Dorsomorphin reverses the mesenchymal phenotype of breast cancer initiating cells by inhibition of bone morphogenetic protein signaling

Increasing evidence supports the theory that tumor growth, homeostasis, and recurrence are dependent on a small subset of cells with stem cell properties, redefined cancer initiating cells (CICs) or cancer stem cells. Bone morphogenetic proteins (BMPs) are involved in cell-fate specification during embryogenesis, in the maintenance of developmental potency in adult stem cells and may contribute to sustain CIC populations in breast carcinoma. Using the mouse A17 cell model previously related to mesenchymal cancer stem cells and displaying properties of CICs, we investigated the role of BMPs in the control of breast cancer cell plasticity. We showed that an autocrine activation of BMP signaling is crucial for the maintenance of mesenchymal stem cell phenotype and tumorigenic potential of A17 cells. Pharmacological inhibition of BMP signaling cascade by Dorsomorphin resulted in the acquisition of epithelial-like traits by A17 cells, including expression of Citokeratin-18 and E-cadherin, through downregulation of Snail and Slug transcriptional factors and Cyclooxygenase-2 (COX2) expression, and in the loss of their stem-features and self-renewal ability. This phenotypic switch compromised A17 cell motility, invasiveness and in vitro tumor growth. These results reveal that BMPs are key molecules at the crossroad between stemness and cancer

SIRT6 promotes metastasis and relapse in HER2-positive breast cancer

The histone deacetylase sirtuin 6 (SIRT6) has been endowed with anti-cancer capabilities in many tumor types. Here, we investigate the impact of SIRT6-overexpression (SIRT6-OE) in Delta16HER2 mice, which are a bona fide model of HER2-positive breast cancer. After an initial delay in the tumor onset, SIRT6-OE induces a more aggressive phenotype of Delta16HER2 tumors promoting the formation of higher number of tumor foci and metastases than controls. This phenotype of SIRT6-OE tumors is associated with cancer stem cell (CSC)-like features and tumor dormancy, and low senescence and oxidative DNA damage. Accordingly, a sub-set of HER2-positive breast cancer patients with concurrent SIRT6-OE has a significant poorer relapse-free survival (RFS) probability than patients with low expression of SIRT6. ChIP-seq, RNA-seq and RT-PCR experiments indicate that SIRT6-OE represses the expression of the T-box transcription factor 3 (Tbx3) by deacetylation of H3K9ac. Accordingly, loss-of-function mutations of TBX3 or low TBX3 expression levels are predictive of poor prognosis in HER2-positive breast cancer patients. Our work indicates that high levels of SIRT6 are indicative of poor prognosis and high risk of metastasis in HER2-positive breast cancer and suggests further investigation of TBX3 as a downstream target of SIRT6 and co-marker of poor-prognosis. Our results point to a breast cancer subtype-specific effect of SIRT6 and warrant future studies dissecting the mechanisms of SIRT6 regulation in different breast cancer subtypes

Antioxidant and antiproliferative activities of different varieties of cauliflower (Brassica oleracea var. botrytis) after cooking processes.

