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Objective To explore the biological function and downstream mechanism of ETS1 in glioma. Methods Bioinformatics and immunohistochemistry were used to analyze the differential expression characteristics of ETS1 in gliomas; qRT-PCR was employed to detect the expression level of ETS1 mRNA and lncRNA X-inactive specific transcript (XIST). CCK-8 and 5-ethyl-2′-deoxyuridine experiments were conducted to detect cell growth. Western blot was used to detect the expression of apoptosis-related proteins (Bax, Bak, Bcl-2). PROMO database was utilized to predict the binding sites between ETS1 and XIST promoter. Dual-luciferase reporter gene assay and chromatin immunoprecipitation-quantitative polymerase chain reaction assays were performed to verify the binding relationship between ETS1 and the XIST promoter region. cBioPortal database was used to analyze the correlation between the expression of ETS1 mRNA and XIST in glioma tissues. Results The expression levels of ETS1 mRNA and protein were significantly upregulated in glioma (P<0.05). The depletion of ETS1 significantly inhibited the proliferation of glioma cells and promoted cell apoptosis (P<0.05). ETS1 could target and bind with the XIST promoter and promote the expression of XIST (P<0.05). The overexpression of XIST reversed the effects of ETS1 on the proliferation of glioma cells and the promotion of cell apoptosis (P<0.05). Conclusion ETS1 is highly expressed in glioma tissues. It could promote the expression of lncRNA XIST, boost the proliferation of glioma cells, and inhibit cell apoptosis.
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@#Ets transcription factor ELK 1,a member of the ternary complex factor(TCF) subfamily in the Ets family,is directly downstream signal of MAPK/ERK pathway and is activated by phosphorylation to execute the function of ERK signal.ELK1,which is highly expressed and phosphorylated in stem cells and tumor cells,plays a role in promoting proliferation,inhibiting apoptosis and differentiation in stem cells.In tumor cells,ELK1 has shown to promote proliferation,migration,and inhibit apoptosis.In neural cells,ELK1 is involved in long-term memory,learning,addiction and other functions.In this paper,the research progress on the main structure and basic biological characteristics of ELK1,the function and mechanism of ELK 1 in tumor cells,stem cells and nerve cells are reviewed in order to provide new ideas for the follow-up research.
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Objective To compare the prediction effect of combined model and single model in HFRS incidence fitting and prediction, and to provide a reference for optimizing HFRS prediction model. Methods The province with the highest incidence in China (Heilongjiang Province) in recent years was selected as the research site. The monthly incidence data of HFRS in Heilongjiang Province from 2004 to 2017 were collected. The data from 2004 to 2016 was used as training data, and the data from January to December 2017 was used as test data. The training data was used to train SARIMA , ETS and NNAR models, respectively. The reciprocal variance method and particle swarm optimization algorithm (PSO) were used to calculate the model coefficients of SARIMA, ETS and NNAR, respectively, to construct combined model A and combined model B. The established models were used to predict the incidence of HFRS from January to December 2017. The fitted and predicted values of the five models were compared with the training data and test data, respectively. Mean Absolute Percentage Error (MAPE), Mean Absolute Error (MAE), Root Mean Standard Deviation (RMSE), and Mean Error Rate (MER) were used to evaluate the model fitting and prediction effects. Results The optimal SARIMA model was SARIMA(1,0,2)(2,1,1)12. The optimal ETS model was ETS(M, N, M), and the smoothing parameter =0.738,=1*10. The optimal NNAR model was NNAR(13,1,7)12. The residuals of the three single models were white noise (P>0.05). The expression of combined model A was ŷ=0.134*ySARIMA+0.162*yETS+0.704*yNNAR; the expression of combined model B was ŷ=0.246*ySARIMA+0.435*yETS+0.319*yNNAR. The MAPE, MAE, RMSE, and MER fitted by SARIMA, ETS, NNAR, combined model A and combined model B were 24.10%, 0.11, 0.17, 23.29%; 17.14%, 0.08, 0.14, 17.96%; 6.33%, 0.02, 0.03, 4.25%; 9.03%, 0.03, 0.05, 7.51%; 13.16%, 0.06, 0.09, 12.33%, respectively. The MAPE, MAE, RMSE, and MER predicted by the five models were 18.70%, 0.05, 0.06, 19.62%; 23.83%, 0.06, 0.07, 24.49%; 28.30%, 0.07, 0.10, 29.21%; 21.69%, 0.06, 0.08, 22.63%; 17.39%, 0.05, 0.07, 18.76%, respectively. Conclusion The fitting and prediction effects of the combined models are better than the single models. The combined model based on PSO to calculate the weight of the single model is the optimal model.
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To explore the role of forkhead box protein O1 (FOXO1) in the progression of glioblastoma multiforme (GBM) and related drug resistance, we deciphered the roles of FOXO1 and miR-506 in proliferation, apoptosis, migration, invasion, autophagy, and temozolomide (TMZ) sensitivity in the U251 cell line using in vitro and in vivo experiments. Cell viability was tested by a cell counting kit-8 (CCK8) kit; migration and invasion were checked by the scratching assay; apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and flow cytometry. The construction of plasmids and dual-luciferase reporter experiment were carried out to find the interaction site between FOXO1 and miR-506. Immunohistochemistry was done to check the protein level in tumors after the in vivo experiment. We found that the FOXO1-miR-506 axis suppresses GBM cell invasion and migration and promotes GBM chemosensitivity to TMZ, which was mediated by autophagy. FOXO1 upregulates miR-506 by binding to its promoter to enhance transcriptional activation. MiR-506 could downregulate E26 transformation-specific 1 (ETS1) expression by targeting its 3'-untranslated region (UTR). Interestingly, ETS1 promoted FOXO1 translocation from the nucleus to the cytosol and further suppressed the FOXO1-miR-506 axis in GBM cells. Consistently, both miR-506 inhibition and ETS1 overexpression could rescue FOXO1 overactivation-mediated TMZ chemosensitivity in mouse models. Our study demonstrated a negative feedback loop of FOXO1/miR-506/ETS1/FOXO1 in GBM in regulating invasiveness and chemosensitivity. Thus, the above axis might be a promising therapeutic target for GBM.
