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1.
World J Gastroenterol ; 27(28): 4667-4686, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34366628

RESUMO

BACKGROUND: Sorafenib is the first-line treatment for patients with advanced hepatocellular carcinoma (HCC). Y-box binding protein 1 (YB-1) is closely correlated with tumors and drug resistance. However, the relationship between YB-1 and sorafenib resistance and the underlying mechanism in HCC remain unknown. AIM: To explore the role and related mechanisms of YB-1 in mediating sorafenib resistance in HCC. METHODS: The protein expression levels of YB-1 were assessed in human HCC tissues and adjacent nontumor tissues. Next, we constructed YB-1 overexpression and knockdown hepatocarcinoma cell lines with lentiviruses and stimulated these cell lines with different concentrations of sorafenib. Then, we detected the proliferation and apoptosis in these cells by terminal deoxynucleotidyl transferase dUTP nick end labeling, flow cytometry and Western blotting assays. We also constructed a xenograft tumor model to explore the effect of YB-1 on the efficacy of sorafenib in vivo. Moreover, we studied and verified the specific molecular mechanism of YB-1 mediating sorafenib resistance in hepatoma cells by digital gene expression sequencing (DGE-seq). RESULTS: YB-1 protein levels were found to be higher in HCC tissues than in corresponding nontumor tissues. YB-1 suppressed the effect of sorafenib on cell proliferation and apoptosis. Consistently, the efficacy of sorafenib in vivo was enhanced after YB-1 was knocked down. Furthermore, KEGG pathway enrichment analysis of DGE-seq demonstrated that the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was essential for the sorafenib resistance induced by YB-1. Subsequently, YB-1 interacted with two key proteins of the PI3K/Akt signaling pathway (Akt1 and PIK3R1) as shown by searching the BioGRID and HitPredict websites. Finally, YB-1 suppressed the inactivation of the PI3K/Akt signaling pathway induced by sorafenib, and the blockade of the PI3K/Akt signaling pathway by LY294002 mitigated YB-1-induced sorafenib resistance. CONCLUSION: Overall, we concluded that YB-1 augments sorafenib resistance through the PI3K/Akt signaling pathway in HCC and suggest that YB-1 is a key drug resistance-related gene, which is of great significance for the application of sorafenib in advanced-stage HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Proteínas de Transporte , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Sorafenibe/farmacologia , Proteína 1 de Ligação a Y-Box
2.
Clin Exp Med ; 21(3): 479-492, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33677646

RESUMO

REC8 is a member of the cohesin family, and its abnormal activation has been detected in cancer cells. This study explored the role and possible mechanism of REC8 in hepatocellular carcinoma (HCC). A total of 40 pairs of HCC and adjacent tissues were collected, and the clinical significance of REC8 expression in HCC was evaluated. REC8 expression in human HCC tissues and HCC cell lines was investigated by quantitative real-time PCR, Western blotting, immunohistochemistry and immunofluorescence staining. The biological functions of REC8 in HCC cell lines were detected by wound-healing assay, Matrigel invasion assay and tube formation assay. The proteins interacting with REC8 were identified by mass spectrometry after immunoprecipitation screening. There was a correlation between the high expression of REC8 and positive alpha-fetoprotein levels. The expression level of REC8 protein in HCC tissues was higher than that in adjacent tissues. REC8 has mainly located in the nucleus of HCC tissue cells and HCC cell lines, but it was expressed in the cytoplasm of adjacent normal tissue cells and hepatocytes. The results of wound healing, transwell invasion and tubular formation assays indicated that the overexpression of REC8 accelerated the metastasis of HCC in vitro; however, metastasis was suppressed after REC8 was silenced by small interference RNA. A total of 57 differentially expressed proteins were identified by mass spectrometry, and it was found that REC8 and PKA RII-α staining was colocalized in the nucleus. The expression levels of MMP-9 and VEGF-C were decreased after treatment with the PKA inhibitor H89. Overall, REC8 promotes the migration, invasion and angiogenesis of HCC cells through the PKA pathway.

