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1.
Int Health ; 11(S1): S64-S71, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670819

RESUMO

BACKGROUND: We aimed to examine the associations of cognitive and structural social capital with subjective well-being (SWB) and mental health among internal migrants in five cities in China. METHODS: We conducted healthy cities surveys from June 2017 to April 2018. In total, 3038 migrants submitted surveys. Generalized linear regressions for SWB and logistic regressions for mental health were used to examine the associations of social capital, SWB and mental health after controlling for covariates. RESULTS: The median level of SWB was 75.7 (interquartile range 62.9-85.7). Self-rated health and physical activity were positively associated with SWB. The SWB level among migrants who perceived high individual social cohesion was much higher than that of their counterparts (unstandardized coefficients, ß=7.01 [95% confidence interval {CI} 5.82 to 8.21]). The prevalence of poor mental health was 10.0%. High social cohesion (odds ratio [OR] 0.32 [95% CI 0.24 to 0.44]) and high social participation (OR 0.77 [95% CI 0.57 to 0.97]) were significantly associated with a low ratio of poor mental health when compared with their counterparts. CONCLUSIONS: Cognitive social capital is positively associated with SWB, while both cognitive and structural social capitals were negatively associated with poor mental health. It is beneficial to migrants' mental health and SWB to promote social participation and social cohesion.

2.
Thorac Cancer ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31602787

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutation status is essential to the optimal management of lung adenocarcinoma. Liquid biopsy has advantages such as noninvasiveness, speediness, and convenience. This study aimed to detect EGFR gene mutations using next-generation sequencing (NGS) from different types of body fluids from patients with lung adenocarcinoma. METHODS: This was a prospective study of 20 patients with lung adenocarcinoma recruited between January 2017 and December 2018 at the Beijing Hospital. All patients had adenocarcinoma with confirmed sensitizing EGFR mutations. Body fluid specimens included pleural effusion, ascites, pericardial effusion, and cerebrospinal fluid. NGS was conducted to test for nine lung cancer-related gene in body fluid supernatant free DNA, sedimentary tumor cells, and plasma free DNA. RESULTS: The EGFR gene mutation abundance of body fluid supernatant free DNA was higher than that of body fluid sedimentary tumor cells and plasma free DNA specimens (100% vs. 90% vs. 80%, respectively, all P < 0.05). The results of EGFR mutation from the body fluid supernatants were consistent with the results from the tissue biopsy. CONCLUSIONS: This study showed that compared with body fluid sediment tumor cells and plasma free DNA samples, body fluid supernatant free DNA has a higher detection rate and sensitivity of tumor-specific mutations. Free DNA obtained from body fluid supernatants could be used as high-quality specimens for gene mutation detection in patients with lung cancer. This could be applied in treatment decisions and patient management.

3.
Life Sci ; : 116910, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31610211

RESUMO

AIMS: Tomoregulin-2 (TMEFF2) is a single-pass transmembrane protein whose specific functions and mechanisms in endometrial carcinoma (EC) remain unclear. The aim of this study was to investigate the expression, prognostic role, and potential regulatory mechanisms of TMEFF2 in EC. MATERIALS AND METHODS: The expression and prognosis of TMEFF2 in EC were analyzed via bioinformatics and verified by immunohistochemistry and survival analysis. Proliferation, invasion, and migration of EC cells in vitro were assessed by cell functional assays, while epithelial-mesenchymal transition (EMT) markers and key signaling pathway proteins were evaluated by western blotting. KEY FINDINGS: The expression of TMEFF2 in EC was significantly higher than that in atypical hyperplasia and normal endometrium, the high expression of TMEFF2 was correlated with advanced stage, poor differentiation, and lymph node metastasis, and also predicted a poor prognosis of EC. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that TMEFF2 and its related genes were enriched in the central nervous system, cell adhesion, signal transduction, and several critical signaling pathways. We also elucidated TMEFF2 networks of kinase, microRNA, and transcription factor targets. In vitro, the proliferation, invasion, and migration abilities of EC cells decreased after TMEFF2 downregulation. Downregulation of TMEFF2 reduced the activation of MAPK and PI3K signaling pathways, and inhibited EMT. SIGNIFICANCE: TMEFF2 plays an important role in the initiation, development, and malignant behavior of EC and can be a potential target for early diagnosis and treatment in EC.

