Article
Biochemistry & Molecular Biology
Keum-Jin Yang, Won Jung Choi, Yoon-Kyung Chang, Cheol Whee Park, Suk Young Kim, Yu Ah Hong
Summary: Xanthine oxidase (XO) inhibition showed renoprotective effects in diabetic kidney disease (DKD) by inhibiting vascular endothelial growth factor (VEGF) and NADPH oxidase (NOX) and reducing oxidative stress. This study provides important insights into the therapeutic potential of XO inhibition in DKD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Plant Sciences
Yun Yang, Qiu Wei, Ran An, Hua-mei Zhang, Jia-yuan Shen, Xiao-yan Qin, Xiao-ling Han, Jie Li, Xiao-wei Li, Xiu-mei Gao, Jun He, Hao-ping Mao
Summary: This study aimed to investigate the potential effect of Semen Cuscutae on ovariectomy (OVX)-induced osteoporosis in mice and clarify the exact mechanisms by which Semen Cuscutae exert the anti-osteoporosis effect.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Guizhen Zhao, Ziyi Chang, Yang Zhao, Yanhong Guo, Haocheng Lu, Wenying Liang, Oren Rom, Huilun Wang, Jinjian Sun, Tianqing Zhu, Yanbo Fan, Lin Chang, Bo Yang, Minerva T. Garcia-Barrio, Y. Eugene Chen, Jifeng Zhang
Summary: The study indicates that endothelial KLF11 plays an important role in maintaining vascular homeostasis, with its deficiency exacerbating AAA formation and overexpression inhibiting AAA occurrence. KLF11 not only inhibits endothelial cell inflammatory response, but also reduces the production of reactive oxygen species, exerting a protective effect against AAA.
Article
Pharmacology & Pharmacy
Zhiyuan Guan, Zheng Xuanqi, Junxiong Zhu, Wanqiong Yuan, Jialin Jia, Chenggui Zhang, Tiantong Sun, Huijie Leng, Changtao Jiang, Yingsheng Xu, Chunli Song
Summary: Postmenopausal osteoporosis is a common bone metabolic disease, and gut microbiota (GM) imbalance plays an important role in its development. This study found that ovariectomized mice had gut microbiota dysbiosis, and reducing gut microbiota through antibiotic treatment improved bone health. G-protein coupled bile acid receptor and systemic inflammatory factors were identified as key players in bone metabolism.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Hironori Mizutani, Yoshifumi Sato, Masaya Yamazaki, Tatsuya Yoshizawa, Yukio Ando, Mitsuharu Ueda, Kazuya Yamagata
Summary: This study found that the expression of SIRT7 is increased in the brain of Alzheimer's disease patients. Treatment with A beta(42) increased the expression of NOX4, leading to the production of reactive oxygen species (ROS) and apoptosis. Knockdown of SIRT7 inhibited A beta(42)-induced ROS production and apoptosis by suppressing the upregulation of NOX4. These findings suggest that inhibiting SIRT7 may be beneficial in the pathogenesis of AD by regulating ROS production.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ruixue Huang, Liyan Hou, Xingyue Zhai, Zhengzheng Ruan, Wei Sun, Dongdong Zhang, Xiulan Zhao, Qingshan Wang
Summary: Chronic exposure to n-hexane can cause sensorimotor neuropathy mediated by the toxic metabolite 2,5-hexanedione. The activation of NLRP3 inflammasome has been associated with various neurodegenerative diseases, and in this study, it was found that HD-induced neurotoxicity involves the activation of NLRP3 inflammasome. Inhibition of NADPH oxidase can mitigate the activation of NLRP3 inflammasome and subsequent neurodegeneration, suggesting a critical role of NADPH oxidase-dependent activation of microglial NLRP3 inflammasome in HD-induced neurotoxicity.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Jiuchun Qiu, Daiqi Liu, Pengsha Li, Lingling Zhou, Lu Zhou, Xing Liu, Yue Zhang, Meng Yuan, Gary Tse, Guangping Li, Tong Liu
Summary: Oxidative stress and mitochondrial dysfunction play important roles in the development of diabetic cardiomyopathy in type 2 diabetes mellitus. This study established a type 2 diabetes model and found that inhibiting NADPH oxidase can improve ventricular remodeling and reduce the incidence of DCM.
Article
Oncology
Abdulrhman Alsayari, Yahya I. Asiri, Abdullatif Bin Muhsinah, Mohd. Zaheen Hassan
Summary: This study focused on developing anticancer agents through structure optimization of pyrazole analogues, achieving promising results against human colon cancer cell lines. The research demonstrates the potential of pyrazolyl analogues containing a pyridine nucleus as lead molecules in the development of novel anticancer agents.
