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1.
J Cell Mol Med ; 23(6): 4097-4110, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31016850

RESUMO

The pathogenesis of Cushing's disease, which is caused by pituitary corticotroph adenoma, remains to be studied. Secreted angioinhibitory factor thrombospondin-1 (TSP-1) is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions and is associated with platelet aggregation, angiogenesis and tumorigenesis. We have found that the expression of TSP-1 is significantly lower in human pituitary corticotroph tumours compared with normal adenohypophysis. This study aims to elucidate the role of TSP-1 in regulating the tumour function of pituitary adenomas. Forced overexpression of TSP-1 in a murine AtT20 pituitary corticotroph tumour cell line decreased corticotroph precursor hormone proopiomelanocortin (POMC) transcription and adrenocorticotropic hormone (ACTH) secretion. Functional studies showed that TSP-1 overexpression in pituitary adenoma cells suppressed proliferation, migration and invasion. We have demonstrated that TSP-1 is a direct target of miR-449c. Further study showed that miR-449c activity enhanced tumorigenesis by directly inhibiting TSP-1 expression. Low expression of lncTHBS1, along with low expression of TSP-1, was associated with the high expression of miR-449c in Cushing's disease patients. Furthermore, RNA-immunoprecipitation associates miR-449c with lncTHBS1 suggesting that lncTHBS1 might be a negative regulator of miR-449c. Taken together, this study has demonstrated that lncTHBS1 might function as competing endogenous RNA for miR-449c, which could suppress the development of Cushing's disease.


Assuntos
Regulação para Baixo/genética , MicroRNAs/genética , Hipersecreção Hipofisária de ACTH/genética , Trombospondina 1/genética , Adenoma Hipofisário Secretor de ACT/genética , Animais , Linhagem Celular , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Hipófise/metabolismo , Neoplasias Hipofisárias/genética
2.
Biochem Biophys Res Commun ; 510(1): 8-12, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30661788

RESUMO

A square-planar Cu(II) complex, [Cu(Me-Im)(gly-gly)]∙H2O 1 (Me-Im = 1-methyl-imidazole, gly-gly = glycylglycinato), has been prepared and structurally characterized by single crystal X-ray. The complex 1 was tested for its ability to the transfer RNA by UV-vis spectroscopy, cyclic voltammetry (CV), capillary electrophoresis (CE). Comparative spectroscopic analysis shows a maximum fluorescence-quenching ratio of 0.41 of 1 upon binding to RNA, which gives a binding constant (Kb) of 1.24 × 105 M-1. Cyclic voltammograms of complex 1 attached on the mercaptoethanol (-SH) linked Au electrodes in phosphate buffer solution give a well-defined and quasi-reversible redox couple, indicate complex 1 can efficiently degrade the high-order structure of RNA in physiological conditions (pH 7.0 phosphate buffer solution at 37 °C) without additional co-reactants, yielding a digestion coefficient more than 90% within 113 h. This study targeting the genetic biomacromolecule degradation based on the strong binding of chemical nucleases paves an important way to the novel materials in the decontamination of microorganisms (e.g., bacteria and viruses) at mild condition.


Assuntos
Complexos de Coordenação/química , Cobre/química , RNA de Transferência/metabolismo , Complexos de Coordenação/metabolismo , Cristalografia por Raios X , Glicina/química , Imidazóis/química , Estrutura Molecular , Esterilização/métodos
3.
Molecules ; 23(1)2018 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-29351191

RESUMO

Anionic water clusters have long been studied to infer properties of the bulk hydrated electron. In particular, the question of whether the excess electron is on the surface of the cluster or in the interior of the clusters has been the subject of much speculation. The successes of solid-state physics are built on exploiting the regularity of atomic arrangements in crystal. Describing the crystalline order of solids is relatively straightforward. Here we report the crystal structure of an anionic water cluster polymer [(H2O)18(OH)2]n2n- moiety that is stabilized by bis(2,2'-bipyridine) cupric chloride [Cu(bipy)2Cl]- host.