4.
Curr Drug Metab ; 2019 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-31608838

RESUMO

Background: Our study aims to detect the sensitivity of the new biomarker miR-212 existing in serum exosomes along with other hepatocellular carcinoma biomarkers such as AFP (alpha-fetoprotein), CA125 (carbohydrate antigen-ca125), and Hbx protein in the diagnosis of HBV-related liver diseases. We also aim to study the roles of these biomarkers in the progression of chronic hepatitis B and provide scientific data to show the clinical value of these biomarkers. Methods: We selected 200 patients with HBV-infection (58 cases of chronic hepatitis B, 47 cases of hepatocellular carcinoma, 30 cases of compensatory phase cirrhosis, and 65 cases of decompensatory phase cirrhosis), 31 patients with primary liver cancer without HBV infection, and 70 healthy individuals as the control group. The expression level of serum AFP and CA125 was detected with electrochemiluminescence immunoassay. The expression level of the Hbx protein was detected with ELISA. Meanwhile, the expression level of miR-212 in serum was analyzed with RT-qPCR. We collected patients' clinical information following the Child-Pugh classification and MELD score criterion, and statistical analysis was made between the expression level of miR-212 and the collected clinical indexes. Lastly, we predicted the target genes of the miR-212 and its functions using bioinformatics methods such as cluster analysis and survival prediction. Results: Compared to the control group, the expression level of miR-212 in HBV infected patients was remarkably increased (P<0.05), especially between the HBV-infection Hepatocellular carcinoma group and the non-HBV-infection liver cancer group (P<0.05). The expression of miR-212 was increased in patients' Child-Pugh classification, MELD score, and TNM staging. Moreover, the sensitivity and specificity of miR-212 were superior to AFP, CA125, and HBx protein. Conclusion: There is a linear relationship between disease progression and expression level of miR-212 in the serum of HBV infected patients. This demonstrates that miR-212 plays a significant role in liver diseases. miR-212 is expected to be a new biomarker use in the diagnosis and assessment of patients with HBV-infection-related liver diseases.

5.
Int J Biochem Cell Biol ; 116: 105617, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31550546

RESUMO

Previously, we reported that the expression of human epididymis protein (HE4) was correlated with the expression of RAB23 in ovarian cancer cells. Rab23 is a member of the Ras-related small GTPase superfamily, which plays a key role in the Sonic Hedgehog (Shh) signaling pathway. However, the function of Rab23 in ovarian cancer remains unclear. In this study, we explored the location and expression of Rab23 in ovarian cancer tissues and cells (CaoV3 and A2780), and further investigated the function and potential mechanism of Rab23 in malignant biological behaviors including the epithelial-mesenchymal transition (EMT) process in ovarian cancer for the first time. Rab23 is highly expressed in ovarian cancer tissues and associated with advanced stage, and shortened overall survival time of ovarian cancer patients. We are the first to report that human epididymis protein (HE4) can regulate the expression of the Rab23 protein, and that knockdown of RAB23 decreases the proliferation, invasion, and migration abilities as well as inhibits the epithelial-mesenchymal transition (EMT) process in ovarian cancer cells. Furthermore, downregulation of Rab23 significantly inhibited Shh-Gli1 and PI3K-AKT signaling pathways. Collectively, our results indicate that Rab23 plays a critical role in the malignant biological behavior of ovarian cancer and may serve as a potential biomarker and therapeutic target for ovarian cancer.