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Animais , Camundongos , Humanos , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Retroalimentação , Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , MicroRNAs/metabolismo , Temozolomida/uso terapêutico , Proteína Forkhead Box O1/metabolismoRESUMO
@#Objective To investigate the effects of miR-130b-5p targeting E26 transformation specific-1(ETS1)on proliferation,migration and invasion of prostatic cancer(PCa)cells and its mechanism. Methods The mRNA transcription level of miR-130b-5p gene in PCa tissues,adjacent tissues,(LNCap,PC-3,DU-145)and normal prostate cells(RPWE-1)PCa cells was measured by qRT-PCR,and the expression of ETS1 protein in PCa cells was detected by Western blot. Bioinformatics,fluorescein experiment,qRT-PCR and Western blot were used to predict and verify the targeting relationship between miR-130b-5p and ETS1. PC-3 cells were divided into control group(without any treatment),mimic group(transfected with miR-130b-5p mimic)and mimic + ETS1 group(transfected with miR-130b-5p mimic + pcDNA-ETS1). The cells were detected for the proliferation and viability by clone formation assay and CCK-8 respectively,measured for the migration and invasion by scratch test and Transwell chamber assay,and detected for the expression of invasion-related proteins and PI3K/AKT/mTOR pathway-related proteins by Western blot. Results The transcription level of miR-130b-5p mRNA in PCa tissues was significantly lower than that in adjacent tissues(t = 12. 450,P < 0. 001);Compared with RPWE-1 cells,the transcription level of miR-130b-5p mRNA in LNCap,PC-3 and DU-145 cells decreased significantly(t = 4. 463,7. 103 and 5. 741,P = 0. 001 2,< 0. 001 and < 0. 001,respectively),while the expression level of ETS1protein increased significantly(t = 4. 850,9. 325 and 7. 723,P = 0. 008,< 0. 001 and = 0. 002,respectively). miR-130-5p targeted and negatively regulated the expression of ETS1. Compared with the control group,the cloning rate,viability and scratch healing rate of cells in mimic group decreased significantly(t = 11. 370,10. 640 and 15. 660,respectively,each P < 0. 001),the number of invasive cells decreased significantly(t = 10. 160,P < 0. 001),the expression levels of matrix metalloproteinase-2(MMP-2),MMP-9 and vimentin decreased significantly(t = 15. 120,9. 992 and 12. 600,P < 0. 001,< 0. 001 and = 0. 002,respectively),while the expression level of E-cadherin increased significantly(t = 6. 928,P < 0. 001),and the phosphorylation levels of phosphatidylinositol-3 kinase(PI3K),protein kinase B(AKT)and mammalian target of rapamycin(mTOR)decreased significantly(t = 7. 746,8. 041 and 11. 510,P = 0. 002,0. 002,and < 0. 001,respectively);Compared with mimic group,the cell cloning rate,viability,scratch healing rate significantly increased in mimic + ETS1 group(t = 6. 988,6. 642 and 6. 660,respectively,each P < 0. 001),the number of invasive cells significantly increased(t = 4. 082,P = 0. 002),the expression levels of MMP-2,MMP-9 and vimentin proteins were significantly up-regulated(t = 10. 410,6. 754 and 8. 521,P = 0. 002,0. 003 and 0. 002,respectively),however,the expression level of E-cadherin was significantly down-regulated(t = 4. 648,P < 0. 01),and the phosphorylation levels of PI3K,AKT and mTOR were significantly up-regulated(t = 4. 850,4. 323 and 10. 840,P = 0. 008,0. 008 and < 0. 001,respectively)Conclusion miR-130b-5p targets ETS1 to inhibit the proliferation,migration and invasion of PC-3 cells,which may be through the regulation of PI3K/AKT/mTOR signaling pathway.
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The genus Artemisia L. of the family Asteraceae is systematically very complex. The aim of this study was to evaluate taxonomic positions of taxa of the subgenus Artemisia belonging to the genus Artemisia in Turkey using some molecular techniques. In this molecular study, 44 individuals belong to 14 species of the subgenus Artemisia were examined. Analyses were performed on the combined dataset using maximum parsimony, maximum likelihood and Bayesian inference and Molecular parameters obtained from co-evaluations of sequences of the psbA-trnH, ITS and ETS regions of examined individuals were used in the phylogenetic tree drawing. According to the results of this study, two molecular groups have been formed based on the DNA sequence similarity of the species, but there are no obvious morphological characters corresponding to two molecular groups. There is no also agreement between the two molecular groups and the two morphological groups formed according to the hairiness condition of the receptacle of species. Due to the lack of molecular significance of their receptacles with or without hair, dividing of the subgenus Artemisia species into new subgenera or sections was not considered appropriate. Likewise, it has been found that with or without hair on the corolla lobes of the central hermaphrodite disc flowers have no molecular significance. It was found that there were no gene flow and hybridization between the 14 species of the subgenus Artemisia and these 14 species were found completed their speciation. This study is important as it is the first molecular based study relating with belong to subgenus Artemisia species growing naturally in Turkey. In addition, new haplotypes related to the populations of Turkey belonging to the subgenus Artemisia taxa were reported by us for the first time and added to the GenBank database.
