Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 454
Filtrar
1.
Appl Opt ; 59(6): 1524-1528, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32225656

RESUMO

Compared with high-performance liquid chromatography and mass spectroscopy, fluorescence spectroscopy has attracted considerable attention in the field of pesticide residue detection due to its practical advantages of providing rapid, simultaneous analysis and non-destructive detection. However, given that the concentration of pesticide residue detected via fluorescence spectroscopy is calculated in accordance with the Beer-Lambert law, this method can only detect samples containing a single kind of pesticide or several kinds of pesticides with completely different fluorescences. Multiple partial least-squares (PLS) models are introduced in this work to overcome this disadvantage and achieve the concentration of zhongshengmycin, paclobutrazol, boscalid, and pyridaben, whose fluorescences are overlapping. The R squares of the models for zhongshengmycin, paclobutrazol, boscalid, and pyridaben were 0.9942, 0.9912, 0.9913, and 0.9847, respectively. Results indicated that fluorescence spectroscopy combined with multiple PLS models can be used to detect multiple kinds of pesticides in the water.

2.
Zhongguo Zhong Yao Za Zhi ; 45(1): 188-195, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237429

RESUMO

To systematically assess the efficacy and safety of Jinqi Jiangtang Tablets for patients with insulin resistance in type 2 diabetes, literatures were retrieved in 7 databases: PubMed, EMbase, Cochrane Library, Chinese National Knowledge Infrastructure(CNKI), WanFang database, Chinese BioMedical Database(CBM), VIP Chinese Science and Technique Journals Database, from the date of its inception up to November 2018. Review Manager 5.3 software was used for risk bias assessment, data synthesis and subgroup analysis. Begg's and Egger's tests were performed for assessing symmetries of funnel plot by software Stata 14.0. GRADE system was used to assess the quality of evidence. A total of 10 trials involving 797 participants were eligible. Compared with Western medicine alone, Jinqi Jiangtang Tablets showed a statistical significance in FBG(WMD=-0.63, 95%CI[-1.00,-0.26]). Jinqi Jiangtang Tablets showed a significant decrease in 2 h BG combined with Western medicine compared with Western medicine alone(WMD=-1.46, 95%CI[-1.71,-1.21], P<0.000 01). Jinqi Jiangtang Tablets combined with Western medicine showed a significant decrease in HbA1 c(WMD=-0.75, 95%CI[-0.97,-0.53], P<0.000 01), FINS(WMD=-0.65, 95%CI[-0.80,-0.50], P<0.000 01), 2 h INS(SMD=-1.67, 95%CI[-2.26,-1.09], P<0.000 01) and HOMA-IR(WMD=-1.22, 95%CI[-1.67,-0.76], P<0.000 01). Jinqi Jiangtang Tablets combined with Western medicine was beneficial for ISI(WMD=1.00, 95%CI[0.84, 1.17], P<0.000 01). Egger's and Begg's test showed no publication bias(P=0.379). Sensitivity analysis showed no impact on the overall results. The GRADE quality of the evidence was low. Despite of the apparently positive results, we cannot draw a rational conclusion that Jinqi Jiangtang Tablets has a positive effect in patients with IR, because of the low evidence grade.

3.
Zhongguo Zhong Yao Za Zhi ; 45(5): 1128-1134, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32237456

RESUMO

A combination of LC-MS technology and activity evaluation was used to identify the antipyretic ingredients in rhubarb. The rat model of fever was established with dried yeast and then was administered ethanol extract and different polar fractions of rhubarb. Next, the anal temperature of these rats was measured and recorded at 0.5, 1, 2, 3, 4 and 5 h after administration, and the inhibition rate of each part on the rise of body temperature was calculated. The inhibition rate is higher and the antipyretic effect is better. The chemical composition of the effective fraction was analyzed with UPLC-ESI-Orbitrap-MS/MS technology. Compared with the model group, the increase of body temperature of ethanol extract group all reduced at each measurement time especially after 3 h, and the inhibition rate were 38.7%(P<0.05), 78.2%(P<0.01) and 72.4%(P<0.01) at 3 h, 4 h, and 5 h after administration, respectively. Both n-butanol and water fraction showed some antipyretic activity in the early stage, with the inhibition rate of 28.1%(P<0.01) and 24.9%(P<0.05) at 1 h after administration, respectively, while other fractions were not active. Thirty-three and twelve compounds were identified from n-butanol and water fraction by LC-MS/MS analysis, respectively, including ten tannins, fifteen anthraquinone glycosides, four anthrone glycosides, one phenolic glycoside, one naphthaline derivative, one anthraquinone and one sucrose. These results revealed that rhubarb had antipyretic activity on rats, and tannin and anthraquinone glycosides were the main active ingredients inside.

