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1.
J Agric Food Chem ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31791125

RESUMO

Chemical residues in the environment are considered to be important factors that cause obesity. Bifenthrin is one of the pyrethroid pesticides and is widely used worldwide. However, its effect on adipose tissue is ill defined. Here, we administered bifenthrin/corn oil to adult C57BL/6 mice by gavage. After six weeks, the bifenthrin treatment significantly increased body weight (P = 0.015) and fat mass (P < 0.001). Then, we identified 246 differently expressed proteins by proteomic analysis and they highly involved in fatty acid uptake and lipid metabolism process. Interestingly, protein hormone-sensitive lipase (HSL) and adipose triacylglyceride lipase (ATGL) were down-regulated while lipoprotein lipase (LPL) is up-regulated after bifenthrin treatment. Similar effects in 3T3-L1 cells treated with bifenthrin validated the in vivo results. Thus, this study suggests that long-term exposure to low-dose bifenthrin induces fat deposition in mice by improving fatty acid uptake and inhibiting lipolysis, and it may cause obesity in human.

2.
Ann Neurol ; 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31788832

RESUMO

OBJECTIVE: Restless legs syndrome is a frequent neurological disorder with substantial burden on individual wellbeing and public health. Genetic risk loci have been identified but the causatives genes at these loci are largely unknown, so that functional investigation and clinical translation of molecular research data are still inhibited. To identify putatively causative genes we searched for highly significant mutational burden in candidate genes. METHODS: We analyzed 84 candidate genes in 4,649 patients and 4,982 controls by next generation sequencing using molecular inversion probes that targeted mainly coding regions. The burden of low-frequency and rare variants was assessed, and in addition, an algorithm (binomial performance deviation analysis) was established to estimate independently the sequence variation in the probe binding regions from the variation in sequencing depth. RESULTS: Highly significant results (considering the number of genes in the genome) of the conventional burden test and the binomial performance deviation analysis overlapped significantly. Fourteen genes were highly significant by one method and confirmed with nominal significance by the other to show a differential burden of low-frequency and rare variants in restless legs syndrome. Nine of them (AAGAB, ATP2C1, CNTN4, COL6A6, CRBN, GLO1, NTNG1, STEAP4, VAV3) resided in the vicinity of known restless legs syndrome loci while five (BBS7, CADM1, CREB5, NRG3, SUN1) have not previously been associated with restless legs syndrome. Burden test and binomial performance deviation analysis also converged significantly in fine-mapping potentially causative domains within these genes. INTERPRETATION: Differential burden with intragenic low-frequency variants reveals putatively causative genes in restless legs syndrome. This article is protected by copyright. All rights reserved.

3.
Environ Int ; 134: 105297, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31785527

RESUMO

High spatiotemporal resolution fine particulate matter (PM2.5) simulations can provide important exposure data for the assessment of long-term and short-term health effects. Satellite-based aerosol optical depth (AOD) data, meteorological data, and topographic data have become key variables for PM2.5 estimation. In this study, a random forest model was developed and used to estimate the highest resolution (0.01°â€¯× 0.01°) daily PM2.5 concentrations in the Beijing-Tianjin-Hebei region. Our model had a suitable performance (cv-R2 = 0.83 and test-R2 = 0.86). The regional test-R2 value in southern Beijing-Tianjin-Hebei was higher than that in northern Beijing-Tianjin-Hebei. The model performance was excellent at medium to high PM2.5 concentrations. Our study considered meteorological lag effects and found that the boundary layer height of the one-day lag had the most important contribution to the model. AOD and elevation factors were also important factors in the modeling process. High spatiotemporal resolution PM2.5 concentrations in 2010-2016 were estimated using a random forest model, which was based on PM2.5 measurements from 2013 to 2016.

