MTOR and STAT3 pathway hyper-activation is associated with elevated interleukin-6 levels in patients with shwachman-diamond syndrome: Further evidence of lymphoid lineage impairment

Shwachman–Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome, resulting in neutropenia and a risk of myeloid neoplasia. A mutation in a ribosome maturation factor accounts for almost all of the cases. Lymphoid involvement in SDS has not been well characterized. We recently reported that lymphocyte subpopulations are reduced in SDS patients. We have also shown that the mTOR-STAT3 pathway is hyper-activated in SDS myeloid cell populations. Here we show that mTOR-STAT3 signaling is markedly upregulated in the lymphoid compartment of SDS patients. Furthermore, our data reveal elevated IL-6 levels in cellular supernatants obtained from lymphoblasts, bone marrow mononuclear and mesenchymal stromal cells, and plasma samples obtained from a cohort of 10 patients. Of note, everolimus-mediated inhibition of mTOR signaling is associated with basal state of phosphorylated STAT3. Finally, inhibition of mTOR-STAT3 pathway activation leads to normalization of IL-6 expression in SDS cells. Altogether, our data strengthen the hypothesis that SDS affects both lymphoid and myeloid blood compartment and suggest everolimus as a potential therapeutic agent to reduce excessive mTOR-STAT3 activation in SDS

Approaches in biotechnological applications of natural polymers

Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)

History and scientific production of clinica medica and clinica ematologica in ancona

Clinica Medica and Ematologica in Ancona stemmed some 30 years ago from one originator medical team dedicated to Internal Medicine practice with a special interest towards immunological and hematological studies. This original scientific interest has spread over a multitude of fellows, some of whom have reached outstanding academic and clinical results, maintaining and extending the excellent reputation of the founding group over the years and until the present time. The best scientific achievements have been obtained in the field of systemic sclerosis and chronic graft versus host disease, whereas the clinical activity has been successfully dedicated to the management of autoimmune diseases and hematological disorders, with particular attention to innovative immunomodulatory therapies and stem cell transplantation

CoPE Project (Consumer Protection Effectiveness) - Towards a Digital Effectiveness of Consumer Protection Through Self-Executing Remedies and ADR Systems: An Empirical Approach to European Private Law

L\u2019effettivit\ue0 dei diritti del consumatore costituisce oggetto di una letteratura giuridica ed economica fortemente critica verso il modello europeo tradizionale. Com\u2019\ue8 noto, tale modello si fonda sulla strutturale asimmetria informativa fra soggetti deboli e professionisti. Per evitare il rischio di fallimenti del mercato causati dalla selezione avversa e dall\u2019azzardo morale, il diritto europeo si avvale principalmente di regole di informazione standardizzate, lasciando poi ai singoli Stati nazionali la scelta dei rimedi pi\uf9 idonei ad assicurare l\u2019effettivit\ue0 della loro applicazione. Recenti indagini hanno tuttavia dimostrato che le regole informative dettate dal diritto privato europeo non tengono conto dei profili personali delle parti che concludono una certa operazione, ad es. per quanto riguarda alcuni tratti della personalit\ue0 del consumatore o le conoscenze tecniche sottese ai profili dell\u2019operazione (Ben-Shahar, Bar-Gill, 2013, p. 109 ss.; Ben-Shahar, Golan, 2014). La conseguenza \ue8 che, sebbene apparentemente informato, il consumatore rischia di concludere un contratto senza avere effettiva conoscenza delle condizioni di quella stipulazione e delle conseguenze che da essa derivano. Ci\uf2 in quanto le informazioni fornite sono sostanzialmente inadeguate rispetto alla preparazione tecnica di cui il soggetto debole dispone ovvero all\u2019attenzione da lui (normalmente) riposta nella fase precontrattuale. Inoltre, la tutela giurisdizionale dei diritti del consumatore \ue8 spesso inefficace, soprattutto quando riguarda controversie che hanno a oggetto modeste somme di denaro o beni di consumo: \ue8 allora razionale la scarsa propensione del consumatore a far valere i propri diritti in sede giudiziaria. Sul piano nazionale, il tentativo di assicurare l\u2019effettivit\ue0 dei diritti del consumatore risulta peraltro frustrato dal sostanziale fallimento dell\u2019istituto della mediazione civile obbligatoria (v. i dati forniti dall\u2019Osservatorio Unioncamere sulla mediazione e la conciliazione: https://www.unioncamere.gov.it/). La sua introduzione fu motivata proprio della necessit\ue0 di deflazionare il contenzioso, e segnatamente di evitare, per quanto possibile, la fase processuale, la quale implica ingenti costi per le parti e tempi lunghi per la decisione giudiziale. Se a ci\uf2 si aggiungono le note e gravi sofferenze che da tempo affliggono il processo civile (Comm. from the Commission to the Europ. Parl., the Council, the European Central Bank, the European Economic and Social Committee and the Committees of the Regions, 2020 EU Just. Scor.), l\u2019esigenza di riflettere sul ricorso a strumenti di autotutela e a sistemi stragiudiziali di risoluzione delle controversie diviene pressante e indifferibile, al fine di offrire maggiore effettivit\ue0 ai diritti del consumatore. Ci\uf2 spiega la crescente diffusione dei sistemi di ADR nelle societ\ue0 contemporanee, quantomeno in Europa (Sirena, 2018, p. 1372). Infatti, almeno in determinati settori, i sistemi di risoluzione stragiudiziale delle controversie dei consumatori non risultano intimamente congegnati solo allo scopo di addivenire a una giustizia pi\uf9 evoluta ovvero di deflazionare il contenzioso. Le procedure di ADR, soprattutto se basate su una combinazione di private enforcement e public enforcement, perseguono l\u2019obiettivo finale di indurre i professionisti ad aderire alle best practices e agli standards pi\uf9 elevati di correttezza nei confronti dei loro clienti e di trasparenza dei loro contratti, anzitutto predisponendo adeguati sistemi di gestione in-house dei reclami da parte degli acquirenti di beni e servizi. La progettazione di un sistema pi\uf9 avanzato di risoluzione delle controversie tra consumatori e fornitori di beni e servizi, in linea con le istanze provenienti dalla revisione del diritto europeo (v. Comm. from the Commission to the Europ. Parl., 2020 EU Just. Scor.), si dimostrerebbe maggiormente efficace nel modificare i comportamenti degli intermediari rispetto alla giurisdizione dello Stato, il cui esercizio ha un impatto spesso trascurabile sul livello di compliance degli intermediari e sulla effettivit\ue0 della regolazione del mercato. La letteratura italiana e internazionale ha messo in luce che, in uno scenario del genere, i consumatori assumerebbero il ruolo di co-regolatori del mercato, in quanto i loro reclami potrebbero profondamente influenzare i comportamenti degli intermediari grazie alla stretta interazione con l\u2019esercizio dei poteri di vigilanza da parte delle autorit\ue0 competenti