Cauliflowers are well-known for their health benefits and they are becoming increasingly popular as a fresh vegetable significant source of nutritional antioxidants, such as vitamins and carotenoids, or biologically active dietary components, such as the polyphenols and glucosinolates [1]. Cauliflowers are also a rich source of nutrients such as calcium, zeaxanthin and lutein which have a protective action in eye health and they can also help in the prevention of cancer through the flavonoids known as quercetin or phytonutrient as sulforaphane [2]. Cultivation of coloured cauliflowers (Brassica oleracea var. botrytis) is spreading in Italy and this is also a consequence of the significant genetic improvement on the white type “Tardivo di Fano”, the green types “Verde di Macerata” and the violet type “Violetto di Catania” [3]. Recently, in the framework of a genetic improvement programme, pure lines of “orange type” were obtained [4]. Cooking as a domestic processing method has a great impact on food nutrients. Most vegetables are mainly consumed after being cooked, and cooking considerably affects their health-promoting compounds (glucosinolates, phenolic compounds, phytochemicals, and vitamin C). The cooking process is more important also to determine the quality and recovery of biological active components that characterized the different variety of cauliflowers selected. The aim of this work was to study the influence of these conditions during boiling water and microwave cooking on some properties of coloured cauliflowers. Total polyphenols, antioxidant activity, and antiproliferative activity on human breast adenocarcinoma cell line MDA-MB 231 were evaluated after cooking processes. The results showed that the antioxidant activity, tested using ABTS assay, was reduced during the cooking in all cauliflower varieties. An increase of antioxidant activity in orange and violet varieties was observed when tested with DPPH and FRAP assays. Furthermore, the phenolic substances increase in methanol extracts after cooking processes, especially with microwave treatment. The antiproliferative activity on MDA-MB 231 tumour cell line shows an increase in orange and violet cauliflower aqueous extracts cooked with microwave. In conclusion, the change of properties results lower for orange and violet cauliflowers respect to white or green varieties after cooking processes. In some case the cooking processes increase the antioxidant and antiproliferative activity. The best cooking method that preserves the healthy properties of all varieties of cauliflower is the microwave treatment. [1] Raiola A, Errico A, Petruk G, Monti DM, Barone A, Rigano MM. Bioactive Compounds In Brassicaceae Vegetables With A Role In The Prevention Of Chronic Diseases. Molecules. 2017;23(1), pii: E15. [2] Rosa EAS, Heaney RK, Fenwick GR, Portas CAM. Glucosinolates in Crop Plants, in Horticultural Reviews, Volume 19 (ed J. Janick), 2010, John Wiley & Sons, Inc., Oxford, UK. [3] Acciarri N, Sabatini E, Rotino GL, Ciriaci T, Pulcini L, Della Campa M, Maestrelli A. Breeding In Progress In New Typologies Of Orange Cauliflowers (Brassica oleracea var. botrytis) Proceedings of 5th International Symposium on Brassicas and the 16th Crucifer genetic Workshop. Lillehammer, Norway. 8-12 September 2008. [4] Lu S,Van Eck J, Zhou X, Lopez AB, O’Halloran DM, Cosman KM, Conlin BJ, Paolillo DJ, Garvin DF, Vrebalov J, Kochian, LV, Kupper H, Earle ED, Cao J, Lia L. The Cauliflower Or Gene Encodes A Dnaj Cysteine-Rich Domain-Containing Protein That Mediates High Levels Of β-Carotene Accumulation. Plant Cell 2006;18:3594-3605

HER2-Displaying M13 Bacteriophages induce Therapeutic Immunity against Breast Cancer

The advent of trastuzumab has significantly improved the prognosis of HER2-positive (HER2+) breast cancer patients; nevertheless, drug resistance limits its clinical benefit. Anti-HER2 active immunotherapy represents an attractive alternative strategy, but effective immunization needs to overcome the patient's immune tolerance against the self-HER2. Phage display technology, taking advantage of phage intrinsic immunogenicity, permits one to generate effective cancer vaccines able to break immune tolerance to self-antigens. In this study, we demonstrate that both preventive and therapeutic vaccination with M13 bacteriophages, displaying the extracellular (EC) and transmembrane (TM) domains of human HER2 or its Δ16HER2 splice variant on their surface (ECTM and Δ16ECTM phages), delayed mammary tumor onset and reduced tumor growth rate and multiplicity in ∆16HER2 transgenic mice, which are tolerant to human ∆16HER2. This antitumor protection correlated with anti-HER2 antibody production. The molecular mechanisms underlying the anticancer effect of vaccine-elicited anti-HER2 antibodies were analyzed in vitro against BT-474 human breast cancer cells, sensitive or resistant to trastuzumab. Immunoglobulins (IgG) purified from immune sera reduced cell viability mainly by impairing ERK phosphorylation and reactivating retinoblastoma protein function in both trastuzumab-sensitive and -resistant BT-474 cells. In conclusion, we demonstrated that phage-based HER2 vaccines impair mammary cancer onset and progression, opening new perspectives for HER2+ breast cancer treatment

