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1.
Curr Mol Med ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347777

RESUMO

OBJECTIVE: Ulcerative colitis (UC) is a chronic non-specific inflammatory disease of the rectum and colon with unknown etiology. A growing number of evidence suggest that the pathogenesis of UC is related to excessive apoptosis and production of inflammatory cytokines. However, the functions and molecular mechanisms associated with UC remain unclear. MATERIALS AND METHODS: The in vivo and in vitro models of UC were established in this study. MiRNA or gene expression was measured by qRT-PCR assay. ELISA, CCK-8, TUNEL, and flow cytometry assays were applied for analyzing cellular functions. The interactions between miR-146a and TAB1 were verified by luciferase reporter and miRNA pull-down assays. RESULTS: MiR-146a was obviously increased in UC patients, DSS-induced colitis mice, and TNF-ɑ-induced YAMC cells, when compared to the corresponding controls. MiR- 146a knockdown inhibited the inflammatory response and apoptosis in DSS-induced colitis mice and TNF-ɑ-induced YAMC cells. Mechanistically, we found that TAB1 was the target of miR-146a and miR-146a knockdown suppressed the activation of NF-κB pathway in UC. More importantly, TAB1 could overturn the inhibitory effect of antagomiR-146a on cell apoptosis and inflammation in UC. CONCLUSION: MiR-146a knockdown inhibited cell apoptosis and inflammation via targeting TAB1 and suppressing NF-κB pathway, suggesting that miR-146a may be a new therapeutic target for UC treatment.

2.
World J Psychiatry ; 14(1): 26-35, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38327895

RESUMO

BACKGROUND: With the continuous growth of the modern elderly population, the risk of fracture increases. Hip fracture is a common type of fracture in older people. Total hip arthroplasty (THA) has significant advantages in relieving chronic pain and promoting the recovery of hip joint function. AIM: To investigate the effect of ulinastatin combined with dexmedetomidine (Dex) on the incidences of postoperative cognitive dysfunction (POCD) and emergence agitation in elderly patients who underwent THA. METHODS: A total of 397 patients who underwent THA from February 2019 to August 2022. We conducted a three-year retrospective cohort study in Shaanxi Provincial People's Hospital. Comprehensive demographic data were obtained from the electronic medical record system. We collected preoperative, intraoperative, and postoperative data. One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group. One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group. One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex + ulinastatin group. The patients' perioperative conditions, hemodynamic indexes, postoperative Mini-Mental State Examination (MMSE) scores, Ramsay score, incidence of POCD, and serum inflammatory cytokines were evaluated. RESULTS: There was a significant difference in the 24 h visual analogue scale score among the three groups, and the score in the Dex + ulinastatin group was the lowest (P < 0.05). Compared with the Dex and ulinastatin group, the MMSE scores of the Dex + ulinastatin group were significantly increased at 1 and 7 d after the operation (all P < 0.05). Compared with those in the Dex and ulinastatin groups, incidence of POCD, levels of serum inflammatory cytokines in the Dex + ulinastatin group were significantly decreased at 1 and 7 d after the operation (all P < 0.05). The observer's assessment of the alertness/sedation score and Ramsay score of the Dex + ulinastatin group were significantly different from those of the Dex and ulinastatin groups on the first day after the operation (all P < 0.05). CONCLUSION: Ulinastatin combined with Dex can prevent the occurrence of POCD and emergence agitation in elderly patients undergoing THA.

3.
Pathol Oncol Res ; 28: 1610396, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388433

RESUMO

Background: Typically, liver cancer patients are diagnosed at an advanced stage and have a poor prognosis. N-recognin 5 (UBR5), a component of the ubiquitin protein ligase E3, is involved in the genesis and progression of several types of cancer. As of yet, it is unknown what the exact biological function of UBR5 is in liver cancer. Methods: A Kaplan-Meier survival curve (OS) was used to examine the effect of UBR5 expression on overall survival based on the TCGA database. To determine the molecular functions of UBR5 in liver cancer, we used the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. A protein-protein interaction (PPI) network was established for the screening of UBR5-related proteins in liver cancer. Western blot analysis was used to determine the expression levels of UBR5 and YWHAZ (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta), and in order to detect cell proliferation, an MTT assay was used. Results: The expression of UBR5 in liver cancer patient samples is significantly higher than in adjacent normal tissues. A high level of UBR5 expression was associated with older patients, a higher tumor grade, lymph node metastasis, and poor survival. We discovered YWHAZ with high connectivity, and UBR5 expression correlated positively with YWHAZ expression (r = 0.83, p < 0.05). Furthermore, we found that elevated UBR5 levels directly correlated with YWHAZ overexpression, and that UBR5 promoted cell proliferation by affecting YWHAZ expression. Additionally, the TCGA databases confirmed that patients with liver cancer who expressed higher levels of YWHAZ had poorer outcomes. Conclusion: This suggests that UBR5 associated with YWHAZ may influence prognosis in patients with liver cancer, and that UBR5 may be a candidate treatment target for liver cancer. Therefore, UBR5 associated with YWHAZ may influence prognosis in patients with liver cancer, and UBR5 could serve as a potential target for liver cancer treatment.


