Enhancer of rudimentary homologue interacts with scaffold attachment factor B at the nuclear matrix to regulate SR protein phosphorylation

Scaffold attachment factor B1 (SAFB1) is an integral component of the nuclear matrix of vertebrate cells. It binds to DNA on scaffold/matrix attachment region elements, as well as to RNA and a multitude of different proteins, affecting basic cellular activities such as transcription, splicing and DNA damage repair. In the present study, we show that enhancer of rudimentary homologue (ERH) is a new molecular partner of SAFB1 and its 70% homologous paralogue, scaffold attachment factor B2 (SAFB2). ERH interacts directly in the nucleus with the C-terminal Arg-Gly-rich region of SAFB1/2 and co-localizes with it in the insoluble nuclear fraction. ERH, a small ubiquitous protein with striking homology among species and a unique structure, has also been implicated in fundamental cellular mechanisms. Our functional analyses suggest that the SAFB/ERH interaction does not affect SAFB1/2 function in transcription (e.g. as oestrogen receptor α co-repressors), although it reverses the inhibition exerted by SAFB1/2 on the splicing kinase SR protein kinase 1 (SRPK1), which also binds on the C-terminus of SAFB1/2. Accordingly, ERH silencing decreases lamin B receptor and SR protein phosphorylation, which are major SRPK1 substrates, further substantiating the role of SAFB1 and SAFB2 in the co-ordination of nuclear function. © 2017 Federation of European Biochemical Societie

Determinants of quality of life in children and adolescents with CHD: A systematic review

Purpose This review aims to outline a systematic approach for the assessment of quality of life in children and adolescents with CHD and to cite its main determinants. Methods A systematic critical literature search in PubMed, Scopus, and Cinahl databases resulted in 954 papers published after 2000. After the quality assessment, 32 original articles met the inclusion criteria. Results Methodological quality of the included studies varied greatly, showing a moderate quality. Impaired quality of life was associated with more severe cardiac lesions. Children with CHD, after cardiac surgery, reported diminished quality of life concerning physical, psycho-social, emotional, and school functioning. The majority of clinical studies showed significant differences among children and their parents' responses regarding their quality of life, with a tendency of children to report greater quality of life scores than their parents. According to our analysis, concerning children with CHD, the most cited determinants of their quality of life were as follows: (a) parental support; (b) lower socio-economic status; (c) limitations due to physical impairment; (d) sense of coherence; as well as (e) the level of child's everyday anxiety and depression. These findings suggest that differences in quality of life issues may exist across lesion severities. Conclusion Quality of life in children with CHD should be assessed according to age; severity; therapeutic approach; acceptance of the disease; and personality features. Effective management and early recognition of significant impairments in quality of life could impact clinical outcomes in children with CHD. © © Cambridge University Press 2015

The association of sedentary lifestyle with childhood asthma. The role of nurse as educator

Background: To provide a summary of the existing published knowledge on the association between sedentary lifestyle and childhood asthma. Twelve years ago, the first longitudinal studies carried out in children showed a relationship between physical activity and asthma. Several epidemiological studies confirmed these findings, with sedentary lifestyle predicting the onset of asthma. Methods: A systematic review of epidemiological studies was conducted within the MEDLINE database. Epidemiological studies on children subjects, published in English were included in the review. A comprehensive literature search yielded 50 studies for further consideration. Following the application of the eligibility criteria, we identified 11 studies. Results: A positive association and an excess risk of asthma during childhood were revealed to sedentary lifestyle. The findings proved the association between childhood asthma and sedentary lifestyle. The correlation between bronchial asthma and sedentary life during childhood and identifying whether preventable or treatable risk factors exist needs to be determined. Further research on the topic is essential for safer and standardised conclusions. Conclusions and practice implication: Asthma can be controlled when managed properly. The role of the nurse as an educator should establish and maintain a relationship with patients in order to help them manage their disease. The steps towards asthma management will help paediatric patients to guide their approach to the condition. © 2013 SEICAP

UVB-mediated down-regulation of proteasome in cultured human primary pterygium fibroblasts

Background: Pterygium is a condition characterized by epithelial overgrowth of the cornea, inflammatory cell infiltration and an abnormal extracellular matrix accumulation. Chronic UV exposure is considered as a pathogenic factor of this disease. Proteasome is an intracellular multi-subunit protease complex that degrades intracellular proteins. Among proteasome subunits the β5 (PSMB5), bearing chymotrypsin-like activity. It is considered as the main proteasome subunit and its expression is mediated by Nrf2-ARE pathway in many cell types. This study investigates the expression of PSMB5 in pterygium and the effect of UVB irradiation on its expression and activity in pterygium fibroblasts. Methods: Normal conjunctival and pterygium specimens were obtained from the bulbar conjunctiva of patients undergoing cataract surgery and from patients with pterygium undergoing surgical removal of primary tissue, respectively. Fibroblasts were isolated upon treatment of specimens with clostridium collagenase. The expression of PSMB5 and Nrf2 in tissues and cells was ascertained by RT-PCR analysis and western blotting. Cell survival was measured by the MTT method and the proteasome chymotrypsin-like activity was determined by fluorometry. Results: RT-PCR analysis showed that the expression of PSMB5 was significantly lower in pterygium than in normal conjunctiva. The expression of PSMB5 was mediated by the Nrf2/ARE pathway as indicated by using the Nrf2 activator Oltipraz. The expression of PSMB5 and Nrf2 by pterygium fibroblasts was suppressed in a dose dependent manner following UVB radiation of 0-50 mJ/cm2 doses. The expression of PSMB5, but not of Nrf2, remained at almost the control levels, when UVB exposure was performed after pre-incubation of cells with the src kinases inhibitor PP2. UVB irradiation had very low deleterious effect on fibroblasts survival, while it did not affect the proteasome chymotrypsin-like activity. Conclusion: In pterygium fibroblasts, UVB exposure leads to down-regulation of Nrf2/ARE-mediated PSMB5 gene expression, in which src kinases may be implicated. This effect may be partially responsible for the lower expression of PSMB5 detected in pterygium as compared to normal conjunctiva. © 2018 The Author(s)

