Tyndallized bacteria prime bronchial epithelial cells to mount an effective innate immune response against infections.

Airway epithelium represents a physical barrier against toxic substances and pathogens but also presents pattern recognition receptors on the epithelial cells that detect pathogens leading to molecule release and sending signals that activate both the innate and adaptive immune responses. Thus, impaired airway epithelial function and poor integrity may increase the recurrence of infections. Probiotic use in respiratory diseases as adjuvant of traditional therapy is increasingly widespread. There is growing interest in the use of non-viable heat-killed bacteria, such as tyndallized bacteria (TB), due to safety concerns and to their immunomodulatory properties. This study explores in vitro the effects of a TB blend on the immune activation of airway epithelium. 16HBE bronchial epithelial cells were exposed to different concentrations of TB. Cell viability, TB internalization, TLR2 expression, IL-6, IL-8 and TGF-ßl expression/release, E-cadherin expression and wound healing were assessed. We found that TB were tolerated, internalized, increased TLR2, E-cadherin expression, IL-6 release and wound healing but decreased both IL-8 and TGF-ßl release. In conclusion, TB activate TLR2 pathway without inducing a relevant pro-inflammatory response and improve barrier function, leading to the concept that TB preserve epithelial homeostasis and could be used as strategy to prevent and to manage respiratory infection, exacerbations included.

First validation of the technical and administrative staff quality of life at work tool (TASQ@work) in academia.

Introduction: Based on the job demands-resources (JD-R) model, the present study aimed to validate "The Technical and Administrative Staff Quality of Life At Work" (TASQ@work), a new tool to assess the quality of life at work in academia focused on technical and administrative staff. Methods: This tool was developed by the QoL@Work research team, a group of expert academics in the field of work and organizational psychology affiliated with the Italian Association of Psychologists. The TASQ@work was elaborated in different steps. The first phase was aimed at the identification of the dimensions of the tool. The second phase was aimed to assess the psychometric properties of the tool. The validation process involved confirmatory analysis and measurement invariance of the various constructs selected. The analyses were performed in a convenience sample of two Italian universities in different regions (one in the Northwest and the second in Central Italy). Results: The sample was composed of 1820 Administrative Staff, comprising 69.4% from University 1 (N = 1,263) and 30.6% from University 2 (N = 557). The TASQ@work presented satisfactory psychometric properties (normality of the items, reliability and content, construct and nomological validity) and measurement invariance across gender, seniority, and Athenaeum. Discussion: The results indicate that the tool can be considered a reliable and valid instrument to assess job demands, job resources, and outcomes in the working life of technical and administrative academic staff. In this perspective, the present study represents the first contribution to the debate on the psychosocial risks in academic contexts by presenting a new tool, the TASQ@work, aimed at contextualizing the JD-R model to understand the role played by psychosocial aspects in affecting the well-being of the academic employees.

Formoterol Exerts Anti-Cancer Effects Modulating Oxidative Stress and Epithelial-Mesenchymal Transition Processes in Cigarette Smoke Extract Exposed Lung Adenocarcinoma Cells.

Lung cancer frequently affects patients with Chronic Obstructive Pulmonary Disease (COPD). Cigarette smoke (CS) fosters cancer progression by increasing oxidative stress and by modulating epithelial-mesenchymal transition (EMT) processes in cancer cells. Formoterol (FO), a long-acting ß2-agonist widely used for the treatment of COPD, exerts antioxidant activities. This study explored in a lung adenocarcinoma cell line (A549) whether FO counteracted the effects of cigarette smoke extract (CSE) relative to oxidative stress, inflammation, EMT processes, and cell migration and proliferation. A549 was stimulated with CSE and FO, ROS were evaluated by flow-cytometry and by nanostructured electrochemical sensor, EMT markers were evaluated by flow-cytometry and Real-Time PCR, IL-8 was evaluated by ELISA, cell migration was assessed by scratch and phalloidin test, and cell proliferation was assessed by clonogenic assay. CSE significantly increased the production of ROS, IL-8 release, cell migration and proliferation, and SNAIL1 expression but significantly decreased E-cadherin expression. FO reverted all these phenomena in CSE-stimulated A549 cells. The present study provides intriguing evidence that FO may exert anti-cancer effects by reverting oxidative stress, inflammation, and EMT markers induced by CS. These findings must be validated in future clinical studies to support FO as a valuable add-on treatment for lung cancer management.