Assuntos
Neoplasias Hepáticas , Humanos , Prognóstico , Neoplasias Hepáticas/genética , Ubiquitina-Proteína Ligases/genética , Proliferação de Células/genética , Estimativa de Kaplan-Meier
4.
Cancer Res ; 80(12): 2599-2611, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32312832

RESUMO

Zinc finger protein 143 (ZNF143) belongs to the zinc finger protein family and possesses transcription factor activity by binding sequence-specific DNA. The exact biological role of ZNF143 in hepatocellular carcinoma (HCC) has not been investigated. Here we report that ZNF143 is overexpressed in HCC tissues and its overexpression correlates with poor prognosis. Gain- and loss-of-function experiments showed that ZNF143 promoted HCC cell proliferation, colony formation, and tumor growth in vitro and in vivo. ZNF143 accelerated HCC cell-cycle progression by activating cell division cycle 6 (CDC6). Mechanistically, ZNF143 promoted expression of CDC6 by directly activating transcription of histone demethylase mineral dust-induced gene (MDIG), which in turn reduced H3K9me3 enrichment in the CDC6 promoter region. Consistently, ZNF143 expression correlated significantly with MDIG and CDC6 expression in HCC. Collectively, we propose a model for a ZNF143-MDIG-CDC6 oncoprotein axis that provides novel insight into ZNF143, which may serve as a therapeutic target in HCC. SIGNIFICANCE: These findings describe the mechanism by which ZNF143 promotes HCC proliferation and provide important clues for exploring new targets and strategies for clinical treatment of human liver cancer.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/genética , Dioxigenases/genética , Regulação Neoplásica da Expressão Gênica , Histona Desmetilases/genética , Neoplasias Hepáticas/genética , Proteínas Nucleares/genética , Transativadores/metabolismo , Animais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Linhagem Celular Tumoral , Estudos de Coortes , Metilação de DNA , Conjuntos de Dados como Assunto , Dioxigenases/metabolismo , Células HEK293 , Hepatectomia , Histona Desmetilases/metabolismo , Histonas/genética , Humanos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Camundongos , Proteínas Nucleares/metabolismo , Prognóstico , Regiões Promotoras Genéticas/genética , Análise Serial de Tecidos , Ativação Transcricional , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Cell Death Dis ; 8(5): e2766, 2017 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-28471446

RESUMO

MDIG is known to be overexpressed in many types of human cancers and has demonstrated predictive power in the prognosis of cancer, although the functions and mechanisms of MDIG in liver cancer, especially in hepatocellular carcinoma (HCC), are still unknown. In this study, we report that MDIG and MYC were negatively regulated by IKZF1. MDIG overexpression substantially promoted HCC cell proliferation, cell migration and spreading, whereas knockdown of MDIG would reverse above-mentioned effect. MDIG effects on tumour cell growth were further demonstrated in a tumour xenograft model. Moreover, MDIG had effects on the level of p21(CIP1/WAF1) via H3K9me3 expression in HCC. MDIG was also found to be closely related to the sorafenib resistance of HCC cells in vitro. Clinically, we found that MDIG was frequently overexpressed in human HCCs (69.7%; n=155) and was significantly associated with histological grade and hepatitis B virus infection. Our findings indicate that MDIG plays an important role in HCC progression via MDIG/H3K9me3/p21(CIP1/WAF1) signalling and serves as a potential therapeutic target.


