Article
Biochemistry & Molecular Biology
Adrian T. Press, Luisa Ungelenk, Anna Medyukhina, Samantha A. Pennington, Sandor Nietzsche, Chunyi Kan, Amelie Lupp, Uta Dahmen, Rui Wang, Utz Settmacher, Reinhard Wetzker, Marc Thilo Figge, Mark G. Clemens, Michael Bauer
Summary: Ischemia-reperfusion injury, characterized by the deprivation of antioxidants and energy, poses a critical threat to the liver during transplantation, trauma, or shock. This study examines the role of hydrogen sulfide as an antioxidant in the liver and the therapeutic potential of sodium sulfide (Na2S) and sodium thiosulfate (STS) as hydrogen sulfide donors. The results demonstrate that STS refuels and protects the liver's antioxidant pool, effectively reducing lipid peroxidation and mitochondrial damage, leading to the preservation of liver tissue architecture.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Immunology
Yongxin Huang, Qinyuan Xu, Jiang Zhang, Yanze Yin, Yixiao Pan, Yuanyi Zheng, Xiaojun Cai, Qiang Xia, Kang He
Summary: The study suggests that PB scavenger could be a potential therapeutic agent for treating HIRI, providing an alternative treatment for ROS-associated and inflammatory liver diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Qingchun Mu, Kai Yao, Madiha Zahra Syeda, Min Zhang, Qian Cheng, Yufei Zhang, Rui Sun, Yuting Lu, Huamiao Zhang, Zhicheng Luo, Hanning Huang, Xiaojing Liu, Chunmei Luo, Xiulong Zhu, Shuyu Wu, Liao Cui, Chunming Huang, Xiaoyuan Chen, Longguang Tang
Summary: Ischemic stroke is a refractory disease caused by cerebral ischemia, which induces inflammatory reactions and accumulation of neutrophils at the site of inflammation. This study modifies a nanoplatform to specifically bind to neutrophils' formyl peptide receptor and achieves higher drug accumulation at the inflammatory site by hitchhiking with neutrophils.
Article
Biochemistry & Molecular Biology
Athina G. Mantelou, Alexandra Barbouti, Anna Goussia, Argyro Zacharioudaki, Alexandra Papoudou-Bai, Chara Vlachou, Stelios Kokkoris, Apostolos Papalois, Dimitrios Galaris, Georgios K. Glantzounis
Summary: The study showed that a combination of iron chelators with varying lipophilicity and iron-binding properties can enhance protection against hepatic I/R injury. Through investigations in cell lines and a rabbit model, the protective effects of these iron chelator combinations were observed.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Nanoscience & Nanotechnology
Dong Chen, Chaoqun Wang, Hongjun Yu, Guanxiong Liu, Baolin Qian, Bangliang Chen, Zhongyu Li, Yongzhi Zhou, Shangha Pan, Baoqiang Li, Yong Ma
Summary: In this study, chitosan-derived nitrogen-doped carbon dots (CNDs) with reactive oxygen species (ROS) scavenging capabilities were synthesized and applied in the prevention of hepatic ischemia-reperfusion injury (HIRI). CNDs showed scavenging ability against ROS, especially hydroxyl radicals. The results demonstrate that CNDs can alleviate liver damage, suppress the inflammatory response, and inhibit apoptosis triggered by liver ischemia/reperfusion operation.
ACS APPLIED NANO MATERIALS
(2023)
Article
Cardiac & Cardiovascular Systems
Guangyu Zhang, Xiaoding Wang, Chao Li, Qinfeng Li, Yu A. An, Xiang Luo, Yingfeng Deng, Thomas G. Gillette, Philipp E. Scherer, Zhao Wang
Summary: The study demonstrates the significant role of the ISR in myocardial ischemia/reperfusion injury by selectively suppressing mitochondrial protein synthesis and reducing oxidative stress to improve cell survival and mitigate reperfusion damage.
Article
Polymer Science
Anna Blasi-Romero, Carlos Palo-Nieto, Corine Sandstrom, Jonas Lindh, Maria Stromme, Natalia Ferraz
Summary: The study developed a bioactive material by incorporating cysteine into wood-derived cellulose nanofibrils, which showed efficient control over metalloprotease collagenase activity and inhibition of free radical activity. The stability of the bioactivity of the material was challenged over time, but preparing it as an aerogel and storing it in an inert atmosphere proved to be valid approaches to increase stability. No signs of toxicity were observed on dermal fibroblasts exposed to the bioactive material.
