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Academic Emergency Medicine : Official... Sep 2019
PubMed: 31002448
DOI: 10.1111/acem.13767 -
Global Heart 2022Atrial natriuretic peptide (ANP) has been associated with cardiovascular disease (CVD) and related risk factors, but the clinical application is limited and the...
BACKGROUND
Atrial natriuretic peptide (ANP) has been associated with cardiovascular disease (CVD) and related risk factors, but the clinical application is limited and the underlying mechanisms are not very clear. Here, we aimed to examine whether proANP and its coding gene methylation were associated with CVD in the Chinese population.
METHODS
Serum proANP and peripheral blood DNA methylation of natriuretic peptide A gene () promoter was quantified at baseline for 2,498 community members (mean aged 53 years, 38% men) in the Gusu cohort. CVD events were obtained during 10 years of follow-up. A competing-risks survival regression model was applied to examine the prospective associations of proANP and promoter methylation with incident CVD.
RESULTS
During follow-up, 210 participants developed CVD events, 50 participants died from non-cardiovascular causes, and 214 participants were lost. Per 1-nmol/L increment of serum proANP was associated with a 22% (HR = 1.22, 95%CI: 1.03-1.44, = 0.025) higher risk of CVD during follow-up. Of the 9 CpG sites assayed, per 2-fold increment of DNA methylation at CpG3 (located at Chr1:11908299) was significantly associated with a half lower risk of CVD (HR = 0.50, 95%CI: 0.30-0.82, = 0.006). The gene-based analysis found that DNA methylation of the 9 CpGs at promoter as a whole was significantly associated with incident CVD ( < 0.05).
CONCLUSIONS
Increased proANP and hypomethylation at promoter at baseline predicted an increased future risk of CVD in Chinese adults. Aberrant DNA methylation of the gene may participate in the mechanisms of CVD.
Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; China; DNA Methylation; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptides; Procainamide; Promoter Regions, Genetic
PubMed: 35586748
DOI: 10.5334/gh.1116 -
Journal of Visualized Experiments : JoVE Sep 2021Glycosylation is a vital modification found in proteins. N-glycan profiling of glycoproteins is required to detect novel biomarker candidates and determine glycan...
Glycosylation is a vital modification found in proteins. N-glycan profiling of glycoproteins is required to detect novel biomarker candidates and determine glycan alterations in diseases. Most commercially available biopharmaceutical proteins are glycoproteins. The efficacy of these drugs is affected by glycosylation patterns. Therefore, an in-depth characterization method for the N-glycans is necessary. Here, we present a comprehensive approach for qualitative and quantitative analysis of N-glycans using hydrophilic interaction liquid chromatography equipped with fluorescence detection and tandem mass spectrometry (HILIC-FLD-MS/MS). N-glycans were released from glycoproteins with a facile method and labeled by a procainamide fluorophore tag in the strategy. Subsequently, the procainamide labeled N-glycans were analyzed by a HILIC-FLD-MS/MS technique. In this approach, N-glycan structures were confirmed by the tandem mass spectrometric analysis, whereas fluorescence detection was used for the quantitative analysis. An application for data analysis of the detected N-glycan peaks is described in the study. This protocol can be applied to any glycoprotein extracted from various species.
Topics: Chromatography, Liquid; Glycoproteins; Hydrophobic and Hydrophilic Interactions; Polysaccharides; Tandem Mass Spectrometry
PubMed: 34633372
DOI: 10.3791/62751 -
JACC. Clinical Electrophysiology Jun 2024Abnormal ventricular activation at rest is reported in Brugada syndrome (BrS).
BACKGROUND
Abnormal ventricular activation at rest is reported in Brugada syndrome (BrS).
OBJECTIVES
The aim of this study was to evaluate the usefulness of dynamic changes in ventricular activation during exercise to improve disease phenotyping and diagnosis of BrS.
METHODS
Digital 12-lead electrocardiograms during stress testing were analyzed retrospectively at baseline, peak exercise, and recovery in 53 patients with BrS and 52 controls. Biventricular activation was assessed from QRS duration (QRSd), whereas right ventricular activation was assessed from S wave duration in the lateral leads (I and V) and terminal R wave duration in aVR. Exercise-induced changes in QRS parameters to predict a positive procainamide response were assessed in separate test and validation cohorts with suspected BrS.