3.
Ying Yong Sheng Tai Xue Bao ; 31(4): 1341-1348, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32530210

RESUMO

To investigate the characteristics of heavy metal pollution caused by traffic and its potential ecological risks, we measured the amount of metal elements in samples collected from a traffic trunk road in Lanzhou City with atomic absorption spectrophotometer. The single factor index method and potential ecological risk index method were used to evaluate the degree of pollution and potential ecological risks, and then the effects of heavy metal pollution on chlorophyll and calcium (Ca) contents in greening plants were analyzed. The results showed that the amount of heavy metals including chromium (Cr), manganese (Mn), zinc (Zn), copper (Cu) and nickel (Ni) in the soils increased significantly, with Cr, Cu and Pb reaching moderate pollution level. The degree of potential ecological risk was Cu>Pb>Cr>Ni>Zn>Mn. Sophora japonica, Rosa chinesis, Prunus ceraifera, and Euonymus japonicas showed different accumulation effects on Pb, Mn, Zn, and Ni. The content of chlorophyll in the leaves of deciduous species S. japonica, R. chinesis and P. ceraifera was higher in the roadside sampling point than that in the control point, while the pattern was just the opposite in evergreen species E. japonicas and P. orientalis. Foliar Ca content of greening plants in the roadside sampling point was higher than that in the control point, suggesting that high chlorophyll and Ca contents might be beneficial to plant survival in the heavy metal contaminated area. Taken together, traffic operation led to the accumulation of heavy metals (Cr, Mn, Zn, Cu, and Ni) in the soil of the study area. S. japonica, R. chinesis, P. ceraifera and E. japonicas could accumulate Pb, Mn, Zn and Ni, which could be used as greening plants in soils polluted by those heavy metals.


Assuntos
Metais Pesados , Poluentes do Solo , China , Cidades , Monitoramento Ambiental , Medição de Risco , Solo
4.
Dalton Trans ; 49(11): 3408-3412, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32129387

RESUMO

A series of host-guest materials containing polyoxometalate anions and lanthanide-organic layers have been synthesized and structurally characterized. By anion-π interactions between the anions and the π-acidic naphthalenediimide moieties, the materials emit strong red room-temperature phosphorescence and exhibit reversible photochromism.

5.
Ther Adv Neurol Disord ; 13: 1756286420902664, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32071616

RESUMO

Background: Cerebral cavernous malformation (CCM), especially the familial form, is a relatively rare congenital and occult vascular disease of the central nervous system. The familial form of CCM has been linked to three different genes: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3; however, the genetic basis of CCM is not well understood. The PDCD10/CCM3 is the most recent gene to be identified that results in worse clinical symptoms. Early diagnosis and treatment is important for patient prognosis. Case report: The proband is a 38-year-old male who has been suffering from weakness in the limbs for 7 months. Investigation of his family history revealed that his mother also suffered from limbs paralysis and had been bedridden for a long time. His older brother suffered from headache for years, whereas his younger brother was asymptomatic. Brain computed tomography analysis of all family members showed multiple high-density shadows. Subsequently, magnetic resonance imaging analysis identified more prominent and similar multiple intracranial lesions in all family members. The lesions were hypo-intense, or showed mixed signs on T1-weighted imaging, and were significantly more intense on T2-weighted imaging. To understand the genetic basis of the disease in the family, DNA sequencing analysis was performed. A novel deletion mutation in the PDCD10/CCM3 gene was identified in the proband and his relatives. The deletion resulted in a frameshift mutation and premature termination of translation of the protein, and potentially caused the disease in this family. Conclusions: Our study identified a novel PDCD10/CCM3 heterozygous deletion (c.165delT) associated with CCM. This finding expands the CCM gene mutation profile, which will be beneficial for genetic counseling and clinical therapy.

