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1.
Mol Carcinog ; 62(9): 1295-1311, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37212496

RESUMO

TMEM147 was identified as a core component of ribosome-bound translocon complex at ER/NE. So far, sparse studies reported its expression profiling and oncological implications in hepatocellular carcinoma (HCC) patients. Here we inspected TMEM147 expression levels in HCC cohorts from public databases and tumor tissues. TMEM147 was augmented at transcriptional levels (p < 0.001) and protein levels in HCC patients. A series of bioinformatics tools implemented in R studio were orchestrated in TCGA-LIHC to evaluate the prognostic significance, compile relevant gene clusters, and explore the oncological functions and therapy responses. It is suggested that TMEM147 could predict poor clinical outcomes effectively and independently (p < 0.001, HR = 2.231 for overall survival (OS) vs. p = 0.04, HR = 2.296 for disease-specific survival), and was related to risk factors including advanced histologic tumor grade (p < 0.001), AFP level (p < 0.001) and vascular invasion (p = 0.007). Functional enrichment analyses indicated that TMEM147 was involved in cell cycle, WNT/MAPK signaling pathways and ferroptosis. Expression profiling in HCC cell lines, mouse model, and a clinical trial revealed that TMEM147 was a considerable target and marker for adjuvant therapy in vitro and in vivo. Subsequentially, in vitro wet-lab experimentation authenticated that TMEM147 would be downregulated by Sorafenib administration in hepatoma cells. Lentivirus-mediated overexpression of TMEM147 could promote cell cycle progression from S phase into G2/M phase, and enhance cell proliferation, thus attenuating drug efficacy and sensitivity of Sorafenib. Further explorations into TMEM147 may inspire a fresh perspective to predict clinical outcomes and improve therapeutic efficacy for HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Ciclo Celular , Divisão Celular , Linhagem Celular Tumoral
2.
Front Med (Lausanne) ; 9: 799642, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433733

RESUMO

Background: Blood gas analyzers (BGAs) and dry biochemistry analyzers for potassium and sodium are based on direct electrode methods, and both involve glucose oxidase for glucose detection. However, data are lacking regarding whether the results of the two assay systems can be used interchangeably. In addition, there remains controversy over the consistency between BGA-measured hemoglobin and complete blood count analyzer data. Here, we compared the consistency of sodium, potassium, glucose, and hemoglobin levels measured by BGA and dry chemistry and complete blood count analyzers. Methods: Data from two teaching hospitals, the Zhejiang Provincial People's Hospital (ZRY) and the Qianfoshan Hospital (QY), were retrospectively analyzed based on dry biochemistry and complete blood count analyzer results as the reference system (X) and BGA as the experimental system (Y). Plasma was used for biochemical analysis at the ZRY Hospital, and serum at the QY Hospital. Paired data from the respective hospitals were evaluated for consistency, and biases between methods were assessed by simple correlation, Passing-Bablok regression, and Bland-Altman analyses. Results: The correlations of potassium, sodium, glucose, and hemoglobin measured by BGA and dry biochemistry and complete blood count analyzers were high, at 0.9573, 0.8898, 0.9849, and 0.9883 for the ZRY Hospital and 0.9198, 0.8591, 0.9764, and 0.8666, respectively, for the QY Hospital. The results of Passing to Bablok regression analysis showed that the predicted biases at each medical decision level were within clinically acceptable levels for potassium, sodium, glucose, and hemoglobin at the ZRY Hospital. Only the predicted bias of glucose was below the clinically acceptable medical decision levels at the QY Hospital, while potassium, sodium, and hemoglobin were not. Compared with the reference system, the mean bias for BGA measurements at the ZRY Hospital was -0.08 mmol/L (95% confidence interval [CI] -0.091 to -0.069) for potassium, 1.2 mmol/L (95% CI 1.06 to 1.42) for sodium, 0.20 mmol/L (95% CI 0.167 to 0.228) for glucose, and -2.8 g/L for hemoglobin (95% CI -3.14 to -2.49). The mean bias for potassium, sodium, glucose, and hemoglobin at the QY Hospital were -0.46 mmol/L (95% CI -0.475 to -0.452), 3.7 mmol/L (95% CI 3.57 to 3.85), -0.36 mmol/L (95% CI -0.433 to -0.291), and -8.7 g/L (95% CI -9.40 to -8.05), respectively. Conclusion: BGA can be used interchangeably with plasma electrolyte results from dry biochemistry analyzers but does not show sufficient consistency with serum electrolyte results from dry biochemistry analyzers to allow data interchangeability. Good consistency was observed between BGA and plasma or serum glucose results from dry biochemistry analyzers. However, BGA-measured hemoglobin and hematocrit assay results should be treated with caution.

3.
PLoS One ; 13(9): e0204868, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30261049

RESUMO

Mice immunized with recombinant Echinococcus granulosus antigens Eg10 and Eg mMDH do not show elevated resistance to E. granulosus infection but show aggravated infection instead. To gain a deeper insight in the immune tolerance mechanisms in mice immunized with Eg10 and Eg mMDH, this study simulated the immune tolerance process in vitro by culturing bone marrow-derived dendritic cells (BMDCs) in the presence of Eg10 or Eg mMDH. Scanning electron microscopy revealed that Eg10- and Eg mMDH-treated DCs exhibited immature cell morphology, while addition of LPS to the cells induced changes in cell morphology and an increase in the number of cell-surface protrusions. This observation was consistent with the increased expression of the cell-surface molecules MHCII and CD80 in Eg10- and Eg mMDH-treated DCs pretreated with LPS. DCs exposed to the two antigens had a very weak ability to induce T-cell proliferation, but could promote the formation of Treg cells. Introduction of the indoleamine 2,3-dioxygenase (IDO) inhibitor, 1-methyl tryptopha (1-MT) enhanced the ability of the antigens to induce T cells and inhibited the induction of Treg cells. Eg mMDH-treated DCs showed a strong response to 1-MT: the DCs had high mRNA levels of IDO, IL-6, and IL-10, while 1-MT decreased the expression. In contrast, DCs treated with Eg10 did not show significant changes after 1-MT treatment. Eg mMDH inhibited DC maturation and promoted IDO expression, which, on the one hand, decreased the ability of DCs to induce T-cell proliferation, resulting in T-cell anergy, and on the other hand, induced the formation of Tregs, resulting in an immunosuppressive effect. In contrast, the escape mechanisms induced by Eg10 did not primarily depend on the IDO pathway and might involve other mechanisms that need to be further explored.


Assuntos
Antígenos de Helmintos/imunologia , Células da Medula Óssea/imunologia , Células Dendríticas/imunologia , Equinococose/imunologia , Tolerância Imunológica , Linfócitos T Reguladores/imunologia , Animais , Antígenos de Helmintos/genética , Antígenos de Helmintos/farmacologia , Células da Medula Óssea/patologia , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/patologia , Equinococose/patologia , Echinococcus granulosus , Masculino , Camundongos , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia , Linfócitos T Reguladores/patologia
4.
Parasitology ; 142(7): 879-89, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25711466

RESUMO

Cystic echinococcosis is a chronic infectious disease that results from a host/parasite interaction. Vaccination with ferritin derived from Echinococcus granulosus is a potential preventative treatment. To understand whether ferritin is capable of inducing a host immune response, we investigated the response of dendritic cells (DCs) to both recombinant ferritin protein and the hydatid fluid (HF) of E. granulosus. We evaluated the immunomodulatory potential of these antigens by performing, immunocytochemistry, electron microscopy and in vivo imaging of monocyte-derived murine DCs. During antigen stimulation of DCs, ferritin cause DCs maturation and induced higher levels of surface marker expression and activated T-cell proliferation and migration. On contrary, HF failed to induce surface marker expression and to stimulate T-cell proliferation. In response to HF, DCs produced interleukin-6 (IL-6), but no IL-12 and IL-10. DCs stimulated with ferritin produced high levels of cytokines. Overall, HF appears to induce host immunosuppression in order to ensure parasite survival via inhibits DC maturation and promotes Th2-dependent secretion of cytokines. Although ferritin also promoted DC maturation and cytokine release, it also activates CD4+T-cell proliferation, but regard of the mechanism of the Eg.ferritin induce host to eradicate E. granulosus were not clear.


Assuntos
Antígenos de Helmintos/farmacologia , Células Dendríticas/efeitos dos fármacos , Echinococcus granulosus/química , Ferritinas/farmacologia , Proteínas de Helminto/farmacologia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Diferenciação Celular , Movimento Celular , Proliferação de Células , Misturas Complexas/química , Misturas Complexas/farmacologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Equinococose/parasitologia , Echinococcus granulosus/crescimento & desenvolvimento , Echinococcus granulosus/imunologia , Ferritinas/biossíntese , Expressão Gênica , Interleucina-10/biossíntese , Interleucina-10/imunologia , Interleucina-12/biossíntese , Interleucina-12/imunologia , Interleucina-6/biossíntese , Interleucina-6/imunologia , Teste de Cultura Mista de Linfócitos , Camundongos , Camundongos Endogâmicos C57BL , Cultura Primária de Células , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/farmacologia , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
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