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)
Review
Engineering, Chemical
Xuewen Mu, Yun Xu, Zheng Wang, Dunyun Shi
Summary: NAD(P)H:quinone oxidoreductase 1 is an enzyme highly expressed in tumors and can be targeted for cancer therapy. Quinone-based bioimaging probes and nanosystems can be used for tumor diagnosis and treatment, improving effectiveness and reducing side effects.
FRONTIERS OF CHEMICAL SCIENCE AND ENGINEERING
(2023)
Article
Chemistry, Medicinal
Kuojun Zhang, Kaizhen Wang, Xiangyu Zhang, Zhenlong Qian, Wenbo Zhang, Xiao Zheng, Jiaying Wang, Yin Jiang, Wanheng Zhang, Zhiyu Lu, Haiping Hao, Sheng Jiang
Summary: Targeting NAD(+) metabolism is an effective anticancer strategy. Small molecules that simultaneously target NQO1 and NAMPT were discovered, and one of these compounds, 10d, showed excellent in vivo antitumor efficacy without significant toxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
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
Chemistry, Multidisciplinary
Naveen J. Roy, Shreyada N. Save, Virender Kumar Sharma, Benchamin Abraham, Abhijith Kuttanamkuzhi, Shilpy Sharma, Mayurika Lahiri, Pinaki Talukdar
Summary: NQO1, a detoxifying enzyme overexpressed in tumors, can protect cancer cells against oxidative stress. The activation of 'protransporter' systems in cancer cells has been achieved using NQO1 activatable quinones, leading to cell apoptosis. The ion transport activity of salicylamides was effectively inhibited by caging the OH group with NQO1-activatable quinones. Activation of the trapped 'protransporters' following reduction by NQO1 was verified. Both the transporters and trapped protransporters exhibited significant toxicity towards MCF-7 breast cancer cells, mediated through oxidative stress, mitochondrial membrane depolarization, and lysosomal deacidification. Induction of cell death via the intrinsic apoptotic pathway was confirmed by monitoring PARP1 cleavage.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
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)
Review
Pharmacology & Pharmacy
Jie Yu, Bingling Zhong, Lin Zhao, Ying Hou, Nana Ai, Jin-Jian Lu, Wei Ge, Xiuping Chen
Summary: Drug resistance is a significant challenge in cancer treatment, and a natural NQO1 substrate called MAM has been found to have a potent anticancer effect. This study aimed to investigate the efficacy of MAM against drug-resistant non-small cell lung cancer. The results showed that MAM induces ferroptosis by targeting NQO1, leading to ROS generation, LIP increase, and lipid peroxidation. Furthermore, MAM significantly suppressed tumor growth in a zebrafish model. These findings provide a novel therapeutic strategy for overcoming drug resistance in NSCLC by inducing NQO1-mediated ferroptosis.
DRUG RESISTANCE UPDATES
(2023)
Article
Chemistry, Multidisciplinary
Evelyn Y. Xue, Fangyuan Kang, Yimin Zhou, Dennis K. P. Ng
Summary: In this study, a far-red-absorbing boron dipyrromethene-based photosensitizer responsive to cancer-associated human NAD(P)H:quinone oxidoreductase 1 was developed, allowing controlled restoration of photodynamic activity for selective elimination of cancer cells.
CHEMICAL COMMUNICATIONS
(2023)
Review
Nutrition & Dietetics
Jyothi Dhuguru, Ryan W. W. Dellinger, Marie E. E. Migaud
Summary: Dietary vitamin B3 components have been found to increase NAD(+) levels, which decline with age and disease. Supplementation with NAD(+) biosynthetic intermediates, such as NR and NMN, can effectively raise NAD(+) levels. In addition, inhibiting NAD(+)-consuming enzymes or activating biosynthetic pathways is also a viable approach to increase NAD(+) and NADH. However, the pharmacological significance of NAD(H) catabolites is often overlooked, despite some of these metabolites serving as biomarkers in physiological disorders.
Article
Microbiology
Nathan M. Lewis, Abigail Sarne, Kathryn R. Fixen
Summary: There is increasing evidence that protein electron carriers like Fd evolved to form specific partnerships with select electron donors and acceptors to keep native electron transfer pathways insulated from one another. This study shows that amino acid substitutions enabled electron transfer to nitrogenase, providing a model system to understand electron transfer chain specificity and how new electron transfer pathways can be evolved for biotechnologically valuable pathways like nitrogen fixation.
Article
Chemistry, Multidisciplinary
Cancan Yang, Zhenling Huang, Xiuguo Zhang, Chunyuan Zhu
Summary: Soluble quinone oxidoreductases facilitate electron transfer from NADPH to quinones for detoxification of synthetic compounds. The crystal structure of NADPH-dependent QOR from Phytophthora capsici (Pc) reveals a bimodular architecture with NADPH-binding grooves and substrate-binding pockets. The enzyme functions as a tetramer in solution and exhibits conserved topology among homologous structures, but with varying substrate specificities. PcQOR prefers catalyzing large substrates like 9,10-phenanthrenequinone, potentially aiding in detoxification of harmful chemicals during invasion by P. capsici.
