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Relative fat mass (RFM) is a novel indicator for measuring body fat. This cross-section study aims to explore the association between RFM and periodontitis and to investigate possible effect modifiers in U.S. adults based on the National Health and Nutrition Examination Survey 2009-2014. The category of periodontitis was defined by the CDC/AAP. Mean clinical attachment loss and mean pocket probing depth (PPD) were calculated. The RFM formula is: 64 - (20 × height/WC) + (12 × sex), with sex coded as 1 for female and 0 for male. Natural cubic spline and weighted multivariable regression analyses were conducted to investigate the relationship between RFM and periodontal status. Subgroup and interaction analyses were also employed to assess the moderating roles of age, gender, and race. A total of 10,307 participants were included in our study. Compared to the lowest quartiles, individuals in the highest quartiles of RFM levels were more likely to have moderate/severe periodontitis (ORQ4vs1 = 1.64, 95% CI 1.30-2.06) and had a higher mean PPD (ßQ4vs1 = 0.15, 95% CI 0.09-0.22). This association was particularly stronger in populations under the age of 60, with significant interactions. Taken together, RFM is positively associated with periodontitis, particularly in those under 60 years old.
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Encuestas Nutricionales , Periodontitis , Humanos , Masculino , Periodontitis/epidemiología , Femenino , Persona de Mediana Edad , Adulto , Estudios Transversales , Estados Unidos/epidemiología , Tejido Adiposo/patología , Anciano , Adulto Joven , Índice de Masa CorporalRESUMEN
BACKGROUND: This study aimed to investigate the relationship between the pan-immune-inflammation value (PIV) and periodontitis based on a large national survey. METHODS: In the present cross-sectional study, data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014, which included a total of 10,300 participants. The categorization of periodontitis was based on the 2017 classification scheme. The PIV was determined using the formula: (neutrophils count × monocyte count × platelet count)/lymphocytes count. Restricted cubic spline and weighted multivariable logistic regression analyses were employed to evaluate the associations between the PIV with periodontitis. RESULTS: The associations between PIV and stage III/IV periodontitis followed a U-shaped pattern (Pnon-linearity < 0.001). The risk of developing stage III/IV periodontitis showed an increasing trend among participants in the first quartile (odds ratio [OR] = 1.21; 95% confidence interval [CI]: 1.01-1.46), third quartile (OR = 1.34; 95% CI: 1.11-1.61), and fourth quartile (OR = 1.47; 95% CI: 1.25-1.73) compared to those in the second quartile. Subgroup analysis indicated stronger associations of PIV with periodontitis in males (ORQ4vs2 = 1.72, 95% CI: 1.36-2.18) and individuals with hypertension (ORQ4vs2 = 1.78, 95% CI: 1.38-2.28) with significant interactions (Pinteraction < 0.05). CONCLUSIONS: There is a U-shaped association between PIV and stage III/IV periodontitis, which suggests a potential adjunctive treatment strategy for periodontitis. Higher PIV values were found to have a stronger correlation with stage III/IV periodontitis in males and individuals with hypertension. Further prospective trials are needed to confirm the validity of our results. PLAIN LANGUAGE SUMMARY: A U-shaped association exists between the pan-immune inflammation value and periodontitis in US adults, suggesting that maintaining a moderate immune inflammation response is crucial for periodontal health.
