Endogenous production of prostaglandins has been demonstrated in the cochlea, but no information is available on the distribution of the cyclo-oxygenase (COX) enzymes, or prostanoid receptors in the cochlea. The purpose of the present study was to investigate the localization of the FP, EP(1) and EP(3) prostanoid receptors as well as the COX-1 and COX-2 enzymes in the cochlea of guinea pig and man. Cochleas were processed for immunohistochemistry using routine techniques. Appropriate controls comprised incubation with specific blocking peptides, or incubation without primary antibodies. Both in guinea pig and man the FP prostanoid receptor was abundantly distributed in the cochlea, e.g., in stria vascularis, the spiral ligament, spiral ganglion, and organ of Corti. The immunohistochemical staining of the EP(1) and EP(3) receptors in the same structures was significantly weaker and sometimes lacking altogether (e.g., EP(3) receptor in human cochlea). Weak, but mostly consistent immunostaining of the COX-1 enzyme was found in the cochlear structures. The COX-2 enzyme appeared to be lacking. The abundant distribution of the FP receptor in several important cochlear structures both in guinea pig and man suggests a physiological function for PGF(2alpha) in the cochlea. The COX-1 enzyme seems to be constitutively expressed in the cochlea in contrast to COX-2.
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Int J Antimicrob Agents
January 2025
School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China. Electronic address:
The prevalence of herpes simplex virus type 1 (HSV-1) infection and the emergence of drug-resistant HSV-1 strains posts a significant global health challenge, necessitating the urgent development of effective anti-HSV-1 drugs. As one of the most prevalent molecular chaperones, heat shock protein 90 α (Hsp90α) has been extensively demonstrated to regulate a range of viral infections, thus representing a promising antiviral target. In this study, we identified JD-13 as a novel Hsp90α inhibitor and explored its capability in inhibiting HSV-1 infection.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA.
An understanding of intracellular mechanisms by which fentanyl and other synthetic opioids exert adverse effects on breathing is needed. Using freely moving adult male guinea pigs, we administered the nitric oxide synthase (NOS) inhibitor, L-NAME (N-nitro-L-arginine methyl ester), to determine whether nitrosyl factors, such as nitric oxide and S-nitrosothiols, play a role in fentanyl-induced respiratory depression. Ventilatory parameters were recorded by whole body plethysmography to determine the effects of fentanyl (75 μg/kg, IV) in guinea pigs that had received a prior injection of vehicle (saline), L-NAME or the inactive D-isomer, D-NAME (both at 50 μmol/kg, IV), 15 min beforehand.
View Article and Find Full Text PDFNutrients
January 2025
Section of Preclinical Disease Biology, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark.
Children and teenagers display a distinct metabolic dysfunction-associated steatohepatitis (MASH) phenotype, yet studies of childhood MASH are scarce and validated animal models lacking, limiting the development of treatments. Poor vitamin C (VitC) status may affect MASH progression and often co-occurs with high-fat diets and related metabolic imbalances. As a regulator of DNA methylation, poor VitC status may further contribute to MASH by regulating gene expression This study investigated guinea pigs-a species that, like humans, depends on vitC in the diet-as a model of pediatric MASH, examining the effects of poor VitC status on MASH hallmarks and global DNA methylation levels.
View Article and Find Full Text PDFMolecules
January 2025
Anhui Province Key Laboratory of Bioactive Natural Products, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.
Natural products and botanicals continue to play a very important role in the development of cosmetics worldwide. The chemical constituents of a fine active fraction of the whole plant extract of Walp., and the tyrosinase and matrix metalloproteinase-1 (MMP-1) inhibitory and antioxidant activities of this fraction were investigated.
View Article and Find Full Text PDFPLoS Negl Trop Dis
January 2025
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
Background: Machupo virus (MACV) is a New World mammarenavirus (hereafter referred to as "arenavirus") and the etiologic agent of Bolivian hemorrhagic fever (BHF). No vaccine or antiviral therapy exists for BHF, which causes up to 35% mortality in humans. New World arenaviruses evolve separately in different locations.
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