Article
Gastroenterology & Hepatology
Steffen Landerer, Sandra Kalthoff, Christian P. Strassburg
Summary: The study found that coffee exerts a protective effect in cholestasis-induced liver fibrosis by activating UGT1A enzymes, reducing collagen deposition, oxidative stress, and the expression of profibrotic markers. The inductive effect of coffee on UGT1A genes plays a key role in hepatic protection and antioxidative effects.
HEPATOBILIARY SURGERY AND NUTRITION
(2021)
Article
Pharmacology & Pharmacy
Urs Duthaler, Fabio Bachmann, Agustos C. Ozbey, Kenichi Umehara, Neil Parrott, Stephen Fowler, Stephan Krahenbuhl
Summary: In this study, the impact of liver cirrhosis on the activity of UDP-glucuronosyltransferases (UGTs) was investigated. It was found that liver cirrhosis may affect the activity of UGTs according to liver function, with significant changes in glucuronidation capacity observed in some substrates in patients with liver cirrhosis. However, clinically significant glucuronide accumulation did not occur in the population studied.
CLINICAL PHARMACOKINETICS
(2023)
Article
Pharmacology & Pharmacy
Ana Loureiro, Carlos Fernandes-Lopes, Maria Joao Bonifacio, Filipa Sousa, Laszlo E. Kiss, Patricio Soares-da-Silva
Summary: Opicapone is a selective catechol-O-methyltransferase inhibitor that has been authorized for marketing in Europe, Japan, and the United States. This study investigated the metabolism and excretion of Opicapone in rats and found that it is rapidly absorbed, widely distributed in peripheral tissues, metabolized mainly through conjugation pathways, and primarily excreted in feces.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2022)
Article
Biochemistry & Molecular Biology
Alexandra N. Boix De Jesus, Ahmad Taha, David Wang, Paulomi M. M. Mehta, Sunali Mehta, Ashley Reily-Bell, Sasini Polwatta Lekamlage, Adriana Machado Saraiva, Tahmeed Tahmeedzaman, Fouzia Ziad, Ziad Thotathil, Peter Y. C. Gan, Janice Royds, Antony Braithwaite, Noelyn Hung, Tania L. L. Slatter
Summary: The expression of delta 133p53 beta is increased in various primary tumors and is associated with increased proliferation, migration, and inflammation. In this study, it was found that delta 133p53 beta expression is also related to the development and survival of brain metastases. Furthermore, delta 133p53 beta-expressing cells have increased cancer-promoting properties and invasiveness.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Anoushka Joglekar, Andrey Prjibelski, Ahmed Mahfouz, Paul Collier, Susan Lin, Anna Katharina Schlusche, Jordan Marrocco, Stephen R. Williams, Bettina Haase, Ashley Hayes, Jennifer G. Chew, Neil I. Weisenfeld, Man Ying Wong, Alexander N. Stein, Simon A. Hardwick, Toby Hunt, Qi Wang, Christoph Dieterich, Zachary Bent, Olivier Fedrigo, Steven A. Sloan, Davide Risso, Erich D. Jarvis, Paul Flicek, Wenjie Luo, Geoffrey S. Pitt, Adam Frankish, August B. Smit, M. Elizabeth Ross, Hagen U. Tilgner
Summary: The study revealed variations in alternative RNA splicing across different brain regions, with unclear single-cell resolution of such differences. Certain genes can be influenced by multiple cell types, allowing regional identity to occasionally override cell-type specificity. Through spatial transcriptomics and long-read sequencing, a deeper understanding of brain integration of molecular and cellular complexities is achieved.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Suramya Waidyanatha, Bradley J. Collins, Helen Cunny, Kristin Aillon, Felicia Riordan, Katie Turner, Sandra McBride, Laura Betz, Vicki Sutherland
Summary: The study on the potential toxicity of BPAF in rodent models found significant transfer of BPAF from mother to offspring during gestation and lactation, with higher concentrations of free BPAF compared to total BPAF. Additionally, direct exposure of pups via feed and development of conjugating enzymes in pups by PND 28 were observed. The data from rodent BPAF studies may be useful in predicting human risk from exposure to BPAF considering the similar ontogeny of conjugating enzymes in rodents and humans.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Cell Biology