Article
Biochemistry & Molecular Biology
Sudipta Panja, David Siegel, Simonetta Camandola, Rafael de Cabo, David Ross, Krishna M. G. Mallela
Summary: This study explores the pathogenesis of Alzheimer's disease (AD) and finds that the FAD-deficient forms of NQO1 may accelerate the aggregation of Alzheimer's amyloid-beta peptide (A beta(1-42)), shedding light on the development of AD.
BIOSCIENCE REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Juan Luis Pacheco-Garcia, Ernesto Anoz-Carbonell, Pavla Vankova, Adithi Kannan, Rogelio Palomino-Morales, Noel Mesa-Torres, Eduardo Salido, Petr Man, Milagros Medina, Athi N. Naganathan, Angel L. Pey
Summary: The study reveals that disease-associated mutations and phosphorylation events on human flavoproteins can affect protein stability, propagating to different functional sites leading to specific phenotypic manifestations.
Article
Chemistry, Applied
Yu Wang, Ting Ma, Junqiang Dong
Summary: This study designed a new near-infrared and large Stokes shift fluorescence probe (HHW-1) for the accurate detection of NQO1 activity, which is widely over-expressed in many cancers and could be used for early cancer screening. HHW-1 showed an off-on fluorescent signal and large Stokes shift in a time-dependent manner, exhibiting high selectivity and low detection limit. It could track the change of NQO1 activity in cells and tumor bearing mice, making it a promising indicator for early tumor diagnosis.
Article
Dermatology
Kyung-Il Kim, Kyung Eun Jung, Young-Bin Shin, Chang-Deok Kim, Tae-Jin Yoon
Summary: In this study, we conducted a large-scale screening test on drugs approved for other diseases to find pigmentation-modulating agents. Among the potential drugs, sorafenib was selected for further investigation on its effect on pigmentation in melanoma cells. The results showed that sorafenib promoted pigmentation by increasing the melanin content and tyrosinase activity. Mechanistic studies revealed that this effect was mediated by the activation of beta-catenin signaling through the regulation of GSK3 beta phosphorylation.
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Chemistry, Medicinal
Nurul Farah Adni Mat Zian, Puspanjali Swain, Siti Munirah Mohd Faudzi, Norzalina Zakaria, Wan Norhamidah Wan Ibrahim, Noraini Abu Bakar, Khozirah Shaari, Johnson Stanslas, Tae-Ik Choi, Cheol-Hee Kim
Summary: In this study, the ethyl acetate fraction of butterfly pea flower was analyzed and found to have neuroprotective and anti-neuroinflammatory properties. The metabolome analysis identified flavonol 3-O-glycosides, hydrocinnamic acids, and primary metabolites as potential bioactive compounds. Molecular docking studies suggested that the fraction targets iNOS and decreases nitric oxide levels. In vivo toxicity tests in zebrafish models showed no harmful effects on development, blood vessel formation, and apoptosis. These preliminary findings provide scientific support for the anti-neuroinflammatory and neuroprotective effects of butterfly pea.
Article
Environmental Sciences
Noraini Abu Bakar, Wan Norhamidah Wan Ibrahim, Che Azurahanim Che Abdullah, Nurul Farhana Ramlan, Khozirah Shaari, Shamarina Shohaimi, Ahmed Mediani, Nurrul Shaqinah Nasruddin, Cheol-Hee Kim, Siti Munirah Mohd Faudzi
Summary: This study provides new insight into the potential mechanism of arsenic toxicity leading to long-term learning impairment in zebrafish. The researchers found that exposure to arsenic trioxide (As2O3) resulted in increased mortality and various behavioral deficits in zebrafish, including motor behavior deficits and impaired color preference. The study also identified changes in gene regulation and metabolic pathways associated with the toxic effects of As2O3. These findings may be useful for future risk assessments of environmental toxins.
Article
Biochemistry & Molecular Biology
Yu-Ri Lee, Myeongjoo Son, Young Sook Kim, Jin Sook Kim, Cheol-Hee Kim, Seung-Hyun Jung
Summary: The evaluation of retinal vascular structures is crucial for studying ophthalmic diseases. This study introduces a rapid and convenient method to investigate the fine vessel structures in the intact retinal vasculature of adult zebrafish. The method allows for detailed examination of tight junction structures and identification of different cell types in the retinal vasculature. The findings also show the potential of using this method to study retinal vascular diseases in zebrafish models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Joo-Yeon Lim, Ye-Eun Jung, Hye-Eun Hwang, Cheol-Hee Kim, Nese Basaran-Akgul, Sri Harshini Goli, Steven P. Templeton, Hee-Moon Park
Summary: Deletion of SvfA in Aspergillus nidulans leads to decreased cell wall components, biofilm formation, and protease activity, and increased extracellular signal-regulated kinase (ERK) activation, resulting in reduced virulence.