6.
Exp Cell Res ; 389(2): 111855, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31978385

RESUMO

Takeda-G-protein-receptor-5 (TGR5) is a G-protein-coupled receptor (GPCR) activated by bile acids, and mortalin is a multipotent chaperone of the HSP70 family. In the present study, TGR5 was detected by immunohistochemistry (IHC) in extrahepatic cholangiocarcinoma (ECC) specimens, and TGR5 expression in ECC tissues and adjacent tissues was compared. In vitro TGR5 was overexpressed and knocked down in human intrahepatic cholangiocarcinoma (ICC) cell line RBE and human extrahepatic cholangiocarcinoma (ECC) cell line QBC-939 to observe its effects on the biological behavior of cholangiocarcinoma (CC) cells, including proliferation, apoptosis and migration. In vivo xenograft model was constructed to explore the role of TGR5 in CC growth. Proteins that interacted with TGR5 were screened using an immunoprecipitation spectrometry approach, and the identified protein was down-regulated to investigate its contribution to CC growth. The present study demonstrated that TGR5 is highly expressed in CC tissues, and strong TGR5 expression may indicate high malignancy in CC. Furthermore, TGR5 promotes CC cell proliferation, migration, and apoptosis resistance. TGR5 boosts CC growth in vivo. In addition, TGR5 combines with mortalin and regulates mortalin expression in the CC cell line. Mortalin participates in the TGR5-induced increase in CC cell proliferation. In conclusion, TGR5 is of clinical significance based on its implications for the degree of malignancy in patients with CC. Mortalin may be a downstream component regulated by TGR5, and TGR5 promotes cholangiocarcinoma at least partially by interacting with mortalin and upregulating its expression. Both TGR5 and mortalin are positive regulators, and may serve as potential therapeutic targets for CC.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/patologia , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas Mitocondriais/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Apoptose , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Biomarcadores Tumorais/genética , Proliferação de Células , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico HSP70/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Prognóstico , Domínios e Motivos de Interação entre Proteínas , Receptores Acoplados a Proteínas G/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Oncol Rep ; 42(1): 263-272, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115555

RESUMO

Piwi­interacting RNAs (piRNAs), a novel class of non­coding RNAs, are enriched in germ cells and implicated in spermatogenesis. Emerging evidence demonstrated deregulated expression of piRNAs in numerous tumor types. However, changes in piRNA expression profiles in colorectal cancer (CRC) have not yet been investigated. In the present study, small RNA sequencing was used to evaluate the differences in piRNA expression profiles between CRC and adjacent non­tumor tissues, as well as to screen for differentially expressed piRNAs. The present results demonstrated that the percentage of unique piRNA reads had no notable difference between the paired CRC and adjacent non­tumor samples (0.12% vs. 0.13%); however, the counts of total piRNA reads in CRC samples were increased, compared with those in adjacent non­tumor samples (0.15% vs. 0.07%). Differential expression analysis identified 33 upregulated piRNAs and 2 downregulated piRNAs in CRC samples, among which piR­18849, piR­19521 and piR­17724 were the top three upregulated piRNAs. Reverse transcription­quantitative polymerase chain reaction further confirmed that the expression levels of piR­18849, piR­19521 and piR­17724 were increased in 80 CRC tissues, compared with paired adjacent non­tumor tissues. Furthermore, the high expression of piR­18849 and piR­19521 was associated with a poor degree of differentiation. The increased expression of piR­18849 was also associated with high lymph node metastasis. However, no associations were determined between piR­17724 expression and clinicopathological characteristics of patients. In summary, the present study is the first to provide an overview of the changes in piRNA expression patterns in CRC, shedding new light on the regulatory roles of piRNAs in colorectal carcinogenesis. piR­18849 and piR­19521 may be prognostic biomarkers for patients with CRC.


Assuntos
Neoplasias Colorretais/genética , Perfilação da Expressão Gênica/métodos , RNA Interferente Pequeno/genética , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sequência de RNA/métodos
8.
Exp Mol Med ; 51(1): 1-13, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30635551

