Inflamm-aging of the stem cell niche: Breast cancer as a paradigmatic example: Breakdown of the multi-shell cytokine network fuels cancer in aged people.

Inflamm-aging is a relatively new terminology used to describe the age-related increase in the systemic pro-inflammatory status of humans. Here, we represent inflamm-aging as a breakdown in the multi-shell cytokine network, in which stem cells and stromal fibroblasts (referred to as the stem cell niche) become pro-inflammatory cytokine over-expressing cells due to the accumulation of DNA damage. Inflamm-aging self-propagates owing to the capability of pro-inflammatory cytokines to ignite the DNA-damage response in other cells surrounding DNA-damaged cells. Macrophages, the major cellular player in inflamm-aging, amplify the phenomenon, by broadcasting pro-inflammatory signals at both local and systemic levels. On the basis of this, we propose that inflamm-aging is a major contributor to the increase in cancer incidence and progression in aged people. Breast cancer will be presented as a paradigmatic example for this relationship

androgen receptor in breast cancer a wolf in sheep s clothing a lesson from prostate cancer

Abstract The possibility that a receptor for androgen is expressed in Breast Cancer (BC) is fascinating given that the tumor is predominantly estrogen-dependent. The androgen receptor (AR) is emerging as a new marker and a potential new therapeutic target in the treatment of BC patients. The recent availability of selective AR inhibitors ( e.g. bicalutamide, enzalutamide, apalutamide) approved for the treatment of prostate cancer has opened up the possibility to use them in BC patients whose tumors express AR. However, AR appears to have various functions according to the BC subtype, e.g. ER-positive or triple negative BC and the patient prognosis is different on the basis of the presence or absence of estrogen and progesterone receptors. Moreover, a different AR expression was seen according to the various ethnicities. Of note, in population at low economical income, the availability of anti-AR compounds at low cost could open the possibility to treat AR-positive triple negative BC that are highly present in these populations. Up to now, AR detection is not routinely performed in BC. The standardization of AR detection methods could render AR an easily detectable marker in primary BC and metastatic samples. Nevertheless, the overall concordance of 60% of AR expression in primary tumor and metastasis implies that a clinician who need the AR value to give anti-AR therapy should have the data on both the tumor materials. Following the comprehensive studies on prostate cancer the possibility to test AR on liquid biopsies suggest the use of this biomarker for a real-time disease monitoring. Finally, considering the possibility to treat patients with immune checkpoint inhibitors there is the need to know the relation between microenvironment and AR in BC

Studio e caratterizzazione di sensori di ossigeno a base di PEDOT:PSS per applicazioni in coltura cellulare

Questa tesi si inserisce nell’ambito dell’elettronica organica e ha lo scopo di studiare nuovi sensori di ossigeno per valutare il livello di ipossia in cui crescono culture cellulari. Per farlo sono stati realizzati dei transistor elettrochimici organici (OECT) basati sul poli(3,4-etilenedoissitiofene) drogato con polistirene sulfonato (PEDOT:PSS). Le misure sono state effettuate in una soluzione 0.1 M di KCl e in un mezzo di coltura cellulare, con concentrazioni di ossigeno comprese tra lo 0% e il 5%. Si è studiata la risposta dei dispositivi in soluzione 0.1 M di KCl al variare delle tre aree di gate disponibili (0.2, 0.7, 1.9 cm^2), fornendone una caratterizzazione tramite l’analisi delle transcaratteristiche e delle curve di output in tre ambienti (aria, azoto, ossigeno al 5%). Si è poi analizzato l’incremento della corrente di drain nel tempo al seguito di incrementi periodici della concentrazione di ossigeno in soluzione. Gli esperimenti mostrano una correlazione lineare tra incremento relativo di corrente ed aumento di concentrazione di ossigeno, ma eseguendo fit lineari si ottengono pendenze delle rette molto disomogenee tra loro e apparentemente non correlate con i parametri geometrici dei campioni. Si è quindi ipotizzato che le anomalie ottenute siano legate alla degradazione di campioni a causa della loro sovraossidazione durante l’esecuzione delle misure e suggerito nuovi esperimenti per valutare tali effetti. Si sono infine analizzati i risultati ottenuti nel medium cellulare al variare delle due aree di gate che hanno fornito le risposte migliori nelle misure precedenti (0.2 e 1.9 cm^2). In questo caso il gate con area minore si è rivelato più sensibile, ma si sono ottenuti andamenti anomali della corrente di drain in funzione del tempo, probabilmente dovuti alla natura elettrochimica del mezzo di coltura cellulare

Charge Carrier Mobility in Organic Mixed Ionic–Electronic Conductors by the Electrolyte-Gated van der Pauw Method

