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1.
Biochem Biophys Res Commun ; 509(2): 354-358, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30587337

RESUMO

The o-phenanthroline gly Cu(II) complex, [CuCl(phen)(gly)]∙4H2O 1, has been prepared and structurally characterized. The transfer RNA binding and degradation properties of complex 1 have been investigated by UV-vis spectroscopy, cyclic voltammetry (CV), capillary electrophoresis (CE) and atomic force microscopy (AFM) methods. The results showed that 1 can efficiently cleave tRNA in the physiological conditions (pH 7.0, and 37 °C), and has a digestion coefficient nearly up to 100% within 75 h. AFM image for 1/RNA exhibited arrayed tandem repetitions of tRNA segments. This study is targeting the destruction of the high-order structures of genetic biomacromolecules which paves an important way to novel materials for the decontamination of microorganisms (e.g., bacteria and viruses).


Assuntos
Complexos de Coordenação/química , Cobre/química , Glicina/química , Fenantrolinas/química , RNA de Transferência/química , Catálise , Cinética , Clivagem do RNA , Saccharomyces cerevisiae/química
2.
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
3.
Brain Res ; 1665: 80-87, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28438531

RESUMO

Exposure to chronic hypercortisolism has multiple adverse effects on brain biology in humans. Cushing's disease (CD) represents a unique and natural human model for examining the effects of hypercortisolism on the brain. This cross-sectional study used Diffusional Kurtosis Imaging (DKI) to investigate the microstructure alterations in both white matter (WM) and gray matter (GM) of CD patients and to determine the relationship of these changes with clinical characteristics. DKI images were obtained from 15 active CD patients. DKI parametric maps were estimated through voxel-based analyses (VBA) and compared with 15 healthy controls matched for age, sex and education. In addition, correlations were analyzed between the altered DKI parameters and clinical characteristics. Compared with healthy controls, CD patients mainly exhibited significantly altered diffuse parameters in the GM and WM of the left medial temporal lobe (MTL). The mean values of increased radial diffusivity (RD) of CD patients in GM of the left hippocampus/parahippocampal gyrus correlated positively with the clinical severity of CD. Additionally, we also found altered kurtosis parameters in the cerebellum and frontal lobe. DKI imaging of CD patients could represent complementary information in both white matter and gray matter. The impairment of the left MTL might explain some part of the memory and cognition impairments in CD patients.


Assuntos
Substância Cinzenta/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Algoritmos , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade
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.
Chin Med J (Engl) ; 129(17): 2102-8, 2016 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-27569239

RESUMO

BACKGROUND: Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 (USP8) gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor (EGFR) signaling and promote adrenocorticotropic hormone (ACTH) production. This study was to investigate whether the inhibition of USP8 activity could be a strategy for the treatment of Cushing's disease (CD). METHODS: The anticancer effect of USP8 inhibitor was determined by testing cell viability, colony formation, apoptosis, and ACTH secretion. The immunoblotting and quantitative reverse transcription polymerase chain reaction were conducted to explore the signaling pathway by USP8 inhibition. RESULTS: Inhibition of USP8-induced degradation of receptor tyrosine kinases including EGFR, EGFR-2 (ERBB2), and Met leading to a suppression of AtT20 cell growth and ACTH secretion. Moreover, treatment with USP8 inhibitor markedly induced AtT20 cells apoptosis. CONCLUSIONS: Inhibition of USP8 activity could be an effective strategy for CD. It might provide a novel pharmacological approach for the treatment of CD.


Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Endopeptidases/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/antagonistas & inibidores , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Ubiquitina Tiolesterase/antagonistas & inibidores , Ubiquitina Tiolesterase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Inibidores Enzimáticos/farmacologia , Receptores ErbB/metabolismo , Humanos , Indenos/farmacologia , Camundongos , Pirazinas/farmacologia
6.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 6): m682, 2010 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-21579322

RESUMO

The title compound, [Cu(C(2)Cl(3)O(2))(2)(C(3)H(4)N(2))(4)], was prepared by the reaction of imidazole and trichloro-acetatocopper(II). The Cu(II) atom adopts a distorted octa-hedral coordination geometry, binding the N atoms of four imidazole ligands and the carboxyl-ate O atoms of two trichloro-acetate anions. The mol-ecular structure and packing are stabilized by N-H⋯O hydrogen-bonding inter-actions. Close inter-molecular Cl⋯Cl contacts [3.498 (3) Å] are also found in the structure.

7.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 6): o1378, 2010 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-21579459

RESUMO

In the title compound, C(22)H(23)NO(4)·C(2)H(6)O, the pyridyl ring is aligned at 89.39 (2) and 87.41 (2)° with respect to the benzene rings, and the three rings connected to the methine C atom are arranged in a propeller-like conformation. The heterocycle is linked to the solvent mol-ecule by an O-H⋯N hydrogen bond.

