Publications by authors named "Yanda Li"

72 Publications

The loss of heterochromatin is associated with multiscale three-dimensional genome reorganization and aberrant transcription during cellular senescence.

Genome Res 2021 Jun 17. Epub 2021 Jun 17.

MOE Key Laboratory of Bioinformatics; Center for Synthetic and Systems Biology; Department of Automation, Tsinghua University, Beijing 100084, China.

Heterochromatin remodeling is critical for various cell processes. In particular, the "loss of heterochromatin" phenotype in cellular senescence is associated with the process of aging and age-related disorders. Although biological processes of senescent cells, including senescence-associated heterochromatin foci (SAHF) formation, chromosome compaction, and redistribution of key proteins, have been closely associated with high-order chromatin structure, the relationship between the high-order chromatin reorganization and the loss of heterochromatin phenotype during senescence has not been fully understood. By using senescent and deep senescent fibroblasts induced by DNA damage harboring the "loss of heterochromatin" phenotype, we observed progressive 3D reorganization of heterochromatin during senescence. Facultative and constitutive heterochromatin marked by H3K27me3 and H3K9me3, respectively, show different alterations. Facultative heterochromatin tends to switch from the repressive B-compartment to the active A-compartment, whereas constitutive heterochromatin shows no significant changes at the compartment level but enhanced interactions between themselves. Both types of heterochromatin show increased chromatin accessibility and gene expression leakage during senescence. Furthermore, increased chromatin accessibility in potential CTCF binding sites accompanies the establishment of novel loops in constitutive heterochromatin. Finally, we also observed aberrant expression of repetitive elements, including LTR (long terminal repeat) and satellite classes. Overall, facultative and constitutive heterochromatin show both similar and distinct multiscale alterations in the 3D map, chromatin accessibility, and gene expression leakage. This study provides an epigenomic map of heterochromatin reorganization during senescence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/gr.275235.121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256869PMC
June 2021

Prevention and treatment of COVID-19 using Traditional Chinese Medicine: A review.

Phytomedicine 2021 May 20;85:153308. Epub 2020 Aug 20.

National Resource Center for Chinese Materia Medica, State Key Laboratory Breeding Base of Dao-di Herbs, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address:

Background: A novel coronavirus (SARS-CoV2) outbreak in more than 200 countries recently caused viral pneumonia that was extremely infectious and pathogenic. The Chinese government proposes that both Traditional Chinese medicine (TCM) and Western medicine can be used in combination to treat pneumonia caused by SARS-CoV2, and TCM effectively provides continuous prevention and treatment.

Methods: The present review analyzes and summarizes the prevention and treatment of the novel coronavirus disease (COVID-19) with TCM. A classified analysis of the efficacy and advantages of TCM for the prevention and treatment of COVID-19 was performed, and the mechanisms of TCM in treating COVID-19 are summarized.

Results: TCM is effective in preventing COVID-19, and medical staff can prevent an iatrogenic infection by taking a decoction made based on the principles of TCM. As of March 13, 2020, new cases of COVID-19 in China have decreased in number to single digits. TCM's curative effect was outstanding, with a national participation rate of over 90%. More than 70,000 people were cured of COVID-19 and discharged from the hospital. Only approximately 10,000 patients are currently being treated, and the total treatment time is approximately 2 months.

Conclusions: TCM is currently the best choice for the treatment and prevention of COVID-19, and it is expected that it will be promoted by countries around the world.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2020.153308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439087PMC
May 2021

Cardiac injury associated with severe disease or ICU admission and death in hospitalized patients with COVID-19: a meta-analysis and systematic review.

Crit Care 2020 07 28;24(1):468. Epub 2020 Jul 28.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Background: Cardiac injury is now a common complication of coronavirus disease (COVID-19), but it remains unclear whether cardiac injury-related biomarkers can be independent predictors of mortality and severe disease development or intensive care unit (ICU) admission.

Methods: Two investigators searched the PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI), Wanfang, MedRxiv, and ChinaXiv databases for articles published through March 30, 2020. Retrospective studies assessing the relationship between the prognosis of COVID-19 patients and levels of troponin I (TnI) and other cardiac injury biomarkers (creatine kinase [CK], CK myocardial band [CK-MB], lactate dehydrogenase [LDH], and interleukin-6 [IL-6]) were included. The data were extracted independently by two investigators.

Results: The analysis included 23 studies with 4631 total individuals. The proportions of severe disease, ICU admission, or death among patients with non-elevated TnI (or troponin T [TnT]), and those with elevated TnI (or TnT) were 12.0% and 64.5%, 11.8% and 56.0%, and 8.2% and. 59.3%, respectively. Patients with elevated TnI levels had significantly higher risks of severe disease, ICU admission, and death (RR 5.57, 95% CI 3.04 to 10.22, P < 0.001; RR 6.20, 95% CI 2.52 to 15.29, P < 0.001; RR 5.64, 95% CI 2.69 to 11.83, P < 0.001). Patients with an elevated CK level were at significantly increased risk of severe disease or ICU admission (RR 1.98, 95% CI 1.50 to 2.61, P < 0.001). Patients with elevated CK-MB levels were at a higher risk of developing severe disease or requiring ICU admission (RR 3.24, 95% CI 1.66 to 6.34, P = 0.001). Patients with newly occurring arrhythmias were at higher risk of developing severe disease or requiring ICU admission (RR 13.09, 95% CI 7.00 to 24.47, P < 0.001). An elevated IL-6 level was associated with a higher risk of developing severe disease, requiring ICU admission, or death.

Conclusions: COVID-19 patients with elevated TnI levels are at significantly higher risk of severe disease, ICU admission, and death. Elevated CK, CK-MB, LDH, and IL-6 levels and emerging arrhythmia are associated with the development of severe disease and need for ICU admission, and the mortality is significantly higher in patients with elevated LDH and IL-6 levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-020-03183-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386170PMC
July 2020

A Pooled Analysis of the Prognostic Significance of Brugada Syndrome with Atrial Fibrillation.

