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1.
J Cell Biochem ; 124(9): 1366-1378, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37565579

RESUMO

Bone morphogenic protein 9 (BMP9) is one of the most potent inducers of osteogenic differentiation among the 14 BMP members, but its mechanism of action has not been fully demonstrated. Hes1 is a transcriptional regulator with basic helix-loop-helix (bHLH) domain and is a well-known Notch effector. In this study, we investigated the functional roles of early induction of Hes1 by BMP9 in a mouse mesenchymal stem cell line, ST2. Hes1 mRNA was transiently and periodically induced by BMP9 in ST2, which was inhibited by BMP signal inhibitors but not by Notch inhibitor. Interestingly, Hes1 knockdown in ST2 by siRNA increased the expression of osteogenic differentiation markers such as Sp7 and Ibsp and matrix mineralization in comparison with control siRNA transfected ST2. In contrast, forced expression of Hes1 by using the Tet-On system suppressed the expression of osteogenic markers and matrix mineralization by BMP9. We also found that the early induction of Hes1 by BMP9 suppressed the expression of Alk1, an essential receptor for BMP9. In conclusion, BMP9 rapidly induces the expression of Hes1 via the SMAD pathway in ST2 cells, which plays a negative regulatory role in osteogenic differentiation of mesenchymal stem cells induced by BMP9.


Assuntos
Fator 2 de Diferenciação de Crescimento , Células-Tronco Mesenquimais , Animais , Camundongos , Diferenciação Celular/genética , Fator 2 de Diferenciação de Crescimento/genética , Fator 2 de Diferenciação de Crescimento/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osteogênese/genética , RNA Interferente Pequeno/metabolismo , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/metabolismo
2.
Int J Mol Sci ; 23(20)2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36293485

RESUMO

Lipoteichoic acid (LTA) and lipopolysaccharide (LPS) are cell wall components of Gram-positive and Gram-negative bacteria, respectively. Notably, oral microflora consists of a variety of bacterial species, and osteomyelitis of the jaw caused by dental infection presents with symptoms of bone resorption and osteosclerosis. However, the effects of LTA and LPS on osteogenic differentiation have not yet been clarified. We examined the effects of LTA and LPS on osteoblasts and found that LTA alone promoted alizarin red staining at low concentrations and inhibited it at high concentrations. Additionally, gene expression of osteogenic markers (ALP, OCN, and OPG) were enhanced at low concentrations of LTA. High concentrations of LPS suppressed calcification potential, and the addition of low concentrations of LTA inhibited calcification suppression, restoring the gene expression levels of suppressed bone differentiation markers (ALP, BSP, and OCN). Moreover, the suppression of p38, a signaling pathway associated with bone differentiation, had opposing effects on gene-level expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), suggesting that mixed LTA and LPS infections have opposite effects on bone differentiation through concentration gradients, involving inflammatory markers (TNF-α and IL-6) and the p38 pathway.


Assuntos
Lipopolissacarídeos , Fator de Necrose Tumoral alfa , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/genética , Osteogênese , Antibacterianos , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Positivas/metabolismo , Biomarcadores
3.
J Oral Maxillofac Surg ; 79(11): 2268.e1-2268.e5, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34273277

RESUMO

PURPOSE: This study assessed the relationship between changes in autonomic nervous system activity during impacted mandibular third molar extraction and a patient's postoperative psychological status, with the overarching aim of informing the development of interventions to reduce dental phobia and anxiety. We hypothesized that changes in autonomic nervous system activity during tooth extraction are related to postoperative psychology. METHODS: In our prospective cohort study, heart rate variability, heart rate (HR), and systolic blood pressure (SBP) were recorded during impacted mandibular third molar extraction. Heart rate variability values were dichotomized as either low frequency (LF 0.04-0.15 Hz) or high frequency (HF >0.15 Hz). The relative ratios (intraoperative vs baseline) of LF/HF, HF, HR, and SBP were divided into high and low groups based on their median values; the State Anxiety Inventory (STAI-S) results were compared between the groups with high and low relative ratios. RESULTS: Data of 34 female patients (age, 28.23 ± 1.05 years) were analyzed. Postoperative STAI-S values were significantly lower than preoperative values. Patients in the high LF/HF group had a significantly lower change in STAI-S values than those in the low LF/HF group (P < .05). There were no significant differences in the change in STAI-S values between the groups with high and low HF, HR, or SBP. CONCLUSIONS: Patients with low sympathetic nervous system activity had lower anxiety; the LF/HF index was the most sensitive indicator for changes in stress. Additional studies are required to develop optimal interventions for reducing sympathetic nerve activity in patients with dental phobia.