STATO DI SALUTE DELLE POPOLAZIONI RESIDENTI NELLE AREE GEOTERMICHE DELLA TOSCANA

Objective The limited scientific knowledge on relationship between exposure and health effects in relation to geothermal activity motivated an epidemiologic investigation in Tuscan geothermal area. The study aims to describe the health status of populations living in Tuscany municipalities where concessions for exploitation of geothermal resources were granted. Design This is an ecological study, so it is not useful to produce evidence to sustain a judgment on the cause-effect link. The major limits of this type of study are the use of the residence at municipal level as a proxy of exposure to both environmental and socioeconomic factors and the use of aggregated data of health outcomes that can lead to the well-known ecological fallacy. Setting and participants Sixteen municipalities were included in the study area: eight are part of the so-called "traditional" geothermal area, defined as Northern Geothermal Area (NGA) and eight located in the Amiata Mountain defined as Southern Geothermal Area (SGA). In 2000-2006, the average resident population in the overall area was approximately 43,000 inhabitants. Thirty-one geothermal power plants were active, with a production capacity of 811 MW, 5 of them with 88 MW located in the SGA. Statistical analyses on the entire geothermal area, NGA and SGA subareas, and the sixteen municipalities were performed. Main outcome measures Mortality data were obtained from Tuscany Regional Mortality Registry for the 1971-2006 period, analysing 60 causes of death, of interest for population health status or consistent with "Project SENTIERI" criteria. Hospital discharge records of residents in Tuscany Region in 2004-2006, anywhere admitted to hospital, were analyzed considering only the main diagnosis, excluding repeated admissions for the same cause. The causes taken into account are the same analysed for mortality were considered. Age-standardized mortality rates (TSDM) and the temporal trends of TSDM for four periods (1971-1979, 1980- 1989, 1990-1999, 2000-2006) were computed. Age-standardized mortality/hospitalization ratios (SMR/SHR), with and without adjustment for the deprivation index based on 2001 census data, were calculated: mortality in the years 2000-2006 and hospitalization in 2004-2006. The expected number of events were computed using rates of residents in neighbouring municipalities (municipalities included in 50 km radius circle centred on the study area). Bayesian estimates of mortality/hospitalization ratios (BMR/BHR) at municipal level only and relating maps of the Bayesian risk estimators were elaborated. Congenital malformations (MC) were analysed using data from Tuscan Registry of Birth Defect in 1992-2006 period, relative to outcomes of pregnancies in women resident in the municipalities of study area, wherever the birth or termination of pregnancy occurred. The ratio between observed and expected cases (O/A), with expected defined according to regional rate, were calculated and O/A Bayesian estimates (BMR) are showed only at municipal level . The low weight and the males/females ratio at birth were analysed using data from Tuscany Birth Certificates, covering period 2001-2007, excluding biths occurred in facilities outside Tuscany Region. For Low birth weight (<2,500 grams), very low birth weight (<1,500 grams), low birth weight in women with normal gestational age or greater than 36 weeks, gestational age less than 36 weeks, and the frequency of males, the observed/expected ratio was calculated, with the expected number defined according to regional rate. Results Environmental background High levels of arsenic in drinking water distribution emerges as a critical element, so that several municipalities resorted to granting exemptions for the parameters laid down by the Legislative Decree in force (DLgs 31/01). However, during the final phase of the study, new blast systems activated in the SGA decreased the arsenic levels in the water supply, reaching values not