Synthesis of Curcumin Derivatives and Analysis of Their Antitumor Effects in Triple Negative Breast Cancer (TNBC) Cell Lines

We analyzed antitumor effects of a series of curcumin analogues. Some of them were obtained by reaction of substitution involving the two phenolic OH groups of curcumin while the analogues with a substituent at C-4 was prepared following an original procedure that regards the condensation of benzenesulfenic acid onto the nucleophilic central carbon of the curcumin skeleton. We analyzed cytotoxic effects of such derivatives on two TNBC (triple negative breast cancer) cell lines, SUM 149 and MDA-MB-231, but only three of them showed an IC50 in a lower micromolar range with respect to curcumin. We also focused on these three derivatives that in both cell lines exhibited a higher or at least equivalent pro-apoptotic effect than curcumin. The analysis of molecular mechanisms of action of the curcumin derivatives under study has highlighted that they decreased NF-κB transcriptional factor activity, and consequently the expression of some NF-κB targets. Our data confirmed once again that curcumin may represent a very good lead compound to design analogues with higher antitumor capacities and able to overcome drug resistance with respect to conventional ones, even in tumors difficult to treat as TNBC

Distributed Leadership Agency and Work Outcomes: Validation of the Italian DLA and Its Relations With Commitment, Trust, and Satisfaction

Forms of collective leadership, such as distributed leadership, have become increasingly important. The need for measurement of the variables involved in the delegation processes represents a new challenge for organizations that want to ensure high-level working. The present study aimed to validate the Italian version of the distributed leadership agency (DLA). The study was carried out on 704 employees (doctors, nurses, clerks, staff workers, healthcare assistants, consultants, management) of an Italian public hospital, who were selected to complete a survey on organizational perceptions. Multiple confirmatory factor analyses (maximum likelihood) have been computed to explore the factorial structure of the DLA, along with associations with other work outcomes. Results about the Italian DLA confirmed the original trifactorial structure of the construct, suggested by Yukl (2002), through good fit indexes and reliability scores; moreover, consistent with the literature, DLA was strongly related to satisfaction, commitment, and trust. Results contribute to underline the robustness of the construct of DLA in different cultural sectors and provide a useful tool to be adopted in the Italian context

Mindfulness as a protective factor for dissatisfaction in HCWS: The moderating role of mindful attention between climate stress and job satisfaction

With the aim of investigating the possible moderating effect of job control and dispositional mindfulness between different sources of organizational stress and job satisfaction, a correlational study was designed involving health care workers (HCWs). The following questionnaires were administered and completed by 237 HCWs: (1) Occupational Stress Indicator (OSI), to measure the sources of stress at work (managerial role, climate power, climate structure, internal relationships), and job satisfaction; (2) Mindfulness Attention Awareness Scale (MAAS) to assess the individual's level of attention to what is taking place in the present; (3) Job Control Scale (JCS) to assess the perceived control at work. Hierarchical regression analyses were used to test the hypothesized relationships between variables; the results showed that, between the different sources of stress, the organizational climate dimension was negatively associated with job satisfaction; moreover, mindfulness attention moderated the relationship between climate stress and job satisfaction; unexpectedly, the interaction between job control and the organizational climate dimension was not significant in affecting job satisfaction. This study can provide useful information for Human Resources Management (HRM) practices regarding job and mental control interventions and empowerment, and possibly offer a new interpretation of the role of attention to what is happening in the present moment and autonomy between climate stressors and occupational satisfaction

Study of uptake mechanisms of halloysite nanotubes in different cell lines

Purpose: Halloysite nanotubes (HNTs) are a natural aluminosilicate clay with a chemical formula of Al2Si2O5(OH)4×nH2O and a hollow tubular structure. Due to their peculiar structure, HNTs can play an important role as a drug carrier system. Currently, the mechanism by which HNTs are internalized into living cells, and what is the transport pathway, is still unclear. Therefore, this study aimed at establishing the in vitro mechanism by which halloysite nanotubes could be internalized, using phagocytic and non-phagocytic cell lines as models. Methods: The HNT/CURBO hybrid system, where a fluorescent probe (CURBO) is confined in the HNT lumen, has been used as a model to study the transport pathway mechanisms of HNTs. The cytocompatibility of HNT/CURBO on cell lines model was investigated by MTS assay. In order to identify the internalization pathway involved in the cellular uptake, we performed various endocytosis-inhibiting studies, and we used fluorescence microscopy to verify the nanomaterial internalization by cells. We evaluated the haemolytic effect of HNT/CURBO placed in contact with human red blood cells (HRBCs), by reading the absorbance value of the supernatant at 570 nm. Results: The HNT/CURBO is highly biocompatible and does not have an appreciable haemolytic effect. The results of the inhibition tests have shown that the internalization process of nanotubes occurs in an energy-dependent manner in both the investigated cell lines, although they have different characteristics. In particular, in non-phagocytic cells, clathrin-dependent and independent endocytosis are involved. In phagocytic cells, in addition to phagocytosis and clathrin-dependent endocytosis, microtubules also participate in the halloysite cellular trafficking. Upon internalization by cells, HNT/CURBO is localized in the cytoplasmic area, particularly in the perinuclear region. Conclusion: Understanding the cellular transport pathways of HNTs can help in the rational design of novel drug delivery systems and can be of great value for their applications in biotechnology