Assuntos
2,2'-Dipiridil/química , Ânions/química , Cobre/química , Polímeros/química , Água/química , Ligação de Hidrogênio , Modelos Moleculares , Conformação Molecular , Estrutura Molecular
4.
Clin Endocrinol (Oxf) ; 86(3): 367-376, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27859451

RESUMO

CONTEXT AND OBJECTIVE: Cushing's disease (CD) provides a unique and naturalist model for studying the influence of hypercortisolism on the human brain and the reversibility of these effects after resolution of the condition. This cross-sectional study used resting-state fMRI (rs-fMRI) to investigate the altered spontaneous brain activity in CD patients and the trends for potential reversibility after the resolution of the hypercortisolism. We also aim to determine the relationship of these changes with clinical characteristics and cortisol levels. SUBJECTS AND METHODS: Active CD patients (n = 18), remitted CD patients (n = 14) and healthy control subjects (n = 22) were included in this study. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were calculated to represent spontaneous brain activity. RESULTS: Our study resulted in three major findings: (i) active CD patients showed significantly altered spontaneous brain activity in the posterior cingulate cortex (PCC)/precuneus (PCu), occipital lobe (OC)/cerebellum, thalamus, right postcentral gyrus (PoCG) and left prefrontal cortex (PFC); (ii) trends for partial restoration of altered spontaneous brain activity after the resolution hypercortisolism were found in several brain regions; and (iii) active CD patients showed a significant correlation between cortisol levels and ALFF/ReHo values in the PCC/PCu, a small cluster in the OC and the right IPL. CONCLUSIONS: This study provides a new approach to investigating brain function abnormalities in patients with CD and enhances our understanding of the effect of hypercortisolism on the human brain. Furthermore, our explorative potential reversibility study of patients with CD may facilitate the development of future longitudinal studies.


Assuntos
Encéfalo/fisiopatologia , Hipersecreção Hipofisária de ACTH/fisiopatologia , Adulto , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Estudos Transversais , Síndrome de Cushing/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Adulto Jovem
5.
Clin Endocrinol (Oxf) ; 87(4): 367-374, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28543178

RESUMO

OBJECTIVE: The data on patients with short-term remission of Cushing's disease (CD) might provide information that is not available from previous long-term remission studies. We aimed to investigate structural changes in the brain in these patients and to examine whether these changes were associated with clinical characteristics. DESIGN: A cross-sectional study was performed. METHODS: Thirty-four patients with CD (14 with CD in short-term remission and 20 with active CD) and 34 controls matched for age, sex and education underwent clinical evaluation and magnetic resonance imaging brain scans. Biometric measurements, disease duration and remission duration data were collected. Grey matter volumes in the whole brain were examined using voxel-based morphometry (VBM). RESULTS: No differences were observed in the grey matter volumes of the medial frontal gyrus (MFG) and cerebellum between the patients with remitted CD and healthy controls, whereas patients with active CD had smaller grey matter volumes in these two regions compared with controls and patients with remitted CD. Furthermore, significant correlations were found between remission time and grey matter values in these regions in short-term remission patients with CD. Additionally, greater grey matter volumes in the bilateral caudate of short-term remission patients with CD were observed. CONCLUSIONS: Trends for structural restoration were found in CD patients with short-term remission. This finding was associated with the number of days elapsed since curative surgery and the current age of the patients. This study enhances our understanding of potential reversibility after the resolution of hypercortisolism in CD patients.


Assuntos
Imageamento por Ressonância Magnética/métodos , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Hipersecreção Hipofisária de ACTH/patologia , Adulto , Estudos Transversais , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/patologia , Adulto Jovem
6.
Molecules ; 22(12)2017 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29261117

RESUMO

The crystal structure of compound (1), [CuCl(phen)(H2NCH2COO)]∙4H2O, reveals an unusual hydrogen-bond water cluster aggregate T6(2)6(2). Four water molecules in (1) form an isolated water cluster, [(H2O)14]n, resembling a "phenanthro-[1,2]phenanthrene polymer structure shape" along the ac plane. The two face-face parallel [(H2O)14]n planes are bridged by Cl atoms in [CuCl(phen) (H2NCH2COO)] with a strong O-H∙∙∙Cl hydrogen bond to form a water cluster conduit.