Short-term hypoxia triggers ROS and SAFB mediated nuclear matrix and mRNA splicing remodeling

The cellular response to hypoxia, in addition to HIF-dependent transcriptional reprogramming, also involves less characterized transcription-independent processes, such as alternative splicing of the VEGFA transcript leading to the production of the proangiogenic VEGF form. We now show that this event depends on reorganization of the splicing machinery, triggered after short-term hypoxia by ROS production and intranuclear redistribution of the nucleoskeletal proteins SAFB1/2. Exposure to low oxygen causes fast dissociation of SAFB1/2 from the nuclear matrix, which is reversible, inhibited by antioxidant treatment, and also observed under normoxia when the mitochondrial electron transport chain is blocked. This is accompanied by altered interactions between SAFB1/2 and the splicing machinery, translocation of kinase SRPK1 to the cytoplasm, and dephosphorylation of RS-splicing factors. Depletion of SAFB1/2 under normoxia phenocopies the hypoxic and ROS-mediated switch in VEGF mRNA splicing. These data suggest that ROS-dependent remodeling of the nuclear architecture can promote production of splicing variants that facilitate adaptation to hypoxia. © 202

Childhood Overweight/Obesity and Asthma: Is There a Link? A Systematic Review of Recent Epidemiologic Evidence

Asthma and overweight/obesity prevalence are both increasing worldwide. Overweight/ obesity has been suggested as a risk factor for developing asthma. The aim of this review is to present and evaluate recent publications that help answer the question: "Is increased body weight (at least overweight status) related to asthma in children?" A systematic review of epidemiologic literature was carried out using the MEDLINE database. Epidemiologic studies on young human subjects (ie, infants, children, and adolescents), published in English during the period 2006-2011 were included. A comprehensive literature search yielded 434 studies for further consideration. Forty-eight studies fulfilled the review's eligibility criteria. Two researchers applied the MOOSE Guidelines for Meta-Analysis and Systematic Reviews of Observational Studies on all identified studies. Current evidence supports a weak yet significant association between high body weight and asthma. New information indicates that central obesity in children increases asthma risk. Also, the link between high body weight and asthma may be stronger in nonallergic asthma. There are mixed results about the importance of sex. Although the nature of the association between overweight/obese status and asthma remains unclear, prospective studies point that high body weight precedes asthma symptoms. These data add weight to the importance of preventing and treating a high body weight against asthma outcomes. Available research in children has not studied adequately the influence of weight change (either gain or loss) on asthma symptoms, an area of clinical importance. Beyond energy control, the role of diet as a possible inflammatory stimulus warrants further investigation. Limited data seem to favor the promotion of breastfeeding in attenuating the overweight/obesity-asthma relationship. Finally, future research should include weight intervention studies assessing various measures of body fat in relation to well-defined asthma outcomes. © 2013 Academy of Nutrition and Dietetics

Associations of sport participation with selfperception, exercise self-efficacy and quality of life among children and adolescents with a physical disability or chronic disease—a cross-sectional study.

Background: Little evidence is available about how sports participation influences psychosocial health and quality of life in children and adolescents with a disability or chronic disease. Therefore, the aim of the current study is to assess the association of sports participation with psychosocial health and with quality of life, among children and adolescents with a disability. Methods: In a cross-sectional study, 195 children and adolescents with physical disabilities or chronic diseases (11% cardiovascular, 5% pulmonary, 8% metabolic, 8% musculoskeletal/orthopaedic, 52% neuromuscular and 9% immunological diseases and 1% with cancer), aged 10–19 years, completed questionnaires to assess sports participation, health-related quality of life (DCGM-37), self-perceptions and global self-worth (SPPC or SPPA) and exercise self-efficacy. Results: Regression analyses showed that those who reported to participate in sports at least twice a week had more beneficial scores on the various indicators compared to their peers who did not participate in sport or less than twice a week. Those participating in sports scored better on all scales of the DCGM-37 scale, on the scales for feelings of athletic competence and children but not adolescents participating in sports reported greater social acceptance. Finally, we found a strong association between sport participation and exercise self-efficacy. Conclusions: This study provides the first indications that participating in sports is beneficial for psychosocial health among children and adolescents with a disability. However, more insight is needed in the direction of the relationships. (aut. ref.