Pharmaceutical Compounds Research Articles

Conjugation of Doxorubicin and Carbon-based-nanostructures for Drug Delivery against HT-29 Colon Cancer Cells.

A drug delivery system is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. Such systems release the drugs at specific amounts in a specific site. The carbon based-nanomaterials have been actively used as drug carriers to treat various cancer. This study aimed to evaluate the cytotoxic effects of DOX-GO, DOX-OMC and DOXCNT in colon cancer cells (HT29). We reported platforms based on graphene oxide (GO), ordered mesoporous carbon (OMC) and carbon nanotubes (CNT) to conjugate with doxorubicin (DOX). The conjugation of DOX with carbon nanomaterial was investigated by UV-Vis spectroscopy, field emission scanning electron microscope (FE-SEM) and cyclic voltammetry (CV) methods. We showed that graphene oxide was a highly efficient matrix. Efficient loading of DOX, 89%, 78%, and 73.5% at pH 7.0 was seen onto GO, OMC and CNT, respectively. Upon pH 4. 0 after 15 h, 69%, 61% and 61% of DOX could be released from the DOX-GO, DOX-OMC and DOX-CNT, respectively, which illustrated the significant benefits of the developed approach for carbon nanomaterial applications. In vitro cytotoxicity analysis showed greater cytotoxicity of DOX/GO, DOX/OMC and DOX/CNT in comparison with GO, OMC and CNT against HT29 colon cancer cells with cell viability of 22%, 40% and 44% after 48 h for DOX-GO, DOX-OMC and DOX-CNT, respectively. The nanohybrids based on DOX-carbon nanomaterial, because of their unique physical and chemical properties, will remarkably enhance the anti-cancer activity.

Scaffold Hopping Method for Design and Development of Potential Allosteric AKT Inhibitors.

Targeting AKT is a practical strategy for cancer therapy in many cancer types. Targeted inhibitors of AKT are attractive solutions for inhibiting the interconnected signaling pathways, like PI3K/Akt/mTOR. Allosteric inhibitors are more desirable among different classes of AKT inhibitors as they could be more specific with fewer off-target proteins. In this study, a ligand/structure-based pipeline was developed to design new allosteric AKT inhibitors by employing the core hopping method. Triciribine, a traditional allosteric AKT inhibitor was used as the template, and the FDA-approved kinase inhibitors for cancer treatment were considered as the cores. The allosteric site in the crystal structure of AKT1 was used to screen the designed compounds. The results were further evaluated using molecular docking, ADME/T analysis, molecular dynamics (MD) simulation, and binding free energy calculations. The outcomes introduced 24 newly designed inhibitors, amongst which three compounds C6, C20, and C16 showed remarkable binding affinity to AKT1. While the docking scores for triciribine was around -8.6 kcal/mol, the docking scores of these compounds were about -11 to -13 kcal/mol. The MD results indicated that designed compounds target the essential residues of the PH domain and kinase domain of AKT, such as Trp80, Thr211, Tyr272, Asp274, and Asp292. Scaffold hopping is a tremendous tool for designing novel anti-cancer agents by improving already known and potential drug compounds. The designed compounds are worth to be examined by experimental investigation in vitro and in vivo.

Dual Role of Ibuprofen and Indomethacin in Promoting Peripheral Nerve Regeneration In Vitro.

Peripheral nerve injuries (PNI) can result in significant losses of motor and sensory function. Although peripheral nerves have an innate capacity for regeneration, restoration of function after severe injury remains suboptimal. The gold standard for peripheral nerve regeneration (PNR) is autologous nerve transplantation, but this method is limited by the generation of an additional surgical site, donor-site morbidity, and neuroma formation at the site of harvest. Although targeted drug compounds have the potential to influence axonal growth, there are no drugs currently approved to treat PNI. Therefore, we propose to repurpose commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) to enhance PNR, facilitating easier clinical translation. Additionally, calcium signaling plays a crucial role in neuronal connectivity and regeneration, but how specific drugs modulate this process remains unclear. We developed an in vitro hollow channel collagen gel platform that successfully supports neuronal network formation. This study evaluated the effects of commonly used NSAIDs, namely ibuprofen and indomethacin, in our in vitro model of axonal growth, regeneration, and calcium signaling as potential treatments for PNI. Our results demonstrate enhanced axonal growth and regrowth with both ibuprofen and indomethacin, suggesting a positive influence on PNR. Further, these drugs showed enhanced calcium signaling dynamics, which we posit is a crucial aspect for nerve repair. Taken together, these findings highlight the potential of ibuprofen and indomethacin to be used as treatment options for PNI, given their dual capability to promote axonal growth and enhance calcium signaling.

