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1.
Oral Dis ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656694

RESUMO

OBJECTIVE: To investigate the production of leucine-rich α-2-glycoprotein-1 (LRG1) in periodontitis patients and its effectiveness as a new diagnostic marker for periodontitis. SUBJECTS AND METHODS: In vitro experiments were conducted to analyze LRG1 mRNA expression in human gingival epithelial cells and fibroblasts via quantitative real-time PCR. In vivo experiments were conducted to analyze LRG1 localization in periodontitis patients. The correlation between the serum LRG1 levels and alveolar bone resorption in the mouse periodontitis model was also investigated. RESULTS: A positive correlation existed between the periodontal inflamed surface area and serum LRG1 levels (Spearman's rank correlation coefficient: 0.60). LRG1 mRNA expression in human gingival epithelial cells and fibroblasts was upregulated by Porphyromonas gingivalis stimulation or tumor necrosis factor-α stimulation. Interleukin-6 in human gingival epithelial cells and fibroblasts induced the production of LRG1 and transforming growth factor-ß. LRG1 levels in the periodontal tissue and serum in the periodontitis model were higher than those in control mice. LRG1 local administration resulted in alveolar bone resorption, whereas the administration of interleukin-6R antibody inhibited bone resorption. CONCLUSIONS: LRG1 levels in serum and periodontal tissue are upregulated in periodontitis and are implicated in periodontal tissue destruction through interleukin-6 production.

2.
Int J Mol Sci ; 25(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38892262

RESUMO

The impact of gut and oral microbiota on the clinical outcomes of patients with oral squamous cell carcinoma (OSCC) is unknown. We compared the bacterial composition of dental plaque and feces between patients with OSCC and healthy controls (HCs). Fecal and dental plaque samples were collected from 7 HCs and 18 patients with OSCC before treatment initiation. Terminal restriction fragment-length polymorphism analysis of 16S rRNA genes was performed. Differences in bacterial diversity between the HC and OSCC groups were examined. We compared the occupancy of each bacterial species in samples taken from patients with OSCC and HCs and analyzed the correlation between PD-L1 expression in the tumor specimens and the occupancy of each bacterial species. The gut and oral microbiota of patients with OSCC were more varied than those of HCs. Porphyromonas and Prevotella were significantly more abundant in patients with OSCC than in HCs. The abundance of Clostridium subcluster XIVa in the gut microbiota of the PD-L1-positive group was significantly greater than that in the PD-L1-negative group. The oral and gut microbiomes of patients with OSCC were in a state of dysbiosis. Our results suggest the possibility of new cancer therapies targeting these disease-specific microbiomes using probiotics and synbiotics.


Assuntos
Carcinoma de Células Escamosas , Microbioma Gastrointestinal , Neoplasias Bucais , RNA Ribossômico 16S , Humanos , Microbioma Gastrointestinal/genética , Neoplasias Bucais/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/microbiologia , RNA Ribossômico 16S/genética , Idoso , Fezes/microbiologia , Boca/microbiologia , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Microbiota/genética , Adulto , Disbiose/microbiologia , Placa Dentária/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Estudos de Casos e Controles
3.
Support Care Cancer ; 31(9): 552, 2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37658917

RESUMO

PURPOSE: Chemotherapy-induced taste alteration is a side effect that can result in malnutrition and reduced quality of life in cancer patients. However, the underlying causes of this phenomenon remain unclear, and evidence-based treatments have not been established. This study focused on patients' subjective symptoms of taste alterations aimed to explore how the sensitivity to basic tastes changes due to anticancer agents and how alterations in one taste perception are associated with changes in other tastes during chemotherapy. METHODS: A cross-sectional questionnaire-based interview survey was conducted on 215 patients undergoing chemotherapy. The subjective sensitivity to each basic taste was assessed using a visual analog scale, and the incidence of taste alterations due to different chemotherapy regimens was calculated. Multivariate logistic regression analysis was performed to determine whether there were associations between changes in one taste sensitivity and changes in other taste sensitivities. RESULTS: Approximately half (49.5%) of the patients experienced chemotherapy-induced taste alterations. An analysis of subjective changes in basic tastes revealed that the salt and umami taste systems were more sensitive to chemotherapy than other taste systems. Patients with altered sensitivity to sweet taste were significantly more likely to report altered sensitivity to salt, bitter, and sour tastes. Moreover, umami-salt and bitter-sour taste sensitivities were significantly related to each other. CONCLUSION: This study suggests that changes in subjective sensitivities to one basic taste during chemotherapy may be accompanied by changes in other tastes in specific combinations. Considering taste associations in dietary guidance may help improve the nutritional status of cancer patients experiencing taste alterations due to chemotherapy.


