Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
1.
J Ethnopharmacol ; 264: 113212, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32768643

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia-reperfusion (CIR) injury is one of the main diseases leading to death and disability. Acanthopanax senticosus (Rupr. & Maxim.) Harms (AS), also known as Panax ginseng, has neuroprotective effects on anti-CIR injury. However, the underlying molecular mechanism of its therapeutic effects is not clear. AIM OF THE STUDY: To systematically study and explore the mechanism of Acanthopanax senticosus (Rupr. & Maxim.) Harms extract (ASE) in the treatment of CIR injury based on metabolomics and transcriptomics. MATERIALS AND METHODS: The pharmacological basis of ASE in the treatment of CIR was evaluated, and samples were used in plasma metabolomics and brain tissue transcriptomics to reveal potential biomarkers. Finally, according to online database, we analyzed biomarkers identified by the two technologies, explained reasons for the therapeutic effect of ASE, and identify therapeutic targets. RESULTS: A total of 53 differential metabolites (DMs) were identified in plasma and 3138 differentially expressed genes (DEGs) were identified in brain tissue from three groups of rats, including sham, ischemia-reperfusion (I/R), and ASE groups. Enrichment analysis showed that Nme6, Tk1, and Pold1 that are involved in the production of deoxycytidine and thymine were significantly up-regulated and Dck was significantly down-regulated by the intervention with ASE. These findings indicated that ASE participates in the pyrimidine metabolism by significantly regulating the balance between dCTP and dTTP. In addition, ASE repaired and promoted the lipid metabolism in rats, which might be due to the significant expression of Dgkz, Chat, and Gpcpd1. CONCLUSIONS: The findings of this study suggest that ASE regulates the significant changes in gene expression in metabolites pyrimidine, and lipid metabolism in CIR rats and plays an active role in the treatment of CIR injury through multiple targets and pathways.

2.
World J Gastroenterol ; 26(30): 4465-4478, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32874058

RESUMO

BACKGROUND: Lenvatinib has become an indispensable part of treatment regimens for patients with advanced hepatocellular carcinoma (aHCC). Several recent real-world studies appear to have confirmed this; however, there are etiological differences. This necessitates further real-world studies of lenvatinib across diverse populations, such as in China. AIM: To investigate the efficacy and safety of lenvatinib in a Chinese HCC patient population under real-world conditions. METHODS: This is a retrospective and multiregional study involving patients with aHCC receiving lenvatinib monotherapy. Efficacy was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Baseline characteristics and adverse events (AEs) were recorded throughout the entire study. RESULTS: In total, 54 HCC patients treated with lenvatinib monotherapy were included for final analysis. The objective response rate was 22% (n = 12) with a progression-free survival (PFS) of 168 d; however, AEs occurred in 92.8% of patients. Multivariate analysis showed that the Barcelona Clinic Liver Cancer stage [hazard ratio (HR) 0.465; 95%CI: 0.23-0.93; P = 0.031], portal vein tumor thrombus (HR 0.38; 95%CI: 0.15-0.94; P = 0.037) and Child-Pugh classifications (HR 0.468; 95%CI: 0.22-0.97; P = 0.042) were significant factors affecting PFS. The sensitivity (56.7%) and specificity (83.3%) of decreasing serum biomarkers including alpha-fetoprotein were calculated in order to predict tumor size reduction. Gene sequencing also provided insights into potential gene mutation signatures related to the effect of lenvatinib. CONCLUSION: Our findings confirm previous evidence from the phase III REFLECT study. The majority of patients in this Chinese sample were suffering from concomitant hepatitis B virus-related HCC. However, further analysis suggested that baseline characteristics, changes in serum biomarkers and gene sequencing may hold the key for predicting lenvatinib responses. Further large-scale prospective studies that incorporate more basic medical science measures should be conducted.

4.
ACS Chem Neurosci ; 10(2): 812-823, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30714719

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disorder. To date, the diagnosis of PD relies mainly on clinical manifestations whereas neuropathological confirmation of the brain is only possible with postmortem studies. Neuronal loss in the substantia nigra pars compacta (SNc) associated with Lewy bodies/neurites is the pathological hallmark feature of PD. The major component of Lewy pathology (LP) is misfolded alpha-synuclein (α-SYN). There is evidence that the distribution of LP is not only limited to the brain but extends to peripheral tissues, including gastrointestinal tract, salivary glands, olfactory mucosa, skin, retina, adrenal gland, and heart. Sensitivity and specificity of α-SYN detection in PD vary greatly among studies due to methodological heterogeneity, such as sampling sites and size, tissue preparation, staining techniques, and antibodies used. Of note, α-SYN has also been found in preclinical and prodromal PD. Further in vivo studies focusing on favorable biopsy sites and standard techniques are needed to get better understanding of α-SYN deposits in preclinical, prodromal, and clinical PD.