Curr Pharm Des 2020 ;26(1):129-137

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Background: Guidelines have previously suggested that atrial fibrillation (AF) is associated with an increased risk of arrhythmic death in Brugada syndrome (BrS) patients. However, only two articles consisting of 17 AF patients with BrS supported these views. The risk stratification of BrS patients with AF remains controversial. Thus, a meta-analysis is used to estimate the risk stratification of BrS patients with AF.

Methods: We searched for relevant studies published from 2000 to December 30, 2018. A total of 1712 patients with BrS from five studies were included: 200 patients (12%) were reported with AF, among whom 37 patients (19%) had arrhythmic events.

Results: BrS patients with AF in all studies (OR 1.92, 95% CI:0.91to 4.04, P =0.09; Heterogeneity: P = 0.03, I2=61%) and some European studies (OR 1.12, 95% CI: 0.18 to 6.94, P=0.91; Heterogeneity: P = 0.006, I2=80%) did not display a higher risk of arrhythmic events than those without AF, but BrS patients with AF in Japanese studies (OR 2.32, 95% CI: 1.37 to 3.93, P=0.002; Heterogeneity: P = 0.40, I2=0%) had a higher risk of arrhythmic events than those without AF. The proportion of BrS patients with AF was greater in Japanese studies than in some European studies (16% vs. 9%, P<0.001).

Conclusion: On the whole, BrS patients with AF showed no higher risk of arrhythmic events than those without AF, but BrS patients with AF in Japan had a higher risk of arrhythmic events than those without AF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1381612826666200114112029DOI Listing
November 2020

Role of cardioprotective agents on chemotherapy-induced heart failure: A systematic review and network meta-analysis of randomized controlled trials.

Pharmacol Res 2020 01 29;151:104577. Epub 2019 Nov 29.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address:

Background: Although previous clinical randomized controlled trials (RCTs) have tested the effect of a variety of cardioprotective agents on cancer therapy-induced cardiotoxicity, the number of included patients was limited, and the results remained controversial. In this study, we aimed to evaluate the preventive or therapeutic effects of cardioprotective agents on heart failure (HF) caused by cardiotoxicity induced by cancer therapy.

Methods: We included trials of the following cardioprotective drugs: Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, aldosterone antagonists and stains. We extracted the relevant information with predefined data extraction forms, and assessed the risk of bias in randomized controlled trials with the Cochrane risk of bias tool. The primary outcome was the left ventricular ejection fraction of patients after chemotherapy. We used the random-effects model to carry out pair-wise meta-analysis, and then carry out the random-effects network meta-analysis within the Bayesian framework.

Results: Twenty-two relevant RCTs, including 1 916 patients (79.6 % women) with a mean age of 48.4 years, were included. Based on the evaluation of all drug species from 20 studies (26 comparisons), the analysis found that 4 therapies, aldosterone antagonists (MD, 12.78 [95 % CI, 2.87-22.69] and MD, 13.75 [95 % CI, 2.21-25.30]), ACEIs (MD, 6.79 [95 % CI, 2.11-11.48] and MD, 7.76 [95 % CI, 2.64-12.88]), statin (MD, 8.35 [95 % CI, 1.11-15.59]), and beta-blockers (MD, 4.00 [95 % CI, 0.87-7.14]), had a higher efficacy than placebo and/or control, suggesting an LVEF protective effect of cardioprotective therapy. In the analysis classified by single drug or drug combination, based on 22 studies (31 comparisons), spironolactone (MD, 12.77 [95 % CI, 1.76-23.79] and MD, 14.62 [95 % CI, 1.70-27.55]), a combination of candesartan and carvedilol (MD, 12.40 [95 % CI, 0.99-23.81]), enalapril (MD, 7.35 [95 % CI, 1.16-13.54] and MD, 9.20 [95 % CI, 2.61-15.79]), and statin (MD, 8.36 [95 % CI, 0.36-16.36]) showed significant benefits in protecting left ventricular (LV) systolic function compared with the placebo and/or control.

Conclusion: When classified according to drug type, aldosterone antagonists, ACEIs, statins, and beta-blockers could substantially improve the LV systolic function. In the analysis classified by single drug or drug combination, spironolactone, enalapril, and statin have a significant cardioprotective effect. However, ARBs have no cardioprotective effect and fail to improve the LVEF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2019.104577DOI Listing
January 2020

Dynamic transcriptome profiling in DNA damage-induced cellular senescence and transient cell-cycle arrest.

Genomics 2020 03 31;112(2):1309-1317. Epub 2019 Jul 31.

Ministry of Education Key Laboratory of Bioinformatics, Center for Synthetic and System Biology, BNRist, Department of Automation, Tsinghua University, Beijing 100084, China. Electronic address:

Cellular senescence is an irreversible cell cycle arrest process associated with aging and senescence-related diseases. DNA damage is an extensive feature of cellular senescence and aging. Different levels of DNA damage could lead to cellular senescence or transient cell-cycle arrest, but the genetic regulatory mechanisms determining cell fate are still not clear. In this work, high-resolution time course analysis of gene expression in DNA damage-induced cellular senescence and transient cell-cycle arrest was used to explore the transcriptomic differences between different cell fates after DNA damage response and to investigate the key regulatory factors affecting senescent cell fates. Pathways such as the cell cycle, DNA repair and cholesterol metabolism showed characteristic differential response. A number of key transcription factors were predicted to regulating cell cycle and DNA repair. Our study provides genome-wide insights into the molecular-level mechanisms of senescent cell fate decisions after DNA damage response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygeno.2019.07.020DOI Listing
March 2020

Transcriptomic Analysis of Seed Germination Under Salt Stress in Two Desert Sister Species ( and ).

Front Genet 2019 25;10:231. Epub 2019 Mar 25.

State Key Laboratory of Grassland Agro-Ecosystem, School of Life Sciences, Lanzhou University, Lanzhou, China.