Assuntos
Ansiedade ao Tratamento Odontológico , Extração Dentária , Adulto , Sistema Nervoso Autônomo , Feminino , Humanos , Estudos Prospectivos , Sistema Nervoso Simpático
4.
J Oral Maxillofac Surg ; 79(12): 2462-2471, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34656516

RESUMO

PURPOSE: To observe the long-term postoperative bone formation and eruption of adjacent teeth after octacalcium phosphate granule and atelocollagen complex (OCP/Col) grafting in the treatment of alveolar cleft of patients with unilateral cleft lip with or without cleft palate (UCL ± P). METHODS: Four patients with UCL ± P who underwent OCP/Col grafting (OCP group), and 55 patients with UCL ± P who underwent autologous bone grafting (AB group) were enrolled in this study. OCP/Col or autologous bone grafting was performed before the eruption of canines or lateral incisors in mixed dentition, followed by orthodontic management. Patients in the OCP group underwent radiography before and after surgery at 1, 2, 3, 6, and over 30 months postoperatively. The volume and area of the bony defect in the alveolar cleft area were compared between the OCP and AB groups before and after 6 months of surgery. RESULTS: The bone bridge in all patients in the OCP/Col group was successfully formed, and by 6 months postoperatively, the permanent teeth adjacent to the alveolar cleft had erupted at the site of the OCP/Col complex graft. Comparison of the pre- and postoperative bone defects between the 2 groups revealed almost the same extent of bone bridge formation. CONCLUSIONS: OCP/Col grafting could be considered as an alternative to autologous bone grafting as it yielded successful bone bridge formation and facilitated permanent tooth eruption.


Assuntos
Enxerto de Osso Alveolar , Fenda Labial , Fissura Palatina , Transplante Ósseo , Fosfatos de Cálcio/uso terapêutico , Fenda Labial/diagnóstico por imagem , Fenda Labial/cirurgia , Fissura Palatina/diagnóstico por imagem , Fissura Palatina/cirurgia , Colágeno , Seguimentos , Humanos
5.
J Oral Maxillofac Surg ; 78(4): 538-544, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31884076

RESUMO

PURPOSE: Dental anxiety about extraction of impacted mandibular third molars changes the activity of the autonomic nervous system. Thus, to provide safe dental treatment, it is important that a surgeon be aware of a patient's pretreatment anxiety and autonomic nervous system state. Therefore, we analyzed how a scheduled treatment to extract mandibular third molars affects the pretreatment electroencephalogram (EEG), autonomic nervous system, and psychological state of patients. We compared their findings with those of volunteers not scheduled to undergo dental treatment. PATIENTS AND METHODS: The study enrolled 30 patients who were scheduled to undergo impacted mandibular third molar extraction (ie, pretreatment group) and 30 volunteers who were not (ie, control group). Heart rate variability and an EEG were recorded during the experiment. The State Anxiety Inventory-State Anxiety scale (STAI-S) scores were recorded before the procedure. For the statistical analysis, P < .05 was deemed statistically significant. RESULTS: High-frequency (HF) variability was significantly decreased and the STAI-S score was significantly increased in the pretreatment group compared with the control group (P < .01 for both). The low frequency (LF)/HF ratio and alpha-wave activity showed a significant negative correlation on both sides in the control group (P < .01); however, no correlation existed in the pretreatment group. The LF/HF ratio and STAI-S score showed a significant positive correlation in the pretreatment group (P < .05); however, no correlation existed in the control group. CONCLUSIONS: Predicting a patient's autonomic nervous system state before dental treatment based on the EEG was difficult. The STAI-S psychological test was a useful method.


