Article
Chemistry, Analytical
Zhengyin Yan, Li Ma, Julie Huang, Pasquale Carione, Jane R. Kenny, Cornelis E. C. A. Hop, Matthew Wright
Summary: Determination of drug binding kinetics in plasma is challenging, and this study introduces a new parameter called dynamic free fraction to describe drug-protein binding kinetics. The dynamic free fraction can be determined by coupling the drug binding assay with a reporter enzyme and high-resolution mass spectrometry. This methodology bypasses the challenges in existing methods and allows assessment of the impact of protein binding kinetics on drug properties.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Mitesh Patel, Julia Riede, Dallas Bednarczyk, Birk Poller, Sujal V. Deshmukh
Summary: In this study, the applicability of the Extended Clearance Concept Classification System (EC3S) in drug discovery was investigated. A relationship between hepatocyte uptake clearance, MDCK permeability, and intrinsic clearance from human liver microsomes was established. The simplified EC3S was able to predict systemic clearance for certain compounds.
PHARMACEUTICAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Urban Fagerholm, Ola Spjuth, Sven Hellberg
Summary: In vitro-in vivo prediction results for hepatic metabolic clearance (CLH) and intrinsic CLH (CLint) vary widely among studies. The selection of reference data appears to play a major role for demonstrated predictions, and the in silico method shows higher accuracy and wider range than hepatocytes for human in vivo CLint-predictions.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Agronomy
Zijian Li, Peter Fantke
Summary: The degradation kinetics of pesticides in plants play a crucial role in modeling pesticide residual concentrations. This study proposes a modeling approach using potatoes as a model crop to estimate the degradation rate constants of pesticides in plants. The simulations show that the growth dynamics of potatoes and variations in weather conditions and soil properties can significantly affect the degradation kinetics of pesticides in plants.
PEST MANAGEMENT SCIENCE
(2023)
Article
Environmental Sciences
Silvia Fraissinet, Daniele Arduini, Olaya Vidal, Antonio Pennetta, Giuseppe Egidio De Benedetto, Cosimino Malitesta, Adriana Giangrande, Sergio Rossi
Summary: Microplastics pose a serious threat to the marine environment, impacting ecosystem functioning and biodiversity. While there is a vast literature on the uptake of microplastics in different trophic levels, there is limited knowledge on potential strategies to mitigate microplastic pollution. Bioremediation, specifically focusing on three species (Sabella spallanzanii, Mytilus galloprovincialis, Phallusia mammillata), has shown promise in effectively removing microplastics.
MARINE POLLUTION BULLETIN
(2023)
Article
Oncology
Edwin Pun Hui, Brigette B. Y. Ma, W. K. Jacky Lam, K. C. Allen Chan, Frankie Mo, Qi-Yong Hemis Ai, Ann D. King, Chi Hang Wong, Kenneth C. W. Wong, Daisy C. M. Lam, Macy Tong, Darren M. C. Poon, Leung Li, Thomas K. H. Lau, Kwan Hung Wong, Y. M. Dennis Lo, Anthony T. C. Chan
Summary: The dynamic changes in plasma Epstein-Barr virus (pEBV) DNA after radiotherapy have a significant impact on the survival of nasopharyngeal cancer patients, with clearing pEBV DNA associated with improved survival. Post-radiotherapy pEBV DNA clearance may serve as an early surrogate endpoint for long-term survival in NPC.
CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Tingjun Liu, Ranran Li, Lili Sun, Zhongjin Xu, Shengxuan Wang, Jingxuan Zhou, Xuanning Wu, Kerong Shi
Summary: The scaffold protein Menin, encoded by the Men1 gene, plays a crucial role in regulating hepatic energy uptake and metabolic homeostasis. It interacts with cellular energy sensors SIRT1, PPAR gamma, and/or FoxO1 to target downstream gene expression levels, maintaining metabolic balance. These findings provide new insights into the potential therapeutic targeting of Menin in hepatic steatosis, NAFLD or MAFLD, and other hepatic diseases.
