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1.
Clin Cancer Res ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32234760

RESUMO

PURPOSE: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens. EXPERIMENTAL DESIGN: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321). RESULTS: The four-CpG-based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P < 0.001). This classifier also showed good predictive value in the internal testing cohort (P < 0.001) and the independent validation cohort (P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation. CONCLUSIONS: Our four-CpG-based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.

2.
Arterioscler Thromb Vasc Biol ; 40(6): 1464-1478, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32268789

RESUMO

OBJECTIVE: Despite the current antiatherosclerotic and antithrombotic therapies, the incidence of advanced atherosclerosis-associated clinical events remains high. Whether long noncoding RNAs (lncRNAs) affect the progression of atherosclerosis and whether they are potential targets for the treatment of advanced atherosclerosis are poorly understood. Approach and Results: The progression of atherosclerotic lesions was accompanied by dynamic alterations in lncRNA expression, as revealed by RNA sequencing and quantitative polymerase chain reaction. Among the dynamically changing lncRNAs, we identified a novel lncRNA, lncRNA Associated with the Progression and Intervention of Atherosclerosis (RAPIA), that was highly expressed in advanced atherosclerotic lesions and in macrophages. Inhibition of RAPIA in vivo not only repressed the progression of atherosclerosis but also exerted atheroprotective effects similar to those of atorvastatin on advanced atherosclerotic plaques that had already formed. In vitro assays demonstrated that RAPIA promoted proliferation and reduced apoptosis of macrophages. A molecular sponge interaction between RAPIA and microRNA-183-5p was demonstrated by dual-luciferase reporter and RNA immunoprecipitation assays. Rescue assays indicated that RAPIA functioned at least in part by targeting the microRNA-183-5p/ITGB1 (integrin ß1) pathway in macrophages. In addition, the transcription factor FoxO1 (forkhead box O1) could bind to the RAPIA promoter region and facilitate the expression of RAPIA. CONCLUSIONS: The progression of atherosclerotic lesions was accompanied by dynamic changes in the expression of lncRNAs. Inhibition of the pivotal lncRNA RAPIA may be a novel preventive and therapeutic strategy for advanced atherosclerosis, especially in patients resistant or intolerant to statins.

3.
PLoS One ; 15(3): e0229272, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32119704

RESUMO

BACKGROUND AND AIMS: Radiotherapy is one of the major remedies for the treatment of cancer, including nasopharyngeal carcinoma (NPC). Radioresistance occurs very often in target cells that is a large drawback in cancer treated with radiotherapy. Livin involves the over-growth of cancer cells. This study aims to investigate the role of livin in the radioresistance formation in NPC cells. METHODS: NPC cell lines were exposed to small doses of irradiation to establish a cell model of radioresistance, in which the role of livin in the development of radioresistance was evaluated. RESULTS: The expression of livin was observed in NPC cells, which was significantly increased after exposing to small doses of irradiation. A negative correlation was detected between livin and Fas expression in NPC cells. Livin formed a complex with heat shock factor-1 (HSF1, the transcription factor of Fas) in NPC cells after irradiation, which sped up ubiquitination of HSF1. Livin was involved in suppressing Fas expression in NPC cells with radioresistance. Exposure to livin inhibitors prevented radioresistance development and overcame the established radioresistance in NPC cells. CONCLUSIONS: Livin expression in NPC cells plays a critical role in the development of radioresistance. Depletion of livin increases the sensitiveness of NPC cells to irradiation. Target therapy against livin may have the translational potential for the treatment of NPC.

4.
Leukemia ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080345

RESUMO

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565-6.628; p < 0.001), disease-free survival (DFS: HR 3.148, 95% CI 1.857-5.339; p < 0.001), and overall survival (OS: HR 3.790, 95% CI 2.237-6.423; p < 0.001) compared with low-risk patients. The prognostic accuracy of the classifier was validated in the internal testing (n = 84) and independent validation cohorts (n = 360). A prognostic nomogram consisting of five independent variables including the classifier, lactate dehydrogenase levels, ECOG-PS, central nervous system involvement, and NOTCH1/FBXW7 status showed significantly greater prognostic accuracy than each single variable alone. The addition of a five-miRNA-based signature further enhanced the accuracy of this nomogram. Furthermore, patients with a nomogram score ≥154.2 significantly benefited from the BFM protocol. In conclusion, our nomogram comprising the 11-gene-based classifier may make contributions to individual prognosis prediction and treatment decision-making.

