MiR-182-3p targets TRF2 and impairs tumor growth of triple-negative breast cancer

Target therapy; Telomeres; Triple-negative breast cancerTerapia dirigida; Telómeros; Cáncer de mama triple negativoTeràpia dirigida; Telòmers; Càncer de mama triple negatiuThe telomeric repeat-binding factor 2 (TRF2) is a telomere-capping protein that plays a key role in the maintenance of telomere structure and function. It is highly expressed in different cancer types, and it contributes to cancer progression. To date, anti-cancer strategies to target TRF2 remain a challenge. Here, we developed a miRNA-based approach to reduce TRF2 expression. By performing a high-throughput luciferase screening of 54 candidate miRNAs, we identified miR-182-3p as a specific and efficient post-transcriptional regulator of TRF2. Ectopic expression of miR-182-3p drastically reduced TRF2 protein levels in a panel of telomerase- or alternative lengthening of telomeres (ALT)-positive cancer cell lines. Moreover, miR-182-3p induced DNA damage at telomeric and pericentromeric sites, eventually leading to strong apoptosis activation. We also observed that treatment with lipid nanoparticles (LNPs) containing miR-182-3p impaired tumor growth in triple-negative breast cancer (TNBC) models, including patient-derived tumor xenografts (PDTXs), without affecting mouse survival or tissue function. Finally, LNPs-miR-182-3p were able to cross the blood–brain barrier and reduce intracranial tumors representing a possible therapeutic option for metastatic brain lesions.The research leading to these results has been funded by Italian Association for Cancer Research (AIRC # 21579) and Ministry of Health (CO-2019-12369662) to AB. This work was financially supported by Ministry of Health Ricerca Corrente 2022 and intramural grant-in-aid to EP. RD, LP and EP were supported by AIRC fellowships

Duration of constant rate infusion with diazepam or propofol for canine cluster seizures and status epilepticus

IntroductionConstant rate infusion (CRI) of benzodiazepines or propofol (PPF) is a therapeutic option for cluster seizures (CS) and status epilepticus (SE) in canine patients non-responding to first-line benzodiazepines or non-anesthetics. However, specific indications for optimal duration of CRI are lacking. The aim of this study was to determine the effect of duration of anesthetic CRI on outcome and length of hospital stay in dogs with refractory seizure activity of different etiology.Study designOpen-label non-randomized clinical trial.Materials and methodsSeventy-three client-owned dogs were enrolled. Two groups [experimental (EXP) vs. control (CTRL)] were compared. The EXP group received diazepam (DZP) or PPF CRI for 12 h (±1 h) and the CTRL group received DZP or PPF CRI for 24 h (±1 h) in addition to a standardized emergency treatment protocol identical for both study groups. The historical control group was made up of a population of dogs already reported in a previously published paper by the same authors. Favorable outcome was defined as seizure cessation after CRI, no seizure recurrence, and clinical recovery. Poor outcome was defined as seizure recurrence, death in hospital or no return to acceptable clinical baseline. Univariate statistical analysis was performed.ResultsThe study sample was 73 dogs: 45 (62%) received DZP CRI and 28 (38%) received PPF CRI. The EXP group was 39 dogs (25 DZP CRI and 14 PPF CRI) and the CTRL group 34 dogs (20 DZP CRI and 14 PPF CRI). We found no statistically significant difference in outcomes between the groups. The median length of stay was 56 h (IQR, 40–78) for the ALL EXP group and 58.5 h (IQR, 48–74.5) for the ALL CTRL group (p = 0.8).ConclusionEven though a shorter DZP or PPF CRI duration was not associated with a worse outcome, the study failed to identify a clear superiority of shorter CRI duration on outcome or length of hospital stay in dogs with refractory seizure activity of different etiology

Oltre il Segno/OltreMare

La realizzazione di un volume contenente le incisioni scelte all’interno della Scuola di Grafica d’Arte dell’Accademia di Belle Arti di Palermo, coordinata dai Proff. Giovanni D’Alessandro e Riccardo Mazzarino rappresenta motivo di orgoglio e di soddisfazione per la nostra Istituzione che costruisce i percorsi didattici dei propri corsi a partire dall’esperienza laboratoriale. L’incisione grafica è tra le tecniche artistiche più antiche ma nel contempo più contemporanee. La gestualità intrinseca al segno, che si manifesta nella carta, svela universi della visione inaspettati.(Mario Zito - Direttore dell’Accademia di Belle Arti di Palermo) Il segno è il risultato di un gesto a volte deciso, a volte contorto, a volte leggero, i cui risultati spesso sono inattesi e sorprendenti. Il volume contiene esemplari di incisioni fortemente caratterizzanti della scuola di Grafica d’Arte che vanta all’interno del proprio corso di studi docenti-artisti che consapevoli della ricchezza del loro bagaglio esperienziale offrono agli studenti gli strumenti necessari per far sì che l’arte del saper fare artigianale, si trasformi in mera poetica artistica

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Ex-Vivo Tissues Engineering Modeling for Reconstructive Surgery Using Human Adult Adipose Stem Cells and Polymeric Nanostructured Matrix

The major challenge for stem cell translation regenerative medicine is the regeneration of damaged tissues by creating biological substitutes capable of recapitulating the missing function in the recipient host. Therefore, the current paradigm of tissue engineering strategies is the combination of a selected stem cell type, based on their capability to differentiate toward committed cell lineages, and a biomaterial, that, due to own characteristics (e.g., chemical, electric, mechanical property, nano-topography, and nanostructured molecular components), could serve as active scaffold to generate a bio-hybrid tissue/organ. Thus, effort has been made on the generation of in vitro tissue engineering modeling. Here, we present an in vitro model where human adipose stem cells isolated from lipoaspirate adipose tissue and breast adipose tissue, cultured on polymeric INTEGRA® Meshed Bilayer Wound Matrix (selected based on conventional clinical applications) are evaluated for their potential application for reconstructive surgery toward bone and adipose tissue. We demonstrated that human adipose stem cells isolated from lipoaspirate and breast tissue have similar stemness properties and are suitable for tissue engineering applications. Finally, the overall results highlighted lipoaspirate adipose tissue as a good source for the generation of adult adipose stem cells

Clinical benefits and acceptability of two commercial arm exoskeletons for patients with muscular dystrophy

Restore a lost function is a special experience for people affected by neuromuscular evolutive diseases as muscular dystrophy. Upper limb stiffness and activity limitations have a crucial role in reducing patients’ autonomy and worsening quality of life. Even if the commercial products might assure a benefit to some users and meet most of their requirements, so far a validation of the use of such devices by people with neuromuscular diseases is missing. We aim at field-testing the improvement in arm functions provided by the use of two commercial devices (Jaeco Wrex and Armon Ayura) and assessing their impact on users’ quality of life and independence. This step is essential to assure a widespread access to these devices for most of the potential users, possibly presenting direction and guidance to health providers. The results acquired from the first three subjects, with a different disease progression, showed that the functional improvements gained with the use of these exoskeletons are limited and largely depends on the user’s impairment. Results showed that if the patient is severely impaired, the exoskeletons are not sufficient to gain functional movements. In contrast, if the patient is moderately impaired, both devices help the subject, even if some limitations of the movements occur. Finally, if the subject is slightly impaired, both devices decrease the performance. However, all the patients have appreciated the good usability of both devices