LC enantioseparation of active pharmaceutical ingredients using rationally synthesized CDRs and chiral molecules with high molar absorptivity.

The synthesis of optically active compounds requires determination of ee, er, and enantiomeric purity. The aim of the present paper is to review the synthesis of several chiral derivatizing reagents (CDRs) in a rational manner, which were successful for the separation and isolation of enantiomers of a variety of active pharmaceutical ingredients and other important and useful racemates. Besides, the application of (i) certain enantiomerically pure amines, either directly or by incorporating each of them as chiral auxiliary in difluorodinitrobenzene or cyanuric chloride moieties to construct the CDR, (ii) (S)-ketoprofen and (S)-levofloxacin as chiral platforms, and (iii) a few isothiocyanates, have been suitably included. Attention is drawn to the use of water micellar mobile phase as the "green" RP-HPLC method and the use of simple achiral derivatization with ninhydrin, particularly. Synthesis of CDRs and their application for enantioseparation of racemates and detagging of certain chromophoric reagent components for obtaining native enantiomers are other interesting features included herein. The methods can be easily used to determine and control enantiomeric purity with advantages over a variety of commercial chiral phases. This comprehensive review not only highlights innovative methodologies for enantioseparation but also underscores their practical applications in controlling and ensuring the enantiomeric purity of pharmaceutical compounds.

Identification of key signaling pathways and novel computational drug target for oral cancer, metabolic disorders and periodontal disease

AimDue to conventional endocrinological methods, there is presently no shared work available, and no therapeutic options have been demonstrated in oral cancer (OC) and periodontal disease (PD), type 2 diabetes (T2D), and obese patients. The aim of this study is to determine the similar molecular pathways and potential therapeutic targets in PD, OC, T2D, and obesity that may be used to anticipate the progression of the disease. MethodsFour Gene Expression Omnibus (GEO) microarray datasets (GSE29221, GSE15773, GSE16134, and GSE13601) are used for finding differentially expressed genes (DEGs) for T2D, obese, and PD patients with OC in order to explore comparable pathways and therapeutic medications. Gene ontology (GO) and pathway analysis were used to investigate the functional annotations of the genes. The hub genes were then identified using protein-protein interaction (PPI) networks, and the most significant PPI components were evaluated using a clustering approach. ResultsThese three gene expression-based datasets yielded a total of seven common DEGs. According to the GO annotation, the majority of the DEGs were connected with the microtubule cytoskeleton structure involved in mitosis. The KEGG pathways revealed that the concordant DEGs are connected to the cell cycle and progesterone-mediated oocyte maturation. Based on topological analysis of the PPI network, major hub genes (CCNB1, BUB1, TTK, PLAT, and AHNAK) and notable modules were revealed. This work additionally identified the connection of TF genes and miRNAs with common DEGs, as well as TF activity. ConclusionPredictive drug analysis yielded concordant drug compounds involved with T2D, OC, PD, and obesity disorder, which might be beneficial for examining the diagnosis, treatment, and prognosis of metabolic disorders and Oral cancer.

Environmental Stress-Induced Alterations in Embryo Developmental Morphokinetics.

