Corrigendum: Sestrin2 protects against hypoxic nerve injury by regulating mitophagy through SESN2/AMPK pathway.

[This corrects the article DOI: 10.3389/fmolb.2023.1266243.].

Mitochondrial dysfunction of peripheral blood mononuclear cells is associated with lung carcinogenesis.

The composition, quantity, and function of peripheral blood mononuclear cells (PBMCs) are closely correlated with tumorigenesis. However, the mechanisms of PBMCs in lung cancer are not clear. Mitochondria are energy factories of cells, and almost all cellular functions rely on their energy metabolism level. The present study aimed to test whether the mitochondrial function of PBMCs directly determines their tumor immune monitoring function. We recruited 211 subjects, including 105 healthy controls and 106 patients with recently diagnosed with lung cancer. The model of lung carcinogenesis induced by BaP was used in animal experiment, and the Bap carcinogenic metabolite, Benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide (BPDE), was used in cell experiment. We found that mitochondrial function of PBMCs decreased significantly in patients with new lung cancer, regardless of age. In vivo, BaP caused PBMC mitochondrial dysfunction in mice before the appearance of visible malignant tissue. Moreover, mitochondrial function decreased significantly in mice with lung cancers induced by BaP compared to those without lung cancer after BaP intervention. In vitro, BPDE also induced mitochondrial dysfunction and reduced the aggressiveness of PBMCs toward cancer cells. Furthermore, the changes in mitochondrial energy metabolism gene expression caused by BPDE are involved in this process. Thus, the mitochondrial function of PBMCs is a potential prognostic biomarker or therapeutic target to improve clinical outcomes in patients with lung cancer.

SIRT1 regulates mitochondrial fission to alleviate high altitude hypoxia inducedcardiac dysfunction in rats via the PGC-1α-DRP1/FIS1/MFF pathway.

High-altitude exposure has been linked to cardiac dysfunction. Silent information regulator factor 2-related enzyme 1 (sirtuin 1, SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, plays a crucial role in regulating numerous cardiovascular diseases. However, the relationship between SIRT1 and cardiac dysfunction induced by hypobaric hypoxia (HH) remains unexplored. This study aims to assess the impact of SIRT1 on HH-induced cardiac dysfunction and delve into the underlying mechanisms, both in vivo and in vitro. In this study, we have demonstrated that exposure to HH results in cardiomyocyte injury, along with the downregulation of SIRT1 and mitochondrial dysfunction. Upregulating SIRT1 significantly inhibits mitochondrial fission, improves mitochondrial function, reduces cardiomyocyte injury, and consequently enhances cardiac function in HH-exposed rats. Additionally, HH exposure triggers aberrant expression of mitochondrial fission-regulated proteins, with a decrease in PPARγ coactivator 1 alpha (PGC-1α) and mitochondrial fission factor (MFF) and an increase in mitochondrial fission 1 (FIS1) and dynamin-related protein 1 (DRP1), all of which are mitigated by SIRT1 upregulation. Furthermore, inhibiting PGC-1α diminishes the positive effects of SIRT1 regulation on the expression of DRP1, MFF, and FIS1, as well as mitochondrial fission. These findings demonstrate that SIRT1 alleviates HHinduced cardiac dysfunction by preventing mitochondrial fission through the PGC-1α-DRP1/FIS1/MFF pathway.

Isoquercitrin attenuates the osteoclast-mediated bone loss in rheumatoid arthritis via the Nrf2/ROS/NF-κB pathway.