6.
Mol Med Rep ; 20(5): 4425-4432, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545493

RESUMO

Dendritic cells (DCs) have an important role in initiating and maintaining the immune inflammatory response in allergic asthma, and CC chemokine receptor 7 (CCR7) is directly involved in the pathogenesis of DC­ and T cell­mediated allergic asthma. The present study aimed to investigate the effects of CCR7 on DC­mediated immune tolerance in allergic asthma. In the present study, bone marrow­derived DCs were transfected with an adenovirus encoding the rat CCR7 gene or a short hairpin RNA targeting CCR7 (sh­CCR7). Rats injected with DCs overexpressing CCR7 or presenting CCR7 knockdown were examined. After the rats were injected with DCs via the tail vein, bronchoalveolar lavage fluid was collected to assess its cellular composition. The protein expression levels of CCR7 in DCs were determined using immunohistochemistry and western blot analysis. The protein expression levels of interferon­Î³ (IFN­Î³), interleukin­4 (IL­4), IL­10, IL­12, transforming growth factor­ß (TGF­ß) and immunoglobulin E (IgE) were determined by ELISA. Compared with the control group, the protein expression level of CCR7 was significantly higher in the CCR7 overexpression group and significantly lower in sh­CCR7 group. Similarly, the number of DCs was higher in the CCR7 overexpression group and lower in the sh­CCR7 group. The protein expression levels of IL­10 and TGF­ß were significantly lower in the CCR7 overexpression group and higher in the sh­CCR7 group. In addition, the expression levels of IL­4, IL­12, IFN­Î³ and IgE were higher in the CCR7 overexpression group and lower in the sh­CCR7 group. The present results suggested that the role of cytokines and IgE in immune inflammation and immune tolerance in allergic asthma may be associated with the expression level of CCR7 in DCs, suggesting that CCR7 may serve a role in DC­mediated immune tolerance in allergic asthma.

7.
Front Immunol ; 10: 1895, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440258

RESUMO

Procyanidins, a subclass of flavonoids found in commonly consumed foods, possess potential anti-inflammatory activity. Manipulation of M1/M2 macrophage homeostasis is an effective strategy for the treatment of metabolic inflammatory diseases. The objective of this study was to determine the effect of procyanidins on macrophage polarization. Procyanidin B2 (PCB2), the most widely distributed natural procyanidins, enhanced the expressions of M2 macrophage markers (Arg1, Ym1, and Fizz1). PCB2 activated peroxisome proliferator-activated receptor γ (PPARγ) activity and increased the expressions of PPARγ target genes (CD36 and ABCG1) in macrophages. Inhibition of PPARγ using siRNA or antagonist GW9662 attenuated the PCB2-induced expressions of M2 macrophage markers. In addition, we identified cognate PPAR-responsive elements (PPREs) within the 5'-flanking regions of the mouse Arg1, Ym1, and Fizz1 genes. Furthermore, macrophages isolated from db/db diabetic mice showed lower expressions of M2 markers. PCB2 effectively restored the Arg1, Ym1, and Fizz1 expressions in a PPARγ-dependent manner. These findings support the notion that PCB2 regulated macrophage M2 polarization via the activation of PPARγ. Our results provide a new mechanism by which procyanidins exert their beneficial anti-inflammatory effects.

8.
BMC Public Health ; 19(1): 1093, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409316

RESUMO

BACKGROUND: Urban green open space is a valuable resource for physical activities of urban inhabitants and has the potential to reduce chronic illness and improve health. Research on the relationships between green open space and physical activity is incomplete and limited in China. Thus, the study examines how the urban green open space contributes to physical activity. METHODS: A questionnaire was designed based on the social ecology theory to investigate the physical activity of 513 residents in urban green open space. We use the time and frequency of residents exercising in urban green space to measure physical activity, and use the factor analysis to synthesize a large number of original factors (i.e., infrastructure, safety, accessibility, landscape quality, and space environment) into relatively few composite indicators. Based on the collected data of the cross-sectional population, the Order Probit regression model was constructed to analyze how urban green open space affects the residents' physical activity from the perspective of social ecology. RESULTS: ① in community factors: accessibility is significantly positive correlation with residents' physical activity, and there is no significant correlation between safety and physical activity; ②in natural factors: space environment and landscape quality are not significantly correlated with residents' physical activity; ③ in built environmental factors: infrastructures, the area of green space, the size of open space, and entertainment facilities are significantly correlated to residents' activity. Basketball courts, volleyball courts, swimming pools, and sports equipment will promote physical activity; ④ apart from the attributes of green open space, other factors are significantly correlated to physical activity in the green open space, e.g. having a companion. CONCLUSIONS: Urban green open space plays an important role in promoting physical activity especially among the women and the old, and improving the attributes (such as accessibility, infrastructures, the area of green space, the size of open space and entertainment facilities) of the urban green open space and trying to set up group sports proper to play with companion (like "square dancing" and "Tai Chi") can promote Chinese residents' physical activity so as to improve public health. The results are significant to facilitate environment health.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31369351

