RESUMO
Small cell lung cancer (SCLC) is a malignant tumor characterized by aggressiveness and dismal prognosis. The specific role of ubiquitin-like PHD and RING finger domain (UHRF1), a frequently overexpressed cancer-promoting gene in various tumors, is poorly understood in SCLC. Herein, we explored the potential carcinogenic role of UHRF1 in SCLC. First, public databases were used to analyze the expression of UHRF1 in SCLC, and tissue specimens in our center were examined to confirm the results while clinical outcomes were collected to analyze its relationship with UHRF1. Then, UHRF1 knockdown and overexpression cell lines were established to evaluate the carcinogenic function of UHRF1 in vitro and in vivo. The mechanism of the biological consequences was determined by co-inmunoprecipitation. Moreover, we also analyzed the influence of UHRF1 on cisplatin (DDP) sensitivity of SCLC. The expression of UHRF1 was significantly higher in SCLC tissues than in normal tissues, and high levels of UHRF1 suggested a poor prognosis for SCLC. Mechanistically, UHRF1 promoted SCLC growth through yes-associated protein 1 (YAP1). Specifically, UHRF1 bound to YAP1 and inhibited YAP1 ubiquitin degradation, thus stabilizing the YAP1 protein in SCLC cells. UHRF1 downregulation enhanced DDP sensitivity in SCLC cells and was correlated with a favorable prognosis in patients with SCLC treated with platinum-based chemotherapy. UHRF1 plays an oncogenic role in SCLC by modulating YAP1. Therefore, UHRF1 could be used as a biomarker to predict the prognosis of SCLC patients and serve as a potential therapeutic target for SCLC patients.
Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Linhagem Celular Tumoral , Fatores de Transcrição/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Ubiquitinas/genética , Ubiquitinas/metabolismo , Ubiquitinas/uso terapêutico , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Recurrent aphthous stomatitis remains the most common disease of the oral mucosa. The aim of this study was to investigate the clinical significance of serum interleukin-6, interleukin-17A, and tumor necrosis factor-alpha in recurrent aphthous stomatitis. METHODS: Using flow cytometry analysis, we detect the level of serum interleukin-2, interleukin-6, interleukin-17A, tumor necrosis factor-alpha, and interferon-gamma in 127 patients with recurrent aphthous stomatitis and 20 healthy control cases; compare; and analyze the correlation of each index. RESULTS: The levels of serum interleukin-2, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma in the recurrent aphthous stomatitis group were higher than in the control group, and the differences were statistically significant (P < .05). There was no significant difference in interleukin-17A between the two groups. CONCLUSION: The levels of serum interleukin-6 and tumor necrosis factor-alpha in recurrent aphthous stomatitis patients were significantly increased. Considering that serum TNF-α was mostly within the normal range, its role in the pathology of RAS needed to be further explored.
Assuntos
Estomatite Aftosa , Fator de Necrose Tumoral alfa , Humanos , Interleucina-17 , Interleucina-2 , Interleucina-6 , RecidivaRESUMO
Brusatol (Bru), a main extract from traditional Chinese medicine Brucea javanica, has been reported to exist antitumor effect in many tumors including melanoma. However, the underlying mechanism in its anti-melanoma effect still need further exploration. Here, we reported that the protein expression of KLF4 in melanoma cells were significantly downregulated in response to brusatol treatment. Overexpression of KLF4 suppressed brusatol-induced melanoma cell apoptosis; while knockdown of KLF4 enhanced antitumor effects of brusatol on melanoma cells not only in vitro but also in vivo. Further studies on the mechanism revealed that KLF4 bound to the promoter of NCK2 directly and facilitated NCK2 transcription, which suppressed the antitumor effect of brusatol on melanoma. Furthermore, our findings showed that miR-150-3p was dramatically upregulated under brusatol treatment which resulted in the downregulation of KLF4. Our results suggested that the miR-150-3p/KLF4/NCK2 axis might play an important role in the antitumour effects of brusatol in melanoma.