An excess of osteoclastogenesis significantly contributes to the development of rheumatoid arthritis (RA). Activation of the nuclear factor erythroid-2 related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) ligand (RANKL)-induced reactive oxygen species (ROS)-to-NF-κB signaling cascade are important mechanisms regulating osteoclastogenesis; however, whether Nrf2 is involved in RANKL-induced NF-κB activation is controversial. Isoquercitrin, a natural flavonoid compound, has been shown to have Nrf2-dependent antioxidant effects inprevious studies. We sought to verify whether isoquercitrin could modulate RANKL-induced NF-κB activation by activating Nrf2, thereby affecting osteoclastogenesis. Tartrate-resistant acid phosphatase staining, F-actin ring staining and resorption pit assay suggested that isoquercitrin significantly inhibited osteoclastogenesis and osteolytic function. Mitosox staining showed that RANKL-induced ROS generation was significantly inhibited by isoquercitrin from day 3 of the osteoclast differentiation cycle. Quantitative real-time PCR, Western blot, and immunofluorescence indicated that isoquercitrin activated the Nrf2 signaling pathway and inhibited NF-κB expression. And when we used the Nrf2-specific inhibitor ML385, the inhibition of NF-κB by isoquercitrin disappeared. Moreover, we found that Nrf2 is not uninvolved in RANKL-induced NF-κB activation and may be related to the timing of ROS regulation. When we limited isoquercitrin administration to 2 days, Nrf2 remained activated and the inhibition of NF-κB disappeared. In vivo experiments suggested that isoquercitrin attenuated RA modeling-induced bone loss. Overall, isoquercitrin-activated Nrf2 blocked the RANKL-induced ROS-to-NF-κB signaling cascade response, thereby inhibiting osteoclastogenesis and bone loss. These findings provide new ideas for the treatment of RA.

Sestrin2 protects against hypoxic nerve injury by regulating mitophagy through SESN2/AMPK pathway.

Hypoxia induced by high altitude can lead to severe neurological dysfunction. Mitophagy is known to play a crucial role in hypoxic nerve injury. However, the regulatory mechanism of mitophagy during this injury remains unclear. Recent studies have highlighted the role of Sestrin2 (SESN2), an evolutionarily conserved stress-inducible protein against acute hypoxia. Our study demonstrated that hypoxia treatment increased SESN2 expression and activated mitophagy in PC12 cells. Furthermore, the knock-out of Sesn2 gene led to a significant increase in mitochondrial membrane potential and ATP concentrations, which protected the PC12 cells from hypoxic injury. Although the AMPK/mTOR pathway was significantly altered under hypoxia, it does not seem to participate in mitophagy regulation. Instead, our data suggest that the mitophagy receptor FUNDC1 plays a vital role in hypoxia-induced mitophagy. Moreover, SESN2 may function through synergistic regulation with other pathways, such as SESN2/AMPK, to mediate cellular adaptation to hypoxia, including the regulation of mitophagy in neuron cells. Therefore, SESN2 plays a critical role in regulating neural cell response to hypoxia. These findings offer valuable insights into the underlying molecular mechanisms governing the regulation of mitophagy under hypoxia and further highlight the potential of SESN2 as a promising therapeutic target for hypoxic nerve injury.

LAMC2 regulates proliferation, migration, and invasion mediated by the Pl3K/AKT/mTOR pathway in oral.

Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor. Recently, Laminin Gamma 2 (LAMC2) has been shown to be abnormally expressed in OSCC; however, how LAMC2 signaling contributes to the occurrence and development of OSCC and the role of autophagy in OSCC has not been fully explored. This study aimed to analyze the role and mechanism of LAMC2 signaling in OSCC and the involvement of autophagy in OSCC. Methods: To explore the mechanism by which LAMC2 is highly expressed in OSCC, we used small interfering RNA (siRNA) to knock down LAMC2 to further observe the changes in the signaling pathway. Furthermore, we used cell proliferation assays, Transwell invasion assays, and wound-healing assays to observe the changes in OSCC proliferation, invasion, and metastasis. RFP-LC3 was used to detect the level of autophagy intensity. A cell line-derived xenograft (CDX) model was used to detect the effect of LAMC2 on tumor growth in vivo. Results: This study found that the level of autophagy was correlated with the biological behavior of OSCC. The downregulation of LAMC2 activated autophagy and inhibited OSCC proliferation, invasion, and metastasis via inhibiting the PI3K/AKT/mTOR pathway. Moreover, autophagy has a dual effect on OSCC, and the synergistic downregulation of LAMC2 and autophagy can inhibit OSCC metastasis, invasion, and proliferation via the PI3K/AKT/mTOR pathway. Conclusions: LAMC2 interacts with autophagy to regulate OSCC metastasis, invasion, and proliferation via the PI3K/AKT/mTOR pathway. LAMC2 down-regulation can synergistically modulate autophagy to inhibit OSCC migration, invasion, and proliferation.

