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Frontiers in Cell and Developmental... 2022Female reproductive cycle, also known as menstrual cycle or estrous cycle in primate or non-primate mammals, respectively, dominates the reproductive processes in...
Female reproductive cycle, also known as menstrual cycle or estrous cycle in primate or non-primate mammals, respectively, dominates the reproductive processes in non-pregnant state. However, in addition to reproductive tissues, reproductive cycle could also perform global regulation because the receptors of two major female hormones fluctuating throughout the cycle, estrogen and progesterone, are widely distributed. Therefore, a multi-tissue gene expression landscape is in continuous demand for better understanding the systemic changes during the reproductive cycle but remains largely undefined. Here we delineated a transcriptomic landscape covering 15 tissues of C57BL/6J female mice in two phases of estrous cycle, estrus and diestrus, by RNA-sequencing. Then, a number of genes, pathways, and transcription factors involved in the estrous cycle were revealed. We found the estrous cycle could widely regulate the neuro-functions, immuno-functions, blood coagulation and so on. And behind the transcriptomic alteration between estrus and diestrus, 13 transcription factors may play important roles. Next, bioinformatics modeling with 1,263 manually curated gene signatures of various physiological and pathophysiological states systematically characterized the beneficial/deleterious effects brought by estrus/diestrus on individual tissues. We revealed that the estrous cycle has a significant effect on cardiovascular system (aorta, heart, vein), in which the anti-hypertensive pattern in aorta induced by estrus is one of the most striking findings. Inspired by this point, we validated that two hypotensive drugs, felodipine and acebutolol, could exhibit significantly enhanced efficacy in estrus than diestrus by mouse and rat experiments. Together, this study provides a valuable data resource for investigating reproductive cycle from a transcriptomic perspective, and presents models and clues for investigating precision medicine associated with reproductive cycle.
PubMed: 36589755
DOI: 10.3389/fcell.2022.983712 -
Molecules (Basel, Switzerland) Nov 2020In this work, one of the most prevalent polypharmacology drug-drug interaction events that occurs between two widely used beta-blocker drugs-i.e., acebutolol and...
In this work, one of the most prevalent polypharmacology drug-drug interaction events that occurs between two widely used beta-blocker drugs-i.e., acebutolol and propranolol-with the most abundant blood plasma fibrinogen protein was evaluated. Towards that end, molecular docking and Density Functional Theory (DFT) calculations were used as complementary tools. A fibrinogen crystallographic validation for the three best ranked binding-sites shows 100% of conformationally favored residues with total absence of restricted flexibility. From those three sites, results on both the binding-site druggability and ligand transport analysis-based free energy trajectories pointed out the most preferred biophysical environment site for drug-drug interactions. Furthermore, the total affinity for the stabilization of the drug-drug complexes was mostly influenced by steric energy contributions, based mainly on multiple hydrophobic contacts with critical residues (THR22: P and SER50: Q) in such best-ranked site. Additionally, the DFT calculations revealed that the beta-blocker drug-drug complexes have a spontaneous thermodynamic stabilization following the same affinity order obtained in the docking simulations, without covalent-bond formation between both interacting beta-blockers in the best-ranked site. Lastly, experimental ultrasound density and velocity measurements were performed and allowed us to validate and corroborate the computational obtained results.
Topics: Adrenergic beta-Antagonists; Binding Sites; Density Functional Theory; Drug Interactions; Fibrinogen; Ligands; Molecular Conformation; Molecular Docking Simulation; Reproducibility of Results; Thermodynamics
PubMed: 33228181
DOI: 10.3390/molecules25225425 -
Chemistry (Weinheim An Der Bergstrasse,... Sep 2020Chemical exchange saturation transfer (CEST) MRI has recently emerged as a versatile molecular imaging approach in which diamagnetic compounds can be utilized to...
