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The discovery of SARS-CoV-2 RNA in the periodontal tissues of patients who tested positive for COVID-19, 24 days post the initial symptom onset, indicates the oral cavity could serve as a viral reservoir. This research aims to investigate the antiviral capabilities of Ovatodiolide, introducing a novel periodontal ligament organoid model for the study of SARS-CoV-2. We have successfully established a reliable and expandable organoid culture from the human periodontal ligament, showcasing characteristics typical of epithelial stem cells. This organoid model enables us to delve into the lesser-known aspects of dental epithelial stem cell biology and their interactions with viruses and oral tissues. We conducted a series of in vitro and ex vivo studies to examine the inhibitory impacts of Ova on SARS-CoV-2. Our findings indicate that Ovatodiolide molecules can bind effectively to the NRP1 active domain. Our study identifies potential interaction sites for Ovatodiolide (OVA) within the b1 domain of the NRP1 receptor. We generated point mutations at this site, resulting in three variants: Y25A, T44A, and a double mutation Y25A/T44A. While these mutations did not alter the binding activity of the spike protein, they did impact the concentration of OVA required for inhibition. The inhibitory concentrations for these variants are 15 µM for Y25A, 15.2 µM for T44A, and 25 µM for the double mutant Y25A/T44A. In addition, in vitro inhibition experiments demonstrate that the EC50 of Ova against the main protease (Mpro) of the SARS-CoV-2 virus is 7.316 µM. Our in vitro studies and the use of the periodontal ligament organoid model highlight Ovatodiolide's potential as a small molecule therapeutic agent that impedes the virus's ability to bind to the Neuropilin-1 receptor on host cells. The research uncovers various pathways and biochemical strategies through which Ovatodiolide may function as an effective antiviral small molecule drug.
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Tratamento Farmacológico da COVID-19 , Neuropilina-1 , Organoides , Ligamento Periodontal , SARS-CoV-2 , Ligamento Periodontal/metabolismo , Ligamento Periodontal/citologia , Ligamento Periodontal/virologia , Humanos , Organoides/virologia , Organoides/metabolismo , Organoides/efeitos dos fármacos , Neuropilina-1/metabolismo , SARS-CoV-2/efeitos dos fármacos , Antivirais/farmacologia , COVID-19/metabolismo , COVID-19/virologia , Diterpenos/farmacologiaRESUMO
The present study investigated the in vivo bone-forming efficacy of an innovative titanium (Ti) dental implant combined with a collagen sponge containing recombinant human bone morphogenetic protein-2 (BMP-2) in a pig model. Two different concentrations of BMP-2 (20 and 40 µg/mL) were incorporated into collagen sponges and placed at the bottom of Ti dental implants. The investigated implants were inserted into the edentulous ridge at the canine-premolar regions of Lanyu small-ear pigs, which were then euthanized at weeks 1, 2, 4, 8, and 12 post-implantation. Specimens containing the implants and surrounding bone tissue were collected for histological evaluation of their bone-to-implant contact (BIC) ratios and calculation of maximum torques using removal torque measurement. Analytical results showed that the control and BMP-2-loaded implants presented good implant stability and bone healing for all testing durations. After 1 week of healing, the BMP-2-loaded implants with a concentration of 20 µg/mL exhibited the highest BIC ratios, ranging from 58% to 76%, among all groups (p = 0.034). Additionally, they also possessed the highest removal torque values (50.1 ± 1.3 N-cm) throughout the 8-week healing period. The BMP-2-loaded implants not only displayed excellent in vivo biocompatibility but also presented superior osteoinductive performance. Therefore, these findings demonstrate that BMP-2 delivered through a collagen sponge can potentially enhance the early-stage osseointegration of Ti dental implants.
