Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Hepatobiliary Pancreat Dis Int ; 22(5): 504-511, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35909061

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for severe acute pancreatitis (AP). The underlying mechanism remains unclear. We sought to determine how bacterial translocation and cholesterol metabolism in the liver and pancreas affect the severity of AP in NAFLD mice. METHODS: C57BL/6N mice were fed on a high-fat diet (HFD) to generate the NAFLD model, and mice in the control group were provided with a normal diet (ND). After being anesthetized with ketamine/xylazine, mice got a retrograde infusion of taurocholic acid sodium into the pancreatic duct to induce AP, and sham operation (SO) was used as control. Serum amylase and Schmidt's pathological score system were used to evaluate AP severity. Bacterial loads, total cholesterol level, and cholesterol metabolic-associated molecules [low-density lipoprotein receptor (LDLR) and ATP-binding cassette transporter A1 (ABCA1)] were analyzed in the liver and pancreas. RESULTS: Compared with the ND-AP group, mice in the HFD-AP group had severer pancreatitis, manifested with higher serum amylase levels and higher AP pathologic scores, especially the inflammation and hemorrhage scores. Compared with the HFD-SO group and ND-AP group, bacterial loads in the liver and pancreas were significantly higher in the HFD-AP group. Mice in the HFD-AP group showed a decreased LDLR expression and an increased ABCA1 expression in the pancreas, although there was no significant difference in pancreas total cholesterol between the HFD-AP group and the ND-AP group. CONCLUSIONS: NAFLD aggravates AP via increasing bacterial translocation in the liver and pancreas and affecting pancreas cholesterol metabolism in mice.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Pancreatite , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Pancreatite/patologia , Translocação Bacteriana , Doença Aguda , Camundongos Endogâmicos C57BL , Fígado/patologia , Pâncreas/patologia , Colesterol/metabolismo , Dieta Hiperlipídica , Amilases/metabolismo
3.
Int J Biol Sci ; 17(10): 2380-2398, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34326682

RESUMO

Tamoxifen (TAM) resistance has indicated a significant challenge during endocrine therapy for hormone-sensitive breast cancer. Thus, it is significant to elucidate the molecular events endowing TAM resistance to endocrine therapy. In this study, we found that epithelial-mesenchymal transition (EMT) was an important event to confer TAM resistance, and attenuating EMT by elevating connexin (Cx) 43 expression could reverse TAM resistance. Specifically, Cx43 overexpression improved TAM sensitivity, while Cx43 depletion facilitated TAM insensitivity by modulating EMT in T47D TAM-resistant and -sensitive cells, and transplanted xenografts. Importantly, we found a novel reciprocal regulation between Cx43 and c-Src/PI3K/Akt pathway contributing to EMT and TAM resistance in breast cancer. Moreover, we identified that Cx43 deficiency was significantly correlated with poor relapse-free survival in patients undergoing TAM treatment. Therefore, Cx43 represents a prognostic marker and an attractive target for breast cancer treatments. Therapeutic strategies designed to increase or maintain Cx43 function may be beneficial to overcome TAM resistance.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Conexina 43/metabolismo , Transição Epitelial-Mesenquimal/genética , Transdução de Sinais/efeitos dos fármacos , Tamoxifeno/farmacologia , Animais , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Conexina 43/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases da Família src/genética , Quinases da Família src/metabolismo
4.
Rev Esp Enferm Dig ; 113(6): 418-422, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33233904

RESUMO

BACKGROUND AND AIM: Glasgow prognostic score is a systemic inflammatory-based score. The aim of this study was to determine whether the Glasgow prognostic score was a useful predictor of short-term outcomes in patients who undergo total proctocolectomy for ulcerative colitis. METHODS: eighty ulcerative colitis patients who underwent a total proctocolectomy with ileal pouch-anal anastomosis or permanent end ileostomy from June 2014 to March 2020 were retrospectively analyzed. Patients were divided into a lower Glasgow prognostic score group and a higher Glasgow prognostic score group. RESULTS: postoperative infectious complication occurred more frequently in the higher Glasgow prognostic score group (8.3 % vs 29.5 %, p = 0.018). According to the univariate and multivariate analysis, only a higher Glasgow prognostic score was associated with an increased risk of postoperative infectious complication (OR: 5.478, 95 % CI: 1.236-24.279). CONCLUSION: Glasgow prognostic score is a simple and useful indicator of postoperative infectious complications.


