Hydrogen Sulfide Promotes Tet1- and Tet2-Mediated Foxp3 Demethylation to Drive Regulatory T Cell Differentiation and Maintain Immune Homeostasis.

Regulatory T (Treg) cells are essential for maintenance of immune homeostasis. Here we found that hydrogen sulfide (H2S) was required for Foxp3(+) Treg cell differentiation and function and that H2S deficiency led to systemic autoimmune disease. H2S maintained expression of methylcytosine dioxygenases Tet1 and Tet2 by sulfhydrating nuclear transcription factor Y subunit beta (NFYB) to facilitate its binding to Tet1 and Tet2 promoters. Transforming growth factor-ß (TGF-ß)-activated Smad3 and interleukin-2 (IL-2)-activated Stat5 facilitated Tet1 and Tet2 binding to Foxp3. Tet1 and Tet2 catalyzed conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in Foxp3 to establish a Treg-cell-specific hypomethylation pattern and stable Foxp3 expression. Consequently, Tet1 and Tet2 deletion led to Foxp3 hypermethylation, impaired Treg cell differentiation and function, and autoimmune disease. Thus, H2S promotes Tet1 and Tet2 expression, which are recruited to Foxp3 by TGF-ß and IL-2 signaling to maintain Foxp3 demethylation and Treg-cell-associated immune homeostasis.

Biomechanical effects of clear aligner with different shape design at extraction space area during anterior teeth retraction.

OBJECTIVE: This study aimed to investigate the biomechanical effects of clear aligner (CA) with different shape designs at extraction space (CAES) area during space closing. MATERIALS AND METHODS: A finite-element method (FEM) model of mandibular dentition, periodontal ligaments, attachments, and corresponding CA was established. The connecting rod design of CAES was modelled for the control group. Eight test groups with different heights of CAES from -4 mm to +4 mm were designed. Tooth displacement tendencies were calculated. The maximum principal stress in PDLs, teeth, and CAs was analysed. Both global coordinate system and local coordinate system were also used to evaluate individual tooth movements. RESULTS: Across all groups, stresses concentrated on the lingual outer surface of CAESs. For the lowered CAES groups, both the stress value and the stress distribution area at CAESs were increased. The lowered CAES groups showed reduced movement in anterior teeth and less tipping tendency of the canines. CONCLUSION: The shape of CAES has a biomechanical impact on anterior teeth movement and should be considered in aligner design. The results suggest that increasing the height of CAES can enhance anterior teeth retraction, while lowered CAES may facilitate controlled root movement. Changes in the shape of CAES represent a potential direction for biomechanical improvement of clear aligner in extraction cases and are worth exploring.

[Soft and hard tissue changes of hyperdivergent class â ¡ patients before and after orthodontic extraction treatment].