The association between embryo morphokinetics and its developmental competence is well documented. For instance, early cleaved embryos are more competent in developing to blastocysts, whereas the proportion of abnormally cleaved embryos that further developed to blastocysts is low. Numerous factors, such as the parental age, lifestyle, health, and smoking habits have been reported to affect the embryo morphokinetics and, consequently, its development. However, less is known about the effect of environmental stressors on embryo morphokinetics. The current review discusses the effect of the most concerning environmental stressors on embryo morphokinetics. These stresses include heat stress and human-made chemicals such as phthalates (e.g., bis-(2-ethylhexyl phthalate, dibutyl phthalate, dimethyl phthalate, and their primary metabolites), herbicides (e.g., diaminochlorotriazine, the primary metabolite of atrazine), pharmaceutical compounds (e.g., carbamazepine, nocodazole) and pro-oxidant agents (cumene hydroperoxide, Triton X-100), as well as naturally occurring toxins such as mycotoxin (e.g., aflatoxin B1 and its metabolite, and ochratoxin A). In addition, this review discusses the effect of ionizing or non-ionizing radiation and viral infections (e.g., SARS-CoV-2, papillomavirus). Finally, it points out some potential mechanisms that underlie the impairment of embryo morphokinetics, and it suggests protective compounds, mainly the supplementation of antioxidants to improve the morphokinetics, and consequently, the embryo developmental competence.

Removal of Ibuprofen from Aqueous Solutions by Using Graphene Oxide@MgO

In this study, a new composite adsorbent, namely magnesium oxide modified graphene oxide (hereafter abbreviated GO@MgO), was prepared for the removal of Ibuprofen (IBU), a non-steroidal anti-inflammatory drug (NSAID) compound. Graphene oxide was modified with MgO to improve its properties. Several factors important for the evolution of the adsorption process were investigated, such as the dose of the adsorbent, the pH, and the initial IBU content, as well as the duration of the procedure and temperature. According to the results obtained, it was found that at pH 3.0 ± 0.1, by applying 0.5 g/L GO@MgO to 100 mg/L IBU, more than 80% was removed, reaching 96.3% with the addition of 1.5 g/L adsorbent in 24 h. After 30 min, the equilibrium was reached (77% removal) by adding 0.5 g/L of GO@MgO. This study proves that GO@MgO is capable of economical and efficient adsorption. The IBU kinetic data followed the pseudo-second-order kinetic model. Langmuir and Freundlich isotherm models were used to interpret the adsorption, but the Freundlich model described the adsorption method more accurately. The positive values of ΔH0 (14.465 kJ/mol) confirm the endothermic nature of the adsorption. Due to the increase of ΔG0 values with temperature, the adsorption of IBU on GO@MgO is considered to be spontaneous.

SMCVdb: a database of experimental cellular toxicity information for drug candidate molecules.

Many drug discovery exercises fail because small molecules that are effective inhibitors of target proteins exhibit high cellular toxicity. Early and effective assessment of toxicity and pharmacokinetics is essential to accelerate the drug discovery process. Conventional methods for toxicity profiling, including in vitro and in vivo assays, are laborious and resource-intensive. In response, we introduce the Small Molecule Cell Viability Database (SMCVdb), a comprehensive resource containing toxicity data for over 24 000 compounds obtained through high-content imaging (HCI). SMCVdb seamlessly integrates chemical descriptions and molecular weight data, offering researchers a holistic platform for toxicity data aiding compound prioritization and selection based on biological and economic considerations. Data collection for SMCVdb involved a systematic approach combining HCI toxicity profiling with chemical information and quality control measures ensured data accuracy and consistency. The user-friendly web interface of SMCVdb provides multiple search and filter options, allowing users to query the database based on compound name, molecular weight range, or viability percentage. SMCVdb empowers users to access toxicity profiles, molecular weights, compound names, and chemical descriptions, facilitating the exploration of relationships between compound properties and their effects on cell viability. In summary, the database provides experimentally derived cellular toxicity information for over 24 000 drug candidate molecules to academic researchers, and pharmaceutical companies. The SMCVdb will keep growing and will prove to be a pivotal resource to expedite research in drug discovery and compound evaluation. Database URL: http://smcvdb.rcb.ac.in:4321/.

