Inhibition of the FGF/FGFR System Induces Apoptosis in Lung Cancer Cells via c-Myc Downregulation and Oxidative Stress

Lung cancer represents an extremely diffused neoplastic disorder with different histological/molecular features. Among the different lung tumors, non-small-cell lung cancer (NSCLC) is the most represented histotype, characterized by various molecular markers, including the expression/overexpression of the fibroblast growth factor receptor-1 (FGFR1). Thus, FGF/FGFR blockade by tyrosine kinase inhibitors (TKi) or FGF-ligand inhibitors may represent a promising therapeutic approach in lung cancers. In this study we demonstrate the potential therapeutic benefit of targeting the FGF/FGFR system in FGF-dependent lung tumor cells using FGF trapping (NSC12) or TKi (erdafitinib) approaches. The results show that inhibition of FGF/FGFR by NSC12 or erdafitinib induces apoptosis in FGF-dependent human squamous cell carcinoma NCI-H1581 and NCI-H520 cells. Induction of oxidative stress is the main mechanism responsible for the therapeutic/pro-apoptotic effect exerted by both NSC12 and erdafitinib, with apoptosis being abolished by antioxidant treatments. Finally, reduction of c-Myc protein levels appears to strictly determine the onset of oxidative stress and the therapeutic response to FGF/FGFR inhibition, indicating c-Myc as a key downstream effector of FGF/FGFR signaling in FGF-dependent lung cancers.     

The Perceptual Quality of the Oculus Rift for Immersive Virtual Reality

The recent release of the Oculus Rift, originally developed for entertainment applications, has reignited the interest of researchers and clinicians toward the use of head-mounted-displays in basic behavioral research and physical and psychological rehabilitation. However, careful evaluation of the Oculus Rift is necessary to determine whether it can be effectively used in these novel applications. In this article we address two issues concerning the perceptual quality of the Oculus Rift. (a) Is the Oculus able to generate an acceptable degree of immersivity? In particular, is it possible to elicit the sensation of presence via the virtual stimuli rendered by the device? (b) Does the Virtual Reality experienced through the Oculus Rift induce physical discomfort? To answer these questions, we employed four virtual scenarios in three separate experiments and evaluated performance with objective and subjective outcomes. In Experiment 1 we monitored observers’ heart rate and asked them to rate their Virtual Reality experience via a custom questionnaire. In Experiment 2 we monitored observers’ head movements in reaction to virtual obstacles and asked them to fill out the Simulator Sickness Questionnaire (Kennedy et al., 1993) both before and after experiencing Virtual Reality. In Experiment 3 we compared the Oculus Rift against two other low-cost devices used in immersive Virtual Reality: the Google cardboard and a standard 3DTV monitor. Observers’ heart rate increased during exposure to Virtual Reality, and they subjectively reported the experience to be immersive and realistic. We found a strong relationship between observers’ fear of heights and vertigo experienced during one of the virtual scenarios involving heights, suggesting that observers felt a strong sensation of presence within the virtual worlds. Subjects reacted to virtual obstacles by moving to avoid them, suggesting that the obstacles were perceived as real threats. Observers did not experience simulator sickness when the exposure to Virtual Reality was short and did not induce excessive amounts of vection. Compared to the other devices the Oculus Rift elicited a greater degree of immersivity. Thus our investigation suggests that the Oculus Rift head-mounted-display is a potentially powerful tool for a wide array of basic research and clinical applications.     

Tetrazine‐Responsive Self‐immolative Linkers

Molecules that undergo activation or modulation following the addition of benign external small‐molecule chemical stimuli have numerous applications. Here, we report the highly efficient “decaging” of a variety of moieties by activation of a “self‐immolative” linker, by application of water‐soluble and stable tetrazine, including the controlled delivery of doxorubicin in a cellular context.     

The Seniors’ Outdoor Survey (SOS Tool): comparing ratings and reliability between Italy and the USA

To test applicability of an environmental assessment instrument in new settings, the ratings and reliability of the SOS Tool were compared in diverse settings with a similar climate: Milan, Italy; and Bryan/College Station, Texas, USA. This instrument evaluates physical environment support for outdoor usage by residents at senior facilities. Two trained raters assigned ratings (using a 1–7 scale) to the 60 instrument items at each setting (Italy: 94 outdoor spaces, 67 facilities; US: 22 outdoor spaces, 12 facilities). Overall mean ratings were similar across both sites (6% difference), and three of the five domains had comparable mean ratings. Mean inter-rater reliability was good in both settings but higher in Italy (ICC = .97 versus .82). Despite geographic/cultural differences, mean ratings for most items and domains were surprisingly similar between Italy and the US. This finding, and the high inter-rater reliability found in both settings, suggest this instrument may be useful in a wide range of settings.     

SPR-Based Detection of ASF Virus in Cells

African swine fever (ASF) is one of the most dangerous hemorrhagic infectious diseases that affect domestic and wild pigs. Currently, neither a vaccine nor effective treatments are available for this disease. As regards the degree of virulence, ASFV strains can be divided into high, moderate, or low virulence. The main detection methods are based on the use of the polymerase chain reaction (PCR). In order to prevent an uncontrolled spread of ASF, new on-site techniques that can enable the identification of an early-stage disease are needed. We have developed a specific immunological SPR-based assay for ASFV antigen detection directly in liquid samples. The developed assay allows us to detect the presence of ASFV at the dose of 10³ HAD₅₀/_mL.     

Evaluating the Protective Properties of a Xyloglucan-Based Nasal Spray in a Mouse Model of Allergic Rhinitis

A breached nasal epithelial barrier plays an important role in driving allergic rhinitis (AR). Corticosteroids remain the standard of care (SoC) but come with side effects, thus alternative safe and effective treatments able to avoid inflammation and restore barrier integrity are needed. The aim of the present study is to evaluate the barrier-forming capacity of a xyloglucan-based nasal spray (XG) and compare its efficacy to several SoC treatments (corticosteroid spray, oral mast-cell stabilizer and oral antihistamine) in reducing allergic responses in addition to its effect when concomitantly administered with an antihistamine. An ovalbumin (OVA)-induced mouse AR model was used. XG shows a significant efficacy in reducing histological damage in AR mice; improves nasal rubbing and histamine-induced hyper-responsiveness. Total and OVA-specific IgE as well as pro-inflammatory cytokines are significantly reduced compared to OVA challenged-mice, with im-proved efficacy when used as an add-on treatment. However, XG reduces mucous secreting cells (PAS-positive) and mucin mRNA expression similar to the corticosteroid-treated mice. XG-spray maintains tight junction protein expression (ZO-1) and conversely decreases HDAC1 significantly; the latter being highly expressed in AR patients. Moreover, the concomitant treatment showed in all of the endpoints a similar efficacy to the corticosteroids. This innovative approach may represent a novel therapeutic strategy for nasal respiratory diseases like AR, reducing undesirable side effects and improving the quality of life in patients.