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2.
Neuroimage Clin ; 24: 102037, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31704545

RESUMO

Poor insight in obsessive-compulsive disorder (OCD) is associated with several adverse clinical outcomes. However, the neurobiological basis of this insight deficit is not clearly understood. The present study thus aimed to investigate associations of cortical thickness, cortical surface area and subcortical volumes with insight in a sample of drug-naïve adults with OCD. Forty-seven OCD patients and 42 healthy controls (HCs) underwent MRI scanning, depression and anxiety assessments. The Brown Assessment of Beliefs Scale (BABS) measured insight levels and patients were divided into two groups: poor insight (OCD-PI; n = 21), and good insight (OCD-GI; n = 26). Cortical thickness and surface area between groups were compared with whole-brain exploratory vertex-by-vertex analyses, while subcortical volumes were compared on a structure-by-structure basis. Partial correlation analyses were then performed to assess associations between regional cortical and subcortical measures and insight levels. OCD-GI and OCD-PI groups displayed partly shared, but also partly distinct brain structural alterations. Strikingly, OCD-PI showed decreased cortical thickness in the left superior frontal gyrus, left anterior cingulate cortex (ACC) and right inferior parietal gyrus, compared to both OCD-GI and HCs. Average cortical thickness extracted from these areas was further negatively correlated with BABS scores in the OCD-PI patients. Our findings suggest that poor insight in patients with OCD may have a neural substrate involving the left medial frontal and the right inferior parietal cortices.

3.
Compr Psychiatry ; 96: 152144, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31707312

RESUMO

BACKGROUND: Obsessive-compulsive personality disorder (OCPD) is one of the most prevalent personality disorders in general population. However, neural mechanisms underlying OCPD remain elusive. The aim of this study is to use functional magnetic resonance imaging (fMRI) to examine whether OCPD patients will exhibit altered spontaneous brain activity as compared to healthy controls (HC). METHODS: Resting-state fMRI data were acquired in 37 OCPD patients and 37 matched HC. Amplitudes of low-frequency fluctuation (ALFF) were calculated and compared between the two groups. Correlation analysis was performed between regional ALFF values and OCPD severity scores. RESULTS: Significant group differences in regional ALFF were found in multiple brain regions. Compared to HCs, OCPD subjects had increased ALFF in bilateral caudate, left precuneus, left insula, and left medial superior frontal gyrus, and decreased ALFF in the right fusiform gyrus and left lingual gyrus. The ALFF values in the left precuneus correlated with OCPD severity scores. LIMITATIONS: We excluded patients with comorbidity and did not conduct cognitive function assessments. Our findings are also limited to cross-sectional analysis. CONCLUSIONS: OCPD patients exhibit altered spontaneous neural activity as compared to healthy controls in multiple brain regions, which may reflect different characteristic symptoms of OCPD pathophysiology, including cognitive inflexibility, excessive self-control, lower empathy, and visual attention bias.

5.
Mil Med Res ; 6(1): 33, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31651369

RESUMO

The lung plays a vital role in maintaining homeostasis, as it is responsible for the exchange of oxygen and carbon dioxide. Pulmonary homeostasis is maintained by a network of tissue-resident cells, including epithelial cells, endothelial cells and leukocytes. Myeloid cells of the innate immune system and epithelial cells form a critical barrier in the lung. Recently developed unbiased next generation sequencing (NGS) has revealed cell heterogeneity in the lung with respect to physiology and pathology and has reshaped our knowledge. New phenotypes and distinct gene signatures have been identified, and these new findings enhance the diagnosis and treatment of lung diseases. Here, we present a review of the new NGS findings on myeloid cells in lung development, homeostasis, and lung diseases, including acute lung injury (ALI), lung fibrosis, chronic obstructive pulmonary disease (COPD), and lung cancer.

