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1.
J Gene Med ; 26(9): e3728, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39183385

RESUMO

BACKGROUND: Lung cancer is a prevalent form of cancer worldwide. A possible link between lung cancer and chronic obstructive pulmonary disease (COPD) has been suggested by recent studies. The objective of our research was to analyze the mRNA expression patterns in both situations, with a specific emphasis on their biological functions and the pathways they are linked to. METHOD: Data on COPD mRNA expression was collected from the NCBI-GEO database, while information regarding lung cancer mRNA was acquired from The Cancer Genome Atlas database. To examine the association of COPD-related scores in lung cancer patients, we utilized the ssGSEA algorithm for single sample gene set enrichment analysis. The possible routes were examined through the utilization of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Risk models were developed using Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Moreover, a GSEA was performed to investigate significant pathways among various risk groups. RESULT: After identifying 17 genes that were differentially expressed and linked to COPD, we found that they met the criteria of having a false discovery rate < 0.05 and an absolute log2 fold change > 0.585. By utilizing the ssGSEA algorithm, it became possible to classify individuals with lung cancer into two distinct groups based on their COPD status. Consequently, a seven-gene risk model was developed specifically for these patients. The risk score was determined by applying the given formula: risk score = AC022784.1 × 0.0423737993775888 + CRISP3 × 0.0415322046890524 + MELTF × 0.0661848418476596 + MT2P1 × 0.111843227536117 + FAM83A-AS1 × 0.045295939710361 + ZNF506 × -0.309489953363417 + ITGA6 × 0.01813978449589. The risk model associated with COPD showed a notable connection with different immune cells found in the lung cancer sample, including macrophages of M0/M1/M2 types, hematopoietic stem cells, mast cells, NK T cells and regulatory T cells. Overexpression of crucial genes was seen to enhance cell proliferation and invasive potential in the lung cancer sample. In the lung cancer sample, it was observed that an increase in ZNF506 expression enhanced both cell proliferation and invasion. CONCLUSION: In conclusion, this study effectively examines the potential correlation between COPD and lung cancer. A prognostic model based on seven COPD-associated genes demonstrated robust predictive potential in the lung cancer sample. Our analysis offers comprehensive insights for lung cancer patients.


Assuntos
Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , RNA Mensageiro , Humanos , Doença Pulmonar Obstrutiva Crônica/genética , Neoplasias Pulmonares/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Perfilação da Expressão Gênica , Algoritmos , Regulação Neoplásica da Expressão Gênica , Biologia Computacional/métodos , Bases de Dados Genéticas , Ontologia Genética
2.
Int J Med Sci ; 21(3): 562-570, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322593

RESUMO

Background: Cleavage factor Im25 (CFIm25) regulates cell function by affecting mRNA editing processes and plays diverse roles in various diseases. Studies have found that peripheral blood monocytes are valuable in diagnosing and prognosing coronary atherosclerosis. However, no studies have examined the predictive value of CFIm25 expression in peripheral blood monocytes for coronary atherosclerosis. Methods and Results: We collected the coronary angiography results of 267 patients and calculated the Gensini score to evaluate their degree of coronary atherosclerosis. We isolated peripheral blood monocytes and detected CFIm25 RNA expression. Based on their Gensini score, we divided the patients into negative (0, n = 46), mild lesion (≤ 8, n = 71), moderate lesion (8-23, n = 76), and severe lesion (≥ 23, n = 74) groups. Results showed that CFIm25 expression correlated negatively with the Gensini score and the number of involved coronary vessels. Univariate and multivariate binary logistic regression analyses showed that CFIm25 expression in peripheral blood monocytes was a protective factor for severe lesions, ≥ 50% stenosis, and three-vessel lesions. The areas under the receiver operating characteristic curve of CFIm25 expression for predicting lesions, severe lesions, ≥50% stenosis, and three-vessel lesions were 0.743, 0.735, 0.791, and 0.736, respectively. Conclusions: CFIm25 expression in peripheral blood monocytes correlates negatively with the degree of coronary atherosclerosis and helps predict the severity and number of coronary artery lesions.