OBJECTIVE: To investigate the hard and soft tissue changing trend and contributing factors of skeletal class Ⅱ hyperdivergent patients before and after orthodontic camouflage treatment by analyzing the cephalogram and the three dimensional (3D) facial scan data. METHODS: Eighteen skeletal class Ⅱ hyperdivergent adult female patients who finished camouflage orthodontic treatment were selected. Skeletal and dental measurements were carried out with the cephalometric analysis before and after the treatment. 3D facial data before and after orthodontic treatment were acquired and the anatomical landmarks were set after the repositioning and superimposition process. Hard tissue measurement included 17 mea-surement indicators (sella-nasion-subspinale angle, sella-nasion-supramental angle, subspinale-nasion-supramental angle, facial angle, angle of convexity, Frankfort horizontal plane-mandibular plane angle (FH-MP), Y axis angle, sella-nasion plane-mandibular plane angle (MP-SN), pogonion-nasion-supramental distance, upper incisor-nasion-subspinale distance, upper incisor to sella-nasion, lower incisor-nasion-supramental distance, lower incisor-nasion-supramental angle, upper incisor to lower incisor, upper incisor to sella-nasion, lower incisor-mandibular plane angle, and Z angle), and the changes before and after treatment were measured for 11 of them. Twenty soft tissue landmarks (left/right cheekbone, left/right chelion, left/right crista philtra, soft tissue gnathion, left/right gonion, glabella, labrale infe-rius, labrale superius, soft tissue menton, left/right mid-mandibular border, soft tissue pogonion, stomion superius, sublabial, subnasale, and supralabial) and 9 soft tissue indicators (lower lip height, facial convexity, lower vermilion height, mandibular contour, nasolabial angle, philtral length, philtral width, upper lip height, and upper vermilion height) were measured and recorded for treatment changes. Linear-regression analysis and correlation analysis were carried out for analyzing the relationship between hard and soft tissue changes before and after the treatment. RESULTS: Significant differences were noticed for 18 out of the 20 cephalometric measurements and facial measurements before and after the treatment (P < 0.05), which mainly represented the sagittal retraction of lip area after the treatment. Significant vertical displacements were revealed for soft tissue menton after treatment [(1.88±2.61) mm, P < 0.05]. Significant sagittal displacements were revealed for left/right cheilion [(-2.95±1.9) mm, (-2.90±1.92) mm], labrale inferius[(-4.94±1.95) mm], labrale superius[(-3.25±1.44) mm], sublabial [(-3.10±3.5) mm], and subnasale [(-1.23±1.06) mm] after treatment (P < 0.05). An average of 4.10°±2.57° increasement was noticed for Z angle after treatment. High correlation (r>0.7) was noticed for the displacement of menton after treatment with FH-MP, with the rate of -0.183 :1, and MP-SN, with the rate of -0.157 :1. Moderate correlations (0.7≥r>0.4) were noticed for the other measurements with correlations (P < 0.05). CONCLUSION: A certain extent of facial improvements could be achieved with orthodontic camouflage treatment for skeletal class Ⅱ hyperdivergent patients, which were mostly represented by the improvement of sagittal relationship of nose, lips, and chin. Certain correlations were noticed for the hard and soft tissue changes.

A quantitative analysis of facial changes after orthodontic treatment with vertical control in patients with idiopathic condylar resorption.

OBJECTIVE: This study aimed to investigate temporomandibular joint (TMJ) stability and three-dimensional (3D) facial changes in class II hyperdivergent patients with stable idiopathic condylar resorption (ICR) after orthodontic camouflage treatment with vertical control by using temporary anchorage devises (TADs). METHODS: Nineteen skeletal class II hyperdivergent patients who were diagnosed with stable ICR underwent bicuspid extraction orthodontic treatment with vertical control via TADs were enrolled. TMJ was evaluated with the cone beam computerized tomography (CBCT) and clinical records before and after treatment. Changes in dental and skeletal parameters were evaluated with cephalometric and dental cast measurements. The 3D morphable model (3DMM) method was performed with the MeshMonk toolbox for the 3D facial analysis. After the reposition and landmark setting process, 3D facial heatmaps were used to illustrate facial changes, and the 3D deviations of landmarks were calculated. RESULTS: Both the imaging evaluation and clinical examination proved that TMJs remained stable after treatment. The retrusion of the upper and lower incisors reached 6.63 ± 0.79 mm and 3.78 ± 1.49 mm. The intrusion of the upper first molar reached 2.65 ± 0.75 mm, with a 2.27 ± 0.82° counterclockwise rotation of the mandibular plane. An upward shift of the soft tissue pogonion (2.34 ± 2.03 mm) and protrusion of Po-NB (0.82 ± 0.70 mm) was gained. Larger intrusion was found in the lower lip (3.29 ± 0.80 mm) than in the upper lip (2.20 ± 0.69 mm). CONCLUSION: Camouflage orthodontic treatment with TAD for vertical control is acceptable for skeletal class II hyperdivergent patients with ICR, which can improve the facial profile.

Dental Pulp Stem Cell-Derived Exosomes Alleviate Mice Knee Osteoarthritis by Inhibiting TRPV4-Mediated Osteoclast Activation.

