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1.
Environ Pollut ; 343: 123287, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38171426

RESUMO

This study reported a new strategy for enhanced Pb2+ and Cu2+ sequestration by Artemia cyst shell (shell) supported nano-Mg from aqueous solutions and the carbonated exhausted-adsorbents sequenced potential application in photo-catalyst, which obtained two expected results. One is that the immobilization of nano-Mg onto Artemia cyst shell (shell-Mg) can greatly strengthen the adsorption effect of the neat cyst shell on Pb2+ and Cu2+. The adsorption capacities of shell-Mg for both metal ions reached to 622.01 and 313.91 mg/g, which was 10-15 and 30-50 times that of the neat shell respectively. And shell-Mg has strong selectivity, which was approximately 2-4 times that of shell. The shell-Mg can be used to retrieve Pb2+ and Cu2+ from aqueous solutions efficiently. Another is that the carbonated exhausted-adsorbents (C-shell-Mg-Pb and C-shell-Mg-Cu) showed their potential photocatalytic degradation effects on congo red under pH = 4 condition, the decolorization rate reached to 61.19% and 80.39% respectively. Reuse of exhausted adsorbents can avoid the secondary pollution caused by the regeneration, extend the utilization value of exhausted adsorbents, and provide a new viewpoint for the reuse of spent bio-nanomaterial adsorbents.


Assuntos
Nanoestruturas , Poluentes Químicos da Água , Animais , Artemia , Chumbo , Poluentes Químicos da Água/análise , Vermelho Congo , Adsorção , Concentração de Íons de Hidrogênio , Cinética
2.
Front Endocrinol (Lausanne) ; 14: 1237260, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711905

RESUMO

Objective: This study aims to evaluate the effect of acupuncture on the emotion domain and metabolic parameters of Chinese women with polycystic ovarian syndrome (PCOS) by secondary analysis of a randomized clinical trial, conducted from 6 July 2012 to 7 October 2015. Method: In this study, we investigated the effects of acupuncture (458 patients) and sham acupuncture (468 patients) on metabolic parameters, serum ions, and all quality-of-life scale scores related to PCOS. The quality of life of patients was evaluated using five relevant scales, operated by the research assistant, namely, PCOSQ, SF-36, and ChiQOL, as well as Zung-SAS and Zung-SDS. Metabolic parameters and serum ions were measured. Results: A reduction in acne score, AN, Hcy, and LDL-C, and an increase in the level of lipoprotein α, Apo A1, and Apo A1/Apo B were observed in the acupuncture group after 4 months' intervention after adjusting clomiphene and reproductive outcome (p< 0.05). An increase in SF-36 total scores, RP and RE scores, ChiQOL total scores, and emotion domain scores was observed in the acupuncture group after 4 months' intervention, while PF and HT scores were decreased (adjusted p< 0.05). Those same changes were observed in sham acupuncture. Meanwhile, the serum levels of Ca, K, and Cl were elevated in the acupuncture group after the interventions (adjusted p< 0.005). There were no significant differences in HOMA-IR, MetS, FPG, FINS, HDL-C, TG, Apo B, and level of serum P, Mg, and Na. Also, no changes in BP, GH, VT, SF, physical form domain, and spirit domain were observed after treatment. Conclusion: Acupuncture can improve not only the emotional changes in SF-36 scores and ChiQOL scores, but also lipid metabolism, implying that it may have a correlation between emotional change and lipid metabolism. Furthermore, acupuncture can also regulate the changes of serum Ca, K, and Cl. Clinical trial registration: ClinicalTrials.gov, identifier NCT01573858.


Assuntos
Terapia por Acupuntura , Síndrome do Ovário Policístico , Humanos , Feminino , Apolipoproteína A-I , Síndrome do Ovário Policístico/terapia , Qualidade de Vida , Apolipoproteínas B , Emoções
4.
Int J Biol Sci ; 19(3): 994-1006, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36778116