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Oral squamous cell carcinoma (OSCC) is a prevalent type of oral cancer. While therapeutic innovations have made strides, radioresistance persists as a significant hindrance in OSCC treatment. Despite identifying numerous targets that could potentially suppress the oncogenic attributes of OSCC, the exploration of oncogenic protein kinases for cancer therapy remains limited. Consequently, the functions of many kinase proteins in OSCC continue to be largely undetermined. In this research, we aim to disclose protein kinases that target OSCC and elaborate their roles and molecular mechanisms. Through the examination of the kinome library of radiotherapy-resistant/sensitive OSCC cell lines (HN12 and SAS), we identified a key gene, the tyrosine phosphorylation-regulated kinase 3 (DYRK3), a member of the DYRK family. We developed an in vitro cell model, composed of radiation-resistant OSCC, to scrutinize the clinical implications and contributions of DYRK3 and phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS) signaling in OSCC. This investigation involves bioinformatics and human tissue arrays. We seek to comprehend the role of DYRK3 and PAICS signaling in the development of OSCC and its resistance to radiotherapy. Various in vitro assays are utilized to reveal the essential molecular mechanism behind radiotherapy resistance in connection with the DYRK3 and PAICS interaction. In our study, we quantified the concentrations of DYRK3 and PAICS proteins and tracked the expression levels of key pluripotency markers, particularly PPAT. Furthermore, we extended our investigation to include an analysis of Glut-1, a gene recognized for its linkage to radioresistance in oral squamous cell carcinoma (OSCC). Furthermore, we conducted an in vivo study to affirm the impact of DYRK3 and PAICS on tumor growth and radiotherapy resistance, focusing particularly on the role of DYRK3 in the radiotherapy resistance pathway. This focus leads us to identify new therapeutic agents that can combat radiotherapy resistance by inhibiting DYRK3 (GSK-626616). Our in vitro models showed that inhibiting PAICS disrupts purinosome formation and influences the survival rate of radiation-resistant OSCC cell lines. These outcomes underscore the pivotal role of the DYRK3/PAICS axis in directing OSCC radiotherapy resistance pathways and, as a result, influencing OSCC progression or therapy resistance. Our findings also reveal a significant correlation between DYRK3 expression and the PAICS enzyme in OSCC radiotherapy resistance.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/radioterapia , Neoplasias Bucais/metabolismo , Linhagem Celular Tumoral , Neoplasias de Cabeça e Pescoço/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas Tirosina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
Declines in oral consumption and swallowing function are common reasons which may elevate the risk of malnutrition in the older adults. This study aimed to provide valuable information and contribute to the existing body of knowledge in this field as well as highlight the importance of a comprehensive assessment of oral health, swallowing function, and nutritional status in long-term care residents. This was a cross-sectional study. Thirty-nine participants were recruited from a nursing home. The comprehensive assessment was evaluated in participants, including oral health (Oral Health Assessment Tool (OHAT)), swallowing function (Functional Oral Intake Scale (FOIS) and Eating Assessment Tool (EAT)-10), and nutritional status (Mini Nutritional Assessment-Short Form (MNA-SF). The average age of participants was 80.4 ± 11.7 years, and 46% of these older adults were found to be at the risk of malnutrition. There was a negative correlation between the OHAT and MNA-SF scores. In addition, subjects with poor oral health (OHAT score = 5~8), oral consumption of a modified diet (FOIS score = 4~6), and reduced swallowing function (EAT-10 score ≥ 3) were more likely to be at risk of malnutrition. A comprehensive evaluation of oral health and swallowing function was closely connected with the nutritional status of older nursing home dwellers.
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Desnutrição , Estado Nutricional , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Deglutição , Saúde Bucal , Desnutrição/epidemiologia , Casas de Saúde , Avaliação GeriátricaRESUMO
ABSTRACT: Although dental treatment with sedation is performed increasingly in special needs patients, data on adding midazolam to intravenous propofol sedation are very limited for this group. The purpose of this study was to identify the factors and procedure time associated with the use of intravenous sedation with propofol alone or propofol combined with midazolam in dental patients with special needs.This was a retrospective data analysis. The sedation medications and relevant covariates, including demographic parameters, disability levels, oral health conditions, dental procedures, treatment time, and side effects, of 718 patients with special needs were collected between April 2013 and September 2014. The unfavorable side effects by sedation types were reported. Factors associated with procedure time and the sedation medications were assessed with multiple logistic regression analyses.Of 718 patients, 8 patients experienced unfavorable side effects (vomiting, sleepiness, or emotional disturbance) after the dental procedures; the rate was 0.6% in the 509 patients who received propofol only. In 209 patients who received propofol and midazolam, 2.4% experienced the side effects. Sedation time was associated with body mass index (BMI)â<â25 (adjusted odds ratio [aOR]â=â1.45, 95% confidence interval [CI]: 1.04-2.04) and the performance of multiple dental procedures (aORâ=â1.44, 95% CI: 1.06-1.97) but not associated with the sedation types. A significant odds ratio for the combined use of propofol and midazolam was shown for adolescents (aORâ=â2.22, 95% CI: 1.28-3.86), men (aORâ=â2.05, 95% CI: 1.41-2.98), patients with cognitive impairment (aORâ=â1.99, 95% CI: 1.21-3.29), and patients undergoing scaling procedures (aORâ=â1.64, 95% CI: 1.13-2.39).With the acceptable side effects of the use of propofol alone and propofol combined with midazolam, multiple dental procedures increase the sedation time and the factors associated with the combined use of propofol and midazolam are younger age, male sex, recognition problems, and the type dental procedure in the dental treatment of patients with special needs.