Assuntos
Colite Ulcerativa , Bolsas Cólicas , Proctocolectomia Restauradora , Colite Ulcerativa/cirurgia , Humanos , Ileostomia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Proctocolectomia Restauradora/efeitos adversos , Prognóstico , Estudos Retrospectivos
5.
Int J Mol Sci ; 21(3)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028746

RESUMO

Acute kidney injury (AKI) causes over 1 million deaths worldwide every year. AKI is now recognized as a major risk factor in the development and progression of chronic kidney disease (CKD). Diabetes is the main cause of CKD as well. Renal fibrosis and inflammation are hallmarks in kidney diseases. Various cytokines contribute to the progression of renal diseases; thus, many drugs that specifically block cytokine function are designed for disease amelioration. Numerous studies showed IL-20 functions as a pro-inflammatory mediator to regulate cytokine expression in several inflammation-mediated diseases. In this review, we will outline the effects of pro-inflammatory cytokines in the pathogenesis of AKI and CKD. We also discuss the role of IL-20 in kidney diseases and provide a potential therapeutic approach of IL-20 blockade for treating renal diseases.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/patologia , Interleucinas/metabolismo , Terapia de Alvo Molecular , Injúria Renal Aguda/metabolismo , Animais , Humanos , Transdução de Sinais
6.
Cell Mol Immunol ; 17(4): 369-379, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31363171

RESUMO

Adipocyte-macrophage crosstalk plays a critical role to regulate adipose tissue microenvironment and cause chronic inflammation in the pathogenesis of obesity. Interleukin-29 (IL-29), a member of type 3 interferon family, plays a role in host defenses against microbes, however, little is known about its role in metabolic disorders. We explored the function of IL-29 in the pathogenesis of obesity-induced inflammation and insulin resistance. We found that serum IL-29 level was significantly higher in obese patients. IL-29 upregulated IL-1ß, IL-8, and monocyte chemoattractant protein-1 (MCP-1) expression and decreased glucose uptake and insulin sensitivity in human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes through reducing glucose transporter 4 (GLUT4) and AKT signals. In addition, IL-29 promoted monocyte/macrophage migration. Inhibition of IL-29 could reduce inflammatory cytokine production in macrophage-adipocyte coculture system, which mimic an obese microenvironment. In vivo, IL-29 reduced insulin sensitivity and increased the number of peritoneal macrophages in high-fat diet (HFD)-induced obese mice. IL-29 increased M1/M2 macrophage ratio and enhanced MCP-1 expression in adipose tissues of HFD mice. Therefore, we have identified a critical role of IL-29 in obesity-induced inflammation and insulin resistance, and we conclude that IL-29 may be a novel candidate target for treating obesity and insulin resistance in patients with metabolic disorders.


Assuntos
Inflamação/etiologia , Resistência à Insulina , Interferons/metabolismo , Interleucinas/metabolismo , Obesidade/complicações , Adipócitos/patologia , Tecido Adiposo/patologia , Animais , Arritmias Cardíacas/patologia , Diferenciação Celular , Movimento Celular , Quimiocina CCL2/metabolismo , Dieta Hiperlipídica , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Gigantismo/patologia , Transportador de Glucose Tipo 4/metabolismo , Cardiopatias Congênitas/patologia , Inflamação/sangue , Deficiência Intelectual/patologia , Interferons/sangue , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Interleucinas/sangue , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/sangue , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Interleucina/metabolismo , Regulação para Cima
7.
J Zhejiang Univ Sci B ; 20(11): 928-932, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31595729

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer and is the second leading cause of cancer mortality with an estimated 745 500 deaths annually (Jemal et al., 2011). Although new therapeutic modalities including novel chemotherapeutic interventions and targeted therapy have been applied, the prognosis of HCC patients remains unsatisfactory due to the high incidence of intrahepatic and distal metastases (Siegel et al., 2018).