requiring derogations, which, instead, are still effective in some NGA municipalities. Air quality data, from Tuscany Regional Agency for Environmental Protection-ARPAT, show that geothermal activities are able to affect air quality, especially with hydrogen sulphide in NGA, and hydrogen sulphide and mercury in SGA. A significant contribution to the presence of mercury in air is due to previous metallurgical sites. Although mercury levels are belowWHO guideline values, in SGA nearby Siena, values were significantly higher than in other geothermal areas, because of power plant PC2 (turned off in July 2011) in Piancastagnaio municipality. The hydrogen sulphide concentration levels were generally lower than WHO reference values, with occasional excesses over guideline value for health protection (150 &#956;g/m3 as average of the 24 hours). Olfactory pollution was more critic with values exceeding 7-10 &#956;g/m3 range even in areas without geothermal plants.Obiettivo Le limitate conoscenze scientifiche sui rapporti tra esposizione a fattori ambientali correlati all\u27attivit? geotermica e lo stato di salute della popolazione esposta hanno motivato la conduzione di una indagine epidemiologica nell\u27area geotermica toscana basata sull\u27analisi dei dati ambientali e sanitari disponibili negli archivi regionali. Lo studio ha lo scopo di descrivere lo stato di salute delle popolazioni residenti nelle aree geotermiche toscane, identificate con i territori comunali per i quali sono state rilasciate concessioni di sfruttamento della risorsa geotermica. Disegno Lo studio ? di tipo ecologico e quindi non adatto a produrre evidenze che permettano di esprimere un giudizio sul nesso causa-effetto. I maggiori limiti degli studi ecologici derivano dall\u27assunzione che la residenza anagrafica a livello comunale rappresenti una valida misura di esposizione a fattori sia ambientali sia socioeconomici e dall\u27utilizzo di dati aggregati degli esiti sanitari che possono portare a risultati affetti da fallacia ecologica. Setting e partecipanti I comuni inclusi nell\u27area geotermica dello studio sono 16, di cui 8 compresi nell\u27area geotermica cosiddetta ?tradizionale?, che include le localit? di Larderello, Val di Cornia e Radicondoli-Travale (area geotermica Nord) e gli altri 8 situati nella zona dell\u27Amiata senese e grossetana (area geotemica Sud). Nel periodo 2000-2006 la popolazione media residente nell\u27area geotermica complessiva era di oltre 43.000 abitanti. Al momento dello studio erano attive 31 centrali geotermoelettriche con capacit? di produzione di 811 MW, di cui 5 con 88 MW totali nell\u27area geotermica Sud. Le analisi statistiche sono state effettuate a livello di intera area geotermica, delle due subaree geotermiche (Nord e Sud) e dei 16 comuni. Principali misure di outcome La mortalit? ? stata analizzata utilizzando i dati del Registro di mortalit? regionale della Toscana per l\u27intero periodo disponibile (1971-2006), con dettaglio per 60 cause, scelte in quanto di interesse generale per il profilo di salute della popolazione o perch? coerenti con i criteri adottati dal Progetto SENTIERI. L\u27ospedalizzazione ? stata valutata analizzando i dati delle schede di dimissione ospedaliera (SDO) della Re-gione Toscana nel periodo 2004-2006, includendo i ricoverati residenti in Toscana ovunque abbiano effettuato un ricovero, considerando solo la diagnosi principale di ricovero, escludendo i ricoveri ripetuti degli stessi soggetti per la stessa causa. Le cause di ospedalizzazione selezionate per l\u27analisi dei ricoveri sono le stesse utilizzate per l\u27analisi della mortalit?. Per la mortalit? sono stati calcolati i tassi di mortalit? standardizzati per et? (TSDM) e i trend temporali dei TSDM in quattro periodi (1971- 1979, 1980-1989, 1990-1999, 2000-2006). Sia per la mortalit? del periodo 2000-2006, sia per l\u27ospedalizzazione del periodo 2004-2006,sono stati calcolati: &#61692; i rapporti di mortalit?