A review of the role of intermittent fasting in the management of inflammatory bowel disease.

Intermittent fasting (IF) may be a weight management strategy for patients with inflammatory bowel disease (IBD). The aim of this short narrative review is to summarize the evidence related to IF in the management of IBD. A literature search of English publications related to IF or time-restricted feeding and IBD, Crohn's disease, or ulcerative colitis was conducted in PubMed and Google Scholar. Four publications on studies of IF in IBD were found: three randomized controlled trials in animal models of colitis and one prospective observational study in patients with IBD. The results from animal studies suggest either moderate or no changes in weight but improvements in colitis with IF. These improvements may be mediated through changes in the gut microbiome, decreased oxidative stress and increased colonic short-chain fatty acids. The study in humans was small and uncontrolled, and it did not assess changes in weight, making it difficult to draw conclusions around the effects of IF on changes in weight or disease course. Given that preclinical evidence suggests intermittent fasting may play a beneficial role in IBD, randomized controlled trials in large patients with active disease are warranted to determine whether intermittent fasting could be an integrated therapy for patients with IBD management, either for weight or for disease management. These studies should also explore the potential mechanisms of action related to intermittent fasting.

Effect of Semaglutide on Subclinical Atherosclerosis and Cardiometabolic Compensation: A Real-World Study in Patients with Type 2 Diabetes.

BACKGROUND: Semaglutide is a recently approved glucagon-like peptide-1 receptor agonist. Several trials reported the protective effect of injectable semaglutide on cardiovascular (CV) risk by reducing major adverse cardiovascular events in type 2 diabetes patients. Strong preclinical evidence supports the CV benefits of semaglutide through an effect on atherosclerosis. However, scant evidence is available about the protective mechanisms of semaglutide in clinical practice. METHODS: A retrospective observational study was conducted among consecutive type 2 diabetes patients treated with injectable semaglutide in Italy between November 2019 and January 2021 when the drug was first available in the country. The primary aims were the assessment of the carotid intima-media thickness (cIMT) and hemoglobin A1c (HbA1c) levels. The secondary aims were the evaluation of anthropometric, glycemic, and hepatic parameters and plasma lipids, including the assessment of the triglyceride/high-density lipoprotein ratio as an indirect marker of atherogenic small, dense low-density lipoprotein particles. RESULTS: Injectable semaglutide reduced HbA1c and cIMT. An improvement in CV risk factors and the triglyceride/high-density lipoprotein ratio was reported. Moreover, through correlation analyses, we found that hepatic fibrosis and steatosis indices and the anthropometric, hepatic, and glycemic parameters, as well as plasma lipids, were unrelated to the variations in cIMT and HbA1c. CONCLUSIONS: Our findings suggest the effect of injectable semaglutide on atherosclerosis as a key CV protective mechanism. Considering the favorable effects on atherogenic lipoproteins and hepatic steatosis indices, our results support the pleiotropic effect of semaglutide beyond glycemic control.

The Role of Intermittent Fasting in the Management of Nonalcoholic Fatty Liver Disease: A Narrative Review.

