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Turkish Journal of Chemistry 2022Glycosylation is an essential posttranslational modification observed in the living proteome. Glycosylation profiles in glycoproteins can change in commonly observed...
Glycosylation is an essential posttranslational modification observed in the living proteome. Glycosylation profiles in glycoproteins can change in commonly observed diseases such as cancer. Identifying these changes is crucial in discovering new biomarkers for the early diagnosis of cancer. One of the main steps of -glycan analysis is to release -glycans from glycoproteins by specific enzymes. The study compares common denaturing agent combinations used in -glycan release methods. In the study, human plasma was used to test the release methods of -glycans containing different detergent combinations. The released -glycans were labeled with the procainamide tag, purified using cellulose-containing solid-phase extraction cartridges, and analyzed by high-performance liquid chromatography-hydrophilic interaction liquid chromatography equipped with fluorescence detection (HPLC-HILIC-FLD). The results showed that the sodium dodecyl sulfate and sodium deoxycholate (SDS + SDC) detergent combination provided the highest average FLD signal areas and intensities in the -glycan analysis. The protocol with SDS resulted in more reproducible average FLD signal areas and intensities. It was also found that the average signal FLD signal areas and intensities of the detected -glycans were reduced when SDS and SDC were used with 1,4-dithiothreitol (DTT) reducing agents. In addition, deglycosylation of glycoproteins with various denaturing agents resulted in relatively minor variation in human plasma -glycosylation profiles.
PubMed: 37529735
DOI: 10.55730/1300-0527.3457 -
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 -
Analytical Chemistry May 2022Sialic acids have diverse biological roles, ranging from promoting up to preventing protein and cellular recognition in health and disease. The various functions of...
Sialic Acid Derivatization of Fluorescently Labeled -Glycans Allows Linkage Differentiation by Reversed-Phase Liquid Chromatography-Fluorescence Detection-Mass Spectrometry.
Sialic acids have diverse biological roles, ranging from promoting up to preventing protein and cellular recognition in health and disease. The various functions of these monosaccharides are owed, in part, to linkage variants, and as a result, linkage-specific analysis of sialic acids is an important aspect of glycomic studies. This has been addressed by derivatization strategies using matrix-assisted laser desorption/ionization mass spectrometry (MS) or sialidase digestion arrays followed by liquid chromatography (LC)-MS. Despite this, these approaches are unable to simultaneously provide unambiguous assignment of sialic acid linkages and assess further isomeric glycan features within a single measurement. Thus, for the first time, we present the combination of procainamide fluorescent labeling with sialic acid linkage-specific derivatization via ethyl esterification and amidation for the analysis of released plasma -glycans using reversed-phase (RP)LC-fluorescence detection (FD)-MS. As a result, α2,3- and α2,6-sialylated -glycans, with the same mass prior to derivatization, are differentiated based on retention time, precursor mass, and fragmentation spectra, and additional sialylated isomers were also separated. Furthermore, improved glycan coverage and protocol precision were found via the novel application using a combined FD-MS quantification approach. Overall, this platform achieved unambiguous assignment of -glycan sialic acid linkages within a single RPLC-FD-MS measurement, and by improving their retention on RPLC, this technique can be used for future investigations of released -glycans as an additional or orthogonal method to current analytical approaches.
Topics: Chromatography, Reverse-Phase; N-Acetylneuraminic Acid; Polysaccharides; Sialic Acids; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 35482581
DOI: 10.1021/acs.analchem.1c02610 -
Cureus Feb 2022While a large proportion of ST-segment elevation on EKG is related to myocardial ischemia, the differential diagnosis must include pericarditis, channelopathies, and...
While a large proportion of ST-segment elevation on EKG is related to myocardial ischemia, the differential diagnosis must include pericarditis, channelopathies, and various genetic conditions. Identifying and working up such abnormalities present a challenge to primary care providers (PCPs). We present two clinical cases of young male patients with ST-segment elevation in anteroseptal leads suspicious for Brugada syndrome and show how to risk stratify and manage them. Our first case presents a 23-year-old male with no past medical history with acute onset substernal chest pain, shortness of breath, and palpitations. Initial workup revealed negative serial troponins and normal B-type natriuretic peptide (BNP). The EKG revealed ST elevation in lead V2. An evaluation for Brugada syndrome was pursued. Upon completion of a procainamide challenge, it was determined that he did not have Brugada syndrome and was shortly discharged. Our second case presents a 33-year-old male with no pertinent cardiac medical history who presented to an outpatient cardiology clinic after discovering an incidental ST elevation in V2 on EKG. His family history was negative for early atherosclerotic cardiovascular events or sudden cardiac death. The patient's initial workup was negative. Suspicion for Brugada syndrome leads to performing a procainamide challenge, which was significant for ST changes in the anterolateral leads. He was asymptomatic during the challenge and initial presentation, and no further intervention was indicated. He was advised to avoid sodium channel blocking medications and treat any fevers and was sent for genetic testing. These cases illustrate the importance of maintaining an appropriate suspicion for Brugada syndrome in young patients with minimal ischemic risk factors. We discuss a guideline-directed algorithmic workup for PCPs in suspicious individuals. Stratifying patients based on the presence of symptoms, history of tachyarrhythmias, and EKG findings before and after drug challenge allows physicians to guide further management of these patients.