Osteoarthritis (OA) is a degenerative disease that causes chronic pain and joint swelling and even disables millions of patients. However, current non-surgical treatment for OA can only relieve pain without obvious cartilage and subchondral bone repair. Mesenchymal stem cell (MSC)-secreted exosomes have promising therapeutic effects on knee OA, but the efficacy of MSC-exosome therapy is not well determined, and the mechanisms involved are still unclear. In this study, we isolated dental pulp stem cell (DPSC)-derived exosomes by ultracentrifugation and determined the therapeutic effects of a single intra-articular injection of DPSC-derived exosomes in a mice knee OA model. The results showed that the DPSC-derived exosomes effectively improved abnormal subchondral bone remodeling, inhibited the occurrence of bone sclerosis and osteophytes, and alleviated cartilage degradation and synovial inflammation in vivo. Moreover, transient receptor potential vanilloid 4 (TRPV4) was activated during the progression of OA. Enhanced TRPV4 activation facilitated osteoclast differentiation, and TRPV4 inhibition blocked this process in vitro. DPSC-derived exosomes repressed osteoclast activation in vivo by inhibiting TRPV4 activation. Our findings demonstrated that a topical, single injection of DPSC-derived exosomes is a potential strategy for knee OA treatment, and that the exosomes regulated osteoclast activation by TRPV4 inhibition, which may act as a promising target for clinical OA treatment.

Oral microbiome contributes to the failure of orthodontic temporary anchorage devices (TADs).

BACKGROUND: The stability of temporary anchorage devices (TADs) is critical in orthodontic clinics. The failure of TADs is multifactorial, and the role of the oral microbiome has not been clearly defined. Herein, we attempted to analyze the contribution of the oral microbiome to the failure of TADs. METHODS: Next-generation sequencing was adopted for analyzing the microbiome on the TADs from orthodontic patients. 29 TADs (15 failed TADs and 14 successful TADs) were used for 16S rRNA gene sequencing. A total of 135 TADs (62 failed TADs and 73 successful TADs) were collected to conduct metagenomic sequencing. Additionally, 34 verified samples (18 failed TADs and 16 successful TADs) were collected for quantitative real-time polymerase chain reaction analysis (qRT-PCR). RESULTS: Successful and failed TADs demonstrated discrepancies in microbiome structure, composition, and function. Clear separations were found in ß-diversity in 16S rRNA gene sequencing as well as metagenomic sequencing (p < 0.05). Metagenomic sequencing showed that Prevotella intermedia, Eikenella corrodens, Parvimonas spp., Neisseria elongata, and Catonella morbi were enriched in the failed groups. qRT-PCR also demonstrated that the absolute bacteria load of Prevotella intermedia was higher in failed TADs (p < 0.05). Considering functional aspects, the failed group showed enriched genes involved in flagellar assembly, bacterial chemotaxis, and oxidative phosphorylation. CONCLUSIONS: This study illustrated the compositional and functional differences of microorganisms found on successful and failed TADs, indicating that controlling bacterial adhesion on the surface of TADs is essential for their success rate.

Subjective evaluation of facial asymmetry with three-dimensional simulated images among the orthodontists and laypersons: a cross-sectional study.