Assuntos
Antineoplásicos , Disgeusia , Neoplasias , Percepção Gustatória , Inquéritos e Questionários , Disgeusia/induzido quimicamente , Estudos Transversais , Neoplasias/tratamento farmacológico , Antineoplásicos/efeitos adversos , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
4.
J Clin Periodontol ; 50(11): 1520-1529, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37666748

RESUMO

AIM: To retrospectively investigate the relationship between the CD4+ T-cell counts at baseline and the efficacy of the initial periodontal treatment of patients undergoing treatment for human immunodeficiency virus (HIV) infection using the periodontal inflamed surface area (PISA). MATERIALS AND METHODS: Thirty-three patients with chronic periodontitis who had undergone periodontal examination at baseline and after the initial periodontal treatment were enrolled. PISA was calculated from the periodontal probing depth and bleeding on probing, and the ratio of PISA after treatment to that at baseline (PISA response ratio) was calculated. Groups with a response ratio of <1 and ≥1 were defined as the improvement and the non-improvement groups, respectively. RESULTS: PISA after the initial periodontal treatment significantly decreased compared with that at baseline (p < .05). A weak negative correlation was found between the PISA response ratio and CD4+ T-cell counts at baseline (p < .05). The CD4+ T-cell counts at baseline were significantly higher in the improvement group than in the non-improvement group (p < .05). Multivariate analysis revealed that the CD4+ T-cell counts at baseline was an independent factor that affects the PISA (p < .05). CONCLUSIONS: The higher the CD4+ T-cell counts at baseline in patients undergoing treatment for HIV infection, the more effective the initial periodontal treatment.

5.
BMC Oral Health ; 23(1): 159, 2023 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-36934261

RESUMO

BACKGROUND: Dysgeusia is a relatively early symptom of zinc deficiency, and zinc replacement is effective in treating dysgeusia. The administration of zinc acetate hydrate (ZAH) was approved in 2017 for patients with hypozincemia in Japan. This retrospective study was conducted to explore the efficacy and safety of ZAH administration in patients with hypozincemia-induced dysgeusia. METHODS: Patients with hypozincemia-induced dysgeusia who visited our hospital from May 2013 to December 2019 were included in this study. ZAH (zinc content; 50 mg/day) was administered to 42 patients for 24 weeks. The taste test was performed using the filter paper disk method, and the total cognitive thresholds of the left and right chorda tympani regions were used. Changes in taste function, serum zinc and copper levels, and copper/zinc ratio were analyzed. A total of 28 patients who received polaprezinc (PPZ, zinc content; 34 mg/day) for 24 weeks, who were prescribed until ZAH was approved, were registered as controls. RESULTS: Serum zinc levels at 12 and 24 weeks after ZAH or PPZ administration were higher than those before administration. These levels were significantly higher in the ZAH-treated group than in the PPZ-treated group. However, serum copper levels did not significantly change before and after administration. In the taste test, the taste thresholds for the acidity and salty at 12 and 24 weeks after ZAH administration were significantly decreased compared to before administration. In contrast, in the PPZ group, the taste thresholds for the acidity and salty were significantly decreased 24 weeks after administration. CONCLUSIONS: ZAH (50 mg/day) administration was effective in improving the gustatory sensitivity of patients with dysgeusia and hypozincemia 12 weeks after administration without affecting the serum copper level. ZAH was also more effective than PPZ.


Assuntos
Disgeusia , Acetato de Zinco , Humanos , Disgeusia/induzido quimicamente , Disgeusia/tratamento farmacológico , Acetato de Zinco/uso terapêutico , Estudos Retrospectivos , Cobre/uso terapêutico , Zinco/uso terapêutico
6.
J Stroke Cerebrovasc Dis ; 31(3): 106301, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35032756

