Current Pharmaceutical Design - Volume 31, Issue 18, 2025
Volume 31, Issue 18, 2025
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A Comparative Review on the Production of Factor VIII in Human and Non-human Hosts
Authors: Amirhossein Ghaemi, Hamid Moghimi and Mohammad-Hossein SarrafzadehHemophilia A (HA) is an inherited condition that is characterized by a lack of coagulation factor VIII (FVIII), which is needed for blood clotting. To produce Recombinant Factor VIII (rFVIII) for treatment, innovative methods are required. This study presents a thorough examination of the genetic engineering and biotechnological methods that are essential for the production of this complex process. Multiple host cells, such as animal, microbial, and human cell lines, are examined. Cultivating genetically modified cells enables the production of rFVIII, with further changes after protein synthesis, such as glycosylation, taking place in eukaryotic cells to guarantee correct folding. The extraction and purification of rFVIII require advanced methods, including affinity chromatography, to improve the purity of the protein. The purified protein undergoes rigorous quality control, which includes Sodium Dodecyl-Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE) analysis, to assess its identity, purity, and functioning. The scalability of this approach allows for the synthesis of significant amounts of rFVIII for therapeutic purposes. Optimization strategies include modifying B-Domain-Deleted (BDD) FVIII, including introns in FVIII Complementary DNA (cDNA) sequences to boost synthesis and storage, and making changes to chaperone-binding areas to optimize protein release. Furthermore, the search for a modified form of FVIII that has a longer duration of action in the body shows potential for enhancing the effectiveness of synthetic FVIII and progressing the treatment of hemophilia A. Future research should focus on improving the treatment of hemophilia A by developing a variant of FVIII that has increased stability and reduced immunogenicity.
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Metabolic Tagging Technology of Exosomes-An Updated Review
Exosomes are small extracellular vesicles secreted by various cell types, playing a crucial role in intercellular communication by carrying proteins, lipids, and nucleic acids, thus holding significant potential in diagnostics and therapeutics. Accurate labeling of exosomes is vital for studying their biogenesis, trafficking, and functional properties, enabling precise tracking and manipulation. This review examines current labeling techniques, including metabolic glycan labeling, chemical tagging, membrane fluorescent dyes, bio-conjugation, non-covalent labeling, and cell-engineering approaches. Each method is analyzed for its efficiency, specificity, and practicality, with attention to potential artifacts and challenges. Advancements in these techniques are essential for improving our understanding of exosome biology and developing exosome-based diagnostic and therapeutic strategies, providing researchers with valuable insights into state-of-the-art techniques and their applications in exosome research.
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Prospective Utilization of Nanocarriers Loaded with Drug Combination for Treating Alzheimer's Disease
Authors: Saif Ahmad Khan, Zufika Qamar, Aashish Rohilla, Pirthi Pal Singh, Suhel Parvez, Sanjula Baboota and Javed AliAlzheimer's disease (AD) is a debilitating condition that significantly affects the elderly. Early diagnosis is not only critical for improving patient outcomes but also directly influences the success of emerging therapeutic interventions. A therapeutic strategy targeting only one pathogenic mechanism is unlikely to be very effective, as there is increasing evidence that AD does not have a single pathogenic cause. Therefore, combining medications or developing therapies that address multiple pathways may be beneficial. Most clinical trials can be classified under added therapy rather than combination therapy. Effective treatment of AD likely requires targeting multiple mechanisms, such as amyloid-beta (Aβ) and tau pathology. However, many medications face challenges, including poor solubility, low permeability, and the inability to cross the blood-brain barrier (BBB). This is where nanocarriers come into play, as they can be loaded with these medications to facilitate targeted drug delivery. This approach enhances the pharmacokinetic profile of drugs in both the blood and the brain. Therefore, this paper provides a concise overview of the use of various nanocarriers loaded with drug combinations for treating AD.