OBJECTIVES: We used three-dimensional (3D) virtual images to undertake a subjective evaluation of how different factors affect the perception of facial asymmetry among orthodontists and laypersons with the aim of providing a quantitative reference for clinics. MATERIALS AND METHODS: A 3D virtual symmetrical facial image was acquired using FaceGen Modeller software. The left chin, mandible, lip and cheek of the virtual face were simulated in the horizontal (interior/exterior), vertical (up/down), or sagittal (forward or backward) direction in 3, 5, and 7 mm respectively with Maya software to increase asymmetry for the further subjective evaluation. A pilot study was performed among ten volunteers and 30 subjects of each group were expected to be included based on 80% sensitivity in this study. The sample size was increased by 60% to exclude incomplete and unqualified questionnaires. Eventually, a total of 48 orthodontists and 40 laypersons evaluated these images with a 10-point visual analog scale (VAS). The images were presented in random order. Each image would stop for 30 s for observers with a two-second interval between images. Asymmetry ratings and recognition accuracy for asymmetric virtual faces were analyzed to explore how different factors affect the subjective evaluation of facial asymmetry. Multivariate linear regression and multivariate logistic regression models were used for statistical data analysis. RESULTS: Orthodontists were found to be more critical of asymmetry than laypersons. Our results showed that observers progressively decreased ratings by 1.219 on the VAS scale and increased recognition rates by 2.301-fold as the degree of asymmetry increased by 2 mm; asymmetry in the sagittal direction was the least noticeable compared with the horizontal and vertical directions; and chin asymmetry turned out to be the most sensitive part among the four parts we simulated. Mandible asymmetry was easily confused with cheek asymmetry in the horizontal direction. CONCLUSIONS: The degree, types and parts of asymmetry can affect ratings for facial deformity as well as the accuracy rate of identifying the asymmetrical part. Although orthodontists have higher accuracy in diagnosing asymmetrical faces than laypersons, they fail to correctly distinguish some specific asymmetrical areas.

The accuracy of a three-dimensional face model reconstructing method based on conventional clinical two-dimensional photos.

BACKGROUND: This study aims to investigate the accuracy of a three-dimensional (3D) face reconstruction method based on conventional clinical two-dimensional (2D) photos. METHODS: Twenty-three patients were included, and Character Creator v3.2 software with the Headshot v1.0 plugin was used for 3D face model reconstruction. Various facial landmarks were finely adjusted manually to refine the models. After preprocessing and repositioning, 3D deviation analysis was performed. The accuracy of the landmarks in different dimensions was determined, and twelve facial soft tissue measurements were compared to validate the clinical potential of the method. RESULT: The reconstructed 3D face models showed good facial morphology with fine texture. The average root mean square errors between face scan models and reconstructed models at perioral area (1.26 ± 0.24 mm, 95%CI: 1.15-1.37 mm) were significantly smaller than the entire facial area (1.77 ± 0.23 mm, 95%CI:1.67-1.88 mm), P < 0.01. The deviation of menton of soft tissue was significantly larger than pronasale (P < 0.01). The deviations of all landmarks in the Y-direction were significantly larger than those in the other 2 dimensions (Y > Z > X, P < 0.01). A significant difference (P < 0.05) of approximately 1.5 mm was found for facial height. Significant differences (P < 0.05) were also identified in the remaining 6 soft tissue measurements, with average deviations no greater than 0.5 mm (linear measurement) or 1.2° (angular measurements). CONCLUSION: A 3D face modeling method based on 2D face photos was revealed and validated. The reconstruction accuracy of this method is clinically acceptable for orthodontic measurement purposes, but narrow clinical indications and labor-intensive operations remain problems.

T cells participate in bone remodeling during the rapid palatal expansion.

Palatal expansion has been widely used for the treatment of transverse discrepancy or maxillae hypoplasia, but the biological mechanism of bone formation during this procedure is largely unknown. Osteoclasts, which could be regulated by T cells and other components of the immune system, play a crucial role in force-induced bone remodeling. However, whether T cells participate in the palatal expansion process remains to be determined. In this study, we conducted the tooth borne rapid palatal expansion model on the mouse, and detect whether the helper T cells (Th) and regulatory T cells (Treg) could affect osteoclasts and further bone formation. After bonding open spring palatal expanders for 3-day, 5-day, 7-day, and retention for 28-day, micro-computed tomography scanning, histologic, and immunofluorescence staining were conducted to evaluate how osteoclasts were regulated by T cells during the bone remodeling process. We revealed that the increased osteoclast number was downregulated at the end of the early stage of rapid palatal expansion. Type 1 helper T (Th1) cells and Type 17 helper T (Th17) cells increased initially and promoted osteoclastogenesis. Thereafter, the regulatory T (Treg) cells emerged and maintained a relatively high level at the late stage of the experiment to downregulate the osteoclast number by inhibiting Th1 and Th17 cells, which governed the new bone formation. In conclusion, orchestrated T cells are able to regulate osteoclasts at the early stage of rapid palatal expansion and further facilitate bone formation during retention. This study identifies that T cells participate in the palatal expansion procedure by regulating osteoclasts and implies the potential possibility for clinically modulating T cells to improve the palatal expansion efficacy.