As a major abiotic stress, soil salinity limits seed germination and plant growth, development and production. Seed germination is highly related not only to the seedlings survival rate but also subsequent vegetative growth. and are closely related species that show a distinguished adaptability to salinity stress. In this study, we performed an integrative transcriptome analyses of three seed germination phases from and under salt stress. A two-dimensional data set of this study provides a comprehensive view of the dynamic biochemical processes that underpin seed germination and salt tolerance. Our analysis identified 12831 differentially expressed genes (DEGs) for seed germination processes and 8071 DEGs for salt tolerance in the two species. Furthermore, we identified the expression profiles and main pathways in each growth phase. For seed germination, a large number of DEGs, including those involved in energy production and hormonal regulation pathways, were transiently and specifically induced in the late phase. In the comparison of salt tolerance between the two species, the flavonoid and brassinosteroid pathways were significantly enriched. More specifically, in the flavonoid pathway, and '' exhibited significant differential expression. In the brassinosteroid pathway, the expression levels of , and were notably higher in than in . Our results describe transcript dynamics and highlight secondary metabolite pathways involved in the response to salt stress during the seed germination of two desert poplars.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2019.00231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442517PMC
March 2019

Meta-Analysis of Risk Stratification of SCN5A With Brugada Syndrome: Is SCN5A Always a Marker of Low Risk?

Front Physiol 2019 19;10:103. Epub 2019 Feb 19.

Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, China.

with Brugada syndrome (BrS) is not commonly considered as an independent risk marker for subsequent cardiac events. However, the risk of combined with other clinical characteristics has not been fully investigated. The aim of this study is to investigate and evaluate risk stratification and related risk factors of in BrS. The databases of PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI) and Wanfang Data were searched for related studies published from January 2002 to May 2018 followed by meta-analysis. The BrS patients who underwent gene tests were included. The prognosis and risk stratification of combined with symptoms and asymptoms diagnosis in BrS, electrophysiology study (EPS) were then investigated and evaluated. Outcomes were defined as ventricular tachycardia/fibrillation (VT/VF), sudden cardiac death (SCD). Eleven suitable studies involving 1892 BrS patients who underwent gene tests were identified. (+) was not considered to be a significant predictor of future cardiac events (95% CI: 0.89-2.11; = 0.15; = 0%). However, (+) patients with symptoms at diagnosis revealed a higher prevalence of future VT/VF, SCD compared to (-) patients with symptoms at diagnosis. (95% CI: 1.06-3.70; = 0.03 = 0%) Among asymptomatic patients, the risk did not significantly differ between (+) patients and (-) patients. (95% CI: 0.51-4.72; = 0.45 = 0 %). In an investigation involving patients in EPS (-) BrS electrocardiogram (ECG), the risk of (+) is higher than that of (-) ( < 0.001). In BrS patients with symptoms at diagnosis or EPS (-), the meta-analysis suggests that (+) are at a higher risk of arrhythmic events than (-).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2019.00103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389868PMC
February 2019

Pooled Analysis of Risk Stratification of Spontaneous Type 1 Brugada ECG: Focus on the Influence of Gender and EPS.

Front Physiol 2018 31;9:1951. Epub 2019 Jan 31.

Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, China.

Risk stratification of patients with Brugada syndrome (BrS) is vital for accurate prognosis and therapeutic decisions. Spontaneous Type 1 ST segment elevation is generally considered to be an independent risk factor for arrhythmic events. Other risk factors include gender, syncope, sudden cardiac arrest (SCA), and positive electrophysiological study (EPS). However, the further risk stratification of spontaneous type 1 combined with the other risk factors remains unclear. The present study pooled data from 4 large trials aiming to systematically evaluate the risk of spontaneous Type-1 ECG when combined with one or more of these other recognized risk factors. We searched for related studies published from November 2, 2002 to February 10, 2018 in PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Databases. The pooled data were evaluated combining each risk factor with the presence of a spontaneous Type-1 ECG. All analyses were performed using Review Manager, version 5.0.12. Four eligible studies involving 1,338 patients (85% males, mean age: 48.1 ± 18.1 years) were enrolled. Spontaneous Type-1 ECG was associated with higher risk for ventricular tachycardia/fibrillation (VT/VF) than cases with non-Type 1 ECG in males (odds ratio: 95% CI: 1.84-5.17; < 0.0001), but not in females ( = 0.29). Among spontaneous Type-1 cases with syncope or with positive EPS, the difference was not statistically significant ( = 0.06 and 0.07, respectively). Patients with Type-1 ECGs and positive EPS were at higher risk than those with negative EPS (95% CI: 1.10-5.04; = 0.03). Pooled analysis showed an association of Spontaneous Type-1 ECG, Type-1 ECGs combined with male, and Type-1 ECGs combined with positive EPS between increased risk of arrhythmic events. Our results indicate that in BrS patients, a spontaneous Type-1 ECG is an independent risk factor for SCD in males, but not in females. A spontaneous Type-1 BrS is associated with a worse prognosis when combined with positive EPS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2018.01951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365464PMC
January 2019

Network-Based Combinatorial CRISPR-Cas9 Screens Identify Synergistic Modules in Human Cells.

ACS Synth Biol 2019 03 21;8(3):482-490. Epub 2019 Feb 21.

MOE Key Laboratory of Bioinformatics and TCM-X Center/Bioinformatics Division/TFIDT, BNRist, Department of Automation , Tsinghua University , Beijing 100084 , China.

Tumorigenesis is a complex process that is driven by a combination of networks of genes and environmental factors; however, efficient approaches to identifying functional networks that are perturbed by the process of tumorigenesis are lacking. In this study, we provide a comprehensive network-based strategy for the systematic discovery of functional synergistic modules that are causal determinants of inflammation-induced tumorigenesis. Our approach prioritizes candidate genes selected by integrating clinical-based and network-based genome-wide gene prediction methods and identifies functional synergistic modules based on combinatorial CRISPR-Cas9 screening. On the basis of candidate genes inferred de novo from experimental and computational methods to be involved in inflammation and cancer, we used an existing TGFβ1-induced cellular transformation model in colonic epithelial cells and a new combinatorial CRISPR-Cas9 screening strategy to construct an inflammation-induced differential genetic interaction network. The inflammation-induced differential genetic interaction network that we generated yielded functional insights into the genes and functional module combinations, and showed varied responses to the inflammation agents as well as active traditional Chinese medicine compounds. We identified opposing differential genetic interactions of inflammation-induced tumorigenesis: synergistic promotion and suppression. The synergistic promotion state was primarily caused by deletions in the immune and metabolism modules; the synergistic suppression state was primarily induced by deletions in the proliferation and immune modules or in the proliferation and metabolism modules. These results provide insight into possible early combinational targets and biomarkers for inflammation-induced tumorigenesis and highlight the synergistic effects that occur among immune, proliferation, and metabolism modules. In conclusion, this approach deepens the understanding of the underlying mechanisms that cause inflammation to potentially increase the cancer risk of colonic epithelial cells and accelerate the translation into novel functional modules or synergistic module combinations that modulate complex disease phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acssynbio.8b00237DOI Listing
March 2019

Mechanisms and Treatments of Oxidative Stress in Atrial Fibrillation.

