Developmental roles of glomerular epithelial protein-1 in mice molar morphogenesis.

Glomerular epithelial protein-1 (Glepp1), a R3 subtype family of receptor-type protein tyrosine phosphatases, plays important role in the activation of Src family kinases and regulates cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, we firstly examined the functional evaluation of Glepp1 in tooth development and morphogenesis. The precise expression level and developmental function of Glepp1 were examined by RT-qPCR, in situ hybridization, and loss and gain of functional study using a range of in vitro organ cultivation methods. Expression of Glepp1 was detected in the developing tooth germs in cap and bell stage of tooth development. Knocking down Glepp1 at E13 for 2 days showed the altered expression levels of tooth development-related signaling molecules, including Bmps, Dspp, Fgf4, Lef1, and Shh. Moreover, transient knock down of Glepp1 revealed alterations in cellular physiology, examined by the localization patterns of Ki67 and E-cadherin. Similarly, knocking down of Glepp1 showed disrupted enamel rod and interrod formation in 3-week renal transplanted teeth. In addition, due to attrition of odontoblastic layers, the expression signals of Dspp and the localization of NESTIN were almost not detected after knock down of Glepp1; however, their expressions were increased after Glepp1 overexpression. Thus, our results suggested that Glepp1 plays modulating roles during odontogenesis by regulating the expression levels of signaling molecules and cellular events to achieve the proper structural formation of hard tissue matrices in mice molar development.

Patterns of Anterior Inferior Tibiofibular Ligament Avulsion Fracture Accompanied by Ankle Fracture.

The anterior inferior tibiofibular ligament (AITFL) avulsion fracture accompanying an ankle fracture can compromise ankle stability, necessitating accurate evaluation and a clear understanding of its pathophysiology.. The aim of this study was to investigate the association between AITFL avulsion fracture and Lauge-Hansen, Wagstaffe classification. A retro-prospective study was conducted at a university-affiliated tertiary care medical center. We selected 128 patients who underwent surgery at our institution between January 2013 and July 2017 and analyzed the association between AITFL avulsion fracture and the foot position. According to the modified Wagstaffe classification system, there were 39 cases of type II, followed by 9 cases of type III and 8 cases of type IV. Of the7 pronation-abduction fractures, 3 were AITFL avulsion fracture (43%), while of the 21 pronation-external rotation fractures, 9 were AITFL avulsion fracture (43%). Of the 95 supination-external rotation fractures, there were 56 cases (59%) of AITFL avulsion fractures. Of the pronation fractures, 0% were fibular avulsion fractures and 43% were tibial avulsion fractures. Of the supination fractures, 44% were fibular avulsion fractures and 16% were tibial avulsion fracture. The difference in the ratio of fibular to tibial avulsion fractures between pronation and supination fractures was significant (p < .001). These results suggest that tibial avulsion fractures of type IV in the modified Wagstaffe classification and pronation fractures occur due to collision with the anterolateral corners of the distal bone when the talus externally rotates. Moreover, in cases of pronation fractures, a new type of AITFL avulsion fracture has been observed.

A 3-Fluoropyridine Manipulating the Aggregation and Fibril Network of Donor Polymers for Eco-Friendly Solution-Processed Versatile Organic Solar Cells.