Assuntos
Dente Serotino , Dente Impactado , Sistema Nervoso Autônomo , Ansiedade ao Tratamento Odontológico , Frequência Cardíaca , Humanos , Extração Dentária
6.
J Oral Maxillofac Surg ; 78(2): 215.e1-215.e8, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31654643

RESUMO

PURPOSE: Complications during local anesthesia include increased blood pressure and vasovagal reflex, which are caused by changes in the autonomic nervous system. The commonly used local anesthetic preparations are lidocaine to which the vasoconstrictor epinephrine is added (lidocaine-epinephrine) and prilocaine to which the vasoconstrictor felypressin is added (prilocaine-felypressin); however, their effects during dental treatment are unclear. We examined the effects of these 2 different local anesthetic preparations on the autonomic nervous system and circulation during extraction of the impacted mandibular third molar. MATERIALS AND METHODS: In this randomized controlled trial, 40 female patients scheduled for extraction of an impacted mandibular third molar were randomized to the lidocaine-epinephrine group or prilocaine-felypressin group. Heart rate variability, heart rate, and systolic blood pressure were recorded during the experiment. Descriptive and bivariate statistics were computed, and the P value was set at .05. RESULTS: The low frequency-high frequency ratio was significantly increased in the prilocaine-felypressin group during extraction compared with that in the lidocaine-epinephrine group (P < .05). In the lidocaine-epinephrine group, a significant decrease in the high-frequency component was observed during bone removal and extraction compared with that at rest (P < .05). In both groups, a significant increase in systolic blood pressure was observed during local anesthesia, incision and reflection of the flap, bone removal, separation of the tooth crown, extraction, and suturing compared with that at rest (P < .01). CONCLUSIONS: This study is the first to investigate the differences in the influence of 2 different local anesthetic preparations on the autonomic nervous system during extraction of the mandibular third molar. Changes in circulatory dynamics during tooth extraction with the 2 different local anesthetic preparations were the result of a decrease in parasympathetic nervous activity with lidocaine-epinephrine and an increase in sympathetic nervous activity with prilocaine-felypressin.


Assuntos
Anestesia Dentária , Felipressina , Anestésicos Locais , Sistema Nervoso Autônomo , Epinefrina , Feminino , Humanos , Lidocaína , Dente Serotino , Prilocaína , Vasoconstritores
7.
J Oral Maxillofac Surg ; 77(6): 1153.e1-1153.e8, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30902602

RESUMO

PURPOSE: Pain, anxiety, and nervousness related to dental procedures can cause acute changes in the autonomic nervous system. Music is widely accepted as a relaxation method during dental treatment; however, its effects during dental treatment are unclear. The authors explored the effects of listening to music during extraction of the impacted mandibular third molar on the autonomic nervous system and the psychological state and hypothesized that listening to music would suppress sympathetic nervous activity and decrease anxiety. MATERIALS AND METHODS: In this prospective study, 40 patients scheduled for extraction of an impacted mandibular third molar were randomized into 2 groups: extraction without music (control group) and extraction while listening to music (music group). Heart rate variability was recorded during the experiment, and Modified Dental Anxiety Scale and State-Trait Anxiety Inventory (STAI) scores were recorded before and after the procedure. Descriptive and bivariate statistics were computed and the P value was set at .05. RESULTS: An increased low-to-high frequency ratio was observed in the control group during incision and flap reflection, bone removal, and separation of the tooth crown; the ratio was significantly decreased in the music group during these time points (P < .05). Compared with the control group, the music group had a significantly greater decrease in postoperative STAI State Anxiety scores from preoperative levels (P < .05). CONCLUSIONS: This study suggested that listening to music while undergoing extraction of the impacted mandibular third molar suppresses activity of the sympathetic nerves during incision, flap reflection, bone removal, and separation of the tooth crown and relieves anxiety after treatment. Future studies will focus on the mechanisms involved and methods to prevent the onset of systemic incidents.


