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1.
Artigo em Inglês | MEDLINE | ID: mdl-39351998

RESUMO

BACKGROUND: The risk of sarcopenia in older adults with chronic kidney disease (CKD) not yet on dialysis is controversial. The aims of this study were to investigate the association among sarcopenia, diabetes and predialysis CKD and evaluate the impact of gender and ageing on the risk of sarcopenia statuses in older patients with predialysis CKD. METHODS: The participants aged ≥60 years old were recruited from the community of New Taipei City, Taiwan. Handgrip strength, appendicular skeletal muscle mass and the 6-m walk were measured. The diagnosis of sarcopenia was established based on the consensus of Asian Sarcopenia Working Group 2019. These older adults were categorised into G1, G2 and G3-5 according to the guidelines of Kidney Disease Improving Global Outcomes (KDIGO) after calculating the estimated glomerular filtration rate by the Modification of Diet in Renal Disease equation. The Chi-square test and ANOVA were used to estimate the difference of categorical and continuous variables, respectively. Polytomous logistic regression was employed to assess the odds ratio (OR) and 95% confidence intervals (CIs) of the sarcopenia status and sarcopenia-associated risk factors in the predialysis CKD patients. All tests were two-sided, and p < 0.05 was defined as statistical significance. RESULTS: Among the 3648 older adults (mean age: 71.9 ± 6.07 years), including 1701 males and 1947 females, 870 (23.9%), 94 (2.58%) and 48 (1.32%) had possible sarcopenia, sarcopenia and severe sarcopenia, respectively. After adjustment, the risk for possible sarcopenia, sarcopenia and severe sarcopenia significantly increased with ageing (OR = 1.11, 1.10 and 1.23; 95% CI = 1.10-1.13, 1.07-1.15 and 1.18-1.30, respectively) and male gender (OR = 2.26, 20.3 and 25.4; 95% CI = 1.87-2.73, 11.5-36.0 and 11.3-57.2, respectively). Compared with KDIGO G1, no significant association between KDIGO G3-5 and the statuses of sarcopenia was observed (OR = 0.97, 0.88 and 0.91; 95% CI = 0.75-1.26, 0.43-1.78 and 0.37-2.27, p = 0.821, 0.718, 0.838, for possible sarcopenia, sarcopenia and severe sarcopenia, respectively). Ageing and male gender indicated a significant risk for higher sarcopenia status in older patients with predialysis CKD (0.027-fold/year and 0.284-fold, respectively) (p < 0.0001). CONCLUSIONS: This study illuminated the importance of the male sex and the ageing process on the risk of sarcopenia progression in patients with predialysis CKD. Early clinical screening and aggressive treatment for the prevention of higher sarcopenia status in advanced older male adults with predialysis CKD are recommended.

2.
Cell Death Discov ; 10(1): 407, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39285205

RESUMO

Stem cells have the potential to replace damaged or defective cells and assist in the development of treatments for neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease. iPS cells derived from patient-specific somatic cells are not only ethically acceptable, but they also avoid complications relating to immune rejection. Currently, researchers are developing stem cell-based therapies for PD using induced pluripotent stem (iPS) cells. iPS cells can differentiate into cells from any of the three germ layers, including neural stem cells (NSCs). Transplantation of neural stem cells (NSCs) is an emerging therapy for treating neurological disorders by restoring neuronal function. Nevertheless, there are still challenges associated with the quality and source of neural stem cells. This issue can be addressed by genetically edited iPS cells. In this study, shRNA was used to knock down the expression of mutant α-synuclein (SNCA) in iPS cells that were generated from SNCA A53T transgenic mice, and these iPS cells were differentiated to NSCs. After injecting these NSCs into SNCA A53T mice, the therapeutic effects of these cells were evaluated. We found that the transplantation of neural stem cells produced from SNCA A53T iPS cells with knocking down SNCA not only improved SNCA A53T mice coordination abilities, balance abilities, and locomotor activities but also significantly prolonged their lifespans. The results of this study suggest an innovative therapeutic approach that combines stem cell therapy and gene therapy for the treatment of Parkinson's disease.

