We describe a case of apparent mineralocorticoid excess (AME) secondary to posaconazole therapy and suggest the biochemical mechanism. Clinical and laboratory investigation confirmed 11β-hydroxysteroid dehydrogenase inhibition and withholding therapy led to a resolution of all clinical and laboratory abnormalities. Posaconazole was later restarted at a lower dose and prevented recurrence of this syndrome. Additional studies are necessary to determine the frequency of posaconazole-induced AME and whether other azole antifungals can be associated with this phenomenon.
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http://dx.doi.org/10.1128/AAC.00760-17 | DOI Listing |
Oper Neurosurg (Hagerstown)
November 2024
Department of Neurosurgery, University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Background And Objectives: IDH-wildtype glioblastoma multiforme (GBM) and grade 4 IDH-mutant astrocytoma are challenging to manage in oncology. This study explores the contrast between gross total resection (GTR) and supratotal resection (SupTR) for IDH-wildtype GBM and grade 4 IDH-mutant astrocytoma, aiming to summarize their influence on crucial clinical outcomes.
Methods: This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.
Science
January 2025
Redox and Metalloprotein Research Group, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
In the ancient microbial Wood-Ljungdahl pathway, carbon dioxide (CO) is fixed in a multistep process that ends with acetyl-coenzyme A (acetyl-CoA) synthesis at the bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS). In this work, we present structural snapshots of the CODH/ACS from the gas-converting acetogen , characterizing the molecular choreography of the overall reaction, including electron transfer to the CODH for CO reduction, methyl transfer from the corrinoid iron-sulfur protein (CoFeSP) partner to the ACS active site, and acetyl-CoA production. Unlike CODH, the multidomain ACS undergoes large conformational changes to form an internal connection to the CODH active site, accommodate the CoFeSP for methyl transfer, and protect the reaction intermediates.
View Article and Find Full Text PDFPLoS One
January 2025
Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Casablanca, Morocco.
Cognitive dysfunction in Alzheimer's disease results from a complex interplay of various pathological processes, including the dysregulation of key enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase B (MAO-B). This study proposes and designs a series of novel molecules derived from 8-hydroxyquinoline (Azo-8HQ) as potential multi-target lead candidates for treating AD. An exhaustive in silico analysis was conducted, encompassing docking studies, ADMET analysis, density functional theory (DFT) studies, molecular dynamics simulations, and subsequent MM-GBSA calculations to examine the pharmacological potential of these molecules with the specific targets of interest.
View Article and Find Full Text PDFBiochemistry
January 2025
School of Biology, Biomedical Sciences Research Complex, University of St Andrews, St Andrews KY16 9ST, United Kingdom.
The enzyme 4-oxo-l-proline reductase (BDH2) has recently been identified in humans. BDH2, previously thought to be a cytosolic ()-3-hydroxybutyrate dehydrogenase, actually catalyzes the NADH-dependent reduction of 4-oxo-l-proline to -4-hydroxy-l-proline, a compound with known anticancer activity. Here we provide an initial mechanistic characterization of the BDH2-catalyzed reaction.
View Article and Find Full Text PDFGut Microbes
December 2025
Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Ischemia-reperfusion injury (IRI) is a major obstacle in liver transplantation, especially with steatotic donor livers. Dysbiosis of the gut microbiota has been implicated in modulating IRI, and plays a pivotal role in regulating host inflammatory and immune responses, but its specific role in liver transplantation IRI remains unclear. This study explores whether can mitigate IRI and its underlying mechanisms.
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