Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy.

Androgen receptor (AR) signaling remains the major oncogenic pathway in prostate cancer (PCa). Androgen-deprivation therapy (ADT) is the principle treatment for locally advanced and metastatic disease. However, a significant number of patients acquire treatment resistance leading to castration resistant prostate cancer (CRPC). Epigenetics, the study of heritable and reversible changes in gene expression without alterations in DNA sequences, is a crucial regulatory step in AR signaling. We and others, recently described the technological advance Chem-seq, a method to identify the interaction between a drug and the genome. This has permitted better understanding of the underlying regulatory mechanisms of AR during carcinogenesis and revealed the importance of epigenetic modifiers. In screening for new epigenomic modifiying drugs, we identified SD-70, and found that this demethylase inhibitor is effective in CRPC cells in combination with current therapies. The aim of this review is to explore the role of epigenetic modifications as biomarkers for detection, prognosis, and risk evaluation of PCa. Furthermore, we also provide an update of the recent findings on the epigenetic key processes (DNA methylation, chromatin modifications and alterations in noncoding RNA profiles) involved in AR expression and their possible role as therapeutic targets

Electron-phonon interaction in n-doped cuprates: an Inelastic X-ray Scattering study

Inelastic x-ray scattering (IXS) with very high (meV) energy resolution has become a valuable spectroscopic tool, complementing the well established coherent inelastic neutron scattering (INS) technique for phonon dispersion investigations. In the study of crystalline systems IXS is a viable alternative to INS, especially in cases where only small samples are available. Using IXS, we have measured the phonon dispersion of Nd_{1.86}Ce_{0.14}CuO_{4+\delta} along the [x,0,0] and [x,x,0] in-plane directions. Compared to the undoped parent compound, the two highest longitudinal optical (LO) phonon branches are shifted to lower energies because of Coulomb-screening effects brought about by the doped charge carriers. An additional anomalous softening of the highest branch is observed around q=(0.2,0,0). This anomalous softening, akin to what has been observed in other compounds, provides evidence for a strong electron-phonon coupling in the electron-doped high-temperature superconductors.Comment: Proceedings of the SATT11 conference, Vietri sul Mare - Italy (March 2002); accepted for publication on Int. J. Mod. Phys.

Role of Chlamydia Trachomatis infection in young men : what we need to know?

Chlamydia Trachomatis infections are the most common sexually transmitted bacterial infections worldwide: Because Chlamydia Trachomatis infections are asymptomatic in approximately 50% of infected men and 70% of infected women, there is a high risk for reproductive tract sequelae and high diffusion of the disease. Recently some studies improved the comprehension of this infection and its natural history highlighting the fact that severe complications can be avoided only by a proper early diagnosis and appropriate treatment. We reviewed the literature related to the new findings in the treatment of Chlamydia Trachomatis infection in sexually active young men. Articles from 1960-2014 were identified through a Medline search using the keywords "Chlamydia Trachomatis" combined with "urethritis", "epididymitis", "prostatitis" "treatment" or "management". Several studies highlighted that Chlamidia are only metabolically active in the host cell and therefore only targeted intracellularly by antibiotics. However, even if the standard therapy includes intracellularly-accumulated antibiotics such as tetracyclines or macrolides, recent evidences highlight the role of quinolones. In particular recent studies hilight the role of prulifloxacin in the treatment of chronic prostatitis patients for improving patient's quality of life and decreasing the IL-8 level. However, there is a need for future studies and to diffuse the knowledge about Chlamydia Trachomatis especially in urological clinical practice, in order to reduce the risk of diagnosis failure

The role of flower pollen extract in managing patients affected by chronic prostatitis/chronic pelvic pain syndrome. a comprehensive analysis of all published clinical trials

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still a challenge to manage for all physicians. We feel that a summary of the current literature and a systematic review to evaluate the therapeutic efficacy of flower pollen extract would be helpful for physicians who are considering a phytotherapeutic approach to treating patients with CP/CPPS. Methods: A comprehensive search of the PubMed and Embase databases up to June 2016 was performed. This comprehensive analysis included both pre-clinical and clinical trials on the role of flower pollen extract in CP/CPPS patients. Moreover, a meta-analysis of available randomized controlled trials (RCTs) was performed. The NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and Quality of Life related questionnaires (QoL) were the most commonly used tools to evaluate the therapeutic efficacy of pollen extract. Results: Pre-clinical studies demonstrated the anti-inflammatory and anti-proliferative role of pollen extract. 6 clinical, non-controlled studies including 206 patients, and 4 RCTs including 384 patients were conducted. The mean response rate in non-controlled studies was 83.6% (62.2%-96.0%). The meta-analysis revealed that flower pollen extract could significantly improve patients’ quality of life [OR 0.52 (0.34-.0.81); p = 0.02]. No significant adverse events were reported. Conclusion: Most of these studies presented encouraging results in terms of variations in NIH-CPSI and QoL scores. These studies suggest that the use of flower pollen extract for the management of CP/CPPS patients is beneficial. Future publications of robust evidence from additional RCTs and longer-term follow-up would provide more support encouraging the use of flower pollen extracts for CP/CPPS patients

