HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors

An important target in the understanding of the pathogenesis of acute myeloid leukemias (AML) relies on deciphering the molecular features of normal and leukemic hemopoietic progenitors. In particular, the analysis of the mechanisms involved in the regulation of cell proliferation is decisive for the establishment of new targeted therapies. To gain further insight into this topic we report herein a novel approach by analyzing the role of HERG K+ channels in the regulation of hemopoietic cell proliferation. These channels, encoded by the human ether-a-go-go-related gene (herg), belong to a family of K, channels, whose role in oncogenesis has been recently demonstrated. We report here that herg is switched off in normal peripheral blood mononuclear cells (PBMNC) as well as in circulating CD34(+) cells, however, it is rapidly turned on in the latter upon induction of the mitotic cycle. Moreover, herg appears to be constitutively activated in leukemic cell lines as well as in the majority of circulating blasts from primary AML. Evidence is also provided that HERG channel activity regulates cell proliferation in stimulated CD34(+) as well as in blast cells from AML patients. These results open new perspectives on the pathogenetic role of HERG K+ channels in leukemias

A Small Molecule SMAC Mimic LBW242 Potentiates TRAIL- and Anticancer Drug-Mediated Cell Death of Ovarian Cancer Cells

BACKGROUND: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (SMAC) has been described to sensitize for apoptosis. We have explored the pro-apoptotic activity of LBW242, a mimic of SMAC/DIABLO, on ovarian cancer cell lines (A2780 cells and its chemoresistant derivative A2780/ADR, SKOV3 and HEY cells) and in primary ovarian cancer cells. The effects of LBW242 on ovarian cancer cell lines and primary ovarian cancer cells was determined by cell proliferation, apoptosis and biochemical assays. PRINCIPAL FINDINGS: LBW242 added alone elicited only a moderate pro-apoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or anticancer drugs in inducing apoptosis of both ovarian cancer cell lines and primary ovarian cancer cells. Mechanistic studies show that LBW242-induced apoptosis in ovarian cancer cells is associated with activation of caspase-8. In line with this mechanism, c-FLIP overexpression inhibits LBW242-mediated apoptosis. CONCLUSION: LBW242 sensitizes ovarian cancer cells to the antitumor effects of TRAIL and anticancer drugs commonly used in clinic. These observations suggest that the SMAC/DIABLO mimic LBW242 could be of value for the development of experimental strategies for treatment of ovarian cancer

Advances in Electronic-Nose Technologies Developed for Biomedical Applications

The research and development of new electronic-nose applications in the biomedical field has accelerated at a phenomenal rate over the past 25 years. Many innovative e-nose technologies have provided solutions and applications to a wide variety of complex biomedical and healthcare problems. The purposes of this review are to present a comprehensive analysis of past and recent biomedical research findings and developments of electronic-nose sensor technologies, and to identify current and future potential e-nose applications that will continue to advance the effectiveness and efficiency of biomedical treatments and healthcare services for many years. An abundance of electronic-nose applications has been developed for a variety of healthcare sectors including diagnostics, immunology, pathology, patient recovery, pharmacology, physical therapy, physiology, preventative medicine, remote healthcare, and wound and graft healing. Specific biomedical e-nose applications range from uses in biochemical testing, blood-compatibility evaluations, disease diagnoses, and drug delivery to monitoring of metabolic levels, organ dysfunctions, and patient conditions through telemedicine. This paper summarizes the major electronic-nose technologies developed for healthcare and biomedical applications since the late 1980s when electronic aroma detection technologies were first recognized to be potentially useful in providing effective solutions to problems in the healthcare industry

Aerobic activity for elderly people. Improvement of muscolar strenght in the lower limbs and joint mobility in the upper limbs. Testing for elderly people