4.
J Hazard Mater ; : 121754, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31796362

RESUMO

Copper modified carbon nitride (CuCN) was prepared by a hydrothermal self-assembly reaction and following high temperature thermal polymerization process. Finally, the sample exhibits uniform one-dimensional tubular structure. Interestingly, the separation efficiency of electron-hole pair is improved, and more catalytic active sites are exposed due to the special hollow structure. Meanwhile, the presence of copper element narrows its band gap, leading to the enhancement of photocatalytic degradation performance under simulated sunlight. In addition, the effect of CuCN on dehydrogenase activity of activated sludge was determined by TTC reduction method. After adding CuCN-2, the activity of activated sludge reached 0.134 µmol g-1 min-1, which indicated that the prepared CuCN-2 had good biocompatibility. It is suitable for both photocatalytic process and activated sludge treatment process. Therefore, the combination of photocatalytic technology and activated sludge process can further completely degrade organic pollutants. We found that CuCN could protect the survival and growth of microorganisms in activated sludge, so that the degradation efficiency of CuCN to nitrobenzene could reach 94.4 %. Therefore, CuCN has broad application prospects in photocatalytic-activated sludge combined treatment.

5.
FEMS Microbiol Lett ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31800029

RESUMO

A nuclease from Yersinia enterocolitica subsp. palearctica (Nucyep) is a newly found thermostable nonspecific nuclease. The heat-resisting ability of this nuclease would be extremely useful in biological research or pharmaceutical production. However, the application of this nuclease is limited because of its poor yield. This research aimed to improve Nucyep productivity by producing a novel genetically engineered Escherichia coli and optimizing the production procedures. After 4 h of induction by lactose, the new genetically engineered E. coli can express a substantial amount of Nucyep in the form of inclusion bodies. The yield was approximately 0.3 g of inclusion bodies in 1 g of bacteria pellets. The inclusion bodies were extracted by sonication and solubilized in an 8 M urea buffer. Protein renaturation was successfully achieved by dilution method. Pure enzyme was obtained after subjecting to anion exchange. The Nucyep showed its nonspecific and heat resistant properties as previous report. Through quantification method, its activity was determined to be 1.3 × 106 K.U./mg. These results can serve as a reference for increasing Nucyep production.

6.
BMC Complement Altern Med ; 19(1): 299, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694626

RESUMO

BACKGROUND: Physical identical and pharmacological inert are the basic requirements for placebo design, which are essential in clinical trials to evaluate the efficacy of an intervention. However, it is difficult to makeup a placebo of Chinese herbal medicine (CHM) because of special color, taste and smell, etc. Currently, there is no specific requirements and standards for the creation of a CHM-placebo. The purpose of this study is to review the characteristics of the CHM-placebo design and application in registered clinical trials with CHM interventions and identify the common problems, if any. METHODS: The World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) was systematically searched for CHM interventional trials with placebo-controlled design up to 31 December 2017. Registered information of each included trial was collected from specific registries involved in ICTRP through hyperlinks. Descriptive statistics were used to analyze the characteristics of placebo design in CHM trial registrations. RESULTS: A total of 889 CHM interventional trials were registered from 1999 to 2017, and 40.8% (363) of them included CHM-placebo control design. The common ways of their design were: placebo as sole control (191, 52.6%); placebo as add-on control with baseline treatment (84, 23.1%); and placebo as double-dummy control (57, 15.7%). Among 363 included trials, 46 (12.7%) reported the compositions of placebos, including CHM ingredients (17 trials), excipients and other agents (29 trials). 2 (0.6%) reported pharmacological inert testing, and 52 (14.3%) descripted their placebos to be physically identical with the CHMs. 14 (3.9%) reported quality control of placebos, and 2 (0.6%) provided blinding assessment of placebos. CONCLUSIONS: The placebos included in most CHM trial registrations is not optimal in terms of placebo design, application, evaluation and reporting. Specific guidelines or standards of CHM-placebo design, including usage requirements, preparation specifications, quality assessments and reporting guidelines should be developed thus to improve their quality.