Assuntos
Ansiedade ao Tratamento Odontológico , Música , Manejo da Dor , Dente Impactado , Ansiedade , Sistema Nervoso Autônomo , Ansiedade ao Tratamento Odontológico/terapia , Humanos , Dente Serotino , Estudos Prospectivos , Extração Dentária
8.
Cleft Palate Craniofac J ; 56(7): 953-959, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30602307

RESUMO

OBJECTIVE: There is debate on the reliability of the Americleft Yardstick (AY) global nasolabial appearance assessment method. The objective was to analyze the effect of the additional basal view (BV) feature on the reliability of the AY method for Japanese children with complete cleft lip and palate (CUCLP). DESIGN: Blind retrospective analysis of clinical records on 43 patients (5- to 7-year-old) with nonsyndromic CUCLP who underwent primary lip repair from 2005 to 2011. MAIN OUTCOME MEASURE: Color pictures published in AY and Rubin's studies were used as reference pictures. Patients' photographs were cropped and rated on a 5-point scale for the vermilion border (VB), nasolabial frontal (NLF), and nasolabial profile (NLP) according to AY with/without BV assessment by Rubin's methods. Rating was performed twice by 3 oral surgeons. Intra- and inter-rater reliabilities were analyzed using weighted κ, and correlations between BV and other features were analyzed. RESULTS: Overall average assessment scores were 2.742 (0.573) with AY and 2.702 (0.489) with AY+BV methods (P = .728). Average intra-rater reliabilities were 0.605 and 0.611 and average inter-rater reliabilities were 0.525 and 0.48 with AY and AY+BV, respectively. Inter-rater reliability was the lowest for NLP. ρ scores between BV versus VB, NLF, and NLP were 0.025, 0.659, and 0.092, respectively. CONCLUSIONS: Present study demonstrates moderate intra- and inter-rater reliabilities obtained with the AY assessment method for Japanese children with CUCLP. Nasolabial profile standard ambiguity may lead to the poor reliability of AY assessment. Addition of the BV feature does not improve overall reliability.


Assuntos
Fenda Labial , Fissura Palatina , Lábio , Nariz , Criança , Pré-Escolar , Fenda Labial/complicações , Fenda Labial/cirurgia , Fissura Palatina/complicações , Fissura Palatina/cirurgia , Estética , Humanos , Japão , Lábio/anatomia & histologia , Nariz/anatomia & histologia , Fotografação , Reprodutibilidade dos Testes , Estudos Retrospectivos
9.
Cleft Palate Craniofac J ; 56(7): 960-969, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30587013

RESUMO

OBJECTIVE: To visualize and quantitatively analyze facial surface asymmetry following primary cleft lip repair in patients with unilateral cleft lip and palate (UCLP) and to compare this with noncleft controls. DESIGN: Retrospective comparative study. PATIENTS: Twenty-two patients with complete UCLP who underwent primary lip repair from 2009 to 2013 were enrolled in this study. The preserved 3-dimensional (3D) data of 23 healthy Japanese participants with the same age were used as controls. INTERVENTIONS: All patients had received primary labioplasty in accordance with Cronin triangular flap method with orbicular oris muscle reconstruction. MAIN OUTCOME MEASURES: Shadow and zebra images established from moiré images, which were reconstructed from 3D facial data using stereophotogrammetry, were bisected and reversed by the symmetry axes (the middle line of the face). The discrepancies of the gravity and density between cleft and noncleft sides in 2 regions of interest, facial and lip areas, were then calculated and compared with those of healthy participants. RESULTS: In the UCLP group, the mean discrepancies of gravity on shadow and zebra images were 1.76 ± 0.70 and 2.63 ± 1.72 pixels, respectively, in the facial area and 1.31 ± 0.36 and 3.83 ± 2.08 pixels, respectively, in the lip area. There was a significant difference in the mean discrepancies of gravity and density on zebra images in the lip area between the UCLP and control groups. CONCLUSIONS: Our image analysis of digital facial surface asymmetry in patients with UCLP provides visual and quantitative information, and it may contribute to improvements in muscle reconstruction on cleft lip repair.