The development of eco-friendly solvent-processed organic solar cells (OSCs) suitable for industrial-scale production should be now considered the imperative research. Herein, asymmetric 3-fluoropyridine (FPy) unit is used to control the aggregation and fibril network of polymer blends. Notably, terpolymer PM6(FPy = 0.2) incorporating 20% FPy in a well-known donor polymer poly[(2,6-(4,8-bis(5-(2-ethylhexyl-3-fluoro)thiophen-2-yl)-benzo[1,2-b:4,5-b']dithiophene))-alt-(5,5-(1',3'-di-2-thienyl-5',7'-bis(2-ethylhexyl)benzo[1',2'-c:4',5'-c']dithiophene-4,8-dione)] (PM6) can reduce the regioregularity of the polymer backbone and endow them with much-enhanced solubility in eco-friendly solvents. Accordingly, the excellent adaptability for fabricating versatile devices based on PM6(FPy = 0.2) by toluene processing is demonstrated. The resulting OSCs exhibit a high power conversion efficiency (PCE) of 16.1% (17.0% by processed with chloroform) and low batch-to-batch variation. Moreover, by controlling the donor-to-acceptor weight ratio at 0.5:1.0 and 0.25:1.0, semi-transparent OSCs (ST-OSCs) yield significant light utilization efficiencies of 3.61% and 3.67%, respectively. For large-area (1.0 cm2 ) indoor OSC (I-OSC), a high PCE of 20.6% is achieved with an appropriate energy loss of 0.61 eV under a warm white light-emitting diode (3,000 K) with the illumination of 958 lux. Finally, the long-term stability of the devices is evaluated by investigating their structure-performance-stability relationship. This work provides an effective approach to realizing eco-friendly, efficient, and stable OSCs/ST-OSCs/I-OSCs.

Developmental function of Piezo1 in mouse submandibular gland morphogenesis.

Mechanically activated factors are important in organogenesis, especially in the formation of secretory organs, such as salivary glands. Piezo-type mechanosensitive ion channel component 1 (Piezo1), although previously studied as a physical modulator of the mechanotransduction, was firstly evaluated on its developmental function in this study. The detailed localization and expression pattern of Piezo1 during mouse submandibular gland (SMG) development were analyzed using immunohistochemistry and RT-qPCR, respectively. The specific expression pattern of Piezo1 was examined in acinar-forming epithelial cells at embryonic day 14 (E14) and E16, which are important developmental stages for acinar cell differentiation. To understand the precise function of Piezo1 in SMG development, siRNA against Piezo1 (siPiezo1) was employed as a loss-of-function approach, during in vitro organ cultivation of SMG at E14 for the designated period. Alterations in the histomorphology and expression patterns of related signaling molecules, including Bmp2, Fgf4, Fgf10, Gli1, Gli3, Ptch1, Shh, and Tgfß-3, were examined in acinar-forming cells after 1 and 2 days of cultivation. Particularly, altered localization patterns of differentiation-related signaling molecules including Aquaporin5, E-cadherin, Vimentin, and cytokeratins would suggest that Piezo1 modulates the early differentiation of acinar cells in SMGs by modulating the Shh signaling pathway.

Eight-Month Follow-up After the Third Dose of BNT162b2 Vaccine in Healthcare Workers: The Question of a Fourth Dose.

BACKGROUND: A fourth dose of vaccination is known to help reduce the severity and mortality rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The South Korean vaccination guidelines for the fourth dose do not include healthcare workers (HCWs) as priority candidates. We investigated the necessity of the fourth dose in South Korean HCWs based on an 8-month follow-up period after the third vaccination. METHODS: Changes in the surrogate virus neutralization test (sVNT) inhibition (%) score were measured at one month, four months and eight months after the third vaccination. The sVNT values were analyzed between infected and uninfected groups, and their trajectories were compared. RESULTS: A total of 43 HCWs were enrolled in this study. In total, 28 cases (65.1%) were confirmed to be infected with SARS-CoV-2 (presumed omicron variant), and all had mild symptoms. Meanwhile, 22 cases (78.6%) were infected within four months of the third dose (median, 97.5 days). Eight months after the third dose, the SARS-CoV-2 (presumed omicron variant)-infected group showed significantly higher sVNT inhibition than that in the uninfected group (91.3% vs. 30.7%; P < 0.001). The antibody response due to hybrid immunity, provided by a combination of infection and vaccination, was maintained at sufficient levels for more than four months. CONCLUSION: For HCWs who had coronavirus disease 2019 infection after completing a third vaccination, a sufficient antibody response was maintained until eight months after the third dose. The recommendation of the fourth dose may not be prioritized in subjects with hybrid immunity.

Effects of Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers.