Assuntos
Complexos de Coordenação/química , Cobre/química , Água/química , Cristalização , Cristalografia por Raios X/métodos , Glicina/química , Ligação de Hidrogênio , Modelos Moleculares , Estrutura Molecular , Nanoestruturas/química , Polímeros/química
7.
Biochim Biophys Acta ; 1840(1): 577-85, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24144566

RESUMO

BACKGROUND: It has been recognized that insulin hypersecretion can lead to the development of insulin resistance and type 2 diabetes mellitus. There is substantial evidence demonstrating that thiazolidinediones are able to delay and prevent the progression of pancreatic ß-cell dysfunction. However, the mechanism underlying the protective effect of thiazolidinediones on ß-cell function remains elusive. METHODS: We synchronously detected the effects of troglitazone on insulin secretion and AMP-activated protein kinase (AMPK) activity under various conditions in isolated rat islets and MIN6 cells. RESULTS: Long-term exposure to high glucose stimulated insulin hypersecretion and inhibited AMPK activity in rat islets. Troglitazone-suppressed insulin hypersecretion was closely related to the activation of AMPK. This action was most prominent at the moderate concentration of glucose. Glucose-stimulated insulin secretion was decreased by long-term troglitazone treatment, but significantly increased after the drug withdrawal. Compound C, an AMPK inhibitor, reversed troglitazone-suppressed insulin secretion in MIN6 cells and rat islets. Knockdown of AMPKα2 showed a similar result. In MIN6 cells, troglitazone blocked high glucose-closed ATP-sensitive K(+) (KATP) channel and decreased membrane potential, along with increased voltage-dependent potassium channel currents. Troglitazone suppressed intracellular Ca(2+) response to high glucose, which was abolished by treatment with compound C. CONCLUSION: Our results suggest that troglitazone provides ß-cell "a rest" through activating AMPK and inhibiting insulin hypersecretion, and thus restores its response to glucose. GENERAL SIGNIFICANCE: These data support that AMPK activation may be an important mechanism for thiazolidinediones preserving ß-cell function.


Assuntos
Cálcio/metabolismo , Cromanos/farmacologia , Hipoglicemiantes/farmacologia , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Proteínas Quinases/metabolismo , Tiazolidinedionas/farmacologia , Quinases Proteína-Quinases Ativadas por AMP , Animais , Células Cultivadas , Eletrofisiologia , Glucose/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Masculino , Proteínas Quinases/química , Proteínas Quinases/genética , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Troglitazona
8.
Molecules ; 20(8): 14435-50, 2015 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-26262606

RESUMO

By treating a suitable Wittig reagent under acid conditions, the phosphonate ester 1,4-bimethylenebenzene phosphonate ethyl ester (H2[BBPE], 1) was obtained. As a building block, compound 1 has been reacted with the Lewis-base N,N-dimethylpiperazine, ammonia and NaOH yielded compounds 2-4. The crystal structures show that a 1D chain forming a tubular channel is constructed through hydrogen bonds in 1; hydrogen bonds form two 1D chains with left-hand and right-hand helixes and form 3D networks in compound 2; 1D hydrogen-bond chains are further connected together to afford a 3D network architecture in compound 3; the phosphonate is coordinated by two Na atoms which present different coordination environments in compound 4. Additionally, the relationships between the structure and fluorescence of the four compounds in the solid state and in different solvents have also been studied at room temperature.


Assuntos
Difosfonatos/química , Bases de Lewis/química , Organofosfonatos/química , Cristalografia por Raios X , Difosfonatos/síntese química , Modelos Moleculares , Conformação Molecular , Organofosfonatos/síntese química , Solventes/química , Espectrometria de Fluorescência
9.
Biochim Biophys Acta ; 1822(11): 1815-25, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22968147

