Runx2/Cbfa1/Pebp2aA is a global regulator of osteogenesis and is crucial for regulating the expression of bone-specific genes. Runx2 is a major target of the bone morphogenetic protein (BMP) pathway. Genetic analysis has revealed that Runx2 is degraded through a Smurf-mediated ubiquitination pathway, and its activity is inhibited by HDAC4. Here, we demonstrate the molecular link between Smurf, HDACs and Runx2, in BMP signaling. BMP-2 signaling stimulates p300-mediated Runx2 acetylation, increasing transactivation activity and inhibiting Smurf1-mediated degradation of Runx2. HDAC4 and HDAC5 dea-cetylate Runx2, allowing the protein to undergo Smurf-mediated degradation. Inhibition of HDAC increases Runx2 acetylation, and potentiates BMP-2-stimulated osteoblast differentiation and increases bone formation. These results demonstrate that the level of Runx2 is controlled by a dynamic equilibrium of acetylation, deacetylation, and ubiquitination. These findings have important medical implications because BMPs and Runx2 are of tremendous interest with regard to the development of therapeutic agents against bone diseases.
The Runt domain transcription factors (RUNXs) play essential roles in normal development and neoplasias. Genetic analyses of animals and humans have revealed the involvement of RUNX1 in hematopoiesis and leukemia, RUNX2 in osteogenesis and cleidocranial dysplasia, and RUNX3 in the development of T-cells and dorsal root ganglion neurons and in the genesis of gastric cancer. Here we report that RUNX3 is a target of the acetyltransferase activity of p300. The p300-dependent acetylation of three lysine residues protects RUNX3 from ubiquitin ligase Smurf-mediated degradation. The extent of the acetylation is up-regulated by the transforming growth factor-␤ signaling pathway and down-regulated by histone deacetylase activities. Our findings demonstrate that the level of RUNX3 protein is controlled by the competitive acetylation and deacetylation of the three lysine residues, revealing a new mechanism for the posttranslational regulation of RUNX3 expression.
ObjectivesThe factors affecting the acceptance of mobile obesity-management applications (apps) by the public were analyzed using a mobile healthcare system (MHS) technology acceptance model (TAM).Methods The subjects who participated in this study were Android smartphone users who had an intent to manage their weight. They used the obesity-management app for two weeks, and then completed an 18-item survey designed to determine the factors influencing the acceptance of the app. Three questions were asked pertaining to each of the following six factors: compatibility, self-efficacy, technical support and training, perceived usefulness, perceived ease of use, and behavior regarding intention to use. Cronbach's alpha was used to assess the reliability of the scales. Pathway analysis was also performed to evaluate the MHS acceptance model.ResultsA total of 94 subjects participated in this study. The results indicate that compatibility, perceived usefulness, and perceived ease of use significantly affected the behavioral intention to use the mobile obesity-management app. Technical support and training also significantly affected the perceived ease of use; however, the hypotheses that self-efficacy affects perceived usefulness and perceived ease of use were not supported in this study.ConclusionsThis is the first attempt to analyze the factors influencing mobile obesity-management app acceptance using a TAM. Further studies should cover not only obesity but also other chronic diseases and should analyze the factors affecting the acceptance of apps among healthcare consumers in general.
Mesenchymal stem cells (MSCs) have emerged as a therapeutic approach in a range of medical fields, including regenerative medicine, cancer, autoimmune diseases, and inflammatory diseases, because of their unique properties of tissue repair and major histocompatibility complex-unmatched immunosuppression. Because both in vitro and in vivo findings demonstrate that MSCs possess potent immunoregulatory functions, there has been increasing interest in the role of MSCs in allogeneic hematopoietic stem cell transplantation, especially in the prevention and treatment of graft-versus-host disease (GVHD). GVHD is a major cause of transplantation-related mortality, and conventional immunosuppressants frequently fail to treat patients suffering from GVHD. Following Ringden's pilot study that used third-party MSCs to treat a steroid-refractory GVHD patient, MSCs have created growing interest as a therapeutic agent for GVHD. There have been further studies which demonstrated the potentials of MSC treatment in steroid-refractory GVHD, de novo GVHD, and also GVHD prevention. However, MSCs still present limitations. The need for MSCs to be "licensed" in a pro-inflammatory environment, especially in the presence of interferon gamma, allows only a narrow window for their administration. Thus, their effects have been less clear as a preventive measure before the inflammatory environment of GVHD is established and also when administered during a chronic setting where MSCs may be alternatively licensed. In this review, we focus on the immunomodulatory properties of MSCs and their effects in relation to GVHD. Given the efficacy of MSCs in murine models of GVHD and their safety in clinical trials, it is crucial that larger clinical trials are conducted and further modifications are investigated.
