c-myb Proto-Oncogene Is Expressed by Quiescent Scleroderma Fibroblasts and, Unlike B-myb Gene, Does Not Correlate With Proliferation

Systemic sclerosis (scleroderma) is characterized by excessive deposition of extracellular matrix constituents. Although it has been proposed that tissue fibrosis is due to increased fibroblast synthesis of various collagen polypeptides, there is some experimental evidence that patients with systemic sclerosis have a defect in the control of fibroblast growth. The myb family of genes includes, among others, the c-myb proto-oncogene and the structurally related gene, B-myb, which are both implicated in the regulation of differentiation and/or proliferation of hematopoietic and nonhematopoietic cells. To elucidate the molecular basis responsible for scleroderma fibroblast proliferation, we therefore elected to investigate the expression of c-myb and B-myb genes in scleroderma and control cells. Using the reverse transcriptase polymerase chain reaction technique, we detected c-myb transcripts in scleroderma skin fibroblasts rendered quiescent by serum deprivation. Under the game experimental conditions, c-myb message was not found in normal skin fibroblasts, but, after serum stimulation, c-myb RNA was clearly evident from 3 to 72h in both normal and pathologic cells. Treatment of these cells with c-myb antisense oligonucleotides caused downregulation of c-myb expression, and the inhibition of scleroderma fibroblast proliferation was 42%, whereas in normal fibroblasts the inhibition was weaker (22%). In contrast to c-myb, in normal and scleroderma fibroblasts the level of expression of B-myb correlated with cell proliferation assessed by cell count, and densitometric analysis showed that B-myb message was 1.5–5 times higher in most of pathologic cells studied. The antisense B-myb oligonucleotides had a weaker antiproliferative effect compared with antisense c-myb, inhibiting scleroderma and normal fibroblasts by 23% and 13%, respectively. These data suggest that the B-myb and c-myb genes may play a role in scleroderma fibroblast proliferation and function

NT-proBNP and Its Correlation with In-Hospital Mortality in the Very Elderly without an Admission Diagnosis of Heart Failure

Background The diagnosis of heart failure (HF) is often difficult and underestimated in very elderly comorbid patients, especially when an echocardiographic evaluation is not available or feasible. Aim: to evaluate NT-proBNP values and their correlation with in-hospital mortality in a population of very elderly hospitalized for medical conditions other than HF. Methods We performed a prospective observational study on 403 very elderly admitted to an Internal Medicine and Geriatrics Department. Exclusion criterion was an admission diagnosis of HF. Patients with at least one symptom or sign compatible with HF were tested for NT-proBNP. NT-proBNP values < 300 pg/ml were considered as an age-independent exclusion criterion for HF (high negative predictive value), while NT-proBNP values 1800 pg/ml were considered as a diagnostic criterion. Main comorbidities and laboratory parameters were considered to adjust regression analyses between NT-proBNP and in-hospital mortality. Results NT-proBNP values 1800 pg/ml were present in 61.0% of patients and 32.8% of patients laid between 300 NT-proBNP < 1800 pg/ml values. NT-proBNP values were associated with the main indices of disease severity/organ failure considered such as reduced eGFR, reduced albumin and elevated CRP. NT-proBNP values 1800 pg/ml and ln(NT-proBNP) values were significantly associated with in-hospital mortality independently from the main comorbidities and lab parameters considered. The patients, who were already taking ACE inhibitors/Angiotensin Receptor Blockers before admission, showed lower in-hospital mortality

General Characteristics.

<p>General Characteristics.</p

In-hospital mortality according to NT-proBNP levels.

<p>In-hospital mortality according to NT-proBNP levels.</p

Logistic Regression for HF (NT-proBNP ≥ 1800 pg/ml).

<p>Logistic Regression for HF (NT-proBNP ≥ 1800 pg/ml).</p

Circulating Inflamma-miRs as Potential Biomarkers of Cognitive Impairment in Patients Affected by Alzheimer's Disease

none17noAlzheimer's disease (AD), the most prevalent neurodegenerative disease in the growing population of elderly people, is still lacking minimally-invasive circulating biomarkers that could facilitate the diagnosis and the monitoring of disease progression. MicroRNAs (miRNAs) are emerging as tissue-specific and/or circulating biomarkers of several age-related diseases, but evidence on AD is still not conclusive. Since a systemic pro-inflammatory status was associated with an increased risk of AD development and progression, we focused our investigation on a subset of miRNAs modulating the inflammatory process, namely inflamma-miRNAs. The expression of inflamma-miR-17-5p, -21-5p, -126-3p, and -146a-5p was analyzed in plasma samples from 116 patients with AD compared with 41 age-matched healthy control (HC) subjects. MiR-17-5p, miR-21-5p, and miR-126-3p plasma levels were significantly increased in AD patients compared to HC. Importantly, a strong inverse relationship was observed between miR-21-5p and miR-126-3p, and the cognitive impairment, assessed by Mini-Mental State Examination (MMSE). Notably, miR-126-3p was able to discriminate between mild and severe cognitive impairment. Overall, our results reinforce the hypothesis that circulating inflamma-miRNAs could be assessed as minimally invasive tools associated with the development and progression of cognitive impairment in AD.restrictedGiuliani, Angelica; Gaetani, Simona; Sorgentoni, Giulia; Agarbati, Silvia; Laggetta, Maristella; Matacchione, Giulia; Gobbi, Mirko; Rossi, Tommaso; Galeazzi, Roberta; Piccinini, Gina; Pelliccioni, Giuseppe; Bonfigli, Anna Rita; Procopio, Antonio Domenico; Albertini, Maria Cristina; Sabbatinelli, Jacopo; Olivieri, Fabiola; Fazioli, FrancescaGiuliani, Angelica; Gaetani, Simona; Sorgentoni, Giulia; Agarbati, Silvia; Laggetta, Maristella; Matacchione, Giulia; Gobbi, Mirko; Rossi, Tommaso; Galeazzi, Roberta; Piccinini, Gina; Pelliccioni, Giuseppe; Bonfigli, Anna Rita; Procopio, Antonio Domenico; Albertini, Maria Cristina; Sabbatinelli, Jacopo; Olivieri, Fabiola; Fazioli, Francesc