Pharmaceutical Compounds Research Articles

In-depth study of adsorption mechanisms and interactions in the removal of pharmaceutical contaminants via activated carbon: a physicochemical analysis.

This study presents a theoretical analysis of the adsorption process of pharmaceutical pollutants, specifically acetaminophen (ATP) and diclofenac (DFC), onto activated carbon (AC) derived from avocado biomass waste. The adsorption isotherms of ATP and DFC were analyzed using a multilayer model, which revealed the formation of two to four adsorption layers depending on the temperature of the aqueous solution. The saturation adsorption capacities for ATP and DFC were 52.71 and 116.53mg/g, respectively. A steric analysis suggested that the adsorption mechanisms of ATP and DFC involved a multi-molecular process. The calculated adsorption energies (ΔE1 and ΔE2) varied between 12.86 and 22.58kJ/mol, with the highest values observed for DFC removal. Therefore, the adsorption of these organic molecules was associated with physisorption interactions: van der Waals forces and hydrogen bonds. These findings enhance the understanding of the depollution processes of pharmaceutical compounds using carbon-based adsorbents and highlight the potential of utilizing waste biomass for environmental remediation.

Next-generation membranes for verapamil removal: Graphene oxide quantum dot-modified polyethersulfone membranes

The presence of verapamil in water sources has gained attention due to its potential risks to ecosystems and human health. Because of its great separation performance and simplicity of integration into existing treatment processes, membrane filtration could be a viable alternative. Polyethersulfone (PES) membrane is usually employed for filtration processes due to its good mechanical and thermal stability. However, pristine PES membrane exhibits low flux and lower fouling properties due to its poor antibacterial properties. Thus, the phase inversion approach was used in the current study to develop graphene oxide quantum dots (GOQDs)-modified PES ultrafiltration (UF) membranes with varying quantities of GOQDs loading (0.01–0.07 wt%). With 0.03 wt% GOQDs, the PES composite membrane exhibited a water flux of 75.23 ±10.43 L/m2 h with a verapamil retention capability of 80.36%. All the modified PES membranes containing GOQDs exhibited the formation of inhibition zones, with PES-0.07 membranes (21.00 mm) showing more pronounced zones. The incorporation of GOQDs proved to be a promising and sustainable approach for modifying PES membranes, enhancing their flux, rejection performance, and antibacterial properties, which could be beneficial in removing pharmaceutical compounds from aqueous solution.

PREDICTING DRUG-DRUG INTERACTION USING MACHINE LEARNING

The ever-expanding landscape of pharmaceutical compounds and medical treatments has underscored the critical need for an advanced system to predict drug-drug interactions (DDIs) using machine learning. This paper delves into the development of a novel predictive model that leverages diverse data sources, including chemical structures, pharmacological properties, and scientific literature, to comprehensively analyse and foresee potential DDIs. The current state of DDIs is rife with limitations in scope and accuracy, making the development of an advanced system not only a necessity for enhancing patient safety but also a boon to pharmaceutical research and regulatory oversight. The relationship between two medications in which one drug’s pharmacological actions are altered by another is known as a drug-drug interaction (DDI). Favourable drug-drug interactions (DDIs) generally contribute to improved therapeutic results for patients. On the contrary, adverse DDIs pose a significant risk, often resulting in undesirable drug reactions that can potentially lead to the withdrawal of a drug from the market and even patient fatalities. Consequently, the identification of DDIs is essential for advancing new drug development and effectively managing diseases. Keywords: Drug, Drug-drug interaction, Machine learning, Bioinformatics, Drug development.

