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Biomolecules May 2023A newly developed analytical strategy was applied to profile the total serum -glycome of 64 colorectal cancer (CRC) patients before and after surgical intervention. In...
A newly developed analytical strategy was applied to profile the total serum -glycome of 64 colorectal cancer (CRC) patients before and after surgical intervention. In this cohort, it was previously found that serum -glycome alterations in CRC were associated with patient survival. Here, fluorescent labeling of serum -glycans was applied using procainamide and followed by sialic acid derivatization specific for α2,6- and α2,3-linkage types via ethyl esterification and amidation, respectively. This strategy allowed efficient separation of specific positional isomers on reversed-phase liquid chromatography-fluorescence detection-mass spectrometry (RPLC-FD-MS) and complemented the previous glycomics data based on matrix-assisted laser desorption/ionization (MALDI)-MS that did not include such separations. The results from comparing pre-operative CRC to post-operative samples were in agreement with studies that identified a decrease in di-antennary structures with core fucosylation and an increase in sialylated tri- and tetra-antennary -glycans in CRC patient sera. Pre-operative abundances of -glycans showed good performance for the classification of adenocarcinoma and led to the revisit of the previous MALDI-MS dataset with regard to histological and clinical data. This strategy has the potential to monitor patient profiles before, during, and after clinical events such as treatment, therapy, or surgery and should also be further explored.
Topics: Humans; Glycosylation; Chromatography, Reverse-Phase; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Polysaccharides; Colorectal Neoplasms
PubMed: 37371476
DOI: 10.3390/biom13060896 -
Cellular and Molecular Life Sciences :... Dec 2020The natriuretic peptides (NPs) family, including a class of hormones and their receptors, is largely known for its beneficial effects within the cardiovascular system to... (Review)
Review
The natriuretic peptides (NPs) family, including a class of hormones and their receptors, is largely known for its beneficial effects within the cardiovascular system to preserve regular functions and health. The concentration level of each component of the family is of crucial importance to guarantee a proper control of both systemic and local cardiovascular functions. A fine equilibrium between gene expression, protein secretion and clearance is needed to achieve the final optimal level of NPs. To this aim, the regulation of gene expression and translation plays a key role. In this regard, we know the existence of fine regulatory mechanisms, the so-called epigenetic mechanisms, which target many genes at either the promoter or the 3'UTR region to inhibit or activate their expression. The gene encoding ANP (NPPA) is regulated by histone modifications, DNA methylation, distinct microRNAs and a natural antisense transcript (NPPA-AS1) with consequent implications for both health and disease conditions. Notably, ANP modulates microRNAs on its own. Histone modifications of BNP gene (NPPB) are associated with several cardiomyopathies. The proBNP processing is regulated by miR30-GALNT1/2 axis. Among other components of the NPs family, CORIN, NPRA, NPRC and NEP may undergo epigenetic regulation. A better understanding of the epigenetic control of the NPs family will allow to gain more insights on the pathological basis of common cardiovascular diseases and to identify novel therapeutic targets. The present review article aims to discuss the major achievements obtained so far with studies on the epigenetic modulation of the NPs family.
Topics: Animals; Atrial Natriuretic Factor; Disease; Epigenesis, Genetic; Gene Expression Regulation; Humans; MicroRNAs; Natriuretic Peptides; Procainamide; Protein Processing, Post-Translational; Receptors, Atrial Natriuretic Factor
PubMed: 32556416
DOI: 10.1007/s00018-020-03573-0 -
International Journal of Molecular... Mar 2023The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global concern since its outbreak in 2019, with one of the main solutions being...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global concern since its outbreak in 2019, with one of the main solutions being vaccination. Altered glycosylation has been described in patients after SARS-CoV-2 infection, while the effect of vaccination on serum glycoproteins remained unexplored. In this study, total serum glycosylation was analyzed in patients after SARS-CoV-2 infection and/or mRNA vaccination in order to identify potential glycosylation-based alterations. Enzyme-linked immunosorbent assay was applied to identify post-COVID-19 and post-Vaccinated patients and rule out potential outliers. Serum samples were deglycosylated by PNGase F digestion, and the released glycans were fluorescently derivatized using procainamide labeling. Solid-phase extraction was used to purify the labeled glycans followed by the analysis of hydrophilic-interaction liquid chromatography with fluorescence and mass-spectrometric detection. Alterations of serum N-glycome in response to SARS-CoV-2 infection and mRNA vaccination were revealed by linear discriminant analysis.