Chemical exchange saturation transfer (CEST) MRI has recently emerged as a versatile molecular imaging approach in which diamagnetic compounds can be utilized to generate an MRI signal. To expand the scope of CEST MRI applications, herein, we systematically investigated the CEST properties of N-aryl amides with different N-aromatic substitution, revealing their chemical shifts (4.6-5.8 ppm) and exchange rates (up to thousands s ) are favorable to be used as CEST agents as compared to alkyl amides. As the first proof-of-concept study, we used CEST MRI to detect the enzymatic metabolism of the drug acebutolol directly by its intrinsic CEST signal without any chemical labeling. Our study implies that N-aryl amides may enable the label-free CEST MRI detection of the metabolism of many N-aryl amide-containing drugs and a variety of enzymes that act on N-aryl amides, greatly expanding the scope of CEST MR molecular imaging.
Topics: Amides; Contrast Media; Magnetic Resonance Imaging; Molecular Imaging
PubMed: 32639618
DOI: 10.1002/chem.202002415 -
Arhiv Za Higijenu Rada I Toksikologiju Mar 2020Beta-blockers are chiral compounds with enantiomers that have different bioactivity, which means that while one is active, the other can be inactive or even harmful. Due...
Beta-blockers are chiral compounds with enantiomers that have different bioactivity, which means that while one is active, the other can be inactive or even harmful. Due to their high consumption and incomplete degradation in waste water, they may reach surface waters and affect aquatic organisms. To address this issue we developed a chromatographic method suitable for determining beta-blocker enantiomers in surface waters. It was tested on five beta-blockers (acebutolol, atenolol, bisoprolol, labetalol and metoprolol) and validated on bisoprolol enantiomers. Good enantioseparation of all analysed beta-blockers was achieved on the Chirobiotic V column with the mobile phase composed of methanol/acetic acid/triethylamine (100/0.20/0.15 v/v/v) at a flow rate of 0.5 mL/min and column temperature of 45 °C. Method proved to be linear in the concentration range from 0.075 µg/mL to 5 µg/mL, and showed good recovery. The limits of bisoprolol enantiomer detection were 0.025 µg/mL and 0.026 µg/mL and of quantification 0.075 µg/mL and 0.075 µg/mL. Despite its limitations, it seems to be a promising method for bisoprolol enantiomer analysis in surface water samples. Further research could focus on waste water analysis, where enantiomer concentrations may be high. Furthermore, transferring the method to a more sensitive one such as liquid chromatography coupled with tandem mass spectrometry and using ammonium acetate as the mobile phase additive instead of acetic acid and triethylamine would perhaps yield much lower limits of detection and quantification.
Topics: Acebutolol; Adrenergic beta-Antagonists; Atenolol; Bisoprolol; Chromatography, High Pressure Liquid; Labetalol; Metoprolol; Water
PubMed: 32597137
DOI: 10.2478/aiht-2020-71-3318 -
Journal of Chromatography. A Jan 2023In conventional reversed-phase liquid chromatography (RPLC) with hydro-organic solvents, basic cationic solutes yield retained, broad, asymmetric peaks, owing to their...
In conventional reversed-phase liquid chromatography (RPLC) with hydro-organic solvents, basic cationic solutes yield retained, broad, asymmetric peaks, owing to their interaction with free anionic silanols in the stationary phase. RPLC mobile phases to which the anionic surfactant sodium dodecyl sulphate (SDS), or an ionic liquid (IL) are added, have been proposed as solutions, since these additives are able to block the silanol effect thus improving the chromatographic performance. With these additives, it is however necessary to increase the elution strength by adding an organic solvent, such as an alcohol or acetonitrile. A novel aqueous liquid chromatographic mode (in the absence of organic solvent) is here proposed, where the mobile phases contain only a mixture of aqueous solutions of SDS and an IL derived from 1-alkyl-3-methylimidazolium associated to chloride, both environmentally friendly. When these reagents are added, the anionic surfactant adsorbed on the stationary phase is able to attract the cationic solutes, whereas the adsorbed IL cation repels them. The combination of both effects (attraction and repulsion) allows the modulation of retention, by varying the IL/SDS ratio. Given the character of the additives, a type of green liquid chromatography is achieved. In this work, the chromatographic behavior of six basic compounds of pharmaceutical interest, the β-adrenoceptor antagonists acebutolol, atenolol, carteolol, metroprolol, oxprenolol and propranolol, is examined. In order to assess the chromatographic behavior of the mixed mobile phases containing SDS and IL, changes in retention, peak profile and resolution of mixtures of the analytes were explored at varying concentration of the additives.