Michele Zanoni, Alba Clara Sarti, Alice Zamagni, Michela Cortesi, Sara Pignatta, Chiara Arienti, Michela Tebaldi, Anna Sarnelli, Antonino Romeo, Daniela Bartolini, Luigino Tosatto, Elena Adinolfi, Anna Tesei, Francesco Di Virgilio
Summary: Glioblastoma (GBM) is the most lethal brain tumor in adults and is often treated with radiation and temozolomide. However, relapse is common. This study found that after radiation treatment, ATP is released into the tumor microenvironment, activating P2X7 receptors. Different GBM cells vary in P2X7 isoform expression and sensitivity to extracellular ATP. Radiation treatment causes changes in P2X7 isoform expression, leading to cell death and overexpression of stemness and senescence markers. Blocking P2X7 receptors during post-irradiation recovery enhances radiation-dependent cytotoxicity. These findings suggest that P2X7 receptor isoforms play a role in radiation resistance in GBM cells.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Morgan C. Panitchpakdi, Kelly Weldon, Alan Jarmusch, Emily Gentry, Arianna Choi, Yadira D. Sepulveda, Shaden C. Aguirre, Kunyang M. Sun, Jeremiah Momper, Pieter Dorrestein, Shirley Tsunoda
Summary: This study demonstrates the kinetics and metabolism of diphenhydramine in healthy volunteers using skin swab samples in combination with mass spectrometry. The results show that diphenhydramine and its metabolites can be detected on the skin surface non-invasively.
Article
Biochemical Research Methods
Yuqian Zhang, Weiwei Xie, Jian Liu, Zhiqing Zhang, Yiran Jin
Summary: This study describes a specific ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry method for the simultaneous determination of the metabolites of tacrine, bupropion, diclofenac, dextromethorphan, and midazolam. The inhibition degree of these drugs on five cytochrome P450 isoforms was evaluated using IC50 values.
BIOMEDICAL CHROMATOGRAPHY
(2022)
Article
Chemistry, Organic
Megan K. Fraser, Aleksandra Gorecka, Edwin A. Yates, Jonathan A. Iggo, Krzysztof Baj, Andrew V. Stachulski
Summary: The two isomeric monoglucuronides of resveratrol are believed to have valuable biological activities similar to resveratrol itself. Through selective deacylation and subsequent glucuronidation, the desired products were obtained. The stability of these glucuronides in aqueous solution was found to vary significantly, especially the 3-glucuronide's propensity for E/Z isomerisation.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Pharmacology & Pharmacy
Barbara Sanchez-Dengra, Isabel Gonzalez-Alvarez, Marival Bermejo, Marta Gonzalez-Alvarez
Summary: This study developed a new in vitro system combined with a PBPK model to predict brain concentration levels of different drugs in rats. Through internal validation, it was concluded that the model, incorporating MDCK data, provided the best predictions for passive diffusion and carrier-mediated transported drugs.
Article
Toxicology
Christiane Wiemann, Stephanie Melching-Kollmuss, Nina Hambruch, Lucille Wiss, Franz Stauber, Lysiane Richert
Summary: The fungicide boscalid induces thyroid histopathological and hormone effects in rats by inducing liver enzymes. To evaluate the human relevance of liver enzyme induction and its effect on thyroid hormone disruption, an in vitro study was conducted on T4-glucuronidation comparing rat and human hepatocytes. The study found that boscalid induced CYP enzymes and increased T4-glucuronidation in both rat and human hepatocytes, but there were species differences in the induction pattern of UGT genes. Overall, significant increases in T4-glucuronidation were observed in rat hepatocytes but not in human hepatocytes with boscalid exposure.