RESUMO

Cardiac fibrosis is a common pathological cardiac remodeling in a variety of heart diseases, characterized by the activation of cardiac fibroblasts. Our previous study uncovered that promyelocytic leukemia protein (PML)-associated SUMO processes is a new regulator of cardiac hypertrophy and heart failure. The present study aimed to explore the role of PML in cardiac fibroblasts activation. Here we found that PML is significantly upregulated in cardiac fibrotic tissue and activated cardiac fibroblasts treated with transforming growth factor-ß1 (TGF-ß1). Gain- and loss-of-function experiments showed that PML impacted cardiac fibroblasts activation after TGF-ß1 treatment. Further study demonstrated that p53 acts as the transcriptional regulator of PML, and participated in TGF-ß1 induced the increase of PML expression and PML nuclear bodies (PML-NBs) formation. Knockdown or pharmacological inhibition of p53 produced inhibitory effects on the activation of cardiac fibroblasts. We further found that PML also may stabilize p53 through inhibiting its ubiquitin-mediated proteasomal degradation in cardiac fibroblasts. Collectively, this study suggests that PML crosstalk with p53 regulates cardiac fibroblasts activation, which provides a novel therapeutic strategy for cardiac fibrosis.


Assuntos
Proteína da Leucemia Promielocítica , Fator de Crescimento Transformador beta1 , Proteína Supressora de Tumor p53 , Humanos , Fibroblastos/metabolismo , Fibrose , Coração , Fator de Crescimento Transformador beta1/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteína da Leucemia Promielocítica/metabolismo
5.
Acta Trop ; 238: 106772, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36423700

RESUMO

The parasitic lice of Hominidae are a class of blood-sucking insects, having a large fragment expansion region in ribosome 18S V4 region. In this study, the value of the E23-5-E23-6 stem-loop structure in the insertion region for molecular identification of lice were explored through motif analysis and secondary structure construction. Five pubic lice samples from China were morphologically identified, and primers for the rRNA 18S V4 region were designed for molecular identification. The V4 sequence of the parasitic lice of Hominidae was retrieved from GenBank for sequence analysis. The five samples were identified as pubic lice based on V4 region, which were of the same specie but geographically different from Australian strains in Genbank, with the identity of 99.06-99.46%. Compared with the human lice, both the chimpanzee lice and pubic lice had large indel fragments in the V4 region. Comparison results showed that Muscle and MAFFT had better alignment and phylogeny results than Clustal. The large expansion region, comprising E23-5 and E23-6, was located between E23-4 and E23-7. The V4 secondary structure showed that the stem-loop structures of the lice parasitizing on pubic area, human, and chimpanzee were different in the E23-5 and E23-6, which could effectively distinguish the three parasitic lice and divide the human lice into five genotypes. This is suitable not only for the identification of three lice species in higher taxonomic ranks but also for genotype identification of human lice in lower taxonomic ranks. The difference between the stem-loop structure is more intuitive than that between the primary sequences.


Assuntos
Anoplura , Hominidae , Animais , Humanos , RNA Ribossômico 18S/genética , Sequência de Bases , Hominidae/genética , Pan troglodytes/genética , Austrália , Filogenia
6.
Nucleic Acids Res ; 51(D1): D232-D239, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36373614

RESUMO

Noncoding RNAs (ncRNAs) play key regulatory roles in biological processes by interacting with other biomolecules. With the development of high-throughput sequencing and experimental technologies, extensive ncRNA interactions have been accumulated. Therefore, we updated the NPInter database to a fifth version to document these interactions. ncRNA interaction entries were doubled from 1 100 618 to 2 596 695 by manual literature mining and high-throughput data processing. We integrated global RNA-DNA interactions from iMARGI, ChAR-seq and GRID-seq, greatly expanding the number of RNA-DNA interactions (from 888 915 to 8 329 382). In addition, we collected different types of RNA interaction between SARS-CoV-2 virus and its host from recently published studies. Long noncoding RNA (lncRNA) expression specificity in different cell types from tumor single cell RNA-seq (scRNA-seq) data were also integrated to provide a cell-type level view of interactions. A new module named RBP was built to display the interactions of RNA-binding proteins with annotations of localization, binding domains and functions. In conclusion, NPInter v5.0 (http://bigdata.ibp.ac.cn/npinter5/) provides informative and valuable ncRNA interactions for biological researchers.