RESUMO

Background: Osteomyelitis of the diabetic foot is a costly health problem worldwide. Early and accurate diagnosis of the disease in patients with diabetic foot infections is needed urgently and will have an important role in diabetic foot management. Methods: This was a case-control study of subjects with diabetic foot ulcers admitted to Beijing Shijitan Hospital from September 2015 to April 2018. We compared differences in the atherogenic index of plasma (AIP) in patients with or without osteomyelitis. Results: The mean AIP of 165 patients with osteomyelitis was 0.23 ± 0.24, which was significantly higher than the mean AIP of patients without osteomyelitis. Higher AIP values were associated with a considerably higher risk of osteomyelitis with an odds ratio of 1.81 (95% confidence interval [CI] 0.71-4.61), 4.70 (1.88-11.75), 5.03 (2.06-12.25) and 1.74 (1.33-2.28). Moreover, at a cut-off of 0.184, the AIP value showed a sensitivity of 84.3% and a specificity of 83.1% in the discriminatory identification of diabetic foot osteomyelitis. Conclusions: Elevated AIP was significantly associated with diabetic foot osteomyelitis, supporting the use of this index as a biomarker for the diagnosis in clinical practice.

10.
Aging (Albany NY) ; 11(12): 4198-4215, 2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31257224

RESUMO

In this study, we identified prognostic biomarkers in ovarian carcinoma by integrating multi-omics DNA copy number variation (CNV) and methylation variation (MET) data. CNV, MET, and messenger RNA (mRNA) expression were examined in 351 ovarian carcinoma patients. Genes for which expression was correlated with DNA copy-number or DNA methylation were identified; three ovarian carcinoma gene subtypes were defined based on these correlations. Overall survival and B cell scores were lower, while the macrophage cell score was higher, in the DNA imprinting centre 1 (iC1) subtype than in the iC2 and iC3 subtypes. Comparison of CNV, MET, and mRNA expression among the subtypes identified two genes, ubiquitin B (UBB) and interleukin 18 binding protein (IL18BP), that were associated with prognosis. Mutation spectrum results based on subtype indicated that UBB and IL18BP expression may be influenced by mutation loci. Mutation levels were higher in iC1 samples than in iC2 or iC3 samples, indicating that the iC1 subtype is associated with disease progression. This integrated multi-omics analysis of genomics, epigenomics, and transcriptomics provides new insight into the molecular mechanisms of ovarian carcinoma and may help identify biomolecular markers for early disease diagnosis.

11.
Biomed Res Int ; 2019: 2686875, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355251

RESUMO

Objectives: A growing body of evidence has shown that aberrant alternative splicing (AS) is closely related to the occurrence and development of cancer. However, prior studies mainly have concentrated on a few genes that exhibit aberrant AS. This study aimed to determine AS events through whole genome analysis and construct a prognostic model of endometrial cancer (EC). Methods: We downloaded gene expression RNAseq data from UCSC Xena, and seven types of AS events from TCGA SpliceSeq. Univariate Cox regression was employed to analyze the prognostic-related alternative splicing events (PASEs) and splicing factors; multivariate Cox regression was conducted to analyze the effect of risk score (All) and clinicopathological parameters on EC prognosis. An underlying interaction network of PASEs of EC was constructed by Cytoscape Reactome FI, GO, and KEGG pathway enrichment was performed by DAVID. ROC curves and Kaplan-Meir analysis were used to assess the diagnostic value of prognostic model. The correlation between PASEs and splicing factors was analyzed by GraphPad Prism; then a network was constructed using Cytoscape. Results: In total, 28,281 AS events in EC were identified, which consisted of 1166 PASEs. RNPS1, NEK2, and CTNNB1 were the hub genes in the network of the top 600 PASEs. The area under the curve (AUC) of risk score (All) reached 0.819. Risk score (All) together with FIGO stage, cancer status, and primary therapy outcome success was risk factors of the prognosis of EC patients. Splicing factors YBX1, HNRNPDL, and HNRNPA1 were significantly related to the overall survival (OS). The splicing network indicated that the expression of splicing factors was significantly correlated with percent-splice-in (PSI) value of PASEs. Conclusion: We constructed a model for predicting the prognosis of EC patients based on PASEs using whole genome analysis of AS events and thereby provided a reliable theoretical basis for EC clinical prognosis evaluation.

12.
J Am Chem Soc ; 141(33): 13212-13221, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31353892

RESUMO

Proton-coupled electron transfer (PCET) reactions at various interfaces (liquid/membrane, solid/electrolyte, liquid/liquid) lie at the heart of many processes in biology and chemistry. Mechanistic study can provide profound understanding of PCET and rational design of new systems. However, most mechanisms of PCET reactions at a liquid/liquid interface have been proposed based on electrochemical and spectroscopic data, which lack direct evidence for possible intermediates. Moreover, a liquid/liquid interface as one type of soft interface is dynamic, making the investigation of interfacial reactions very challenging. Herein a novel electrochemistry method coupled to mass spectrometry (EC-MS) was introduced for in situ study of the oxygen reduction reaction (ORR) by ferrocene (Fc) under catalysis from cobalt tetraphenylporphine (CoTPP) at liquid/liquid interfaces. The key units are two types of gel hybrid ultramicroelectrodes (agar-gel/organic hybrid ultramicroelectrodes and water/PVC-gel hybrid ultramicroelectrodes), which were made based on dual micro- or nanopipettes. A solidified liquid/liquid interface can be formed at the tip of these pipettes, and it serves as both an electrochemical cell and a nanospray emitter for mass spectrometry. We demonstrated that the solidified L/L interfaces were very similar to typical L/L interfaces. Key CoTPP intermediates of the ORR at the liquid/liquid interfaces were identified for the first time, and the four-electron oxygen reduction pathway predominated, which provides valuable insights into the mechanism of the ORR. Theoretical simulation has further supported the possibility of formation of intermediates. This type of platform is promising for in situ tracking and identifying intermediates to study complicated reactions at liquid/liquid interfaces or other soft interfaces.

14.
Sensors (Basel) ; 19(12)2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31226855

RESUMO

In this study, the transient multichannel analysis of surface waves (MASW) is proposed to detect the existence, the location and the length of interface debonding defects in rectangular concrete-filled steel tubes (CFST). Mesoscale numerical analysis is performed to validate the feasibility of MASW-based interfacial debonding detection. Research findings indicate that the coaxial characteristics in the Rayleigh wave disperse at the starting point of the debonding area and gradually restores at the end of the defect. For healthy specimens, the surface wave mode in CFST is closer to the Rayleigh wave. However, it can be treated as a Lamb wave since the steel plate is boundary-free on both sides in the debonding area. The displacement curves are further investigated with forward analysis to obtain the dispersion curves. The mesoscale numerical simulation results indicate that the propagation characteristic of the surface wave is dominated by the debonding defect. The detectability of interfacial debonding detection for rectangular CFST using the MASW approach is numerically verified in this study. The proposed MASW-based nondestructive testing technique can achieve bond-slip detection by comparing the variation trend of the coaxial characteristics in the time-history output signals and the dispersion curves obtained from the forward analysis, for avoiding misjudgment of the experimental observations.

15.
Technol Cancer Res Treat ; 18: 1533033819859448, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31248330

RESUMO

PURPOSE: We investigated the dosimetric effect of intrafraction tumor motion in lung stereotactic body radiotherapy using the CyberKnife static tracking system. METHODS: Four-dimensional computed tomography scans of a dynamic thorax phantom were acquired. Two motion ranges, 3 collimator sizes, and 4 treatment starting phases were investigated. Monte Carlo dose distributions were calculated on internal target volume with a treatment-specific setup margin for 6 Gy/1 fraction. Dosimetric effects of intrafractional tumor motion were assessed with Gafchromic films. γ (5%/3 mm), dose differences, and distance to agreement were analyzed. RESULTS: With 30 mm collimator plans, the measured dose passed the criteria γ (5%/3 mm) in all tumor motion ranges. The γ passing rates of the plans using 20 mm or 20+35 mm collimators were much lower than that with 30 mm collimator, especially with the 30 mm tumor motion range. The measured dose of 10 mm tumor motion ranges all passed the 90% criteria of γ (5%/3 mm), the results being much better than those of 30 mm tumor motion ranges, which were below 80%. The results of same delivered plan but treated with different starting phases varies greatly. CONCLUSION: Xsight Lung Tracking technique should be used with caution in lung cancer stereotactic body radiation therapy because the temporal dose variations can be significant.

16.
Virus Genes ; 55(4): 550-556, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31161411

RESUMO

Japanese encephalitis virus SA14-14-2 (JEV SA14-14-2) is a widely used vaccine in China and other southeastern countries to prevent Japanese encephalitis in children. In this study, a stable infectious cDNA clone of JEV SA14-14-2 with a low copy number pACYC177 vector dependent on the T7 promoter and T7 terminator was developed. Two introns were inserted into the capsid gene and envelope gene of JEV cDNA for gene stability. Hepatitis delta virus ribozyme (HDVr) was engineered into the 3' UTR cDNA of JEV for authentic 3' UTR transcription. The rescued virus showed biological properties indistinguishable from those of the parent strain (JEV SA14-14-2). The establishment of a JEV SA14-14-2 reverse genetics system lays the foundation for the further development of other flavivirus vaccines and viral pathogenesis studies.

17.
Zhongguo Zhong Yao Za Zhi ; 44(3): 559-565, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30989923

RESUMO

This paper aimed to predict and explore the mechanism of multiple components, targets and pathways of Siwu decoction for treatment of primary dysmenorrhea, and to establish a network pharmacological model of "compound-target-pathway-disease". According to the active ingredients in Siwu Decoction, Swiss Target Prediction server was used to predict the active component targets based on the reverse pharmacodynamic group matching method, and the primary dysmenorrhea targets approved by FDA were selected by database including DrugBank, OMIM and TTD. According to the enrichment analysis of the target pathways by using KEGG, the Cytoscape software was used to construct the network of "compound-target-pathway-disease" of Siwu Decoction. Network analysis showed that there were 20 active components involved in 114 pathways. And 16 components, 16 target proteins and 24 pathways were related to primary dysmenorrhea. Siwu Decoction may play a role in treating primary dysmenorrhea by acting on protein targets and pathways related to hormone regulation, central analgesia, spasmolysis,inflammation and immunity. This study revealed the potential active compounds and possible mechanism of Siwu Decoction for treatment of primary dysmenorrhea, providing theoretical references for further systematic laboratory experiments on effective compounds and action mechanism of Siwu Decoction.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Dismenorreia/tratamento farmacológico , Feminino , Humanos , Software
18.
Cancer Med ; 8(4): 1779-1792, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30907073

RESUMO

Radiotherapy is the mainstay and primary curative treatment modality in nasopharyngeal carcinoma (NPC), whose efficacy is limited by the development of intrinsic and acquired radioresistance. Thus, deciphering new molecular targets and pathways is essential for enhancing the radiosensitivity of NPC. SALL4 is a vital factor in the development and prognosis of various cancers, but its role in radioresistance remains elusive. This study aimed to explore the association of SALL4 expression with radioresistance of NPC. It was revealed that SALL4 expression was closely correlated with advanced T classification of NPC patients. Inhibition of SALL4 reduced proliferation and sensitized cells to radiation both in vitro and in vivo. Furthermore, SALL4 silencing increased radiation-induced DNA damage, apoptosis, and G2/M arrest in CNE2 and CNE2R cells. Moreover, knockdown of SALL4 impaired the expression of p-ATM, p-Chk2, p-p53, and anti-apoptosis protein Bcl-2, while pro-apoptosis protein was upregulated. These findings indicate that SALL4 could induce radioresistance via ATM/Chk2/p53 pathway and its downstream proteins related to apoptosis. Targeting SALL4 might be a promising approach for the development of novel radiosensitizing therapeutic agents for radioresistant NPC patients.