Assuntos
Fator de Especificidade de Clivagem e Poliadenilação , Doença da Artéria Coronariana , Humanos , Constrição Patológica , Angiografia Coronária , Monócitos , Índice de Gravidade de Doença , Fator de Especificidade de Clivagem e Poliadenilação/genética
3.
J Integr Neurosci ; 19(4): 663-671, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33378840

RESUMO

The effects of Danggui Sini decoction on peripheral neuropathy in oxaliplatin-induced peripheral is established. The results indicated that Danggui Sini decoction treatment significantly reduced the current amplitude of dorsal root ganglia cells undergoing agonists stimuli compared to the model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment significantly inhibited the inflammatory response of dorsal root ganglia cells compared to the model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment significantly enhanced the amounts of Nissl bodies in dorsal root ganglia cells compared to the Model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment improved ultra-microstructures of dorsal root ganglia cells. In conclusion, Danggui Sini decoction protected against neurotoxicity of oxaliplatin-induced peripheral neuropathy in rats by suppressing inflammatory lesions, improving ultra-microstructures, and enhancing amounts of Nissl bodies.


Assuntos
Antineoplásicos/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Gânglios Espinais/efeitos dos fármacos , Síndromes Neurotóxicas/prevenção & controle , Oxaliplatina/toxicidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Animais , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Masculino , Técnicas de Patch-Clamp , Ratos , Ratos Wistar
4.
Lipids Health Dis ; 17(1): 289, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30572889

RESUMO

BACKGROUND: The present study evaluated the predictive ability of five known "best" obesity and lipid-related parameters, including body mass index (BMI), waist-to-height ratio (WHtR), triglyceride-to-high-density-lipoprotein-cholesterol (TG/HDL-C), lipid accumulation product (LAP) and visceral adiposity index (VAI), in identifying metabolic syndrome (MetS) in Chinese elderly population. METHODS: A total of 6722 elderly Chinese subjects (≥60 years) were recruited into our community-based cross-sectional study from April 2015 to July 2017. The anthropometrics, blood pressure, fasting plasma glucose, blood lipid profiles, family history and health-related behaviours were assessed. RESULTS: The prevalence of MetS was 40.4% (32.5% in males and 47.2% in females). With the increase in the number of MetS components (from 0 to 5), all the five parameters showed an increase trend in both genders (all P for trend < 0.001). According to receiver operating characteristic curve (ROC) analyses, all the five parameters performed high predictive value in identifying MetS. The statistical significance of the areas under the curves (AUCs) differences suggested that the AUCs of LAP were the greatest among others in both genders (AUCs were 0.897 in males and 0.875 in females). The optimal cut-off values of LAP were 26.35 in males and 31.04 in females. After adjustment for potentially confounding factors, LAP was strongly associated with the odds of having MetS in both genders, and ORs for MetS increased across quartiles using multivariate logistic regression analysis (P < 0.001). CONCLUSION: LAP appeared to be a superior parameter for predicting MetS in both Chinese elderly males and females, better than VAI, TG/HDL-C, WHtR and BMI.


Assuntos
Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Idoso , Área Sob a Curva , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Produto da Acumulação Lipídica , Lipoproteínas HDL , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Triglicerídeos
5.
Tumour Biol ; 35(11): 11329-35, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25119598

RESUMO

In recent years, the role of long noncoding RNAs (lncRNAs) in cancer is increasingly focused. ncRuPAR is a newly detected lncRNA; in previous study, we found out that ncRuPAR could inhibit tumor progression by downregulating protease-activated receptor-1 (PAR-1), but its role in colorectal cancer (CRC) is never elucidated. Here, we conducted a self-control study which includes 105 CRC samples. By quantitative real time PCR (qRT-PCR) and immunohistochemical staining, we detected the expression of ncRuPAR and PAR-1 as well as their correlation; we further associated these data with the clinicopathologic parameters. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of ncRuPAR and PAR-1, respectively. Our results indicated that the expression of ncRuPAR was significantly downregulated in CRC compared with paired adjacent nontumor tissues, but the level of PAR-1 mRNA in cancerous tissues was significantly higher than in adjacent normal areas. The expression of ncRuPAR was significantly correlated with lymph node metastasis, distant metastasis, Duck's stage, differentiation, and TNM stage and was potentially negatively associated with the mRNA levels and EI scores of PAR-1. The area under the ROC curve of ncRuPAR was 0.81 (95% confidence interval (CI): 0.75-0.87); at a cutoff value of 8.34, the ncRuPAR measurement had a sensitivity of 97.14%, a specificity of 65.87%, and an accuracy of 82.86% to predict CRC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , RNA Longo não Codificante/genética , Receptor PAR-1/antagonistas & inibidores , Estudos de Casos e Controles , Colo/metabolismo , Neoplasias Colorretais/metabolismo , Regulação para Baixo , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Receptor PAR-1/genética , Receptor PAR-1/metabolismo , Reto/metabolismo , Taxa de Sobrevida
6.
Chemistry ; 20(39): 12655-62, 2014 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-25124384

