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OBJECTIVES: To compare the accuracy of transvaginal ultrasound (TVUS) with laparoscopy in detecting and characterizing uterosacral ligament (USL) nodules of deep infiltrative endometriosis (DIE) between patients with and without pouch of Douglas (POD) fluid. METHODS: This prospective study was conducted between June 2021 and July 2023. We included patients from the Second People's Hospital of Shenzhen with two TVUS tests: no POD fluid on the first TVUS test and POD fluid on the second TVUS test. POD fluid was obtained in two ways: naturally occurring fluid during the luteal phase of the menstrual cycle and SonoPODography. Laparoscopic results are the gold standard. To compare the diagnostic performance of TVUS in the diagnosis of DIE on USLs with and without POD fluid. RESULTS: We included 42 patients with a mean age of 36.4 ± 5.4 years. The maximum length diameter for DIE nodules on USLs with and without POD fluid was 13.3 ± 3.3 mm and 10.2 ± 2.5 mm (P < .001), respectively, while the depth of infiltration was 8.1 ± 2.4 mm and 6.1 ± 1.4 mm (P < .001), respectively. When compared to laparoscopic findings, TVUS findings with and without POD fluid resulted in a sensitivity, specificity, accuracy, positive predictive value, negative predictive value area under the curve, and Cohen kappa of 92.3%, 93.8%, 92.9%, 96.0%, 88.2%, 0.930, and 0.850 and 61.5%, 93.8%, 73.8%, 94.1%, 50.0%, 0.766, and 0.499, respectively. Laparoscopy showed USL involvement in up to 59.5% of patients. With or without fluid, the most common ultrasound features of DIE lesions were USL thickening, irregular morphology, clear boundaries, low echo, and no blood flow signal. CONCLUSIONS: For patients with clinical suspicion of DIE, TVUS with POD fluid has a higher accuracy for diagnosing USL DIE than TVUS without POD fluid.
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Heart failure is a leading cause of death in the elderly. Traditional Chinese medicine, a verified alternative therapeutic regimen, has been used to treat heart failure, which is less expensive and has fewer adverse effects. In this study, a total of 15 active ingredients of Astragalus membranaceus (Huangqi, HQ) were obtained; among them, Isorhamnetin, Quercetin, Calycosin, Formononetin, and Kaempferol were found to be linked to heart failure. Ang II significantly enlarged the cell size of cardiomyocytes, which could be partially reduced by Quercetin, Isorhamnetin, Calycosin, Kaempferol, or Formononetin. Ang II significantly up-regulated ANP, BNP, ß-MHC, and CTGF expressions, whereas Quercetin, Isorhamnetin, Calycosin, Kaempferol or Formononetin treatment partially downregulated ANP, BNP, ß-MHC and CTGF expressions. Five active ingredients of HQ attenuated inflammation in Ang II-induced cardiomyocytes by inhibiting the levels of TNF-α, IL-1ß, IL-18 and IL-6. Molecular docking shows Isorhamnetin, Quercetin, Calycosin, Formononetin and Kaempferol can bind with its target protein ESR1 in a good bond by intermolecular force. Quercetin, Calycosin, Kaempferol or Formononetin treatment promoted the expression levels of ESR1 and phosphorylated ESR1 in Ang II-stimulated cardiomyocytes; however, Isorhamnetin treatment had no effect on ESR1 and phosphorylated ESR1 expression levels. In conclusion, our results comprehensively illustrated the bioactives, potential targets, and molecular mechanism of HQ against heart failure. Isorhamnetin, Quercetin, Calycosin, Formononetin and Kaempferol might be the primary active ingredients of HQ, dominating its cardioprotective effects against heart failure through regulating ESR1 expression, which provided a basis for the clinical application of HQ to regulate cardiac hypertrophy and heart failure.