O gênero Artemisia L. da família Asteraceae é sistematicamente muito complexo. O objetivo deste estudo foi avaliar as posições taxonômicas de táxons do subgênero Artemisia pertencentes ao gênero Artemisia na Turquia usando algumas técnicas moleculares. Neste estudo molecular, 44 indivíduos pertencentes a 14 espécies do subgênero Artemisia foram examinados. As análises foram realizadas no conjunto de dados combinado usando máxima parcimônia, máxima verossimilhança e inferência bayesiana e parâmetros moleculares obtidos a partir de coavaliações de sequências das regiões psbA-trnH, ITS e ETS de indivíduos examinados foram usados no desenho da árvore filogenética. De acordo com os resultados deste estudo, dois grupos moleculares foram formados com base na similaridade da sequência de DNA das espécies, mas não há caracteres morfológicos óbvios correspondentes a dois grupos moleculares. Também não há concordância entre os dois grupos moleculares e os dois grupos morfológicos formados de acordo com a condição de pilosidade do receptáculo da espécie. Devido à falta de significado molecular de seus receptáculos com ou sem cabelo, a divisão das espécies do subgênero Artemisia em novos subgêneros ou seções não foi considerada apropriada. Da mesma forma, verificou-se que com ou sem cabelo nos lobos da corola das flores do disco hermafrodita central não tem significado molecular. Constatou-se que não houve fluxo gênico e hibridização entre as 14 espécies do subgênero Artemisia e essas 14 espécies concluíram sua especiação. Este estudo é importante porque é o primeiro estudo de base molecular relacionado com espécies pertencentes ao subgênero Artemisia crescendo naturalmente na Turquia. Além disso, novos haplótipos relacionados às populações da Turquia pertencentes ao subgênero Artemisia taxa foram relatados por nós pela primeira vez e adicionados ao banco de dados do GenBank.
Assuntos
Artemisia/classificação , Artemisia/genéticaRESUMO
Abstract The genus Artemisia L. of the family Asteraceae is systematically very complex. The aim of this study was to evaluate taxonomic positions of taxa of the subgenus Artemisia belonging to the genus Artemisia in Turkey using some molecular techniques. In this molecular study, 44 individuals belong to 14 species of the subgenus Artemisia were examined. Analyses were performed on the combined dataset using maximum parsimony, maximum likelihood and Bayesian inference and Molecular parameters obtained from co-evaluations of sequences of the psbA-trnH, ITS and ETS regions of examined individuals were used in the phylogenetic tree drawing. According to the results of this study, two molecular groups have been formed based on the DNA sequence similarity of the species, but there are no obvious morphological characters corresponding to two molecular groups. There is no also agreement between the two molecular groups and the two morphological groups formed according to the hairiness condition of the receptacle of species. Due to the lack of molecular significance of their receptacles with or without hair, dividing of the subgenus Artemisia species into new subgenera or sections was not considered appropriate. Likewise, it has been found that with or without hair on the corolla lobes of the central hermaphrodite disc flowers have no molecular significance. It was found that there were no gene flow and hybridization between the 14 species of the subgenus Artemisia and these 14 species were found completed their speciation. This study is important as it is the first molecular based study relating with belong to subgenus Artemisia species growing naturally in Turkey. In addition, new haplotypes related to the populations of Turkey belonging to the subgenus Artemisia taxa were reported by us for the first time and added to the GenBank database.
Resumo O gênero Artemisia L. da família Asteraceae é sistematicamente muito complexo. O objetivo deste estudo foi avaliar as posições taxonômicas de táxons do subgênero Artemisia pertencentes ao gênero Artemisia na Turquia usando algumas técnicas moleculares. Neste estudo molecular, 44 indivíduos pertencentes a 14 espécies do subgênero Artemisia foram examinados. As análises foram realizadas no conjunto de dados combinado usando máxima parcimônia, máxima verossimilhança e inferência bayesiana e parâmetros moleculares obtidos a partir de coavaliações de sequências das regiões psbA-trnH, ITS e ETS de indivíduos examinados foram usados no desenho da árvore filogenética. De acordo com os resultados deste estudo, dois grupos moleculares foram formados com base na similaridade da sequência de DNA das espécies, mas não há caracteres morfológicos óbvios correspondentes a dois grupos moleculares. Também não há concordância entre os dois grupos moleculares e os dois grupos morfológicos formados de acordo com a condição de pilosidade do receptáculo da espécie. Devido à falta de significado molecular de seus receptáculos com ou sem cabelo, a divisão das espécies do subgênero Artemisia em novos subgêneros ou seções não foi considerada apropriada. Da mesma forma, verificou-se que com ou sem cabelo nos lobos da corola das flores do disco hermafrodita central não tem significado molecular. Constatou-se que não houve fluxo gênico e hibridização entre as 14 espécies do subgênero Artemisia e essas 14 espécies concluíram sua especiação. Este estudo é importante porque é o primeiro estudo de base molecular relacionado com espécies pertencentes ao subgênero Artemisia crescendo naturalmente na Turquia. Além disso, novos haplótipos relacionados às populações da Turquia pertencentes ao subgênero Artemisia taxa foram relatados por nós pela primeira vez e adicionados ao banco de dados do GenBank.
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Abstract The genus Artemisia L. of the family Asteraceae is systematically very complex. The aim of this study was to evaluate taxonomic positions of taxa of the subgenus Artemisia belonging to the genus Artemisia in Turkey using some molecular techniques. In this molecular study, 44 individuals belong to 14 species of the subgenus Artemisia were examined. Analyses were performed on the combined dataset using maximum parsimony, maximum likelihood and Bayesian inference and Molecular parameters obtained from co-evaluations of sequences of the psbA-trnH, ITS and ETS regions of examined individuals were used in the phylogenetic tree drawing. According to the results of this study, two molecular groups have been formed based on the DNA sequence similarity of the species, but there are no obvious morphological characters corresponding to two molecular groups. There is no also agreement between the two molecular groups and the two morphological groups formed according to the hairiness condition of the receptacle of species. Due to the lack of molecular significance of their receptacles with or without hair, dividing of the subgenus Artemisia species into new subgenera or sections was not considered appropriate. Likewise, it has been found that with or without hair on the corolla lobes of the central hermaphrodite disc flowers have no molecular significance. It was found that there were no gene flow and hybridization between the 14 species of the subgenus Artemisia and these 14 species were found completed their speciation. This study is important as it is the first molecular based study relating with belong to subgenus Artemisia species growing naturally in Turkey. In addition, new haplotypes related to the populations of Turkey belonging to the subgenus Artemisia taxa were reported by us for the first time and added to the GenBank database.