Assuntos
Bases de Dados de Ácidos Nucleicos , RNA não Traduzido , Humanos , COVID-19/genética , DNA/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo
7.
Oxid Med Cell Longev ; 2022: 3082969, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275892

RESUMO

Aim: Thin endometrium remains a severe clinical challenge with no effective therapy to date. We aimed at exploring the role and molecular mechanism of human umbilical cord mesenchymal stem cell- (hucMSC-) derived exosomes (hucMSC-Ex) in repairing hypoxic injury of endometrial epithelial cells (EECs). Methods: Exosomes were harvested from the conditioned medium of hucMSC and characterized using western blot, transmission electron microscopy (TEM), flow cytometry, and nanoparticle tracking analysis (NTA). EECs were subjected to hypoxic conditions before cocultured with hucMSC-Ex. Cell viability, apoptosis, and migration were determined with CCK-8, flow cytometry, and wound healing assay, respectively. Apoptosis/EMT-related proteins were detected by western blot. The miRNA profiling was determined by RNA sequencing. The expression of miR-663a and CDKN2A was measured by qRT-PCR. MiR-663a in EECs was overexpressed by transfecting with miR-663a mimics. Results: Mesenchymal stem cells (MSCs) markers CD73, CD90, and CD106 were positively expressed in hucMSCs. Exosome isolated from hucMSC expressed CD63 and TSG101, and were 100-150 nm in diameter. HucMSC-Ex promoted cell proliferation inhibited by hypoxia. And hucMSC-Ex also inhibited hypoxia-induced apoptosis, migration, and EMT of EECs by upregulating the expression of Bcl-2 and E-cadherin and downregulating Bax and N-cadherin levels. Further, bioinformatics research found that hucMSC-Ex coculture can significantly upregulate the expression of miR-663a and decrease the expression of CDKN2A in hypoxia-induced EECs. Furthermore, miR-663a overexpression inhibited CDKN2A expression and increased the expression of Bcl-2 and E-cadherin in hypoxia-induced EECs. Conclusions: HucMSC-Ex promoted cell proliferation, inhibited cell apoptosis, migration, and EMT in hypoxia-induced EECs, thereby alleviating hypoxia-induced EECs injury, which may be related to its regulation of miR-663a/CDKN2A expression. Our study indicated that hucMSC-Ex might benefit for repairing thin endometrium.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Feminino , Humanos , Exossomos/metabolismo , Meios de Cultivo Condicionados/farmacologia , Sincalida/metabolismo , Sincalida/farmacologia , Proteína X Associada a bcl-2/metabolismo , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical , Endométrio/metabolismo , Células Epiteliais/metabolismo , Hipóxia/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Caderinas/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina
8.
BMC Womens Health ; 22(1): 76, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35300659

RESUMO

BACKGROUND: Primary ovarian carcinoid is a very rare ovarian low-grade neuroendocrine tumor, accounting for about 0.1% of all ovarian neoplasms. CASE PRESENTATION: We reported a case of primary ovarian carcinoid arising from a mature cystic teratoma in a 50-year-old woman. Intraoperative frozen section of left ovarian mass was assessed and a malignant epithelial tumor was considered. Morphologically, the main tumor was composed of cells forming trabeculae, and mature cystic teratoma was observed adjacent to the main part. Immunohistochemistry revealed that the trabecular cells were diffuse positive for pan Cytokeratin, CD56 and synaptophysin with low Ki-67 index (about 1%). CONCLUSIONS: Careful morphological observation combined with appropriate accessory examination are essential for the diagnosis of primary ovarian carcinoid arising from mature cystic teratoma. In addition, the classification criteria of the primary ovarian neuroendocrine tumor are discussed.


Assuntos
Tumor Carcinoide , Tumores Neuroendócrinos , Neoplasias Ovarianas , Teratoma , Tumor Carcinoide/diagnóstico por imagem , Tumor Carcinoide/cirurgia , Feminino , Humanos , Neoplasias Intestinais , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Pancreáticas , Neoplasias Gástricas , Teratoma/diagnóstico , Teratoma/patologia , Teratoma/cirurgia
10.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298979

RESUMO

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the ß2-integrin, CD18 (CD18hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs passing through endothelial pores. In contrast, injured CD18hypo mice showed significantly less venule engorgement and markedly reduced platelet and RBC extravasation; mast cell degranulation was also reduced compared to WT mice. Corneal abrasion in mast cell-deficient (KitW-sh/W-sh) mice showed less venule engorgement, delayed PMN extravasation, reduced platelet and RBC extravasation and delayed wound healing compared to WT mice. Finally, antibody-induced depletion of circulating PMNs prior to corneal abrasion reduced mast cell degranulation, venule engorgement, and extravasation of PMNs, platelets, and RBCs. In summary, in the injured cornea, platelet and RBC extravasation depends on CD18, PMNs, and mast cell degranulation.