7.
Pain Med ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722404

RESUMO

OBJECTIVES: Central neuropathic pain (CNP) often appears following spinal cord injury (SCI), but current treatments are not always successful. In this study, we evaluated the analgesic effects of repetitive transcranial magnetic stimulation (rTMS) applied over the hand area of the motor cortex in patients with acute CNP after SCI. METHODS: A total of 48 patients with complete or incomplete SCI and acute CNP participated in this study and were randomized to receive either rTMS (10 Hz, 1,500 stimuli; N = 24) or a sham intervention (N = 24) for three weeks. The numeric rating scale (NRS) and Short-Form McGill Pain Questionnaire-2 (Chinese Edition; SF-MPQ-2-CN) were analyzed to assess the degree of pain. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were collected to explore expression influenced by rTMS. Motor-evoked potential (MEP) latency and maximal amplitude were measured to determine neurophysiological changes. The assessments were carried out at baseline (T0), three days (T1), one week (T2), two weeks (T3), and three weeks (T4) after onset of treatment. RESULTS: The analysis showed significant treatment-time interactions for the quality and intensity of pain, as measured by NRS (P < 0.001, η2 = 0.441) and SF-MPQ-2 (P < 0.001, η2 = 0.590). Compared with the sham group, the NRS and SF-MPQ2-CN scores were significantly lower on the third day (P < 0.001, Cohen's d = 1.135; P = 0.006, Cohen's d = 0.616) and after one week (P < 0.001, Cohen's d = 0.846; P = 0.012, Cohen's d = 0.557) of treatment. In addition, the serum levels of BDNF and NGF were significantly higher in the treated group after three weeks (P = 0.015, Cohen's d = 0.539; P = 0.009, Cohen's d = 0.580), and the MEP amplitude increased by 109.59% (P = 0.033, Cohen's d = 0.464). CONCLUSIONS: These findings indicate that 10 Hz rTMS over the hand area of the motor cortex could alleviate acute CNP in the early phase of SCI and could enhance MEP parameters and modulate BDNF and NGF secretion.

8.
Blood ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31697816

RESUMO

NF-kB and Notch signaling can be simultaneously activated in a variety of B cell lymphomas. Patients with B cell lymphoma occasionally develop clonally-related myeloid tumors with poor prognosis. Whether concurrent activation of both pathways is sufficient to induce B cell transformation and the signaling initiates B-myeloid conversion in a pathological context are largely unknown. Here, we provide genetic evidence that concurrent activation of NF-kB and Notch signaling in committed B cells is sufficient to induce B cell lymphomatous transformation and primes common progenitor cells to convert to myeloid lineage through dedifferentiation, not transdifferentiation. Intriguingly, the converted myeloid cells can further transform, albeitat low frequency, to myeloid leukemia. Mechanistically, coactivation of NF-kB and Notch signaling endows committed B cells with the ability to self-renew. Downregulation of BACH2, a lymphoma and myeloid gene suppressor, but not upregulation of CEBPa and/or downregulation of B cell transcription factors, is one of the early events for both B cell transformation and myeloid conversion. Interestingly, a DNA hypomethylating drug not only effectively eliminated the converted myeloid leukemia cells, but also restored the expression of GFP, which was lost in converted myeloid leukemia cells. Collectively, our results suggest that targeting NF-kB and Notch signaling will not only improve lymphoma treatment, but also prevent the lymphoma-to-myeloid tumor conversion. Importantly, DNA hypomethylating drugs might efficiently treat these converted myeloid neoplasms.

9.
PLoS Comput Biol ; 15(11): e1007468, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31738746

RESUMO

Macrophages respond to signals in the microenvironment by changing their functional phenotypes, a process known as polarization. Depending on the context, they acquire different patterns of transcriptional activation, cytokine expression and cellular metabolism which collectively constitute a continuous spectrum of phenotypes, of which the two extremes are denoted as classical (M1) and alternative (M2) activation. To quantitatively decode the underlying principles governing macrophage phenotypic polarization and thereby harness its therapeutic potential in human diseases, a systems-level approach is needed given the multitude of signaling pathways and intracellular regulation involved. Here we develop the first mechanism-based, multi-pathway computational model that describes the integrated signal transduction and macrophage programming under M1 (IFN-γ), M2 (IL-4) and cell stress (hypoxia) stimulation. Our model was calibrated extensively against experimental data, and we mechanistically elucidated several signature feedbacks behind the M1-M2 antagonism and investigated the dynamical shaping of macrophage phenotypes within the M1-M2 spectrum. Model sensitivity analysis also revealed key molecular nodes and interactions as targets with potential therapeutic values for the pathophysiology of peripheral arterial disease and cancer. Through simulations that dynamically capture the signal integration and phenotypic marker expression in the differential macrophage polarization responses, our model provides an important computational basis toward a more quantitative and network-centric understanding of the complex physiology and versatile functions of macrophages in human diseases.