3.
BMC Oral Health ; 24(1): 1080, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39272161

RESUMO

BACKGROUND: The microvascular free fibula (MFF) flap is a reliable treatment modality for mandibular reconstruction and is suitable for dental implant placement after oncologic surgery. The most common issue with the MFF flap is its limited bone height, which typically results in excessive interarch space and complicates prosthodontic therapy. Overcoming the physical limitations from tumor excision and reducing the treatment time for prosthodontic rehabilitation to improve quality of life are critical clinical challenges. CASE PRESENTATION: A 64-year-old male with lower left gum and bilateral buccal cancer received a single-layer microvascular MFF flap to reconstruct a mandibular defect post-tumor excision. He underwent a bilateral modiolus Z-plasty combined with a skin flap debulking procedure to relieve oral contracture, achieving adequate mouth opening for prosthodontic rehabilitation. Scar tissue bands on the bilateral cheeks significantly affected retention and stability, hampering dental impression performance. The patient sought prosthodontic rehabilitation to enhance his chewing function and quality of life promptly. Prosthodontic rehabilitation with all-on-4 implant therapy, utilizing computer-aided design and computer-assisted manufacturing (CAD/CAM), was completed within one month. CONCLUSION: This case utilized the all-on-4 implant system to address the insufficient fibular height for conventional dental implant placements. Dental CAD/CAM was employed to mill custom prosthetic abutments and a large titanium framework for the implant bar overdenture, compensating for the excessive interarch space between the grafted fibula and maxilla. This treatment approach successfully shortened the prosthodontic rehabilitation time and overcame anatomical limitations.


Assuntos
Desenho Assistido por Computador , Prótese Dentária Fixada por Implante , Humanos , Masculino , Pessoa de Meia-Idade , Reconstrução Mandibular/métodos , Fíbula/transplante , Neoplasias Bucais/cirurgia , Neoplasias Bucais/reabilitação , Implantes Dentários , Retalhos de Tecido Biológico , Implantação Dentária Endóssea/métodos
4.
Cells ; 12(24)2023 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-38132173

RESUMO

Head and neck cancer (HNC) ranks among the top ten prevalent cancers worldwide. Radiotherapy stands as a pivotal treatment component for HNC; however, radioresistance in cancerous cells often leads to local recurrence, becoming a substantial factor in treatment failure. MicroRNAs (miRNAs) are compact, non-coding RNAs that regulate gene expression by targeting mRNAs to inhibit protein translation. Although several studies have indicated that the dysregulation of miRNAs is intricately linked with malignant transformation, understanding this molecular family's role in radioresistance remains limited. This study determined the role of miR-630 in regulating radiosensitivity in HNC. We discovered that miR-630 functions as an oncomiR, marked by its overexpression in HNC patients, correlating with a poorer prognosis. We further delineated the malignant function of miR-630 in HNC cells. While it had a minimal impact on cell growth, the miR-630 contributed to radioresistance in HNC cells. This result was supported by decreased cellular apoptosis and caspase enzyme activities. Moreover, miR-630 overexpression mitigated irradiation-induced DNA damage, evidenced by the reduced levels of the γ-H2AX histone protein, a marker for double-strand DNA breaks. Mechanistically, the overexpression of miR-630 decreased the cellular ROS levels and initiated Nrf2 transcriptional activity, resulting in the upregulation of the antioxidant enzyme GPX2. Thus, this study elucidates that miR-630 augments radioresistance by inducing an anti-apoptotic effect via the Nrf2-GPX2 molecular axis in HNC. The modulation of miR-630 may serve as a novel radiosensitizing target for HNC.


Assuntos
Neoplasias de Cabeça e Pescoço , MicroRNAs , Humanos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/radioterapia , MicroRNAs/metabolismo , Tolerância a Radiação/genética , Proliferação de Células/genética , Glutationa Peroxidase
5.
Dysphagia ; 38(5): 1430-1439, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37106228

RESUMO

Swallowing function can deteriorate with age, leading to a risk of dysphagia. Swallowing evaluation by surface electromyography (sEMG) can be easily and extensively applied for an elderly population. This study evaluated the temporal events observed by sEMG to clarify how aging affects the coordination among the masticatory and suprahyoid muscles. We recruited elderly individuals (over 65 years old) who denied dysphagia. The sEMG activities of anterior temporalis, masseter, and suprahyoid muscles were recorded during 3, 15, and 30 ml water swallowing tests (WST). We calculated the time interval between anterior temporalis and suprahyoid peak activity (T-SH interval) and masseter and suprahyoid peak activity (M-SH interval) and analyzed their correlation with age. The subjects who could and could not swallow 30 ml of water in one gulp were further assigned into the one-gulp and piecemeal groups, respectively, for subgroup analysis. We recruited 101 subjects, among whom 75 (26 males and 49 females) were analyzed after excluding those with suspected dysphagia or low-quality sEMG recordings. Age was significantly correlated with the bilateral T-SH (left: r = 0.249, p = 0.031; right: r = 0.412, p < 0.01) and right M-SH (r = 0.242, p = 0.037) intervals in the 30 ml WST. The correlation between intervals and age were observed in both subgroups. sEMG can be used to investigate the effect of aging on the temporal coordination between masticatory and suprahyoid contraction. Further studies are needed to verify the validity of screening subclinical dysphagia in the elderly.


