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AIM: Platycodin D (PD), an oleanane kind of triterpenoid saponin, possesses various pharmacological activities. We aimed to investigate the effects of PD in pulmonary fibrosis. METHOD: MRC-5 cells were induced by transforming growth factor-beta1 (TGF-ß1) to simulate the pulmonary fibrosis in vitro. Cell viability was determined using a CCK-8 kit in the absence or presence of PD. Then, the expression of proliferation-related proteins was detected using immunofluorescence assay or western blot analysis. Moreover, the levels of inflammatory factors were examined. Subsequently, the ability of cell migration was evaluated using wound healing assay. Additionally, western blot analysis was employed to determine migration- and extracellular matrix accumulation (ECM)-related proteins expression. RESULTS: Results indicated that PD exposure significantly dose-dependently inhibited TGF-ß1 induced proliferation in MRC-5 cells. Additionally, the contents of inflammatory factors were notably inhibited with PD treatment. Furthermore, significant decrease in migration of TGF-ß1-stimulated MRC-5 cells was observed after PD intervention. Afterwards, PD remarkably suppressed the expression of alpha smooth muscle actin (α-SMA), collagen I (Col I), collagen III (Col III) and E-cadherin (E-cad). CONCLUSIONS: PD attenuated proliferation and ECM accumulation in TGF-ß1 induced lung fibroblasts, providing experimental support for the clinical application of PD in the treatment of pulmonary fibrosis (Fig. 6, Ref. 33).
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Fibrose Pulmonar , Actinas , Proliferação de Células , Matriz Extracelular , Fibroblastos , Pulmão , Saponinas/farmacologia , Fator de Crescimento Transformador beta1 , TriterpenosRESUMO
Objective: To identify the expression of apoptosis-associated genes of high- intensity focused ultrasound(HIFU) in xenograft with human pancreatic cancer. Methods: Mice implated with human pancreatic cancer cells (YY-1) were divided into HIFU group or control group. Tumor cell apoptosis was verified by TUNEL. The expression of the apoptosis-associated genes was analyzed by Agilent Human Gene Expression. Selected genes was validated by quantitative real-time PCR(RT-PCR)and Western blot. Results: The rate of tumor cell apoptosis in HIFU group was higher than that of control group at 7, 14 days after HIFU treatment ((63.6%±15.2%)vs (19.0%±2.4%), P<0.01)and ((41.4%±7.3%)vs(18.0%±2.4%), P<0.01). Gene expression profiling revealed a total of 69 differentially expressed genes in related to apoptosis pathway, among which 44 genes were up-regulated, and 25 genes down-regulated. The RT-PCR results of selected 4 genes were consistent with those of gene expression profiling. The results of Western blot analysis at 7, 14 days after HIFU treatment showed that the expressions level of Bax protein in HIFU group was greater that of in control group ((0.39±0.11)vs (0.20±0.09), P<0.05)and ((0.46±0.12)vs(0.24±0.10), P<0.05), while the expressions level of Bcl-2 protein in HIFU group was lower than that of in control group ((0.68±0.14)vs(1.56±0.21), P<0.05)and((0.51±0.16)vs(1.57±0.22), P<0.05). Conclusions: HIFU could induce apoptosis and results in dramatic changes in gene expression, indicating that multiple pathways are involved. Although intrinsic pathway might be predominantly involved in HIFU-elicited apoptosis, further research is needed to clarify the detailed mechanisms.
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Ablação por Ultrassom Focalizado de Alta Intensidade , Neoplasias Pancreáticas , Animais , Apoptose , Expressão Gênica , Perfilação da Expressão Gênica , Xenoenxertos , Humanos , Camundongos , Transplante HeterólogoRESUMO
OBJECTIVE: To explore the white light bronchoscopic signs and ultrasound features of respiratory mucosal protrusions and to investigate the practical application value of endobronchial ultrasound. METHODS: This study was a prospective observation. Endobronchial ultrasound was performed in 30 patients with respiratory mucosal protrusions, which were discovered by white light bronchoscopic examination in the Second Affiliated Hospital of Fujian Medical University on October 2013 to November 2014.The 43 lesions found in 30 patients were grouped into submucosal vascular lesions, mucosal thickening, and submucosal cysts based on the result of EBUS. Following white light bronchoscopy, signs such as respiratory mucosal protrusion location, shape, color and lustre, mucosal surface expansion and ultrasonic bronchoscopic image were recorded. We analyzed the results to explore the bronchoscopic signs and ultrasound features of different respiratory mucosal protrusions. RESULTS: Of the 43 respiratory mucosal protrusions by endobronchial ultrasound examination, 21 were submucosal vascular lesions, 19 showed mucosal thickening, and 3 were submucosal cysts. Morphologically, zoster protrusions, flat protrusions and semicircle protrusions were found in the submucosal vessel group, mucosal thickening group and cyst group. One nodular protrusion, 1 surface capillary expansion, and 2 mucosal surface pulsations were found in cases with submucosal vascular lesions. CONCLUSIONS: Submucosal vascular lesions were common causes of respiratory mucosal protrusions, for which biopsy should be cautious. White light bronchoscopy has limited value for diagnosing respiratory mucosal protrusions, while endobronchial ultrasound could be an important diagnostic tool for these lesions.