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Background: The majority of patients of lung cancer have already lost the chance of surgery at the time of diagnosis. Percutaneous local thermal ablation is a precise minimally invasive technique and a viable alternative to surgical treatment. Compared with radiofrequency ablation and microwave ablation, percutaneous laser ablation for the treatment of lung tumors is less commonly used and reported, especially for primary lung cancer. Case presentation: A 63-year-old male patient with mixed pulmonary nodules selected computed tomography-guided electromagnetic navigation system for percutaneous biopsy and laser ablation therapy. The puncture point was determined through Computed tomography scanning, along with the placement of the electromagnetic navigation system locators. After rapid on-site evaluation and pathological examination of the puncture tissue specimen, the diagnosis of lung adenocarcinoma was confirmed. A 980-nanometer wavelength semiconductor laser fiber was inserted into the appropriate position guided by the electromagnetic navigation system. Subsequently, a power of 7 watt was applied to ablate the tumor for 30 seconds, then pause for 60 seconds before repeating the procedure. Positron emission tomography-Computed tomography examination was performed 1 month after operation, suggesting complete response of the tumor. Conclusion: Here, we present a case of percutaneous laser ablation treatment for primary lung cancer guided by computed tomography-electromagnetic navigation system. As a more precise, shorter duration, impedance-independent, safe and effective minimally invasive thermal ablation method, it is expected to gain wider application and become a novel alternative for surgical treatment.
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COVID-19 , Humanos , COVID-19/diagnóstico , Estudios Retrospectivos , Pronóstico , Biomarcadores/sangre , Masculino , Femenino , Persona de Mediana Edad , SARS-CoV-2 , AncianoRESUMEN
The role of the integrin family in malignancy has received increasing attention. Many studies have confirmed that ITGB4 could activate multiple signal pathways and promote cell migration in various cancers. However, the regulatory role of integrin ß4 (ITGB4) in lung adenocarcinoma (LUAD) is still unclear. Examination of the expression or survival analysis of ITGB4 in cells, pathological samples, and bioinformatics lung adenocarcinoma databases showed ITGB4 was highly expressed in LUAD and significantly associated with poor prognosis. Small interfering RNA and plasmids were performed to investigate the effect of changes in ITGB4 expression on lung adenocarcinoma. Focal adhesion kinase (FAK) inhibitor defactinib was used to further explore the molecular mechanism of ITGB4. The results showed depletion of ITGB4 inhibited migration and activation of FAK signaling pathways in lung adenocarcinoma cells. Moreover, increased ITGB4 expression activated FAK signaling and promoted cell migration, which can be reversed by defactinib. In addition, ITGB4 could interact with FAK in lung adenocarcinoma cells. ITGB4 may promote cell migration of lung adenocarcinoma through FAK signaling pathway and has the potential to be a biomarker for lung adenocarcinoma.
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The most prevalent cause of lung cancer is smoking tobacco, but exposure to second hand smoke, air pollution, and certain chemicals and substances at work can also raise the risk of disease. In this study, we scrutinized the chemoprotective effect of the metformin and atorvastatin combination against benzo[a]pyrene (BaP)-induced lung cancer in mice of Swiss albino. BaP (50 mg/kg) was used for induction of lung cancer and mice were treated with metformin, atorvastatin or their combination. Metformin + atorvastatin combination significantly (p< 0.001) improved the body weight, liver weight, suppressed the lung weight and tumor incidence and altered the levels of immunocompetent cells, polyamines, lung tumor markers, lung parameters and antioxidant parameters, respectively. Metformin + atorvastatin combination also suppressed cytokines levels, inflammatory parameters and caspase parameters. On the basis of the results, we can conclude that metformin + atorvastatin combination remarkably suppressed lung cancer via the inflammatory pathway.