Topics: Humans; COVID-19; COVID-19 Vaccines; SARS-CoV-2; Vaccination; RNA, Messenger
PubMed: 37047177
DOI: 10.3390/ijms24076203 -
Drug Safety - Case Reports Sep 2019Systemic lupus erythematosus (SLE) can be induced by various medications, such as hydralazine, procainamide, isoniazid, methyldopa, chlorpromazine, quinidine, and...
Systemic lupus erythematosus (SLE) can be induced by various medications, such as hydralazine, procainamide, isoniazid, methyldopa, chlorpromazine, quinidine, and minocycline. A patient was admitted complaining of fever with chills and rigor. After being diagnosed with tuberculous meningitis, the patient was given antituberculosis treatment. As the patient did not improve, detailed investigations were conducted, and elevated antinuclear antibody levels were found. The consulting physician diagnosed that the patient was suffering from SLE. As isoniazid is associated with an increased risk of developing SLE, it was suspected as the culprit drug. After withdrawing isoniazid from the antituberculosis treatment regimen, the patient improved and was discharged. Based on the WHO-UMC and Naranjo's causality assessment criteria, an association between the reaction and isoniazid was deemed probable. The reaction was moderately severe (level 4b) according to the modified Hartwig and Siegel scale.
PubMed: 31541371
DOI: 10.1007/s40800-019-0102-y -
International Journal of Molecular... Aug 2022Glycosylation is vital for well-functioning glycoproteins and is reportedly altered in chronic inflammatory disorders, including multiple sclerosis (MS). High-throughput...
Glycosylation is vital for well-functioning glycoproteins and is reportedly altered in chronic inflammatory disorders, including multiple sclerosis (MS). High-throughput quantitative measurement of protein glycosylation is challenging, as glycans lack fluorophore groups and require fluorescent labeling. The attachment of fluorescent tags to each glycan moiety necessitates sample clean-up for reliable quantitation. The use of magnetic particles in glycan sample preparation is reportedly an easy-to-use solution to accomplish large-scale biomarker discovery studies. In this study, NH-funtionalized magnetic nanoparticles were synthetized, characterized and applied for the glycosylation analysis of serum samples from patients diagnosed with multiple sclerosis and corresponding healthy controls. Serum samples were PNGase F digested and labeled by procainamide via reductive amination, followed by magnetic nanoparticle-based purification. The prepared samples were analyzed by hydrophilic interaction liquid chromatography, allowing for the relative quantitation of the individual glycan species. Significant glycosylation alterations were detected between MS patients and healthy controls, especially when analyzing the different gender groups.
Topics: Glycomics; Glycosylation; Humans; Magnetite Nanoparticles; Multiple Sclerosis; Polysaccharides
PubMed: 36012360
DOI: 10.3390/ijms23169095 -
Molecules (Basel, Switzerland) Feb 2023The 4-amino-N-[2 (diethylamino) ethyl] benzamide (procainamide)-tetraphenylborate complex was synthesized by reacting sodium tetraphenyl borate with 4-amino-N-[2...
