RESUMO
AIMS: In an era of evolving diagnostic possibilities, existing diagnostic systems are not fully sufficient to promptly recognize patients with early-stage hypertrophic cardiomyopathy (HCM) without symptomatic and instrumental features. Considering the sudden death of HCM, developing a novel diagnostic model to clarify the patients with early-stage HCM and the immunological characteristics can avoid misdiagnosis and attenuate disease progression. METHODS AND RESULTS: Three hundred eighty-five samples from four independent cohorts were systematically retrieved. The weighted gene co-expression network analysis, differential expression analysis (|log2(foldchange)| > 0.5 and adjusted P < 0.05), and protein-protein interaction network were sequentially performed to identify HCM-related hub genes. With a machine learning algorithm, the least absolute shrinkage and selection operator regression algorithm, a stable diagnostic model was developed. The immune-cell infiltration and biological functions of HCM were also explored to characterize its underlying pathogenic mechanisms and the immune signature. Two key modules were screened based on weighted gene co-expression network analysis. Pathogenic mechanisms relevant to extracellular matrix and immune pathways have been discovered. Twenty-seven co-regulated genes were recognized as HCM-related hub genes. Based on the least absolute shrinkage and selection operator algorithm, a stable HCM diagnostic model was constructed, which was further validated in the remaining three cohorts (n = 385). Considering the tight association between HCM and immune-related functions, we assessed the infiltrating abundance of various immune cells and stromal cells based on the xCell algorithm, and certain immune cells were significantly different between high-risk and low-risk groups. CONCLUSIONS: Our study revealed a number of hub genes and novel pathways to provide potential targets for the treatment of HCM. A stable model was developed, providing an efficient tool for the diagnosis of HCM.
Assuntos
Cardiomiopatia Hipertrófica , Aprendizado de Máquina , Humanos , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/diagnóstico , Perfilação da Expressão Gênica/métodos , Gerenciamento Clínico , MasculinoRESUMO
Renal dysfunction (RD) often characterizes the worse course of patients with advanced heart failure (AHF). Many prognosis assessments are hindered by researcher biases, redundant predictors, and lack of clinical applicability. In this study, we enroll 1736 AHF/RD patients, including data from Henan Province Clinical Research Center for Cardiovascular Diseases (which encompasses 11 hospital subcenters), and Beth Israel Deaconess Medical Center. We developed an AI hybrid modeling framework, assembling 12 learners with different feature selection paradigms to expand modeling schemes. The optimized strategy is identified from 132 potential schemes to establish an explainable survival assessment system: AIHFLevel. The conditional inference survival tree determines a probability threshold for prognostic stratification. The evaluation confirmed the system's robustness in discrimination, calibration, generalization, and clinical implications. AIHFLevel outperforms existing models, clinical features, and biomarkers. We also launch an open and user-friendly website www.hf-ai-survival.com , empowering healthcare professionals with enhanced tools for continuous risk monitoring and precise risk profiling.
Assuntos
Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Masculino , Feminino , Idoso , Prognóstico , Pessoa de Meia-Idade , Inteligência Artificial , Medição de Risco/métodos , Análise de Sobrevida , Insuficiência Renal/mortalidade , Insuficiência Renal/fisiopatologia , Insuficiência Renal/diagnóstico , BiomarcadoresRESUMO
Coronary atherosclerotic heart disease (CAD) is among the most prevalent chronic diseases globally. Circadian rhythm disruption (CRD) is closely associated with the progression of various diseases. However, the precise role of CRD in the development of CAD remains to be elucidated. The Circadian rhythm disruption score (CRDscore) was employed to quantitatively assess the level of CRD in CAD samples. Our investigation revealed a significant association between high CRDscore and adverse prognosis in CAD patients, along with a substantial correlation with CAD progression. Remarkably distinct CRDscore distributions were also identified among various subtypes. In summary, we have pioneered the revelation of the relationship between CRD and CAD at the single-cell level and established reliable markers for the development, treatment, and prognosis of CAD. A deeper understanding of these mechanisms may offer new possibilities for incorporating "the therapy of coronary heart disease based circadian rhythm" into personalized medical treatment regimens.