Resumo O gênero Artemisia L. da família Asteraceae é sistematicamente muito complexo. O objetivo deste estudo foi avaliar as posições taxonômicas de táxons do subgênero Artemisia pertencentes ao gênero Artemisia na Turquia usando algumas técnicas moleculares. Neste estudo molecular, 44 indivíduos pertencentes a 14 espécies do subgênero Artemisia foram examinados. As análises foram realizadas no conjunto de dados combinado usando máxima parcimônia, máxima verossimilhança e inferência bayesiana e parâmetros moleculares obtidos a partir de coavaliações de sequências das regiões psbA-trnH, ITS e ETS de indivíduos examinados foram usados no desenho da árvore filogenética. De acordo com os resultados deste estudo, dois grupos moleculares foram formados com base na similaridade da sequência de DNA das espécies, mas não há caracteres morfológicos óbvios correspondentes a dois grupos moleculares. Também não há concordância entre os dois grupos moleculares e os dois grupos morfológicos formados de acordo com a condição de pilosidade do receptáculo da espécie. Devido à falta de significado molecular de seus receptáculos com ou sem cabelo, a divisão das espécies do subgênero Artemisia em novos subgêneros ou seções não foi considerada apropriada. Da mesma forma, verificou-se que com ou sem cabelo nos lobos da corola das flores do disco hermafrodita central não tem significado molecular. Constatou-se que não houve fluxo gênico e hibridização entre as 14 espécies do subgênero Artemisia e essas 14 espécies concluíram sua especiação. Este estudo é importante porque é o primeiro estudo de base molecular relacionado com espécies pertencentes ao subgênero Artemisia crescendo naturalmente na Turquia. Além disso, novos haplótipos relacionados às populações da Turquia pertencentes ao subgênero Artemisia taxa foram relatados por nós pela primeira vez e adicionados ao banco de dados do GenBank.
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Humanos , Artemisia/genética , Filogenia , Turquia , Teorema de Bayes , Hibridização GenéticaRESUMO
OBJECTIVES@#Nasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignant tumor with unique geographical and ethnic distribution characteristics. NPC is mostly found in south China and Southeast Asia, and its treatment mainly depends on radiotherapy and chemotherapy. However, NPC is usually found in the late stage, and local recurrence and distant metastasis are common, leading to poor prognosis. The receptor tyrosine kinase AXL is up-regulated in various tumors and it is involved in tumor proliferation, migration, invasion, and other processes, which are associated with poor prognosis of tumors. This study aims to detect the expression of AXL in NPC cell lines and tissues, and to investigate its biological function of AXL and the underlying molecular mechanisms in regulation of NPC.@*METHODS@#The expression levels of AXL in normal nasopharyngeal epithelial tissues and NPC tissues were analyzed by GSE68799, GSE12452, and GSE53819 data sets based on Gene Expression Omnibus (GEO) database. The Cancer Genome Atlas (TCGA) database was used to analyze the relationship between AXL and prognosis of head and neck squamous cell carcinoma (HNSC). The indicators of prognosis included overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS), and progression-free interval (PFI). Western blotting assay was used to detect the AXL protein expression levels in normal nasopharyngeal epithelial cell line and NPC cell lines. Immunohistochemical method was used to detect AXL expression levels in normal nasopharyngeal epithelial tissues and NPC tissues. Cell lines with stable AXL knockdown were established by infecting 5-8F and Fadu cells with lentivirus interference vector, and cell lines with stable AXL overexpression were established by infecting C666-1 and HK-1 cells with lentivirus expression vector. Real-time PCR and Western blotting were used to detect the efficiency of knockdown and overexpression in stable cell lines. The effects of AXL knockdown or overexpression on proliferation, migration, and invasion of NPC cells were detected by CCK-8, plate colony formation, and Transwell assays, and the effect of AXL knockdown on tumor growth in nude mice was detected by subcutaneous tumor formation assay. The sequence of AXL upstream 2.0 kb promoter region was obtained by UCSC online database. The PROMO online database was used to predict AXL transcription factors with 0% fault tolerance, and the JASPAR online database was used to predict the binding sites of ETS1 to AXL. Real-time PCR and Western blotting were used to detect the effect of ETS1 on AXL protein and mRNA expression. The AXL upstream 2.0 kb promoter region was divided into 8 fragments, each of which was 250 bp in length. Primers were designed for 8 fragments. The binding of ETS1 to AXL promoter region was detected by chromatin immuno-precipitation (ChIP) assay to determine the direct regulatory relationship between ETS1 and AXL. Rescue assay was used to determine whether ETS1 affected the proliferation, migration, and invasion of NPC cells through AXL.@*RESULTS@#Bioinformatics analysis showed that AXL was highly expressed in NPC tissues (P<0.05), and AXL expression was positively correlated with OS, DFI, DSS, and PFI in HNSC patients. Western blotting and immunohistochemical results showed that AXL was highly expressed in NPC cell lines and tissues compared with the normal nasopharyngeal epithelial cell line and tissues. Real-time PCR and Western blotting results showed that knockdown and overexpression efficiency in the stable cell lines met the requirements of subsequent experiments. The results of CCK-8, plate colony formation, Transwell assays and subcutaneous tumor formation in nude mice showed that down-regulation of AXL significantly inhibited the proliferation, migration, invasion of NPC cells and tumor growth (all P<0.05), and the up-regulation of AXL significantly promoted the proliferation, migration, and invasion of NPC cells (all P<0.05).As predicted by PROMO and JASPAR online databases, ETS1 was a transcription factor of AXL and had multiple binding sites in the AXL promoter region. Real-time PCR and Western blotting results showed that knockdown or overexpression of ETS1 down-regulated or up-regulated AXL protein and mRNA expression levels. ChIP assay result showed that ETS1 bound to AXL promoter region and directly regulate AXL expression. Rescue assay showed that AXL rescued the effects of ETS1 on proliferation, migration and invasion of NPC cells (P<0.05).@*CONCLUSIONS@#AXL is highly expressed in NPC cell lines and tissues, which can promote the malignant progression of NPC, and its expression is regulated by transcription factor ETS1.