RESULTS
Baseline electrocardiogram parameters were similar between BrS and controls. QRSd shortened with exercise in all controls but prolonged in all BrS (-6.1 ± 6.0 ms vs 7.1 ± 6.5 ms [P < 0.001] in V). QRSd in recovery was longer in BrS compared with controls (90 ± 12 ms vs 82 ± 11 ms in V; P = 0.002). Both groups demonstrated exercise-induced S duration prolongation in V6, with greater prolongation in BrS (8.2 ± 14.3 ms vs 1.2 ± 12.4 ms; P < 0.001). Any exercise-induced QRSd prolongation in V differentiated those with a positive vs negative procainamide response with 100% sensitivity and 95% specificity in the test cohort, and 87% sensitivity and 93% specificity in the validation cohort.
CONCLUSIONS
Exercise-induced QRSd prolongation is ubiquitous in BrS primarily owing to delayed right ventricular activation. This electrocardiogram phenotype predicts a positive procainamide response and may provide a noninvasive screening tool to aid in the diagnosis of BrS before drug challenge.
PubMed: 38934974
DOI: 10.1016/j.jacep.2024.04.016 -
Materials Today. Bio Jan 2022Controlling the crystal size and surface chemistry of MOF materials, and understanding their multifunctional effect are of great significance for the biomedical...
Controlling the crystal size and surface chemistry of MOF materials, and understanding their multifunctional effect are of great significance for the biomedical applications of MOF systems. Herein, we designed and synthesized a new anionic MOF, ZJU-64-NSN, which features 1D channels decorated with highly polarized thiadiazole groups, and its crystal size could be systematically tuned from 200 μm to 300 nm through a green and simple approach. As a result, the optimal nanosized ZJU-64-NSN is found to enable an ultrafast loading of cationic drug procainamide (PA) (21.2 wt% within 1 min). Moreover, the undesirable chemical stability of PA@ZJU-64-NSN is greatly improved by the surface coating of polyethylene glycol (PEG) biopolymer. The final drug delivery system PEG/PA@ZJU-64-NSN is found to effectively prevent PA from premature release under the harsh stomach environments due to the intense host-guest interaction, and mainly release PA to the targeted intestinal surroundings. Such controlled drug delivery is proved to be triggered by endogenic Na ions instead of H ions, well revealed by the study on the dynamics behavior of drug release and UV-Vis absorption spectrum. Good biocompatibility of ZJU-64-NSN and PEG-coated ZJU-64-NSN has been fully demonstrated by MTT assay as well as confocal microscopy imaging.
PubMed: 34927044
DOI: 10.1016/j.mtbio.2021.100180 -
International Heart Journal Sep 2021High-degree atrioventricular block (HAVB) or complete heart block (CHB) is a common complication associated with transcatheter aortic valve replacement (TAVR). However,... (Observational Study)
Observational Study
High-degree atrioventricular block (HAVB) or complete heart block (CHB) is a common complication associated with transcatheter aortic valve replacement (TAVR). However, some patients with HAVB/CHB recover with time. The results of electrophysiological studies (EPSs) using permanent pacemaker implantation (PPI) in patients with suspicious HAVB/CHB are considered controversial.This study aimed to evaluate whether HAVB/CHB induction at the bedside using a temporary pacemaker can predict recurrence in patients who had recovered from HAVB/CHB after TAVR.We enrolled a total of 11 patients who had recovered from HAVB/CHB and evaluated their electrophysiology using right ventricular pacing and/or procainamide administration.HAVB/CHB induction was positive. Three patients tested positive for HAVB/CHB, whereas 8 tested negative. The ejection fraction and the interval between HAVB/CHB onset and EPS were found to be significant. HAVB/CHB positive patients underwent PPI. A patient with a balloon-expandable valve tested positive just before recovery of CHB, but tested negative 5 days later and was included in the negative group. The 4 patients who tested negative received a cardiovascular implantable electric device (CIED). We observed HAVB/CHB in 2 patients who had previously tested positive after 3 months. Among those who tested negative, those with CIED had no HAVB/CHB, and others showed neither HAVB/CHB on electrocardiogram nor experienced syncope or sudden death.Our EPS revealed that HAVB/CHB induction may predict HAVB/CHB recurrence after TAVR. Valve type and EPS timing may affect the results.
Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Aortic Valve Stenosis; Atrioventricular Block; Bundle-Branch Block; Cardiac Electrophysiology; Electrocardiography; Female; Heart Valve Prosthesis; Humans; Male; Pacemaker, Artificial; Point-of-Care Testing; Predictive Value of Tests; Procainamide; Recurrence; Retrospective Studies; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 34544981
DOI: 10.1536/ihj.21-145 -
PLoS Neglected Tropical Diseases Feb 2021African sleeping sickness is caused by Trypanosoma brucei, a parasite transmitted by the bite of a tsetse fly. Trypanosome infection induces a severe transcriptional...
African sleeping sickness is caused by Trypanosoma brucei, a parasite transmitted by the bite of a tsetse fly. Trypanosome infection induces a severe transcriptional downregulation of tsetse genes encoding for salivary proteins, which reduces its anti-hemostatic and anti-clotting properties. To better understand trypanosome transmission and the possible role of glycans in insect bloodfeeding, we characterized the N-glycome of tsetse saliva glycoproteins. Tsetse salivary N-glycans were enzymatically released, tagged with either 2-aminobenzamide (2-AB) or procainamide, and analyzed by HILIC-UHPLC-FLR coupled online with positive-ion ESI-LC-MS/MS. We found that the N-glycan profiles of T. brucei-infected and naïve tsetse salivary glycoproteins are almost identical, consisting mainly (>50%) of highly processed Man3GlcNAc2 in addition to several other paucimannose, high mannose, and few hybrid-type N-glycans. In overlay assays, these sugars were differentially recognized by the mannose receptor and DC-SIGN C-type lectins. We also show that salivary glycoproteins bind strongly to the surface of transmissible metacyclic trypanosomes. We suggest that although the repertoire of tsetse salivary N-glycans does not change during a trypanosome infection, the interactions with mannosylated glycoproteins may influence parasite transmission into the vertebrate host.
Topics: Animals; Chromatography, Liquid; Concanavalin A; Glycoproteins; Glycoside Hydrolases; Insect Vectors; Lectins, C-Type; Polysaccharides; Saliva; Salivary Glands; Salivary Proteins and Peptides; Tandem Mass Spectrometry; Trypanosoma; Trypanosoma brucei brucei; Trypanosomiasis, African; Tsetse Flies
PubMed: 33529215
DOI: 10.1371/journal.pntd.0009071 -
Cell Reports. Medicine Oct 2020Enteroviruses are suspected to contribute to insulin-producing β cell loss and hyperglycemia-induced diabetes. However, mechanisms are not fully defined. Here, we show...
Enteroviruses are suspected to contribute to insulin-producing β cell loss and hyperglycemia-induced diabetes. However, mechanisms are not fully defined. Here, we show that coxsackievirus B type 4 (CVB4) infection in human islet-engrafted mice and in rat insulinoma cells displays loss of unconventional prefoldin RPB5 interactor (URI) and PDX1, affecting β cell function and identity. Genetic URI ablation in the mouse pancreas causes PDX1 depletion in β cells. Importantly, diabetic PDX1 heterozygous mice overexpressing URI in β cells are more glucose tolerant. Mechanistically, URI loss triggers estrogen receptor nuclear translocation leading to DNA methyltransferase 1 (DNMT1) expression, which induces promoter hypermethylation and silencing. Consequently, demethylating agent procainamide-mediated DNMT1 inhibition reinstates PDX1 expression and protects against diabetes in pancreatic URI-depleted mice . Finally, the β cells of human diabetes patients show correlations between viral protein 1 and URI, PDX1, and DNMT1 levels. URI and DNMT1 expression and PDX1 silencing provide a causal link between enterovirus infection and diabetes.
Topics: Animals; Capsid Proteins; Coxsackievirus Infections; DNA (Cytosine-5-)-Methyltransferase 1; Diabetes Mellitus, Type 2; Disease Models, Animal; Enterovirus B, Human; Female; Gene Expression Regulation; Glucose; Homeodomain Proteins; Humans; Insulin-Secreting Cells; Male; Mice; Mice, Transgenic; Procainamide; Rats; Repressor Proteins; Signal Transduction; Trans-Activators; Transplantation, Heterologous
PubMed: 33205075
DOI: 10.1016/j.xcrm.2020.100125 -
The International Journal of... Apr 2024Circadian genes play an important role in the field of drug metabolism. Flavin-containing monooxygenase 3 is a well-known phase I enzyme which participates in metabolism...
Circadian genes play an important role in the field of drug metabolism. Flavin-containing monooxygenase 3 is a well-known phase I enzyme which participates in metabolism of many exogenous and endogenous substances, especially production of trimethylamine N-oxide. Here, we aimed to decipher diurnal rhythms of flavin-containing monooxygenase 3 expression and activity, and explore the regulation mechanism by clock genes. Our results showed that its mRNA and protein exhibited robust diurnal rhythms in mouse liver and cell lines. Consistently, significant alterations were observed for in vitro microsomal N-oxidation rates of procainamide, which kept in line with its protein expression at different time in wild-type and reverse erythroblastosis virus α knockout mice. Further, flavin-containing monooxygenase 3 was negatively regulated by E4 promoter-binding protein 4 in AML12 and Hepa1-6 cells, while it was positively influenced by reverse erythroblastosis virus α and brain and muscle ARNT-like protein-1. Moreover, luciferase reporter assays and electrophoretic mobility shift assays showed E4 promoter-binding protein 4 inhibited the transcription of flavin-containing monooxygenase 3 by binding to a D-box1 element (-1606/-1594 bp), while brain and muscle ARNT-like protein-1 positively activated the transcription via direct binding to three E-boxes (-863/-858 bp, -507/-498 bp, and -115/-104 bp) in this enzyme promoter. Taken together, this study would be helpful to reveal the mechanism of clock-controlled drug metabolism and facilitate the practice of chrono-therapeutics.
Topics: Animals; Mice; Mice, Inbred Strains; Oxygenases; Circadian Rhythm; Liver
PubMed: 38320728
DOI: 10.1016/j.biocel.2024.106538 -
Cureus Apr 2021Myocardial ischemia may lead to lethal arrhythmias. Treatment of these arrhythmias without addressing the cause of ischemia may be futile. The length of resuscitation is...
BACKGROUND
Myocardial ischemia may lead to lethal arrhythmias. Treatment of these arrhythmias without addressing the cause of ischemia may be futile. The length of resuscitation is an important parameter for determining when to stop resuscitation but with shockable rhythms and reversible cause of the cardiac arrest, the decision to terminate resuscitation is complex. Case Summary: A patient with a three-month history of shortness of breath with effort developed pulseless ventricular tachycardia (VT) at the early stages of a stress test. In coronary angiography, a critical lesion in the right coronary artery (RCA) was observed and treated with two stents. During the procedure and for a total of five hours, the patient had more than 100 separate episodes of VT and ventricular fibrillation (VF) that were treated by 150 defibrillations, artificial ventilation, intra-aortic counter-pulsation balloon insertion, and multiple drugs. One hour after the initial stenting procedure, thrombosis of the RCA was demonstrated and treated successfully with angioplasty. Use of procainamide resolved the arrhythmias and the patient recovered completely without neurological deficit, ejection fraction of 45%, and is asymptomatic at one year following the event.
DISCUSSION
Our case shows that with a revisable cause of cardiac arrest, resuscitation should be directed at maintaining perfusion of essential organs and treating the reversible cause. Without re-opening the RCA, we could not have saved the patient's life. The use of an extracorporeal membrane oxygenator, if available, should be considered in similar cases. Finally, the quality of cardiopulmonary resuscitation determines the neurological outcome regardless of the length of resuscitation, as was evident in our patient who recovered completely.
PubMed: 33954068
DOI: 10.7759/cureus.14255