Antileukemia Activity and Mechanism of Platinum(II)-Based Metal Complexes.

Transition metal complexes have continued to constitute an appealing class of medicinal compounds since the exceptional discovery of cisplatin in the late 1960s. Pt(II)-based complexes are endowed with a broad range of biological properties, which are mainly exerted by targeting DNA. In this study, we report a significant biological investigation into and computation analyses of four Pt(II)-complexes, namely, LDP-1-4, synthesized and characterized according to previously reported procedures. Molecular-modelling studies highlighted that the top two LDP compounds (i.e., LDP-1 and LDP-4) might bind to both matched and mismatched base pair sites of the oligonucleotide 5'-(dCGGAAATTACCG)2-3', supporting their anticancer potential. These two complexes displayed noteworthy cytotoxicity in vitro (sub-micromolar-micromolar range) against two leukaemia cell lines, i.e., CCRF-CEM and its multi-drug-resistant counterpart CEM/ADR5000, and remarkable anti-angiogenic properties (in the sub-micromolar range) evaluated in an in vivo model, i.e., a chick embryo chorioallantoic membrane (CAM) assay.

Design, Synthesis, and in Vitro Evaluation of 4-(4-Hydroxyphenyl)piperazine-Based Compounds Targeting Tyrosinase.

Melanin biosynthesis is enzymatically regulated by tyrosinase (TYR, EC 1.14.18.1), which is efficiently inhibited by natural and synthetic phenols, demonstrating potential therapeutic application for the treatment of several human diseases. Herein we report the inhibitory effects of a series of (4-(4-hydroxyphenyl)piperazin-1-yl)arylmethanone derivatives, that were designed, synthesised and assayed against TYR from Agaricus bisporus (AbTYR). The best inhibitory activity was predominantly found for compounds bearing selected hydrophobic ortho-substituents on the aroyl moiety (IC50 values in the range of 1.5-4.6 µM). They proved to be more potent than the reference compound kojic acid (IC50 =17.8 µM) and displayed competitive mechanism of inhibition of diphenolase activity of AbTYR. Docking simulation predicted their binding mode into the catalytic cavities of AbTYR and the modelled human TYR. In addition, these compounds displayed antioxidant activity combined with no cytotoxicity in MTT tests. Notably, the best inhibitor affected tyrosinase activity in α-MSH-stimulated B16F10 cells, thus demonstrating anti-melanogenic activity.

Ziziphus lotus (L.) Lam. as a Source of Health Promoting Products: Metabolomic Profile, Antioxidant and Tyrosinase Inhibitory Activities.

The methanolic extract of the stem bark of a wild species of jujube, Ziziphus lotus (L.) Lam., growing in Sicily, was chemically and biologically investigated. The chemical profile was defined by UHPLC-HR-ESI-Orbitrap/MS analysis whereas antioxidant and tyrosinase inhibitory activities were investigated by in vitro assays. The extract showed a high total phenolic and flavonoid content (TPC=271.65 GAE/g and TFC=188.11 RE/g extract). Metabolomic analysis revealed a rich phytocomplex characterized by phenols, cyclopeptide alkaloids, and triterpenoid saponins, some of which here detected for the first time. The mushroom tyrosinase inhibition assay displayed that the methanolic extract efficiently inhibits the monophenolase and diphenolase activity. Furthermore, the extract showed a strong ability to scavenge DPPH, a good Fe3+ reducing antioxidant power, in addition to a Fe2+ chelating activity. Taken together, these results suggest possible novel applications of wild jujube stem bark as a source of potential skin-care agents with several uses in pharmaceutical and cosmetic industries.

[Burnout and occupational stress in nurses]. / Burnout e stress lavorativo in infermieri professionali.

BACKGROUND: In the last few years there has been a growing interest in the psychosocial work environment of health care workers, since they are both at high risk of burnout, role conflict and job dissatifaction. Burnout, as a type of prolonged response to chronic job-related stress, has a special significance in health care settings, where staff experience both psychological--emotional and physical stress. OBJECTIVES: The present study investigated the interrelationship between burnout, occupational stress and personality characteristics in a sample of 120 nurses employed in the Infectious Diseases Department and the Department of Medical Oncology of two major hospitals in Messina, Italy. METHODS: Three questionnaire surveys were administered: The Maslach Burnout Inventory (MBI) to estimate the job stress level, Occupational Stress Inventory to measure occupational stress and the Comrey Personality Scale to identify major personality characteristics. RESULTS: The results showed a significant statistical diference regarding the burnout levels in the two groups under study, with a higher burnout level in the Medical Oncology staff with respect to the Infectious Diseases Staff. The latter group also showed a higher occupational stress compared to the second group, with a significant statistical difference regarding "stress sources", coping strategies" and psychological health". Concerning the CPS results, some personality characteristics, as predictors for burnout syndrome, were found in the Medical Oncology staff. CONCLUSIONS: The study results underline the importance of the role ofpsychosocial work environment and the interrelationships between burnout, occupational stress and psychosomatic health in health care workers. In addition, in order to reduce a burnout risk, the Authors suggest improving the psychosocial work environment as a preventive measure.

Modification of interleukin-15 serum levels in workers exposed to chemotherapeutic agents.

Cytostatic anticancer drugs are known as carcinogenic, mutagenic, and teratogenic risk factors for health care workers occupationally exposed. It has been demonstrated that the administration of interleukin-15 in rat models of colon carcinoma protects against chemotherapy-induced gastrointestinal toxicities. We found that occupational exposure to chemotherapeutic antiblastic agents in vivo modified circulating levels of interleukin-15 in 17 health care workers exposed to antineoplastic drugs in relation to their jobs and in as many healthy age- and sex-matched subjects. Health care workers displayed significantly higher circulating interleukin-15 levels compared to their age-matched controls. If this increase representing an anticancer response remains to be established, these findings strengthen the idea of a therapeutic use of interleukin-15 in the field of cancer.