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Astragalus propinquus , Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Simulação de Acoplamento Molecular , Miócitos Cardíacos , Farmacologia em Rede , Astragalus propinquus/química , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Quercetina/farmacologia , Quercetina/química , Quercetina/análogos & derivados , Angiotensina II/metabolismo , Quempferóis/farmacologia , Quempferóis/química , Ratos , Humanos , Isoflavonas/farmacologia , Isoflavonas/químicaRESUMO
OBJECTIVES: To investigate the application value of shear wave dispersion (SWD) in healthy adults with the lumbar multifidus muscle (LMM), to determine the range of normal reference values, and to analyze the influences of factors on the parameter. METHODS: Ninety-five healthy volunteers participated in the study, from whom 2-dimensional, shear wave elastography (SWE), and SWD images of the bilateral LMM were acquired in three positions (prone, standing, and anterior flexion). Subcutaneous fat thickness (SFH), SWE velocity, and SWD slope were measured accordingly for analyses. RESULTS: The mean SWD slope of the bilateral LMM in the prone position was as follows: left: 14.8 ± 3.1 (m/second)/kHz (female) and 13.0 ± 2.5 (m/second)/kHz (male); right: 14.8 ± 3.7 (m/second)/kHz (female) and 14.2 ± 3.4 (m/second)/kHz (male). In the prone position, there was a weak negative correlation between the bilateral LMM SWD slope of activity level 2 and level 1 (ß = -1.5 (2 versus 1, left), -1.9 (2 versus 1, right), all P < .05), and between the left SWD slope of activity level 3 and level 1 (ß = -2.3 [3 versus 1, left], P < .05). The correlation between SWE velocity and SWD slope value changed with the position: there was a weak positive correlation in the prone position (r = 0.3 [left], 0.37 [right], both P < .05), and a moderate positive correlation in the standing and anterior flexed positions (r = 0.49-0.74, both P < .001). SFH was moderately negatively correlated with bilateral SWD slope values in the anterior flexion (left: r = -0.4, P = .01; right: r = -0.7, P < .01). CONCLUSIONS: SWD imaging can be used as an adjunct tool to aid in the assessment of viscosity in LMM. Further, activity level, and position are influencing factors that should be considered in clinical practice.
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Técnicas de Imagem por Elasticidade , Músculos Paraespinais , Adulto , Humanos , Masculino , Feminino , Músculos Paraespinais/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Região Lombossacral/diagnóstico por imagem , Voluntários Saudáveis , ViscosidadeRESUMO
Fibroblast growth factor (FGF) and its receptor (FGFR) play crucial roles in gastric cancer (GC). Long non-coding RNAs (lncRNAs) are defined as RNA molecules of around 200 nucleotides or more, which are not translated into proteins. As well-known regulatory factors, lncRNAs are considered as biomarkers for prognosis and treatment response in GC. It is of importance to identify FGF/FGFR-related lncRNAs in GC. Here, some FGF/FGFR-related lncRNAs were identified in GC based on the data from public databases, the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Then a four-lncRNAs (FGF10-AS1, MIR2052HG, POU6F2-AS2, and DIRC1) risk score (RS) model was established for predicting GC's prognosis by using Cox analysis. According to the median value of RS, GC patients were divided into low and high RS group. Low RS group displayed high tumor mutation burden and infiltration of immune cells, as well as more sensitivity to immunotherapy or chemotherapy. High RS group showed high infiltration of stromal cells and more oncogenic signatures. In addition, a comprehensive analysis was carried out and found that high RS group may exhibit specific sensitivity to Panobinostat (histone deacetylases inhibitor) and Tivantinib (MET inhibitor). In summary, our study not only offers a novel personalized prognostication classification model according to FGF/FGFR-related lncRNAs, but also provides a new strategy for subclass-specific precision treatment in GC.
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Although the emerging of immunotherapy conferred a new landscape of gastric cancer (GC) treatment, its response rate was of significant individual differences. Insight into GC immune microenviroment may contribute to breaking the dilemma. To this end, the enrichment score of NF-κB signaling pathway was calculated in each GC sample from The Cancer Genome Atlas (TCGA) via ssGSEA algorithm, and its association with immune infiltration was estimated. Based on NF-κB-related genes, a risk score was established and its involvement in immune infiltration, tumor mutational burden (TMB), and N6-methyladenosine (M6A) modification was analyzed in GC. The results showed that NF-κB signaling pathway promoted the infiltration of immune cells in GC. In addition, GC samples were divided into low- and high-risk groups according to a seven-gene (CARD11, CCL21, GADD45B, LBP, RELB, TRAF1, and VCAM1) risk score. Although the high-risk group displayed high immune infiltration and high expression of M6A regulatory genes, it remains in an immunosuppressive microenviroment and whereby suffers a poorer outcome. Of note, most of hub genes were related to immune infiltration and could serve as an independent prognostic biomarker. Conclusively, our study emphasized the crucial role of NF-κB signaling pathway in GC immune microenviroment and provided several candidate genes that may participate in immune infiltration.