RESUMO

Sirtuin 1 (SIRT1), a nicotinamide adenosine dinucleotide-dependent histone deacetylase, is an important regulator of energy homeostasis in response to nutrient availability. In pancreatic ß-cells, SIRT1 has been shown to up-regulate insulin secretion in response to glucose stimulation. However, the potential roles of SIRT1 in islet ß-cells against lipotoxicity remain poorly understood. Here, we demonstrated that SIRT1 mRNA and protein expressions were markedly reduced in the islets isolated from rats infused with 20% Intralipid for 24h. Long-term exposure to 0.4mmol/L palmitate also decreased SIRT1 expression in cultured INS-1 cells and isolated rat islets, which was prevented by 10µmol/L resveratrol, a SIRT1 agonist. In addition, resveratrol improved glucose-stimulated insulin secretion decreased by palmitate, which was abrogated by EX527, a specific SIRT1 inhibitor. Furthermore, inhibition of SIRT1 activity by EX527 or a knockdown of SIRT1 suppressed insulin promoter activity, along with decreased insulin, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), and NK6 homeodomain 1 (NKX6.1) mRNA expressions. Activation of SIRT1 by resveratrol or overexpression of SIRT1 antagonized palmitate-inhibited insulin transcriptional activity. SIRT1 overexpression exerted an additive effect on pancreatic and duodenal homeobox 1 (PDX1)-stimulated insulin promoter activity and abolished forkhead box O1 protein (FOXO1)-decreased insulin transcriptional activity. Resveratrol reversed FOXO1 nuclear translocation induced by palmitate. Our findings indicate that SIRT1 protects against palmitate-induced ß-cell dysfunction.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Insulina , Palmitatos/farmacologia , Sirtuína 1/metabolismo , Animais , Carbazóis/farmacologia , Linhagem Celular , Fatores de Transcrição Forkhead/metabolismo , Glucose/farmacologia , Proteínas de Homeodomínio/metabolismo , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Lectinas Tipo C/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Ratos , Ratos Sprague-Dawley , Resveratrol , Estilbenos/farmacologia , Transativadores/metabolismo
10.
Food Chem ; 414: 135706, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-36821922

RESUMO

This study aimed to evaluate the change of digestibility and antioxidant activity of protein and lipid after mixing walnuts, cashews, and pistachios using in vitro and in vivo models. The results showed that mixed nuts significantly reduced the digested particle size and the degree of hydrolysis of protein and triacylglycerol compared to single nuts in vitro. As a consequence of co-digestion, bioaccessibility and antioxidant activity for amino acids and fatty acids were increased by 1.12-1.87 fold and 1.62-3.81 fold, respectively. In vivo studies, the mixed nuts diet increased the concentration of amino acids and fatty acids in the small intestine by 27.69%-158.26% and 18.13%-152.09%, respectively, and enhanced levels of antioxidant enzymes in the liver and serum, all without causing weight gain. These findings highlight the positive interaction between single and mixed nuts, where mixed nuts enhanced the digestibility and antioxidant activity of single nuts both in vitro and in vivo.


Assuntos
Juglans , Nozes , Nozes/química , Antioxidantes/análise , Juglans/química , Ácidos Graxos/análise , Aminoácidos/análise
11.
Front Microbiol ; 14: 1208816, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37560527

RESUMO

Introduction: Previous studies have found that unique patterns of gut microbial colonization in infancy associated with the development of allergic diseases. However, there is no research on the gut microbiota characteristics of AR children in Chinese Mainland. Objective: To investigate the changes of gut microbial of AR children in Chinese Mainland and evaluate the correlation between gut microbial and clinical indexes. Methods: In this clinical study, fecal samples from 24 AR children and 25 healthy control children (HCs) were comparative via next generation sequencing of the V3-V4 regions of the 16S rRNA gene. Analyzed the relationship between clinical features and gut microbial using Spearman correlation. Results: Compared to HCs, AR children showed significant decreases in Shannon index and significant increases in Simpson index at both the family and genera levels (all p < 0.05). In terms of bacterial composition, at the phylum level, AR children had higher abundance of Bacteroidetes than that in the HCs group (p < 0.05) and were significantly positively correlated with TNSS (p < 0.05). At the family level, AR children had higher abundance of Prevotellaceae and Enterobacteriaceae higher than that in the HCs group (all p < 0.05) and had a significantly positive correlation with TNSS, eosinophils (EOS) and total immunoglobulin E (tIgE) (all p < 0.05). At the genus level, reduced abundance of Agathobacter, Parasutterella, Roseburia and Subdoligranulum were also observed in the AR cohorts compared to HCs (all p < 0.05) and significantly negatively associated with TNSS, EOS, tIgE, QOL, and FeNO (all p < 0.05). Conclusion: AR children in Chinese Mainland were characterized by reduced microbial diversity and distinguished microbial characteristics in comparison with HCs. The observations of this study offer proof that distinctive gut microbiota profiles were present in AR children and necessitate further investigation in the form of mechanistic studies.