Assuntos
Encéfalo/metabolismo , Doença de Parkinson/metabolismo , alfa-Sinucleína/metabolismo , Glândulas Suprarrenais/metabolismo , Animais , Encéfalo/patologia , Trato Gastrointestinal/metabolismo , Humanos , Miocárdio/metabolismo , Mucosa Olfatória/metabolismo , Doença de Parkinson/patologia
5.
J Gastroenterol Hepatol ; 34(9): 1563-1570, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30597598

RESUMO

BACKGROUND AND AIM: Salivary characteristics are altered in gastrointestinal diseases and related to oral taste disorder. However, specific salivary biochemical characteristics and their relationships with oral taste disturbances in chronic non-atrophy gastritis (CNAG) remain uncertain. METHODS: Seventy patients with CNAG and 70 subjects in healthy control group (HCG) were enrolled in our study. The levels of salivary flow rate (SFR), pH, salivary α-amylase (sAA) activity, total protein density (TPD), chloride concentration, and calcium concentration were determined before and after citric acid stimulation and compared between CNAG with and without oral taste disturbances. RESULTS: Average body mass index (BMI) of CNAG (17.75 ± 2.08) was lower than that of HCG (21.96 ± 1.72, P < 0.01). Compared with HCG, CNAG showed increased TPD and calcium concentration but decreased SFR both before and after acid stimulation (P < 0.01), as well as reduced sAA and salivary chloride responses to acid stimulation (P < 0.01). Compared with CNAG with normal BMI (24.29%, 17/70), sAA activity response to acid stimulation was reduced in those with low BMI (75.71%, 53/70, P < 0.05). Under resting condition, CNAG with dry mouth (55.71%, 39/70) showed increased SFR and decreased TPD (P < 0.05), as compared with CNAG without dry mouth (44.29%, 31/70). Compared with CNAG without bitter taste (57.14%, 40/70), pH was decreased in those with bitter taste (42.86%, 30/70) under both resting and stimulated conditions (P < 0.05). CONCLUSION: Decreased sAA activity may reflect malnutrition state and be one potential marker of poor digestion, decreased salivary pH may contribute to bitter taste perception, and reduced TPD might be a cause of dry mouth in CNAG.


Assuntos
Ácido Cítrico/administração & dosagem , Gastrite/metabolismo , Saliva/metabolismo , Salivação , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Doença Crônica , Estudos Transversais , Digestão , Feminino , Gastrite/diagnóstico , Gastrite/fisiopatologia , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Proteínas/metabolismo , alfa-Amilases Salivares/metabolismo , Paladar , Xerostomia/metabolismo , Xerostomia/fisiopatologia
6.
Cancer Lett ; 408: 23-32, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28842285

RESUMO

Aberrant expression of microRNAs (miRNAs) plays an important role in gastric cancer (GC) development. miR-93-5p has shown opposing functions in different types of cancers, but the exact expression pattern and molecular mechanism of miR-93-5p in GC development remain to be elucidated. Here, we reported that miR-93-5p expression was increased in GC tissues compared with the adjacent normal tissues and that its overexpression was correlated with distant metastasis and poor survival in GC patients. miR-93-5p knockdown inhibited the migration, invasion and proliferation of GC cells in vitro and in vivo, while its overexpression displayed an opposite result. Using an mRNA microarray, we found that miR-93-5p significantly downregulated IFNAR1 expression in GC cells, which was further identified as a direct target of miR-93-5p. IFNAR1 knockdown promoted GC cell migration and invasion, but its restoration could rescue GC cell migration and invasion induced by miR-93-5p overexpression. Moreover, miR-93-5p-IFNAR1 axis increased MMP9 expression via STAT3 pathway in GC cells. Taken together, we reveal that miR-93-5p overexpression is associated with the poor survival of GC patients and miR-93-5p-IFNAR1 axis promotes GC metastasis through activation of STAT3 pathway.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Peritoneais/secundário , Receptor de Interferon alfa e beta/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias Gástricas/patologia , Animais , Apoptose , Movimento Celular , Proliferação de Células , Feminino , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/metabolismo , Prognóstico , Receptor de Interferon alfa e beta/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Oncol Rep ; 35(2): 939-47, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26555012

RESUMO

Colon cancer is one of the most common malignancies of the digestive system. Although more effective therapeutic strategies have been developed in the last decades, there is still a great clinical need to explore new treatment regimens for colon cancer due to the undesirable prognosis. In the present study, we investigated the anticancer activity of resveratrol (Res) in human colon cancer cells, and the possible mechanism underlying this effect. We employed crystal violet staining, flow cytometry and western blotting to test the antiproliferation- and apoptosis-inducing effects of Res in LoVo cells. A xenograft tumor model was also introduced to confirm the in vivo anticancer effect of Res. Using PCR, western blotting, a recombinant adenovirus and a specific inhibitor of p38 MAPK or bone morphogenetic protein receptor (BMPR) to explore the possible molecular mechanisms. We found that Res markedly inhibited the proliferation and promoted the apoptosis of LoVo cells, and suppressed the in vivo tumor growth of colon cancer. Res substantially upregulated the expression of bone morphogenetic protein 9 (BMP9). Exogenous expression of BMP9 enhanced the anticancer effect of Res in LoVo cells, while BMP9 knockdown partly reduced this activity. Res increased the activation of p38 MAPK, which was enhanced by the exogenous expression of BMP9. The anticancer activity of Res, or Res combined with BMP9, was reduced partly by the p38 MAPK inhibitor. The BMPR inhibitor almost abolished the Res-induced activation of p38 MAPK, and attenuated the antiproliferative effect of Res in the LoVo cells. Our findings strongly suggest that the anticancer effect of Res in human colon cancer cells may be partly mediated by upregulation of BMP9 to activate p38 MAPK in a BMPR-dependent manner.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/patologia , Fatores de Diferenciação de Crescimento/metabolismo , Estilbenos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Nus , Resveratrol , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Mar Drugs ; 13(12): 7433-45, 2015 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-26694424

RESUMO

Okadaic acid (OA) is produced by Dinophysis and Prorocentrum dinoflagellates and primarily accumulates in bivalves, and this toxin has harmful effects on consumers and operators. In this work, we first report the use of aptamers as novel non-toxic probes capable of binding to a monoclonal antibody against OA (OA-mAb). Aptamers that mimic the OA toxin with high affinity and selectivity were generated by the magnetic bead-assisted systematic evolution of ligands by exponential enrichment (SELEX) strategy. After 12 selection rounds, cloning, sequencing and enzyme-linked immunosorbent assay (ELISA) analysis, four candidate aptamers (O24, O31, O39, O40) were selected that showed high affinity and specificity for OA-mAb. The affinity constants of O24, O31, O39 and O40 were 8.3 × 108 M(-1), 1.47 × 108 M(-1), 1.23 × 108 M(-1) and 1.05 × 108 M(-1), respectively. Indirect competitive ELISA was employed to determine the internal-image function of the aptamers. The results reveal that O31 has a similar competitive function as free OA toxin, whereas the other three aptamers did not bear the necessary internal-image function. Based on the derivation of the curvilinear equation for OA/O31, the equation that defined the relationship between the OA toxin content and O31 was Y = 2.185X - 1.78. The IC50 of O31 was 3.39 ng·mL(-1), which was close to the value predicted by the OA ELISA (IC50 = 4.4 ng·mL(-1)); the IC10 was 0.33 ng·mL(-1). The above data provides strong evidence that internal-image functional aptamers could be applicable as novel probes in a non-toxic assay.