Intermittent fasting is a non-pharmacological dietary approach to management of obesity and metabolic syndrome, involving periodic intervals of complete or near-complete abstinence from food and energy-containing fluids. This dietary strategy has recently gained significant popularity in mainstream culture and has been shown to induce weight loss in humans, reduce gut and systemic inflammation, and improve gut microbial diversity and dysbiosis (largely in animal models). It has been hypothesized that intermittent fasting could be beneficial in the management of nonalcoholic fatty liver disease, given the condition's association with obesity. This review summarizes protocols, potential mechanisms of action, and evidence for intermittent fasting in nonalcoholic fatty liver disease. It also highlights practical considerations for implementing intermittent fasting in clinical practice. A search of the literature for English-language articles related to intermittent fasting or time-restricted feeding and liver disease was completed in PubMed and Google Scholar. Potential mechanisms of action for effects of intermittent fasting included modulation of circadian rhythm, adipose tissue and adipokines, gut microbiome, and autophagy. Preclinical, epidemiological, and clinical trial data suggested clinical benefits of intermittent fasting on metabolic and inflammatory markers in humans. However, there was a paucity of evidence of its effects in patients with nonalcoholic fatty liver disease. More clinical studies are needed to determine mechanisms of action and to evaluate safety and efficacy of intermittent fasting in this population.

The Protective Anticancer Effect of Natural Lycopene Supercritical CO2 Watermelon Extracts in Adenocarcinoma Lung Cancer Cells.

Carotenoids may have different effects on cancer and its progression. The safety of carotenoid supplements was evaluated in vitro on human non-small cell lung cancer (NSCLC) adenocarcinoma A549 cells by the administration of three different oleoresins containing lycopene and other lipophilic phytochemicals, such as tocochromanols. The oleoresins, obtained by the supercritical CO2 green extraction technology from watermelon (Lyc W), gac(Lyc G) and tomato (Lyc T) and chlatrated in α-cyclodextrins, were tested in comparison to synthetic lycopene (Lyc S), by cell cycle, Annexin V-FITC/PI, clonogenic test, Mytosox, intracellular ROS, Western Blot for NF-kB and RT-PCR and ELISA for IL-8. The extracts administered at the same lycopene concentration (10 µM) showed conflicting behaviors: Lyc W, with the highest lycopene/tocochromanols ratio, significantly increased cell apoptosis, mitochondrial stress, intracellular ROS, NF-kB and IL-8 expression and significantly decreased cell proliferation, whereas Lyc G and Lyc T significantly increased only cell proliferation. Lyc S treatment was ineffective. The highest amount of lycopene in Lyc W was able to counteract and revert the cell survival effect of tocochromanols supporting the importance of evaluating the lycopene bio-availability and the real effect of antioxidant tocochromanols' supplementation which may not only have no anticancer benefits but may even increase cancer aggressivity.

A New Academic Quality at Work Tool (AQ@workT) to Assess the Quality of Life at Work in the Italian Academic Context.

The present study provides evidence for a valid and reliable tool, the Academic Quality at Work Tool (AQ@workT), to investigate the quality of life at work in academics within the Italian university sector. The AQ@workT was developed by the QoL@Work research team, namely a group of expert academics in the field of work and organizational psychology affiliated with the Italian Association of Psychologists. The tool is grounded in the job demands-resources model and its psychometric properties were assessed in three studies comprising a wide sample of lecturers, researchers, and professors: a pilot study (N = 120), a calibration study (N = 1084), and a validation study (N = 1481). Reliability and content, construct, and nomological validity were supported, as well as measurement invariance across work role (researchers, associate professors, and full professors) and gender. Evidence from the present study shows that the AQ@workT represents a useful and reliable tool to assist university management to enhance quality of life, to manage work-related stress, and to mitigate the potential for harm to academics, particularly during a pandemic. Future studies, such as longitudinal tests of the AQ@workT, should test predictive validity among the variables in the tool.

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract.

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.

Relationship among Body Composition, Adipocytokines, and Irisin on Exercise Capacity and Quality of Life in COPD: A Pilot Study.