Article
Chemistry, Multidisciplinary
Bing Bai, Shaolong Qi, Kai Yang, Xinyang Yu, Ruijun Jian, Tianfang Zhang, Daming Wang, Hongbo Meng, Yifan Zhao, Yu Xia, Huaping Xu, Guocan Yu, Zuobing Chen
Summary: In this study, self-assembled Se-CQDs-lecithin nanoparticles (Se-LEC NPs) were developed to effectively scavenge ROS and accumulate in the liver, exerting beneficial therapeutic efficacy on HIRI. This work may open a new avenue for the design of self-assembled Se-CQDs NPs for the treatment of HIRI and other ROS-related diseases.
Article
Cardiac & Cardiovascular Systems
Hiran A. Prag, Dunja Aksentijevic, Andreas Dannhorn, Abigail Giles, John F. Mulvey, Olga Sauchanka, Luping Du, Georgina Bates, Johannes Reinhold, Duvaraka Kula-Alwar, Zhelong Xu, Luc Pellerin, Richard J. A. Goodwin, Michael P. Murphy, Thomas Krieg
Summary: Malonate selectively enters cardiomyocytes during reperfusion in a low pH environment caused by ischemia, protecting against cardiac ischemia/reperfusion injury.
CIRCULATION RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Aazam Shaikh, Prashant Kesharwani, Virendra Gajbhiye
Summary: Dendrimers have a wide range of applications in biomedical fields, including cargo delivery, nucleic acid delivery, and macromolecule delivery. They can also be used to crosslink synthetic and natural polymeric scaffolds and mimic the extracellular matrix. Dendrimers play a crucial role in regulating cell behavior and delivering bioactive molecules, and have shown significant results in stem cell survival, osteogenesis, and repair.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Gastroenterology & Hepatology
Zhilin Sha, Yajie Yang, Ruling Liu, Haili Bao, Shaohua Song, Junfeng Dong, Meng Guo, Yuanyu Zhao, Hu Liu, Guoshan Ding
Summary: This study demonstrates the protective effect of Rac1 inhibition on hepatic IRI by reducing ROS production and oxidative stress, and uncovers an interaction between Rac1 and HIF-1 alpha signaling pathways during hepatic IRI.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nouf Alwadei, Mamunur Rashid, Devaraj Venkatapura Chandrashekar, Simin Rahighi, Jennifer Totonchy, Ajay Sharma, Reza Mehvar
Summary: In this study, a HepG2 cell line with stable overexpression of CYP2E1 was generated to investigate its role in hypoxia/reperfusion injury. The results showed that the high expression of CYP2E1 in the cells led to increased reactive oxygen species production and cell death in the hypoxia/reperfusion model, suggesting a detrimental role of CYP2E1 in hepatic ischemia/reperfusion injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Biomedical
Eunkyeong Jung, Nanhee Song, Yujin Lee, Gayoung Kwon, Soonyoung Kwon, Dongwon Lee
Summary: Self-assembling RABA nanoassemblies show superior therapeutic efficacy in protecting the liver from ischemia/reperfusion injury compared to the combination of atRA and HBA.
Article
Biochemistry & Molecular Biology
Chaoqun Wang, Hongjun Yu, Shounan Lu, Shanjia Ke, Yanan Xu, Zhigang Feng, Baolin Qian, Miaoyu Bai, Bing Yin, Xinglong Li, Yongliang Hua, Liqian Dong, Yao Li, Bao Zhang, Zhongyu Li, Dong Chen, Bangliang Chen, Yongzhi Zhou, Shangha Pan, Yao Fu, Hongchi Jiang, Dawei Wang, Yong Ma
Summary: This study reveals that elevated Hnf4α os in hepatic ischemia/reperfusion injury (HIRI) leads to severe liver damage. Hnf4α os exerts its function by regulating ROS metabolism and stabilizing Hnf4α mRNA, resulting in the inhibition of PGC1α. These findings shed light on the pathogenesis of HIRI.
Article
Biochemistry & Molecular Biology
Panagiotis Chronopoulos, Caroline Manicam, Jenia Kouchek Zadeh, Panagiotis Laspas, Johanna Charlotte Unkrig, Marie Luise Goebel, Aytan Musayeva, Norbert Pfeiffer, Matthias Oelze, Andreas Daiber, Huige Li, Ning Xia, Adrian Gericke
Summary: This study demonstrates that resveratrol has a protective effect against ischemia-reperfusion injury in the murine retina, reducing the loss of retinal ganglion cells and endothelial dysfunction of retinal blood vessels. This protective effect may be achieved by suppressing upregulation of nitric oxide synthase 2 and alleviating nitro-oxidative stress.
