β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

Organochlorine pesticides constitute the majority of the total environmental pollutants, and a wide range of compounds have been found to be carcinogenic to humans. Among all, growing interest has been focused on β-hexachlorocyclohexane (β-HCH), virtually the most hazardous and, at the same time, the most poorly investigated member of the hexachlorocyclohexane family. Considering the multifaceted biochemical activities of β-HCH, already established in our previous studies, the aim of this work is to assess whether β-HCH could also trigger cellular malignant transformation toward cancer development. For this purpose, experiments were performed on the human normal bronchial epithelium cell line BEAS-2B exposed to 10 µM β-HCH. The obtained results strongly support the carcinogenic potential of β-HCH, which is achieved through both non-genotoxic (activation of oncogenic signaling pathways and proliferative activity) and indirect genotoxic (ROS production and DNA damage) mechanisms that significantly affect cellular macroscopic characteristics and functions such as cell morphology, cell cycle profile, and apoptosis. Taking all these elements into account, the presented study provides important elements to further characterize β-HCH, which appears to be a full-fledged carcinogenic agent

β-Caryophyllene Counteracts Chemoresistance Induced by Cigarette Smoke in Triple-Negative Breast Cancer MDA-MB-468 Cells

Exposure to cigarette smoke (CS) has been associated with an increased risk of fatal breast cancers and recurrence, along with chemoresistance and chemotherapy impairment. This strengthens the interest in chemopreventive agents to be exploited both in healthy and oncological subjects to prevent or repair CS damage. In the present study, we evaluated the chemopreventive properties of the natural sesquiterpene beta-caryophyllene towards the damage induced by cigarette smoke condensate (CSC) in triple negative breast cancer MDA-MB-468 cells. Particularly, we assessed the ability of the sesquiterpene to interfere with the mechanisms exploited by CSC to promote cell survival and chemoresistance, including genomic instability, cell cycle progress, autophagy/apoptosis, cell migration and related pathways. beta-Caryophyllene was found to be able to increase the CSC-induced death of MDA-MB-468 cells, likely triggering oxidative stress, cell cycle arrest and apoptosis; moreover, it hindered cell recovery, autophagy activation and cell migration; at last, a marked inhibition of the signal transducer and activator of transcription 3 (STAT3) activation was highlighted: this could represent a key mechanism of the chemoprevention by beta-caryophyllene. Although further studies are required to confirm the in vivo efficacy of beta-caryophyllene, the present results suggest a novel strategy to reduce the harmful effect of smoke in cancer patients and to improve the survival expectations in breast cancer women

Health technology assessment of pathogen reduction technologies applied to plasma for clinical use

Although existing clinical evidence shows that the transfusion of blood components is becoming increasingly safe, the risk of transmission of known and unknown pathogens, new pathogens or re-emerging pathogens still persists. Pathogen reduction technologies may offer a new approach to increase blood safety. The study is the output of collaboration between the Italian National Blood Centre and the Post-Graduate School of Health Economics and Management, Catholic University of the Sacred Heart, Rome, Italy. A large, multidisciplinary team was created and divided into six groups, each of which addressed one or more HTA domains.Plasma treated with amotosalen + UV light, riboflavin + UV light, methylene blue or a solvent/detergent process was compared to fresh-frozen plasma with regards to current use, technical features, effectiveness, safety, economic and organisational impact, and ethical, social and legal implications. The available evidence is not sufficient to state which of the techniques compared is superior in terms of efficacy, safety and cost-effectiveness. Evidence on efficacy is only available for the solvent/detergent method, which proved to be non-inferior to untreated fresh-frozen plasma in the treatment of a wide range of congenital and acquired bleeding disorders. With regards to safety, the solvent/detergent technique apparently has the most favourable risk-benefit profile. Further research is needed to provide a comprehensive overview of the cost-effectiveness profile of the different pathogen-reduction techniques. The wide heterogeneity of results and the lack of comparative evidence are reasons why more comparative studies need to be performed

Negotiating meaning at a distance: peer feedback in electronic learning translation environments

Recent research has contributed to an understanding of the positive impact that peer feedback has on student learning, but there is a lack of experimental studies that focus on how peer feedback affects student translation competence. Our study investigates whether the latter are enhanced in the Trans-Atlantic & Pacific Project (TAPP) with an experiment that included the explicit practice of student peer feedback competence and the negotiation of meaning among peers. Students – whether writing, translating or usability testing – collaborated online both within their own university peer group and with a partner university. The results of this intervention, however, suggest no clear tendencies or relation between peer feedback and meaning-related translation competence.FGW – Publications without University Leiden contrac