Article
Dermatology
Jung-Min Shin, Kyung Min Kim, Chang Deok Kim, Young Lee, Sanghyun Park
EXPERIMENTAL DERMATOLOGY
(2023)
Article
Dermatology
Jung-Min Shin, Kyung Min Kim, Mi Soo Choi, Sanghyun Park, Dongkyun Hong, Kyung-Eun Jung, Young-Joon Seo, Chang Deok Kim, Hanseul Yang, Young Lee
Summary: Alopecia areata (AA) is a T-cell-mediated autoimmune disease causing chronic hair loss, with its exact pathogenesis still unclear. Recent studies have shown the importance of crosstalk between inflammasomes and mitophagy, a process that removes damaged mitochondria. This study found mitochondrial DNA damage in AA-affected scalp tissues and treated cells, as well as increased mitochondrial reactive oxygen species (ROS) levels with treatment. Mitophagy induction was shown to alleviate NLRP3 inflammasome activation, and PINK1-mediated mitophagy played a critical role in inflammasome activation. These findings highlight the significance of mitophagy-inflammasome crosstalk in AA pathogenesis and suggest potential therapeutic targets.
EXPERIMENTAL DERMATOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Seong-Kyu Choe, Cheol-Hee Kim
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Hannah C. Rudolph, April M. Stafford, Hye-Eun Hwang, Cheol-Hee Kim, Jeremy W. Prokop, Daniel Vogt
Summary: There are several rare genes, including the WAC gene, that are disrupted and contribute to neurological dysfunction. In this study, we explored the role of the WAC protein in brain cells associated with DeSanto-Shinawi syndrome (DESSH), a rare disorder characterized by cranio-facial changes, autism, and attention deficit hyperactivity disorder. We identified novel regions in the WAC protein necessary for its localization to the nucleus and found that the amino-terminus of the protein is responsible for localizing it to distinct cell regions in brain neurons.
Article
Multidisciplinary Sciences
Muhammad Syafiq Akmal Mohd Fahmi, Puspanjali Swain, Amirah Hani Ramli, Wan Norhamidah Wan Ibrahim, Nur Atikah Saleh Hodin, Noraini Abu Bakar, Yee Seng Tan, Siti Munirah Mohd Faudzi, Cheol-Hee Kim
Summary: Epilepsy is a common brain disease and the available antiepileptic drugs often have side effects. In this study, 18 newly designed fluorine-containing pyrrolylated chalcones were tested as potential new AEDs. Compound 8 showed good drug-like properties and binding affinity to GABAA receptor. It effectively reduced convulsive behavior in zebrafish models and had no cardiotoxic effects. Pyrrolylated chalcones could be alternative AEDs and further studies are needed to understand their mechanism of action.
Article
Dermatology
Kyung-Il Kim, Seung-Mee Kim, Young-Yoon Lee, Young Lee, Chang-Deok Kim, Tae-Jin Yoon
Summary: This study investigates the action mechanisms of the cholesterol-lowering drug pitavastatin on cutaneous squamous cell carcinoma (SCC) cells. The results show that pitavastatin dose-dependently induces apoptosis of cutaneous SCC cells, but has no effect on normal keratinocytes. Further experiments reveal that pitavastatin-induced apoptosis is achieved through GGPP-dependent JNK activation.
ANNALS OF DERMATOLOGY
(2023)
Article
Dermatology
Sang-Hoon Lee, Hee-Seok Seo, Seong Jun Seo, Chang-Deok Kim, Seung-Phil Hong
Summary: This study investigated the potential of plant extracts to enhance skin-barrier function by promoting lipid synthesis in keratinocytes. The results showed that Melia toosendan extract had the highest expression of lipid synthase and could improve skin-barrier function.
ANNALS OF DERMATOLOGY
(2022)
Article
Dermatology
Kyung-Il Kim, Chang-Il Kwon, Jeung-Hoon Lee, Chang-Deok Kim, Tae-Jin Yoon
Summary: This study found that mitoxantrone reduces collagen synthesis by inhibiting TGF-(3/SMAD signaling and LARP6 expression in fibroblasts.
ANNALS OF DERMATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Myeongjoo Son, Dae Yu Kim, Cheol-Hee Kim
Summary: Rare diseases are medical conditions that affect a small number of people and often lack viable treatment options. Neurological and neurodevelopmental disorders make up approximately 40% of rare diseases. Model organisms like roundworms, fruit flies, and zebrafish have been extensively used to study the characteristics and causative genes of rare neurological disorders, with a particular focus on zebrafish disease modeling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Obstetrics & Gynecology
Soo Youn Song, Si Yeo Lee, Young Bok Ko, Jinju Kim, Tae-Young Choi, Ki Hwan Lee, Heon Jong Yoo, Jae Min Yuk
Summary: This study demonstrated the effects of fenofibrate on human cervical cancer cells, showing that it induced cell cycle arrest and apoptosis while also activating autophagy. However, the anticancer effects of fenofibrate were reduced due to the activation of autophagy. Therefore, a combination therapy of an autophagy inhibitor and fenofibrate could be a potential new strategy for treating cervical cancer.
GYNECOLOGIC AND OBSTETRIC INVESTIGATION
(2022)