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Broncoscopia/métodos , Mucosa Respiratória/diagnóstico por imagem , Mucosa Respiratória/patologia , Ultrassonografia , Biópsia , Humanos , Estudos ProspectivosRESUMO
OBJECTIVE: To observe the activity of histone deacetylase and the mRNA expression level of HDAC1 and HDAC2 in human bone marrow mononuclear cells, which induced by hydroquinone and exposed to hydroquinone plus Trichostatin as a histone deacetylase inhibitor for 10 hours respectively. METHODS: Collect the bone marrow mononuclear cells suspension,divided into control group,HQ group (3 h, 6 h, 12 h, 24 h) , HQ+TSA 10 h group and HQ 10 h group. Extract the nuclear proteins and RNA, test the activity of histone deacetylase with the colorimetric HDAC assay kit and detect the mRNA expression level of HDAC1 and HDAC2 by real-time Polymerase Chain Reaction (PCR). RESULTS: The HDAC activity of HQ3 h group, HQ6 h group and HQ12 h group were 1.31 times, 1.53 times and 1.148 times than that of control group respectively. And the difference was statistically significant (P<0.05). Except the HQ24 h group (P>0.05) , the HDAC1 mRNA expression of HQ3 h group, HQ6 h group and HQ12 h group were 1.173 times, 1.901 times and 2.348 times than that of control group respectively. And the difference was statistically significant (P<0.05). The HDAC2 mRNA expression of HQ6 h group and HQ12 h group were 1.426 times and 1.766 times than that of the control group respectively. And the difference was statistically significant (P<0.05). No significant difference was observed between HQ3 h group, HQ24 h group and control group (P>0.05). The cells were treated by hydroquinone plus TSA for 10 hours. The HDAC activity of HQ+TSA 10h group was reduced by 25.6% than that of HQ 10 h group (P<0.05) and rised 13.0% compared to the control group (P<0.05). And the difference was statistically significant between groups (P<0.05) .The cells were treated by hydroquinone plus TSA for 10 hours. The HDAC1 mRNA expression of the HQ+TSA 10h group is reduced by 26.9% than that of HQ10h group. The HDAC2 mRNA expression is reduced by 19.3% compared to the HQ 10h group.And the difference was statistically significant between groups (P<0.05). The HDAC1 and HDAC2 mRNA expression is obviously higher than the control group, the difference was statistically significant (P<0.05). CONCLUSION: Treatment of hydroquinone, the histone deacetylase activity and the mRNA expression of HDAC1 and HDAC2 were increased in a certain time range. The histone deacetylase inhibitor (TSA) can reduce the histone deacetylase activity and the mRNA expression level of HDAC1 and HDAC2 in the bone marrow mononuclear cell induce by hydroquinone.It can be confirmed that hematopoietic damage induced by the benzene metabolites is related to the histone acetylation modification level.
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Células da Medula Óssea , Medula Óssea , Histona Desacetilase 1 , Histona Desacetilase 2 , Inibidores de Histona Desacetilases , Histona Desacetilases , Humanos , Hidroquinonas , Ácidos Hidroxâmicos , RNA MensageiroRESUMO
BACKGROUND: The aim of this study is to determine whether PAQR3, a protein specifically localized in the Golgi apparatus, is associated with tumor progression, metastasis and survival of human patients with gastric cancer. PATIENTS AND METHODS: PAQR3 expression status was investigated in a large panel of gastric cancer (n = 300) and their corresponding para-cancerous histological normal tissues (PCHNT) at both mRNA and protein levels. The correlation of PAQR3 expression levels with clinical features such as metastasis and prognosis was analyzed. The effect of PAQR3 on the growth and migration of gastric cancer cells was also determined. RESULTS: PAQR3 was frequently down-regulated in gastric cancer samples compared with PCHNT at both mRNA and protein levels (both P < 0.0001). The expression level of PAQR3 was negatively correlated with Helicobacter pylori infection (P < 0.0001), tumor size (P < 0.0001), tumor stage (P < 0.0001), venous and lymphatic invasion (P < 0.0001), distant and nodal metastasis (P < 0.0001), and patient survival (P < 0.0001). Down-regulation of PAQR3 was highly correlated with increased epithelial-mesenchymal transition (EMT) in gastric cancer samples. In addition, PAQR3 overexpression was able to negatively modulate cell proliferation, migration and EMT of gastric cancer cells. CONCLUSION: PAQR3 is markedly down-regulated in human gastric cancers. PAQR3 expression level is closely associated with the progression and metastasis of gastric cancers. PAQR3 is also a new genetic signature that can predict the prognosis of the patients with gastric cancer.