RESUMO

A novel type of uranium-containing microspheres with an urchin-like hierarchical nano/microstructure has been successfully synthesized by a facile template-free hydrothermal method with uranyl nitrate hexahydrate, urea, and glycerol as the uranium source, precipitating agent, and shape-controlling agent, respectively. The as-synthesized microspheres were usually a few micrometers in size and porous inside, and their shells were composed of nanoscale rod-shaped crystals. The growth mechanism of the hydrothermal reaction was studied, revealing that temperature, ratios of reactants, solution pH, and reaction time were all critical for the growth. The mechanism study also revealed that an intermediate compound of 3 UO3 ⋅NH3 ⋅5 H2 O was first formed and then gradually converted into the final hydrothermal product. These uranium-containing microspheres were excellent precursors to synthesize porous uranium oxide microspheres. With a suitable calcination temperature, very uniform microspheres of uranium oxides (UO2+x , U3 O8 , and UO3 ) were successfully synthesized.

7.
Sci Total Environ ; 935: 173382, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38777050

RESUMO

With the development of monitoring technology, the variety of ozone precursors that can be detected by monitoring stations has been increased dramatically. And this has brought a great increment of information to ozone prediction and explanation studies. This study completes feature mining and reconstruction of multi-source data (meteorological data, conventional pollutant data, and precursors data) by using a machine learning approach, and built a cross-stacked ensemble learning model (CSEM). In the feature engineering process, this study reconstructed two VOCs variables most associated with ozone and found it works best to use the top seven variables with the highest contribution. The CSEM includes three base models: random forest, extreme gradient boosting tree, and LSTM, learning the parameters of the model under the integrated training of cross-stacking. The cross-stacked integrated training method enables the second-layer learner of the ensemble model to make full use of the learning results of the base models as training data, thereby improving the prediction performance of the model. The model predicted the hourly ozone concentration with R2 of 0.94, 0.97, and 0.96 for mild, moderate, and severe pollution cases, respectively; mean absolute error (MAE) of 4.48 µg/m3, 5.01 µg/m3, and 8.71 µg/m3, respectively. The model predicted ozone concentrations under different NOx and VOCs reduction scenarios, and the results show that with a 20 % reduction in VOCs and no change in NOx in the study area, 75.28 % of cases achieved reduction and 15.73 % of cases got below 200 µg/m3. In addition, a comprehensive evaluation index of the prediction model is proposed in this paper, which can be extended to any prediction model performance comparison and analysis. For practical application, machine learning feature selection and cross-stacked ensemble models can be jointly applied in ozone real-time prediction and emission reduction strategy analysis.

8.
iScience ; 27(3): 109258, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38433899

RESUMO

Brain metastases (BM) of lung adenocarcinoma (LUAD) are the most common intracranial malignancy leading to death. However, the cellular origins and drivers of BM from LUAD have not been clarified. Cellular composition was characterized by single-cell sequencing analysis of primary lung adenocarcinoma (pLUAD), BM and lymph node metastasis (LNM) samples in GSE131907. Our study briefly analyzed the tumor microenvironment (TME), focusing on the role of epithelial cells (ECs) in BM. We have discovered a population of brain metastasis-associated epithelial cells (BMAECs) expressing SPP1, SAA1, and CDKN2A, and it has been observed that this population is mainly composed of aneuploid cells from pLUAD, playing a crucial role in brain metastasis. Our study concluded that both LNM and BM in LUAD originated from pLUAD lesions, but there is currently insufficient evidence to prove a direct association between BM lesions and LNM lesions, which provides inspiration for further investigation of the TME in BM.