A State-of-the-Art Review on Chromatographic Analysis of Alcaftadine

This paper provides an extensive overview of chromatography techniques utilized in the analysis of Alcaftadine, a pharmaceutical compound used in ophthalmic formulations. Various chromatographic methods including UV Spectrophotometric, HPLC, RP-HPLC, HPTLC, and UPLC have been developed and validated for the accurate quantification of Alcaftadine in bulk and dosage forms. The methods described offer specific advantages such as ease of use, precision, and sensitivity, ensuring reliable results in pharmaceutical analysis. Key parameters of method validation, including accuracy, precision, linearity, limit of detection, limit of quantitation, specificity, range, and robustness, are comprehensively discussed, highlighting the stringent criteria required for analytical method validation in accordance with regulatory guidelines. The importance of stability-indicating methods for assessing the stability of Alcaftadine formulations is emphasized, underscoring the need for robust analytical techniques to ensure product quality and efficacy. The review underscores the crucial role of chromatography in pharmaceutical research, providing valuable insights for researchers and practitioners involved in drug development and quality control.

Approach to Spirocyclohexadienes via Visible Light‐Mediated ipso‐Cyclization of Amino Acid Derivatives with N‐(2‐Phenyl)benzoyl Groups

AbstractSpirocycles are important structural motifs, found in natural and pharmaceutical compounds, which have attracted considerable interest in modern drug discovery research. Herein, we describe the development of a visible light‐mediated ipso‐cyclization of amino acid derivatives with N‐(2‐phenyl)benzoyl groups, allowing easy access to a variety of spirocyclohexadienes. The addition of water was found to be beneficial in promoting the reaction progress. Investigation of the substrate scope revealed that incorporating an electron‐donating moiety at the 3′‐position of the biphenyl group resulted in a more favorable outcome for spirocycle formation.

Chemical genomic analysis reveals the interplay between iron chelation, zinc homeostasis, and retromer function in the bioactivity of an ethanol adduct of the feijoa fruit-derived ellagitannin vescalagin.

Nature has been a rich source of pharmaceutical compounds, producing 80% of our currently prescribed drugs. The feijoa plant, Acca sellowiana, is classified in the family Myrtaceae, native to South America, and currently grown worldwide to produce feijoa fruit. Feijoa is a rich source of bioactive compounds with anticancer, anti-inflammatory, antibacterial, and antifungal activities; however, the mechanism of action of these compounds is largely not known. Here, we used chemical genetic analyses in the model organism Saccharomyces cerevisiae to investigate the mechanism of action of a feijoa-derived ethanol adduct of vescalagin (EtOH-vescalagin). Genome-wide barcode sequencing analysis revealed yeast strains lacking genes in iron metabolism, zinc metabolism, retromer function, or mitochondrial function were hypersensitive to 0.3 µM EtOH-vescalagin. This treatment increased expression of iron uptake proteins at the plasma membrane, which was a compensatory response to reduced intracellular iron. Likewise, EtOH-vescalagin increased expression of the Cot1 protein in the vacuolar membrane that transports zinc into the vacuole to prevent cytoplasmic accumulation of zinc. Each individual subunit in the retromer complex was required for the iron homeostatic mechanism of EtOH-vescalagin, while only the cargo recognition component in the retromer complex was required for the zinc homeostatic mechanism. Overexpression of either retromer subunits or high-affinity iron transporters suppressed EtOH-vescalagin bioactivity in a zinc-replete condition, while overexpression of only retromer subunits increased EtOH-vescalagin bioactivity in a zinc-deficient condition. Together, these results indicate that EtOH-vescalagin bioactivity begins with extracellular iron chelation and proceeds with intracellular transport of zinc via the retromer complex. More broadly, this is the first report of a bioactive compound to further characterize the poorly understood interaction between zinc metabolism and retromer function.

A novel g-C3N4@La:Y2O3 nanocomposite fluorescence sensor for simultaneous determination and photocatalytic degradation of Ulipristal acetate and Tacrolimus using Doehlert design optimization

