Risultati per: Università di Padova: scoperta molecola a base di rame che colpisce i tumori solidi

Un ceppo produce molecole che ‘smascherano le cellule tumorali’

Nuovo sistema di diagnosi avanzate integra dati sanitari e IA

Oncologa, alimentazione aspetto importante per una buona qualità di vita

Corsa solidale in 24 città italiane, raccolti 400mila euro

Circulation, Ahead of Print. BACKGROUND:Cardiovascular diseases are the main cause of worldwide morbidity and mortality, highlighting the need for new therapeutic strategies. Autophosphorylation and subsequent overactivation of the cardiac stress-responsive enzyme CaMKIIδ (Ca2+/calmodulin-dependent protein kinase IIδ) serves as a central driver of multiple cardiac disorders.METHODS:To develop a comprehensive therapy for heart failure, we used CRISPR-Cas9 adenine base editing to ablate the autophosphorylation site of CaMKIIδ. We generated mice harboring a phospho-resistant CaMKIIδ mutation in the germline and subjected these mice to severe transverse aortic constriction, a model for heart failure. Cardiac function, transcriptional changes, apoptosis, and fibrosis were assessed by echocardiography, RNA sequencing, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and standard histology, respectively. Specificity towardCaMKIIδgene editing was assessed using deep amplicon sequencing. Cellular Ca2+homeostasis was analyzed using epifluorescence microscopy in Fura-2–loaded cardiomyocytes.RESULTS:Within 2 weeks after severe transverse aortic constriction surgery, 65% of all wild-type mice died, and the surviving mice showed a dramatically impaired cardiac function. In contrast to wild-type mice, CaMKIIδ phospho-resistant gene-edited mice showed a mortality rate of only 11% and exhibited a substantially improved cardiac function after severe transverse aortic constriction. Moreover, CaMKIIδ phospho-resistant mice were protected from heart failure–related aberrant changes in cardiac gene expression, myocardial apoptosis, and subsequent fibrosis, which were observed in wild-type mice after severe transverse aortic constriction. On the basis of identical mouse and human genome sequences encoding the autophosphorylation site ofCaMKIIδ, we deployed the same editing strategy to modify this pathogenic site in human induced pluripotent stem cells. It is notable that we detected a >2000-fold increased specificity for editing ofCaMKIIδcompared with otherCaMKIIisoforms, which is an important safety feature. Although wild-type cardiomyocytes showed impaired Ca2+transients and an increased frequency of arrhythmias after chronic β-adrenergic stress,CaMKIIδ-edited cardiomyocytes were protected from these adverse responses.CONCLUSIONS:Ablation of CaMKIIδ autophosphorylation by adenine base editing may offer a potential broad-based therapeutic concept for human cardiac disease.

Cure personalizzate sono il presente e il futuro dell’ematologia

A dominare i ranking realizzate da Newsweek sono soprattutto gli ospedali americani quasi sempre da soli sul podio, ma le strutture italiane sono molto presenti in tutti i ranking

Al Broad Institute di Mit e Harvard, verso nuovi farmaci

Lo studio appena pubblicato su Bmj Oncology prevede che i nuovi casi di cancro precoci e i decessi associati aumenteranno rispettivamente nel 2030 di un ulteriore 31% e 21% . E i più a rischio saranno i quarantenni

Italia all’avanguardia, ma ancora troppo pochi professionisti 

L’obiettivo di valutare se la stimolazione elettrica neuromuscolare possa essere uno strumento utile per un migliore adattamento del corpo umano nello spazio avrà importanti ricadute anche sulla Terra per pazienti anziani o con ridotta mobilità. A coordinarlo è Alessandra Bosutti, del dipartimento di Scienze della Vita

Al via a Bologna simposio internazionale sull’oncoematologia

‘Si corona un sogno’, dice il 25enne che ha risposto all’appello

Un tumor board vede impegnati numerosi specialisti dell’Aou

La carenza associata a un maggiore rischio di decesso

In aiuto per individuarla in fase precoce nella forma sporadica