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Sedação Consciente/estatística & dados numéricos , Assistência Odontológica/normas , Midazolam/administração & dosagem , Propofol/administração & dosagem , Adjuvantes Anestésicos/administração & dosagem , Adjuvantes Anestésicos/efeitos adversos , Administração Intravenosa , Adolescente , Adulto , Sintomas Afetivos/induzido quimicamente , Criança , Disfunção Cognitiva/complicações , Sedação Consciente/efeitos adversos , Assistência Odontológica/estatística & dados numéricos , Raspagem Dentária/estatística & dados numéricos , Combinação de Medicamentos , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Masculino , Midazolam/efeitos adversos , Pessoa de Meia-Idade , Propofol/efeitos adversos , Estudos Retrospectivos , Sonolência , Vômito/induzido quimicamenteRESUMO
Oral squamous cell carcinoma (OSCC) is among the most prevalent cancers of the head and neck. This study revealed that isoorientin attenuates OSCC cell stemness and epithelial-mesenchymal transition potential through the inhibition of JAK/signal transducer and activator of transcription 3 (STAT3) and Wnt/ß-catenin signaling in cell lines. Our findings indicated that isoorientin is a potential inhibitor of ß-catenin/STAT3 in vitro and in vivo. We analyzed possible synergism between isoorientin and cisplatin in OSCC. A sulforhodamine B assay, colony formation assay, tumorsphere-formation assay, and Wnt reporter activity assay were used for determining cell invasion, cell migration, drug cytotoxicity, and cell viability with potential molecular mechanisms in vitro. Isoorientin reduced the expression of p-STAT3, ß-catenin, and p-GSK3 as well as downstream effectors TCF1/TCF7 and LEF1 and significantly reduced ß-catenin colocalization in the nucleus. Isoorientin markedly strengthened the cytotoxic effects of cisplatin against SAS and SCC-25. Therefore, combining isoorientin and cisplatin treatments can potentially improve the anticancer effect of cisplatin. Isoorientin inhibited the tumorigenicity and growth of OSCC through the abrogation of Wnt/ß-catenin/STAT3 signaling in vivo. Thus, isoorientin disrupted the ß-catenin signaling pathway through the inactivation of STAT3 signaling. In conclusion, targeting OSCC-SC-mediated stemness with isoorientin to eradicate OSCC-SCs may be an effective strategy for preventing relapse and metastasis of OSCC and providing long-term survival benefits.
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Carcinoma de Células Escamosas/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Luteolina/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Luteolina/administração & dosagem , Luteolina/química , Camundongos , Estrutura Molecular , Neoplasias Experimentais , Células-Tronco Neoplásicas , Interferência de RNA , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , beta Catenina/metabolismoRESUMO
Locally advanced oral squamous cell carcinoma (OSCC) requires multimodal therapy, including surgery and concurrent chemoradiotherapy (CCRT). CCRT-resistant and recurrent cancer has a poor prognosis. We investigated the effects of Bruton's tyrosine kinase (BTK) on CCRT-resistant OSCC tissues. The effect of ibrutinib, a first-in-class BTK inhibitor, was tested on stem cell-like OSCC tumorspheres. A tissue array was constructed using tissue samples from 70 patients with OSCC. Human OSCC cell lines, SAS, TW2.6 and HSC-3, were examined. Wound healing, Matrigel invasion, and tumorsphere formation assays, as well as immunofluorescence analysis and flow cytometry, were used to investigate the effects of BTK knockdown (shBTK), ibrutinib, cisplatin, and ibrutinib/cisplatin combination on OSCC cells. We demonstrated that BTK was aberrantly highly expressed in the clinical CCRT-resistant OSCC tissue array, which resulted in poor overall survival in our local Tri-Service General Hospital and freely accessible TCGA OSCC cohorts. shBTK significantly downregulated the stemness markers Nanog, CD133, T cell immunoglobulin-3 (TIM-3), and Krüppel-like factor 4 (KLF4) in SAS tumorspheres and attenuated OSCC cell migration and colony formation. Ibrutinib reduced the number of aldehyde dehydrogenase (ALDH)-rich OSCC cells and reduced tumorsphere formation, migration, and invasion in a dose-dependent manner. Compared with ibrutinib or cisplatin monotherapy, the ibrutinib/cisplatin combination significantly reduced the formation of ALDH + OSCC tumorspheres and enhanced apoptosis. These results demonstrate that ibrutinib effectively inhibits the CSCs-like phenotype of OSCC cells through dysregulation of BTK/CD133 signaling. The ibrutinib/cisplatin combination may be considered for future clinical use.