Assuntos
Melanoma , MicroRNAs , Quassinas , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/metabolismo , Quassinas/farmacologia , Apoptose , MicroRNAs/genética , MicroRNAs/farmacologia , Proteínas Oncogênicas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismoRESUMO
This study has used machine learning algorithms to develop a predictive model for differentiating between dermoscopic images of basal cell carcinoma (BCC) and actinic keratosis (AK). We compiled a total of 904 dermoscopic images from two sources - the public dataset (HAM10000) and our proprietary dataset from the First Affiliated Hospital of Dalian Medical University (DAYISET 1) - and subsequently categorised these images into four distinct cohorts. The study developed a deep learning model for quantitative analysis of image features and integrated 15 machine learning algorithms, generating 207 algorithmic combinations through random combinations and cross-validation. The final predictive model, formed by integrating XGBoost with Lasso regression, exhibited effective performance in the differential diagnosis of BCC and AK. The model demonstrated high sensitivity in the training set and maintained stable performance in three validation sets. The area under the curve (AUC) value reached 1.000 in the training set and an average of 0.695 in the validation sets. The study concludes that the constructed discriminative diagnostic model based on machine learning algorithms has excellent predictive capabilities that could enhance clinical decision-making efficiency, reduce unnecessary biopsies, and provide valuable guidance for further treatment.
RESUMO
Root canal irrigation is an important step in root canal preparation procedures and has a great impact on the success rate of root canal treatment. Computational fluid dynamics (CFD) is a new method to study root canal irrigation. It can be used to simulate and visualize the process of root canal irrigation, and quantitatively evaluate the effect of root canal irrigation through parameters such as flow velocity and wall shear stress. In recent years, researchers have conducted extensive studies on the factors that influence root canal irrigation efficiency, such as the position of the irrigation needle, the size of root canal preparation, the types of irrigation needles, and so on. This article reviewed the development of root canal irrigation research methods, the steps of CFD simulation in root canal irrigation, and the application of CFD in root canal irrigation in recent years. It aimed to provide new research ideas for the application of CFD to root canal irrigation and to provide a reference for the clinical application of CFD simulation results.
Assuntos
Cavidade Pulpar , Hidrodinâmica , Reologia , Irrigantes do Canal Radicular , Irrigação TerapêuticaRESUMO
Background: Diabetes-associated periodontal disease is caused by diabetes-enhanced host immune-inflammatory responses to bacterial insult. An increasing number of papers related to diabetes-associated periodontal disease have been published. This study analyzed research on diabetes-associated periodontal disease with bibliometrics methods. The objective of this study was to identify hotspots and frontiers in the diabetes-associated periodontal disease research field. Methods: Publications were extracted from the Web of Science core collection database, and the document types included were limited to articles and reviews. The bibliometric analysis software CiteSpace5 was used to analyze the number of articles, research fields, countries/regions, institutions, authors, keywords, and other information. Outcomes were visualized to analyze the hotspots and research frontiers of diabetes-associated periodontal disease. Results: A total of 3,572 articles were retrieved. Among the research fields, dentistry, oral surgery, and medicine accounted for the highest proportion of publications, and public, environmental, and occupational health had the highest betweenness centrality. The number of publications from the United States ranked first among all the countries, while Columbia University ranked first among all the institutions. Global cooperation was not frequent. Keyword analysis showed that inflammatory pathways were the hotspots. Burst words analysis indicated that early prevention was a research frontier. Conclusions: The bibliometric method helped identify research hotspots and frontiers. Inflammatory pathways were hotspots, and early prevention was a frontier in diabetes-associated periodontal disease.
RESUMO
Background: Anti-silencing function 1B (ASF1B), a histone H3-H4 chaperone, is crucial for S-phase progression and cell proliferation. Recent studies have shown that ASF1B may be used as a new proliferation marker for cancer prognosis. However, the prognostic value and effect of ASF1B on tumor cells and the immune microenvironment in hepatocellular carcinoma (HCC) remain unclear. Methods: We analyzed the expression of ASF1B and its prognostic value using The Cancer Genome Atlas (TCGA) database (as a training set) and other databases, and we validated the findings by immunohistochemistry in our clinical database, containing 141 HCC patients (as a validation set). Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to probe the tumor-associated biological processes of ASF1B in HCC. The interrelationships between ASF1B expression and tumor immunological characteristics were analyzed by multiple databases. The Imvigor210 cohort was retrieved to assess the ability of ASF1B to predict immunotherapy efficacy. Results: ASF1B was highly expressed in tumor tissue compared to paracancerous tissue. High ASF1B expression was associated with worse overall survival (OS) and progression-free survival (PFS) in the training set (p = 0.005, p < 0.001) and validation set (p < 0.001, p < 0.001). Multivariate analysis revealed that ASF1B was an independent prognostic factor associated with OS and PFS. GSEA and GSVA suggested that ASF1B was involved in tumor-associated biological processes, including the cell cycle, DNA replication, base excision repair, mismatch repair, RNA degradation, ubiquitin-mediated proteolysis, and nucleotide excision repair. Further analysis revealed that the levels of ASF1B were positively correlated with the immune cells infiltration of B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells. However, ASF1B was positively correlated with Treg cell infiltration and inhibitory immune checkpoints in exhausted T cells. Patients who received anti-PD-L1 immunotherapy with high ASF1B expression had a higher objective response. Conclusion: The ASF1B level is an independent prognostic factor and may serve as a potential immunotherapeutic target.