BACKGROUND: Although the primary vaccine coverage rate for coronavirus disease 2019 (COVID-19) in South Korea has exceeded 80%, the coronavirus continues to spread, with reports of a rapid decline in vaccine effectiveness. South Korea is administering booster shots despite concerns about the effectiveness of the existing vaccine. METHODS: Neutralizing antibody inhibition scores were evaluated in two cohorts after the booster dose. For the first cohort, neutralizing activity against the wild-type, delta, and omicron variants after the booster dose was evaluated. For the second cohort, we assessed the difference in neutralizing activity between the omicron infected and uninfected groups after booster vaccination. We also compared the effectiveness and adverse events (AEs) between homologous and heterologous booster doses for BNT162b2 or ChAdOx1 vaccines. RESULTS: A total of 105 healthcare workers (HCWs) that were additionally vaccinated with BNT162b2 at Soonchunhyang University Bucheon Hospital were enrolled in this study. Significantly higher surrogate virus neutralization test (sVNT) inhibition (%) was observed for the wild-type and delta variants compared to sVNT (%) for the omicron after the booster dose (97%, 98% vs. 75%; P < 0.001). No significant difference in the neutralizing antibody inhibition score was found between variants in the BNT/BNT/BNT group (n = 48) and the ChA/ChA/BNT group (n = 57). Total AEs were not significantly different between the ChA/ChA/BNT group (85.96%) and the BNT/BNT group (95.83%; P = 0.11). In the second cohort with 58 HCWs, markedly higher sVNT inhibition to omicron was observed in the omicron-infected group (95.13%) compared to the uninfected group (mean of 48.44%; P < 0.001) after four months of the booster dose. In 41 HCWs (39.0%) infected with the omicron variant, no difference in immunogenicity, AEs, or effectiveness between homogeneous and heterogeneous boosters was observed. CONCLUSION: Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination. Further studies are needed to understand the characteristics of immunogenicity in these populations.

Application of entire dental panorama image data in artificial intelligence model for age estimation.

BACKGROUND: Accurate age estimation is vital for clinical and forensic purposes. With the rapid advancement of artificial intelligence(AI) technologies, traditional methods relying on tooth development, while reliable, can be enhanced by leveraging deep learning, particularly neural networks. This study evaluated the efficiency of an AI model by applying the entire panoramic image for age estimation. The outcome performances were analyzed through supervised learning (SL) models. METHODS: Total of 27,877 dental panorama images from 5 to 90 years of age were classified by 2 types of grouping. In type 1 they were classified by each age and in type 2, applying heuristic grouping, the age over 20 years were classified by every 5 years. Wide ResNet (WRN) and DenseNet (DN) were used for supervised learning. In addition, the analysis with ± 3 years of deviation in both types were performed. RESULTS: For the DN model, while the type 1 grouping achieved an accuracy of 0.1016 and F1 score of 0.058, the type 2 achieved an accuracy of 0.3146 and F1 score of 0.2027. Incorporating ± 3years of deviation, the accuracy of type 1 and 2 were 0.281, 0.7323 respectively; and the F1 score were 0.1768, 0.6583 respectively. For the WRN model, while the type 1 grouping achieved an accuracy of 0.1041 and F1 score of 0.0599, the type 2 achieved an accuracy of 0.3182 and F1 score of 0.2071. Incorporating ± 3years of deviation, the accuracy of type 1 and 2 were 0.2716, 0.7323 respectively; and the F1 score were 0.1709, 0.6437 respectively. CONCLUSIONS: The application of entire panorama image data for supervised with classification by heuristics grouping with ± 3years of deviation for supervised learning models and demonstrated satisfactory outcome for the age estimation.

Resveratrol enhances bone formation by modulating inflammation in the mouse periodontitis model.