RESUMO

OBJECTIVES: There is accumulating evidence that periodontal disease is associated with atrial fibrillation (AF) or stroke, but it is unclear which causative species of periodontal disease are present in stroke patients with AF. We aimed to investigate the associations between AF and specific periodontal pathogens using serum titers of IgG antibodies of bacteria in acute stroke patients. MATERIALS AND METHODS: Acute stroke patients were registered at two hospitals. Serum samples were evaluated for titers of antibodies against 9 periodontal pathogens (16 genotypes) using ELISAs. We identified AF in patients according to the following criteria: (1) a history of sustained or paroxysmal AF or (2) AF detection upon arrival or during admission. We carried out propensity score matching to categorize the patients as those with AF and those without. RESULTS: Of the 664 acute stroke patients, 123 (18.5%) had AF. After propensity score matching, 234 patients were selected. Patients with AF had a higher prevalence of positive serum titers of antibodies against Porphyromonas gingivalis (FimA type III) and Porphyromonas gingivalis (FimA type V) than those without AF (59.0% vs. 39.3%, p=0.004 and 58.2% vs. 40.2%, p=0.009, respectively). CONCLUSIONS: Porphyromonas gingivalis, especially FimA type III and type V, might be associated with AF in stroke patients.


Assuntos
Fibrilação Atrial , Imunoglobulina G , Doenças Periodontais , Porphyromonas gingivalis , Acidente Vascular Cerebral , Fibrilação Atrial/sangue , Fibrilação Atrial/epidemiologia , Humanos , Imunoglobulina G/sangue , Doenças Periodontais/epidemiologia , Doenças Periodontais/microbiologia , Porphyromonas gingivalis/imunologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia
7.
J Cardiovasc Electrophysiol ; 32(5): 1240-1250, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33590642

RESUMO

INTRODUCTION: Inflammation is one of the main causes of atrial fibrillation (AF) recurrence after ablation. Porphyromonas gingivalis is a key periodontal pathogen in the oral-systemic disease connection and serum immunoglobulin G (IgG) antibody titers against P. gingivalis reflect the clinical status of periodontitis. This study aimed to investigate the relationship between late recurrence of AF after radiofrequency catheter ablation (RFCA) and serum IgG antibody titers against P. gingivalis. METHODS: A total of 596 AF patients (mean age, 64.9 ± 10.0 years; 69% male; 61% paroxysmal AF) who underwent a first session of RFCA were enrolled. Patients were carefully examined for late recurrence during a mean follow-up period of 17.1 ± 14.5 months. Serum IgG antibody titers against P. gingivalis (types I-IV) were measured using enzyme-linked immunosorbent assay. The results of serum antibody titers were divided into a high-value and a low-value group. RESULTS: Among the five P. gingivalis subtypes, serum antibody titer against P. gingivalis type IV was associated with late recurrence (odds ratio, 1.937; 95% confidence interval [CI], 1.301-2.884; p = .002). Multivariate Cox proportional-hazards regression analysis revealed that high-value serum antibody titer against P. gingivalis type IV independently predicted late recurrence (paroxysmal AF: adjusted hazard ratio [HR], 1.569; 95% CI, 1.010-2.427; p = .04; non-paroxysmal AF: adjusted HR, 1.909; 95% CI, 1.213-3.005; p = .004). CONCLUSION: Periodontitis was related to the late recurrence of AF after RFCA. P. gingivalis type IV may be pathogenic for AF recurrence after RFCA.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Periodontite , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Periodontite/diagnóstico , Porphyromonas gingivalis , Recidiva , Resultado do Tratamento
8.
Heart Vessels ; 36(11): 1721-1729, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34021383

RESUMO

Atrial fibrillation (AF) is associated with a fivefold risk of stroke and thrombotic embolism, which are usually derived from the left atrial appendage (LAA). Spontaneous echo contrast (SEC) is known as a risk factor for thrombosis. Porphyromonas gingivalis (P. gingivalis) has some prothrombotic effects and plays a key role in periodontitis and oral-systemic disease connection. We aimed to clarify the relationship between P. gingivalis and LAA SEC among AF patients. A total of 569 AF ablation candidates were enrolled in the present study. LAA SEC was categorized into nondense SEC and dense SEC based on transesophageal echocardiography. Serum immunoglobulin G antibody titers of P. gingivalis fimA subtypes (types I-IV) were measured with an enzyme-linked immunosorbent assay. The levels of antibody titers were categorized into high (> mean + 3 standard deviation) and low values. A total of 513 (90%) patients were included in the nondense SEC group, and 56 (10%) were included in the dense SEC group. Multivariate regression analysis revealed that the high-value serum antibody titers of P. gingivalis types II and IV were independently associated with dense SEC [type II: adjusted odds ratio (OR) 2.220; 95% confidence interval (CI) 1.062-4.643; P = 0.02; and type IV: adjusted OR 3.169; 95% CI 1.058-6.657; P = 0.002]. The results revealed that P. gingivalis types II and IV are related to LAA SEC severity among AF patients who receive appropriate anticoagulation therapy.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Trombose , Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ecocardiografia Transesofagiana , Humanos , Porphyromonas gingivalis
9.
J Oral Maxillofac Surg ; 75(12): 2593-2598, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28577371