RESUMO

The clearance of activated hepatic stellate cells (HSCs) by apoptosis is critical for the reversibility of hepatic fibrosis. Mitochondrial homeostasis is regulated by mitophagy, which is an efficient way of clearing injured mitochondria that plays an important role in apoptosis. However, the role of mitophagy in apoptosis in HSCs and hepatic fibrosis is still unclear. Here, we show that mitophagy is enhanced in parallel with increased apoptosis in hepatic stellate cells during the reversal of hepatic fibrosis. The inhibition of mitophagy suppressed apoptosis in HSCs and aggravated hepatic fibrosis in mice. In contrast, the activation of mitophagy induced apoptosis in HSCs. Furthermore, we confirmed that BCL-B, which is a member of the BCL-2 family, is a regulator mediating mitophagy-related apoptosis. The knockdown of BCL-B resulted in increased apoptosis and mitophagy in HSCs, while the overexpression of BCL-B caused the opposite effects. BCL-B inhibited the phosphorylation of Parkin (a key regulator of mitophagy) and directly bound phospho-Parkin. Altogether, enhanced mitophagy promotes apoptosis in HSCs during the reversal of hepatic fibrosis. BCL-B suppresses mitophagy in HSCs by binding and suppressing phospho-Parkin, thereby inhibiting apoptosis. BCL-B-dependent mitophagy is a new pathway for the regulation of apoptosis in HSCs during the regression of hepatic fibrosis.


Assuntos
Apoptose , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , Mitofagia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Animais , Linhagem Celular , Células Cultivadas , Cirrose Hepática/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
9.
Small ; 14(14): e1703680, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29488317

RESUMO

Molybdenum ditelluride nanosheets encapsulated in few-layer graphene (MoTe2 /FLG) are synthesized by a simple heating method using Te and Mo powder and subsequent ball milling with graphite. The as-prepared MoTe2 /FLG nanocomposites as anode materials for lithium-ion batteries exhibit excellent electrochemical performance with a highly reversible capacity of 596.5 mAh g-1 at 100 mA g-1 , a high rate capability (334.5 mAh g-1 at 2 A g-1 ), and superior cycling stability (capacity retention of 99.5% over 400 cycles at 0.5 A g-1 ). Ex situ X-ray diffraction and transmission electron microscopy are used to explore the lithium storage mechanism of MoTe2 . Moreover, the electrochemical performance of a MoTe2 /FLG//0.35Li2 MnO3 ·0.65LiMn0.5 Ni0.5 O2 full cell is investigated, which displays a reversible capacity of 499 mAh g-1 (based on the MoTe2 /FLG mass) at 100 mA g-1 and a capacity retention of 78% over 50 cycles, suggesting the promising application of MoTe2 /FLG for lithium-ion storage. First-principles calculations exhibit that the lowest diffusion barrier (0.18 eV) for lithium ions along pathway III in the MoTe2 layered structure is beneficial for improving the Li intercalation/deintercalation property.

10.
Cancer Sci ; 108(9): 1746-1756, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28618124

RESUMO

Piwi-interacting RNAs (piRNAs), a novel class of small non-coding RNAs, were first discovered in germline cells and are thought to silence transposons in spermatogenesis. Recently, piRNAs have also been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. However, the function of piR-823 in colorectal cancer (CRC) remains unclear. Here, we first found that piR-823 was significantly upregulated in CRC tissues compared with its expression in the adjacent tissues. Inhibition of piR-823 suppressed cell proliferation, arrested the cell cycle in the G1 phase and induced cell apoptosis in CRC cell lines HCT116 and DLD-1, whereas overexpression of piR-823 promoted cell proliferation in normal colonic epithelial cell line FHC. Interestingly, Inhibition of piR-823 repressed the expression of heat shock protein (HSP) 27, 60, 70. Furthermore, elevated HSPs expression partially abolished the effect of piR-823 on cell proliferation and apoptosis. In addition, we further demonstrated that piR-823 increased the transcriptional activity of HSF1, the common transcription factor of HSPs, by binding to HSF1 and promoting its phosphorylation at Ser326. Our study reveals that piR-823 plays a tumor-promoting role by upregulating phosphorylation and transcriptional activity of HSF1 and suggests piR-823 as a potential therapeutic target for CRC.


