Correlating Jaw Bone Growth and Nasal Morphology Among Adult Patients With Cleft Lip and Palate: A Retrospective Cephalometric Study.

This retrospective cross-sectional study reviewed adult patients with operated cleft lip and/or palate (CL/P) and normal control, and performed comprehensive craniofacial and nasal morphological analyses based on lateral cephalometric radiographs. Pearson or Spearman correlation coefficient assessed intraclass correlation. Seven hundred fifty-seven operated patients with CL/P, and 165 noncleft normal controls were enrolled. Among the normal and CL/P groups, S-N-A angle registered positive correlations with nasal base prominence (S-N'-Sn, degrees). Upper facial height (N-ANS, mm) had positive correlations with nasal dorsum length (N'-Prn, mm) and nasal bone length (N-Na, mm). Although in patients with bilateral cleft lip and palate, there were moderate negative correlations ( r =-0.541, P <0.05) with soft tissue facial profile angle (FH-N'Pog', degree) and nasolabial angle (Cm-Sn-ULA, degree). Correlation exists between the morphology of jaw bones and external nose among patients with CL/P. Maxillary sagittal insufficiency is associated with concave nasal profile, and maxilla height is associated with nasal length.

Alpha-ketoglutarate up-regulates autophagic activity in peri-implant environment and enhances dental implant osseointegration in osteoporotic mice.

AIM: The osseointegration of dental implants is impaired in patients with osteoporosis, leading to significantly higher failure rates. This study set out to investigate the potential effects of alpha-ketoglutarate (α-KG) on implant osseointegration in an osteoporotic mouse model. MATERIALS AND METHODS: Female C57BL/6 mice received ovariectomy and bilateral first maxillary molar extraction at the age of 7 weeks. Dental implants were inserted 8 weeks after tooth extraction. In one of the groups, α-KG was administered via drinking water throughout the experimental period. Specimens were collected on post-implant days (PIDs) 3, 7, 14, and 21 for micro-CT, histological, and immunohistochemical analyses. At the same time, bone-marrow-derived mesenchymal stem cells (BMMSCs) treated with α-KG were interrogated for osteogenic differentiation, autophagic activity, and apoptosis. RESULTS: α-KG supplementation in drinking water resulted in enhanced dental implant osseointegration in ovariectomized mice, with up-regulated osteogenic and autophagic activity and down-regulated osteoclast differentiation and cell apoptosis. α-KG-treated BMMSCs showed enhanced activity in proliferation, survival, colony formation, and osteogenic differentiation, as well as autophagic activity. CONCLUSIONS: Systemic α-KG supplementation effectively prevents the failure of dental implant osseointegration in mice under an osteoporotic state.

Liposome-Based Carriers for CRISPR Genome Editing.

The CRISPR-based genome editing technology, known as clustered regularly interspaced short palindromic repeats (CRISPR), has sparked renewed interest in gene therapy. This interest is accompanied by the development of single-guide RNAs (sgRNAs), which enable the introduction of desired genetic modifications at the targeted site when used alongside the CRISPR components. However, the efficient delivery of CRISPR/Cas remains a challenge. Successful gene editing relies on the development of a delivery strategy that can effectively deliver the CRISPR cargo to the target site. To overcome this obstacle, researchers have extensively explored non-viral, viral, and physical methods for targeted delivery of CRISPR/Cas9 and a guide RNA (gRNA) into cells and tissues. Among those methods, liposomes offer a promising approach to enhance the delivery of CRISPR/Cas and gRNA. Liposomes facilitate endosomal escape and leverage various stimuli such as light, pH, ultrasound, and environmental cues to provide both spatial and temporal control of cargo release. Thus, the combination of the CRISPR-based system with liposome delivery technology enables precise and efficient genetic modifications in cells and tissues. This approach has numerous applications in basic research, biotechnology, and therapeutic interventions. For instance, it can be employed to correct genetic mutations associated with inherited diseases and other disorders or to modify immune cells to enhance their disease-fighting capabilities. In summary, liposome-based CRISPR genome editing provides a valuable tool for achieving precise and efficient genetic modifications. This review discusses future directions and opportunities to further advance this rapidly evolving field.

Intermittent parathyroid hormone improves orthodontic retention via insulin-like growth factor-1.

