Stabilization of Intrinsically Disordered DKK2 Protein by Fusion to RNA-Binding Domain.

Intrinsic disorders are a common feature of hub proteins in eukaryotic interactomes controlling the signaling pathways. The intrinsically disordered proteins (IDPs) are prone to misfolding, and maintaining their functional stability remains a major challenge in validating their therapeutic potentials. Considering that IDPs are highly enriched in RNA-binding proteins (RBPs), here we reasoned and confirmed that IDPs could be stabilized by fusion to RBPs. Dickkopf2 (DKK2), Wnt antagonist and a prototype IDP, was fused with lysyl-tRNA synthetase (LysRS), with or without the fragment crystallizable (Fc) domain of an immunoglobulin and expressed predominantly as a soluble form from a bacterial host. The functional competence was confirmed by in vitro Wnt signaling reporter and tube formation in human umbilical vein endothelial cells (HUVECs) and in vivo Matrigel plug assay. The removal of LysRS by site-specific protease cleavage prompted the insoluble aggregation, confirming that the linkage to RBP chaperones the functional competence of IDPs. While addressing to DKK2 as a key modulator for cancer and ischemic vascular diseases, our results suggest the use of RBPs as stabilizers of disordered proteinaceous materials for acquiring and maintaining the structural stability and functional competence, which would impact the druggability of a variety of IDPs from human proteome.

Medial canthopexy using Y-V epicanthoplasty incision in the correction of telecanthus.

BACKGROUND: Telecanthus occurs because of the disruption of the medial canthal tendon (MCT). The deformity of medial canthus can result from nasoorbitoethmoid fractures, tumor resection, craniofacial exposure, congenital malposition, or aging. Repair of the MCT using transnasal wiring is regarded as a method of choice to treat telecanthus. We have introduced an oblique transnasal wiring using Y-V epicanthoplasty incision rather than the well-known classical bicoronal approach. METHODS: Eight patients with telecanthus were treated with this method. Through the medial canthal horizontal and periciliary incision, we could have an access to the medial orbital wall and the MCT. An oblique transnasal wiring was performed with the following steps: (1) after slit skin incision on the nasal recession of the contralateral frontoglabella area, 2 drill holes were made from this point to the superior and posterior region of the lacrimal fossa of the affected orbit; (2) a 2-0 wire was passed through the MCT and the holes; (3) the wire was pulled and tightened until the MCT was ensured and was twisted in the contralateral side. After the repositioning of the MCT, the skin was simply sutured. The excess skin was trimmed, and then the skin was sutured with nylon 7-0. The remaining "dog ear" in the lateral portion can be removed by additional periciliary skin incision and excision. RESULTS: All the patients achieved an improvement and a prompt recovery. The interepicanthal distance was decreased by 6.3 mm on average compared with that in the preoperative condition. All patients had no complication associated with surgeries. Of posttraumatic telecanthus, 5 patients were much satisfied with the outcomes, and 1 patient had recurrence on postoperative month 3. In cases of congenital anomaly or neoplasm, the telecanthus was also improved. CONCLUSIONS: An oblique transnasal wiring using Y-V epicanthoplasty incision could be a simple, safe method to correct the telecanthus with the following advantages: first, we could fix the MCT to the appropriate position with oblique transnasal wiring; second, a horizontal incision and a periciliary incision could be acquired with enough operative fields; third, Y-V epicanthoplasty incision is an effective method for minimizing unsightly scar formation.

Treatment of complex facial fractures: clinical experience of different timing and order.

Given the variability of the timing and order of surgeries, it is difficult to choose the best treatment for patients with complex facial fractures. Based on the clinical experiences, the authors have reviewed their experience with the timing and order of operations depending on the sites of complex facial fractures and their concurrent injuries. The current study was based on a total of 105 patients with complex facial fractures from the year 2002 to 2011. After assessing the patients' clinical records, radiological data, and clinical photographs, the following data were analyzed: patients' age and sex, causes of injury, concurrent injuries, sites of fractures, the interval between trauma and the operations, the presence of additional surgeries, and the aesthetic and functional outcomes.For most of the patients, early operation was performed (within 2 weeks in 95.2%). Additional surgeries within 1 month after injuries were performed in 22 patients. Usually, a top-to-bottom direction repair was applied when head injuries were involved, and bottom-to-top direction repair was applied when occlusal problems were involved. Of 105 patients whom we were able to follow up, 49 patients showed complications or were dissatisfied with the outcomes. However, except them, most of the patients were satisfied with the outcomes of surgical treatments. There were 14 cases of cheek asymmetry, 9 enophthalmos, 30 paresthesia, 4 malocclusion, and a single case of persistent trismus.In the current study, satisfactory results could be achievable under the following principles: a repair should be done in the early stage after the onset of the injury; supportive surgeries should be done, if necessary, within 2 weeks (no later than 4 weeks); and the order of surgical treatment should be determined by the severity of bone fracture and the systemic status.