Assuntos
Transformação Celular Neoplásica/metabolismo , Neoplasias Colorretais/metabolismo , Proteínas de Ligação a DNA/fisiologia , Regulação Neoplásica da Expressão Gênica , RNA Interferente Pequeno/fisiologia , Fatores de Transcrição/fisiologia , Apoptose , Proliferação de Células , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Células HCT116 , Fatores de Transcrição de Choque Térmico , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Ligação Proteica , Processamento de Proteína Pós-Traducional , Transcrição Genética , Ativação Transcricional , Regulação para Cima
11.
Artigo em Inglês | MEDLINE | ID: mdl-28182543

RESUMO

In this paper, an approach that incorporates a turbulence mechanism and a circular elimination strategy is presented to strengthen the performance of multi-objective particle swarm optimization (MOPSO). For convergence enhancement, the turbulence mechanism derived from bacteria quorum sensing behavior is introduced to MOPSO to preserve the swarm diversity. Meanwhile, the circular elimination strategy is used to select particles for next iteration for better distribution of the Pareto-optimal solutions. The improved MOPSO algorithm has been tested on a set of benchmark functions and compared with representative multi-objective optimization algorithms. Simulation results illustrate that the algorithm outperforms the other algorithms on convergence while keep good spread performance, and could be used as an effective global optimization tool.


Assuntos
Algoritmos , Fenômenos Fisiológicos Bacterianos , Biomimética/métodos , Interações Microbianas/fisiologia , Modelos Biológicos , Modelos Estatísticos , Percepção de Quorum/fisiologia , Simulação por Computador
12.
Nanomedicine ; 13(3): 999-1010, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27993727

RESUMO

Nanoparticle (NP) interactions with biological tissues are affected by the size, shape and surface chemistry of the NPs. Here we use in vivo (zebrafish) and in vitro (HUVEC) models to investigate association of quantum dots (QDs) with endothelial cells and the effect of fluid flow. After injection into the developing zebrafish, circulating QDs associate with endothelium and penetrate surrounding tissue parenchyma over time. Amino-functionalized QDs cluster, interact with cells, and clear more rapidly than carboxy-functionalized QDs in vivo, highlighting charge influences. QDs show stronger accumulation in slow-flowing, small caliber venous vessels than in fast-flowing high caliber arterial vessels. Parallel-plate flow experiments with HUVEC support these findings, showing reduced QD-EC association with increasing flow. In vivo, flow arrest after nanoparticle injection still results in venous accumulation at 18 h. Overall our results suggest that both QD charge and blood flow modulate particle-endothelial cell interactions.


Assuntos
Vasos Sanguíneos/fisiologia , Células Endoteliais/metabolismo , Pontos Quânticos/metabolismo , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/metabolismo , Resinas Acrílicas/toxicidade , Aminação , Animais , Velocidade do Fluxo Sanguíneo , Vasos Sanguíneos/efeitos dos fármacos , Ácidos Carboxílicos/administração & dosagem , Ácidos Carboxílicos/metabolismo , Ácidos Carboxílicos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/metabolismo , Polietilenoglicóis/toxicidade , Pontos Quânticos/administração & dosagem , Pontos Quânticos/toxicidade , Peixe-Zebra
13.
Mol Carcinog ; 56(3): 1137-1149, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27770580

RESUMO

BCL2L10 is an apoptosis-related member of the BCL-2 protein family. The role of BCL2L10 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. This study was aimed to investigate the function and underlying mechanisms of BCL2L10 in HCC. BCL2L10 expression in human HCC and corresponding adjacent normal tissues was investigated by quantitative real-time PCR and Western blot. The biological functions of BCL2L10 in HCC cell lines were determined by cell viability, colony formation, cell apoptosis, cell cycle, and cell metastasis assays, and in vivo by tumorigenicity and lung metastasis assays in nude mice. Human cancer pathway PCR array was employed to explore the genes regulated by BCL2L10 in HCC. BCL2L10 was down-regulated in human HCC tissues compared to their adjacent non-tumor tissues. Ectopic expression of BCL2L10 in HepG2 and Huh7 cells suppressed cell growth as evidenced by cell viability and colony formation assay, and induced cell apoptosis. HCC cells transfected with BCL2L10 revealed an increased cell proportion arrested at G2/M phase, concomitant with a reduction in the cell proportion in S-phase as compared with control cells. Additional, BCL2L10 repressed cell migration and angiogenesis. Over-expression of BCL2L10 also restrained the tumorigenecity and lung metastasis capacity in nude mice. The activation of JAK-STAT3 signaling was suppressed by BCL2L10 in HCC. BCL2L10 was down-regulated in human HCC tissues compared to adjacent normal tissues. BCL2L10 suppressed HCC progression through inhibiting cell growth and metastasis. Thus, BCL2L10 functions as a tumor-suppressor in HCC. © 2016 Wiley Periodicals, Inc.