RESUMO

PURPOSE: There have been only a few reports on the prevalence of torus mandibularis (TM) in young adult patients, and TM can have various adverse effects on oral and occlusal states in middle-age patients. This study was designed to determine the association between TM status and oral and occlusal states in young healthy dentate adults. MATERIALS AND METHODS: This was a cross-sectional study; the sample population included students at Hiroshima University (Hiroshima, Japan) who participated for practical education. The predictor variables in this study included oral symptoms (temporomandibular joint noise, tooth clenching and grinding, buccal mucosa ridging, dental attrition, and tongue habit), oral anatomy (occlusal vertical dimension), and oral function (average occlusal pressure, occlusal contact area, and maximum voluntary tongue pressure). The outcome variable was TM status (present or absent). Additional variables were demographic in nature and included age, number of residual teeth, body weight, and gender. These variables were compared among participants with and without TM using univariate analysis and multiple logistic regression analysis. Statistical analyses were carried out using SPSS Statistics 19 for Windows (IBM Corp, Armonk, NY); a P value less than .05 was considered significant. RESULTS: Of 204 participants included in the study, 50% were men and 50% were women. The mean age was 22.4 ± 2.7 years. TM was present in 119 (58.3%). Multiple logistic regression analysis showed that TM status was associated with dental attrition and occlusal contact area (P < .05). CONCLUSIONS: This study showed that TM was present in more than half the young healthy dentate participants and was closely associated with dental attrition and occlusal contact area. This study will provide readers with useful information to help prevent the development of TM before middle age.


Assuntos
Exostose/epidemiologia , Mandíbula/anormalidades , Adulto , Estudos de Casos e Controles , Estudos Transversais , Exostose/congênito , Exostose/diagnóstico , Feminino , Humanos , Japão/epidemiologia , Modelos Logísticos , Masculino , Prevalência , Estudos Prospectivos , Adulto Jovem
10.
In Vitro Cell Dev Biol Anim ; 60(6): 583-589, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38713345

RESUMO

Heparin-binding protein 17 (HBp17), first purified in 1991 from the conditioned medium of the human A431 squamous cell carcinoma (SCC) cell line, was later renamed fibroblast growth factor-binding protein 1 (FGFBP-1). HBp17/FGFBP-1 is specifically expressed and secreted by epithelial cells, and it reversibly binds to fibroblast growth factor (FGF)-1 and FGF-2, as well as FGFs-7, -10, and -22, indicating a crucial involvement in the transportation and function of these FGFs. Our laboratory has investigated and reported several studies to elucidate the function of HBp17/FGFBP-1 in SCC cells and its potential as a molecular therapeutic target. HBp17/FGFBP-1 transgene exoression in A431-4 cells, a clonal subline of A431 that lacks tumorigenicity and does not express HBp17/FGFBP-1, demonstrated a significantly enhanced proliferation in vitro compared with A431-4 cells, and it acquired tumorigenicity in the subcutis of nude mice. Knockout (KO) of the HBp17/FGFBP-1 by genome editing significantly suppressed tumor growth, cell motility, and tumorigenicity compared with control cells. A comprehensive analysis of expressed molecules in both cell types revealed that molecules that promote epithelial cell differentiation were highly expressed in HBp17/FGFBP-1 KO cells. Additionally, we reported that 1α,25(OH)2D3 or eldecalcitol (ED-71), which is an analog of 1α,25(OH)2D3, suppresses HBp17/FGFBP-1 expression and tumor growth in vitro and in vivo by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. Here, we discuss the prospects of molecular targeted therapy targeting HBp17/FGFBP-1 with 1α,25(OH)2D3 or ED71 in SCC and oral SCC.


