1,721,044 research outputs found
Epigenetics and PCBs : Commentary to “Androgen receptor activation by polychlorinated biphenyls : Epigenetic effects mediated by the histone demethylase Jarid1b.”
Full text linkEpigenetic links genetics and environment in shaping several physiological mechanisms including endocrine functions. Growing evidences suggest an interplay among endocrine system, environment, and epigenetics in the etiology of many complex diseases, including some neuropsychiatric disorders. We have demonstrated that a prenatal exposure to polychlorinated biphenyls (PCBs) is able to modulate some epigenetic marks related to the steroid receptors, which (in particular androgen receptor, AR) are cofactors of histone remodeling enzymes; in our recent paper we focused on the interaction between PCBs–AR and the demethylase Jarid1b. Our studies indicate that PCBs induce AR transactivation in a dose-dependent way. Jarid1b potentiates transcriptional activity independently of ligand and of cell phenotype; in particular, Jarid1b increase the AR transactivation in the isoforms with a short polyQ expansion, which are normally present in the population. Since an inverse relationship appears to exist between the AR transcriptional activity and the polyQ repeat length, it is possible to hypothesize that Jarid1b–AR interaction strength depends on the polyQ lenght. PCBs auto-downregulate AR expression and this negative feedback is potentiated by Jarid1b and depends on AR promoter length. These results open new perspectives in the PCBs/AR/Jarid1b interplay possibly occurring in the pathogenesis of some neurological diseases like autism
Targeting Epigenome As An Innovative Pharmacological Strategy For Castration-resistant Prostate Cancer
No full textBackground: The importance of epigenetics in cancer is well known. Since
many epigenetic mechanisms are involved in cancer progression, they may represent a target
for a new pharmacological approach. Prostate cancer is the most common malignancy in
men. After failure of the androgen deprivation therapy, the recurrent disease is termed castration-
resistant cancer (CRPC). Since CRPC remains an incurable disease, new studies are
focusing on the mechanisms critical for CRPC development, to identify new pharmacological targets.
Methods: A MEDLINE research related to CRPC and epigenome has been carried out.
Results: CRPC is probably due to several genetic and epigenetic mechanisms involved in AR activation, even
in the presence of low androgen levels. Increasing evidence suggests that an aberrant DNA methylation may
promote CRPC progression, augmenting genomic instability. Deregulated miRNAs are involved in initiation,
progression, and metastatization of prostate cancers. MiRNAs may act like oncogenes (oncomirs) which can
promote cancer progression, or tumor suppressors (anti-oncomirs) which inhibit CRPC progression. miRNA
replacement therapy represents the most promising anticancer strategy, however only MRX34 (a doublestranded
RNA mimic of the anti-oncomir, miR-34) has reached phase I clinical trial. Also, the deregulation of
long non coding RNAs (lncRNAs) has been involved in CRPC development and lncRNAs may gain diagnostic/
therapeutic relevance. Recently research was focused on the chromatin reader proteins containing bromodomain
and extraterminal domain (BET family). Since BET inhibitors act downstream of AR, these compounds
might be effective in a condition of mediated AR resistance to androgen deprivation.
Conclusions: The recent finding about CRPC epigenome might provide several emerging treatment strategies
to counteract efficiently the tumor progression
The Dangers of Rooting: Data Leakage Detection in Android Applications
Full text linkMobile devices are widely spread all over the world, and Android is the most popular operative system in use. According to Kaspersky Lab's threat statistic (June 2017), many users are tempted to root their mobile devices to get an unrestricted access to the 2 le system, to install different versions of the operating system, to improve performance, and so on. The result is that unintended data leakage flaws may exist. In this paper, we (i) analyze the security issues of several applications considered relevant in terms of handling user sensitive information, for example, financial, social, and communication applications, showing that 51.6% of the tested applications suffer at least of an issue and (ii) show how an attacker might retrieve a user access token stored inside the device thus exposing users to a possible identity violation. Notice that such a token, and a number of other sensitive information, can be stolen by malicious users through a man-in-the-middle (MITM) attack
PRP e rimodellamento citoscheletrico : dagli effetti cellulari all'impiego clinico
No full textThe use of platelet-enriched plasma has been proposed as a source of growth factors in tissue regeneration. The molecular mechanism at the basis of PRP action is not yet understood. The recent finding that PRP is a potent chemoattractive agent for osteoblasts, prompted us to investigate whether the increased cell migration might be due to cytoskeleton rearrangements.
PRP pretreatment of SaOS-2 cells (osteoblastic cell line) increases the capacity of migration in a dose and time dependent manner. Interestingly, PRP pre-treatment induces cytoskeleton reorganization of the actin microfilaments, promoting the acquisition of a migratory phenotype in a time dose dependent manner. We also investigated the effects of a PRP pretreatment on microtubules and also in this case we observe an acquisition of a migratory phenotype. Adding an antibody against PDGF in PRP pretreatment the effect on migration capacity and actin remodelling was completely abolished. We observe also that a PRP pretreatment induces the induction of the mRNA espression of alpha chain of PDGF receptor in a short time, while for a long time the pretreatment inhibits the mRNA espression of the same chain. In conclusion we can say that the pretreatment with PRP is able to increase the migratory ability of osteoblastic cells by cytoskeleton reorganization. The molecular pathway linking PRP to microfilaments and microtubules rearrangement is probably mediated by PDGF signalling
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