Neural EGFL-Like 1 Regulates Cartilage Maturation through Runt-Related Transcription Factor 3-Mediated Indian Hedgehog Signaling.

The pro-chondrogenic function of runt-related transcription factor 2 (Runx2) was previously considered to be dependent on direct binding with the promoter of Indian hedgehog (Ihh)-the major regulator of chondrocyte differentiation, proliferation, and maturation. The authors' previous studies identified neural EGFL like 1 (Nell-1) as a Runx2-responsive growth factor for chondrogenic differentiation and maturation. In this study, it was further revealed that the pro-chondrogenic activities of Nell-1 also rely on Ihh signaling, by showing: i) Nell-1 significantly elevated Ihh signal transduction; ii) Nell-1 deficiency markedly reduced Ihh activation in chondrocytes; and iii) Nell-1-stimulated chondrogenesis was significantly reduced by the specific hedgehog inhibitor cyclopamine. Importantly, the authors demonstrated that Nell-1-responsive Ihh signaling and chondrogenic differentiation extended to Runx2-/- models in vitro and in vivo. In Runx2-/- chondrocytes, Nell-1 stimulated the expression and signal transduction of Runx3, another transcription factor required for complete chondrogenic differentiation and maturation. Furthermore, knocking down Runx3 in Runx2-/- chondrocytes abolished Nell-1's stimulation of Ihh-associated molecule expression, which validates Runx3 as a major mediator of Nell-1-stimulated Ihh activation. For the first time, the Runx2→Nell-1→Runx3→Ihh signaling cascade during chondrogenic differentiation and maturation has been identified as an alternative, but critical, pathway for Runx2 to function as a pro-chondrogenic molecule via Nell-1.

Neural EGFL-Like 1 Is a Downstream Regulator of Runt-Related Transcription Factor 2 in Chondrogenic Differentiation and Maturation.

Recent studies indicate that neural EGFL-like 1 (Nell-1), a secretive extracellular matrix molecule, is involved in chondrogenic differentiation. Herein, we demonstrated that Nell-1 serves as a key downstream target of runt-related transcription factor 2 (Runx2), a central regulator of chondrogenesis. Unlike in osteoblast lineage cells where Nell-1 and Runx2 demonstrate mutual regulation, further studies in chondrocytes revealed that Runx2 tightly regulates the expression of Nell-1; however, Nell-1 does not alter the expression of Runx2. More important, Nell-1 administration partially restored Runx2 deficiency-induced impairment of chondrocyte differentiation and maturation in vitro, ex vivo, and in vivo. Mechanistically, although the expression of Nell-1 is highly reliant on Runx2, the prochondrogenic function of Nell-1 persisted in Runx2-/- scenarios. The biopotency of Nell-1 is independent of the nuclear import and DNA binding functions of Runx2 during chondrogenesis. Nell-1 is a key functional mediator of chondrogenesis, thus opening up new possibilities for the application of Nell-1 in cartilage regeneration.

A Precisely Assembled Carbon Source to Synthesize Fluorescent Carbon Quantum Dots for Sensing Probes and Bioimaging Agents.