Graphitic carbon nitride nanocomposite doped with La:Y2O3 was used as a new sensor for detection and determination of two hazardous active pharmaceutical compounds, Tacrolimus and Ulipristal acetate, by fluorescence spectrophotometry. This novel nanosensor has a fantastic ability to detect these drugs quickly, accurately, and simultaneously. The effect of Tacrolimus on this nanosensor is the quenching of fluorescence emission intensity at the wavelength of 369 nm while the Ulipristal acetate increases the fluorescence emission at 433 nm. Doehlert design was used to optimize the effective factors to reach the maximum fluorescence emission intensity of the nanosensor. Factors including pH, buffer solution concentration and the ratio of La:Y2O3 dopant in the nanocomposite structure. Under optimal conditions, the limit of detection of 17 nM and the limit of qualification of 58 nM for Tacrolimus and the limit of detection of 11 nM and the limit of qualification of 36 nM for Uipristal acetate were obtained with good accuracy. The prepared g-C3N4@La:Y2O3 nanocomposite has a reasonable ability to photodegrade these two drugs. In this regard, the process of photocatalytic degradation of Tacrolimus and Ulipristal acetate was investigated under visible light irradiation. The effect of active species in photocatalytic degradation was evaluated in order to determine the exact degradation mechanism, and the effect of Fenton factors on analytes degradation was also investigated.

Enhancing photocatalytic tetracycline degradation through the fabrication of high surface area CeO2 from a cerium-organic framework.

Water pollution is a global environmental issue, and the presence of pharmaceutical compounds, such as tetracyclines (TCs), in aquatic ecosystems has raised growing concerns due to the potential risks to both the environment and human health. A high surface area CeO2 was prepared via atmospheric thermal treatment of a metal-organic framework of cerium and benzene-1,3,5-tricarboxylate. The effects of calcination temperature on the morphology, structure, light absorption properties and tetracycline removal efficiency were studied. The best activity of the photocatalysts could be achieved when the heat treatment temperature is 300 °C, which enhances the photocatalytic degradation performance towards tetracycline under visible light. The resulting CeO2 particles have high capacity for adsorbing TCs from aqueous solution: 90 mg g-1 for 60 mg L-1 TCs. As a result, 98% of the initial TC can be removed under simulated sunlight irradiation. The cooperation of moderate defect concentration and disordered structure showed tetracycline removal activity about 10 times higher than the initial Ce-MOF. An embryotoxicity assessment on zebrafish revealed that treatment with CeO2 particles significantly decreased the toxicity of TC solutions.

Occurrence, analysis and removal processes of emerging pharmaceuticals from waters for the protection and preservation of a sustainable environment: A review

Pharmaceuticals are a group of man-made commercial and synthetic products and an important mainstay of modern society. However, their presence in aquatic environments is identified as a potential risk, causing harm to living things even at low concentrations ranging from ng L−1 to μg L−1. Due to their pseudo-persistence, bio-accumulation, and low elimination rate by conventional treatments, the majority of these xenobiotic contaminants and their metabolites are routinely released into the environment by sewage treatment plants and last longer in an aquatic environment. This review aims to provide an extensive report and a current state of knowledge concerning various classes of pharmaceutical compounds (PCs). It also discusses the occurrence, the analytical methods for the determination of PC micro-pollutants, and the remediation methods noted in recent literature focusing on the most recent advances. In this context, this review highlights the statistical data regarding the status of PCs in detection, analysis, and removal methods in aqueous media. In addition, this review provides an overview of the conventional and advanced technologies for the removal of PCs from water sources, offering critical comments, and discussing the challenges related to improving existing technologies for sustainable and eco-friendly management of water resources. It likewise emphasizes the importance of the combination of different treatment methods to reach up to 100% PC removal.Finally, gaps in the literature were found, and recommendations for further research were also cited in accordance with this paper. To the best of our knowledge, this review paper is among the rare works that deal with both: i) the analysis of large varieties of PCs in different water matrices, ii) the removal and identification of target analytes and their by-products generated during the elimination processes, and iii) the possible degradation pathways proposed by different studies.