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Neoplasias Pulmonares , Metformina , Ratones , Animales , Metformina/efectos adversos , Metformina/metabolismo , Atorvastatina/efectos adversos , Atorvastatina/metabolismo , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Benzo(a)pireno/toxicidad , Benzo(a)pireno/metabolismo , Transducción de Señal , Pulmón/patologíaRESUMEN
Lung adenocarcinoma (LUAD) is a clinically challenging disease due to its poor prognosis and limited therapeutic methods. The aim of the present study was to identify prognosis-related genes and therapeutic targets for LUAD. Raw data from the GSE32863, GSE41271 and GSE42127 datasets were downloaded from the Gene Expression Omnibus database. Following normalization, the data were merged into a matrix, which was first used to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) and survival analysis were performed to screen potential prognosis-related genes. Gene overlaps among DEGs, survival-related genes and WGCNA genes were finally constructed to obtain candidate genes. An analysis with the STRING database was performed to construct a protein-protein interaction network and hub genes were selected using Cytoscape. The candidate genes were finally identified by univariate and multivariate Cox regression analysis. Furthermore, in vivo and in vitro experiments, including immunohistochemistry, immunofluorescence, Cell Counting Kit-8, colony-formation and migration assays, were performed to validate the potential mechanism of these genes in LUAD. Two genes, namely forkhead box M1 (FOXM1) and centromere protein F (CENPF), were identified as unfavorable indicators of prognosis in patients with LUAD. High expression of FOXM1 and CENPF were associated with poor survival. Furthermore, LUAD cells with FOXM1 and CENPF knockdown showed a significant reduction in proliferation and migration (P<0.05). FOXM1 and CENPF may have an essential role in the prognosis of patients with LUAD by influencing cell proliferation and migration, and they provide potential molecular targets for LUAD therapy.
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The AHNAK family currently consists of two members, namely AHNAK and AHNAK2, both of which have a molecular weight exceeding 600 kDa. Homologous sequences account for approximately 90% of their composition, indicating a certain degree of similarity in terms of molecular structure and biological functions. AHNAK family members are involved in the regulation of various biological functions, such as calcium channel modulation and membrane repair. Furthermore, with advancements in biological and bioinformatics technologies, research on the relationship between the AHNAK family and tumors has rapidly increased in recent years, and its regulatory role in tumor progression has gradually been discovered. This article briefly describes the physiological functions of the AHNAK family, and reviews and analyzes the expression and molecular regulatory mechanisms of the AHNAK family in malignant tumors using Pubmed and TCGA databases. In summary, AHNAK participates in various physiological and pathological processes in the human body. In multiple types of cancers, abnormal expression of AHNAK and AHNAK2 is associated with prognosis, and they play a key regulatory role in tumor progression by activating signaling pathways such as ERK, MAPK, Wnt, and MEK, as well as promoting epithelial-mesenchymal transition.
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OBJECTIVES: The aim of this study is to explore the association between serum human epididymal protein (HE4) levels and poor periodontal health. MATERIALS AND METHODS: Data used in our study from the National Health and Nutrition Examination Survey (NHANES) 2001-2002 and Gene Expression Omnibus database (GSE10334 and GSE16134). Periodontitis category was defined by the 2017 classification scheme based on clinical periodontal parameters. Univariate and multivariate logistic regression analyses were used to explore the relationship between serum HE4 levels and the risk of periodontitis. GSEA analysis was performed to investigate the function of HE4. RESULTS: A total of 1715 adult women over the age of 30 were included in our study. Compared with the lowest tertile, individuals in the highest tertile of HE4 levels were more likely to be Stage III/IV periodontitis (ORtertile3vs1 = 2.35, 95% CI: 1.35-4.21). The association was still significant in populations who were less than 60 years old, non-Hispanic white, high school graduate, 1.3 < PI ≤ 3.5, non-smoker, current smoker, non-obese, obese, and who had not diabetes mellitus or had not hypertension. In addition, HE4 expression was upregulated in diseased gingival tissues and involved in cell proliferation and immunity. CONCLUSIONS: Serum HE4 is positively associated with poor periodontal health in adult women. CLINICAL RELEVANCE: Patients with high serum HE4 levels are more likely to have Stage III/IV periodontitis. HE4 has the potential to be used as a biomarker to predict the severity of periodontitis.
