD1 expression. In vitro and in vivo assays were performed to investigate the functional…
Label-free quantitative proteomic profiling of colon cancer cells identifies acetyl-CoA carboxylase alpha as antitumor target of Citrus limon-derived nanovesicles
Abstract We have previously isolated exosome-like nanoparticles from Citrus-limon juice, able to inhibit in vitro and in vivo tumor cell growth. In order to deeply understand the mechanism underlying nanovesicle effects, we performed a proteomic profile of treated colorectal cancer cells. Among the proteins differentially expressed after nanovesicle treatment, we found a significant downregulation of the Acetyl-CoA Carboxylase 1 (ACACA) and we demonstrated that silencing ACACA in cancer cells leads to a reduction of cell growth. Our study proved that the anti-tumor effects of Citrus-limon nanovesicles is partly mediated by lipid metabolism inhibition, in particular via ACACA downregulation.…
Human exfoliated deciduous teeth and oral mucosa: promising applications in tissue regeneration
In the last three decades, the constantly increasing need for therapies, efficiently preventing and/or treating human diseases, has raised the interest in Regenerative Medicine (RM). RM is based on employing mesenchymal stem cells (MSCs), that showed to have great proliferation, self-renewal and multilineage differentiation potential, in vitro as well as in vivo. The opportunity of an accessible, painless and low-cost reservoir of MSCs constitutes the first important step of a successful regenerative therapy to include in the current clinical practice. Oral cavity has recently demonstrated to contain different MSCs niches: dental pulp from permanent and deciduous teeth, periodontal ligament…
Dental pulp stem cells for bone tissue engineering: a review of the current literature and a look to the future.
The aim of this narrative review is to investigate the implication of mesenchymal stem cells harvested from human dental pulp in in vivo bone tissue regeneration. We focused on studies related to roles of human dental pulp stem cells in in vivo bone regeneration. A total of 1021 studies were identified; after the assessment of eligibility, only 39 studies were included in the review. The evaluated information of the studies regards the experimental strategies (e.g., the isolation method, the scaffold, the in vivo animal models). The overall main evidences highlighted from the analysis are that dental pulp stem cells and human-exfoliated deciduous teeth stem cells supported by a suitable sc…
PO-053 The phospholipase ddhd1 as a new target in colorectal cancer therapy
Introduction We have recently demonstrated that Citrus-limon derived nanovesicles are able to decrease colon cancer cell viability and that this effect is associated with the down-regulation of the intracellular phospholipase DDHD domain-containing protein 1 (DDHD1). While few studies are currently available on DDHD1 contribution in neurological disorders, information on its involvement in cancer is missing. Here we investigate the role of DDHD1 in colon cancer. Material and methods DDHD1 siRNAs and overexpression vector were transfected into colorectal cancer and normal cells to down-regulate or up-regulate DDHD1 expression. In vitro and in vivo assays were performed to investigate the fun…
Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract
Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molec…
Additional file 1: of The phospholipase DDHD1 as a new target in colorectal cancer therapy
Supplementary Material and Methods. (DOCX 24Â kb)
In vitro and in vivo investigations of osteogenic differentiation ability of dental pulp stem cells (DPSCs) and gingival mesenchymal stem cells (GMSCs) by use of nanostructured scaffolds
Thanks to the use of human mesenchymal stem cells (hMSCs), smart biomaterials and active biomolecules, Regenerative Medicine (RM) and Bone Tissue Engineering (BTE) can restore structure and function of injured tissues. Among the different sources of hMSCs, the oro-facial hMSCs have promising in vitro and in vivo regeneration potential; in particular, dental pulp and gingiva are valuable sources of autologous hMSCs. The aim of this PhD thesis is testing the in vitro and in vivo bone regeneration ability of hMSCs isolated from dental pulp and inflamed gingiva of periodontally-compromised teeth, up to now considered biological waste tissues and discarded during surgical procedures, on two comm…
Additional file 3: of The phospholipase DDHD1 as a new target in colorectal cancer therapy
Table S1. Data from SWATH-MS Gene Ontology analysis. (XLSX 740Â kb)
Additional file 4: of The phospholipase DDHD1 as a new target in colorectal cancer therapy
Figure S2. Effects of DDHD1-expressing cells conditioned medium on DDHD1-silenced cell growth. Cell viability was measured by MTT assay on DDHD1-silenced SW480 cells in the presence of the conditioned medium (CM) of mock cells and DDHD1 overexpressing cells. (TIFF 3275Â kb)
Additional file 2: of The phospholipase DDHD1 as a new target in colorectal cancer therapy
Figure S1. DDHD1 silencing. To evaluate DDHD1 silencing a. Real-time PCR and b. Western blot analysis were performed on SW480, HCT116, HS5 and HUVEC transfected for 48 or 72Â h with scrambled siRNA or DDHD1 siRNA. (TIFF 6629Â kb)