Assuntos
Transtornos de Deglutição , Deglutição , Masculino , Feminino , Humanos , Idoso , Eletromiografia , Deglutição/fisiologia , Transtornos de Deglutição/diagnóstico , Músculos do Pescoço/fisiologia , Envelhecimento
6.
Medicina (Kaunas) ; 59(3)2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36984629

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is a universal emergency public health issue. A large proportion of the world's population has had several spike antigen exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and/or COVID-19 vaccinations in a relatively short-term period. Although sporadic hematopoietic adverse events after COVID-19 vaccine inoculation were reported, there is currently no sufficient evidence correlating anti-spike protein immune responses and hematopoietic adverse events of vaccinations. We reported the first case of Ph-positive B-cell acute lymphoblastic leukemia (ALL) occurring after a bivalent mRNA COVID-19 vaccine inoculation. The otherwise healthy 43-year-old female patient had a total of six spike antigen exposures in the past 1.5 years. Informative pre-vaccine tests and bone marrow study results were provided. Although the causal relationship between bivalent vaccinations and the subsequent development of Ph-positive B-cell ALL cannot be determined in the case report, we propose that anti-spike protein immune responses could be a trigger for leukemia. Clinicians must investigate the hematopoietic adverse events closely after COVID-19 vaccinations. Further pre-clinical studies to investigate the safety of bivalent mRNA COVID-19 vaccine are required.


Assuntos
COVID-19 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Feminino , Humanos , Adulto , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2 , COVID-19/prevenção & controle , Anticorpos Antivirais , Vacinas de mRNA
7.
Int J Mol Sci ; 23(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36555553

RESUMO

Head and neck cancer (HNC) is the fifth most common cancer worldwide, and its incidence and death rates have been consistently high throughout the past decades. MicroRNAs (miRNAs) have recently gained significant attention because of their role in the regulation of a variety of biological processes via post-transcriptional silencing mechanisms. Previously, we determined a specific profile of miRNAs associated with HNC using a miRNA microarray analysis. Of the 23 miRNAs with highly altered expression in HNC cells, miR-503 was the most significantly downregulated miRNA. In this study, we confirmed that miR-503 acts as a tumor suppressor, as our results showed decreased levels of miR-503 in cancer cells and patients with HNC. We further characterized the role of miR-503 in the malignant functions of HNC. Although there was a minimal effect on cell growth, miR-503 was found to inhibit cellular invasion significantly. Algorithm-based studies identified multiple potential target genes and pathways associated with oncogenic mechanisms. The candidate target gene, WNT3A, was confirmed to be downregulated by miR-503 at both the mRNA and protein levels and validated by a reporter assay. Furthermore, miR-503 modulated multiple invasion-associated genes, including matrix metalloproteinases (MMPs), through the Wnt downstream signaling pathway. Overall, this study demonstrates that miR-503 suppresses HNC malignancy by inhibiting cell invasion through the Wnt signaling pathway via the WNT3A/MMP molecular axis. The modulation of miR-503 may be a novel therapeutic approach to intervene in cancer invasion.


Assuntos
Neoplasias de Cabeça e Pescoço , MicroRNAs , Via de Sinalização Wnt , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Neoplasias de Cabeça e Pescoço/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Via de Sinalização Wnt/genética , Proteína Wnt3A/metabolismo
8.
Clin Oral Investig ; 26(5): 3843-3852, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35482084

RESUMO

OBJECTIVES: To determine the relation between the severity of periodontitis and osteonecrosis of the jaw (ONJ) occurrence among different cancer locations and estimate the effect of dental care on ONJ prevention in cancer patients. MATERIALS AND METHODS: This population-based cross-sectional study was conducted through the Longitudinal Health Insurance Database, Taiwan. Patients with malignancies were collected and subdivided into groups according to their different cancer locations, the severity of periodontitis, and dental care. Multivariable logistic regression analysis was performed to assess the associations between ONJ and ONJ-related factors. RESULTS: A total of 8,234 ONJ patients and 32,912 control patients were investigated. Lip, oral cavity, and pharynx malignancies had the highest ONJ risk among all cancer locations (OR from 3.07 to 9.56, P < 0.01). There is a linear relationship between different severities of periodontitis and ONJ. Patients with radiotherapy and severe periodontitis had the highest ONJ risk (adjusted OR, 9.56; 95% CI, 5.34-17.1). Patients with good dental care had a lower ONJ risk. CONCLUSIONS: The periodontal condition and cancer location showed a significant impact on the risk of developing ONJ after adjusting for bisphosphonate use. Good dental care could decrease the risk of ONJ in cancer patients. The severity of periodontitis might be a target to predict the potency of ONJ. CLINICAL RELEVANCE: Dentists must be vigilant about the increased risk of ONJ in cancer patients with periodontitis, especially in the head and neck cancer population. Good dental care is advised for cancer patients with severe periodontitis.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Neoplasias de Cabeça e Pescoço , Osteonecrose , Periodontite , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Conservadores da Densidade Óssea/efeitos adversos , Estudos Transversais , Difosfonatos/efeitos adversos , Humanos , Osteonecrose/induzido quimicamente , Periodontite/complicações , Periodontite/epidemiologia , Fatores de Risco
9.
Oral Oncol ; 128: 105827, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35364549