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NF-kappa B , Neoplasias Gástricas , Biologia Computacional , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMO
To deeply analyze the influences of doctor-nurse-patient integrated nursing management on cardiac interventional surgery, 120 patients with coronary heart disease undergoing cardiac interventional therapy were selected as the subjects and randomly divided into two groups, 60 cases in each group. The experimental group used the doctor-nurse-patient integrated nursing, while the control group adopted the routine nursing. The Hessian matrix enhanced filter segmentation algorithm was used to process the cardiac computed tomography angiography (CTA) images of patients to assess the algorithm performance and the safety of nursing methods. The results showed that the Jaccard, Dice, sensitivity, and specificity of cardiac CTA images of patients with coronary heart disease processed by Hessian matrix enhanced filter segmentation algorithm were 0.86, 0.93, 0.94, and 0.95, respectively; the disease self-management ability score and quality of life score of patients in the experimental group after nursing intervention were significantly better than those before nursing intervention, with significant differences (P < 0.05). The number of cases with adverse vascular events in the experimental group was 3 cases, which was obviously lower than that in the control group (15 cases). The diagnostic accuracy of the two groups of patients after segmentation algorithm processing was 0.87 and 0.88, respectively, which was apparently superior than the diagnostic accuracy of conventional CTA (0.58 and 0.61). In summary, cardiac CTA evaluation of doctor-nurse-patient integrated nursing management cardiac interventional surgery based on segmentation algorithm had good safety and was worthy of further promotion in clinical cardiac interventional surgery.
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Angiografia por Tomografia Computadorizada , Qualidade de Vida , Algoritmos , Angiografia , Angiografia Coronária , Humanos , Tomografia Computadorizada por Raios XRESUMO
The development of highly active and earth-rich electrocatalysts remains a formidable challenge for the commercialization of fuel cells. Herein, a composite carrier composed of cobaltous telluride (CoTe) and carbon (C) has been designed for the first time to enhance the electrocatalytic performance of palladium (Pd) nanoparticles (NPs) for the electro-oxidation of ethylene glycol (EG). Remarkably, the mass activity for the as-prepared Pd/CoTe-C catalyst during the ethylene glycol oxidation reaction (EGOR) is found to reach up to 3917.3 mA mg-1, which is 2.2 times higher than that of Pd/Co-C (1785.0 mA mg-1) and 4.1 times greater than that of commercial Pd/C catalyst (962.4 mA mg-1), exceeding that obtained for most Pd-based electrocatalysts reported thus far. In particular, the Pd/CoTe-C catalyst shows better electrochemical stability toward the EGOR than the Pd/Co-C and commercial Pd/C catalysts. Thus, the Pd/CoTe-C electrocatalyst is expected to exhibit broad application prospects in the field of fuel cells.
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BACKGROUND: Sufficient evidence indicated the crucial role of NF-κB family played in gastric cancer (GC). The novel discovery that NF-κB could regulate cancer metabolism and immune evasion greatly increased its attraction in cancer research. However, the correlation among NF-κB, metabolism, and cancer immunity in GC still requires further improvement. METHODS: TCGA, hTFtarget, and MSigDB databases were employed to identify NF-κB-related metabolic genes (NFMGs). Based on NFMGs, we used consensus clustering to divide GC patients into two subtypes. GSVA was employed to analyze the enriched pathway. ESTIMATE, CIBERSORT, ssGSEA, and MCPcounter algorithms were applied to evaluate immune infiltration in GC. The tumor immune dysfunction and exclusion (TIDE) algorithm was used to predict patients' response to immunotherapy. We also established a NFMG-related risk score by using the LASSO regression model and assessed its efficacy in TCGA and GSE62254 datasets. RESULTS: We used 27 NFMGs to conduct an unsupervised clustering on GC samples and classified them into two clusters. Cluster 1 was characterized by high active metabolism, tumor mutant burden, and microsatellite instability, while cluster 2 was featured with high immune infiltration. Compared to cluster 2, cluster 1 had a better prognosis and higher response to immunotherapy. In addition, we constructed a 12-NFMG (ADCY3, AHCY, CHDH, GUCY1A2, ITPA, MTHFD2, NRP1, POLA1, POLR1A, POLR3A, POLR3K, and SRM) risk score. Followed analysis indicated that this risk score acted as an effectively prognostic factor in GC. CONCLUSION: Our data suggested that GC subtypes classified by NFMGs may effectively guide prognosis and immunotherapy. Further study of these NFMGs will deepen our understanding of NF-κB-mediated cancer metabolism and immunity.