Assuntos
Plaquetas/fisiologia , Antígenos CD18/fisiologia , Degranulação Celular , Córnea/irrigação sanguínea , Eritrócitos/fisiologia , Hiperemia/fisiopatologia , Mastócitos/fisiologia , Neutrófilos/fisiologia , Migração Transendotelial e Transepitelial/fisiologia , Vasculite/imunologia , Vênulas/metabolismo , Animais , Antígenos CD18/deficiência , Movimento Celular , Quimiotaxia de Leucócito , Lesões da Córnea/metabolismo , Lesões da Córnea/patologia , Epitélio Corneano/fisiologia , Feminino , Hiperemia/sangue , Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microcirculação , Microscopia Eletrônica , Modelos Animais , Fagocitose , Regeneração/fisiologia , Vasculite/sangue , Vênulas/patologia , Cicatrização/fisiologia
11.
Sci Rep ; 11(1): 6084, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727635

RESUMO

Oestradiol, an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization-embryo transfer (IVF-ET) cycles. A supraphysiologic E2 level is inevitable during controlled ovarian hyper-stimulation (COH), and its effect on the outcome of IVF-ET is controversial. The aim of this retrospective study is to evaluate the association between elevated serum oestradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and neonatal birthweight after IVF-ET cycles. The data of 3659 infertile patients with fresh IVF-ET cycles were analysed retrospectively between August 2009 and February 2017 in First Hospital of Zhengzhou University. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 230), group 2 (serum E2 levels between 1001 and 2000 pg/mL, n = 524), group 3 (serum E2 levels between 2001 and 3000 pg/mL, n = 783), group 4 (serum E2 levels between 3001 and 4000 pg/mL, n = 721), group 5 (serum E2 levels between 4001 and 5000 pg/mL, n = 548 ), and group 6 (serum E2 levels > 5000 pg/mL, n = 852). Univariate linear regression was used to evaluate the independent correlation between each factor and outcome index. Multiple logistic regression was used to adjust for confounding factors. The LBW rates were as follows: 3.0% (group 1), 2.9% (group 2), 1.9% (group 3), 2.9% (group 4), 2.9% (group 5), and 2.0% (group 6) (P = 0.629), respectively. There were no statistically significant differences in the incidences of neonatal LBW among the six groups. We did not detect an association between peak serum E2 level during ovarian stimulation and neonatal birthweight after IVF-ET. The results of this retrospective cohort study showed that serum E2 peak levels during ovarian stimulation were not associated with birth weight during IVF cycles. In addition, no association was found between higher E2 levels and increased LBW risk. Our observations suggest that the hyper-oestrogenic milieu during COS does not seem to have adverse effects on the birthweight of offspring after IVF. Although this study provides some reference, the obstetric-related factors were not included due to historical reasons. The impact of the high estrogen environment during COS on the birth weight of IVF offspring still needs future research.


Assuntos
Peso ao Nascer , Gonadotropina Coriônica/administração & dosagem , Transferência Embrionária , Estradiol/sangue , Fertilização in vitro , Nascido Vivo , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez
12.
Arq Bras Oftalmol ; 84(3): 258-266, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33567029

RESUMO

PURPOSE: The present study aimed to investigate the inhibitory effect of fluorofenidone against transforming growth factor ß2-induced proliferation and epithelial-mesenchymal transition in human lens epithelial cell line FHL 124 and its potential mechanism. METHODS: We evaluated the effect of fluorofenidone on proliferation and epithelial-mesenchymal transition of human lens epithelial cell line FHL 124 in vitro. After treatment with 0, 0.1, 0.2, 0.4, 0.6, and 1.0 mg/mL fluorofenidone, cell proliferation was measured via MTT assay. Cell viability was evaluated by lactate dehydrogenase activity from damaged cells. FHL 124 cells were treated with different transforming growth factor ß2 concentrations (0-10 ng/mL) for 24 h and the expression of CTGF, α-SMA, COL-I, E-cadherin, and Fn were detected via quantitative polymerase chain reaction and Western blot analysis. After treatment with 0, 0.2, and 0.4 mg/ml fluorofenidone, the expressions of transforming growth factor ß2 and SMADs were detected with real-time polymerase chain reaction and Western blot analysis. Expressions of CTGF, α-SMA, COL-I, and Fn were analyzed by immunocytochemistry assay. RESULTS: The viability of FHL 124 cells was not inhibited when the fluorofenidone concentration was ≤0.4 mg/mL after the 24h treatment. Cytotoxicity was not detected via lactate dehydrogenase assay after the 24h and 36h treatment with 0.2 and 0.4 mg/mL fluorofenidone. Transforming growth factor ß2 increased mRNA and protein expression of CTGF, α-SMA, COL-I, and Fn. However, fluorofenidone significantly suppressed expression of SMADs, CTGF, α-SMA, COL-I, and Fn in the absence or presence of transforming growth factor ß2 stimulation. CONCLUSIONS: Fluorofenidone significantly inhibited expression of SMADs, CTGF, α-SMA, COL-I, and Fn in FHL 124 cells. Due to noncompliance in infants, fluorofenidone may become a novel therapeutic drug against posterior capsular opacification in infants.