Citrus tangerine pith extract alleviates hypoxia-induced ileum damage in mice by modulating intestinal microbiota.

Visitors to high altitude are susceptible to hypoxia-induced acute intestinal mucosal barrier injury and severe gastrointestinal disorders, which are life-threatening. Citrus tangerine pith extract (CTPE) is rich in pectin and flavonoids and has been proved to enhance intestinal health and improve gut dysbiosis. In this study, we aim to explore the protective effect of CTPE on ileum injury induced by intermittent hypobaric hypoxia in a mouse model. Balb/c mice were divided into blank normoxia (BN), blank hypobaric hypoxia (BH), hypobaric hypoxia plus CTPE (TH), and hypobaric hypoxia plus Rhodiola extract (RH) groups. From the 6th day of gavage, mice in BH, TH, and RH groups were transferred into a hypobaric chamber at a simulated elevation of 6000 m for 8 hours per day for 10 days. Then half the mice were tested for small intestine movement, and others were used to evaluate intestinal physical barrier function, inflammation, and gut microbiota. Results showed that CTPE reversed the increase of intestinal peristalsis, effectively attenuated impaired structural integrity of ileum, improved the mRNA and protein expression levels of tight junction proteins, and reduced serum D-LA content in mice to alleviate hypoxia-induced mucosal barrier damage. Moreover, CTPE supplementation ameliorated hypoxia-induced intestinal inflammation response by significantly downregulating the proinflammatory cytokines IL-6, TNF-α and IFN-γ. By 16S rDNA gene sequencing of gut microbiota, CTPE significantly increased the abundance of probiotic Lactobacillus, suggesting that CTPE may be used as a prebiotic to regulate ecology of intestinal microorganisms. In addition, Spearman rank correlation analysis revealed that changed gut microbiota were significantly correlated with alteration of intestinal barrier function indexes. Taken together, these results indicate that CTPE effectively alleviates hypoxia-induced intestinal injury in mice and enhances intestinal integrity and barrier function by altering intestinal microbiota composition.

The predictability of orthodontic tooth movements through clear aligner among first-premolar extraction patients: a multivariate analysis.

BACKGROUND: The purpose was to determine the predictability of tooth movements through clear aligner among premolar extraction patients and to explore the effects of various factors on tooth movements. METHODS: A total of 31 extraction patients (10 males and 20 females; age 14-44) receiving clear aligner treatment (Invisalign) were enrolled in this study. The actual post-treatment models and pre-treatment models were superimposed using the palatal area as a reference and registered with virtual post-treatment models. A paired t test was used to compare the differences between actual and designed tooth movements of maxillary first molars, canines, and central incisors. A multivariate linear mixed model was performed to examine the influence of variables on actual tooth movements. RESULTS: Compared to the designed tooth movements, the following undesirable tooth movements occurred: mesial movement (2.2 mm), mesial tipping (5.4°), and intrusion (0.45 mm) of first molars; distal tipping (11.0°), lingual tipping (4.4°), and distal rotation of canines (4.9°); lingual tipping (10.6°) and extrusion (1.5 mm) of incisors. Age, crowding, mini-implant, overbite, and attachments have differential effects on actual tooth movements. Moreover, vertical rectangular attachments on canines are beneficial in achieving more predictable canine and incisor tooth movements over optimized attachments. Lingual tipping and extrusion of incisors were significantly influenced by the interaction effects between incisor power ridge and different canine attachments (p < 0.05). CONCLUSIONS: Incisors, canines, and first molars are subject to unwanted tooth movements with clear aligners among premolar extraction patients. Age, crowding, mini-implant, overbite, and attachments influence actual tooth movements. Moreover, vertical rectangular attachments on canines are beneficial in achieving more predictable incisor tooth movements over optimized canine attachments.