Assuntos
Carcinoma de Células Escamosas , Humanos , Animais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Vitamina D/análogos & derivados , Vitamina D/farmacologia , Vitamina D/metabolismo , Proliferação de Células/efeitos dos fármacos , Camundongos , Camundongos Nus
11.
Mol Med Rep ; 29(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38275130

RESUMO

Keratoameloblastoma (KA) and solid variant of odontogenic keratocyst (SOKC) are rare odontogenic lesions, and their relationship and differences are unclear. The present study described a case that started as an odontogenic keratocyst (OKC) and transformed to SOKC/KA upon recurrence. Briefly, a 26­year­old man presented with swelling in the right cheek and was referred to the Department of Oral and Maxillofacial surgery, Hiroshima University Hospital (Hiroshima, Japan). At the initial visit, unicystic bone permeation was observed extending from the right canine to the molar, maxillary sinus and nasal cavity. After the biopsy, the patient underwent excisional surgery and was diagnosed with OKC. Thereafter, the lesion recurred six times over a period of 13 years and showed different histopathological features from those of the primary lesion, all consisting of numerous cysts with keratinization, which were diagnosed as SOKC/KA. The Ki­67 positivity rate was ~10%, which was higher than that of the primary lesion, but there was no atypia. Genetic analysis of the recurrent lesion revealed mutations in adenomatous polyposis coli and Kirsten rat sarcoma viral oncogene homolog. This case originated from OKC, and the morphological features of OKC and KA were mixed upon recurrence, supporting the commonality and association between the two. However, multiple mutations different from those of OKC and ameloblastoma were detected, suggesting an association of SOKC/KA with increased proliferative activity and a high recurrence rate.


Assuntos
Ameloblastoma , Cistos Odontogênicos , Masculino , Humanos , Adulto , Ameloblastoma/diagnóstico , Ameloblastoma/genética , Ameloblastoma/cirurgia , Cistos Odontogênicos/diagnóstico , Cistos Odontogênicos/cirurgia , Cistos Odontogênicos/genética , Mutação , Biópsia , Osso e Ossos/patologia
12.
Oncogenesis ; 13(1): 25, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39004623

RESUMO

The Hippo pathway and its downstream effectors, Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ), are essential for cell growth and organ development. Emerging evidence revealed that the Hippo pathway and YAP/TAZ are frequently dysregulated by multiple genetic alterations in solid cancers including head and neck squamous cell carcinoma (HNSCC); however, the YAP/TAZ-nuclear interactome remains unclear. RNA-binding motif protein 39 (RBM39) enhances transcriptional activity of several transcription factors and also regulates mRNA splicing. Indisulam degrading RBM39 induces alternative splicing, leading to cell death. However, clinical trials of indisulam have failed to show effectiveness. Therefore, clarifying the resistance mechanism against splicing inhibitors is urgently required. In this study, we identified RBM39 as a novel YAP/TAZ-interacting molecule by proteome analysis. RBM39 promoted YAP/TAZ transcriptional activity. We further elucidated that indisulam reduces RBM39/YAP/TAZ-mediated integrin or collagen expression, thereby inactivating focal adhesion kinase (FAK) important for cell survival. Moreover, indisulam also induced alternative splicing of cell cycle- or DNA metabolism-related genes. YAP/TAZ hyperactivation delayed indisulam-induced RBM39 degradation, which restored the integrin/collagen expression to activate FAK, and alternative splicing, thereby conferring resistance against indisulam in vitro and in vivo. Our findings may aid to develop a novel cancer therapy focusing on YAP/TAZ/RBM39 interaction.

13.
Pathol Oncol Res ; 30: 1611571, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38312516

RESUMO

Objectives: Integrins are heterodimeric transmembrane plasma membrane proteins composed of α- and ß-chains. They bind to extracellular matrix (ECM) and cytoskeletal proteins as ECM protein receptors. Upon ECM protein binding, integrins activate focal adhesion kinase (FAK) and transduce various signals. Despite their importance, integrin and FAK expression in oral squamous cell carcinoma (OSCC) tissue and the prognosis of patients with OSCC remains elusive. Methods: In a retrospective observational study, we immunohistochemically evaluated integrin αV, ß1, ß3, ß5, ß6, FAK, and phosphorylated-FAK (pFAK) expressions as prognostic predictors in 96 patients with OSCC. Patients were classified as positive or negative based on staining intensity, and clinicopathologic characteristics and survival rates of the two groups were compared. The association between above integrin-related proteins and PD-1 or PD-L1 in OSCC tissues was investigated. Results: We observed immunohistochemical integrin αV, ß1, ß6, ß8, and FAK expressions in the cell membrane and cytoplasm but not integrin ß3 and ß5 in the OSCC tissues. pFAK was expressed in the cytoplasm of OSCC cells. The overall survival rate significantly decreased in pFAK-positive OSCC patients compared to the negative group, and cervical lymph node metastasis significantly increased in integrin ß8-positive patients with OSCC (p < 0.05). No association between integrin-related proteins and PD-1 or PD-L1 in OSCC tissues was observed. Conclusion: Our results indicate that pFAK and integrin ß8 are prognostic factors for OSCC. Therefore, pFAK- and integrin ß8-targeting new oral cancer diagnostic and therapeutic methods hold a promising potential.


