Recent developments in software technology have made it possible to create a virtual three-dimensional model of the dental arches from digitally scanned casts of a patient's dentition. This modelmay then be manipulated with software to produce stages of tooth movement from the initial malocclusion to the final desired occlusion. A sterolithograghic model is made for each stage of tooth movement which is the basis for construction of a series of clear and thin overlay appliances. These appliances are worn full time by the patient to move the teeth according to the programmed stages of movement. Malocclusions involving mild to moderate crowding and space closure have been proven to be successfully treated with this appliance. Experience with this appliance has demonstrated excellent patient compliance with less discomfort, improved esthetics and oral hygiene control, when compared with fixed orthodontic appliances. Orthodontic treatment with this appliance is a potentially useful alternative approach to fixed appliances for treatment of a variety of malocclusions in patients with fully erupted permanent teeth.
Crowding ; Dental Arch ; Dentition ; Diagnosis* ; Esthetics ; Humans ; Malocclusion* ; Oral Hygiene ; Orthodontic Appliances ; Patient Compliance ; Tooth ; Tooth Movement

TCR signaling leading to thymocyte apoptosis is mediated through the expression of the Nur77 family of orphan nuclear receptors. It has been shown that the Nur77 promoter is activated by at least two signaling pathways, one mediated by calcium and the other by protein kinase C (PKC). MEF2D has been known to regulate Nur77 expression in a calcium- dependent manner. The mechanism by which calcium regulates MEF2D is through dissociation of calcium-sensitive MEF2 corepressors (Cabin1/ HDACs, HDAC4/5) and the association with calcineurin-activated transcription factor NF-AT and the coactivator p300. However, little is known about how PKC activates the Nur77 promoter. Herein, we report that PKC theta targets AP-1 like response element in the Nur77 promoter where JunD constitutively binds. PKC theta triggers mitogen-activated protein kinase- inediated phosphorylation of JunD, and increases transcriptional activity of JunD, cooperatively with p300. Menin is identified as the transcriptional corepressor for JunD via recruitment of mSin3-istone deacetylases. In fact, Menin represses PKC theta/ p300-mediated transcriptional activity of JunD in T cell. Its dynamic regulation of histone modifiers with JunD is responsible for PKCq-synergistic effect on Nur77 expression in T cell.
Cell Line, Tumor ; DNA-Binding Proteins/*genetics ; Enzyme Activation ; *Gene Expression Regulation ; Humans ; Isoenzymes/*metabolism ; Mitogen-Activated Protein Kinases/metabolism ; *Multiple Endocrine Neoplasia Type 1 ; Promoter Regions (Genetics)/genetics ; Protein Kinase C/*metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; Proto-Oncogene Proteins c-jun/*antagonists & inhibitors/metabolism ; Receptors, Cytoplasmic and Nuclear/*genetics ; Receptors, Steroid/*genetics ; Research Support, Non-U.S. Gov't ; Response Elements ; Transcription Factors/*genetics ; Transcription, Genetic/*genetics

Objective: Patients presenting with fingertip skin defect injuries without exposed bone can avail of two treatment options at the emergency department (ED). This study compared outcomes between dressing and composite graft (CG) using skin stump for patients visiting the ED with fingertip skin defect injuries without exposed bone. Methods: This was a single-center, retrospective, observational study. We reviewed 244 patients with fingertip skin defect injuries without exposed bone who visited the ED from September 2018 to February 2021. We compared the outcomes of the patients who were treated by CG using skin stump and those who received a dressing in the ED. Results: In all, 142 patients were treated by CG using skin stump, and 102 patients were given a dressing only. In the CG group, good outcomes were obtained in 140 patients, whereas additional skin graft treatment was required for two patients with bad outcomes. In the dressing group, 81 patients had good outcomes and 21 patients had bad outcomes which required additional skin graft treatment. Conclusion Results of our study revealed that compared to traditional dressing, ED treatment for fingertip skin defects without exposed bone showed good outcomes when administered CG using skin stump. Hence, we recommend that instead of simple dressing, CG using skin stump is the preferred mode of treatment for patients presenting in the ED with fingertip skin defect injuries without exposed bone.

In this study, we investigated the role of Nur77, an orphan nuclear receptor, in HIF-alpha transcriptional activity. We found that Nur77 associates and stabilizes HIF-1alpha via indirect interaction. Nur77 was found to interact with pVHL in vivo via the alpha-domain of pVHL. By binding to pVHL, Nur77 competed with elongin C for pVHL binding. Moreover, Nur77-binding to pVHL inhibited the pVHL-mediated ubiquitination of HIF-1alpha and ultimately increased the stability and transcriptional activity of HIF-1alpha. The ligand-binding domain of Nur77 was found to interact with pVHL and the expression of this ligand-binding domain was sufficient to stabilize and transactivate HIF-1alpha. Under the conditions that cobalt chloride was treated or pVHL was knocked down, Nur77 could not stabilize HIF-alpha. Moreover, Nur77 could not further stabilize HIF-2alpha in A498/VHL stable cells, which is consistent with our finding that Nur77 indirectly stabilizes HIF-alpha by binding to pVHL. Thus, our results suggest that an orphan nuclear receptor Nur77 binds to pVHL, thereby stabilizes and increases HIF-alpha transcriptional activity under the non- hypoxic conditions.
Animals ; DNA-Binding Proteins/chemistry/*metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*genetics ; Models, Biological ; PC12 Cells ; Protein Binding ; *Protein Processing, Post-Translational ; Protein Structure, Tertiary ; Rats ; Receptors, Cytoplasmic and Nuclear/chemistry/*metabolism ; Receptors, Steroid/chemistry/*metabolism ; Thermodynamics ; Transcription Factors/chemistry/*metabolism ; Transcriptional Activation/genetics ; Ubiquitination ; Up-Regulation/*genetics ; Von Hippel-Lindau Tumor Suppressor Protein/*antagonists & inhibitors/chemistry/*metabolism

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with 20 μM bosentan+200 μM rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.
Cytochrome P-450 CYP2C9 ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System* ; Cytochromes* ; Gene Expression ; HEK293 Cells ; Hepatocytes* ; Humans* ; In Vitro Techniques ; Incidence ; Organic Anion Transporters ; Polypharmacy ; Rifampin*