6.
BMC Genomics ; 20(1): 776, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653200

RESUMO

BACKGROUND: Aphid (Macrosiphoniella sanbourni) stress drastically influences the yield and quality of chrysanthemum, and grafting has been widely used to improve tolerance to biotic and abiotic stresses. However, the effect of grafting on the resistance of chrysanthemum to aphids remains unclear. Therefore, we used the RNA-Seq platform to perform a de novo transcriptome assembly to analyze the self-rooted grafted chrysanthemum (Chrysanthemum morifolium T. 'Hangbaiju') and the grafted Artermisia-chrysanthemum (grafted onto Artemisia scoparia W.) transcription response to aphid stress. RESULTS: The results showed that there were 1337 differentially expressed genes (DEGs), among which 680 were upregulated and 667 were downregulated, in the grafted Artemisia-chrysanthemum compared to the self-rooted grafted chrysanthemum. These genes were mainly involved in sucrose metabolism, the biosynthesis of secondary metabolites, the plant hormone signaling pathway and the plant-to-pathogen pathway. KEGG and GO enrichment analyses revealed the coordinated upregulation of these genes from numerous functional categories related to aphid stress responses. In addition, we determined the physiological indicators of chrysanthemum under aphid stress, and the results were consistent with the molecular sequencing results. All evidence indicated that grafting chrysanthemum onto A. scoparia W. upregulated aphid stress responses in chrysanthemum. CONCLUSION: In summary, our study presents a genome-wide transcript profile of the self-rooted grafted chrysanthemum and the grafted Artemisia-chrysanthemum and provides insights into the molecular mechanisms of C. morifolium T. in response to aphid infestation. These data will contribute to further studies of aphid tolerance and the exploration of new candidate genes for chrysanthemum molecular breeding.

7.
Cell Prolif ; : e12696, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599060

RESUMO

OBJECTIVES: Panax ginseng, a well-known traditional Chinese medicine with multiple pharmacological activities, plays a crucial role in modulating mood disorders. Several recent studies have identified an underlying role of Panax ginseng in the prevention and treatment of depression. However, the cellular and molecular mechanisms remain unclear. MATERIALS AND METHODS: In this review, we summarized the recent progress of antidepressant effects and underlying mechanisms of Panax ginseng and its representative herbal formulae. RESULTS: The molecular and cellular mechanisms of Panax ginseng and its herbal formulae include modulating monoamine neurotransmitter system, upregulating the expression of neurotrophic factors, regulating the function of HPA axis, and anti-inflammatory action. CONCLUSIONS: Therefore, this review may provide theoretical bases and clinical applications for the treatment of depression by Panax ginseng and its representative herbal formulae.

8.
Biomark Med ; 13(16): 1387-1397, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31631674

RESUMO

Aim: The value of the peripheral blood lymphocyte subpopulation ratios and tumor diameter for prognosis in bladder cancer (BC) patients needs to be explored. Materials & methods: A total of 161 male BC patients and 68 male normal controls were retrospectively reviewed. The value of combining predictor consisted of both CD4+CD25+/CD4+ and computed tomography urography tumor diameter (CTU-D) on stage, overall survival (OS) and recurrence probability was analyzed by logistic regression, Kaplan-Meier method and log-rank test. Results: The combining predictor was a statistically independent risk for stage; dramatic differences in OS and recurrence probability were found between the combining predictor-high (cut-off point >0.08) and combining predictor-low groups (cut-off point ≤0.08). Conclusion: The combining predictor could be a significant predictor for advanced stage, OS and recurrence probability in male patients with BC.

9.
Adv Mater ; : e1904641, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31595592

RESUMO

Consecutively tailoring few-layer transition metal dichalcogenides MX2 from 2H to Td phase may realize the long-sought topological superconductivity in a single material system by incorporating superconductivity and the quantum spin Hall effect together. Here, this study demonstrates that a consecutive structural phase transition from Td to 1T' to 2H polytype can be realized by increasing the Se concentration in Se-substituted MoTe2 thin films. More importantly, the Se-substitution is found to dramatically enhance the superconductivity of the MoTe2 thin film, which is interpreted as the introduction of two-band superconductivity. The chemical-constituent-induced phase transition offers a new strategy to study the s+- superconductivity and the possible topological superconductivity, as well as to develop phase-sensitive devices based on MX2 materials.

