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Accumulating evidence indicates that toll-like receptor 4 (TLR4) plays a critical role in promoting adaptive immune responses and are definitively involved in the expansion and maintenance of the neuropathic pain. Though the application of docking in virtual-screening methods to drug discovery has some challenge, it allows directed and meaningful design of drugs for a target protein; which can lead to low costing approaches with shortcuts; resulting in evolution and discovery of promising new drugs. Nevertheless, in parallel with virtual screening methods, attendant developments in cell culture and studies must be achieved. In the present paper, we aimed to discover new drugs that have the ability to bind and inhibit TLR4 functions. So, after using the Pathway studio to investigate the biological pathways and protein interaction maps between TLR4 and neuropathy, we reported the application of the affinity-based approach of different pharmaceuticals; these agents contained all of the approved drugs; which could bind to Toll-like receptor 4 in blind high-throughput screening. Our results demonstrated that among the primary list of 1945 retrieved compounds, 39 approved compounds could be the right candidate to perform a biological test in different and conditions and as a lead for further neurophysiological and neuropathological studies and treatment of neuropathic pain.
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http://dx.doi.org/10.22037/ijpr.2019.2394 | DOI Listing |
Drug Saf
September 2025
School of Health Policy and Management, York University, 4700 Keele St., Toronto, ON, M3J 1P3, Canada.
Introduction: At times it is necessary to withdraw drugs after they have been approved because of lack of effectiveness or safety concerns. Health Canada does not keep a list of withdrawn drugs.
Objective: The aim of this study was to generate a list of all drugs approved since 1990 and subsequently withdrawn from the Canadian market for safety or effectiveness reasons until the end of 2024.
Anal Bioanal Chem
September 2025
GuangDong Engineering Technology Research Center of Antibody Drug and Immunoassay, Department of Biological Sciences and Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Illicit drug abuse poses a significant global threat to public health and social security, highlighting the urgent need for rapid, sensitive, and versatile detection technologies. To address the limitations of traditional chromatographic techniques-such as high costs and slow response times-and the drawbacks of conventional immunochromatographic sensors (ICS), including low sensitivity and non-intuitive signal outputs, a fluorescence-quenching ICS (FQICS) was developed. This sensor leverages fluorescence resonance energy transfer (FRET) between aggregation-induced emission fluorescent microspheres (AIEFMs) and gold nanoparticles (AuNPs).
View Article and Find Full Text PDFOncogene
September 2025
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Resistance to platinum-based drugs and PARP inhibitors (PARPi) is the leading cause of treatment failure in epithelial ovarian cancer (EOC). This study aimed to identify resistance mechanisms shared by both. Using bioinformatic analyses, EOC tissues, primary tumor cells and organoids, and chemoresistant cell lines, we identified lymphoid enhancer-binding factor 1 (LEF1) as a candidate, whose expression was increased in both platinum-resistant and PARPi-resistant tumors.
View Article and Find Full Text PDFBMJ Open
September 2025
Department of Gastroenterology, Hepatology, Infectious Diseases and Intoxication, University Hospital Heidelberg, Heidelberg, Germany.
Introduction: Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade.
View Article and Find Full Text PDFCell Genom
September 2025
Department of Genetics, Stanford University, Stanford, CA, USA. Electronic address:
Non-olfactory G-protein-coupled receptors (GPCRs) regulate vital physiological functions and are targets for ∼34% of US Food and Drug Administration (FDA)-approved drugs. While small-molecule-activated GPCRs are well studied, there is growing interest in peptide GPCRs, particularly the melanocortin-4 receptor (MC4R), a key regulator of energy balance and appetite. Activation of MC4R by β-melanocyte-stimulating hormone (β-MSH) reduces food intake, and pathway dysfunction leads to obesity.
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