Curr Pharm Des 2018 ;24(26):3062-3071

Guang'an men Hospital, Chinese Academy of Chinese Medical Sciences, Beijing 100053, China.

Atrial fibrillation (AF) is a frequent cardiac arrhythmia. It is a common major cause of serious diseases and is an increasing health-care burden. AF is associated with an excess amount of reactive oxygen species. In this review, we summarize several possible reactive oxygen species pathways that induce AF based on atrial electrical and structural remodeling data. The sources and factors implicated in AF-related oxidative stress include NADPH oxidase activation, calcium overloading and mitochondrial damage, angiotensin system activation, nitric oxide synthase uncoupling, and xanthine oxidase activation-associated cardiovascular conditions. Scavenging oxidative stress markers and related substances are essential aspects of these molecular mechanisms, and may be a therapeutic target in AF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1381612824666180903144042DOI Listing
October 2019

Mitochondria and the Pathophysiological Mechanism of Atrial Fibrillation.

Curr Pharm Des 2018 ;24(26):3055-3061

Guang'an men Hospital, Chinese Academy of Chinese Medical Sciences, Beijing 100053, China.

Atrial fibrillation (AF) is the most common and significant cardiac arrhythmia in clinical practice, however the pathophysiological mechanism of AF has not been fully explained. At present, there are no available treatment options that can target the underlying pathophysiological processes of AF. Research on improving management strategies for AF can start with a further understanding of the changes of cells in AF. Mitochondria play central roles in the function of cardiac myocytes and many of the pathophysiological processes implicated in AF are relative to mitochondrial function, including formation of reactive oxygen species (ROS), calcium homeostasis, and alterations of oxygen consumption. The changes of levels of phosphocreatine, electron transfer chain proteins and differences in mitochondrial distribution further imply that mitochondria play a role in AF. Related studies of recent years are summarized, in order to elucidate the causal relationship between mitochondria and AF, and provide potential therapeutic target for the treatment and prevention of AF in clinical practice. In the article, we summarize the direct or indirect factors that affect mitochondria function and thus cause AF, including anticancer agents, surgery, gene, age, air pollution, oxidative stress, and β3-adrenoceptor (β3-AR). There is a close relationship between mitochondrial dysfunction and the occurrence of AF, which cannot be ignored, and further research in this area is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1381612824666180903125300DOI Listing
October 2019

esATAC: an easy-to-use systematic pipeline for ATAC-seq data analysis.

Bioinformatics 2018 08;34(15):2664-2665

Ministry of Education Key Laboratory of Bioinformatics, Center for Synthetic and System Biology, BNRist, Department of Automation, Tsinghua University, Beijing, China.

Summary: ATAC-seq is rapidly emerging as one of the major experimental approaches to probe chromatin accessibility genome-wide. Here, we present 'esATAC', a highly integrated easy-to-use R/Bioconductor package, for systematic ATAC-seq data analysis. It covers essential steps for full analyzing procedure, including raw data processing, quality control and downstream statistical analysis such as peak calling, enrichment analysis and transcription factor footprinting. esATAC supports one command line execution for preset pipelines and provides flexible interfaces for building customized pipelines.

Availability And Implementation: esATAC package is open source under the GPL-3.0 license. It is implemented in R and C++. Source code and binaries for Linux, MAC OS X and Windows are available through Bioconductor (https://www.bioconductor.org/packages/release/bioc/html/esATAC.html).

Supplementary Information: Supplementary data are available at Bioinformatics online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/bty141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061683PMC
August 2018

The Effects of Tai Chi Training in Patients with Heart Failure: A Systematic Review and Meta-Analysis.

Front Physiol 2017 7;8:989. Epub 2017 Dec 7.

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.

Heart Failure (HF) is associated with significantly high morbidity and mortality. We performed a meta-analysis and updated new evidences from randomized controlled trials (RCTs) to determine the effects of Tai Chi (TC) in patients with HF. Electronic literature search of Medline, PubMed, EMBASE, the Cochrane Library, China national knowledge infrastructure (CNKI), and Wan Fang Database was conducted from inception of their establishment until 2017. And we also searched Clinical Trials Registries (https://clinicaltrials.gov/ and www.controlled-trials.com) for on-going studies. A total of 11 trials with 656 patients were available for analysis. The results suggested that TC was associated with an obviously improved 6-min walk distance [6MWD, weighted mean difference (WMD) 65.29 m; 95% CI 32.55-98.04] and quality of life (Qol, WMD -11.52 points; 95% CI -16.5 to -6.98) and left ventricular ejection fraction (LVEF, WMD 9.94%; 95% CI 6.95 to 12.93). TC was shown to reduce serum B-type natriuretic peptide [BNP, standard mean difference (SMD) -1.08 pg/mL; 95% CI -1.91 to -0.26] and heart rate (HR, WMD -2.52 bpm; 95% CI -3.49 to -1.55). In summary, our meta-analysis demonstrated the clinical evidence about TC for HF is inconclusive. TC could improve 6MWD, Qol and LVEF in patients with HF and may reduce BNP and HR. However, there is a lack of evidence to support TC altering other important long-term clinical outcomes so far. Further larger and more sustainable RCTs are urgently needed to investigate the effects of TC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2017.00989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770613PMC
December 2017

Immediate/Early vs. Delayed Invasive Strategy for Patients with Non-ST-Segment Elevation Acute Coronary Syndromes: A Systematic Review and Meta-Analysis.

Front Physiol 2017 27;8:952. Epub 2017 Nov 27.

Department of Cardiology, Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, China.

