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61.
Leslie Calapre Elin S. Gray Sandrine Kurdykowski Anthony David Pascal Descargues Mel Ziman 《BMC dermatology》2017,17(1):8
Background
Exposure to heat stress after UVB irradiation induces a reduction of apoptosis, resulting in survival of DNA damaged human keratinocytes. This heat-mediated evasion of apoptosis appears to be mediated by activation of SIRT1 and inactivation of p53 signalling. In this study, we assessed the role of SIRT1 in the inactivation of p53 signalling and impairment of DNA damage response in UVB plus heat exposed keratinocytes.Results
Activation of SIRT1 after multiple UVB plus heat exposures resulted in increased p53 deacetylation at K382, which is known to affect its binding to specific target genes. Accordingly, we noted decreased apoptosis and down regulation of the p53 targeted pro-apoptotic gene BAX and the DNA repair genes ERCC1 and XPC after UVB plus heat treatments. In addition, UVB plus heat induced increased expression of the cell survival gene Survivin and the proliferation marker Ki67. Notably, keratinocytes exposed to UVB plus heat in the presence of the SIRT1 inhibitor, Ex-527, showed a similar phenotype to those exposed to UV alone; i.e. an increase in p53 acetylation, increased apoptosis and low levels of Survivin.Conclusion
This study demonstrate that heat-induced SIRT1 activation mediates survival of DNA damaged keratinocytes through deacetylation of p53 after exposure to UVB plus heat62.
Juliane Winkler Pengyuan Liu Kiet Phong Johanna H. Hinrichs Nassim Ataii Katherine Williams Elin Hadler-Olsen Susan Samson Zev J. Gartner Susan Fisher Zena Werb 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(11)
Environmental chemicals such as bisphenol A (BPA) are thought to contribute to carcinogenesis through their endocrine-disrupting properties. Due to accumulating evidence about negative human health effects, BPA is being phased out, but in parallel, exposures to replacement chemicals such as bisphenol S (BPS) and bisphenol F (BPF) are increasing. Little is known about their biologic effects, but because of their high degree of chemical relatedness, they may have overlapping as well as distinct actions as compared with BPA. We investigated this theory using a nonmalignant, human breast tissue-derived organoid system and two end points: morphologic and proteomic alterations. At low-nanomolar doses, replacement chemicals—particularly BPS—disrupted normal mammary organoid architecture and led to an increased branching phenotype. Treatment with the various bisphenols (vs. 17-β-estradiol or a vehicle control) produced distinct proteomic changes. For example, BPS up-regulated Cdc42-interacting protein 4, which supports the formation of invadopodia and a mesenchymal phenotype. In summary, this study used a highly physiologically relevant organoid system to provide evidence that replacement bisphenols have protumorigenic effects on the mammary gland at morphologic and proteomic levels, highlighting the importance of studies to evaluate the potential harmful effects of structurally related environmental chemicals.Bisphenols, of which the most prevalent is bisphenol A (BPA), are environmental chemicals that are used as plasticizers in a variety of goods, including plastic bottles, children''s toys, eyeglass lenses, food containers, and some types of thermal paper (e.g., cash register receipts). They leach from these products, contaminating humans (and animals) either directly or indirectly via other environmental media, such as household dust. Thus, in most adults, BPA is detected in serum, tissues, and urine (1, 2). Children (ages 6 to 11) have the highest concentrations of urinary BPA (3, 4). This chemical has structural similarities to estrogen (17-β-estradiol [E2]) and as a result, weakly mimics its activity (5). Hormones and growth factors play an important role in controlling prenatal mammary gland development and later on, the morphologic and functional alterations that occur during puberty, pregnancy, and eventually, menopause. Due to this plasticity, the mammary gland is particularly susceptible to the actions of endocrine-disrupting chemicals (EDCs), such as BPA (6–8). In vivo and in vitro studies have consistently shown that exposures to BPA at crucial developmental stages impair mammary gland development and increase neoplastic transformation (9–12). Treating rats with BPA results in mammary epithelial hyperplasia and enhances proliferation (13), common features of precancerous lesions. Additionally, BPA induces cell cycle progression and increases proliferation of human breast cancer cells in vitro via the up-regulated expression of estrogen-dependent genes (14).Based on these and other data, BPA has been removed from many commercial products. Most commonly, this chemical