9.
Chin Med ; 19(1): 58, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38584284

RESUMO

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

10.
J Cancer Res Clin Oncol ; 149(17): 15687-15696, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37665405

RESUMO

PURPOSE: The purpose of this study was to use the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the survival rate of primary malignant cardiac tumors (PMCTs), assess the risk factors affecting survival, and calculate the number of PMCT cases in recent years. METHODS: SEER 22 registries were used to calculate the number of cases PMCT. Data on age, sex, race, marital status, tumor size, the American Joint Committee on Cancer (AJCC) stage, lymph node involvement, metastasis, treatment, and survival were collected to analyze the survival and prognostic factors of SEER 17 registries. Using the Kaplan-Meier estimation method, a survival curve was obtained according to the influencing factors, and a multivariable Cox regression model was established. RESULTS: In recent years, the average annual number of PMCT cases was 20.56 ± 7.12, significantly higher than the average before 2004 (P = 0.015; 95% CI 1.14-8.98). The 1-, 3-, and 5-year survival rates were 45.6%, 18.8%, and 11.2%, respectively. Multivariate analysis revealed that age (risk ratio [HR], 2.047; 95% CI 1.381-3.034), AJCC stage III (HR, 1.786; 95% CI 1.123-2.839), AJCC staging with distant metastasis (HR, 2.666; 95% CI 1.509-4.709), no chemotherapy (HR, 2.011; 95% CI 1.561-2.590), and tumor size larger than 99 mm (HR, 1.766; 95% CI 1.132-2.756) were independent risk factors for poor prognosis. Only age over 76 years and distant metastasis were independent risk factors for prognosis in the chemotherapy group. CONCLUSION: In recent years, the annual number of patients with PMCT has increased significantly. Due to developments in chemotherapy, we should re-evaluate the traditional tumor staging and prognostic risk indicators to improve clinical applications.


Assuntos
Neoplasias Cardíacas , Humanos , Idoso , Prognóstico , Programa de SEER , Estadiamento de Neoplasias , Sistema de Registros , Neoplasias Cardíacas/epidemiologia , Neoplasias Cardíacas/terapia
11.
Nat Commun ; 14(1): 3118, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37253723

RESUMO

De novo DNA methylation in plants relies on transcription of RNA polymerase V (Pol V) along with KTF1, which produce long non-coding RNAs for recruitment and assembly of the DNA methylation machinery. Here, we report a cryo-EM structure of the Pol V transcription elongation complex bound to KTF1. The structure reveals the conformation of the structural motifs in the active site of Pol V that accounts for its inferior RNA-extension ability. The structure also reveals structural features of Pol V that prevent it from interacting with the transcription factors of Pol II and Pol IV. The KOW5 domain of KTF1 binds near the RNA exit channel of Pol V providing a scaffold for the proposed recruitment of Argonaute proteins to initiate the assembly of the DNA methylation machinery. The structure provides insight into the Pol V transcription elongation process and the role of KTF1 during Pol V transcription-coupled DNA methylation.


Assuntos
RNA Polimerases Dirigidas por DNA , RNA Polimerase II , Microscopia Crioeletrônica , RNA Polimerases Dirigidas por DNA/metabolismo , RNA Polimerase II/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , RNA/metabolismo , Metilação de DNA , Transcrição Gênica
12.
Heliyon ; 9(9): e19817, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809930

RESUMO

In the context of cancer expansion, epithelial-mesenchymal transition (EMT) plays an essential role in driving invasion and metastasis potential of cancer cells. Tumor-associated macrophages (TAMs)-derived factors involved in the initiation and progression of EMT. We assess the role of M2 macrophage in suppressing lung tumors of a natural compound (-)-Guaiol by using macrophage depleted model. Bone marrow-derived monocytes (BMDMs) were extracted and induced to M2-like phenotype in vitro. The co-culture of M2 macrophage and lung cancer cells was established to observe that inhibition of lung tumor growth by (-)-Guaiol requires presence of macrophages. This suppressed effect of (-)-Guaiol was alleviated when mice macrophage was depleted. The expression of M2-like macrophages was strongly reduced by (-)-Guaiol treated mice, but not the changes of M1-like macrophages. In vitro studies, we demonstrated that (-)-Guaiol suppressed M2 polarization of BMDMs, as well as migration, invasion, and EMT of lung cancer cells in co-culture. M2 macrophage-derived interleukin 10 (IL-10) was investigated as a critical signaling molecule between M2 macrophage and lung cancer cells. We have also verified that the mechanism of (-)-Guaiol inhibiting the EMT process of lung cancer is related to the activation of IL-10-mediated signal transducer and activator of transcription 3 (STAT3). These results suggested that the suppressive effect role of (-)-Guaiol in M2 macrophage promoting EMT of lung cancer, which was associated with inhibition of IL-10 mediated STAT3 signaling pathway.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38062335