Global Virtual Teams Create And Translate Technical Documentation: Communication Strategies, Challenges And Recommendations

Since 2013, students from the University of Limerick (UL), the University of Central Florida (UCF), and Université Paris Diderot (UPD) have collaborated on a documentation and translation assignment in virtual teams. The UL and UCF students, who study technical communication, collaborate to write procedural documents. The UPD students translate the documents into French. A key feature of the project design is the need for collaboration among the document writers and translators throughout the process. This paper provides a theoretical background to the project and describes the assignment that student teams collaborate on. It then offers guidelines for faculty wishing to organize similar projects

Developing strategies for success in a cross-disciplinary global virtual team project: collaboration among student writers and translators

This article reports on a qualitative study of strategies and competencies used by technical communication and translation students to address challenges inherent in global virtual team collaboration. The study involved students from three universities collaborating in virtual teams to write and translate instructional documents. Qualitative content analysis of students’ reflective blogs and team transcripts was used to examine their experiences while collaborating. Students faced challenges related to communication, leadership, and technology, and developed various strategies to address those challenges. Although the students did not face cultural challenges, they reported increased awareness of cultural issues. Students also reported that the project helped them better understand the workplace and define career goals

A comparative analysis of punicalagin interaction with PDIA1 and PDIA3 by biochemical and computational approaches

In a previous work, it was shown that punicalagin, an active ingredient of pomegranate, is able to bind to PDIA3 and inhibit its disulfide reductase activity. Here we provide evidence that punicalagin can also bind to PDIA1, the main expressed form of protein disulfide isomerase (PDI). In this comparative study, the affinity and the effect of punicalagin binding on each protein were evaluated, and a computational approach was used to identify putative binding sites. Punicalagin binds to either PDIA1 or PDIA3 with a similar affinity, but the inhibition efficacy on protein reductase activity is higher for PDIA3. Additionally, punicalagin differently affects the thermal denaturation profile of both proteins. Molecular docking and molecular dynamics simulations led to propose a punicalagin binding mode on PDIA1 and PDIA3, identifying the binding sites at the redox domains a’ in two different pockets, suggesting different effects of punicalagin on proteins’ structure. This study provides insights to develop punicalagin-based ligands, to set up a rational design for PDIA3 selective inhibitors, and to dissect the molecular determinant to modulate the protein activity

Emergence of a colistin-resistant KPC-3-producing Klebsiella pneumoniae ST512 clone in an Italian university hospital.

The spread of multidrug-resistant gram-negative pathogens is one of the major hazards for patients requiring long-term hospitalization in intensive care units. We investigated phenotypic and molecular features and clonal relatedness of carbapenem-resistant K. pneumoniae clones circulating in our 1077-beds teaching hospital. Methods: Starting from April 2010, an outbreak of multiresistent Klebsiella pneumoniae occurred in Pisa hospital; after seventeen months (September 2011), 41 patients resulted infected (41/92, 45%), with 17 cases of sepsis (41%) and 51 colonized (51/92, 55%). Lethality was 22%. Clinical strains were isolated from different body sites (blood, urine, rectal swabs or sputum), during the patient hospitalization, in particular when the antibiotic resistance profile changed. Species identification and antimicrobial susceptibilities were obtained by Vitek2 System (bioMérieux). All of isolates were suspected for KPC production based on synergistic activity with phenylboronic acid. Imipenem, meropenem, ertapenem, colistin and tigecycline susceptibility was assessed also by Etest. A total of 52 isolates were chosen as representative and further investigated by genotyping. PCR for blaKPC-like genes and sequencing were performed. PFGE and multilocus sequence typing (MLST) were used to investigate clonal relatedness. Results: All 52 isolates resulted KPC-positive, harbouring blaKPC-3 gene. Carbapenem MICs ranged from 4 mg/L to > 32 mg/L and 18 isolates were resistant to colistin (in the range of 4 to 24 mg/L), whereas only five isolates were still sensitive to tigecycline. PFGE analysis revealed the spread of one prevalent clone belonging to ST512 and showing 7 pulsotypes clonal variants (pt A1-A7), and two sporadic clones, belonging to ST258 (pt A8) and ST101 (pt B). Several isolates with distinct genotypes in the same patient were found, suggesting that the colonizing strain may occasionally be replaced. Conclusions: The phenotypic and molecular heterogeneity of the CC258 circulating in our hospital supports the hypothesis that K. pneumoniae infection and colonization was a very dynamic process, where the ST512 clone could be the result of a single locus mutation occurred in the high risk clone ST258 worldwide distributed. The emergence of colistin-resistant could be attributed to selection pressure from excessive and inadequate colistin use