A broad range of carbon sources have been used to fabricate varieties of carbon quantum dots (CQDs). However, the majority of these studies concern the influence of primary structures and chemical compositions of precursors on the CQDs; it is still unclear whether or not the superstructures of carbon sources have effects on the physiochemical properties of the synthetic CQDs. In this work, the concept of molecular assembly is first introduced into the design of a new carbon source. Compared with the tropocollagen molecules, the hierarchically assembled collagen scaffolds, as a new carbon source, immobilize functional groups of the precursors through hydrogen bonds, electrostatic attraction, and hydrophobic forces. Moreover, the accumulation of functional groups in collagen self-assembly further promotes the covalent bond formation in the obtained CQDs through a hydrothermal process. Both of these two chemical superiorities give rise to high quality CQDs with enhanced emission. The assembled collagen scaffold-based CQDs with heteroatom doping exhibit superior stability, and could be further applied as effective fluorescent probes for Fe3+ detection and cellular cytosol imaging. These findings open a wealth of possibilities to explore more nanocarbons from precursors with assembled superstructures.

Sexual dimorphism of estrogen-sensitized synoviocytes contributes to gender difference in temporomandibular joint osteoarthritis.

OBJECTIVES: Temporomandibular joint osteoarthritis (TMJOA) is approximately twice as prevalent in women than in men. Synoviocytes are believed to play a critical role in joint inflammation. However, it is unknown whether synoviocytes from different genders possess sexual dimorphisms that contribute to female-predominant TMJOA. MATERIALS AND METHODS: Freund's complete adjuvant combined with monosodium iodoacetate was used to induce TMJOA in female and male rats. Histologic and radiographic features were used to evaluate TMJOA. The expression of CD68, MCP-1, iNOS, and IL-1ß was detected by immunohistochemistry and real-time PCR. Primary fibroblast-like synoviocytes (FLSs) isolated from the synovial membrane of female and male rats were used for in vitro experiments. RESULTS: Female rats showed aggravated TMJOA features as compared to male rats. Increased expression of iNOS and IL-1ß was detected in synovial membrane from female TMJOA rats as compared to male rats. Furthermore, greater amounts of CD68-positive macrophage infiltration and increased MCP-1 expression around the synovial membrane were detected in female TMJOA rats compared to males. Primary cultured FLSs from female rats showed higher sensitivity to TNF-α treatment and recruited increased macrophage migration than male FLSs. More important, ovariectomy (OVX) by ablation in female rats repressed the sensitivity of female FLSs to TNF-α treatment due to the loss of estrogen production. Blockage of the estrogen receptor repressed estrogen-potentiated TNF-α-induced pro-inflammatory cytokine expression in OVX-FLSs. Moreover, the injection of estrogen receptor antagonists relieved the cartilage destruction and bone deterioration of TMJOA in female rats. CONCLUSION: Estrogen-sensitized synoviocytes in female rats may contribute to gender differences in the incidence and progression of TMJOA.

Novel method of constructing a stable reference frame for 3-dimensional cephalometric analysis.

INTRODUCTION: Three-dimensional (3D) cephalometric analysis has provided the ability to overcome the limitations of 2-dimensional cephalometrics. However, there is no international standard method for 3D cephalometric analysis yet. Determining the position of the midsagittal plane (MSP) practically is the most important step when constructing a 3D cephalometric reference frame. Recent studies have used several approaches to construct the MSP. In this study, we aimed to determine the true MSP of the skull to establish a stable reference frame for 3D cephalometric analysis. METHODS: Cone-beam computed tomography data of 12 adult patients were divided into 2 groups: symmetry (n = 6) and asymmetry (n = 6). The anterior cranial base region model and its mirror model were registered and used to determine the MSP to prevent any influence of the degree of symmetry on the registration of other parts of the skull, particularly for subjects with severe facial or cranial asymmetry. Intraclass correlation coefficients were used to assess intraexaminer and interexaminer reliabilities of the x, y, and z coordinates of all landmarks measured by 2 investigators. RESULTS: The intraclass correlation coefficient values were greater than 0.9, indicating almost perfect agreement. CONCLUSIONS: The candidate reference planes constructed using this novel method were thought to be reliable for 3D cephalometric analysis and may expand its clinical applicability in patients with cranial asymmetry.