Assuntos
Neoplasias Bucais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Antígeno B7-H1 , Relevância Clínica , Proteína-Tirosina Quinases de Adesão Focal/uso terapêutico , Integrina alfaV/metabolismo , Integrinas/metabolismo , Neoplasias Bucais/patologia , Receptor de Morte Celular Programada 1 , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
14.
Stem Cell Rev Rep ; 20(1): 347-361, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37917410

RESUMO

Mesenchymal stem cells (MSCs) have gained significant attention in cell therapies due to their multipotency and immunomodulatory capacities. The transcriptional co-activators YAP/TAZ, central to the mechanotransduction system in MSCs, dominantly direct MSCs lineage commitment. However, their role in immunomodulation remains elusive. Accordingly, this present study aimed to investigate the role of mechanotransducer YAP/TAZ and their binding target transcriptional factor, TEAD, in the immunomodulatory capacities of human bone marrow-derived MSCs. Reducing YAP/TAZ activity by altering the matrix stiffness, disrupting the F-actin integrity with chemical inhibitors, or using siRNAs increased the expression of immunomodulatory genes, such as TSG-6 and IDO, upon TNF-α stimulation. Similarly, transfection of TEAD siRNA also increased the immunomodulatory capacities in MSCs. RNA-seq analysis and inhibition assays demonstrated that the immunomodulatory capacities caused by YAP/TAZ-TEAD axis disruption were due to the NF-κB signaling pathway activation. Then, we also evaluated the in vivo anti-inflammatory efficacy of MSCs in a dextran sulfate sodium (DSS)-induced mice colitis model. The administration of human MSCs transfected with TEAD siRNA, which exhibited enhanced immunomodulatory properties in vitro, significantly ameliorated inflammatory bowel disease symptoms, such as body weight loss and acute colon inflammation, in the DSS-induced mice colitis model. Our findings underscore the mechanosignaling YAP/TAZ-TEAD axis as a regulator of MSCs immunomodulation. Targeting these signaling pathways could herald promising MSCs-based therapies for immune disorders.


Assuntos
Colite , Células-Tronco Mesenquimais , Proteínas de Sinalização YAP , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Colite/metabolismo , Imunomodulação , Mecanotransdução Celular , RNA Interferente Pequeno/metabolismo , Transativadores/genética , Transativadores/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Fatores de Transcrição de Domínio TEA/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-39294092

RESUMO

OBJECTIVES: Claudin (CLD), a major component of tight junctions, is a four-transmembrane protein, and 24 subtypes have been reported in humans. CLD expression is highly tissue-specific; CLD1 has been reported to be expressed in the skin and mucosa. There have been few reports on CLD1 expression and its function in oral cancer. MATERIALS AND METHODS: This retrospective study immunohistochemically evaluated CLD1 expression as prognostic predictors in 84 participants with oral squamous cell carcinoma (OSCC). Participants were classified as positive or negative based on staining intensity; the clinicopathologic characteristics and survival rates of the two groups were compared. To clarify the biological role of CLD1 in OSCC cells, we examined the effects of CLD1 overexpression on the invasion and proliferation of the OSCC cell line, SCCKN. RESULTS: We observed the immunohistochemical CLD1 expression in the cell membranes of OSCC cells. The disease-free survival rate was significantly lower in patients with CLD1-positive OSCC than in patients with CLD1-negative OSCC (P < .05). In vitro studies showed that cell proliferative capacity, motility, proteolytic activity, and invasive growth were promoted in CLD1-overexpressing SCCKN cells compared to those in control SCCKN cells. CONCLUSION: CLD1 may be a useful and potential prognostic factor for OSCC treatment.