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Diabetes Mellitus , Periodontitis , Humanos , Adulto , Femenino , Persona de Mediana Edad , Encuestas Nutricionales , FumadoresRESUMEN
As an important element in regulating the tumor microenvironment (TME), integrin plays a key role in tumor progression. This study aimed to establish prognostic signatures to predict the overall survival and identify the immune landscape of patients with lung adenocarcinoma based on integrins. The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD) and Gene Expression Omnibus datasets were used to obtain information on mRNA levels and clinical factors (GSE72094). The least absolute shrinkage and selection operator (LASSO) model was used to create a prediction model that included six integrin genes. The nomogram, risk score, and time-dependent receiver operating characteristic analysis all revealed that the signatures had a good prognostic value. The gene signatures may be linked to carcinogenesis and TME, according to a gene set enrichment analysis. The immunological and stromal scores were computed using the ESTIMATE algorithm, and the data revealed, the low-risk group had a higher score. We discovered that the B lymphocytes, plasma, CD4+ T, dendritic, and mast cells were much higher in the group with low-risk using the CiberSort. Inflammatory processes and several HLA family genes were upregulated in the low-risk group. The low-risk group with a better prognosis is more sensitive to immune checkpoint inhibitor medication, according to immunophenoscore (IPS) research. We found that the patients in the high-risk group were more susceptible to chemotherapy than other group patients, according to the prophetic algorithm. The gene signatures could accurately predict the prognosis, identify the immune status of patients with lung adenocarcinoma, and provide guidance for therapy.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Microambiente Tumoral , Carcinogénesis , IntegrinasRESUMEN
BACKGROUND AND OBJECTIVES: Whether acupuncture is effective for chronic tension-type headache (CTTH) is inconclusive. We aimed to examine the effectiveness of acupuncture with a follow-up period of 32 weeks. METHODS: We conducted a randomized controlled trial, and 218 participants who were diagnosed with CTTH were recruited from June 2017 to September 2020. The participants in the intervention group received 20 sessions of true acupuncture (TA group) over 8 weeks. The acupuncture treatments were standardized across participants, and each acupuncture site was needled to achieve deqi sensation. Each treatment session lasted 30 minutes. The participants in the control group received the same sessions and treatment frequency of superficial acupuncture (SA group)-defined as a type of sham control by avoiding deqi sensation at each acupuncture site. The main outcome was the responder rate at 16 weeks after randomization (week 16) and was followed up at week 32. A responder was defined as a participant who reported at least a 50% reduction in the monthly number of headache days (MHDs). RESULTS: Our study included 218 participants (mean age: 43.1 years, mean disease duration: 130 months, MHDs: 21.5 days). The responder rate was 68.2% in the TA group (n=110) versus 48.1% in the SA group (n=108) at week 16 (odds ratio, 2.65; 95%CI, 1.5 to 4.77; p<0.001); and it was 68.2% in the TA group versus 50% in the SA group at week 32 (odds ratio, 2.4; 95%CI, 1.36 to 4.3; p<0.001). The reduction in MHDs was 13.1±9.8 days in the TA group versus 8.8±9.6 days in the SA group at week 16 (mean difference, 4.3 days; 95%CI, 2.0 to 6.5; p<0.001), and the reduction was 14±10.5 days in the TA group versus 9.5±9.3 days in the SA group at week 32 (mean difference, 4.5 days; 95%CI, 2.1 to 6.8; p<0.001). Four mild adverse events were reported; three in the TA group versus one in the SA group. CONCLUSION: The 8-week TA treatment was effective for the prophylaxis of CTTH. Further studies might focus on the cost-effectiveness of the treatment. TRIAL: Registration Information: ClinicalTrials.gov: NCT03133884 (https://clinicaltrials.gov/ct2/show/NCT03133884) CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that acupuncture (achieving deqi sensation) reduces mean headache days (per month) in patients with chronic tension-type headache.