Adipose tissue is an endocrine organ that interferes with the severity of chronic obstructive pulmonary disease (COPD). Although inflammatory markers, body composition, and nutritional status have a significant impact on pulmonary function, the real contribution of adipocytokines and myokines in COPD is still controversial. We aimed to evaluate the role played by the body composition, leptin, adiponectin, haptoglobin, and irisin on the functional exercise capacity, respiratory function, and quality of life (QoL) in COPD. In 25 COPD (20% GOLD-1; 60% GOLD-2; 20% GOLD-3) patients and 26 matched control subjects, we find that leptin, total adiponectin and haptoglobin are significantly increased whereas the 6 min walk test (6MWT) and physical functioning scores are significantly decreased in COPD versus controls. A significant positive relationship is found between leptin and fat mass and between 6MWT and the good health indicators of nutritional status. A significant inverse relationship is found between 6MWT and leptin and fat mass, FEV1 and haptoglobin, and irisin and haptoglobin. Phase angle and leptin level are significant predictors for functional exercise capacity assessed with 6MWT. Taken altogether, the results of this pilot study further support the role played by body composition and adipocytokines on exercise capacity respiratory function and QoL in COPD.

Leptin and TGF-ß1 Downregulate PREP1 Expression in Human Adipose-Derived Mesenchymal Stem Cells and Mature Adipocytes.

Adipose tissue is widely recognized as an extremely active endocrine organ producing adipokines as leptin that bridge metabolism and the immune system. Pre-B-cell leukemia homeobox (Pbx)-regulating protein-1 (PREP1) is a ubiquitous homeodomain transcription factor involved in the adipogenic differentiation and insulin-sensitivity processes. Leptin, as pleiotropic adipokine, and TGF-ß, known to be expressed by primary pre-adipocytes [adipose-derived stem cells (ASCs)] and mature differentiated adipocytes, modulate inflammatory responses. We aimed to assess for the first time if leptin and TGF-ß interfere with PREP1 expression in both ASCs and mature differentiated adipocytes. Human ASCs were isolated from subcutaneous adipose liposuction and, after expansion, fully differentiated to mature adipocytes. In both ASCs and adipocytes, leptin and TGF-ß1 significantly decreased the expression of PREP1, alone and following concurrent Toll-like receptor 4 (TLR4) activation. Moreover, in adipocytes, but not in ASCs, leptin increased TLR4 and IL-33 expression, whereas TGF-ß1 enhanced TLR4 and IL-6 expression. Taken together, we provide evidence for a direct regulation of PREP1 by leptin and TGF-ß1 in ASCs and mature adipocytes. The effects of leptin and TGF-ß1 on immune receptors and cytokines, however, are limited to mature adipocytes, suggesting that modulating immune responses depends on the differentiation of ASCs. Further studies are needed to fully understand the regulation of PREP1 expression and its potential for the development of new therapeutic approaches in obesity-related diseases.

Working during a Pandemic between the Risk of Being Infected and/or the Risks Related to Social Distancing: First Validation of the SAPH@W Questionnaire.

BACKGROUND: The COVID-19 pandemic led the worldwide healthcare system to a severe crisis in which personnel paid the major costs. Many studies were promptly dedicated to the physical and psychological consequences of the COVID-19 exposure among healthcare employees, whereas the research on the other working populations has been substantially ignored. To bridge the current lack of knowledge about safe behaviors related to the risk of COVID-19 contagion at work, the aim of the study was to validate a new tool, the SAPH@W (Safety at Work), to assess workers' perceptions of safety. METHODS: A total of 1085 participants, employed in several organizations sited across areas with different levels of risk of contagion, completed an online questionnaire. To test the SAPH@W validity and measurement invariance, the research sample was randomly divided in two. RESULTS: In the first sub-sample, Confirmatory Factor Analysis demonstrated the adequacy of the SAPH@W factorial structure. In the second sub-sample, multi-group Confirmatory Factor Analysis revealed that the SAPH@W was invariant across gender, ecological risk level, and type of occupation (in-person vs. remote working). CONCLUSIONS: The study evidenced the psychometric properties of the SAPH@W, a brief tool to monitor workers' experiences and safety perceptions regarding the COVID-19 risk in any organisational setting.