10.
Toxicol Lett ; 318: 12-21, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31622651

RESUMO

Maternal smoking during pregnancy and lactation is associated with increased fat mass in the offspring, but the mechanism by which this occurs is not fully understood. Our study focused on the relationships among maternal nicotine exposure, adipose angiogenesis and adipose tissue function in female offspring. Pregnant rats were randomly assigned to nicotine or control groups. Microvascular density, lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins were tested in 4-, 12- and 26-week female offspring. In vitro, nicotine concentration- and time-response experiments were conducted in 3T3-L1. Lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins were tested. The conditioned media of differentiated 3T3-L1 treated with nicotine were used to observe tube formation in human umbilical vein endothelial cells (HUVECs). Nicotine-exposed females presented higher adipose microvascular density. The gene expression of α7nAChR, Egr1 and FGF2 was significantly increased in gonadal white adipose tissue (gWAT) and inguinal subcutaneous WAT (igSWAT) of nicotine-exposed females at 4 weeks of age. The protein expression of α7nAChR, Egr1 and FGF2 was increased in gWAT and igSWAT of nicotine-exposed females at 4 weeks of age, and increased in gWAT at 26 weeks. In vitro, nicotine increased the expression of lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins in a concentration- and time-dependent manner. In the tube formation experiment, adipocytes affected by nicotine promoted HUVEC angiogenesis. Therefore, maternal nicotine exposure promoted the early angiogenesis of adipose tissue via the α7nAChR-Egr1-FGF2 signaling pathway, and this angiogenesis mechanism was associated with increased adipogenesis in adipose tissue of female offspring.

11.
Soft Matter ; 15(44): 9066-9075, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31650138

RESUMO

Effective removal of oil spills or organic pollutant oils from water is of global significance for environmental protection. However, traditional techniques usually suffer from the limits of low efficiency and high cost. In this study, sponge-like polyamide 6/organic montmorillonite (PA 6/OMMT) composite absorbents were fabricated through a large-scale solution foaming method. Aqueous sodium carbonate solution was injected into a PA/formic acid solution with well-dispersed nanoclay to generate CO2 and meanwhile initiate the phase separation of PA molecules from the solvent. Both mesopores and macropores existed in the prepared sponges. The effect of OMMT content on the microstructures and adsorption properties was investigated. Upon increasing the OMMT fraction in composite sponges, the pore size decreased and the fraction of mesopore increased. Better adsorption properties were thus obtained. When OMMT nanoplatelets accounted for 10%, the corresponding sponge had an uptake capacity of 12.5-22.1 g g-1 for diverse oils or organic solvents. Moreover, the composite sponges absorbed oils and organic solvents rapidly and reached saturation in 20 s. When it was coated with methyltrichlorosilane (MTS), the static water contact angle on the surface of the sponge increased from 88° to 115°. The selective absorption of oil from an oil/water mixture was improved. A greatly promising approach is provided to make commercial polyamide into highly porous functional materials for the cleanup of large-scale oil spills.

12.
Colloids Surf B Biointerfaces ; 183: 110371, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31408783

RESUMO

The abuse of antibiotics has led to widespread antimicrobial resistance (AMR) and environmental pollution. In order to solve these problems, a lot of studies have been carried out mainly focusing on the modification and recombination of organic reagents, but bacteria are still easy to adapt to it, so they cannot be thoroughly solved. Here, we present an integrated pollution-free synergistic antibacterial nanotechnology using inorganic nano-Cu2O, which could not only enhance the efficacy of aminoglycoside antibiotics, but also eliminate their environmental pollution by photocatalytic degradation. It was found that Cu2O showed significantly synergistic antibacterial effect (1+1>2) when combined with aminoglycoside antibiotics against Escherichia coli. The inhibition zone area increased by 59.0% when Cu2O combined with neomycin. This reduces dosage and the risk of AMR, and does not pollute the environment after degradation. Next, to explore the synergistic mechanisms, we have studied the interaction of antibiotics with nanoparticles, as well as the interaction of antibacterial agents with bacteria. At last, we believe that the destruction of cell walls by Cu2O facilitates the entry of antibiotics into cells is the reason for their synergy.