OBJECTIVES: This study aimed to investigate the effects of intermittent parathyroid hormone (iPTH) on the stability of orthodontic retention and to explore the possible regulatory role of insulin-like growth factor-1 (IGF-1) in this process. METHODS: Forty-eight 6-week-old male Wistar rats were adopted in this study. An orthodontic relapsing model was established to investigate the effects of iPTH on orthodontic retention. In vitro, an immortalized mouse cementoblast cell line OCCM-30 was detected by flow cytometry to study the effects of iPTH on cell proliferation and apoptosis. By application of a specific IGF-1 receptor inhibitor, the role of IGF-1 was also explored. RESULTS: In vivo study found that daily injection of PTH significantly reduced the relapsing distance. Histological staining and ELISA assay showed faster periodontal regeneration during retention period in PTH group with increased RANKL/OPG ratio and greater amount of OCN, ALP, and IGF-1 in gingival cervical fluid (GCF). Cell experiment revealed that iPTH promoted proliferation and suppressed apoptosis of cementoblast. IGF-1 receptor inhibitor significantly restrained the anabolic effect of iPTH on OCCM-30 cells. CONCLUSIONS: These findings suggest that iPTH could improve the stability of tooth movement by promoting periodontal regeneration. IGF-1 is essential in mediating the anabolic effects of iPTH.

The role of EphB4/ephrinB2 signaling in root repair after orthodontically-induced root resorption.

INTRODUCTION: This study aimed to investigate the effect of EphB4/ephrinB2 signaling on orthodontically-induced root resorption repair and the possible molecular mechanism behind it. METHODS: Seventy-two 6-week-old male Wistar rats were randomly divided into 3 groups: blank control group, physiological regeneration group (PHY), and EphB4 inhibitor local injection group (INH). A root repair model was built on experimental rats of the PHY and INH groups. The animals in the INH groups received a daily periodontal local injection of EphB4 inhibitor NVP-BHG712, whereas the blank control group and PHY groups received only the vehicle. RESULTS: Histologic staining and microcomputed tomography analysis showed that root regeneration was inhibited in the INH group compared with the PHY group with a greater number of osteoclasts. Immunohistochemical staining showed active EphB4/ephrinB2 signaling activities during root regeneration. The cementogenesis-related factors cementum attachment protein, alkaline phosphatase, osteopontin, and runt-related transcription factor 2, and osteoclastic-related factors RANKL and osteoprotegerin were affected by regulated EphB4/ephrinB2 signaling. CONCLUSIONS: These findings demonstrated that the EphB4/ephrinB2 signaling might be a promising therapeutic target for novel therapeutic approaches to reduce orthodontically-induced root resorption through enhancement of cementogenesis.

The role of sphingosine-1-phosphate signaling pathway in cementocyte mechanotransduction.

Iatrogenic external root resorption can become a serious pathological condition with clinical tooth movement. Little is known regarding how cementum responds to mechanical loading in contrast to bone, especially under compressive stress. In the field of bone biology, several studies have established the contribution of sphingosine-1-phosphate (S1P) signaling in bone remodeling, mechanical transduction and homeostasis. As osteocytes and cementocytes share similar morphological and functional characteristics, this study aimed to investigate the mechanotransduction ability of cementocytes and to explore the contribution of S1P signaling under compressive stress induced mechanotransduction. We found that compressive stress inhibited major S1P signaling and promoted the expression of anabolic factors in IDG-CM6 cells, a novel immortalized murine cementocyte cell line. By inhibiting S1P signaling, we verified that S1P signaling played a vital role in regulating the expression of the mechanotransduction factors prostaglandin E2 (PGE2) and ß-catenin, as well as factors responsible for cementogenesis and cementoclastogenesis in IDG-CM6 cells. These results support the hypothesis that cementocytes act as key mechanically responsive cells in cementum, responding to compressive stress and directing local cementum metabolism.

Bone formation around unstable implants is enhanced by a WNT protein therapeutic in a preclinical in vivo model.