Letter
Pharmacology & Pharmacy
Mitsuru Hashida
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Multidisciplinary Sciences
Ryosaku Ota, Kanako So, Masahiro Tsuda, Yuriko Higuchi, Fumiyoshi Yamashita
Summary: The paper presents a method for predicting HIV drug resistance using genotypes, utilizing techniques such as homology modeling and Bayesian conditional mutual information theory to handle incomplete sequencing data, proposing a way to effectively incorporate uncertain information into the modeling process.
Article
Multidisciplinary Sciences
Yoshihisa Tanaka, Kako Higashihara, Mai Adachi Nakazawa, Fumiyoshi Yamashita, Yoshinori Tamada, Yasushi Okuno
Summary: Researchers used Bayesian networks to analyze gene regulatory networks in response to SARS-CoV-2, revealing dynamic changes from interferon signaling to inflammatory cytokine signaling cascades. They successfully captured a COVID-19 patient-specific network and explored local regulatory systems influenced by SARS-CoV-2 in host cells.
SCIENTIFIC REPORTS
(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
Chemistry, Multidisciplinary
Emi Sano, Sayaka Deguchi, Naoki Matsuoka, Masahiro Tsuda, Mengyang Wang, Kaori Kosugi, Chihiro Mori, Keisuke Yagi, Aya Wada, Shinsuke Yamasaki, Tsuyoshi Kawai, Masahide Yodogawa, Hiroyuki Mizuguchi, Norihito Nakazawa, Fumiyoshi Yamashita, Yu-suke Torisawa, Kazuo Takayama
Summary: The study investigated the feasibility of using a FEPM-based hepatocyte chip with lower drug absorption for drug discovery research. The FEPM-based chip showed higher detection of drug metabolites and lower hepatocyte cytotoxicity compared to the PDMS-based chip, indicating its potential utility in drug metabolism and toxicity studies.
Article
Pharmacology & Pharmacy
Mohammad Karim Haidar, Fumiyoshi Yamashita, Mitsuru Hashida
Summary: Regardless of the PLGA type with different lactic/glycolic acid ratios, microspheres prepared via the solid-in-oil-in-water (S/O/W) method showed a much higher encapsulation efficiency (EE) and faster drug release compared to microspheres prepared via the co-solvent method. Preparation methods, pH of the aqueous phase, and volume of the aqueous phase were the most influencing parameters on the EE. Confirmation experiment results indicated a 5.76 db increase in signal-to-noise ratio from the initial condition. Minocycline release was fastest with PLGA (50:50) microspheres, followed by PLGA (75:25) and PLGA (85:15).
TURKISH JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Physiology
Nagomi Kurebayashi, Takashi Murayama, Ryosaku Ota, Junji Suzuki, Kazunori Kanemaru, Takuya Kobayashi, Seiko Ohno, Minoru Horie, Masamitsu Iino, Fumiyoshi Yamashita, Takashi Sakurai
Summary: Type 2 ryanodine receptor (RYR2) is a cardiac Ca2+ release channel that is associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). This study demonstrates that CPVT mutations lower the threshold [Ca-2(+)](ER) for spontaneous Ca-2(+) release by enhancing the [Ca-2(+)](cyt)-dependent activity of RYR2, without modulating the [Ca-2(+)](ER) sensitivity of RYR2.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Chanikarn Chantarasrivong, Ryu Okada, Yuuki Yamane, Xue Yang, Yuriko Higuchi, Miku Konishi, Naoko Komura, Hiromune Ando, Ryuji Yokokawa, Fumiyoshi Yamashita
Summary: Tumor spheroids with a perfusable vascular network were constructed to evaluate drug delivery systems targeting tumor vasculature. The results suggest that 3'-CE sLeX mimic liposomes are a promising carrier for targeting tumor vasculature, and proinflammatory cytokine treatment may be beneficial in pharmacokinetic studies.