of concern is replaced by bisphenol S (BPS) and bisphenol F (BPF) compounds that share close structural similarities with BPA. However, little is known about their endocrine effects and more broadly, their biological activities. Marketing a product as “BPA free” suggests to the consumer that a product is safer, but research shows that replacement bisphenols have adverse effects similar to, or even greater than, BPA. For example, studies in zebrafish, rodents, and human cell culture models show that BPS and BPF have endocrine-disrupting activities. In zebrafish, despite species-specific differences in estrogen receptor (ER) affinity and specificity, BPF and BPS have estrogenic activities similar to BPA (15–17). In rats, exposure to BPF induces uterine growth, which suggests estrogenic effects (18). BPA, BPF, and BPS promote estrogen-dependent cell cycle progression, proliferation, and migration of human MCF-7 breast cancer cells along with epigenetic changes (19, 20). BPS exposure of pregnant and lactating mice limits milk production, suggesting alterations in mammary gland composition (21). In addition to estrogen signaling, BPF affects other endocrine pathways; in rats, oral administration of this compound alters thyroid hormone levels (22).Current research on bisphenol actions is mainly focused on endocrine effects. It is less well understood whether these chemicals have additional protumorigenic effects independent of their endocrine-disrupting activity. Moreover, tumor development is a multistep process involving heterogeneous cell types and numerous factors, including the potential roles of a variety of environmental chemicals (23, 24). Recapitulating this complexity in an experimental setup is challenging. In this context, tissue organoids are valuable models for understanding the early steps of carcinogenesis. They can be derived from nonmalignant primary tissues ex vivo. When grown for short periods of time in vitro, they maintain many of the genetic and epigenetic features of their normal cognates. Also, organoids have the added advantage of consisting of multiple cell types that are representative of the complexity of the tissue from which they are derived (25, 26).In this study, we exploited the strengths of the human mammary gland organoid culture system to understand the impact of the BPA replacements, BPF and BPS. Organoids established from nonmalignant human mammary gland tissues were exposed to one of the bisphenols, E2, or the vehicle control. The results showed that BPA replacements, in particular BPS, disrupted organoid architecture, enhanced branching, and caused compound-specific proteomic alterations—effects that were mostly E2 independent. Together, these observations suggested that the mammary gland effects of BPA substitutes should be equally or more concerning than those of the compound they are replacing. 相似文献
63.
Elin M. Svensson Francesca Aweeka Jeong-Gun Park Florence Marzan Kelly E. Dooley Mats O. Karlsson 《Antimicrobial agents and chemotherapy》2013,57(6):2780-2787
Safe, effective concomitant treatment regimens for tuberculosis (TB) and HIV infection are urgently needed. Bedaquiline (BDQ) is a promising new anti-TB drug, and efavirenz (EFV) is a commonly used antiretroviral. Due to EFV''s induction of cytochrome P450 3A4, the metabolic enzyme responsible for BDQ biotransformation, the drugs are expected to interact. Based on data from a phase I, single-dose pharmacokinetic study, a nonlinear mixed-effects model characterizing BDQ pharmacokinetics and interaction with multiple-dose EFV was developed. BDQ pharmacokinetics were best described by a 3-compartment disposition model with absorption through a dynamic transit compartment model. Metabolites M2 and M3 were described by 2-compartment models with clearance of BDQ and M2, respectively, as input. Impact of induction was described as an instantaneous change in clearance 1 week after initialization of EFV treatment and estimated for all compounds. The model predicts average steady-state concentrations of BDQ and M2 to be reduced by 52% (relative standard error [RSE], 3.7%) with chronic coadministration. A range of models with alternative structural assumptions regarding onset of induction effect and fraction metabolized resulted in similar estimates of the typical reduction and did not offer a markedly better fit to data. Simulations to investigate alternative regimens mitigating the estimated interaction effect were performed. The results suggest that simple adjustments of the standard regimen during EFV coadministration can prevent reduced exposure to BDQ without increasing exposures to M2. However, exposure to M3 would increase. Evaluation in clinical trials of adjusted regimens is necessary to ensure appropriate dosing for HIV-infected TB patients on an EFV-based regimen. 相似文献
64.
