Core-binding factor fusion downregulation of ADAR2 RNA editing contributes to AML leukemogenesis.

Adenosine-to-inosine RNA editing, which is catalyzed by adenosine deaminases acting on RNA (ADAR) family of enzymes, ADAR1 and ADAR2, has been shown to contribute to multiple cancers. However, other than the chronic myeloid leukemia blast crisis, relatively little is known about its role in other types of hematological malignancies. Here, we found that ADAR2, but not ADAR1 and ADAR3, was specifically downregulated in the core-binding factor (CBF) acute myeloid leukemia (AML) with t(8;21) or inv(16) translocations. In t(8;21) AML, RUNX1-driven transcription of ADAR2 was repressed by the RUNX1-ETO additional exon 9a fusion protein in a dominant-negative manner. Further functional studies confirmed that ADAR2 could suppress leukemogenesis specifically in t(8;21) and inv16 AML cells dependent on its RNA editing capability. Expression of 2 exemplary ADAR2-regulated RNA editing targets coatomer subunit α and component of oligomeric Golgi complex 3 inhibits the clonogenic growth of human t(8;21) AML cells. Our findings support a hitherto, unappreciated mechanism leading to ADAR2 dysregulation in CBF AML and highlight the functional relevance of loss of ADAR2-mediated RNA editing to CBF AML.

Perspectives of Allied Health Professionals on Implementation of the Lifestyle Polycystic Ovary Syndrome Guidelines: A Qualitative Study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common condition affecting up to 13% of reproductive-aged women. Weight and lifestyle management are key initial treatment strategies for individuals with PCOS, as recommended in international evidence-based guidelines. Allied health professionals, including dietitians, exercise physiologists, and psychologists, are crucial in delivering support for lifestyle and weight management. OBJECTIVE: Our aim was to explore the barriers and enablers to lifestyle and weight management for individuals with PCOS from the perspectives of allied health professionals. DESIGN: This was a qualitative study using a phenomenology approach to understand the allied health professionals lived experiences managing the lifestyles of individuals with PCOS. Semi-structured interviews were conducted with allied health professionals (ie, dietitians, exercise physiologists, and psychologist). Interviews were audio-recorded and professionally transcribed. Transcripts were coded inductively and analyzed thematically. PARTICIPANTS/SETTING: Participants were 15 allied health professionals (ie, 9 dietitians, 5 exercise physiologists, and 1 psychologist) involved in the management of PCOS in Australia (n = 10 in Victoria, n = 5 in other states) and interviewed between June and September 2019. MAIN OUTCOME MEASURES: Barriers and enablers of allied health professionals relating to the provision of lifestyle and weight management in individuals with PCOS were analyzed. RESULTS: Barriers relating to individuals with PCOS included insufficient knowledge on lifestyle management; lack of time; socioeconomic disadvantage preventing access to lifestyle support; and psychological issues, such as eating disorders or depression. Barriers relating to health professionals included insufficient knowledge about PCOS and insufficient time during consultation. Barriers relating to the health system included lifestyle recommendations in the PCOS guidelines that are too general and weight-focused, funding system that does not facilitate long-term care, and low integration of care among health professionals. CONCLUSIONS: Barriers for the individual, health professional, and health system all need to be addressed to improve the implementation of lifestyle management in PCOS care to optimize consistency with the PCOS international evidence-based guidelines.

Novel three-dimensional nerve tissue engineering scaffolds and its biocompatibility with Schwann cells.

OBJECTIVE: To develop a novel scaffolding method for the copolymers poly lactide-co-glycolide acid (PLGA) to construct a three-dimensional (3-D) scaffold and explore its biocompatibility through culturing Schwann cells (SCs) on it. METHODS: The 3-D scaffolds were made by means of melt spinning, extension and weaving. The queueing discipline of the micro-channels were observed under a scanning electronic microscope (SEM).The sizes of the micropores and the factors of porosity were also measured. Sciatic nerves were harvested from 3-day-old Sprague Dawley (SD) rats for culture of SCs. SCs were separated, purified, and then implanted on PLGA scaffolds, gelatin sponge and poly-L-lysine (PLL)-coated tissue culture polystyrene (TCPS) were used as biomaterial and cell-supportive controls, respectively. The effect of PLGA on the adherence, proliferation and apoptosis of SCs were examined in vitro in comparison with gelatin sponge and TCPS. RESULTS: The micro-channels arrayed in parallel manners, and the pore sizes of the channels were uniform. No significant difference was found in the activity of Schwann cells cultured on PLGA and those on TCPS (P larger than 0.05), and the DNA of PLGA scaffolds was not damaged. CONCLUSION: The 3-D scaffolds developed in this study have excellent structure and biocompatibility, which may be taken as a novel scaffold candidate for nerve-tissue engineering.