Invasive coronary revascularization has been shown to improve prognoses in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), but the optimal timing of intervention remains unclear. This meta-analysis is to evaluate the outcomes in immediate (<2 h), early (<24 h), and delayed invasive group and find out which is the optimal timing of intervention in NSTE-ACS patients. Studies were identified through electronic literature search of Medline, PubMed Central, Embase, the Cochrane Library, and CNKI. Data were extracted for populations, interventions, outcomes, and risk of bias. All-cause mortality was the pre-specified primary end point. The longest follow-up available in each study was chosen. The odds ratio (OR) with 95% CI was the effect measure. The fixed or random effect pooled measure was selected based on the heterogeneity test among studies. In the comparison between early and delayed intervention, we found that early intervention led to a statistical significant decrease in mortality rate ( = 6,624; OR 0.78, 95% CI: 0.61-0.99) and refractory ischemia ( = 6,127; OR 0.50, 95% CI: 0.40-0.62) and a non-significant decrease in myocardial infarction (MI), major bleeding and revascularization. In the analysis comparing immediate and delayed invasive approach, we found that immediate intervention significantly reduced major bleeding ( = 1,217; OR 0.46, 95% CI: 0.23-0.93) but led to a non-significant decrease in mortality rate, refractory ischemia and revascularization and a non-significant increase in MI. In conclusion, early invasive strategy may lead to a lower mortality rate and reduce the risk of refractory ischemia, while immediate invasive therapy shows a benefit in reducing the risk of major bleeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2017.00952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712112PMC
November 2017

Multiscale Modeling of Inflammation-Induced Tumorigenesis Reveals Competing Oncogenic and Oncoprotective Roles for Inflammation.

Cancer Res 2017 11 26;77(22):6429-6441. Epub 2017 Sep 26.

MOE Key Laboratory of Bioinformatics and TCM-X Center/Bioinformatics Division, TNLIST, Department of Automation, Tsinghua University, Beijing, China.

Chronic inflammation is a serious risk factor for cancer; however, the routes from inflammation to cancer are poorly understood. On the basis of the processes implicated by frequently mutated genes associated with inflammation and cancer in three organs (stomach, colon, and liver) extracted from the Gene Expression Omnibus, The Cancer Genome Atlas, and Gene Ontology databases, we present a multiscale model of the long-term evolutionary dynamics leading from inflammation to tumorigenesis. The model incorporates cross-talk among interactions on several scales, including responses to DNA damage, gene mutation, cell-cycle behavior, population dynamics, inflammation, and metabolism-immune balance. Model simulations revealed two stages of inflammation-induced tumorigenesis: a precancerous state and tumorigenesis. The precancerous state was mainly caused by mutations in the cell proliferation pathway; the transition from the precancerous to tumorigenic states was induced by mutations in pathways associated with apoptosis, differentiation, and metabolism-immune balance. We identified opposing effects of inflammation on tumorigenesis. Mild inflammation removed cells with DNA damage through DNA damage-induced cell death, whereas severe inflammation accelerated accumulation of mutations and hence promoted tumorigenesis. These results provide insight into the evolutionary dynamics of inflammation-induced tumorigenesis and highlight the combinatorial effects of inflammation and metabolism-immune balance. This approach establishes methods for quantifying cancer risk, for the discovery of driver pathways in inflammation-induced tumorigenesis, and has direct relevance for early detection and prevention and development of new treatment regimes. .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-17-1662DOI Listing
November 2017

Oxidative Stress-Mediated Atherosclerosis: Mechanisms and Therapies.

Front Physiol 2017 23;8:600. Epub 2017 Aug 23.

Key Laboratory of Chinese Internal Medicine of the Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese MedicineBeijing, China.

Atherogenesis, the formation of atherosclerotic plaques, is a complex process that involves several mechanisms, including endothelial dysfunction, neovascularization, vascular proliferation, apoptosis, matrix degradation, inflammation, and thrombosis. The pathogenesis and progression of atherosclerosis are explained differently by different scholars. One of the most common theories is the destruction of well-balanced homeostatic mechanisms, which incurs the oxidative stress. And oxidative stress is widely regarded as the redox status realized when an imbalance exists between antioxidant capability and activity species including reactive oxygen (ROS), nitrogen (RNS) and halogen species, non-radical as well as free radical species. This occurrence results in cell injury due to direct oxidation of cellular protein, lipid, and DNA or via cell death signaling pathways responsible for accelerating atherogenesis. This paper discusses inflammation, mitochondria, autophagy, apoptosis, and epigenetics as they induce oxidative stress in atherosclerosis, as well as various treatments for antioxidative stress that may prevent atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2017.00600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572357PMC
August 2017

Comparative Effectiveness of Acupuncture and Antiarrhythmic Drugs for the Prevention of Cardiac Arrhythmias: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Front Physiol 2017 8;8:358. Epub 2017 Jun 8.

Masonic Medical Research LaboratoryNew York, NY, United States.

This study was designed to systematically evaluate the effectiveness of acupuncture treatment for arrhythmia compared to existing drug therapy. Randomized controlled trials (RCTs) were identified through searches of the MEDLINE, CNKI, Embase, and Cochrane databases (1970 through 2016) and hand searches of cross-references from original articles and reviews. Clinical trials that randomized arrhythmia patients to acupuncture therapy vs. conventional drugs, sham acupuncture, or bed rest were included for analysis. A total of 13 trials with 797 patients met the criteria for analysis. The results of the meta-analysis showed no statistically significant difference between acupuncture and conventional treatment for paroxysmal supraventricular tachycardia (PSVT) ( = 203; RR, 1.18; 95% CI 0.78-1.79; = 80%; = 0.44). However, in the ventricular premature beat (VPB) group, it showed a significant benefit of acupuncture plus oral administration of anti-arrhythmic drug (AAD) on response rates compared with the oral administration of AAD ( = 286; RR, 1.15; 95% CI 1.05-1.27; = 0%; = 0.002). Finally, when compared with the sinus tachycardia (ST) cases without any treatment, acupuncture has benefited these patients ( = 120; MD, 18.80, 95% CI 12.68-24.92; = 81%; < 0.00001). In summary, our meta-analysis demonstrates that clinical efficacy of acupuncture is not less than AAD for PSVT. Furthermore, in sub-group analysis, acupuncture with or without AAD, shows a clear benefit in treating VPB and ST. However, more definitive RCTs are warranted to guide clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2017.00358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463903PMC
June 2017

A Systematic Review and Meta-Analysis on the Treatment of Cerebral Hemorrhage with NaoXueShu Oral Liquid.

