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1.
Sensors (Basel) ; 24(2)2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38257483

RESUMEN

With the continuous operation of analog circuits, the component degradation problem gradually comes to the forefront, which may lead to problems, such as circuit performance degradation, system stability reductions, and signal quality degradation, which could be particularly evident in increasingly complex electronic systems. At the same time, due to factors, such as continuous signal transformation, the fluctuation of component parameters, and the nonlinear characteristics of components, traditional fault localization methods are still facing significant challenges when dealing with large-scale complex circuit faults. Based on this, this paper proposes a fault-diagnosis method for analog circuits using the ECWGEO algorithm, an enhanced version of the GEO algorithm, to de-optimize the 1D-CNN with an attention mechanism to handle time-frequency fusion inputs. Firstly, a typical circuit-quad op-amp dual second-order filter circuit is selected to construct a fault-simulation model, and Monte Carlo analysis is used to obtain a large number of samples as the dataset of this study. Secondly, the 1D-CNN network structure is improved for the characteristics of the analog circuits themselves, and the time-frequency domain fusion input is implemented before inputting it into the network, while the attention mechanism is introduced into the network. Thirdly, instead of relying on traditional experience for network structure determination, this paper adopts a parameter-optimization algorithm for network structure optimization and improves the GEO algorithm according to the problem characteristics, which enhances the diversity of populations in the late stage of its search and accelerates the convergence speed. Finally, experiments are designed to compare the results in different dimensions, and the final proposed structure achieved a 98.93% classification accuracy, which is better than other methods.

2.
Sensors (Basel) ; 23(14)2023 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-37514668

RESUMEN

Vibration monitoring and analysis play a crucial role in the fault diagnosis of hydroelectric units. However, accurate extraction and identification of fault features from vibration signals are challenging because of noise interference. To address this issue, this study proposes a novel denoising method for vibration signals based on improved complementary ensemble empirical mode decomposition with adaptive noise (ICEEMDAN), permutation entropy (PE), and singular value decomposition (SVD). The proposed method is applied for the analysis of hydroelectric unit sway monitoring. Firstly, the ICEEMDAN method is employed to process the signal and obtain several intrinsic mode functions (IMFs), and then the PE values of each IMF are calculated. Subsequently, based on a predefined threshold of PE, appropriate IMFs are selected for reconstruction, achieving the first denoising effect. Then, the SVD is applied to the signal after the first denoising effect, resulting in the SVD spectrum. Finally, according to the principle of the SVD spectrum and the variation in the singular value and its energy value, the signal is reconstructed by choosing the appropriate reconstruction order to achieve the secondary noise reduction effect. In the simulation and case analysis, the method is better than the commonly used wavelet threshold, SVD, CEEMDAN-PE, and ICEEMDAN-PE, with a signal-to-noise ratio (SNR) improvement of 6.9870 dB, 4.6789 dB, 8.9871 dB, and 4.3762 dB, respectively, and where the root-mean-square error (RMSE) is reduced by 0.1426, 0.0824, 0.2093 and 0.0756, respectively, meaning that our method has a better denoising effect and provides a new way for denoising the vibration signal of hydropower units.

3.
Nanomaterials (Basel) ; 13(7)2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37049287

RESUMEN

The environmental problems in the world are attracting increasing amounts of attention, and heavy metal pollution in the water has become one of the focuses of the ecological environment. Molybdenum disulfide (MoS2) has excellent adsorption performance because of its extremely high specific surface area and unique active site structure, which has attracted an increasing amount of attention in the field of heavy metal disposal in various types of water. In this paper, two sorts of MoS2 nanoparticles, spherical and lamellar, were synthesized by different chemical methods. Their morphology and structure were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and a Raman spectrometer. The adsorption properties of two sorts of MoS2 nanoparticles for copper (Ⅱ) ions in water were investigated by changing the pH value, adsorption time, initial concentration of solution, adsorption temperature, etc. Finally, the adsorption mechanism was analyzed by kinetic, isothermal, and thermodynamic models. The results show that two microstructures of MoS2 nanoparticles can be used as efficient adsorption materials for removing heavy metal ions from water, although there are differences in adsorption capacity between them, which expands the theoretical basis of heavy metal adsorption in a water environment.