Breaking resistance: in silico subtractive and comparative genomics approaches for drug targeting in Bacteroides fragilis.

The purpose of this study was to identify potential novel drug targets for Bacteroides fragilis infections using bioinformatics techniques, such as subtractive and comparative genomics. Bacteroides fragilis is a frequently isolated anaerobic pathogen, particularly in the human digestive tract, where its pathogenesis and persistence are influenced by various virulence factors. By understanding these factors, the study aims to explore alternative therapeutic strategies and provide insights for the development of treatments against B. fragilis infections, particularly as alternatives to antibiotic therapy. A comparative subtractive genomic analysis was performed against the B. fragilis (strain CL07T12C05) to identify unique drug targets. The analysis includes the identification of non-paralogous, non-homologous, essential, and drug target like proteins. Moreover, a comprehensive structural analysis of the protein was conducted utilizing structure modeling and validation techniques, along with network topology analysis. Furthermore, a library comprising approximately 9000 FDA-approved compounds accessible in the DrugBank database was employed to conduct virtual screenings for compounds effective against the designated drug target. The top shortlisted compounds were further studied by employing MD simulations using GROMACS. This approach was chosen due to the established safety, efficacy, pharmacokinetics, and toxicity profiles of these compounds. As a result, B. fragilis (strain CL07T12C05) was found to possess 4595 proteins. Among these, 3518 were identified as non-homologous, 1508 deemed essential for bacterial viability, 348 exhibited drug-like properties, 203 were implicated in virulence, and 135 displayed antibiotic resistance. Following an extensive literature review, the protein Sialic acid O-acetyltransferase was chosen through a hierarchical shortlisting process as a potential therapeutic target. The ongoing research facilitated the repurposing of drug compounds: DB12411, DB02112, DB03591, and DB00192, as cost-effective medications against B. fragilis related infections. MD simulations analysis showed that DB12411 may be a potential drug candidate against Sialic acid O-acetyltransferase from B. fragilis. Through subtractive and comparative genomic analysis, Sialic acid O-acetyltransferase was identified as a promising drug target against Bacteroides fragilis. The findings indicate that compounds targeting this protein could potentially be effective in treating B. fragilis infections. However, further experimental validation is required to conclusively confirm their efficacy.

Reconfiguring the Escherichia coli Electron Transport Chain to Enhance trans-2-Decenoic Acid Production.

trans-2-Decenoic acid is a pivotal α,β-medium-chain unsaturated fatty acid that serves as an essential intermediary in the synthesis of 10-hydroxy-2-decenoic acid and various pharmaceutical compounds. Biosynthesis yield of trans-2-decenoic acid by decanoic acid has significantly improved in recent years; however, the oxidative stress of Escherichia coli at high fatty acid concentrations restricts the conversion rate. Here, we introduced a combination of rational design and metabolic rewiring of the E. coli electron transport chain (ETC) to improve trans-2-decenoic acid production. Overexpressing ubiquinone (UbQ) biosynthesis genes enhanced the expression of ETC complex III: UbQ to reduce reactive oxygen species (ROS) accumulation. Furthermore, applying rotenone to inhibit ETC complex I improved the electron transfer efficiency of complex II. The integration of Vitamin B5 and B2 into the fermentation process increased the activities of fatty acyl-CoA synthetase (MaMACS) and fatty acyl-CoA dehydrogenase (PpfadE). Finally, the constructed E. coli BL21(DE3)(ΔfadBJR/pCDFDuet-1-PpfadE-MaMACS/pRSFDuet-1-sumo-CtydiI-ubiI) strain exhibited a 51.50% decrease in ROS and a 93.33% enhancement in trans-2-decenoic acid yield, reaching 1.45 g/L after 66 h, which is the highest yield reported for flask fermentation. This study reports the feasibility of rewiring the ETC regulation and energy metabolism to improve α,β-UCA biosynthesis efficiency.

Cocrystal screening of benznidazole based on electronic transition, molecular reactivity, hydrogen bonding, and stability.