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Biomarcadores Tumorais/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , NF-kappa B/metabolismo , Proteínas de Neoplasias/imunologia , Neoplasias Gástricas , Microambiente Tumoral/imunologia , Humanos , Proteínas de Neoplasias/metabolismo , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/terapia , Microambiente Tumoral/genéticaRESUMO
Cardiac hypertrophy is the uppermost risk factor for the development of heart failure, leading to irreversible cardiac structural remodeling and sudden death. As a major mediator of cardiac remodeling, oncostatin M (OSM) and its receptor, OSMR, attract plenty of interest. Recent studies have demonstrated key effects of noncoding RNAs on myocardial remodeling. However, whether noncoding RNAs that regulate the expression of OSMR would regulate the process of remodeling remain unclear. Herein, we observed that long noncoding RNA (lncRNA) Pvt1 expression showed to be significantly elicited by aortic banding (AB) operation in vivo and by angiotensin (Ang II) treatment in vitro. Pvt1 knockdown significantly attenuated the myocardial hypertrophy caused by pressure overload within rats and the cardiac myocyte hypertrophy caused by Ang II in vitro. Moreover, Pvt1 knockdown also decreased cellular myomesin and B-raf, which was involved in OSM function in cardiac remodeling. Based on online tools prediction, miR-196b may simultaneously target Pvt1 and OSMR 3' untranslated region (UTR). In rat H9c2 cells and primary cardiac myocyte, Pvt1 and miR-196b exerted negative regulatory effects on each other and miR-196b negatively regulated OSMR expression. Pvt1 directly targeted miR-196b to relieve miR-196b-induced OSMR suppression via acting as a competing endogenous RNA (ceRNA). Moreover, the effect of miR-196b suppression upon the B-raf was opposite to Pvt1 knockdown, and miR-196b suppression might significantly attenuate the effect of Pvt1 knockdown. In summary, Pvt1/miR-196b axis modulating cardiomyocyte hypertrophy and remodeling via OSMR. Our findings provide a rationale for further studies on the potential therapeutic benefits of Pvt1 function and mechanism in cardiac and cardiomyocyte hypertrophy by a lncRNA-miRNA-mRNA network.
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MicroRNAs , RNA Longo não Codificante , Animais , Cardiomegalia/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RatosRESUMO
Computed tomography (CT) is the preferred imaging method for diagnosing 2019 novel coronavirus (COVID19) pneumonia. We aimed to construct a system based on deep learning for detecting COVID-19 pneumonia on high resolution CT. For model development and validation, 46,096 anonymous images from 106 admitted patients, including 51 patients of laboratory confirmed COVID-19 pneumonia and 55 control patients of other diseases in Renmin Hospital of Wuhan University were retrospectively collected. Twenty-seven prospective consecutive patients in Renmin Hospital of Wuhan University were collected to evaluate the efficiency of radiologists against 2019-CoV pneumonia with that of the model. An external test was conducted in Qianjiang Central Hospital to estimate the system's robustness. The model achieved a per-patient accuracy of 95.24% and a per-image accuracy of 98.85% in internal retrospective dataset. For 27 internal prospective patients, the system achieved a comparable performance to that of expert radiologist. In external dataset, it achieved an accuracy of 96%. With the assistance of the model, the reading time of radiologists was greatly decreased by 65%. The deep learning model showed a comparable performance with expert radiologist, and greatly improved the efficiency of radiologists in clinical practice.