13.
J Affect Disord ; 259: 47-55, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31437701

RESUMO

BACKGROUD: Converging evidence indicated the presence of clinically significant anhedonia in patients with obsessive-compulsive disorder (OCD). Studying anhedonia and its neural correlates in OCD may be beneficial in understanding the pathophysiology and treatment of OCD. However, the neural mechanisms that underlie anhedonia in OCD still remain unclear. The present study was designed to bridge this research gap by using resting-state functional magnetic resonance imaging (fMRI). METHODS: 29 OCD patients with anhedonia (OCD-AH), 31 OCD patients with normal hedonia (OCD-NH), and 30 healthy controls (HC) received the fMRI scan. The low-frequency fluctuation (ALFF) approach was applied to compare spontaneous neural activity among the three groups. Relationships between the regional ALFFs and anhedonia levels were examined in OCD patients. RESULT: OCD-AH and OCD-NH manifested overlapping but partially distinct brain alterations. Notably, compared to OCD-NH, the OCD-AH showed decreased ALFF in right superior temporal gyrus (STG) and increased ALFF in medial prefontal cortex (MPFC). Moreover, ALFF values in the right STG were negatively correlated with social anhedonia severity, and ALFFs in the MPFC were positively correlated with both physical and social anhedonia severity in patients with OCD. LIMITATIONS: Relatively small sample size; ALFF could not provide more holistic information of brain network. CONCLUSION: The present study revealed that abnormal spontaneous neural activity in MPFC is associated with both physical and social anhedonia, while altered intrinsic brain function in right STG is specifically associated with social anhedonia in OCD. These findings contribute to our understandings of the neurobiological mechanisms underlying anhedonia in OCD.

14.
Int J Mol Sci ; 20(14)2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295892

RESUMO

Absorption, distribution, metabolism, and excretion (ADME) studies are critical for drug discovery. Conventionally, these tasks, together with other chemical property predictions, rely on domain-specific feature descriptors, or fingerprints. Following the recent success of neural networks, we developed Chemi-Net, a completely data-driven, domain knowledge-free, deep learning method for ADME property prediction. To compare the relative performance of Chemi-Net with Cubist, one of the popular machine learning programs used by Amgen, a large-scale ADME property prediction study was performed on-site at Amgen. For all 13 data sets, Chemi-Net resulted in higher R2 values compared with the Cubist benchmark. The median R2 increase rate over Cubist was 26.7%. We expect that the significantly increased accuracy of ADME prediction seen with Chemi-Net over Cubist will greatly accelerate drug discovery.

15.
J Colloid Interface Sci ; 554: 565-571, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31326788

RESUMO

Traditional method to functionalize mesoporous silica nanoparticles with organic groups for removal of contaminants from wastewater was surface modification. However, this surface modification could not cover the entire surface, leading to incomplete utilization of the high surface area of MSNs. In this work, we designed and prepared a novel inorganic-organic hybrid nanomaterial: ferrocene incorporated mesoporous organosilica nanoparticles (MONs). Owing to the mesoporous structure, large surface area and the ferrocene group in the framework, MONs could adsorb phosphate anion more efficiently with adsorption capacities up to 1299 mg/g than surface modified MSNs (SiO2-Fe) (488 mg/g). Congo red (CR) and Pb2+ were also used as the model contaminants, and the results indicated that MONs is a superior absorbent comparing with ferrocene surface modified MSNs.

16.
Medicine (Baltimore) ; 98(30): e16610, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348308

RESUMO

The purpose of this study was to investigate the influences of varied anesthetic methods and depths on inflammatory cytokines and stress hormone levels in radical operation among colon cancer patients during perioperative period.A total of 120 patients were collected in the study and randomly divided into 4 groups, A: general anesthesia + Narcotrend D1, B: general anesthesia + Narcotrend D2, C: general anesthesia + epidural anesthesia + Narcotrend D1, D: general anesthesia + epidural anesthesia + Narcotrend D2. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, cortisol (Cor), adrenocorticotropic hormone (ACTH), and endothelin-1 (ET-1) were measured adopting commercial kits before anesthesia (T0), 4 hours after surgery (T1), 24 hours after surgery (T2), and 72 hours after surgery (T3).There was no significant difference in basic clinical characteristics among the groups. In comparison with group A, B and C, group D showed significantly lower levels of TNF-α, IL-6, IL-10, Cor, ACTH, and ET-1 at T1 and T2 (all, P < .05). Significantly higher levels of TNF-α, IL-6, IL-10, Cor, and ACTH were detected at T1 and T2 than those at T0 (all, P < .05), whereas, at T3, the levels of inflammatory cytokines and stress hormones were all decreased near to preoperation ones.General anesthesia combined with epidural anesthesia at Narcotrend D2 depth plays an important role in reducing immune and stress response in patients with colon cancer from surgery to 24 hours after surgery.