CELL AND BIOSCIENCE
(2023)
Article
Endocrinology & Metabolism
Tingwan Du, Lian Xiang, Jingjing Zhang, Chunmei Yang, Wenxin Zhao, Jialu Li, Yong Zhou, Ling Ma
Summary: This study aimed to explore the association between serum 25(OH)D-3 and hepatic steatosis in NAFLD patients and investigate whether vitamin D has an effect on activating the PPAR alpha pathway. The study consisted of a case-control study, in vivo experiments with rats, and in vitro experiments with HepG2 cells. The results showed that NAFLD patients had impaired liver function, dyslipidemia, and insulin resistance. Adequate vitamin D levels were found to have a protective effect on NAFLD patients. In addition, vitamin D treatment ameliorated hepatic steatosis in both rats and cells. MK886, a PPARa antagonist, inhibited the anti-steatosis effect of vitamin D. These findings suggest that vitamin D may protect against NAFLD and alleviate hepatic steatosis through the PPAR alpha signaling pathway.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Physics, Multidisciplinary
A. N. Pavlov, O. N. Pavlova, O. V. Semyachkina-Glushkovskaya, J. Kurths
Summary: EDFA is a method that characterizes time series with varying nonstationarity by evaluating two scaling exponents. Different types of nonstationarity have varying effects on different types of time series. Additionally, EDFA can be applied to studying the activation of brain lymphatic drainage.
EUROPEAN PHYSICAL JOURNAL PLUS
(2021)
Article
Nanoscience & Nanotechnology
Datong Zhang, Hiroyuki Nakano, Kentaro Yamamoto, Kenta Tanaka, Tatsuma Yahara, Kazuyuki Imai, Takuya Mori, Hidenori Miki, Shinji Nakanishi, Hideki Iba, Toshiki Watanabe, Tomoki Uchiyama, Koji Amezawa, Yoshiharu Uchimoto
Summary: This study investigated the modification of tetragonal beta-Pb0.78Sn1.22F4 for all-solid-state fluoride-ion batteries by annealing under various atmospheres, resulting in enhanced ionic conductivities. The rate-determining factor at the electrode/electrolyte interface reactions was found to be mass transfer, suggesting that developing high-conductivity solid electrolytes could lead to FIBs with superior rate capabilities similar to those of Li-ion batteries.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Biochemistry & Molecular Biology
Sutharinee Likitnukul, Sumpun Thammacharoen, Orada Sriwatananukulkit, Chanathip Duangtha, Ruedee Hemstapat, Chotchanit Sunrat, Supachoke Mangmool, Darawan Pinthong
Summary: Obesity is connected to metabolic disorders like type 2 diabetes and NAFLD. Lower GH levels and higher insulin levels are observed in obese individuals. Long-term GH treatment increases lipolytic activity but has no significant effect on insulin sensitivity. This study investigates the impact of short-term GH administration on liver lipid metabolism in DIO rats. Short-term GH administration reduces the expression of fatty acid synthase and CD36 while increasing the expression of CPT1A in the liver. It also promotes fatty acid oxidation and decreases fatty acid uptake and lipogenesis.
Article
Multidisciplinary Sciences
Daxing Liu, Jules Cohen, Nashaat Turkman
Summary: Coating liposomes with DBCO can significantly enhance their internalization by breast cancer cells.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, General & Internal
Miriam Longo, Erika Paolini, Marica Meroni, Lorena Duca, Irene Motta, Anna Ludovica Fracanzani, Elena Di Pierro, Paola Dongiovanni
Summary: The study showed that PBGD-silenced hepatocytes exhibit impaired glycolysis and mitochondrial dynamics, leading to energy metabolism dysfunction during fasting. Alpha-lipoic acid may improve energy supply in these cells by enhancing glucose utilization.
Article
Multidisciplinary Sciences
Yuki Noguchi, Kazuhisa Ozeki, Hiroaki Takesue, Hidetaka Akita
Summary: This study developed a cell-based assay for evaluating the binding and uptake of an antibody in liver non-parenchymal cells, demonstrating its feasibility in mice and monkeys. The findings suggest that this approach is a useful tool for determining the binding and uptake of biologics and predicting pharmacokinetics.
SCIENTIFIC REPORTS
(2021)
Editorial Material
Multidisciplinary Sciences
Patricia M. Nunes, Dimitrios Anastasiou
Summary: Feeding mice high-fructose corn syrup has been found to increase gut surface area, enhancing absorption of dietary nutrients and resulting in weight gain.