5.
Br J Cancer ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32203224

RESUMO

BACKGROUND: DAXX is a transcription repressor that has been implicated in several types of cancers, but its role in the development of gastric cancer remains unknown. METHODS: We analysed the expression of DAXX in 83 pairs of gastric cancer samples, including neoplastic and adjacent tissues, and correlated the expression levels with clinical stages. We also investigated the molecular mechanisms by which DAXX downregulation promotes cancer growth using both in vitro and in vivo models. RESULTS: DAXX was downregulated in advanced gastric cancer samples. The expression of DAXX inversely correlates with that of cancer stem cell markers CD44 and Oct4 in gastric cancer lines. DAXX overexpression in gastric cancer cells inhibited migration, invasion and epithelial- mesenchymal transition (EMT). The inhibition of EMT was achieved through the repression of SNAI3, a key inducer of EMT, by recruiting HDAC-1 into the nucleus. Using a xenograft mouse model, we demonstrated that the MKN45 cells formed smaller tumours when DAXX was overexpressed. Wild-type AGS cells were not able to form tumours in nude mice, but in contrast, formed visible tumours when DAXX was silenced in the cells. CONCLUSION: We for the first time demonstrated that DAXX functions as a tumour suppressor in gastric cancer by inhibiting stem cell growth and EMT.

6.
Chem Commun (Camb) ; 56(27): 3907-3910, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32142087

RESUMO

In this study, we have constructed a binary supramolecular nanoassembly composed of α-cyclodextrin-modified hyaluronic acid and an azobenzene-modified diphenylalanine derivative with a positively charged imidazole group. This nanoassembly can bind with siRNA through electrostatic interactions and efficiently delivered them into cancer cells and inhibited their growth.

7.
ACS Appl Mater Interfaces ; 12(12): 13709-13717, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32118400

RESUMO

Actin cytoskeleton disruption is a promising and intriguing anticancer strategy, but their efficiency is frequently compromised by severe side effects of the actin cytoskeleton-disrupting agents. In this study, we constructed the biocompatible actin cytoskeleton-targeting multivalent supramolecular assemblies that specifically target and disrupt the tumor actin cytoskeleton for cancer therapy. The assemblies were composed of ß-cyclodextrin-grafted hyaluronic acid (HACD) and iron oxide magnetic nanoparticles (MNPs) grafted by an actin-binding peptide (ABP) and adamantane (Ada)-modified polylysine. Owing to the multivalent binding between cyclodextrin and Ada, HACD, and peptide-grafted MNPs (MNP-ABP-Ada) could self-assemble to form MNP-ABP-Ada⊂HACD nanofibers in a geomagnetism-dependent manner. Furthermore, the presence of ABP rendered the assemblies to efficiently target the actin cytoskeleton. Interestingly, with the acid of a low-frequency alternating magnetic field (200 Hz), the actin cytoskeleton-targeting nanofibers could induce severe actin disruption, leading to a remarkable cell cycle arrest and drastic cell death of tumor cells both in vitro and in vivo, but showed no obvious toxicity to normal cells. The actin cytoskeleton-targeting/disrupting supramolecular assembly implies an excellent strategy for realizing efficient cancer therapy.

8.
Adv Mater ; : e1906641, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32191372

RESUMO

Development of high-performance carbon dots (CDs) with emission wavelength longer than 660 nm (deep red emission) is critical in deep-tissue bioimaging, yet it is still a major challenge to obtain CDs with both narrow full width at half maximum (FWHM) and high deep red/near-infrared emission yield. Here, deep red emissive carbonized polymer dots (CPDs) with unprecedented FWHM of 20 nm are synthesized. The purified CPDs in dimethyl sulfoxide (DMSO) solution possess quantum yield (QY) as high as 59% under 413 nm excitation, as well as recorded QY of 31% under 660 nm excitation in the deep red fluorescent window. Detailed characterizations identify that CPDs have unique polymer characteristics, consisting of carbon cores and the shells of polymer chains, and π conjugated system formed with N heterocycles and aromatic rings govern the single photoluminescence (PL) center, which is responsible for high QY in deep red emissive CPDs with narrow FWHM. The CPDs exhibit strong absorption and emission in the deep red light region, low toxicity, and good biocompatibility, making them an efficient probe for both one-photon and two-photon bioimaging. CPDs are rapidly excreted via the kidney system and hepatobiliary system.