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Virtual Screening Identifies Inhibitors of SARS-CoV-2 Main Protease through Pharmacophore and Similarity Approaches
Authors: Mohammad A. Khanfar and Mohammad SalehIntroductionThe emergence of SARS-CoV-2 and the COVID-19 pandemic highlighted the urgent need for novel antiviral therapies. The main protease (Mpro) of SARS-CoV-2 is a key enzyme in viral replication and a promising therapeutic target.
MethodsThis study employed virtual screening approaches to identify potential Mpro inhibitors, leveraging both structure- and ligand-based methods.
ResultsTwo optimum pharmacophore models were built from hundreds of crystallographic structures of Mpro, validated through ROC curve analysis and Dynophores dynamic simulations. These models captured ≈ 60K hits from six diverse compound libraries made of more than 3 million compounds. Additionally, a ligand-based similarity search using ROCS software identified 1024 potential hits based on shape and atom-based comparisons with co-crystallized ligands. Subsequent molecular docking and filtering based on physicochemical properties and structural diversity yielded 16 and 6 hits from structure- and ligand-based screening, respectively. Molecular dynamics simulations were conducted on the top-scoring hits to assess their binding stability within the Mpro active site. SCR00943 demonstrated stable binding, interacting favorably with key residues, including the catalytic dyad, resulting in a binding affinity of -61.2 kcal/mol.
ConclusionThis virtual screening campaign identified promising Mpro inhibitors, showcasing the potential of computational approaches to accelerate drug discovery efforts against COVID-19.
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Unraveling the Therapeutic Potential of Sophora flavescens Aiton in Myocardial Infarction: An Integrative Approach Combining Bioinformatics, Network Pharmacology, and Experimental Validation
Authors: Zhongbai Zhang, Yang Tong, Hongwei Xie, Mengting Jiang, Yanchun Li and Chun LiangAimsThis study aims to elucidate the relationship between potential MI targets and SFA’s mechanism of action, providing a theoretical basis for clinical development of new drugs.
BackgroundMyocardial infarction (MI) has been identified as one of the major cardiovascular diseases with adverse consequences. Sophora flavescens Aiton (SFA) is indicated for the therapeutic treatment of MI. However, there is no systematic research on the new therapeutic targets for MI and the exact action mechanism of SFA.
ObjectivesThis study explores the potential mechanisms of SFA in treating MI by integrating bioinformatics, network pharmacology analyses and experimental verification.
MethodsNew MI targets were predicted using bioinformatics techniques. Network pharmacology and molecular docking jointly served for predicting the key targets and underlying mechanisms of SFA. A machine learning model was developed to identify the core MI targets. Subsequently, H9c2 cardiomyocytes hypoxia model was established for experimental verification.
Results140 active components were ascertained in SFA and 59 differentially expressed genes (DEGs) were screened for MI. Eighty-seven shared genes were obtained by WGCAN. Eighty proteins and 413 interactions were identified by PPI network. After building the machine model, three core targets were identified (STAT1, TNFRSF1A and MCL1). According to in vitro experiments, SFA exerts a protective effect relying on three core targets and biological processes, including cell viability, the inflammatory response, and antiapoptotic effects, etc.
ConclusionThis study finds new core targets for MI and the therapeutic activity of SFA against MI, of which the experimental verification provides valuable insights into the molecular mechanisms underlying SFA’s efficacy in MI treatment and paves the way for targeted drug development strategies.
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Volumes & issues
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Volume 31 (2025)
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Volume (2025)
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Volume 30 (2024)
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Volume 29 (2023)
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Volume 28 (2022)
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Volume 27 (2021)
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Volume 26 (2020)
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Volume 25 (2019)
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Volume 24 (2018)
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Volume 23 (2017)
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Volume 22 (2016)
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Volume 21 (2015)
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Volume 20 (2014)
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Volume 19 (2013)
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Volume 18 (2012)
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Volume 17 (2011)
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Volume 16 (2010)
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Volume 15 (2009)
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Volume 14 (2008)
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Volume 13 (2007)
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Volume 12 (2006)
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Volume 11 (2005)
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Volume 10 (2004)
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Volume 9 (2003)
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Volume 8 (2002)
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Volume 7 (2001)
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Volume 6 (2000)
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