DRUG METABOLISM AND PHARMACOKINETICS
(2022)
Article
Pharmacology & Pharmacy
Mengyang Wang, Masahiro Tsuda, Sayaka Deguchi, Yuriko Higuchi, Kanako So, Yu-suke Torisawa, Kazuo Takayama, Fumiyoshi Yamashita
Summary: Recently, liver-on-a-chip models have gained increasing attention for pharmacokinetics and toxicity screenings. Researchers have found that perfluoropolyether (PFPE) elastomer, a chemically repellent material, could be an alternative to the commonly used polydimethylsiloxane (PDMS) material in microfluidic devices. The PFPE devices showed improved cell performance with increased production of albumin and urea, as well as enhanced metabolic activity of hepatocytes under dynamic flow conditions compared to static conditions. Although PFPE devices still exhibited some sorption, they demonstrated better chemical repellency and may provide better performance in ADMET evaluation than PDMS devices.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Chemistry, Analytical
Ryohei Ueno, Masahiro Kuninori, Takumi Sumi, Ramin Banan Sadeghian, Yuji Takata, Azusa Iguchi, Masahiro Tsuda, Fumiyoshi Yamashita, Kentaro Ichikawa, Ryuji Yokokawa
Summary: Microphysiological systems (MPS) are emerging as a technology for next-generation non-clinical drug screening. These microfluidic devices mimic the physiological functions of human organs and have the potential to reduce animal experiments, improve drug efficacy prediction, and lower drug discovery costs.
Article
Pharmacology & Pharmacy
Shoko Nomura, Erike W. Sukowati, Yuko Shigeno, Maiko Takahashi, Akari Kato, Yoshimi Benno, Fumiyoshi Yamashita, Hidefumi Mukai
Summary: We demonstrate the potential use of Blautia coccoides JCM1395(T) as a tumor-targeted live bacterial therapeutic. We developed a reliable quantitative analysis method for bacterial detection in biological tissues, overcoming the hindrance caused by the thick outer layer of peptidoglycans in Gram-positive bacteria. Using this method, we individually detected Blautia coccoides JCM1395(T) and Bacteroides vulgatus JCM5826(T) in tumors of mice receiving intravenous mixture injection. This simple and reproducible method, without genetic modification, can be applied to explore a wide range of bacterial species.
Article
Chemistry, Multidisciplinary
Ryosaku Ota, Fumiyoshi Yamashita
Summary: This review discusses the current status and challenges of applying machine-learning techniques to the analysis and prediction of pharmacokinetic data. While traditional mathematical models have limitations in explaining ADME processes and predicting pharmacokinetic time profiles, machine learning offers a data-driven approach for handling complex phenomena. Machine-learning models generally outperform linear models and new structures, such as transfer learning and generative adversarial networks, are continuously being proposed. The key issue now is how to apply these emerging machine-learning technologies to the field of pharmacokinetics/pharmacodynamics.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Pharmacology & Pharmacy
Yuko Sasaki, Hirotaka Tatsuoka, Masahiro Tsuda, Takumi Sumi, Yuka Eguchi, Kanako So, Yuriko Higuchi, Kazuo Takayama, Yusuke Torisawa, Fumiyoshi Yamashita
Summary: Microfluidic devices are a promising tool for studying drug transport and metabolism. This study investigated drug transport across Caco-2 cell layers in microfluidic devices and found that drug lipophilicity influenced permeability. Fluidic conditions also promoted drug metabolism. These findings provide valuable information for the application of microfluidic devices in drug research.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Toxicology
Qiyue Zhang, Shiori Taniguchi, Kanako So, Masahiro Tsuda, Yuriko Higuchi, Mitsuru Hashida, Fumiyoshi Yamashita
Summary: Drug-induced liver injury (DILI) is a major cause of drug development failure and post-approval withdrawal. This study identified CREB as a potential sensitive biomarker for DILI prediction and suggested that its response to stress induced by high-risk drugs might be primarily regulated by the PKA/CREB signaling pathway.
JOURNAL OF TOXICOLOGICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Yukinobu Kodama, Ayako Tokunaga, Junya Hashizume, Hiroo Nakagawa, Hitomi Harasawa, Tomoaki Kurosaki, Tadahiro Nakamura, Koyo Nishida, Mikiro Nakashima, Mitsuru Hashida, Shigeru Kawakami, Hitoshi Sasaki
Summary: A biocompatible splenic vector for a DNA vaccine against melanoma was developed, showing strong luciferase activity and suppression of melanoma growth and metastasis in mice. The ternary complex mainly transfected into macrophages in the spleen, indicating its suitability for DNA vaccination. The ternary complex also exhibited low acute and liver toxicities in mice, confirming its safety profile.