JOURNAL OF APPLIED TOXICOLOGY
(2023)
Editorial Material
Biochemical Research Methods
Arunima Singh
Summary: Long-read proteogenomics technology can help to delineate the diversity of isoforms in full-length proteins.
Article
Biochemistry & Molecular Biology
Paul Wei-Che Hsu, Po-Cheng Liao, Yu-Hsiang Kao, Xin-Yu Lin, Rong-Nan Chien, Chau-Ting Yeh, Chi-Chun Lai, Yu-Chiau Shyu, Chih-Lang Lin
Summary: This study investigated the possibility of other mutations causing Gilbert's syndrome in the Han population in Taiwan and found a good association between 27 SNPs and the syndrome. Prediction models were developed, providing a reference for future diagnosing of Gilbert's syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Computer Science, Artificial Intelligence
Guoxian Yu, Jie Zeng, Jun Wang, Hong Zhang, Xiangliang Zhang, Maozu Guo
Summary: The paper introduces an imbalanced deep multi-instance learning approach (IDMIL-III) applied to predicting genome-wide isoform-isoform interactions (IIIs), which outperforms competitive methods at both the gene-level and isoform-level. By fusing different data types and introducing novel loss functions and attention strategies, IDMIL-III effectively addresses the challenges of imbalanced classification problems in predicting IIIs.
INTERNATIONAL JOURNAL OF INTELLIGENT SYSTEMS
(2021)
Article
Pharmacology & Pharmacy
Yuki Asai, Yukiko Sakakibara, Miyabi Kondo, Masayuki Nadai, Miki Katoh
Article
Pharmacology & Pharmacy
Yuki Asai, Takanori Yamamoto, Yasuharu Abe
Summary: Drug-induced thrombocytopenia (DITP) can be triggered by various antibiotics, with different onset times and hazard types. The JADER database revealed signals for DITP associated with antibiotics such as fluconazole, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole. Further analysis on factors affecting DITP, including age and sex, showed significant associations with certain antibiotics.
INTERNATIONAL JOURNAL OF TOXICOLOGY
(2021)
Article
Infectious Diseases
Yuki Asai, Takanori Yamamoto, Yoshiharu Sato
Summary: This study made important progress in elucidating the feasibility and relevant factors of micafungin-induced liver injury by using the JADER database for signal detection associated with antifungal-induced liver injuries and medical records for risk assessment.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Yuki Asai, Tatsuki Yanagawa, Takanori Yamamoto, Yoshiharu Sato
Summary: This study investigated the efficacy of serum magnesium monitoring by protocol-based pharmaceutical management (PBPM) and the effect of left ventricular function on hypermagnesemia in heart failure patients. The results suggest that serum magnesium monitoring by PBPM can contribute to the early detection of hypermagnesemia and prevent its progression. Exacerbation of heart failure and reduced left ventricular diastolic capacity are associated with hypermagnesemia.
JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Yuki Asai, Takuya Shintani, Takanori Yamamoto, Yoshiharu Sato
Summary: The management of syncope is crucial for heart failure patients. This case report suggests that disopyramide may be effective in treating refractory syncope in patients with HFpEF. The use of disopyramide improved syncope symptoms and stabilized heart rate and heart rate variability.
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN
(2022)
Article
Pharmacology & Pharmacy
Yukiko Sakakibara, Ayaka Kojima, Yuki Asai, Masayuki Nadai, Miki Katoh
Summary: This study found that valproic acid induced UGT1A6 mRNA expression through AhR and Nrf2 pathways, but not through ERK or JNK pathways.