Assuntos
Carcinoma Hepatocelular/patologia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Histonas/metabolismo , Fator de Transcrição Ikaros/metabolismo , Neoplasias Hepáticas/patologia , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Animais , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Dioxigenases , Progressão da Doença , Histona Desmetilases , Humanos , Fator de Transcrição Ikaros/antagonistas & inibidores , Fator de Transcrição Ikaros/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Metilação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Compostos de Fenilureia/uso terapêutico , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-myc/genética , Transdução de Sinais , Sorafenibe , Transplante Heterólogo
6.
Carcinogenesis ; 38(2): 207-217, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27993894

RESUMO

Increasing evidence has shown that zinc-alpha2-glycoprotein (AZGP1) is associated with the progression and prognosis of several tumor types. However, little is known regarding the underlying molecular mechanisms of AZGP1 in hepatocellular carcinoma (HCC). In this study, we report that transcription factor Ikaros bound to the AZGP1 promoter and increased its expression in HCC cells. The downregulation of AZGP1 was associated with histone deacetylation in HCC. In addition, the positive feedback regulation via acetylation of histone H4-mediated transactivation of the Ikaros promoter and the Ikaros-mediated transactivation of the acetylation of histone H4 were crucial for regulating AZGP1 expression in HCC cells. Moreover, low serum AZGP1 level in HCC patients was associated with poor prognosis. The ectopic overexpression of AZGP1 or recombinant AZGP1 protein inhibited HCC cell proliferation, migration and invasion in vitro and in vivo, whereas silencing AZGP1 expression resulted in increased cell proliferation, migration and invasion in vitro. In addition, we found that AZGP1 inhibited cell migration and invasion through the regulation of the PTEN/Akt and CD44s pathways. Collectively, our findings revealed the molecular mechanism of AZGP1 expression in HCC, providing new insights into the mechanisms underlying tumor progression.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Transporte/biossíntese , Transição Epitelial-Mesenquimal/genética , Glicoproteínas/biossíntese , Neoplasias Hepáticas/genética , Adipocinas , Animais , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/genética , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/genética , Histona Desacetilases/genética , Humanos , Receptores de Hialuronatos/genética , Fator de Transcrição Ikaros/genética , Neoplasias Hepáticas/patologia , Camundongos , Proteína Oncogênica v-akt/genética , PTEN Fosfo-Hidrolase/genética , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Oncotarget ; 7(28): 43534-43545, 2016 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-27259277

RESUMO

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and the mechanisms underlying the development of HCC remain to be elucidated. Forkhead box N3 (FOXN3) is an important member of the FOX family of transcription factors that plays an essential role in several cancers but has not been investigated in HCC. In this study, we demonstrate that FOXN3 is downregulated in human primary HCC tissues compared with their matched adjacent liver tissues. Functional tests of FOXN3 demonstrated that FOXN3 inhibits the proliferation of HCC cells in vitro and in vivo. Additionally, FOXN3 repressed the mRNA and protein expression of E2F5, a reported potential oncogene, by inhibiting the promoter activity of E2F5. Collectively, our findings indicate that FOXN3 functions as a tumor suppressor in HCC by downregulating the expression of E2F5.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/genética , Fator de Transcrição E2F5/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Proteínas Repressoras/metabolismo , Animais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Regulação para Baixo , Fatores de Transcrição Forkhead , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oncogenes , Prognóstico , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Artigo em Inglês | MEDLINE | ID: mdl-27236205

