322 research outputs found
The role played by Wnt/beta-catenin signaling pathway in acute lymphoblastic leukemia.
No full textAcute lymphoblastic leukemia (ALL) is an aggressive hematologic neoplastic disorder that arises from the clonal expansion of transformed T-cell or B-cell precursors. Thanks to progress in chemotherapy protocols, ALL outcome has significantly improved. However, drug-resistance remains an unresolved issue in the treatment of ALL and toxic effects limit dose escalation of current chemotherapeutics. Therefore, the identification of novel targeted therapies to support conventional chemotherapy is required. The Wnt/β-catenin pathway is a conserved signaling axis involved in several physiological processes such as development, differentiation, and adult tissue homeostasis. As a result, deregulation of this cascade is closely related to initiation and progression of various types of cancers, including hematological malignancies. In particular, deregulation of this signaling network is involved in the transformation of healthy HSCs in leukemic stem cells (LSCs), as well as cancer cell multi-drug-resistance. This review highlights the recent findings on the role of Wnt/β-catenin in hematopoietic malignancies and provides information on the current status of Wnt/β-catenin inhibitors with respect to their therapeutic potential in the treatment of ALL
Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL)
No full textThe Hedgehog (HH) signaling network is one of the main regulators of invertebrate and vertebrate embryonic development. Along with other networks, such as NOTCH and WNT, HH signaling specifies both the early patterning and the polarity events as well as the subsequent organ formation via the temporal and spatial regulation of cell proliferation and differentiation. However, aberrant activation of HH signaling has been identified in a broad range of malignant disorders, where it positively influences proliferation, survival, and therapeutic resistance of neoplastic cells. Inhibitors targeting the HH pathway have been tested in preclinical cancer models. The HH pathway is also overactive in other blood malignancies, including T-cell acute lymphoblastic leukemia (T-ALL). This review is intended to summarize our knowledge of the biological roles and pathophysiology of the HH pathway during normal T-cell lymphopoiesis and in T-ALL. In addition, we will discuss potential therapeutic strategies that might expand the clinical usefulness of drugs targeting the HH pathway in T-ALL
"Guerra alla Droga" o Crimini contro l'Umanità? Una valutazione processuale del caso delle Filippine davanti alla Corte Penale Internazionale. “War on Drugs” or Crimes Against Humanity? A Procedural Appraisal of the situation in the Philippines before the International Criminal Court.
No full textL’Autore, dopo aver ripercorso il caso della cosiddetta “guerra alla droga” nelle Filippine, attualmente pendente innanzi la Procura della Corte Penale Internazionale, si sofferma su tre principali problematiche: una sostanziale, riguardante le fattispecie di reato previste dallo Statuto di Roma; due processuali, attinenti rispettivamente alle questioni di giurisdizione ed alle le condizioni di procedibilità, con un approfondimento della c.d. preliminary examination e del principio di complementarità.
The Author, after examining the situation of the so-called “war on drugs” in the Philippines, currently under the attention of the Office of the Prosecutor of the International Criminal Court, dwells on three main issues: one concerning the crimes established in the Rome Statute; the other two regarding the procedural issues of jurisdiction and admissibility, with a thorough analysis of both the preliminary examination and the complementarity principle
Anatomia del reato di tortura. Riflessi attuali e conseguenze processuali.
No full textCo-author Avv. Alessandro Continiello.
Con questo breve scritto si vuole approfondire tale nuova fattispecie di reato, che è stata oggetto di varie polemiche, sia da parte della dottrina che da parte dell’opinione pubblica e politica. La sua introduzione nel nostro ordinamento ha luogo con la legge 14 luglio del 2017 numero 110, che ha recepito, con enorme ritardo, le indicazioni contenute nell'ormai risalente, ma attualissima, Convenzione di New York del 1984 . Nella predetta Convenzione si faceva infatti riferimento ai principi generali proclamati nella Carta delle Nazioni Unite, per quanto concerne il “riconoscimento dei diritti uguali e inalienabili della famiglia umana” quale fondamento della libertà e della giustizia.Nello specifico, in virtù dell’articolo 55 della Carta, gli Stati sono tenuti “a promuovere il rispetto universale ed effettivo dei diritti dell’uomo e delle libertà fondamentali”, alla luce dell’articolo 5 della Dichiarazione Universale dei Diritti dell’Uomo nonché dell’articolo 7 del Patto Internazionale sui Diritti Civili e Politici. Tale fattispecie viene introdotta nel codice penale per colmare un vuoto, in quanto, prima della sua entrata in vigore, l'unico reato previsto in punizione della tortura, nell'ordinamento italiano, era quello di cui all'art. 185 bis del codice penale militare di guerra
Age-Related Alterations Affecting the Chondrogenic Differentiation of Synovial Fluid Mesenchymal Stromal Cells in an Equine Model
No full textOsteoarthritis is a degenerative disease that strongly correlates with age and promotes the breakdown of joint cartilage and subchondral bone. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stromal cells (MSCs) isolated from adult tissues. It seems that MSCs derived from synovial joint tissues exhibit superior chondrogenic ability, but their unclear distribution and low frequency actually limit their clinical application. To date, the influence of aging on synovial joint derived MSCs' biological characteristics and differentiation abilities remains unknown, and a full understanding of the mechanisms involved in cellular aging is lacking. The aim of this study was therefore to investigate the presence of age-related alterations in synovial fluid MSCs and their influence on the potential ability of MSCs to differentiate toward chondrogenic phenotypes. Synovial fluid MSCs, isolated from healthy equine donors from 3 to 40 years old, were cultured in vitro and stimulated towards chondrogenic differentiation for up to 21 days. An equine model was chosen due to the high degree of similarity of the anatomy of the knee joint to the human knee joint and as spontaneous disorders develop that are clinically relevant to similar human disorders. The results showed a reduction in cell proliferation correlated with age and the presence of age-related tetraploid cells. Ultrastructural analysis demonstrated the presence of morphological features correlated with aging such as endoplasmic reticulum stress, autophagy, and mitophagy. Alcian blue assay and real-time PCR data showed a reduction of efficiency in the chondrogenic differentiation of aged synovial fluid MSCs compared to young MSCs. All these data highlighted the influence of aging on MSCs' characteristics and ability to differentiate towards chondrogenic differentiation and emphasize the importance of considering age-related alterations of MSCs in clinical applications
Industry 4.0, quality management and TQM world. A systematic literature review and a proposed agenda for further research - DOI 10.1108/TQM-04-2020-0082
No full textPurpose – The main purpose of this paper is to analyse the current literature situation in terms of relationships between Industry 4.0 and quality management and TQM. The author wanted to understand what topics and issues can be considered the most relevant referring to the so-called Quality 4.0, what the literature is missing opening avenues for further research. Design/methodology/approach – This research employed a systematic literature review. In total, 75 papers from different sources were reviewed using specific inclusion and exclusion criteria. Findings – Four categories of topics emerged, namely: creating value within the company through quality (big) data, analytics and artificial intelligence; developing Quality 4.0 skills and culture for quality people; customer value co-creation; cyber–physical systems and ERP for quality assurance and control. This paper also tried to understand if there is a definition of Quality 4.0 based on determined methods. Research limitations/implications – Systematic literature review could have introduced some limitations in terms of the number and reliability of reviewed papers. Probably some interesting papers had been not intentionally missed. Practical implications – Consultants and managers in developing and implementing their own Quality 4.0 models could use many practical and discussed implications concerning I4.0 technologies and quality management. Originality/value – This is one of the first papers which employed the systematic literature review for researching Industry 4.0, quality management and TQM relationships
Le Procedure In Caso Di Ammissione Di Colpevolezza Nella Corte Penale Internazionale: Una “Terza Via” Tra Common Law E Civil Law The proceedings on an admission of guilt in the International Criminal Court: a «third avenue» between Common Law and Civil Law
No full textL’Autore, dopo essersi soffermato sull’analisi strettamente processuale del caso Al Mahdi, appro- fondisce la problematica questione della natura giuridica delle «procedure in caso di ammissione di colpevolezza» nella CPI. In un’ottica di recente emancipazione dell’International Criminal Procedure emerge una “terza via” non riconducibile né alla common law né alla civil law, caratterizzata da quattro particolarità: 1) la possibilità delle parti di proporre alla Corte un accordo contenente una forbice edittale di pena; 2) la celebrazione del dibattimento dopo l’accordo sulla pena; 3) il potere del giudice di riconoscere circostanze aggravanti o attenuanti non contenute nell’accordo; 4) la rinuncia all’appello condizionata al margine di pena proposto.
The Author, after analyzing the Al Mahdi case with a strictly procedural approach, goes in-depth into the problematic issue of the juridical nature of “proceedings on an admission of guilt” in the ICC. In a recent view of emancipation of International Criminal Procedure, a “third avenue” emerges, as highlighted in the judgment of the ICC, not attributable to either the Common Law or Civil Law, with these four characteristics: 1) the possibility to present the Court with a bargain containing a range of years defined for sentence; 2) the hearing after the agreement; 3) the possibility for the judge to enforce aggravating or mitigating circumstances not contained in the bargain; 4) the renouncement to the right of appeal, depending on the years defined in the bargain
ABDOMINAL AORTIC ANEURYSM: CELLULAR SENESCENCE IN MESENCHYMAL STROMAL CELLS OF THE AORTIC WALL
No full textAGE-RELATED ALTERATION AFFECTING THE BEHAVIOR OF SYNOVIAL FLUID MESENCHYMAL STROMAL CELLS IN AN EQUINE MODEL
No full textDevelopment and 3D Printing of AESO-Based Composites Containing Olive Pit Powder
No full textBio-based polymeric composites were prepared by dispersing different amounts of olive pit (OP) powder within an acrylate epoxidized soybean oil (AESO) photocurable resin using tetrahydrofurfuryl acrylate (THFA) as diluent and (2,4,6-trimethylbenzoyl), phosphine oxide (BAPO) as photo-initiator, and they were photocured by Vat Photopolymerization (VP) using a Liquid Crystal Display (LCD) 3D printer. Formulation viscosity was studied because of its important role in a VP process able to influence the printability of the final parts. Different 3D printed architectures were successfully realized with good resolution and accuracy, high level of detail, and flexibility. The effect of OP addition was investigated by thermal (TGA and DSC), morphological (SEM and PSD), viscoelastic (DMA), and mechanical (tensile testing) characterization. The filler led to an increase in the Tg, storage modulus, and tensile properties, underlining the stiffening effect induced by the OP particles onto the polymeric starting resin. This underlines the possibility to apply these bio-based composites in many application fields by valorizing agro-wastes, developing more sustainable materials, and taking advantages of VP 3D printing, such as low costs, minimal wastage, and customized geometry. Biocompatibility tests were also successfully carried out. The results clearly indicate that the AESO-based composites promote cell adhesion and viability
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