ObjectivesThis study developed a diabetes self-management mobile application based on the information-motivation-behavioral skills (IMB) model, evidence extracted from clinical practice guidelines, and requirements identified through focus group interviews (FGIs) with diabetes patients.MethodsWe developed a diabetes self-management (DSM) app in accordance with the following four stages of the system development life cycle. The functional and knowledge requirements of the users were extracted through FGIs with 19 diabetes patients. A system diagram, data models, a database, an algorithm, screens, and menus were designed. An Android app and server with an SSL protocol were developed. The DSM app algorithm and heuristics, as well as the usability of the DSM app were evaluated, and then the DSM app was modified based on heuristics and usability evaluation.ResultsA total of 11 requirement themes were identified through the FGIs. Sixteen functions and 49 knowledge rules were extracted. The system diagram consisted of a client part and server part, 78 data models, a database with 10 tables, an algorithm, and a menu structure with 6 main menus, and 40 user screens were developed. The DSM app was Android version 4.4 or higher for Bluetooth connectivity. The proficiency and efficiency scores of the algorithm were 90.96% and 92.39%, respectively. Fifteen issues were revealed through the heuristic evaluation, and the app was modified to address three of these issues. It was also modified to address five comments received by the researchers through the usability evaluation.ConclusionsThe DSM app was developed based on behavioral change theory through IMB models. It was designed to be evidence-based, user-centered, and effective. It remains necessary to fully evaluate the effect of the DSM app on the DSM behavior changes of diabetes patients.
Mesenchymal stem cells (MSCs) have been considered to be an ideal cellular source for graft-versus-host disease (GVHD) treatment due to their unique properties, including tissue repair and major histocompatibility complex (MHC)-unmatched immunosuppression. However, preclinical and clinical data have suggested that the immunomodulatory activity of MSCs is not as effective as previously expected. This study was performed to investigate whether the immunomodulatory capacity of MSCs could be enhanced by combination infusion of regulatory T (Treg) cells to prevent acute GVHD (aGVHD) following MHC-mismatched bone marrow transplantation (BMT). For GVHD induction, lethally irradiated BALB/c (H-2d) mice were transplanted with bone marrow cells (BMCs) and spleen cells of C57BL/6 (H-2b) mice. Recipients were injected with cultured recipient-derived MSCs, Treg cells, or MSCs plus Treg cells (BMT + day 0, 4). Systemic infusion of MSCs plus Treg cells improved clinicopathological manifestations and survival in the aGVHD model. Culture of MSCs plus Treg cells increased the population of Foxp3+ Treg cells and suppressed alloreactive T-cell proliferation in vitro. These therapeutic effects were associated with more rapid expansion of donor-type CD4+CD25+Foxp3+ Treg cells and CD4+IL-4+ type 2 T-helper (Th2) cells in the early posttransplant period. Furthermore, MSCs plus Treg cells regulated CD4+IL-17+ Th17 cells, as well as CD4+IFN-γ + Th1 cells. These data suggest that the combination therapy with MSCs plus Treg cells may have cooperative effects in enhancing the immunomodulatory activity of MSCs and Treg cells in aGVHD. This may lead to development of new therapeutic approaches to clinical allogeneic hematopoietic cell transplantation.
ObjectivesThe purpose of the study was to develop and evaluate a clinical-guideline-based smartphone application ('app') for obesity management.MethodsObesity-related knowledge and functional requirements were extracted from clinical practice guidelines, a literature review, and consultations with experts. The extracted knowledge was used to design obesity-management algorithms, and the functions of the developed app are presented through a use case diagram and activity diagrams. The database and user interface were designed and then an app was developed. The proficiency and efficiency of the algorithm were evaluated using scenarios, while the user interface was assessed using a mobile heuristics evaluation tool, with its usability determined using the Post-Study System Usability Questionnaire.ResultsIn total, 131 obesity-related knowledge statements and 11 functions for the app were extracted, and 5 algorithms (comprising 1 main algorithm and 4 subalgorithms) were developed. The database comprised 11 tables and 41 screens. The app was developed using the Android SDK platform 4.0.3, JDK 1.7.0, and Eclipse. The overall proficiency and efficiency scores of the algorithm were 88.0 and 69.1, respectively. In heuristics tests, 57 comments were made, and the mean usability score was 3.47 out of 5. Thirteen usability problems were identified by the heuristics and usability evaluations.ConclusionsThe app developed in this study might be helpful for weight management because it can provide high-quality health information and intervention without spatial or temporal constraints. However, the clinical effectiveness of this app still requires further investigation.
ObjectivesThis study analyzed smartphone obesity-management applications developed in Korea and the quality of the information that they provide.MethodsObesity-management smartphone applications were searched using the keywords 'obesity + management,' 'weight + management,' 'weight + loss,' 'weight + exercise,' 'weight + diet,' 'weight + calories,' and 'diet,' with a search application programming interface (provided by Apple) between September 23 and September 27, 2013. These applications were then classified according to their main purpose, type of interventions used, price, type of developer, and user ratings. The information quality of the applications was analyzed using the Silberg scale.ResultsIn total, 148 smartphone applications for obesity management were found. The main purpose of most of these applications (70.95%) was to provide information regarding weight control. The most frequently used intervention (34.62%) was to provide information on exercise management. More than half of the applications (58.78%) were free of charge. The mean of users' rating of these applications was 3.68 out of 5. The quality of information provided by these applications was evaluated as 4.55 out of 9: specifically, 1.79 out of 3 for authorship, 0.22 out of 2 for attribution, 1.29 out of 2 for disclosure, and 1.25 out of 2 for currency. Only three of the applications (2.88%) had a score on the Silberg scale greater than or equal to 7 points.ConclusionsThe findings of this study suggest that the quality of information provided by smartphone applications in the healthcare domain urgently need to be evaluated to prevent users being misinformed by these applications.
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