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Background: Continuous fermentation offers advantages in improving production efficiency and reducing costs, making it highly competitive for industrial ethanol production. A key requirement for Saccharomyces cerevisiae strains used in this process is their tolerance to high ethanol concentrations, which enables them to adapt to continuous fermentation conditions. To explore how yeast cells respond to varying levels of ethanol stress during fermentation, a two-month continuous fermentation was conducted.

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Characterization of human alcohol dehydrogenase 4 and aldehyde dehydrogenase 2 as enzymes involved in the formation of 5-carboxylpirfenidone, a major metabolite of pirfenidone.

Drug Metab Dispos

January 2025

Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, Japan.

Pirfenidone (PIR) is used in the treatment of idiopathic pulmonary fibrosis. After oral administration, it is metabolized by cytochrome P450 1A2 to 5-hydroxylpirfenidone (5-OH PIR) and further oxidized to 5-carboxylpirfenidone (5-COOH PIR), a major metabolite excreted in the urine (90% of the dose). This study aimed to identify enzymes that catalyze the formation of 5-COOH PIR from 5-OH PIR in the human liver.

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Natural products, particularly plants, remain a vital source of bioactive compounds owing to their unparalleled metabolic diversity across pharmaceuticals, cosmetics, foods, and agriculture. However, this diversity, encompassing not only a multitude of compounds but also their varying chemical and physical properties, presents a challenge in their effective utilization. Targeted analysis of specific metabolites, as well as untargeted approaches covering a wide metabolite range, necessitate optimal extraction solvents tailored to meet diverse requirements.

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An Update on Animal Models of Alcohol-Associated Liver Disease.

Am J Pathol

January 2025

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA; Department of Internal Medicine, Division of Gastroenterology, Hepatology & Mobility, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. Electronic address:

Alcohol-associated liver disease (ALD) is a significant global health concern and a leading cause of liver disease-related deaths. However, the treatment options are limited due to the lack of animal models that accurately replicate ALD pathogenesis. An ideal ALD animal model should have pathological characteristics similar to those of human ALD, with a clear pathological process and ease of drug intervention.

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Background: Adding pembrolizumab, an anti-PD-1 antibody approved for treatment of head and neck squamous cell carcinoma (HNSCC) to neoadjuvant (induction-) chemotherapy utilizing docetaxel and cisplatin (TP) followed by radiotherapy may improve outcome in larynx organ-preservation (LOP) that is investigated in the European Larynx-Organ preservation Study (ELOS). As biomarkers for response to TP and pembrolizumab +TP are missing but may include cytokines, this work aims on determining cytokines potentially linked to outcome as prognostic markers sufficient to predict and/or monitor response to successful LOP.

Methods: Collagenase IV digests were generated from 47 histopathological confirmed HNSCC tumor samples and seeded in 96-well plates containing pembrolizumab, docetaxel, cisplatin either solely or in binary or ternary combination.

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