Assuntos
Ritmo Circadiano , Humanos , Ritmo Circadiano/fisiologia , Masculino , Feminino , Pessoa de Meia-Idade , Isquemia Miocárdica , Prognóstico , Doença da Artéria Coronariana , Idoso , Biomarcadores , Progressão da DoençaRESUMO
Objectives: α-tricalcium phosphate (α-TCP) and ß-dicalcium silicate (ß-C2S) have attracted much attention since these two types of self-curing Ca-phosphate and Ca-silicate are valuable biomaterials for bone defect or endodontic therapy. However, the injectable paste of their individual with high liquid/solid ratio is junior for root canal sealing due to very long self-setting time, low pH value and/or much volume shrinkage during paste-to-cement transformation. Methods: Our studies evaluated the effect of biphasic ratio, liquid/solid ratio and pH condition of aqueous medium on setting time and mechanical strength of this biphasic composite cement, and also the hydroxyapatite re-mineralization potential and anti-microleakage level of the cements with different α-TCP/ß-C2S ratio were explored in vitro. A control group free of paste filler was included in the extracted teeth model. Dentine re-mineralization and microleakage degree were observed by scanning electron microscopy and microCT reconstruction analysis. Results: It indicated that the weak acidic solution with pH value of 6.0 may produce a significantly shorter initial setting time (from 90 min to less 20 min) and expected final setting time (<150 min) for the biphasic composite (2:1 or 1:2) in comparison with the pure ß-C2S. Notably, the phasic composites exhibited limited microleakage and induced hydroxyapatite mineralization in the dentine tubules. These hydraulic pastes also produced strong alkaline feature and appreciable compressive resistance (12-18 MPa) after setting for a very short time stage. Moreover, a link between the addition of α-TCP leading to fast re-mineralization reaction was established. Significance: Our findings suggest that the appreciable self-setting and physicochemical properties adaption to root canal sealability make α-TCP/ß-C2S composites as preferential candidates for endodontic treatments.
RESUMO
Background: Synovial macrophages play important roles in the formation and progression of osteoarthritis (OA). This study aimed to explore the biological and clinical significance of macrophage-associated genes (MAGs) in OA. Methods: The OA synovial gene expression profiles GSE89408 and GSE82107 were obtained from the GEO database. Single-sample gene set enrichment analysis (ssGSEA) and GSEA were employed to decipher differences in immune infiltration and macrophage-associated biological pathways, respectively. Protein-protein interaction (PPI) network analysis and machine learning were utilized to establish a macrophage-associated gene diagnostic signature (MAGDS). RT-qPCR was performed to test the expression of key MAGs in murine models. Results: OA synovium presented high levels of immune infiltration and activation of macrophage-associated biological pathways. A total of 55 differentially expressed MAGs were identified. Using PPI analysis and machine learning, a MAGDS consisting of IL1B, C5AR1, FCGR2B, IL10, IL6, and TYROBP was established for OA diagnosis (AUC = 0.910) and molecular pathological evaluation. Patients with high MAGDS scores may possess higher levels of immune infiltration and expression of matrix metalloproteinases (MMPs), implying poor biological alterations. The diagnostic value of MAGDS was also validated in an external cohort (AUC = 0.886). The expression of key MAGs was validated in a murine model using RT-qPCR. Additionally, a competitive endogenous RNA network was constructed to reveal the potential posttranscriptional regulatory mechanisms. Conclusions: We developed and validated a MAGDS model with the ability to accurately diagnose and characterize biological alterations in OA. The six key MAGs may also be latent targets for immunoregulatory therapy.