5.
Environ Res ; 184: 109247, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32065976

RESUMO

In this study, three microbial fuel cells (MFCs) with different numbers of anodes (i.e., 1A, 3A, and 5A) were constructed to study the effects of a multi-anode (MA) system on power generation performance and nitrogen (N) removal from low carbon (C)/N wastewater. The maximum power density of 3A-MFC was 236.7 mW m-3, which was 2.6-fold and 1.2-fold that of 1A-MFC and 5A-MFC, respectively. The 3A-MFC system produced the highest total energy output in one cycle, approximately 41.7 mW h, which was 1.5-fold and 1.3-fold that of 1A-MFC and 5A-MFC, respectively. 3A-MFC also had the highest total N (TN) removal efficiency (71.1 ± 3.9%) and simultaneous nitrification and denitrification (SND) rate (93.5 ± 2.4%). An analysis of electron flow distribution in the 3A-MFC biocathode showed that electro-autotrophic denitrification accounted for 19% of the total denitrification in the last 135 h. Thereafter, the relationships between TN removal, anode number, and bioelectricity were systematically evaluated. TN removal efficiency had a good linear relationship with energy production (R2 = 0.97539); TN removal was mainly dependent on SND. Generally, the MA-MFC configuration proposed in this study produced more electrical energy and improved TN removal by enhancing nitrification and heterotrophic and electro-autotrophic denitrification of the biocathode. The proposed method is therefore effective for enhancing N removal.

6.
Biomed Pharmacother ; 125: 109944, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32062386

RESUMO

Cardiac fibrosis is a common pathological condition that contributes to the progression of many cardiac diseases. Circular RNAs (circRNAs) are emerging as new regulators of cardiac fibrosis. However, the expression and function of circRNAs in cardiac fibrosis remain largely unknown. The present study aims to investigate the circRNA expression profile and identify the roles of circRNAs in cardiac fibrosis. Transforming growth factor-ß1 (TGF-ß1) was used to establish an in vitro model of cardiac fibrosis in cardiac fibroblasts. CircRNA sequencing revealed that a total of 283 circRNAs were aberrantly expressed in fibrotic cardiac fibroblasts, with 79 upregulated and 204 downregulated. The expression changes of randomly selected circRNAs were validated by real-time PCR. A circRNA-based competing endogenous RNA network 1755 nodes and 30394 edges was established, and module analysis was conducted using the plug-in MCODE. KEGG pathway enrichment analysis was performed for mRNAs involved in the top three enriched modules. The results showed that these mRNAs were enriched in cardiac fibrosis-related signalling pathways, including the 'TGF-beta signaling pathway', 'MAPK signaling pathway', 'AMPK signaling pathway', and 'PI3K-Akt signaling pathway'. The predicted ceRNAs and bioinformatics analysis revealed the potential role of circRNAs in cardiac fibrosis, which would provide useful information for understanding the mechanism and finding effective prevention and treatment targets for cardiac fibrosis.

7.
Bioresour Technol ; 300: 122709, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901771

RESUMO

Bio-valorization of organic waste streams, such as food waste and waste activated sludge, to lactic acid (LA) has recently drawn much attention. It offers an opportunity for resource recovery, alleviates environmental issues and potentially turns a profit. In this study, both stable and high LA yield (0.72 ± 0.15 g/g total chemical oxygen demand) and productivity rate (0.53 g/L•h) were obtained through repeated batch fermentation. Moreover, stable solubilization and increase in the critical hydrolase activities were achieved. Depletions of ammonia and phosphorus were correlated with the LA production. The relative abundance of the key LA bacteria genera (i.e., Alkaliphilus, Dysgonomonas, Enterococcus and Bifidobacterium) stabilized in the repeated batch reactor at a higher level (44.5 ± 2.53%) in comparison with the batch reactor (26.2 ± 4.74%). This work show a practical way for the sustainable valorization of organic wastes to LA by applying the repeated batch mode during biological treatment.