12.
Microbiol Spectr ; 11(6): e0120723, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37787547

RESUMO

IMPORTANCE: HPV DNA screening is an effective approach for the prevention of cervical cancer. The novel real-time recombinase polymerase amplification-based HPV detection systems we developed constitute an improvement over the HPV detection methods currently used in clinical practice and should help to extend cervical cancer screening in the future, particularly in point-of-care test settings.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Neoplasias do Colo do Útero/diagnóstico , Recombinases , Infecções por Papillomavirus/diagnóstico , Detecção Precoce de Câncer/métodos , DNA Viral/genética
13.
Front Oncol ; 12: 998032, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249027

RESUMO

Cervical and anal carcinoma are neoplastic diseases with various intraepithelial neoplasia stages. The underlying mechanisms for cancer initiation and progression have not been fully revealed. DNA methylation has been shown to be aberrantly regulated during tumorigenesis in anal and cervical carcinoma, revealing the important roles of DNA methylation signaling as a biomarker to distinguish cancer stages in clinics. In this research, several machine learning methods were used to analyze the methylation profiles on anal and cervical carcinoma samples, which were divided into three classes representing various stages of tumor progression. Advanced feature selection methods, including Boruta, LASSO, LightGBM, and MCFS, were used to select methylation features that are highly correlated with cancer progression. Some methylation probes including cg01550828 and its corresponding gene RNF168 have been reported to be associated with human papilloma virus-related anal cancer. As for biomarkers for cervical carcinoma, cg27012396 and its functional gene HDAC4 were confirmed to regulate the glycolysis and survival of hypoxic tumor cells in cervical carcinoma. Furthermore, we developed effective classifiers for identifying various tumor stages and derived classification rules that reflect the quantitative impact of methylation on tumorigenesis. The current study identified methylation signals associated with the development of cervical and anal carcinoma at qualitative and quantitative levels using advanced machine learning methods.

14.
Front Oncol ; 12: 976262, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36033519

RESUMO

CD19-targeted CAR T cell immunotherapy has exceptional efficacy for the treatment of B-cell malignancies. B-cell acute lymphocytic leukemia and non-Hodgkin's lymphoma are two common B-cell malignancies with high recurrence rate and are refractory to cure. Although CAR T-cell immunotherapy overcomes the limitations of conventional treatments for such malignancies, failure of treatment and tumor recurrence remain common. In this study, we searched for important methylation signatures to differentiate CAR-transduced and untransduced T cells from patients with acute lymphoblastic leukemia and non-Hodgkin's lymphoma. First, we used three feature ranking methods, namely, Monte Carlo feature selection, light gradient boosting machine, and least absolute shrinkage and selection operator, to rank all methylation features in order of their importance. Then, the incremental feature selection method was adopted to construct efficient classifiers and filter the optimal feature subsets. Some important methylated genes, namely, SERPINB6, ANK1, PDCD5, DAPK2, and DNAJB6, were identified. Furthermore, the classification rules for distinguishing different classes were established, which can precisely describe the role of methylation features in the classification. Overall, we applied advanced machine learning approaches to the high-throughput data, investigating the mechanism of CAR T cells to establish the theoretical foundation for modifying CAR T cells.

15.
J Cancer ; 12(7): 2083-2091, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754007

RESUMO

Objective: To identify critical roles played by NEK2 in prolactinomas and to clarify the corresponding underlying mechanisms. Methods: We performed RNA-seq on MMQ cell lines treated with the dopamine receptor agonist cabergoline (CAB) to identify genes involved in prolactinoma progression and dopamine receptor-agonist (DA) sensitivity. NEK2 was then selected for further study. The expression of NEK2 was examined using quantitative real-time PCR, western immunoblotting, and immunohistochemistry - both in pituitary adenomas (PA) and in normal pituitary tissue. We used gain-of-function and loss-of-function assays to explore the biologic roles of NEK2 in cell growth in vivo and in vitro. Co-immunoprecipitation was also used to detect the binding between NEK2 and USP7. Results: Herein, we reported that NEK2 was upregulated in prolactinomas, particularly dopamine-resistant prolactinomas. NEK2 overexpression significantly promoted pituitary tumor GH3 and MMQ cell proliferation, and it impaired cellular sensitivity to CAB. Conversely, knockdown of NEK2 inhibited GH3 and MMQ cell growth, and sensitized the cells to CAB. Mechanistically, NEK2 regulated cell proliferation via the Wnt-signaling pathway; and in addition, we demonstrated that USP7 interacted with, deubiquitylated, and stabilized NEK2. Conclusions: Collectively, our results suggest that NEK2 might be a potential therapeutic target for prolactinoma.

