Calcitonin-Induced Effects on Amniotic Fluid-Derived Mesenchymal Stem Cells

Background/Aims: Mesenchymal stem cells from human amniotic fluid (huAFMSCs) can differentiate into multiple lineages and are not tumorigenic after transplantation, making them good candidates for therapeutic purposes. The aim was to determine the effects of calcitonin on these huAFMSCs during osteogenic differentiation, in terms of the physiological role of calcitonin in bone homeostasis. Methods: For huAFMSCs cultured under different conditions, we assayed: expression of the calcitonin receptor, using immunolabelling techniques; proliferation and osteogenesis, using colorimetric and enzymatic assays; intracellular Ca2+ and cAMP levels, using videomicroscopy and spectrophotometry. Results: The calcitonin receptor was expressed in proliferating and osteo-differentiated huAFMSCs. Calcitonin triggered intracellular Ca2+ increases and cAMP production. Its presence in cell medium also induced dose-dependent inhibitory effects on proliferation and increased osteogenic differentiation of huAFMSCs, as also indicated by enhancement of specific markers and alkaline phosphatase activity. Conclusions: These data show that huAFMSCs represent a potential osteogenic model to study in-vitro cell responses to calcitonin (and other members of the calcitonin family). This leads the way to the opening of new lines of research that will add new insight both in cell therapies and in the pharmacological use of these molecules

Calcitonin-Induced Effects on Amniotic Fluid-Derived Mesenchymal Stem Cells

Background/Aims: Mesenchymal stem cells from human amniotic fluid (huAFMSCs) can differentiate into multiple lineages and are not tumorigenic after transplantation, making them good candidates for therapeutic purposes. The aim was to determine the effects of calcitonin on these huAFMSCs during osteogenic differentiation, in terms of the physiological role of calcitonin in bone homeostasis. Methods: For huAFMSCs cultured under different conditions, we assayed: expression of the calcitonin receptor, using immunolabelling techniques; proliferation and osteogenesis, using colorimetric and enzymatic assays; intracellular Ca2+ and cAMP levels, using videomicroscopy and spectrophotometry. Results: The calcitonin receptor was expressed in proliferating and osteo-differentiated huAFMSCs. Calcitonin triggered intracellular Ca2+ increases and cAMP production. Its presence in cell medium also induced dose-dependent inhibitory effects on proliferation and increased osteogenic differentiation of huAFMSCs, as also indicated by enhancement of specific markers and alkaline phosphatase activity. Conclusions: These data show that huAFMSCs represent a potential osteogenic model to study in-vitro cell responses to calcitonin (and other members of the calcitonin family). This leads the way to the opening of new lines of research that will add new insight both in cell therapies and in the pharmacological use of these molecules

Translation-Dependent Mechanisms Lead to PML Upregulation and Mediate Oncogenic K-RAS-Induced Cellular Senescence

Expression of oncogenic K-RAS in primary cells elicits oncogene-induced cellular senescence (OIS), a form of growth arrest that potently opposes tumourigenesis. This effect has been largely attributed to transcriptional mechanisms that depend on the p53 tumour suppressor protein. The PML tumour suppressor was initially identified as a component of the $PML-RAR\alpha$ oncoprotein of acute promyelocytic leukaemia (APL). PML, a critical OIS mediator, is upregulated by oncogenic K-RAS in vivo and in vitro. We demonstrate here that oncogenic K-RAS induces PML protein upregulation by activating the RAS/MEK1/mTOR/eIF4E pathway even in the absence of p53. Under these circumstances, PML mRNA is selectively associated to polysomes. Importantly, we find that the PML 5′ untranslated mRNA region plays a key role in mediating PML protein upregulation and that its presence is essential for an efficient OIS response. These findings demonstrate that upregulation of PML translation plays a central role in oncogenic K-RAS-induced OIS. Thus, selective translation initiation plays a critical role in tumour suppression with important therapeutic implications for the treatment of solid tumours and APL

Association of the 1q25 diabetes-specific coronary heart disease locus with slterations of the γ-glutamyl cycle and increased methylglyoxal levels in endothelial cells

A chromosome 1q25 variant (rs10911021) has been associated with coronary heart disease (CHD) in type 2 diabetes. In human umbilical vein endothelial cells (HUVECs), the risk allele "C" is associated with lower expression of the adjacent gene GLUL encoding glutamine synthase, converting glutamic acid to glutamine. To further investigate the mechanisms through which this locus affects CHD risk, we measured 35 intracellular metabolites involved in glutamic acid metabolism and the γ-glutamyl cycle in 62 HUVEC strains carrying different rs10911021 genotypes. Eight metabolites were positively associated with the risk allele (17-58% increase/allele copy, P = 0.046-0.002), including five γ-glutamyl amino acids, β-citryl-glutamate, N-acetyl-aspartyl-glutamate, and ophthalmate-a marker of γ-glutamyl cycle malfunction. Consistent with these findings, the risk allele was also associated with decreased glutathione-to-glutamate ratio (-9%, P = 0.012), decreased S-lactoylglutathione (-41%, P = 0.019), and reduced detoxification of the atherogenic compound methylglyoxal (+54%, P = 0.008). GLUL downregulation by shRNA caused a 40% increase in the methylglyoxal level, which was completely prevented by glutamine supplementation. In summary, we have identified intracellular metabolic traits associated with the 1q25 risk allele in HUVECs, including impairments of the γ-glutamyl cycle and methylglyoxal detoxification. Glutamine supplementation abolishes the latter abnormality, suggesting that such treatment may prevent CHD in 1q25 risk allele carriers