Assuntos
Eliminação de Resíduos , Esgotos , Reatores Biológicos , Fermentação , Alimentos , Ácido Láctico
8.
Environ Technol ; : 1-11, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31538864

RESUMO

A multi-anode microbial fuel cell (MA-MFC) was developed to investigate simultaneous nitrification and denitrification (SND) in the bio-cathode. As the chemical oxygen demand to nitrogen (COD/N) ratio of the cathode was increased from 0 to 4.5, the electricity-producing quantity ranged between 498 and 543 C and the attained total nitrogen (TN) removal rate reached 12.07 g TN·m-3·d-1, resulting in a TN removal efficiency of 78.8% under the target COD/N ratio of 3.5. The removal of pollutants in series and parallel, open-circuit and closed-circuit were compared, respectively. The removal rates of TN, NH4+-N , and cathode and anode COD were all higher in the parallel connection configuration than in the series configuration. In parallel connection, the TN removal rate reached 14.4 g TN·m-3·d-1, which was 1.9 times that in series connection. Compared with the open-circuit system, the removal rate of TN in the closed-circuit system was improved by 17.8%, which could be ascribed to electrochemical denitrification. The results of high-throughput sequencing confirmed and clarified the presence of autotrophic denitrification and heterotrophic denitrification, including aerobic denitrification, when the MA-MFC had been operated for 18 months.

9.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(8): 824-829, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31416510

RESUMO

OBJECTIVE: To construct a W203X-mutant mouse model of cblC type methylmalonic acidemia based on the CRISPR/Cas9 technology. METHODS: At first, BLAST was used to compare the conservative nature of the cblC gene and protein sequences in humans and mice, and then, the CRISPR/Cas9 technology was used for microinjection of mouse fertilized eggs to obtain heterozygous F1 mice. Hybridization was performed for these mice to obtain homozygous W203X-mutant mice. The blood level of the metabolite propionyl carnitine (C3) was measured for homozygous mutant mice, heterozygous littermates, and wild-type mice. RESULTS: The gene and protein sequences of MMACHC, the pathogenic gene for cblC type methylmalonic acidemia, were highly conserved in humans and mice. The homozygous W203X-mutant mice were successfully obtained by the CRISPR/Cas9 technology, and there was a significant increase in C3 in these mice at 24 hours after birth (P<0.001). CONCLUSIONS: A W203X-mutant mouse model of cblC type methylmalonic acidemia is successfully constructed by the CRISPR/Cas9 technology.


Assuntos
Sistemas CRISPR-Cas , Erros Inatos do Metabolismo dos Aminoácidos , Animais , Proteínas de Transporte , Heterozigoto , Camundongos , Mutação , Oxirredutases
10.
Atherosclerosis ; 287: 134-139, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31272069

RESUMO

BACKGROUND AND AIMS: Plaque progression increases the risk of a cardiovascular event. This study aims to determine whether intraplaque neovascularization (NV) associates with a greater risk of plaque progression. METHODS: Baseline and 12-month follow-up IVUS was used in combination with baseline OCT to assess 164 non-culprit plaques in 118 CAD patients. A generalized estimating equation approach with exchangeable correlation structure was used to correct for the dependency of repeated measurements. RESULTS: Patients were divided into two groups according to NV (52 patients with 62 NV plaques, 66 patients with 102 non-NV plaques). Non-culprit plaques in the NV group exhibited a more frequent occurrence of TCFA (p = 0.004), macrophage (p = 0.005), cholesterol crystal (p = 0.012), calcification (p = 0.030), thinner fibrous cap thickness (FCT) [(86.8 ±â€¯55.1) vs. (127.4 ±â€¯70.1) µm, p = 0.015], larger lipid arc [(219.5 ±â€¯66.9) vs. (179.8 ±â€¯61.4), p = 0.002] compared to the non-NV group. A large change in percent atheroma volume (PAV), plaque plus media cross-sectional area (P&M CSA), plaque volume, and plaque burden was observed from baseline to follow-up in the NV group. Changes in P&M CSA, plaque volume, and plaque burden showed significant differences in fibroatheroma with NV. Intraplaque NV could predict a high risk of plaque progression despite statin therapy [OR 6.521 (95% CI 2.457-17.308), p < 0.001]. CONCLUSIONS: NV might attenuate the benefits of statin therapy in plaque progression. This study may provide a new basis for anti-angiogenic strategies to prevent atherosclerotic plaque progression.