Diuretic and Anti-Hypertensive Activity of Clerodendrum Chinense (OSBECK) MABB. Aqueous Extract in 8% Salt Diet-Induced Hypertensive Rats

Diuresis refers to an increase in the rate of urine flow and sodium excretion from the system via the urine. It is a necessary excretory process that may prove difficult for some disease systems e.g. enlarged prostates. Hypertension occurs as a result of systolic blood pressure higher than 140 mmHg or a diastolic blood pressure higher than 90 mmHg. It is one of the most common chronic diseases affecting more than a billion people worldwide. A high dietary sodium intake is one of the factors associated with the development of hypertension. Clerodendrum chinensis is used by local communities in West Africa for its diuretic and anti-hypertensive properties. We analyze the phytochemical properties of the mixed leaf, root, and stem aqueous extract of the plant and investigate its anti-hypertensive and diuretic activity in Sodium chloride diet-induced hypertensive rats. The anti-hypertensive effect of extract at different concentrations (100, 200, and 300 mg/kg) was studied and compared with a known drug compound; Furosemide. Treated animal urine was analyzed for urinary excretion and diuretic action. The anti-hypertensive effect was statistically significant when compared with the control p < 0.001. The extract at 100mg/kg demonstrated the best systolic and diastolic blood pressure lowering potential as compared to other concentrations. The diuretic action of the plant extract at the lowest dose (100 mg/kg) was high and quantitatively similar to the standard drug. The combined powdered leaf, stem and roots aqueous extract of C. chinense possesses anti-hypertensive and diuretic potential in salt-loaded hypertensive rats.

Multi-wall carbon Nanotube surface-based functional nanoparticles for stimuli-responsive dual pharmaceutical compound delivery

Carbon nanotubes (CNTs) have the potential to serve as delivery systems for medicinal substances and gene treatments, particularly in cancer treatment. Co-delivery of curcumin (CUR) and Methotrexate (MTX) has shown promise in cancer treatment, as it uses fewer drugs and has fewer side effects. This study used MTX-conjugated albumin (BSA)-based nanoparticles (BSA-MTX) to enhance and assess the efficiency of CUR. In-vitro cytotoxicity tests, DLS, TEM, FTIR, UV/Vis, SEM, and DSC studies assessed the formulations' physical and chemical properties. The Proteinase K enzyme was used to severe amidic linkages between MTX and BSA. The findings demonstrated the efficacy of using ƒ-MWCNT-CUR-BSA-MTX as a vehicle for efficient co-delivery of CUR and MTX in cancer treatment. The MTT colorimetric method was used to evaluate the effect of chemical and medicinal compounds. Cell division was studied using the MTT method to investigate the effect of pure MWCNT, pure CUR, MTX-BSA, and ƒ-MWCNT-CUR-MTX-BSA. Studies on cell lines have shown that the combination of curcumin and MTX with CNT can increase and improve the effectiveness of both drugs against cancer. A combination of drugs curcumin and methotrexate simultaneously had a synergistic effect on MCF-7 cells, which indicated that these drugs could potentially be used as a strategy for both prevention and treatment of breast cancer. Also, ƒ-MWCNT-CUR-MTX-BSA was found to have a significant effect on cancer treatment with minimal toxicity compared to pure curcumin, pure MTX-BSA, MTX, and ƒ-MWCNT alone. Unique properties such as a high ratio of specific surface area to volume, high chemical stability, chemical adsorption ability, high capacity of drug and biomolecules of carbon nanotubes, as well as multiple drug loading at the same time The combination of ƒ-MWCNT-CUR-BSA MTX significantly impacts cancer therapy), are desirable as an alternative option for targeted drug delivery and high therapeutic efficiency.

Sequential high-recovery nanofiltration and electrochemical degradation for the treatment of pharmaceutical wastewater

The presence of antibiotics in aquatic ecosystems poses a significant concern for public health and aquatic life, owing to their contribution to the proliferation of antibiotic-resistant bacteria. Effective wastewater treatment strategies are needed to ensure that discharges from pharmaceutical manufacturing facilities are adequately controlled. Here we propose the sequential use of nanofiltration (NF) for concentrating a real pharmaceutical effluent derived from azithromycin production, followed by electrochemical oxidation for thorough removal of pharmaceutical compounds. The NF membrane demonstrated its capability to concentrate wastewater at a high recovery value of 95 % and 99.7 ± 0.2 % rejection to azithromycin. The subsequent electrochemical oxidation process completely degraded azithromycin in the concentrate within 30 min and reduced total organic carbon by 95 % in 180 min. Such integrated treatment approach minimized the electrochemically-treated volume through a low-energy membrane approach and enhanced mass transfer towards the electrodes, therefore driving the process toward zero-liquid-discharge objectives. Overall, our integrated approach holds promises for cost-effective and sustainable removal of trace pharmaceutical compounds and other organics in pharmaceutical wastewater.