JOURNAL OF ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jin Han, Donghwi Park, Ji Young Park, Seungwoo Han
Summary: Increased oxidative stress in OA cartilage leads to extracellular matrix degradation and chondrocyte apoptosis. This study found that inhibiting NOX can decrease ROS production, suppress oxidative stress marker genes and catabolic proteases, and protect against OA by modulating oxidative stress and gene expression.
Article
Cell Biology
Francis Rousset, German Nacher-Soler, Vivianne Beatrix Christina Kokje, Stephanie Sgroi, Marta Coelho, Karl-Heinz Krause, Pascal Senn
Summary: This study demonstrates the active role of NOX3 in the pathophysiology of noise-induced hearing loss and the absence of functional NOX3 enhances the hearing recovery phase following noise trauma. This opens an interesting clinical window for pharmacological or molecular intervention aiming at post prevention of noise-induced hearing loss.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Xiao-Juan Zhang, Lu Li, Ai-Ling Wang, Hong-Xia Guo, Hui-Ping Zhao, Rui-Fang Chi, Hui-Yu Xu, Li-Guo Yang, Bao Li, Fu-Zhong Qin, Jia-Pu Wang
Summary: This study suggests that GSK2795039 can prevent cardiomyocyte necroptosis in DOX-induced heart failure through inhibition of NADPH oxidase. The findings provide evidence for the potential therapeutic effect of GSK2795039 in improving myocardial remodeling and function in patients with DOX-induced cardiomyopathy.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Jingwei Liu, Xueying Chang, Daming Dong
Summary: This study investigates the role of miR-181a-5p in osteogenic differentiation and bone formation, and reveals its mechanism through the modulation of the Runx1/AIF-1 axis.
ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Neurosciences
Ke Wang, Yongquan Shi, Wei Liu, Shuqing Liu, Ming-Zhong Sun
Summary: The study found that taurine could improve cognitive impairment in PD mice by inhibiting microglial activation, reducing neuron loss, and increasing PSD95 levels in the hippocampus.
Article
Food Science & Technology
Xiangyuan Liu, Li Song
Summary: DDT exposure can cause liver cell toxicity, which can be alleviated by quercetin through inhibition of reactive oxygen species production.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Geriatrics & Gerontology
Seul Gi Kim, Jin Young Sung, Young Jin Kang, Hyoung Chul Choi
Summary: Reactive oxygen species (ROS) are a key risk factor of cellular senescence and age-related diseases, and protein kinase C (PKC) has been shown to activate NADPH oxidases (NOXs), which generate ROS. The correlation between PKC and senescence has not been reported in vascular smooth muscle cell (VSMC). Our study revealed that H2O2 decreased PTEN expression, increased PKC delta phosphorylation, upregulated NOX1 subunits, and induced VSMC senescence via p53-p21 signaling pathway. However, fisetin inhibited cellular senescence induced by the PTEN-PKC delta-NOX1-ROS signaling pathway, suggesting that downregulation of PKC delta by flavonoids provides a potential means of treating age-associated diseases.
ARCHIVES OF GERONTOLOGY AND GERIATRICS
(2023)
Article
Multidisciplinary Sciences
Dae Gyu Kim, Yongseok Choi, Yuno Lee, Semi Lim, Jiwon Kong, JaeHa Song, Younah Roh, Dipesh S. Harmalkar, Kwanshik Lee, Ja-il Goo, Hye Young Cho, Ameeq Ul Mushtaq, Jihye Lee, Song Hwa Park, Doyeun Kim, Byung Soh Min, Kang Young Lee, Young Ho Jeon, Sunkyung Lee, Kyeong Lee, Sunghoon Kim
Summary: AIMP2-DX2 acts as a cancer-specific regulator of KRAS stability and enhances KRAS-driven tumorigenesis by blocking ubiquitin-mediated degradation of KRAS. A small molecule that inhibits the interaction between AIMP2-DX2 and KRAS reduces KRAS levels and suppresses KRAS-dependent cancer cell growth in vitro and in vivo.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Seongchun Min, Ji Yeon Kim, Hyo Min Cho, Sujin Park, Ji Min Hwang, Hyejin You, Young Chan Chae, Won-Jae Lee, Woong Sun, Dongmin Kang, Sanghyuk Lee, Sang Won Kang
Summary: This study reveals a novel signaling pathway in which mitochondria communicate with the cytosol via the release of heat shock protein 60, leading to the activation of survival genes in the nucleus.
