Prediction for Plasma Trough Concentration and Optimal Dosing of Imatinib under Multiple Clinical Situations Using Physiologically Based Pharmacokinetic Modeling.

(1) Purpose: This study aimed to develop a physiologically based pharmacokinetic (PBPK) model to predict the trough concentration (C trough) of imatinib (IMA) at steady state in patients and to explore the role of free concentration (f up), α1-acid glycoprotein (AGP) level, and organic cation transporter 1 (OCT1) activity/expression in clinical efficacy. (2) Methods: The population PBPK model was built using physicochemical and biochemical properties, metabolizing and transporting kinetics, tissue distribution, and human physiological parameters. (3) Results: The PBPK model successfully predicted the C trough of IMA administered alone in chronic phase (CP) and accelerated phase (AP) patients, the C trough of IMA co-administered with six modulators, and C trough in CP patients with hepatic impairment. Most of the ratios between predicted and observed data are within 0.70-1.30. Additionally, the recommendations for dosing adjustments for IMA have been given under multiple clinical uses. The sensitivity analysis showed that exploring the f up and AGP level had a significant influence on the plasma C trough of IMA. Meanwhile, the simulations also revealed that OCT1 activity and expression had a significant impact on the intracellular C trough of IMA. (4) Conclusion: The current PBPK model can accurately predict the IMA C trough and provide appropriate dosing adjustment recommendations in a variety of clinical situations.

Advances in Fluorescent Sensing Carbon Dots: An Account of Food Analysis.

Illuminating the use of nanomaterials, carbon quantum dots (CQDs) have transfigured the food safety arena because of their bright luminescence, optical properties, low toxicity, and enhanced biocompatibility. Therefore, fluorescent resonance energy transfer, photoinduced electron transfer, and an internal filtering effect mechanism allow precise detection of food additives, heavy metal ions, pathogenic bacteria, veterinary drug residues, and food nutrients. In this review, we describe the primal mechanism of CQD-based fluorescence sensors for food safety inspection. This is an abridged description of the nanodesign and future perspectives of more advanced CQD-based sensors for food safety analysis.

Red ginseng extract improves skeletal muscle energy metabolism and mitochondrial function in chronic fatigue mice.

Background: Skeletal muscles are organs with high energy requirements, especially during vigorous exercise. Adequate mitochondrial function is essential to meet the high energy needs of skeletal muscle cells. Recent studies have reported that red ginseng can significantly improve chronic fatigue; however, the specific mechanism of action is still not clear. Methods: A chronic fatigue syndrome mouse model was developed using C57BL/6J mice through long-term compound stimulation of stress factors. Following this, the animals were orally administered 200, 400, or 600 mg/kg red ginseng extracts for 28 days. Skeletal muscle lactate acid, serum lactate dehydrogenase, urea concentrations, ATP level, mitochondrial membrane potential, activities of Na+-K+-ATPase and cytochrome c oxidase were determined using assay kits or an automatic biochemical analyser detection system. Skeletal muscle mitochondria morphology was observed using electron microscopy and the expression of p-AMPK, PGC-1α, ACO2 and complex I in skeletal muscle protein was determined by western blotting. Results: Oral administration of 400 or 600 mg/kg red ginseng extract in mice with chronic fatigue reduced lactic acid, lactate dehydrogenase and urea, rescued the density and morphology of skeletal muscle mitochondria, increased the activities of Na+-K+-ATPase and cytochrome c oxidase, and activated the AMPK/PGC-1α cascade pathway, resulting in improved skeletal muscle mitochondrial function by restoring ATP level, mitochondrial membrane potential, complex I and mitochondrial biogenesis. Conclusion: The anti-fatigue effects of red ginseng are partly related to its potent mitochondrial improving activity, including decreasing mitochondrial swelling and mitochondrial membrane permeability, increasing mitochondrial biogenesis, thus ameliorating mitochondrial dysfunction.