PEGylated Poly-HDACi: A Designer Polyprodrug from Optimized Drug Units.

We designed, synthesized, and characterized a tri-block copolymer. Its hydrophobic part, a chain of histone deacetylase inhibitor (HDACi) prodrug, was symmetrically flanked by two identical PEG blocks, whereas the built-in HDACi was a linear molecule, terminated with a thiol at one end, and a hydroxyl group at the other. Such a feature facilitated end-to-end linkage of prodrugs through alternatively aligned disulfides and carbonates. The disulfides served dual roles: redox sensors of smart nanomedicine, and warheads of masked HDACi drugs. This approach, carefully designed to benefit both control-release and efficacy, is conceptually novel for optimizing drug units in nanomedicine. Micelles from this designer polyprodrug released only PEG, CO2 and HDACi, and synergized with DOX against HCT116 cells, demonstrating its widespread potential in combination therapy. Our work highlights, for the first time, the unique advantage of thiol-based drug molecules in nanomedicine design.

Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancer.

BACKGROUND: Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly designed PEO-PCL micelles that were self-assembled and modified by spermine ligand, DCL ligand and TAT peptide to carry docetaxel and anti-nucleostemin siRNA. RESULTS: The particle size of the micelles was 42 nm, the zeta potential increased from - 12.8 to 15 mV after grafting with spermine, and the optimal N/P ratio was 25:1. Cellular MTT experiments suggested that introduction of the DCL ligand resulted in high toxicity toward PSMA-positive cells and that the TAT peptide enhanced the effect. The expression of nucleostemin was significantly suppressed in vitro and in vivo, and the tumour-inhibition experiment showed that the dual-drug delivery system suppressed CRPC tumour proliferation. CONCLUSIONS: This targeted drug delivery system inhibited the G1/S and G2/M mitotic cycle via synergistic interaction of chemotherapeutics and gene drugs.

Sodium fluoride induces apoptosis and autophagy via the endoplasmic reticulum stress pathway in MC3T3-E1 osteoblastic cells.

Fluorosis and bone pathologies can be caused by chronic and/or excessive fluoride intake. Despite this, few studies have been conducted on the cellular mechanisms underlying osteoblast toxicity in the presence of NaF. Here, we investigated the effects of fluoride on MC3T3-E1 cells. We showed that the proliferation of MC3T3-E1 cells was inhibited by exposure to NaF. In addition, apoptosis was induced by NaF, as caspase-associated proteins showed a higher level of expression and apoptotic bodies were formed. Furthermore, endoplasmic reticulum (ER) stress induced by NaF activated the unfolded protein response (UPR) and upregulated the expression of the glucose-regulated proteins 94 (GRP94) and 78 (BiP). Therefore, ER stress plays a vital role in NaF-induced autophagy and apoptosis. Furthermore, apoptosis is promoted following the inhibition of NaF-induced autophagy. In conclusion, under NaF treatment, the ER stress-signaling pathway is activated, leading to apoptosis and autophagy and affecting the proliferation and survival of MC3T3-E1 cells.

The role of Rho-GEF Trio in regulating tooth root development through the p38 MAPK pathway.

Trio, the Rho guanine nucleotide exchange factor (Rho-GEF), plays diverse roles in cell migration, cell axon guidance and cytoskeleton reorganization. Conserved during evolution, Trio encodes two guanine nucleotide exchange factor domains (GEFs) and activates small GTPases. The Rho-family small GTPases RhoA and Rac1, which are target molecules of Trio, have been described to engage in craniofacial development and tooth formation. However, the exact role of Trio in tooth development remains elusive. In this study, we generated Wnt1-cre;Triofl/fl mice to address the potential function of Trio in tooth development. Wnt1-cre;Triofl/fl mice showed short root deformity as well as decreased expression of odontogenic makers such as RUNX2, OSX, OCN, and OPN. In vitro, Trio was silenced in human stem cells of dental papilla (SCAPs). Compared with the control group, the proliferation and migration ability in the experimental group was disrupted. After knocking down Trio in SCAPs, the cells showed phenotypes of poor odontogenic differentiation and weak mineralized nodules. To study the underlying mechanism, we investigated the p38 MAPK pathway and found that loss of Trio blocked the cascade transduction of p38 MAPK signaling. In conclusion, we identified Trio as a novel coordinator in regulating root development and clarified its relevant molecular events.