Biomed Res Int 2017 29;2017:8542576. Epub 2017 May 29.

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Key Office of Encephalopathy TCM Research, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.

NaoXueShu oral liquid invigorates Qi and promotes blood circulation, which is mainly used for treating the acute stage of the meridian of hemorrhagic apoplexy and acute blood stasis syndrome during early convalescence. Its main clinical manifestations include hemiplegia, mouth askew, hemianesthesia, and inarticulateness. It is used mainly in patients with lobar hemorrhage, basal ganglia, and thalamus of the small amount of bleeding without disturbing consciousness of hypertensive cerebral. The purpose of this study was to evaluate the efficacy and adverse effects of NaoXueShu oral liquid on the treatment of cerebral hemorrhage. In this study, literature on randomized controlled trials was collected from seven databases to evaluate the clinical efficiency of the treatment of cerebral hemorrhage alone or combined with Western medicine. The methodologic quality of the included studies was assessed using a standard Cochrane system review and analyzed using RevMan 5.3.0 software. The study included 14 eligible randomized controlled trials. The results showed that the use of NaoXueShu oral liquid alone or combined with other drugs or auxiliary methods can play a significant role in the treatment of cerebral hemorrhage, especially hypertensive intracerebral hemorrhage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2017/8542576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467282PMC
March 2018

Effects of Wenxin Keli on Cardiac Hypertrophy and Arrhythmia via Regulation of the Calcium/Calmodulin Dependent Kinase II Signaling Pathway.

Biomed Res Int 2017 9;2017:1569235. Epub 2017 May 9.

The Key Laboratory of Chinese Internal Medicine of the Ministry of Education, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.

We investigated the effects of Wenxin Keli (WXKL) on the Calcium/Calmodulin dependent kinase II (CaMK II) signal transduction pathway with transverse aortic constriction (TAC) rats. Echocardiographic measurements were obtained 3 and 9 weeks after the surgery. Meanwhile, the action potentials (APDs) were recorded using the whole-cell patch clamp technique, and western blotting was used to assess components of the CaMK II signal transduction pathway. At both 3 and 9 weeks after treatment, the fractional shortening (FS%) increased in the WXKL group compared with the TAC group. The APD of the TAC group was longer than that of the Sham group and was markedly shortened by WXKL treatment. Western blotting results showed that the protein expressions of CaMK II, phospholamban (PLB), and ryanodine receptor 2 (RYR2) were not statistically significant among the different groups at both treatment time points. However, WXKL treatment decreased the protein level and phosphorylation of CaMK II (Thr-286) and increased the protein level and phosphorylation of PLB (Thr-17) and the phosphorylation of RYR2 (Ser-2814). WXKL also decreased the accumulation of type III collagen fibers. In conclusion, WXKL may improve cardiac function and inhibit the arrhythmia by regulating the CaMK II signal transduction pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2017/1569235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440795PMC
March 2018

Development of a Critical Nitrogen Dilution Curve of Double Cropping Rice in South China.

Front Plant Sci 2017 28;8:638. Epub 2017 Apr 28.

Jiangsu Key Laboratory for Information Agriculture, National Engineering and Technology Center for Information Agriculture, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural UniversityNanjing, China.

The concept of critical nitrogen () concentration can be implemented to diagnose in-season plant nitrogen (N) status for optimizing N fertilizer management. The dilution curves have been established for rice ( L.) grown in different climatic regions, yet no attempt has been made to develop the dilution curve for double cropping rice regions. This study was undertaken to develop the dilution curves for double cropping rice in south China for assessment of in-season N status and to establish the relationships N nutrition index (NNI) and relative yield (RY) for in-season prediction of rice grain yield. Three different N application rate field experiments using six Indica rice varieties, including two early rice hybrids and four late rice hybrids were carried out in east China. The dilution curves based on whole plant N concentration were determined and described as, N = 3.37 W for early rice and N = 3.69 W for late rice. The constant N concentration at early growth stage was 3.31 and 3.15% DM for early and late rice, respectively. Late rice showed a higher capacity of N accumulation and a lower rate of N decline per unit shoot biomass as compared to early rice. The curves for present study were different from the existing reference curves for Indica and Japonica rice grown in different rice growing regions. Integrated N nutrition index (NNI) based on N was used to estimate RY at different growth periods using linear regression functions. The results showed that the critical curves and relationship between NNI and RY could be used as a reliable indicator of N status diagnosis, grain yield prediction as well as to provide technical support in N management for double cropping rice in south China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2017.00638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408224PMC
April 2017

Effects of exercise-based cardiac rehabilitation in patients after percutaneous coronary intervention: A meta-analysis of randomized controlled trials.

Sci Rep 2017 03 17;7:44789. Epub 2017 Mar 17.

Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing 100053, China.

In this study, we assessed the effect of rehabilitation exercise after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). We performed a meta-analysis to determine the effects of exercise in patients after PCI. The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, the Embase database, China National Knowledge Internet (CNKI), China Biology Medicine (CBM), and the Wanfang Database were searched for randomized controlled trials (RCTs). The key words used for the searches were PCI, exercise, walking, jogging, Tai Chi, and yoga. Six studies with 682 patients met our inclusion criteria; we chose the primary endpoint events of cardiac death, recurrence of myocardial infarction (MI), repeated PCI, coronary artery bypass grafting (CABG), and restenosis, and the secondary endpoint measures included recurrent angina, treadmill exercise (total exercise time, ST-segment decline, angina, and maximum exercise tolerance). The results showed that exercise was not clearly associated with reductions in cardiac death, recurrence of MI, repeated PCI, CABG, or restenosis. However, the exercise group exhibited greater improvements in recurrent angina, total exercise time, ST-segment decline, angina, and maximum exercise tolerance than did the control group. Future studies need to expand the sample size and improve the quality of reporting of RCTs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep44789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356037PMC
March 2017

The Role of Biologically Active Ingredients from Chinese Herbal Medicines in the Regulation of Autophagy in Treating Cardiovascular Diseases and Other Chronic Diseases.