Assuntos
Fenda Labial , Fissura Palatina , Assimetria Facial , Imageamento Tridimensional , Fenda Labial/complicações , Fenda Labial/cirurgia , Fissura Palatina/complicações , Fissura Palatina/cirurgia , Humanos , Projetos Piloto , Estudos Retrospectivos
10.
J Oral Maxillofac Surg ; 74(7): 1465.e1-1465.e21, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27113318

RESUMO

PURPOSE: A surgical strategy for definitive cleft lip-nasal correction that stably provides symmetric and natural nasal forms has not been established to date. The purpose of this study was to describe our surgical techniques and 3-dimensional (3D) assessment results after the definitive correction of cleft lip-nose deformity using an extended spreader cartilage graft with a cross-lap joint technique to achieve a rigid strut for lower lateral cartilage repositioning to obtain a desirable nasal tip projection. PATIENTS AND METHODS: This study enrolled 14 patients with unilateral cleft lip (UCL) with or without cleft palate and 8 patients with bilateral cleft lip (BCL) with or without cleft palate who underwent definitive nose correction and were followed for 1 to 3 years. All patients were treated by open rhinoplasty, repositioning of the lower lateral cartilage, use of an extended spreader cartilage graft with a cross-lap joint technique for nasal tip support, and medial-upward advancement of nasolabial components with vestibular expansion by a free mucosal graft. For the BCL nose, pedicle flaps from rim skin were used for columella lengthening. Preoperative and postoperative nasal forms were 3-dimensionally analyzed by use of 3D images serially obtained in 12 patients. RESULTS: The postoperative nasal forms were satisfactorily improved in all patients, without any serious postoperative complications. Preoperative and postoperative 3D analyses showed a significantly projected nasal tip in the postoperative noses of patients in both the UCL group and the BCL group (P < .01 and P < .05, respectively) and a sharper nasal tip angle in the BCL group (P < .05). Lateral deviation of the nasal tip was significantly improved in the center of the face in patients in the UCL group (P < .01). CONCLUSIONS: The results of this study suggest that the extended spreader cartilage graft using the cross-lap joint graft technique is useful to provide a desirable projection of the nasal tip in the center of the face on definitive correction of both UCL and BCL nose deformities.


Assuntos
Fenda Labial/cirurgia , Cartilagens Nasais/transplante , Nariz/anormalidades , Nariz/cirurgia , Rinoplastia/métodos , Adolescente , Adulto , Fissura Palatina/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Mucosa Nasal/transplante , Retalhos Cirúrgicos , Resultado do Tratamento
11.
Cleft Palate Craniofac J ; 53(4): 469-80, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26606277

RESUMO

OBJECTIVE: Although the goal of cleft palate (CP) repair is to achieve normal speech, no standard procedure ensures that patients' speech will be at the same level as speech in children without CP. In this study, postoperative speech outcomes following primary CP repair combined with or without a mucosal graft was analyzed in comparison with that of control subjects without CP. PARTICIPANTS: Eighty-two patients who underwent modified V-Y palatoplasty with a mucosal graft on the nasal side for symmetrical muscular reconstruction during 2006-2012 (MG group) and 109 patients who previously underwent modified V-Y palatoplasty without a mucosal graft (non-MG group) were enrolled in this study. Speech data on 37 Japanese subjects without CP were used as a control. MAIN OUTCOME MEASURES: Perceptual rating of resonance and nasal emission and nasometry were carried out for all participants. Furthermore, cephalometric analyses were performed to assess postoperative velopharyngeal morphology and velar movement. RESULTS: Normal resonance was achieved at a significantly higher rate (90.3% of patients) in the MG group than in the non-MG group (68.8%) (P < .01). The mean nasalance scores in the MG group were significantly lower (P < .01) and were almost at the same level as in controls. Cephalometric analyses revealed a greater velar length and velar elevation angle during phonation in the MG group (P < .01 and P < .05, respectively). CONCLUSIONS: Modified V-Y palatoplasty combined with a mucosal graft on the nasal side of the velum for symmetrical muscular reconstruction facilitates speech outcomes for children with cleft palate that are comparable with those for peers without CP.