/ospedalizzazione standardizzati per et? (SMR/SHR), con e senza aggiustamento per l\u27indice di deprivazione (ID), utilizzando per il calcolo dell\u27ID i dati del censimento 2001, con gli attesi calcolati usando il tasso di mortalit?/ospedalizzazione della popolazione residente nei comuni limitrofi (comuni con la coordinata geografica del municipio compresa in un cerchio con raggio di 50 km centrato sull\u27area in studio); &#61692; le stime bayesiane dei rapporti di mortalit? (BMR) e di ospedalizzazione (BHR) a livello esclusivamente comunale; &#61692; le mappe (disease mapping) dei rischi bayesiani di mortalit?/ospedalizzazione comunali. Le malformazioni congenite (MC) sono state analizzate utilizzando i dati del Registro toscano dei difetti congeniti (RTDC) nel periodo 1992-2006, relativi a esiti di gravidanze di donne residenti nei comuni dell\u27area in studio, ovunque sia avvenuto il parto o l\u27interruzione di gravidanza. Per le MC ? stato calcolato il rapporto tra casi osservati e casi attesi (O/A), con gli attesi definiti in base al tasso regionale e vengono fornite le stime bayesiane del rapporto O/A (BMR) a livello esclusivamente comunale. Per valutare il basso peso e il rapporto tra maschi e femmine alla nascita sono stati utilizzati i dati dei certificati di assistenza al parto della Regione Toscana, relativi al periodo 2001-2007, con esclusione degli eventi occorsi in presidi di altre regioni. L\u27analisi ? stata condotta considerando i nati con: basso peso alla nascita (LW: peso <2.500 grammi), bassissimo peso alla nascita (VLW: peso <1.500 grammi), basso peso alla nascita nelle donne con et? gestazionale normale e maggiore di 36 settimane (LW36), et? gestazionale inferiore a 36 settimane, e il numero di maschi osservato. Per tutti gli indicatori ? stato calcolato il rapporto osservato/atteso, con l\u27atteso definito in base al tasso regionale. Risultati Il contesto ambientale Dalla descrizione del contesto ambientale, per quanto riguarda l\u27acqua, emerge come elemento di criticit? il riscontro talvolta di elevati livelli di arsenico nelle acque della rete di distribuzione degli acquedotti, tanto che in diverse realt? comunali si ? dovuto far ricorso alla concessione di deroghe ai parametri previsti dal decreto legislativo vigente (DLgs 31/01). Comunque, durante la fase conclusiva dello studio, nell\u27area geotermica Sud i nuovi sistemi abbattitori hanno ridotto i livelli di arsenico nella rete idrica fino a valori tali da non dover pi? ricorrere alle deroghe, ancora attive, invece, in alcuni comuni dell\u27area geotermica Nord. Le informazioni dell\u27ARPAT sui dati dell\u27aria evidenziano che l\u27attivit? geotermica ? in grado di modificare la qualit? dell\u27aria, soprattutto per l\u27acido solfidrico nell\u27area geotermica Nord, e per l\u27acido solfidrico e il mercurio nell\u27area geotermica Sud, in particolare nel versante senese dell\u27Amiata. Per il mercurio nell\u27aria, un contributo rilevante ? legato anche alle emissioni dagli ex siti metallurgici. Sebbene i livelli di mercurio nelle postazioni di monitoraggio rientrino sempre al di sotto dei valori guida raccomandati dall\u27OMS, le concentrazioni riscontrate nell\u27aria dell\u27Amiata senese, e perlopi? legate alla centrale PC2 di Piancastagnaio (spenta nel luglio 2011), sono significativamente superiori a quelle rilevate nelle altre aree geotermiche che, al contrario, sono assestate sugli stessi livelli registrati nei territori non geotermici. I livelli di concentrazione di acido solfidrico sono inferiori ai valori di riferimento, con occasionali superamenti del valore guida di tutela sanitaria OMS (150 &#956;g/m3 come media delle 24 ore). Pi? critici sono i dati di inquinamento olfattivo, che si verifica con il superamento del valore di 7-10 g/m3 di acido solfidrico nell\u27aria, riscontrato con vario grado di intensit? in tutte le postazioni di monitoraggio, anche in aree dove non sono presenti impianti geotermici. In alcune aree con insediamenti produttivi geotermici la frequenza, la persistenza e l\u27intensit? dei cattivi odori sono tali da comportare condizioni di qualit? dell\u27aria scadente