Assuntos
Anticorpos Monoclonais/imunologia , Aptâmeros de Nucleotídeos/metabolismo , Ácido Okadáico/metabolismo , Técnica de Seleção de Aptâmeros/métodos , Aptâmeros de Nucleotídeos/imunologia , Dinoflagelados/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Concentração Inibidora 50 , Ácido Okadáico/imunologia
9.
Oncol Rep ; 34(6): 3203-11, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26503233

RESUMO

Colon cancer is one of the most common malignancies. Although the current treatment regimes for colon cancer have been well-developed in the past decades, the prognosis remains still undesirable. It is still urgent to explore new treatment strategies for colon cancer. Natural products is one of the most useful sources for anticancer agents, although some of them have serious side-effects. Evodiamine (Evo) is an quinolone alkaloid from the traditional herb medicine Evodia rutaecarpa. In the present study, we investigated the anticancer effect of Evo in human colon cancer cells. We found that Evo exhibits prominent antiproliferation and apoptosis inducing effects in LoVo cells. Evo leads to apparent downregulation of HIF-1α either in vitro or in vivo; exogenous expression of HIF-1α can attenuate the antiproliferation effect of Evo in LoVo cells, while HIF-1α knockdown potentiates this effect greatly. Further analysis indicated that Evo can also inhibit the phosphorylation of Akt1/2/3 and decrease greatly the expression of IGF-1. Thus, our findings strongly suggested that the anticancer effect of Evo in human colon cancer may be partly mediated by downregulating HIF-1α expression, which is initiated by inactivating PI3K/Akt signaling transduction though decreasing the expression of IGF-1 in colon cancer cells. Therefore, Evo may be used alone or in combination as a potential anticancer agent for colon cancer treatment.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Fator de Crescimento Insulin-Like I/biossíntese , Quinazolinas/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Fator de Crescimento Insulin-Like I/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos
10.
DNA Cell Biol ; 34(10): 618-25, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26237452

RESUMO

Mesenchymal stem cells (MSCs) were reported to accelerate the curing of ulcerative colitis (UC). Altered expression of microRNAs (miRNAs) has recently revealed association with UC. However, the effect of adipose-derived MSCs (ASCs) on UC and the mechanism of how miRNAs regulate UC remain unclear. We investigated the effect of ASCs on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced UC in rat colon tissues. qRT-PCR and immunofluorescence analyses were performed to monitor the expression of miR-1236 and its target molecule, retinoid-related orphan receptor γ (RORγ). Regulation of the expression of RORγ by miR-1236 was assessed using luciferase reporter construct assays and miR-1236 mimic transfection. The relationship between miR-1236 and RORγ was further investigated in HT29 cells induced by TNF-α. ASCs highly ameliorated UC and decreased the inflammation markers in rats with TNBS-induced UC. In addition, ASCs upregulated the expression of miR-1236 and decreased the expression of RORγ in the TNBS-induced rat model of UC. The luciferase reporter assay and bioinformatic analysis demonstrated that the expression of RORγ was directly targeted and regulated by miR-1236. Specifically, the expression of RORγ was suppressed by miR-1236 mimic and enhanced by miR-1236 inhibitor. Furthermore, we demonstrated that exogenous miR-1236 mimic could inhibit the expression of RORγ in HT29 cell induced by TNF-α. ASCs effectively alleviated UC in rats with the expression of miR-1236 alteration, and miR-1236 may play important roles in UC by downregulating the expression of RORγ.


Assuntos
Colite Ulcerativa/terapia , Transplante de Células-Tronco Mesenquimais/métodos , MicroRNAs/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Regiões 3' não Traduzidas , Tecido Adiposo/citologia , Animais , Células Cultivadas , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Injeções Intravenosas , Masculino , Células-Tronco Mesenquimais/fisiologia , MicroRNAs/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Ratos Wistar , Ácido Trinitrobenzenossulfônico/toxicidade , Fator de Necrose Tumoral alfa/farmacologia
11.
Int J Oncol ; 46(3): 1205-13, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25524807