RESUMO

By utilizing the hydrothermal in situ acylation of organic acids with N2H4, three acylhydrazidate-coordinated compounds [Mn(L1)2(H2O)2] (L1=2,3-quinolinedicarboxylhydrazidate; HL1=2,3-dihydropyridazino[4,5-b] quinoline-1,4-dione) 1, [Mn2(ox)(L2)2(H2O)6]·2H2O (L2=benzimidazolate-5,6-dicarboxylhydrazide; HL2=6,7-dihydro-1H-imidazo[4,5-g]phthalazine-5,8-dione; ox=oxalate) 2, and [Cd(HL3)(bpy)] (L3=4,5-di(3'-carboxylphenyl)phthalhydrazidate; H3L3=6,7-dihydro-1H-imidazo[4,5-g]phthalazine-5,8-dione; bpy=2,2'-bipyridine) 3, as well as two acylhydrazide molecules L4 (L4=oxepino[2,3,4-de:7,6,5-d'e']diphthalazine-4,10(5H,9H)-dione) 4 and L5 (L5=4,5-dibromophthalhydrazide; L5=6,7-dibromo-2,3-dihydrophthalazine-1,4-dione) 5 were obtained. X-ray single-crystal diffraction analysis reveals that (i) 1 only possesses a mononuclear structure, but it self-assembles into a 2-D supramolecular network via the NhydrazineH⋯Nhydrazine and OwH⋯Ohydroxylimino interactions; (ii) 2 exhibits a dinuclear structure. Ox acts as the linker, while L2 just serves as a terminal ligand; (iii) In 3, L3 acts as a 3-connected node to propagate the 7-coordinated Cd(2+) centers into a 1-D double-chain structure; (iv) 4 is a special acylhydrazide molecule. Two OH groups for the intermediates 3,3'-biphthalhydrazide further lose one water molecule to form 4; (v) 5 is a common monoacylhydrazide molecule. Via the NhydrazineH⋯Ohydrazine, OhydroxyliminoH⋯Oacylamino and the π⋯π interactions, it self-assembles into a 2-D supramolecular network. The photoluminescence analysis reveals that 4 emits light with the maxima at 510nm.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 161: 138-43, 2016 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-26971022

RESUMO

A new 3-D Zn(2+) coordination polymer (CP) [(CH3)2NH2]3[Zn6(ox)4.5(trz)6]⋅4H2O (ox=oxalate; trz=1,2,4-triazolate) 1 was obtained by a simple solvothermal self-assembly. The crystal structural analysis demonstrates that the trz molecules link the Zn(2+) ions into a two-dimensional (2-D) layer network, which is based on the trinuclear Zn3(trz)6 clusters. The ox molecules serve as the linkers to propagate the 2-D layers into a three-dimensional (3-D) network of 1. The thermogravimetry (TG) behavior, photoluminescence property, and the sensing ability of 1 are investigated. The sensing experiment on nitrobenzene (NB) reveals that 1 can serve as a fluorescence probe to detect NB at the ppm concentration.

10.
Sci Rep ; 6: 22412, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26926099

RESUMO

Functional molecules synthesized by self-assembly between inorganic salts and amino acids have attracted much attention in recent years. A simple method is reported here for fabricating hybrid organic-inorganic nanoflowers using copper (II) ions as the inorganic component and natural amino acids as the organic component. The results indicate that the interactions between amino acid and copper ions cause the growth of the nanoflowers composed by C, N, Cu, P and O elements. The Cu ions and Cu(AA)n complexes containing Cu-O bond are present in the nanoflowers. The nanoflowers have flower-like porous structure dominated by the R groups of amino acids with high surface-to-volume ratios, which is beneficial for exerting its peroxidase-like activity depending on Fenton-like reaction mechanism with ABTS and Rhodamine B as the substrates. It is expected that the nanoflowers hold great promise as enzyme mimics for application in the field of biosensor, bioanalysis and biocatalysis.


Assuntos
Aminoácidos/química , Biocatálise , Cobre/química , Nanoestruturas/química , Peroxidases/metabolismo , Técnicas Biossensoriais
11.
Dalton Trans ; 45(6): 2562-73, 2016 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-26727614

RESUMO

Five new organic-inorganic hybrid compounds based on different polyoxoanions [HxGeW12O40](n-) or [H3As2W18O62](3-) (x = 0, 2; n = 4, 2), namely [Cu3(2,2'-bpy)3(inic)(OH)(H2O)][GeW12O40]·1.5H2O (1), [Cu2(phen)2(µ2-Cl)2(inic)]2[H2GeW12O40]·2H2O (2), [Cu2(phen)2(µ2-Cl)Cl(nic)]2[H2GeW12O40] (3), [Cu2(2,2'-bpy)2(hnic)Cl]2[H2GeW12O40] (4), [Cu(phen)(inic)H2O][Cu2(phen)2(inic)2(H2O)][H3As2W18O62]·3H2O (5) (inic = isonicotinic acid, nic = nicotinic acid, hnic = 2-hydroxy-nicotinic acid, 2,2'-bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline), have been synthesized and characterized by IR, UV-Vis, XRD, cyclic voltammetric measurements and single crystal X-ray diffraction analysis. Single crystal X-ray analysis reveals that compound 1 is isomorphous and isostructural with a compound reported by us recently, the main difference between the two is the heteroatom of the polyoxoanions in the two compounds. Compound 2 is a supramolecular structure constructed from polyoxoanions and transition metal mixed-organic-ligand complexes. Compound 3 is a novel polyoxoanion bi-supported transition metal mixed-organic-ligand complex. Compound 4 is a 1-D chain structure constructed from polyoxoanions and transition metal mixed-organic-ligand complexes. The photodegradation properties of compounds 1-5 have been analyzed.