9.
Neuroscience ; 431: 222-236, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32081723

RESUMO

Chronic sleep-restriction (SR) is shown to be correlated with neurodevelopmental disorders. However, the effects of SR during stroke recovery on neurorepair remain unclear. In this study, mice were subjected to 60 min of cerebral ischemia followed by reperfusion. The SR protocol was accomplished by depriving mice of sleep for 20 h/day for 14 days starting at 14 days post-ischemia. We found that SR increased CD169+ macrophages infiltration into the ischemic brain parenchyma and inhibited neurogenesis and functional recovery. SR decreased CD169+ macrophages infiltration into the choroid plexus (CP) and cerebrospinal fluid (CSF), accompanied by increased expression of Chemokine C-X3-C-Motif Ligand 1 (CX3CL1) and intercellular adhesion molecule (ICAM-1) via IFN-γ/IFN-γR signaling in the CP. When splenic CD169+ macrophages sorted from Kaede transgenic mice were administered into CSF of C57BL/6 mice, they homed to the ischemic brain parenchyma. Moreover, blockade of IFN-γ/IFN-γR signaling, CX3CL1 or ICAM-1 decreased CD169+ macrophages infiltration into the CP, CSF and ischemic brain parenchyma, as well as decreasing neurogenesis and functional recovery after SR. The promoting roles of infiltrated CD169+ macrophages in post-stroke neurogenesis were due to increasing regulatory T cells (Tregs) in the ischemic brain parenchyma. Furthermore, dexmedetomidine treatment during SR increased CD169+ macrophages infiltration into the CP, CSF and ischemic brain parenchyma, and promoted neurogenesis and functional recovery. Taken together, our results showed that SR during stroke recovery decreased Tregs in the ischemic brain parenchyma by decreasing CD169+ macrophages infiltration to the ischemic brain parenchyma across the CP, which inhibited neurogenesis and functional recovery.

10.
Biosens Bioelectron ; 155: 112102, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32090874

RESUMO

A molecularly imprinted magnetic sensor with electroluminescent tags (MIP-ECL sensor) was developed for ultrasensing diethylstilbestrol (DES). A strategy is exploited to enhance ECL emission of the [Ru(bpy)3]2 +-tripropyl amine (TPrA) system by CdTe@ZnS quantum-dots (QDs) through energy transfer. Magnetically molecularly imprinted nanoparticles (MMIPs NPs) based on Fe3O4@SiO2 carriers are artificial, easily reproducible, and could replace easily inactivated first antibodies for capturing more DES molecules. Functionalized bio-conjugates of single antibody-CdTe@ZnS (Ab-CdTe@ZnS) are for the first time loaded on signal labels of Ru(bpy)32 +-doped silica nanocomposites (Ru@SiO2) for signal amplification. The final bio-conjugated signal probes are denoted as Ab-DES/CdTe@ZnS-Ru@SiO2. MMIPs beads that have captured antigens are bio-conjugated with antibody-labeled luminescent probes by specific immunoreactive reaction, and then the luminescent immunocomplex generates ECL signal on the magnetic electrode. The logarithm of ECL intensities depend linearly on the logarithm of DES concentrations in the range from 4.8 × 10- 4 to 36.0 nM with a detection limit of 0.025 pM. This novel assay is much more sensitive than other MIP sensors, and achieves lower cost and more enhanced stability than other immunosensors. The sensor is significantly potential and has been applied to DES detection in actual environment.