19.
J Cell Physiol ; 234(7): 11023-11036, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30633343

RESUMO

BACKGROUND: Ovarian cancer is one of the three major malignant tumors of the female reproductive system, and the mortality associated with ovarian cancer ranks first among gynecologic malignant tumors. The pathogenesis of ovarian cancer is not yet clearly defined but elucidating this process would be of great significance for clinical diagnosis, prevention, and treatment. For this study, we used bioinformatics to identify the key pathogenic genes and reveal the potential molecular mechanisms of ovarian cancer; we used immunohistochemistry to validate them. METHODS: We analyzed and integrated four gene expression profiles (GSE14407, GSE18520, GSE26712, and GSE54388), which were downloaded from the Gene Expression Omnibus (GEO) database, with the aim of obtaining a common differentially expressed gene (DEG). Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We then established a protein-protein interaction (PPI) network of the DEGs through the Search Tool for the Retrieval of Interacting Genes (STRING) database and selected hub genes. Finally, survival analysis of the hub genes was performed using a Kmplotter online tool. RESULTS: A total of 226 DEGs were detected after the analysis of the four gene expression profiles; of these, 87 were upregulated genes and 139 were downregulated. GO analysis results showed that DEGs were significantly enriched in biological processes including the G2/M transition of the mitotic cell cycle, the apoptotic process, cell proliferation, blood coagulation, and positive regulation of the canonical Wnt signaling pathway. KEGG analysis results showed that DEGs were particularly enriched in the cell cycle, the p53 signaling pathway, the Wnt signaling pathway, the Ras signaling pathway, the Rap1 signaling pathway, and tyrosine metabolism. We selected 50 hub genes from the PPI network, which had 147 nodes and 655 edges, and 30 of them were associated with the prognosis of ovarian cancer. We performed immunohistochemistry on phosphoserine aminotransferase 1 (PSAT1). PSAT1 was highly expressed in cancer tissues, and its expression level was related to clinical stage and tissue differentiation in ovarian cancer. A Cox proportional risk model suggested that high expression of PSAT1 and late clinical stage were independent risk factors for survival and prognosis of ovarian cancer patients. CONCLUSION: The detection of DEGs using bioinformatics analysis might be crucial to understanding the pathogenesis of ovarian cancer, especially the molecular mechanisms of its development. The association between PSAT1 expression and the occurrence, development, and prognosis of ovarian cancer was further verified by immunohistochemistry. The PSAT1 expression can be used as a prognostic marker to provide a potential target for the diagnosis and treatment of ovarian cancer.

20.
Cancer Immunol Res ; 7(3): 487-497, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30651289

RESUMO

The immunocheckpoint protein PD-1/PD-L1 is considered a promising target for cancer immunotherapeutics. However, the objective response rate using antibodies that block the interaction between PD-1 and PD-L1 was less than 40%, and the mechanism underlying regulation of PD-1/PD-L1 expression is poorly understood. In this study, we identified the miRNA let-7 that posttranscriptionally suppresses PD-L1 expression. LIN28, an RNA binding protein upregulated in most cancer cells, inhibits the biogenesis of let-7, thus promoting PD-L1 expression. Therefore, inhibition of LIN28 may be a strategy to prevent immune evasion of cancer cells. We found that treatment with a LIN28 inhibitor, the small compound C1632, increases let-7 and suppresses PD-L1 expression, leading to reactivation of antitumor immunity in vitro and in vivo In addition, C1632 also displayed the capacity to inhibit cancer cell proliferation and tumor growth in mice. Altogether, these findings identified LIN28/let-7 as a target for PD-L1-mediated immunotherapeutics and reveal the potential of C1632 and its derivatives as promising oncotherapeutic agents.

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