Preserving the Fibrous Layer of the Mandibular Condyle Reduces the Risk of Ankylosis in a Sheep Model of Intracapsular Condylar Fracture.

PURPOSE: The aim of this experimental study was to investigate the role of the fibrous layer of the condylar head in the formation of temporomandibular joint (TMJ) ankylosis in a sheep model of intracapsular condylar fracture. MATERIALS AND METHODS: Six growing Xiao-wei Han sheep were used in the study, and bilateral TMJ surgery was performed in each sheep. In the left TMJ, sagittal fracture of the condyle, removal of the fibrous layer of the condylar head, excision of two thirds of the disc, and removal of the fibrous zone of the glenoid fossa were performed. In the right TMJ, the same surgical management was performed, except that in each sheep, the fibrous layer of the condylar head was preserved. Three sheep were killed humanely at 1 month postoperatively, and the other 3 sheep were killed humanely at 3 months postoperatively. The TMJ complexes were examined by histologic evaluation. RESULTS: Fibrous ankylosis was observed on the left side in 3 sheep at 1 month postoperatively and in 2 of 3 sheep at 3 months postoperatively. Fibro-osseous ankylosis was achieved on the left side in 1 sheep at 3 months postoperatively. In the right TMJ, the main postoperative histologic findings included condylar fracture healing, topical rupture or exfoliation of the fibrous layer of the condyle, and fissure between the fibrous layer and the proliferative zone of the condyle. However, no evidence of ankylosis was observed. The TMJ ankylosis scores on the right side were significantly lower than those on the left side at different time points (P < .05). CONCLUSIONS: This study showed that the presence of the fibrous layer of the condylar head prevented the development of TMJ ankylosis in a sheep model of intracapsular condylar fracture.

Treatment of retinal detachment secondary to macular hole in highly myopic eyes: pars plana vitrectomy with internal limiting membrane peel and silicone oil tamponade.

PURPOSE: To evaluate efficacy of vitrectomy with internal limiting membrane peel and silicone oil tamponade in highly myopic eyes with retinal detachment secondary to macular hole (MH). METHODS: Twenty-one consecutive cases of MH-retinal detachment in highly myopic eyes were retrospectively reviewed. Eyes underwent pars plana vitrectomy, internal limiting membrane peeling, and silicone oil tamponade. A face-down or side-lying position was maintained postoperatively. Silicone oil was removed 3 months to 12 months later. Outcomes included MH closure and retinal reattachment rates, best-corrected visual acuity, and complication rates. RESULTS: Mean patient age was 59.3 ± 6.5 years and mean spherical equivalent was -15.2 ± 4.3 diopters. After silicone oil removal, 18 eyes (86%) had MH closure with retinal reattachment and 2 eyes needed reattachment with endolaser photocoagulation and fluid/gas exchange, and 1 patient refused further treatment. At the last follow-up, median best-corrected visual acuity was +1.48 ± 0.12, up from preoperative +2.11 ± 0.17 (P = 0.03). Transient intraocular pressure elevation was observed in 11 eyes (52%). Iatrogenic retinal break occurred in one case. CONCLUSION: Combining pars plana vitrectomy with internal limiting membrane peel and silicone oil tamponade was safe and effective in treating MH-retinal detachment in highly myopic eyes. Silicone oil tamponade may improve initial anatomical success rates because of longer tamponade duration.

4-Coumarate-CoA ligase (4-CL) enhances flavonoid accumulation, lignin synthesis, and fruiting body formation in Ganoderma lucidum.

