New bis-pyridinium oxime reactivators 6 with CH(2)O(CH(2))(2)OCH(2) and CH(2)O(CH(2))(4)OCH(2) linkers between the two pyridinium rings were designed and synthesized. In the in vitro test of their potency to reactivate AChE inhibited by organophosphorus agents at 5 x 10(-3)M concentration, the reactivation ability of 1,2-dimethoxy-ethylene-bis-N,N'-4-pyridiumaldoxime dichloride (6a) was 63% for housefly (HF) AChE inhibited by diisopropyl fluorophosphates (DFP), 51% for bovine red blood cell (RBC) AChE inhibited by DFP, 67% for HF-AChE inhibited by paraoxon, and 81% for RBC-AChE inhibited by paraoxon. Except in the case of DFP-inhibited HF AChE test of 2-PAM, the activities of 6a are much higher than the activities of 2-PAM and HI-6 which are AChE reactivators currently in use.
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http://dx.doi.org/10.1016/j.bmc.2007.08.056 | DOI Listing |
Mol Neurobiol
January 2025
Guizhou Key Laboratory of Brain Science, Zunyi Medical University, Xinpu New District Campus No. 1 Street, Zunyi, 563000, China.
Previous studies have shown that astrocyte activation in the anterior cingulate cortex (ACC), accompanied by upregulation of the astrocyte marker S100 calcium binding protein B (S100B), contributes to comorbid anxiety in chronic inflammatory pain (CIP), but the exact downstream mechanism is still being explored. The receptor for advanced glycation end-products (RAGE) plays an important role in chronic pain and psychosis by recognizing ligands, including S100B. Therefore, we speculate that RAGE may be involved in astrocyte regulation of the comorbidity between CIP and anxiety by recognizing S100B.
View Article and Find Full Text PDFLancet Neurol
February 2025
Department of Neurology, International University of Health and Welfare, Narita, Japan.
Background: Evidence from preclinical studies suggests that IL-6 signalling has the potential to modulate immunopathogenic mechanisms upstream of autoantibody effector mechanisms in patients with generalised myasthenia gravis. We aimed to assess the safety and efficacy of satralizumab, a humanised monoclonal antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis.
Methods: LUMINESCE was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study at 105 sites, including hospitals and clinics, globally.
Phytomedicine
January 2025
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Changle West Street 15, Xi'an, Shaanxi, 710032, China. Electronic address:
Background: The pathogenesis of neuropathic pain is complex and lacks effective clinical treatment strategies. Medical plants and herbal extracts from traditional Chinese medicine with multi-target comprehensive effects have attracted great attention from scientists.
Purpose: To investigate the pharmacological active components and mechanism underlying the anti-neuralgia effect of classic analgesic formulas Duhuo Jisheng Mixture (DJM).
Bioorg Chem
January 2025
Laboratorio de Peptidos Bioactivos, Department of Organic Chemistry, Faculty of Biochemistry and Biological Sciences, National University of the Littoral, Ciudad Universitaria UNL, 3000 Santa Fe, Argentina; National Scientific and Technical Research Council (CONICET), Ministry of Science, Technology and Innovation, Godoy Cruz 2290, Ciudad de Buenos Aires, Argentina. Electronic address:
The search for novel cholinesterase inhibitors is essential for advancing treatments for neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we employed the Rosetta pepspec module, originally developed for designing peptides targeting protein-protein interactions, to design de novo peptides targeting the peripheral aromatic site (PAS) of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). A total of nine peptides were designed for human AChE (hAChE), T.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Joseph Maxwell Cleland Atlanta VA Medical Center, Decatur, GA 30033, USA; Department of Orthopaedics, Emory Musculoskeletal Institute, Emory University, Atlanta, GA 30329, USA. Electronic address:
There is currently no cure or disease-modifying treatment for post-traumatic osteoarthritis (PTOA). This study aims to assess the efficacy of dimethyl fumarate (DMF), a US-FDA approved drug for multiple sclerosis, as a treatment for PTOA. PTOA was induced in male Lewis rats by medial meniscal transection (MMT) surgery, and DMF was intra-articularly administered once, one week following surgery.
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