Malignant pleural mesothelioma (MPM) is an aggressive tumour whose main aetiology is the long-term exposure to asbestos fibres. The diagnostic procedure of MPM is difficult and often requires ...invasive approaches; therefore, it is clinically important to find accurate markers for MPM by new noninvasive methods that may facilitate the diagnostic process and identify patients at an earlier stage. In the present study, the exhaled breath of 13 patients with histology-established diagnosis of MPM, 13 subjects with long-term certified professional exposure to asbestos (EXP) and 13 healthy subjects without exposure to asbestos (healthy controls, HC) were analysed. An analytical procedure to determine volatile organic compounds by sampling of air on a bed of solid sorbent and thermal desorption GC-MS analysis was developed in order to identify the compounds capable of discriminating among the three groups. The application of univariate (ANOVA) and multivariate statistical treatments (PCA, DFA and CP-ANN) showed that cyclopentane and cyclohexane were the dominant variables able to discriminate among the three groups. In particular, it was found that cyclohexane is the only compound able to differentiate the MPM group from the other two; therefore, it can be a possible marker of MPM. Cyclopentane is the dominant compound in the discrimination between EXP and the other groups (MPM and HC); then, it can be considered a good indicator for long-term asbestos exposure. This result suggests the need to perform frequent and thorough investigations on people exposed to asbestos in order to constantly monitor their state of health or possibly to study the evolution of disease over time.
Post-traumatic stress disorder (PTSD) in the occupational context, especially following workplace robbery, is still under-investigated.
To evaluate PTSD incidence and risk factors among bank employee ...victims of robbery voluntarily joining an employer-sponsored post-robbery support programme.
The programme entailed a structured support interview with robbery victims within 15 days of the robbery and a follow-up psychological assessment 45 days after. A self-reported questionnaire on personal variables and robbery characteristics was administered to participants at the first support session (T1). Interviews on employees' psychophysical health and their opinion about the support programme were administered individually at follow-up (T2). The Impact of Event Scale (IES) was administered both at T1 and T2.
There were 383 participants. At T2, 13% of subjects had an IES score >34, a cut-off suggestive of PTSD. In a multi-variate model, feelings of helplessness and terror during the robbery and the number of previous robberies were associated with a PTSD diagnosis. After including IES score at T1, other variables lost statistical significance.
Our findings showed that PTSD is common among employee victims of workplace robbery. Our results also suggest the importance of subjective variables, such as personal perception of robbery severity and early emotional reaction, in identifying people at higher risk of developing PTSD.
The proto-oncogene-encoded transcription factor c-Jun activates genes in response to a number of inducers that act through mitogen-activated protein kinase (MAPK) signal transduction pathways. The ...activation of c-Jun after phosphorylation by MAPK is accompanied by a reduction in c-Jun ubiquitination and consequent stabilization of the protein. These results illustrate the relevance of regulated protein degradation in the signal-dependent control of gene expression.
The c-Jun N-terminal kinase (JNK) has been shown to mediate tamoxifen-induced apoptosis in breast cancer cells. However, the downstream mediators of the JNK pathway linking tamoxifen to effectors of ...apoptosis have yet to be identified. In this study, we analysed whether c-Jun, the major nuclear target of JNK, has a role in tamoxifen-induced apoptosis of SkBr3 breast cancer cells. We show that before DNA fragmentation and caspase 3/7 activation, cytotoxic concentrations of 4-hydroxytamoxifen (OHT) induced JNK-dependent phosphorylation of c-Jun at JNK sites earlier shown to regulate c-Jun-mediated apoptosis. In addition, OHT induced ERK-dependent expression of c-Fos and transactivation of an AP-1-responsive promoter. In particular, the ectopic expression of dominant-negative constructs blocking either AP-1 activity or c-Jun N-terminal phosphorylation prevented DNA fragmentation after OHT treatment. Furthermore, both c-Fos expression and c-Jun N-terminal phosphorylation preceded OHT-dependent activation of caspase 3-7 in different types of tamoxifen-sensitive cancer cells, but not in OHT-resistant LNCaP prostate cancer cells. Taken together, our results indicate that the c-Jun/c-Fos AP-1 complex has a pro-apoptotic role in OHT-treated cancer cells and suggest that pharmacological boosts of c-Jun activation may be useful in a combination therapy setting to sensitize cancer cells to tamoxifen-mediated cell death.
A school based health promotion intervention was performed with the aim of increasing physical activity and improving the dietary habits of primary school pupils, using integrated educational ...strategies involving schools, families, public bodies, sports associations and public health operators.
The intervention concerned 11 classes during 3 school years from 2009-10 (231 third-year school children) to 2011-12 (234 fifth-year school children). Information was collected both before and after the intervention about the dietary habits and the physical activities practised by the children, using the questionnaires of the project !OKkio alla Salute! which were administered to both children and parents. At the same time anthropometric measurements were taken (height, weight, BMI) and motor skills were assessed using standardized tests: Sit & Reach, medicine-ball forward throw, standing long jump, 20 m running speed, and forward roll. At the end of the intervention 12 different expected outcomes were assessed (5 about dietary habits, 5 about motor habits, 1 about anthropometric characteristics, 1 about motor skills).