Assuntos
Anestesia Epidural/métodos , Anestesia Geral/métodos , Neoplasias do Colo/cirurgia , Citocinas/biossíntese , Mediadores da Inflamação/metabolismo , Hormônio Adrenocorticotrópico/biossíntese , Citocinas/sangue , Quimioterapia Combinada , Endotelina-1/biossíntese , Feminino , Humanos , Hidrocortisona/biossíntese , Mediadores da Inflamação/sangue , Interleucinas/biossíntese , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/biossíntese
17.
Environ Sci Pollut Res Int ; 26(25): 26229-26241, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31286375

RESUMO

China is currently the largest CO2 emitter in the world. Within China, more than 60% of CO2 emissions originate from high energy-intensive (HEI) industries. Therefore, controlling and reducing CO2 emissions from HEI industries is crucial if China is to achieve its 2030 emission reduction targets. This study aims to investigate regional differences in the impact of HEI industries on CO2 emissions in China. This paper presents an analysis of the impact of HEI industries on CO2 emissions at the national and regional levels using a modified STIRPAT model and provincial panel data from 2000 to 2015 in China. The results show that HEI industries are significant contributors to China's CO2 emissions owing to the growth in industries, coal-based energy structure, low level of technology, and outstanding conduction effects. The impact intensity of HEI industries on CO2 emissions decreases from the western to the central and eastern regions in China because of a huge regional difference in industrial structure, energy structure, R&D investment, and industrial transfer. Our findings have important implications for policymakers in China by indicating that regional policies concerning HEI industries should be differentiated to successfully reduce CO2 emissions and meet national targets.


Assuntos
Poluentes Atmosféricos/análise , Dióxido de Carbono/análise , Poluentes Atmosféricos/química , Dióxido de Carbono/química , China , Indústrias , Investimentos em Saúde , Tecnologia
18.
J Clin Hypertens (Greenwich) ; 21(8): 1075-1081, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31282098

RESUMO

Insulin resistance (IR) plays a crucial role in the development of hypertension, so early recognition of IR is of substantial clinical importance for the management of hypertension. But traditional IR indexes are invasive, complex, and impractical. We aimed to evaluate the associations between three simple IR indexes and hypertension in different body mass index (BMI) categories. A total of 142 005 adults who did not take antihypertensive medication were included in this analysis. The ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDLc), the product of fasting triglycerides and glucose (TyG), and metabolic score for IR (METS-IR) were calculated according to the corresponding formulas. The associations between them and hypertension were analyzed by logistic regression. Among the three indicators, only METS-IR had positive correlations with blood pressure levels (all P < 0.001). After full adjustment, METS-IR was significantly associated with hypertension in the normal BMI group but not in the elevated BMI group. The OR for hypertension in the normal BMI group in the highest quartile of METS-IR was 2.884 (95% CI: 2.468-3.369) in the total sample, 1.915 (95% CI: 1.614-2.271) in females and 2.083 (95% CI: 1.717-2.527) in males. Our findings indicate that METS-IR, a simple and cost-effective IR index, was strongly associated with hypertension in normal-weight Chinese subjects. It could help monitor and manage hypertension in normal-weight individuals.

19.
J Mol Cell Cardiol ; 134: 74-85, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31302118

RESUMO

Sick sinus syndrome (SSS) is primarily a disease of the elderly, and age-dependent decrease in Cav1.2 and Cav1.3 Ca2+ channels within the sinus node has been shown to play an important role in sinoatrial node (SAN) degeneration; however, posttranscriptional mechanisms regulating decrease in Cav1.2 and Cav1.3 Ca2+ channels remain unclear. Some studies have reported that microRNAs (miRNAs) are involved in age-related cardiovascular diseases. Nevertheless, little is known about the roles of miRNAs in age-related SSS. This study investigated whether miR-1976 was involved in the regulation of SAN degeneration by targeting Cav1.2 and Cav1.3 Ca2+ channels. First, using microarray-based miRNA expression profiling and qRT-PCR, we confirmed that miR-1976 was upregulated in the plasma of patients with age-related SSS relative to healthy controls. By employing target gene prediction software, luciferase assay and western blotting, we further confirmed Cav1.2 and Cav1.3 as direct targets of miR-1976. Furthermore, miR-1976 levels in rabbit SAN tissues were negatively correlated with Cav1.2 and Cav1.3 expression and intrinsic heart rates but positively correlated with corrected sinus node recovery time (CSNRT). Additionally, miR-1976 transgenic mice displayed attenuated Cav1.2 and Cav1.3 protein expression, which led to sinus node dysfunction. These results suggest that miR-1976 plays an important role in the SAN aging process by targeting Cav1.2 and Cav1.3. Thus, miR-1976 could have great potential as a noninvasive diagnostic tool and therapeutic target for SSS. These findings may reveal important insights into the pathogenesis of SSS.