RESUMO

OBJECTIVES: This study aimed to investigate how different timelines of various dental therapies were related to osteoradionecrosis development under consideration of radiotherapy dosage in patients with oral cancer. MATERIALS AND METHODS: A total of 7,107 oral cancer patients were enrolled, including 88 osteoradionecrosis patients treated with low radiotherapy dosages (<60 Gy) or high radiotherapy dosages (≥60 Gy), from the Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan. Cox proportional hazard regression was used to compare the osteoradionecrosis risk of various dental treatment timelines under different irradiation dosages. RESULTS: In the oral cancer population with low irradiation dosages (<60 Gy), performing periodontal therapy combined with irradiation significantly raised the risk of osteoradionecrosis by 2.21-fold. Starting radiotherapy within three months after dental surgery greatly increased the risk of developing osteoradionecrosis by 1.87-fold. The oral cancer patients treated with high radiation doses (≥60 Gy) receiving dental surgery within one month prior to radiotherapy had a significantly raised osteoradionecrosis occurrence by 1.60-fold. While the dental surgery was performed during the radiotherapy course, the risk of osteoradionecrosis was greatly increased by 2.21-fold. CONCLUSION: For oral cancer patients, performing dental surgery within three months before radiotherapy might significantly induce osteoradionecrosis. Patients that were treated with high irradiation dosages (≥60 Gy) had a higher tendency to develop osteoradionecrosis if they received dental surgery during radiotherapy. Those who were treated with low radiation dosages (<60 Gy) and received periodontal therapy during radiotherapy might have an increased risk in developing osteoradionecrosis.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Osteorradionecrose , Estudos de Coortes , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Neoplasias Bucais/cirurgia , Osteorradionecrose/epidemiologia , Osteorradionecrose/etiologia , Doses de Radiação , Dosagem Radioterapêutica , Fatores de Risco
10.
Diagnostics (Basel) ; 11(8)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34441345

RESUMO

BACKGROUND: Liquid biopsy is a rapidly growing field, for it may provide a minimally invasive way to acquire pathological data for personalized medicine. This study developed a systemic strategy to discover an effective salivary biomarker for early detection of patients with head-neck squamous carcinoma (HNSC) and oral precancer lesion (OPC). METHODS: A total of 10 miRNAs were examined in parallel with multiple independent cohorts. These included a training set of salivary samples from HNSC patients, the TCGA-HNSC and GSE31277 cohorts to differentiate miRNAs between tumor and normal tissues, and groups of salivary samples from healthy individuals, patients with HNSC and OPC. RESULTS: The combined results from the salivary training set and the TCGA-HNSC cohort showed that four miRNAs (miR-148b, miR-155, miR-196b, and miR-31) consistently increased in HNSC patients. Further integration with the GSE31277 cohort, two miRNAs (miR-31 and miR-196b) maintained at high significances. Further assessment showed that salivary miR-196b was a prominent diagnostic biomarker, as it remarkably discriminated between healthy individuals and patients with HNSC (p < 0.0001, AUC = 0.767, OR = 5.64) or OPC (p < 0.0001, AUC = 0.979, OR = 459). CONCLUSION: Salivary miR-196b could be an excellent biomarker for diagnosing OPC and early detection of HNSC. This molecule may be used for early screening high-risk groups of HNSC.

11.
Support Care Cancer ; 29(6): 3163-3171, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33074358

RESUMO

PURPOSE: This study investigated the impact of dental prophylaxis on 5-fluorouracil (5-FU)-related oral mucositis (OM) according to the head and neck cancer (HNC) locations and treatment times. METHODS: A total of 13,969 HNC participants, including 482 5-FU-related OM subjects and 13,487 comparisons were enrolled from the Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan between 2000 and 2008. All subjects were stratified into subgroups based on the times to perform chlorhexidine use, scaling, and fluoride application before 5-FU administration. The dental prophylaxis related to 5-FU-related OM was estimated by multiple logistic regression and represented with odds ratio (OR) and 95% confidence interval (CI). RESULTS: Fluoride gel application and scaling significantly impacted on OM development (p < 0.001), and the joint effect of fluoride gel and scaling induced 5-FU-related OM (OR = 3.46, 95% CI = 2.39-5.01). The risk of OM was raised 2.25-fold as scaling within 3 weeks before 5-FU-related chemotherapy (95% CI = 1.81-2.81), and a 3.22-fold increased risk of OM while fluoride gel was applied during 5-FU-related treatment (95% CI = 1.46-7.13). CONCLUSION: Dental prophylaxis significantly affected 5-FU-related OM in the HNC population. A short interval between dental scaling or fluoride application and 5-FU administration may be associated with higher prevalence of OM. Scaling simultaneously combined with chlorohexidine promoted 5-FU-related OM in specific HNC patients excluding the oral cancer and nasopharyngeal cancer population. Proper timing of the prophylactic dental treatments prior to 5-FU therapy could reduce the risk to develop 5-FU-related OM.


Assuntos
Profilaxia Dentária/efeitos adversos , Fluoruracila/efeitos adversos , Neoplasias de Cabeça e Pescoço/complicações , Estomatite/induzido quimicamente , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Profilaxia Dentária/métodos , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
FASEB J ; 34(6): 7283-7294, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32277848

RESUMO

MicroRNAs (miRNAs) have been reported to directly alter the virus life cycle and virus-host interactions, and so are considered promising molecules for controlling virus infection. In the present study, we observed that miR-155 time-dependently downregulated upon dengue virus (DENV) infection. In contrast, exogenous overexpression of miR-155 appeared to limit viral replication in vitro, suggesting that the low levels of miR-155 would be beneficial for DENV replication. In vivo, overexpression of miR-155 protected ICR suckling mice from the life-threatening effects of DENV infection and reduced virus propagation. Further investigation revealed that the anti-DENV activity of miR-155 was due to target Bach1, resulting in the induction of the heme oxygenase-1 (HO-1)-mediated inhibition of DENV NS2B/NS3 protease activity, ultimately leading to induction of antiviral interferon responses, including interferon-induced protein kinase R (PKR), 2'-5'-oligoadenylate synthetase 1 (OAS1), OAS2, and OAS3 expression, against DENV replication. Collectively, our results provide a promising new strategy to manage DENV infection by modulation of miR-155 expression.


Assuntos
Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Dengue/tratamento farmacológico , Dengue/genética , Heme Oxigenase-1/genética , Interferons/farmacologia , Proteínas de Membrana/genética , MicroRNAs/genética , Animais , Linhagem Celular , Linhagem Celular Tumoral , Cricetinae , Dengue/virologia , Humanos , Camundongos , Camundongos Endogâmicos ICR , Replicação Viral/efeitos dos fármacos
13.
J Prosthet Dent ; 124(3): 395-399, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31864639

RESUMO

STATEMENT OF PROBLEM: Prosthetic rehabilitation is challenging after tumor excision in patients with oral cancer. Prosthetic parameters may be compromised because of the physical limitations of the oral cavity. Although microvascular free fibular flaps are a common treatment modality for mandibular reconstruction and allow the placement of dental implants, fibular resorption under long-term functional loading is still a controversial issue. Research focusing on how prosthetic design affects fibular resorption around dental implants in an oral cancer population is lacking. PURPOSE: The purpose of this retrospective clinical study was to correlate the success of implant-supported prostheses in microvascular free fibular flaps with occlusal force and fibular resorption around the implants 7 years after functional loading. MATERIAL AND METHODS: The T-Scan III was used to measure occlusal force in 13 participants with oral cancer. Forty-seven successful endosseous dental implants (Biomet 3i) under functional loading in the participants from 2010 to 2017 were analyzed retrospectively. Prosthetic design including fibular length, rehabilitated arch length, and crown-to-implant ratios was estimated from panoramic radiographs. The intergonial distance was used to calibrate the panoramic radiographs to enhance accuracy. To compensate for panoramic distortion, all parameters were represented as a ratio such as fibular length/mandibular width; implant-supported prosthesis length/mandibular dental arch length; implant-supported prosthesis length/maxillary dental arch length; and mandibular dental arch length/maxillary dental arch length. A generalized estimating equation was used for longitudinal analysis to estimate the impact of variables on fibular resorption around the implants. RESULTS: Increased length of the implant-supported prostheses compared with maxillary and mandibular dental arch length significantly impaired the maximal occlusal force (P=.045 and P=.029). The crown-to-implant ratios in the fibular flaps were not correlated with fibular resorption around the implants under long-term functional occlusion (P>.05). The increased ratio of the implant-rehabilitated mandibular to maxillary dental arch length showed a statistically significant tendency to reduce fibular resorption around the implants (P=.007). CONCLUSIONS: Crown-to-implant ratios were not significantly correlated with maximal occlusal force or fibular resorption around dental implants. Increasing the length of the reconstructed mandibular implant-supported prosthesis in the fibular flap will reduce occlusal force. The rehabilitated mandibular dental length should be as long as the maxillary arch for optimum occlusal stress distribution to maintain the peri-implant fibula bone level.