It is now understood that 4-Coumarate-CoA ligases (4-CL) are pivotal in bridging the phenylpropanoid metabolic pathway and the lignin biosynthesis pathway in plants. However, limited information on 4-CL genes and their functions in fungi is available. In this study, we cloned the 4-CL gene (Gl21040) from Ganoderma lucidum, which spans 2178 bp and consists of 10 exons and 9 introns. We also developed RNA interference and overexpression vectors for Gl21040 to investigate its roles in G. lucidum. Our findings indicated that in the Gl21040 interference transformants, 4-CL enzyme activities decreased by 31 %-57 %, flavonoids contents decreased by 10 %-22 %, lignin contents decreased by 20 %-36 % compared to the wild-type (WT) strain. Conversely, in the Gl21040 overexpression transformants, 4-CL enzyme activity increased by 108 %-143 %, flavonoids contents increased by 8 %-37 %, lignin contents improved by 15 %-17 % compared to the WT strain. Furthermore, primordia formation was delayed by approximately 10 days in the Gl21040-interferenced transformants but occurred 3 days earlier in the Gl21040-overexpressed transformants compared to the WT strain. These results underscored the involvement of the Gl21040 gene in flavonoid synthesis, lignin synthesis, and fruiting body formation in G. lucidum.

Associated predictors of therapeutic response to uvulopharyngopalatoplasty for severe obstructive sleep apnea hypopnea syndrome.

The aim of this study was to determine the associated factors affecting the outcome of uvulopharyngopalatoplasty (UPPP) in patients with severe obstructive sleep apnea hypopnea syndrome (OSAHS), and to investigate whether cephalometric measurements were predictive of the therapeutic response to UPPP in patients with severe OSAHS. We retrospectively studied 51 consecutive patients who underwent revised UPPP with uvula preservation (H-UPPP), or Z-palatopharyngoplasty (ZPPP) for severe OSAHS [apnea-hypopnea index (AHI) >30]. All patients were evaluated using physical examination, Epworth Sleepiness Scale (ESS), cephalometry, and nocturnal polysomnography (PSG) before surgery and at 6-12 months after surgery. Based on the success criteria defined as an AHI of <20 and a decrease >50 %, the overall success rate was 45.1 %. The preoperative distance from the posterior border of the uvula to the middle pharyngeal wall (U-MPW) was significantly longer in the responder group than in the nonresponder group, when considering the whole group or the H-UPPP group alone. Among all study subjects, U-MPW and change in body mass index (△BMI) were the significant predictors of surgical success. U-MPW was the key predictor for H-UPPP surgical success, whereas mandibular plane angle (MPA) and Friedman stage were the key predictors for ZPPP surgical success. In conclusion, U-MPW was a significant predictor of UPPP surgical success. Patients with U-MPW >10 mm who are unwilling to receive nasal continuous positive airway pressure (CPAP) therapy might be suitable candidates for UPPP surgery.

Outcomes of transarterial embolization for large symptomatic focal nodular hyperplasia in 17 pediatric patients.

BACKGROUND: To evaluate the safety and the long-term outcomes of transarterial embolization (TAE) with lipiodol-bleomycin emulsion (LBE) plus N-Butyl cyanoacrylate (NBCA) in the treatment of children with large symptomatic focal nodular hyperplasia (FNH). METHODS: This is a retrospective case serial study. Children (aged <18 years) with FNH were treated. Indications for TAE were patients who were presenting with FNH related abdominal pain and the maximum diameter of FNH is more than 7 cm, and who were not candidates for surgical treatment. Technical success, adverse events, symptoms relief rate, and changes in the lesion size after TAE were evaluated. RESULTS: Between January 2003 and February 2018, 17 pediatric patients were included. Technical success was achieved in all patients. Mean follow-up was 67.5 months. All patients had complete resolution of abdominal symptom. The mean largest diameter of the lesions decreased from 10.5 cm to 1.9 cm (P < 0.01). The mean volume reduction rate was 96.9%. The complete resolution of the FNH was observed in 16 patients. No further therapy was needed for all patients. CONCLUSIONS: TAE with LBE plus NBCA appears to be a safe and effective treatment in pediatric patients with large symptomatic FNH. It could be considered as the first-line treatment for symptomatic large FNH.

