Amphiphilicity-Controlled Localization of Red Emitting Bicationic Fluorophores in Tumor Cells Acting as Bio-Probes and Anticancer Drugs

Small organic molecules arouse lively interest for their plethora of possible biological applications, such as anticancer therapy, for their ability to interact with nucleic acids, or bioimaging, thanks to their fluorescence emission. Here, a panchromatic series of styryl-azinium bicationic dyes, which have already proved to exhibit high water-solubility and significant red fluorescence in water, were investigated through spectrofluorimetric titrations to assess the extent of their association constants with DNA and RNA. Femtosecond-resolved transient absorption spectroscopy was also employed to characterize the changes in the photophysical properties of these fluorophores upon interaction with their biological targets. Finally, in vitro experiments conducted on tumor cell lines revealed that some of the bicationic fluorophores had a peculiar localization within cell nuclei exerting important antiproliferative effects, others were instead found to localize in the cytoplasm without leading to cell death, being useful to mark specific organelles in light of live cell bioimaging. Interestingly, this molecule-dependent behavior matched the different amphiphilicity featured by these bioactive compounds, which are thus expected to be caught in a tug-of-war between lipophilicity, ensured by the presence of aromatic rings and needed to pass cell membranes, and hydrophilicity, granted by charged groups and necessary for stability in aqueous media

SHARK (System for coronagraphy with High order Adaptive optics from R to K band): A proposal for the LBT 2nd generation instrumentation

This article presents a proposal aimed at investigating the technical feasibility and the scientific capabilities of high contrast cameras to be implemented at LBT. Such an instrument will fully exploit the unique LBT capabilities in Adaptive Optics (AO) as demonstrated by the First Light Adaptive Optics (FLAO) system, which is obtaining excellent results in terms of performance and reliability. The aim of this proposal is to show the scientific interest of such a project, together with a conceptual opto-mechanical study which shows its technical feasibility, taking advantage of the already existing AO systems, which are delivering the highest Strehl experienced in nowadays existing telescopes. Two channels are foreseen for SHARK, a near infrared channel (2.5-0.9 um) and a visible one (0.9 - 0.6 um), both providing imaging and coronagraphic modes. The visible channel is equipped with a very fast and low noise detector running at 1.0 kfps and an IFU spectroscopic port to provide low and medium resolution spectra of 1.5 x 1.5 arcsec fields. The search of extra solar giant planets is the main science case and the driver for the technical choices of SHARK, but leaving room for several other interesting scientific topics, which will be briefly depicted here

Dermatological applications of EPR : skin-deep or in-depth?

The skin is often referred to as the biggest uniform human body organ, and also as the "brain outside", exposed not only, like the lung epithelium, to the atmospheric air but to other constituents of the open environment including changeable temperature and solar irradiation. The importance of what happens in the skin is therefore not to be overestimated for general condition of the whole organism. Techniques of electron paramagnetic resonance (EPR; called also electron spin resonance, ESR) spectroscopy and imaging belong to the important experimental and diagnostic approaches in dermatology, but the size and shape of skin often make technical problems. The present chapter will cover the basic and clinical applications of EPR to study the skin (including skin tumors) and hair. As the numerous available review papers usually describe the specificity of the EPR-related methods for dermatologists, we decided to cover also some basic aspects of dermatology, to make the chapter more useful also to the specialists in EPR theory and instrumentation. A particular emphasis will be put on the most recent discoveries and innovations, to show that the apparently purely dermatological aspects of such investigations reveal also deeper, systemic implications

Statins, ACE/ARBs drug use, and risk of pneumonia in hospitalized older patients: a retrospective cohort study

: The aims of this study is to evaluate the association between angiotensin-converting enzyme inhibitor (ACE-I), angiotensin II receptor blocker (ARBs) and/or statin use with the risk of pneumonia, as well as and with in-hospital and short-term outpatient mortality in hospitalized older patients with pneumonia. Patients aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro Politerapuie SIMI-Società Italiana di Medicina Interna) register from 2010 to 2019 were screened to assess the diagnosis of pneumonia and classified on whether or not they were prescribed with at least one drug among ACE-I, ARBs, and/or statins. Further study outcomes were mortality during hospital stay and at 3 months after hospital discharge. Among 5717 cases included (of whom 18.0% with pneumonia), 2915 (51.0%) were prescribed at least one drug among ACE-I, ARBs, and statins. An inverse association was found between treatment with ACE-I or ARBs and pneumonia (OR = 0.79, 95% CI 0.65-0.95). A higher effect was found among patients treated with ACE-I or ARBs in combination with statins (OR = 0.67, 95% CI 0.52-0.85). This study confirmed in the real-world setting that these largely used medications may reduce the risk of pneumonia in older people, who chronically take them for cardiovascular conditions

The Molecular Taxonomy of Primary Prostate Cancer

There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defectsclose