16.
J Am Heart Assoc ; 13(8): e033740, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38597139

RESUMO

BACKGROUND: Periodontitis has not been recognized as a modifiable risk factor for atrial fibrillation (AF). This prospective nonrandomized study investigated whether periodontal treatment improves the AF ablation outcome. METHODS AND RESULTS: We prospectively enrolled 288 AF patients scheduled to undergo initial radiofrequency catheter ablation. Each patient underwent periodontal inflamed surface area (PISA; a quantitative index of periodontal inflammation) measurement. All eligible patients were recommended to receive periodontal treatment within the blanking period, and 97 consented. During the mean follow-up period of 507±256 days, 70 (24%) AF recurrences were documented. Patients who exhibited AF recurrences had a higher PISA than those who did not (456.8±403.5 versus 277.7±259.0 mm2, P=0.001). These patients were categorized into high-PISA (>615 mm2) and low-PISA (<615 mm2) groups according to the receiver operating characteristic analysis for AF recurrence (area under the curve, 0.611; sensitivity, 39%; specificity, 89%). A high PISA, as well as female sex, AF duration, and left atrial volume, were the statistically significant predicter for AF recurrence (hazard ratio [HR], 2.308 [95% CI, 1.234-4.315]; P=0.009). In patients with a high PISA, those who underwent periodontal treatment showed significantly fewer AF recurrences (P=0.01, log-rank test). The adjusted HR of periodontal treatment for AF recurrence was 0.393 (95% CI, 0.215-0.719; P=0.002). CONCLUSIONS: Periodontitis may serve as a modifiable risk factor for AF. PISA is a hallmark of AF recurrence, and periodontal treatment improves the AF ablation outcome, especially for those with poor periodontal condition.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Periodontite , Humanos , Feminino , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/etiologia , Estudos Prospectivos , Átrios do Coração , Ablação por Cateter/efeitos adversos , Recidiva , Resultado do Tratamento
17.
Am J Med ; 137(3): 273-279.e2, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37984772

RESUMO

BACKGROUND: We determined the effects and an accurate marker of periodontal treatment on serum interleukin (IL)-6 and high-sensitivity C-reactive protein (HsCRP) levels in systemically healthy individuals with periodontal disease. METHODS: This multicenter study included systemically healthy individuals with periodontal disease who received initial periodontal treatment and had no periodontal treatment history. Periodontal parameters, including periodontal inflamed surface area, masticatory efficiency, and periodontal disease classification; serum IL-6 and HsCRP levels; and serum immunoglobulin (Ig)G titers against periodontal pathogens were evaluated at baseline and after treatment. Subjects were classified as low or high responders (group) based on periodontal inflamed surface area changes. RESULTS: There were 153 participants. Only periodontal inflamed surface area changes were markedly different between low and high responders. Periodontal treatment (time point) decreased both serum IL-6 and HsCRP levels. The interaction between group and time point was remarkable only for serum IL-6 levels. Changes in serum immunoglobulin (Ig)G titers against periodontal pathogens were not associated with IL-6 changes in high responders. We analyzed the indirect effect of serum anti-Porphyromonas gingivalis type 2 IgG titer changes using mediation analysis and found no significance. However, the direct effect of group (low or high responder) on IL-6 changes was considerable. CONCLUSIONS: Periodontal treatment effectively decreased serum IL-6 levels, independent of periodontal pathogen infection, in systemically healthy individuals with periodontal disease.


Assuntos
Proteína C-Reativa , Doenças Periodontais , Humanos , Proteína C-Reativa/análise , Interleucina-6 , Inflamação , Doenças Periodontais/terapia , Imunoglobulinas
18.
Sci Rep ; 14(1): 11114, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750118