Screening of cocrystals of active pharmaceutical ingredients is important in the development of pharmaceutical compounds because it improves bioavailability, stability, solubility, and many other physicochemical properties. In this work, quantum chemical calculations were utilized for the computational evaluation of the cocrystal screening of benznidazole (BZN) API via hydrogen bonding with four coformers (maleic acid, malonic acid, oxalic acid, and salicylic acid), and they contain carboxylic groups. The nitrogen of the imidazole ring in benznidazole and the carboxylic group of the coformer form a hetero-synthon connected by a strong hydrogen bond. The strength of the hydrogen bonding interaction O-H…N was measured using various tools. It was found that in comparison to BZN cocrystals with malonic acid, oxalic acid, and salicylic acid, the O-H…N interaction in the BZN-maleic acid cocrystal had higher interaction energy, indicating it had stronger hydrogen bonding. The strength of the hydrogen bond O-H…N for synthons was discovered to be more beneficial than the C-H…O interaction, as confirmed by ESP analysis. The BZN-salicylic acid cocrystal was found to be more reactive and polarizable, whereas the BZN-malonic acid cocrystal was more stable. Cocrystals of benznidazole exhibited better physicochemical characteristics than API benznidazole, as indicated by electron transition properties between the most significant orbitals. The computational evaluation for the screening of benznidazole cocrystals was performed in Gaussian 16 software using density functional theory (DFT) with the hybrid functional B3LYP and the basis set 6-311 + + G(d,p). The UV-Vis absorption spectrum in solvent water was analyzed using the TD-DFT/6-311 + + G(d,p) method to determine the influence of the solvent in cocrystals using a polarizable continuum model. The strength of the hydrogen bonding interactions O-H…N in each of those mentioned cocrystals was used to screen the cocrystals using tools such as thermodynamic probability, ESP analysis, QTAIM analysis, and NBO analysis. The pairing energy of interaction was measured by determining H-bond donor ( ) and H-bond acceptor ) parameters for hydrogen bonds from maxima and minima on the ESP surface. GaussView 06 software was used to create, visualize, and plot the optimized structure of the cocrystal and HOMO-LUMO orbitals. The AIMALL (10.05.04) software package generated the molecular graph for intra- and intermolecular interactions. The RDG-scatter plot, MEP map, and ELF plot were rendered from Multiwfn 8.0 and VMD 1.9.1 software.

Melt-extruded formulations of fenofibrate with various grades of hydrogenated phospholipid exhibit promising in-vitro biopharmaceutical behavior

In the current study, it was demonstrated that three commercially available grades of hydrogenated phospholipids (HPL) differing in their content of phosphatidylcholine may be used as components for hot melt-extruded binary (HPL as sole excipient) or ternary (in combination with copovidone) solid dispersions of fenofibrate (FEN) at mass fractions between 0.5 and 20% (ternary) or 80% (binary). X-ray powder diffraction indicated complete conversion of crystalline fenofibrate into the amorphous state by hot melt extrusion for all ternary blends. In contrast, both the binary blends (HPL- and copovidone-based) contained minor remaining crystallites. Irrespectively, all solid dispersions induced during dissolution studies a supersaturated state of FEN, where the ternary ASDs showed enhanced and more complete release of FEN as compared to the binary blends and, even more pronounced, in comparison to the marketed micronized and nano-milled formulations. In terms of the cumulated amount permeated, there were marginal differences between the various formulations when combined dissolution/permeation was done using FeSSIF as donor medium; with FaSSIF as donor medium, the binary HPL-ASD containing the grade with the highest phosphatidylcholine fraction performed best in terms of permeation, even significantly better than the marketed nano-crystal formulation. Otherwise, no significant differences were seen between the various grades of HPL when FEN dissolution and permeation were analyzed for ternary solid dispersions. In conclusion, the in-vitro biopharmaceutical behaviour of hydrogenated phospholipid-containing blends manufactured by hot melt extrusion appears promising. They can be a viable formulation option for poorly water-soluble and lipophilic drug compounds like FEN.

Pharmaceuticals removal from hospital wastewater by fluidized aerobic bioreactor in combination with tubesettler

Micropollutants, especially pharmaceutical compounds, are of significant concern owing to their ngL− 1 to µgL− 1 concentration, making them difficult for conventional treatment plants to remove from wastewater. Despite municipal wastewater treatment plant being a primary source of these compounds to be released into the wastewater, on comparison little attention has been given to hospital wastewater. The major focus of studies addressing pharmaceutical compounds is based on synthetic wastewater. This study addresses this research gap by treating wastewater to remove micropollutants (Fluvastatin, ketoprofen, paracetamol, ciprofloxacin, carbamazepine, sulfamethoxazole, and lorazepam) by employing a fluidized aerobic bioreactor. Tubesettler was attached to a fluidized-bed bioreactor to see if it could be used as a polishing unit rather than a secondary clarifier. The environmental risk from the effluent discharge into the environment was assessed regarding the hazard quotient. The paracetamol and ketoprofen were removed at an efficiency of 51% and 60%, respectively, followed by carbamazepine at 50%, ciprofloxacin at 40%, fluvastatin at 47%, sulfamethoxazole at 31%, and lorazepam at 20%. The influent posed moderate environmental risk with (Hazard Quotient) HQ > 0.5, while in effluent the risk was reduced with HQ value 0.4. For effluent from fluidized bed bioreactors (HQ 0.13) and tube setters (HQ 0.15). The associated tube settler was found suitable for polishing units with additional removal efficiencies of 15–43% for all the targeted pharmaceutical compounds. Further studies are required to explore disinfectants’ effect on the reactor’s biodegradation efficiency. Also, further modification and a hybrid version of the fluidized bed bioreactor can be used.

Enhancing Albendazole Delivery Using Mesoporous Santa Barbara Amorphous‐15: A Box‐Behnken Design Study

Over 70% of pharmaceutical compounds face the challenge of poor water solubility, which impacts on their bioavailability. This study focuses on the use of Santa Barbara Amorphous‐15 (SBA‐15) mesoporous silica material as carrier, which is synthesized and characterized to address this limitation. Albendazole (ABZ), an antiparasitic agent with low water solubility, serves as model drug. A Box‐Behnken design (BBD) is used to investigate the impact of immersion method loading factors (temperature: 25–50 °C, time: 24–72 h, and SBA‐15 amount: 83.2–252.0 mg) on drug loading percentage (DL%) and dissolution efficiency (DE%). The ABZ loading is confirmed by elemental analysis and Fourier transform infrared spectroscopy. Stability tests are performed, comparing drug dissolution profiles and X‐ray diffraction patterns immediately after loading and after 12 months of storage at 25 °C and 60% relative humidity (RH%). DL% varies between 18% and 36% (w/w), showing that the amount of SBA‐15 is the most significant factor on DL%. The lowest SBA‐15 amount yielded the highest DL%. Regarding DE%, all the design samples exhibit higher values than pure ABZ, with the amount of SBA‐15 being the primary influencing factor. Several samples from the BBD show high DE% (>70%) corresponding to high DL% values. After 12 months, most samples maintain similar dissolution profiles, demonstrating the good stability of the drug in the carrier over time. This study provides valuable insights into optimizing the loading process to enhance ABZ solubility and long‐term stability using mesoporous SBA‐15.

An in vitro platform for the enzymatic characterization of the rhomboid protease RHBDL4.

Rhomboid proteases are ubiquitous intramembrane serine proteases that can cleave transmembrane substrates within lipid bilayers. They exhibit many and diverse functions, such as but not limited to, growth factor signaling, immune and inflammatory response, protein quality control, and parasitic invasion. Human rhomboid protease RHBDL4 has been demonstrated to play a critical role in removing misfolded proteins from the Endoplasmic Reticulum and is implicated in severe diseases such as various cancers and Alzheimer's disease. Therefore, RHBDL4 is expected to constitute an important therapeutic target for such devastating diseases. Despite its critical role in many biological processes, the enzymatic properties of RHBDL4 remain largely unknown. To enable a comprehensive characterization of RHBDL4's kinetics, catalytic parameters, substrate specificity, and binding modality we expressed and purified recombinant RHBDL4, and employed it in a Förster Resonance Energy Transfer-based cleavage assay. Until now, kinetic studies have been limited mostly to bacterial rhomboid proteases. Our in vitro platform offers a new method for studying RHBDL4's enzymatic function and substrate preferences. Furthermore, we developed and tested potential inhibitors using our assay and successfully identifying peptidyl α-ketoamide inhibitors of RHBDL4 that are highly effective against recombinant RHBDL4. We utilize ensemble docking and molecular dynamics (MD) simulations to explore the binding modality of substrate-derived peptides bound to RHBDL4. Our analysis focused on key interactions and dynamic movements within RHBDL4's active site that contributed to binding stability, offering valuable insights for optimizing the non-prime side of RHBDL4 ketoamide inhibitors. In summary, our study offers fundamental insights into RHBDL4's catalytic activities and substrate preferences, laying the foundation for downstream applications such as drug inhibitor screenings and structure-function studies, which will enable the identification of lead drug compounds for RHBDL4.

Gene expression differences associated with alcohol use disorder in human brain.

Excessive alcohol consumption is a leading cause of preventable death worldwide. To improve understanding of neurobiological mechanisms associated with alcohol use disorder (AUD) in humans, we compared gene expression data from deceased individuals with and without AUD across two addiction-relevant brain regions: the nucleus accumbens (NAc) and dorsolateral prefrontal cortex (DLPFC). Bulk RNA-seq data from NAc and DLPFC (N ≥50 with AUD, ≥46 non-AUD) were analyzed for differential gene expression using modified negative binomial regression adjusting for technical and biological covariates. The region-level results were meta-analyzed with those from an independent dataset (NNAc = 28 AUD, 29 non-AUD; NPFC = 66 AUD, 77 non-AUD). We further tested for heritability enrichment of AUD-related phenotypes, gene co-expression networks, gene ontology enrichment, and drug repurposing. We identified 176 differentially expressed genes (DEGs; 12 in both regions, 78 in NAc only, 86 in DLPFC only) for AUD in our new dataset. After meta-analyzing with published data, we identified 476 AUD DEGs (25 in both regions, 29 in NAc only, 422 in PFC only). Of these DEGs, 17 were significant when looked up in GWAS of problematic alcohol use or drinks per week. Gene co-expression analysis showed both concordant and unique gene networks across brain regions. We also identified 29 and 436 drug compounds that target DEGs from our meta-analysis in NAc and PFC, respectively. This study identified robust AUD-associated DEGs, contributing novel neurobiological insights into AUD and highlighting genes targeted by known drug compounds, generating opportunity for drug repurposing to treat AUD.

Pharmaceutical Wastewater and Sludge Valorization: A Review on Innovative Strategies for Energy Recovery and Waste Treatment

Currently, a large amount of pharmaceutical waste (PW) and its derivatives are being produced and, in some cases, inadequate management or treatment practices are applied. In this regard, this research explores the adoption of several alternatives to deal with these problems, including biocarbon within the framework of the circular economy. Photocatalytic nanomaterials have been also extensively discussed as a feasible way to remove pharmaceutical compounds in wastewater. Although there are existing reports in this area, this document provides a detailed study of the synthesis process, experimental conditions, the integration of photocatalysts, and their impact on enhancing photocatalytic efficiency. Additionally, the low cost and ease of fabrication of lab-scale microbial fuel cells (MFCs) are thoroughly examined. This innovative technology not only facilitates the degradation of hazardous compounds in wastewater but also harnesses their energy to generate electricity simultaneously. The aforementioned approaches are covered and discussed in detail by documenting interesting recently published research and case studies worldwide. Furthermore, this research is of significant importance because it addresses the valorization of PW by generating valuable by-products, such as H2 and O2, which can occur simultaneously during the photodegradation process, contributing to more sustainable industrial practices and clean energy technologies.

Innovation of Lipid‐Based Nanoparticles: the Design and Applications in the Cardiovascular Disease Management

AbstractCardiovascular diseases (CVDs) represent a prominent cause of global mortality, posing considerable challenges for traditional therapies due to their limited bioavailability and notable side effects. Similarly, imaging diagnostic modalities have inherent limitations. Lipid‐based nanoparticles (LNPs) have emerged as promising tools for precise diagnosis and treatment of CVDs, owing to their exceptional biocompatibility, modifiability, and compatibility with payloads, showcasing extensive potential for diverse applications. LNPs excel in encapsulating diverse drug compounds, protecting against drug degradation, and enabling targeted drug delivery at lesion sites. Moreover, in conjunction with multimodal imaging techniques, LNPs enhance the accuracy of diagnosing and treating CVDs. Nevertheless, this field lacks comprehensive and up‐to‐date reviews. Therefore, this review delineates the foundational principles governing nano‐strategies employing LNP systems for addressing CVDs. It explores recent advancements in utilizing these strategies for diagnosing and treating different cardiovascular conditions while also pointing out their limitations. This review aims to provide insights for future research endeavors.

Polymeric additives to sustain the dissolution enhancement of niclosamide nanocrystals formed via freeze drying

Nanocrystal formation is an effective method to increase the dissolution of drug compounds with limited solubilities. Niclosamide is a sparingly soluble compound, and it also tends to become an even less soluble monohydrate upon contact with dissolution media. We utilized freeze drying to successfully generate niclosamide nanocrystals, which displayed rapid initial dissolution but also suffered from the expedited formation of the monohydrate. Therefore, we explored some pharmaceutically acceptable polymers to overcome the unfavorable anhydrate-to-monohydrate transformation. Poly(vinylpyrrolidone-co-vinyl acetate) (Mw 45000–70000) effectively retarded the monohydrate formation in a concentration-dependent manner, and 3–5% in the drug-polymer mixture was enough to sustain the enhanced initial dissolution of niclosamide nanocrystals. The area under the dissolution curve tripled due to the combined effect of the nanocrystal formation and the monohydrate inhibition. This study demonstrates an example of the one-pot freeze-drying process to form an optimized drug-additive mixture to realize the full potential of drug nanocrystals.

Photocatalytic degradation of acetaminophen, ciprofloxacin and amoxicillin using UV/ZnO in a suspended photocatalytic reactor

Abstract This study aims at evaluation of the photocatalytic degradation of pharmaceutical compounds acetaminophen (ATM), ciprofloxacin (CXN), and amoxicillin (AMX) using zinc oxide (ZnO) nano powder as a photocatalyst in a suspended reactor using a 16 W UV lamp. Operating parameters pH, catalyst dosage, and pollutant concentration were optimised for a working volume of 1.3 litres of model pharmaceutical compounds. The photo degradation efficiency was 95% at pH 6 after 5 h of irradiation for ATM, 98% at pH 6 after 2 h of irradiation for CXN, and 100% at pH 10 after 3 h of irradiation for AMX. The reaction kinetics for the degradation of ATM, CXN, and AMX followed pseudo-first order with the rate constants in the order of kAMX>kCXN>kATM 0.0321 min−1, 0.0232 min−1 and 0.0070 min−1 respectively. TOC (Total Organic Carbon) analysis was carried out for the model compounds, among which compound amoxicillin was found having a higher rate constant of about 0.0108 min−1, which is 1.2 times higher than ciprofloxacin and 2.5 times greater than acetaminophen. This study concludes that ZnO nano powder is efficient in degrading the model pharmaceutical compounds ATM, CXN, and AMX by utilising the UV light, which is evident from the results of the UV–vis spectrophotometer, HPLC analysis, and mineralisation study. In addition, ANOVA was performed on the results obtained from optimisation studies, which confirms the substantial influence of the operating parameters on the degradation of the compounds.