Article
Pharmacology & Pharmacy
Daiki Mori, Hiroo Ishida, Tadahaya Mizuno, Sojiro Kusumoto, Yusuke Kondo, Saki Izumi, Genki Nakata, Yoshitane Nozaki, Kazuya Maeda, Yasutsuna Sasaki, Ken-ichi Fujita, Hiroyuki Kusuhara
DRUG METABOLISM AND DISPOSITION
(2020)
Correction
Medicine, Research & Experimental
Saki Izumi, Yoshitane Nozaki, Hiroyuki Kusuhara, Koichiro Hotta, Toshiki Mochizuki, Takafumi Komori, Kazuya Maeda, Yuichi Sugiyama
MOLECULAR PHARMACEUTICS
(2020)
Article
Environmental Sciences
Takashi Kudo, Akihiro Inano, Sanae Midorikawa, Hitoshi Kubo, Kino Hayashi, Sawako Nakashima, Chizu Fukushima, Kazuya Maeda, Noboru Oriuchi, Shin Irie, Shunichi Yamashita, Hiroyuki Kusuhara
Article
Medicine, Research & Experimental
Takayoshi Nakaoka, Yuta Uetake, Ken-ichi Kaneko, Takashi Niwa, Hidenori Ochiai, Satsuki Irie, Yoshie Suezaki, Natsumi Otsuka, Emi Hayashinaka, Yasuhiro Wada, Yilong Cui, Kazuya Maeda, Hiroyuki Kusuhara, Yuichi Sugiyama, Takamitsu Hosoya, Yasuyoshi Watanabe
MOLECULAR PHARMACEUTICS
(2020)
Article
Pharmacology & Pharmacy
Wooin Lee, Satoshi Koyama, Kiyoe Morita, Aya Kiriake, Ryota Kikuchi, Xiaoyan Chu, Nora Lee, Renato J. Scialis, Hong Shen, Emi Kimoto, Larry Tremaine, Naoki Ishiguro, Ralf Lotz, Kazuya Maeda, Hiroyuki Kusuhara, Yuichi Sugiyama
Article
Pharmacology & Pharmacy
Kazuyoshi Michiba, Kazuya Maeda, Ko Kurimori, Tsuyoshi Enomoto, Osamu Shimomura, Tomoyo Takeuchi, Hiroyuki Nishiyama, Tatsuya Oda, Hiroyuki Kusuhara
Summary: This study characterized the functions of major intestinal uptake/efflux drug transporters in freshly isolated human jejunum sections using the Ussing chamber system. The findings showed a good correlation between the mucosal-to-serosal apparent permeability coefficient of various drugs and reported human FaFg values, highlighting the importance of intestinal uptake transporters in facilitating drug absorption in humans.
DRUG METABOLISM AND DISPOSITION
(2021)
Review
Pharmacology & Pharmacy
Tatsuki Mochizuki, Tadahaya Mizuno, Kazuya Maeda, Hiroyuki Kusuhara
Summary: Drug transporters play crucial roles in eliminating compounds from the blood, with genetic variation and drug-drug interactions being underlying factors for pharmacokinetic differences of transporter substrates. Some endogenous substrates of drug transporters have been identified as biomarkers to assess transporter activity differences. Metabolomic analysis is a promising approach for identifying endogenous substrates through metabolites.
DRUG METABOLISM AND PHARMACOKINETICS
(2021)
Article
Chemistry, Medicinal
Takashi Yoshikado, Wooin Lee, Kota Toshimoto, Kiyoe Morita, Aya Kiriake, Xiaoyan Chu, Nora Lee, Emi Kimoto, Manthena V. S. Varma, Ryota Kikuchi, Renato J. Scialis, Hong Shen, Naoki Ishiguro, Ralf Lotz, Albert P. Li, Kazuya Maeda, Hiroyuki Kusuhara, Yuichi Sugiyama
Summary: Hepatic uptake clearances of OATP1B substrates were compared between plated human hepatocytes (PHH) and suspended human hepatocytes (SHH), showing differences in uptake kinetics and cell-to-medium concentration ratios. PHH is useful for high-throughput evaluation of hepatic uptake/efflux clearances and Kp,Kuu, with caution needed for hydrophilic drugs with low uptake/cellular binding.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Cell & Tissue Engineering
Shinpei Yoshida, Takayuki Honjo, Keita Iino, Ryunosuke Ishibe, Sylvia Leo, Tomoka Shimada, Teruhiko Watanabe, Masaya Ishikawa, Kazuya Maeda, Hiroyuki Kusuhara, Nobuaki Shiraki, Shoen Kume
Summary: This study aimed to generate matured small intestinal cells mimicking human small intestine from human-induced pluripotent stem cells (iPSCs). By culturing iPSC-derived intestinal progenitor cells on collagen vitrigel membrane and treating with a simple maturation medium, enterocyte-like cells were successfully generated, showing potential applications in drug transport and metabolism studies.