[Construction and evaluation of a gradient stress model of PC12 cells induced by corticosterone].

Objective: A gradient stress model of PC12 cells induced by corticosterone was established to provide a basis for the evaluation and regulation of cell stress. Methods: The effect of corticosterone on cell viability was observed by measuring PC12 cell viability at different concentrations of corticosterone (0~1 000 µmol/L) after different intervention times (8~48 h) to screen the cell models for optimal intervention conditions. Key stress indicators (MDA, SOD, NADH, LDH) were measured spectrophotometrically and microscopically to evaluate the models. Results: When the concentration of corticosterone was below 200 µmol/L and the intervention time was 12 h, the cell viability was below half inactivation rate, which could reduce the confounding factors due to the decrease of cell viability in each group. Compared with the blank control group, corticosterone increased the levels of MDA, NADH and LDH,and decreased the levels of SOD in the model group in a concentration-dependent manner (P＜0.01), which was consistent with the construction of the gradient stress model. Conclusion: A gradient stress injury model of PC12 cells was successfully established, with intervention concentrations of 0 µmol/L, 25 µmol/L, 50 µmol/L, 100 µmol/L, 150 µmol/L and 200 µmol/L corticosterone at an intervention time of 12 h. The degree of stress injury of the cell model was increased gradually, which could be used as a basis and object for conducting cell stress injury assessment and regulation experiments.

Is the response rate of oral appliance therapy for subjects with and without position-dependent obstructive sleep apnoea different?

Objective To compare the effect of oral appliance (OA) treatment on non-position-dependent obstructive sleep apnoea (non-POSA) and position-dependent obstructive sleep apnoea (POSA).Methods The investigational sample was 205 patients with obstructive sleep apnoea at baseline and they were classified as non-POSA and POSA. Polygraphic registration was employed to compare the proportion of treatment responders between non-POSA and POSA groups at eight-week and one-year follow-ups. The treatment responder was defined as apnoea-hypopnoea index (AHI) <10 and/or ≥50% reduction in AHI.Results At the eight-week follow-up, the proportions of responders were 56% and 69% for the non-POSA and POSA groups (not significant), respectively. The responder proportions were increased to 68% and 77% for the two groups, respectively, at the one-year follow-up (not significant between the two groups). At the two follow-ups, there was no significant difference in absolute change in overall AHI between the two groups. However, the decrease in supine AHI was significantly greater in the POSA group, while the decrease in non-supine AHI was significantly greater in the non-POSA group.Conclusions The response rate for OA treatment did not differ between POSA and non-POSA groups. However, greater decreases in supine AHI and non-supine AHI were found among POSA and non-POSA patients, respectively.

Resveratrol Ameliorates High Altitude Hypoxia-Induced Osteoporosis by Suppressing the ROS/HIF Signaling Pathway.

