Filamin A cooperates with the androgen receptor in preventing skeletal muscle senescence.

Aging induces a slow and progressive decrease in muscle mass and function, causing sarcopenia. Androgens control muscle trophism and exert important anabolic functions through the binding to the androgen receptor. Therefore, analysis of the androgen receptor-mediated actions in skeletal muscle might provide new hints for a better understanding of sarcopenia pathogenesis. In this study, we report that expression of the androgen receptor in skeletal muscle biopsies from 20 subjects is higher in young, as compared with old subjects. Co-immunoprecipitation experiments reveal that the androgen receptor is complexed with filamin A mainly in young, that in old subjects. Therefore, we have in depth analyzed the role of such complex using C2C12 myoblasts that express a significant amount of the androgen receptor. In these cells, hormone stimulation rapidly triggers the assembly of the androgen receptor/filamin A complex. Such complex prevents the senescence induced by oxidative stress in C2C12 cells, as disruption of the androgen receptor/filamin A complex by Rh-2025u stapled peptide re-establishes the senescent phenotype in C2C12 cells. Simultaneously, androgen stimulation of C2C12 cells rapidly triggers the activation of various signaling effectors, including Rac1, focal adhesion kinase, and mitogen-activated kinases. Androgen receptor blockade by bicalutamide or perturbation of androgen receptor/filamin A complex by Rh-2025u stapled peptide both reverse the hormone activation of signaling effectors. These findings further reinforce the role of the androgen receptor and its extranuclear partners in the rapid hormone signaling that controls the functions of C2C12 cells. Further investigations are needed to promote clinical interventions that might ameliorate muscle cell function as well the clinical outcome of age-related frailty.

RIZ2 at the crossroad of the EGF/EGFR signaling in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most deadly and fourth most diagnosed cancer worldwide. Despite the progress in early diagnosis and advanced therapeutic options, CRC shows a poor prognosis with a 5 year survival rate of ~ 45%. PRDM2/RIZ, a member of PR/SET domain family (PRDM), expresses two main molecular variants, the PR-plus isoform (RIZ1) and the PR-minus (RIZ2). The imbalance in their expression levels in favor of RIZ2 is observed in many cancer types. The full length RIZ1 has been extensively investigated in several cancers where it acts as a tumor suppressor, whereas few studies have explored the RIZ2 oncogenic properties. PRDM2 is often target of frameshift mutations and aberrant DNA methylation in CRC. However, little is known about its role in CRC. METHODS: We combined in-silico investigation of The Cancer Genome Atlas (TCGA) CRC datasets, cellular and molecular assays, transcriptome sequencing and functional annotation analysis to assess the role of RIZ2 in human CRC. RESULTS: Our in-silico analysis on TCGA datasets confirmed that PRDM2 gene is frequently mutated and transcriptionally deregulated in CRC and revealed that a RIZ2 increase is highly correlated with a significant RIZ1 downregulation. Then, we assayed several CRC cell lines by qRT-PCR analysis for the main PRDM2 transcripts and selected DLD1 cell line, which showed the lowest RIZ2 levels. Therefore, we overexpressed RIZ2 in these cells to mimic TCGA datasets analysis results and consequently to assess the PRDM2/RIZ2 role in CRC. Data from RNA-seq disclosed that RIZ2 overexpression induced profound changes in CRC cell transcriptome via EGF pathway deregulation, suggesting that RIZ2 is involved in the EGF autocrine regulation of DLD1 cell behavior. Noteworthy, the forced RIZ2 expression increased cell viability, growth, colony formation, migration and organoid formation. These effects could be mediated by the release of high EGF levels by RIZ2 overexpressing DLD1 cells. CONCLUSIONS: Our findings add novel insights on the putative RIZ2 tumor-promoting functions in CRC, although additional efforts are warranted to define the underlying molecular mechanism.

Agri-Food By-Products in Cancer: New Targets and Strategies.

The globalization and the changes in consumer lifestyles are forcing us to face a deep transformation in food demand and in the organization of the entire food production system. In this new era, the food-loss and food-waste security nexus is relevant in the global debate and avoiding unsustainable waste in agri-food systems as well as the supply chain is a big challenge. "Food waste" is useful for the recovery of its valuable components, thus it can assume the connotation of a "food by-product". Sustainable utilization of agri-food waste by-products provides a great opportunity. Increasing evidence shows that agri-food by-products are a source of different bioactive molecules that lower the inflammatory state and, hence, the aggressiveness of several proliferative diseases. This review aims to summarize the effects of agri-food by-products derivatives, already recognized as promising therapeutics in human diseases, including different cancer types, such as breast, prostate, and colorectal cancer. Here, we examine products modulating or interfering in the signaling mediated by the epidermal growth factor receptor.

[Home-based telemonitoring of simple vital signs to reduce hospitalization in heart failure patients: real-world data from a community-based hospital]. / Telemetria per il controllo domiciliare della pressione arteriosa, della frequenza cardiaca e della saturimetria di ossigeno nello scompenso cardiaco: impatto sulle ospedalizzazioni in un contesto non sperimentale.

BACKGROUND: Whether home telemonitoring after acute episodes of heart failure (HF) may reduce de-novo cardiac decompensation is disputed. We tested home telemonitoring of blood pressure (BP), heart rate (HR), and blood oxygen saturation (SO2) to reduce rehospitalization in patients with recent admission for acute HF. METHODS; We screened patients hospitalized in Cardiology due to prominent cardiac cause of acute dyspnea, and pulmonary/peripheral congestion, and with one admission or more for similar symptoms/signs in the previous year. Patients with acute coronary syndrome, poor prognosis due to extracardiac causes, and reduced self-sufficiency and cognitive ability were excluded. Of the selected patients, 63% accepted and received a device for BP, HR and SO2 measurement connected to an analogical modem for data transmission to a hospital server. Patients were educated to measure vital signs 3 times/week. A dedicated doctor-nurse unit monitored the patients' data twice weekly to manage therapeutic adjustments of diuretic dosage or in-hospital visits if necessary. HF treatment was standardized based on current guidelines. Unplanned hospitalizations for HF or all-cause death were primary endpoints; unplanned hospitalizations (total) for any cause, and all-cause death were the composite endpoints. RESULTS: Twenty-three patients (mean age 70 years, range 44-80 years) were recruited: 26% were women, 61% had coronary heart disease, 52% chronic lung disease, 57% renal insufficiency, 30% anemia; 17% had moderate or severe mitral regurgitation. At a mean follow-up of 302 days (range 55-622 days), 12 patients experienced the composite endpoints (52%, p=0.1), with the primary endpoint occurring in 8 patients (35%, 1 sudden death, p=0.058), the secondary endpoints occurring in 2 patients, and hospitalization not for HF occurring in 2 patients. The total number of hospitalizations/patient/year decreased from 2.2 ± 1.3 in the previous year to 0.9 ± 1.2 during the study period (p<0.01). On average, systolic BP tended to decrease, but BP, HR and SO 2 values prior to the index event (1-7 days) did not significantly differ from those recorded at the beginning of telemonitoring. CONCLUSIONS: In HF, home telemonitoring of simple variables had no significant impact on all-cause hospitalization/mortality, but was associated with a higher patient compliance and achievement of therapeutic targets, which may translate into a reduction in hospitalization rates for HF.