Primary maxillomandibular advancement with concomitant revised uvulopalatopharyngoplasty with uvula preservation for severe obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: This study aimed to evaluate the efficacy and safety of primary maxillomandibular advancement (MMA) with concomitant adjunctive revised uvulopalatopharyngoplasty with uvula preservation (H-UPPP) in selected patients with severe obstructive sleep apnea-hypopnea syndrome (OSASH). METHODS: Eleven consecutive male patients with velo-orohypopharyngeal and hypopharyngeal narrowing underwent MMA with concomitant H-UPPP for severe OSAHS. All patients underwent a physical examination, Epworth Sleepiness Scale evaluation, cephalometry, nocturnal polysomnogram, and velopharyngeal insufficiency questionnaire survey before and at 6 to 12 months after surgery. RESULTS: On the basis of the success criteria, defined as an apnea-hypopnea index less than 20 and a decrease greater than 50%, the success rate was 91%. The apnea-hypopnea index decreased from 67.44 (13.30) to 9.41 (7.20) events per hour (P < 0.001) and the lowest oxygen saturation increased from 63.0% (10.70%) to 88.55% (4.59%) (P < 0.001) after surgery. All patients showed a significant decrease in mandibular plane to hyoid bone and increase in PAS after surgery. One patient reported regurgitation of liquids when drinking hastily after surgery. Two patients reported regurgitation as occasional occurrences. Half a year later, 2 patients reported complete resolution of the symptoms. One patient still complained of rare regurgitation of liquids when drinking quickly. Five patients had paresthesia of the lower lip; in 4 patients, the paresthesia had resolved by 12 months after surgery. One patient still complained of paresthesia of the lower lip after 2 years of follow-up. No major complication (eg, upper airway obstruction) occurred. CONCLUSIONS: Primary MMA with concomitant adjunctive H-UPPP is effective in selected patients with severe OSAHS without major complications.

High-performance free-standing microbial fuel cell anode derived from Chinese date for enhanced electron transfer rates.

Traditional anode materials have disadvantages like low specific surface area and poor electrical conductivity. Herein, carbonized Chinese dates (CCD) were synthesized as microbial fuel cells (MFC) anodes. The obtained materials exhibited excellent biocompatibility with fast start-up (within one day) and charge transfer (Rct 4.0 Ω). Their porous structure allows efficient ion transport and microbial community succession, favorable for long-term operation. The biomass analysis shows that CCD anodes can load higher weight of biomass. High-throughput sequencing (16S rRNA) discovered that CCD anode can enrich Geobacter spp., with highest abundance of 73.4%, much higher than carbon felt (CF, 39.2%). Benefit from these properties, the MFC with CCD anodes possess a maximum power density of 12.17 W m-3 (1.62 times of commercial carbon felt). In all, the CCD anode exhibits high performance with low cost and easy fabrication, certificating it a promising candidate for an ideal MFC anode material.

Biocompatible Nanotube-Strontium/polydopamine-arginine-glycine-aspartic acid coating on Ti6Al4V enhances osteogenic properties for biomedical applications.

Titanium (Ti) alloys, particularly Ti6 Al4 V, are the most commonly used biomedical implant material. Ti alloys are biologically inert, so there have been continuous efforts to improve their osteogenic properties and clinical performance. Since TiO2 nanotubes (NT) appear to be excellent drug platforms, and strontium reportedly enhances osteogenesis, we constructed a TiO2 nanotube coating on the surface of Ti6 Al4 V and immersed it in Sr (OH)2 solution in order to incorporate Sr into TiO2 nanotubes (NT-Sr). The results of field emission scanning electron microscope and X-ray diffraction analysis verified the fabrication of NT-Sr. We next added polydopamine (PDA) and cyclo- (arginine-glycine-aspartic acid-phenylalanine-cysteine) [c(RGDfC)] peptides to further promote biocompatibility of the implant. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the existence of PDA and c(RGDfC). Mesenchymal stem cells (MSCs) were planted on Ti, NT, NT-Sr, NT-Sr/PDA, and NT-Sr/PDA-RGD surfaces. The adhesion and differentiation of MSCs on different surfaces were evaluated. The mRNA expression of alkaline phosphatase, runt-related transcription factor 2 (Runx2) and type I collagen (Col I) of different groups were also tested. Finally, we observed that the NT-Sr/PDA-RGD group showed significantly better performance than other groups in terms of the differentiation and osteogenesis-related gene expression of MSCs. Thus, the NT-Sr/PDA-RGD complex may be an important modification strategy for Ti, as it shows excellent osteogenic potential.

[Study on optimization of formulation of Danggui Liuhuang effervescent granules].