Article
Chemistry, Medicinal
Seunghwan Shim, Da Un Jeong, Hyemi Kim, Chae Yun Kim, Hyejun Park, Yinglan Jin, Kyung Min Kim, Hwa Jeong Lee, Dong Hwan Kim, Yun Soo Bae, Yongseok Choi
Summary: This study designed and synthesized a series of novel Nox inhibitors, which showed regulatory effects on neuronal inflammation in vitro and in vivo experiments, and demonstrated therapeutic efficacy in a PD animal model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Microbiology
Su-Man Kim, Shinhye Park, Seung-Ho Hwang, Eun-Young Lee, Jong-Hwan Kim, Ga Seul Lee, Giljae Lee, Dong-Ho Chang, Jae-Geun Lee, Jungwon Hwang, Youngjin Lee, Minsoo Kyung, Eun-Kyoung Kim, Jae-Hoon Kim, Tae-Hwan Kim, Jeong Hee Moon, Byoung-Chan Kim, Gwangpyo Ko, Seon-Young Kim, Ji-Hwan Ryu, Jeong-Soo Lee, Chul-Ho Lee, Jeong-Yoon Kim, Sunghoon Kim, Won-Jae Lee, Myung Hee Kim
Summary: In this study, it was discovered that the gut-associated bacterium Akkermansia muciniphila secretes threonyl-tRNA synthetase (AmTARS) to monitor and modulate immune homeostasis. AmTARS activates the MAPK and PI3K/AKT signaling pathways by interacting with TLR2, leading to the production of the anti-inflammatory IL-10. Furthermore, AmTARS restores IL-10 positive macrophages, increases IL-10 levels in the serum, and attenuates the pathological effects in colitis mice.
CELL HOST & MICROBE
(2023)
Review
Biochemistry & Molecular Biology
Sreenivasulu Godesi, Joohan Lee, Hossam Nada, Guofeng Quan, Ahmed Elkamhawy, Yongseok Choi, Kyeong Lee
Summary: The proto-oncogenic protein c-KIT is crucial in regulating cellular transformation and differentiation, and dysregulation of c-KIT can lead to various human cancers, especially GISTs. Current approved drugs have limitations, highlighting the need for selective c-KIT inhibitors. Recent research efforts in medicinal chemistry discuss the development of potent c-KIT inhibitors with high selectivity for GISTs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Hossam Nada, Aneesh Sivaraman, Qili Lu, Kyoungho Min, Sungdo Kim, Ja-Il Goo, Yongseok Choi, Kyeong Lee
Summary: Interleukin-6 (IL-6) is a significant factor in inflammatory and autoimmune diseases, and its targeted therapy is promising but still faces challenges. This study focuses on the development of small molecule inhibitors for IL-6 through analysis of protein-protein inhibitors targeting the IL-6/IL-6 receptor/gp130 complex.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Seung Hwan Son, Na-Rae Lee, Min Sung Gee, Chae Won Song, Soo Jin Lee, Sang-Kyung Lee, Yoonji Lee, Hee Jin Kim, Jong Kil Lee, Kyung-Soo Inn, Nam-Jung Kim
Summary: The researchers reported a protein degrader, PRZ-18002, that selectively binds to an active form of p38 MAPK and induces degradation of phosphorylated p38 MAPK. Treatment with PRZ-18002 reduces p-p38 levels, alleviates microglia activation and amyloid beta (Aβ) deposition, and improves spatial learning and memory, suggesting its potential therapeutic effect for Alzheimer's disease (AD).
ACS CENTRAL SCIENCE
(2023)
Article
Chemistry, Medicinal
Sreenivasulu Godesi, Jeong-Ran Han, Jang-Keun Kim, Dong-Ik Kwak, Joohan Lee, Hossam Nada, Minkyoung Kim, Hyun-A Yang, Joo-Young Im, Hyun Seung Ban, Chang Hoon Lee, Yongseok Choi, Misun Won, Kyeong Lee
Summary: In this study, a series of novel dual MDH1/2 inhibitors were designed and synthesized, and their structure-activity relationship was investigated. Among the tested compounds, compound 50 containing a piperidine ring showed improved growth inhibition of A549 and H460 lung cancer cell lines compared to LW1497. Compound 50 reduced the total ATP content in A549 cells in a dose-dependent manner and suppressed the accumulation of HIF-1a and expression of HIF-1a target genes such as GLUT1 and PDK1. Furthermore, compound 50 inhibited HIF-1a-regulated CD73 expression under hypoxia in A549 lung cancer cells. These results suggest that compound 50 may be a potential candidate for the development of next-generation dual MDH1/2 inhibitors to target lung cancer.
Article
Environmental Sciences
Yeong-Kyeong Kim, Yunkyung Eom, Hongryul Yoon, Yoonji Lee, Sung Hoon Lee
Summary: Humans are exposed to the common carcinogen benzo[a]pyrene (BaP) through ingestion and inhalation. BaP accumulates in the brain and causes toxicity, leading to impairments in learning and memory, increased anxiety behavior, and neuronal death. This study investigates the toxicity of BaP at presynaptic terminals, observing that it inhibits Ca2+ entry and suppresses synaptic vesicle exocytosis. These findings provide insights into the neurotoxicity of BaP and contribute to the evaluation of the risk it poses.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Biochemistry & Molecular Biology
Sreenivasulu Godesi, Hossam Nada, Joohan Lee, Joon-Hee Kang, Soo-Youl Kim, Yongseok Choi, Kyeong Lee
Summary: Each year, millions of new cancer cases are reported, resulting in millions of deaths worldwide. Breast and colon cancers are the most commonly detected variations. To address this increase, the development of innovative therapies is crucial. Small molecules containing pyridine and urea have been found in many anticancer agents, particularly VEGFR2 inhibitors. Hybrid small molecules combining urea and pyridine were designed and tested against breast and colon cancer cell lines, showing potent anticancer activity. Compound 8a displayed a remarkable GI(50) value of 0.06 μM against the MCF7 cancer cell line, while compound 8h exhibited the highest cytotoxic activity against the HCT116 cell line, with a GI(50) of 0.33 ± 0.042 μM. Importantly, compounds 8a, 8h, and 8i demonstrated excellent safety profiles on normal cells. Molecular docking, dynamic studies, and free energy calculations confirmed the affinity of these compounds as VEGFR2 inhibitors.
Article
Physics, Multidisciplinary
Aihua Zhang, Sun Choi
Summary: We have developed efficient techniques to solve the first-time problems of Brownian motion. Using a time-scale separation of recrossings, we have shown that Eyring's transmission coefficient (kappa) equals the one (kappa V) corresponding to an absorbing boundary consistent with the transition state theory, which is greater than the one (kappa K) derived by Kramers. We have also proposed methods for reaction rate determination by analyzing short-time trajectories from the barrier maximum, and discussed the relation to the reactive flux method and the significance of reaction coordinates.
PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS
(2023)
Article
Chemistry, Medicinal
Min-Jung Kim, Kyung Lee Yu, Ri Han, Yoonji Lee, Kyungsoo Oh, Ji Chang You
Summary: The HIV-1 infection epidemic is still a global health problem. This study identified a new HIV-1 reverse transcriptase inhibitor (Compound #8) through chemical library screening and medicinal chemistry research, which shows unique structure and high efficacy against HIV-1, and has great therapeutic potential.
ACS INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Kwanshik Lee, Hossam Nada, Minkyoung Kim, Hyejun Park, Kiho Lee, Dongho Seo, Kyeong Lee, Yongseok Choi
Summary: The diamondback moth is a resistant insect pest that poses a threat to brassicaceous crops worldwide. Scientists have synthesized new cantharidin-based compounds that exhibit strong insecticidal activity against the diamondback moth, including a 100% mortality rate at a concentration of 100 mg/L. These compounds also show an anti-feeding effect on cabbage leaves.
Review
Chemistry, Medicinal
Ri Han, Hongryul Yoon, Gahee Kim, Hyundo Lee, Yoonji Lee
Summary: This review article explores the application of artificial intelligence in medicinal chemistry, specifically focusing on the use of machine learning and deep learning techniques in drug screening and design. Research has shown that artificial intelligence can accelerate the drug discovery process and has great potential in predicting and understanding drug interactions and properties. However, data quality issues and technological constraints remain challenges that require interdisciplinary collaboration to fully realize its potential.
Review
Biochemistry & Molecular Biology
Danbi Yoon, Ju Heun Moon, Anna Cho, Hyejoon Boo, Jeong Seok Cha, Yoonji Lee, Jiho Yoo
Summary: N-glycosylation is a common post-translational modification that affects protein stability and folding. GlcNAc-1-P-transferase (GPT) plays a crucial role in initiating N-glycosylation in the endoplasmic reticulum (ER). Tunicamycin, a natural product that inhibits N-glycosylation and induces ER stress, is used to investigate the molecular mechanisms of GPT and its inhibition by tunicamycin. This review provides insights into the role of GPT in N-glycosylation and suggests the potential use of tunicamycin as an antibiotic.
MOLECULES AND CELLS
(2023)