Topics: Sodium Dodecyl Sulfate; Ionic Liquids; Chromatography, Liquid; Solvents; Surface-Active Agents; Water; Ethanol; Chromatography, High Pressure Liquid
PubMed: 36580766
DOI: 10.1016/j.chroma.2022.463740 -
Journal of Hazardous Materials Feb 2022The excessive cost, unsustainability or complex production of new highly selective electrocatalysts for HO production, especially noble-metal-based ones, is prohibitive...
The excessive cost, unsustainability or complex production of new highly selective electrocatalysts for HO production, especially noble-metal-based ones, is prohibitive in the water treatment sector. To solve this conundrum, biomass-derived carbons with adequate textural properties were synthesized via agarose double-step pyrolysis followed by steam activation. A longer steam treatment enhanced the graphitization and porosity, even surpassing commercial carbon black. Steam treatment for 20 min yielded the greatest surface area (1248 m g), enhanced the mesopore/micropore volume distribution and increased the activity (E = 0.609 V) and yield of HO (40%) as determined by RRDE. The upgraded textural properties had very positive impact on the ability of the corresponding gas-diffusion electrodes (GDEs) to accumulate HO, reaching Faradaic current efficiencies of ~95% at 30 min. Acidic solutions of β-blocker acebutolol were treated by photoelectro-Fenton (PEF) process in synthetic media with and without chloride. In urban wastewater, total drug disappearance was reached at 60 min with almost 50% mineralization after 360 min at only 10 mA cm. Up to 14 degradation products were identified in the Cl-containing medium.
Topics: Acebutolol; Chlorides; Electrodes; Hydrogen Peroxide; Iron; Oxidation-Reduction; Sepharose; Water Pollutants, Chemical
PubMed: 34479080
DOI: 10.1016/j.jhazmat.2021.127005 -
The Cochrane Database of Systematic... Sep 2019Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and...
BACKGROUND
Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in unselected patients remains a controversial issue. A previous version of this review assessing the effectiveness of perioperative beta-blockers in cardiac and non-cardiac surgery was last published in 2018. The previous review has now been split into two reviews according to type of surgery. This is an update and assesses the evidence in cardiac surgery only.
OBJECTIVES
To assess the effectiveness of perioperatively administered beta-blockers for the prevention of surgery-related mortality and morbidity in adults undergoing cardiac surgery.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, Biosis Previews and Conference Proceedings Citation Index-Science on 28 June 2019. We searched clinical trials registers and grey literature, and conducted backward- and forward-citation searching of relevant articles.
SELECTION CRITERIA
We included RCTs and quasi-randomized studies comparing beta-blockers with a control (placebo or standard care) administered during the perioperative period to adults undergoing cardiac surgery. We excluded studies in which all participants in the standard care control group were given a pharmacological agent that was not given to participants in the intervention group, studies in which all participants in the control group were given a beta-blocker, and studies in which beta-blockers were given with an additional agent (e.g. magnesium). We excluded studies that did not measure or report review outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE.
MAIN RESULTS
We included 63 studies with 7768 participants; six studies were quasi-randomized and the remaining were RCTs. All participants were undergoing cardiac surgery, and in most studies, at least some of the participants were previously taking beta-blockers. Types of beta-blockers were: propranolol, metoprolol, sotalol, esmolol, landiolol, acebutolol, timolol, carvedilol, nadolol, and atenolol. In twelve studies, beta-blockers were titrated according to heart rate or blood pressure. Duration of administration varied between studies, as did the time at which drugs were administered; in nine studies this was before surgery, in 20 studies during surgery, and in the remaining studies beta-blockers were started postoperatively. Overall, we found that most studies did not report sufficient details for us to adequately assess risk of bias. In particular, few studies reported methods used to randomize participants to groups. In some studies, participants in the control group were given beta-blockers as rescue therapy during the study period, and all studies in which the control was standard care were at high risk of performance bias because of the open-label study design. No studies were prospectively registered with clinical trials registers, which limited the assessment of reporting bias. We judged 68% studies to be at high risk of bias in at least one domain.Study authors reported few deaths (7 per 1000 in both the intervention and control groups), and we found low-certainty evidence that beta-blockers may make little or no difference to all-cause mortality at 30 days (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.47 to 1.90; 29 studies, 4099 participants). For myocardial infarctions, we found no evidence of a difference in events (RR 1.05, 95% CI 0.72 to 1.52; 25 studies, 3946 participants; low-certainty evidence). Few study authors reported cerebrovascular events, and the evidence was uncertain (RR 1.37, 95% CI 0.51 to 3.67; 5 studies, 1471 participants; very low-certainty evidence). Based on a control risk of 54 per 1000, we found low-certainty evidence that beta-blockers may reduce episodes of ventricular arrhythmias by 32 episodes per 1000 (RR 0.40, 95% CI 0.25 to 0.63; 12 studies, 2296 participants). For atrial fibrillation or flutter, there may be 163 fewer incidences with beta-blockers, based on a control risk of 327 incidences per 1000 (RR 0.50, 95% CI 0.42 to 0.59; 40 studies, 5650 participants; low-certainty evidence). However, the evidence for bradycardia and hypotension was less certain. We found that beta-blockers may make little or no difference to bradycardia (RR 1.63, 95% CI 0.92 to 2.91; 12 studies, 1640 participants; low-certainty evidence), or hypotension (RR 1.84, 95% CI 0.89 to 3.80; 10 studies, 1538 participants; low-certainty evidence).We used GRADE to downgrade the certainty of evidence. Owing to studies at high risk of bias in at least one domain, we downgraded each outcome for study limitations. Based on effect size calculations in the previous review, we found an insufficient number of participants in all outcomes (except atrial fibrillation) and, for some outcomes, we noted a wide confidence interval; therefore, we also downgraded outcomes owing to imprecision. The evidence for atrial fibrillation and length of hospital stay had a moderate level of statistical heterogeneity which we could not explain, and we, therefore, downgraded these outcomes for inconsistency.
AUTHORS' CONCLUSIONS
We found no evidence of a difference in early all-cause mortality, myocardial infarction, cerebrovascular events, hypotension and bradycardia. However, there may be a reduction in atrial fibrillation and ventricular arrhythmias when beta-blockers are used. A larger sample size is likely to increase the certainty of this evidence. Four studies awaiting classification may alter the conclusions of this review.
Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Bradycardia; Cardiac Surgical Procedures; Cerebrovascular Disorders; Humans; Hypotension; Morbidity; Myocardial Infarction; Myocardial Ischemia; Perioperative Care; Postoperative Complications; Randomized Controlled Trials as Topic
PubMed: 31544227
DOI: 10.1002/14651858.CD013435 -
Molecules (Basel, Switzerland) Jun 2024The sustainable catalytic efficacy of transition metal oxides (TMO) and rare earth element-based oxides positions them as pivotal materials for effectively treating...
The sustainable catalytic efficacy of transition metal oxides (TMO) and rare earth element-based oxides positions them as pivotal materials for effectively treating contaminated wastewater. This study successfully synthesized a series of Ce@MnO photocatalysts using a straightforward hydrothermal method. These photocatalysts were thoroughly characterized for their optical properties, structural morphology, and phase purity. Among the synthesized materials, the Ce@MnO (40:60) exhibited the highest photocatalytic activity for the degradation of Acebutolol (ACB), achieving a remarkable degradation efficiency of 92.71% within 90 min under visible light irradiation. This superior performance is attributed to the increased presence of active species and the efficient separation of photogenerated carriers. Additionally, the photocatalytic reaction mechanism was elucidated, highlighting the catalyst's surface charge properties which significantly enhanced performance in a solution with pH 8. The outstanding photo-response in the visible spectrum renders this method not only cost-effective but also environmentally benign, presenting a promising approach for large-scale water purification.
PubMed: 38930919
DOI: 10.3390/molecules29122854 -
Turkish Journal of Pharmaceutical... Dec 2020Acebutolol HCl (ABL) is a selective β-adrenergic receptor blocking agent that is preferably administered by the oral route despite its low bioavailability (30-50%). The...
OBJECTIVES
Acebutolol HCl (ABL) is a selective β-adrenergic receptor blocking agent that is preferably administered by the oral route despite its low bioavailability (30-50%). The purpose of this study was to evaluate the effect of verapamil HCl (VER) [as P-glycoprotein inhibitor (P-gp)] on the intestinal absorption of ABL by comparing the changes in the absorption rate constant (k) of ABL.
MATERIALS AND METHODS
intestinal perfusion was conducted in healthy male Wistar albino rats to study the absorption phase of ABL. Eighteen rats were divided into three groups. The first group (the control group) was perfused with ABL alone (260 μg/mL). The second and third groups were perfused with ABL (260 μg/mL) in combination with VER at different concentrations (200 and 400 μg/mL, respectively). The analysis was performed using a simple, rapid, and validated spectroscopic method.
RESULTS
The absorption study showed that k of ABL in the first group was 0.47±0.045 h-. In the third group k increased 3-fold (1.37±0.031 h-); however, the second group showed a statistically insignificant change in k (0.39±0.076 h-).
CONCLUSION
The results revealed that VER at a concentration of 400 μg/mL has a pronounced effect on the absorption kinetics of ABL (increased k). This could be linked to the inhibition of P-gp, which is considered a contributing factor in low bioavailability of ABL.
PubMed: 33389978
DOI: 10.4274/tjps.galenos.2019.59862 -
Ultrasonics Sonochemistry Sep 2019This study mainly covered the cavitation erosion in probe sonication and its electrochemical behavior. The activated graphite was exfoliated by the probe sonication...
This study mainly covered the cavitation erosion in probe sonication and its electrochemical behavior. The activated graphite was exfoliated by the probe sonication wherein the titanium alloy (TA) is used as a probe (micro-tip). The sonication performed in the aqueous solution contains a mixture of sulfuric acid and nitric acid (1:1). The exfoliated graphite (EG) was examined by field emission scanning electron microscope, Raman and X-ray diffraction pattern analysis. The results showed that some TA particles dissolute from the TA micro-tip accompanied with graphite exfoliation. This dissolution experienced from the cavitation erosion, because the acoustic cavitation makes severe deformation on probe tips due to the bubble collapse. The dissolution rate increased when increasing sonication time; the resultant TA particles are randomly distributed over the EG. These EGTAs applied to the electrochemical oxidation of acebutolol which revealed an appreciable electrochemical performance and also exhibited better analytical performances to the electrochemical determinations. The obtained analytical parameters viz., sensitivity (0.234 µA µM cm), linear range (0.01-15.1 µM), and limit of detection (0.003 µM) are highly comparable with the previous reports. Moreover, it has an acceptable tolerance with the interfering substances.
PubMed: 31101266
DOI: 10.1016/j.ultsonch.2019.04.025