10.
Nat Prod Res ; : 1-8, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674834

RESUMO

Investigation into the chemical diversity of Artemisia argyi led to the discovery of two new (1, 4) and four known (2-3, 5-6) sesquiterpenoids. The new structures were determined via extensive spectroscopic data, including IR, UV, MS, and NMR, and the absolute configurations of these compounds were elucidated by calculated ECD method. All isolates were tested for their inhibitory activity against NO production in RAW 264.7 macrophages, and the isolated sesquiterpenoids exhibited NO production inhibitory activity with IC50 values ranging from 1.91 to 36.52 µM.

11.
J Orthop Sci ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669118

RESUMO

BACKGROUND: Our study aimed to explore more mechanistic insights into the epigenetic regulation of osteoarthritis (OA). METHODS: The expression profiles (accession number: GSE64393 and GSE64394) were downloaded from the Gene Expression Omnibus database. The differentially hydroxymethylated regions (DhMRs) and differentially expressed genes (DEGs) between OA and control groups were identified. The distribution of DhMRs in the whole genome and the correlation between DhMRs and DEGs were analyzed. Functional module mining for the DEGs and DhMRs was conducted, followed by protein-protein interaction (PPI) analysis. The transcriptional factor (TF) was predicted. RESULTS: Total 52,282 DhMRs were obtained, among which 31,452 ones were annotated to 9726 genes. Additionally, 1806 DEGs were selected. Hydroxymethylation mainly occurred in gene body region. Correlation analysis revealed that more than 70% of DhMRs were uncorrelated with DEGs expression. Functional module mining for the DEGs and DhMRs identified 2 functional modules, which were involved in pathways of regulation of actin cytoskeleton, and TGF-ß signaling pathway. A PPI network was constructed, and ITGB3 had the highest degree. Furthermore, 7 TFs were predicted, which regulated 12 candidate genes, such as HES1-PTEN. CONCLUSIONS: The onset and progression of OA may be associated with the upregulated hydroxymethylation in gene body region of PTEN. HES1 may be important TF in the pathogenesis of OA. Additionally, pathways of regulation of actin cytoskeleton, and TGF-beta signaling pathway may also play important roles in OA progression.

12.
Int Immunopharmacol ; : 106015, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31780369

RESUMO

Lymphocyte antigen 6Chigh (Ly-6Chigh) inflammatory monocytes, as novel mononuclear cells in the innate immune system, participate in infectious diseases. In this study, we investigated the potential role of these monocytes in ventilator-induced lung injury (VILI) and the possible mechanism involved in their migration to lung tissue. Our results showed that mechanical ventilation with high tidal volume (HTV) increased the accumulation of Ly-6Chigh inflammatory monocytes in lung tissues and that blocking C­C chemokine receptor 2 (CCR2) could significantly reduce Ly-6Chigh inflammatory-monocyte migration and attenuate the degree of inflammation of lung tissues. In addition, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) activity could decrease the secretion of monocyte chemoattractant protein 1 (MCP-1), which in turn decreased the migration of Ly-6Chigh inflammatory monocytes into lung tissue. We also demonstrated that high ventilation caused Ly-6Chigh inflammatory monocytes in the bone marrow to migrate into and aggregate in the lungs, creating inflammation, and that the mechanism was quite different from that of infectious diseases. Ly-6Chigh inflammatory monocytes might play a pro-inflammatory role in VILI, and blocking their infiltration into lung tissue might become a new target for the treatment of this injury.

13.
Int J Mol Sci ; 20(23)2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31775357

RESUMO

Carbon dioxide is commonly used as one of the significant environmental factors to control pileus expansion during mushroom cultivation. However, the pileus expansion mechanism related to CO2 is still unknown. In this study, the young fruiting bodies of a popular commercial mushroom Flammulina filiformis were cultivated under different CO2 concentrations. In comparison to the low CO2 concentration (0.05%), the pileus expansion rates were significantly lower under a high CO2 concentration (5%). Transcriptome data showed that the up-regulated genes enriched in high CO2 concentration treatments mainly associated with metabolism processes indicated that the cell metabolism processes were active under high CO2 conditions. However, the gene ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with cell division processes contained down-regulated genes at both 12 h and 36 h under a high concentration of CO2. Transcriptome and qRT-PCR analyses demonstrated that a high CO2 concentration had an adverse effect on gene expression of the ubiquitin-proteasome system and cell cycle-yeast pathway, which may decrease the cell division ability and exhibit an inhibitory effect on early pileus expansion. Our research reveals the molecular mechanism of inhibition effects on early pileus expansion by elevated CO2, which could provide a theoretical basis for a CO2 management strategy in mushroom cultivation.