OBJECTIVES: Our objective was to test the hypothesis that local delivery of a WNT protein therapeutic would support osseointegration of an unstable implant placed into an oversized osteotomy and subjected to functional loading. MATERIALS AND METHODS: Using a split-mouth design in an ovariectomized (OVX) rat model, 50 titanium implants were placed in oversized osteotomies. Implants were subjected to functional loading. One-half of the implants were treated with a liposomal formulation of WNT3A protein (L-WNT3A); the other half received an identical liposomal formulation containing phosphate-buffered saline (PBS). Finite element modeling estimated peri-implant strains caused by functional loading. Histological, molecular, cellular, and quantitative micro-computed tomographic (µCT) imaging analyses were performed on samples from post-implant days (PID) 3, 7, and 14. Lateral implant stability was quantified at PID 7 and 14. RESULTS: Finite element analyses predicted levels of peri-implant strains incompatible with new bone formation. Micro-CT imaging, histological, and quantitative immunohistochemical (IHC) analyses confirmed that PBS-treated implants underwent fibrous encapsulation. In those cases where the peri-implant environment was treated with L-WNT3A, µCT imaging, histological, and quantitative IHC analyses demonstrated a significant increase in expression of proliferative (PCNA) and osteogenic (Runx2, Osterix) markers. One week after L-WNT3A treatment, new bone formation was evident, and two weeks later, L-WNT3A-treated gaps had a stiffer interface compared to PBS-treated gaps. CONCLUSION: In a rat model, unstable implants undergo fibrous encapsulation. If the same unstable implants are treated with L-WNT3A at the time of placement, then it results in significantly more peri-implant bone and greater interfacial stiffness.

Enhancing osseointegration of titanium implants through large-grit sandblasting combined with micro-arc oxidation surface modification.

PURPOSE: The demand for titanium dental implants has risen sharply. However, the clinical success rate of implant surgery needs to be improved. In this paper, we report a novel surface modification strategy, large-grit sandblasting combined with micro-arc oxidation (SL-MAO), aiming to promote peri-implant bone formation and osseointegration of titanium implants. MATERIALS AND METHODS: Modified titanium samples were prepared by large-grit sandblasting and acid etching (SLA), micro-arc oxidation (MAO), and SL-MAO. The resulting topographical changes and chemical composition of the samples were examined by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), respectively, and the biocompatibility and bioactivity were analyzed by bone-marrow mesenchymal stem cells (BMMSC) adhesion tests. Modified titanium implants were also inserted into the femurs of beagle dogs, and their competence of osseointegration was appraised by quantitative histomorphometry and micro-computed-tomography (micro-CT) analyses. RESULTS: Compared to SLA and MAO techniques, SL-MAO surface modification further enhanced titanium surfaces by creating a topographic morphology characterized by both micron-sized craters and sub-micron-scale pits, and resulted in superior chemical composition, which promoted cell adhesion, proliferation, and osteogenic differentiation. SL-MAO-modified titanium implants osseointegrated more efficiently than SLA or MAO controls, with significantly higher bone-area (BA) ratio and bone-implant contact (BIC) in the peri-implant region. CONCLUSIONS: The SL-MAO surface modification technique optimized the surface properties of titanium implants and enhanced peri-implant bone formation and osseointegration.

From restoration to regeneration: periodontal aging and opportunities for therapeutic intervention.

With the march of time our bodies start to wear out: eyesight fades, skin loses its elasticity, teeth and bones become more brittle and injuries heal more slowly. These universal features of aging can be traced back to our stem cells. Aging has a profound effect on stem cells: DNA mutations naturally accumulate over time and our bodies have evolved highly specialized mechanisms to remove these damaged cells. Whilst obviously beneficial, this repair mechanism also reduces the pool of available stem cells and this, in turn, has a dramatic effect on tissue homeostasis and on our rate of healing. Simply put: fewer stem cells means a decline in tissue function and slower healing. Despite this seemingly intractable situation, research over the past decade now demonstrates that some of the effects of aging are reversible. Nobel prize-winning research demonstrates that old cells can become young again, and lessons learned from these experiments-in-a-dish are now being translated into human therapies. Scientists and clinicians around the world are identifying and characterizing methods to activate stem cells to reinvigorate the body's natural regenerative process. If this research in dental regenerative medicine pans out, the end result will be tissue homeostasis and healing back to the levels we appreciated when we were young.

Rescuing failed oral implants via Wnt activation.