Assuntos
Cefalometria , Fissura Palatina/cirurgia , Fala , Qualidade da Voz , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Fonação , Resultado do Tratamento
12.
Biochem Biophys Res Commun ; 451(4): 491-6, 2014 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-25124663

RESUMO

Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave interactively via these cytokines to create a microenvironment that leads to the extension of ameloblastomas.


Assuntos
Ameloblastoma/fisiopatologia , Comunicação Celular/fisiologia , Interleucina-1alfa/farmacologia , Interleucina-6/biossíntese , Interleucina-8/biossíntese , Células Estromais/fisiologia , Linhagem Celular Tumoral , Humanos , Neoplasias Maxilomandibulares/fisiopatologia , Receptores de Interleucina-1/antagonistas & inibidores
13.
Materials (Basel) ; 16(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38138766

RESUMO

Autologous bone grafting is the primary method for treating alveolar clefts. However, bone grafting materials are desired as alternatives to autogenous bone to reduce surgical invasiveness. Here, we present an animal study evaluating the effect of carbonate apatite (CA) on the spontaneous eruption of permanent teeth. The bone grafting materials included CA, natural bovine bone (BB), and hydroxyapatite (HA). In 15 8-week-old male beagle dogs, the left mandibular deciduous premolars (DP) two and three were extracted and subsequently filled with CA, BB, and HA. The animals were euthanized after a predetermined number of days, and samples were collected for microcomputed tomography and histological evaluation. Spontaneous eruption of the succeeding permanent teeth (P3 and P4) was observed in the CA group at 14 weeks. Delayed eruption of the succeeding permanent teeth was observed in the BB and HA groups. CA could serve as a viable alternative to autogenous bone for treating alveolar clefts.

14.
Cancers (Basel) ; 15(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36612306

RESUMO

Here, we describe the expression of Bruton's Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, particularly in B cells, we identified the 80 kDa and 65 kDa BTK isoforms in HNSCC, recently described as oncogenic. Importantly, we revealed that both isoforms are products of the same mRNA. By investigating the mechanism regulating oncogenic BTK-p80/p65 expression in HNSSC versus healthy or benign tissues, our data suggests that the epigenetic process of methylation might be responsible for the initiation of BTK-p80/p65 expression in HNSCC. Our findings demonstrate that chemical or genetic abrogation of BTK activity leads to inhibition of tumor progression in terms of proliferation and vascularization in vitro and in vivo. These observations were associated with cell cycle arrest and increased apoptosis and autophagy. Together, these data indicate BTK-p80 and BTK-p65 as novel HNSCC-associated oncogenes. Owing to the fact that abundant BTK expression is a characteristic feature of primary and metastatic HNSCC, targeting BTK activity appears as a promising therapeutic option for HNSCC patients.

15.
Biochem Biophys Rep ; 30: 101233, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35243014

RESUMO

Ameloblastoma is an odontogenic tumor located in the bone jaw with clinical characteristics of extensive bone resorption. It is a locally invasive tumor with a high recurrence rate despite adequate surgical removal. In bone disease, tumors and other cells including osteoblasts, osteoclasts, and osteocytes in the bone microenvironment contribute to the pathogenesis of tumor growth. However, the effect of osteoblasts on ameloblastoma cells is not well-understood, and there has been limited research on interactions between them. This study investigated interactions between ameloblastoma cells and osteoblasts using a human ameloblastoma cell line (AM-3 ameloblastoma cells) and a murine pre-osteoblast cell line (MC3T3-E1 cells). We treated each cell type with the conditioned medium by the other cell type. We analyzed the effect on cytokine production by MC3T3-E1 cells and the production of MMPs by AM-3 cells. Treatment with AM-3-conditioned medium induced inflammatory cytokine production of IL-6, MCP-1, and RANTES from MC3T3-E1 cells. The use of an IL-1 receptor antagonist suppressed the production of these inflammatory cytokines by MC3T3-E1 cells stimulated with AM-3-conditioned medium. The MC3T3-E1-conditioned medium triggered the expression of MMP-2 from AM-3 cells. Furthermore, we have shown that the proliferation and migration activity of AM-3 cells were accelerated by MC3T3-E1 conditioned media. In conclusion, these intercellular signalings between ameloblastoma cells and osteoblasts may play multiple roles in the pathogenesis of ameloblastoma.