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Infecções por Coronavirus/complicações , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Pneumonia Viral/complicações , Pneumonia/complicações , Pneumonia/diagnóstico por imagem , Razão Sinal-Ruído , Tomografia Computadorizada por Raios X , Adulto , COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos RetrospectivosRESUMO
Prostate cancer (PCa) is one of the most common types of malignant tumor, which places a major burden on the health of men, worldwide. A prerequisite to ensure good treatment outcomes for patients with PCa is an accurate diagnosis. The present study aimed to investigate the diagnostic value of prostate-specific antigen (PSA) and α-methylacyl-CoA racemase (P504S) in PCa, using the tumor-associated immunolabels. In total, clinical data was collected from 125 patients undergoing prostate biopsy or surgery between January 2015 and September 2019, and stratified into: PCa (45), benign prostatic hyperplasia (BPH) (60) and unconfirmed diagnosis (20). Immunohistochemistry analysis was performed to assess PSA and P504S expression levels in each group compared with that in the controls (the normal tissue in each group was the internal control). The results demonstrated that the expression level of P504S was significantly higher in the PCa group compared with that in the BPH group. Furthermore, no significant association was observed in the PCa group between PSA and P504S expression levels, and the Gleason grading groups. A total of 20 unconfirmed diagnoses was verified via PSA/P504S. Taken together, the results suggest that combination PSA and P504S have a positive effect in identifying prostate cancer. However, PSA and P504S still have limitations in their diagnosis and the final results need to be carefully and comprehensively analyzed, thus further studies are required to determine their diagnostic values.
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Resistance becomes major clinical issue in cancer treatment, which strongly limits patients to benefit from oncotherapy. Growing evidences have been indicative of the critical role of fibroblast growth factor (FGF)/receptor (FGFR) signaling played in resistance to oncotherapy. In this review we discussed the underlying mechanisms of FGF/FGFR signaling mediated resistance to chemotherapy, radiotherapy and target therapy in various cancers. Meanwhile, we summarized the reported mechanism of FGF/FGFR inhibitors resistance in cancers.
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BACKGROUND: The hunt for the molecular markers with specificity and sensitivity has been a hot area for the tumor treatment. Due to the poor diagnosis and prognosis of pancreatic cancer (PC), the excision rate is often low, which makes it more urgent to find the ideal tumor markers. METHODS: Robust Rank Aggreg (RRA) methods was firstly applied to identify the differentially expressed genes (DEGs) between PC tissues and normal tissues from GSE28735, GSE15471, GSE16515, and GSE101448. Among these DEGs, the highly correlated genes were clustered using WGCNA analysis. The co-expression networks and molecular complex detection (MCODE) Cytoscape app were then performed to find the sub-clusters and confirm 35 candidate genes. For these genes, least absolute shrinkage and selection operator (lasso) regression model was applied and validated to build a diagnostic risk score model. Cox proportional hazard regression analysis was used and validated to build a prognostic model. RESULTS: Based on integrated transcriptomic analysis, we identified a 19 gene module (SYCN, PNLIPRP1, CAP2, GNMT, MAT1A, ABAT, GPT2, ADHFE1, PHGDH, PSAT1, ERP27, PDIA2, MT1H, COMP, COL5A2, FN1, COL1A2, FAP and POSTN) as a specific predictive signature for the diagnosis of PC. Based on the two consideration, accuracy and feasibility, we simplified the diagnostic risk model as a four-gene model: 0.3034*log2(MAT1A)-0.1526*log2(MT1H) + 0.4645*log2(FN1) -0.2244*log2(FAP), log2(gene count). Besides, a four-hub gene module was also identified as prognostic model = - 1.400*log2(CEL) + 1.321*log2(CPA1) + 0.454*log2(POSTN) + 1.011*log2(PM20D1), log2(gene count). CONCLUSION: Integrated transcriptomic analysis identifies two four-hub gene modules as specific predictive signatures for the diagnosis and prognosis of PC, which may bring new sight for the clinical practice of PC.
