Review
Biochemistry & Molecular Biology
Peter Szatmari, Eszter Ducza
Summary: ABC transporters are essential for drug efflux in the human body, with significant impact on pharmacokinetics and pharmacologic properties of drugs. P-gp and BCRP transporters, in particular, play a crucial role in barrier tissues. During pregnancy, placental and intestinal ABC transporters are of great importance for drug absorption and distribution. Their expression changes with gestational age and can affect the efficacy of various therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Shabi Parvez, Archana Karole, Yirivinti Hayagreeva Dinakar, Shyam Lal Mudavath
Summary: Transporter-based nanoformulations are gaining more attention in pharmaceutical research due to their ability to enhance drug properties and achieve targeted delivery. This study aimed to investigate the effectiveness of nanoformulation in overcoming the P-gp efflux pump and its potential mechanisms using an in vitro model. The results showed that the nanoformulation significantly improved the permeability of the P-gp substrate, Rhodamine 123, and inhibited the efflux kinetics of the substrate. It also reduced ATPase activity and caused conformational changes in P-gp. Overall, nanoformulation could be an efficient system for evading or modulating P-gp.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Severin Mairinger, Irene Hern, Thomas Filip, Michael Sauberer, Mathilde Lobsch, Johann Stanek, Thomas Wanek, Johannes A. Sake, Thomas Pekar, Carsten Ehrhardt, Oliver Langer
Summary: This study used positron emission tomography (PET) imaging to investigate the influence of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) on the pulmonary distribution of inhaled drugs. The results showed functional activity of P-gp and BCRP in the lungs and suggested that these transporters play a role in limiting the uptake of drugs in the lungs, similar to the blood-brain barrier. The study highlights the importance of pulmonary efflux transporters in the efficacy and safety of inhaled drugs.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemistry & Molecular Biology
Yunmoon Oh, Jin-Sol Lee, Ji Sun Lee, Jae Hyeon Park, Hyung Sik Kim, Sungpil Yoon
Summary: This study found that co-treatment with the JAK2 inhibitor fedratinib can enhance cytotoxicity in P-gp-overexpressing drug-resistant cancer cells when used in combination with the anticancer drug vinicristine. The cytotoxic effects are specific to resistant cancer cells and are mediated through cell cycle regulation and induction of apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Applied
Marielle Margier, Cedric Le May, Tiffany Antoine, Charlotte Halimi, Marion Nowicki, Anne Lespine, Emmanuelle Reboul
Summary: The study found that ABCB1 is involved in the efflux of vitamin K and regulates its absorption in mice models.
Article
Polymer Science
Artem A. Rybyan, Julia V. Bilichenko, Vyacheslav V. Kireev, Alexander A. Kolenchenko, Evgeniy M. Chistyakov
Summary: This research determines that the replacement rates of chlorine atoms in hexa-chlorocyclotriphosphazene by o-, m-, and p-methylanilines greatly depend on reaction temperatures. The polarity of the synthesis solvent is not significantly influenced by the reaction speed. Fully substituted o-, m-, and p-arilaminocyclotriphosphazenes can be formed through a 5-hour reaction in diglyme at its boiling temperature. The synthesized AAP's structure is confirmed by P-31 and H-1 NMR spectroscopy and MALDI-TOF mass spectrometry. The thermal destruction of the synthesized AAP follows a stepped character and involves the removal of three aniline molecules simultaneously.
Article
Pharmacology & Pharmacy
Flavia Storelli, Olena Anoshchenko, Jashvant D. Unadkat
Summary: Accurate prediction of the drug's human steady-state unbound brain interstitial fluid-to-plasma concentration ratio (Kp,Kuu,Kbrain) is crucial in optimizing CNS drug development, especially for drugs effluxed by multiple drug resistance transporters. The use of a proteomics-informed relative expressive factor (REF) approach has shown success in predicting Kp,Kuu,Kbrain, particularly for P-gp substrates, enhancing the development success of CNS candidate drugs.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Cell Biology
Jin-Xing Wang, Xiao Xiao, Xuan-Cheng He, Bao-Dong He, Chang-Mei Liu, Zhao-Qian Teng
Summary: Traumatic brain injury triggers glial scar formation, neuroinflammation, and neurodegeneration. This study found that miR-331 is downregulated in the early stage of injury and treatment with agomir-331 can suppress these pathological features and improve cognitive function.
Article
Pharmacology & Pharmacy
Lei Zhang, Biwei Ye, Yunfeng Lin, Yi-Dong Li, Jing-Quan Wang, Zhuo Chen, Feng-Feng Ping, Zhe-Sheng Chen
Summary: In this study, the researchers investigated the effect of the CDK4/6 inhibitor, ribociclib, on multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) in human epidermoid carcinoma cells. They found that ribociclib increased the efficacy of a P-gp substrate drug, colchicine, by down-regulating the expression of P-gp and increasing its ATPase activity. Docking studies suggested that ribociclib interacted with the drug-substrate binding site of P-gp. Additionally, ribociclib inhibited the drug efflux activity of P-gp, leading to increased intracellular accumulation of doxorubicin. These findings suggest that ribociclib may be a potential agent for combined therapy in cancers with P-gp-mediated MDR.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Margarida L. F. Martins, Paniz Heydari, Wenlong Li, Alejandra Martinez-Chavez, Nikkie Venekamp, Maria C. Lebre, Luc Lucas, Jos H. Beijnen, Alfred H. Schinkel
Summary: This study investigated the impact of drug transporters and drug-metabolizing complex on the pharmacokinetics of ibogaine and its metabolites. The results showed that drug efflux and uptake transporters have a modest restricting effect on the systemic exposure and brain penetration of ibogaine, while drug-metabolizing complex had negligible impact on ibogaine pharmacokinetics.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Chemistry, Medicinal
Hang Zhang, Haiwei Xu, Charles R. Ashby, Yehuda G. Assaraf, Zhe-Sheng Chen, Hong-Min Liu
Summary: This review highlights the recent achievements in drug design and mechanism studies of newly synthetic P-gp inhibitors in the past 5 years, which will help overcome multidrug resistance in cancer chemotherapy.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Plant Sciences
Haihua Shang, Yinghui Sun, Ze Wang, Ying Zhou, Huajiao Yang, Xiaoyan Ci, Tao Cui, Yuanyuan Xia, Yuan Gu, Maoliang Liao, Quansheng Li, Duanyun Si, Changxiao Liu
Summary: This study investigates the oral absorption mechanism of rotundic acid (RA), a major compound in Ilicis Rotundae Cortex, and suggests that it may involve multiple transport pathways and paracellular pathways.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Review
Medicine, Research & Experimental
Li Zeng, Rong Xiang, Chunyan Fu, Zhihao Qu, Changwei Liu
Summary: This review comprehensively explores the regulatory role and mechanism of chlorogenic acid (CGA) in the intestine and brain, as well as its potential biological actions in the gut-brain axis. It provides a scientific foundation for CGA research in the brain and intestines and promotes the translation of basic research and the application of CGA in food nutrition and healthcare.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Food Science & Technology
Yajing Fang, Fuqiang Liang, Mengmeng Xia, Weiwei Cao, Siyi Pan, Ting Wu, Xiaoyun Xu
Summary: This study found that certain flavonoids can effectively reverse multidrug resistance mediated by P-glycoprotein (P-gp) by inhibiting its activity, with specific structural groups and substitutions playing a crucial role in their inhibitory effects. Additionally, flavonoids can impact P-gp ATPase activity and expression levels, thereby influencing its drug transport activity.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Multidisciplinary Sciences
Victoria C. Young, Pablo Artigas
Summary: Utilizing state-specific engineered-disulfide cross-linking, it was demonstrated that the transmembrane segment 2 (M2) of the Na+/K+ pump moves in directions inconsistent with distances observed in existing crystal structures of the pump. This movement was characterized using voltage-clamp fluorometry in single-cysteine mutants, revealing state-dependent fluorescence changes upon labeling with tetramethylrhodamine-6-maleimide (TMRM).
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Rui Liu, Kate Marshall, Rui Ma, Kim Lien Thi Pham, Gauri Shetye, Zhihao Liu, Sanghyun Cho, Hyunyoung Jeong, Scott G. Franzblau, Garrett C. Moraski, Marvin J. Miller
Summary: This article describes the research on the design and synthesis of potent deuterated IAPs and investigates the effect of deuteration on metabolism through microsomal stability studies.
BIOORGANIC CHEMISTRY
(2022)
Correction
Pharmacology & Pharmacy
Xue Sun, Xingping Duan, Changyuan Wang, Zhihao Liu, Pengyuan Sun, Xiaokui Huo, Xiaodong Ma, Huijun Sun, Kexin Liu, Qiang Meng
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Agriculture, Multidisciplinary
Yanfang Li, Zhihao Liu, Gillian Manka Tamia, Xiaohua He, Jianghao Sun, Pei Chen, Seong-Ho Lee, Thomas T. Y. Wang, Boyan Gao, Zhuohong Xie, Liangli Lucy Yu
Summary: Different types of phenolic compounds in tomato seeds were analyzed, with the insoluble bound fraction showing stronger antioxidant activity and anti-cancer cell proliferation effects. The soluble free and insoluble bound fractions significantly inhibited colorectal cancer cell proliferation, providing a basis for the future use of tomato seeds as nutraceuticals in dietary supplements and functional foods.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Won Kyung Kim, Adam W. Olson, Jiaqi Mi, Jinhui Wang, Dong-Hoon Lee, Vien Le, Alex Hiroto, Joseph Aldahl, Christian H. Nenninger, Alyssa J. Buckley, Robert Cardiff, Sungyong You, Zijie Sun
Summary: Activation of the androgen receptor (AR) plays a crucial role in prostate tumorigenesis. The study demonstrates that the activation of AR in a specific subpopulation of prostate cells leads to the formation of prostatic intraepithelial neoplasia and promotes prostate cancer development through the IGF1 and Wnt/beta-catenin signaling pathways. These findings highlight the importance of understanding the mechanisms underlying AR as a tumor promoter and suggest potential therapeutic strategies for advanced prostate cancer.
NATURE COMMUNICATIONS
(2022)
Article
Agriculture, Multidisciplinary
Yanfang Li, Zhihao Liu, Melody Zeng, Alem El Kadiri, Jhongyan Huang, Ashley Kim, Xiaohua He, Jianghao Sun, Pei Chen, Thomas T. Y. Wang, Yaqiong Zhang, Boyan Gao, Zhuohong Xie, Liangli Lucy Yu
Summary: In this study, clove water and ethanol extracts were found to have potential in reducing the risk of SARS-CoV-2 infection by suppressing the binding between spike protein and ACE2, reducing ACE2 availability, and scavenging free radicals. Clove water extract showed stronger inhibitory effects and free radical scavenging activities than ethanol extract.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Review
Agriculture, Multidisciplinary
Zhihao Liu, Mengliang Zhang, Pei Chen, James M. Harnly, Jianghao Sun
Summary: This review discusses the applications of mass spectrometry (MS) techniques in food and agricultural research, including targeted and nontargeted analysis. It summarizes recent publications in the field, such as flow injection MS fingerprinting, chromatography-tandem MS metabolomics, and ambient mass spectrometry. The review also highlights the development of MS data deconvolution software packages and databases for metabolomic studies.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Shuai Liu, Keming Zheng, Yilin Jiang, Susu Gai, Bohan Li, Dehai Li, Shuang Yang, Zhihua Lv
Summary: In this study, the metabolic route of PND in rats was revealed using UHPLC-HRMS. A total of 25 metabolites were identified in rat bile, feces, and urine, and the metabolic pathways were proposed. It was found that PND was mainly eliminated through glucuronide conjugation in bile and excreted in feces, with significant species differences in the metabolism of PND in rat, mouse, and human liver microsomes.
Article
Biochemistry & Molecular Biology
Zhihao Liu, Roderick Moore, Ying Gao, Pei Chen, Liangli Yu, Mengliang Zhang, Jianghao Sun
Summary: This study used UHPLC-HRMS-based metabolomic approach to analyze the secondary metabolites of wild and cultivated American ginsengs, and found significant differences in ginsenoside profiles between the two. Wild American ginsengs had more abundant and diverse octillol-type ginsenosides, while cultivated American ginsengs had a wider distribution of protopanaxadiol and oleanolic acid-type ginsenosides. The results suggested that the in-house metabolite library and UHPLC-HRMS were effective for identifying characteristic components for distinguishing wild and cultivated American ginseng.
Article
Agriculture, Multidisciplinary
Zhuohong Xie, Yanfang Li, Zhihao Liu, Melody Zeng, Jeffrey C. Moore, Boyan Gao, Xianli Wu, Jianghao Sun, Thomas T. Y. Wang, Pamela Pehrsson, Xiaohua He, Liangli Lucy Yu
Summary: In this study, the bioactives in cinnamon water and ethanol extracts were identified, and it was found that they can suppress the binding of SARS-CoV-2 spike protein to ACE2, reduce ACE2 availability, and scavenge free radicals. Furthermore, new compounds were discovered in cinnamon.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Agriculture, Multidisciplinary
Boyan Gao, Lin Zhu, Zhihao Liu, Yanfang Li, Xiaohua He, Xianli Wu, Pamela Pehrsson, Jianghao Sun, Zhuohong Xie, Margaret Slavin, Liangli Lucy Yu
Summary: This study examined the chemical compositions of water and ethanol extracts of honeysuckle, as well as their potential in inhibiting SARS-CoV-2 spike protein binding to ACE2, suppressing ACE2 activity, and scavenging reactive free radicals. The results showed that both extracts inhibited the binding of SARS-CoV-2 spike protein to ACE2 and ACE2 activity. The water extract had stronger inhibitory effects on ACE2 activity and higher scavenging activities against free radicals compared to the ethanol extract. These findings suggest that honeysuckle may reduce the risk of SARS-CoV-2 infection and severe COVID-19 symptoms.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Food Science & Technology
Uyory Choe, Yanfang Li, Zhihao Liu, Yuanhang Yao, Xiaohua He, Jianghao Sun, Xianli Wu, Pamela Pehrsson, Yaqiong Zhang, Boyan Gao, Thomas T. Y. Wang, Liangli Lucy Yu
Summary: This study evaluates dill's potential in preventing SARS-CoV-2 infiltration and alleviating COVID-19 symptoms. The results show that dill extracts have the ability to inhibit the interaction between SARS-CoV-2 spike protein and ACE2 receptor, as well as ACE2 enzyme activity. Additionally, dill exhibits high total phenolic content and free radical scavenging capacity.
ACS FOOD SCIENCE & TECHNOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Yuanhang Yao, Monica Whent, Yanfang Li, Zhihao Liu, Pamela Pehrsson, Jianghao Sun, Pei Chen, Dejian Huang, Thomas T. Y. Wang, Xianli Wu, Liangli Yu
Summary: In this study, water and ethanol extracts of dried thyme were analyzed for their chemical composition and their effects on the SARS-CoV-2 spike protein-ACE2 interaction, ACE2 activity, and free radical scavenging capacity. The results showed that thyme extracts inhibited the spike protein-ACE2 interaction, inhibited ACE2 activity, and exhibited free radical scavenging capacity. The findings suggest that thyme extract could potentially be used to prevent SARS-CoV-2 infection and mitigate the complications from the infection.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Food Science & Technology
Zhihao Liu, Jenna Shi, Jiawei Wan, Quynchi Pham, Zhi Zhang, Jianghao Sun, Liangli Yu, Yaguang Luo, Thomas T. Y. Wang, Pei Chen
Summary: This study provides the first report on the polyphenol and glucosinolate composition of kale and broccoli microgreens grown in different environments. The results showed a clear variation in secondary metabolites between growth chamber and windowsill conditions, suggesting that the growing environment affects the composition of health-beneficial components in vegetables.
ACS FOOD SCIENCE & TECHNOLOGY
(2022)
Article
Food Science & Technology
Yanfang Li, Katherine Wu, Zhihao Liu, Xiaohua He, Jianghao Sun, Melody Zeng, Seong-Ho Lee, Thomas T. Y. Wang, Boyan Gao, Zhuohong Xie, Cheng- Wei, Liangli Lucy Yu
Summary: This study investigated the effects of different thermal treatments (steaming and baking) on the chemical compositions, antioxidant components, and antioxidant properties of tomato seeds. The results showed that thermal treatments can alter the phenolic compositions of tomato seeds and steaming can effectively enhance their antioxidant activities.
ACS FOOD SCIENCE & TECHNOLOGY
(2022)
Article
Food Science & Technology
Zhihao Liu, Zi Teng, Daniel J. Pearlstein, Pei Chen, Liangli Yu, Bin Zhou, Yaguang Luo, Jianghao Sun
Summary: This research investigated the effect of LED light wavelengths on the phytochemical profiles of Ruby Streaks mustard microgreens, and found that red and magenta light promoted the accumulation of anthocyanins and aliphatic GLs, while blue light was dominant in the accumulation of non-anthocyanin phenolics.
ACS FOOD SCIENCE & TECHNOLOGY
(2022)