Curr Pharm Des 2017 ;23(7):1060-1069

Department of cardiology, Guang`anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, China.

Autophagy, a highly conserved starvation response mechanism with both defensive and protective effects in eukaryotic cells, is a lysosome-mediated degradation process for non-essential or damaged cellular constituents. It plays an important role in the cell survival, differentiation and development to maintain homeostasis. Autophagy is involved in cardiovascular diseases, cerebrovascular diseases, and neurodegenerative diseases, as well as tumours. Thus, modulating autophagy may provide potential therapeutic strategies. Recently, many active components of Chinese herbal medicines (CHM) have been found to modulate autophagy in myocardial cells, cerebral vascular cells, endothelial cells and tumour cells. This paper reviews the advances in studies on the active components of CHM that modulating autophagy in treating cardiovascular diseases and other chronic diseases over the past five years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1381612822666161021161850DOI Listing
February 2018

TPL-2 Regulates Macrophage Lipid Metabolism and M2 Differentiation to Control TH2-Mediated Immunopathology.

PLoS Pathog 2016 08 3;12(8):e1005783. Epub 2016 Aug 3.

Allergy and Anti-Helminth Immunity Laboratory, The Francis Crick Institute, London, United Kingdom.

Persistent TH2 cytokine responses following chronic helminth infections can often lead to the development of tissue pathology and fibrotic scarring. Despite a good understanding of the cellular mechanisms involved in fibrogenesis, there are very few therapeutic options available, highlighting a significant medical need and gap in our understanding of the molecular mechanisms of TH2-mediated immunopathology. In this study, we found that the Map3 kinase, TPL-2 (Map3k8; Cot) regulated TH2-mediated intestinal, hepatic and pulmonary immunopathology following Schistosoma mansoni infection or S. mansoni egg injection. Elevated inflammation, TH2 cell responses and exacerbated fibrosis in Map3k8-/-mice was observed in mice with myeloid cell-specific (LysM) deletion of Map3k8, but not CD4 cell-specific deletion of Map3k8, indicating that TPL-2 regulated myeloid cell function to limit TH2-mediated immunopathology. Transcriptional and metabolic assays of Map3k8-/-M2 macrophages identified that TPL-2 was required for lipolysis, M2 macrophage activation and the expression of a variety of genes involved in immuno-regulatory and pro-fibrotic pathways. Taken together this study identified that TPL-2 regulated TH2-mediated inflammation by supporting lipolysis and M2 macrophage activation, preventing TH2 cell expansion and downstream immunopathology and fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1005783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972396PMC
August 2016

Tumor progression locus 2 reduces severe allergic airway inflammation by inhibiting Ccl24 production in dendritic cells.

J Allergy Clin Immunol 2017 02 5;139(2):655-666.e7. Epub 2016 Jul 5.

Francis Crick Institute, Mill Hill Laboratory, the Ridgeway, London, United Kingdom. Electronic address:

Background: The molecular and cellular pathways driving the pathogenesis of severe asthma are poorly defined. Tumor progression locus 2 (TPL-2) (COT, MAP3K8) kinase activates the MEK1/2-extracellular-signal regulated kinase 1/2 MAP kinase signaling pathway following Toll-like receptor, TNFR1, and IL-1R stimulation.

Objective: TPL-2 has been widely described as a critical regulator of inflammation, and we sought to investigate the role of TPL-2 in house dust mite (HDM)-mediated allergic airway inflammation.

Methods: A comparative analysis of wild-type and Map3k8 mice was conducted. Mixed bone marrow chimeras, conditional knockout mice, and adoptive transfer models were also used. Differential cell counts were performed on the bronchoalveolar lavage fluid, followed by histological analysis of lung sections. Flow cytometry and quantitative PCR was used to measure type 2 cytokines. ELISA was used to assess the production of IgE, type 2 cytokines, and Ccl24. RNA sequencing was used to characterize dendritic cell (DC) transcripts.

Results: TPL-2 deficiency led to exacerbated HDM-induced airway allergy, with increased airway and tissue eosinophilia, lung inflammation, and IL-4, IL-5, IL-13, and IgE production. Increased airway allergic responses in Map3k8 mice were not due to a cell-intrinsic role for TPL-2 in T cells, B cells, or LysM cells but due to a regulatory role for TPL-2 in DCs. TPL-2 inhibited Ccl24 expression in lung DCs, and blockade of Ccl24 prevented the exaggerated airway eosinophilia and lung inflammation in mice given HDM-pulsed Map3k8 DCs.

Conclusions: TPL-2 regulates DC-derived Ccl24 production to prevent severe type 2 airway allergy in mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2016.05.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292997PMC
February 2017

Meta-Analysis of the Effects of Xingnaojing Injection on Consciousness Disturbance.

Medicine (Baltimore) 2016 Feb;95(7):e2875

From the Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing (LW, YG, XR, BN, LZ, HS); Key office of Encephalopathy TCM Research (LW, HZ, YG, LZ, Ying Gao), State Administration of Traditional Chinese Medicine, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine; Guang'anmen Hospital (YX, YL), Chinese Academy of Chinese Medical Sciences, Beijing; and Shandong University of Traditional Chinese Medicine (JL), Jinan, China.

Xingnaojing (XNJ) is commonly extracted from Angongniuhuang, a classic Chinese emergency prescription, and widely used in the treatment of nervous system disorders including consciousness disturbance in China. To evaluate the beneficial and adverse effects of XNJ injection, on consciousness disturbance. Seven major electronic databases were searched to retrieve randomized controlled trials designed to evaluate the clinical efficacy of XNJ alone or combined with Western medicine in treating consciousness disturbance caused by conditions such as high fever, poisoning, and stroke. The methodological quality of the included studies was assessed using criteria from the Cochrane Handbook for Systematic Review of Interventions, and analyzed using the RevMan 5.3.0 software. Seventeen randomized controlled trials on XNJ were included in this study and the trials generally showed low methodological quality. The results revealed that XNJ alone or in combination with other medicines and adjuvant methods had a positive effect on patients with fever-, poisoning-, and stroke-induced coma. XNJ effectively treated consciousness disturbances that were caused by high fever, poisoning, or stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000002875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998655PMC
February 2016

CRISPR-ERA: a comprehensive design tool for CRISPR-mediated gene editing, repression and activation.