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Complexo de Golgi/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Metástase Neoplásica , Neoplasias Gástricas/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/metabolismoRESUMO
AIM: Digital rectal examination (DRE) is an essential skill which all newly qualified doctors should have. There is evidence in the literature that junior doctors lack this important examination technique. The aim of our study was to determine, with the help of a questionnaire, the abilities of foundation year 1 (FY1) doctors to perform DRE. METHOD: A questionnaire was developed and sent to newly qualified FY1 doctors qualified in two universities (Nottingham and Sheffield) within the first 4 weeks of starting as a FY1 doctor. RESULTS: Ninety (75%) out of 120 questionnaires were completed. Most FY1 doctors had very little experience in performing DRE on a patient, and 68 (76%) had performed less than 10 procedures prior to qualification. Very few of these doctors had their clinical findings on DRE checked by a senior doctor (n = 7, 8%). Comparing DRE with other forms of examination, newly qualified doctors were most confident at groin hernia examination followed by testicular examination. They were least confident with vaginal examination and DRE (ANOVA P = 0.0082). CONCLUSION: Digital rectal examination is frequently performed by the most inexperienced doctor and may not be verified by a more senior colleague. More training and supervision of junior doctors are required both prior to qualification and during the early stages of their medical career.
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Competência Clínica/estatística & dados numéricos , Exame Retal Digital/estatística & dados numéricos , Médicos/estatística & dados numéricos , Doenças Retais/diagnóstico , Análise de Variância , Educação de Pós-Graduação em Medicina/normas , Educação de Graduação em Medicina/normas , Inglaterra , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: This study aims to uncover the function of long non-coding RNA (lncRNA) AWPPH in the progression of non-small cell lung cancer (NSCLC) and the potential mechanism. PATIENTS AND METHODS: AWPPH and microRNA (miRNA-204) levels in NSCLC tissues and adjacent normal tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Kaplan-Meier curves were introduced for assessing overall survival in NSCLC patients expressing high or low level of AWPPH. Potential correlation between expression levels of AWPPH and miRNA-204 in NSCLC tissues was analyzed by Spearman correlation test. Through Dual-Luciferase reporter gene assay, the interaction among AWPPH, miRNA-204, and CDK6 was identified. Potential impacts of AWPPH/miRNA-204/CDK6 regulatory loop on mediating proliferative, migratory, and invasive capacities of A549 cells were evaluated through cell counting kit-8 (CCK-8) and transwell assay. RESULTS: Upregulated AWPPH and downregulated miRNA-204 were determined in NSCLC tissues. AWPPH level was negatively correlated to overall survival in NSCLC patients and miRNA-204 level in NSCLC tissues. Silence of AWPPH attenuated proliferative, migratory, and invasive capacities in A549 cells. MiRNA-204 was the downstream gene of AWPPH. Knockdown of miRNA-204 reversed the decreased viability, migratory, and invasive rates in A549 cells with AWPPH knockdown. In addition, CDK6 was the target gene of miRNA-204. Overexpression of miRNA-204 downregulated CDK6 level in A549 cells. The attenuated proliferative, migratory, and invasive capacities in A549 cells overexpressing miRNA-204 were reversed after CDK6 overexpression. CONCLUSIONS: LncRNA AWPPH serves as the miRNA-204 sponge to upregulate CDK6 level, thus aggravating the progression of NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Regulação para Cima , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Movimento Celular , Proliferação de Células , Células Cultivadas , Quinase 6 Dependente de Ciclina/genética , Humanos , Neoplasias Pulmonares/diagnóstico , MicroRNAs/genética , RNA Longo não Codificante/genéticaRESUMO
Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA OR3A4 promotes metastasis of ovarian cancer via inhibiting KLF6, by F.-F. Guo, M.-M. Jiang, L.-L. Hong, B. Qiao, X.-M. Lin, W.-Y. Xu, X.-Q. Fu, published in Eur Rev Med Pharmacol Sci 2019; 23 (6): 2360-2365-DOI: 10.26355/eurrev_201903_17380-PMID: 30964160" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17380.