11.
Trials ; 21(1): 49, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915058

RESUMO

BACKGROUND: Cerebrovascular reactivity (CVR) is the change in cerebral blood flow in response to a vaso-active stimulus, and may assist the treatment strategy of ischemic stroke. However, previous studies reported that a therapeutic strategy for stroke mainly depends on the degree of vascular stenosis with steady-state vascular parameters (e.g., cerebral blood flow and CVR). Hence, measurement of CVR by multimodal imaging techniques may improve the treatment of ischemic stroke. METHODS/DESIGN: This is a prospective, randomized, controlled clinical trial that aimed to examine the capability of multimodal imaging techniques for the evaluation of CVR to improve treatment of patients with ischemic stroke. A total of 66 eligible patients will be recruited from Renji Hospital, Shanghai Jiaotong University School of Medicine. The patients will be categorized based on CVR into two subgroups as follows: CVR > 10% group and CVR < 10% group. The patients will be randomly assigned to medical management, percutaneous transluminal angioplasty and stenting, and intracranial and extra-cranial bypass groups in a 1:1:1 ratio. The primary endpoint is all adverse events and ipsilateral stroke recurrence at 6, 12, and 24 months after management. The secondary outcomes include the CVR, the National Institute of Health stroke scale and the Modified Rankin Scale at 6, 12, and 24 months. DISCUSSION: Measurement of cerebrovascular reserve by multimodal image is recommended by most recent studies to guide the treatment of ischemic stroke, and thus its efficacy and evaluation accuracy need to be established in randomized controlled settings. This prospective, parallel, randomized, controlled registry study, together with other ongoing studies, should present more evidence for optimal individualized accurate treatment of ischemic stroke. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-IOR-16009635; Registered on 16 October 2016. All items are from the World Health Organization Trial Registration Data Set and registration in the Chinese Clinical Trial Registry: ChiCTR-IOR-16009635.

12.
Mol Med Rep ; 21(2): 851-857, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31974625

RESUMO

Hexavalent chromium [Cr(VI)], is a well­known toxic form of the heavy metal chromium in the natural environment. Clinical evidence has indicated that exposure to Cr(VI) can cause severe renal damage. The production of reactive oxygen species (ROS) due to intracellular reduction of Cr(VI) is the main mechanism underlying the induction of cellular dysfunction and apoptosis. The present study aimed to investigate in detail the apoptotic pathways induced by Cr(VI)­exposure in a human immortalized proximal tubular epithelial cell line HK­2, in order to understand the mechanism involved therein. Exposure to 10 µM potassium dichromate (K2Cr2O7), a toxic compound of Cr(VI), significantly decreased cell viability after 24 and 48 h of incubation and induced intracellular ROS generation. The expression levels of markers that activate the apoptotic pathway including cleaved caspase­3 and poly (ADP­ribose) polymerase were significantly upregulated in K2Cr2O7­exposed HK­2 cells. In addition, the induction of intrinsic and extrinsic apoptotic markers was detected in K2Cr2O7­exposed HK­2 cells. In summary, the present study described for the first time the novel apoptotic mechanism of Cr(VI)­toxicity in human renal cells which may be beneficial in designing optimal clinical treatment for renal damage caused by acute Cr(VI) toxicity.

13.
J Hazard Mater ; 384: 121498, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31796349

RESUMO

Tetracycline antibiotics (TCs) are a kind of commonly used antibiotics for treating infections, however, the overuse of TCs has adversely affected human health and the ecosystem. Thus, detection of TCs in water is important but challenging. In this work, a luminescent lanthanide metal-organic framework (LnMOF) sensor (1) for immediate detection of oxytetracycline (OTC) and tetracycline (TC) is developed. The sensor has high acid-base and water stability. Investigation reveals that among the 27 species of antibiotics, anions and cations under investigation, 1 shows highly selective sensing towards OTC and TC, and the detection is not disturbed by the presence of other species. The limit of detection (LOD) for OTC and TC are ultra-sensitive value of 1.95 and 2.77 nM, respectively. Investigation reveals the sensing mechanism is due to the inner filter effect. Further studies reveal that the sensor can be used in real sample monitoring. More importantly, test strips based on 1 are manufactured. They are an easy-to-use, low-cost, highly selective and sensitive sensing device for detecting OTC and TC. The sensing can be distinguished immediately and easily by the naked eyes, making it an excellent candidate to monitor OTC and TC in real use.

14.
Org Biomol Chem ; 18(2): 205-210, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31808774

RESUMO

An effective approach to realize the direct methylation of imidazo[1,2-a]pyridines and quinoxalin-2(1H)-ones with peroxides under metal-free conditions is described. In this protocol, peroxides serve as both the radical initiator and methyl source. Methylated imidazopyridines and quinoxalin-2(1H)-ones were smoothly synthesized in moderate to good yields. A free radical reaction mechanism was proposed to describe the methylation process.