The 4-amino-N-[2 (diethylamino) ethyl] benzamide (procainamide)-tetraphenylborate complex was synthesized by reacting sodium tetraphenyl borate with 4-amino-N-[2 (diethylamino) ethyl] benzamide, chloride salt, and procainamide in deionized water at room temperature through an ion-associate reaction (green chemistry) at room temperature, and characterized by several physicochemical methods. The formation of ion-associate complex between bio-active molecules and/or organic molecules is crucial to comprehending the relationships between bioactive molecules and receptor interactions. The solid complex was characterized by infrared spectra, NMR, elemental analysis, and mass spectrometry, indicating the formation of ion-associate or ion-pair complex. The complex under study was examined for antibacterial activity. The ground state electronic characteristics of the S1 and S2 complex configurations were computed using the density functional theory (DFT) approach, using B3LYP level 6-311 G(d,p) basis sets. R = 0.9765 and 0.9556, respectively, indicate a strong correlation between the observed and theoretical H-NMR, and the relative error of vibrational frequencies for both configurations was acceptable, as well. HOMO and LUMO frontier molecular orbitals and molecular electrostatics using the optimized were used to obtain a potential map of the chemical. The → π* UV absorption peak of the UV cutoff edge was detected for both configurations of the complex. Spectroscopic methods were structures used to characterize the structure (FT-IR and 1HNMR). In the ground state, DFT/B3LYP/6-311G(d,p) basis sets were used to determine the electrical and geometric properties of the S1 and S2 configurations of the title complex. Comparing the observed and calculated values for the S1 and S2 forms, the HOMO-LUMO energy gap of compounds was 3182 and 3231 eV, respectively. The small energy gap between HOMO and LUMO indicated that the compound was stable. In addition, the MEP reveals that positive potential sites were around the PR molecule, whereas negative potential sites were surrounding the TPB site of atoms. The UV absorption of both arrangements is comparable to the experimental UV spectrum.
PubMed: 36903501
DOI: 10.3390/molecules28052256 -
Journal of Medicinal Chemistry Jul 2021Epigenetic post-translational modifications are essential for human malaria parasite survival and progression through its life cycle. Here, we present new functionalized...
Epigenetic post-translational modifications are essential for human malaria parasite survival and progression through its life cycle. Here, we present new functionalized suberoylanilide hydroxamic acid (SAHA) derivatives that chemically combine the pan-histone deacetylase inhibitor SAHA with the DNA methyltransferase inhibitor procainamide. A three- or four-step chemical synthesis was designed starting from cheap raw materials. Compared to the single drugs, the combined molecules showed a superior activity in and a potent inhibition against human HDAC6, exerting no cytotoxicity in human cell lines. These new compounds are fully active in multidrug-resistant Cambodian isolates. They target transmission of the parasite by inducing irreversible morphological changes in gametocytes and inhibiting exflagellation. The compounds are slow-acting and have an additive antimalarial effect in combination with fast-acting epidrugs and dihydroartemisinin. The lead compound decreases parasitemia in mice in a severe malaria model. Taken together, this novel fused molecule offers an affordable alternative to current failing antimalarial therapy.
Topics: Antimalarials; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Histone Deacetylase 6; Histone Deacetylase Inhibitors; Hydroxamic Acids; Malaria, Falciparum; Molecular Structure; Plasmodium falciparum; Procainamide; Structure-Activity Relationship
PubMed: 34185525
DOI: 10.1021/acs.jmedchem.1c00821 -
Diagnostics (Basel, Switzerland) Feb 2021In the last few years, cardiac magnetic resonance (CMR) imaging has progressively acquired a central role in the diagnosis and management of patients with ventricular...
In the last few years, cardiac magnetic resonance (CMR) imaging has progressively acquired a central role in the diagnosis and management of patients with ventricular arrhythmias (VA) [...].
PubMed: 33672729
DOI: 10.3390/diagnostics11020357 -
JACC. Clinical Electrophysiology Aug 2022The diagnosis of Brugada syndrome by 12-lead electrocardiography (ECG) is challenging because the diagnostic type 1 pattern is often transient.
BACKGROUND
The diagnosis of Brugada syndrome by 12-lead electrocardiography (ECG) is challenging because the diagnostic type 1 pattern is often transient.