Walking a Tightrope: A Perspective of Resveratrol Effects on Breast Cancer.

It is an acknowledged fact that health benefits are derived from fruit- and vegetables-enriched diets. In particular, polyphenols, compounds bearing one or more hydroxyl groups attached to an aromatic ring, are ascribed for most of such beneficial effects. Among them, resveratrol, a phytoalexin found in numerous plant species, and more notably in grapes, has widely piqued the interest of the scientific community by virtue of its anti-aging, anti-inflammatory and anti-oxidant properties. Moreover, evidence claiming resveratrol ability to hinder processes underlying all the three steps of carcinogenesis (tumor initiation, progression and metastasization) has propelled an incredibly massive number of studies aimed at enquiring its eventual clinical potential in the fight against cancer. However, despite a large body of data pointing to the advantages of dietary resveratrol intake in respect of certain disease conditions, and cancer inter alia, its real position still remains quite ambiguous. In this uncertain scenario, the present review focuses its attention on the highly entangled relationship between resveratrol and breast cancer, attempting to shape the plethora of controversial results stemming from studies carried out on several in vitro and in vivo breast cancer models. Coping with such a tricky matter, there are so many variabilities concerning both resveratrol itself (dosage, administration, bioavailabilty, among others) and the unique molecular traits of each specific breast cancer subtype that must be taken into account when facing the dilemma: "might resveratrol be protective against breast cancer or does it rather fuel it?

Foreigners living in Tuscany at the time of coronavirus outbreak

Background: During the coronavirus outbreak, a worldwide state of emergency and lockdown significantly affected the volunteer services for foreigners. The SARS-CoV-2 surveillance program was strengthened among migrants arriving in Italy. However, few screening measures for SARS-CoV2 infection have been conducted on the foreign population already present in Italy. In Tuscany, a great effort was made to know the epidemiological features of coronavirus outbreaks in the foreigners. Based on these premises, this study describes the prevalence and characteristics of SARS-CoV-2 infection in foreigners present in the Tuscan territory during the months of the highest incidence of this pandemic. Methods: Ministry of Health established the COVID-19 surveillance and predisposed the methods for reporting cases of SARS-CoV-2 infection in agreement with the Department of Infectious Diseases of the Istituto Superiore di Sanità. Data on SARS-CoV-2, updated daily, were collected based on the platform of the Istituto Superiore di Sanità.For each patient were available data on diagnosis, gender, age, nationality, exposure place, hospitalization and symptoms severity. Symptoms severity was classified using a 6-level scale (asymptomatic, paucisymptomatic, mild symptoms, severe symptoms, critic, and died). Results: By July 14, 2020, 10,090 SARS-CoV-2 cases were recorded. Out of 10,090 cases, 8,947 were Italians (88.7%), 608 foreigners (6%); in 535 patients (5.3%) citizenship was missing. The average age of foreigners was 44.1 years (range: 42.9–45.4), compared to 61.1 years (range: 60.7–61.5) of Italians. Chronic pathologies affected 16.8% of foreigners (14.0% -20.0%) and 36.4% of Italians (35.4% -37.4%). Foreigners with asymptomatic or mild symptoms of COVID-19 were 81.7% (78.4% -84.6%), while the Italians were 67% (66.6% -68.5%). Foreigners with severe COVID-19 were 15.2% (12.6% -18.4%) and Italians were 17.6% (16.8% -18.4%). Foreigners in critical conditions were 1.0% (0.5% -2.2%) and Italians were 2.6% (2.3% -3.0%). 38.6% (33.7% -43.7%) of foreigners were infected at the workplace as a health or social-health worker, compared to 24.2% (23.1% -25.4%) of Italians. Conclusion: The time between the onset of symptoms and the execution of the laboratory tests was similar between foreigners and Italians. The foreigners infected by SARS-COV-2 were younger compared to the Italians. Foreigners showed few comorbidities, and asymptomatic or mild symptomatic COVID-19, and consequently, a low lethality index. National and Tuscany policy decisions are needed to create equity in the access to the health care system for immigrants and their families, regardless of their immigration status