OBJECTIVE: To evaluate the effect of resveratrol on periodontal bone regeneration after local delivery and to determine its effect on inflammatory mediators. BACKGROUND: Resveratrol is considered an anti-inflammatory polyphenolic stilbene involved in the modulation of inflammation. MATERIALS AND METHODS: Periodontitis was induced in mouse molars using a 5-day ligature model followed by the left second molar extraction and 50 µM resveratrol treatment for 1 and 2 weeks. We then examined specimens treated for 1 week histologically and with immunostaining. Microfocus-computed tomography (micro-CT) was used to examine the bone volume formation. RESULTS: After 1 week of treatment, proinflammatory cytokine levels (TNF-alpha and IL6), cells exhibiting neutrophil and macrophage marker (MPO), cell proliferation marker (Ki67), and preosteoblastic marker (RUNX2) reactivity decreased in the resveratrol-treated specimens compared to the control group. In contrast, we observed a higher number of CD31-, F4/80-, and osteocalcin- (OCN-) positive cells in the resveratrol-treated specimens. After 2 weeks, micro-CT confirmed an increased bone mass in the region of the extraction socket in the resveratrol-treated group. CONCLUSION: After 1 week, the resveratrol-treated specimens revealed evidence of inflammation modulation compared to the control group. These data suggest that resveratrol not only affects inflammation control but also is useful for treating periodontitis-related tissue defects and bone regeneration.

USP1 inhibitor ML323 enhances osteogenic potential of human dental pulp stem cells.

LIM homeobox 8 (LHX8) is expressed during embryonic development of craniofacial tissues, including bone and teeth. In a previous study, the overexpression of LHX8 inhibited osteodifferentiation of human dental pulp stem cells (DPSCs). In this study, a cDNA microarray analysis was performed to reveal the molecular changes which occur in response to LHX8 overexpression in DPSCs and discover possible targets for an osteoinductive agent. There were 345 differentially expressed genes (DEGs) in response to osteoinductive signaling and 53 DEGs in response to LHX8 overexpression and osteoinductive signaling, respectively. Thirty-eight genes were common in both conditions, and among these, genes upregulated in LHX8 DPSCs but downregulated in osteodifferentiated DPSCs were chosen. Five of them had commercial inhibitors available. Among the tested inhibitors, ML323, which target DNA-binding protein inhibitor ID-1, promoted osteodifferentiation of DPSCs. In conclusion, inhibition of ID-1 led to increased osteogenesis of human DPSCs.

Effects of resveratrol on bone-healing capacity in the mouse tooth extraction socket.

BACKGROUND AND OBJECTIVE: After tooth extraction, the extraction socket undergoes several steps of soft and hard tissue healing. The healing process of the extraction socket is modulated by a range of signaling factors and biochemical agents. It has been reported that resveratrol, a polyphenolic compound, exhibits various biological effects, including anti-inflammatory, anti-carcinogenic, antioxidant, and anti-aging effects, and protects cardiovascular and bone tissues. In this study, we examined the cellular effects of resveratrol on human periodontal ligament (hPDL) cells and osteoblast-like (MC3T3-E1) cells and evaluated the bone-healing capacity of tooth extraction sockets in mice. MATERIAL AND METHODS: Resveratrol was applied to hPDL and MC3T3-E1 cells to detect cell proliferation and alkaline phosphatase (ALP) activity, and qPCR was employed to understand the gene expression level in vitro. For in vivo experiment, six-week-old C57BL/6 male mice were randomly divided into control (n = 15) and experimental (n = 15) groups and maxillary first molars were extracted by surgery. Experimental groups received 50-µM resveratrol on extraction sockets and analyzed the degree of new bone formation. RESULTS: Treatment of hPDL and MC3T3-E1 cells with resveratrol increased the cell proliferation and ALP activity and enhanced the expression of ALP, BMP-2, BMP-4, and OC genes. Resveratrol enhanced new bone formation in the lingual extraction socket in mice. CONCLUSION: These results suggest that resveratrol increases the cellular physiology of PDL and osteoblast including their proliferation and differentiation and may play an important role in bone-healing capacity after tooth extraction.

Application of Blind Deconvolution Based on the New Weighted L1-norm Regularization with Alternating Direction Method of Multipliers in Light Microscopy Images.