Kinetics of antibody and memory B cell responses after MMR immunization in children and young adults
Maria Kakoulidou Hanna Ingelman-Sundberg Elin Johansson Alberto Cagigi Salah Eldin Farouk Anna Nilsson Kari Johansen 《Vaccine》2013
The persistence of antigen-specific memory B-cells (MBCs) in children and young adults long time after vaccination against measles, mumps and rubella (MMR) is not known. Here we have looked at the Swedish immunization program and examined children 1–10 years after the first MMR dose in early childhood, as well as young adults 7–18 years after the second dose of MMR. We show that Ab titers and MBCs against measles and rubella have different kinetics, indicating that the MBC pool and the corresponding Ab titers are regulated independently. These data fit well with other findings that continuous IgG secretion comes from long-lived plasma cells and not MBCs. We also demonstrate that individuals with low post-vaccination Ab titers might have an adequate MBC response. It remains to be shown if memory B-cells provide the same protection as specific antibodies, but our data is a valuable complement to the incomplete knowledge about correlates of protection after vaccination. 相似文献
65.
Anners Lerdal Britt Moe Elin Digre Thomas Harding Frode Kristensen Ellen K. Grov Linda N. Bakken Marthe L. Eklund Ireen Ruud & Joseph S. Rossi 《Journal of advanced nursing》2009,65(1):193-202
Title. Stages of Change – Continuous Measure (URICA-E2): psychometrics of a Norwegian version.
Aim. This paper is a report of research to translate the English version of the Stages of Change continuous measure questionnaire (URICA-E2) into Norwegian and to test the validity of the questionnaire and its usefulness in predicting behavioural change.
Background. While the psychometric properties of the Stages of Change categorical measure have been tested extensively, evaluation of the psychometric properties of the continuous questionnaire has not been described elsewhere in the literature.
Method. Cross-sectional data were collected with a convenience sample of 198 undergraduate nursing students in 2005 and 2006. The English version of URICA-E2 was translated into Norwegian according to standardized procedures.
Findings. Principal components analysis clearly confirmed five of the dimensions of readiness to change (Precontemplation Non-Believers, Precontemplation Believers, Contemplation, Preparation and Maintenance), while the sixth dimension, Action, showed the lowest Eigenvalue (0·93). Findings from the cluster analysis indicate distinct profiles among the respondents in terms of readiness to change their exercise behaviour.
Conclusion. The URICA-E2 was for the most part replicated from Reed's original work. The result of the cluster analysis of the items associated with the factor 'Action' suggests that these do not adequately measure the factor. 相似文献
Aim. This paper is a report of research to translate the English version of the Stages of Change continuous measure questionnaire (URICA-E2) into Norwegian and to test the validity of the questionnaire and its usefulness in predicting behavioural change.
Background. While the psychometric properties of the Stages of Change categorical measure have been tested extensively, evaluation of the psychometric properties of the continuous questionnaire has not been described elsewhere in the literature.
Method. Cross-sectional data were collected with a convenience sample of 198 undergraduate nursing students in 2005 and 2006. The English version of URICA-E2 was translated into Norwegian according to standardized procedures.
Findings. Principal components analysis clearly confirmed five of the dimensions of readiness to change (Precontemplation Non-Believers, Precontemplation Believers, Contemplation, Preparation and Maintenance), while the sixth dimension, Action, showed the lowest Eigenvalue (0·93). Findings from the cluster analysis indicate distinct profiles among the respondents in terms of readiness to change their exercise behaviour.
Conclusion. The URICA-E2 was for the most part replicated from Reed's original work. The result of the cluster analysis of the items associated with the factor 'Action' suggests that these do not adequately measure the factor. 相似文献
66.