Amino acids at positions 3, 168, and 169 are associated with the ability of Nef proteins from HIV-1 CRF01_AE to downmodulate CD4.

Several HIV-1 subtypes are co-circulating among various high-risk groups in China, and an increasing prevalence of CRF01_AE was observed among MSM (men who have sex with men) within recent years. Patients infected with CRF01_AE may experience a more rapid disease progression than patients infected with non-CRF01_AE; however, the underlying mechanisms remains elusive. HIV-1 Nef is a multifunctional protein and plays critical roles in viral pathogenesis. Nef downregulates CD4 and human leukocyte antigen (HLA) to promote viral transmission and escape from the host immune response. In this study, we investigated the CD4 downmodulation activity of Nef proteins isolated from HIV-1 CRF01_AE and analyzed a potential relationship of Nef's capacity to downregulate CD4 with disease progression. We found that the majority of these Nefs from HIV-1 CRF01_AE efficiently downregulated CD4; Nefs with weaker CD4 downmodulation activity tended to be associated with higher CD4 levels and lower viral loads. Further elucidation revealed that amino acid residues at positions 3, 168, and 169 of CRF01_AE Nefs were associated with the capacity to downregulate CD4. Our data suggest that the capacity of Nef-mediated CD4 downregulation is not the only determinant for controlling disease progression, and other host and viral factors should be considered to explain the rapid disease progression of patients infected with HIV-1 CRF01_AE.

Estradiol promotes M1-like macrophage activation through cadherin-11 to aggravate temporomandibular joint inflammation in rats.

Macrophages play a major role in joint inflammation. Estrogen is involved in rheumatoid arthritis and temporomandibular disorders. However, the underlying mechanism is still unclear. This study was done to verify and test how estrogen affects M1/M2-like macrophage polarization and then contributes to joint inflammation. Female rats were ovariectomized and treated with increasing doses of 17ß-estradiol for 10 d and then intra-articularly injected with CFA to induce temporomandibular joint (TMJ) inflammation. The polarization of macrophages and expression of cadherin-11 was evaluated at 24 h after the induction of TMJ inflammation and after blocking cadherin-11 or estrogen receptors. NR8383 macrophages were treated with estradiol and TNF-α, with or without blocking cadherin-11 or estrogen receptors, to evaluate the expression of the M1/M2-like macrophage-associated genes. We found that estradiol increased the infiltration of macrophages with a proinflammatory M1-like predominant profile in the synovium of inflamed TMJ. In addition, estradiol dose-dependently upregulated the expressions of the M1-associated proinflammatory factor inducible NO synthase (iNOS) but repressed the expressions of the M2-associated genes IL-10 and arginase in NR8383 macrophages. Furthermore, estradiol mainly promoted cadherin-11 expression in M1-like macrophages of inflamed TMJ. By contrast, blockage of cadherin-11 concurrently reversed estradiol-potentiated M1-like macrophage activation and TMJ inflammation, as well as reversed TNF-α-induced induction of inducible NO synthase and NO in NR8383 macrophages. The blocking of estrogen receptors reversed estradiol-potentiated M1-like macrophage activation and cadherin-11 expression. These results suggested that estradiol could promote M1-like macrophage activation through cadherin-11 to aggravate the acute inflammation of TMJs.

Miniscrew-assisted customized lingual appliances for predictable treatment of skeletal Class II malocclusion with severe deep overbite and overjet.

This report describes the use of miniscrew-assisted customized lingual fixed appliances in a patient with severe skeletal Class II malocclusion. The patient was a 12-year-old Chinese girl with the chief complaint of protrusive lips and anterior teeth. Her diagnosis included a skeletal Class II relationship with maxillary protrusion, a backward-rotated mandible, a full Angle Class II molar relationship, and severe deep overjet and overbite. Four premolars were extracted, and miniscrew anchorage was placed in the maxillary posterior lingual segment to provide maximum anchorage and to achieve vertical control of the intruding molars. The customized lingual fixed appliance and temporary anchorage devices created a smooth and invisible treatment progress, resulting ultimately in a well-aligned dentition with ideal intercuspation and a dramatically improved profile. The 3-year follow-up examination indicated that the excellent treatment outcome was stable.