Essendo il nostro campo di ricerca rivolto alle Scienze dell' Uomo, questa volta il nostro interesse si è incentrato sulla terza età anche perchè la nostra regione, le Marche, è la più longeva a livello nazionale dato che emerge dal rapporto Istat: nelle Marche, infatti, la speranza di vita alla nascita è maggiore rispetto alle altre regioni italiane. Gli uomini possono sperare di superare i 78 anni e le donne di arrivare agli 84 e visto che l’invecchiamento fisiologico produce modificazioni di ordine degenerativo a carico di apparati ed organi, bisogna far in modo che ci si arrivi al meglio. In particolare la diminuzione della mobilità articolare costituisce una limitazione delle capacità fisiche i cui effetti nei soggetti molto anziani, conducono ad una riduzione dell’autonomia personale; la forza muscolare si riduce con l’età, diminuisce la massa muscolare, si verifica una riduzione del numero di fibre muscolari, le quali, soprattutto a livello degli arti inferiori, costituiscono uno dei principali fattori correlati con il rischio di caduta dell’anziano. Questo triplice aspetto ci ha spinto a svolgere una ricerca per vedere se, attraverso un’attività di tipo aerobico (ginnastica aerobica), è possibile arrivare al miglioramento delle suddette capacità. Metodi: E' stato contattato il responsabile del Centro Ricreativo per anziani “Le Conce” di Camerino (Macerata) il quale ha con entusiasmo acconsentito alla proposta. Si è individuato all’interno del centro un gruppo di lavoro e un gruppo di controllo composti da 15 soggetti ciascuno di età compresa tra i 59 e gli 86 anni. Il gruppo di lavoro è stato sottoposto a prove motorie e a test psicologici come il gruppo di controllo, inoltre ha praticato un’attività di ginnastica aerobica volta a migliorare la forza muscolare degli arti inferiori e la mobilità articolare degli arti superiori, della durata di 3 mesi con frequenza di 3 volte alla settimana; la durata delle lezioni è stata gradualmente aumentata fino a raggiungere i 75 minuti. Risultati: I risultati dei Test standardizzati a livello internazionale hanno mostrato miglioramenti significativi sia in ambito motorio sia in ambito relazionale nel gruppo di lavoro. Conclusioni: Dai risultati registrati, possiamo affermare che la ginnastica aerobica, praticata in età senile, è utile per il miglioramento della forza muscolare e della mobilità articolare, in più, il miglior consenso che il soggetto riceve circa le sue capacità è di per sé di fondamentale importanza nel condizionare lo stato di umore; il miglioramento della condizione psicologica dei soggetti, è un’ulteriore dimostrazione dell’efficacia della pratica di attività fisica da parte dei soggetti anziani

Is the dating of short tree-ring series still a challenge? New evidence from the pile dwelling of Lucone di Polpenazze (northern Italy)

International audienc

Pattern of medication use among older inpatients in seven hospitals in Italy: results from the CRiteria to assess Appropriate Medication use among Elderly complex patients (CRIME) project

Prescribing pharmacological treatment for hospitalized older patients represents a challenge for physicians. In particular, hospitalized older adults present with acute and chronic diseases, which may require multiple treatments and increase their susceptibility to adverse drug reactions. Patterns of drugs use have rarely been investigated in these patients

Association of frailty with the serine protease HtrA1 in older adults

Frailty is a geriatric syndrome characterized by multi system dysregulation. It has been suggested that chronic inflammation may be involved in the pathogenesis of frailty. No study so far has identified accurate, specific and sensitive molecular biomarkers for frailty. High-temperature requirement serine protease A1 (HtrA1) is a secreted multidomain serine protease implicated in the inhibition of signaling of active transforming growth factor-β (TGF-β)1, a cytokine which has an important anti-inflammation role. The aim of the present study was to investigate the association of circulating levels of HtrA1 with frailty in a sample of older adults.The study was performed in 120 older adults aged >. 65 years and admitted to a geriatric outpatient clinic. The frailty status of participants was assessed by both the Fried's criteria (physical frailty, PF) and a modified Rockwood's frailty index (FI). Plasma HtrA1 concentration was measured using commercial ELISA kit. Frailty was identified in 61/120 participants (50.8%) using PF, and in 60/118 subjects (50.8%) using FI. Plasma levels of HtrA1 were significantly higher in individuals classified as frail according to PF (75.9 ng/mL, 95% CI 67.4-85.6) as compared with non-frail participants (48.4 ng/mL, 95% CI 42.5-54.6, p < 0.001). A significant association was also observed between frailty, assessed by FI, and HtrA1 levels (72.2 ng/mL, 95% CI 63.4-82.3, vs. 50.4 ng/mL, 95% CI 44.3-58.0, p < 0.001). These associations were confirmed after adjusting for potential confounders. This study demonstrates for the first time the association of plasma levels of HtrA1 with frailty status. Future investigations are needed to validate the potential value of HtrA1 as possible biomarker for frailty

Shorter telomeres in peripheral blood mononuclear cells from older persons with sarcopenia: results from an exploratory study

Telomere shortening in peripheral blood mononuclear cells (PBMCs) has been associated with biological age and several chronic degenerative diseases. However, the relationship between telomere length and sarcopenia, a hallmark of the aging process, is unknown. The aim of the present study was therefore to determine whether PBMC telomeres obtained from sarcopenic older persons were shorter relative to non-sarcopenic peers. We further explored if PBMC telomere length was associated with frailty, a major clinical correlate of sarcopenia