Hypoxia at high-altitude leads to osteoporosis. Resveratrol (RES), as an antioxidant, has been reported to promote osteoblastogenesis and suppress osteoclastogenesis. However, the therapeutic effect of RES against osteoporosis induced by high-altitude hypoxia remains unclear. Thus, this study was intended to investigate the potential effects of RES on high-altitude hypoxia-induced osteoporosis both in vivo and in vitro. Male Wistar rats were given RES (400 mg/kg) once daily for nine weeks under hypoxia, while the control was allowed to grow under normoxia. Bone mineral density (BMD), the levels of bone metabolism-related markers, and the changes on a histological level were measured. Bone marrow-derived mesenchymal stem cells (BMSCs) and RAW264.7 were incubated with RES under hypoxia, with a control growing under normoxia, followed by the evaluation of proliferation and differentiation. The results showed that RES inhibited high-altitude hypoxia-induced reduction in BMD, enhanced alkaline phosphatase (ALP), osteocalcin (OCN), calcitonin (CT) and runt-related transcription factor 2 (RUNX2) levels, whereas it reduced cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I) levels and tartrate-resistant acid phosphatase (TRAP) activity in vivo. In addition, RES attenuated histological deteriorations in the femurs. In vitro, RES promoted osteoblastogenesis and mineralization in hypoxia-exposed BMSCs, along with promotion in RUNX2, ALP, OCN and osteopontin (OPN) levels, and inhibited the proliferation and osteoclastogenesis of RAW264.7. The promotion effects of RES on osteoblastogenesis were accompanied by the down-regulation of reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α) induced by hypoxia. These results demonstrate that RES can alleviate high-altitude hypoxia-induced osteoporosis via promoting osteoblastogenesis by suppressing the ROS/HIF-1α signaling pathway. Thus, we suggest that RES might be a potential treatment with minimal side effects to protect against high-altitude hypoxia-induced osteoporosis.

Orthodontic traction of an impacted maxillary third molar through a miniscrew-anchored cantilever spring to substitute the adjacent second molar with severe root resorption.

BACKGROUND: An orthodontic traction technique with a miniscrew-anchored cantilever spring was used for the traction of a deeply impacted maxillary third molar to substitute its adjacent second molar with severe root resorption. CASE DESCRIPTION: A 30-year-old woman sought multidisciplinary treatment planning for a second molar with severe root resorption caused by a deeply impacted third molar. Panoramic radiographs and cone-beam computed tomographic images showed that the third molar was located on the apical and palatal side of the second molar and that the second molar had severe root resorption. The second molar was removed, and the impacted third molar was orthodontically tractioned occlusally with the aid of a miniscrew-anchored cantilever spring. After 12 months of orthodontic treatment, the maxillary left third molar was successfully tractioned occlusally and well aligned with adjacent teeth for the substitution of the second molar. The patient was satisfied with the treatment outcome. PRACTICAL IMPLICATIONS: A palatal miniscrew-anchored cantilever spring is an effective and viable technique for the orthodontic traction of deeply impacted third molars to substitute second molars with severe root resorption.

[Resveratrol attenuates cardiac function impairment in plateau hypobaric hypoxia rats].