Assuntos
Opacificação da Cápsula , Cristalino , Células Epiteliais , Transição Epitelial-Mesenquimal , Humanos , Piridonas
13.
Front Nutr ; 8: 779912, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35174195

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases worldwide. Dietary vitamin C intake might play an important role in reducing the risk of NAFLD. This study assesses the relationship between dietary vitamin C intake and diagnostic biomarkers of NAFLD. METHODS: The data from the 2009 China Health and Nutrition Survey (CHNS), nine provinces across four diverse regions (Northeast, East Coast, Central, and West) were included in the study. The dietary vitamin C intake of participants was calculated based on 3-day 24-h diet questionnaires at the individual level. The associations of dietary vitamin C intake and the biochemical indicators of liver function and glucose/lipid metabolism were determined. RESULTS: A total of 8,307 participants were included in the final analysis. The mean dietary vitamin C intake for the overall, male and female subjects was 79.8 ± 58.6, 81.6 ± 55.3, and 78.2 ± 61.2 mg/day, respectively. The prevalence of inadequate dietary vitamin C intake for the overall, male and female subjects was 24.4, 26.5, and 22.6%, respectively. Intake of vitamin C was associated with both lower concentrations of plasma ferritin and hemoglobin A1c (HbA1c). Higher dietary vitamin C intake was associated with higher albumin, even further adjusted for body mass index (BMI), residence, and smoking status. No improvement in lipid metabolism was found. CONCLUSION: This study demonstrated that higher dietary vitamin C intake is a benefit for improving glucose metabolism and liver function in which reducing ferritin, a biomarker of iron accumulation, may be involved.

14.
Eur J Radiol ; 110: 97-104, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30599880

RESUMO

PURPOSE: To investigate the factors that could cause a misdiagnosis in virtual touch tissue imaging and quantification (VTIQ) when differentiating benign and malignant breast lesions, and to analyze the imaging characteristics of those lesions with incorrect findings. METHODS: The conventional ultrasound (CUS) features and the VTIQ parameters of 153 benign lesions and 99 malignant lesions were retrospectively analyzed and compared with histopathological and/or core-needle biopsy (CNB)-proven results. Independent variables that led to inaccurate VTIQ results were selected by binary logistic regression analysis. RESULTS: The maximum shear wave speed (SWS-max), the mean SWS (SWS-mean), the minimum SWS (SWS-min), the lesion-to-fat SWS ratio (SWS-L/F), and the lesion-to-gland SWS ratio (SWS-L/G) in malignant lesions were significantly higher than those in benign lesions (all P < 0.001). The false-positive rate (FPR) of benign lesions and the false-negative rate (FNR) of malignant lesions were 9.8% and 19.2%, respectively, using an SWS-max cut-off value of 4.46 m/s. Diameter, depth, and posterior acoustic features were independent variables related to false-positive VTIQ findings (P: 0.049, 0.010 and 0.032, respectively). The invasive status and the histologic grade of infiltrating carcinoma were significantly associated with false-negative VTIQ findings (P: 0.026 and 0.015). CONCLUSION: Diameter, depth, posterior acoustic features, invasive status, and histologic grade have a significant influence on the accuracy of VTIQ results, and these characteristics of breast lesions should be taken into account when interpreting the results of VTIQ examinations.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Erros de Diagnóstico , Técnicas de Imagem por Elasticidade/métodos , Adolescente , Adulto , Idoso , Biópsia com Agulha de Grande Calibre/normas , Feminino , Humanos , Pessoa de Meia-Idade , Exame Físico/normas , Estudos Retrospectivos , Adulto Jovem
15.
Oncotarget ; 7(37): 59098-59114, 2016 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-27385209

