The long-lasting protective effect of HGF in cardiomyoblasts exposed to doxorubicin requires a positive feed-forward loop mediated by ERK1,2-TIMP1-STAT3

Previous studies showed that the hepatocyte growth factor (HGF)–Met receptor axis plays long-lasting cardioprotection against doxorubicin anti-cancer therapy. Here, we explored the mechanism(s) underlying the HGF protective effect. DNA damage was monitored by histone H2AX phosphorylation and apoptosis by proteolytic cleavage of caspase 3. In doxorubicin-treated H9c2 cardiomyoblasts, the long-lasting cardioprotection is mediated by activation of the Ras/Raf/Mek/Erk (extracellular signal-regulated kinase 1,2) signaling pathway and requires Stat3 (signal transducer and activator of transcription 3) activation. The HGF protection was abrogated by the Erk1,2 inhibitor, PD98059. This translated into reduced Y705 phosphorylation and impaired nuclear translocation of Stat3, showing crosstalk between Erk1,2 and Stat3 signaling. An array of 29 cytokines, known to activate Stat3, was interrogated to identify the molecule(s) linking the two pathways. The analysis showed a selective increase in expression of the tissue inhibitor of metalloproteinases-1 (Timp1). Consistently, inhibition in cardiomyoblasts of Timp1 translation by siRNAs blunted both Stat3 activation and the cardioprotective effect of HGF. Thus, Timp1 is responsible for the generation of a feed-forward loop of Stat3 activation and helps cardiomyocytes to survive during the genotoxic stress induced by anthracyclines

Brain activity pattern changes after adaptive working memory training in multiple sclerosis

Cognitive impairment and related abnormal brain activity are common in people with multiple sclerosis (PwMS). Adaptive training based on working memory (WM) has been shown to ameliorate cognitive symptoms, although the effects at a neural level are unclear. The aim of this study was to expand the existing research on the effects of an adaptive WM rehabilitative intervention on brain functional activity in PwMS. A sample of eighteen PwMS performed an 8-week home-based cognitive rehabilitation treatment based on adaptive WM training. PwMS were assessed before and after treatment using a validated neuropsychological battery and undergoing an fMRI session while carrying out a cognitive task (i.e., Paced Visual Serial Addition Test - PVSAT). fMRI activations were compared to the activation pattern elicited by eighteen matched healthy subjects performing the same task. At baseline, we found abnormal brain activity during PVSAT in PwMS when compared to healthy subjects, with a pattern including several bilateral activation clusters. Following rehabilitation, PwMS improved cognitive performance, as evaluated by the neuropsychological battery, and showed a different activation map with clusters mainly located in the right cerebellum and in the left hemisphere. The only significant cluster in the right hemisphere was located in the inferior parietal lobule, and the BOLD signal extracted in this area significantly correlated with cognitive performance both before and after the treatment. We suggest that WM training can improve the cognitive performance and reduce the abnormal activation of PwMS by partially maintaining or even restoring brain cognitive function

Solar retinopathy: a new setting of red, green, and blue channels

PURPOSE: To introduce a new color imaging technique using improved settings of red, green, and blue channels for improved delineation of retinal damage in patients with solar retinopathy. METHODS: A retrospective case series of patients with poor vision secondary to solar retinopathy were analyzed. All patients underwent visual acuity, refraction, and dilated fundus examination. A spectral domain–optical coherence tomography of the macula and color fundus imaging using optimized red, green, and blue color setting was performed. Patients were reviewed over a 6-month period. The data were analyzed for statistical significance using an independent t test and a receiver operating characteristic curve. RESULTS: In total, 20 eyes of 10 patients were included between 2009 and 2017. The mean age was 24.9 ± 18.1 years. Best corrected visual acuity at first consultation was 0.78 ± 0.11 and after 6 months was 0.83 ± 0.09. Spectral domain–optical coherence tomography demonstrated retinal abnormalities at the myoid zone, ellipsoid zone, and the outer segment of photoreceptors. Receiver operating characteristic curve analysis showed an improving effect (area under the curve = 0.62; 95% confidence interval = 0.42–0.79). The color channels parameters, which improve visualization of the lesions were found to be 67-0.98-255 for the R-guided setting, 19-0.63-121 for the B-guided setting, and 7-1.00-129 for the G-guided setting. The ideal red, green, and blue setting was in 24-0.82-229. CONCLUSIONS: The use of a new setting of red, green, and blue channels could improve the diagnosis and monitoring of solar retinopathy, hence improving patient care

A multicentric study on prevalence of clinical patterns and clinical phenotypes in adult atopic dermatitis

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Identification of novel circulating microRNAs in advanced heart failure by next-generation sequencing

Abstract Aims Risk stratification in patients with advanced chronic heart failure (HF) is an unmet need. Circulating microRNA (miRNA) levels have been proposed as diagnostic and prognostic biomarkers in several diseases including HF. The aims of the present study were to characterize HF‐specific miRNA expression profiles and to identify miRNAs with prognostic value in HF patients. Methods and results We performed a global miRNome analysis using next‐generation sequencing in the plasma of 30 advanced chronic HF patients and of matched healthy controls. A small subset of miRNAs was validated by real‐time PCR (P < 0.0008). Pearson's correlation analysis was computed between miRNA expression levels and common HF markers. Multivariate prediction models were exploited to evaluate miRNA profiles' prognostic role. Thirty‐two miRNAs were found to be dysregulated between the two groups. Six miRNAs (miR‐210‐3p, miR‐22‐5p, miR‐22‐3p, miR‐21‐3p, miR‐339‐3p, and miR‐125a‐5p) significantly correlated with HF biomarkers, among which N‐terminal prohormone of brain natriuretic peptide. Inside the cohort of advanced HF population, we identified three miRNAs (miR‐125a‐5p, miR‐10b‐5p, and miR‐9‐5p) altered in HF patients experiencing the primary endpoint of cardiac death, heart transplantation, or mechanical circulatory support implantation when compared with those without clinical events. The three miRNAs added substantial prognostic power to Barcelona Bio‐HF score, a multiparametric and validated risk stratification tool for HF (from area under the curve = 0.72 to area under the curve = 0.82). Conclusions This discovery study has characterized, for the first time, the advanced chronic HF‐specific miRNA expression pattern. We identified a few miRNAs able to improve the prognostic stratification of HF patients based on common clinical and laboratory values. Further studies are needed to validate our results in larger populations

Highly specialized Breast Centers did not experience delay of care during COVID-19 pandemic in Italy: the Senonetwork experience

The study aims to evaluate the performance of selected, high-volume, highly specialized, Italian Breast Centers at the time of COVID-19 pandemic (year 2020), compared to pre-pandemic time (year 2019), highlighting differences in terms of clinical presentation of breast cancer (BC) and therapeutic strategies