11.
Theranostics ; 9(10): 2800-2811, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244924

RESUMO

Rationale: Immune dysfunction is thought to play an important role in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). However, the underlying mechanism requires further investigation. Vasoactive intestinal peptide (VIP) has immune regulatory functions, but its role in immune regulatory activities in the intestinal mucosa is not fully understood. This study aims to elucidate the role of VIP in the regulation of regulatory B cell (Breg) function in the intestine. Methods: Peripheral blood samples were collected from UC patients and healthy control (HC) subjects. Bregs were isolated from these samples and their immune regulatory function was analyzed. A murine colitis model was established to test the role of VIP in inhibiting inflammation in the intestine. Results: Serum IL-10 and VIP levels were lower in IgE+ (≥0.35 IU/mL) UC patients than that in HC subjects. The immune suppressive function of Bregs isolated from IgE+ UC patients was impaired. IL-10 mRNA decayed spontaneously in Bregs, which was reversed by VIP added to the culture. Tristetraprolin (TTP) bound IL-10 mRNA to speed its decay, which was blocked by VIP in the culture. Administration of VIP efficiently inhibited experimental colitis. Conclusions: Insufficient VIP levels in the microenvironment speeds IL-10 mRNA decay to cause Breg dysfunction. Administration of VIP can inhibit experimental colitis, suggesting the translational potential of VIP in the treatment of IgE+ UC.

12.
EBioMedicine ; 44: 71-85, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31129099

RESUMO

BACKGROUND: Increased frequency of CCR9+ CD4+ T cells in peripheral blood is linked to several gastrointestinal inflammatory diseases; however, its relationship with necrotizing enterocolitis (NEC) is not understood. We investigated whether the frequencies of CCR9+ CD4+ T cells and related subsets were increased in peripheral blood of both patients and mice with NEC. METHODS: CCR9+ CD4+ T cells and related subsets were evaluated by flow cytometry in peripheral blood collected from both patients and mice with NEC and controls. The suppressive function of CCR9+ regulatory T (Treg) cells in NEC was assessed via in vitro suppression assay. An in vitro T cell polarization assay was performed to investigate the role of proinflammatory cytokines in Treg cell polarization. In vivo Treg cell polarization analysis was performed using NEC mice treated with anti-interleukin-6 (IL-6) receptor antibody. FINDINGS: A higher proportion of CCR9+ CD4+ T cells occurred in peripheral blood of both patients and mice with NEC than in controls. Elevated CCR9+ CD4+ T cells were primarily CCR9+ IL-17-producing Treg cells, possessing features of conventional Treg cells, but their suppressive activity was seriously impaired and negatively correlated with the severity of intestinal tissue injury. IL-6 promoted polarization of CCR9+ Treg cells to CCR9+ IL-17-producing Treg cells, and blocking IL-6 signalling inhibited this conversion in vitro and ameliorated experimental NEC in vivo. INTERPRETATION: Collectively, these data suggested that CCR9+ IL-17-producing Treg cells may be a biomarker of severity and highlight the possibility that antibodies targeting IL-6R could ameliorate NEC by modulating lymphocyte balance. FUND: This work was supported by the Science and Technology Planning Project of Guangdong Province, China (2017A020215100), the Science and Technology Foundation of Guangzhou, China (201704020086 and 201604020154), the Medical Scientific Research Foundation of Guangdong Province, China (A2017304 and A2014704), and the Social Science and Technology Development Foundation of Dongguan, China (2016108101037).


Assuntos
Enterocolite Necrosante/etiologia , Enterocolite Necrosante/metabolismo , Interleucina-17/biossíntese , Ativação Linfocitária/imunologia , Receptores CCR/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Enterocolite Necrosante/diagnóstico , Feminino , Humanos , Imunomodulação , Imunofenotipagem , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Camundongos , Células T Invariáveis Associadas à Mucosa/imunologia , Células T Invariáveis Associadas à Mucosa/metabolismo , Índice de Gravidade de Doença , Células Th17/imunologia , Células Th17/metabolismo
13.
Leukemia ; 33(10): 2454-2465, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30953029

RESUMO

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.