4.
Angew Chem Int Ed Engl ; 62(25): e202303868, 2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37086028

RESUMEN

The atom- and step-efficient synthesis of chiral fused tricyclic lactams from readily available ketoesters using cheap ammonium salts as the nitrogen source is reported. This ruthenium-catalyzed system operates through an efficient tandem dynamic kinetic asymmetric reductive amination (ARA)/lactamization and produces chiral fused tricyclic lactams in high yields with excellent diastereo- and enantioselectivity (up to >99 % ee, >20 : 1 dr and 98 % yield). The robust method was also applied to the concise synthesis of key intermediates in the synthesis of rivastigmine analogues and chiral N-heterocyclic carbene catalysts.


Asunto(s)
Compuestos de Amonio , Lactamas , Aminación , Sales (Química) , Catálisis
5.
J Oncol ; 2023: 3538928, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36761433

RESUMEN

Background: The prognosis is poor for hepatocellular carcinoma (HCC), a tumor and cancer associated with inflammation that is common. New data showed that significant levels of KIAA1522 were expressed in HCC tissues and cell lines, suggesting that KIAA1522 may be a highly useful prognostic marker for HCC. However, its biochemical processes and impacts on the immune system go deeper. Objective: To verify the significance of KIAA1522 in HCC and investigate its related carcinogenic mechanisms. Methods: Studies examining the relationship between KIAA1522 expression and clinical-pathologic characteristics in HCC have been checked in the Cancer Genome Atlas (TCGA) database. A receiver operating characteristic (ROC) curve was used to assess the diagnostic efficacy of KIAA1522 in HCC. Western blot analysis was used to find the presence of the KIAA1522 protein in the tumor and paraneoplastic tissues of eight randomly chosen HCC patients. The GSVA program in R language was used to evaluate the relationship between KIAA1522 and immune cell infiltration in HCC. We searched the Search Tool for the Retrieval of Interacting Genes (STRING) database for interacting proteins connected to the expression of KIAA1522. Pathways were involved in the enrichment analysis of KIAA1522 to anticipate potential mechanisms through which KIAA1522 may affect immunological infiltration. Results: Our study found that KIAA1522 was commonly elevated in HCC tumor tissues and that it also signaled a bad outcome. We found an inverse link between KIAA1522 and cytotoxic cells and an inverse relationship between KIAA1522 and Th2 cell infiltration. In STRING analysis, the top 5 coexpressed proteins of KIAA1522 were BAIAP2, NCK2, TSNAXIP1, POGK, and KLHL31. The effect of KIAA1522 on HCC may entail cell cycle alteration, an immunological response, and suppression of the PPAR signaling pathway. Conclusion: High expression of KIAA1522 was linked to HCC immune cell infiltration, disease progression, and a poor prognosis.

6.
Environ Res ; 220: 115244, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36632882

RESUMEN

Water transfer is an effective measure to enhance hydrodynamic and water quality in highly urbanized areas. The effect of water transfer in highly urbanized areas is affected by strong artificial interventions, and it is difficult to evaluate the improvement of multiple indicators of many sections after water transfer. At present, there is no analysis framework directly evaluates the improvement of water environment under strong artificial interventions, making it difficult to determine the optimal scheduling of hydraulic projects. This study constructed a multi-criteria analysis framework for evaluating the improvement of water environment including index layers of water quality improvement, hydrodynamic improvement and economic cost, and designed corresponding element layers for each index layer. The weights of each element were determined based on fuzzy analytical hierarchy process, and the fuzzy comprehensive evaluation method was used for comprehensive evaluation. The framework was applied in Xishan District in highly urbanized Taihu Lake Basin, and the results showed that the proposed framework could effectively determine the optimal scheduling of hydraulic projects. Water quality compliance rate for the optimal water transfer scheme achieved in Xishan District was 82%, average rate of water quality improvement was 31%, and proportion of cross-sections meeting the Class III water quality standard was 61%. Average flow velocity was 0.10 m/s, proportion of the optimal velocity was 39%, and proportion of stagnant sections was 32%. Furthermore, the impact of regional control projects on the effect of water transfer was much greater than local projects, consequently, the best scheduling mode for regional control projects should be first determined, and then the scheduling combination for local projects. This study can provide a new framework for the assessment of water transfers to improve the water environments and a scientific basis for the dispatching of hydraulic projects in Taihu Lake Basin.