Straining at work and its relationship with personality profiles and individual consequences in healthcare workers (HCWs)

Straining is an attenuated form of mobbing, in which the continuity of vexatious actions is not driven by a discriminatory intent. With the objective of testing the possible moderating role of personality in the relationship between perceptions about straining at work and individual consequences, a correlational design research involved 374 healthcare workers (HCWs) from two Italian hospitals. The following questionnaires were administered: (1) Short Negative Acts Questionnaire (S‐NAQ), to assess discriminative actions at work); (2) the Italian version of the Big Five Inventory (BFI‐10 scale), to assess personality factors; (3) Occupational Stress Indicator (OSI), to measure psychological and physical health. Regression analysis and Structural Equation Models (SEM) were computed in order to test the relationships between variables. Perceived straining showed significant correlations with both psychological and physical health. Conscientiousness was inversely proportional to work‐related bullying (WB), as agreeableness was to personal bullying (PB). Emotional stability was negatively correlated with all the three component scales of S‐NAQ: WB, PB, and social bullying. The results seem to confirm that straining perceptions especially elicit, through emotional stability, psychological consequences. As regards the role of emotional stability in risk perceptions, it seems management has to pay thorough attention to personal factors in organizational perceptions and to straining actions

A Time-Lagged Examination of the Greenhaus and Allen Work-Family Balance Model

The work-family interface is a compelling topic that calls into question labor market dynamics and work processes, together with important social and family composition changes. The present study aimed at examining the antecedents of Work-Family Balance (WFB) in Italy consistent with Greenhaus and Allen’s (2011) conceptual model in which the characteristics of work and family roles have an indirect impact on work-family balance through Work-Family Conflict (WFC) and Work-Family Enrichment (WFE), and where job and family satisfaction are considered as predictors of WFB. A total of 568 workers participated in a time-lagged correlational study, filling a questionnaire. The theoretical model was tested by assessing the mediating role of job and family satisfaction as well as related antecedents, conflict, and enrichment between the family and work contexts, through Structural Equation Modeling (SEM). The results partially confirmed the theoretical model: work-to-family enrichment and work-to-family conflict predicted family satisfaction, which also mediated their association with WFB. The results in the family-to-work direction did not support the initial research hypotheses. The hypotheses about associations between demands and resources, conflict and enrichment in both directions, and of the moderating role of core self-evaluations were partially confirmed. The results highlighted that organizations need to carry out periodic assessments of WFC and WFE, in order to provide benefits and resources, to reduce conflict, and increase enrichment, through proper interventions (training activities, professional development, mentoring, and forms of flexibility)

Addizione di Acidi Solfenici ad Alchini Monosostituiti : Aspetti Teorici e Sperimentali del Meccanismo di Reazione

La sin-addizione di acido benzensolfenico, generato in situ per decomposizione termica del 3-(fenilsolfinil)propanonitrile, ad alchini monosostituiti 3 è stata studiata tramite un approccio combinato sperimentale e teorico, con l’obiettivo di razionalizzare l’effetto del sostituente al carbonio sp sulla regiochimica della reazione. I valori di energia di attivazione calcolati concordano con le osservazioni sperimentali, supportando la validità del modello teorico scelto. L’analisi delle coordinate di reazione è a favore di un meccanismo concertato asincrono,1 con un unico stato di transizione in cui la protonazione anticipa l’attacco dello zolfo. E’ stato osservato che la reazione generalmente procede con una selettività di tipo Markovnikov. Gli studi da noi condotti mostrano una diminuzione di selettività quando il triplo legame è sostituito con un gruppo elettronattrattore, e una regioselettività anti-Markovnikov per gruppi particolarmente ingombranti. Inoltre, la asincronicità è decisamente più marcata per sostituenti elettrondonatori, mentre la reazione dell’acido benzensolfenico con il propiolato di metile risulta quasi completamente sincrona. Tale comportamento è ben spiegato dall’analisi degli stati di transizione: l’iniziale trasferimento del protone dall’ossigeno solfenico al carbonio sp genera uno stato di transizione che possiede un certo carattere carbocationico ed è stabilizzato da sostituenti elettrondonatori. Questo giustifica l’osservata selettività secondo Markovnikov e, in accordo con il postulato di Hammond, la forte asincronicità. D’altra parte, i sostituenti elettronattrattori destabilizzano la carica positiva nello stato di transizione e ciò si traduce in una perdita di regioselettività e in una maggiore sincronicità dell’addizion