Assuntos
MicroRNAs/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Linfócitos T/metabolismo , Linfócitos T/patologia , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão/métodos
14.
Cancer Sci ; 110(6): 2014-2021, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31033100

RESUMO

This study aimed to analyze the association between driver mutations and predictive markers for some anti-tumor agents in non-small cell lung cancer (NSCLC). A cohort of 785 Chinese patients with NSCLC who underwent resection from March 2016 to November 2017 in the First Affiliated Hospital of Guangzhou Medical University was investigated. The specimens were subjected to hybridization capture and sequence of 8 important NSCLC-related driver genes. In addition, the slides were tested for PD-L1, excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), thymidylate synthase (TS) and ß-tubulin III by immunohistochemical staining. A total of 498 (63.4%) patients had at least 1 driver gene alteration. Wild-type, EGFR rare mutation (mut), ALK fusion (fus), RAS mut, RET fus and MET mut had relatively higher proportions of lower ERCC1 expression. EGFR 19del, EGFR L858R, EGFR rare mut, ALK fus, HER2 mut, ROS1 fus and MET mut were more likely to have TS low expression. Wild-type, EGFR L858R, EGFR rare mut and BRAF mut were associated with lower ß-tubulin III expression. In addition, wild-type, RAS mut, ROS1 fus, BRAF and MET mut had higher proportion of PD-L1 high expression. As a pilot validation, 21 wild-type patients with advanced NSCLC showed better depth of response and response rate to taxanes compared with pemetrexed/gemcitabine (31.2%/60.0% vs 26.6%/45.5%). Our study may aid in selecting the optimal salvage regimen after targeted therapy failure, or the chemo-regimen where targeted therapy has not been a routine option. Further validation is warranted.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Mutação , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Pemetrexede/administração & dosagem , Prognóstico , Taxoides/uso terapêutico
15.
Oncol Rep ; 41(5): 2987-2996, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896844

RESUMO

Lung cancer is the most common and lethal cancer worldwide, especially in developing countries. Non­small cell lung cancer (NSCLC) accounts for 85% of all cases of lung cancer. In aprevious study, the protein expression of ubiquitin conjugating enzyme E2 C (UBE2C/UbcH10) in NSCLC tissues and cells was found to be significantly higher than that in adjacent tissues and normal lung epithelial cells. Further study revealed that the aberrant expression of UbcH10 in NSCLC tumors or cancer cells was caused by inactivation of the post­transcriptional regulation mechanism, and thus microRNAs (miRNAs) may play an important. In the present study, it was demonstrated that the expression of microRNA, hsa­miR661­3p, was downregulated and UbcH10 was upregulated in 12 pairs of NSCLC tumors and three NSCLC cell lines. A reporter gene assay revealed that overexpression of hsa­miR661­3p effectively reduced the activity of luciferase expressed by a vector bearing the 3' untranslated region of UbcH10 mRNA. Ectopic hsa­miR661­3p overexpression mediated by lentiviral infection decreased the expression of UbcH10. Infection of Lv­miR661­3p inhibited cell growth and invasion in A549 and SK­MES­1 cells. Mechanistically, hsa­miR661­3p induced cell cycle G2 arrest through regulation of spindle assembly checkpoint (SAC) function. On the basis of the proposed mechanisms, the objective of the study was to inhibit the proliferation of A549 and SK­MES­1 by expressing hsa­miR661­3p in vivo and in vitro. Collectively, our results indicated that downregulation of hsa­miR661­3p was involved in NSCLC and restoration of hsa­miR661­3p impaired the growth of NSCLC cell lines A549 and SK­MES­1, suggesting that hsa­miR661­3p may be a potential target molecule for the therapy of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Células A549 , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Interferência de RNA , Enzimas de Conjugação de Ubiquitina/metabolismo , Regulação para Cima
16.
J Cardiovasc Med (Hagerstown) ; 20(8): 518-524, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30889077

