Article
Pharmacology & Pharmacy
Gang Ren, Yu-Wei Ding, Lu-Lu Wang, Jian-Dong Jiang
Summary: This study investigated the mechanism of berberine (BBR) on lysosomal AMPK activation at low doses, and found that AXIN1 mediated BBR's effect on AMPK activation, while PEN2 did not. BBR maintained cellular AMPK activity by reducing UHRF1 expression and its interaction with AMPKa1. The mode of action of BBR was different from that of metformin on AMPK activation.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Neurosciences
Yu-Ju Liu, Hung-Chih Kuo, Yijuang Chern
Summary: This study found that in ALS patients, AMPK activation leads to the abnormal localization of importin-alpha 1 in motor neurons, resulting in mislocalization of multiple RNA binding proteins during AMPK activation. Various molecular and cellular approaches were used to confirm this hypothesis, and it was shown that this abnormality affects RNA processing and protein translation mechanisms.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Multidisciplinary Sciences
Dimitra Panagaki, Jacob T. Croft, Katharina Keuenhof, Lisa Larsson Berglund, Stefanie Andersson, Verena Kohler, Sabrina Buttner, Markus J. Tamas, Thomas Nystrom, Richard Neutze, Johanna L. Hoog
Summary: Nuclear envelope budding (NEB) is an alternative pathway for nucleocytoplasmic communication that is evolutionarily conserved from early protists to human cells. In yeast cells, NEB events occur more frequently under stress conditions such as heat shock, exposure to harmful chemicals, and inhibition of the proteasome. NEB may play a role in aiding the transport of protein aggregates across the nuclear envelope, particularly in response to protein misfolding and heat shock.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Kaja Kostyrko, Marta Roman, Alex G. Lee, David R. Simpson, Phuong T. Dinh, Stanley G. Leung, Kieren D. Marini, Marcus R. Kelly, Joshua Broyde, Andrea Califano, Peter K. Jackson, E. Alejandro Sweet-Cordero
Summary: In this study, researchers used RNAi screens to identify UHRF1 as an epigenetic regulator that is specifically vulnerable in KRAS mutant lung cancer cells. Knocking out UHRF1 selectively impaired the growth and induced apoptosis in KRAS mutant cells by causing global DNA hypomethylation and upregulation of tumor suppressor genes. In vivo experiments showed that UHRF1 knock-out inhibits tumor growth in KRAS-driven mouse lung cancer models. High UHRF1 expression in lung cancer patients is associated with low TSG expression and predicts worse outcomes in KRAS mutant tumors. These findings suggest that UHRF1 could be a potential target for therapeutic intervention in KRAS-driven cancer.
NATURE COMMUNICATIONS
(2023)
Review
Immunology
Yusi Chen, Li Tang
Summary: Non-parenchymal cells (NPCs) and parenchymal cells (PCs) perform tissue-specific functions together. Tissue-resident macrophages (TRMs), a vital type of NPCs, interact with PCs and regulate their functions. The interaction between PCs and TRMs is critical for maintaining tissue homeostasis and physiological functions.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Emily S. Reardon, Vivek Shukla, Sichuan Xi, Sudheer K. Gara, Yi Liu, David Straughan, Mary Zhang, Julie A. Hong, Eden C. Payabyab, Anju Kumari, William G. Richards, Assunta De Rienzo, Raffit Hassan, Markku Miettinen, Liqiang Xi, Mark Raffeld, Lisa T. Uechi, Xinmin Li, Ruihong Wang, Haobin Chen, Chuong D. Hoang, Raphael Bueno, David S. Schrump
Summary: The study revealed the significant role of UHRF1 in malignant pleural mesothelioma (MPM), with its overexpression affecting patient survival. Experiments such as RNA sequencing showed that inhibiting UHRF1 can reduce DNA hypomethylation, inhibit the growth and spread of MPM cells, and correspond with certain chemotherapeutic agents.
JOURNAL OF THORACIC ONCOLOGY
(2021)
Article
Biochemical Research Methods
Carsen Stringer, Tim Wang, Michalis Michaelos, Marius Pachitariu
Summary: Cellpose is a generalist, deep learning-based segmentation method that can precisely segment cells from various types of images without requiring retraining or parameter adjustments. It was trained on a highly diverse image dataset and supports a three-dimensional extension. Software has been developed to support community contributions to the training data.
