Article
Microbiology
Saurav Howlader, Min-Jung Kim, M. Rasheduzzaman Jony, Nguyen Phuoc Long, Yong-Soon Cho, Dong-Hyun Kim, Jae-Gook Shin
Summary: This study characterized the metabolic pathways and enzymes responsible for the metabolism of clofazimine in human liver microsomes. Eight metabolites, including oxidative metabolites, glucuronide conjugates, and sulfate conjugates, were identified. CYP1A2 and CYP3A were involved in the formation of oxidative metabolites, while UGT1A1, 1A3, 1A4, 1A9, and 2B4 were involved in the formation of glucuronide conjugates of oxidative metabolites of clofazimine.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Oncology
Dong Gui Hu, Shashikanth Marri, Julie-Ann Hulin, Ross A. McKinnon, Peter Mackenzie, Robyn Meech
Summary: The UDP-glycosyltransferase (UGT) superfamily plays a critical role in the metabolism of anticancer drugs and pro/anti-cancer molecules. A comprehensive analysis of 10,069 tumors from 33 different types of cancers revealed widespread somatic mutations in UGT genes, which may impact the ability of cancer cells to metabolize drugs and endobiotics involved in cancer signaling pathways.
Article
Biochemistry & Molecular Biology
Jiri Vrba, Barbora Papouskova, Katerina Lnenickova, Pavel Kosina, Vladimir Kren, Jitka Ulrichova
Summary: 2,3-Dehydrosilybin A and B are preferentially metabolized through conjugation reactions, with several human UGT and SULT enzymes potentially playing a role in these conjugations.
Review
Pharmacology & Pharmacy
John O. Miners, Thomas M. Polasek, Julie-Ann Hulin, Andrew Rowland, Robyn Meech
Summary: Drug-drug interactions (DDIs) involving glucuronidated drugs have been historically overlooked but are clinically significant and can result in altered exposure of these drugs. This review examines the mechanisms, scope, and aetiology of these DDIs, including the inhibition and induction of UDPglucuronosyltransferase (UGT) enzymes and the potential involvement of drug transporters. It highlights the common occurrence and importance of UGT induction as a DDI mechanism and the need for dose individualisation due to clinically relevant DDIs. Comprehensive reaction phenotyping studies and rigorous assessment of new chemical entities with significant glucuronidation are recommended for early-stage drug development.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Sangeeta Shrestha Sharma, Shishir Sharma, Jie Zhao, Matthias Bureik
Summary: Cytochromes P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) are important human drug metabolizing enzymes, and this study explores their mutual interactions. The study used recombinant co-expression of 19 human UGTs with CYP enzymes in yeast and found that UGT co-expression had a significant effect on P450 activity in most cases. The study also observed varying degrees of influence of CYP co-expression on UGT activity.
Article
Pharmacology & Pharmacy
Xiaoyu Wang, Zhe Wang, Xiaoyu Fan, Mingrui Yan, Lili Jiang, Yangliu Xia, Jun Cao, Yong Liu
Summary: Ibrutinib demonstrated strong inhibition on UGT enzymes, especially UGT1A1, UGT1A3, and UGT1A7, suggesting a potential risk for drug-drug interactions. In contrast, acalabrutinib exhibited weak inhibition on UGT enzymes, indicating a lower risk for causing clinically significant UGT-mediated DDIs.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Florian Gabel, Volodya Hovhannisyan, Virginie Andry, Yannick Goumon
Summary: This study found that female mice have weaker morphine antinociception and faster induction of tolerance than males. Additionally, female mice have higher levels of M3G in the blood and pain-related CNS regions than male mice, while lower levels of morphine were observed in these regions. These differences are mainly attributed to morphine metabolism in pain-related CNS regions.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Toxicology
Xiaoyu Wang, Zhe Wang, Zhen Wang, Xiuyuan Chen, Hang Yin, Lili Jiang, Jun Cao, Yong Liu
Summary: Belinostat is a pan-HDAC inhibitor approved for PTCL treatment, showing inhibition on UGTs activities, particularly UGT1A3 and UGT1A1, leading to potential DDIs. Intravenous infusion of Belinostat may significantly increase AUC of co-administered drugs primarily cleared by UGT1A3 or UGT1A1, while oral administration of Belinostat is unlikely to cause significant DDIs through glucuronidation inhibition.
TOXICOLOGY LETTERS
(2021)
Review
Pharmacology & Pharmacy
William A. Murphy, Jeffry Adiwidjaja, Noora Sjostedt, Kyunghee Yang, James J. Beaudoin, Jessica Spires, Scott Q. Siler, Sibylle Neuhoff, Kim L. R. Brouwer
Summary: This review provides a detailed summary of the impact of nonalcoholic fatty liver disease (NAFLD) on drug absorption, distribution, metabolism, and excretion (ADME) in the human body. The use of in vitro-to-in vivo extrapolation coupled with physiologically based pharmacokinetic and pharmacodynamic (IVIVE-PBPK/PD) modeling and quantitative systems pharmacology/toxicology (QSP/QST) modeling offers opportunities to optimize drug predictions and reduce clinical studies in patients with NAFLD. However, there are limitations and knowledge gaps in understanding the pharmacokinetic alterations at different stages of NAFLD and the use of these methodologies.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Dmitri R. Davydov, Bikash Dangi, Guihua Yue, Deepak S. Ahire, Bhagwat Prasad, Victor G. Zgoda
Summary: This study used chemical crosslinking mass spectrometry (CXMS) to explore the protein-protein interactions of alcohol-induced cytochrome P450 2E1 (CYP2E1) in human liver microsomes. By analyzing the crosslinked complexes, it was found that CYP2E1 is tightly integrated with other drug-metabolizing enzymes through protein-protein interactions.
Article
Pharmacology & Pharmacy
Ria Park, Eun Jeong Park, Yong-Yeon Cho, Joo Young Lee, Han Chang Kang, Im-Sook Song, Hye Suk Lee
Summary: Tetrahydrofurofuranoid lignans, such as eudesmin and magnolin, were found to inhibit UGT1A1 and UGT1A3 activities in human liver microsomes. This suggests a potential for drug-drug interactions involving these lignans with UGT1A1 and UGT1A3 substrates in vivo.
Article
Pharmacology & Pharmacy
Xin Lv, Zhe Wang, Zhen Wang, Hang Yin, Yangliu Xia, Lili Jiang, Yong Liu
Summary: Ripretinib is the first FDA-approved fourth-line therapy for advanced gastrointestinal stromal tumor (GIST). It has been shown to inhibit the activity of several UDP-glucosyltransferase (UGTs) enzymes. However, its effects on different UGT isoforms and potential drug-drug interactions (DDIs) are still unclear.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Oncology
Dong Gui Hu, Shashikanth Marri, Peter Mackenzie, Julie-Ann Hulin, Ross A. McKinnon, Robyn Meech
Summary: The study comprehensively assessed the expression profiles of UGT genes and their impact on patient survival in nearly 30 different cancers primarily derived from non-drug-metabolizing organs. The results showed widespread expression of UGT genes in cancers, indicating the potential of specific UGT genes to serve as prognostic biomarkers or therapeutic targets in cancers.
Article
Environmental Sciences
Chengcheng Fan, Zexiao Cui, Tianying Yang, Lili Sun, Chuanwang Cao
Summary: UDP-glucuronosyltransferases (UGTs) play a role in detoxification of pesticides in insects by transforming different compounds. The study identified four UGT genes in Chironomus kiiensis and found that they are involved in the metabolism of pesticides, especially in larval and adult stages. The expression and activity of UGTs increased significantly when exposed to sublethal concentrations of carbaryl, deltamethrin, and phoxim. Specifically, the CkUGT308N1 gene was found to contribute to pesticide metabolism and provide a scientific basis for evaluating water pollution caused by pesticides.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Biology
Yifan Tu, Lu Wang, Yi Rong, Vincent Tam, Taijun Yin, Song Gao, Rashim Singh, Ming Hu
Summary: Research has shown that the distribution of orally administered phenolic drugs is mediated by intestinal glucuronidation and hepatic recycling, revealing a new mechanism of distribution called "Hepatoenteric Recycling (HER)."
Article
Gastroenterology & Hepatology
Jumin Huang, Di Liu, Yuwei Wang, Liang Liu, Jian Li, Jing Yuan, Zhihong Jiang, Zebo Jiang, W. L. Wendy Hsiao, Haizhou Liu, Imran Khan, Ying Xie, Jianlin Wu, Yajia Xie, Yizhong Zhang, Yu Fu, Junyi Liao, Wenjun Wang, Huanling Lai, Axi Shi, Jun Cai, Lianxiang Luo, Runze Li, Xiaojun Yao, Xingxing Fan, Qibiao Wu, Zhongqiu Liu, Peiyu Yan, Jingguang Lu, Mingrong Yang, Lin Wang, Yabing Cao, Hong Wei, Elaine Lai-Han Leung
Summary: This study demonstrated that the combination of GPs and alpha PD-1 mAb enhanced the antitumor response by modulating gut microbiota. The GPs increased microbial metabolites and reshaped gut microbiota towards responders, sensitizing non-small cell lung cancer patients to anti-PD-1 immunotherapy. Additionally, gut microbiota could serve as a novel biomarker to predict the response to anti-PD-1 immunotherapy.
Article
Pharmacology & Pharmacy
Juan Liu, Yuxin Zhuang, Jianlin Wu, Qiang Wu, Meixian Liu, Yue Zhao, Zhongqiu Liu, Caiyan Wang, Linlin Lu, Yingjiao Meng, Kawai Lei, Xiaojuan Li, Qibiao Wu, Elaine Lai-Han Leung, Zhengyang Guo, Liang Liu, Ting Li
Summary: This study found that IKKβ is constitutively activated in healthy individuals and knock-in mice, and its activation may play a role in maintaining homeostasis instead of causing inflammation. Inhibition of IKKβ can disrupt homeostasis, while activation of AMPK can rebuild homeostasis and reduce mortality induced by inflammation.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Pharmacology & Pharmacy
Tao Su, Suchao Huang, Yanmin Zhang, Yajuan Guo, Shuwei Zhang, Jiaji Guan, Mingjing Meng, Linxin Liu, Caiyan Wang, Dihua Yu, Hiu-Yee Kwan, Zhiying Huang, Qiuju Huang, Elaine Lai-Han Leung, Ming Hu, Ying Wang, Zhongqiu Liu, Linlin Lu
Summary: Acidosis is a harsh tumor microenvironment that promotes lung cancer metastasis by inhibiting miR-7-5p expression and increasing TGF-beta 2 expression. The study identifies miR-7-5p as a novel biomarker and therapeutic target for lung cancer treatment.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Chemistry, Multidisciplinary
Biao Qu, Xiao-lin Wang, De-chong Zheng, Chu-tian Mai, Zhong-qiu Liu, Hua Zhou, Ying Xie
Summary: This study developed a novel treatment for refractory rheumatoid arthritis by co-delivering total glucosides of paeony and the P-gp inhibitor nobiletin in a nano-SNEDDS formulation, which significantly increased the bioavailability of TGPs and inhibited P-gp function and expression. The co-loaded formulation not only enhanced the therapeutic effects of TGP but also reduced P-gp expression in an adjuvant-induced arthritis rat model, partly through the inhibition of phosphorylated AKT and HIF-1 alpha pathways.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Chemistry, Multidisciplinary
Qiu-ju Huang, Guo-chao Liao, Xue-rong Zhuang, Meng-lan Yang, Jing-jing Yao, Jian-hua Deng, Yan-min Zhang, Ying Wang, Xiao-xiao Qi, Dong-feng Pan, Yang Guan, Zhi-ying Huang, Feng-xue Zhang, Zhong-qiu Liu, Lin-lin Lu
Summary: The study demonstrates the significant improvement in the properties of FTS by conjugating it with IR783, enhancing its anti-cancer potential and tumor-targeting ability. The conjugate shows superior therapeutic effects in breast cancer cells, increasing drug bioavailability and targeting through various pathways.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Engineering, Environmental
Meijia Sun, Baokuan Li, Zhongqiu Liu, Lixin Tang
Summary: The study investigates the transient multiscale bubble behaviors in the electrolysis process of CuSO4 aqueous solution under the anode, demonstrating bubble nucleation, growth, collision, and detachment. The experimental and numerical methods reveal the characteristics of bubbles and their interactions. Results show that controlling current and anode inclination angle can affect bubble velocity and diameter.
CHEMICAL ENGINEERING JOURNAL
(2022)
Review
Pharmacology & Pharmacy
Dan Liu, Qi Yu, Qing Ning, Zhongqiu Liu, Jie Song
Summary: UGT1A1 is the only enzyme capable of metabolizing detoxified bilirubin, and its inactivation can lead to diseases like GS and CN. UGT1A1 polymorphisms may be associated with neurological diseases, hepatobiliary diseases, cardiovascular diseases, etc., with ongoing research in this area.
DRUG METABOLISM REVIEWS
(2022)
Article
Chemistry, Multidisciplinary
Lin Zhang, Wei Xie, Xiaojun Teng, Kui Wang, Caiyan Wang
Summary: Active ingredient extraction from medicinal plants can be improved using XynA-assisted extraction technology, specifically the use of XynA_Delta N36 enzyme, leading to higher efficiency in extracting salvianic acid A and berberine from Salvia miltiorrhiza and Phellodendron chinense.
JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Physical
Shengnan Li, Xiaotong Lu, Qi Liu, Limin Wang, Yujing Liu, Zhongqiu Liu, Anguo Ying
Summary: Green sustainable production is crucial for human society and the environment. This study presents the synthesis of Pickering interfacial catalysts with CO2 and magnetic double response, showcasing excellent catalytic performance and recyclability.
JOURNAL OF MATERIALS CHEMISTRY A
(2022)
Article
Pharmacology & Pharmacy
Xiaoyan Li, Imran Khan, Guoxin Huang, Yiyan Lu, Liping Wang, Yuanyuan Liu, Linlin Lu, W. L. Wendy Hsiao, Zhongqiu Liu
Summary: The study found that kaempferol effectively reduces tumor burden in mice with colorectal cancer by modulating the bile acid signaling and gut microbiota homeostasis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Agriculture, Multidisciplinary
Xianfeng Xiao, Xuerong Zhang, Zhenkun Yang, Aijia Ji, Caiyan Wang, Qian Feng, Zhongqiu Liu, Rong-Rong Zhang
Summary: In this study, six unusual meroterpenoids were isolated from the leaves of Psidium guajava L. These compounds showed inhibitory activities against PTP1B, and molecular docking studies were performed to predict their inhibition mechanisms at the atomic level.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Materials Science, Multidisciplinary
Fang Wang, Jianpeng Tan, Xuechi Huang, Qiang Wang, Zhongqiu Liu, Jakov Baleta, Baokuan Li
Summary: The desulfurization behavior in the electromagnetically controlled vibrating-electrode electroslag remelting furnace was analyzed, modeled, and numerically simulated. Results show that different vibration modes affect the sulfur content differently. The applied current, frequency, filling ratio, slag thickness, and insertion depth all have an impact on the desulfurization effect.
METALLURGICAL AND MATERIALS TRANSACTIONS B-PROCESS METALLURGY AND MATERIALS PROCESSING SCIENCE
(2022)
Review
Pharmacology & Pharmacy
Yuanping Wang, Yuntao Liu, Zhongqiu Liu, Yuanyuan Cheng, Dawei Wang
Summary: This study demonstrated that Xinbao pill as an adjunctive treatment for chronic heart failure showed efficacy in improving left ventricular function, increasing total effective rate, reducing cardiac load, and improving exercise capacity with good safety profile. However, further well-designed trials are needed to confirm its therapeutic efficacy and safety due to the poor quality of included studies.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Jia Huang, Yaru She, Jingyang Yue, Yidu Chen, Yu Li, Jing Li, Yonger Hu, Deying Yang, Jiabo Chen, Lu Yang, Zhongqiu Liu, Ruibo Wu, Pengfei Jin, Lixin Duan
Summary: Anemarrhena asphodeloides, a popular medicinal herb in China, contains mangiferin which has various pharmacological activities. A promiscuous C-glycosyltransferase (AaCGT) was identified from Anemarrhena asphodeloides, which was capable of catalyzing mono-C-glycosylation and di-C-glycosylation reactions. AaCGT showed potential as a biocatalyst for synthesizing high-value C-glycosides.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2022)
Article
Plant Sciences
Caiyan Wang, Xiaojun Teng, Chuang Wang, Binjie Liu, Runze Zhou, Huawei Qiu, Yu Fu, Rongjin Sun, Zuhui Liang, Rong Zhang, Zhongqiu Liu, Lin Zhang, Lijun Zhu
Summary: In this study, it was demonstrated that Xiao-Chai-Hu-Tang (XCHT) can alleviate CPT-11-induced diarrhea by improving the abundance of beneficial gut microbiota and reducing inflammation.
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)