OBJECTIVE: To optimize the formulation of Danggui Liuhuang effervescent granules. METHODS: By means of quadratic regression rotation-orthogonal combination design, the effect of the proper proportion between citric acid and sodium bicarbonate, as well as the proper quantity of polyethylene glycol 6000 and sodium cyclamate on the dissolubility and pH of effervescent granules was studied. RESULTS: The best formulation was as follows: citric acid: sodium bicarbonate = 0.75: 1, the percentage of polyethylene glycol 6000 and cyclamate was 3.25% and 0.89%, respectively. CONCLUSION: The dissolubility and pH of the effervescent granules are better and the taste is satisfactory.

Trio cooperates with Myh9 to regulate neural crest-derived craniofacial development.

Trio is a unique member of the Rho-GEF family that has three catalytic domains and is vital for various cellular processes in both physiological and developmental settings. TRIO mutations in humans are involved in craniofacial abnormalities, in which patients present with mandibular retrusion. However, little is known about the molecular mechanisms of Trio in neural crest cell (NCC)-derived craniofacial development, and there is still a lack of direct evidence to assign a functional role to Trio in NCC-induced craniofacial abnormalities. Methods:In vivo, we used zebrafish and NCC-specific knockout mouse models to investigate the phenotype and dynamics of NCC development in Trio morphants. In vitro, iTRAQ, GST pull-down assays, and proximity ligation assay (PLA) were used to explore the role of Trio and its potential downstream mediators in NCC migration and differentiation. Results: In zebrafish and mouse models, disruption of Trio elicited a migration deficit and impaired the differentiation of NCC derivatives, leading to craniofacial growth deficiency and mandibular retrusion. Moreover, Trio positively regulated Myh9 expression and directly interacted with Myh9 to coregulate downstream cellular signaling in NCCs. We further demonstrated that disruption of Trio or Myh9 inhibited Rac1 and Cdc42 activity, specifically affecting the nuclear export of ß-catenin and NCC polarization. Remarkably, craniofacial abnormalities caused by trio deficiency in zebrafish could be partially rescued by the injection of mRNA encoding myh9, ca-Rac1, or ca-Cdc42. Conclusions: Here, we identified that Trio, interacting mostly with Myh9, acts as a key regulator of NCC migration and differentiation during craniofacial development. Our results indicate that trio morphant zebrafish and Wnt1-cre;Triofl/fl mice offer potential model systems to facilitate the study of the pathogenic mechanisms of Trio mutations causing craniofacial abnormalities.

Mir24-2-5p suppresses the osteogenic differentiation with Gnai3 inhibition presenting a direct target via inactivating JNK-p38 MAPK signaling axis.