Objective: To study the protective effects of resveratrol (RSV) on cardiac function in rats with high altitude hypobaric hypoxia and its mechanisms. Methods: Thirty-six rats were randomly divided into control group, hypobaric hypoxia group (HH) and hypobaric hypoxia + RSV group (HH+RSV) according to the random number, 12 rats in each group. Rats in the HH and HH+RSV groups were subjected to chronic long-term high altitude hypobaric hypoxia intervention for 8 weeks in a hypobaric chamber at a simulated altitude of 6 000 m for 20 h / d. The rats of HH + RSV were fed with RSV at a dose of 400 mg/(kg·d). The rats were tested once a week for body weight and twice a week for food intake. Before execution, the rats were tested by blood cell analyzer for routine blood parameters and echocardiogram for cardiac function parameters in each group. The routine blood indexes of each group were measured by blood cell analyzer, the cardiac function indexes of each group were measured by echocardiography, myocardial hypertrophy was evaluated by HE staining, myocardial tissue reactive oxygen levels were evaluated by dihydroethidium (DHE) staining. Oxidative stress was evaluated by serum and myocardial tissue total antioxidant capacity (T-AOC), superoxide dismutase activity (SOD) and malondialdehyde (MDA) content. Results: Compared with the C group, the body mass and food intake of rats were decreased significantly (P＜0.05) in HH group, while compared with the C group, RSV had no significant effects on the body mass and food intake of rats in the HH+RSV group (P＞0.05). Compared with the C group, the levels of erythrocytes and hemoglobin of rats in the HH group were increased significantly (P＜0.05), while the platelet concentration was decreased significantly(P＜0.05); compared with the HH group, the erythrocyte and hemoglobin levels were decreased significantly (P＜0.05) and platelet concentration was increased significantly(P＜0.05) in rats of the HH+RSV group. Compared with the C group, the cardiac coefficient, myocardial fiber diameter and thickness were significantly increased in the HH group (P＜0.05); compared with the HH group, the cardiac coefficient and myocardial fiber thickness were significantly decreased in the HH+RSV group (P＜0.05). Echocardiographic analysis showed a significant increase in ventricular wall thickness (P＜0.05) and a significant decrease in ejection fraction and cardiac output (P＜0.05) in the HH group compared with the C group, and a significant decrease in ventricular wall thickness and a significant improvement in cardiac function (P＜0.05) in the HH+RSV group compared with the HH group. The results of DHE staining showed that myocardial tissue reactive oxygen levels were increased significantly in the HH group compared with the C group (P＜0.05); myocardial tissue reactive oxygen levels were significantly restored in the HH+RSV group compared with the HH group (P＜0.05). The oxidative/antioxidant results showed that the serum and myocardial T-AOC and SOD activities were decreased significantly (P＜0.05) and the MDA level was increased significantly (P＜0.05) in the HH group compared with the C group; the serum and myocardial T-AOC and SOD activities were increased significantly (P＜0.05) and the MDA level was decreased significantly(P＜0.05) in the HH+RSV group compared with the HH group. Conclusion: Long-term plateau hypobaric hypoxia exposure leads to myocardial hypertrophy and reduced cardiac function in rats. Resveratrol intervention significantly improves myocardial hypertrophy and cardiac function in rats caused by altitude hypobaric hypoxia exposure, which is closely related to reducing of reactive oxygen species and improving myocardial oxidative stress levels.

Optimal sites and angles for the insertion of orthodontic mini-implants at infrazygomatic crest: a cone beam computed tomography (CBCT)-based study.

BACKGROUND AND OBJECTIVES: Both cortical and overall bone thicknesses of the infrazygomatic crest (IZC) were measured to determine the optimal areas for mini-implants into the IZC. The impact of insertion sites, heights and angles, sex and age on bone thickness were evaluated. MATERIALS AND METHODS: In this study, cone beam computed tomography (CBCT) images of 32 patients were included. The cortical bone thickness (CBT) and overall bone thicknesses (OBT) of IZC were measured at different insertion sites between the maxillary first and second molars (site 61, 62, 63, 67, 71, 72 and 73), different heights (0 to 12 mm from alveolar bone crest) and different angles (0 to 90 degrees from the reference line). RESULTS: OBT was the thickest at site 63, followed by site 73. For each site, the insertion height where OBT was the thickest decreased with the increase of angle CBT and OBT were significantly influenced by sex and age. The percentage of root contact was significantly influenced by insertion heights and angles, not by sites. The recommended regions in the IZC for mini-implants were mapped. CONCLUSIONS: Both CBT and OBT in the infrazygomatic crest were influenced by insertion sites, heights, and angles. Sex and age had an impact on CBT and OBT. The optimal insertion heights and angles were 12 mm to 18 mm from the occlusal plane, and 40 to 70 degrees for mini-implants at IZC.

Development of an Artificial Intelligence System for the Automatic Evaluation of Cervical Vertebral Maturation Status.