16.
J Craniomaxillofac Surg ; 50(1): 86-92, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34657791

RESUMO

The aim of this retrospective cohort study was to compare the recurrence rate and speech outcomes between two techniques for palatal fistula closure of cleft palate (CP). Patients with CP who underwent secondary palatal fistula closure using the single hinge-flap method with double-breasted mattress suture (hinge-flap group) and those who were treated with the conventional sliding palatal flap method (sliding-flap group) were retrospectively evaluated for demographic and perioperative variables. Recurrence rate of palatal fistula, perceptual speech outcomes, and nasalance scores were further reviewed in patients who met the inclusion criteria. A total of 31 patients, 21 in the hinge-flap group and 10 in the sliding-flap group, were included in this study. The fistula recurrence rate in the hinge-flap group (0%) was significantly lower than that in the sliding-flap group (30.0%) (P = 0.027). In the speech assessment, hypernasality and nasalance scores decreased post-operatively in both groups and significance was observed in the hinge-flap group (P = 0.013, P < 0.001, respectively). Articulation disorders were significantly improved in the hinge-flap group (P = 0.001). Within the limitations of the study it seems that the single hinge-flap method with double-breasted mattress suture should be preferred whenever appropriate.


Assuntos
Fissura Palatina , Fístula , Fissura Palatina/cirurgia , Humanos , Fístula Bucal/cirurgia , Estudos Retrospectivos , Fala , Resultado do Tratamento
17.
Pathol Res Pract ; 236: 153991, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35759940

RESUMO

We recently demonstrated that Semaphorin 3 A (Sema3A), the expression of which is negatively regulated by Wnt/ß-catenin signaling, promotes odontogenic epithelial cell proliferation, suggesting the involvement of Sema3A in tooth germ development. Salivary glands have a similar developmental process to tooth germ development, in which reciprocal interactions between the oral epithelium and adjacent mesenchyme proceeds via stimulation with several growth factors; however, the role of Sema3A in the development of salivary glands is unknown. There may thus be a common mechanism between epithelial morphogenesis and pathogenesis; however, the role of Sema3A in salivary gland tumors is also unclear. The current study investigated the involvement of Sema3A in submandibular gland (SMG) development and its expression in adenoid cystic carcinoma (ACC) specimens. Quantitative RT-PCR and immunohistochemical analyses revealed that Sema3A was expressed both in epithelium and in mesenchyme in the initial developmental stages of SMG and their expressions were decreased during the developmental processes. Loss-of-function experiments using an inhibitor revealed that Sema3A was required for AKT activation-mediated cellular growth and formation of cleft and bud in SMG rudiment culture. In addition, Wnt/ß-catenin signaling decreased the Sema3A expression in the rudiment culture. ACC arising from salivary glands frequently exhibits malignant potential. Immunohistochemical analyses of tissue specimens obtained from 10 ACC patients showed that Sema3A was hardly observed in non-tumor regions but was strongly expressed in tumor lesions, especially in myoepithelial neoplastic cells, at high frequencies where phosphorylated AKT expression was frequently detected. These results suggest that the Sema3A-AKT axis promotes cell growth, thereby contributing to morphogenesis and pathogenesis, at least in ACC, of salivary glands.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias das Glândulas Salivares , Carcinoma Adenoide Cístico/patologia , Proliferação de Células , Humanos , Morfogênese , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologia , Semaforina-3A/metabolismo , beta Catenina/metabolismo
18.
Cancer Sci ; 102(3): 540-8, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21205070

