Molybdenum sputtering film characterization for high gradient accelerating structures

Technological advancements are strongly required to fulfill the demands of new accelerator devices with the highest accelerating gradients and operation reliability for the future colliders. To this purpose an extensive R&D regarding molybdenum coatings on copper is in progress. In this contribution we describe chemical composition, deposition quality and resistivity properties of different molybdenum coatings obtained via sputtering. The deposited films are thick metallic disorder layers with different resistivity values above and below the molibdenum dioxide reference value. Chemical and electrical properties of these sputtered coatings have been characterized by Rutherford backscattering, XANES and photoemission spectroscopy. We will also present a three cells standing wave section coated by a molybdenum layer $\sim$ 500 nm thick designed to improve the performance of X-Band accelerating systems.Comment: manuscript has been submitted and accepted by Chinese Physics C (2012

Trends in h2s-donors chemistry and their effects in cardiovascular diseases

Hydrogen sulfide (H2S) is an endogenous gasotransmitter recently emerged as an important regulatory mediator of numerous human cell functions in health and in disease. In fact, much evidence has suggested that hydrogen sulfide plays a significant role in many physio-pathological processes, such as inflammation, oxidation, neurophysiology, ion channels regulation, cardiovascular protection, endocrine regulation, and tumor progression. Considering the plethora of physiological effects of this gasotransmitter, the protective role of H2S donors in different disease models has been extensively studied. Based on the growing interest in H2S-releasing compounds and their importance as tools for biological and pharmacological studies, this review is an exploration of currently available H2S donors, classifying them by the H2S-releasing-triggered mechanism and highlighting those potentially useful as promising drugs in the treatment of cardiovascular diseases

Serotoninergic receptor ligands improve Tamoxifen effectiveness on breast cancer cells

Background: Serotonin (or 5-Hydroxytryptamine, 5-HT) signals in mammary gland becomes dysregulated in cancer, also contributing to proliferation, metastasis, and angiogenesis. Thus, the discovery of novel compounds targeting serotonin signaling may contribute to tailor new therapeutic strategies usable in combination with endocrine therapies. We have previously synthesized serotoninergic receptor ligands (SER) with high affinity and selectivity towards 5-HT2A and 5-HT2C receptors, the main mediators of mitogenic effect of serotonin in breast cancer (BC). Here, we investigated the effect of 10 SER on viability of MCF7, SKBR3 and MDA-MB231 BC cells and focused on their potential ability to affect Tamoxifen responsiveness in ER+ cells. Methods: Cell viability has been assessed by sulforhodamine B assay. Cell cycle has been analyzed by flow cytometry. Gene expression of 5-HT receptors and Connective Tissue Growth Factor (CTGF) has been checked by RT-PCR; mRNA levels of CTGF and ABC transporters have been further measured by qPCR. Protein levels of 5-HT2C receptors have been analyzed by Western blot. All data were statistically analyzed using GraphPad Prism 7. Results: We found that treatment with SER for 72 h reduced viability of BC cells. SER were more effective on MCF7 ER+ cells (IC50 range 10.2 μM - 99.2 μM) compared to SKBR3 (IC50 range 43.3 μM - 260 μM) and MDA-MB231 BC cells (IC50 range 91.3 μM - 306 μM). This was paralleled by accumulation of cells in G0/G1 phase of cell cycle. Next, we provided evidence that two ligands, SER79 and SER68, improved the effectiveness of Tamoxifen treatment in MCF7 cells and modulated the expression of CTGF, without affecting viability of MCF10A non-cancer breast epithelial cells. In a cell model of Tamoxifen resistance, SER68 also restored drug effect independently of CTGF. Conclusions: These results identified serotoninergic receptor ligands potentially usable in combination with Tamoxifen to improve its effectiveness on ER+ BC patients