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BACKGROUND: Lung adenocarcinoma (LUAD), as the main subtype of lung cancer, is one of the common causes of cancer-related deaths worldwide. The AHNAK family is correlated with cell structure and migration, cardiac calcium channel signaling, and tumor metastasis. Previous studies showed AHNAK2 could promote tumor progression and cell migration in melanoma and renal clear cell carcinoma. However, the role of AHNAK2 in LUAD remains unknown. METHODS: We examined the levels of AHNAK2 in pathological specimens and the database of Clinical Proteomic Tumor Analysis Consortium-Lung adenocarcinoma (CPTAC-LUAD), The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD), Gene Expression Omnibus dataset (GSE72094, GSE26939), and The Genotype-Tissue Expression (GTEx) of lung tissue samples. Univariate Cox regression, multivariate Cox regression, and Kaplan-Meier survival analysis were performed to reveal the relationship between AHNAK2 and prognosis. A nomogram was constructed to predict 2- or 3-year overall survival and validated via calibration curves, receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA). Furthermore, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to explore the functional role of AHNAK2 in lung adenocarcinoma. Finally, by transfecting siRNA, we examined the regulatory effect of AHNAK2 on cell migration. RESULTS: The expression of AHNAK2 was upregulated in tumor samples and correlated with poor prognosis in LUAD patients. Nomogram with AHNAK2 and clinical parameters showed a good prediction in overall survival (OS), especially the 2-year OS. In addition, functional analyses and wound healing assay suggested that AHNAK2 might be involved in the regulation of migration in LUAD. CONCLUSION: In summary, our study showed that AHNAK2 might be a novel biomarker in LUAD and revealed the potential mechanism of AHNAK2 in LUAD progression which could provide new insights for target therapy.
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Adenocarcinoma del Pulmón/genética , Biomarcadores de Tumor/genética , Proteínas del Citoesqueleto/genética , Neoplasias Pulmonares/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/fisiopatología , Biomarcadores de Tumor/fisiología , Línea Celular Tumoral , Movimiento Celular/genética , Movimiento Celular/fisiología , Proteínas del Citoesqueleto/antagonistas & inhibidores , Proteínas del Citoesqueleto/fisiología , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , Regulación hacia ArribaRESUMEN
Metabolic genes have been reported to act as crucial roles in tumor progression. Lung adenocarcinoma (LUAD) is one of the most common cancers worldwide. This study aimed to predict the potential mechanism and novel markers of metabolic signature in LUAD. The gene expression profiles and the clinical parameters were obtained from The Cancer Genome Atlas-Lung adenocarcinoma (TCGA-LUAD) and Gene Expression Omnibus data set (GSE72094). A total of 105 differentially expressed metabolic genes of intersect expression in TCGA-LUAD and GSE72094 were screened by R language. Univariate Cox regression model found 18 survival-related genes and then the least absolute shrinkage and selection operator model was successfully constructed. Six significant genes prognostic model was validated though independent prognosis analysis. The model revealed high values for prognostic biomarkers by time-dependent receiver operating characteristic (ROC) analysis, risk score, Heatmap, and nomogram. In addition, Gene Set Enrichment Analysis showed that multiplex metabolism pathways correlated with LUAD. Furthermore, we found the six genes aberrantly expressed in LUAD samples. Our study showed that metabolism pathways play important roles in LUAD progression. The six metabolic genes could predict potential prognostic and diagnostic biomarkers in LUAD.
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Adenocarcinoma del Pulmón/genética , Biomarcadores de Tumor/genética , Neoplasias Pulmonares/genética , Aciltransferasas/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/mortalidad , Aldehído Deshidrogenasa Mitocondrial/genética , Biomarcadores de Tumor/metabolismo , Biología Computacional , Bases de Datos Genéticas , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Glucosamina 6-Fosfato N-Acetiltransferasa/genética , Humanos , Estimación de Kaplan-Meier , L-Lactato Deshidrogenasa/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Masculino , Redes y Vías Metabólicas/genética , Pronóstico , Modelos de Riesgos Proporcionales , Prostaglandina-E Sintasas/genética , Curva ROC , Timidilato Sintasa/genéticaRESUMEN
The description of user behavior in social networks is an important issue for studying social networks. Given that Petri nets can describe the resource flow problem, this study utilizes the features of Petri nets to portray the user behavior states during the message propagation of a micro-blog network and presents an information propagation formalized representation method of a micro-blog network. On this basis, this study analyzed the proposed formalized representation method in detail. We provide examples of applying formalized representation (e.g., micro-blog network addiction of users, user behavior influence, and public opinion analysis). In addition, we introduce the algorithms of formalized representation. We conduct experiments using Sina micro-blog data. Results show that the information propagation formalized representation method of micro-blog network based on Petri nets can depict user behaviors of micro-blog network intuitively and accurately. This study reveals a new perspective for information transmission of a micro-blog network and provides some tools to support public opinion monitoring and micro-blog marketing applications.