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Animais , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/metabolismo , RNA Mensageiro/genética , Sincalida/metabolismo , Fatores de Transcrição/genéticaRESUMO
@#Objective To explore the clinical effect of tubeless 3 mm ultra-fine thoracoscope combined with needle electrocoagulation hook thoracic sympathicotomy in the treatment of primary palmar hyperhidrosis. Methods The clinical data of 77 patients with primary palmar hyperhidrosis who underwent surgery in the First Hospital of Lanzhou University from September 2017 to July 2021 were retrospectively analyzed, including 50 males and 27 females, with an average age of 23.60±5.60 years. A total of 36 patients were treated with tubeless 3 mm ultra-fine thoracoscopic electrocoagulation hook thoracic sympathicotomy (an observation group), and 41 patients were treated with conventional thoracoscopic thoracic sympathicotomy (a control group). The baseline data, perioperative data and the results of 12 hours after operation were compared between the two groups. Results All the 77 patients completed the operation successfully, no conversion to thoracotomy, no intraoperative bleeding, and no conversion to endotracheal intubation in the observation group. In the observation group, the time of anesthesia before operation [19.00 (17.00, 23.75) min vs. 25.00 (21.00, 27.00) min, P=0.001] and postoperative hospital stay [2.00 (1.00, 2.00) d vs. 2.00 (1.00, 3.00) d, P=0.012] were shorter than those in the control group. The operation time [22.50 (21.00, 25.75) min vs. 26.00 (23.50, 28.50) min, P=0.001], intraoperative blood loss [5.00 (2.25, 5.00) mL vs. 6.00 (5.00, 10.00) mL, P=0.003], postoperative pain index [2.00 (1.00, 2.00) vs. 3.00 (2.00, 3.00), P=0.001], hospitalization cost (14 246.58±879.28 yuan vs. 15 085.90±827.15 yuan, P<0.001) and postoperative inflammation index: white blood cell count [(12.96±2.32)×109/L vs. (14.47±2.05)×109/L, P=0.003], percentage of neutrophils (76.31%±5.40% vs. 79.97%±7.12%, P=0.014) were significantly lower or less than those in the control group. There was no significant difference in the incidence of major postoperative complications or adverse consequences between the two groups (P>0.05). In the evaluation of 12 hours after operation, the time of getting out of bed [2.00 (1.00, 2.00) h vs. 2.00 (2.00, 3.00) h, P=0.017], the time of drinking water after operation [1.50 (1.00, 2.00) h vs. 2.00 (1.00, 3.00) h, P=0.005], and the heart rate (80.25±14.42 bpm vs. 91.07±15.08 bpm, P=0.002), the incidence of dizziness, nausea and other uncomfortable symptoms (5.6% vs. 25.0%, P=0.040) at 12 hours after operation were shorter or lower than those in the control group. There was no significant difference in blood oxygen saturation (non-inhaled oxygen state) 12 hours after the operation between the two groups [97.00% (95.25%, 98.00%) vs. 97.00% (96.00%, 98.00%), P=0.763]. Conclusion Compared with conventional thoracoscopic thoracic sympathicotomy, tubeless 3 mm ultra-fine thoracoscopic electrocoagulation hook thoracic sympathicotomy can significantly shorten the operation time, reduce postoperative pain and promote postoperative recovery, in line with the concept of accelerated rehabilitation surgery and minimally invasive surgery, and is worth popularizing in clinical practice.
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The present study investigated the mechanism of polyphyllin A(PPA) in inhibiting gastric cancer(GC) cells. GC cells(SGC7901 and MGC803 cell lines) were treated with PPA at different concentrations. The effect of PPA on the proliferation of GC cells was detected by MTT assay, real-time cell analysis(RTCA) assay, and clone-forming assay, respectively. Reactive oxygen species(ROS) of GC cells was detected by flow cytometry. The change of mitochondrial membrane potential was detected by JC-1 assay. The expression and phosphorylation levels of apoptosis-related proteins(caspase-9, caspase-3, and PARP) and proteins related to the signaling pathway(ETS-1, CIP2 A, and Akt) were detected by Western blot. The binding sites of PPA to ETS-1 were analyzed by molecular docking. The affinity of PPA and ETS-1 was detected by drug affinity responsive target stability(DARTS) assay. PPA had a significant inhibitory effect on the proliferation and colony formation of GC cells at a low concentration. The PPA groups showed increased ROS and decreased mitochondrial membrane potential. PPA down-regulated the precursor expression of caspase-9 and caspase-3 and promoted the cleavage of PARP, suggesting that PPA induced the apoptosis of GC cells through the mitochondrial pathway. PPA significantly reduced expression levels of CIP2 A and the phosphorylation of downstream Akt. Molecular docking showed that PPA bound to the ETS domain of ETS-1, the transcription factor of CIP2 A, and formed hydrogen bonds with Pro319 and Asp317. DARTS assay further confirmed that PPA significantly prevented the hydrolysis of ETS-1 by pronase, which was inductive of the direct binding effect of PPA and ETS-1. PPA inhibits the proliferation and induces the apoptosis of GC cells by directly targeting ETS-1 to down-regulate the ETS-1/CIP2 A/Akt signaling pathway.
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Humanos , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Simulação de Acoplamento Molecular , Neoplasias Gástricas/metabolismoRESUMO
Resumo O artigo objetivou analisar conhecimentos, percepções, práticas de cuidado e Itinerrários Terapêuticos (IT) para o diagnóstico e tratamento das Infecções Sexualmente Transmissíveis (IST), com destaque para sífilis, entre Travestis e Mulheres Trans (TrMT) em Salvador, Brasil. Foram realizados 05 grupos focais e 06 entrevistas semiestruturadas com 30 TrMT. Os achados apontam amplo desconhecimento e percepções contraditórias sobre as IST, especialmente a sífilis; identificação de duas importantes trajetórias de cuidado às IST e o destaque para IT marcados por estigmas e discriminação nos serviços de saúde. Sugere-se a ampliação das ações de saúde para essa população reconhecendo suas necessidades e a construção de novas estratégias de prevenção e tratamento para IST, dialogadas com as TrMT, e garantia de autonomia, ética e sigilo na produção do cuidado.