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Bony injuries lead to compromised skeletal functional ability which further increase in aging population due to decreased bone mineral density. Therefore, we aimed to investigate the therapeutic potential of platelet-derived biomaterials (PDB) against bone injury. Specifically, we assessed the impact of PDB on osteo-inductive characteristics and migration of mouse embryonic fibroblasts (MEFs). Osteogenic lineage, matrix mineralization and cell migration were determined by gene markers (RUNX2, OPN and OCN), alizarin Red S staining, and migration markers (FAK, pFAK and Src) and EMT markers, respectively. The therapeutic impact of TGF-ß1, a key component of PDB, was confirmed by employing inhibitor of TGF-ß receptor I (Ti). Molecular imaging-based in vivo cellular migration in mice was determined by establishing bone injury at right femurs. Results showed that PDB markedly increased expression of osteogenic markers, matrix mineralization, migration and EMT markers, revealing higher osteogenic and migratory potential of PDB-treated MEFs. In vivo cell migration was manifested by expression of migratory factors, SDF-1 and CXCR4. Compared to control, PDB-treated mice exhibited higher bone density and volume. Ti treatment inhibited both migration and osteogenic potential of MEFs, affirming impact of TGF-ß1. Collectively, our study clearly indicated PDB-rescued bone injury through enhancing migratory potential of MEFs and osteogenesis.
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Materiais Biocompatíveis , Plaquetas/metabolismo , Regeneração Óssea , Movimento Celular , Fêmur/lesões , Fibroblastos/metabolismo , Osteogênese , Fator de Crescimento Transformador beta1/metabolismo , Animais , Densidade Óssea , Calcificação Fisiológica , Linhagem da Célula , Quimiocina CXCL12 , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Transição Epitelial-Mesenquimal , Fêmur/metabolismo , Fêmur/patologia , Fibroblastos/citologia , Quinase 1 de Adesão Focal , Técnicas In Vitro , Camundongos , Células NIH 3T3 , Osteocalcina/genética , Osteopontina/genética , Receptores CXCR4 , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Quinases da Família srcRESUMO
Traditional Chinese medicines Antler's extract (A) and Ganoderma lucidum (G) and Antrodia Camphorata (A) have been known to individually contain a plethora of bioactive factors including triterpenoids, polysaccharides etc., exerting various curative impacts such as anti-inflammatory, anti-oxidative, anti-atherosclerotic and anti-viral activities. However, their combinatorial therapeutic efficacy for oral cancer has not been investigated. Hence, we synthesized a robust cocktail called AGA and investigated its anti-oral cancer potential in vitro and in vivo. An MTT assay revealed the IC50 of AGA to be about 15 mg at 72 h. Therefore, 10 mg and 20 mg doses were selected to study the effect of AGA. The AGA significantly inhibited proliferation of oral cancer cells (HSC3, SAS, and OECM-1) in a dose- and time-dependent manner. AGA retarded cell cycle regulators (CDK4, CDK6, cyclin A, B1, D1 and E2) and apoptosis inhibitory protein Bcl-2, but enhanced pro-apoptotic protein Bax and a higher percentage of cells in Sub-G1 phase. Mechanistically, AGA suppressed all EMT markers; consequently, it decreased the migration ability of cancer cells. AGA significantly reduced xenograft tumor growth in nude mice with no adverse events in liver and renal toxicity. Conclusively, AGA strongly inhibited oral cancer through inducing apoptosis and inhibiting the migration and promotion of cell cycle arrest at subG1 phase, which may be mediated primarily via cocktail-contained triterpenoids and polysaccharides.