Background: Congenital anomalies are increasingly becoming a global pediatric health concern, which requires immediate attention to its early diagnosis, preventive strategies, and efficient treatments. Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 (Gnai3) gene mutation has been demonstrated to cause congenital small jaw deformity, but the functions of Gnai3 in the disease-specific microRNA (miRNA) upregulations and their downstream signaling pathways during osteogenesis have not yet been reported. Our previous studies found that the expression of Mir24-2-5p was significantly downregulated in the serum of young people with overgrowing mandibular, and bioinformatics analysis suggested possible binding sites of Mir24-2-5p in the Gnai3 3'UTR region. Therefore, this study was designed to investigate the mechanism of Mir24-2-5p-mediated regulation of Gnai3 gene expression and explore the possibility of potential treatment strategies for bone defects. Methods: Synthetic miRNA mimics and inhibitors were transduced into osteoblast precursor cells to regulate Mir24-2-5p expression. Dual-luciferase reporter assay was utilized to identify the direct binding of Gnai3 and its regulator Mir24-2-5p. Gnai3 levels in osteoblast precursor cells were downregulated by shRNA (shGnai3). Agomir, Morpholino Oligo (MO), and mRNA were microinjected into zebrafish embryos to control mir24-2-5p and gnai3 expression. Relevant expression levels were determined by the qRT-PCR and Western blotting. CCK-8 assay, flow cytometry, and transwell migration assays were performed to assess cell proliferation, apoptosis, and migration. ALP, ARS and Von Kossa staining were performed to observe osteogenic differentiation. Alcian blue staining and calcein immersions were performed to evaluate the embryonic development and calcification of zebrafish. Results: The expression of Mir24-2-5p was reduced throughout the mineralization process of osteoblast precursor cells. miRNA inhibitors and mimics were transfected into osteoblast precursor cells. Cell proliferation, migration, osteogenic differentiation, and mineralization processes were measured, which showed a reverse correlation with the expression of Mir24-2-5p. Dual-luciferase reporter gene detection assay confirmed the direct interaction between Mir24-2-5p and Gnai3 mRNA. Moreover, in osteoblast precursor cells treated with Mir24-2-5p inhibitor, the expression of Gnai3 gene was increased, suggesting that Mir24-2-5p negatively targeted Gnai3. Silencing of Gnai3 inhibited osteoblast precursor cells proliferation, migration, osteogenic differentiation, and mineralization. Promoting effects of osteoblast precursor cells proliferation, migration, osteogenic differentiation, and mineralization by low expression of Mir24-2-5p was partially rescued upon silencing of Gnai3. In vivo, mir24-2-5p Agomir microinjection into zebrafish embryo resulted in shorter body length, smaller and retruded mandible, decreased cartilage development, and vertebral calcification, which was partially rescued by microinjecting gnai3 mRNA. Notably, quite similar phenotypic outcomes were observed in gnai3 MO embryos, which were also partially rescued by mir24-2-5p MO. Besides, the expression of phospho-JNK (p-JNK) and p-p38 were increased upon Mir24-2-5p inhibitor treatment and decreased upon shGnai3-mediated Gnai3 downregulation in osteoblast precursor cells. Osteogenic differentiation and mineralization abilities of shGnai3-treated osteoblast precursor cells were promoted by p-JNK and p-p38 pathway activators, suggesting that Gnai3 might regulate the differentiation and mineralization processes in osteoblast precursor cells through the MAPK signaling pathway. Conclusions: In this study, we investigated the regulatory mechanism of Mir24-2-5p on Gnai3 expression regulation in osteoblast precursor cells and provided a new idea of improving the prevention and treatment strategies for congenital mandibular defects and mandibular protrusion.

Preferential capture of phosphate by an Enteromorpha prolifera-based biopolymer encapsulating hydrous zirconium oxide nanoparticles.

Preferential removal of phosphate from aqueous was conducted by a novel biomass-based nanocomposite (EP-N+-Zr) with encapsulated hydrous zirconium oxide, and the biopolymer EP-N+-Zr features were described. EP-N+-Zr exhibited high selective sequestration toward phosphate when humic acid or other competing anions (Cl-, SO42-, NO3-, ClO4-) coexisted at relatively high levels. Such excellent performance of EP-N+-Zr was attributed to its specific two site structures; the embedded HZO nanoparticles and quaternary ammonia groups [N+(CH2CH3)3Cl-] bonded inside the biomass-Enteromorpha prolifera, which facilitated preferable capture towards phosphate through specific affinity and nonspecific preconcentration of phosphate ions on the basis of the ion exchange, respectively. The maximum adsorption capacity of phosphate (20 °C) as calculated by Langmuir model was 88.5 mg(P)/g. Regeneration tests showed that EP-N+-Zr could be recycled at least five times without noticeable capacity losses using binary NaOH-NaCl as eluent.

Electrophoretic deposition of GHK-Cu loaded MSN-chitosan coatings with pH-responsive release of copper and its bioactivity.

Despite the fact that titanium has been widely applied in the replacement of bone defects, prosthesis failure still occurred because of the lack of adequate bone-bonding ability and the incidence of post-surgery infections. Concentration-dependent effects of therapeutic copper ions (Cu2+) for antibacterial and osteogenic activity have been well-established in the field of biomedical application. In this study, we prepared mesoporous silica nanoparticles (MSN) and MSN-COOH with uniform sphere size (~100 nm) and developed multifunctional chitosan coatings loaded with MSN@GHK-Cu (glycyl-L-histidyl-l-lysine-Cu2+) as a suitable strategy by electrophoretic deposition (EPD). The microstructure and composition of the coating were comprehensively characterized by using SEM, XRD, FTIR, and TEM, respectively. The functional activity of Cu2+ releasing from the surface was dependent on the pH value of the titanium surface. Through the controllable release of Cu2+, the coating achieved not only inhibited adhesion of bacteria but also had good cytocompatibility. The coating based on EPD technique could be considered as a promising surface modification approach for the controlled delivery in situ of drug or other biomolecules.