Assuntos
Carcinoma Hepatocelular/genética , Genoma , Neoplasias Hepáticas/genética , MicroRNAs/análise , Proteínas Reguladoras de Apoptose/fisiologia , Biomarcadores , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Hipóxia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Estadiamento de Neoplasias , Prognóstico , Proteínas Repressoras/fisiologia
8.
J Biophotonics ; 10(12): 1586-1596, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28417552

RESUMO

In spite of the promising initial treatment responses presented by photodynamic therapy (PDT), 5-year recurrence rates remain high level. Therefore, improvement in the efficacy of PDT is needed. There are reports showing that connexin(Cx) 26-composed gap junctional intercellular communication (GJIC) enhances the intercellular propagation of "death signal", thereby increasing chemotherapeutic cytotoxicity. However, it is unclear whether Cx26-formed GJIC has an effect on PDT phototoxicity. The results in the present study showed that Cx26-composed GJ formation at high density enhances the phototoxicity of Photofrin-PDT. When the Cx26 is not expressed or Cx26 channels are blocked, the phototoxicity in high-density cultures substantially reduces, indicating that the enhanced PDT phototoxicity at high density is mediated by Cx26-composed GJIC. The GJIC-mediated increase in PDT phototoxicity was associated with ROS, calcium and lipid peroxide-mediated stress signaling pathways. The work presents the ability of Cx26-composed GJIC to enhance the sensitivity of malignant cells to PDT, and indicates that maintenance or increase of Cx26-formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency. Picture: The survival response of Photofrin-PDT in Dox-treated (Cx26 expressing, GJ-formed) and Dox-untreated cells (Cx26 non-expressing, GJ-unformed) at high-cell density condition.


Assuntos
Cálcio/metabolismo , Comunicação Celular/efeitos dos fármacos , Comunicação Celular/efeitos da radiação , Conexinas/metabolismo , Junções Comunicantes/metabolismo , Peróxidos Lipídicos/metabolismo , Fotoquimioterapia , Aldeídos/metabolismo , Ceramidas/biossíntese , Conexina 26 , Éter de Diematoporfirina/farmacologia , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Espaço Extracelular/efeitos da radiação , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/efeitos da radiação , Células HeLa , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Espaço Intracelular/efeitos da radiação
9.
Artigo em Inglês | MEDLINE | ID: mdl-28250789

RESUMO

Most of the existing chemotherapeutic drugs have plenty of side effects. Chinese herbal medicine has been used for pharmaceutical and dietary therapy for thousands of years with more effective and fewer side effects. Cestrum nocturnum (CN) has long been used to treat digestive diseases for centuries in China. Our previous study first proved that the n-butanol part isolated from the flowers of CN produced an inhibitory effect on the proliferation of malignant cells. However, the fractions responsible for the antiproliferation effect of n-butanol part from CN flowers and related mechanisms remain unknown. Thus, in this study, we extracted fractions C4 and C5 from n-butanol part of CN flowers and investigated their immune toxicity and antitumor activities. It was found that fractions C4 and C5 exhibited great cytotoxicity to cancer cell lines but had low immune toxicity towards T and B lymphocytes in vitro. The tested fractions also attenuated proliferation and induced apoptosis at G0/G1 and G2/M phases in Bel-7404 cells through inducing DNA damage and inhibiting topoisomerase II relaxation activity. These results suggest that fractions C4 and C5 may represent important sources of potential antitumor agents due to their pronounced antitumor effects and low immune toxicity.

10.
Neuroreport ; 27(6): 462-8, 2016 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-26966783

RESUMO

It has been reported that the decimation of honey bees was because of pesticides of imidacloprid. The imidacloprid is a wildly used neonicotinoid insecticide. However, whether imidacloprid toxicity interferes with the spatial memory of echolocation bats is still unclear. Thus, we compared the spatial memory of Formosan leaf-nosed bats, Hipposideros terasensis, before and after chronic treatment with a low dose of imidacloprid. We observed that stereotyped flight patterns of echolocation bats that received chronic imidacloprid treatment were quite different from their originally learned paths. We further found that neural apoptosis in hippocampal CA1 and medial entorhinal cortex areas of echolocation bats that received imidacloprid treatment was significantly enhanced in comparison with echolocation bats that received sham treatment. Thus, we suggest that imidacloprid toxicity may interfere with the spatial memory of echolocation bats through neural apoptosis in hippocampal CA1 and medial entorhinal cortex areas. The results provide direct evidence that pesticide toxicity causes a spatial memory disorder in echolocation bats. This implies that agricultural pesticides may pose severe threats to the survival of echolocation bats.