Resilience, Coping Strategies and Posttraumatic Growth in the Workplace Following COVID-19: A Narrative Review on the Positive Aspects of Trauma

The COVID-19 pandemic represents a traumatic event that has profoundly changed working conditions with detrimental consequences for workers’ health, in particular for the healthcare population directly involved in addressing the emergency. Nevertheless, previous research has demonstrated that traumatic experiences can also lead to positive reactions, stimulating resilience and feelings of growth. The aim of this narrative review is to investigate the positive aspects associated with the COVID-19 pandemic and the possible health prevention and promotion strategies by analyzing the available scientific evidence. In particular, we focus on the constructs of resilience, coping strategies and posttraumatic growth (PTG). A literature search was performed on the PubMed, EMBASE, Scopus, Web of Science, Google Scholar and Psycinfo databases. Forty-six articles were included in the literature synthesis. Psychological resilience is a fundamental variable for reducing and preventing the negative psychological effects of the pandemic and is associated with lower levels of depression, anxiety and burnout. At the individual and organizational level, resilience plays a crucial role in enhancing wellbeing in healthcare and non-healthcare workers. Connected to resilience, adaptive coping strategies are essential for managing the emergency and work-related stress. Several positive factors influencing resilience have been highlighted in the development of PTG. At the same time, high levels of resilience and positive coping strategies can enhance personal growth. Considering the possible long-term coexistence and consequences of COVID-19, organizational interventions should aim to improve workers’ adaptive coping skills, resilience and PTG in order to promote wellbeing

Inflammation and autoimmunity in patients anti-neutrophil nuclear antibodies positive

Two patients, female, with overlap syndrome AIH/PSC and pANNA positive, was placed at two extremities of the bimodal curve that characterised the AIH I° behaviour.Therefore they show difference of age (V.L. 76 years and E.G. 8 years) and different prognosis and therapy answer: the disease of the young patient has an aggressive outcome and fails the treatment more commonly.The more important theory to explain this different features was the “molecular footprint hypothesis” that considers decisive the type of HLA II°. The two patients considered have the same HLADR3. The serological analysis and the recent pathogenically orientations show that the local motives regulate the features of disease: in the child the inflammatory component prevails and maintains a chronic granulomatous aggression, whereas in the old patient the non specific autoimmune IgG prevails and drives a fibrosis evolution and immunosuppressive therapy response.The common positive pANNA can be expression of common chronic auto-inflammatory granulomatous origin

Surfing the web during pandemic flu: Availability of world health organization recommendations on prevention

Abstract Background: People often search for information on influenza A(H1N1)v prevention on the web. The extent to which information found on the Internet is consistent with recommendations issued by the World Health Organization is unknown. Methods: We conducted a search for "swine flu" accessing 3 of the most popular search engines through different proxy servers located in 4 English-speaking countries (Australia, Canada, UK, USA). We explored each site resulting from the searches, up to 4 clicks starting from the search engine page, analyzing availability of World Health Organization recommendations for swine flu prevention. Results: Information on hand cleaning was reported on 79% of the 147 websites analyzed; staying home when sick was reported on 77.5% of the websites; disposing tissues after sneezing on 75.5% of the websites. Availability of other recommendations was lower. The probability of finding preventative recommendations consistent with World Health Organization varied by country, type of website, and search engine. Conclusions: Despite media coverage on H1N1 influenza, relevant information for prevention is not easily found on the web. Strategies to improve information delivery to the general public through this channel should be improved

Surfing the web during pandemic flu: availability of World Health Organization recommendations on prevention

<p>Abstract</p> <p>Background</p> <p>People often search for information on influenza A(H1N1)v prevention on the web. The extent to which information found on the Internet is consistent with recommendations issued by the World Health Organization is unknown.</p> <p>Methods</p> <p>We conducted a search for "swine flu" accessing 3 of the most popular search engines through different proxy servers located in 4 English-speaking countries (Australia, Canada, UK, USA). We explored each site resulting from the searches, up to 4 clicks starting from the search engine page, analyzing availability of World Health Organization recommendations for swine flu prevention.</p> <p>Results</p> <p>Information on hand cleaning was reported on 79% of the 147 websites analyzed; staying home when sick was reported on 77.5% of the websites; disposing tissues after sneezing on 75.5% of the websites. Availability of other recommendations was lower. The probability of finding preventative recommendations consistent with World Health Organization varied by country, type of website, and search engine.</p> <p>Conclusions</p> <p>Despite media coverage on H1N1 influenza, relevant information for prevention is not easily found on the web. Strategies to improve information delivery to the general public through this channel should be improved.</p