RESUMO

The diagnostic role of T-cell immunoglobulin and mucin domain 3 (Tim-3) expression levels in circulating monocytes in coronary artery disease (CAD) remains to be determined. Here, we enrolled of 265 patients and isolated circulating monocytes from the blood of all participants. We found that the Tim-3 expression levels in monocytes were lower in CAD patients than in the control group. Spearman correlation analysis verified that the Tim-3 levels in monocytes were negatively correlated with the Gensini score and the number of coronary vessels. Multivariate logistic regression analysis showed that the Tim-3 levels in circulating monocytes were negatively correlated with CAD, severe CAD, and three-vessel CAD. The ROC curve showed that Tim-3 possessed high diagnostic value for CAD, severe CAD, and three-vessel CAD, with CAD prediction being the most significant of these values. In conclusion, Tim-3 in circulating monocytes is a novel biomarker for CAD. T-cell immunoglobulin and mucin domain 3 (Tim-3) in circulating monocytes as a novel biomarker for coronary artery disease.

14.
Aging (Albany NY) ; 14(6): 2736-2747, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35333773

RESUMO

BACKGROUND: Accumulated studies have pointed out the striking association between variants in or near APOC3, GCKR, PNPLA3, and nonalcoholic fatty liver disease (NAFLD) at various ages from multiple ethnic groups. This association remained unclear in the Chinese Han elderly population, and whether this relationship correlated to any clinical parameters was also unclear. OBJECTIVES: This study aims to decipher the complex relevance between gene polymorphisms, clinical parameters, and NAFLD by association study and mediation analysis. METHODS: Eight SNPs (rs2854116, rs2854117, rs780093, rs780094, rs1260362, rs738409, rs2294918, and rs2281135) within APOC3, GCKR, and PNPLA3 were genotyped using the MassARRAY® platform in a large Chinese Han sample comprising of 733 elderly NAFLD patients and 824 age- and ethnic-matched controls. Association and mediation analysis were employed by R. RESULTS: The genotypic frequencies of rs1260326 and rs780094 were significantly different between NAFLD and control (rs1260326: P=0.004, Pcorr=0.020, OR [95%CI]= 0.69 [0.54-0.89]; rs780094: P=0.005, Pcorr=0.025, OR [95%CI]= 0.70 [0.55-0.90]). Particularly, an increased triglyceride level was observed in carriers of rs1260326 T allele (1.94±1.19 mmol/L) compared with non-carriers (1.73±1.05 mmol/L).no significant results were observed in rs780094. Notably, triglyceride levels had considerably indirect impacts on association between NAFLD and rs1260326 (ß =0.01, 95% CI: 0.01-0.02), indicating that 12.7% of the association of NAFLD with rs1260326 was mediated by triglyceride levels. CONCLUSIONS: Our results identified a prominent relationship between GCKR rs1260326 and NAFLD, and highlighted the mediated effect of triglyceride levels on the that association in the Chinese Han elderly.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Idoso , Estudos de Casos e Controles , China/epidemiologia , Predisposição Genética para Doença , Genótipo , Humanos , Lipase/genética , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo Único , Triglicerídeos
15.
Aging (Albany NY) ; 13(8): 11381-11410, 2021 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-33839701

RESUMO

Interferon-gamma (IFN-γ) plays a complex role in modulating tumor microenvironment during lung adenocarcinoma (LUAD) development. In order to define the role of IFN-γ response genes in LUAD progression, we characterized the gene expression, mutation profile, protein-protein interaction of 24 IFN-γ response genes, which exhibited significant hazard ratio in overall survival. Two subgroups of LUAD from the TCGA cohort, which showed significant difference in the survival rate, were identified based on the expression of these genes. Furthermore, LASSO penalized cox regression model was used to derive a risk signature comprising seven IFN-γ response genes, including CD74, CSF2RB, PTPN6, MT2A, NMI, LATS2, and PFKP, which can serve as an independent prognostic predictor of LUAD. The risk signature was validated in an independent LUAD cohort. The high risk group is enriched with genes regulating cell cycle and DNA replication, as well as a high level of pro-tumor immune cells. In addition, the risk score is negatively correlated with the expression of immune metagenes, but positively correlated with DNA damage repair genes. Our findings reveal that seven-gene risk signature can be a valuable prognostic predictor for LUAD, and they are crucial participants in tumor microenvironment of LUAD.


