Article
Chemistry, Analytical
Bo Peng, Gang Chen, Yahui Li, Hao Zhang, Jianliang Shen, Ji-Ting Hou, Zhipeng Li
Summary: In this study, a new pancreatic cancer-specific probe was developed, which can trigger near-infrared emission and selectively induce cell death. The probe showed good imaging results in both experimental and clinical samples, suggesting its potential clinical application for the treatment and diagnosis of pancreatic cancer.
ANALYTICAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Peter Tsvetkov, Julia Adler, Romano Strobelt, Yaarit Adamovich, Gad Asher, Nina Reuven, Yosef Shaul
Summary: This passage demonstrates the interaction between SIRT1 and NQO1, indicating that SIRT1 can regulate the expression of NQO1 and exert a protective role under mitochondrial stress.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biology
Wang-Soo Lee, Woojin Ham, Jaetaek Kim
Summary: NQO1 is an antioxidant flavoprotein that exerts antioxidant activities, anti-inflammatory effects, and interacts with tumor suppressors. Recent studies have highlighted the promising roles of NQO1 in protecting against cardiovascular damage and related diseases.
Article
Nanoscience & Nanotechnology
Haili Zhang, Xiao Xu, Dan Yan, Chunlin Ren, Jinghan Zhang, Mengzhen Gu, Yun Wang, Peiye Wu, Zhongrui Li, Lingyi Kong, Chao Han
Summary: Researchers developed a new nanodrug delivery system (PN) to increase ROS production by degrading the NQO1 protein, leading to enhanced anti-tumor effects. In vitro and in vivo studies demonstrated that PN significantly increased ROS production and exhibited potent antitumor properties. This nanoplatform might provide an alternative approach for treating tumors with NQO1 overexpression.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Engineering, Biomedical
Shanshan Zhu, Tian Zhang, Huan Gao, Guorui Jin, Jin Yang, Xiaocong He, Hui Guo, Feng Xu
Summary: Chemotherapy for breast cancer treatment is commonly used in clinics but has limited efficacy due to poor specificity and tumor microenvironment-induced diffusion barrier. A combination therapy strategy based on an extracellular matrix modulator and tumor microenvironment-responsive drug is developed, demonstrating outstanding therapeutic efficacy in vitro and in vivo. This mechanochemical approach provides a promising approach for breast cancer therapy.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Guo Li, Yongxiao Xu, Xiaojie Kong, Liuwei Gu, Yuling Qin, Li Wu
Summary: An NQO1-responsive precursor called R848-QPA has been developed to induce an anti-tumor immune response. When activated by overexpressed NQO1 in the tumor microenvironment, R848-QPA can activate innate immunity, but it shows lower activity in NQO1-deprived environments. This strategy offers a new approach for the development of tumor-microenvironment-responsive prodrugs for antitumor immunotherapy.
CHEMICAL COMMUNICATIONS
(2023)
Article
Environmental Sciences
Chi Chen, Guan-Chung Wu, Yao-Tse Chung, Hau-Wen Li, Pei-Hsuan Chou, Yung-Che Tseng, Chieh-Jhen Chen, Sylvie Dufour, Ching-Fong Chang
Summary: This study investigated the sulfide tolerance and detoxification mechanisms of the hydrothermal crab, Xenograpsus testudinatus (xtcrab). The results showed that xtcrabs have a high sulfide tolerance and detoxify sulfide by converting it into less toxic thiosulfate. Two SQR genes, xtSQR1 and xtSQR2, were found in xtcrabs and were expressed in different tissues, suggesting their involvement in detoxification. The expression and activity of xtSQR1 were higher in the gill of xtcrabs in sulfide-rich habitats. This study provides insights into the adaptation of xtcrabs to high-sulfide hydrothermal environments.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Biotechnology & Applied Microbiology
Tomoya Maeda, Abigail Koch-Koerfges, Michael Bott
Summary: The oxidation of NADH and reduction of quinone is crucial for cellular metabolism. In this study with Corynebacterium glutamicum, Ndh was found to be the main enzyme for NADH oxidation, while Mdh and LdhA can functionally replace Ndh. The study also showed that Mdh and LdhA, along with Mqo and LldD, play active roles in NADH oxidation and menaquinone reduction.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Biology
Anamika Battu, Rajaram Purushotham, Rupinder Kaur
Summary: Fld-LPs are important components of the oxidative stress defense system in organisms, with the ability to convert quinones to hydroquinones using NAD(P)H as an electron donor. The activity of Fld-LPs can be measured in whole cell extracts and their assembly and activity can be regulated by posttranslational modifications. This assay provides a reliable method to study fungal oxidative stress response systems and screen inhibitors specific for fungal Fld-LPs.