Assuntos
Redes Reguladoras de Genes , Osteoartrite , Animais , Perfilação da Expressão Gênica , Humanos , Macrófagos/metabolismo , Camundongos , Osteoartrite/diagnóstico , Osteoartrite/genética , Osteoartrite/metabolismo , Membrana Sinovial/patologiaRESUMO
It is still a challenge to overcome the extended setting process of pure Ca-silicate as root canal fillers. We investigated the effects of attapulgite (a basic hydrous silicate of magnesium and aluminum) and ball-milling liquid medium on the self-curing properties of conventional ß-dicalcium silicate (C2Si)-based cements. It was shown that a minor amount of attapulgite nanofibers (1-4%) had only a slight influence on setting time but caused a large increase in compressive resistance and structural stability. In particular, the ball milling media with different acetone/water ratios (3:0, 2:1, 1:2, 0:3) could directly influence the particle size distribution of C2Si powders, and the co-existence of liquid media (2:1 or 1:2) may be beneficial for shortening the setting time, enhancing early-stage compressive strength, and significantly improving the anti-microleakage ability of cement. Moreover, the composite cements also exhibited appreciable antibacterial efficacy in vitro. These findings demonstrated that the physicochemical properties of the Ca-silicate powders could be tuned by adding a minor amount of inorganic silicate nanofibers and a simple ball milling condition, and such a facile strategy is favorable for developing novel (pre-mixed) Ca silicate-based cements as root canal sealers.
RESUMO
Metastatic dissemination represents a hallmark of cancer that is responsible for the high mortality rate. Recently, emerging evidence demonstrates a time-series event-pre-metastatic niche (PMN) has a profound impact on cancer metastasis. Exosomes, cell-free DNA (cfDNA), circulating tumor cells (CTC), and tumor microenvironment components, as critical components in PMN establishment, could be monitored by liquid biopsy. Intensive studies based on the molecular profile of liquid biopsy have made it a viable alternative to tissue biopsy. Meanwhile, the complex molecular mechanism and intercellular interaction are great challenges for applying liquid biopsy in clinical practice. This article reviews the cellular and molecular components involved in the establishment of the PMN and the promotion of metastasis, as well as the mechanisms of their interactions. Better knowledge of the characteristics of the PMN may facilitate the application of liquid biopsy for clinical diagnosis, prognosis, and treatment.
Assuntos
Exossomos , Células Neoplásicas Circulantes , Exossomos/genética , Humanos , Biópsia Líquida , Células Neoplásicas Circulantes/patologia , Prognóstico , Microambiente TumoralRESUMO
Background: Dilated cardiomyopathy (DCM) is characterized by left ventricular dilatation and systolic dysfunction. The pathogenesis and etiologies of DCM remain elusive. This study aims to identify the key genes to construct a genetic diagnosis model of DCM. Methods: A total of 257 DCM samples from five independent cohorts were enrolled. The Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to identify the key modules associated with DCM. The latent mechanisms and protein-protein interaction network underlying the key modules were further revealed. Subsequently, we developed and validated a LASSO diagnostic model in five independent cohorts. Results: Two key modules were identified using WGCNA. Novel mechanisms related to the extracellular, mitochondrial matrix or IL-17 signaling pathway were pinpointed, which might significantly influence DCM. Besides, 23 key genes were screened out by combining WGCNA and differential expression analysis. Based on the key genes, a genetic diagnosis model was constructed and validated using five cohorts with excellent AUCs (0.975, 0.954, 0.722, 0.850, 0.988). Finally, significant differences in immune infiltration were observed between the two groups divided by the diagnostic model. Conclusion: Our study revealed several novel pathways and key genes to provide potential targets and biomarkers for DCM treatment. A key genes' diagnosis model was built to offer a new tool for diagnosing DCM.
RESUMO
Introduction: Pyroptosis was recently implicated in the initiation and progression of tumors, including glioblastoma (GBM). This study aimed to explore the clinical significance of pyroptosis-related lncRNAs (PRLs) in GBM. Methods: Three independent cohorts were retrieved from the TCGA and CGGA databases. The consensus clustering and weighted gene coexpression network analysis (WGCNA) were applied to identify PRLs. The LASSO algorithm was employed to develop and validate a pyroptosis-related lncRNA signature (PRLS) in three independent cohorts. The molecular characteristics, clinical significances, tumor microenvironment, immune checkpoints profiles, and benefits of chemotherapy and immunotherapy regarding to PRLS were also explored. Results: In the WGCNA framework, a key module that highly correlated with pyroptosis was extracted for identifying PRLs. Univariate Cox analysis further revealed the associations between PRLs and overall survival. Based on the expression profiles of PRLs, the PRLS was initially developed in TCGA cohort (n = 143) and then validated in two CGGA cohorts (n = 374). Multivariate Cox analysis demonstrated that our PRLS model was an independent risk factor. More importantly, this signature displayed a stable and accurate performance in predicting prognosis at 1, 3, and 5 years, with all AUCs above 0.7. The decision curve analysis also indicated that our signature had promising clinical application. In addition, patients with high PRLS score suggested a more abundant immune infiltration, higher expression of immune checkpoint genes, and better response to immunotherapy but worse to chemotherapy. Conclusion: A novel pyroptosis-related lncRNA signature with a robust performance was constructed and validated in multiple cohorts. This signature provided new perspectives for clinical management and precise treatments of GBM.