Assuntos
Adenocarcinoma de Pulmão/mortalidade , Biomarcadores Tumorais/genética , Interferon gama/metabolismo , Neoplasias Pulmonares/mortalidade , Microambiente Tumoral/imunologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Biologia Computacional , Reparo do DNA/imunologia , Conjuntos de Dados como Assunto , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Estimativa de Kaplan-Meier , Pulmão/imunologia , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco/métodos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Taxa de Sobrevida , Transcriptoma/imunologia
16.
Science ; 374(6575): 1579-1586, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34941388

RESUMO

DNA methylation affects gene expression and maintains genome integrity. The DNA-dependent RNA polymerase IV (Pol IV), together with the RNA-dependent RNA polymerase RDR2, produces double-stranded small interfering RNA precursors essential for establishing and maintaining DNA methylation in plants. We determined the cryo­electron microscopy structures of the Pol IV­RDR2 holoenzyme and the backtracked transcription elongation complex. These structures reveal that Pol IV and RDR2 form a complex with their active sites connected by an interpolymerase channel, through which the Pol IV­generated transcript is handed over to the RDR2 active site after being backtracked, where it is used as the template for double-stranded RNA (dsRNA) synthesis. Our results describe a 'backtracking-triggered RNA channeling' mechanism underlying dsRNA synthesis and also shed light on the evolutionary trajectory of eukaryotic RNA polymerases.


Assuntos
Proteínas de Arabidopsis/química , Arabidopsis/enzimologia , Arabidopsis/genética , RNA Polimerases Dirigidas por DNA/química , RNA de Cadeia Dupla/biossíntese , RNA de Plantas/biossíntese , RNA Polimerase Dependente de RNA/química , Motivos de Aminoácidos , Proteínas de Arabidopsis/metabolismo , Domínio Catalítico , Microscopia Crioeletrônica , Metilação de DNA , DNA de Plantas/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Holoenzimas/química , Modelos Moleculares , Complexos Multiproteicos/química , Conformação Proteica , Domínios Proteicos , RNA Polimerase II/química , RNA Interferente Pequeno/biossíntese , RNA Polimerase Dependente de RNA/metabolismo , Elongação da Transcrição Genética , Fatores de Transcrição/metabolismo
17.
J Nanosci Nanotechnol ; 20(2): 779-788, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383073

RESUMO

N and F co-doped La-TiO2 (La-TONF) samples were prepared through the solvothermal method by using HMT and NaF as precursors. The obtained samples were characterized by UV-Vis DRS, XRD, XPS and PL measurements for light-harvesting properties, crystal phase and optical characteristics, respectively. Interestingly, the TONF sample had a different fluorescence emission intensity than the TON or TOF samples, thus suggesting a clear synergistic effect of N and F co-doping. The optimal doping amount of La was 2 wt.%, and the absorption edge was red-shifted from 453 nm to 464 nm for La-TiO2 and La-TONF. The photocatalytic activity was evaluated by degradation of MO and oxidation of TMB under visible light irradiation. La-TONF exhibited excellent photocatalytic activity and a degradation rate of 92.4%, 4.4 times that of undoped TiO2 (20.8%). The photocatalytic degradation activity remained above 85.8%, even after five runs. In addition, the MO photodegradation catalyzed by La-TONF followed first order kinetics. According these results, a possible synergistic effect mechanism for the enhanced photocatalytic performance is proposed.