Bioinformatics 2015 Nov 23;31(22):3676-8. Epub 2015 Jul 23.

Stanford Chemistry, Engineering & Medicine for Human Health (ChEM-H), Department of Bioengineering and Department of Chemical and Systems Biology, Stanford University, 443 Via Ortega, Shriram Center 376, Stanford, CA 94305-4125, USA.

Unlabelled: The CRISPR/Cas9 system was recently developed as a powerful and flexible technology for targeted genome engineering, including genome editing (altering the genetic sequence) and gene regulation (without altering the genetic sequence). These applications require the design of single guide RNAs (sgRNAs) that are efficient and specific. However, this remains challenging, as it requires the consideration of many criteria. Several sgRNA design tools have been developed for gene editing, but currently there is no tool for the design of sgRNAs for gene regulation. With accumulating experimental data on the use of CRISPR/Cas9 for gene editing and regulation, we implement a comprehensive computational tool based on a set of sgRNA design rules summarized from these published reports. We report a genome-wide sgRNA design tool and provide an online website for predicting sgRNAs that are efficient and specific. We name the tool CRISPR-ERA, for clustered regularly interspaced short palindromic repeat-mediated editing, repression, and activation (ERA).

Availability And Implementation: http://CRISPR-ERA.stanford.edu.

Contact: [email protected] or [email protected]

Supplementary Information: Supplementary data are available at Bioinformatics online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btv423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757951PMC
November 2015

Model-guided quantitative analysis of microRNA-mediated regulation on competing endogenous RNAs using a synthetic gene circuit.

Proc Natl Acad Sci U S A 2015 Mar 23;112(10):3158-63. Epub 2015 Feb 23.

Ministry of Education Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and Systems Biology, Tsinghua National Laboratory for Information Science and Technology/Department of Automation, Tsinghua University, Beijing 100084, China; and

Competing endogenous RNAs (ceRNAs) cross-regulate each other at the posttranscriptional level by titrating shared microRNAs (miRNAs). Here, we established a computational model to quantitatively describe a minimum ceRNA network and experimentally validated our model predictions in cultured human cells by using synthetic gene circuits. We demonstrated that the range and strength of ceRNA regulation are largely determined by the relative abundance and the binding strength of miRNA and ceRNAs. We found that a nonreciprocal competing effect between partially and perfectly complementary targets is mainly due to different miRNA loss rates in these two types of regulations. Furthermore, we showed that miRNA-like off targets with high expression levels and strong binding sites significantly diminish the RNA interference efficiency, but the effect caused by high expression levels could be compensated by introducing more small interference RNAs (siRNAs). Thus, our results provided a quantitative understanding of ceRNA cross-regulation via shared miRNA and implied an siRNA design strategy to reduce the siRNA off-target effect in mammalian cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1413896112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364186PMC
March 2015

Inferring the perturbed microRNA regulatory networks from gene expression data using a network propagation based method.

BMC Bioinformatics 2014 Jul 29;15:255. Epub 2014 Jul 29.

MOE Key Laboratory of Bioinformatics, TNLIST Bioinformatics Division & Center for Synthetic and Systems Biology, Department of Automation, Tsinghua University, Beijing 100084, China.

Background: MicroRNAs (miRNAs) are a class of endogenous small regulatory RNAs. Identifications of the dys-regulated or perturbed miRNAs and their key target genes are important for understanding the regulatory networks associated with the studied cellular processes. Several computational methods have been developed to infer the perturbed miRNA regulatory networks by integrating genome-wide gene expression data and sequence-based miRNA-target predictions. However, most of them only use the expression information of the miRNA direct targets, rarely considering the secondary effects of miRNA perturbation on the global gene regulatory networks.

Results: We proposed a network propagation based method to infer the perturbed miRNAs and their key target genes by integrating gene expressions and global gene regulatory network information. The method used random walk with restart in gene regulatory networks to model the network effects of the miRNA perturbation. Then, it evaluated the significance of the correlation between the network effects of the miRNA perturbation and the gene differential expression levels with a forward searching strategy. Results show that our method outperformed several compared methods in rediscovering the experimentally perturbed miRNAs in cancer cell lines. Then, we applied it on a gene expression dataset of colorectal cancer clinical patient samples and inferred the perturbed miRNA regulatory networks of colorectal cancer, including several known oncogenic or tumor-suppressive miRNAs, such as miR-17, miR-26 and miR-145.

Conclusions: Our network propagation based method takes advantage of the network effect of the miRNA perturbation on its target genes. It is a useful approach to infer the perturbed miRNAs and their key target genes associated with the studied biological processes using gene expression data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2105-15-255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124158PMC
July 2014

MIROR: a method for cell-type specific microRNA occupancy rate prediction.

Mol Biosyst 2014 Jun 25;10(6):1377-84. Epub 2014 Mar 25.

Bioinformatics Division, Center for Synthetic and Systems Biology, TNLIST/Department of Automation, Tsinghua University, Beijing 100084, China.

MicroRNA (miRNA) regulation is highly cell-type specific. It is sensitive to both the miRNA-mRNA relative abundance and the competitive endogenous RNA (ceRNA) effect. However, almost all existing miRNA target prediction methods neglected the influence of the cellular environment when analyzing miRNA regulation effects. In this study, we proposed a method, MIROR (miRNA Occupancy Rate predictor), to predict miRNA regulation intensity in a given cell type. The major considerations were the miRNA-mRNA relative abundance and the endogenous competition between different mRNA species. The output of MIROR is the predicted miRNA occupancy rates of each target site. The predicted results significantly correlated with Ago HITS-CLIP experiment that indicated miRNA binding intensities. When applied to the analysis of the breast invasive carcinoma dataset, MIROR identified a number of differentially regulated miRNA-mRNA pairs with significant miRNA occupancy rate changes between tumor and normal tissues. Many of the predictions were supported by previous research studies, including the ones without a significant change in the mRNA expression level. These results indicate that MIROR provides a novel strategy to study the miRNA differential regulation in different cell types.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c3mb70610aDOI Listing
June 2014
-->