20.
Gastroenterology ; 157(3): 744-759.e4, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31154022

RESUMO

BACKGROUND & AIMS: Many genetic and environmental factors, including family history, dietary fat, and inflammation, increase risk for colon cancer development. Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that regulates systemic lipid homeostasis. We explored the role of intestinal PPARα in colon carcinogenesis. METHODS: Colon cancer was induced in mice with intestine-specific disruption of Ppara (PparaΔIE), Pparafl/fl (control), and mice with disruption of Ppara that express human PPARA (human PPARA transgenic mice), by administration of azoxymethane with or without dextran sulfate sodium (DSS). Colons were collected from mice and analyzed by immunoblots, quantitative polymerase chain reaction, and histopathology. Liquid chromatography coupled with mass spectrometry-based metabolomic analyses were performed on urine and colons. We used molecular biology and biochemical approaches to study mechanisms in mouse colons, primary intestinal epithelial cells, and colon cancer cell lines. Gene expression data and clinical features of patients with colorectal tumors were obtained from Oncomine, and human colorectal-tumor specimens and adjacent normal tissues were collected and analyzed by immunohistochemistry. RESULTS: Levels of Ppara messenger RNA were reduced in colon tumors from mice. PparaΔIE mice developed more and larger colon tumors than control mice following administration of azoxymethane, with or without DSS. Metabolomic analyses revealed increases in methylation-related metabolites in urine and colons from PparaΔIE mice, compared with control mice, following administration of azoxymethane, with or without DSS. Levels of DNA methyltransferase 1 (DNMT1) and protein arginine methyltransferase 6 (PRMT6) were increased in colon tumors from PparaΔIE mice, compared with colon tumors from control mice. Depletion of PPARα reduced the expression of retinoblastoma protein, resulting in increased expression of DNMT1 and PRMT6. DNMT1 and PRMT6 decreased expression of the tumor suppressor genes Cdkn1a (P21) and Cdkn1b (p27) via DNA methylation and histone H3R2 dimethylation-mediated repression of transcription, respectively. Fenofibrate protected human PPARA transgenic mice from azoxymethane and DSS-induced colon cancer. Human colon adenocarcinoma specimens had lower levels of PPARA and retinoblastoma protein and higher levels of DNMT1 and PRMT6 than normal colon tissues. CONCLUSIONS: Loss of PPARα from the intestine promotes colon carcinogenesis by increasing DNMT1-mediated methylation of P21 and PRMT6-mediated methylation of p27 in mice. Human colorectal tumors have lower levels of PPARA messenger RNA and protein than nontumor tissues. Agents that activate PPARα might be developed for chemoprevention or treatment of colon cancer.


Assuntos
Adenocarcinoma/prevenção & controle , Colo/enzimologia , Neoplasias do Colo/prevenção & controle , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Metilação de DNA , Proteínas Nucleares/metabolismo , PPAR alfa/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Animais , Anticarcinógenos/farmacologia , Estudos de Casos e Controles , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Colo/patologia , Neoplasias do Colo/enzimologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , DNA (Citosina-5-)-Metiltransferase 1/genética , Metilação de DNA/efeitos dos fármacos , Bases de Dados Genéticas , Modelos Animais de Doenças , Fenofibrato/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Nucleares/genética , PPAR alfa/agonistas , PPAR alfa/deficiência , PPAR alfa/genética , Proteína-Arginina N-Metiltransferases/genética , Transdução de Sinais
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