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OBJECTIVE: Recently, long noncoding RNAs (lncRNAs) have attracted much attention for their roles in tumor progression. The aim of this study was to investigate the exact role of lncRNA OR3A4 in the development of ovarian cancer (OC), and to explore the possible underlying mechanism. PATIENTS AND METHODS: OR3A4 expression in OC tissue samples was detected by Real-time quantitative polymerase chain reaction (qRT-PCR). Moreover, wound healing assay and transwell assay were performed to evaluate the effect of OR3A4 on the metastasis of OC. Furthermore, the underlying mechanism was explored by RT-qPCR and Western blot assay. RESULTS: The expression level of OR3A4 in OC samples was significantly higher than that of adjacent tissues. Moreover, cell migration and invasion were significantly repressed after OR3A4 knockdown in vitro. Moreover, the mRNA and protein expressions of kruppel-like factor 6 (KLF6) were remarkably upregulated after knockdown of OR3A4. Furthermore, the expression level of KLF6 was negatively correlated with the expression of OR3A4 in OC tissues. CONCLUSIONS: Our results showed that OR3A4 could enhance OC cell metastasis and invasion via suppressing KLF6. Moreover, OR3A4 might be a potential therapeutic target for OC.
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To study the regulation of major histocompatibility complex class II antigen by central nervous system cells, the expression of one of these antigens, human leukocyte antigenDR (HLADR) in three human glioblastoma cell lines (HTB14, 16 and 17) and a neuroblastoma cell line (HTB11) was determined. Interferon-gamma (IFN gamma) induced HTB16 and HTB17 cells to express HLADR, and enhanced the antigen expression in HTB14 cells, but it failed to induce HLADR expression in HTB11 cells. Tumor necrosis factor-alpha amplified and accelerated the expression of HLADR induced by IFN gamma in HTB16 cells. Interleukin-1 beta, prostaglandin E2 and transforming growth factor-beta suppressed IFN gamma-induced HLADR expression in HTB16 cells. Several other substances tested did not affect HLADR expression or IFN gamma-induced HLADR. These findings confirm that IFN gamma plays a role in the regulation of HLADR expression in cells derived from the brain and that some other cytokines modify IFN gamma-HLADR interactions.
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Citocinas/farmacologia , Glioma/imunologia , Antígenos HLA-DR/imunologia , Interferon gama/farmacologia , Dinoprostona/farmacologia , Imunofluorescência , Glioma/patologia , Humanos , Interleucina-1/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
A distinct subpopulation of tissue-associated pulmonary macrophages (TAPM) displayed tumoricidal activity towards syngeneic and xenogeneic targets following in vitro incubation with N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP). This subpopulation, as well as, the predominant population of freely lavagable alveolar macrophages destroyed allogeneic targets following a similar incubation with either 6-0-stearoyl MDP (S-MDP) or recombinant interferon-gamma (IFN-gamma). IFN-gamma-induced in vivo tumoricidal activation of both populations of pulmonary macrophage was most effective when delivered either intravenously or via osmotic minipump infusion and least effective when administered by direct intratracheal instillation. The separate populations also displayed in vivo activation in response to liposome-encapsulated i.v. administered S-MDP. Under comparable conditions, IFN-alpha was not nearly as effective. Metabolic activation of TAPM, assessed by the release of increased levels of superoxide free radicals during phagocytosis, occurred following 24 hr exposure to S-MDP or lipopolysaccharide. Incorporation of these agents into multilamellar vesicle liposomes further augmented the release of superoxide observed at 24 hrs. Our results collectively demonstrated that a subpopulation of lung macrophage, a tissue-associated pulmonary macrophage, may be activated to a tumoricidal state and to release pronounced levels of oxygen free radicals following either in vitro or in situ treatment with several biological response modifiers.
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Fatores Imunológicos/imunologia , Ativação de Macrófagos/imunologia , Macrófagos Alveolares/imunologia , Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Acetilmuramil-Alanil-Isoglutamina/imunologia , Adjuvantes Imunológicos , Animais , Citotoxicidade Imunológica/imunologia , Vias de Administração de Medicamentos , Feminino , Fatores Imunológicos/administração & dosagem , Interferon gama/imunologia , Macrófagos Alveolares/classificação , Masculino , Camundongos , Camundongos Endogâmicos C3H , Ratos , Ratos Endogâmicos F344 , Proteínas Recombinantes , Superóxidos/metabolismo , Células Tumorais CultivadasRESUMO
From 1978 to 1992,the clinical data of 59 patients with intramuscular hemangioma in oral and maxillofacial regions were reviewed and analysed.The average age and the duration were 23 years old and eight years respectively.All patients were treated surgically,53 cases (89.83%)were completely resected and those of other 6 cases(10.1%) partially resected without any complications,Follow-up for 11 months to 12 years showed that 2 cases relapsed,and thus the cure rate was 96.6%(57/59),The author affirmed the significance of surgical operation in treatment and put forward the view of classification of hemangioma the vascular deformities.