Psychological distress in the academic population and its association with socio-demographic and lifestyle characteristics during COVID-19 pandemic lockdown: Results from a large multicenter Italian study.

Measures implemented in many countries to contain the COVID-19 pandemic resulted in a change in lifestyle with unpredictable consequences on physical and mental health. We aimed at identifying the variables associated with psychological distress during the lockdown between April and May 2020 in the Italian academic population. We conducted a multicenter cross-sectional online survey (IO CONTO 2020) within five Italian universities. Among about 240,000 individuals invited to participate through institutional communications, 18 120 filled the questionnaire. Psychological distress was measured by the self-administered Hospital Anxiety and Depression Scale (HADS). The covariates collected included demographic and lifestyle characteristics, trust in government, doctors and scientists. Associations of covariates with influenza-like symptoms or positive COVID-19 test and with psychological distress were assessed by multiple regression models at the local level; a meta-analysis of the results was then performed. Severe levels of anxiety or depression were reported by 20% of the sample and were associated with being a student or having a lower income, irrespective of their health condition and worries about contracting the virus. The probability of being severely anxious or depressed also depended on physical activity: compared to those never exercising, the highest OR being for those who stopped during lockdown (1.53; 95% CI, 1.28 to 1.84) and the lowest for those who continued (0.78; 95% CI, 0.64 to 0.95). Up to 21% of severe cases of anxiety or depression might have been avoided if during lockdown participants had continued to exercise as before. Socioeconomic insecurity contributes to increase mental problems related to the COVID-19 pandemic and to the measures to contain it. Maintaining or introducing an adequate level of physical activity is likely to mitigate such detrimental effects. Promoting safe practice of physical activity should remain a public health priority to reduce health risks during the pandemic.

Leptin in the Respiratory Tract: Is There a Role in SARS-CoV-2 Infection?

Leptin is a pleiotropic adipocytokine involved in several physiologic functions, with a known role in innate and adaptive immunity as well as in tissue homeostasis. Long- and short-isoforms of leptin receptors are widely expressed in many peripheral tissues and organs, such as the respiratory tract. Similar to leptin, microbiota affects the immune system and may interfere with lung health through the bidirectional crosstalk called the "gut-lung axis." Obesity leads to impaired protective immunity and altered susceptibility to pulmonary infections, as those by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although it is known that leptin and microbiota link metabolism and lung health, their role within the SARS-CoV2 coronavirus disease 2019 (COVID-19) deserves further investigations. This review aimed to summarize the available evidence about: (i) the role of leptin in immune modulation; (ii) the role of gut microbiota within the gut-lung axis in modulating leptin sensitivity; and (iii) the role of leptin in the pathophysiology of COVID-19.

Notch-1 decreased expression contributes to leptin receptor downregulation in nasal epithelium from allergic turbinates.

BACKGROUND: Allergic rhinitis is characterized by a remodeling of nasal epithelium. Since the Notch and TGF-ß signaling pathways are known to be involved in cell differentiation and remodeling processes and leptin adipokine has already been identified as a marker for homeostasis in human bronchial and nasal epithelial cells of asthmatics, roles played by these pathways have been investigated for chronic allergic rhinitis. METHODS: The leptin/leptin receptor expression has been investigated in a study with 40 biopsies from allergic (AR, n = 18) and non-allergic (C, n = 22) inferior turbinates, using immunohistochemistry, immunofluorescence staining and RT-PCR. In addition, extracts from in vitro samples prepared from primary cells of inferior turbinates as well as in vitro cultured human nasal epithelial RPMI 2650 cells (ATCC-CCL-30) were also tested for leptin expression and activation of the Notch-1 pathway. RESULTS: With regards to AR, in vivo expression levels of both leptin and its receptor significantly decreased in comparison to C. Furthermore, leptin receptor mRNA was significantly reduced in AR as compared to C. Immunofluorescence showed an apparent co-expression of leptin receptor with Notch-1, which was not seen with TGF-ß. In vitro, in primary turbinate epithelial cells, the expression of leptin receptor and Notch-1 significantly decreased in AR as compared to C. Moreover, in RPMI 2650 cells, leptin receptor expression was shown to be induced by Notch-1 ligand signaling. CONCLUSION: Thus, both the leptin and Notch-1 pathways appear to represent markers for epithelial homeostasis in allergic rhinitis.