RESUMO

Oral bacteria are known to be associated with perioperative complications during hospitalization. However, no presented reports have clarified the relationship of oral bacterial number with medical costs for inpatients. The Diagnosis Procedure Combination (DPC) database system used in Japan provides clinical information regarding acute hospital patients. The present study was conducted to determine the association of oral bacterial numbers in individual patients treated at a single institution with length of hospital stay and medical costs using DPC data. A total of 2369 patients referred by the medical department to the dental department at Hiroshima University Hospital were divided into the low (n = 2060) and high (n = 309) oral bacterial number groups. Length of hospital stay and medical costs were compared between the groups, as well as the associations of number of oral bacteria with Charlson comorbidity index (CCI)-related diseases in regard to mortality and disease severity. There was no significant difference in hospital stay length between the low (24.3 ± 24.2 days) and high (22.8 ± 20.1 days) oral bacterial number groups. On the other hand, the daily hospital medical cost in the high group was significantly greater (US$1456.2 ± 1505.7 vs. US$1185.7 ± 1128.6, P < 0.001). Additionally, there was no significant difference in CCI score between the groups, whereas the daily hospital medical costs for patients in the high group treated for cardiovascular disease or malignant tumors were greater than in the low number group (P < 0.05). Multivariate regression analysis was also performed, which showed that oral bacterial number, age, gender, BMI, cardiovascular disease, diabetes, malignant tumor, and hospital stay length were independently associated with daily hospitalization costs. Monitoring and oral care treatment to lower the number of oral bacteria in patients affected by cardiovascular disease or cancer may contribute to reduce hospitalization costs.


Assuntos
Hospitalização , Tempo de Internação , Humanos , Feminino , Masculino , Japão/epidemiologia , Idoso , Tempo de Internação/economia , Pessoa de Meia-Idade , Hospitalização/economia , Boca/microbiologia , Bases de Dados Factuais , Idoso de 80 Anos ou mais , Custos Hospitalares , Carga Bacteriana , Bactérias/isolamento & purificação , Bactérias/classificação , Custos de Cuidados de Saúde , Adulto
19.
Physiol Behav ; 267: 114224, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37148986

RESUMO

OBJECTIVES: The causes of hypogeusia include zinc deficiency, systemic illness, and consumption of drugs. Notably, patients with oral cavity diseases such as oral candidiasis and salivary gland hypofunction may present with risk factors that remain unreported. Hence, this study aimed to investigate the relationship between age, sex, smoking status, serum zinc concentration, oral candidiasis, saliva volume, and taste function in patients with hypogeusia. SUBJECTS AND METHODS: Overall, 335 participants who complained of taste abnormalities underwent a taste test. Based on the recognition threshold value, the participants were classified as normal individuals (recognition threshold of 1 and 2) and patients with hypogeusia (recognition threshold of ≥3). The clinical characteristics, including resting saliva volume (RSV) and stimulated saliva volume (SSV), were compared, and a multivariate logistic regression analysis focusing on RSV was performed. RESULTS: Patients with hypogeusia had a lower RSV than normal individuals for all tastes, but not for SSV. Based on the results of regression analysis, RSV was identified as an independent predictor of hypogeusia for salty and bitter tastes. Moreover, the proportion of patients with decreased RSV increased as the number of taste qualities exceeding the reference recognition threshold increased. Furthermore, a decrease in RSV was associated with an increase in the recognition threshold for salty and bitter tastes. CONCLUSIONS: Based on the results of the present study, moisturizing the oral cavity may be useful against hypogeusia.


Assuntos
Ageusia , Candidíase Bucal , Humanos , Ageusia/etiologia , Saliva , Estudos Retrospectivos , Candidíase Bucal/complicações , Paladar , Fatores de Risco , Zinco , Limiar Gustativo
20.
Dent J (Basel) ; 11(11)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37999021

RESUMO

Palmoplantar pustulosis (PPP) is a stubborn skin disease involving repeated aseptic small pustules on the palms and soles of the feet, which is triggered and exacerbated by metals and dental focal infections. There are few reports of an exacerbation of PPP symptoms after orthognathic surgery. The patient is a 40-year-old female who consulted an orthodontist at our hospital, complaining of a protruding maxilla and malocclusion. Under the diagnosis of skeletal prognathism, she underwent surgery for jaw deformity. Although no allergic symptoms were observed during the orthodontic treatment prior to surgery, postoperative scaling on the palms and soles of her feet worsened, and itching was observed on the skin, especially on the titanium plate used to secure the bone fragments. Under the diagnosis of metal allergy, treatment with steroids and vitamin D ointment failed to improve the condition, so surgery was performed to replace the metal plate with a non-metallic absorbable plate in the third postoperative month. Afterwards, the pruritus resolved, and erythema and scale on the palms and soles nearly disappeared. In the present case, though, oral bacterial infection, a past history of smoking, and stress from surgery were also considered to be possible causes of PPP exacerbation, and we concluded that one of the causes of PPP exacerbation was metal allergy from the plates or screws used to fix the bone fragments.

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