OBJECTIVES
This study sought to improve Brugada syndrome diagnosis by using deep learning (DL) to continuously monitor for Brugada type 1 in 24-hour ambulatory 12-lead ECGs (Holters).
METHODS
A convolutional neural network was trained to classify Brugada type 1. The training cohort consisted of 10-second standard/high precordial leads from 12-lead ECGs (n = 1,190) and 12-lead Holters (n = 380) of patients with definite and suspected Brugada syndrome. The performance of the trained model was evaluated in 2 testing cohorts of 10-second standard/high precordial leads from 12-lead ECGs (n = 474) and 12-lead Holters (n = 716).
RESULTS
DL achieved a receiver-operating characteristic area under the curve of 0.976 (95% CI: 0.973-0.979) in classifying Brugada type 1 from 12-lead ECGs and 0.975 (95% CI: 0.966-0.983) from 12-lead Holters. Compared with cardiologist reclassification of Brugada type 1, DL had similar performance and produced robust results in experiments evaluating scalability and explainability. When DL was applied to consecutive 10-second, clean ECGs from 24-hour 12-lead Holters, spontaneous Brugada type 1 was detected in 48% of patients with procainamide-induced Brugada syndrome and in 33% with suspected Brugada syndrome. DL detected no Brugada type 1 in healthy control patients.
CONCLUSIONS
This novel DL model achieved cardiologist-level accuracy in classifying Brugada type 1. Applying DL to 24-hour 12-lead Holters significantly improved the detection of Brugada type 1 in patients with procainamide-induced and suspected Brugada syndrome. DL analysis of 12-lead Holters may provide a robust, automated screening tool before procainamide challenge to aid in the diagnosis of Brugada syndrome.
Topics: Brugada Syndrome; Deep Learning; Electrocardiography; Humans; Procainamide; Wearable Electronic Devices
PubMed: 35981788
DOI: 10.1016/j.jacep.2022.05.003 -
Brazilian Journal of Medical and... 2023Procainamide (PA) and its in vivo metabolite, N-acetylprocainamide (NAPA), display some pharmacological differences. Although it is agreed that PA is a class IA...
Molecular basis of the different effects of procainamide and N-acetylprocainamide on the maximum upstroke velocity and half-decay time of the cardiac action potential in guinea pig papillary muscle.
Procainamide (PA) and its in vivo metabolite, N-acetylprocainamide (NAPA), display some pharmacological differences. Although it is agreed that PA is a class IA antiarrhythmic, it has been reported that NAPA is a pure class III antiarrhythmic that affects only the repolarizing phase of the cardiac action potential. This last concept, observed exclusively in dogs, gained wide acceptance, appearing in classic pharmacology textbooks. However, evidence in species such as mice and rats indicates that NAPA can affect cardiac Na+ channels, which is unexpected for a pure class III antiarrhythmic drug. To further clarify this issue, the effects of PA (used as a reference drug) and NAPA on the maximum upstroke velocity (Vmax) and half-decay time (HDT) of the cardiac action potential were examined in the isolated right papillaris magnus of the guinea pig heart. Both PA and NAPA affected Vmax at lower concentrations than required to affect HDT, and NAPA had weaker effects on both variables. Thus, NAPA displayed typical class IA antiarrhythmic behavior. Therefore, the concept that NAPA is a pure class III antiarrhythmic drug is more species-dependent than previously envisioned. In addition, we demonstrated that the differential pharmacology of PA and NAPA is explainable, in molecular terms, by steric hindrance of the effects of NAPA and the greater number of potent aromatic-aromatic and cation π interactions with Na+ or K+ cardiac channels for PA.
Topics: Guinea Pigs; Animals; Dogs; Mice; Rats; Procainamide; Acecainide; Papillary Muscles; Anti-Arrhythmia Agents; Action Potentials
PubMed: 36722655
DOI: 10.1590/1414-431X2023e12073