RESUMO
PURPOSE: The high fatality-to-case ratio of hepatocellular carcinoma is directly related to metastasis. The signal transducer and activator of transcription-3 is a key mediator of the cytokine and growth factor signaling pathways and drives the transcription of genes responsible for cancer-associated phenotypes. However, so far, no specific inhibitor for signal transducer and activator of transcription-3 has been used in clinical practice. Therefore, targeting the signal transducer and activator of transcription-3 for cancer therapy is highly desired to improve outcomes in patients with hepatocellular carcinoma. EXPERIMENTAL DESIGN: Using the small-molecule inhibitor NT157, the effect of signal transducer and activator of transcription-3 inhibition on cell migration was tested in hepatocellular carcinoma cell lines and a lung metastasis model of the disease. RESULTS: NT157 significantly inhibited the migration of hepatocellular carcinoma cell lines in vitro and lung metastasis of hepatocellular carcinoma in vivo. Mechanistically, it inhibited the phospho-signal transducer and activator of transcription-3 in a dose- and time-dependent manner. Furthermore, NT157 treatment suppressed the c-Jun activation domain-binding protein-1 levels in the nucleus but no significant decrease was observed in its expression in the cytoplasm. Finally, high mRNA expression levels of signal transducer and activator of transcription-3 and c-Jun activation domain-binding protein-1 in hepatocellular carcinoma were associated with significantly low survival rates. CONCLUSION: NT157 inhibits hepatocellular carcinoma migration and metastasis by downregulating the signal transducer and activator of transcription-3/c-Jun activation domain-binding protein-1 signaling pathway and targeting it may serve as a novel therapeutic strategy for the clinical management of hepatocellular carcinoma in the future.
Assuntos
Antineoplásicos/farmacologia , Complexo do Signalossomo COP9/metabolismo , Movimento Celular/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeo Hidrolases/metabolismo , Pirogalol/análogos & derivados , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/farmacologia , Animais , Complexo do Signalossomo COP9/genética , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Feminino , Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hepáticas , Masculino , Camundongos , Gradação de Tumores , Estadiamento de Neoplasias , Neovascularização Patológica , Peptídeo Hidrolases/genética , Pirogalol/farmacologia , RNA Mensageiro , Fator de Transcrição STAT3/genéticaRESUMO
OBJECTIVE: To summarize evidence and data from experimental studies regarding the role and mechanism of the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in the pathogenesis of several representative oral diseases. MATERIALS AND METHODS: A literature search of PubMed and EBSCO was performed. The literature was searched using a combination of keywords, e.g., NLRP3 inflammasome, inflammation, microorganisms, oral inflammatory diseases, and oral immunological diseases. RESULTS: The initiation and activation of the NLRP3 inflammasome are associated with the pathogenesis and progression of several representative oral diseases, including periodontitis, oral lichen planus, dental pulp disease, and oral cavity squamous cell carcinoma. CONCLUSIONS: The NLRP3 inflammasome plays a crucial role in the progression of inflammatory and adaptive immune responses. The possible role of the NLRP3 inflammasome in several oral diseases, including not only periodontitis and pulpitis but also mucosal diseases and oral cavity squamous cell carcinoma, may involve the aberrant regulation of inflammatory and immune responses. Understanding the cellular and molecular biology of the NLRP3 inflammasome is necessary because the NLRP3 inflammasome may be a potential therapeutic target for the treatment and prevention of oral inflammatory and immunological diseases.