Abstract The article aimed to analyze knowledge, perceptions, care practices and Therapeutic Itineraries (TI) for the diagnosis and treatment of Sexually Transmitted Diseases (STD), with emphasis on syphilis, among travesti and transgender women (TGW) in Salvador, Brazil. 05 focus groups and 06 semi-structured interviews with travesti/TGW were carried out with a total of 30 participants. The findings point to a wide lack of knowledge and contradictory perceptions about STD, especially syphilis; identification of two important trajectories of care for STD and the emphasis on TI marked by stigma and discrimination in health services. The expansion of health actions for this population is suggested, recognizing their needs and the construction of new prevention and treatment strategies for STD, in dialogue with the travesti/TGW, and guaranteeing autonomy, ethics and confidentiality in the production of care.
Resumen El artículo tuvo como objetivo analizar conocimientos, percepciones, prácticas de atención y Rutas Terapêuticas (RT) para el diagnóstico y tratamiento de las Enfermedades de Transmisión Sexual (ETS), con énfasis en la sífilis, entre las travestidas y mujeres trans (TrMT) en Salvador, Brasil. Se realizaron 05 grupos focales y 06 entrevistas semiestructuradas con 30 TrMT. Los hallazgos apuntan a una amplia falta de conocimiento y percepciones contradictorias sobre las ETS, especialmente la sífilis; identificación de dos importantes trayectorias de atención a las ETS y el énfasis en las RT marcadas por el estigma y la discriminación en los servicios de salud. Se sugiere ampliar las acciones de salud para esta población, reconociendo sus necesidades y la construcción de nuevas estrategias de prevención y tratamiento de las ETS, en diálogo con el TrMT, y garantizando la autonomía, ética y confidencialidad en la producción de cuidados.
Assuntos
Humanos , Masculino , Feminino , Travestilidade , Sífilis/terapia , Infecções Sexualmente Transmissíveis/terapia , Estigma Social , Pessoas Transgênero , Itinerário Terapêutico , Preconceito , Sistema Único de Saúde , Brasil , Sífilis/diagnóstico , Sífilis/prevenção & controle , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/prevenção & controle , Saúde Sexual , Sexismo , Serviços de Saúde para Pessoas Transgênero , Barreiras ao Acesso aos Cuidados de Saúde , Acessibilidade aos Serviços de SaúdeRESUMO
@#Introduction: Hyperhidrosis is a disorder of excessive and uncontrollable sweating beyond the body’s physiological needs. It can be categorised into primary or secondary hyperhidrosis based on its aetiology. Detailed history review including onset of symptoms, laterality of disease and family history are crucial which may suggest primary hyperhidrosis. Secondary causes such as neurological diseases, endocrine disorders, haematological malignancies, neuroendocrine tumours and drugs should be adequately examined and investigated prior to deciding on further management. The diagnosis of primary hyperhidrosis should only be made only after excluding secondary causes. Hyperhidrosis is a troublesome disorder that often results in social, professional, and psychological distress in sufferers. It remains, however, a treatment dilemma among some healthcare providers in this region. Methods: The medical records and clinical outcomes of 35 patients who underwent endoscopic thoracic sympathectomy for primary hyperhidrosis from 2008 to 2018 in Department of Cardiothoracic Surgery were reviewed. Results: The mean age of the patients was 27±10.1years, with male and female distribution of 18 and 17, respectively. Fifty-one percent of patients complained of palmar hyperhidrosis, while 35% of them had concurrent palmaraxillary and 14% had palmar-plantar-axillary hyperhidrosis. Our data showed that 77% (n=27) of patients were not investigated for secondary causes of hyperhidrosis, and they were not counselled on the non-surgical therapies. All patients underwent single-staged bilateral endoscopic thoracic sympathectomy. There was resolution of symptoms in all 35 (100%) patients with palmar hyperhidrosis, 13(76%) patients with axillary hyperhidrosis and only 2 (50%) patients with plantar hyperhidrosis. Postoperatively 34.3% (n=12) of patients reported compensatory hyperhidrosis. There were no other complications such as pneumothorax, chylothorax, haemothorax and Horner’s Syndrome. Conclusion: Clinical evaluation of hyperhidrosis in local context has not been well described, which may inadvertently result in the delay of appropriate management, causing significant social and emotional embarrassment and impair the quality of life of the subjects. Detailed clinical assessment and appropriate timely treatment, be it surgical or non-surgical therapies, are crucial in managing this uncommon yet distressing disease.
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The rearrangement of the gene encoding the transcription factor ETS-related gene (ERG) is thought to play a key role in the development of prostate cancer. However, the studies on the ERG mutations have been rarely reported in non-small cell lung carcinoma (NSCLC). Here, we reported genetic features regarding a case of a 68-year-old male patient who presented the primary synchronous multiple tumor lesions in the separated lungs. The patient was hospitalized due to the presence of tumor lesions at the right and left lungs revealed by a chest computerized tomography (CT) scan. After conducting lobectomies at the both lungs, the tumor nodules were all removed, and the histological analysis suggested adenocarcinoma at the both tumor lesions. The patient was diagnosed with synchronous multiple primary lung cancer (SMPLC) based on Martini-Melamed criteria and American College of Chest Physicians practice guidelines. An exome analysis of 315 genes in the two tumor lesions and a non-tumor lesion was conducted by using Illumina Nextseq500 platform from each tumor region to decipher a potential evolutional progress of SMPLC. Single or pair-end reads were first mapped to a human genome reference and filtered based on the mapping quality score. The read depth was ≥ 1 000× and the depth of coverage was 95%. The data revealed a discordant epidermal growth factor receptor (EGFR) from the separate lungs; additionally, a high frequency of point mutation on exon 9 H310P of the ERG gene was detected at the both sites of the tumor lesions. This case showed that a potential role of the molecular features analysis from each tumor lesion might contribute to the understanding of the evolutional development of SMPLC. This study suggests that the same environment may contribute certain gene(s) mutations in the same sites in the early stages of polyclonal tumor origins; meanwhile the extensive studies on these genes may help us understand the evolution and progress of tumor clones.