14.
Pain Res Manag ; 2019: 5930627, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781318

RESUMO

Objectives: To review the evidence of acupuncture for acute and preventive treatment of migraine for further awareness of the effect of acupuncture for migraine. Design: An overview of systematic reviews and meta-analyses (SR/MAs) for randomized controlled trials. Material and Methods: We searched PubMed, Embase, the Cochrane Library, China Knowledge Resource Integrated Database, VIP Chinese Journal Full Text Database, WANFANG Data, and China Biology Medicine disc from their establishment to May 27, 2018. SR/MAs of randomized controlled trials comparing the effect of the acupuncture intervention with another treatment control in migraine patients were included. Results: 428 SRs were identified, and 15 of them were included. Only 4 SR/MAs were assessed by GRADE, which showed certainty of most evidence being low or very low. Assessed by AMSTAR-2, fourteen was critically low rating overall confidence in the results, and 1 was low rating overall confidence in the results. Evidence suggested that acupuncture has a significant advantage of pain improvement, efficacy, and safety relative to blank control, sham acupuncture, or drug treatment, but some of these results are contradictory. Conclusions: We found that acupuncture on treating migraine has the advantage for pain improvement and safety, but the quality of SR/MAs of acupuncture for migraine remains to be improved.

15.
Hum Mutat ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31705731

RESUMO

Exonic deletions and duplications within DMD are the main pathogenic variants in Duchenne and Becker muscular dystrophies (DMD/BMD). However, few studies have profiled the flanking sequences of breakpoints and the potential mechanism underlying the breakpoints in different fragile regions of DMD. In this study, 896 Chinese male probands afflicted with DMD/BMD were selected from unrelated families and analyzed using multiplex ligation-dependent probe amplification of the DMD gene, in which we identified exon deletions in 784 subjects and duplications in 112 subjects. Deletions occurred most frequently in the genomic region encompassing exons 45-55, accounting for 73% of all deletion patterns. Furthermore, to unravel the potential mechanism that induced breaks, DMD gene capture and sequencing were performed to identify the breakpoints in 37 subjects with deletions encompassing exons 45-55 of DMD; we found that DMD instability did not arise from a single cause; instead, long-sequence motifs, nonconsensus microhomologies, low-copy repeats, and microindels were embedded around the breakpoints, which may predispose DMD to instability. In summary, this study highlights the heterogeneous characteristics of the flanking sequences around the breakpoints and helps us to understand the mechanism underlying DMD gene instability.

16.
Org Biomol Chem ; 17(47): 10073-10087, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31750499

RESUMO

We developed a general and sustainable approach for the regioselective deoxygenative chalcogenation of 7-azindole N-oxides; the combination of an internal oxidant and a green solvent has been used successfully for the synthesis of mono- and dichalcogenyl 7-azaindoles which are of pharmaceutical interest. The regioselectivity is tunable by the variation of the reaction conditions. I2/PEG was established as an efficient and reusable catalytic system for C-H chalcogenation. This developed methodology has great potential for practical utility, with a broad substrate scope, green reaction conditions, and operational simplicity.

17.
Chemosphere ; 243: 125309, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31751925

RESUMO

In the present work, a serial of Cu0.02Fe0.2CeyTi1-yOx catalysts are prepared by sol-gel method and applied for NH3-SCR of NO, meanwhile Cu0.02Fe0.2Ce0.2Ti0.8Ox shows good low-temperature NH3-SCR performance with/without water and an outstanding water resistance. The bulk structure, redox ability, surface acidity and surface species of Cu0.02Fe0.2CeyTi1-yOx are measured and discussed by series of characterization in details to illuminate the reasons for the good low-temperature activity and water resistance. The Ce modification can tune the surface acidic distribution, improve the surface oxygen content and surface oxidation reduction cycle (Ce4+ + Fe2+ ↔ Ce3+ + Fe3+), which contribute the good activity. In addition, the effect of water on NH3-SCR performance over Cu0.02Fe0.2TiOx and Cu0.02Fe0·2Ce0·2Ti0.8Ox are investigated emphatically by in situ DRIFTS.