Assuntos
Trifosfato de Adenosina/imunologia , Imunidade Inata , Inflamassomos/imunologia , Doenças da Boca/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Animais , Humanos , Doenças da Boca/microbiologia , Estresse Oxidativo , Transdução de SinaisRESUMO
Superficial mucoceles are a relatively rare variant of common mucoceles and have an unclear etiology. Clinically, they are small, translucent, subepithelial vesicles affecting the oral mucosa in the retromolar region, the lower labial and buccal regions, and the bilateral soft palate. Superficial mucocele is easily misdiagnosed as pemphigoid, bullous lichen planus, herpes lesion, or venous lake when it is concomitant with oral lichen planus (OLP) or lichenoid disorders on the basis of the initial impression. An inflammatory mechanism related to OLP has been hypothesized to induce the development of superficial mucoceles. It is essential to be familiar with this entity. This report presents 9 cases of multiple superficial mucoceles that occurred sequentially concomitant with OLP and with consistent clinical and histopathologic features. Relevant studies reported in the literature are also reviewed to provide additional clarification of the etiology, clinicopathologic characteristics, and differential diagnosis.
Assuntos
Líquen Plano Bucal , Líquen Plano , Mucocele , Bochecha , Humanos , Mucosa BucalRESUMO
Objective: Oral lichen planus (OLP) is a relatively common immunological mucocutaneous disease that causes pain and poor quality of life. Curcumin has been reported to be a safe and effective treatment for OLP. The objective of this review is to evaluate the existing evidence for the safety of curcumin in treating OLP as well as its efficacy compared with that of corticosteroids. Methods: We reviewed the published literature by searching PubMed, EMBASE, EBSCO, and Cochrane Library, and then retrieved and analyzed several variables from patient records. Results: Nine studies met the inclusion criteria, including six randomized, double-blind clinical trials; two pilot clinical trials; and one case report. A total of 259 OLP patients were included in the systematic review. Seven studies showed statistically significant differences in pain severity and clinical appearance of oral lesions after treatment with curcumin for a period of time, compared to baseline (p < .05). Three controlled clinical trials compared the efficacy of curcumin to that of corticosteroids; all of these trials showed no statistically significant differences in pain severity and clinical appearance of oral lesions. Conclusions: Curcumin is a safe treatment and can be used as an adjunct in combination with corticosteroids to reduce pain, burning sensations, and the clinical appearance of oral lesions in OLP patients.
Assuntos
Curcumina/uso terapêutico , Líquen Plano Bucal/tratamento farmacológico , Corticosteroides/uso terapêutico , Ensaios Clínicos como Assunto , Curcumina/efeitos adversos , Bases de Dados Factuais , Gastroenteropatias/etiologia , Humanos , Qualidade de Vida , Resultado do TratamentoRESUMO
PURPOSE: The aim of this study was to investigate the severity and status of oral mucosa and periodontal status in early and late stage after receiving hematopoietic stem cell transplantation(HSCT). METHODS: This study enrolled patients submitted to hematopoietic stem cell transplantation. Through a survey questionnaire, clinical examination, we collected clinical data from 108 HSCT recipients and divided them into 2 groups: transplantation time less than 1 year and more than 1 year. The oral mucosal and periodontal status were recorded and statistically analyzed with SPSS 21.0 software package. RESULTS: The incidence of oral features after HSCT was 78.95%. The incidence of mild symptoms with HSCT less than 1year (n=32) and HSCT more than 1 year (n=43) was 59.38% and 18.60%, respectively. There was significant difference between the two groups (P=0.001).The percent of lichenoid/hyperkeratotic plaques was 31.25% and 60.47%, respectively. The lichenoid/hyperkeratotic plaques were significantly different between the two groups (P=0.012). The detection rate of shallow and moderate pockets was 49.38% and 40.74%, respectively. Visual plaque, calculus and bleeding on probing were 62.96%, 64.20% and 50.62%, respectively. CONCLUSIONS: The incidence of periodontal and mucosal lesions after HSCT is high. The mild symptoms of oral graft versus host disease in early stage are identified obviously, mainly like lichenoid/hyperkeratotic plaques in late stage.