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Blogging , Conducta Social , Red Social , Interfaz Usuario-Computador , Algoritmos , Humanos , Opinión Pública , Mercadeo SocialRESUMEN
BACKGROUND: Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play an important role in the competitive endogenous RNA (ceRNA) networks in that they regulate protein-coding gene expression by sponging microRNAs (miRNAs). However, the understanding of the ceRNA network in tongue squamous cell carcinoma (TSCC) remains limited. METHODS: Expression profile data regarding mRNAs, miRNAs and lncRNAs as well as clinical information on 122 TSCC tissues and 15 normal controls from The Cancer Genome Atlas (TCGA) database were collected. We used the edgR package to identify differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs) and miRNAs (DEmiRNAs) between TSCC samples and normal samples. In order to explore the functions of DEmRNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed. Subsequently, a ceRNA network was established based on the identified DElncRNAs-DEmiRNAs and DEmiRNAs-DEmRNAs interactions. The RNAs within the ceRNA network were analyzed for their correlation with overall disease survival. Finally, lncRNAs were specifically analyzed for their correlation with clinical features in the included TSCC patient samples. RESULTS: A total of 1867 mRNAs, 828 lncRNAs and 81 miRNAs were identified as differentially expressed in TSCC tissues (-log 2fold change- ≥ 2; adjusted P value <0.01). The resulting ceRNA network included 16 mRNAs, 56 lncRNAs and 6 miRNAs. Ten out of the 56 lncRNAs were found to be associated with the overall survival in TSCC patients (P < 0.05); 10 lncRNAs were correlated with TSCC progression (P < 0.05). CONCLUSION: Our study deepens the understanding of ceRNA network regulatory mechanisms in TSCC. Furthermore, we identified ten lncRNAs (PART1, LINC00261, AL163952.1, C2orf48, FAM87A, LINC00052, LINC00472, STEAP3-AS1, TSPEAR-AS1 and ERVH48-1) as novel, potential prognostic biomarkers and therapeutic targets for TSCC.
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Paths and cycles are the two pivotal elements in a network. Here, we demonstrate that paths, particularly the shortest ones, are incomplete in information network. However, based on such paths, many network centrality measures are designed. While extensive explorations on paths have been made, modest studies focus on the cycles on measuring network centrality. We study the relationship between the shortest cycle and the shortest path from extensive real-world networks. The results illustrate the incompleteness of the shortest paths on measuring network centrality. Noticing that the shortest cycle is much more robust than the shortest path, we propose two novel cycle-based network centrality measures to address the incompleteness of paths: the shortest cycle closeness centrality (SCC) and the all cycle betweenness centrality (ACC). Notwithstanding we focus on the network centrality problem, our findings on cycles can be applied to explain the incompleteness of paths in applications and could improve the applicability into more scenarios where the paths are employed in network science.
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The cholinergic signaling pathways have been recently implicated in the development of various human cancers. However, the underlying molecular mechanism remains largely unclear. In the present study, we reported that α7 nicotinic acetylcholine receptor (α7nAChR), an important member of nicotinic acetylcholine receptors, interacts with Protein Phosphatase-1γ (PP1γ) in human Hepatocellular Carcinoma (HCC) tissues. In addition, we found that α7nAChR facilitates the ubiquitination and activation of TRAF6 in a PP1γ-dependent manner in HCC cells. Furthermore, we showed that ligand-bounded α7nAChR induces the degradation of IκBα, leading to resultant phosphorylation and nuclear accumulation of NF-κB p65. Accordingly, acetylcholine triggers the expression of critical NF-κB target genes, such as Cyclin D1 and PCNA, as well as the proliferation of HCC cells in a PP1γ- and α7nAChR-dependent manner. Furthermore, we revealed that nicotine-triggered α7nAChR activation promotes oncosphere formation and in vivo tumor growth of HCC cells. Moreover, we showed that the protein levels of both α7nAChR and PP1γ are significantly upregulated in human HCC specimens compared with adjacent non-cancerous ones, and that upregulated expression of the two proteins predict significantly worsened prognosis in HCC patients. These findings together indicate that the cholinergic receptor α7nAChR exerts a facilitating role in HCC development through PP1γ-dependent TRAF6/NF-κB signaling.
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Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , FN-kappa B/metabolismo , Proteína Fosfatasa 1/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismo , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Adulto , Anciano , Animales , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Femenino , Xenoinjertos , Humanos , Neoplasias Hepáticas/patología , Ratones , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Unión Proteica , Transducción de Señal , UbiquitinaciónRESUMEN
NKD2 is a member of the Naked cuticle (Nkd) protein family and functions as a negative regulator of the Wnt signaling pathway. We investigated the prognostic value of NKD2 expression in hepatocellular carcinoma (HCC). Western blot and immunohistochemical analyses revealed that NKD2 was significantly downregulated in HCC specimens compared with adjacent nontumorous tissues. Next, we found that NKD2 expression correlated significantly with several clinicopathologic features, such as tumor grade, tumor size, and Ki-67 expression. Univariate and multivariate analyses demonstrated that NKD2 was an independent prognostic factor for the survival of HCC patients. In particular, Kaplan-Meier survival curves suggested that low NKD2 was statistically associated with poor overall survival. Furthermore, serum refeeding of cultured HCC cells led to impaired amounts of NKD2 and induced HepG2 and Huh7 cells to transition from the G1 to the S phase. Small interfering RNA-mediated depletion of NKD2 in LO2 hepatocytes caused accelerated cell growth. To further clarify the role of NKD2 in cell cycle progression, a Flag-tagged NKD2 construct was used to overexpress NKD2 exogenously in Huh7 cells. These results showed that overexpression of NKD2 induced G1-phase cell cycle arrest. Reduced expression of NKD2 correlated with hyperactivation of the Wnt/ß-catenin pathway and doxorubicin resistance in HCC cells. On the basis of these findings, we conclude that NKD2 may be a novel prognostic marker and therapeutic target in HCC.
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Carcinoma Hepatocelular/patología , Proteínas Portadoras/metabolismo , Proliferación Celular/fisiología , Neoplasias Hepáticas/patología , Proteínas Adaptadoras Transductoras de Señales , Anciano , Biomarcadores de Tumor/metabolismo , Proteínas de Unión al Calcio , Carcinoma Hepatocelular/diagnóstico , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Persona de Mediana Edad , Clasificación del Tumor/métodos , Vía de Señalización Wnt/fisiologíaRESUMEN
Acupuncturists in all ages emphasize deqi(qi arrival). We arranged and analyzed contents on deqi and qi arrival electronic texts in 1156 ancient medical books through Chinese Medical Code, the major electronic series of books on TCM, with medical classics as well as acupuncture-moxibustion and tuina parts as the emphasis. It is found that deqi is a standard for traditional acupuncture effect evaluation. Meanwhile, it acts on regulating body cold, heat, insufficiency and excess, guiding reinforce-reducing manipulation, determining needle depth, retaining and withdrawing, as well as prognosis, etc. Deqi takes the priority in clinical and scientific research.