H2s donors and their use in medicinal chemistry

Hydrogen sulfide (H2S) is a ubiquitous gaseous signaling molecule that has an important role in many physiological and pathological processes in mammalian tissues, with the same importance as two others endogenous gasotransmitters such as NO (nitric oxide) and CO (carbon monoxide). Endogenous H2S is involved in a broad gamut of processes in mammalian tissues including inflammation, vascular tone, hypertension, gastric mucosal integrity, neuromodu-lation, and defense mechanisms against viral infections as well as SARS-CoV-2 infection. These results suggest that the modulation of H2S levels has a potential therapeutic value. Consequently, synthetic H2S-releasing agents represent not only important research tools, but also potent therapeutic agents. This review has been designed in order to summarize the currently available H2S donors; furthermore, herein we discuss their preparation, the H2S-releasing mechanisms, and their-biological applications

New Insights into the Structure-Activity Relationship and Neuroprotective Profile of Benzodiazepinone Derivatives of Neurounina-1 as Modulators of the Na+/Ca2+Exchanger Isoforms

Due to the neuroprotective role of the Na+/Ca2+ exchanger (NCX) isoforms NCX1 and NCX3, we synthesized novel benzodiazepinone derivatives of the unique NCX activator Neurounina-1, named compounds 1-19. The derivatives are characterized by a benzodiazepinonic nucleus linked to five- or six-membered cyclic amines via a methylene, ethylene, or acetyl spacer. The compounds have been screened on NCX1/NCX3 isoform activities by a high-throughput screening approach, and the most promising were characterized by patch-clamp electrophysiology and Fura-2AM video imaging. We identified two novel modulators of NCX: compound 4, inhibiting NCX1 reverse mode, and compound 14, enhancing NCX1 and NCX3 activity. Compound 1 displayed neuroprotection in two preclinical models of brain ischemia. The analysis of the conformational and steric features led to the identification of the molecular volume required for selective NCX1 activation for mixed NCX1/NCX3 activation or for NCX1 inhibition, providing the first prototypal model for the design of optimized isoform modulators

Melanoma management during the covid-19 pandemic emergency: A literature review and single-center experience

Background: The current COVID-19 pandemic has influenced the modus operandi of all fields of medicine, significantly impacting patients with oncological diseases and multiple comorbidi-ties. Thus, in recent months, the establishment of melanoma management during the emergency has become a major area of interest. In addition to original articles, case reports and specific guidelines for the period have been developed. Purpose: This article aims to evaluate whether melanoma management has been changed by the outbreak of COVID-19, and if so, what the consequences are. We summarized the main issues concerning the screening of suspicious lesions, the diagnosis of primary melanoma, and the management of early-stage and advanced melanomas during the pandemic. Additionally, we report on the experience of our dermatological clinic in northern Italy. Methods: We performed a literature review evaluating articles on melanomas and COVID-19 published in the last two years on PubMed, as well as considering publications by major healthcare organizations. Concerning oncological practice in our center, we collected data on surgical and therapeutic procedures in patients with a melanoma performed during the first months of the pandemic. Conclusions: During the emergency period, the evaluation of suspicious skin lesions was ensured as much as possible. However, the reduced level of access to medical care led to a documented delay in the diagnosis of new melanomas. When detected, the management of early-stage and advanced melanomas was fully guaranteed, whereas the follow-up visits of disease-free patients have been postponed or replaced with a teleconsultation when possible

Synthesis, Chiral Resolution and Enantiomers Absolute Configuration of 4-Nitropropranolol and 7-Nitropropranolol

We recently identified 6-nitrodopamine and other nitro-catecholamines (6-nitrodopa, 6-nitroadrenaline), indicating that the endothelium has the ability to nitrate the classical catecholamines (dopamine, noradrenaline, and adrenaline). In order to investigate whether drugs could be subject to the same nitration process, we synthesized 4-nitro- and 7-nitropropranolol as probes to evaluate the possible nitration of the propranolol by the endothelium. The separation of the enantiomers in very high yields and excellent enantiopurity was achieved by chiral HPLC. Finally, we used Riguera’s method to determine the absolute configuration of the enantiomers, through double derivatization with MPA and NMR studies