Teachers' work ability: a study of relationships between collective efficacy and self-efficacy beliefs.

INTRODUCTION: Work ability constitutes one of the most studied well-being indicators related to work. Past research highlighted the relationship with work-related resources and demands, and personal resources. However, no studies highlight the role of collective and self-efficacy beliefs in sustaining work ability. PURPOSE: The purpose of this study was to examine whether and by which mechanism work ability is linked with individual and collective efficacies in a sample of primary and middle school teachers. MATERIALS AND METHODS: Using a dataset consisting of 415 primary and middle school Italian teachers, the analysis tested for the mediating role of self-efficacy between collective efficacy and work ability. RESULTS: Mediational analysis highlights that teachers' self-efficacy totally mediates the relationship between collective efficacy and perceived work ability. CONCLUSION: Results of this study enhance the theoretical knowledge and empirical evidence regarding the link between teachers' collective efficacy and self-efficacy, giving further emphasis to the concept of collective efficacy in school contexts. Moreover, the results contribute to the study of well-being in the teaching profession, highlighting a process that sustains and promotes levels of work ability through both collective and personal resources.

Developing Organizational Competences for Conflict Management: The Use of the Prisoner's Dilemma in Higher Education.

Interpersonal relationship require sophisticated competences of cohabitation. However, the availability of training tools to develop conflict management skills is limited and problematic. The prisoner's dilemma game (PDG), the most widely known example of game theory, a nonzero-sum game, has been used, in higher education, to provide students with an opportunity of active learning and for understanding counterintuitive concepts. It creates a condition of emotive, moral and decisional conflict in and between agents. This paper presents a case-study in higher education in which PDG was proposed to enhance organizational competences for conflict management, according to the psychoanalytic approach to organizational studies. The study aims to explore: (1) the significant characteristics of PDG used in an affective-emotional key in higher education; (2) the learning outcomes that PDG enables to activate in the participants in relation to the development of organizational skills for conflict management. Twenty students' reflective journals were analyzed using thematic analysis. Findings indicated that PDG is perceived as a useful device in students' learning experience, which is appreciated in relation to its concreteness, intensity and debriefing phase. Learning outcomes allow new meanings about conflict, by emphasizing its defensive, automatic and interpersonal dimension. This paper contributes to the understanding of PDG as a tool to develop competences in dealing with the challenges of conflict management, since it seems to favor the overcoming of the individualistic stereotype in conflict representation by highlighting the interdependence of social interaction.

Electrophilic derivatives of omega-3 fatty acids counteract lung cancer cell growth.

PURPOSE: 17-oxo-DHA is an electrophilic keto-derivative of the omega-3 fatty acid docosahexaenoic acid (DHA) endogenously generated by cyclooxygenase-2 and a cellular dehydrogenase. 17-oxo-DHA displays anti-inflammatory and cytoprotective actions. DHA, alone or in combination with standard chemotherapy, displays antitumor activity. However, the effects of electrophilic keto-derivatives of DHA on cancer growth have never been evaluated. We investigated whether 17-oxo-DHA, alone or in combination with gemcitabine, displayed antitumor effects. Furthermore, we evaluated whether the enzyme 15-prostaglandin dehydrogenase (15-PGDH) was required for transducing the antitumor effects of DHA. METHODS: A panel of five histologically different human non-small cell lung cancer (NSCLC) cell lines was used. Cells were treated with 17-oxo-DHA and gemcitabine, alone or in combination, and apoptosis, proliferation, Fas and FasL expression (mRNA and protein) and active caspase-3/7 and -8 were assessed. Furthermore, an inhibitor of 15-PGDH was used to test the involvement of this enzyme in mediating the antitumor effects of DHA. RESULTS: 17-oxo-DHA (50 µM, 72 h) significantly reduced proliferation, increased cell apoptosis, Fas and FasL expression as well as active caspase-8 and -3/7. When 17-oxo-DHA was given in combination with gemcitabine, stronger effects were observed compared to gemcitabine alone. The enzyme 15-PGDH was required for DHA to promote its full anti-apoptotic effect suggesting that enzymatically generated keto-derivatives of DHA mediate its antitumor actions. CONCLUSIONS: Data herein provided, demonstrate that 17-oxo-DHA displays antitumor effects in NSCLC cell lines. Of note, the combination of 17-oxo-DHA plus gemcitabine, resulted in stronger anticancer effects compared to gemcitabine alone.

SIRT1/FoxO3 axis alteration leads to aberrant immune responses in bronchial epithelial cells.

Inflammation and ageing are intertwined in chronic obstructive pulmonary disease (COPD). The histone deacetylase SIRT1 and the related activation of FoxO3 protect from ageing and regulate inflammation. The role of SIRT1/FoxO3 in COPD is largely unknown. This study evaluated whether cigarette smoke, by modulating the SIRT1/FoxO3 axis, affects airway epithelial pro-inflammatory responses. Human bronchial epithelial cells (16HBE) and primary bronchial epithelial cells (PBECs) from COPD patients and controls were treated with/without cigarette smoke extract (CSE), Sirtinol or FoxO3 siRNA. SIRT1, FoxO3 and NF-κB nuclear accumulation, SIRT1 deacetylase activity, IL-8 and CCL20 expression/release and the release of 12 cytokines, neutrophil and lymphocyte chemotaxis were assessed. In PBECs, the constitutive FoxO3 expression was lower in patients with COPD than in controls. Furthermore, CSE reduced FoxO3 expression only in PBECs from controls. In 16HBE, CSE decreased SIRT1 activity and nuclear expression, enhanced NF-κB binding to the IL-8 gene promoter thus increasing IL-8 expression, decreased CCL20 expression, increased the neutrophil chemotaxis and decreased lymphocyte chemotaxis. Similarly, SIRT1 inhibition reduced FoxO3 expression and increased nuclear NF-κB. FoxO3 siRNA treatment increased IL-8 and decreased CCL20 expression in 16HBE. In conclusion, CSE impairs the function of SIRT1/FoxO3 axis in bronchial epithelium, dysregulating NF-κB activity and inducing pro-inflammatory responses.

Customer Orientation and Leadership in the Health Service Sector: The Role of Workplace Social Support.

Health care is a critical context due to unpredictable situations, demanding clients, workload, and intrinsic organizational complexity. One key to improve the quality of health services is connected to the shift in organization perspective of viewing patients as active consumers rather than passive users. Therefore, higher levels of customer orientation (CO) are expected to improve organizational service effectiveness. According to a cultural perspective to CO, the aim of the study was to explore how different leaders' behaviors (task-oriented and relationship-oriented) interact with CO of health organizations. Specifically, the aim of the paper was to contribute to this topic, by considering the leaders' point of view. Since leader's experience of CO is influenced by social processes in the work environment, workplace social support (WSS) was inserted as moderator in the relationship between leader behavior and CO. A survey study was conducted among 57 Health Department directors belonging to the National Health Service in the North of Italy in 2016. Findings showed that WSS moderated the influence of leadership concern for relationship on CO. Practical implications of the study are discussed.