Assuntos
Idoso , Humanos , Masculino , Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares/genética , Neoplasias Primárias Múltiplas/genética , Mutação Puntual , Regulador Transcricional ERGRESUMO
INTRODUCCIÓN la información sobre anticoncepción es importante antes que se inicie la vida sexual. OBJETIVO determinar el nivel de conocimiento y uso de métodos anticonceptivos por adolescentes en medio rural. MÉTODOS estudio transversal analítico, se encuestó a adolescentes de 15-19 años de edad de ambos sexos, que asistían a un centro de salud rural, 70% sin vida sexual y 30% que ya habían iniciado su vida sexual. Se empleó una cuestionario auto-administrado que incluyó variables sociodemográficas, socioeducativas y de uso de métodos anticonceptivos. RESULTADOS el nivel de conocimientos fue medio en 38% y bajo en 31%. El condón fue el método anticonceptivo más utilizado (88%) y del que se tenía más conocimiento. Tiene un conocimiento bajo el 48,7%, el 30% y el 29,7% de adolescentes de 15, 16 y 17 años respectivamente. El conocimiento va aumentando con la edad; es "medio y alto" en 48,7% y 86,6% a los 15 y 19 años, respectivamente. Se observa que a mayor conocimiento, mayor uso de métodos anticonceptivos. CONCLUSIONES es necesaria mayor información sobre el uso adecuado de los métodos anticonceptivos en la escuela y en la familia a nivel rural antes del inicio de la vida sexual, para prevenir las enfermedades de transmisión sexual y los embarazos no deseados.
INTRODUCTION information on contraception is important before sexual life begins. OBJECTIVE to determine the level of knowledge and use of contraceptive methods by adolescents in rural areas. METHODS analytical cross-sectional study, surveyed adolescents aged 15-19 years of both sexes, who attended a rural health center, 70% without sexual life and 30% who had already started their sexual life. A self-administered questionnaire was used that included sociodemographic, socio-educational and use of contraceptive variables. RESULTS the level of knowledge was medium in 38% and low in 31%. The condom was the most widely used contraceptive method (88%) and the most widely known. 48,7%, 30%, and 29,7% of adolescents aged 15, 16, and 17, respectively, have low knowledge. Knowledge increases with age; it is "medium and high" in 48,7% and in 86,6% at 15 and 19 years, respectively. It is observed that the greater the knowledge, the more frequent use of contraceptive methods. CONCLUSIONS more information is needed on the proper use of contraceptive methods at school and in the family at the rural level before the start of sexual life, to prevent sexually transmitted diseases and unwanted pregnancies.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Conhecimentos, Atitudes e Prática em Saúde , Comportamento Contraceptivo/psicologia , Comportamento Sexual , Infecções Sexualmente Transmissíveis/prevenção & controle , Zona Rural , Estudos Transversais , Inquéritos e Questionários , Comportamento do Adolescente , Planejamento Familiar , Saúde Reprodutiva , MéxicoRESUMO
ETS-1 is a transcription factor that is a member of the E26 transformation-specific (ETS) family. Galanin receptor 2 (GalR2), a subtype of receptors of the neuropeptide galanin, has been shown to have an antidepressant-like effect after activation in rodents. Our previous study has shown that overexpression of ETS-1 increases the expression of GalR2 in PC12 phaeochromocytoma cells. However, whether ETS-1 has an antidepressant-like effect is still unclear. In this study, we found that chronic mild stress (CMS) decreased the expression of both ETS-1 and GalR2 in the ventral hippocampus of rats. Meanwhile, we demonstrated that overexpression of ETS-1 increased the expression of GalR2 in primary hippocampal neurons. Importantly, we showed that overexpression of ETS-1 in the ventral hippocampus counteracted the depression-like behaviors of CMS rats. Furthermore, we found that overexpression of ETS-1 increased the level of downstream phosphorylated extracellular signal-regulated protein kinases 1 and 2 (p-ERK1/2) of GalR2 in the ventral hippocampus of CMS rats. Taken together, our findings suggest that ETS-1 has an antidepressant-like effect in rats, which might be mediated by increasing the level of GalR2 and its downstream p-ERK1/2 in the ventral hippocampus.
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Objective@#Investigate the clinicopathological features for secretory carcinoma of breast (SCB).@*Methods@#The clinical data of 3 SCB cases were collected, immunohistochemical staining was performed by the streptavidin-peroxidase (SP) method to test the expression of the antibodies: ER, PR, HER-2, Ki-67, S100, CK5/6, p63, SMA, calponin, GCDFP-15, and EGFR. Fluorescence in situ hybridization (FISH) was used to detect the ETV6-NTRK3 gene fusion.@*Results@#ER was focal weakly positive in case 1 and case 2 (about 5%) , and negative in case 3. PR was focal weakly positive in case 1 (about 5%) and completely negative in case 2 and case 3. Three cases showed that HER-2, SMA, calponin, GCDFP-15 were negative, while S100, CK5/6, EGFR were diffuse strongly positive. The proliferation index was nearly 15% in case 1 and case 2, and 10% in case 3. p63 was negative in mostly tumor cells of case 1, and focal positive expression in the nucleus and cytoplasm. In case 2, p63 was completely negative. However, p63 was observed positive in the cytoplasm as well as some secretory material in case 3. ETV6-NTRK3 gene fusion detection by FISH was positive in all cases.@*Conclusions@#SCB is a rare low grade triple-negative breast cancer with the unique pathomorphologic features, while its recurrent t (12; 15) (p13; q25) translocation resulting in ETV6 -NTRK3 gene fusion. It has the indolent clinical behavior and good prognosis.