18.
J Water Health ; 17(5): 683-690, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31638020

RESUMO

The presence of disinfection by-products (DBPs) increases the mutagenicity of water and may pose adverse health effects. Gut microbiota exerts a fundamental role on host physiology, and how extrinsic perturbations influence its composition has been increasingly examined. However, the effect of DBPs on gut microbiota is still poorly understood. In the present study, adult zebrafish were exposed to different concentrations of dichloroacetamide (DCAcAm, an emerging nitrogenous DBP) for 30 days. Sequencing of 16S rRNA amplicons revealed a significant change in the richness and diversity of microbiota in the gut of DCAcAm-exposed zebrafish. At the phylum level, the abundance of Proteobacteria decreased and the abundance of Fusobacteria and Firmicutes increased significantly in the gut after exposure to 100 and 500 µg/L DCAcAm. At the genus level, the abundances of several bacteria which are considered pathogens or opportunistic pathogens in fish and closely related to fish metabolism, disease and inflammation (Aeromonas, Stenotrophomonas, Bacteroides and Ralstonia) increased in the DCAcAm-treated groups. Our results reveal that DBPs in drinking water potentially affect gut microbiota composition, which may contribute to the toxicity assessment of DBPs in future and provide new insight into the complex interactions between the DBPs in drinking water and host health.


Assuntos
Acetamidas/toxicidade , Desinfetantes/toxicidade , Microbioma Gastrointestinal , Purificação da Água , Peixe-Zebra/microbiologia , Animais , Desinfecção , Água Potável/química , RNA Ribossômico 16S
19.
Pancreas ; 48(9): 1136-1147, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593017

RESUMO

OBJECTIVE: The objective of this study was to assess the efficacy and safety of acupuncture plus routine treatment (RT) for acute pancreatitis (AP). METHODS: Literature searches were performed in 8 databases up to October 31, 2018. Randomized controlled trials comparing acupuncture plus RT with RT alone for AP were included. RESULTS: Twelve eligible studies were included finally. The meta-analysis showed that acupuncture plus RT compared with RT alone could significantly improve the total effective rate and gastrointestinal function and reduce the Acute Physiology, Age, Chronic Health Evaluation II score, tumor necrosis factor α count, the time of resuming to diets, and the length of hospital stay. Only 3 of the studies reported adverse events or reactions. CONCLUSIONS: This study suggested that acupuncture combined with RT may be effective for AP. However, more rigorously designed randomized controlled trials are warranted to confirm the current findings.

20.
Sci Rep ; 9(1): 15340, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653960

RESUMO

To explore the association between methylation of antisense non-coding RNA in the INK4 locus (ANRIL) and coronary artery disease (CAD) development. Methylation levels of ANRIL in 100 subjects with CAD and 100 controls were quantitatively analyzed using Sequenom MassARRAY. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify novel pathways. Our analyses indicated that 7 to 8 CpG sites within the 2nd CpG island located upstream of ANRIL, also known as cyclin-dependent kinase inhibitor 2B - antisense 1 (CDKN2B-AS1), are hyper-methylated in CAD subjects compared to controls (p = 0.034). The 40th CpG site within the 2nd CpG island located upstream of CDKN2B-AS1 was methylated to a lesser extent in CAD subjects compared to controls (p = 0.045). Both Pearson and Spearman analyses indicated that methylation levels were significantly associated with total cholesterol (r = 0.204, p = 0.004), fasting high-density lipoprotein cholesterol (r = 0.165, p = 0.020), and fasting low-density lipoprotein cholesterol (r = 0.265, p = 0.000). KEGG pathway analysis revealed a significant enrichment of genes associated with the tumor necrosis factor (TNF) signaling pathway. Among them, CCAAT/enhancer binding protein (C/EBPß) was identified as a key transcription factor that promotes expression of CDKN2B-AS1 through promotor interaction. DNA methylation of the ANRIL promoter was significantly associated with CAD development in our study. Our analyses suggest that C/EBPß is a key transcription factor that promotes CDKN2B-AS1 expression by directly interacting with the gene promotor mediated by TNF signaling.

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