Assuntos
Reabsorção Óssea , Implantes Dentários , Neoplasias Bucais , Implantação Dentária Endóssea , Prótese Dentária Fixada por Implante , Fíbula/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
14.
Clin Oral Investig ; 24(1): 455-463, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31111283

RESUMO

OBJECTIVES: The study aimed to investigate the timeline association with specific dental therapy and osteoradionecrosis (ORN) in oral cancer patients. MATERIALS AND METHODS: A total of 7394 oral cancer patients, including 198 ORN subjects, were retrieved from a Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan and were analyzed with the Cox proportional hazard regression to compare the ORN risk of individual dental treatments under different dental treatments. RESULTS: The initial dental treatment time significantly impacted on the risk of ORN in oral cancer patients (P<0.05). Pre-radiotherapy endodontic treatment and post-radiotherapy scaling or subgingival curettage increased ORN prevalence (hazard ratio [HR], 2.28 and 1.77, respectively). Endodontic treatment within 2 weeks to 1 month prior to radiotherapy increased the ORN risk by 5.83-fold. Dental scaling or subgingival curettage initialized from three to 6 months post-radiotherapy raised the ORN prevalence by 2.2-fold. Exodontia initialized within 2 weeks before radiotherapy (HR=1.49) or 1 to 3 months after radiotherapy (HR=2.63) greatly increased ORN prevalence. To perform oral surgery from 3 months pre-radiotherapy to 6 months after radiotherapy increased the 1.85-fold ORN risk. The chemotherapy combined oral surgery increased the ORN prevalence by 2.55-fold. CONCLUSIONS: Timing of dental treatment, including pre-radiotherapy endodontic treatment, post-radiotherapy scaling or subgingival curettage, and oral surgery or exodontia before and after radiotherapy, could closely relate to ORN development in oral cancer patients. CLINICAL RELEVANCE: Choosing right time to perform appropriate dental treatment could effectively reduce oral infection and ORN risk.


Assuntos
Neoplasias de Cabeça e Pescoço , Osteorradionecrose , Estudos de Coortes , Assistência Odontológica , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Masculino , Osteorradionecrose/complicações , Osteorradionecrose/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
15.
J Oral Maxillofac Surg ; 77(7): 1392-1400, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30826391

RESUMO

PURPOSE: The impact of sialadenitis on osteoradionecrosis (ORN) is controversial. The aim of this study was to determine the association between sialadenitis and ORN. MATERIALS AND METHODS: Participants were derived from the Taiwanese Longitudinal Health Insurance Database. From January 1, 2000 to December 31, 2008, cases of sialadenitis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 527.2, 527.3, 527.5 to 527.7, 527.9, and 710.2) and ORN (ICD-9-CM codes 526.89, 526.5, 730.0, and 730.1) were identified. Different treatment modalities, including surgery versus medicine, were used to distinguish the severity of sialadenitis. The primary predictor variable was sialadenitis. The secondary predictor variable was severity of sialadenitis. The primary outcome variable was time to developing ORN. Other study variables were grouped for age, gender, risk factor, and medical treatment. Cox proportional hazard regression was used to investigate the associations between sialadenitis and ORN after adjusting for statistical confounders. RESULTS: The sample was composed of 47,385 patients with a mean age of 46.6 years (standard deviation, 19.9 yr) and 37.2% were men. Twenty percent had a diagnosis of sialadenitis and 1.13% had a diagnosis of ORN. Sialadenitis was associated with an increased risk of ORN (hazard ratio [HR] = 1.93; 95% confidence interval [CI], 1.61-2.31; P < .0001). After adjustment for confounders, sialadenitis was associated with ORN (multivariable HR = 1.83; 95% CI, 1.52-2.19; P < .0001). Severity of sialadenitis was associated with an increased risk of ORN; risks for ORN were 1.79 (95% CI, 1.49-2.16; P < .0001) and 3.52 (95% CI, 1.67-7.44; P < .001) in patients with mild and serious sialadenitis, respectively, compared with the no-sialadenitis cohort. For the joint effect of ORN between sialadenitis and malignancy type, patients with sialadenitis had 11.6-fold risk for ORN (95% CI, 5.58-23.9) compared with patients without malignancy. CONCLUSIONS: Sialadenitis markedly increased the risk to develop ORN. The severity of sialadenitis was positively correlated with the incidence of ORN.