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The accuracy of static guided implant surgery (sGIS) using conventional planning workflow has been extensively examined; however, more information is required to justify the application of fully digital planning protocol. The purpose of this study was to investigate the clinical accuracy of sGIS with a fully digital planning workflow. Twenty-one partially edentulous patients were enrolled in this prospective study. Cone-beam computed tomography (CBCT) and intraoral scans were taken and superimposed by matching the dental surface images directly (surface registration protocol) or by matching fiducial markers on a stereolithographic (SLA) radiographic template fabricated from the digital data of the intraoral scan (fiducial marker registration protocol). Virtual implant treatment plans were then determined, and tooth-supported SLA surgical guides were fabricated according to the plans. Twenty-six implant surgeries were performed via the surgical guide by one surgeon. Pre- and post-operative CBCT images were superimposed, and the positional and angular deviations between placed and planned implants were measured with metrology software. A total of 43 fully guided implants were placed, in which 25 implants were planned with the surface registration protocol. Implants planned based on the surface registration protocol had a larger mean angular deviation than the fiducial marker registration protocol. No significant differences were found for any deviations of the examined variables. Within the limits of this study, we concluded that the clinical accuracy of the sGIS planned with a fully digital workflow was consistent with the conventional workflow for partially edentulous patients.
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INTRODUCTION: This study aimed to compare the attitudes towards people with dementia, knowledge of dementia and ageism amongst Taiwanese and Japanese dental hygiene students. MATERIAL AND METHODS: A total of 328 students participated in this cross-sectional study. Attitudes, knowledge and ageism were assessed using self-reports. Participants' association with older adults or persons with dementia was also assessed. Primary outcomes included attitude, knowledge and ageism amongst students. Secondary outcomes were the factors related to their desire to work with persons with dementia. RESULTS: Data of 175 Taiwanese and 91 Japanese students were analysed. There were significantly more Japanese (69.2%) than Taiwanese (33.2%) students without experience of cohabitation with older adults. More Taiwanese (45.1%) than Japanese students (30.8%) gave a neutral answer regarding their desire to work with persons with dementia. Japanese students scored significantly higher on the attitude and ageism scales than did Taiwanese students; however, the scores of knowledge assessment were approximately the same. Attitude or ageism did not correlate with knowledge amongst students from either country. Logistic regression analysis revealed that the desire to work with persons having dementia was related to ageism and the relationship with these people, irrespective of country. CONCLUSION: Although the students had comparable levels of knowledge, there existed significant difference in the attitudes and the degree of ageism between students from Taiwan vs Japan. This finding may prompt improvement of education on dementia, where differences in nationality and lifestyle, including the rate of ageing and family structure, are taken into consideration.
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Etarismo , Demência , Idoso , Atitude do Pessoal de Saúde , Estudos Transversais , Educação em Odontologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Japão , TaiwanRESUMO
: Elevated activity of sterol regulatory element-binding protein 1 (SREBP1) has been implicated in the tumorigenesis of different cancer types. However, the functional roles of SREBP1 in esophageal cancer are not well appreciated. Here, we aimed to investigate the therapeutic potential of SREBP1 and associated signaling in esophageal cancer. Our initial bioinformatics analyses showed that SREBP1 expression was overexpressed in esophageal tumors and correlated with a significantly lower overall survival rate in patients. Additionally, tumor suppressor miR-142-5p was predicted to target SREBP1/ZEB1 and a lower miR-142-5p was correlated with poor prognosis. We then performed in vitro experiments and showed that overexpressing SREBP1 in OE33 cell line led to increased abilities of colony formation, migration, and invasion; the opposite was observed in SREBP1-silenced OE21cells and SREBP1-silencing was accompanied by the reduced mesenchymal markers, including vimentin (Vim) and ZEB1, while E-cadherin and tumor suppressor miR-142-5p were increased. Subsequently, we first demonstrated that both SREBP1 and ZEB1 were potential targets of miR-142-5p, followed by the examination of the regulatory circuit of miR-142-5p and SREBP1/ZEB1. We observed that increased miR-142-5p level led to the reduced tumorigenic properties, such as migration and tumor sphere formation, and both observations were accompanied by the reduction of ZEB1 and SREBP1, and increase of E-cadherin. We then explored the potential therapeutic agent targeting SREBP1-associated signaling by testing fatostatin (4-hydroxytamoxifen, an active metabolite of tamoxifen). We found that fatostatin suppressed the cell viability of OE21 and OE33 cells and tumor spheres. Interestingly, fatostatin treatment reduced CD133+ population in both OE21 and OE33 cells in concert of increased miR-142-5p level. Finally, we evaluated the efficacy of fatostatin using a xenograft mouse model. Mice treated with fatostatin showed a significantly lower tumor burden and better survival rate as compared to their control counterparts. The treatment of fatostatin resulted in the reduced staining of SREBP1, ZEB1, and Vim, while E-cadherin and miR-142-5p were increased. In summary, we showed that increased SREBP1 and reduced miR-142-5p were associated with increased tumorigenic properties of esophageal cancer cells and poor prognosis. Preclinical tests showed that suppression of SREBP1 using fatostatin led to the reduced malignant phenotype of esophageal cancer via the reduction of EMT markers and increased tumor suppressor, miR-142-5p. Further investigation is warranted for the clinical use of fatostatin for the treatment of esophageal malignancy.