Asunto(s)
Monitoreo del Ambiente , Calidad del Agua , China , Monitoreo del Ambiente/métodos , Lagos , Urbanización
7.
Zhongguo Zhong Yao Za Zhi ; 47(19): 5140-5157, 2022 Oct.
Artículo en Chino | MEDLINE | ID: mdl-36472021

RESUMEN

Angelicae Sinensis Radix, as a medicinal and edible Chinese medicinal herb, is widely used in clinical practice. It is mainly cultivated in Minxian, Tanchang, Zhangxian and Weiyuan counties of Gansu province. In recent years, with the comprehensive and in-depth study of Angelicae Sinensis Radix in China and abroad, its chemical composition, pharmacological effects and application and development have attracted much attention. In this study, the chemical composition, traditional efficacy, and modern pharmacological effects of Angelicae Sinensis Radix were summarized. On this basis, combined with the core concept of quality markers(Q-markers), the Q-markers of Angelicae Sinensis Radix were discussed from the aspects of mass transfer and traceability and chemical composition specificity, availability, and measurability, which provided scientific basis for the quality evaluation of Angelicae Sinensis Radix.


Asunto(s)
Angelica sinensis , Medicamentos Herbarios Chinos , Angelica sinensis/química , Medicamentos Herbarios Chinos/farmacología , Raíces de Plantas/química , China
8.
J Oncol ; 2022: 9395876, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36504560

RESUMEN

Background: Infantile Hemangiomas (IHs) are common benign vascular tumors of infancy that may have serious consequences. The research on diagnostic markers for IHs is scarce. Methods: The "limma" R package was applied to identify differentially expressed genes (DEGs) in developing IHs. Plugin ClueGO in Cytoscape software performed functional enrichment of DEGs. The Search Tool for Retrieving Interacting Genes (STRING) database was utilized to construct the PPI network. The least absolute shrinkage and selection operator (LASSO) regression model and support vector machine recursive feature elimination (SVM-RFE) analysis were used to identify diagnostic genes for IHs. The receiver operating characteristic (ROC) curve evaluated diagnostic genes' discriminatory ability. Single-gene based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted by Gene Set Enrichment Analysis (GSEA). The chemicals related to the diagnostic genes were excavated by the Comparative Toxicogenomics Database (CTD). Finally, the online website Network Analyst was used to predict the transcription factors targeting the diagnostic genes. Results: A total of 205 DEGs were singled out from IHs samples of 6-, 12-, and 24-month-old infants. These genes principally participated in vasculogenesis and development-related, endothelial cell-related biological processes. Then we mined 127 interacting proteins and created a network with 127 nodes and 251 edges. Furthermore, LASSO and SVM-RRF algorithms identified five diagnostic genes, namely, TMEM2, GUCY1A2, ISL1, WARS, and STEAP4. ROC curve analysis results indicated that the diagnostic genes had a powerful ability to distinguish IHs samples from normal samples. Next, the results of GSEA for a single gene illustrated that all five diagnostic genes inhibited the "valine, leucine, and isoleucine degradation" pathway in the development of IHs. WARS, TMEM2, and STEAP4 activated the "blood vessel development" and "vasculature development" in IHs. Subsequently, inhibitors targeting TMEM2, GUCY1A2, ISL1, and STEAP4 were mined. Finally, 14 transcription factors regulating GUCY1A2, 14 transcription factors regulating STEAP4, and 26 transcription factors regulating ISL1 were predicted. Conclusion: This study identified five diagnostic markers for IHs and further explored the mechanisms and targeting drugs, providing a basis for diagnosing and treating IHs.

9.
Dis Markers ; 2022: 6138941, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36330204

RESUMEN

Methods and Results: The levels of MCF2L were detected by PCR and western blotting assay. The effect of MCF2L on ferroptosis was confirmed by MTT, colony formation assay, Brdu, in vivo animal experiment, and the content of Iron, GSH, ROS, and MDA. The underlying mechanisms were explored by PCR, western blotting, and affinity precipitation assay. Our findings demonstrated that MCF2L is remarkedly upregulated in HCC tissues, and sorafenib can induce the levels of MCF2L, suggesting that MCF2L might function in sorafenib resistance of HCC. Further analysis showed that downregulation of MCF2L enhances HCC cell death induced by sorafenib, and ferroptosis inhibitor can reverse this process. Subsequent experiments showed that downregulation of MCF2L elevates the content of Iron, ROS, and MDA, which are all indicators of ferroptosis. Finally, mechanism analysis showed that MCF2L regulates the PI3K/AKT pathway in a RhoA/Rac1 dependent manner. Conclusions: Our study showed that targeting MCF2L may be a hopeful method to overcome sorafenib-resistance through inducing ferroptosis in HCC.


Asunto(s)
Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Animales , Sorafenib/farmacología , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Regulación hacia Abajo , Especies Reactivas de Oxígeno/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Hierro/metabolismo , Línea Celular Tumoral
10.
Chem Commun (Camb) ; 58(60): 8408-8411, 2022 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-35796162

RESUMEN

Owing to the biological significance and great synthetic value of chiral lactones and their derivatives, increasing attention has been paid to developing effective synthetic methods for chiral lactones. We herein report an efficient asymmetric hydrogenation of benzo-fused ketoesters, γ-ketoesters and biaryl-bridged ketoesters catalyzed by chiral iridium complexes bearing ferrocene-based chiral ligands, furnishing a series of chiral lactones in superb yields and excellent enantioselectivities (up to 99% yields and up to 99% ee).


Asunto(s)
Iridio , Lactonas , Catálisis , Hidrogenación , Estereoisomerismo
11.
Sensors (Basel) ; 22(15)2022 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-35898010

RESUMEN

Sensors are devices that output signals for sensing physical phenomena and are widely used in all aspects of our social production activities. The continuous recording of physical parameters allows effective analysis of the operational status of the monitored system and prediction of unknown risks. Thanks to the development of deep learning, the ability to analyze temporal signals collected by sensors has been greatly improved. However, models trained in the source domain do not perform well in the target domain due to the presence of domain gaps. In recent years, many researchers have used deep unsupervised domain adaptation techniques to address the domain gap between signals collected by sensors in different scenarios, i.e., using labeled data in the source domain and unlabeled data in the target domain to improve the performance of models in the target domain. This survey first summarizes the background of recent research on unsupervised domain adaptation with time series sensor data, the types of sensors used, the domain gap between the source and target domains, and commonly used datasets. Then, the paper classifies and compares different unsupervised domain adaptation methods according to the way of adaptation and summarizes different adaptation settings based on the number of source and target domains. Finally, this survey discusses the challenges of the current research and provides an outlook on future work. This survey systematically reviews and summarizes recent research on unsupervised domain adaptation for time series sensor data to provide the reader with a systematic understanding of the field.


Asunto(s)
Aclimatación , Redes Neurales de la Computación , Factores de Tiempo
12.
Chem Commun (Camb) ; 58(4): 513-516, 2022 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-34897338

RESUMEN

We report an efficient and straightforward method to synthesize enantio-enriched N-unprotected α-amino acetals via ruthenium-catalyzed direct asymmetric reductive amination. The α-amino acetal products are versatile and valuable platform molecules that can be converted to the corresponding α-amino acids, amino alcohols, and other derivatives by convenient transformations.

13.
Zhongguo Zhen Jiu ; 41(7): 725-9, 2021 Jul 12.
Artículo en Chino | MEDLINE | ID: mdl-34259402

RESUMEN

OBJECTIVE: To observe the effect of intradermal needling combined with heat-sensitive moxibustion for moderate to severe cancer pain. METHODS: A total of 60 patients with moderate to severe cancer pain were randomly divided into an observation group and a control group,30 cases in each one. In the control group,opioids were taken to relief pain according to the three-step analgesic method of World Health Organization. On the base of the treatment as the control group, intradermal needling combined with heat-sensitive moxibustion were applied at Neiguan (PC 6), Hegu (LI 4), Zusanli (ST 36), Taichong (LR 3), etc. in the observation group, 14 days of treatment were required. The equivalent morphine consumption at the first day and whole course, the scores of cancer quality of life questionnaire-C30 (QLQ-C30) and Hamilton anxiety scale before and after treatment, and the adverse reaction rate were compared in the two groups. The total analgesic effective rate was evaluated. RESULTS: The total analgesic effective rate was 93.3% (28/30) in the observation group, higher than 73.3% (22/30) in the control group (P<0.05). The total equivalent morphine consumption in the observation group was less than the control group (P<0.05). After treatment, the QLQ-C30 scores were increased (P<0.001) and the HAMA scores were decreased (P<0.001) in the both groups, and those in the observation group were superior to the control group (P<0.001). The adverse reaction rates of fatigue, dizziness, nausea and vomiting, constipation in the observation group were lower than the control group (P<0.05). CONCLUSION: Intradermal needling combined with heat-sensitive moxibustion can reduce the dose of opioids, improve the quality of life, relief the anxiety in patients with moderate to severe cancer pain, and reduce the incidence of common adverse reaction of opioids.


Asunto(s)
Dolor en Cáncer , Moxibustión , Neoplasias , Puntos de Acupuntura , Dolor en Cáncer/terapia , Calor , Humanos , Neoplasias/complicaciones , Neoplasias/terapia , Dolor , Calidad de Vida , Resultado del Tratamiento
14.
Org Lett ; 23(15): 5658-5663, 2021 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-34255532

RESUMEN

We report an asymmetric 1,2-reduction of cyclic α,ß-unsaturated ketones to access various enantiomerically enriched cyclic allylic alcohols under mild conditions, catalyzed by in situ generated copper hydride ligated with (R)-DTBM-C3*-TunePhos. α-Brominated cycloalkenones were reduced with excellent enantioselectivities of up to 98% ee, while substrates that were without α-substituents were reduced chemoselectively, with moderate enantioselectivities.

15.
J Am Chem Soc ; 143(6): 2477-2483, 2021 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-33529522

RESUMEN

A catalytic protocol for the enantio- and diastereoselective reduction of α-substituted-ß-keto carbonitriles is described. The reaction involves a DKR-ATH process with the simultaneous construction of ß-hydroxy carbonitrile scaffolds with two contiguous stereogenic centers. A wide range of α-substituted-ß-keto carbonitriles were obtained in high yields (94%-98%) and excellent enantio- and diastereoselectivities (up to >99% ee, up to >99:1 dr). The origin of the diastereoselectivity was also rationalized by DFT calculations. Furthermore, this methodology offers rapid access to the pharmaceutical intermediates of Ipenoxazone and Tapentadol.

16.
Chem Soc Rev ; 49(17): 6141-6153, 2020 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-32666962

RESUMEN

α-Chiral primary amines are one among the most valuable and versatile building blocks for the synthesis of numerous amine-containing pharmaceuticals and natural compounds. They also serve as chiral ligands or organo-catalysts for asymmetric catalysis. However, most of the existing chemocatalytic methods toward enantiopure primary amines rely on multistep manipulations on N-substituted substrates, which are not ideally atom-economical and cost-effective. Among the catalytic methods including the asymmetric transformations of the pre-prepared or in situ formed NH imines, biomimetic chemocatalysis inspired by enzymatic transaminations has recently emerged as an appealing and straightforward method to access chiral primary amines. This tutorial review highlights the state-of-the-art catalytic methods for the direct asymmetric synthesis of α-chiral primary amines and demonstrates their utility in the construction of molecular complexities, which may attract extensive attention and inspire applications in synthetic and medicinal chemistry.


Asunto(s)
Aminas/síntesis química , Catálisis , Estructura Molecular , Estereoisomerismo
17.
Org Lett ; 22(7): 2707-2713, 2020 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-32191039

RESUMEN

Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology.

18.
J Transl Med ; 15(1): 176, 2017 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-28810875

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide owing to its high rates of metastasis and recurrence. The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is ubiquitously overexpressed in several human cancers, including liver, ovary, lung, large intestine, gastric, bone marrow, and breast malignancies and is involved in the invasion and metastasis of cancer cells. Therefore, we aimed to determine the biological role and molecular mechanism of IQGAP3 in HCC. METHODS: We used 120 archived clinical HCC samples, 9 snap-frozen HCC tumor tissues, and 4 normal liver tissues. Expression of IQGAP3 mRNA and protein in HCC cell lines (Hep3B, SMMC-7721, HCCC-9810, HepG2, BEL-7404, HCCLM3, QGY-7701, Huh7, and MHCC97H) and normal liver epithelial cells LO2 was examined by western blot, quantitative polymerase chain reaction, and immunohistochemistry. In addition, wound-healing and transwell matrix penetration assays were used to assess the migratory and invasive abilities of HCC cells, respectively. RESULTS: Expression of the IQGAP3 was robustly upregulated in HCC cells and tissues. High expression of IQGAP3 in HCC correlated with aggressive clinicopathological features and was an independent poor prognostic factor for overall survival. Furthermore, ectopic expression of IQGAP3 markedly enhanced HCC cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) in vitro and promoted metastasis of orthotopic hepatic tumors in nude mice. Conversely, silencing endogenous IQGAP3 showed an opposite effect. Mechanistically, IQGAP3 promoted EMT and metastasis by activating TGF-ß signaling. CONCLUSIONS: IQGAP3 functions as an important regulator of metastasis and EMT by constitutively activating the TGF-ß signaling pathway in HCC. Our findings present new evidence of the role of IQGAP3 in EMT and metastasis, indicating its potential as a prognostic biomarker candidate and a therapeutic target against HCC.


Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Transición Epitelial-Mesenquimal , Proteínas Activadoras de GTPasa/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Proteínas Activadoras de GTPasa/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Metástasis de la Neoplasia , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal/genética , Estadísticas no Paramétricas , Factor de Crecimiento Transformador beta/metabolismo , Regulación hacia Arriba/genética
19.
Int J Oncol ; 50(1): 173-184, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27909716

RESUMEN

TIMELESS is a highly conserved protein required for the maintenance of normal mammalian circadian oscillations and for controlling cellular metabolism and proliferation. Recently, TIMELESS was implicated in the tumorigenesis of certain cancers. However, little is known on TIMELESS protein expression and its potential as a prognostic factor in cervical cancer. Here, we investigate TIMELESS expression pattern and its clinicopathological significance in early-stage cervical carcinoma. TIMELESS mRNA and protein expression was evaluated by real-time PCR and western blot analysis in cervical cancer cell lines, a normal cervical cell line, as well as in six pairs of surgically removed cervical cancer and adjacent normal cervical tissues. A total of 189 paraffin-embedded cervical carcinoma specimens were detected and diagnosed by immunohistochemistry (IHC), and the clinical significance of TIMELESS expression was further analyzed. Aberrant TIMELESS mRNA and protein expression were demonstrated in cervical cancer cell lines compared with the normal cervical cell line. TIMELESS mRNA and protein expression were significantly increased in cervical cancer specimens compared with adjacent non-cancerous cervical specimens. TIMELESS protein expression was significantly associated with the age (P=0.011), clinical stage (P<0.001), pelvic lymph node metastasis (P<0.001), squamous cell carcinoma antigen (P=0.003), tumor recurrence (P=0.015), vital status (P<0.001), tumor differentiation grade (P<0.001), property of the surgical margin (P=0.036) and lymphovascular space involvement (P=0.001). Patients with increased TIMELESS protein expression showed strong tendencies to receive postoperative radiotherapy (P=0.002). Upregulation of TIMELESS correlated with poorer overall survival (OS) and disease-free survival (DFS). Univariate and multivariate Cox-regression analyses showed that TIMELESS can be regarded as an independent predictive biomarker for poor clinical outcome for early-stage cervical carcinoma. Our results show that TIMELESS overexpression correlates with pelvic lymph node metastasis, lymphovascular space involvement, as well as unfavorable OS and DFS in human cervical cancer. Therefore, TIMELESS expression may be a potential prognostic biomarker for cervical cancer patients.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Carcinoma de Células Escamosas/genética , Proteínas de Ciclo Celular/biosíntesis , Péptidos y Proteínas de Señalización Intracelular/biosíntesis , Recurrencia Local de Neoplasia/genética , Neoplasias del Cuello Uterino/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/patología , Proteínas de Ciclo Celular/genética , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Células HeLa , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Ganglios Linfáticos/patología , Metástasis Linfática , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Neoplasias del Cuello Uterino/patología
20.
PLoS One ; 11(12): e0167449, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27941992

RESUMEN

BACKGROUND: The kinesin family member 20a (KIF20A) protein has been implicated in the development and progression of many human cancers; however, its precise function and role in cervical cancer remain largely unclear. This study aimed to investigate the expression profile and prognostic value of KIF20A in patients with early-stage cervical squamous cell carcinoma. METHODS: We examined the mRNA and protein levels of KIF20A in eight cervical cancer cell lines and eight paired cervical cancer samples, compared with normal cervical epithelial cells and adjacent normal cervical tissues, respectively. Immunohistochemistry was performed to detect the expression of KIF20A in paraffin-embedded specimens from 169 early-stage cervical squamous cell carcinoma patients. Statistical analyses were applied to analyze the association between KIF20A expression and clinical variables, as well with patient survival. RESULTS: The mRNA and protein expression levels of KIF20A were significantly elevated in cervical cancer cell lines and lesions compared with normal cells and corresponding normal tissues (P < 0.05). Immunohistochemistry analysis in 169 cervical cancer cases revealed that increased KIF20A expression was strongly associated with human papillomavirus (HPV) infection (P = 0.008), clinical stage (P = 0.001), tumor recurrence (P = 0.016), vital status (P < 0.001), the property of the surgical margin (P = 0.032), the lymphovascular space involvement (P = 0.014), and pelvic lymph node metastasis (P = 0.001). The overall survival and disease-free survival of patients with high levels of KIF20A expression were significantly poorer than those with low KIF20A expression. KIF20A was an independent survival prognostic factor, as evidenced by univariate and multivariate analysis. CONCLUSIONS: Our results illustrate that elevated KIF20A expression correlates with HPV infection, clinical stage, tumor recurrence, lymphovascular space involvement, pelvic lymph node metastasis, and poor outcome in early-stage cervical squamous cell carcinoma patients. KIF20A aberrant expression is a novel independent unfavorable prognostic factor and may present a potential therapeutic target for cervical cancer.


Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Expresión Génica , Cinesinas/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/mortalidad , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Línea Celular Tumoral , Terapia Combinada , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapia
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