12.
Dalton Trans ; 44(33): 14830-41, 2015 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-26223513

RESUMO

Six new organic-inorganic hybrid compounds based on [XM12O40](4-) (X = heteroatom, M = metal atom), namely [Cu(pic)2][H2XM12O40]·2Hapy·2apy (X = Si, M = W for , X = Ge, M = W for and X = Si, M = Mo for ), [Cu(2,2'-bpy)2][Cu(2,2'-bpy)(H2O)][Cu(pic)2]0.5[XM12O40]·nH2O (X = Si, M = Mo, n = 0.5 for , X = Ge, M = W, n = 1 for ) and [Cu(phen)(H2O)]2[Cu(pic)2][GeW12O40]·2.5H2O () (pic = deprotonated picolinic acid, apy = 2-aminopyridine, 2,2'-bpy = 2,2'-bipyridine, phen = phenanthroline), have been synthesized and characterized by IR, UV-Vis, XRD, cyclic voltammetric measurements and single crystal X-ray diffraction analysis. Single crystal X-ray analysis reveals that compounds are isomorphous and isostructural, in which each is based on [H2XM12O40](2-) and [Cu(pic)2]. Compounds and are also isomorphous and isostructural, of which the structures are more interesting than those of compounds . Both structures are constructed from [XM12O40](4-) and metal mixed-organic-ligand complexes. Compound is also constructed from Keggin ions and metal mixed-organic-ligand complexes, which are, however, thoroughly different from those of compounds and . The photodegradation properties of compounds have been analyzed. Compounds also exhibit rapid absorption properties for RhB (Rhodamine B). Detailed analysis of the photodegradation properties of compounds reveals that the molybdate POM has stronger degradation ability for RhB than the tungstate one.


Assuntos
Compostos de Tungstênio/química , 2,2'-Dipiridil/química , Aminopiridinas/química , Corantes/isolamento & purificação , Cristalografia por Raios X , Ligantes , Modelos Moleculares , Molibdênio/química , Fenantrolinas/química , Fotólise , Ácidos Picolínicos/química , Rodaminas/isolamento & purificação
13.
Chem Biol Drug Des ; 86(6): 1548-53, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26216620

RESUMO

The facile synthesis of core-shell magnetic mesoporous silica nanoparticles (Fe3 O4 @mSiO2 NPs) was reported in aqueous phase using cetyltrimethylammonium bromide as a template under alcohol-free conditions. Compared to the conventional synthesis method for core-shell Fe3 O4 @mSiO2 NPs, the approach in this study is rapid (only 5-min reaction time), cheap (without using organic agents), and environmentally friendly (one-step synthesis in alcohol-free medium). Doxorubicin (DOX)-loaded Fe3 O4 @mSiO2 NPs exert extraordinarily high specificity for liver cancer cells, which was due to the pH-sensitive doxorubicin release, as well as higher endocytosis capacity in liver cancer cells rather than normal liver cells. The potential advantages of using such Fe3 O4 @mSiO2 NPs as the vehicle of anticancer drugs were that the Fe3 O4 @mSiO2 NPs exhibit good biocompatibility, high loading and protection of the guest molecules, selective killing effect, and efficient cellular uptake. The exciting pH-dependent release properties of doxorubicin-loaded Fe3 O4 @mSiO2 NPs make their use a promising strategy for enhancing efficient therapy toward tumors, while reducing the cytotoxicity of doxorubicin to human normal neutral tissue or cells.


Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas de Magnetita/química , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Sistemas de Liberação de Medicamentos , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Nanopartículas de Magnetita/ultraestrutura , Microscopia Eletrônica de Transmissão , Nanoconchas/química , Nanoconchas/ultraestrutura , Dióxido de Silício
14.
Dalton Trans ; 44(19): 8971-83, 2015 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-25882351

RESUMO

Five new organic­inorganic hybrid compounds based on the Keggin-type polyoxoanion [SiW12O40]4−, namely [Cu3(2,2'-bpy)3(inic)(µ2-OH)(H2O)][SiW12O40]·2H2O (1), [Cu6(phen)6(µ3-Cl)2(µ2-Cl)2Cl2(inic)2][SiW12O40]·6H2O (2), [Cu2(hnic)(2,2'-bpy)2Cl]2[H2SiW12O40] (3), [Cu2(nic)(phen)2Cl2]2[SiW12O40] (4) and [Cu2(pic)(2,2'-bpy)2Cl]2[SiW12O40] (5) (inic = isonicotinic acid, hnic = 2-hydroxy-nicotinic acid, nic = nicotinic acid, pic = picolinic acid, 2,2'-bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline) have been synthesized and characterized by IR, UV-Vis, XPS, XRD, cyclic voltammetric measurements, photoluminescence analysis and single crystal X-ray diffraction analysis. Crystal analysis reveals that compound 1 exhibits a 2-D double layered framework structure constructed from [SiW12O40]4− and copper-aqua-2,2'-bipy-hydroxyl-isonicotinate complexes. Compound 2 is a 0-D discrete structure formed by [SiW12O40]4− and copper-chloro-isonicotinate-phenanthroline complexes. Compound 3 shows a 1-D single chain structure based on the linkage of copper-2,2-bpy-chloro-2-hydroxy-nicotinate complexes and [SiW12O40]4−. Compounds 4 and 5 both contain polyoxometalate supported transition metal complexes, one is a polyoxometalate supported copper-chloro-nicotinate-phenanthroline complex in 4, and the other is a polyoxometalate supported copper-2,2-bpy-chloro-nicotinate complex in 5. It should be noted that nicotinic, isonicotinic and picolinic acids are structural isomers and 2-hydroxy-nicotinic acid is an in situ hydroxylated product of nicotinic acid. In addition, photocatalytic degradation of Rhodamine B (RhB) by compounds 1­5 has been investigated in aqueous solutions.


Assuntos
Ácidos Carboxílicos/química , Compostos Organometálicos/química , Piridinas/química , Elementos de Transição/química , Compostos de Tungstênio/química , Cristalografia por Raios X , Ligantes , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química
15.
PLoS One ; 8(8): e71071, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23967153

RESUMO

The expression and function of P-glycoprotein (P-gp) is associated with the phenotype of multi-drug resistance (MDR), leading chemotherapy failure of patients suffered with cancer. Grape seed procyanidin(GSP) is a natural polyphenol supplement with anti-inflammatory effect. Present study assessed a new use of GSP on the MDR reversal activity and its possible molecular mechanisms in MDR1-overpressing paclitaxel resistant ovarian cancer cells. Our results showed GSP significantly enhanced the cytotoxicity of paclitaxel and adriamycin in paclitaxel resistant A2780/T cells but its parental A2780 cells. Furthermore, GSP strongly inhibited P-gp expression by blocking MDR1 gene transcription, as well as, increased the intracellular accumulation of the P-gp substrate rhodamine-123 in A2780/T cells. Nuclear factor-κB(NF-κB) activity, IκB degradation level and NF-κB/p65 nuclear translocation induced by lipopolysaccharide (LPS) and receptor activator for nuclear factor-κB ligand (RANKL) were markedly inhibited by pre-treatment with GSP. Meanwhile, GSP inhibited MAPK/ERK pathway by decreasing the phosphorylation of ERK1/2, resulting in reduced the Y-box binding protein 1 (YB-1) activation with blocking its nuclear translocation. Moreover, the up-regulation of P-gp expression, the activation of AKT/NF-κB and MAPK/ERK pathway induced by LPS was attenuated by GSP administration. Compared with PDTC and U1026, inhibitor of NF-κB and MAPK/ERK respectively, GSP showed the same tendency of down-regulating NF-κB and MAPK/ERK mediated YB-1 activities. Thus, GSP reverses P-gp associated MDR by inhibiting the function and expression of P-gp through down-regulation of NF-κB activity and MAPK/ERK pathway mediated YB-1 nuclear translocation, offering insight into the mechanism of reversing MDR by natural polyphenol supplement compounds. GSP could be a new potential MDR reversal agent used for combination therapy with chemotherapeutics in clinic.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Biflavonoides/farmacologia , Catequina/farmacologia , Resistência a Múltiplos Medicamentos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Proantocianidinas/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Proteína 1 de Ligação a Y-Box/metabolismo , Linhagem Celular , Núcleo Celular/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Paclitaxel/farmacologia , Paclitaxel/toxicidade , Transporte Proteico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Rodamina 123/metabolismo , Sementes/química , Vitis/química
16.
Zhonghua Zhong Liu Za Zhi ; 33(6): 421-5, 2011 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-21875481

RESUMO

OBJECTIVE: To investigate the expression variation and significance of ERK1/2 MAPK signaling transduction pathway in the pathogenesis of esophageal squamous cell carcinoma (ESCC) in Kazakh patients. METHODS: The expression level of p-ERK1/2 after serum starvation and treatment with U0126 inhibitor was detected in esophageal cancer cell line EC9706 by Western blot assay. The mRNA level of total ERK1/2 (t-ERK1/2) and expression level of t-ERK1/2 and p-ERK1/2 proteins of 25 pairs of ESCC and adjacent normal esophageal mucosal tissues of Kazakh patients were examined and identified by real-time quantitative PCR (qRT-PCR) and Western blotting, respectively. The expression of p-ERK1/2 protein was verified by immunohistochemistry in 126 paraffin-embeded specimens, including 19 normal esophageal mucosa, 55 esophageal carcinomas in situ and 52 invasive carcinomas. RESULTS: ERK1/2 MAPK signaling transduction pathway was in an active status in the EC9706 cells. The expression level of p-ERK1/2 in Ec9706 cells reached a peak at 10 min after transient serum stimulation, and p-ERK1/2 expression was totally restrained after the treatment with 50 µmol/L U0126. In the 25 pairs of ESCC and adjacent normal mucosa, the t-ERK1 mRNA level was 1.92 ± 3.49 in the ESCC tissues and 3.67 ± 7.47 in the adjacent normal mucosa. The t-ERK1 mRNA level in ESCC tissues was significantly lower than that in adjacent normal mucosa (P < 0.05), whereas there was no significant difference of t-ERK2 mRNA level between them(P > 0.05). The expression levels of p-ERK1 and p-ERK2 proteins were 0.87 ± 0.14 and 0.79 ± 0.10 in the ESCC tissues, and 1.10 ± 0.13 and 1.32 ± 0.12 in the adjacent normal mucosae. p-ERK1/2 protein in the ESCC tissues was significantly lower than that in the adjacent normal tissue (P < 0.01). However, there was no significant difference between their t-ERK1/2 protein levels (P > 0.05). In the 126 cases of paraffin-embeded specimens, positive expressions of both p-ERK1 and p-ERK2 in esophageal cancer tissues were 7.7% (4/52), significantly lower than those in adjacent normal mucosa (31.6%, 6/19) and carcinoma in situ (85.5%, 47/55, P < 0.05). CONCLUSIONS: ERK1/2 MAPK signaling pathway is in an active status in esophageal cancer and adjacent normal mucosa. Our results imply that the activation of p-ERK1/2 MAPK signaling transduction pathway plays a role in the early pathogenesis of ESCC in Kazakh patients.


Assuntos
Carcinoma de Células Escamosas/enzimologia , Neoplasias Esofágicas/enzimologia , Sistema de Sinalização das MAP Quinases , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Butadienos/farmacologia , Carcinoma in Situ/enzimologia , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , China/etnologia , Inibidores Enzimáticos/farmacologia , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Nitrilas/farmacologia , Fosforilação , RNA Mensageiro/metabolismo
17.
Mol Biol Rep ; 38(2): 865-72, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20464500

RESUMO

While there have been more and more studies concerning mitogen-activated protein kinases (MAPKs) signaling pathways, which control many cellular complex programmes, such as cell proliferation, differentiation, cell death and embryogenesis. However, few studies are carried out about expression and activation of classical MAPKs, extracellular signal-regulated kinase1/2 (ERK1/2) in human esophageal cancer cell line. Therefore, in the present study, we investigated the expression and activation of ERK1/2 in human esophageal cancer cell line EC9706 and human normal esophageal epithelial cell line Heepic, which is as control. This study showed that ERK1/2 was transiently phosphorylated both in EC9706 and Heepic, the kinetics of which were slightly different. To further study the ERK/MAPK signaling pathway in EC9706 and Heepic cell line, U0126 a kind of specific inhibitor of MEK was used. This study showed that U0126 can block the phosphorylation of ERK1/2 in a short time, the complete inhibition concentration for EC9706 and Heepic cell line is 50 and 20 µM, respectively. Incidentally, to further investigate the different roles of ERK1 and ERK2, vector-based short hairpin interference vectors targeted on ERK1/2 was constructed. Moreover, the effective interference target sequence was screened out in a transient transfection manner. MTT experiment showed that ERK2 is more important than ERK1 in the proliferation of EC9706 cells.


Assuntos
Neoplasias Esofágicas/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequência de Bases , Butadienos/farmacologia , Relação Dose-Resposta a Droga , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Perfilação da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases , Dados de Sequência Molecular , Nitrilas/farmacologia , Fosforilação , Transdução de Sinais
18.
Chem Commun (Camb) ; 47(4): 1225-7, 2011 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-21103584

RESUMO

Novel multifunctional magnetic-mesoporous Janus particles with controlled aspect ratio were developed by a simple one-step synthesis approach. Due to their superior magnetic properties and well-defined pore structures, these particles will be important in drug delivery, molecule targeting, cellular imaging, and as building blocks for the assembly of complex nanostructures.

19.
J Recept Signal Transduct Res ; 30(3): 170-7, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20415541

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma is one of the most common digestive tract cancers with 5-year survival rate less than 10% owing to its poor prognosis. Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway has been mainly involved in the pathogenesis of various cancers. In present study, we investigated the role of ERK2 in human esophageal cancer cell line Eca109. METHODS: Short-hairpin RNA (shRNA) interference vector targeted ERK2 was constructed using pGeneclip U1 hairpin cloning systems, then transfected into Eca109 cell line. The transfection efficiency was observed by fluorescence microscope and cell growth after transfection with shRNA-ERK2 vector was determined by methylthiazolyl blue tetrazolium (MTT) assay. The ERK2 expression after transfection was detected by western-blotting. The cell apoptosis and cell-cycle was analyzed by flow cytometry. The role of p-ERK2 was confirmed by immunohistochemistry and soft agar colony formation assay. RESULTS: The growth of Eca109 transfected with shRNA-ERK2 vector was obviously inhibited compared to control group via MTT analysis. The inhibition rate after transfection with shRNA-ERK2 for 96 h was 10.45%, the expression of ERK2 was obviously reduced compared to the control analyzed by western-blot, cell apoptosis was 9.7% (compared to control, P < 0.05), and cell-cycle was arrested at G1 phase. CONCLUSIONS: In present study we demonstrated for the first time that transfection with shRNA-ERK2 targeted ERK2 into Eca109 cells can inhibit growth of Eca109, inducing cell apoptosis and influencing cell-cycle. Together, these results we obtained suggested that ERK2 plays an important role in cell growth of Eca109.


Assuntos
Neoplasias Esofágicas/enzimologia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , MAP Quinase Quinase 2/metabolismo , Interferência de RNA , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Citometria de Fluxo/métodos , Humanos , Microscopia de Fluorescência/métodos , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Sais de Tetrazólio/farmacologia , Tiazóis/farmacologia , Transfecção
20.
Zhong Yao Cai ; 32(10): 1560-3, 2009 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-20112721

RESUMO

OBJECTIVE: To study the effects of Qing-Xuan tablets (QXT) on behavior pattern and striatal TNF-alpha in mice model of Parkinson's disease (PD). METHODS: The PD models were established by intraperitoneal injection of MPTP (30 mg/kg). 30 C57BL/6J mice were randomly divided into six groups: control group, PD model group, QXT high dosage group, QXT middle dosage group, QXT low dosage group and trihexyphenidyl hydrochloride group. After 7 days of treatment, the behavior pattern of mice were observed, and striatum were seperated to detect the content of TNF-alpha by ELISA. RESULTS: QXT increased the behavior of mice in behavioral tests (open field, pole test, grid test) (P<0.05 or P<0.01) but depressed TNF-alpha activity in striatum (P<0.05). CONCLUSION: QXT can significantly enhance the behavioral activity of mice,and depress TNF-alpha content in striatum,which suggest QXT can effectively relieve the symptom of PD.


Assuntos
Comportamento Animal/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson Secundária/prevenção & controle , Fator de Necrose Tumoral alfa/biossíntese , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , Animais , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/metabolismo , Doença de Parkinson Secundária/fisiopatologia , Plantas Medicinais/química , Distribuição Aleatória
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