Biosafety evidence for human dedifferentiated adipocytes

Mature adipocytes have shown dynamic plasticity to be converted into fibroblast-like and lipid-free cells. After the dedifferentiation process, these cells re-entered the cell cycle and acquired a high proliferation potential, becoming a valid source of stem cells. However, many aspects of the cellular biosafety about dedifferentiated fat cells remained unclear. This study aimed to elucidate their potential susceptibility to malignant transformation and to ascertain the safety of these cells for clinical use. To evaluate the genomic stability of dedifferentiated adipocytes, telomere length, hTERT gene transcription, the capacity of these cells to grow in an anchorage-independent manner and the presence of DNA damage by single cell gel electrophoresis assay were studied. Spontaneous chromosomal alterations were excluded by cytogenetic analysis and the expression level of c-myc and p53, tumor associated genes, were assessed, evaluating also p53 loss of function mutations. Despite the high proliferation capacity of dedifferentiated adipocytes, these cells showed stable telomere length compared with mature adipocytes, no hTERT transcriptions and consequently no telomerase activity, suggesting that both transformation and senescence were avoided. A constant expression level of c-myc and p53, the inability of dedifferentiated adipocytes to grow in an anchorage-independent manner, the absence ofDNAdamage suggested the safety of these cells. Moreover, a normal karyotype was preserved throughout the dedifferentiation process. Data in vivo showed that dedifferentiated adipocytes analyzed for tumorigenicity did not develop tumors. In conclusion, our data indicated that dedifferentiated adipocytes could be a relatively easily accessible resource for cell therapy and regenerative medicine

Pancreatic cystadenocarcinoma: diagnostic problems

Eleven cases of pancreatic cystadenocarcinoma were studied with respect to the differential diagnosis from that of pancreatic pseudocysts, using diagnostic ultrasound as the initial investigative technique. Most of the cases presented an ultrasonic picture that correlated well with the gross pathology, but this correlation was not reliable enough to be considered characteristic in differentiating such masses from pseudocysts. The authors divide the cystadenocarcinomas of the pancreas into four echographic classes. In all but one of the classes, diagnostic ultrasound was insufficient by itself to render an accurate diagnosis. In such cases other techniques, i.e. CT, tissue biopsy, and especially angiography, were required for a reliable diagnosis