Review
Biochemistry & Molecular Biology
Giovanni Tossetta, Sonia Fantone, Gaia Goteri, Stefano Raffaele Giannubilo, Andrea Ciavattini, Daniela Marzioni
Summary: Ovarian cancer is a dangerous gynecologic malignancy with high fatality rate. Oxidative stress and NQO1 play important roles in the occurrence and progression of ovarian cancer. This review summarizes the evidence from literature regarding the effect of NQO1 on ovarian cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Zengrui Wu, Qiaohui Wang, Hongbin Yang, Jiye Wang, Weihua Li, Guixia Liu, Yi Yang, Yuzheng Zhao, Yun Tang
Summary: The study discovered new compounds targeting NQO1 through network-based analysis and identification of privileged substructures from a natural product library. Experimental validation revealed potential anticancer activity of the compounds, showing the effectiveness of the workflow and computational methods in drug discovery and development.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Multidisciplinary
Ya-ping Dong, Shu-zhen Chen, Hui-si He, Zhuo-ran Sun, Li-xuan Jiang, Yan-qiu Gu, Ying Zhang, Fei Feng, Chun Chen, Zhe-cai Fan, Xiao-fei Chen, Wen Wen, Hong-yang Wang
Summary: In this study, four compounds were screened from Scutellaria baicalensis as potential NQO1 inhibitors. Among them, skullcapflavone II (SFII) showed the most promising inhibitory activity against NQO1. SFII was found to alleviate AAI-induced DNA damage and apoptosis in human liver and renal cells, as well as ameliorate AAI-induced renal fibrosis and dysfunction in adult mice. Furthermore, SFII suppressed AAI-induced hepatocellular carcinoma initiation in infant mice.
ACTA PHARMACOLOGICA SINICA
(2023)
Review
Toxicology
Slobodan P. Rendic, Rachel D. Crouch, F. Peter Guengerich
Summary: This article provides an overview of the metabolic reactions catalyzed by flavin monooxygenase (FMO), monoamine oxidase (MAO), NAD(P)H quinone oxidoreductase (NQO), and molybdenum hydroxylase enzymes (aldehyde oxidase (AOX) and xanthine oxidoreductase (XOR)) for drugs, natural products, physiological compounds, and other chemicals. The article discusses the roles of these enzymes as substrates, inducers, and inhibitors, and explores the metabolism and bioactivation of selected examples from each group. FMO enzymes have a higher fraction of bioactivation reactions, predominantly involving drugs and general chemicals, while MAO enzymes primarily metabolize physiological compounds and may lead to unwanted side effects. AOX and XOR enzymes catalyze the oxidation and reduction of various compounds, with AOX playing a more significant role in drug metabolism over the past decade. XOR has a narrower substrate specificity and less involvement in the metabolism of clinical drugs and candidates.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Oncology
Bowen Weng, Xiaoyue Zhang, Xiaoyun Chu, Xiaohui Gong, Cheng Cai
Summary: The Nrf2-Keap1-antioxidant response element-NQO1 signaling pathway plays a protective role in hyperoxia-induced lung injury by inhibiting apoptosis, as demonstrated by the upregulation of Nrf2, Keap1, and NQO1 expression under hyperoxic conditions, and the downregulation of these genes leading to increased apoptosis after transfection with Nrf2 siRNA.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Guomin Shen, Chaokun Li, Qing Cao, Abhin Kumar Megta, Shuang Li, Meng Gao, Hongli Liu, Yan Shen, Yixiang Chen, Haichuan Yu, Sanqiang Li, Weikai Li
Summary: This study reveals the structural features of the epoxide reductase activity carried out by a subset of the VKOR family in the membrane environment. It also demonstrates that a representative bacterial VKOR homolog can be converted to an epoxide reductase that is also inhibitable by warfarin.
Article
Chemistry, Analytical
Ruth N. Muchiri, Richard B. van Breemen
Summary: The study developed and validated a fast, precise, and sensitive assay for the quantitative analysis of milk thistle flavonolignans extracted from human serum. The method demonstrated good selectivity, accuracy, and linearity, making it suitable for the analysis of flavonolignans.