Assuntos
Carcinoma Hepatocelular/patologia , Regulação para Baixo , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , Metástase Neoplásica , Transplante de Neoplasias , Transdução de Sinais
14.
Transl Res ; 182: 88-102, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28034761

RESUMO

Bile acids stimulate intestinal epithelial proliferation in vitro. We sought to investigate the role of the bile acid receptor TGR5 in the protection of intestinal epithelial proliferation in obstructive jaundice. Intestinal tissues and serum samples were obtained from patients with malignant obstructive jaundice and from bile duct ligation (BDL) rats. Intestinal permeability and morphological changes in the intestinal mucosa were observed. The functions of TGR5 in cell proliferation in intestinal epithelial injury were determined by overexpression or knockdown studies in Caco-2 and FHs 74 Int cells pretreated with lipopolysaccharide (LPS). Internal biliary drainage was superior to external biliary drainage in recovering intestinal permeability and mucosal histology in patients with obstructive jaundice. In BDL rats, feeding of chenodeoxycholic acid (CDCA) decreased intestinal mucosa injury. The levels of PCNA, a marker of proliferation, increased in response to CDCA feeding and were paralleled by elevated TGR5 expression. CDCA upregulated TGR5 expression and promoted proliferation in Caco-2 and FHs 74 Int cells pretreated with LPS. Overexpression of TGR5 resulted in increased PCNA, cell viability, EdU incorporation, and the proportion of cells in S phase, whereas knockdown of TGR5 had the opposite effect. Our data indicate that bile acids promote intestinal epithelial cell proliferation and decrease mucosal injury by upregulating TGR5 expression in obstructive jaundice.


Assuntos
Células Epiteliais/metabolismo , Células Epiteliais/patologia , Mucosa Intestinal/lesões , Mucosa Intestinal/metabolismo , Icterícia Obstrutiva/metabolismo , Icterícia Obstrutiva/patologia , Receptores Acoplados a Proteínas G/metabolismo , Idoso , Animais , Ductos Biliares/efeitos dos fármacos , Ductos Biliares/patologia , Biomarcadores/sangue , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Ácido Quenodesoxicólico/farmacologia , Células Epiteliais/efeitos dos fármacos , Feminino , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Icterícia Obstrutiva/sangue , Ligadura , Lipopolissacarídeos , Masculino , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
15.
Dig Dis Sci ; 61(9): 2522-34, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27146412

RESUMO

BACKGROUND/AIM: Obstructive jaundice (OJ) is frequently complicated by infections and has been associated with increased bacterial translocation, intestinal epithelial hyperpermeability, and oxidative stress, but the mechanism remains unclear. The potential effect of resveratrol (Res) on modifying intestinal epithelial dysfunction was evaluated both in vitro and in vivo. METHODS: Caco-2 cells (in vitro) and male Wistar rats (n = 60; in vivo) were used to evaluate the role of Res on intestinal epithelial dysfunction. Hydrogen peroxide was used to induce oxidative stress in the Caco-2 cells. In bile duct-ligated group, OJ was successfully established on Day 7 after bile duct ligation, whereas sham-operated and vehicle-treated rats served as controls. Western blot and RT-qPCR were performed to analyze TJ proteins expression in epithelium isolated from rat intestine. RESULTS: Intestinal hyperpermeability was associated with decreased expression and phosphorylation of occludin and zonula occluden (ZO-1), but increased oxidation in Caco-2 cells and the intestinal epithelium. Res treatment increased the epithelial expression and phosphorylation of occludin and ZO-1 in a concentration-dependent manner. Moreover, Res which protected Caco-2 cells from H2O2-induced oxidative damage clearly reduced malondialdehyde level and intracellular reactive oxygen species accumulation, but increased the expression levels of superoxide dismutase and heme oxygenase-1 (HO-1). Further studies showed that Res also inhibited H2O2-induced protein kinase C activity and p38 phosphorylation. Interestingly, these effects of Res were abolished by the HO-1 inhibitor zinc protoporphyrin or knockdown of HO-1 by siRNA. CONCLUSIONS: Res protected gut barrier function possibly by initiating HO-1-dependent signaling which is essential for common expression of key tight junction proteins. It also provides a rationale to develop Res clinical applications of intestinal disorders.


