Publications by authors named "L Tang"

10,935 Publications

Atypical kinetics of cytochrome P450 enzymes in pharmacology and toxicology.

Adv Pharmacol 2022 30;95:131-176. Epub 2022 Jun 30.

Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore. Electronic address:

Atypical kinetics are observed in metabolic reactions catalyzed by cytochrome P450 enzymes (P450). Yet, this phenomenon is regarded as experimental artifacts in some instances despite increasing evidence challenging the assumptions of typical Michaelis-Menten kinetics. As P450 play a major role in the metabolism of a wide range of substrates including drugs and endogenous compounds, it becomes critical to consider the impact of atypical kinetics on the accuracy of estimated kinetic and inhibitory parameters which could affect extrapolation of pharmacological and toxicological implications. The first half of this book chapter will focus on atypical non-Michaelis-Menten kinetics (e.g. substrate inhibition, biphasic and sigmoidal kinetics) as well as proposed underlying mechanisms supported by recent insights in mechanistic enzymology. In particular, substrate inhibition kinetics in P450 as well as concurrent drug inhibition of P450 in the presence of substrate inhibition will be further discussed. Moreover, mounting evidence has revealed that despite the high degree of sequence homology between CYP3A isoforms (i.e. CYP3A4 and CYP3A5), they have the propensities to exhibit vastly different susceptibilities and potencies of mechanism-based inactivation (MBI) with a common drug inhibitor. These experimental observations pertaining to the presence of these atypical isoform- and probe substrate-specific complexities in CYP3A isoforms by several clinically-relevant drugs will therefore be expounded and elaborated upon in the second half of this book chapter.
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http://dx.doi.org/10.1016/bs.apha.2022.05.003DOI Listing
June 2022

Single-atom Ru loaded on layered double hydroxide catalyzes peroxymonosulfate for effective E. coli inactivation via a non-radical pathway: Efficiency and mechanism.

J Hazard Mater 2022 Aug 5;440:129720. Epub 2022 Aug 5.

College of Environmental Science and Engineering, Hunan University, Changsha 410082, PR China; Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha 410082, PR China. Electronic address:

The Fenton-like processes are considered to be one of the most promising strategies for inactivating bacteria due to their capacity to produce reactive oxygen species (ROS). Herein, a catalytic system for efficient inactivation of Escherichia coli (E. coli) was developed by anchoring single-atom Ru on layered double hydroxides (LDH). The Ru/NiFe-LDH catalyst showed excellent performance in activating peroxymonosulfate (PMS) to inactivate E. coli. Under the combined action of the ultra-low concentrations of Ru/NiFe-LDH (40 mg/L) and PMS (5 mg/L), 7 log E. coli can be totally inactivated within 90 s. This was attributed to the combined effect of single-atom Ru adsorption to E. coli and the ROS produced in situ. Mechanism studies indicated that the O with electrophilic properties was the key active species responsible for the rapid inactivation of E. coli. The E. coli inactivation process suggested that the ROS produced first attacked the outer membrane of the cell, then the antioxidant enzymes in the cell were induced, the macromolecule substances were released and mineralized, eventually leading to irreversible cell death. This work firstly loads monoatomic Ru on LDH for bacterial inactivation, providing a feasible method for rapid inactivation of E. coli.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129720DOI Listing
August 2022

selection of a single-strand DNA aptamer targeting the receptor-binding domain of SARS-CoV-2 spike protein.

Nucleosides Nucleotides Nucleic Acids 2022 Aug 10:1-14. Epub 2022 Aug 10.

Department of Neurology, Nanhua Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang, China.

Nucleic acid aptamers are developed from a pool of random oligonucleotide libraries with an selection through systematic evolution of ligands via exponential enrichment (SELEX) process, which are capable of specific and high-affinity molecular binding against targets. The receptor-binding domain (RBD) of spike protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is involved in the early stages of viral infection, is a promising target for aptamer selection. Currently, there are no effective approaches to prevent virus from spreading. In this study, a new ssDNA aptamer RBD/S-A1 binding to the RBD of spike protein from SARS-CoV-2 with high affinity (K=1.74 ± 0.2 nM) and low cross-binding activity was selected and evaluated. Although aptamers targeting the RBD of spike protein from SARS-CoV-2 have been described in a handful of previous studies, the RBD/S-A1 aptamer identified in this work may be considered as a potential supplementation for the current diagnosis and research of coronavirus SARS-CoV-2.
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http://dx.doi.org/10.1080/15257770.2022.2109170DOI Listing
August 2022

β-Cyclodextrin-Grafted Chitosan Enhances Intestinal Drug Absorption and Its Preliminary Mechanism Exploration.

AAPS PharmSciTech 2022 Aug 10;23(6):221. Epub 2022 Aug 10.

College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China.

β-Cyclodextrin (CD) and chitosan (CS) have attracted great attention due to their unique properties and structures. β-Cyclodextrin-grafted chitosan (CD-CS) has been widely used as a drug carrier to prepare nano-formulations for drug delivery. However, few researches have been conducted to investigate the effect of CD-CS as an excipient on cellular uptake and intestinal absorption. Herein, Caco-2 cells were used to investigate the influence of CD-CS on cellular uptake. The MTT assay showed that CD-CS was non-toxic to Caco-2 cells in concentrations ranging from 15.62 to 125 μg/mL. Confocal laser microscopy and flow cytometry measurements indicated that the uptake ability of Caco-2 cells was significantly enhanced after being treated with CD-CS at a concentration of 31.25 μg/mL or incubation for 0.5 h, and the uptake enhancement gradually increased with increasing CD-CS concentration and incubation time. The Caco-2 monolayer cell model and the everted intestinal sac method were employed to preliminarily explore the mechanism of the improved intestinal absorption. The results demonstrated that CD-CS might open the tight junctions and enhance the clathrin-dependent endocytosis, macro-pinocytosis, and phagocytosis of the intestinal epithelial cells. Such findings can serve as references and inspiration for the design of absorption enhancers.
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http://dx.doi.org/10.1208/s12249-022-02380-zDOI Listing
August 2022

Highly Selective Electrocatalytic Oxidation of Amines to Nitriles Assisted by Water Oxidation on Metal-Doped α-Ni(OH).

J Am Chem Soc 2022 Aug 10. Epub 2022 Aug 10.

Key Laboratory of Mesoscopic Chemistry, State Key Laboratory of Analytical Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

Selective oxidation to synthesize nitriles is critical for feedstock manufacturing in the chemical industry. Current strategies typically involve substitutions of alkyl halides with toxic cyanides or the use of strong oxidation reagents (oxygen or peroxide) under ammoxidation/oxidation conditions, setting considerable challenges in energy efficiency, sustainability, and production safety. Herein, we demonstrate a facile, green, and safe electrocatalytic route for selective oxidation of amines to nitriles under ambient conditions, assisted by the anodic water oxidation on metal-doped α-Ni(OH) (a typical oxygen evolution reaction catalyst). By controlling the balance between co-adsorption of the amine molecule and hydroxyls on the catalyst surface, we demonstrate that Mn doping significantly promotes the subsequent chemical oxidation of amines, resulting in Faradaic efficiencies of 96% for nitriles under ≥99% conversion. This anodic oxidation is further coupled with cathodic hydrogen evolution for overall atomic economy and additional green energy production.
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http://dx.doi.org/10.1021/jacs.2c05403DOI Listing
August 2022
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