AIM: Implant osseointegration is not always guaranteed and once fibrous encapsulation occurs clinicians have few options other than implant removal. Our goal was to test whether a WNT protein therapeutic could rescue such failed implants. MATERIAL AND METHODS: Titanium implants were placed in over-sized murine oral osteotomies. A lack of primary stability was verified by mechanical testing. Interfacial strains were estimated by finite element modelling and histology coupled with histomorphometry confirmed the lack of peri-implant bone. After fibrous encapsulation was established peri-implant injections of a liposomal formulation of WNT3A protein (L-WNT3A) or liposomal PBS (L-PBS) were then initiated. Quantitative assays were employed to analyse the effects of L-WNT3A treatment. RESULTS: Implants in gap-type interfaces exhibited high interfacial strains and no primary stability. After verification of implant failure, L-WNT3A or L-PBS injections were initiated. L-WNT3A induced a rapid, significant increase in Wnt responsiveness in the peri-implant environment, cell proliferation and osteogenic protein expression. The amount of peri-implant bone and bone in contact with the implant were significantly higher in L-WNT3A cases. CONCLUSIONS: These data demonstrate L-WNT3A can induce peri-implant bone formation even in cases where fibrous encapsulation predominates.

The effect of teeth extraction for orthodontic treatment on the upper airway: a systematic review.

PURPOSE: The purpose of this study was to evaluate the effect of teeth extraction for orthodontic treatment on the upper airway. METHODS: Relevant trials assessing the effect of orthodontic extractions on the upper airway were retrieved electronically through PubMed, Embase, Medline, Web of Knowledge, and the Cochrane Library. The processes of literature search, selection, quality assessment, and data extraction were performed by two authors independently. RESULTS: Seven articles were included in this systematic review. They were categorized into three groups according to their indications for extractions, namely anteroposterior discrepancy (group 1), crowding (group 2), and unspecified indications (group 3). In group 1, enrolled patients were diagnosed with class I bimaxillary protrusion and had four first premolars extracted, with a significant decrease in upper airway dimension. In group 2, increase in the upper airway dimension was reported in patients who were diagnosed with class I crowding and four first premolars extracted. In group 3, all patients were adolescents and no significant change in the upper airway dimension was observed. CONCLUSIONS: Currently, it is difficult to draw evidence-based conclusions because of the exceeding heterogeneity among included studies, and more qualified trials are required to provide reliable evidence. Extractions followed by large retraction of the anterior teeth in adult bimaxillary protrusion cases could possibly lead to narrowing of the upper airway. Mesial movement of the molars appeared to increase the posterior space for the tongue and enlarge the upper airway dimensions. Although the effect of teeth extraction on upper airway dimension seems to be related to indications for extraction, accepted scientific evidence is still insufficient owing to the limited number of included studies. The relationship between the upper airway size and the respiratory function has not been demonstrated. While there may be a decrease in the upper airway volume, there is no evidence that this would turn an airway more collapsible. None of the studies assessed in this review had actual functional assessment of breathing. Additional qualified trials are necessary to verify reliability.

Surgical Management of Airway Obstruction Following Posterior Pharyngeal Flap.

BACKGROUND: Posterior pharyngeal flap (PPF) is effective in managing velopharyngeal insufficiency (VPI) but is of airway obstruction risk. This study compared the effectiveness and complications of two PPF revision procedures and screened potential prognostic factors to postoperative hypernasality and persistent obstruction. METHODS: Patients who received flap division (FD) or port enlargement (PE) for airway obstruction following PPF were reviewed. Ventilation status was assessed using the nasal obstruction symptom evaluation (NOSE) scale, and velopharyngeal closure was assessed using subjective speech evaluation and nasopharyngoscopy. The effectiveness of ventilation relief and complication rate (hypernasality and persistent obstruction) of the two techniques were compared. A comprehensive panel of factors, including age, velopharyngeal mobility, obstruction laterality, body mass index, jaw relationship, and adenoid hypertrophy, were evaluated for correlation with complications. RESULTS: 79 patients were enrolled, with 51 receiving FD and 28 PE. Both techniques significantly improved ventilation dysfunction and hyponasality. Mild hypernasality occurred among 10 cases in the FD group and 3 in the PE group. Age at surgery was significantly associated with persistent obstruction after PPF revision. The occurrence of persistent obstruction was significantly higher among patients below 12 years than those above. Obstruction laterality was suggested in significant correlation with hypernasality post-PPF revision. Among patients with unilateral port obstruction, the occurrence of hypernasality after FD was significantly higher than after PE. CONCLUSION: Both flap division and port enlargement are effective revision procedures to relieve airway obstruction after PPF. Patients below 12 years are more likely to experience persistent ventilation problem after PPF revision.