BACKGROUND: Cervical vertebral maturation (CVM) is widely used to evaluate growth potential in the field of orthodontics. This study is aimed to develop an artificial intelligence (AI) system to automatically determine the CVM status and evaluate the AI performance. METHODS: A total of 1080 cephalometric radiographs, with the age of patients ranging from 6 to 22 years old, were included in the dataset (980 in training dataset and 100 in testing dataset). Two reference points and thirteen anatomical points were labelled and the cervical vertebral maturation staging (CS) was assessed by human examiners as gold standard. A convolutional neural network (CNN) model was built to train on 980 images and to test on 100 images. Statistical analysis was conducted to detect labelling differences between AI and human examiners, AI performance was also evaluated. RESULTS: The mean labelling error between human examiners was 0.48 ± 0.12 mm. The mean labelling error between AI and human examiners was 0.36 ± 0.09 mm. In general, the agreement between AI results and the gold standard was good, with the intraclass correlation coefficient (ICC) value being up to 98%. Moreover, the accuracy of CVM staging was 71%. In terms of F1 score, CS6 stage (85%) ranked the highest accuracy. CONCLUSIONS: In this study, AI showed a good agreement with human examiners, being a useful and reliable tool in assessing the cervical vertebral maturation.

An NADH-selective and sensitive fluorescence probe to evaluate living cell hypoxic stress.

Cellular disease and senescence are often accompanied by an imbalance in the local oxygen supply. Under hypoxia, mitochondrial NADH and FADH2 cannot be oxidized by the mitochondrial electron transport chain, which leads to the accumulation of reducing equivalents and subsequent reduction stress. Detecting changes in intracellular NADH levels is expected to allow an assessment of stress. We synthesized a red fluorescent probe, DPMQL1, with high selectivity and sensitivity for detecting NADH in living cells. The probe DPMQL1 has strong anti-interference abilities toward various potential biological interferences, such as metal ions, anions, redox species, and other biomolecules. In addition, its detection limit can reach the nanomolar level, meaning it can display small changes in NADH levels in living cells, so as to realize the evaluation of cell-based hypoxic stress.

Sox9CreER-mediated deletion of ß-catenin in palatal mesenchyme results in delayed palatal elevation accompanied with repressed canonical Wnt signaling and reduced actin polymerization.

Cleft palate is a good model to pushing us toward a deeper understanding of the molecular mechanisms of spatiotemporal patterns in tissues and organisms because of the multiple-step processes such as elevation and fusion. Previous studies have shown that the epithelial ß-catenin is crucial for palatal fusion, however, the function of the mesenchymal ß-catenin remains elusive. We investigate the role of mesenchymal ß-catenin in palatal development by generating a ß-catenin conditional knockout mouse (CKO) (Sox9CreER; Ctnnb1F/F ). We found that the CKO mice exhibited delayed palatal elevation, leading to cleft palate in both in vivo and ex vivo. Abnormal cell proliferation and repressed mesenchymal canonical Wnt signaling were found in the CKO palate. Interestingly, Filamentous actin (F-actin) polymerization was significantly reduced in the palatal mesenchyme of mutant embryos. Furthermore, overexpression of adenovirus-mediated transfection with Acta1 in the mutant could help to elevate the palatal shelves but could not prevent cleft palate in ex vivo. Our results suggest that conditionally knock out ß-catenin in the palatal mesenchyme by Sox9CreER leading to delayed palatal elevation, which results in repressed mesenchymal canonical Wnt signaling, decreased cell proliferation, and reduced actin polymerization, finally causes cleft palate.

A new congenital cleft palate New Zealand rabbit model for surgical research.