15.
Resuscitation ; 146: 273-274, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31734219
16.
Clin Chim Acta ; 501: 66-71, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31756311

RESUMO

OBJECTIVE: To screen long non-coding RNA (lncRNA) related to glucokinase regulatory protein gene (GCKR), its differential expression was analyzed in patients with Type 2 diabetes mellitus (T2DM) and control samples. The correlation of lncRNA with GCKR was verified and its potential value as a molecular marker of T2DM was assessed. METHODS: Lymphocyte RNA was extracted from five patients with T2DM and five patients with non-T2DM. The expression profiles of circulating lncRNAs and mRNAs were obtained by microarray. Bioinformatics analysis was used to screen lncRNAs associated with the GCKR gene in 127 patients with T2DM and 130 patients with non-T2DM were selected. The expression levels of the GCKR gene and lncRNA (ENST00000588707.1 and TCONS_00004187) in the T2DM group and control group were verified by real-time PCR. Additionally, a correlation analysis was conducted. The value of circulating ENST00000588707.1 and TCONS_00004187 as biomarkers for the diagnosis of T2DM was performed by receiver operating characteristic curve analysis. RESULTS: We identified 68 lncRNAs and 74 mRNAs differentially expressed from the expression profile. Compared with the control group, the expression levels of the GCKR gene and lncRNA ENST00000588707.1 and TCONS_00004187 in the T2DM group were significantly lower (P < 0.05). The correlation analysis revealed that ENST00000588707.1 and TCONS_00004187 were correlated with GCKR gene expression and glycolipid metabolism (P < 0.05). ROC analysis showed that the area under the curve value of ENST00000588707.1 between T2DM patients and non-T2DM patients was 0.816 (95% CI: 0.764-0.869, sensitivity 72.0%, specificity 80.3%) and the AUC value of TCONS_00004187 was 0.826 (95% CI: 0.774-0.879, sensitivity 81.6%, specificity 61.3%). CONCLUSION: lncRNA ENST0000588707.1 and TCONS_00004187 could serve as potential biomarkers for T2DM, which could involve in glycolipid metabolism by regulating the GCKR gene.

17.
Adv Mater ; 32(3): e1806158, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30773709

RESUMO

Cyclodextrins (CDs), which are a class of cyclic oligosaccharides extracted from the enzymatic degradation of starch, are often utilized in molecular recognition and assembly constructs, primarily via host-guest interactions in water. In this review, recent progress in CD-based supramolecular nanoassemblies that are sensitive to chemical, biological, and physical stimuli is updated and reviewed, and intriguing examples of the biological functions of these nanoassemblies are presented, including pH- and redox-responsive drug and gene delivery, enzyme-activated specific cargo release, photoswitchable morphological interconversion, microtubular aggregation, and cell-cell communication, as well as a geomagnetism-controlled nanosystem for the suppression of tumor invasion and metastasis. Moreover, future perspectives and challenges in the fabrication of intelligent CD-based biofunctional materials are also discussed at the end of this review, which is expected to promote the translational development of these nanomaterials in the biomedical field.

18.
Shanghai Kou Qiang Yi Xue ; 28(4): 384-387, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31792478

RESUMO

PURPOSE: To investigate the effect of pit and fissure sealant combined with fluorine protective paint on prevention of children caries aged 5-8 years old. METHODS: Convenience sampling method was used to select 120 children who received oral health care in the First Affiliated Hospital of Zhejiang University and Hangzhou Dental Hospital from January 2014 to January 2017. They were grouped by random number table method: the control group (60 cases, 109 teeth) underwent pit and fissure sealant, and the experimental group (60 cases, 112 teeth) underwent pit and fissure sealant combined with fluorine protective paint. The patients were followed up for 2 years to compare the incident of dental caries. SPSS20.0 software package was used to analyze the data. RESULTS: The incidence of dental caries in the experiment group (2.68%) was significantly lower than that in the control group (10.09%) (P<0.05).The incidence of adjacent caries in the experiment group (1.79%) was significantly lower than that in the control group (9.17%) (P<0.05). At 1 and 2 years after sealing, the shedding rate(0.00%, 3.33%) of the sealant in the experiment group was significantly lower than that in the control group (10.00%, 15.00%)(P<0.05).The mean caries of the experiment group was significantly lower than that of the control group(P<0.05). CONCLUSIONS: The effect of combined pit and fissure sealant and fluoride protective paint on the prevention of dental caries in children aged 5-8 years old is ideal, which can reduce the incidence of dental caries and adjacent caries, reduce the mean caries, and keep the sealant intact. It is worthy of clinical promotion.