This study aimed to develop and evaluate a blind-deconvolution framework using the alternating direction method of multipliers (ADMMs) incorporated with weighted L1-norm regularization for light microscopy (LM) images. A presimulation study was performed using the Siemens star phantom prior to conducting the actual experiments. Subsequently, the proposed algorithm and a total generalized variation-based (TGV-based) method were applied to cross-sectional images of a mouse molar captured at 40× and 400× on-microscope magnifications and the results compared, and the resulting images were compared. Both simulation and experimental results confirmed that the proposed deblurring algorithm effectively restored the LM images, as evidenced by the quantitative evaluation metrics. In conclusion, this study demonstrated that the proposed deblurring algorithm can efficiently improve the quality of LM images.

Experimental Animal Model Systems for Understanding Salivary Secretory Disorders.

Salivary secretory disorders are life-disrupting pathologic conditions with a high prevalence, especially in the geriatric population. Both patients and clinicians frequently feel helpless and get frustrated by the currently available therapeutic strategies, which consist mainly of palliative managements. Accordingly, to unravel the underlying mechanisms and to develop effective and curative strategies, several animal models have been developed and introduced. Experimental findings from these models have contributed to answer biological and biomedical questions. This review aims to provide various methodological considerations used for the examination of pathological fundamentals in salivary disorders using animal models and to summarize the obtained findings. The information provided in this review could provide plausible solutions for overcoming salivary disorders and also suggest purpose-specific experimental animal systems.

Signaling Modulations of miR-206-3p in Tooth Morphogenesis.

MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs that post-transcriptionally regulate gene expression in organisms. Most mammalian miRNAs influence biological processes, including developmental changes, tissue morphogenesis and the maintenance of tissue identity, cell growth, differentiation, apoptosis, and metabolism. The miR-206-3p has been correlated with cancer; however, developmental roles of this miRNA are unclear. In this study, we examined the expression pattern and evaluated the developmental regulation of miR-206-3p during tooth morphogenesis using ex-vivo culture method. The expression pattern of miR-206-3p was examined in the epithelium and mesenchyme of developing tooth germ with stage-specific manners. Perturbation of the expression of miR-206-3p clearly altered expression patterns of dental-development-related signaling molecules, including Axin2, Bmp2, Fgf4, Lef1 and Shh. The gene expression complemented with change in cellular events including, apoptosis and proliferation which caused altered crown and pulp morphogenesis in renal-capsule-calcified teeth. Especially, mislocalization of ß-Catenin and SMAD1/5/8 were observed alongside dramatic alterations in the expression patterns of Fgf4 and Shh. Overall, our data suggest that the miR-206-3p regulate the cellular physiology during tooth morphogenesis through modulation of the Wnt, Bmp, Fgf, and Shh signaling pathways to form proper tooth pulp and crown.

Facilitation of Bone Healing Processes Based on the Developmental Function of Meox2 in Tooth Loss Lesion.

In the present study, we examined the bone healing capacity of Meox2, a homeobox gene that plays essential roles in the differentiation of a range of developing tissues, and identified its putative function in palatogenesis. We applied the knocking down of Meox2 in human periodontal ligament fibroblasts to examine the osteogenic potential of Meox2. Additionally, we applied in vivo periodontitis induced experiment to reveal the possible application of Meox2 knockdown for 1 and 2 weeks in bone healing processes. We examined the detailed histomorphological changes using Masson's trichrome staining and micro-computed tomography evaluation. Moreover, we observed the localization patterns of various signaling molecules, including α-SMA, CK14, IL-1ß, and MPO to examine the altered bone healing processes. Furthermore, we investigated the process of bone formation using immunohistochemistry of Osteocalcin and Runx2. On the basis of the results, we suggest that the knocking down of Meox2 via the activation of osteoblast and modulation of inflammation would be a plausible answer for bone regeneration as a gene therapy. Additionally, we propose that the purpose-dependent selection and application of developmental regulation genes are important for the functional regeneration of specific tissues and organs, where the pathological condition of tooth loss lesion would be.

Developmental Roles of FUSE Binding Protein 1 (Fubp1) in Tooth Morphogenesis.

FUSE binding protein 1 (Fubp1), a regulator of the c-Myc transcription factor and a DNA/RNA-binding protein, plays important roles in the regulation of gene transcription and cellular physiology. In this study, to reveal the precise developmental function of Fubp1, we examined the detailed expression pattern and developmental function of Fubp1 during tooth morphogenesis by RT-qPCR, in situ hybridization, and knock-down study using in vitro organ cultivation methods. In embryogenesis, Fubp1 is obviously expressed in the enamel organ and condensed mesenchyme, known to be important for proper tooth formation. Knocking down Fubp1 at E14 for two days, showed the altered expression patterns of tooth development related signalling molecules, including Bmps and Fgf4. In addition, transient knock-down of Fubp1 at E14 revealed changes in the localization patterns of c-Myc and cell proliferation in epithelium and mesenchyme, related with altered tooth morphogenesis. These results also showed the decreased amelogenin and dentin sialophosphoprotein expressions and disrupted enamel rod and interrod formation in one- and three-week renal transplanted teeth respectively. Thus, our results suggested that Fubp1 plays a modulating role during dentinogenesis and amelogenesis by regulating the expression pattern of signalling molecules to achieve the proper structural formation of hard tissue matrices and crown morphogenesis in mice molar development.

An endoplasmic reticulum stress regulator, Tmbim6, modulates secretory stage of mice molar.

To understand the role of endoplasmic reticulum (ER)-stress in mice molar development, we studied Tmbim6 that antagonizes the unfolded protein response, using Tmbim6 knockout (KO) mice and in vitro organ cultivation with knocking down using small interfering RNA. During molar development, Tmbim6 is expressed in developing tooth at E14-E16, postnatal0 (PN0), and PN6. Mineral content in Tmbim6 KO enamel was reduced while dentin was slightly increased revealing ultrastructural changes in pattern formation of both enamel and dentin. Moreover, odontoblast differentiation was altered with increased Dspp expression at PN0 followed by altered AMELX localizations at PN5. These results were confirmed by in vitro organ cultivation and showed altered Bmp signaling, proliferation, and actin rearrangement in the presumptive ameloblast and odontoblasts that followed the altered expression of differentiation and ER stress-related signaling molecules at E16.5. Overall, ER stress modulated by Tmbim6 would play important roles in patterned dental hard tissue formation in mice molar within a limited period of development.

Effects of oleanolic acid acetate on bone formation in an experimental periodontitis model in mice.

OBJECTIVE: We evaluated the role of oleanolic acid acetate (OAA), a triterpenoid commonly used in the treatment of liver disorders, inflammatory diseases, and metastasis, in bone formation after tooth loss by periodontitis. BACKGROUND: Periodontitis causes the sequential degradation of the alveolar bone and associated structures, resulting in tooth loss. Several studies have attempted to regenerate the bone for implantation following tooth loss. METHODS: Maxillary left second molar was extracted from 8-week-old male mice following induction of periodontitis by ligature for 5 days. The extraction socket was treated with 50 ng/µL OAA for 1, 2, and 3 weeks. Detailed morphological changes were examined using Masson's trichrome staining, and the precise localization patterns of various signaling molecules, including CD31, F4/80, interleukin (IL)-6, and osteocalcin, were observed. The volume of bone formation was examined by Micro-CT. Osteoclasts were enumerated using tartrate-resistant acid phosphatase (TRAP) staining. For molecular dissection of signaling molecules, we employed the hanging-drop in vitro cultivation method at E14 for 1 day and examined the expression pattern of transforming growth factor (TGF)-ß superfamily and Wnt signaling genes. RESULTS: Histomorphometrical examinations showed facilitated bone formation in the extraction socket following OAA treatment. In addition, OAA-treated specimens showed the altered localization patterns of inflammatory and bone formation-related signaling molecules including CD31, F4/80, IL-6, and osteocalcin. Also, embryonic tooth germ mesenchymal tissue cultivation with OAA treatment showed the significant altered expression patterns of signaling molecules such as transforming growth factor (TGF)-ß superfamily and Wnt signaling. CONCLUSIONS: Oleanolic acid acetate induces bone formation and remodeling through proper modulation of osteoblast, osteoclast, and inflammation with regulations of TGF-ß and Wnt signaling.

Quality by Design characterization of the perfusion culture process for recombinant FVIII.

A Quality by Design (QbD) concept was applied to characterize a cell culture process for production of the recombinant Factor VIII (rFVIII). We characterized the production bioreactor process and defined the design space by applying risk assessment to determine potential critical process parameters (CPPs) impacting critical quality attributes (CQAs). Characterization studies were subsequently performed using a qualified scaled-down model (SDM) and a multi-factorial design of experiment (DOE) approach to determine both the individual and combined impacts of the potential CPPs on CQAs. Among the operating parameters characterized, production temperature, production pH and a shift in the timing of production affected rFVIII activity and tyrosine sulfation level. Finally, we identified CPPs and established a design space for the cell culture process to identify appropriate conditions for routine manufacturing.

Regulation of mesenchymal signaling in palatal mucosa differentiation.

Epithelial differentiation is thought to be determined by mesenchymal components during embryogenesis. In mice, palatal mucosa showed the region-specific keratinization pattern along antero-posterior axis. However, developmental mechanisms involved in oral mucosa differentiation with fine tuning of keratinization are not elucidated yet. To reveal this developmental mechanism, first, we conducted tissue recombination assay of the palate at E16 for 2 days which revealed that epithelial differentiation with specific localization of CK10 is modulated by mesenchymal components. Based on the results, we propose that mesenchymal signaling would determine the presumptive fate of developing palatal epithelium in spatiotemporal manner. Genome-wide screening analysis using laser micro-dissection to collect spatiotemporal specific molecules between anterior and posterior palate suggested Meox2 in the posterior mesenchymal tissue to be a candidate regulator controlling epithelial differentiation. To examine the detailed spatiotemporal function of Meox2, we employed in vitro organ cultivation with the loss- and gain-of-function studies at E14.5 for 2 and 4 days, respectively. Our results suggest that posteriorly expressed Meox2 modulates non-keratinized epithelial differentiation through complex signaling regulations in mice palatogenesis.

Exploring the Differences between Adolescents' and Parents' Ratings on Adolescents' Smartphone Addiction.

BACKGROUND: Smartphone addiction has recently been highlighted as a major health issue among adolescents. In this study, we assessed the degree of agreement between adolescents' and parents' ratings of adolescents' smartphone addiction. Additionally, we evaluated the psychosocial factors associated with adolescents' and parents' ratings of adolescents' smartphone addiction. METHODS: In total, 158 adolescents aged 12-19 years and their parents participated in this study. The adolescents completed the Smartphone Addiction Scale (SAS) and the Isolated Peer Relationship Inventory (IPRI). Their parents also completed the SAS (about their adolescents), SAS-Short Version (SAS-SV; about themselves), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). We used the paired t-test, McNemar test, and Pearson's correlation analyses. RESULTS: Percentage of risk users was higher in parents' ratings of adolescents' smartphone addiction than ratings of adolescents themselves. There was disagreement between the SAS and SAS-parent report total scores and subscale scores on positive anticipation, withdrawal, and cyberspace-oriented relationship. SAS scores were positively associated with average minutes of weekday/holiday smartphone use and scores on the IPRI and father's GAD-7 and PHQ-9 scores. Additionally, SAS-parent report scores showed positive associations with average minutes of weekday/holiday smartphone use and each parent's SAS-SV, GAD-7, and PHQ-9 scores. CONCLUSION: The results suggest that clinicians need to consider both adolescents' and parents' reports when assessing adolescents' smartphone addiction, and be aware of the possibility of under- or overestimation. Our results cannot only be a reference in assessing adolescents' smartphone addiction, but also provide inspiration for future studies.