PubMed: 35273866
DOI: 10.7759/cureus.21921 -
Cells Feb 2022Plasma concentrations of natriuretic peptides (NP) contribute to risk stratification and management of patients undergoing non-cardiac surgery. However, genetically...
Plasma concentrations of natriuretic peptides (NP) contribute to risk stratification and management of patients undergoing non-cardiac surgery. However, genetically determined variability in the levels of these biomarkers has been described previously. In the perioperative setting, genetic contribution to NP plasma level variability has not yet been determined. A cohort of 427 patients presenting for non-cardiac surgery was genotyped for single-nucleotide polymorphisms (SNPs) from the NPPA/NPPB locus. Haplotype population frequencies were estimated and adjusted haplotype trait associations for brain natriuretic peptide (BNP) and amino-terminal pro natriuretic peptide (NT-proBNP) were calculated. Five SNPs were included in the analysis. Compared to the reference haplotype TATAT (rs198358, rs5068, rs632793, rs198389, rs6676300), haplotype CACGC, with an estimated frequency of 4%, showed elevated BNP and NT-proBNP plasma concentrations by 44% and 94%, respectively. Haplotype CGCGC, with an estimated frequency of 9%, lowered NT-proBNP concentrations by 28%. ASA classification status III and IV, as well as coronary artery disease, were the strongest predictors of increased NP plasma levels. Inclusion of genetic information might improve perioperative risk stratification of patients based on adjusted thresholds of NP plasma levels.
Topics: Atrial Natriuretic Factor; Coronary Artery Disease; Haplotypes; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Nitrobenzoates; Peptide Fragments; Procainamide
PubMed: 35269388
DOI: 10.3390/cells11050766 -
American Journal of Translational... 2021Intersubject variability in drug response, whether related to efficacy or toxicity, is well recognized clinically. Over the years, drug selection from our pharmacologic... (Review)
Review
Intersubject variability in drug response, whether related to efficacy or toxicity, is well recognized clinically. Over the years, drug selection from our pharmacologic armamentarium has moved from providers' preferred choices to more personalized treatments as clinicians' decisions are guided by data from clinical trials. Since the advent of more accessible and affordable pharmacogenomic (PGx) testing, the promise of precise pharmacotherapy has been made. Results have accumulated in the literature with numerous examples demonstrating the value of PGx to improve drug response or prevent drug toxicity. Unfortunately, limited availability of reimbursement policies has dampened the enthusiasm of providers and organizations. The clinical application of PGx knowledge remains difficult for most clinicians under real-world conditions in patients with numerous chronic conditions and polypharmacy. This may be due to phenoconversion, a condition where there is a discrepancy between the genotype-predicted phenotype and the observed phenotype. This condition complicates the interpretation of PGx results and may lead to inappropriate recommendations and clinical decision making. For this reason, regulatory agencies have limited the transfer of information from PGx laboratories directly to consumers, especially recommendations about the use of certain drugs. This mini-review presents cases (mexiletine, propafenone, clopidogrel, warfarin, codeine, procainamide) from historical observations where drug response was modified by phenoconversion. The cases illustrate, from decades ago, that we are still in great need of advanced clinical decision systems that cope with conditions associated with phenoconversion, especially in patients with polypharmacy.
PubMed: 35035679
DOI: No ID Found -
Heart Rhythm O2 Dec 2021Antiarrhythmic therapy for recurrent ventricular arrhythmias in patients who have undergone catheter ablation, and in whom amiodarone and/or beta-blockers were...
BACKGROUND
Antiarrhythmic therapy for recurrent ventricular arrhythmias in patients who have undergone catheter ablation, and in whom amiodarone and/or beta-blockers were ineffective or contraindicated, is a controversial issue.
OBJECTIVE
The present study sought to evaluate the efficacy and tolerability of oral procainamide in patients with recurrent ventricular arrhythmias when the standard therapy strategy had failed.
