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 blasts compared to normal hematopoietic cells and thus is able to act as a receptor target in a cancer drug delivery system. Here we show that IL3L exosomes, loaded with Imatinib or with BCR-ABL siRNA, are able to target CML cells and inhibit in vitro and in vivo cancer cell growth.

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 standard" of OSCC diagnosis; however, recent studies have evaluated the potential use of non-invasive methods, such as "liquid biopsy," for the detection of diagnostic and prognostic biomarkers in body fluids of oral cancer patients. Saliva is a biofluid containing factors such as cytokines, DNA and RNA molecules, circulating and tissuederived cells, and extracellular vesicles (EVs) that may be used as biomarkers; their analysis may give us useful information to do early diagnosis of OSCC and improve the prognosis. Therefore, the aim of this review is reporting the most recent data on saliva biomarker detection in saliva liquid biopsy from oral cancer patients, with particular attention to circulating tumor DNA (ctDNA), EVs, and microRNAs (miRNAs). Our results highlight that saliva liquid biopsy has several promising clinical uses in OSCC management; it is painless, accessible, and low cost and represents a very helpful source of diagnostic and prognostic biomarker detection. Even if standardized protocols for isolation, characterization, and evaluation are needed, recent data suggest that saliva may be successfully included in future clinical diagnostic processes, with a considerable impact on early treatment strategies and a favorable outcome.

No abstract

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 FISIOGRAFT Bone Granular R and Matriderm R collagen scaffolds on mesenchymal stem cells isolated from periodontally compromised gingiva as a low-cost and painless strategy of autologous bone tissue regeneration. Materials and Methods: We isolated human mesenchymal stem cells from 22 healthy and 26 periodontally compromised gingival biopsy tissues and confirmed the stem cell phenotype by doubling time assay, colony-forming unit assay, and expression of surface and nuclear mesenchymal stem cell markers, respectively by cytofluorimetry and realtime quantitative PCR. Healthy and periodontally compromised gingival mesenchymal stem cells were seeded on FISIOGRAFT Bone Granular R and Matriderm R scaffolds, and in vitro cell viability and bone differentiation were then evaluated. Results: Even though preliminary, the results demonstrate that FISIOGRAFT Bone Granular R is not suitable for in vitro growth and osteogenic differentiation of healthy and periodontally compromised mesenchymal stem cells, which, instead, are able to grow, homogeneously distribute, and bone differentiate in the Matriderm R collagen scaffold.

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 molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.