Effects of a supplementation with tart cherry (Prunus cerasus L.) juice and its kernel extract on antioxidant status and muscle health

Tart cherry (fruit of Prunus cerasus L.) is nowadays consumed as a nutritional supplement due to its beneficial health effects. Indeed, numerous scientific studies have attested, by in vitro and in vivo assays, its high anti-oxidative and anti-inflammatory properties. However, some investigations have also evaluated its potential use in lowering muscle pain, and accelerating muscle repair. This is especially important for aging individuals who experience loss of muscle mass and strength (sarcopenia). In the present study, we specifically evaluated the effect of tart cherry juice and/or kernel extract supplementation on both regenerative capacity of skeletal muscles and antioxidant status of old male BALB/c mice. After three weeks of dietary supplementation, or not (CTRL), with tart cherry juice (1 mg anthocyanins/mouse/day) and/or modified diet (kernel extract 30mg/kg/day), blood and tissue (liver and kidney) samples were collected to evaluate the antioxidant status. In plasma, the AntiOxidant Power, reactive oxygen metabolites and serum lactate dehydrogenase, creatine kinase and aspartate aminotransferase activities were evaluated, whereas, in the tissue samples, the enzyme activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were measured. To evaluate the regenerative capacity of skeletal muscles (gastrocnemius, soleus, and extensor digitorum lateralis muscles), the number of satellite cells (stem cells) were determined by Flow cytometry. Data obtained from our in vivo study showed a significant increase in the number of muscle stem cells upon treatment, especially in old male BALB/c mice supplemented with tart cherry seed extract (p=0.0015). On the contrary, nonsignificant differences have been stated for the antioxidant status. Our results suggest that consumption of innovative nutraceutical formulations based on tart cherries could be useful to prevent many diseases including sarcopenia and degenerative muscle wasting disorder

Anticancer Activity of Imidazolyl Gold(I/III) Compounds in Non-Small Cell Lung Cancer Cell Lines

Lung cancer is a leading cause of cancer-related death worldwide that needs updated therapies to contrast both the serious side effects and the occurrence of drug resistance. A panel of non-small cell lung cancer (NSCLC) cells were herein employed as cancer models. Eight structurally related gold(I) and gold(III) complexes with NHC and halides or triphenylphosphane ligands were investigated as lung cancer cell growth inhibitors. As expected, gold compounds with PPh3 were found to be more cytotoxic than homoleptic [(NHC)2-Au(I)]X or heteroleptic NHC-Au(I)X or NHC-Au(III)X3 complexes. Mixed ligand gold(I) compounds exhibiting the linear NHC-AuPPh3 (compound 7) or the trigonal NHC-Au(Cl)PPh3 (compound 8) arrangements at the central metal were found to be the best lung cancer cytotoxic compounds. Analysis of the TrxR residual activity of the treated cells revealed that these compounds efficiently inhibit the most accredited molecular target for gold compounds, the TrxR, with compound 8 reaching more than 80% activity reduction in lung cells. Some of the current cancer lung therapy protocols consist of specific lung cancer cell cytotoxic agents combined with antifolate drugs; interestingly, the herein gold compounds are both TrxR and antifolate inhibitors. The human DHFR was inhibited with IC50 ranging between 10–21 μM, depending on substrate concentrations, proceeding by a likely allosteric mechanism only for compound 8

Getting the most from gene delivery by repeated DNA transfections

Intracellular delivery of reporter genes causes cells to be luminescent or fluorescent, this condition being of tremendous relevance in applied physics research. Potential applications range from the study of spatial distribution and dynamics of plasma membrane and cytosolic proteins up to the rational design of nanocarriers for gene therapy. Since efficiency of gene delivery is the main limit in most biophysical studies, versatile methods that can maximize gene expression are urgently needed. Here, we describe a robust methodology based on repeated gene delivery in mammalian cells. We find this procedure to be much more efficient than the more traditional route of gene delivery making it possible to get high-quality data without affecting cell viability. Implications for biophysical investigations are discussed