RESUMO

AIMS: This study aimed to investigate the progression and vascular shrinkage of vulnerable plaque lesions with a plaque burden at least 70% among patients with coronary artery disease by optical coherence tomography (OCT) and intravascular ultrasound (IVUS). METHODS: Fifty-six OCT-identified vulnerable plaques from 47 patients were included among coronary angiography-identified nonculprit/nontarget lesions. Serial IVUS images were used to assess plaque progression and vascular shrinkage. RESULTS: Thirty-five small vulnerable plaques (plaque burden <70%, group A) and 21 large vulnerable plaques (plaque burden ≥70%, group B) were identified. The IVUS results at baseline show that mean plaque areas (P < 0.001) and the percentage atheroma volume (PAV) (P < 0.0001) were greater and the minimal lumen area (P < 0.0001) was smaller in group B. The absolute and relative changes in the PAV and mean plaque area from baseline to follow-up were not significantly different. However, the lesions exhibited vessel shrinkage [the mean external elastic membrane (EEM) area (P = 0.02) and mean lumen area (P = 0.03) were significantly smaller in group B] from baseline to follow-up. Patients in group B also exhibited clinical events (recurrent angina symptoms) during the follow-up period. Positive correlations were found between changes in the mean plaque area and the mean EEM area in large vulnerable plaques (r = 0.61, P < 0.0001) and between changes in the mean EEM area and the mean lumen area in large vulnerable plaques (r = 0.61, P < 0.0001). CONCLUSION: Vulnerable plaque progression was not different between small and large vulnerable plaques. However, large vulnerable plaque lesions tended to exhibit vascular shrinkage, which is possible a cause of coronary artery lumen loss in patients with large vulnerable plaques.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Placa Aterosclerótica , Tomografia de Coerência Óptica , Ultrassonografia de Intervenção , Angiografia Coronária , Progressão da Doença , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Recidiva , Ruptura Espontânea , Fatores de Tempo
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 38(11): 1349-1353, 2018 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-30514684

RESUMO

OBJECTIVE: To analyze the changes in tumor lymphatic vessel density (LVD) in patients with lung adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA) and explore the regulatory factors of LVD. METHODS: Complete clinicopathological data were collected form a total of 301 patients with lung adenocarcinoma, including 28 (9.3%) with AIS, 86 (28.6%) with MIA, and 187 (62.1%) with IA. The LVD of all the adenocarcinomas were calculated after D2-40 immunohistochemical staining, and MT1-MMP and VEGF-C expression levels were also evaluated. The differences in LVD among the groups and the correlations of tumor LVD with the expressions of MT1-MMP and VEGF-C and the clinicopathological factors were analyzed. RESULTS: The LVD differed significantly among AIS, MIA, and IA groups (P= 0.000). The LVDs was significantly correlated with the level of VEGF-C protein expression (r=0.917, P=0.009), tumor size (r= 0.686, P=0.017), lymph node metastasis (r=0.739, P=0.000), and clinical stage (r=0.874, P=0.012) of the patients. CONCLUSIONS: Tumor lymphangiogenesis plays an important role in lung adenocarcinoma progression, and VEGF-C may promote this process.


Assuntos
Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/patologia , Linfangiogênese , Vasos Linfáticos/patologia , Adenocarcinoma/química , Adenocarcinoma de Pulmão/química , Humanos , Imuno-Histoquímica , Vasos Linfáticos/química , Estadiamento de Neoplasias , Prognóstico , Carga Tumoral , Fator C de Crescimento do Endotélio Vascular/análise
18.
IET Nanobiotechnol ; 12(7): 915-921, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30247130

RESUMO

Methanobactin (Mb) is a small copper-chelating molecule that functions as an agent for copper acquisition, uptake and copper-containing methane monooxygenase catalysis in methane-oxidising bacteria. The UV-visible spectral and fluorescence spectral suggested that Mb/Cu coordination complex as a monomer (Mb-Cu), dimmer (Mb2-Cu) and tetramer (Mb4-Cu) could be obtained at different ratios of Mb to Cu (II). The kinetics of the oxidation of hydroquinone with hydrogen peroxide catalysed by the different Mb/Cu coordination complex were investigated. The results suggested that Mb2-Cu coordination form has highest catalytic capacity. Further, Mb-modified gold nanoparticles (AuNPs) were obtained by ligand exchange and assembled into two- and three-D nanocluster structure by metal-organic coordination as driving force. It has been found that AuNPs increased the catalytic activity of Mb2-Cu on AuNPs. The more significant catalytic activity was exhibited by the nanocluster assembly with multi-catalytic centres. This may be attributed to the multivalent collaborative characteristics of the catalytic active centres in the nanocluster network assembly. The assembly of Mb-modified AuNPs can act as excellent nanoenzyme models for imitating peroxidase.


