Importance Of The Field: Liver is the major body reservoir for enzymes involved in the metabolism of endogenous and xenobiotic compounds. Recently, it has been shown that hepatocytes release exosome-like vesicles to the extracellular medium, and the proteomic characterization of these hepatocyte-secreted exosomes has revealed the presence of several of these enzymes on them.
Areas Covered In This Review: A systematic bibliographic search focused on two related aspects: i) xenobiotic-metabolizing enzymes that have been detected in microvesicles (MVs); and ii) MVs that are in the blood stream or secreted by cell types with clear interactions with this fluid.
What The Reader Will Gain: A discussion of these hepatocyte-secreted vesicles along with other MVs as enzymatic carriers in the context of extrahepatic drug-metabolizing systems.
Take Home Message: The contribution of many tissues including the liver to the MV plasma population is supported by several reports. On the other hand, many enzymes involved in the metabolism of drugs have been detected in MVs. Together, these observations support a role of hepatic-MVs in spreading the liver metabolizing activities through the body contributing in this manner to extrahepatic drug metabolism systems what could be relevant for body homeostasis and pharmaceutical interests.
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http://dx.doi.org/10.1517/17425251003614766 | DOI Listing |
Diabetes Obes Metab
January 2025
Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, China.
Metabolic syndrome-related diseases frequently involve disturbances in skeletal muscle lipid metabolism. The accumulation of lipid metabolites, lipid-induced mitochondrial stress in skeletal muscle cells, as well as the inflammation of adjacent adipose tissue, are associated with the development of insulin resistance and metabolic dysfunction. Consequently, when antidiabetic medications are used to treat various chronic conditions related to hyperglycaemia, the impact on skeletal muscle lipid metabolism should not be overlooked.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.
The rise of resistance to antiretroviral drugs due to mutations in human immunodeficiency virus-1 (HIV-1) protease is a major obstacle to effective treatment. These mutations alter the drug-binding pocket of the protease and reduce the drug efficacy by disrupting interactions with inhibitors. Traditional methods, such as biochemical assays and structural biology, are crucial for studying enzyme function but are time-consuming and labor-intensive.
View Article and Find Full Text PDFEmergencias
December 2024
Servicio de Análisis Clínicos, Hospital Universitario Santa Lucía, Cartagena, Murcia, España.
Objective: To analyze the usefulness of mean mid-regional pro-adrenomedullin (MR-proADM) level to stratify risk in emergency department patients with solid tumors attended for febrile neutropenia after chemotherapy. To compare risk prediction with MR-proADM to that of conventional biomarkers and scores on the Multinational Association for Supportive Care in Cancer (MASCC) score.
Methods: Prospective observational cohort study enrolling patients with solid tumors who developed febrile neutropenia after chemotherapy.
J Bone Oncol
February 2025
Unit of Oral Medicine and Dentistry for Frail Patients, Department of Rehabilitation, Fragility, and Continuity of Care, Regional Center for Research and Care of MRONJ, University Hospital Palermo, Palermo, PA, Italy.
Background: Low-doses of bone modifying agents (LD-BMAs) compared to those used to treat bone metastases are used in breast or prostate cancer patients on adjuvant endocrine therapy to prevent Cancer Treatment Induced Bone Loss (CTIBL). Their use is associated with an increased risk of developing Medication-Related Osteonecrosis of the Jaw (MRONJ). However, there is not clarity about strategies aimed to minimize the MRONJ risk in cancer patients at different conditions as low- vs high-doses of BMA.
View Article and Find Full Text PDFDrug Des Devel Ther
January 2025
Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
Introduction: The mechanism of remimazolam, a benzodiazepine that activates γ-aminobutyric acid a (GABAa) receptors, in cerebral ischemia/reperfusion (I/R) injury is not well understood. Therefore, we explored whether remimazolam activates protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β)/nuclear factor erythroid 2-related factor 2 (NRF2) to attenuate brain I/R injury in transcerebral I/R-injured rats and transoxygenic glucose deprivation/reperfusion (OGD/R)-injured SY5Y cells.
Material And Methods: Remimazolam was added at the beginning of cell and rat reperfusion, and the PI3K/AKT inhibitor LY294002 was added to inhibit the AKT/GSK-3β/NRF2 pathway 24 h before cellular OGD/R treatment and 30 min before rat brain I/R treatment.
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