Endothelium homeostasis alterations govern the pathogenesis of cardiovascular diseases. Several studies show that vitamins anti-oxidant proprieties rescue the endothelial functions adversely affected by oxidative stress in several diseases. We investigated the vitamin D anti-oxidant potential in human endothelial cells exposed to H2O2 oxidative stress. Vitamin D protected endothelial cells against H2O2 oxidative stress counteracting the superoxide anion generation, the apoptosis and blocking the extrinsic caspase cascade by positively controlling phospho-active ERKs level. MEKs/ERKs inhibitor U0126 reverted the vitamin D anti-oxidant effects. Characterizing the vitamin D downstream effector, we found that vitamin D up-regulated SirT-1 and reverted the SirT-1 down-regulation induced by H2O2. ERKs activation by vitamin D strictly correlated with SirT-1 protein accumulation since both MEKs/ERKs inhibition and ERK1/2 silencing decreased SIRT-1. SirT-1 inhibition by Sirtinol reverted the vitamin D anti-oxidant effects. Thus, vitamin D significantly reduced the endothelial malfunction and damage caused by oxidative stress, through the activation of MEKs/ERKs/SirT-1 axis.
Multimodal treatment has improved the outcome of many solid tumors, and in some cases the use of radiosensitizers has significantly contributed to this gain. Activation of the extracellular signaling kinase pathway (MEK/ERK) generally results in stimulation of cell growth and confers a survival advantage playing the major role in human cancer. The potential involvement of this pathway in cellular radiosensitivity remains unclear. We previously reported that the disruption of c-Myc through MEK/ERK inhibition blocks the expression of the transformed phenotype; affects in vitro and in vivo growth and angiogenic signaling; and induces myogenic differentiation in the embryonal rhabdomyosarcoma (ERMS) cell lines (RD). This study was designed to examine whether the ERK pathway affects intrinsic radiosensitivity of rhabdomyosarcoma cancer cells. Exponentially growing human ERMS, RD, xenograft-derived RD-M1, and TE671 cell lines were used. The specific MEK/ERK inhibitor, U0126, reduced the clonogenic potential of the three cell lines, and was affected by radiation. U0126 inhibited phospho-active ERK1/2 and reduced DNA protein kinase catalytic subunit (DNA-PKcs) suggesting that ERKs and DNA-PKcs cooperate in radioprotection of rhabdomyosarcoma cells. The TE671 cell line xenotransplanted in mice showed a reduction in tumor mass and increase in the time of tumor progression with U0126 treatment associated with reduced DNA-PKcs, an effect enhanced by radiotherapy. Thus, our results show that MEK/ERK inhibition enhances radiosensitivity of rhabdomyosarcoma cells suggesting a rational approach in combination with radiotherapy.
The p38-SirT1 axis is found markedly relevant in modulating the cardiovascular benefit deriving from ACE-inhibitors and might represent a novel target for innovative drugs in cardiovascular prevention.
On 6 April 2009, an earthquake struck L'Aquila. The San Salvatore Hospital was evacuated, and a field hospital was built. The study aimed to assess the epidemiologic impact of the earthquake through the analysis of patient population admitted to the field hospital during a 2-month period following the disaster. We retrospectively evaluated causes of hospitalisation and demographic data of patients admitted to (i) the Division of Internal Medicine and (ii) the Division of Emergency Medicine of the field hospital from 6 April, 2009 to 29 May, 2009. All data were compared with the admissions made at the same divisions of the San Salvatore Hospital during the same period of previous year. (i) Patient group (n = 102) and comparison group (n = 108). Mean patient age was higher, patients living in L'Aquila were more numerous, while mean length of stay was lower after than before the earthquake. Infectious diseases increased, while 'other' diseases decreased after the disaster both in admission and in discharge diagnoses. Gastroenterological diseases decreased with the earthquake but only in admission diagnoses. (ii) Patient group (n = 5255) and comparison group (n = 6564). Triage codes changed with the earthquake. Cardiovascular, psychiatric, gynaecological, infectious and chronic diseases increased, while pneumologic, gastroenterological, traumatic and 'other' diseases decreased after the quake. The number of hospitalised patients decreased with the tremor, while those discharged transferred to other hospitals and those who rejected hospitalisation increased. A natural disaster completely changes causes of hospitalisation in the Divisions of Internal and Emergency Medicine. These findings can be useful for the design of specific intervention programmes and for softening the detrimental effects of quakes.
Our study for the first time shows a marked activation of GpIIb/IIIa receptor in asymptomatic patients with PRP and supports antiplatelet therapy in PRP patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.