#1299 The SGLT2 inhibitor canagliflozin, but not dapagliflozin or empagliflozin, ameliorates vascular calcification in a mouse model of nephrocalcinosis

Abstract Background and Aims Vascular calcification, defined as the abnormal deposition of minerals in blood vessels, is a major cardiovascular risk factor in patients with kidney failure. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, commonly known as gliflozins, are a class of pharmaceutical compounds that have revolutionised the therapeutic management of type 2 diabetes. These drugs target the SGLT2 transporter, increasing glucose elimination through the urine, effectively lowering hyperglycaemia. In addition to their effect on blood sugar control, SGLT2 inhibitors have recently gained attention for potential cardiovascular benefits in patients with type 2 diabetes, chronic kidney disease (CKD) or established cardiovascular disease. Initially thought to be secondary to the promotion of urinary sodium and glucose excretion and weight loss, recent studies have also reported direct effects of gliflozins on the vascular compartment. Given the significant impact of vascular calcification on cardiovascular health in patients with kidney failure, the aim of this study was to investigate whether the three different SGLT2 inhibitors (canagliflozin, empagliflozin and dapagliflozin) could reduce the development of vascular calcification. Method Western blotting was used to investigate SGLT2 expression in mouse and human vascular smooth muscle cells (VSMC) and vascular explants. Human and mouse aortic VSMC and mouse aorta and human epigastric and iliac artery segments were treated with calcification medium supplemented with 1 or 5 µM of gliflozins. A nephrocalcinosis mouse model consisting of 2 weeks of high phosphorus diet (2%) in female DBA/2 mice was used in in vivo experiments. The animals were treated daily with the different gliflozins (3 mg/kg/j) by oral gavage. Calcium deposits were quantified using a quantitative colorimetric assay and alizarin red staining, blood and urine glucose levels were measured using a quantitative colorimetric assay and glomerular filtration rate (GFR) was measured using sinistrin-FITC excretion. Results We observed that SGLT2 is expressed in mouse and human vessels and vascular smooth muscle cells (VSMC). Treatment with canagliflozin, but not dapagliflozin or empagliflozin, reduced calcification in vitro, in human and mouse VSMC and ex vivo, in mouse aorta and human epigastric and iliac artery segments. The high phosphorus diet in mice led to nephrocalcinosis associated with impaired renal function as well as vascular calcification development in the aorta. In this model, although all 3 gliflozins showed efficacy in increasing urinary glucose excretion, blood glucose levels were not affected by gliflozins and renal function was not improved. However, canagliflozin, but not dapagliflozin or empagliflozin, significantly reduced vascular calcification in this nephrocalcinosis mouse model. Conclusion Our study demonstrated that canagliflozin reduces vascular calcification development, highlighting its potential as a therapeutic strategy. This protective effect was found to be drug-dependent and not class-dependent, as the other two SGLT2 inhibitors, dapagliflozin and empagliflozin, showed no significant effect on vascular calcification. Further studies are needed to understand the mechanisms and pathways involved and to determine whether the differential effect of the gliflozins is due to an off-target action of canagliflozin on other SGLT transporters.

Selection of a new aptamer targeting amoxicillin for utilization in a label-free electrochemical biosensor