METHODS
All patients treated with procainamide for recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) in our institution between January 2010 and May 2019 were enrolled. The primary endpoint was the total number of implantable cardioverter-defibrillator (ICD) interventions after the beginning of procainamide therapy. Secondary endpoints were the total number of VTs and VFs recorded on the ICDs' controls and discontinuation of therapy. The events occurring during procainamide treatment were compared with a matched-duration period before the initiation of therapy with procainamide. Patients therefore served as self-controls.
RESULTS
A total of 34 consecutive patients (32 male, 94.1%; mean age 74.4 ± 9.7 years) were included in the retrospective analysis. The mean time of procainamide treatment was 12.9 ± 13.7 months (median 9 [2-20] months). The mean dose of procainamide was 1207 ± 487 mg/day. Procainamide therapy significantly decreased ICD interventions (median 5 [0-22.5] vs 15.5 [3-32.25], < .05). Procainamide also decreased the total number of VT/VF episodes (median 5.5 [0.75-30] vs 19 [7.5-30], < .05). Only 3 patients (8.8%) presented severe side effects (dyspnea or hypotension), requiring discontinuation of therapy.
CONCLUSION
Oral procainamide was associated with a significant decrease in ICD therapies and ventricular arrhythmias, showing an acceptable profile of tolerability.
PubMed: 34988535
DOI: 10.1016/j.hroo.2021.10.002 -
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 -
European Heart Journal. Case Reports Dec 2021Pharmacologic challenge test is often used to diagnose Brugada syndrome (BrS) when spontaneous electrocardiograms (ECG) do not show type I Brugada pattern but reported...
BACKGROUND
Pharmacologic challenge test is often used to diagnose Brugada syndrome (BrS) when spontaneous electrocardiograms (ECG) do not show type I Brugada pattern but reported sensitivity varies. The role of the exercise stress test in diagnosing Brugada syndrome is not well-established.
CASE SUMMARY
A patient had a type I Brugada pattern ECG during the recovery phase of exercise stress test but had a negative procainamide challenge test. He had a loop recorder implanted and later survived a ventricular fibrillation (VF) arrest provoked by coronavirus disease 2019 (COVID-19). Electrocardiogram on arrival showed type 1 Brugada pattern. He was discharged after implantable cardioverter-defibrillator implantation. He later underwent genetic testing and was found to be heterozygous for c.844C>G (p.Arg282Gly) mutation in the SCN5A gene.
DISCUSSION
Type 1 Brugada pattern ECG may be unmasked by ST-segment augmentation during recovery from exercise. Exercise stress test may play a role in the diagnosis of Brugada syndrome when suspicion for Brugada syndrome remains after a negative procainamide challenge test or if the patient has exercise-related symptoms. COVID-19 can unmask BrS and trigger a VF cardiac arrest.
PubMed: 34909573
DOI: 10.1093/ehjcr/ytab454 -
Obesity Facts 2022Atrial natriuretic peptide plays a potential role in obesity with unclear molecular mechanisms. The objective of this study was to examine the association between its...
INTRODUCTION
Atrial natriuretic peptide plays a potential role in obesity with unclear molecular mechanisms. The objective of this study was to examine the association between its coding gene (natriuretic peptide A [NPPA]) methylation and obesity.
METHODS
Peripheral blood DNA methylation of NPPA promoter was quantified at baseline by targeted bisulfite sequencing for 2,497 community members (mean aged 53 years, 38% men) in the Gusu cohort. Obesity was repeatedly assessed by body mass index (BMI) and waist circumference (WC) at baseline and follow-up examinations. The cross-sectional, longitudinal, and prospective associations between NPPA promoter methylation and obesity were examined.
RESULTS
Of the 9 CpG loci assayed, DNA methylation levels at 6 CpGs were significantly lower in participants with central obesity than those without (all p < 0.05 for permutation test). These CpG methylation levels at baseline were also inversely associated with dynamic changes in BMI or WC during follow-up (all p < 0.05 for permutation test). After an average 4 years of follow-up, hypermethylation at the 6 CpGs (CpG2 located at Chr1:11908348, CpG3 located at Chr1:11908299, CpG4 located at Chr1:11908200, CpG5 located at Chr1:11908182, CpG6 located at Chr1:11908178, and CpG8 located at Chr1:11908165) was significantly associated with a lower risk of incident central obesity (all p < 0.05 for permutation test).
CONCLUSIONS
Hypomethylation at NPPA promoter was associated with increased future risk of central obesity in Chinese adults. Aberrant DNA methylation of the NPPA gene may participate in the mechanisms of central obesity.
Topics: Atrial Natriuretic Factor; Body Mass Index; China; Cross-Sectional Studies; DNA Methylation; Female; Humans; Longitudinal Studies; Male; Middle Aged; Obesity; Obesity, Abdominal; Procainamide
PubMed: 34875662
DOI: 10.1159/000521295