18.
Clin Interv Aging ; 15: 1333-1341, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848374

RESUMO

BACKGROUND: As fat and obesity play a vital role in the pathophysiology of metabolic dysfunction-associated fatty liver disease (MAFLD), this study aims to investigate the association between the fat mass and obesity-associated gene (FTO) and MAFLD. METHODS: Six SNPs (rs6499640, rs1421085, rs8050136, rs3751812, rs9939609 and rs9930506) within FTO were genotyped for 741 MAFLD patients (median age, 69.98; interquartile range, 66.55-75.93) and 825 healthy people (median age, 69.94; interquartile range, 66.39-75.64). Allele and genotype frequencies, pairwise linkage disequilibrium (LD) and haplotype analysis were calculated. RESULTS: BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, triglyceride, alanine transaminase, glutamyl transpeptidase and the prevalence of diabetes were found to be higher in the MAFLD individuals comparing to the control ones (P < 0.05). For rs1421085, the C allele frequency was remarkably higher in MAFLD after Bonferroni correction (OR [95% CI] =1.353 [1.095-1.671]; P corr =0.030), and a significantly different genotype result was observed in log-additive model (OR [95% CI] =1.369 [1.108-1.691]; P corr =0.024). For rs8050136, significantly increased A allele frequency was observed in MAFLD (OR [95% CI] =1.371 [1.109-1.695]; P corr =0.024), and A-allele carriers showed increased MAFLD risk (OR [95% CI] =1.393 [1.103-1.759]; P corr =0.030). For rs3751812, the T allele frequency was remarkably higher in MAFLD (OR [95% CI] =1.369 [1.108-1.691]; P corr =0.024), and T-allele carriers demonstrated high MAFLD risk (OR [95% CI] =1.392 [1.103-1.756]; P corr =0.030). For rs9939609, A allele frequency was also remarkably high in MAFLD (OR [95% CI] =1.369 [1.108-1.691]; P corr =0.024), and A-allele carriers were more susceptible to MAFLD (OR [95% CI] =[1.103-1.756]; P corr =0.030). A strong LD was found among rs1421085, rs8050136, rs3751812 and rs9939609 (r2 >0.8), and individuals with C-A-T-A haplotype had an elevated MAFLD risk (P =0.005). CONCLUSION: The case-control study indicated that C variant of rs1421085, A variant of rs8050136, T variant of rs3751812 and A variant of rs9939609 are associated with elevated MAFLD risk in the older Chinese Han population.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Povo Asiático/genética , Hepatopatia Gordurosa não Alcoólica/genética , Idoso , Alelos , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Frequência do Gene , Haplótipos , Humanos , Masculino , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Obesidade/genética , Circunferência da Cintura
19.
Sci Rep ; 8(1): 385, 2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29321674

RESUMO

The purpose of this study was to compare the predictive ability of five obesity indices, including body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHpR) and body adiposity index (BAI), to predict multiple non-adipose metabolic risk factors, including elevated blood pressure (BP), elevated fasting plasma glucose (FPG), elevated triglyceride (TG), reduced high-density lipoprotein cholesterol (HDL-C), elevated serum uric acid (SUA) and non-alcoholic fatty liver disease (NAFLD), in an elderly Chinese population. A total of 5685 elderly Chinese subjects (≥60 years) were recruited into our community-based cross-sectional study. Receiver operating characteristic curve (ROC) analyses were used to compare the predictive ability as well as determine the optimal cut-off values of the obesity indices for multiple metabolic risk factors. According to the areas under the receiver operating characteristic curve (AUC), BMI, WC and WHtR were able to similarly predict high metabolic risk in males (0.698 vs. 0.691 vs. 0.688), while in females, BMI and WC were able to similarly predict high metabolic risk (0.676 vs. 0.669). The optimal cut-off values of BMI, WC and WHtR in males were, respectively, 24.12 kg/m2, 83.5 cm and 0.51, while in females, the values were 23.53 kg/m2 and 77.5 cm.


Assuntos
Índice de Massa Corporal , Síndrome Metabólica/diagnóstico , Circunferência da Cintura , Razão Cintura-Estatura , Idoso , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco , Caracteres Sexuais , Relação Cintura-Quadril
20.
Artigo em Inglês | MEDLINE | ID: mdl-25815040

RESUMO

Primary liver cancer (PLC) is one of the most common malignant tumors because of its high incidence and high mortality. Traditional Chinese medicine (TCM) plays an active role in the treatment of PLC. As the most important part in the TCM system, syndrome differentiation based on the clinical manifestations from traditional four diagnostic methods has met great challenges and questions with the lack of statistical validation support. In this study, we provided evidences for TCM syndrome differentiation of PLC using the method of analysis of latent structural model from clinic data, thus providing basis for establishing TCM syndrome criteria. And also we obtain the common syndromes of PLC as well as their typical clinical manifestations, respectively.

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