Review
Pharmacology & Pharmacy
Kazuya Maeda, Akihiro Hisaka, Kiyomi Ito, Yoshiyuki Ohno, Akihiro Ishiguro, Reiko Sato, Naomi Nagai
Summary: This review highlights the importance of clinical drug interaction studies during new drug development and introduces the general procedures proposed in a recently updated Japanese guideline. Drugs are classified based on their clearance pathway and potential intensity according to systematic reviews of the literature, which is useful for managing drug interactions in clinical practice.
DRUG METABOLISM AND PHARMACOKINETICS
(2021)
Article
Materials Science, Biomaterials
Sayaka Deguchi, Masahiro Tsuda, Kaori Kosugi, Ayaka Sakamoto, Natsumi Mimura, Ryosuke Negoro, Emi Sano, Takuro Nobe, Kazuya Maeda, Hiroyuki Kusuhara, Hiroyuki Mizuguchi, Fumiyoshi Yamashita, Yu-suke Torisawa, Kazuo Takayama
Summary: The study evaluated drug absorption to the PDMS device and investigated the drug responsiveness of human hepatocytes cultured in the PDMS device. The absorption rates of different compounds to the PDMS device were measured and found to be correlated with their octanol/water distribution coefficient values. Furthermore, the hepatocyte-chips were used to examine the response to drugs typically used to evaluate hepatic functions.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2021)
Article
Pharmacology & Pharmacy
Kazuyoshi Michiba, Kazuya Maeda, Osamu Shimomura, Yoshihiro Miyazaki, Shinji Hashimoto, Tatsuya Oda, Hiroyuki Kusuhara
Summary: This study has demonstrated the usefulness of human jejunal spheroid-derived differentiated intestinal epithelial cells as an in vitro model for studying the impact of intestinal drug-metabolizing enzymes and transporters on substrate drugs' absorption in humans. The model was able to maintain the functions of major intestinal drug-metabolizing enzymes and transporters. It could be used for quantitative evaluation of the impact of these enzymes and transporters on drug absorption.
DRUG METABOLISM AND DISPOSITION
(2022)
Review
Pharmacology & Pharmacy
Yoshiki Hashimoto, Kazuyoshi Michiba, Kazuya Maeda, Hiroyuki Kusuhara
Summary: Efflux transport systems play a crucial role in inhibiting the absorption and distribution of drugs in the human body, with genetic variations and coadministered drugs affecting transporter expression and function. Utilizing in vitro experimental tools and mathematical modeling allows for accurate prediction of drug pharmacokinetics.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Tatsuki Mochizuki, Maciej J. Zamek-Gliszczynski, Kenta Yoshida, Jialin Mao, Kunal Taskar, Hideki Hirabayashi, Xiaoyan Chu, Yurong Lai, Tadayuki Takashima, Kevin Rockich, Yoshiyuki Yamaura, Kaku Fujiwara, Tadahaya Mizuno, Kazuya Maeda, Kenichi Furihata, Yuichi Sugiyama, Hiroyuki Kusuhara
Summary: This study assessed the quantitative performance of endogenous biomarkers for OATP1B1/1B3-mediated drug-drug interactions, with CP-I's AUCR and CmaxR showing high correlation with CysA AUC. The findings provide valuable information for accurate DDI predictions and enhance understanding of interindividual variability in DDI magnitude.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Medicine, Research & Experimental
Tatsuki Mochizuki, Yasunori Aoki, Takashi Yoshikado, Kenta Yoshida, Yurong Lai, Hideki Hirabayashi, Yoshiyuki Yamaura, Kevin Rockich, Kunal Taskar, Tadayuki Takashima, Xiaoyan Chu, Maciej J. Zamek-Gliszczynski, Jialin Mao, Kazuya Maeda, Kenichi Furihata, Yuichi Sugiyama, Hiroyuki Kusuhara
Summary: In this study, a physiologically-based pharmacokinetic (PBPK) model analysis was performed to interpret clinical drug-drug interaction (DDI) data, and the results suggest that PBPK model analysis of CP-I is a promising translational approach to predict OATP1B-mediated DDIs in drug development.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)