16.
Cell Death Dis ; 12(4): 351, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824269

RESUMO

Aberrant long-noncoding RNA (lncRNA) expression has been shown to be involved in the pathogenesis of endometrial cancer (EC). Herein, we report a novel tumor suppressor lncRNA SOCS2-AS1 in EC. Quantitative real-time PCR was performed to detect RNA expression. In situ hybridization and nuclear/cytoplasmic fractionation assays were used to detect the subcellular location. We found that SOCS2-AS1 was downregulated in EC tissues. Its reduced expression was correlated with advanced clinical stage and poor prognosis. Forced expression of SOCS2-AS1 suppressed EC cell proliferation and induced cell-cycle arrest and apoptosis. SOCS2-AS1-binding proteins were detected using RNA pull-down assay and mass spectrometry. Mechanistically, SOCS2-AS1 bound to Aurora kinase A (AURKA) and increased its degradation through the ubiquitin-proteasome pathway. In conclusion, SOCS2-AS1 may thus serve as a prognostic predictor and a biomarker for AURKA-inhibitor treatment in EC patients.


Assuntos
Aurora Quinase A/genética , Aurora Quinase A/metabolismo , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Regulação para Baixo , Feminino , Genes Supressores de Tumor/fisiologia , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo
17.
Acta Crystallogr C ; 66(Pt 9): o446-8, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20814103

RESUMO

In the title compound, 2C(19)H(13)N(5).C(8)H(6)O(4).4H(2)O, the terephthalic acid molecule lies on a crystallographic inversion centre and the H atoms of one water molecule exhibit disorder. The maximum deviation of any atom from the mean plane through the C and N atoms of the 2,6-bis(benzimidazol-2-yl)pyridine molecule is only 0.161 (4) A. In the crystal structure, the water molecules play an important role in linking the other molecules via hydrogen bonding. The structure forms a three-dimensional framework via strong intermolecular hydrogen bonding. In addition, there are pi-pi stacking interactions between the imidazole, pyridine and benzene rings.

18.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 6): m680, 2010 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-21579320

RESUMO

In the title complex, [Zn(C(17)H(11)N(6)O)Cl(C(3)H(7)NO)], the Zn(II) atom has a distorted square-pyramidal coordination formed by one Cl, two O and two N atoms. In the crystal structure, inter-molecular N-H⋯Cl hydrogen bonds link mol-ecules into centrosymmetric dimers, which are further assembled by π-π inter-actions [centroid-centroid distances = 3.809 (3) and 3.834 (3) Å] into layers parallel to the ab plane. The crystal packing exhibits also weak inter-molecular C-H⋯Cl inter-actions.

19.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 6): o1423, 2010 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-21579499

RESUMO

In the crystal structure of the title compound, C(28)H(21)Cl(2)N, π-π inter-actions link pairs of mol-ecules into centrosymmetric dimers with a distance of 3.756 (3) Šbetween the centroids of the pyridine rings. Weak inter-molecular C-H⋯Cl hydrogen bonds further link these dimers into chains propagating along [01]. The pyridine ring forms dihedral angles of 21.52 (1) and 55.87 (2)°, respectively, with the phenyl ring and the 4-chlorophenyl ring.

20.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 2): o427, 2010 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-21579842

RESUMO

In the mol-ecule of the title compound, C(20)H(14)N(4), the triazine ring is attached to two phenyl rings and one pyridine ring. In the crystal, mol-ecules are linked by inter-molecular C-H⋯N hydrogen bonds. The crystal packing is also stabilized by C-H⋯π inter-actions.

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