Assuntos
Cárie Dentária , Selantes de Fossas e Fissuras , Criança , Pré-Escolar , Fluoretos , Flúor , Humanos , Pintura
19.
Pulm Circ ; 9(4): 2045894019888416, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827769

RESUMO

Circular RNAs have continuous, stable, and covalently closed circular structures and are not easily degraded by nucleases, thus they are ideal serum biomarkers for detecting diseases. However, research is still lacking on circular RNAs as diagnostic and prognostic markers for idiopathic pulmonary arterial hypertension. This study investigated the potential role of serum circ_0068481 levels in idiopathic pulmonary arterial hypertension diagnosis and prognosis. This prospective cohort study enrolled 82 patients with idiopathic pulmonary arterial hypertension between January 2016 and July 2018 at Guangdong Provincial People's Hospital. Serum circ_0068481 levels were measured using quantitative reverse transcription-polymerase chain reaction. Baseline data, including clinical background, hemodynamic variables, and biochemical variables, were collected. Receiver operating characteristic curves were used to investigate diagnostic effect, the Kaplan-Meier method was used to estimate survival rates, and univariate analysis of prognostic factors was performed with a Cox proportional hazard model. We found that serum circ_0068481 expression levels were significantly higher in patients with idiopathic pulmonary arterial hypertension and had higher sensitivity and specificity for predicting idiopathic pulmonary arterial hypertension. Additionally, we found that circ_0068481 expression correlated significantly with heart function, 6-min walk distance, serum N-terminal pro-B-type natriuretic peptide, serum H2S, the 6th World Symposium on Pulmonary Hypertension risk stratification, right heart failure, and patient death. Moreover, serum circ_0068481 levels were elevated in patients with idiopathic pulmonary arterial hypertension and right heart failure and were able to predict right heart failure. Serum circ_0068481 levels were also elevated in patients who died with idiopathic pulmonary arterial hypertension and were able to predict poorer clinical outcomes. Circ_0068481 is a novel and noninvasive biomarker for diagnosing idiopathic pulmonary arterial hypertension and predicting poor clinical outcome in patients with idiopathic pulmonary arterial hypertension.

20.
Mol Ther Nucleic Acids ; 19: 84-96, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830648

RESUMO

Atherosclerosis is a disorder occurring in the large arteries and the primary cause of heart diseases. Accumulating evidence has implicated long non-coding RNAs (lncRNAs) in atherosclerosis. This study aims to clarify the potential effects of lncRNA growth arrest-specific 5 (GAS5) on cholesterol reverse-transport and intracellular lipid accumulation in atherosclerosis. GAS5 was mainly localized in the nucleus and highly expressed in the human monocytic leukemia cell line (THP-1) macrophage-derived foam cells in coronary heart disease. Overexpressed GAS5 increased THP-1 macrophage lipid accumulation. Of note, GAS5 can inhibit the expression of ATP-binding cassette transporter A1 (ABCA1) by binding to enhancer of zeste homolog 2 (EZH2). Overexpression of EZH2 reduced cholesterol efflux and ABCA1 expression. EZH2 promoted triple methylation of lysine 27 (H3K27) in the ABCA1 promoter region. Subjected to overexpressed GAS5, overexpressed EZH2, or downregulated ABCA1, the Apolipoprotein E (ApoE)-/- mice with atherosclerosis showed increased total cholesterol (TC), free cholesterol (FC), cholesterol ester (CE), low-density lipoprotein (LDL) levels, aortic plaque, and lipid accumulation, accompanied by reduced high-density lipoprotein (HDL) level and cholesterol outflow. Altogether, knockdown of GAS5 can potentially promote reverse-transportation of cholesterol and inhibit intracellular lipid accumulation, ultimately preventing the progression of atherosclerosis via reducing EZH2-mediated transcriptional inhibition of ABCA1 by histone methylation.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA