Wastewater-based epidemiology (WBE) is an approach that uses information obtained from the analysis of various metabolites or residues in wastewater with the aim of assessing the consumption of or exposure to chemicals or pathogens in a population connected to a sewage system. The aim of this work was to develop methods for the isolation and analysis of seven beta-blockers (acebutolol, atenolol, betaxolol, metoprolol, nadolol, pindolol and propranolol) in wastewater samples collected from the influent of the wastewater treatment plant in Cluj-Napoca, Romania, in order to estimate their consumption among the population in two time periods (February and October 2024) using WBE. The selected beta-blockers were extracted by solid phase extraction using a Strata C18-U cartridge and analyzed by liquid chromatography coupled with tandem mass spectrometry. The consumption was estimated using the daily mass load of pharmaceutical products reported per 1000 inhabitants (mg/day/1000inh) and varied in the following ranges: atenolol 0.03-3.74, nadolol 0.03-0.1, propranolol 0.04-0.72, betaxolol 0.07-0.38, and metoprolol 54.85-276.45. From the obtained results, it can be observed that metoprolol is the most used beta-blocker in the investigated population, followed by atenolol, propranolol and betaxolol. Other beta-blockers are consumed in small quantities or occasionally.

Smith-Magenis syndrome (SMS) is characterized by distinctive physical features (particularly facial features that progress with age), developmental delay, cognitive impairment, behavioral abnormalities, sleep disturbance, and childhood-onset abdominal obesity. Infants have feeding difficulties, failure to thrive, hypotonia, hyporeflexia, prolonged napping or need to be awakened for feeds, and generalized lethargy. The majority of individuals function in the mild-to-moderate range of intellectual disability. The behavioral phenotype, including significant sleep disturbance, stereotypies, and maladaptive and self-injurious behaviors, is generally not recognized until age 18 months or older and continues to change until adulthood. Sensory issues are frequently noted; these may include avoidant behavior, as well as repetitive seeking of textures, sounds, and experiences. Toileting difficulties are common. Significant anxiety is common as are problems with executive functioning, including inattention, distractibility, hyperactivity, and impulsivity. Maladaptive behaviors include frequent outbursts / temper tantrums, attention-seeking behaviors, opposition, aggression, and self-injurious behaviors including self-hitting, self-biting, skin picking, inserting foreign objects into body orifices (polyembolokoilamania), and yanking fingernails and/or toenails (onychotillomania). Among the stereotypic behaviors described, the spasmodic upper-body squeeze or "self-hug" seems to be highly associated with SMS. An underlying developmental asynchrony, specifically emotional maturity delayed beyond intellectual functioning, may also contribute to maladaptive behaviors in people with SMS.

Concerns about the safety of titanium dioxide (TiO2), including potential carcinogenicity, have prompted its ban in foods in the European Union, while remaining allowed as pharmaceutical excipient. We aimed to evaluate whether ingesting increasing quantities of TiO2 through medicines is associated with higher cancer risk. Data were derived from the French National Health Data System, a nationwide medico-administrative database. A case-control study was nested within two cohorts: users of metformin (all doses) and users of 200 mg acebutolol, both available in TiO2-containing and TiO2-free formulations. During 2013-2021, 293,101 cancer cases were identified and matched to 2,930,633 controls. TiO2 exposure through metformin and acebutolol consumption was calculated based on drug claims from 2006 up to five years before the index date. Conditional logistic regression models estimated linear associations between TiO2 exposure and cancer risk. RRs of overall cancer per 1000 TiO2-containing tablets and per 10,000 mg of TiO2 increments were both 1.00 (95% CI: 0.99-1.01). Analyses by cancer site also yielded RRs very close to 1.00 or slightly different but not statistically significant, except for breast (RR per 10,000 mg: 1.03, 95% CI:1.00-1.07) and lymphoid/hematopoietic (RR per 1000 tablets: 0.97, 95% CI: 0.95-1.00) cancers, which however lost significance after Bonferroni correction. There was a suggestion of non-linear positive association for central nervous system cancers. This first epidemiological study on TiO2 ingestion and cancer found no meaningful linear association between increasing TiO2 exposure through medicines and overall or site-specific cancer risk. Non-linear associations cannot be excluded.

Osteoporosis is a common metabolic bone disease with aging, characterized by low bone mineral density (BMD) and higher fragility fracture risk. Although current pharmacological interventions provide therapeutic benefits, long-term use is limited by side effects and comorbidities. In this study, we employed driver signaling network identification (DSNI) and drug functional networks (DFN) to identify repurposable drugs from the Library of Integrated Network-Based Cellular Signatures. We constructed osteoporosis driver signaling networks (ODSN) using multi-omics data and developed DFN based on drug similarity. By integrating ODSN and DFN with drug-induced transcriptional responses, we screened 10,158 compounds and identified several drugs with strong targeting effects on ODSN. Mendelian randomization assessed potential causal links between cis-eQTLs of drug targets and BMD using genome-wide association study data. Our findings indicate four drugs, including Ruxolitinib, Alfacalcidol, and Doxercalciferol, may exert anti-osteoporosis effects. Notably, Acebutolol, a β-blocker for hypertension, has not previously been implicated in osteoporosis therapy. For validation, zebrafish osteoporosis models were established using Dexamethasone-induced bone loss, followed by treatment with Acebutolol hydrochloride and Alfacalcidol. Both compounds demonstrated significant protective effects against osteoporosis-related bone deterioration. Furthermore, a population-based data set, utilizing propensity score matching and analyzed via a generalized linear model, revealed that individuals taking β-blocker drugs exhibited significantly higher BMD than users of other cardiovascular medications. In summary, this study integrates multi-omics approaches, experimental validation, and real-world population data to propose acebutolol as a novel candidate for osteoporosis treatment. These findings warrant further mechanistic studies and clinical trials to evaluate its efficacy in osteoporosis management.

Rapid advances in industries and agricultural practices have recently released various toxic pollutants into aquatic systems. Among other pollutants, pharmaceuticals, have been detected in environmental aquatic systems at levels that have negative health impacts on both humans and animals. This study employed an in situ chemical co-precipitation method to fabricate a magnetic amine-based metal organic framework nanocomposite. This nanocomposite was successfully synthesised and applied as a photocatalytic material for the mineralization of acebutolol (ACE) in water. The prepared materials, including the nanocomposite (Fe3O4@NH2-MIL-101(Cr)) were characterised using transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) analysis, Fourier transform infrared spectroscopy (FTIR) and X-ray powder diffraction (XRD). The optoelectronic properties were determined using photoluminescence (PL), electrochemical impedance spectroscopy, diffuse reflectance spectroscopy (UV-Vis DRS) and ultraviolet-visible spectroscopy. The photocatalytic efficacy of the nanocomposite was assessed via the degradation of acebutolol under visible light illumination. The results indicate that adsorption-desorption equilibrium was attained after 60 min in the dark, and 98.3% degradation efficiency was achieved after 180 min with the light on. According to scavenging experiments, superoxide radicals (·O2 -) were the main reactive oxygen species (ROS) during photodegradation. The Nyquist plot obtained from electrochemical impedance spectroscopy (EIS) showed that the Fe3O4@NH2-MIL-101(Cr) nanocomposite had a reduced charge transfer resistance (R ct), indicating separation and accelerated transfer of charges at the interface. The obtained electron lifespan (τ e) supported the results, and was found to be higher for Fe3O4@NH2-MIL-101(Cr) compared to NH2-MIL-101(Cr) and pure Fe3O4. The photocatalytic mechanism revealed that the formed heterojunction followed a Z-scheme mechanism.

The current need to make processes greener encourages us to reduce solvent consumption along with replacing hazardous solvents with ecofriendly solvents. Analytical purification is one of the most solvent-consuming processes in drug discovery, and our present study is a step forward, making it ecofriendly, fast, and cost-effective. Our study evaluated 2-methyl tetrahydrofuran (MTHF) as a sustainable alternative to THF in reverse-phase HPLC, focusing on its impact on peak shapes, resolution, retention time, and sample loading. We screened six commercially available hydrochloride salts of +epinephrine (1), tetramisole (2), acebutolol (3), labetalol (4), +verapamil (5), and amitriptyline (6) with varying polarity indexes using multiple mobile phase combinations, including ACN, ACN-MeOH, 5% MTHF in ACN, and 5% MTHF in ACN-MeOH, alongside various buffers. The choice of ACN and MeOH is based on their remarkable properties, such as complete miscibility with water, relatively low viscosity, low UV cut-off, and low chemical reactivity. This multi-step screening in combination with various buffers (different pH) and solvents was required for identifying the optimal role of MTHF for achieving the best chromatographic performance with the selected analytes. The study showed that using TFA buffer with 10% MTHF in ACN-MeOH has significantly enhanced the peak shape and resolution, which facilitates approximately five-fold higher sample loading as compared to ACN-MeOH alone. This approach resulted in a shorter run time, reducing organic solvent consumption by ∼87% and the overall turnaround time by approximately ∼89%. Thus, the study validates MTHF as a green solvent for high-throughput, cost-effective purification of complex mixtures of small molecules.

Beta-blockers are pharmaceuticals used to treat cardiovascular diseases such as hypertension, angina pectoris, and arrhythmia. Due to high consumption, they are continuously released into the environment, being detected in many aqueous matrices. The aim of this research is to test the effectiveness of two green liquid-phase microextraction procedures, such as dispersive liquid-liquid microextraction (DLLME) and solidification of floating organic droplet microextraction (SFOME) for the selective extraction of eight beta-blockers (atenolol, nadolol, pindolol, acebutolol, metoprolol, bisoprolol, propranolol, and betaxolol) from aqueous matrices for their analysis by gas chromatography (GC) or liquid chromatography (LC). The influence of extraction parameters, such as the type and volume of extraction and disperser solvents, and ionic strength were studied. The developed extraction procedures provide a good enrichment factor for six compounds (61.22-243.97), good extraction recovery (53.04-92.1%), and good sample cleaning for both extraction procedures. Good limits of detection (0.13 to 0.69 µg/mL for GC and 0.07 to 0.15 µg/mL for HPLC) and limits of quantification (0.39 to 2.10 µg/mL for GC and 0.20 to 0.45 µg/mL for LC) were obtained. The developed procedures were successfully applied to the analysis of selected beta-blockers in wastewater samples, proving their applicability to the real samples.

Reaction between Acebutolol hydrochloride and sodium tetraphenylborate in water afforded an Acebutolol-tetraphenyl-borate complex. This ion-pair was characterized by a variety of analytical and spectroscopic tools including X-ray crystallographic analysis. Comprehensive theoretical studies including ground-state geometry optimization, Mulliken atomic charges, and vibrational analysis were executed to get an insight into the nature of the charge transfer between the donor and acceptor ions. The crystal structure demonstrated that three inter- and intramolecular hydrogen-bonds stabilize the molecular packing in the solid state. Natural bond orbital analysis confirmed the presence of many interactions between B(Ph)4 - and particular Acebutolol functional groups, such as NH and OH groups. The positive Mulliken atomic charges of the acidic protons of the NH and OH groups of Acebutolol were increased upon the formation of the ion-pair. This has been experimentally confirmed by IR and NMR spectroscopies. Through the use of frontier molecular orbital models, time-dependent density functional theory calculations have provided more insight into the existence of two electronic transitions, beginning at B(Ph)4 - and terminating at the π* system of mono-protonated Acebutolol ions.

Electrochemistry offers an effective means of mimicking enzymatic metabolic pathways, particularly the oxidative pathways catalyzed by the cytochrome P450 superfamily. The electrochemical generation and identification of metabolites are time-sensitive, necessitating adjustable cell designs for an accurate mechanistic interpretation. We present a thin-layer electrode (TLE) that addresses the needs of both the analytical and synthetic electrochemical generation of drug metabolites. The TLE's ability to conduct experiments on a minute-to-hour time scale allows for detailed observation of reaction mechanisms for metabolites not easily identified by traditional methods. The utility of the TLE for drug metabolites was benchmarked for electrochemical oxidation of acetaminophen, acebutolol, and 2-acetyl-4-butyramidophenol, known to produce quinone imine metabolites, i.e., NAPQI, upon oxidation. When combined with a microelectrode (μE), the TLE enables probing of the concentration profiles for metabolic oxidation of these drugs. The micromole scale and pipette-type structure of the TLE facilitate comprehensive structural elucidation of intermediates and products using chromatographic and spectroscopic techniques.

Drug repurposing is a promising approach towards the discovery of novel treatments against Neglected Tropical Diseases, such as Leishmaniases, presenting the advantage of reducing both costs and duration of the drug discovery process. In previous work, our group developed a Machine Learning pipeline for the repurposing of FDA-approved drugs against Leishmania parasites. The present study is focused on an in vitro validation of this approach by assessing the antileishmanial effects of 10 predicted drug candidates. First, we evaluated the drugs' activity against promastigotes from two strains of L. infantum and one of L. major, which caused distinct clinical manifestations, using an MTT assay. The standard anti-Leishmania drug Amphotericin B was used as a positive control. Five molecules demonstrated anti-Leishmania effects, out of which Acebutolol, Prilocaine and Phenylephrine are described herein for the first time. When tested on promastigote growth, Acebutolol displayed IC50 values ranging from 69.28 to 145.53 µg/mL. Prilocaine exhibited IC50 values between 33.10 and 45.81 µg/mL. Phenylephrine, on the other hand, presented IC50 values >200 µg/mL. The two remaining drugs, Dibucaine and Domperidone, exhibited significantly low IC50 values varying between 0.58 and 1.05 µg/mL, and 6.30 and 8.17 µg/mL, respectively. Both compounds were previously described as anti-Leishmania agents in vivo. All five compounds demonstrated no notable cytotoxic effects on THP-1-derived macrophages at the IC50 concentrations, allowing for their testing on the intracellular form of L. major and L. infantum parasites. Interestingly, all compounds exhibited antileishmanial activity on amastigotes with enhanced IC50 values compared to the corresponding promastigotes. Noticeably, Dibucaine and Domperidone displayed IC50 values of at most 1.99 µg/mL. Acebutolol, Prilocaine and Phenylephrine showed IC50 values ranging from 13.84 to 66.81 µg/mL. Our previously published Computer-Aided repositioning pipelines of FDA-approved drugs as antileishmanial agents identified Dibucaine and Domperidone as candidates in support of previous in vivo studies. This study consolidates such findings through the in vitro validation against 2 Leishmania species, highly prevalent in Africa and Middle East, and reveals Acebutolol, Prilocaine, and Phenylephrine as novel anti-Leishmania effectors, confirming the relevance of our approach and calling for further investigations.

Cell attachment to the extracellular matrix significantly impacts the integrity of tissues and human health. The integrin α5β1 is a heterodimer of α5 and β1 subunits and has been identified as a crucial modulator in several human carcinomas. Integrin α5β1 significantly regulates cell proliferation, angiogenesis, inflammation, tumor metastasis, and invasion. This regulatory role of integrin α5β1 in tumor metastasis makes it an appealing target for cancer therapy. The majority of the drugs targeting integrin α5β1 are limited only to clinical trials. In our study, we have performed 94287 compounds screening to determine potential drugs against α5β1 integrin. We have used ATN-161 as a reference and employed combined bioinformatic methodologies, including molecular modelling, virtual screening, MM-GBSA, cell-line cytotoxicity prediction, ADMET, Density Functional Theory (DFT), Non-covalent Interactions (NCI) and molecular simulation, to identify putative integrin α5β1 inhibitors. We found Taxifolin, PD133053, and Acebutolol that possess inhibitory activity against α5β1 integrin and could act as effective drug for the cancer treatment. Taxifolin, PD133053, and Acebutolol exhibited excellent binding to the druggable pocket of integrin α5β1, and also maintained a unique binding mechanism with extra hydrophobic contacts at molecular level. Overall, our study gives new pharmacological candidates that may act as a potential drug against integrin α5β1.

Acebutolol (ACE) is commonly used to treat hypertension and high blood pressure. Large doses of ACE can have adverse effects with potentially life-threatening consequences. It is, therefore, essential to develop a simple, low-cost, reliable, and reproducible device for detecting ACE in biofluids. This study explores the potential of unique two-dimensional nano-flakes, such as tungsten trioxide (WO3). Graphene oxide (GO) typically exhibits lower electrical conductivity than pristine graphene due to the presence of oxygen-containing functional groups that interfere with the π-conjugated structure. Functionalizing GO with tannic acid (TA) can partially reinstate the π-conjugation and limit the amount of oxygen, resulting in enhanced electrical conductivity. Ultrasonic techniques were utilized to create WO3 NFs@TA-rGO, and a range of spectroscopic and microscopic methods were applied to examine the formation of the resulting WO3 NFs@TA-rGO nanocomposites. Under optimal conditions, modified sensors resulted in lower limits of detection (0.0055 μM) and good sensitivity (0.40 μA μM[-1] cm[-2]). They also exhibited a broad linear range spanning from 0.009 to 568.6 μM. Fabricated sensors have significant anti-interference properties with high specificity and excellent storage stability (RSD = 4.3 %), reproducibility (RSD = 3.9 %), and repeatability (RSD = 3.3 %). Ultimately, the sensor's efficacy was confirmed through the successful detection of ACE in biological samples (with recoveries ranging from 99.1 to 99.6 %). Lastly, this study highlights the substantial potential of ACE detection and extends its applications in biomedical diagnostics and pharmaceutical research.

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@MnO2 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@MnO2 (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.