Pharmaceutical pollution has received considerable attention because of the harmful effects of pharmaceutical compounds on human health, even in trace amounts. Amoxicillin is one of the frequently used antibiotics that was included in the list of emerging water pollutants. Therefore, a highly selective and rapid technique for amoxicillin detection is required. In this work, a new aptamer was selected for amoxicillin and utilized for the development of a label-free electrochemical aptasensor. Aptamer selection was performed using the systematic evolution of ligands by exponential enrichment. The selected aptamer showed good specificity against other antibiotics, including the structurally related antibiotics: ampicillin and ciprofloxacin. Among the selected aptamers, Amx3 exhibited the lowest dissociation constant value of 112.9 nM. An aptasensor was developed by immobilization of thiolated Amx3 aptamer onto gold screen–printed electrodes via self-assembly, which was characterized using cyclic voltammetry and electrochemical impedance spectroscopy. The detection was realized by monitoring the change in the differential pulse voltammetry peak current in the ferro/ferricyanide redox couple upon binding of the aptasensor to amoxicillin. The aptasensor showed very good sensitivity with an ultralow limit of detection of 0.097 nM. When the aptasensor was tested using actual spiked milk samples, excellent recovery percentages were observed. The label-free electrochemical aptasensor developed herein is a promising tool for the selective and sensitive detection of amoxicillin in environmental samples.

Health is the greatest wealth: Quest for a diagnostic check for thermochemistry of pure drug compounds

The development of pharmaceutical formulations and the optimisation of drug synthesis are not possible without knowledge of thermodynamics. At the same time, the quantity and quality of the available data is not at a level that meets modern requirements. A convenient diagnostic approach is desirable to assess the quality of available experimental thermodynamic data of drugs. A comprehensive set of available data on phase transitions of profens family drugs was analysed using new complementary measurements and structure–property correlations. The consistent sets of solid–gas, liquid–gas and solid–liquid phase transitions were evaluated for twelve active pharmaceutical ingredients based on alkanoic acid derivatives and recommended for the calculations of the pharmaceutical processes. A “centerpiece approach” proposed in this work helped to perform the “health check” of the thermochemical data. The evaluated data on the sublimation enthalpies were used to derive the crystal lattice energies of the profens and to correlate the water solubilities with the sublimation vapour pressures and molecular parameters. A “paper-and-pen” approach proposed in this work can be extended to the diagnosis of “sick” or “healthy” thermodynamic data for drugs with a different structure than those studied in this work.

SARS-CoV-2 3CLPro Dihedral Angles Reveal Allosteric Signaling.

In allosteric proteins, identifying the pathways that signals take from allosteric ligand-binding sites to enzyme active sites or binding pockets and interfaces remains challenging. This avenue of research is motivated by the goals of understanding particular macromolecular systems of interest and creating general methods for their study. An especially important protein that is the subject of many investigations in allostery is the SARS-CoV-2 main protease (Mpro), which is necessary for coronaviral replication. It is both an attractive drug target and, due to intense interest in it for the development of pharmaceutical compounds, a gauge of the state-of-the-art approaches in studying protein inhibition. Here we develop a computational method for characterizing protein allostery and use it to study Mpro. We propose a role of the protein's C-terminal tail in allosteric modulation and warn of unintuitive traps that can plague studies of the role of protein dihedrals angles in transmitting allosteric signals.

Interferometric Biosensor for High Sensitive Label-Free Recording of HiPS Cardiomyocytes Contraction in Vitro.

Heart disease remains a leading cause of global mortality, underscoring the need for advanced technologies to study cardiovascular diseases and develop effective treatments. We introduce an innovative interferometric biosensor for high-sensitivity and label-free recording of human induced pluripotent stem cell (hiPSC) cardiomyocyte contraction in vitro. Using an optical cavity, our device captures interference patterns caused by the contraction-induced displacement of a thin flexible membrane. First, we demonstrate the capability to quantify spontaneous contractions and discriminate between contraction and relaxation phases. We calculate a contraction-induced vertical membrane displacement close to 40 nm, which implies a traction stress of 34 ± 4 mN/mm2. Finally, we investigate the effects of a drug compound on contractility amplitude, revealing a significant reduction in contractile forces. The label-free and high-throughput nature of our biosensor may enhance drug screening processes and drug development for cardiac treatments. Our interferometric biosensor offers a novel approach for noninvasive and real-time assessment of cardiomyocyte contraction.