RESUMO
Background: The unknown etiology of sarcoidosis with variable clinical features leads to delayed diagnosis and limited therapeutic strategies. Hence, exploring the latent mechanisms and constructing an accessible and reliable diagnostic model of sarcoidosis is vital for innovative therapeutic approaches to improve prognosis. Methods: This retrospective study analyzed transcriptomes from 11 independent sarcoidosis cohorts, comprising 313 patients and 400 healthy controls. The weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis were performed to identify molecular biomarkers. Machine learning was employed to fit a diagnostic model. The potential pathogenesis and immune landscape were detected by bioinformatics tools. Results: A 10-gene signature SARDS consisting of GBP1, LEF1, IFIT3, LRRN3, IFI44, LHFPL2, RTP4, CD27, EPHX2, and CXCL10 was further constructed in the training cohorts by the LASSO algorithm, which performed well in the four independent cohorts with the splendid AUCs ranging from 0.938 to 1.000. The findings were validated in seven independent publicly available gene expression datasets retrieved from whole blood, PBMC, alveolar lavage fluid cells, and lung tissue samples from patients with outstanding AUCs ranging from 0.728 to 0.972. Transcriptional signatures associated with sarcoidosis revealed a potential role of immune response in the development of the disease through bioinformatics analysis. Conclusions: Our study identified and validated molecular biomarkers for the diagnosis of sarcoidosis and constructed the diagnostic model SARDS to improve the accuracy of early diagnosis of the disease.
RESUMO
Background: Ischemic events after carotid endarterectomy (CEA) in carotid artery stenosis patients are unforeseeable and alarming. Therefore, we aimed to establish a novel model to prevent recurrent ischemic events after CEA. Methods: Ninety-eight peripheral blood mononuclear cell samples were collected from carotid artery stenosis patients. Based on weighted gene co-expression network analysis, we performed whole transcriptome correlation analysis and extracted the key module related to ischemic events. The biological functions of the 292 genes in the key module were annotated via GO and KEGG enrichment analysis, and the protein-protein interaction (PPI) network was constructed via the STRING database and Cytoscape software. The enrolled samples were divided into train (n = 66), validation (n = 28), and total sets (n = 94). In the train set, the random forest algorithm was used to identify critical genes for predicting ischemic events after CEA, and further dimension reduction was performed by LASSO logistic regression. A diagnosis model was established in the train set and verified in the validation and total sets. Furthermore, fifty peripheral venous blood samples from patients with carotid stenosis in our hospital were used as an independent cohort to validation the model by RT-qPCR. Meanwhile, GSEA, ssGSEA, CIBERSORT, and MCP-counter were used to enrichment analysis in high- and low-risk groups, which were divided by the median risk score. Results: We established an eight-gene model consisting of PLSCR1, ECRP, CASP5, SPTSSA, MSRB1, BCL6, FBP1, and LST1. The ROC-AUCs and PR-AUCs of the train, validation, total, and independent cohort were 0.891 and 0.725, 0.826 and 0.364, 0.869 and 0.654, 0.792 and 0.372, respectively. GSEA, ssGSEA, CIBERSORT, and MCP-counter analyses further revealed that high-risk patients presented enhanced immune signatures, which indicated that immunotherapy may improve clinical outcomes in these patients. Conclusion: An eight-gene model with high accuracy for predicting ischemic events after CEA was constructed. This model might be a promising tool to facilitate the clinical management and postoperative surveillance of carotid artery stenosis patients.