RESUMO

Inter-individual variability causing elevated signaling of receptor tyrosine kinases (RTK) may have hampered the efficacy of targeted therapies. We developed a molecular signature for clustering adult diffuse gliomas based on the extent of RTK pathway activities. Glioma gene modules co-expressed with NF1 (NF1-M), Sprouty (SPRY-M) and PTEN (PTEN-M) were identified, their signatures enabled robust clustering of adult diffuse gliomas of WHO grades II-IV from five independent data sets into two subtypes with distinct activities of RAS-RAF-MEK-MAPK cascade and PI3K-AKT pathway (named RMPAhigh and RMPAlow subtypes) in a morphology-independent manner. The RMPAhigh gliomas were associated with poor prognosis compared to the RMPAlow gliomas. The RMPAhigh and RMPAlow glioma subtypes harbored unique sets of genomic alterations in the RTK signaling-related genes. The RMPAhigh gliomas were enriched in immature vessel cells and tumor associated macrophages, and both cell types expressed high levels of pro-angiogenic RTKs including MET, VEGFR1, KDR, EPHB4 and NRP1. In gliomas with major genomic lesions unrelated to RTK pathway, high RMPA signature was associated with short survival. Thus, the RMPA signatures capture RTK activities in both glioma cells and glioma microenvironment, and RTK signaling in the glioma microenvironment contributes to glioma progression.


Assuntos
Glioma/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurofibromina 1/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfoproteínas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Adulto , Análise por Conglomerados , Regulação Neoplásica da Expressão Gênica , Glioma/diagnóstico , Glioma/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Estadiamento de Neoplasias , Proteínas do Tecido Nervoso/genética , Neurofibromina 1/genética , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoproteínas/genética , Receptor Cross-Talk , Transdução de Sinais/genética , Transcriptoma , Microambiente Tumoral
16.
Int J Biochem Cell Biol ; 45(9): 1962-73, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23811124

RESUMO

Glioma is the most common highly malignant primary brain tumor. The molecular pathways that result in the pathogenesis of glioma remain elusive. In this study, we found microRNA-107 (miR-107) was downregulated in glioma tissues and cell lines. Our results revealed miR-107 overexpression suppressed cell proliferation in glioma cells, whereas miR-107 knockdown promoted cell growth in MO59K. miR-107 expression induced apoptosis in glioma cells possibly through the increase in Fas (TNFRSF6)-associated via death domain (FADD) expression and activation of caspases-8 and -3/7. Moreover, the activity of caspase-8 in miR-107-overexpressing SHG44 cells was suppressed with FADD knockdown. The tumor growth in nude mice bearing miR-107-overexpressing SHG44 cells was blocked through apoptosis induction. Sal-like 4 (Drosophila) (SALL4) level was reduced upon miR-107 overexpression in glioma cells, and the inverse was observed upon miR-107 knockdown in MO59K. Using a luciferase reporter system, SALL4 3'-UTR-dependent luciferase activity was reduced by miR-107 mimics or increased by an inhibitor of miR-107. In SHG44, SALL4 downregulation triggered growth inhibition and activated FADD-mediated cell apoptosis pathway. The caspase-8 activity in miR-107-overexpressing SHG44 cells was suppressed with SALL4 upregulation. Furthermore, primary glioma tumors with low miR-107 expression show elevated SALL4 level. An obvious inverse correlation was observed between miR-107 expression and SALL4 level in clinical glioma samples. Therefore, our results demonstrate upregulation of miR-107 suppressed glioma cell growth through direct targeting of SALL4, leading to the activation of FADD/caspase-8/caspase-3/7 signaling pathway of cell apoptosis. These data suggest miR-107 is a potential therapeutic target against glioma.


Assuntos
Apoptose/fisiologia , Glioma/metabolismo , Glioma/patologia , MicroRNAs/biossíntese , Fatores de Transcrição/metabolismo , Regiões 3' não Traduzidas , Animais , Sequência de Bases , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Glioma/genética , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Dados de Sequência Molecular , Transdução de Sinais , Fatores de Transcrição/genética , Transfecção , Regulação para Cima
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