Assuntos
Antioxidantes/farmacologia , Heme Oxigenase-1/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Icterícia Obstrutiva/genética , Estresse Oxidativo/efeitos dos fármacos , Estilbenos/farmacologia , Junções Íntimas/efeitos dos fármacos , Animais , Ductos Biliares/cirurgia , Western Blotting , Células CACO-2 , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Icterícia Obstrutiva/metabolismo , Ligadura , Masculino , Malondialdeído/metabolismo , Ocludina/efeitos dos fármacos , Ocludina/metabolismo , Permeabilidade/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteína Quinase C/efeitos dos fármacos , Proteína Quinase C/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Resveratrol , Junções Íntimas/metabolismo , Regulação para Cima , Proteína da Zônula de Oclusão-1/efeitos dos fármacos , Proteína da Zônula de Oclusão-1/metabolismo
16.
Small ; 9(18): 3118-27, 2013 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-23463664

RESUMO

Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer. The design of nanoparticles for tumor delivery has been largely empirical, owing to a lack of quantitative data on angiogenic tissue sequestration. Using fluorescence correlation spectroscopy, the deposition rate constants of nanoparticles into angiogenic blood vessel tissue are determined. It is shown that deposition is dependent on surface charge. Moreover, the size dependency strongly suggests that nanoparticles are taken up by a passive mechanism that depends largely on geometry. These findings imply that it is possible to tune nanoparticle pharmacokinetics simply by adjusting nanoparticle size.


Assuntos
Nanopartículas/metabolismo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Espectrometria de Fluorescência
17.
Artigo em Chinês | MEDLINE | ID: mdl-24444641

RESUMO

OBJECTIVE: To investigate the feasibility of the endoscope-assisted styloidectomy. METHODS: Sixty patients with Eagle's syndrome undergoing the endoscope-assisted styloidectomy via postauricular incision, including 7 unilateral and 53 bilateral, between June 2010 and March 2013 were reviewed. RESULTS: The styloid processes in all patients were resected successfully via this approach, with the incision length range of 2.0 to 2.5 cm. The mean operative time was (21.3 ± 4.8) min(X(-) ± s), for unilateral surgery and (48.5 ± 11.4) min for bilateral surgery. Fifty-four patients symptom showed complete remission of symptom, 3 cases with decrease in symptom and other 3 cases with no significant relief of symptom after surgery. None case recurred for follow-up of 3 to 70 months. There were 3 sides with ear numbness after surgery for 3 months, and one case had transient facial paralysis and recovered after 3 months. CONCLUSIONS: The endoscope-assisted styloidectomy via postauricular incision is effective and feasible.


Assuntos
Endoscópios , Ossificação Heterotópica/cirurgia , Osso Temporal/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia/métodos
18.
Surg Laparosc Endosc Percutan Tech ; 22(3): 255-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22678323

RESUMO

Thyroidectomy can be performed in a variety of ways, and gasless video-assisted approaches have recently become more popular. We performed a study of thyroidectomy on 77 patients with bilateral thyroid lesions carried out using a gasless video-assisted unilateral anterior chest wall approach. Seventy-seven patients underwent bilateral thyroidectomy by the gasless video-assisted unilateral anterior chest wall approach, whereas 64 patients underwent conventional surgery during the same time frame and were considered to be the control group. The eligibility criteria for thyroid surgery by gasless video-assisted unilateral anterior chest wall approach were: no previous neck surgical history, no radiotherapy history, a diagnosis of benign thyroid tumor according to preoperative computed tomographic scan, no inflammation-related diseases or thyroid hyperfunction, no lymphadenectasis, and bilateral tumors ≤ 4 cm in diameter (1 side ≤ 2 cm, located in the lower part of the thyroid and near the surface of the thyroid). The 2 groups were compared by surgical style, complications, operative time, cosmetic result, and postoperative pain. The 2 groups were matched in terms of age and sex; the scoring for operative procedure (P=0.443), postoperative drainage (P=0.686), and postoperative pain (P=0.294) were not significantly different. The gasless video-assisted group had less bleeding during surgery than the conventional group and had better cosmetic results (P<0.001), but also had longer surgical durations (P=0.003) and higher costs of hospitalization (P<0.001). Neither group had any permanent recurrent laryngeal nerve paralysis or hypocalcemia, nor were there recurrences duration followed up for 21 ± 10 months. The gasless video-assisted group had 1 case of ecchymoma and 1 case of temporary recurrent laryngeal nerve paralysis, but both recovered within a month. The complication rates in the 2 groups were not significantly different (χ=1.423, P=0.292). The gasless video-assisted thyroidectomy by the unilateral anterior chest wall approach is a safe and feasible way to treat patients with benign bilateral thyroid lesion with good cosmetic results. The gasless video-assisted thyroidectomy is a valid surgical option for selected patients and that its application will grow in the future.