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Neoplasias Esofágicas/genética , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , Piridinas/administração & dosagem , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Tiazóis/administração & dosagem , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Piridinas/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Análise de Sobrevida , Tiazóis/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The purpose of the present study was to investigate the effect of local hydroxyapatite (HA) combined with extracted sea cucumber (Stichopus hermanni) collagen as a promising bone graft substitute on bone remodeling. Fourier-transform infrared spectroscopy, X-ray diffractometry, transmission electron microscopy, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and Sprague-Dawley rat model were used to characterize the microstructure, in vitro cytotoxicity, and in vivo bone-healing properties of the investigated biocomposite material. Analytical results found that the hydrothermal reaction-synthesized local HA had a hexagonal close-packed structure. The addition of extracted S. hermanni collagen did not influence the microstructure and functional groups of the local HA. Moreover, the MTT assay indicated that the investigated biocomposite material possessed a good in vitro biocompatibility. The in vivo animal study also revealed that the investigated biocomposite material exhibited the highest number of osteoblasts after 14 days of healing. Therefore, the results demonstrate that the local HA combined with extracted S. hermanni collagen could potentially enhance osteoblast formation in promoting bone healing and regeneration.
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Materiais Biocompatíveis/química , Regeneração Óssea , Substitutos Ósseos/química , Transplante Ósseo , Osso e Ossos , Animais , Remodelação Óssea , Sobrevivência Celular/efeitos dos fármacos , Colágeno/farmacologia , Durapatita/química , Durapatita/farmacologia , Masculino , Microscopia Eletrônica de Transmissão , Modelos Animais , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Pepinos-do-Mar/química , Espectroscopia de Infravermelho com Transformada de Fourier , Engenharia Tecidual/métodos , Cicatrização , Difração de Raios XRESUMO
FAT atypical cadherin 1 (FAT1) regulates cell-cell adhesion and extracellular matrix architecture, while acting as tumor suppressor or oncogene, context-dependently. Despite implication of FAT1 in several malignancies, its role in oral squamous cell carcinoma (OSCC) remains unclear. Herein, we document the driver-oncogene role of FAT1, and its mediation of cell-death evasion, proliferation, oncogenicity, and chemoresistance in OSCC. In-silica analyses indicate FAT1 mutations are frequent and drive head-neck SCC, with enhanced expression defining high-risk population and poor prognosis. We demonstrated aberrant FAT1 mRNA and protein expression in OSCC compared with non-cancer tissues, whereas loss-of-FAT1-function attenuates human primary SAS and metastatic HSC-3 OSCC cell viability, without affecting normal primary human gingival fibroblast cells. shFAT1 suppressed PCNA and upregulated BAX/BCL2 ratio in SAS and HSC-3 cells. Moreover, compared with wild-type cells, shFAT1 concomitantly impaired HSC-3 cell migration, invasion, and clonogenicity. Interestingly, while over-expressed FAT1 characterized cisplatin-resistance (CispR), shFAT1 synchronously re-sensitized CispR cells to cisplatin, enhanced glutathione (GSH)/GSH synthetase (GSS)-mediated oxidative stress and deregulated LRP5/WNT2 signaling. Concisely, FAT1 is an actionable driver-oncogene in OSCC and targeting FAT1 in patients with erstwhile cisplatin-resistant OSCC is therapeutically promising.