Objective.— The objective of this study was to compare the relationship between repeated momentary reports of stress and headaches in female adolescents with varying degrees of headache frequency. Background.— Headaches are the most common form of pain reported by adolescents affecting more than a third of all adolescents. High levels of stress during adolescence may predispose an adolescent to experience headaches in adulthood. Randomized, momentary data collection of stress and headaches provides the most accurate data regarding the adolescent experience of these variables. Methods.— The research methodology, ecological momentary assessment, is a valid approach to better understand the relationship between stress and headaches in adolescence. Data were obtained by each participant's use of an electronic diary (ED), which captured repeated momentary reports of perceived stress, head pain, and stress‐related symptoms in female adolescents with varying degrees of recurrent headache. Seven times per day for the 21‐day study period, teen girls responded to ED questions about their current stress levels, head pain, and stress‐related symptoms. Based on participants' momentary reports of headaches, Low Headache, Moderate Headache, and Chronic Headache groups were created. General estimating equation models were used to analyze the relationship between momentary variables as well as the lag effect between stress and head pain. Results.— Thirty‐one participants, aged 14‐18 years, completed 2841 randomized ED reports and reported 674 occurrences of headache. The Chronic Headache and Moderate Headache groups reported significantly increased levels of stress, head pain, and headaches. The relationship between momentary stress and head pain was significantly strong both within and across participants. The strength of this relationship increased with increased headache activity. A significant lag effect was found between stress and headaches; however, the effect of depression as a moderator of the stress and headache relationship remains unclear. Conclusion.— Perceived stress and head pain was highly correlated in these female adolescents. Given the large population of teens affected by headaches, a plausible next step would be to validate these results in other samples and to determine methods with which to identify teens who may be at risk for a pattern of increasing stress and headaches. 相似文献
67.
Background
The aim of this paper was to study the collaboration between emergency departments (EDs) in general hospitals and community health services (CHS) in Norway when providing psychosocial care and aftercare to patients treated in EDs following a suicide attempt. We wanted to explore the extent to which quality indicators at the hospital level measured in 1999 and 2006 could predict the presence or absence of a chain of care structure in the CHS in 2006. 相似文献68.
Elin Damsgrd Anne Dewar Cecilie Re Torunn Hamran 《Scandinavian journal of caring sciences》2011,25(1):108-116
Scand J Caring Sci; 2011; 25; 108–116 Staying active despite pain: Pain beliefs and experiences with activity‐related pain in patients with chronic musculoskeletal pain Objective: Maintain a level of activity and exercise is advice often given to patients with chronic musculoskeletal pain, but many patients find physical activity painful and consequently hesitate to move. Disability seems to be associated with fear of pain and there is a need to enhance our understanding of patients’ beliefs and attitudes about how fear of pain affects physical activity and why some people are active despite their pain. The aim of this research was to understand thoughts and experiences about pain related to activity in patients with musculoskeletal disorders; the situations that promoted pain and if and how fear was expressed. Methods: Five women and five men, recruited from a larger survey on fear, pain and physical activity were interviewed. The interviews were analysed by qualitative methods for themes about participants’ pain and beliefs about pain. Results: By interpreting signals from the body, patients calculated and planned their daily life to stay active despite pain and participate in their social lives. Pain was a signal with diverse meanings which, with the influence of time, seemed to change from a sign of danger to a reminder to moderate their level of activity. By experimenting with different activities, patients learned how to gradually remain or become physically active. Conclusion: Patients strived to stay active despite pain. The interpretation of pain changed over time, from a threatening signal to a signal with diverse meanings. Practice implications: The findings provide insights that may improve the educational rehabilitation of patients with musculoskeletal pain. 相似文献
69.
Background
Substance abuse during pregnancy may harm the foetus and can cause neonatal abstinence syndrome. Exposure to alcohol and other substances can influence the child for the rest of its life. A special child welfare clinic was set up in 1994 in Kristiansand, Norway, targeting pregnant women with substance abuse problems in the county of Vest-Agder. Pregnancy is not an indication for opioid replacement therapy in Norway, and one of the clinic's aims was to support the drug dependent women through their pregnancy without any replacements. The object of this paper is to describe concurrent health and social problems, as well as the predictors for stopping drug abuse, in the clinic's user group. 相似文献70.
Elin Karlsson Ulla Delle Anna Danielsson Björn Olsson Frida Abel Per Karlsson Khalil Helou 《BMC cancer》2008,8(1):254