Differential regulation of blood vessel formation between traumatic temporomandibular joint fibrous ankylosis and bony ankylosis in a sheep model.

OBJECTIVES: Clinical and experimental studies show that the etiology of traumatic temporomandibular joint (TMJ) fibrous ankylosis and bony ankylosis are associated with the severity of trauma. However, how the injury severity affects the tissue differentiation is not clear. We tested the hypothesis that angiogenesis affects the outcomes of TMJ trauma, and that enhanced neovascularization after severe TMJ trauma would promote the development of bony ankylosis. METHODS: Bilateral condylar sagittal fracture and discectomy were performed for each sheep, with the glenoid fossa receiving either severe trauma to induce bony ankylosis or minor trauma to induce fibrous ankylosis. At days 7, 14, 28, and 56 after surgery, total RNA was extracted from the ankylosed callus. Temporal gene expressions of several molecules functionally important for blood vessel formation were studied by real-time PCR. RESULTS: Histological examination revealed a prolonged hematoma phase and a lack of cartilage formation in fibrous ankylosis. mRNA expression levels of HIF-1α, VEGF, VEGFR2, SDF1, Ang1, Tie2, vWF, CYR61, FGF2, TIMP1, MMP2, and MMP9 were distinctly lower in fibrous ankylosis compared with bony ankylosis at several time points. CONCLUSIONS: Our study indicates that inhibition of angiogenesis after TMJ trauma might be a promising strategy for preventing bony ankylosis in the future.

Guanine and nucleotide binding protein 3 promotes odonto/osteogenic differentiation of apical papilla stem cells via JNK and ERK signaling pathways.

Odonto/osteogenic differentiation of stem cells from the apical papilla (SCAPs) is a key process in tooth root formation and development. However, the molecular mechanisms underlying this process remain largely unknown. In the present study, it was identified that guanine and nucleotide binding protein 3 (GNAI3) was at least in part responsible for the odonto/osteogenic differentiation of SCAPs. GNAI3 was markedly induced in mouse tooth root development in vivo and in human SCAPs mineralization in vitro. Notably, knockdown of GNAI3 by lentiviral vectors expressing short­hairpin RNAs against GNAI3 significantly inhibited the proliferation, cell cycle progression and migration of SCAPs, as well as odonto/osteogenic differentiation of SCAPs in vitro, suggesting that GNAI3 may play an essential role in tooth root development. The promotive role of GNAI3 in odonto/osteogenic differentiation was further confirmed by downregulation of odonto/osteogenic makers in GNAI3­deficient SCAPs. In addition, knockdown of GNAI3 effectively suppressed activity of c­Jun N­terminal kinase (JNK) and extracellular­signal regulated kinase (ERK) signaling pathways that was induced during SCAPs differentiation, suggesting that GNAI3 promotes SCAPs mineralization at least partially via JNK/ERK signaling. Taken together, the present results implicate GNAI3 as a critical regulator of odonto/osteogenic differentiation of SCAPs in tooth root development, and suggest a possible role of GNAI3 in regeneration processes in dentin or other tissues.

Free radial forearm flap and anterolateral thigh flap for reconstruction of hemiglossectomy defects: A comparison of quality of life.

OBJECTIVES: The purpose of the retrospective study was to compare the differences of quality of life (QOL) outcomes 2 or more years postoperatively between the free radial forearm flap (FRFF) and anterolateral thigh flap (ALTF) in reconstruction of defects of a hemiglossectomy. METHODS: Ninety patients who had a lapse ≥2 years since the reconstructive flap surgery were evaluated by the University of Washington quality of life scale (UW-QOL), and Performance Status Scale for Head and Neck (PSS-HN). RESULTS: Patients in the FRFF group reported statistically and clinically significantly better scores in the recreation, swallowing, chewing and speech domains of the UW-QOL compared with those in the ALTF group (P < .05). Similarly, FRFF provided better results in the understandability of speech and normalcy of diet of the PSS-HN, than the ALTF (P < .05). CONCLUSIONS: FRFF had the advantage of oral functions, such as chewing, speech and swallowing, over the ALTF for reconstruction of defect of half of the tongue. These results may provide useful information for surgeons to select a suitable free flap for tongue reconstruction.