Nonsurgical correction using miniscrew-assisted vertical control of a severe high angle with mandibular retrusion and gummy smile in an adult.

Orthodontic treatment in adult patients with a skeletal discrepancy can be challenging. In this case report, we achieved both sagittal and vertical control by combining the classic sliding mechanics straight-wire technique with miniscrew anchorage. We treated a 21-year-old Chinese woman with a severe high mandibular plane angle, a retrusive chin, and a gummy smile. Her diagnosis included a skeletal Class II skull base with a mild anterior open bite, a protrusive maxilla, and a backwardly rotated mandible. This case underscores the importance of anchorage control in both the sagittal and vertical directions. First, we used miniscrews in the maxillary and mandibular buccal segments to obtain rigid anchorage. Next, we achieved good anterior and posterior vertical control with miniscrews in the maxillary anterior labial and posterior buccolingual segments. Intrusion of the maxillary molars contributed to deepening of the anterior overbite and counterclockwise rotation of the mandibular plane, which, in turn, improved the facial profile. Intrusion of the maxillary incisors contributed to correction of the gummy smile. After 1 year of retention, the patient had a stable, well-aligned dentition with ideal intercuspation and an improved facial contour. Our results thus suggest that placement of miniscrews in the anterior and posterior regions of the maxilla is effective for camouflaging a high-angle skeletal Class II defect. This technique requires minimal patient compliance and is particularly useful for correction of a high angle in an adult with a gummy smile.

Minimal presurgical orthodontics for a skeletal Class III patient with mandibular asymmetry.

A 19-year-old man with a skeletal Class III malocclusion was treated using minimal presurgical orthodontics. Orthodontic appliances and miniscrews were placed at the beginning of treatment, and the double-jaw-surgery was performed once the maxillary right and left first premolars were intruded, without worsening the concave profile and facial asymmetry presurgically. Different from the traditional combined orthodontic-orthognathic surgery, the jaw discrepancy was corrected first, followed by the orthodontic tooth movement. Miniscrews were used to intrude the premolars presurgically because of their interference and to provide the skeletal anchorage for intermaxillary elastics after the operation. The patient was pleased with the treatment results and satisfied with his facial and dental appearance, as well as his oral function. The 1-year follow-up photographs show a stable result both esthetically and functionally.

Progressive changes in patients with skeletal Class III malocclusion treated by 2-jaw surgery with minimal and conventional presurgical orthodontics: A comparative study.

INTRODUCTION: In this study, we aimed to compare treatment efficacy and postsurgical stability between minimal presurgical orthodontics and conventional presurgical orthodontics for patients with skeletal Class III malocclusion. METHODS: Forty patients received minimal presurgical orthodontics (n = 20) or conventional presurgical orthodontics (n = 20). Lateral cephalograms were obtained before treatment, before orthognathic surgery, and at 1 week, 3 months, 6 months, and 12 months after surgery. RESULTS: Changes of overjet and mandibular incisal angle before surgery were greater in the conventional presurgical orthodontics group than in the minimal presurgical orthodontics group. Postsurgical horizontal changes in Points A and B, overjet, and mandibular incisal angle showed significant differences among the time points. Most of the horizontal and vertical relapses in the maxilla and the mandible occurred within the first 6 months in both groups. CONCLUSIONS: Minimal presurgical orthodontics and conventional presurgical orthodontics showed similar extents and directions of skeletal changes in patients with Class III malocclusion. However, orthodontists and surgeons should preoperatively consider the postsurgical counterclockwise rotation of the mandible when using minimal presurgical orthodontics. Close and frequent observations are recommended in the early postsurgical stages.