Assuntos
Apoptose/efeitos dos fármacos , Região CA1 Hipocampal/patologia , Córtex Entorrinal/patologia , Imidazóis/toxicidade , Inseticidas/toxicidade , Transtornos da Memória/induzido quimicamente , Nitrocompostos/toxicidade , Animais , Quirópteros , Ecolocação/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Neonicotinoides , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Estatísticas não Paramétricas , Proteína X Associada a bcl-2/metabolismo
11.
Mol Med Rep ; 13(2): 1563-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26708270

RESUMO

The aim of the present study was to determine the role of interleukin-6 (IL-6) in the epithelial-mesenchymal transition (EMT) of human intrahepatic biliary epithelial cell (HIBEC) lines in vitro. HIBECs were stimulated with IL-6 at concentrations of 0, 10, 20, 50 and 100 µg/l for 24 h. A wound healing and Transwell assay were performed to determine the migratory and invasive capacity of HIBECs, respectively. Following 24 h of incubation, IL-6 at 10 and 20 µg/l significantly increased the number of migrated and invaded cells (P<0.05), while stimulation with 50 and 100 µg/l IL-6 resulted in a further increase of the migratory and invasive capacity compared to that in all other groups (P<0.05). Furthermore, reverse-transcription quantitative polymerase chain reaction and western blot analyses were used to detect the mRNA and protein expression of EMT markers E-cadherin and vimentin in HIBECs. Decreased mRNA levels of E-cadherin accompanied by higher mRNA levels of vimentin were observed in the 10, 20, 50, 100 µg/l IL-6 groups compared to those in the 0 µg/l group (all P<0.05). Furthermore, the protein expression of E-cadherin was decreased, while that of vimentin was increased in the 50 and 100 µg/l IL-6 groups compared to those in the 0, 10 and 20 µg/l IL-6 groups (all P<0.05). The present study therefore indicated that IL-6 promoted the process of EMT in HIBECs as characterized by increased migration and invasion of HIBECs and the typical changes in mRNA and protein expression of the EMT markers E-cadherin and vimentin.


Assuntos
Caderinas/biossíntese , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Interleucina-6/administração & dosagem , Vimentina/biossíntese , Ductos Biliares Intra-Hepáticos/efeitos dos fármacos , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Movimento Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Regulação da Expressão Gênica , Humanos , Interleucina-6/metabolismo , Invasividade Neoplásica/patologia , RNA Mensageiro/biossíntese
12.
Sci Rep ; 5: 16566, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26686459

RESUMO

Our study investigated whether microRNA-122 (miR-122) played important roles in the proliferation, invasion and apoptosis of human cholangiocarcinoma (CC) cells. QBC939 and RBE cells lines were chosen and divided into five groups: miR-122 mimic group, anti-miR-122 group, negative control (NC) group, mock group and blank group. MiR-122 expression was measured by qRT-PCR. Roles of miR-122 in cell proliferation, apoptosis and invasion were investigated using MTT assay, flow cytometer and Transwell invasion assay, respectively. MiR-122 expression was lower in CC tissues and QBC939 cell than that in normal bile duct tissues, HCCC-9810 and RBE cells. In both QBC939 and RBE cells lines, miR-122 expression was higher in miR-122 mimic group than that in NC group, mock group and blank group; opposite results were found in anti-miR-122 group. Cell proliferation and invasion were remarkably inhibited in miR-122 mimic group after 48 h/72 h transfection, while apoptotic cells numbers were much greater in miR-122 mimic group; the opposite results were obtained from anti-miR-122 group (all P < 0.05). MiR-122 expression was significantly weaker in CC tissues, and miR-122 overexpression might play pivotal roles in inhibiting proliferation, stimulating apoptosis and suppressing invasion of CC cells, suggesting a new target for CC diagnosis and treatment.


Assuntos
Proliferação de Células/genética , Colangiocarcinoma/genética , MicroRNAs/biossíntese , Invasividade Neoplásica/genética , Apoptose/genética , Ductos Biliares/metabolismo , Linhagem Celular Tumoral , Colangiocarcinoma/patologia , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...