BIOPHARMACEUTICS & DRUG DISPOSITION
(2022)
Article
Infectious Diseases
Hayahide Ooi, Yuki Asai, Yoshiharu Sato
Summary: The relationship between ABPC/SBT-induced DILI and ALBI score was investigated in this study. It was found that patients with a baseline ALBI score >-2.00 may be at higher risk for ABPC/SBT-induced DILI. Therefore, frequent liver function monitoring should be considered in patients with an ALBI score >-2.00 to prevent the occurrence of DILI.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Yuki Asai, Hiroki Arihara, Saki Omote, Ena Tanio, Saena Yamashita, Takashi Higuchi, Ei Hashimoto, Momoko Yamada, Hinako Tsuji, Yoshihiro Kondo, Makoto Hayashi, Yoshiaki Yamamoto
Summary: This study investigated the influence of polypharmacy on plasma bepridil concentrations in patients with heart failure and found that polypharmacy increased the concentration of bepridil. Furthermore, the number of concomitant drugs used was positively correlated with the plasma bepridil concentration, highlighting the importance of periodically monitoring bepridil concentrations for safe use.
JOURNAL OF PHARMACEUTICAL HEALTH CARE AND SCIENCES
(2023)
Article
Infectious Diseases
Yuki Asai, Hayahide Ooi, Yoshiharu Sato
Summary: This study compared the rate of liver injury between meropenem and doripenem and constructed a decision tree model to predict carbapenem-induced liver injury. The results showed that there was no significant difference in the risk of liver injury between meropenem and doripenem. The decision tree model based on ALT and ALBI score can be useful for assessing liver injury before doripenem administration.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Yuki Asai, Tatsuki Yanagawa, Masaaki Takahashi
Summary: This retrospective cohort study investigated the risk factors for postoperative delirium (PD) in cardiovascular surgery patients. It found that polypharmacy was a significant risk factor. Pharmacist-led interventions, including the use of ramelteon and suvorexant instead of benzodiazepines, were effective in reducing the occurrence of PD.
Article
Pharmacology & Pharmacy
Yuki Asai, Takumi Tashiro, Yoshihiro Kondo, Makoto Hayashi, Hiroki Arihara, Saki Omote, Ena Tanio, Saena Yamashita, Takashi Higuchi, Ei Hashimoto, Momoko Yamada, Hinako Tsuji, Yuji Hayakawa, Ryohei Suzuki, Hiroya Muro, Yoshiaki Yamamoto
Summary: A flowchart using decision tree analysis was constructed to predict digoxin toxicity in HF patients. The study found that creatinine clearance <32 mL/min and daily digoxin dose >= 1.6 mu g/kg were independent risk factors for digoxin toxicity.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2023)
Article
Pharmacology & Pharmacy
Yuki Asai, Masayuki Nadai, Miki Katoh
Summary: This study investigated the effects of single-walled carbon nanotubes (SWCNTs) on human uridine 5'-diphosphate-glucuronosyltransferase (UGT) 1A activities. The results showed that different SWCNTs had different impacts on the activities of UGT1A isoforms.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Pharmacology & Pharmacy
Yuki Asai, Tomoaki Sato, Daisuke Kito, Takanori Yamamoto, Iwao Hioki, Yasuhisa Urata, Yasuharu Abe
Summary: The case presented a 62-year-old male with HFpEF and refractory hypotension due to ongoing diuretic use. Combination therapy with midodrine and droxidopa helped maintain blood pressure and improve urine output in the patient, suggesting a potential treatment option for similar cases. Further studies are needed to evaluate the long-term safety and efficacy of this combination therapy for HFpEF patients.
JOURNAL OF PHARMACEUTICAL HEALTH CARE AND SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Yuki Asai, Takanori Yamamoto, Daisuke Kito, Kazuya Ichikawa, Yasuharu Abe
JOURNAL OF PHARMACEUTICAL HEALTH CARE AND SCIENCES
(2020)
Article
Pharmacology & Pharmacy
Yuki Asai, Hatsuna Tanaka, Masayuki Nadai, Miki Katoh
BIOPHARMACEUTICS & DRUG DISPOSITION
(2018)