8.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 6): o1397, 2010 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-21579476

RESUMO

In the title compound, C(11)H(16)N(4)S, an intra-molecular N-H⋯N hydrogen bond generates an S(5) ring. In the crystal, inversion dimers linked by pairs of N-H⋯S bonds occur, generating an R(2) (2)(8) loop.

9.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 6): o1398, 2010 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-21579477

RESUMO

In the title compound, C(13)H(12)N(2)OS, the dihedral angle between the aromatic rings is 14.84 (17)°. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R(2) (2)(8) loops.

10.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 6): o1399, 2010 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-21579478

RESUMO

In the title compound, C(11)H(15)N(3)S, an intra-molecular N-H⋯N hydrogen bond generates an S(5) ring. In the crystal, inversion dimers linked by pairs of N-H⋯S bonds occur, generating an R(2) (2)(8) loop.

11.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 6): o1400, 2010 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-21579479

RESUMO

In the title compound, C(13)H(12)N(2)O(2)S, the dihedral angle between the aromatic rings is 15.20 (11)°. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R(2) (2)(8) loops.

12.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 6): o1429, 2010 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-21579505

RESUMO

The title compound, C(10)H(12)N(2)O(2), was prepared by the reaction of methyl carbazate and 4-methyl-benzaldehyde. The dihedral angle between the benzene ring and the carbazate fragment is 20.86 (10)°. In the crystal structure, mol-ecules are linked by inter-molecular N-H⋯O hydrogen bonds.

13.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 6): o1471, 2010 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-21579539

RESUMO

The title compound, C(13)H(9)N(3)OS, was prepared by the reaction of thio-phene-2-carbohydrazide and 4-formyl-benzonitrile. The dihedral angle between the benzene and thio-phene rings is 11.9 (1)°. In the crystal structure, mol-ecules are linked into centrosymmetric dimers by pairs of N-H⋯O hydrogen bonds.

14.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 2): m141, 2010 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-21579622

RESUMO

In the title compound, [Cu(C(2)HCl(2)O(2))(C(10)H(8)N(2))(2)](C(2)HCl(2)O(2))·2H(2)O, the Cu(II) ion is bonded to two N,N'-bidentate 2,2'-bipyridyl ligands and one O-monodentate 2,2-dichloro-acetate anion in a distorted CuON(4) trigonal-bipyramidal geometry, with the O atom occupying an equatorial site. In the crystal, the components are linked by O-H⋯O and O-H⋯Cl hydrogen bonds.

15.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 2): o251, 2010 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-21579696

RESUMO

In the title compound, C(25)H(20)Br(2)N(2) (2+)·2NO(3) (-), the cation lies on a twofold rotation axis which imposes disorder of the dibromo-fluorene unit. In addition, the unique nitrate anion is disordered over two general sites of equal occupancy. The crystal structure is stabilized by inter-molecular N-H⋯O hydrogen bonds.

16.
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.

17.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 4): o927, 2010 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-21580737

RESUMO

The title compound, C(9)H(9)FN(2)O, was prepared by the reaction between 2-fluoro-benzophenone and acetohydrazide. In the crystal structure, inversion dimers linked by pairs of N-H⋯O hydrogen bonds occur, generating R(2) (2)(8) loops.

18.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 7): o1565, 2010 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-21587808

RESUMO

There are two mol-ecules in the asymmetric unit of the title compound, C(11)H(14)N(2)O(2), which have similar conformations. In the crystal, the mol-ecules are linked by N-H⋯O hydrogen bonds, generating C(4) chains propagating in [001].

19.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 7): o1587, 2010 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-21587827

RESUMO

The title compound, C(17)H(15)N(3)O(3), was prepared from 1-(2-nitro-phen-yl)-3-phenyl-prop-2-en-1-one and hydrazine. The dihedral angle between the benzene and phenyl rings is 74.55 (2)°. The pyrazoline ring is in a slight envelope conformation with the C atom bonded to the phenyl ring forming the flap. In the crystal structure, weak inter-molecular C-H⋯O hydrogen bonds connect mol-ecules into chains along [100].

20.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 7): o1670, 2010 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-21587896

RESUMO

In the title compound, C(13)H(9)N(3)O(2)·H(2)O, the dihedral angle between the aromatic rings is 10.7 (4)° and an intra-molecular N-H⋯O hydrogen bond occurs. In the crystal, the components are linked by N-H⋯O, O-H⋯N and O-H⋯O hydrogen bonds.

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