Cleft palate repair is a challenging procedure for cleft surgeons to teach, and in research, it can be difficult to evaluate different techniques and develop new treatments. In this study, a congenital cleft palate New Zealand rabbit model has been described and could be beneficial in future studies concerning cleft palate repair. Pregnant New Zealand rabbits received 1.0 mg dexamethasone injection intramuscularly once a day from the 13th gestation day (GD13) to GD16. On GD31. Newborn rabbits were delivered by cesarean sections, fed with a standardized gastric tube feeding method, and divided into two groups. The rate of survival and the incidence of cleft palate was calculated. Weight, appearance, behavior, maxillary occlusal view, and regional anatomic and histological comparisons were recorded within 1 month after birth. Infants from the two groups with similar physiological conditions were selected for continuous maxillofacial and mandibular Micro-CT scan and three-dimensional reconstruction analysis. Ten pregnant rabbits gave birth to 48 live infants. The survival and cleft palate rates were 65.6% and 60.4% respectively. Both groups survived over 1 month with no difference in weight, appearance, and behavior. The cleft type was stable, and anatomical defects, histological characteristics, and nasal-maxillary abnormalities of the cleft were similar to those of humans. There was no statistically significant difference in maxillary and mandible development between the two groups within one month after birth. This congenital cleft palate model is considered to have more research possibilities with efficient cleft induction, reliable feeding methods, stable anatomical defects, and maxillofacial development similar to those seen in humans.

Radiologic Evaluation of the Influence of Cleft Treatment on Nasal Dorsum Growth.

OBJECTIVE: The study addresses whether the growth of the nasal dorsum is disturbed by cleft treatments, for cleft lip only (CL) and cleft lip with cleft palate (CLP). DESIGN: A total of 576 patients with cleft (278 CL, 298 CLP) and 333 individuals without orofacial clefts were retrospectively enrolled. Cleft lip only group was treated with a modified Millard technique combined with Tajima incision for rhinoplasty at 3 to 6 months. The CLP group underwent the same lip repair technique and then underwent a Sommerlad palatoplasty at 9 to 12 months. Lateral cephalometric radiographs of all individuals were taken to evaluate the nasal length and nasal dorsum height. Dunn test was used to analyze the difference (P < .001). RESULTS: Compared with control, in CL, nasal bone angle and nasal dorsum angle increase by age similarly (5-18 years, P > .05); the total dorsum is significantly shorter (5-18 years, P < .001), while the upper nasal dorsum length is similar (except in 5-6 years), and the lower nasal dorsum is shorter (5-18 years, P < .001). In CLP, nasal bone angle develops insufficiently as children grow (8-18 years, P < .001); the nasal dorsum angle is notably smaller (5-18 years, P < .001); nasal bone length is not significantly different except 11 to 13 years (P < .05); nasal dorsal length is similar at skeletal maturity (17-18 years, P > .05), although it is shorter during 8 to 16 years (P < .05); the upper nasal dorsum is overdeveloped (14-18 years, P < .05), whereas the lower nasal dorsum is underdeveloped (5-18 years, P < .001). CONCLUSION: Treatments in both CL and CLP could be the important factors in disturbing the growth of cartilaginous portion of the nasal dorsum (including nasal tip) and the nasal dorsum height.

Assessment of available sites for palatal orthodontic mini-implants through cone-beam computed tomography.

OBJECTIVE: To measure the palatal thickness of both hard and soft tissues and to determine safe regions for the placement of mini-implants. The influences of sex and age on palatal thickness were also examined. MATERIALS AND METHODS: Cone-beam computed tomography images of 30 patients (12 males, 18 females), including 15 adults and 15 adolescents, were used in this study. The thicknesses of palatal hard tissue, soft tissue, and hard+soft tissues were measured at the coronal planes of first premolars, second premolars, first molars, and second molars (P1, P2, M1, and M2 planes, respectively). RESULTS: The hard tissue was thickest at the P1 plane, followed by at the P2, M1, and M2 planes, while the thickness of soft tissue was similar among the four planes. The trends in the changes of palatal thickness from midline to the lateral sides (V-pattern) were similar for the four planes. Palatal thickness was influenced by sex, age, and their interaction. Mapping of recommended and optimal sites for palatal mini-implants was accomplished. CONCLUSIONS: Sex and age factors could influence palatal thickness. Therefore, the findings might be helpful for clinicians in guiding them to choose the optimal sites for palatal mini-implants.