Assuntos
Neoplasias de Cabeça e Pescoço , Osteorradionecrose , Sialadenite , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteorradionecrose/complicações , Estudos Retrospectivos , Fatores de Risco , Sialadenite/complicações
16.
Oncol Lett ; 17(1): 127-134, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30655747

RESUMO

Resistance to apoptosis is a characteristic of cancer. Curcumin has become a potential anticancer drug for its pro-apoptotic effects, but the underlying mechanisms remain unclear. Furthermore, the Notch3-p53 signaling axis serves an important role in cell fate. The present study was designed to investigate the antitumor effect of curcumin by the Notch3-p53 axis in mouse myeloma P3X63Ag8 cells. The effects of curcumin on the viability of P3X63Ag8 cells were evaluated using an MTT assay. Quantitative expression of the Notch3-p53 signaling axis-associated genes was measured by reverse transcription-quantitative polymerase chain reaction, and western blot analysis was used to investigate the expression of proteins. Additionally, flow cytometry was used to measure the ratio of apoptosis. The results demonstrated that curcumin could significantly inhibit cell viability. No significant pro-apoptotic effect was observed when the concentration of curcumin was <30 µM. At 30 µM, curcumin-treated cells exhibited an apoptotic phenomenon, and the ratio of late apoptosis increased with the concentration of curcumin, and reached 28.4 and 51.8% in the medium- and high-dose groups, respectively. Curcumin inhibited the expression of Notch3, while the middle- and high-dose groups promoted p53. The expression of Notch3-responsive genes Hes family BHLH transcription factor 1 and Hes-related family transcription factor with YRPW motif 1 were notably promoted. Curcumin treatment significantly downregulated B-cell lymphoma-2 (Bcl-2) at the mRNA and protein levels, but upregulated Bcl-2-associated X. These data indicated that curcumin exhibited antitumor effects in mouse myeloma cells with induction of apoptosis by affecting the Notch3-p53 signaling axis.

17.
Clin Oral Investig ; 23(2): 585-593, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29725850

RESUMO

OBJECTIVES: Determine the association between sialadenitis and osteonecrosis of the jaw (ONJ) in head and neck cancer (HNC) patients with varying severity of sialadenitis, treatment modalities, and cancer locations. MATERIALS AND METHODS: A total of 40,168 HNC patients, including 1907 ONJ subjects and 7559 matched comparisons, were enrolled from a Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan between 2000 and 2006. The association with sialadenitis and ONJ was estimated by logic regression and presented as the odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: The occurrence of sialadenitis increased the risk of ONJ by 2.55-fold in HNC patients (95% CI = 2.20-2.95). The ONJ incidence was proportion to sialadenitis severity (OR = 2.53 to 4.43). Irradiated HNC patients had a higher tendency to develop jaw necrosis (osteoradionecrosis, ORN) (OR = 5.05, 95% CI = 4.39-5.80). When combined with irradiation exposure, sialadenitis significantly induced the occurrence of ORN (OR = 8.94, 95% CI = 7.40-10.8), especially in oral cancer patients (OR = 15.9 95% CI = 12.5-20.3). The risk of ONJ increased with radiotherapy dosage and duration, except for nasopharyngeal cancer (NPC) patients. CONCLUSIONS: There was a close association between sialadenitis and ONJ in the HNC population. The severity of sialadenitis was positive correlated to ONJ risk. Radiotherapy combined with sialadenitis significantly raised ORN incidence in HNC patients except for NPC patients. CLINICAL RELEVANCE: HNC patients complained that xerostomia from sialadenitis might increase the risk to develop ONJ, especially among those who received radiotherapy.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Osteorradionecrose/epidemiologia , Sialadenite/epidemiologia , Xerostomia/epidemiologia , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Estudos de Casos e Controles , Difosfonatos/administração & dosagem , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Osteorradionecrose/etiologia , Dosagem Radioterapêutica , Fatores de Risco , Sialadenite/complicações , Taiwan/epidemiologia , Xerostomia/etiologia
18.
J Craniomaxillofac Surg ; 46(11): 1979-1983, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30301649

RESUMO

PURPOSE: The aim of this study was to investigate how the physical variables of fibular reconstructed mandibles with dental implants affects the relative bite force in oral cancer patients. MATERIALS AND METHODS: Over 7 years of follow-up, 13 oral cancer patients were enrolled who included 51 successful implants in the fibular flap. The tactile sensor analyzer evaluated the bite force. The crown-implant ratio, fibular, and rehabilitated dental length were measured using radiographic images. Linear regression was used to analyze the bite force related to the variables of the implants in the fibular reconstructed mandible. RESULTS: Even when the results showed no statistical significance (P > 0.05), increasing the crown-implant ratio, length of the fibular flap, and implant prosthetic reconstructed dentition had a tendency to decrease the bite force (estimate from -0.08% to -4.27%); there was a positive trend of occlusal force and the length of rehabilitative dentition compared with the dental antagonist (estimate = 6.95). CONCLUSION: In this study, the crown-implant ratio, implant dentition, and fibular flap length revealed no significant impact on the bite force or implant success in oral cancer patients; however, a trend to weaken the bite force was suggested once the numerical values of these variables increased.