RESUMO

Colon cancer is one of the most common malignancies, causes considerable morbidity and mortality. The current treatment for colon cancer is more modest than had been hoped. There is an urgent clinical need to explore new agents or adjuvants for colon cancer treatment. Natural products and their derivates act as one of the major source for anticancer agent. In the present study, we investigated the anti-proliferation and chemoprevention effects of tetrandrine (Tet) on colon cancer cells to uncover the possible molecular basis of this effect. We found that Tet can inhibit proliferation and induce apoptosis in LoVo cells. With dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) induced colon cancer model, we found that Tet can prevent or inhibit DMH plus DSS induced aberrant crypt foci (ACF) and colon cancer formation, as well as suppress tumor growth in the xenograft colon cancer model. Tet can downregulate the expression of IGFBP-5 in LoVo cells. Exogenous expression of IGFBP-5 can attenuate the anti-cancer activity of Tet, while IGFBP-5 knockdown potentiates this effect of Tet on LoVo cells. Tet can inhibit Wnt/ß-catenin signaling transduction, which can be partly reversed by exogenous expression of IGFBP-5, but is enhanced by IGFBP-5 knockdown. Our results demonstrated that the anticancer activity of Tet in colon cancer cells may be mediated partly by downregulating the expression of IGFBP-5, thus inactivating Wnt/ß-catenin signaling transduction.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Benzilisoquinolinas/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/fisiologia , Animais , Proliferação de Células/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Feminino , Humanos , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/antagonistas & inibidores , Masculino , Camundongos , Camundongos Nus , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Sprague-Dawley , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(8): 960-3, 2014 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-25223181

RESUMO

OBJECTIVE: To observe the effect of Qingfei Peiyuan Micro-pill (QPM) on HIV/AIDS patients with pulmonary infection of phlegm heat obstructing lung syndrome (PHOLS). METHODS: Totally 141 HIV/AIDS patients with pulmonary infection of PHOLS were randomly assigned to the treatment group (94 cases) and the control group (47cases). On the basis of Western medicine, patients in the treatment group took QPM. The therapeutic course for all was 28 days. The improvement of symptoms and signs was observed. The body temperature (BT), chest X ray, and white blood cells (WBCs) were detected. RESULTS: The Chinese medical syndrome score was lower in the treatment group than in the control group at the 7th, 21st, and 28th day of treatment, showing statistical difference (P < 0.05). The efficacy was better in the treatment group than in the control group at the 7th, 21st, and 28th day of treatment, showing statistical difference (P < 0.05). The BT was lower in the treatment group than in the control group on the 7th day. There was no statistical difference in the patient number with normal WBCs on the 7th day (P > 0.05). But there was statistical difference in the patient number with normal WBCs on the 14th, 21st, and 28th day of treatment (P < 0.05). There was no statistical difference in the patient number with normal chest X ray on the 7th and 28th day of treatment (P > 0.05). But there was statistical difference in the patient number with normal chest X ray on the 14th and 21 st day of treatment (P < 0.05). CONCLUSION: QPM had certain complementary effect on HIV/AIDS patients with pulmonary infection of PHOLS.


Assuntos
Síndrome de Imunodeficiência Adquirida/complicações , Medicamentos de Ervas Chinesas/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/complicações , Resultado do Tratamento
13.
Biomaterials ; 35(36): 9649-59, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25176064

RESUMO

Mouse embryonic fibroblasts (MEFs) are multi-potent progenitor cells (MPCs), can differentiate into different lineages, such as osteogenic, and adipogenic. PTEN, a tumor suppressor, may be involved in regulating bone development through interacting with COX-2. BMP9, the most potent osteogenic BMPs, can up-regulate COX-2 in MPCs. Whether PTEN is involved in BMP9 induced osteogenic differentiation in MPCs remains unknown. The goal of this investigation is to identify the effect of PTEN on BMP9-induced osteogenic differentiation in MPCs and dissect the possible mechanism underlay this. We found that BMP9 down-regulates PTEN, and PTEN inhibitor (VO) effectively increases different osteogenic markers induced by BMP9 in MEFs. Exogenous expression of PTEN inhibits BMP9 induced ectopic bone formation apparently. Mechanistically, we found that VO can enhance BMP9 induced BMPs/Smads signaling prominently without no substantial effects on cell cycle. Further analysis indicates that VO can promote BMP9-induced expression of COX-2 in MEFs, which can be eliminated by PI3K inhibitor. Additionally, COX-2 knockdown abolishes the effect of VO on BMP9-induced ALP activities in MEFs. Our findings suggest that PTEN plays an important role in regulating BMP9 induced osteogenic differentiation in MPCs, which may be mediated by PTEN/PI3K/Akt signaling to modulate the expression of COX-2.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Fibroblastos/citologia , Fator 2 de Diferenciação de Crescimento/metabolismo , Osteogênese , PTEN Fosfo-Hidrolase/metabolismo , Células-Tronco/citologia , Animais , Diferenciação Celular , Linhagem Celular , Fibroblastos/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Células-Tronco/metabolismo
14.
Int J Oncol ; 45(1): 104-12, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24756222

RESUMO

Colon cancer is one of the most common malignancies and the treatments for colon cancer have been developed substantially in the last decades, but there is still a great clinical need to explore new treatment regimens due to the undesirable prognosis. In this investigation, we demonstrated the anti-proliferative and apoptosis-inducing activities of resveratrol (Res) in human colon cancer cells, and the possible mechanisms underlying these effects. We used crystal violet staining, flow cytometry and western blotting to validate the anti-proliferative and apoptosis-inducing effects of Res on HCT116 cells. A xenograft tumor model was used to confirm the anti-proliferative effects of Res. We employed polymerase chain reaction, western blotting, recombinant adenovirus and luciferase reporter assay to explore the possible mechanism(s) of action. We found that Res inhibits significantly the proliferation and promotes apoptosis in HCT116 cells, as well as inhibits the xenograft tumor growth of colon cancer. Res upregulates the expression of phosphatase and tensin homolog (PTEN) and decreases the phosphorylation of Akt1/2. The exogenous expression of PTEN inhibits the PI3K/Akt signal and promotes the anti-proliferative effects of Res in HCT116 cells, while knockdown of PTEN increases PI3K/Akt signal but reduces the anti-proliferative function of Res. The protein and mRNA expression of ß-catenin are all decreased by Res concentration-dependently. Thus, our findings strongly suggest that the anti-proliferative effects of Res in human colon cancer cells may be mediated by regulating separately the PTEN/PI3K/Akt and Wnt/ß-catenin signaling.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Estilbenos/administração & dosagem , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Células HCT116 , Humanos , Camundongos , Camundongos Nus , Neoplasias Experimentais , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Resveratrol , Transdução de Sinais/efeitos dos fármacos , Estilbenos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Neurol Res ; 36(2): 157-63, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24107488

RESUMO

OBJECTIVES: Here, we reported our experience over 28 years with 133 cases of patients with Wilson's disease (WD) in order to illustrate the diverse clinical presentation and to improve understanding and early diagnosis of WD. METHODS: We reviewed the medical records of patients with WD at Shengjing Hospital of China Medical University from 1993 to 2011. The clinical manifestations and laboratory findings were analyzed. The diagnosis was based on the presence of Kayser-Fleisher (K-F) rings, low serum copper levels, low serum ceruloplasmin levels, increased urinary copper concentrations before or after penicillamine challenge. RESULTS: Among them, 93 patients mainly presented with hepatic manifestations, 27 with neural abnormalities, and 13 presented with others. Age range at diagnosis was wide (3-74 years, average 13·2 years), and five patients were over 40 years. The oldest one was aged 74 years and presented with neuropsychiatric disorder. The positive rate of K-F rings was 93·0%. The serum ceruloplasmin decreased in 83·6% patients, 24-hour urinary copper increased in 88·1% patients, and serum copper decreased in 68·9% patients. About 79·7% of patients were diagnosed within 6 months, but only 33·1% were diagnosed at their initial medical consultation. There was a substantial delay of up to 15 years. CONCLUSIONS: The clinical manifestation of WD is very diverse and no one feature is completely reliable. Doctors in many fields have opportunities to encounter this disease, and the most important thing is to be aware of the possibility of WD.


Assuntos
Degeneração Hepatolenticular/diagnóstico , Adolescente , Adulto , Idoso , Ceruloplasmina/metabolismo , Criança , Pré-Escolar , Cobre/sangue , Cobre/urina , Diagnóstico Diferencial , Feminino , Degeneração Hepatolenticular/metabolismo , Degeneração Hepatolenticular/patologia , Humanos , Fígado/patologia , Hepatopatias/complicações , Hepatopatias/diagnóstico , Hepatopatias/patologia , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/diagnóstico , Transtornos Mentais/patologia , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/patologia , Adulto Jovem
16.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(7): 896-900, 2013 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-24063208

RESUMO

OBJECTIVE: To explore Chinese medicine syndrome distribution laws of asymptomatic HIV infection patients. METHODS: Using Chi-square test, Chinese medicine syndrome distribution laws were compared and analyzed in 1 156 asymptomatic HIV infection patients from March 2009 to October 2011 from four aspects, i.e., age, possible infection time, disease duration, and different routes of infection. RESULTS: Qi deficiency syndrome (QDS) and internal dampness-heat accumulation syndrome (IDHAS) were dominant in all syndrome types. Along with aging, QDS showed a growing tendency, while IDHAS showed obvious declining tendency. There was no obvious change in other syndrome types. There was statistical difference in the distribution of each syndrome type among each age period (P < 0.01). Within 15 years, along with the increase of infection time, QDS showed a growing tendency, while IDHAS ratio showed an obvious declining tendency. No obvious laws were found in other syndrome types. There was statistical difference in the distribution of each syndrome type (P < 0.01). Along with the prolongation of disease duration, the case number of each syndrome showed a decreasing trend, but QDS and IDHAS still accounted for higher ratios in each stage. There was statistical difference in the distribution of each syndrome type (P < 0.01). As for infection routes, QDS was predominant in paid blood donation, blood transfusion infection, intravenous drugs. IDHAS was predominant in sexual transmit. No obvious laws were found in other syndrome types. There was statistical difference in the distribution of each syndrome type (P < 0.01). CONCLUSIONS: DIS, IDHAS, and no confirmable syndrome typing were dominant in asymptomatic HIV infection patients. Deficiency and dampness were important pathological factors for them.


Assuntos
Infecções por HIV/diagnóstico , Medicina Tradicional Chinesa/métodos , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem
17.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(11): 1481-4, 2013 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-24483107

RESUMO

OBJECTIVE: To investigate Chinese medical features of acquired immunodeficiency syndrome (AIDS) patients with pulmonary infection. METHODS: Using cluster analysis method, Chinese medical syndromes of 196 AIDS patients with pulmonary infection were analyzed. The distribution features of each syndrome type were analyzed according to the severity and CD4+ numerical analysis. RESULTS: Basic Chinese medical syndrome types could be summed up as three kinds: exterior invasion of wind heat and phlegm heat obstructing Fei syndrome (61 cases, 31.1%), Fei-Pi deficiency and Fei stagnation of phlegm syndrome (64 cases, 32.7%), Fei-Shen deficiency and yin deficiency induced inner heat syndrome (71 cases, 36.2%). There was statistical difference in the severity degree and the distribution of CD4 among the three syndrome types (P < 0.05). CONCLUSIONS: AIDS patients with pulmonary infection involve Fei, Shen, and Pi. The pathogenic factors were related to "wind", "heat", "phlegm", and "xu". The Chinese medical syndrome distribution was closely correlated with patients' immunity.


Assuntos
Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Síndrome de Imunodeficiência Adquirida/diagnóstico , Adolescente , Adulto , Idoso , Análise por Conglomerados , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa/métodos , Pessoa de Meia-Idade , Infecções Respiratórias/diagnóstico , Deficiência da Energia Yang/diagnóstico , Deficiência da Energia Yin/diagnóstico , Adulto Jovem
18.
Tumour Biol ; 28(4): 238-46, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17717429

RESUMO

BACKGROUND AND AIMS: Dendritic cell-based tumor vaccination is a promising approach in the treatment of cancer. Strategies to modify dendritic cells (DCs) with tumor-associated antigens (TAAs) can elicit specific immune responses against tumors. Heparanase is overexpressed in gastric cancer, especially in invasive and metastatic cells, but is downregulated in differential normal tissue. Therefore, heparanase is a potential target in immunotherapy for patients with advanced gastric cancer who are not candidates for surgery. The present paper was designed to investigate the immune response of a heparanase gene-modified DC-based vaccine against gastric cancer cell lines in vitro. METHODS: DCs from peripheral blood mononuclear cells of healthy HLA-A2-positive donors were transfected with recombinant adenovirus containing the full-length cDNA of heparanase (rAd-Hpa) to generate heparanase gene-modified DC vaccine. T lymphocytes from the same donors were repeatedly activated by genetically modified DC vaccine to generate heparanase-specific cytotoxicity T lymphocytes (CTLs). CTL-mediated cell lysis of gastric cancer cells lines (KATO-III and SGC-7901) was analyzed in vitro by a standard (51)Cr releasing assay. IFN-gamma secretion was measured by ELISA in heparanase-specific CTLs cocultured with those gastric cancer cell lines. RESULTS: Our results showed that the expression of heparanase in DCs transfected with rAd-Hpa was significantly increased. Furthermore, DCs transfected with rAd-Hpa could induce heparanase-specific CTLs against HLA-matched and heparanase-positive gastric cancer cells in vitro, while there were no killing effects on autologous lymphocytes. Meanwhile, these rAd-Hpa-modified DCs could increase IFN-gamma secretion of effector cells when cocultured with KATO-III cells. CONCLUSIONS: These findings demonstrate for the first time that the transduction of DCs with rAd-Hpa can induce CTLs that specifically lyse heparanase-positive gastric cancer cells and increase IFN-gamma secretion in an MHC-restricted fashion. Heparanase gene-modified DC vaccine offers a great opportunity for immunotherapy in patients with advanced gastric cancer and possibly also with other malignancies.


Assuntos
Células Dendríticas/citologia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glucuronidase/biossíntese , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/terapia , Linfócitos T Citotóxicos/metabolismo , Adenoviridae/metabolismo , Linhagem Celular Tumoral , Células Dendríticas/metabolismo , Antígeno HLA-A2/biossíntese , Humanos , Imuno-Histoquímica , Imunoterapia/métodos , Interferon gama/metabolismo , Leucócitos Mononucleares/metabolismo , Peptídeos/química
19.
Zhonghua Yi Xue Za Zhi ; 86(44): 3122-7, 2006 Nov 28.
Artigo em Chinês | MEDLINE | ID: mdl-17313764

RESUMO

OBJECTIVE: To explore the feasibility of heparinase vaccine in active immunity for gastric cancer. METHODS: Dendritic cells originated from the peripheral blood mononuclear cells (PBMC) of healthy HLA-A2 positive donors were transfected with recombinant adenovirus containing heparinase full length cDNA of heparanase to generate heparanase gene modified DC vaccine. T lymphocytes from the same donors were activated by those genetically modified DC vaccine repeatedly to generate heparanase specific cytotoxicity T lymphocytes (CTL). CTL-mediated cell lysis to gastric cancer cells of the lines KATO-III and SGC-7901 was analyzed in vitro by standard (51)Cr releasing assay. Heparinase specific CTL were co-cultured with KATO-III and SGC-7901 cells, and then ELISA was used to detect the IFN-gamma release. RESULTS: Expression of heparanase was significantly increased in the DCs transfected with heparinase recombinant adenovirus. Heparanase specific CTL generated from the genetically modified DC vaccine exhibited potent lysis to the KATO-III gastric cancer cells positive in both heparinase and HLA-A2 at each E/T ratio, whereas, these heparinase specific CTL could not lyse the SGC-7901 cells positive to heparinase but negative to HLA-A2, with a specific lysis rate of only 11.1% +/- 4.6% even at an E:T ratio of 40:1. Further study showed that heparanase vaccination had no detectable lysis on the autologous lymphocytes in vitro with a specific lysis rate of only 11.4% +/- 7.9% even at an E:T ratio of 40:1. The IFN-gamma release amount when the heparanase specific CTL were co-cultured with the KATO-III cells was 280.4 pg/ml +/- 23.5 pg/ml, significantly higher than that when the heparanase specific CTL were co-cultured with the rAd5-Lacz modified DC (120.6 pg/ml +/- 18.9 pg/ml), and that of the IL-2 stimulated T cells (60.0 pg/ml +/- 10.6 pg/ml, both P < 0.05). In contrast the IFN-gamma release amounts of the SGC-7901 cells and autologous lymphocytes remained unchanged when they were co-cultured with either above-mentioned effector cells (both P > 0.05). CONCLUSION: DC genetically modified by heparanase gene activate heparanase specific CTL and induce potent immune response against HLA-matched and heparinase positive gastric cancer cells in vitro, whereas they have no killing effect on autologous lymphocytes. Heparanase is an effective and safe target for immunogen therapy of tumor, thus providing a new biotherapy method for advanced gastric cancer.


Assuntos
Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Glucuronidase/genética , Vacinas Anticâncer/genética , Linhagem Celular Tumoral , Citotoxicidade Imunológica/efeitos dos fármacos , Citotoxicidade Imunológica/imunologia , Células Dendríticas/metabolismo , Glucuronidase/metabolismo , Antígeno HLA-A2/imunologia , Humanos , Imuno-Histoquímica , Interferon gama/metabolismo , Interleucina-2/imunologia , Microscopia Eletrônica , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/ultraestrutura , Transfecção , Fator de Necrose Tumoral alfa/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA