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1.
Sci Rep ; 11(1): 7485, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820934

RESUMO

A field experiment employing the rice cultivars Qyou6 and Yixiangyou2115 as materials and different nitrogen application rates was conducted in Huangping County, Guizhou Province in 2019 to determine the effects of nitrogen application rate on photosynthetic pigments, leaf fluorescence characteristics, yield, and their interrelations in indica hybrid rice. The results showed that photosynthetic pigment contents generally increased with increasing nitrogen application rate. As the nitrogen rate increased, the maximal quantum yield of PSII (Fv/Fm), actual quantum yield of PSII (ΦPSII), and relative electron transfer rate at PSII (ETR) first decreased and then increased at the booting stage; Fv/Fm and ΦPSII decreased while ETR first increased and then decreased at the heading stage; nevertheless, Fv/Fm and ΦPSII first decreased and then increased but ETR was just the opposite at the maturity stage. Non-photochemical quenching coefficient (qN) and quantum yield of regulatory energy dissipation at PSII (Y(NPQ)) first increased and then decreased whereas quantum yield of non-regulatory energy dissipation at PSII (Y(NO)) first decreased and then increased at the booting, heading, and maturity stages with increasing nitrogen application rate. Photochemical quenching coefficient (qP) showed an increasing trend as the nitrogen rate increased in the range of 150-300 kg/ha at the heading and maturity stages. Photosynthetic pigments, leaf fluorescence characteristics, and yield and its components were significantly correlated. First, chlorophylls a and b were significantly negatively correlated with Fv/Fm while significantly positively correlated with qP at the heading stage. Secondly, Carotenoids were significantly positively correlated with the effective panicle number (EPN) at the booting stage while significantly negatively correlated with the spikelets per panicle (SPP) at the heading stage. Chlorophyll a and carotenoids were significantly positively correlated with EPN but significantly negatively correlated with spikelet filling (SF) at the maturity stage. In addition, qP was significantly negatively correlated with EPN at the booting stage. At the heading stage, Fv/Fm and Y(NO) were significantly negatively correlated with EPN and SPP, respectively, and Fv/Fm and ΦPSII were significantly positively related to SF. Moreover, qP was extremely significantly positively related to EPN whereas Fv/Fm was extremely significantly negatively correlated with grain yield at the maturity stage. Appropriate nitrogen application rates can enhance photosynthetic pigment contents, improve the photochemical efficiency and proportion of the open part of the reaction center of PSII, and promote the quantum efficiency and self-protection ability of PSII, thereby increasing photosynthetic efficiency and yield. Under the conditions adopted in this experiment, a parabolic relationship was observed between the nitrogen application rate and grain yield. The regression analysis results showed that the best nitrogen application rate of indica hybrid rice is 168.16 kg ha-1 and the highest yield is 11,804.87 kg ha-1.

2.
Nucleic Acids Res ; 49(7): e37, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33434272

RESUMO

Multiple driver genes in individual patient samples may cause resistance to individual drugs in precision medicine. However, current computational methods have not studied how to fill the gap between personalized driver gene identification and combinatorial drug discovery for individual patients. Here, we developed a novel structural network controllability-based personalized driver genes and combinatorial drug identification algorithm (CPGD), aiming to identify combinatorial drugs for an individual patient by targeting personalized driver genes from network controllability perspective. On two benchmark disease datasets (i.e. breast cancer and lung cancer datasets), performance of CPGD is superior to that of other state-of-the-art driver gene-focus methods in terms of discovery rate among prior-known clinical efficacious combinatorial drugs. Especially on breast cancer dataset, CPGD evaluated synergistic effect of pairwise drug combinations by measuring synergistic effect of their corresponding personalized driver gene modules, which are affected by a given targeting personalized driver gene set of drugs. The results showed that CPGD performs better than existing synergistic combinatorial strategies in identifying clinical efficacious paired combinatorial drugs. Furthermore, CPGD enhanced cancer subtyping by computationally providing personalized side effect signatures for individual patients. In addition, CPGD identified 90 drug combinations candidates from SARS-COV2 dataset as potential drug repurposing candidates for recently spreading COVID-19.


Assuntos
Algoritmos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Quimioterapia Combinada , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Medicina de Precisão/métodos , Neoplasias da Mama/classificação , /genética , Conjuntos de Dados como Assunto , Reposicionamento de Medicamentos , Sinergismo Farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Regulação Neoplásica da Expressão Gênica/genética , Genes Neoplásicos/genética , Humanos , Medição de Risco , Fluxo de Trabalho
3.
BMC Bioinformatics ; 21(1): 419, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32972364

RESUMO

BACKGROUND: The treatment of complex diseases by taking multiple drugs becomes increasingly popular. However, drug-drug interactions (DDIs) may give rise to the risk of unanticipated adverse effects and even unknown toxicity. DDI detection in the wet lab is expensive and time-consuming. Thus, it is highly desired to develop the computational methods for predicting DDIs. Generally, most of the existing computational methods predict DDIs by extracting the chemical and biological features of drugs from diverse drug-related properties, however some drug properties are costly to obtain and not available in many cases. RESULTS: In this work, we presented a novel method (namely DPDDI) to predict DDIs by extracting the network structure features of drugs from DDI network with graph convolution network (GCN), and the deep neural network (DNN) model as a predictor. GCN learns the low-dimensional feature representations of drugs by capturing the topological relationship of drugs in DDI network. DNN predictor concatenates the latent feature vectors of any two drugs as the feature vector of the corresponding drug pairs to train a DNN for predicting the potential drug-drug interactions. Experiment results show that, the newly proposed DPDDI method outperforms four other state-of-the-art methods; the GCN-derived latent features include more DDI information than other features derived from chemical, biological or anatomical properties of drugs; and the concatenation feature aggregation operator is better than two other feature aggregation operators (i.e., inner product and summation). The results in case studies confirm that DPDDI achieves reasonable performance in predicting new DDIs. CONCLUSION: We proposed an effective and robust method DPDDI to predict the potential DDIs by utilizing the DDI network information without considering the drug properties (i.e., drug chemical and biological properties). The method should also be useful in other DDI-related scenarios, such as the detection of unexpected side effects, and the guidance of drug combination.


Assuntos
Interações Medicamentosas , Software , Bases de Dados como Assunto , Humanos , Redes Neurais de Computação
4.
PLoS One ; 15(6): e0233735, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497128

RESUMO

Many fertilization models have been created to scientifically determine the amount of fertilization. With the same purpose, we constructed a nitrogen (N) application model, the leaf value model, which can make N fertilizer decisions in a timely, fast and nondestructive manner during rice planting. However, only one area (A1, Jiuzhou Town, Xixiu District, Guizhou Province) and one cultivar (Qyou6) were involved in the construction of the leaf value model. Its stability and applicability could not be well evaluated. Thus, we chose another area (A2, Jiuzhou Town, Huangping County, Guizhou Province) in Guizhou Province and carried out the experiment by using four cultivars (Nie5you5399, Qyou6, Yixiangyou2115 and Zhongzheyou8) for the leaf value model construction. Compared with the average value of apparent total N uptake (Nz) obtained in 2 years in the A1 area, that in the Qyou6 leaf value model in the A2 area increased by 12%, reaching 635.72 kg ha-1, whereas the corresponding target yield changed slightly, reaching 10,999.90 kg ha-1. Simultaneously, the linear relationship between several good SPAD value-derived indexes (Ys) and apparent N supply of the field (Nx) was still significant or extremely significant in the Qyou6 leaf value model. Compared with the A1 area, it slightly differed, and the R2 of SPADL1 was higher than that of SPADL3×L4/mean. In the leaf value model of the other three cultivars, the relationship between yield and Nx and that between Ys and Nx were significant or extremely significant. The Nz of Yixiangyou2115 and Zhongzheyou8 (618.33 and 617.76 kg ha-1) were close to that of Qyou6 and the corresponding target yields were 10313.36 and 10301.99 kg ha-1, respectively. The Nz and target yield of Nie5you5399 were lowest at 546.63 and 10680.24 kg ha-1, respectively. In general, this study showed that relationships used in the construction of leaf value model had certain stability and applicability to difference areas and cultivars. The leaf value model can be considered in N fertilizer decision-making of rice planting management.


Assuntos
Fertilizantes , Modelos Biológicos , Nitrogênio/administração & dosagem , Oryza/fisiologia , Folhas de Planta/fisiologia , Clorofila/análise , Produção Agrícola/métodos , Oryza/anatomia & histologia , Oryza/química , Folhas de Planta/química , Solo/química
5.
Prostate ; 80(12): 977-985, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32542727

RESUMO

BACKGROUND: Recently, resveratrol (Res) has been suggested to suppress the migration and invasion of prostate cancer (PCa). In the present study, we aimed to investigate the effects of Res on genomic DNA methylation, as well as the migration and invasion of PCa cells. METHODS: The suppression by Res of the growth of PCa cells was verified through a cytotoxicity assay. In addition, the effects of Res on 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and ten-eleven translocation 1 (TET1) levels were assessed, and the cell migration and invasion were also determined. The expressions of TET1, tissue inhibitor of metalloproteinases (TIMP) 2, TIMP3, MMP2, and MMP9 were detected through Western blot analysis. Afterward, TET1 was silenced using lentiviral short hairpin RNA to examine the effect of TET1 on the Res-triggered inhibition of migration and invasion of PCa cells. RESULTS: Our results showed that Res upregulated the 5hmC and TET1 levels and downregulated the 5mC level. Moreover, Res also inhibited the migration and invasion of PCa cells, promoted the demethylation of TIMP2 and TIMP3 to upregulate their expressions, and suppressed the expressions of MMP2 and MMP9. The silencing of TET1 in the presence of Res showed that Res could exert its effect through TET1. CONCLUSIONS: Our findings indicated that Res inhibited the migration and invasion of PCa cells via the TET1/TIMP2/TIMP3 pathway, which might potentially serve as a target for the treatment of PCa.


Assuntos
Oxigenases de Função Mista/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Resveratrol/farmacologia , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Inibidor Tecidual de Metaloproteinase-3/metabolismo , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Células HEK293 , Humanos , Masculino , Oxigenases de Função Mista/biossíntese , Oxigenases de Função Mista/genética , Invasividade Neoplásica , Células PC-3 , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , Resveratrol/farmacocinética , Inibidor Tecidual de Metaloproteinase-2/biossíntese , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-3/biossíntese , Inibidor Tecidual de Metaloproteinase-3/genética , Regulação para Cima
6.
Oncol Lett ; 19(3): 2457-2465, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32194745

RESUMO

Immunotherapy is effective in improving the survival and prognosis of patients with non-small cell lung cancer (NSCLC), and identifying effective immunomarkers is important for immunotherapy. Interleukin (IL)-36γ is a novel immunomarker that has an important function in the antitumor immune response. The present study investigated the association between IL-36γ and NSCLC to provide novel insight into immunotherapy for patients with NSCLC. Tissue microarrays of lung adenocarcinoma and squamous cell carcinoma were purchased for immunohistochemical analysis of IL-36γ expression levels and clinical parameters. In addition, fresh clinical NSCLC and adjacent normal tissue samples were collected to analyze IL-36γ mRNA expression levels using quantitative PCR. IL-36γ protein was primarily located in the cytoplasm, with a small quantity in the nucleus, and IL-36γ mRNA and protein expression levels in lung cancer tissues were significantly higher compared with those in adjacent normal tissues. Elevated IL-36γ protein expression levels were significantly associated with a higher tumor grade of lung adenocarcinoma; however, IL-36γ mRNA expression levels were inversely associated with the clinical Tumor-Node-Metastasis stage in patients with lung squamous cell carcinoma. In addition, patients with adenocarcinoma with high IL-36γ protein expression levels tended to longer post-operative survival times. These findings indicate that IL-36γ may have potential as an immunomarker for prediction of tumor progression and survival in patients with NSCLC.

7.
Diabetes Res Clin Pract ; 157: 107874, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31593744

RESUMO

AIMS: To determine the predictability of diagnosing diabetic nephropathy (DN) versus non-diabetic renal disease (NDRD) from clinical and laboratory data in Chinese patients with type 2 diabetes mellitus (T2DM) manifesting heavy proteinuria. METHODS: We retrospectively analyzed the clinical and laboratory data of patients with T2DM manifesting heavy proteinuria who underwent renal biopsy from January 2014 to December 2017. RESULTS: According to renal biopsy, 220 patients were finally enrolled, including 109 cases diagnosed with DN alone (49.55%), 94 with NDRD alone (42.73%) and 17 with DN plus superimposed NDRD (7.73%). Multivariate analysis showed the significant risk factors for DN alone were age, duration of diabetes, presence of retinopathy, 24-h proteinuria, serum albumin and SBP. Presence of retinopathy achieved the highest overall diagnostic efficiency with the area under the curve of 0.852, sensitivity of 78.9% and specificity of 91.5%. The combined diagnosis with four indicators (duration of diabetes, retinopathy, SBP, and serum albumin) showed the area under the curve of 0.938, sensitivity of 88.1% and specificity of 87.2%. CONCLUSIONS: The prevalence of DN is high in patients with T2DM manifesting heavy proteinuria. Renal biopsy should be performed in diabetics in the atypical clinical scenario.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Rim/patologia , Proteinúria/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
8.
World J Gastroenterol ; 25(10): 1210-1223, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30886504

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality-to-incidence ratios. Nuclear factor erythroid 2-like 3 (NFE2L3), also known as NRF3, is a member of the cap 'n' collar basic-region leucine zipper family of transcription factors. NFE2L3 is involved in the regulation of various biological processes, whereas its role in HCC has not been elucidated. AIM: To explore the expression and biological function of NFE2L3 in HCC. METHODS: We analyzed the expression of NFE2L3 in HCC tissues and its correlation with clinicopathological parameters based on The Cancer Genome Atlas (TCGA) data portal. Short hairpin RNA (shRNA) interference technology was utilized to knock down NFE2L3 in vitro. Cell apoptosis, clone formation, proliferation, migration, and invasion assays were used to identify the biological effects of NFE2L3 in BEL-7404 and SMMC-7721 cells. The expression of epithelial-mesenchymal transition (EMT) markers was examined by Western blot analysis. RESULTS: TCGA analysis showed that NFE2L3 expression was significantly positively correlated with tumor grade, T stage, and pathologic stage. The qPCR and Western blot results showed that both the mRNA and protein levels of NFE2L3 were significantly decreased after shRNA-mediated knockdown in BEL-7404 and SMMC-7721 cells. The shRNA-mediated knockdown of NFE2L3 could induce apoptosis and inhibit the clone formation and cell proliferation of SMMC-7721 and BEL-7404 cells. NFE2L3 knockdown also significantly suppressed the migration, invasion, and EMT of the two cell lines. CONCLUSION: Our study showed that shRNA-mediated knockdown of NFE2L3 exhibited tumor-suppressing effects in HCC cells.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Apoptose/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Conjuntos de Dados como Assunto , Transição Epitelial-Mesenquimal/genética , Técnicas de Silenciamento de Genes , Humanos , Fígado/patologia , Neoplasias Hepáticas/patologia , Invasividade Neoplásica/genética , RNA Interferente Pequeno/metabolismo
9.
Cell Physiol Biochem ; 51(4): 1763-1777, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30504727

RESUMO

BACKGROUND/AIMS: microRNAs (miRNAs) are known to act as oncogenes or tumor suppressors in diverse cancers. Although miR-10b is an oncogene implicated in many tumors, its role in cervical cancer (CC) remains largely unclear. Here, we investigated the function and underlying mechanisms of miR-10b in human CC. METHODS: Quantitative RT-PCR was used to measure miR-10b expression in CC and normal tissues, and its association with clinicopathologic features was analyzed. Methylation of CpG sites in the miR-10b promoter was analyzed by methylation sequencing. Cell proliferation, apoptosis, migration, and invasion assays were used to elucidate the biological effects of miR-10b and expression of the target gene was assayed with Western blot. RESULTS: miR-10b was downregulated in CC tissues compared with normal tissues, and less miR-10b expression was associated with larger tumors, vascular invasion and HPV-type 16 positivity. miR-10b expression decreased in HeLa (HPV18-positive) and SiHa (HPV16-positive) cells compared with C-33A (HPV-negative), but increased after treatment with 5-Aza-CdR. Methylation ratio of site -797 in the miR-10b promoter in C-33A was lower than that in HeLa and SiHa. Further analysis indicates that site -797 is located within a transcription factor AP-2A (TFAP2A) binding element. Functionally, overexpression of miR-10b in HeLa and SiHa suppressed cell proliferation, migration and invasion, and induced apoptosis and miR-10b downregulation had opposite effects. Mechanistically, T-cell lymphoma invasion and metastasis 1 (Tiam1) was identified as a direct and functional target of miR-10b. CONCLUSION: miR-10b acts as a tumor suppressor in CC by suppressing oncogenic Tiam1, and its expression may be downregulated through methylation of TFAP2A binding element by HPV.


Assuntos
Metilação de DNA , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Adulto , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Feminino , Genes Supressores de Tumor , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/patologia
10.
J Interferon Cytokine Res ; 38(11): 491-499, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30452317

RESUMO

Interleukin-33 (IL-33) is a cytokine with pleiotropic functions in various diseases; however, its role in the antitumor immune response is still unclear. We found the expression of IL-33/ST2 in nonsmall cell lung tumor microenvironment. Furthermore, we found that IL-33 promoted effector functions of CD8+ T cells that play a critical role in antitumor immune response. In addition, we found that IL-33 enhanced tumor vaccine effector functions in mice. Altogether, these findings suggest that IL-33, through facilitates CD8+ T cells in microenvironment to provide a profound effect in antitumor immunotherapy.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia , Interleucina-33/imunologia , Neoplasias Pulmonares/terapia , Microambiente Tumoral/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Imunoterapia Adotiva , Interleucina-33/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Microambiente Tumoral/genética
11.
Lipids Health Dis ; 17(1): 200, 2018 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-30144814

RESUMO

BACKGROUND: Scavenger receptor BI (SR-BI) is a classic high-density lipoprotein (HDL) receptor, which mediates selective lipid uptake from HDL cholesterol esters (HDL-C). Apolipoprotein M (ApoM), as a component of HDL particles, could influence preß-HDL formation and cholesterol efflux. The aim of this study was to determine whether SR-BI deficiency influenced the expression of ApoM. METHODS: Blood samples and liver tissues were collected from SR-BI gene knockout mice, and serum lipid parameters, including total cholesterol (TC), triglyceride (TG), high and low-density lipoprotein cholesterol (HDL-C and LDL-C) and ApoM were measured. Hepatic ApoM and ApoAI mRNA levels were also determined. In addition, BLT-1, an inhibitor of SR-BI, was added to HepG2 cells cultured with cholesterol and HDL, under serum or serum-free conditions. The mRNA and protein expression levels of ApoM were detected by RT-PCR and western blot. RESULTS: We found that increased serum ApoM protein levels corresponded with high hepatic ApoM mRNA levels in both male and female SR-BI-/- mice. Besides, serum TC and HDL-C were also significantly increased. Treatment of HepG2 hepatoma cells with SR-BI specific inhibitor, BLT-1, could up-regulate ApoM expression in serum-containing medium but not in serum-free medium, even in the presence of HDL-C and cholesterol. CONCLUSIONS: Results suggested that SR-BI deficiency promoted ApoM expression, but the increased ApoM might be independent from HDL-mediated cholesterol uptake in hepatocytes.


Assuntos
Apolipoproteínas M/metabolismo , HDL-Colesterol/metabolismo , Hepatócitos/metabolismo , Receptores Depuradores Classe B/metabolismo , Animais , Apolipoproteínas M/sangue , Apolipoproteínas M/genética , HDL-Colesterol/sangue , Ciclopentanos/farmacologia , Feminino , Genótipo , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Tiossemicarbazonas/farmacologia
12.
Biochem Biophys Res Commun ; 501(2): 520-526, 2018 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-29750961

RESUMO

Apolipoprotein M (ApoM) is a sphingosine 1-phosphate (S1P) carrier involved in the regulation of S1P. Signaling pathways involving sphingosine kinases (SphKs) and S1P-S1P receptors (S1PRs) play important roles in the oncogenesis of multiple cancers including non-small cell lung cancer (NSCLC). In the present study we have clarified the potential roles of ApoM on the oncogenesis process of NSCLC cells. We detected the ApoM expression in NSCLC tissues and further analyzed its clinical significance. Moreover, we determined effects of ApoM overexpression on tumor cellular behaviours of NSCLC in vitro and in vivo. Our results demonstrated that ApoM protein mass were clearly higher in the NSCLC tissues than in non-NSCLS tissues. Overexpression of ApoM could promote NSCLC cell proliferation and invasion in vitro and tumor growth in vivo, which might be via upregulating S1PR1 and activating the ERK1/2 and PI3K/AKT signaling pathways. It is concluded that up-regulation of ApoM in NSCLC might be associated with the tumor induced inflammation and tumor microenvironment as well as promoting oncogenesis of NSCLC. Further study needs to elucidate the underlying mechanisms.


Assuntos
Apolipoproteínas M/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Invasividade Neoplásica/patologia , Receptores de Lisoesfingolipídeo/metabolismo , Transdução de Sinais , Idoso , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Esfingosina-1-Fosfato
13.
PLoS One ; 13(3): e0193428, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29499051

RESUMO

OBJECTIVE: Lung cancer is one of the deadliest malignancies. The immune checkpoint-blockade (ICB) tumor therapy has led to striking improvement of long-term survival for some lung cancer patients. However, the response rate of immunotherapy is still low for lung cancer. Studying the tumor microenvironment (TME) should shed light on improvement of immunotherapy of lung cancer. Interleukin-33 (IL-33), an "alarmin" cytokine, has been implicated in tumor associated immune responses and inflammatory diseases of the lung. The role of IL-33 in lung cancer progression, however, remains elusive. This study is designed to characterize IL-33 expression in lung tumor tissues and establish the clinical significance of IL-33 in non-small cell lung cancer lung cancer (NSCLC). MATERIALS AND METHODS: Tumor tissue specimens from patients suffering from NSCLC were analyzed for expression of IL-33 protein by immunohistochemistry and expression of IL-33 and ST2 mRNA by RT-quantitative PCR (RT-QPCR). The expression data were analyzed for their association with clinical and pathological parameters of NSCLC. In addition, the association between expression levels of IL-33 mRNA and patient survival was determined using 5 independent expression profiling datasets of human lung cancer. RESULTS AND CONCLUSION: The expression levels of IL-33 and ST2 were significantly down-regulated in both adenocarcinoma and squamous cell carcinoma of the lung when compared to adjacent normal lung tissues. In addition, the level of IL-33 protein was inversely correlated with tumor grade and size. Moreover, analysis of TCGA and GEO lung cancer expression datasets revealed that higher expression levels of IL-33 mRNA were correlated with longer overall survival of patients suffering from adenocarcinoma of the lung. These data indicate that the expression levels of IL-33 are inversely associated with lung cancer progression, consistent with the hypothesis that IL-33 is involved in immune surveillance of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Interleucina-33/metabolismo , Neoplasias Pulmonares/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Regulação para Baixo , Feminino , Humanos , Imuno-Histoquímica , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/genética , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Taxa de Sobrevida
14.
Cancer Cell Int ; 18: 34, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29556138

RESUMO

Background: The aberrant expression of long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been demonstrated to be involved in the tumourigenesis and the development of various cancers. Therefore, we conducted a meta-analysis to assess the prognostic role of lncRNA XIST expression in solid tumors. Methods: The databases of PubMed, EMBase, Web of Science, Cochrane library (up to Dec 31, 2017) were searched for the related studies and identified 15 eligible studies containing 1209 patients to include in the meta-analysis. Hazards ratios (HRs) with corresponding 95% confidence intervals (CIs) were pooled to estimate the association between lncRNA XIST expression and survival of cancer patients from Asian. Results: The result showed that higher lncRNA XIST expression in cancer tissue was related to a worse overall survival (OS) (HR = 1.54, 95% CI 1.07-2.23). In subgroup analysis, it revealed that lncRNA XIST overexpression was significantly associated with worse OS in digestive system tumors (HR = 1.67, 95% CI 1.11-2.51, p = 0.031). In addition, the association between high lncRNA XIST expression and poor OS was also statistically significant in other subgroups, including multivariate analysis (HR = 2.39, 95% CI 1.28-4.46, p = 0.006, random-effect), patients' number was greater than 65 (HR = 1.75, 95% CI 1.24-2.47, p = 0.001, random-effect), and reported in text (HR = 2.50, 95% CI 1.49-4.18, p = 0.000, random-effect). Conclusions: The expression of lncRNA XIST could be regarded as a poor prognostic biomarker for solid tumors, which might shed new light on epigenetic diagnostics and therapeutics in tumors.

15.
Oncotarget ; 9(16): 13088-13099, 2018 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-29560134

RESUMO

Background: Accumulating evidence showed that high expression of toll like receptor 4 (TLR4) was significantly associated with the outcome of patients with solid cancers. However, other studies failed to draw a similar conclusion. Thus, a systematic meta-analysis was performed to assess the prognostic value of TLR4 in solid tumors. Results: Data from 15 studies and 1294 patients were enrolled. Among the 15 studies, 14 studies demonstrated the association between overall survival(OS) and TLR4 expression, and 7 studies described the relationship between disease-free survival(DFS) and TLR4 expression. High expression of TLR4 was significantly associated with poor OS (pooled hazard ratio (HR) = 2.05; 95% confidence interval (CI) (1.49, 2,49), P < 0.001). The results of meta regression analysis indicated that the subgroups of ethnic (PD = 0.924), tumor type (PD = 0.669), HR obtained method (PD = 0.945), analysis type (PD = 0.898), and cut-off value(PD = 0.835) were not the resource of heterogeneity. Moreover, patients with elevated TLR4 had a significantly worse DFS (pooled HR = 1.79; 95% CI (1.11, 2.88), P < 0.05). Materials and Methods: We searched PubMed, Embase and the Cochrane Library (last update by April 18, 2017) to identify literatures evaluating the value of TLR4 in cancer patients. Combined hazard ratios (HRs) for OS and DFS were assessed using fixed-effects models and random effects models respectively. Conclusions: The meta-analysis suggests that elevated expression of TLR4 is associated with poor OS and shorter DFS of patients with solid tumors. The results indicate that TLR4, as a novel prognostic biomarker in solid tumors, could potentially help to improve treatment decision-making of solid tumors in clinical.

16.
Inflammation ; 41(2): 643-653, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29260347

RESUMO

It had been demonstrated that apolipoprotein M (apoM) is an important carrier of sphingosine-1-phosphate (S1P) in blood, and the S1P has critical roles in the pathogenesis of sepsis-induced acute lung injury (ALI). In the present study, we investigated whether apoM has beneficial effects in a mouse model after lipopolysaccharide (LPS)-induced ALI. Forty-eight mice were divided into two groups: male C57BL/6 wild-type (apoM+/+) group (n = 24) and apoM gene-deficient (apoM-/-) group (n = 24) and then randomly subdivided into four subgroups (n = 6 each) according to different intraperitoneal (i.p.) injection: control group, W146 group, LPS group, and LPS + W146 group. Serum levels of interleukin-1 beta (IL-1ß) and mRNA levels of IL-1ß, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), lung histology, wet/dry weight ratio, and immunohistochemistry were measured at 3 h after the baseline and compared in each group. Our results clearly demonstrated that IL-1ß mRNA levels and other inflammatory biomarkers were significantly increased in the lungs of LPS-induced ALI apoM-/- mice compared to those of the apoM+/+ mice. Moreover, when apoM+/+ mice were treated with W146, a S1P receptor (S1PR1) antagonist, these inflammatory biomarkers could be significantly upregulated by LPS-induced ALI. Therefore, it suggests that apoM-S1P-S1PR1 signaling might underlie the pathogenesis of ALI and apoM could have physiological benefits to alleviate LPS-induced ALI.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Apolipoproteínas M/fisiologia , Lisofosfolipídeos/metabolismo , Esfingosina/análogos & derivados , Lesão Pulmonar Aguda/induzido quimicamente , Anilidas/farmacologia , Animais , Biomarcadores/análise , Inflamação , Lipopolissacarídeos , Masculino , Camundongos , Organofosfonatos/farmacologia , Substâncias Protetoras/farmacologia , Receptores de Lisoesfingolipídeo/antagonistas & inibidores , Receptores de Lisoesfingolipídeo/metabolismo , Transdução de Sinais , Esfingosina/metabolismo
17.
Lipids Health Dis ; 16(1): 66, 2017 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-28359281

RESUMO

BACKGROUND: We have previously demonstrated that estrogen could significantly enhance expression of apolipoprotein M (apoM), whereas the molecular basis of its mechanism is not fully elucidated yet. To further investigate the mechanism behind the estrogen induced up-regulation of apoM expression. RESULTS: Our results demonstrated either free 17ß-estradiol (E2) or membrane-impermeable bovine serum albumin-conjugated E2 (E2-BSA) could modulate human apoM gene expression via the estrogen receptor alpha (ER-α) pathway in the HepG2 cells. Moreover, experiments with the luciferase activity analysis of truncated apoM promoters could demonstrate that a regulatory region (from-1580 to -1575 bp (-GGTCA-)) upstream of the transcriptional start site of apoM gene was essential for the basal transcriptional activity that regulated by the ER-α. With the applications of an electrophoresis mobility shift assay and a chromatin immunoprecipitation assay, we could successfully identify a specific ER-α binding element in the apoM promoter region. CONCULSION: In summary, the present study indicates that 17ß-estradiol induced up-regulation of apoM in HepG2 cells is through an ER-α-dependent pathway involving ER-α binding element in the promoter of the apoM gene.


Assuntos
Apolipoproteínas/genética , Estradiol/fisiologia , Receptor alfa de Estrogênio/fisiologia , Lipocalinas/genética , Ativação Transcricional , Apolipoproteínas/metabolismo , Apolipoproteínas M , Sequência de Bases , Sítios de Ligação , Células Hep G2 , Humanos , Lipocalinas/metabolismo , Células MCF-7 , Regiões Promotoras Genéticas , Ligação Proteica , Análise de Sequência de DNA , Regulação para Cima
18.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 32(6): 808-11, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-27371849

RESUMO

Objective To investigate the expression of interleukin 33 (IL-33) in cancer and adjacent non-cancerous tissues from patients with non-small cell lung cancer (NSCLC). Methods Real-time quantitative PCR was performed to detect the mRNA expression of IL-33 in 61 pairs of cancerous and adjacent non-cancerous tissues. In addition, immunohistochemistry was used to evaluate the expression and location of IL-33 on paraffin sections in selected 12 cases with different pathological types, to analyze the correlation of IL-33 expression with clinicopathological variables and overall survival. Results The expression of IL-33 mRNA in cancer tissues was significantly lower than that in adjacent non-cancerous tissues. The immunohistochemical results showed that IL-33 protein was mainly localized in the nucleus, and was obviously down-regulated in NSCLC. Besides, the expression of IL-33 was associated with histological type, but was not associated with age, gender, smoking history, differentiation status and pathological TNM stage. According to the Kaplan-Meier analysis, the expression of IL-33 mRNA was evidently associated with post-operative overall survival of patients suffering from NSCLC. Conclusion IL-33 may play an important role in the development of NSCLC and the targeted therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Interleucina-33/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Imuno-Histoquímica , Interleucina-33/metabolismo , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
J BUON ; 21(2): 390-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27273949

RESUMO

PURPOSE: To identify altered pathways in an individual with clear cell renal cell carcinoma (ccRCC) using accumulated normal sample data. METHODS: Gene expression data of E-GEOD-40435 was downloaded from the ArrayExpress database. Gene-level statistics of genes in tumor and normal samples were computed. Then, the Average Z method was applied to calculate the individual pathway aberrance score (iPAS). Subsequently, the significantly altered pathways in a ccRCC sample were identified using T-test based on the pathway statistics values of normal and ccRCC samples. Moreover, the identified altered pathways were verified through two methods: one was assessing classification capability for microarray data samples, and the other was computing the changed percentage of each pathway in ccRCC samples. RESULTS: Based on the threshold, 886 altered pathways were identified in all samples. The most significant pathways were potassium transport channels, proton-coupled monocarboxylate transport, beta oxidation of octanoyl-CoA to hexanoyl-CoA, antigen presentation: folding, assembly and peptide loading of class I MHC, and so on. Additionally, iPAS separated ccRCC from normal controls with an accuracy of 0.980. Moreover, a total of 5 significant pathways with change in 100% ccRCC samples were extracted including proton-coupled monocarboxylate transport, antigen presentation: folding, assembly and peptide loading of class I MHC, and so on. CONCLUSIONS: iPAS is useful to predict marker pathways for ccRCC with a high accuracy. Pathways of proton-coupled monocarboxylate transport, and antigen presentation: folding, assembly and peptide loading of class I MHC might play crucial roles in ccRCC progression.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Renais/genética , Análise de Sequência com Séries de Oligonucleotídeos , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Estudos de Casos e Controles , Bases de Dados Genéticas , Perfilação da Expressão Gênica/estatística & dados numéricos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Modelos Estatísticos , Análise de Sequência com Séries de Oligonucleotídeos/estatística & dados numéricos , Transdução de Sinais/genética
20.
Biomed Res Int ; 2015: 293512, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26543853

RESUMO

Spleen T-lymphocytes, especially CD4(+) T-cells, have been demonstrated to be involved in broad immunomodulation and host-defense activity in vivo. Apolipoprotein M gene (apoM) may have an important role in the regulation of immunoprocess and inflammation, which could be hypothesized to the apoM containing sphingosine-1-phosphate (S1P). In the present study we demonstrate that the splenic CD4(+) T-lymphocytes were obviously decreased in the apoM gene deficient (apoM(-/-)) mice compared to the wild type (apoM(+/+)). Moreover, these mice were treated with lipopolysaccharide (LPS) and it was found that even more pronounced decreasing CD4(+) T-lymphocytes occurred in the spleen compared to the apoM(+/+) mice. The similar phenomena were found in the ratio of CD4(+)/CD8(+) T-lymphocytes. After administration of LPS, the hepatic mRNA levels of tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) were markedly increased; however, there were no statistical differences observed between apoM(+/+) mice and apoM(-/-) mice. The present study demonstrated that apoM might facilitate the maintenance of CD4(+) T-lymphocytes or could modify the T-lymphocytes subgroups in murine spleen, which may further explore the importance of apoM in the regulation of the host immunomodulation, although the detailed mechanism needs continuing investigation.


Assuntos
Apolipoproteínas/genética , Linfócitos T CD4-Positivos/citologia , Baço/citologia , Imunidade Adaptativa , Animais , Apolipoproteínas M , Linfócitos T CD8-Positivos/citologia , Quimiocina CCL2/genética , Citocinas/metabolismo , Citometria de Fluxo , Inflamação , Lipopolissacarídeos/metabolismo , Fígado/metabolismo , Lisofosfolipídeos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase em Tempo Real , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Baço/imunologia , Fator de Necrose Tumoral alfa/genética
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