Assuntos
Cobre/metabolismo , Ouro/química , Imidazóis , Nanopartículas Metálicas/química , Oligopeptídeos , Peroxidase/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Cobre/química , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Hidroquinonas/análise , Hidroquinonas/química , Hidroquinonas/metabolismo , Imidazóis/química , Imidazóis/metabolismo , Cinética , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Oxirredução , Peroxidase/química
19.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 30(8): 743-747, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30220274

RESUMO

OBJECTIVE: To investigate the protective effect of microRNA-155 (miR-155) antisense oligonucleotid (ASO) on acute lung injury (ALI) mice by establishing a lentiviral expression vector of ASO of miRNA. METHODS: miR-155 antisense oligonucleotides amplified by polymerase chain reaction (PCR) from genomic, using BamH I and Nhe I double digestion, ligated into lentiviral expression vector. Sequence and virus titer were measured. According to the random number table method, 54 male BALB/c mice of 4-6 weeks old were divided into three groups. ALI animal models were prepared by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS). The three groups were injected with 200 µL phosphate buffered saline (PBS) containing 1×108/mL pmiR-155-ASO virus (pmiR-155-ASO group) or 200 µL PBS containing 1×108/mL pSMPUW-miR-GFP empty virus (pmiR-cont group) or the same amount of PBS (PBS group) at 24 hours before the molding. Ten mice in each group were used to observe the 7-day survival rate. Blood samples and lung tissues of the remaining 8 mice were harvested after the model was established, and the levels of serum inflammatory cytokines were determined by enzyme linked immunosorbent assay (ELISA); the expression of miR-155 in lung tissue was detected by real-time reverse transcription-polymerase chain reaction (RT-PCR); histopathological changes of lung and distribution of macrophages were observed under microscope. RESULTS: There was no significant difference in each index between pmiR-cont group and PBS group. The mature miR-155 expression in lung tissue in pmiR-155-ASO group was significantly lower than that in pmiR-cont group (2-ΔΔCt: 4.92±0.72 vs. 15.38±0.60, P < 0.05). Compared with pmiR-cont group, the injury degree of ALI mice after pretreatment with miR-155 ASO was significantly improved, and the 7-day survival rate was significantly increased (72.1% vs. 61.9%, P < 0.05 ); gross lung observation showed that congestion in lung tissue was significantly reduced, and the ratio of wet/dry weight (W/D) of lung was significantly decreased (4.50±0.13 vs. 5.64±0.61, P < 0.05); hematoxylin-eosin (HE) staining showed that inflammatory cell infiltration in lung tissue was decreased, while immunofluorescence assay showed that macrophage infiltration in lung tissue was significant decreased; the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum were significantly decreased [TNF-α (ng/L): 379.8±48.9 vs. 495.9±33.3, IL-6 (ng/L): 262.3±61.8 vs. 355.4±22.6, both P < 0.05], but the level of IL-10 did not change significantly (ng/L: 143.6±32.5 vs. 140.4±22.3, P > 0.05). CONCLUSIONS: miR-155 ASO has the effect of inhibiting LPS-induced inflammatory response and improving prognosis in ALI mice.


Assuntos
Lesão Pulmonar Aguda , Animais , Interleucina-6 , Lipopolissacarídeos , Pulmão , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs , Fator de Necrose Tumoral alfa
20.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 36(2): 128-132, 2018 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-29779271

RESUMO

OBJECTIVE: To investigate the effects of nerve growth factor (NGF) in the osteogenic action of implants and the maturation and reconstruction changes in bone tissues in the early stage of osseointegration. METHODS: The mouse implant model was established by placing titanium in the femoral head of the mouse and locally injecting NGF in the implant zone. On 1, 2 and 4 weeks after operation, stain samples were collected from animals using hematoxylin-eosin (HE) staining and Masson staining. The effect of NGF on the bone maturation was compared at different time points of early stage osseointegration. RESULTS: The results of HE and Masson staining indicated that the local injection of external NGF can up-regulate bone mass, amount of bone trabecula, and bone maturity in the mouse model. The mature bone rate in treatment group of 1 week and 4 weeks after operation were significantly higher than those in the control group (P<0.05). CONCLUSIONS: NGF can shorten the period of bone maturation.


Assuntos
Implantes Dentários , Fator de Crescimento Neural , Osseointegração , Próteses e Implantes , Animais , Camundongos , Fator de Crescimento Neural/administração & dosagem , Osteogênese , Propriedades de Superfície , Titânio
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