Assuntos
Doenças da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Cirurgia Vídeoassistida/métodos , Adulto , Feminino , Gases , Humanos , Masculino , Medição da Dor , Dor Pós-Operatória/etiologia , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Estudos Prospectivos , Resultado do Tratamento
19.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 23(10): 621-4, 2011 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-22005565

RESUMO

OBJECTIVE: To investigate the underlying mechanism for the therapeutic effect of a traditional Chinese medicinal recipe, Antidotal and Myogenic Ointment (AMO), on the foot ulcer in diabetic rat using cDNA microarray technology. METHODS: 45 rats were made diabetic by i. p. injection of streptozocin. The treated animals were then fed for 6 months,and subjected to the dissection of distal popliteal artery after ligation of the vessels. Another month later, grade II burn injury was produced on the bottom of their foot as a model of diabetic foot ulcer. The rats were then randomly divided into three groups (15 each) to receive AMO, epidermal growth factor (EGF) and saline for 30 days, with dressing change in every 2 days. The area of ulcer wound and their healing rate were recorded before and after the treatment. Total RNA was extracted from the tissue samples collected near the wound, and the expression profile of cytokine genes demonstrated using the microarry for rats. RESULTS: In comparison with the saline group, difference in the level of expression was found in 25 genes (23 of them were up-regulated and 2 down-regulated) in EGF group, and 30 genes in AMO groups (29 of them up-regulated and 1 down-regulated ). In comparison with EGF group, difference in level of expression was found in 16 genes in AMO group, with 11 up-regulated and 5 down-regulated. Neurotrophic factors and chemotactic factors, etc were among the genes involved. CONCLUSION: In comparison with EGF, AMO is more effective in the treatment of foot ulcer in diabetic rats. It is possible that AMO produces such effects through the regulation of balance in cytokine expression.


Assuntos
Pé Diabético/tratamento farmacológico , Fitoterapia , Cicatrização , Animais , Diabetes Mellitus Experimental , Pé Diabético/genética , Pé Diabético/metabolismo , Fator de Crescimento Epidérmico/uso terapêutico , Masculino , Pomadas , Análise de Sequência com Séries de Oligonucleotídeos , Ratos , Ratos Wistar , Resultado do Tratamento
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 28(6): 1222-6, 2008 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-18800692

RESUMO

Lithium cobalt oxide was synthesized by sol-gel with citric acid. The crystallization process of LiCoO2 gel precursor was studied by TG-DSC, and then it was calcined from 400 to 800 degrees C. The crystal structures of LiCoO2 powders formed at different temperatures were analyzed through X-ray diffraction, Infrared spectrum, Raman spectrum and transmission electron microscope. The results show that the mean grain sizes of LiCoO2 powders are about 20-40 nm, and increase with calcinating temperature changing from 400 to 700 degrees C, while decrease at 800 degrees C. The structure changed from modified spinel to layered-rock-salt with the calcinating temperature from 400 to 800 degrees C. In the modified spinel structure, Co2+ ions reside at the tetrahedral sites and Co3+ ions reside at the octahedral sites. However, in the layered-rock-salt structure, just only Co3+ ions reside at the octahedral sites.

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