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Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.
Nat Commun
January 2025
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.
View Article and Find Full Text PDFSynthesis of a di-O-acylated deoxynojirimycin (DNJ) derivative and evaluation of its antibacterial and antibiofilm activity against Staphylococcus aureus and Stenotrophomonas maltophilia.
Carbohydr Res
January 2025
Department of Chemical Sciences, University of Naples Federico II, Naples, I-80126, Italy.
Herein we report the synthesis of a novel di-O-acylated DNJ derivative, conceived to study whether iminosugar derivatization with a lipophilic acyl moiety could positively affect its antibacterial properties. The well-known PS-TPP/I/ImH activating system was used to readily install the acyl chains on the iminosugar, leading to the desired compound in high yield. Biological assays revealed that a di-O-lauroyl DNJ derivative enhanced the antibacterial effect of gentamicin and amikacin against S.
View Article and Find Full Text PDFAdipoRon's Impact on Alzheimer's Disease-A Systematic Review and Meta-Analysis.
Int J Mol Sci
January 2025
Autonomic Nervous System Center, School of Philosophy and Sciences, São Paulo State University, Marília 17525-902, São Paulo, Brazil.
Alzheimer's disease (AD) remains a leading cause of cognitive decline and mortality worldwide, characterized by neurodegeneration, synaptic deficiencies, and neuroinflammation. Despite advancements in early detection, diagnosis, and treatment, AD presents substantial challenges due to its complex pathology, heterogeneity, and the limited efficacy of current therapies. Consequently, there is a pressing need for novel therapeutic agents to target the multifaceted aspects of AD pathology, enhance current treatments, and minimize adverse effects.
View Article and Find Full Text PDFThe Rise of Fentanyl: Molecular Aspects and Forensic Investigations.
Int J Mol Sci
January 2025
Legal Medicine, Department of Medical, Surgical and Advanced Technologies "G.F. Ingrassia", University of Catania, 95123 Catania, Italy.
Fentanyl is a synthetic opioid widely used for its potent analgesic effects in chronic pain management and intraoperative anesthesia. However, its high potency, low cost, and accessibility have also made it a significant drug of abuse, contributing to the global opioid epidemic. This review aims to provide an in-depth analysis of fentanyl's medical applications, pharmacokinetics, metabolism, and pharmacogenetics while examining its adverse effects and forensic implications.
View Article and Find Full Text PDFIn situ forming gels as subcutaneous delivery systems of curcumin and piperine.
Sci Rep
January 2025
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121, Ferrara, Italy.
In this study an in situ forming gel for curcumin and piperine delivery is investigated as a long-lasting strategy in the local treatment of inflammatory and degenerative joint disease, such as osteoarthritis and rheumatoid arthritis. Particularly glyceryl monooleate, in association with phosphatidylcholine and ethanol, were employed. Different ratios between excipients were tested, with the aim to obtain a liquid form suitable for subcutaneous injection, gaining a semisolid consistency in contact with biological fluids.
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