Cryo-EM structures elucidate the multiligand receptor nature of megalin

Megalin (low-density lipoprotein receptor-related protein 2) is a giant glycoprotein of about 600 kDa, mediating the endocytosis of more than 60 ligands, including those of proteins, peptides, and drug compounds [S. Goto, M. Hosojima, H. Kabasawa, A. Saito, Int. J. Biochem. Cell Biol. 157, 106393 (2023)]. It is expressed predominantly in renal proximal tubule epithelial cells, as well as in the brain, lungs, eyes, inner ear, thyroid gland, and placenta. Megalin is also known to mediate the endocytosis of toxic compounds, particularly those that cause renal and hearing disorders [Y. Hori et al., J. Am. Soc. Nephrol. 28, 1783-1791 (2017)]. Genetic megalin deficiency causes Donnai-Barrow syndrome/facio-oculo-acoustico-renal syndrome in humans. However, it is not known how megalin interacts with such a wide variety of ligands and plays pathological roles in various organs. In this study, we elucidated the dimeric architecture of megalin, purified from rat kidneys, using cryoelectron microscopy. The maps revealed the densities of endogenous ligands bound to various regions throughout the dimer, elucidating the multiligand receptor nature of megalin. We also determined the structure of megalin in complex with receptor-associated protein, a molecular chaperone for megalin. The results will facilitate further studies on the pathophysiology of megalin-dependent multiligand endocytic pathways in multiple organs and will also be useful for the development of megalin-targeted drugs for renal and hearing disorders, Alzheimer's disease [B. V. Zlokovic et al., Proc. Natl. Acad. Sci. U.S.A. 93, 4229-4234 (1996)], and other illnesses.

Valorization of coffee husks for the sustainable removal of pharmaceuticals from aqueous solutions

ABSTRACT The contamination of wastewater with pharmaceutical compounds represents a growing environmental challenge due to the inefficiency of conventional treatment systems in removing these emerging contaminants. The coffee husk (CH) is a promising bioadsorbent due to its abundant availability as a byproduct of coffee production. This study focuses on using untreated CH as an adsorbent for removing acetaminophen (ACE) and ciprofloxacin (CIP) while exploring the impact of pyrolysis temperature on the adsorption efficiency of these pharmaceutical compounds. The results reveal an excellent CH performance in removing CIP, achieving 64% removal with a maximum adsorption capacity of 37.00 mg/g. Increasing the pyrolysis temperature during the heat treatment of coffee husks significantly affects the adsorption of CIP. This behavior is primarily due to the reduction in functional groups, which are essential for facilitating the adsorption of CIP onto the resulting biochar. Thermodynamic parameters (ΔH° > 0 and ΔG° > 0) indicate that CIP adsorption on CH is an endothermic and not spontaneous process. The removal efficiency of CIP on CH for synthetic wastewater and urine matrices showed that CH can effectively remove CIP from wastewater. Finally, the reuse of CH as a bioadsorbent highlights its potential to contribute to water quality improvement and environmental preservation.

Integrating single cell expression quantitative trait loci summary statistics to understand complex trait risk genes

Transcriptome-wide association study (TWAS) is a popular approach to dissect the functional consequence of disease associated non-coding variants. Most existing TWAS use bulk tissues and may not have the resolution to reveal cell-type specific target genes. Single-cell expression quantitative trait loci (sc-eQTL) datasets are emerging. The largest bulk- and sc-eQTL datasets are most conveniently available as summary statistics, but have not been broadly utilized in TWAS. Here, we present a new method EXPRESSO (EXpression PREdiction with Summary Statistics Only), to analyze sc-eQTL summary statistics, which also integrates 3D genomic data and epigenomic annotation to prioritize causal variants. EXPRESSO substantially improves existing methods. We apply EXPRESSO to analyze multi-ancestry GWAS datasets for 14 autoimmune diseases. EXPRESSO uniquely identifies 958 novel gene x trait associations, which is 26% more than the second-best method. Among them, 492 are unique to cell type level analysis and missed by TWAS using whole blood. We also develop a cell type aware drug repurposing pipeline, which leverages EXPRESSO results to identify drug compounds that can reverse disease gene expressions in relevant cell types. Our results point to multiple drugs with therapeutic potentials, including metformin for type 1 diabetes, and vitamin K for ulcerative colitis.