In-depth insight into improvement of simultaneous nitrification and denitrification/biofouling control by increasing sludge concentration in membrane reactor: performance, microbial assembly and metagenomic analysis.

Currently, severe membrane fouling and inefficient nitrogen removal were two main issues that hindered the sustainable operation and further application of membrane bioreactor (MBR). This study aimed to simultaneously alleviate membrane fouling and improve nitrogen removal by applying high sludge concentration in MBR. Results showed that high sludge concentration (12000 mg/L) enhanced total nitrogen removal efficiency (78 %) and reduced transmembrane pressure development rate. Microbial community analysis revealed that high sludge concentration enriched functional bacteria associated with nitrogen removal, increased filamentous bacteria fraction in bio-cake and inhibited Thiothrix overgrowth in bulk sludge. From molecular level, the key genes involved in nitrogen metabolism, electron donor/adenosine triphosphate production and amino acid degradation were up-regulated under high sludge concentration. Overall, high sludge concentration improved microbial assembly and functional gene abundance, which not only enhanced nitrogen removal but also alleviated membrane fouling. This study provided an effective strategy for sustainable operation of MBR.

Assessment of isthmus filling using two obturation techniques performed by students with different levels of clinical experience.

Background/purpose: Root canal filling is a necessary skill for dental students and an important aspect of endodontic education. This study aimed to evaluate the effect of students' clinical experiences on isthmus filling using different techniques and sealers. Materials and methods: One hundred eight three-dimensional-printed resin replicas of isthmus were divided into six groups and either continuous wave of condensation (CWC) or single-cone obturation (SC) was performed. One of three sealers (AH Plus Jet®, GuttaFlow2, iRoot SP) was used together with a size-fitted gutta-percha master cone. All the obturations were completed by students with three different levels of clinical experience including senior postgraduate students (SPS), junior postgraduate students (JPS), and undergraduate students (US). The percentages of filled areas (PFA) at 2, 4, 6, and 8 mm from the apex were analyzed using a light microscope. Data were analyzed using the Mann-Whitney U test or Kruskal-Wallis 1-way ANOVA with Dunn's tests (α = 0.05). Results: The CWC group exhibited a higher PFA than the SC group (P < 0.05). The PFA was higher in the SPS group than in the JPS group or the US group with CWC (P < 0.05). The three clinical experience groups showed similar PFAs with SC (P > 0.05); however, when using SC with iRoot SP, the PFA was higher than with either of the other two sealers (P < 0.05). Conclusion: CWC was found to be technique-sensitive and required clinical training. With SC, clinical experience did not improve the quality of isthmus filling without additional training. CWC was superior to SC for type IV isthmuses. When using SC, better filling quality was obtained with a bioceramic sealer.

Co-Delivery of Therapeutics and Bioactive Gas Using a Novel Liposomal Platform for Enhanced Treatment of Acute Arterial Injury.

Atherosclerosis is a complex, multi-stage disease characterized by pathological changes across the vascular wall. Endothelial dysfunction, inflammation, hypoxia, and vascular smooth muscle cell proliferation contribute to its progression. An effective strategy capable of delivering pleiotropic treatment to the vascular wall is essential to limit neointimal formation. Echogenic liposomes (ELIP), which can encapsulate bioactive gases and therapeutic agents, have the potential to deliver enhanced penetration and treatment efficacy for atherosclerosis. In this study, liposomes loaded with nitric oxide (NO) and rosiglitazone, a peroxisome proliferator-activated receptor agonist, were prepared using hydration, sonication, freeze-thawing, and pressurization. The efficacy of this delivery system was evaluated in a rabbit model of acute arterial injury induced by balloon injury to the common carotid artery. Intra-arterial administration of rosiglitazone/NO co-encapsulated liposomes (R/NO-ELIP) immediately following injury resulted in reduced intimal thickening after 14 days. The anti-inflammatory and anti-proliferative effects of the co-delivery system were investigated. These liposomes were echogenic, enabling ultrasound imaging to assess their distribution and delivery. R/NO-ELIP delivery exhibited a greater attenuation (88 ± 15%) of intimal proliferation when compared to NO-ELIP (75 ± 13%) or R-ELIP (51 ± 6%) delivery alone. The study demonstrates the potential of echogenic liposomes as a promising platform for ultrasound imaging and therapeutic delivery.

LITTIP/Lgr6/HnRNPK complex regulates cementogenesis via Wnt signaling.