Assuntos
Força de Mordida , Implantação Dentária Endóssea , Implantes Dentários , Fíbula/transplante , Retalhos de Tecido Biológico/cirurgia , Reconstrução Mandibular , Neoplasias Bucais/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Reconstrução Mandibular/métodos , Pessoa de Meia-Idade , Neoplasias Bucais/reabilitação , Radiografia , Radiografia Panorâmica
19.
Clin Implant Dent Relat Res ; 19(2): 253-260, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27665748

RESUMO

BACKGROUND: Clinical conclusions in studying the stability and osseointegration of mandibular implants positioned using the bone expansion techniques are conflicting and limited. PURPOSE: The objective was to examine the implant stability quotient (ISQ) values of mandibular posterior dental implants with 4.1 mm diameter that inserted with osteotome bone expansion technique versus conventional drilling technique during a 12-week observation period. MATERIALS AND METHODS: Twenty-four implants with 4.1mm diameter in 18 patients were included. Twelve implants in 10 patients were positioned using osteotome bone expansion technique, and 12 fixtures in 9 patients were installed using the conventional drilling technique. The ISQ values of a 3.3 mm diameter implant was measured at recipient sites (ISQb ) before final drilling or expansion technique to standardize the increased ISQ value of 4.1 mm diameter implants. The ISQ values at Weeks 0, 1, 2, 3, 4, 6, 8, 10, and 12 post-surgery were recorded. Data were analyzed by Wilcoxon rank sum test, repeated measure ANOVA, and Fisher Lest Significant Difference test. RESULTS: Calibrated according to a 3.3-mm-diameter implant, bone expansion technique was adopted for the sites with ISQ≦65 bone density, and the areas with ISQ >65 bone condition were treated with conventional drilling technique (p =.038). Both groups presented a similar healing pattern and a comparable ISQ reading from Week 0 to Week 12 (p > .05) for 4.1 mm diameter implants. However, bone expansion technique could enhance more stability when the ISQ values were calibrated by 3.3 mm diameter implant (p < .05). CONCLUSIONS: Bone expansion technique substantially increased more ISQ values from primary stability and achieved comparable primary and secondary stabilities with the conventional technique. Both groups reached a stability plateaus at Week 10.


Assuntos
Implantação Dentária Endóssea/métodos , Mandíbula/cirurgia , Osteotomia , Adulto , Idoso , Processo Alveolar , Densidade Óssea , Implantes Dentários , Retenção em Prótese Dentária , Humanos , Arcada Edêntula , Masculino , Pessoa de Meia-Idade , Osseointegração
20.
PLoS One ; 10(8): e0135102, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26266941

RESUMO

BACKGROUND: Chemotherapy plays an important role in current cancer therapy; however, several problems remain unsolved on the issue of host-therapeutics interaction. The purpose of this study was to investigate the host responses after 5-flurouracil (5-FU) administration and to find the target genes and their relationship with other cytokines in the 5-FU-induced oral mucositis (OM) mouse model through transcriptomic analysis. MATERIALS AND METHODS: Thirty-six 6 to 8 week-old male BALB/c mice were randomly divided into the control group and 5-FU-treated group. In the 5-FU group, mice received 5-FU (100 mg/kg, intraperitoneally) on day 1, day 8, day 15, day 22, and day 29, respectively. We evaluated the oral mucosal change under macroanalysis and histological examination at indicated periods, and then applied transcriptomic analysis of gene expression profile and Immunohistochemical stain to identify the target molecules related to 5-FU-induced OM. RESULTS: The most prominent histological change in this model was observed in the fifth week. The gene expression of Bone gamma-carboxyglutamate protein, related sequence 1 (Bglap-rs1) (-12.69-fold) and Chitinase 3-like 4 (Chi3l4) (-6.35-fold) were significantly down-regulated in this phase. The quantitative real-time PCR results also revealed the expression levels were 0.62-fold in Bglap-rs1 and 0.13-fold in Chi3l4 compared with the control group. Immunohistochemical stain showed significant expression of cluster of differentiation 11b (p<0.01), interleukin-1ß (p<0.001) and tumor necrosis factor-α (p<0.05), and down-regulation of Bglap-rs1 (p<0.01) compared with the control group. By Kyoto Encyclopedia of Genes and Genomes pathway analysis, there were twenty-three pathways significantly participated in this study (p<0.05). CONCLUSIONS: Through comprehensively transcriptomic analysis and IHC stain, we discovered several valuable pathways, verified the main pro-inflammatory cytokines, and revealed two significantly down-regulated genes in the 5-FU-induced OM model. These findings highlighted the way of seeking effective therapeutic agents for chemotherapy-induced OM in future.


Assuntos
Estomatite/metabolismo , Transcriptoma , Animais , Quitinases/genética , Quitinases/metabolismo , Fluoruracila/toxicidade , Glicoproteínas/genética , Glicoproteínas/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estomatite/etiologia , Estomatite/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
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