RESUMO
The development of bioactive Ca-silicate-based cements which may simultaneously suppress infection is promising for periapical therapy or alveolar bone defect repair. While these treatments are usually effective in the short term, many of these cements have not been designed to have an affinity with dental tissue in a prolonged anti-infectious manner and are only high alkaline in the early stages. This can lead to less favorable long-term outcomes, such as in bone repair or secondary therapy. Inspired by the strong antibacterial activity of zinc and copper ions, we developed a nonstoichiometric dicalcium silicate (C2S) substituted by 5% or 10% Zn or Cu to endow it with appropriate multifunctions. It was found that the foreign ion substitution could inhibit free CaO content and increase the pH value in the initial â¼6 h. The C2S cement only showed antibacterial activity in the early stage (6-72 h), but the C2S displayed appreciable long-term antibacterial potential against P. aeruginosa, E. faecalis and E. coli (>6 h) and S. aureus (>72 h). Moreover, the enhanced new bone regeneration by Zn substitution in C2S was confirmed in a maxillofacial bone defect model in rabbits. The increases in new bone formation adjacent to C2S-10Zn and C2S after 16 weeks of implantation were 32% and 20%, respectively. And the Tb.N values in the C2S-10Zn and C2S-10Cu groups (â¼5.7 and 4.9 mm-1) were over two-fold higher than in the C2S group (â¼2.0 mm-1). It is considered that Zn- or Cu-substitution in C2S is promising for applications to infectious bone repair.
Assuntos
Materiais Biocompatíveis/farmacologia , Compostos de Cálcio/farmacologia , Cobre/farmacologia , Osteogênese/efeitos dos fármacos , Silicatos/farmacologia , Zinco/farmacologia , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Compostos de Cálcio/química , Cobre/química , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Masculino , Teste de Materiais , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Coelhos , Silicatos/química , Staphylococcus aureus/efeitos dos fármacos , Zinco/químicaRESUMO
Platelet-rich plasma (PRP) has been shown to be a beneficial growth factor for bone tissue healing and is used in implantology. The aim of this study was to investigate the effects of PRP on bone defects in rabbits. Twenty rabbits were used to establish the implant bone defect model in this study. An intrabony defect (5mm × 5mm × 3mm) was created in alveolar bone in the lower jar of each rabbit. The wound was treated with PRP. The expression of platelet-derived growth factor BB (PDGFBB) was assessed by enzyme-linked immunosorbent assay (ELISA). Focal adhesion kinase (FAK) and related phosphatidylinositol 3-kinase (PI3K)/AKT (protein kinase B) levels were measured by Western blot. The results show that PRP could significantly improve the bone healing process when compared with control, and 10% PRP could markedly increase fibroblast proliferation 48-h post treatment. PDGFBB was higher in the PRP group than that in the control group. PRP treatment also could elevate the phosphorylation of FAK and PI3K/AKT, although the inhibitor of PDGFR could reverse this trend. These results suggest that PRP treatment improves the bone healing process through the FAK/PI3K/AKT pathway.
RESUMO
N-acetyltransferase 2 (NAT2) is a key enzyme involved in the metabolism of xenobiotics and plays a significant role in the detoxification of numerous potential carcinogens. According to its acetylation status, NAT2 acetylator may be classified into two phenotypes, rapid and slow. Numerous studies have demonstrated that the polymorphisms of NAT2 were correlated with individual susceptibility to several malignant neoplasms, including head and neck carcinomas (HNC). However, the associations between the acetylator phenotypes and HNC risk in each study were not entirely consistent. To assess these associations more comprehensively, we performed a meta-analysis. In this meta-analysis, 16 eligible studies including 2,965 cases with HNC and 3,919 controls were identified by searching the databases of PubMed, Medline and the ISI Web of Knowledge. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to evaluate the association. No significant associations between the rapid acetylator phenotype in NAT2 and HNC risk were found either in the overall analysis (OR=0.98; 95% CI 0.83, 1.15; I(2)=57%; P(heterogeneity)=0.003) or in the subgroup analysis by ethnicity (for the Caucasian population, OR=1.03, 95% CI 0.85, 1.24, I(2)=63%, P(heterogeneity)=0.002; for other mixed populations, OR=0.78, 95% CI=0.61, 1.00, I(2)=0%, P(heterogeneity)=0.47). In conclusion, this meta-analysis suggested that there is no association between the NAT2 phenotype and the risk of HNC.