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Perfilação da Expressão Gênica/métodos , Neoplasias Pancreáticas , Transcriptoma/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , PrognósticoRESUMO
Pathological cardiac hypertrophy, which may lead to heart failure and sudden death, can be affected by multiple factors. In our previous study, we revealed that IKKi deficiency induced cardiac hypertrophy through the activation of the AKT and NF-kB signaling pathway in response to aortic banding (AB). Non-coding RNAs, mainly long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play a crucial role in normal developmental and pathological processes. In the present study, microarray analysis results from GEO database were analyzed, and upregulated lncRNAs in cardiac hypertrophy were identified. Of them, lncRNA cytoskeleton regulator RNA (CYTOR) obtained a fold-change of 6.16 and was positively correlated with IKBKE according to the data from The GTEx project. CYTOR knockdown significantly enhanced the inducible effect of AB operation on mice myocardial hypertrophy and Angiotensin II on cardiomyocyte hypertrophy. Moreover, miR-155 was significantly related to hypertrophic cardiomyopathy (HCM, |hsa05410) and predicted to target both CYTOR and IKBKE. Luciferase reporter and RIP assays revealed that CYTOR served as a ceRNA for miR-155 to counteract miR-155-mediated repression of IKBKE. Moreover, CYTOR knockdown reduced IKKi protein levels while activated NF-kB signaling pathway, whereas miR-155 inhibition exerted an opposing effect; the effect of CYTOR could be partially attenuated by miR-155 inhibition. Taken together, CYTOR might play a protective role in cardiac hypertrophy through miR-155 and downstream IKKi and NF-κB signaling, most possibly through serving as a ceRNA for miR-155 to counteract miR-155-mediated repression of IKBKE.
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Cardiomegalia/genética , Hipertensão Renovascular/genética , Quinase I-kappa B/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Aorta/metabolismo , Aorta/patologia , Sequência de Bases , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Linhagem Celular , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genes Reporter , Hipertensão Renovascular/metabolismo , Hipertensão Renovascular/patologia , Quinase I-kappa B/metabolismo , Luciferases/genética , Luciferases/metabolismo , Masculino , Camundongos , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
BACKGROUND: ceRNAs have emerged as pivotal players in the regulation of gene expression and play a crucial role in the physiology and development of various cancers. Nevertheless, the function and underlying mechanisms of ceRNAs in esophageal cancer (EC) are still largely unknown. METHODS: In this study, profiles of DEmRNAs, DElncRNAs, and DEmiRNAs between normal and EC tumor tissue samples were obtained from the Cancer Genome Atlas database using the DESeq package in R by setting the adjusted P<0.05 and |log2(fold change)|>2 as the cutoff. The ceRNA network (ceRNet) was initially constructed to reveal the interaction of these ceRNAs during carcinogenesis based on the bioinformatics of miRcode, miRDB, miRTarBase, and TargetScan. Then, independent microarray data of GSE6188, GSE89102, and GSE92396 and correlation analysis were used to validate molecular biomarkers in the initial ceRNet. Finally, a least absolute shrinkage and selection operator logistic regression model was built using an oncogenic ceRNet to diagnose EC more accurately. RESULTS: We successfully constructed an oncogenic ceRNet of EC, crosstalk of hsa-miR372-centered CADM2-ADAMTS9-AS2 and hsa-miR145-centered SERPINE1-PVT1. In addition, the risk-score model -0.0053*log2(CADM2)+0.0168*log2(SERPINE1)-0.0073*log2(ADAMTS9-AS2)+0.0905*log2(PVT1)+0.0047*log2(hsa-miR372)-0.0193*log2(hsa-miR145), (log2[gene count]) could improve diagnosis of EC with an AUC of 0.988. CONCLUSION: We identified two novel pairs of ceRNAs in EC and its role of diagnosis. The pairs of hsa-miR372-centered CADM2-ADAMTS9-AS2 and hsa-miR145-centered SERPINE1-PVT1 were likely potential carcinogenic mechanisms of EC, and their joint detection could improve diagnostic accuracy.
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Due to the complex function of the Notch signal pathway in gastric cancer (GC), the association between Notch homolog 1 (Notch1) intracellular domain (NICD) and differentiation of GC remains unknown. The present study aimed to investigate the potential association between NICD and GC differentiation, and demonstrated that poorly differentiated GC expressed increased NICD levels compared with well differentiated GC. A γ-secretase inhibitor inhibited the growth of AGS cells through downregulating NICD level. Additional data suggested that a COX-2 inhibitor caused a marked reduction of NICD level in comparison with a control group treated with dimethyl sulfoxide. Combined administration of γ-secretase and COX-2 inhibitor produced a marked inhibition of growth in AGS cells, which suggests that patients with poorly differentiated GC may benefit from the blockage of NICD, which potentially serves a role in GC differentiation.
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EF24 is an IKKß inhibitor (IC50: 72 µM) containing various anti-tumor activities. In this study, a series of EF24 analogs targeting IKKß were designed and synthesized. Several IKKß inhibitors with better activities than EF24 were screened out and B3 showed best IKKß inhibitory (IC50: 6.6 µM). Molecular docking and dynamic simulation experiments further confirmed this inhibitory effect. B3 obviously suppressed the viability of Hela229, A549, SGC-7901 and MGC-803 cells. Then, in SGC-7901 and MGC-803 cells, B3 blocked the NF-κB signal pathway by inhibiting IKKß phosphorylation, and followed arrested the cell cycle at G2/M phase by suppressing the Cyclin B1 and Cdc2 p34 expression, induced the cell apoptosis by down-regulating Bcl-2 protein and up-regulating cleaved-caspase3. Moreover, B3 significantly reduced tumor growth and suppressed the IKKß-NF-κB signal pathway in SGC-7901 xenograft model. In total, this study present a potential IKKß inhibitor as anti-tumor precursor.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Compostos de Benzilideno/química , Compostos de Benzilideno/farmacologia , Quinase I-kappa B/antagonistas & inibidores , Piperidonas/química , Piperidonas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Compostos de Benzilideno/síntese química , Compostos de Benzilideno/uso terapêutico , Linhagem Celular Tumoral , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Quinase I-kappa B/metabolismo , Camundongos Nus , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Fosforilação/efeitos dos fármacos , Piperidonas/síntese química , Piperidonas/uso terapêutico , Transdução de Sinais/efeitos dos fármacosRESUMO
Fibroblast growth factor receptor 1 (FGFR1), belonging to receptor tyrosine kinases (RTKs), possesses various biological functions. Over-expression of FGFR1 has been observed in multiple human malignancies. Hence, targeting FGFR1 is an attractive prospect for the advancement of cancer treatment options. Here, we present a novel small molecular FGFR1 inhibitor L16H50, which can inhibit FGFR1 kinase in an ATP-independent manner. It potently inhibits FGFR1-mediated signaling in a gastric cancer cell line, resulting in inhibition of cell growth, survival and migration. It also displays an outstanding anti-tumor activity in a gastric cancer xenograft tumor model by targeting FGFR1 signaling. These results show that L16H50 is a potent non-ATP-competitive FGFR1 inhibitor and may provide strong rationale for its evaluation in gastric cancer patients.
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Trifosfato de Adenosina/metabolismo , Hidrocarbonetos Clorados/uso terapêutico , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fase G2/efeitos dos fármacos , Células HEK293 , Humanos , Hidrocarbonetos Clorados/química , Hidrocarbonetos Clorados/farmacologia , Camundongos , Mitose/efeitos dos fármacos , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: Clinical symptoms of diabetic nephropathy patients and non-diabetic nephropathy are compared and analyzed, hemodialysis effect and quality of life of two kinds of nephrotic patients are analyzed. METHODS: Respectively extract 1300 cases of diabetic nephropathy and non-diabetic nephropathy patients admitted to different hospitals during December 2011-December 2014. Based on whether the patient suffers from diabetes, they were divided into diabetic group and control group. Hemodialysis of two groups of patients were followed up to observe effectiveness of blood treatment, and complications were observed after one year of follow-up. RESULTS: Hematodialysis effectiveness of diabetic nephropathy patients is significantly lower than that of non-diabetic nephropathy group. After 1â¯year's follow-up, it can be found that survival rate of diabetic nephropathy patients is much lower than that of control group. In statistical comparison of data involved in the two groups of patients, Pâ¯<â¯0.05, the difference is statistically significant. CONCLUSION: Treatment effect of diabetic nephropathy patients is relatively poor compared to that of non-diabetic patients. In clinics, management and prevention of diabetic patients should be strengthened to avoid complication of nephropathy which brings serious injury to patients.