JOURNAL OF AOAC INTERNATIONAL
(2021)
Article
Biotechnology & Applied Microbiology
Gregory J. Heller, Michael S. Marshall, Yazan Issa, Jeffrey N. Marshall, Duc Nguyen, Emily Rue, Koralege C. Pathmasiri, Miriam S. Domowicz, Richard B. van Breemen, Leon M. Tai, Stephanie M. Cologna, Stephen J. Crocker, Maria Givogri, Mark S. Sands, Ernesto R. Bongarzone
Summary: Neonatal AAV9 gene therapy of GALC significantly improves neuropathology in Twitcher mice, but leads to the development of multiple small focal demyelinating areas in the brain. These lesions are associated with lysosomal alterations, fibrinogen extravasation, and gliotic response.
Article
Biochemical Research Methods
Daniel G. Nosal, Douglas L. Feinstein, Richard B. van Breemen
Summary: A method was developed to separate and quantify stereoisomers of superwarfarins in human plasma, allowing for the determination of half-lives and potential guidance for the development of safer next-generation anticoagulant rodenticides.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2021)
Article
Instruments & Instrumentation
Ron C. Gaba, Ramzy C. Khabbaz, Ruth N. Muchiri, Joseph D. Morrison, Lobna Elkhadragy, William M. Totura, Jonathan P. Samuelson, Herbert E. Whiteley, Ryan L. Deaton, Peter L. Nguyen, Maria Sverdlov, Jeremy J. Johnson, Richard B. van Breemen, R. Peter Lokken
Summary: In a rabbit VX2 liver tumor model, both conventional and drug-eluting embolic transarterial chemoembolization achieved tumoricidal intra-tumoral DOX levels and high tumor-to-normal liver drug ratios, with conventional method resulting in significantly greater tumor coverage.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2022)
Article
Emergency Medicine
Erik Wright, John W. Hafner, Gregory Podolej, Douglas L. Feinstein, Richard van Breemen, Israel Rubinstein, Steven Aks, Michael Wahl
Summary: Synthetic cannabinoids are designer drugs that have been widely available in the United States since 2008. A study in Illinois found that over 160 cases of bleeding and prolonged coagulopathy were caused by contaminated synthetic cannabinoids in 2018. The study also identified three long-acting anticoagulant rodenticides in patients who had inhaled tainted products, making it the largest presentation of such poisoning via the inhalational route.
WESTERN JOURNAL OF EMERGENCY MEDICINE
(2021)
Article
Plant Sciences
Richard B. van Breemen, Ruth N. Muchiri, Timothy A. Bates, Jules B. Weinstein, Hans C. Leier, Scotland Farley, Fikadu G. Tafesse
Summary: Cannabigerolic acid and cannabidiolic acid from hemp have been found to prevent infection by SARS-CoV-2 and its variants. They are orally bioavailable and safe for human use, making them potential candidates for preventing and treating COVID-19.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Biochemical Research Methods
Ruth N. Muchiri, James Kibitel, Margaret A. Redick, Richard B. van Breemen
Summary: Affinity selection-mass spectrometry is a powerful tool for discovering ligands that bind to pharmacological targets, which can help in the development of therapeutic agents for preventing COVID-19. A new MagMASS assay using robotics was developed for enhanced throughput and sensitivity, leading to the discovery of small molecule ligands in licorice extracts.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Plant Sciences
Tristesse C. J. Burton, David C. Lankin, Dejan Nikolic, Brian Guo, Jianming Ju, Birgit M. Dietz, Chun-Tao Che, Djaja Djendoel Soejarto, Richard B. van Breemen
Summary: A new isoflavonoid, xanthocerin J, along with previously described xanthocerin A, were isolated from the traditional American Indian herb, Amorpha canescens Pursh. These compounds showed dose-dependent antiestrogenic activity in vitro but not in cell-based assays, suggesting possible synergistic or additive activity with other compounds in the herb. The study highlights the potential of Amorpha canescens as a source for future discovery of compounds related to estrogen pathways for women's health.
