Computational identification of microRNAs associated to both epithelial to mesenchymal transition and NGAL/MMP-9 pathways in bladder cancer

Bladder cancer is one of the leading cancer of the urinary tract. It is often diagnosed at advanced stage of the disease. To date, no specific and effective early detection biomarkers are available. Cancer development and progression are associated with the involvement of both epithelial-mesenchymal transition (EMT) and tumor microenvironment of which NGAL/MMP-9 complex represents the main player in bladder cancer. It is known that change in microRNAs (miRNAs) expression may result in gene modulation. Therefore, the identification of specific miRNAs associated with EMT pathway and NGAL/MMP-9 complex may be useful to detect the development of bladder cancer at early stages. On this ground, the expression levels of miRNAs in public available datasets of bladder cancer containing data of non-coding RNA profiling was evaluated. This analysis revealed a group of 16 miRNAs differentially expressed between bladder cancer patients and related healthy controls. By miRNA prediction tool (mirDIP), the relationship between the identified miRNAs and the EMT genes was established. Using the DIANA-mirPath (v.2) software, miRNAs, able to modulate the expression of NGAL and MMP-9 genes, were recognized. The results of this study provide evidence that the downregulated hsa-miR-145-5p and hsa-miR-214-3p may modulate the expression of both EMT and NGAL/MMP-9 pathways. Therefore, further validation analyses may confirm the usefulness of these selected miRNAs for predicting the development of bladder cancer at the early stage of the disease

Influenza vaccination coverage among medical residents: An Italian multicenter survey

Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011-2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P < 0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011-2012 season (P < 0.001). "To avoid spreading influenza among patients" was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future. © 2014 Landes Bioscience

The thromboembolism in COVID-19: the unsolved problem

The recent Sars-Cov-2 pandemic (COVID-19) has led to growing research to explain the poor clinical prognosis in some patients

Increased Levels of NF-kB-Dependent Markers in Cancer-Associated Deep Venous Thrombosis

<div><p>Several studies highlight the role of inflammatory markers in thrombosis as well as in cancer. However, their combined role in cancer-associated deep vein thrombosis (DVT) and the molecular mechanisms, involved in its pathophysiology, needs further investigations. In the present study, C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1β), matrix metalloproteases-9 (MMP-9), vascular endothelial growth factor (VEGF), tissue factor (TF), fibrinogen and soluble P-selectin, were analyzed in plasma and in monocyte samples from 385 cancer patients, of whom 64 were concomitantly affected by DVT (+). All these markers were higher in cancer patients DVT+ than in those DVT-. Accordingly, significantly higher NF-kB activity was observed in cancer patients DVT+ than DVT-. Significant correlation between data obtained in plasma and monocyte samples was observed. NF-kB inhibition was associated with decreased levels of all molecules in both cancer DVT+ and DVT-. To further demonstrate the involvement of NF-kB activation by the above mentioned molecules, we treated monocyte derived from healthy donors with a pool of sera from cancer patients with and without DVT. These set of experiments further suggest the significant role played by some molecules, regulated by NF-kB, and detected in cancer patients with DVT. Our data support the notion that NF-kB may be considered as a therapeutic target for cancer patients, especially those complicated by DVT. Treatment with NF-kB inhibitors may represent a possible strategy to prevent or reduce the risk of DVT in cancer patients.</p></div

Spearman correlation coefficients between <i>in vivo</i> and <i>in vitro</i> marker concentrations.

<p>DVT, deep vein thrombosis. A positive strong correlation between the plasma cytokines, angiogenic and coagulation markers and the secretion <i>in vitro</i> of the same markers in two groups of cancer patients with and without DVT.</p

Cytokines secretion in monocytes from cancer patients with and without DVT.

<p>Levels of IL-6, TNF-α, IL-1β, and VEGF were measured in supernatants of purified monocytes from cancer patients with and without DVT by a sensitive enzyme-linked immunosorbent assay (ELISA). The results are shown as the means ± SD.</p

Serum-dependent activation of nuclear factor (NF)–NF-kB p65 subunit in healthy monocytes.

<p>Monocytes from 25 healthy controls were evaluated for NF-kB activation after they were cultured for 20 hours in medium supplemented with either 40% serum from three groups. Monocytes (5x10⁵) from 25 healthy donors were cultured for 20 hours in medium (RPMI 1640) supplemented with either 40% serum derived from 64 cancer patients DVT+ and 257 DVT- with the highest cytokines plasma levels (> 75th percentile) or 40% serum derived from 100 healthy donors with the lowest cytokines values (< 25th percentile). The incubation of healthy monocytes with pooled sera derived from cancer patients DVT+ (sCADVT+) or DVT- (sCADVT-) induced a significant increase of NF-kB activity compared with that derived from healthy controls (HM) after treatment with sera from healthy controls (SH) (P<0.0001). An higher NF-kB p65 subunit activation was observed in monocytes stimulated by sera from cancer patients DVT+ compared to that stimulated by sera derived from DVT- (P<0.001) (t-test). No NF-kB p65 subunit activation was observed in monocytes stimulated with sera derived from healthy controls.</p