LPS, Oleuropein and Blueberry extracts affect the survival, morphology and Phosphoinositide signalling in stimulated human endothelial cells

Endothelial cells (EC) act as leading actors in angiogenesis. Understanding the complex network of signal transduction pathways which regulate angiogenesis might offer insights in the regulation of normal and pathological events, including tumours, vascular, inflammatory and immune diseases. The effects of olive oil and of Blueberry extracts upon the phosphoinositide (PI)-specific phospholipase C (PLC) enzymes were evaluated both in quiescent and inflammatory stimulated human umbilical vein EC (HUVEC) using molecular biology (multiliquid bioanalysis) and immunofluorescence techniques. Oleuropein significantly increased the number of surviving HUVEC compared to untreated controls, suggesting that it favours the survival and proliferation of EC. Our results suggest that Oleuropein might be useful to induce EC proliferation, an important event during angiogenesis, with special regard to wound healing. Blueberry extracts increased the number of surviving HUVEC, although the comparison to untreated controls did not result statistically significant. Lipopolysaccharide (LPS) administration significantly reduced the number of live HUVEC. LPS can also modify the expression of selected PLC genes. Adding Blueberry extracts to LPS treated HUVEC cultures did not significantly modify the variations of PLC expression induced by LPS. Oleuropein increased or reduced the expression of PLC genes, and statistically significant results were identified for selected PLC isoforms. Oleuropein also modified the effects of LPS upon PLC genes\u2019 expression. Thus, our results corroborate the hypothesis that Oleuropein owns anti-inflammatory activity. The intracellular localization of PLC enzymes was modified by the different treatments we used. Podosome-like structures were observed in differently LPS treated HUVEC

Urothelial bladder carcinoma metastasizing to the eye: A systematic review and case report

The eye is a rare site for disseminated malignancies; nevertheless, several tumors may metastasize to ocular structures. Few cases of urothelial and bladder cancer with eye involvement have been described in the literature thus far. The rarity of metastatic ocular localization implies an accurate differential diagnosis among the possible primary tumor sites. However, a specific diagnostic algorithm is not currently available, nor a defined therapeutic approach. Eye metastases are associated with advanced disease and poor prognosis. Physicians should be made aware of the possibility of eye involvement in patients with a past medical history of urothelial bladder cancer associated with ocular symptoms. The present case reports discusses the first documented case, to the best of our knowledge, of an urothelial bladder cancer metastasizing to the retro bulbar region that infiltrates the lacrimal gland. Furthermore, the report provides a systematic qualitative review of the current literature on eye metastases from urothelial bladder cancer using the Preferred Reporting Items for Systematic Reviews and Meta Analyses

JAK/Stat5-mediated subtype-specific lymphocyte antigen 6 complex, locus G6D (LY6G6D) expression drives mismatch repair proficient colorectal cancer

Background: Human microsatellite-stable (MSS) colorectal cancers (CRCs) are immunologically "cold" tumour subtypes characterized by reduced immune cytotoxicity. The molecular linkages between immune-resistance and human MSS CRC is not clear. Methods: We used transcriptome profiling, in silico analysis, immunohistochemistry, western blot, RT-qPCR and immunofluorescence staining to characterize novel CRC immune biomarkers. The effects of selective antagonists were tested by in vitro assays of long term viability and analysis of kinase active forms using anti-phospho antibodies. Results: We identified the lymphocyte antigen 6 complex, locus G6D (LY6G6D) as significantly overexpressed (around 15-fold) in CRC when compared with its relatively low expression in other human solid tumours. LY6G6D up-regulation was predominant in MSS CRCs characterized by an enrichment of immune suppressive regulatory T-cells and a limited repertoire of PD-1/PD-L1 immune checkpoint receptors. Coexpression of LY6G6D and CD15 increases the risk of metastatic relapse in response to therapy. Both JAK-STAT5 and RAS-MEK-ERK cascades act in concert as key regulators of LY6G6D and Fucosyltransferase 4 (FUT4), which direct CD15-mediated immune-resistance. Momelotinib, an inhibitor of JAK1/JAK2, consistently abrogated the STAT5/LY6G6D axis in vitro, sensitizing MSS cancer cells with an intact JAK-STAT signaling, to efficiently respond to trametinib, a MEK inhibitor used in clinical setting. Notably, colon cancer cells can evade JAK2/JAK1-targeted therapy by a reversible shift of the RAS-MEK-ERK pathway activity, which explains the treatment failure of JAK1/2 inhibitors in refractory CRC. Conclusions: Combined targeting of STAT5 and MAPK pathways has superior therapeutic effects on immune resistance. In addition, the new identified LY6G6D antigen is a promising molecular target for human MSS CRC

Considerazioni sull'art. 2645 ter cod. civ.: destinazione di patrimoni e categorie dell'iniziativa privata

Destinazione è termine non univoco. In senso assai ampio si può forse dire che vi è destinazione quale fenomeno rilevante per il diritto ogni qual volta l’individuazione – da parte dei privati o della legge – di un interesse non coincidente con quello preso in considerazione nella costruzione della disciplina dei rapporti aventi quale terminale oggettivo un bene produca una modificazione di tale disciplina. Ancora, da altra angolatura ma sempre in termini generalissimi, si può forse dire che vi è destinazione quando la mutazione dell’interesse induce una correlativa modificazione della consistenza di bene sub specie juris di una cosa o di una utilità. Tuttavia, l’ampiezza descrittiva porta con sé una sostanziale inutilità costruttiva. Segnatamente, le ipotesi di destinazione esibite dal codice civile in misura cospicua non possono essere comprese nella logica di una categoria unitaria. La destinazione dell’art. 2645 ter si colloca in un novero di fenomeni caratterizzati: dall’individuazione di un interesse diverso da quello fondante la situazione giuridica di partenza; da un conseguente mutamento dello statuto giuridico del patrimonio destinato; in particolare, dalla conseguente irrilevanza degli statuti proprietari e delle discipline ritagliate sulla titolarità; dal rilievo, invece, oggettivo dell’interesse quale dato unificante del patrimonio: non attributo del soggetto, con funzione di garanzia, ma esso stesso centro d’interesse; dalla programmazione di un’attività attuativa della destinazione, e dalla determinazione delle sua regole. Più sinteticamente, nell’ampia ed eterogenea accezione di destinazione è possibile delimitare una categoria di fenomeni caratterizzata da ciò, che prendono vita a mezzo di atti di organizzazione. Ribaltando i termini: gli atti finalizzati a destinare, nel senso (anche) dell’art. 2645 ter , assumono rilievo per il diritto soltanto allorché siano idonei a produrre l’effetto di modificazione del diritto oggettivo che è proprio degli atti di organizzazione. La destinazione senza tale effetto o è mera programmazione (non vincolante) della modalità di esercizio della facoltà di godere da parte del titolare del diritto sul patrimonio, o è programmazione di una destinazione futura

Persona giuridica, destinazione e segregazione

in corso di stamp