Review about the multi-target profile of resveratrol and its implication in the SGK1 inhibition.

Resveratrol (trans-3,4',5-trihydroxystilbene) is a polyphenolic natural product with a well-known polypharmacological profile that places it among the multi-target-directed ligands (MTDLs). Given its protective action against a wide number of chronic diseases, in this review, we introduce a general overview about the cardioprotective and antioxidant effects, the antidiabetic, neuroprotective and anti-inflammatory effects of this polyphenol. In the second part of the manuscript, we focused our attention on the anticancer activity of Resveratrol, given the alteration of many different signaling pathways, leading to suppression of tumor cell proliferation in numerous cancer types. Among the several anticancer targets involved in the mechanism of action of Resveratrol, here we introduce experimental and molecular modeling studies performed against the SGK1 protein as a novel anticancer target of Resveratrol. SGK1 inhibitors have been demonstrated to inhibit cell growth of different cancer cells. We demonstrated that resveratrol inhibits SGK1 in vitro and in intact cells, affecting proliferation and survival of HUH7 human hepatoma cells. Our findings demonstrate that resveratrol may function as a SGK1 inhibitor, suggesting possible applications in sodium retention and cancer.

In Preclinical Model of Ovarian Cancer, the SGK1 Inhibitor SI113 Counteracts the Development of Paclitaxel Resistance and Restores Drug Sensitivity.

Ovarian cancer is the second most common gynecological malignancy worldwide. Paclitaxel is particularly important in the therapy of ovarian carcinomas, but the treatment efficacy is counteracted by the development of resistance to chemotherapy. The identification of target molecules that can prevent or control the development of chemoresistance might provide important tools for the management of patients affected by ovarian cancer. Serum- and glucocorticoid-regulated kinase 1 (SGK1) appears to be a key determinant of resistance to chemo- and radiotherapy. Specifically, SGK1 affects paclitaxel sensitivity in RKO colon carcinoma cells by modulating the specificity protein 1 (SP1)-dependent expression of Ran-specific GTPase-activating protein (RANBP1), a member of the GTP-binding nuclear protein Ran (RAN) network that is required for the organization and function of the mitotic spindle. SGK1 inhibition might thus be useful for counteracting the development of paclitaxel resistance. Here, we present in vitro data obtained using ovarian carcinoma cell lines that indicate that the SGK1 inhibitor SI113 inhibits cancer cell proliferation, potentiates the effects of paclitaxel-based chemotherapy, counteracts the development of paclitaxel resistance, and restores paclitaxel sensitivity in paclitaxel-resistant A2780 ovarian cancer cells. The results were corroborated by preclinical studies of xenografts generated in nude mice through the implantation of paclitaxel-resistant human ovarian cancer cells. The SGK1 inhibitor SI113 synergizes with paclitaxel in the treatment of xenografted ovarian cancer cells. Taken together, these data suggest that SGK1 inhibition should be investigated in clinical trials for the treatment of paclitaxel-resistant ovarian cancer.

Retrospective analysis of dog bites in Southern Italy / Análise retrospectiva de mordidas de cães no sul da Itália

Dog bite is one of the major public health problems involving people worldwide. Although, several studies have investigated this phenomenon in different countries, little information about the incidence of dog bite episodes in Italy is available. We analysed data about dog biting events between 2010 and 2019 provided by the CRIUV, the Regional Reference Centre for Veterinary Urban Hygiene in the largest city of Southern Italy, namely. Naples. We observed severe and profound inconsistencies in the data collection that reveal structural and significant weaknesses of the current data collection system. Given the multifactorial nature of dog bite, we highlight the need to improve the gathering of all the information related to the factors affecting the occurrence of biting episodes for an accurate assessment of the biting phenomenon.

A mordida de cães é um dos maiores problemas de saúde pública que envolve pessoas em todo o mundo. Embora vários estudos tenham investigado esse fenômeno em diferentes países, poucas informações sobre a incidência de episódios de mordidas por cães na Itália estão disponíveis. Analisamos dados sobre eventos de mordidas de cães entre 2010 e 2019 fornecidos pelo CRIUV, Centro de Referência Regional para Higiene Veterinária Urbana na maior cidade do sul da Itália, Nápoles. Observamos inconsistências graves e profundas na coleta de dados que revelam fragilidades estruturais e significativas do sistema de coleta de dados atual. Dada a natureza multifatorial da mordida canina, destaca-se a necessidade de melhorar a coleta de todas as informações relacionadas aos fatores que afetam a ocorrência de episódios de mordida para uma avaliação precisa deste fenômeno.

Internet Use and Access, Behavior, Cyberbullying, and Grooming: Results of an Investigative Whole City Survey of Adolescents.

BACKGROUND: According to the Digital Agenda for Europe, the way children use the Internet and mobile technologies has changed dramatically in the past years. OBJECTIVE: The aims of this study were to: (1) breakdown the modalities of access and use of the Internet by teenagers to assess risks and risky behaviors; and (2) provide scientific data to evaluate and counsel safe use of the Internet and new technologies by teenagers. METHODS: The study was conducted under the program "Strategies for a Better Internet for Children" started in May 2012 by the European Commission. It represents the main result of the project launched by Telecom Italia, "Anche io ho qualcosa da dire" (I too have something to say), thanks to which many contributions were collected and used to develop a survey. The questionnaire was structured in 45 questions, covering three macro areas of interest. It was approved by the Department Board at University of Magna Graecia's School of Medicine. After authorization from the regional high school authority, it was administered to all 1534 students (aged 13-19 years) in the city of Catanzaro, Italy. RESULTS: The data was broken down into three main groups: (1) describing education and access to the Internet; (2) methods of use and social networking; and (3) perception and evaluation of risk and risky behaviors. Among noteworthy results in the first group, we can mention that the average age of first contact with information technologies was around 9 years. Moreover, 78.87% (1210/1534) of the interviewed students reported having access to a smartphone or a tablet. Among the results of the second group, we found that the most used social networks were Facebook (85.78%, 1316/1534), YouTube (61.14%, 938/1534), and Google+ (51.56%, 791/1534). About 71.31% (1094/1534) of the interviewed teenagers use their name and surname on social networks, and 40.09% (615/1534) of them knew all their Facebook contacts personally. Among the results of the third group, we found that 7.69% (118/1534) of the interviewed teenagers have uploaded pictures or movies of which they felt ashamed; 27.05% (415/1534) have received invitations from people they met on the Internet to meet in real life; and 8.67% (133/1534) have accepted such invitations. CONCLUSIONS: The results offer a breakdown of the teenagers' use of the Internet, focusing on how teenagers learn to use and access it while taking into account factors such as parental coaching, schooling, or self-education. It describes how they approach and interact with social networks and how they perceive risks and risky behaviors on the Internet. Information technology must be seen as an instrument and not as a hindrance. For this to happen, parental guidance, schooling, and medical counseling are needed for a sound development of the child in this critical stage.