Soft-x-ray resonant scattering from V/Fe (001) magnetic superlattices

The magnetic properties of Fe and V in (n ML V / 5 ML Fe) (001) superlattices (n = 1, 2, and 5 ML) have been investigated by measuring the magnetization dependent scattering of elliptically polarized soft x rays at various scattering angles and for photon energies across the 2p x-ray-absorption edges of both Fe and V. A quantitative estimate of the magnetic moment induced on vanadium is obtained from the analysis of the resonant scattering data. [S0163-1829(99)50842-4]

Pollen extract in association with vitamins provides early pain relief in patients affected by chronic prostatitis/chronic pelvic pain syndrome

The therapeutic efficacy for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is currently unsatisfactory. The aim of the present study was to assess the safety and efficacy of pollen extract in association with vitamins (DEPROX 500®) in males with CP/CPPS. All patients with a diagnosis of CP/CPPS attending the same urologic centre between March and October 2012 were enrolled in this randomised controlled phase III study. Participants were randomised to receive oral capsules of DEPROX 500® (two capsules every 24 h) or ibuprofen (600 mg, one tablet three times a day) for four weeks. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score and Quality of Well-Being (QoL) questionnaires were used. In the intention-to-treat analysis, 87 males (25 class IIIa and 62 class IIIb) with a mean age of 33.6±5.9 years were randomly allocated to the DEPROX 500® (n=41) or ibuprofen (n=46) treatment groups. At the follow-up examination (following one month of treatment), in the DEPROX 500® group, 31/41 patients (75.6%) reported an improvement in quality of life, defined as a reduction of the NIH-CPSI total score by ≥25%, compared with 19/46 (41.3%) in the control group (P=0.002). The greater improvement in the DEPROX 500® group compared with the ibuprofen group was statistically significant (treatment difference in the NIH-CPSI pain domain, -2.14±0.51, P<0.001; QoL scores, P=0.002). All patients were negative at the Meares-Stamey test evaluation. Adverse events were less frequent in the DEPROX 500® group than in the ibuprofen group. The DEPROX 500® treatment significantly improved total symptoms, pain and quality of life compared with ibuprofen in patients with CP/CPPS, without severe side-effects

Profile of the U 5f magnetization in U/Fe multilayers

Recent calculations, concerning the magnetism of uranium in the U/Fe multilayer system have described the spatial dependence of the 5f polarization that might be expected. We have used the x-ray resonant magnetic reflectivity technique to obtain the profile of the induced uranium magnetic moment for selected U/Fe multilayer samples. This study extends the use of x-ray magnetic scattering for induced moment systems to the 5f actinide metals. The spatial dependence of the U magnetization shows that the predominant fraction of the polarization is present at the interfacial boundaries, decaying rapidly towards the center of the uranium layer, in good agreement with predictions.Comment: 7 pages, 6 figure

E1 and E2 contributions to the L3 resonance line shape in antiferromagnetic holmium

A detailed study of the angular, energy and polarization dependences of the electric dipolar (E1: 2p->5d) and quadrupolar (E2: 2p->4f) contributions to the x-ray scattering cross-section is presented for holmium in its basal plane spiral antiferromagnetic phase at the L3 edge. The corresponding E1 and E2 scattering factors have been extracted from fits to the experimental energy line shapes taking into account for the first time a split dipole resonance. Using the imaginary part of the resonant scattering factors to retrieve the XMCD spectrum, we find qualitative agreement with the dichroic spectrum measured in transmission through a holmium foil.Comment: 16 pages, 8 figures, 5 table

Boosting spatial resolution by incorporating periodic boundary conditions into single-distance hard-x-ray phase retrieval

A simple coherent-imaging method due to Paganin et al. is widely employed for phase-amplitude reconstruction of samples using a single paraxial x-ray propagation-based phase-contrast image. The method assumes that the sample-to-detector distance is sufficiently small for the associated Fresnel number to be large compared to unity. The algorithm is particularly effective when employed in a tomographic setting, using a single propagation-based phase-contrast image for each projection. Here we develop a simple extension of the method, which improves the reconstructed contrast of very fine sample features. This provides first-principles motivation for boosting fine spatial detail associated with high Fourier frequencies, relative to the original method, and was inspired by several recent works employing empirically-obtained Fourier filters to a similar end