RESUMO

Wnts are secreted ligands that consist of 19 members in humans, regulate cell proliferation, differentiation, motility and fate in many stages including the embryonic stage and tumorigenesis. Wnts bind to cell surface receptors named Frizzleds and LRPs, and transduce their signals through ß-catenin-dependent and -independent intracellular pathways. Gliomas are one of the most common intracranial tumors. Gliomas exhibit a progression associated with widespread infiltration into surrounding neuronal tissues. However, the molecular mechanisms that stimulate the invasion of glioma cells are not fully understood. We established two cell lines from human glioma cases and analyzed the expression of all Wnt and Frizzled members in these cell lines and other well-known glioma cell lines by real-time PCR study. The mRNA of Wnt-5a and -7b and Frizzled-2, -6 and -7 were overexpressed in glioma cells. The elevation of Wnt-5a expression was most remarkable. Although Wnt-5a is reported to have oncogenic and antioncogenic activity in several cancers, the role of Wnt-5a signaling in human glioma cells remains unclear. Immunohistochemical study also revealed high expression of Wnt-5a in 26 (79%) of 33 human glioma cases. The positivity of Wnt-5a expression was correlated with the clinical grade. Knockdown of Wnt-5a expression suppressed migration, invasion and expression of matrix metalloproteinase-2 of glioma cells. Reciprocally, treatment with purified Wnt-5a ligand resulted in stimulation of cell migration and invasion. MMP-2 inhibitor suppressed the Wnt-5a-dependent invasion of U251 cells. These results suggested that Wnt-5a is not only a prognostic factor but also a therapeutic target molecule in gliomas for preventing tumor cell infiltration.


Assuntos
Neoplasias Encefálicas/patologia , Movimento Celular , Glioma/patologia , Metaloproteinase 2 da Matriz/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Transdução de Sinais/fisiologia , Proteínas Wnt/fisiologia , Linhagem Celular Tumoral , Humanos , Imuno-Histoquímica , Inibidores de Metaloproteinases de Matriz , Invasividade Neoplásica , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/análise , Proteínas Wnt/análise , Proteínas Wnt/genética , Proteína Wnt-5a , beta Catenina/análise
19.
Cureus ; 13(11): e19433, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34909338

RESUMO

Recently, two cases of oral herpes zoster (HZ) following COVID-19 vaccines were reported. It was suggested that COVID-19 vaccine-related oral HZ cases might be missed or misdiagnosed as stomatitis or isolated oral herpes. In this report, five cases of oral HZ following COVID-19 vaccinations are presented. Four cases were observed on the hard palate (V2), and one case was found on the mandible (V3). Four patients did not receive any treatment for their oral HZ, but one patient also had skin reactions on her right orbit and ear and was thus treated with an antiviral drug. As these cases were seen during such a short period of time and in one practice, the relationship with the COVID-19 vaccination appears to be related.

20.
Photobiomodul Photomed Laser Surg ; 39(9): 612-616, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33539258

RESUMO

Objective: To evaluate the healing of open upper lip vermillion wounds irradiated with CO2 laser immediately after injury. Background: There are reports of using CO2 laser therapy on healed wounds for scar tissue reduction. However, limited data exist regarding its use immediately after an injury. Thus, the role of CO2 laser in wound healing remains unclear. Methods: Two patients with open upper lip vermillion wounds were treated using CO2 laser irradiation to the area postsuturing. Results: Good functional and aesthetic results were obtained from the therapy, with no postoperative pain complaints or infection. Conclusions: CO2 laser irradiation, performed immediately after an injury, could be an effective treatment option for open vermillion wounds.


Assuntos
Dióxido de Carbono , Lasers de Gás , Humanos , Lasers de Gás/uso terapêutico , Lábio/cirurgia , Pele , Cicatrização
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