A decade-long project, led by several international research groups, called the Encyclopedia of DNA Elements (ENCODE), recently released an unprecedented amount of data. The ambitious project covers transcriptome, cistrome, epigenome, and interactome data from more than 1,600 sets of experiments in human. To make use of this valuable resource, it is important to understand the information it represents and the techniques that were used to generate these data. In this review, we introduce the data that ENCODE generated, summarize the observations from the data analysis, and revisit a computational approach that ENCODE used to predict gene expression, with a focus on the human transcriptome and its association with chromatin modifications.
Chromatin ; DNA ; Gene Expression ; Humans ; Statistics as Topic ; Transcriptome

Myocardial fibrosis is characterized by pathological remodeling of extracellular matrix,which is a common pathological change during the development of various cardiovascular diseases.Qi transformation dysfunction in the zang-fu organs,subtle substance accumulation,and endogenous turbid evil production lead to the occurrence of diseases.The theory of turbid blood is widely used to elucidate the pathological changes of diseases and guide the prevention and treatment.Turbid blood,as a special pathogenic factor and pathological product,plays a crucial role in the oxidative stress process of myocardial fibrosis.Qi deficiency of the heart and spleen,stagnation of turbid blood,impaired blood circulation in the heart,and the inability to maintain the oxidative-reductive system balance of myocardial cells are the root causes of disease onset.Accumulation of turbid blood,intermingled phlegm and blood stasis,blockage of heart vessels,and accumulation of metabolic waste products contribute to disease progression.Prolonged turbidity accumulation leads to cardiac enlargement,scattered mental state,and pathological remodeling of the extracellular matrix,indicating a severe disease stage.Early treatment focuses on strengthening the vital qi and spleen,reducing turbidity and recovering clarity.In the middle stage,the key is to resolve phlegm,eliminate stasis,and promote clarity while removing turbidity.In the late stage,detoxification,turbidity elimination,and restoring clarity are emphasized.By adhering to the characteristics of the pathological mechanism and using traditional Chinese medicine intervention,it is possible to suppress oxidative stress,prevent pathological remodeling of the extracellular matrix,and improve myocardial fibrosis.

Asthma is a chronic inflammatory disorder of airways that affects approximately 300 million adults and children worldwide. Most therapy currently uses bronchodilators and corticosteroids. Systemic side effects from chronic use of these drugs are concern. Chinese medicine (CM) has a long history of human use in China and other Asian countries and well received by the patients. But as one component of Western integrative medicine (WIM), it is required that CM use is supported by scientific evidence. On the other hand, there are also suggestions that Western standardized medicine should consider personalized practice. In recent years there have been an increasing studies to narrow the gap between CM, the personalized medicine and Western medicine, evidence based medicine. This communication reviews several CM studies published in the English language in details by reviewing the effects and mechanisms of actions on asthma from clinic and experimental studies.Chinese herbal medicines exhibit broad actions on multiple asthma pathologic mechanisms. These mechanisms may involve antiinflammatory and immunomodulatory effects, inhibiting airway remodeling and normalization of hypothalamus, pituitary and adrenal (HPA)-axis disturbances. However, the mechanisms of actions of Chinese herbal medicines for asthma are not fully understood. More controlled clinical studies are warranted and some anti-asthma CM may be proved to be effective when used as monotherapy or complementary asthma therapies.
Animals ; Anti-Asthmatic Agents ; therapeutic use ; Asthma ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans

OBJECTIVEAnti-asthma herbal medicine intervention (ASHMI(TM)), a combination of three traditional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMI(TM) exhibited synergy.

METHODSEffects of ASHMI and its components aqueous extracts of Lingzhi (Ganoderma lucidum), Kushen (Sophora flavescens) and Gancao (Glycyrrhiza uralensis), on Th2 cytokine secretion by murine memory Th2 cells (D10.G4.1) and eotaxin-1 secretion by human lung fibroblast (HLF-1) cells were determined by measuring levels in culture supernatants by enzyme-linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters.

RESULTSIndividual Lingzhi, Kushen and Gancao extracts and ASHMI (the combination of individual extracts) inhibited production of interleukin (IL)-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration (IC25) values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50 values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-1. The interaction indices at IC50 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC50 values. All interaction indices were below 1 which indicated synergy.

CONCLUSIONBy comparing the interaction index values, we find that constituents in ASHMI(TM) synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.

Animals ; Asthma ; drug therapy ; metabolism ; Cell Line ; Chemokine CCL11 ; metabolism ; Down-Regulation ; drug effects ; Drug Synergism ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Fibroblasts ; drug effects ; metabolism ; Humans ; Interleukin-4 ; metabolism ; Interleukin-5 ; genetics ; immunology ; Mice ; Plants, Medicinal ; chemistry ; Th2 Cells ; drug effects ; metabolism

Objective:To explore the effective components and potential mechanisms of Xiefei Lishui Prescription in the treatment of heart failure.Methods:Ultra high-performance liquid chromatography tandem four stage rod time of flight mass spectrometry (UPLC-Q-TOF-MS) technology was used to analyze and identify the active components of Xiefei Lishui Prescription. Drug targets were predicted through the Swiss Target Prediction database, and disease targets were collected from Gene Cards, Dis GENET, and TTD databases. The intersection of drug targets and disease targets was screened using a STRING database for protein interaction to identify core targets. The core targets were included in the DAVID database for GO enrichment and KEGG analysis. Finally, molecular docking validation was performed between the drug components and the corresponding core targets.Results:The results identified 10 active components of Xiefei Lishui Prescription, and 8 potential active components were screened using network pharmacology for the treatment of heart failure with Xiefei Lishui Prescription, corresponding to 160 related action targets. A total of 1 305 disease-related targets were collected, and a total of 51 targets ad 17 core targets were included in the string database for protein interaction analysis. GO functional enrichment and KEGG analysis indicated that the mechanism of Xiefei Lishui Prescription in treating heart failure may be related to pathways such as protein binding, ATP binding, and negative regulation of the VEGF signaling pathway and T cell receptor pathway during apoptosis. The molecular docking results showed that baicalin exhibited good binding activity with ESR1, sorghum isoflavones with ESR1, and quercetin with AKT1, EGFR, IL2, and ABCB1.Conclusion:Xiefei Lishui Prescription may exert therapeutic effects on heart failure through multiple pathways by targeting ESR1, AKT1, EGFR, and other targets.

Certification ; Laboratories

Background: For anatomic total arthroscopic repair, cementless humeral fixation has recently gained popularity. However, few studies have compared clinical, radiographic, and patient-reported outcomes between cemented and press-fit humeral fixation, and none have performed follow-up for longer than 5 years. In this study, we compared long-term postoperative outcomes in patients receiving a cemented versus press-fit humeral stem anatomic arthroscopic repair. Methods: This study retrospectively analyzed 169 shoulders that required primary anatomic total shoulder arthroplasty (aTSA). Shoulders were stratified by humeral stem fixation technique: cementation or press-fit. Data were collected pre- and postoperatively. Primary outcome measures included range of motion, patient reported outcomes, and radiographic measures. Results: One hundred thirty-eight cemented humeral stems and 31 press-fit stems were included. Significant improvements in range of motion were seen in all aTSA patients with no significant differences between final cemented and press-fit stems (forward elevation: P=0.12, external rotation: P=0.60, and internal rotation: P=0.77). Patient reported outcome metrics also exhibited sustained improvement through final follow-up. However, at final follow-up, the press-fit stem cohort had significantly better overall scores when compared to the cemented cohort (visual analog score: P=0.04, American Shoulder and Elbow Surgeon Score: P<0.01, Simple Shoulder Test score: P=0.03). Humeral radiolucency was noted in two cemented implants and one press-fit implant. No significant differences in implant survival were observed between the two cohorts (P=0.75). Conclusions In this series, we found that irrespective of humeral fixation technique, aTSA significantly improves shoulder function. However, within this cohort, press-fit stems provided significantly better outcomes than cemented stems in terms of patient reported outcome scores.Level of evidence: III.

Methods: Among the patients who underwent TSA, 119 shoulders were retrospectively analyzed. Preoperative and postoperative clinical outcome data were collected. Linear regression analysis (univariate and multivariate) was conducted to evaluate the associations of clinical outcomes with age. Kaplan-Meier curves and Cox regression analyses were performed to evaluate implant survival. Results: At final follow-up, patients of all ages undergoing aTSA experienced significant and sustained improvements in all primary outcome measures compared with preoperative values. Based on multivariate analysis, age at the time of surgery was a significant predictor of postoperative outcomes. Excellent implant survival was observed over the course of this study, and Cox regression survival analysis indicated age and sex to not be associated with an increased risk of implant failure. Conclusions When controlling for sex and follow-up duration, older age was associated with significantly better patient-reported outcome measures. Despite this difference, we noted no significant effects on range of motion or implant survival.Level of evidence: IV.

Objective:Asthma sufferers exhibit high prevalence of anxiety/depression.Elevated tumor-necrosis factor-alpha (TNF-α) levels in peripheral system and central nervous system (CNS) are associated with anxiety/depression,whereas brain-derived neurotropic factor(BDNF) has anti-depressant effects.An anti-asthma herbal medicine intervention ASHMI inhibits peripheral TNF-α secretion in an animal model of asthma.We hypothesize that ASHMI and its compounds may have modulatory effects on CNS TNF-α and BDNF production.We sought to determine the effect of ASHMI and individual herb constituents on brain microglial cell TNF-α production,and identify the active compounds that suppress TNF-α and increase BDNF.Methods:BV-2 mouse microglial cells were pre-treated with ASHMI or extracts of Ganoderma lu-cidum (G.lucidum),Sophora flavescens Ait (S.flavescens),and Glycyrrhiza uralensis Fischer (G.uralensis),the herbal constituents in ASHMI,or individual compounds isolated from G.uralensis at different concentrations and then stimulated with LPS.TNF-α levels in culture supernatants were measured by ELISA.The effect of active compounds on NFκB signaling pathway and on BDNF production were determined by western blotting and ELISA,respectively.Results:ASHMI produced dose-dependent inhibition of TNF-α secretion by cultured-mouse micro-glia BV2 cells.Of the three herb extracts in ASHMI,only G.uralensis significantly and dose-dependently inhibited TNF-α production.Among the 5 flavonoids isolated from G.uralensis,isoliquiritigenin was the most effective.Isoliquiritigenin suppression of TNF-α production was asso-ciated with attenuation of p-NF-κB expression,and was accompanied by increased BDNF secretion.Conclusion:ASHMI and its effective flavonoid,isoliquiritigenin,inhibited TNF-α production by LPS stimulated microglial cells and elevated BDNF levels,which may prove to have anti-CNS inflamma-tory and anti-anxiety effects.

Myocardial infarction is the most common cause of heart failure,and myocardial remodeling can occur after infarction,thus contributing to the progression of heart failure.The occurrence of post-infarction ventricular remode-ling is closely related to m6A methylation.m6A methylation is a reversible and highly dynamic process.This process is mainly mediated by m6A methylation positive and negative regulatory enzymes and is involved in the occurrence of post-in-farction myocardial remodeling through mechanisms such as cellular autophagy.This article mainly reviews relevant litera-ture in recent years.Firstly,a brief introduction is given to m6A methylation,followed by an introduction to the role of m6A methylase in regulating myocardial remodeling.Finally,a summary analysis is conducted on the mechanism of m6A methylation in regulating myocardial remodeling from the perspectives of autophagy,inflammation,cell apoptosis,calcium ion homeostasis,extracellular matrix remodeling,and ferroptosis.The feasibility of using m6A methylation serological de-tection as a diagnostic tool for myocardial remodeling after myocardial infarction is discussed,in order to provide reference for related research.