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EHF [ETS ( E26 transformation-specific) homologous factor/epithelium-specific ETS factor family member 3, ESE3] is a mem-ber of the ETS superfamily. EHF is mainly located in cell nuclei. It is a transcription factor that can directly bind to the promoter region of genes or form a transcription complex with other molecules to enhance or inhibit the transcription of downstream target genes. EHF is involved in multiple cell processes including cell proliferation, differentiation, apoptosis, and senescence. EHF plays a role as a tumor suppressor in cancers such as prostate, pancreatic, esophageal, and colon cancers. However, it acts as an oncogene in oral squa-mous cell carcinoma, gastric cancer, ovarian cancer, thyroid cancer, head and neck squamous cell carcinoma, and breast cancer. In the immune microenvironment, EHF can regulate the expression of some important immune factors and further affect the infiltration and function of the regulatory T cells, myeloid derived suppressor cells, and dendritic cells. In recent years, the pathophysiological function of EHF in tumors and their immune microenvironment has attracted increasing attention. This article reviews the research progress concerning the structure, function, and mechanism of EHF for the identification of new targets and molecular predictive markers for tumor therapy.
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Objective To investigate the effect of sodium arsenite (NaAsO2) on the expression of miRNA-21 (miR-21) mediated by transcription factor ETS-1 in human normal hepatocytes (L-02).Methods Dose-effect study:The L-02 cells were treated with different doses of NaAsO2 [0.0 (control),2.5,5.0,10.0,20.0,40.0 μmol/L] for 24 h.Time-effect study:L-02 cells were exposed to 0 (control) and 20 μmol/L NaAsO2 for 12,24,36 and 48 h (n =6).ETS-1 and miR-21 were treated with ETS-1 shRNA and miR-21 inhibitor,respectively.The cells treated with ETS-1 shRNA (100 nmol/L) were divided into 4 groups:①ETS-1 shRNA NC treatment alone (control group);②ETS-1 shRNA NC combined with NaAsO2 (20 μ,mol/L) treatment group;③ETS-1 shRNA treatment alone group;④Treatment with ETS-1 shRNA and NaAsO2 (20 μmol/L) group.The MiR-21 inhibitor (100 nmol/L) treated cells were also divided into 4 groups:① miR-21 inhibitor NC treatment (control group);② miR-21 inhibitor NC combined with NaAsO2 (20 μmol/L);③miR-21 inhibitor group;④miR-21 inhibitor combined with NaAsO2 (20 μ mol/L) treatment group.The expression of ETS-1 mRNA and miR-21 were detected by quantitative real-time PCR (qRT-PCR);the protein expression of ETS-1 was detected by Western blotting.Results Dose-effect study:The expression of ETS-1 mRNA in the groups of 0.0 (control),2.5,5.0,10.0,20.0 and 40.0 μmol/L was 1.008 ± 0.028,1.552 ± 0.029,1.697 ± 0.050,1.842 ± 0.077,2.233 ± 0.096 and 2.235 ± 0.092;miR-21 expression was 1.025 ± 0.094,1.552 ± 0.072,1.683 ± 0.066,1.915 ± 0.171,2.337 ± 0.195 and 2.592 ± 0.177;the expression of ETS-1 protein was 1.060 ± 0.045,1.267 ± 0.160,1.386 ± 0.087,1.723 ± 0.196,2.208 ± 0.122 and 2.284 ± 0.224,respectively,and the differences were statistically significant (F =47.797,8.959,65.748,all P < 0.05),the NaAsO2 dose groups were significantly higher than those of the control group (all P < 0.05),and there was a dose-effect relationship.Time-effect study:The expression of ETS-1 mRNA in L-02 cells was 1.253 ± 0.175,1.623 ± 0.220,1.771 ± 0.324 and 1.913 ± 0.251,respectively at 12,24,36 and 48 h;the expression of miR-21 was 1.502 ± 0.111,1.716 ± 0.113,1.979 ± 0.186 and 2.452 ± 0.304;the expression of ETS-1 protein was 1.196 ± 0.105,1.502 ± 0.076,1.651 ± 0.074 and 1.839 ± 0.139,respectively,there were significant differences between the groups (F =14.936,39.180,39.441,all P < 0.05).The expression of various time points of exposure to NaAsO2 was significantly higher than those in the control group (1.044 ± 0.115,1.044 ± 0.124,1.108 ± 0.088,1.053 ± 0.061;1.092 ± 0.061,1.096 ± 0.169,1.024 ± 0.111,1.057 ± 0.146;1.020 ± 0.017,1.049 ± 0.121,1.024 ± 0.089,1.031 ± 0.124,all P< 0.05),and there was a time-effect relationship.ETS-1 shRNA and miR-21 inhibitor treatment:compared with ETS-1 shRNA NC combined with NaAsO2 (20 μmol/L),ETS-1 shRNA and NaAsO2 (20 μmol/L) could significantly inhibit the expression of ETS-1 (0.912 ± 0.238 vs 1.641 ± 0.225,P < 0.05),and down-regulated the expression of miR-21 (1.313 ± 0.334 vs 2.363 ± 0.252,P < 0.05).There was no significant difference of ETS-1 mRNA expression between miR-21 inhibitor and NaAsO2 (20.μmol/L) group (1.580 ± 0.077 vs 1.576 ± 0.065,P > 0.05) compared with miR-21 inhibitor NC and NaAsO2 (20 μmol/L).Conclusions The expression of ETS-1 and miR-21 in L-02 cells is significantly higher than those in control.The high expression of ETS-1 mediates NaAsO2-induced miR-21 overexpression,which may be an important molecular mechanism of arsenic-induced expression dysregulation of human hepatic miRNAs and liver damage.
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Ets is one largest family of the transcription factors with complex structure and function of all family members. They play an important role in the regulation of many physiological and pathological processes through regulating embryonic develop-ment,cell growth,differentiation,cell apoptosis and interac-tions of cells under the regulation of MAP kinases(ERK,p38 and JNK),Ca2 + relevant signaling pathways and TGF-β path-ways. Notably,many Ets members involve in tumor genesis,in-vasion and metastasis,and these members may be markers of anticipating tumor genesis,development and prognosis. Here the physiological role of Ets family members and its relationship with human diseases are summarized,aiming to provide a theoretical basis for the study of the role of Ets family in human diseases.