Orthodontically induced tooth root resorption (OIRR) is a serious complication during orthodontic treatment. Stimulating cementum repair is the fundamental approach for the treatment of OIRR. Parathyroid hormone (PTH) might be a potential therapeutic agent for OIRR, but its effects still lack direct evidence, and the underlying mechanisms remain unclear. This study aims to explore the potential involvement of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent PTH and contributing to cementum repair, as identifying lncRNA-disease associations can provide valuable insights for disease diagnosis and treatment. Here, we showed that intermittent PTH regulates cell proliferation and mineralization in immortalized murine cementoblast OCCM-30 via the regulation of the Wnt pathway. In vivo, daily administration of PTH is sufficient to accelerate root regeneration by locally inhibiting Wnt/ß-catenin signaling. Through RNA microarray analysis, lncRNA LITTIP (LGR6 intergenic transcript under intermittent PTH) is identified as a key regulator of cementogenesis under intermittent PTH. Chromatin isolation by RNA purification (ChIRP) and RNA immunoprecipitation (RIP) assays revealed that LITTIP binds to mRNA of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and heterogeneous nuclear ribonucleoprotein K (HnRNPK) protein. Further co-transfection experiments confirmed that LITTIP plays a structural role in the formation of the LITTIP/Lgr6/HnRNPK complex. Moreover, LITTIP is able to promote the expression of LGR6 via the RNA-binding protein HnRNPK. Collectively, our results indicate that the intermittent PTH administration accelerates root regeneration via inhibiting Wnt pathway. The lncRNA LITTIP is identified to negatively regulate cementogenesis, which activates Wnt/ß-catenin signaling via high expression of LGR6 promoted by HnRNPK.

The Gradual Correction of Adult Severe Rigid Equinus Deformity Using Minimal Invasive U-Osteotomy With Taylor Spatial Frame.

BACKGROUND: U-osteotomy with Taylor Spatial Frame correction is a rarely reported treatment method particularly well-suited for severe rigid equinus deformity in adults. The purpose of this study was to evaluate the effectiveness and efficacy of deformity correction and clinical outcome using this technique. METHODS: We present a retrospective review of 30 feet in 26 patients who received U-osteotomy with Taylor Spatial Frame. Radiologic outcomes were measured using the anterior tibiotalar angle (TTA) with conventional weightbearing radiographs. Functional assessments included American Orthopaedic Foot & Ankle Society (AOFAS) ankle and hindfoot scores and patient satisfaction using Likert scale. RESULTS: The etiology included trauma (9), neglected or relapsed clubfoot (6), spina bifida (5), poliomyelitis (4), Charcot-Marie-Tooth disease (4), and iatrogenic (2). All patients had equinus deformity with TTA more than 140 degrees (median 157.5, 141-177). There were varus deformity in 19 feet, limb length discrepancy in 6 legs, and genu procurvatum deformity in 2 legs. The duration of gradual correction was 53.6±13.5 days (33-73 days), and the external fixation time was 147.8±25.2 days (98-203 days). At last follow-up, TTA in all patients improved significantly (P < .001) to 113.5 degrees (111.8-116.0). All patients had plantigrade feet, except for 2 cases of residual mild equinovarus deformity, 2 cases of residual mild hindfoot varus deformity, 1 case of moderate hindfoot varus recurrence. The AOFAS scores significantly improved (P < .001) from 51.0 points (29.0-66.0) to 76.0 points (69.5-88.0). Eighteen patients were very satisfied, 6 patients were somewhat satisfied, and 2 patients were somewhat dissatisfied. CONCLUSION: Using minimally invasive U-osteotomy with Taylor Spatial Frame to gradually correct the adult severe rigid equinus deformity proved to be an effective and relatively safe method associated with high patient satisfaction rates. LEVEL OF EVIDENCE: Level IV, case series.

Enhanced Cerebroprotection of Xenon-Loaded Liposomes in Combination with rtPA Thrombolysis for Embolic Ischemic Stroke.

Xenon (Xe) has shown great potential as a stroke treatment due to its exceptional ability to protect brain tissue without inducing side effects. We have previously developed Xe-loaded liposomes for the ultrasound-activated delivery of Xe into the cerebral region and demonstrated their therapeutic efficacy. At present, the sole FDA-approved thrombolytic agent for stroke treatment is recombinant tissue plasminogen activator (rtPA). In this study, we aimed to investigate the potential of combining Xe-liposomes with an intravenous rtPA treatment in a clinically relevant embolic rat stroke model. We evaluated the combinational effect using an in vitro clot lysis model and an in vivo embolic middle cerebral artery occlusion (eMCAO) rat model. The treatment groups received intravenous administration of Xe-liposomes (20 mg/kg) at 2 h post-stroke onset, followed by the administration of rtPA (10 mg/kg) at either 2 or 4 h after the onset. Three days after the stroke, behavioral tests were conducted, and brain sections were collected for triphenyltetrazolium chloride (TTC) and TUNEL staining. Infarct size was determined as normalized infarct volume (%). Both in vitro and in vivo clot lysis experiments demonstrated that Xe-liposomes in combination with rtPA resulted in effective clot lysis comparable to the treatment with free rtPA alone. Animals treated with Xe-liposomes in combination with rtPA showed reduced TUNEL-positive cells and demonstrated improved neurological recovery. Importantly, Xe-liposomes in combination with late rtPA treatment reduced rtPA-induced hemorrhage, attributing to the reduction of MMP9 immunoreactivity. This study demonstrates that the combined therapy of Xe-liposomes and rtPA provides enhanced therapeutic efficacy, leading to decreased neuronal cell death and a potential to mitigate hemorrhagic side effects associated with late rtPA treatment.

Lithium chloride promotes osteogenesis and suppresses apoptosis during orthodontic tooth movement in osteoporotic model via regulating autophagy.

Osteoporosis is a widely distributed disease that may cause complications such as accelerated tooth movement, bone resorption, and tooth loss during orthodontic treatment. Promoting bone formation and reducing bone resorption are strategies for controlling these complications. For several decades, the autophagy inducer lithium chloride (LiCl) has been explored for bipolar . In this study, we investigated the autophagy-promoting effect of LiCl on bone remodeling under osteoporotic conditions during tooth movement. Ovariectomy was used to induce osteoporosis status in vivo. The results showed that LiCl rejuvenated autophagy, decreased apoptosis, and promoted bone formation, thus protecting tooth movement in osteoporotic mice. Furthermore, in vitro experiments showed that LiCl reversed the effects of ovariectomy on bone marrow-derived mesenchymal stem cells (BMSCs) extracted from ovariectomized mice, promoting osteogenesis and suppressing apoptosis by positively regulating autophagy. These findings suggest that LiCl can significantly decrease adverse effects of osteoporosis on bone remodeling, and that it has great potential significance in the field of bone formation during tooth movement in osteoporosis patients.

A novel customized ceramic bracket for esthetic orthodontics: in vitro study.

BACKGROUND: This study aims to develop a novel process to establish a standardized manufacturing technique of customized esthetic ceramic bracket system (CCB) which could be endowed with individual color and shape to satisfy patients' individual demands. Material characteristics and mechanical parameters of CCB were evaluated. SUBJECTS AND METHODS: CCB virtual models were designed individually according to patient's teeth morphology and clinical demands. 3D printing technology, lost-wax technology, and selected glass-ceramic ingots were employed to fabricate CCB. Scanning electron microscopy (SEM) analyses were performed to characterize the surface morphology of CCB and commercially available brackets (Clarity Advanced; Crystalline VII; Inspire ICE; Damon Q). Static and kinetic frictional resistance (FR), shear bond strength (SBS) and adhesive remnant index (ARI) scores were recorded. One-way analyses of variance (ANOVA) and post-hoc Tukey's HSD multiple tests were used for statistical analyses. RESULTS: Multi-color and multi-transparency raw materials facilitated CCB with a wide range of color options and controllable optical properties to satisfy different esthetic demands of individual orthodontic patients. CCB presented same level of FR as commercially available ceramic brackets did. No significant differences (P ≥ 0.05) of SBS were observed among CCB-ES (treated silane), Clarity Advanced and Crystalline VII groups, and CCB-E (no silane) attained the highest ARI mean score 3. In the preliminary clinical trial, CCB presented excellent color-matching and shape-matching appearances similar to natural teeth, which made it highly invisible from social intercourse distance. CONCLUSIONS: CCB were demonstrated to be an applicable labial orthodontic bracket system with optimized esthetics and biomechanics. We envision that it would be an ideal alternative for patients who pursue esthetic orthodontic treatment but were not likely to take lingual appliances or clear aligners.