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The aim of the present study was to investigate the biomechanical behaviors of the pre-shaped titanium (PS-Ti) cranial mesh implants with different pore structures and thicknesses as well as the surface characteristics of the three-dimensional printed Ti (3DP-Ti) cranial mesh implant. The biomechanical behaviors of the PS-Ti cranial mesh implants with different pore structures (square, circular and triangular) and thicknesses (0.2, 0.6 and 1â¯mm) were simulated using finite element analysis. Surface properties of the 3DP-Ti cranial mesh implant were performed by means of scanning electron microscopy, X-ray diffraction and static contact angle goniometer. It was found that the stress distribution and peak Von Mises stress of the PS-Ti cranial mesh implants significantly decreased at the thickness of 1â¯mm. The PS-Ti mesh implant with the circular pore structure created a relatively lower Von Mises stress on the bone defect area as compared to the PS-Ti mesh implant with the triangular pore structure and square pore structure. Moreover, the spherical-like Ti particle structures were formed on the surface of the 3DP-Ti cranial mesh implant. The microstructure of the 3DP-Ti mesh implant was composed of α and rutile-TiO2 phases. For wettability evaluation, the 3DP-Ti cranial mesh implant possessed a good hydrophilicity surface. Therefore, the 3DP-Ti cranial mesh implant with the thickness of 1â¯mm and circular pore structure is a promising biomaterial for cranioplasty surgery applications.
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Craniotomia/instrumentação , Impressão Tridimensional , Telas Cirúrgicas , Titânio , Materiais Biocompatíveis/química , Fenômenos Biomecânicos , Módulo de Elasticidade , Análise de Elementos Finitos , Humanos , Teste de Materiais , Procedimentos de Cirurgia Plástica/instrumentação , Procedimentos de Cirurgia Plástica/métodos , Crânio/diagnóstico por imagem , Crânio/cirurgia , Propriedades de Superfície , Difração de Raios XRESUMO
The aim of this study was to investigate the relationship of matriptase-2 expression with the clinicopathologic characteristics, the histologic grade, and patient survival in oral squamous-cell carcinoma (OSCC). Immunohistochemical analysis of matriptase-2 expression was performed in 102 surgical specimens from patients with OSCC. The immunohistochemical results were further verified by quantitative real-time reverse transcription-polymerase chain reaction. The immunostaining intensity was scored on a scale ranging from 0 (absence of staining) to 3 (intense staining). The distribution score was determined by the percentage of stained cells on a scale ranging from 0 (<5%), 1 (5% to 25%), 2 (25% to 50%), 3 (50% to 75%), to 4 (75% to 100%). The immunoscore of matriptase-2 expression was the product of the above 2 scores and ranged from 0 to 12 for analysis. Faint matriptase-2 immunostaining was observed in the non-neoplastic oral mucosal epithelia. The matriptase-2 immunoscore was significantly higher in well-differentiated OSCCs than in poorly differentiated tumors (P=0.001). Moreover, a reduced matriptase-2 immunoscore was inversely correlated with the tumor size (P=0.017), a positive nodal stage (P=0.008), distant metastasis (P=0.032), and a late clinical stage (P=0.001). A lower immunoscore of matriptase-2 expression revealed a significant association with poor survival (P=0.003). Our results demonstrate that the inverse expression of matriptase-2 correlates with tumor progression and an advanced TNM stage, and has a poor prognosis in patients with OSCC. These findings suggest that the expression of matriptase-2 may be both a prognostic marker and a potential therapeutic target for this cancer.
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Biomarcadores Tumorais/biossíntese , Carcinoma de Células Escamosas , Regulação para Baixo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/biossíntese , Neoplasias Bucais , Proteínas de Neoplasias/biossíntese , Serina Endopeptidases/biossíntese , Adulto , Idoso , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/enzimologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Taxa de SobrevidaRESUMO
BACKGROUND: Mutans streptococci (MS) are the major causative bacteria involved in human dental decay. Habitual consumption of xylitol has been proved to reduce MS levels in saliva and plaque. AIM: To evaluate the effect of the maternal use of xylitol gum on MS reduction in infants. DESIGN: A structured literature review and meta-analysis. A random effects model was used to assess the relative risks of the incidence of MS in the saliva or plaque of children who were 6, 9, 12, 18, and 24 months old. RESULTS: We reviewed 11 RCTs derived from 5 research teams that included 601 mothers. Our results indicated that the incidence of MS in the saliva or plaque of the infants was significantly reduced in the xylitol group (risk ratio: 0.54; 95% confidence interval: 0.39-0.73, at 12-18 months) and (risk ratio: 0.56; 95% confidence interval: 0.40-0.79, at 36 months) compared with the control groups. The long-term effect of maternal xylitol gum exposure on their children's dental caries was controversial. CONCLUSION: Habitual xylitol consumption by mothers with high MS levels was associated with a significant reduction in the mother-child transmission of salivary MS.
