ABSTRACT
As a member of the AFF (AF4/FMR2) family, AFF4 is a transcription elongation factor that is a component of the super elongation complex. AFF4 serves as a scaffolding protein that connects transcription factors and promotes gene transcription through elongation and chromatin remodelling. Here, we investigated the effect of AFF4 on human dental follicle cells (DFCs) in osteogenic differentiation. In this study, we found that small interfering RNA-mediated depletion of AFF4 resulted in decreased alkaline phosphatase (ALP) activity and impaired mineralization. In addition, the expression of osteogenic-related genes (DLX5, SP7, RUNX2 and BGLAP) was significantly downregulated. In contrast, lentivirus-mediated overexpression of AFF4 significantly enhanced the osteogenic potential of human DFCs. Mechanistically, we found that both the mRNA and protein levels of ALKBH1, a critical regulator of epigenetics, changed in accordance with AFF4 expression levels. Overexpression of ALKBH1 in AFF4-depleted DFCs partially rescued the impairment of osteogenic differentiation. Our data indicated that AFF4 promoted the osteogenic differentiation of DFCs by upregulating the transcription of ALKBH1.
Subject(s)
Humans , Biomarkers , Metabolism , Cell Differentiation , Cells, Cultured , Dental Sac , Metabolism , Gene Expression Regulation , Osteogenesis , Genetics , Repressor Proteins , Transcription Factors , Genetics , Metabolism , Transcriptional Elongation Factors , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To explore the role of mitochondrial DNA 5178 C/A (Mt5178) polymorphism of NADH-dehydrogenase subunit 2 (ND2) gene in type-2 diabetes mellitus (T2DM) among ethnic Han Chinese through a case-control study.</p><p><b>METHODS</b>The Mt5178C/A polymorphism was determined by sequencing 1103 T2DM patients and 791 healthy controls. Logistic regression analysis was conducted to estimate odds ratios (OR) and 95% confidence intervals (CI). To confirm the results, a meta-analysis was conducted based on published literature on the association of Mt5178 variant with T2DM.</p><p><b>RESULTS</b>No significant association was found between the Mt5178C/A variant and T2DM either by our study or the meta-analysis which included eight published studies. Nevertheless, it was found that the T2DM patients with 5178C genotype were at a higher risk for nephropathy complication (OR=1.49, 95%CI: 1.005-2.197, P<0.05) and at significantly lower risk for hypertension complication (OR=0.744, 95%CI: 0.556-0.996, P<0.05) compared with those carrying a 5178A genotype.</p><p><b>CONCLUSION</b>No association was found between the Mt5178C/A polymorphism of mitochondrial ND2 gene with the increased risk of T2DM. However, the polymorphism may affect the development of nephropathy and hypertension complications among T2DM patients.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Blood Glucose , Metabolism , Cholesterol , Blood , Cholesterol, HDL , Blood , DNA, Mitochondrial , Chemistry , Genetics , Diabetes Complications , Blood , Genetics , Diabetes Mellitus, Type 2 , Blood , Genetics , Diabetic Nephropathies , Blood , Genetics , Fasting , Blood , Hypertension , Blood , Genetics , Meta-Analysis as Topic , Odds Ratio , Polymorphism, Single Nucleotide , Sequence Analysis, DNA , Triglycerides , BloodABSTRACT
OBJECTIVE@#To investigate the anatomical influence of the hypertrophic inferior turbinate on computational fluid dynamics (CFD) model of unilateral hypertrophic inferior turbinate nasal cavity, and to analyze the bilateral detailed nasal airflow simulations under both inspiratory and expiratory phases in CFD model.@*METHOD@#One male volunteer troubled with unilateral hypertrophic inferior turbinate accepted CT scan. CFD model was built by CT scans through Simplant 10.0 and ANSYS ICEM. Fluent 6.3.26 simulated the airflow of both nasal cavity in breathing rates 200 ml/s.@*RESULT@#1) In infraturbinal region, the cross-section area (CSA) of the nasal cavity with hypertrophic inferior turbinate was smaller than that in healthy side and the average area difference between two sides was 1.62 cm2. 2) In both inspiration and expiration phases, the hypertrophic infraturbinal produced a markable reduction in intranasal pressures drop along the full length of the infraturbinal region. The volumetric flow rate in the hypertrophic infraturbinal side was 50 ml/s, which equalled to one third of that in healthy side; Mean air speed in the anterior valve region was estimated to be 0.57 m/s at hypertrophic infraturbinal side and 1.83 m/s at healthy side during inspiration; More vortices happened in the hypertrophic infraturbinal side.@*CONCLUSION@#The unilateral hypertrophic infraturbinal change the normal anatomy and influence the aerodynamic of nasal cavity, which is harmful to the functions of human nasal in ventilation, temperature accommodation and olfactory sensation.