PHYTOCHEMISTRY LETTERS
(2021)
Article
Plant Sciences
Jeanmaire Molina, Dejan Nikolic, Jashvanth Raaj Jeevarathanam, Rinat Abzalimov, Eun-Jung Park, Ronniel Pedales, Elmer-Rico E. Mojica, Danilo Tandang, William McLaughlin, Kyle Wallick, James Adams, Ari Novy, Susan K. Pell, Richard B. van Breemen, John M. Pezzuto
Summary: This study compared the metabolites in Rafflesia-infected and non-infected Tetrastigma shoots and found that benzylisoquinoline alkaloids were abundant in non-infected shoots, which has not been reported before in the genus Tetrastigma. Oxylipins and a flavonoid, involved in immune response, were elevated in Rafflesia-infected shoots. These findings provide valuable insights for Rafflesia conservation and propagation.
Article
Neurosciences
Rima Rebiai, Emily Rue, Steve Zaldua, Duc Nguyen, Giuseppe Scesa, Martin Jastrzebski, Robert Foster, Bin Wang, Xuntian Jiang, Leon Tai, Scott T. Brady, Richard van Breemen, Maria I. Givogri, Mark S. Sands, Ernesto R. Bongarzone
Summary: Krabbe Disease is a lysosomal storage disorder caused by a genetic deficiency of the enzyme GALC. Research has shown that different mutations in GALC can impact sphingolipid metabolism, resulting in varying symptoms and manifestations.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Lobna Elkhadragy, Ramzy C. Khabbaz, Ruth N. Muchiri, William M. Totura, Jonathan P. Samuelson, Herbert E. Whiteley, Richard B. van Breemen, R. Peter Lokken, Ron C. Gaba
Summary: This study investigated the pharmacokinetics and early effects of sorafenib and doxorubicin in conventional transarterial chemoembolization (TACE) for VX2 liver tumors in rabbits. The results showed that the addition of sorafenib resulted in high intratumoral concentrations and increased expression of HIF-1α, while the concentrations of doxorubicin were similar between the groups. Tumor volume, necrosis, VEGF expression, and MVD were similar in the two groups.
JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jialin Liu, Suzanne Banuvar, Marlos Viana, Elena Barengolts, Shao-Nong Chen, Guido F. Pauli, Richard B. van Breemen
Summary: Licorice, a herbal plant, has been used for its medicinal and flavoring properties. Recent studies suggest that licorice extracts can alleviate menopausal symptoms in females. However, clinical investigations show that licorice does not cause clinically relevant pharmacokinetic interactions with certain enzymes.
DRUG METABOLISM AND DISPOSITION
(2023)
Review
Medicine, Research & Experimental
Richard B. van Breemen, Daniel Simchuk
Summary: Hemp is an understudied source of pharmacologically active compounds, with over 100 cannabinoids, and recent research has shown antiviral activities of cannabidiol (CBD), A9-tetrahydrocannabinol (A9-THC), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and other cannabinoids against SARS-CoV-2, HIV, and gamma-herpes viruses. The mechanisms of action include inhibition of viral cell entry, viral protease inhibition, and stimulation of cellular innate immune responses. Clinical studies and trials support the antiviral properties of cannabinoids, but further well-designed clinical trials are urgently needed.
Article
Neurosciences
Cory R. Reiter, Rima Rebiai, Angelika Kwak, Jeff Marshall, Dylan Wozniak, Giusepe Scesa, Duc Nguyen, Emily Rue, Chandimal Pathmasiri, Robert Pijewski, Richard van Breemen, Stephanie Cologna, Stephen J. Crocker, M. Irene Givogri, Ernesto R. Bongarzone
Summary: This study found that Psychosine is associated with secreted extracellular vesicles (EVs) and reducing EV secretion in the brain of Twitcher mice led to increased disease severity. The results suggest the secretion of pathogenic lipids via EV pathways and highlight the relevance of this mechanism in spreading pathogenic lipids in neurological lipidoses.
Article
Biochemical Research Methods
Ruth N. Muchiri, Richard B. van Breemen
Summary: Affinity selection-mass spectrometry (AS-MS) was invented to address the high-throughput screening demands of combinatorial chemistry, utilizing binding interactions between ligands and receptors to isolate pharmacologically active compounds from mixtures of small molecules. AS-MS has three main approaches: pulsed ultrafiltration (PUF) AS-MS, size exclusion chromatography (SEC) AS-MS, and magnetic microbead affinity selection screening (MagMASS), with the capacity to screen hundreds of thousands of compounds per day.
JOURNAL OF MASS SPECTROMETRY
(2021)