Assuntos
Goma de Mascar , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mães , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/transmissão , Streptococcus mutans/efeitos dos fármacos , Edulcorantes/farmacologia , Xilitol/farmacologia , Placa Dentária/microbiologia , Feminino , Humanos , Lactente , Ensaios Clínicos Controlados Aleatórios como Assunto , Saliva/microbiologiaRESUMO
OBJECTIVES: SLAffinity is the hybrid topography consisting of micropits and nanoporous TiO2 layers through electrochemical oxidation to mimic the natural bony environment. The aim of this study was to examine the rate of osseointegration in animal models and to further investigate the stability for implants with SLAffinity-treated surface in the clinical trial. MATERIALS AND METHODS: Implants were installed in the mandibular canine-premolar area of 12 miniature pigs. Each pig received 2 implants with the same shapes but with different chemical surfaces. In the clinical trial, 25 patients were included. Each patient received 1 SLAffinity-treated implant on the posterior area of either arch. Resonance frequency analysis and computed tomography were assessed weekly over the first 12 weeks after implant placement. RESULTS: The results found that surface treatment did affect the bone-to-implant contact (BIC) significantly. Comparison of BIC at 3 weeks in animal study showed that the SLAffinity-treated implants presented significantly higher values than machine surface implants. SLAffinity-treated implants also proved clinically successful through 12 months, ready for prosthodontic restoration. CONCLUSION: The effect of SLAffinity treatments enhanced osseointegration significantly, especially at early stages of bone healing. Clinical trial finding, furthermore, ensured that the SLAffinity treatment was a reliable surface modification alternative.
Assuntos
Implantação Dentária Endóssea/instrumentação , Implantação Dentária Endóssea/métodos , Implantes Dentários , Planejamento de Prótese Dentária , Osseointegração/fisiologia , Propriedades de Superfície , Adulto , Animais , Materiais Biocompatíveis , Densidade Óssea , Modelos Animais de Doenças , Feminino , Humanos , Implantes Experimentais , Masculino , Suínos , Porco Miniatura , Titânio , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The purpose of this study was to investigate osseointegration and bone stress resulted during the first 3 months after the installation of functional implants modified with bioactive oxide. METHODS: Several studies have investigated finite element models for dental implants; however, only a few have examined a model for the implants during different stages of osseointegration. In this study, mandible models were reconstructed using computer tomographic data, and bone qualities and stress distributions were investigated as well. RESULTS: Bone quality increased rapidly within the 3-month bone healing time. Data analysis indicated that the bone stresses increased with the progress of osseointegration, and the maximum stresses were obtained at the position around the first screw. CONCLUSION: The results confirmed that functional films could improve the biomechanical properties of the implants and promote the initial bone stability. Furthermore, potential clinical benefit can be obtained due to the inducing superior biomechanical behavior in dental implants.
Assuntos
Densidade Óssea/fisiologia , Implantes Dentários , Osseointegração/fisiologia , Óxidos/farmacologia , Fenômenos Biomecânicos , Feminino , Análise de Elementos Finitos , Seguimentos , Humanos , Imageamento Tridimensional , Masculino , Propriedades de Superfície , Fatores de Tempo , Titânio/farmacologia , Tomografia Computadorizada por Raios X , Cicatrização/fisiologiaRESUMO
AIMS: To investigate the relationship of matriptase expression in oral squamous cell carcinoma (OSCC) to clinicopathological characteristics, patient survival and cell-invasive properties. METHODS AND RESULTS: Matriptase expression in OSCC was evaluated by immunohistochemical staining, and its relationship to clinicopathological features and outcomes was assessed statistically. The shRNA-mediated stable knockdown of matriptase in OSCC cells was used to analyse cell proliferation, migration and invasion in vitro. Matriptase immunostaining score was correlated with histopathological grade, clinical stage, positive lymph node and distant metastasis, and higher matriptase immunostaining score was associated significantly with poor prognosis. Elevated matriptase expression in oral cancer cell lines was a significant promoter of oral cancer cell migration and invasion. CONCLUSIONS: Matriptase expression correlates with tumour progression and invasive capability in OSCC and may be an adverse prognostic marker for this cancer.