Organic mixed ionic–electronic conductors (OMIECs) combine electronic semiconductor functionality with ionic conductivity, biocompatibility, and electrochemical stability in water and are currently investigated as the active material in devices for bioelectronics, neuromorphic computing, as well as energy conversion and storage. Operation speed of such devices depends on fast electronic transport in OMIECs. However, due to contact resistance problems, reliable measurements of electronic mobility are difficult to achieve in this class of materials. To address the problem, the electrolyte-gated van der Pauw (EgVDP) method is introduced for the simple and accurate determination of the electrical characteristics of OMIEC thin films, independent of contact effects. The technique is applied to the most widespread OMIEC blend, poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonic acid) (PEDOT:PSS). By comparing with organic electrochemical transistor (OECT) measurements, it is found that gate voltage dependent contact resistance effects lead to systematic errors in OECT based transport characterization. These observations confirm that a contact-independent technique is crucial for the proper characterization of OMIECs, and the EgVDP method reveals to be a simple, elegant, but effective technique for this scope

AC amplification gain in organic electrochemical transistors for impedance-based single cell sensors

Research on electrolyte-gated and organic electrochemical transistor (OECT) architectures is motivated by the prospect of a highly biocompatible interface capable of amplifying bioelectronic signals at the site of detection. Despite many demonstrations in these directions, a quantitative model for OECTs as impedance biosensors is still lacking. We overcome this issue by introducing a model experiment where we simulate the detection of a single cell by the impedance sensing of a dielectric microparticle. The highly reproducible experiment allows us to study the impact of transistor geometry and operation conditions on device sensitivity. With the data we rationalize a mathematical model that provides clear guidelines for the optimization of OECTs as single cell sensors, and we verify the quantitative predictions in an in-vitro experiment. In the optimized geometry, the OECT-based impedance sensor allows to record single cell adhesion and detachment transients, showing a maximum gain of 20.2±0.9 dB with respect to a single electrode-based impedance sensor

Priming adult stem cells by hypoxic pretreatments for applications in regenerative medicine

The efficiency of regenerative medicine can be ameliorated by improving the biological performances of stem cells before their transplantation. Several ex-vivo protocols of non-damaging cell hypoxia have been demonstrated to significantly increase survival, proliferation and post-engraftment differentiation potential of stem cells. The best results for priming cultured stem cells against a following, otherwise lethal, ischemic stress have been obtained with brief intermittent episodes of hypoxia, or anoxia, and reoxygenation in accordance with the extraordinary protection afforded by the conventional maneuver of ischemic preconditioning in severely ischemic organs. These protocols of hypoxic preconditioning can be rather easily reproduced in a laboratory; however, more suitable pharmacological interventions inducing stem cell responses similar to those activated in hypoxia are considered among the most promising solutions for future applications in cell therapy. Here we want to offer an up-to-date review of the molecular mechanisms translating hypoxia into beneficial events for regenerative medicine. To this aim the involvement of epigenetic modifications, microRNAs, and oxidative stress, mainly activated by hypoxia inducible factors, will be discussed. Stem cell adaptation to their natural hypoxic microenvironments (niche) in healthy and neoplastic tissues will be also considered

LL-Paraoxonase Genotype Is Associated with a More Severe Degree of Homeostasis Model Assessment IR in Healthy Subjects

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A Refined Calibration Procedure of Two-Channel Sun Photometers to Measure Atmospheric Precipitable Water at Various Antarctic Sites

Abstract Two-channel sun photometers can be easily employed at Antarctic sites, where harsh environmental conditions prevail, to carry out measurements of precipitable water W. In the very dry air conditions observed in the Antarctic atmosphere, water vapor does not produce strong absorption features along the sun path. Therefore, these instruments need to be calibrated using analytical forms different from the square root regime, which can be determined by simulating the output voltages measured at Antarctic sites, for the spectral near-IR curves of extraterrestrial solar irradiance, instrumental responsivity parameters, and atmospheric transmittance, relative to various measurement periods. For this purpose, average models of the Antarctic atmosphere from the ground level up to the 30-km altitude were considered for different solar zenith angles and relative humidity conditions. The ratios between the output voltages simulated in the band and window channels were plotted as a function of total water vapor content Cw, for each site and each period, to define the best-fit calibration curves, which were subsequently normalized to the field measurements to take into account the aging effects on the filter transmission characteristics. Each of the five calibration curves was found to present a slope coefficient decreasing gradually with Cw from values higher than 0.8 to about 0.6. Using these curves, measurements of W were obtained, which differ appreciably at both sea level and high-altitude sites from those given by the square root calibration curves, avoiding large overestimation errors of 10%–40% at the high-altitude sites and underestimation errors of 5%–15% at the sea level site

Recent results from the Arctic Radiation and Turbulence Interaction STudy (ARTIST) project

Ground-based measurements were conducted at Ny-˚Alesund in the Svalbard Islands in the framework of the research project ARTIST (Arctic Radiation and Turbulence Interaction STudy) funded by the European Communities. Key objectivesof the campaign were: 1) provide all participantswith ground reference data as input to models describing the development of the atmospheric boundary level, 2) compute the surface roughness length in order to characterise the surface of the site, 3) parameterise the surface energy exchanges, calculating the surface radiation flux, the sensible and latent heat fluxes, and 4) obtain the surface energy balance during both clear and cloudy sky conditions. The cloud radiative forcing has been also estimated. Final results of the analysis of the data set are presented