RESUMO
Simultaneous multiple malignancies of the larynx are rarely reported. In this study, we describe a case with simultaneous laryngeal, moderately differentiated squamous cell carcinoma (SCC) and primary malignant fibrous histiocytoma (MFH) in a patient presenting with progressive hoarseness and without cervical lymphadenopathy. The clinical presentation, intraoperative findings, radiographic images and pathology slides are presented. The diagnosis was confirmed using H&E staining and immunohistochemical testing. A partial laryngectomy with bilateral neck selective dissection was performed. The patient survived for more than 46 months following surgery without recurrence or metastasis. To our knowledge, this is the first report of a case with simultaneous laryngeal SCC and primary MFH in the English literature. The results indicate that the markers used to assess the prognosis of MFH may also be used to assess simultaneous laryngeal SCC and primary MFH, and that laryngectomy to preserve function may be performed in early-stage patients.
Assuntos
Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/diagnóstico , Histiocitoma Fibroso Maligno/complicações , Histiocitoma Fibroso Maligno/diagnóstico , Neoplasias Laríngeas/complicações , Neoplasias Laríngeas/diagnóstico , Idoso , Carcinoma de Células Escamosas/patologia , Feminino , Histiocitoma Fibroso Maligno/cirurgia , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Tooth eruption is an orientating action which migrates teeth coronally during life, even in bone or after occlusion contact is lost. The eruption pathway is due to bone resorption near the enamel crown and bone deposition around the cementum-covered roots. Due to their proximity to bone resorption and deposition, we hypothesize that the hard tissues enamel, dentine or cementum are important during eruption. In the present study, extracted human teeth were cut into enamel samples, enamel-dentine samples or dentine-cementum samples, and implanted into bone defects in rabbit tibia. Hematoxylin and eosin, tartrate-resistant acid phosphatase activity, tetracycline tracing and scanning electron microscopy were used to investigate bone resorption and deposition 1-8 weeks after surgery. The results showed that resorption lacunae with numerous osteoclasts were observed facing enamel and significant new bone deposition occurred near the cementum surface, compared to other hard tooth surfaces. These findings indicate that the enamel crown may stimulate bone resorption and initiate the eruption pathway, and that the cementum root may stimulate bone deposition. Bone regeneration initiated by tooth hard tissues may be a potential motive force during tooth eruption.
Assuntos
Remodelação Óssea/fisiologia , Cimentos Dentários/metabolismo , Esmalte Dentário/metabolismo , Dentina/metabolismo , Erupção Dentária/fisiologia , Raiz Dentária/metabolismo , Animais , Esmalte Dentário/transplante , Dentina/transplante , Humanos , Osteoclastos/metabolismo , Coelhos , Raiz Dentária/transplante , Transplante HeterólogoRESUMO
OBJECTIVE: To investigate the significance of type IV collagen, metalloproteinase-2 (MMP-2), metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression in laryngeal squamous cell carcinomas (LSCCs). METHODS: Expression was quantified in 44 LSCC and 22 adjacent non-cancer normal tissues using a streptavidin-peroxidase conjugated immunohistochemistry and associations between the levels of the four proteins and clinicopathological characteristics in LSCC were analyzed. RESULTS: Significantly different expression of all four proteins was observed in LSCC and adjacent non-cancer normal tissues (P<0.05). Expression of type IV collagen correlated with primary cancer status (P = 0.04), clinical stage (P = 0.04) and histological grade (P = 0.01). Expression of MMP-9 correlated with the location of the tumor (P = 0.04), cervical node metastasis (P = 0.02) and prognosis (P = 0.02). The (MMP-2+MMP-9)/TIMP-1 score was associated with the prognosis of LSCC (P < 0.01). CONCLUSIONS: This study suggests that expression of type IV collagen and its regulators is strongly associated with the development of LSCC. Type IV collagen and MMP-9 may be more valuable than MMP-2 and TIMP-1 for the evaluation of clinical characteristics. Regulation of type IV collagen may contribute to the balance of MMPs and TIMPs in LSCC.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Colágeno Tipo IV/metabolismo , Neoplasias Laríngeas/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Recidiva Local de Neoplasia/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Laríngeas/patologia , Laringe/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , PrognósticoRESUMO
PURPOSE: Several studies have reported influence of the murine double minute 2 (MDM2) 309T>G polymorphism on head and neck squamous cell carcinoma (HNSCC) susceptibility. However, the results remain controversial and ambiguous. We therefore carried out a meta-analysis to explore more precisely the association between MDM2 309T>G variants and the risk of HNSCC. METHODS: Studies on the association between MDM2 309T>G polymorphism and HNSCC were searched in the PubMed database. All relevant studies that met the inclusion criteria were eligible for the analysis. Four genetic models and generalized odds ratios (ORs) and 95% confidence interval (CIs) were used for the assessment. RESULTS: A total of seven articles with 1,629 cases and 2,472 controls were included in our meta-analysis. Overall, significant associations between the MDM2 SNP309T>G and HNSCC risk for TG vs. TT model and the dominant model (TG+GG vs. TT) were observed (OR=0.82, 95%CI=0.70-0.96 and OR=0.83, 95%CI=0.71-0.96, respectively). On subgroup meta-analysis by ethnicity, a negative association was shown in the Caucasian subgroup (for GG vs. TT: OR=0.661, 95%CI=0.455-0.960; for TG vs. TT: OR=0.653, 95%CI=0.496-0.859; for the dominant model GG+TG vs. TT: OR= 0.657, 95%CI=0.463-0.931). However, in the Asian population no significant association was found. Subgroup analysis by the source of controls also yielded non-significant results. None of the results were materially altered in any genetic model after studies which did not fulfill Hardy-Weinberg equilibrium were excluded. CONCLUSION: The present meta-analysis suggested that the MDM2 SNP309 G allele probably acts as an important HNSCC protective factor in Caucasians, but no association exists in Asians.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Intervalos de Confiança , Predisposição Genética para Doença , Genótipo , Humanos , Metanálise como Assunto , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , População Branca/genéticaAssuntos
Periodontite Crônica/terapia , Raspagem Dentária , Tratamento do Canal Radicular , Periodontite Crônica/diagnóstico , Periodontite Crônica/diagnóstico por imagem , Seguimentos , Defeitos da Furca/diagnóstico , Defeitos da Furca/diagnóstico por imagem , Defeitos da Furca/terapia , Hiperplasia Gengival/diagnóstico , Hiperplasia Gengival/diagnóstico por imagem , Hiperplasia Gengival/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Índice Periodontal , Radiografia Panorâmica , Perda de Dente/diagnóstico , Perda de Dente/diagnóstico por imagem , Perda de Dente/terapia , Dente ArtificialRESUMO
OBJECTIVE: To investigate the influence of surface potentials of tooth hard tissue on bone remodeling. METHODS: After insured the surface potentials of human extracted teeth with electrochemical methods, teeth sections and artificial hydroxyapatite were implanted into 25 rabbits' tibiae. The rabbits were sacrificed at 1, 2, 4, 6 and 8 weeks after implantation, respectively. The bone regeneration was compared between opposite two sides (cathode side and anode side) of tooth sections using hematoxylin-eosin (HE) staining, tartrate-resistant acid phosphatase (TRAP) activity detecting and tetracycline tracing method. RESULTS: Resorption lacunae was seen in the tibiae facing to the enamel anode and new bone density in the implant bed near the cathode of tooth samples was much higher than that near the anode, while the number of TRAP positive cells near the cathode was smaller than that near the anode (P < 0.01). The fluorescent area of tetracycline tracing near the cathode was larger than that near the anode (P < 0.05). CONCLUSIONS: The cathode of tooth hard tissue (cementum) could improve or trigger new bone formation, while the other side, anode (enamel), could improve the bone resorption. This study suggests that tooth hard tissue's electrochemical characteristic might affect the remodeling of alveolar bone, and tooth supraeruption and the alveolar bone loss after tooth extraction might result from the redundant or lack of root electrochemical stimulation to bone.