At baseline, 35.8% of the children show excess weight (23.4% overweight; 12.4% obese); this percentage falls to 29.3% (25.3% overweight; 4% obese) after the intervention (p <0.05). The dietary habits improve from the pre- to the post-intervention: there is a rise in the percentage of children who receive an adequate mid-morning snack (p <0.0001), a fall in the percentage of children who consume snacks and drinks after the dinner (p <0.01), and an increase in the percentage of those who take five or more portions of fruits and vegetables daily. The motor habits do not improve in the same way, since there is the increasing tendency with age to skip from a regular daily practice of physical exercise to favour of the occasional practice of a sport. The motor performances, compared after normalization for modifications due to the process of growth, improve between the third and fifth years of primary school, but with no significant differences. To achieve this objective more focused measures are necessary in the administration of moderate to intense physical exercise.
The results point to a positive assessment of the intervention, thus highlighting the importance of planning integrated and multisectorial actions in school-based programmes to promote correct dietary and motor habits and for the control of body weight, also involving non scholastic areas.
A growing body of evidence concerning estrogen effects cannot be explained by the classic model of hormone action, which involves the binding to estrogen receptors (ERs) α and ERβ and the interaction ...of the steroid-receptor complex with specific DNA sequences associated with target genes. Using c-fos proto-oncogene expression as an early molecular sensor of estrogen action in ERα-positive MCF7 and ER-negative SKBR3 breast cancer cells, we have discovered that 17β-estradiol (E2), and the two major phytoestrogens, genistein and quercetin, stimulate c-fos expression through ERα as well as through an ER-independent manner via the G protein-coupled receptor homologue GPR30. The c-fos response is repressed in GPR30-expressing SKBR3 cells transfected with an antisense oligonucleotide against GPR30 and reconstituted in GPR30-deficient MDA-MB 231 and BT-20 breast cancer cells transfected with a GPR30 expression vector. GPR30-dependent activation of ERK1/2 by E2 and phytoestrogens occurs via a Gβγ-associated pertussis toxin-sensitive pathway that requires both Src-related and EGF receptor tyrosine kinase activities. The ability of E2 and phytoestrogens to regulate the expression of growth-related genes such as c-fos even in the absence of ER has interesting implications for understanding breast cancer progression.
This review describes the ecological, clinical and epidemiological features of emerging vibrios and discusses what laboratory methods are being used for the detection of pathogenic vibrios in ...clinical, environmental and food samples. After selecting articles illustrative of the current scientific research on pathogenic vibrios, the review focuses on the need for better insight into the risk factors of emerging infections to establish adequate prevention procedures.
Cerebellar granule cell (CGC) apoptosis by trophic/potassium (TK) deprivation is a model of election to study the interplay of pro-apoptotic and pro-survival signaling pathways in neuronal cell ...death. In this model, the c-Jun N-terminal kinase (JNK) induces pro-apoptotic genes through the c-Jun/activator protein 1 (AP-1) transcription factor. On the other side, a survival pathway initiated by lithium leads to repression of pro-apoptotic c-Jun/AP-1 target genes without interfering with JNK activity. Yet, the mechanism by which lithium inhibits c-Jun activity remains to be elucidated. Here, we used this model system to study the regulation and function of site-specific c-Jun phosphorylation at the S63 and T91/T93 JNK sites in neuronal cell death. We found that TK-deprivation led to c-Jun multiphosphorylation at all three JNK sites. However, immunofluorescence analysis of c-Jun phosphorylation at single cell level revealed that the S63 site was phosphorylated in all c-Jun-expressing cells, whereas the response of T91/T93 phosphorylation was more sensitive, mirroring the switch-like apoptotic response of CGCs. Conversely, lithium prevented T91T93 phosphorylation and cell death without affecting the S63 site, suggesting that T91T93 phosphorylation triggers c-Jun pro-apoptotic activity. Accordingly, a c-Jun mutant lacking the T95 priming site for T91/93 phosphorylation protected CGCs from apoptosis, whereas it was able to induce neurite outgrowth in PC12 cells. Vice versa, a c-Jun mutant bearing aspartate substitution of T95 overwhelmed lithium-mediate protection of CGCs from TK-deprivation, validating that inhibition of T91/T93/T95 phosphorylation underlies the effect of lithium on cell death. Mass spectrometry analysis confirmed multiphosphorylation of c-Jun at T91/T93/T95 in cells. Moreover, JNK phosphorylated recombinant c-Jun at T91/T93 in a T95-dependent manner. On the basis of our results, we propose that T91/T93/T95 multiphosphorylation of c-Jun functions as a sensitivity amplifier of the JNK cascade, setting the threshold for c-Jun pro-apoptotic activity in neuronal cells.
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