Article
Biochemistry & Molecular Biology
Vladimir S. Popov, Ilya B. Brodsky, Maria N. Balatskaya, Alexander V. Balatskiy, Ilia D. Ozhimalov, Maria A. Kulebyakina, Ekaterina V. Semina, Mikhail S. Arbatskiy, Viktoria S. Isakova, Polina S. Klimovich, Veronika Y. Sysoeva, Natalia I. Kalinina, Vsevolod A. Tkachuk, Kseniya A. Rubina
Summary: This study investigates the role of T-cadherin in regulating blood pressure and stamina by generating mice lacking exon 3 in the Cdh13 gene. The results show that Cdh13(?Exon3) mice have slightly higher blood pressure compared to wild-type mice, and their systolic blood pressure increases significantly after intensive physical training. Additionally, Cdh13(?Exon3) mice have significantly higher plasma adiponectin levels, and intensive physical training increases AMPK phosphorylation in their skeletal muscles and myocardium. These findings highlight the critical importance of T-cadherin in blood pressure regulation and stamina in mice and may provide insight into the pathogenesis of hypertension.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Han Xiao, Emanuel Wyler, Miha Milek, Bastian Grewe, Philipp Kirchner, Arif Ekici, Ana Beatriz Oliveira Villela Silva, Doris Jungnickl, Florian Full, Marco Thomas, Markus Landthaler, Armin Ensser, Klaus Ueberla
Summary: The HIV-1 Rev protein is crucial for nuclear export of unspliced and incompletely spliced HIV-1 RNAs. Depletion of proteins like CRNKL1 can significantly enhance levels of unspliced HIV-1 RNA in the cytoplasm, potentially revealing a cellular mechanism exploited by HIV-1 to regulate its complex splicing pattern.
Review
Immunology
Amin Hasanvand
Summary: Metformin suppresses gluconeogenesis and reduces blood sugar by activating AMPK enzyme, which also has various therapeutic effects on diseases by controlling inflammatory conditions, regulating cell differentiation pathways, and improving overall health.
INFLAMMOPHARMACOLOGY
(2022)
Review
Genetics & Heredity
Omeima Abdullah, Ziad Omran, Salman Hosawi, Ali Hamiche, Christian Bronner, Mahmoud Alhosin
Summary: The silencing of tumor suppressor genes through epigenetic mechanisms, mainly via abnormal promoter DNA methylation, is a main mechanism of tumorigenesis. UHRF1 plays a key role in this process as a conductor, and targeting UHRF1 is a promising strategy for cancer therapy. Thymoquinone (TQ) shows potential as a multitarget single epidrug that acts by targeting the UHRF1/DNMT1/HDAC1/G9a complex.
Article
Multidisciplinary Sciences
Brian A. Maxwell, Youngdae Gwon, Ashutosh Mishra, Junmin Peng, Haruko Nakamura, Ke Zhang, Hong Joo Kim, J. Paul Taylor
Summary: Stress-induced ubiquitination is crucial for cellular recovery after heat stress, facilitating the degradation of damaged proteins and promoting the resumption of cellular activities.
Article
Multidisciplinary Sciences
Mateusz T. Madzik, Serwan Asaad, Akram Youssry, Benjamin Joecker, Kenneth M. Rudinger, Erik Nielsen, Kevin C. Young, Timothy J. Proctor, Andrew D. Baczewski, Arne Laucht, Vivien Schmitt, Fay E. Hudson, Kohei M. Itoh, Alexander M. Jakob, Brett C. Johnson, David N. Jamieson, Andrew S. Dzurak, Christopher Ferrie, Robin Blume-Kohout, Andrea Morello
Summary: This study demonstrates universal quantum logic operations using nuclear spins in a silicon nanoelectronic device, achieving high-fidelity entangled states. The precise characterization of quantum operations shows that nuclear spins are approaching the performance required for fault-tolerant quantum processors. Additionally, the entanglement between nuclear spins and electron spins is also demonstrated. The results establish a viable route for scalable quantum information processing using donor nuclear and electron spins.
Article
Chemistry, Applied
Lei Ji, Hongling Fu, Yi Wang, Jiaxin Li, Xiaoqing Yang, Hao Gong, Xiangze Meng, Wendan Jing, Weichang Dai, Youbao Li, Bo Lyu, Hansong Yu
Summary: The alkali method was used to prepare complexes of soybean protein isolate (SPI) and procyanidin B2 (PCB2), and the interaction between SPI and PCB2 was studied using multi-spectroscopic methods. The potential for synergistic hypolipidemia of SPI-PCB2 was explored using a human hepatoma (HepG2) cell hyperlipidemia model. The results showed that PCB2 primarily bonded to SPI through C-S and C-N bonds, and the addition of PCB2 decreased the α-helix structure content of SPI. At the cellular level, the optimal SPI-PCB2 ratio for lowering blood lipids was found to be 1:1.
Editorial Material
Cell Biology
Ji-Man Park, Do-Hyung Kim
Summary: In glucose-starved cells, autophagy is believed to contribute to cell survival by generating energy, with AMPK as the primary energy sensor. The current paradigm suggests that AMPK promotes autophagy by binding and phosphorylating ULK1. However, conflicting findings have cast doubt on this model. In a recent study, it was found that AMPK actually acts as a negative regulator of ULK1 activity, revealing a different role for AMPK in autophagy and its importance in cellular resilience during energy depletion.
Article
Cell Biology
Weili Yang, Xiangyu Guo, Zhuchi Tu, Xiusheng Chen, Rui Han, Yanting Liu, Sen Yan, Qi Wang, Zhifu Wang, Xianxian Zhao, Yunpeng Zhang, Xin Xiong, Huiming Yang, Peng Yin, Huida Wan, Xingxing Chen, Jifeng Guo, Xiao-Xin Yan, Lujian Liao, Shihua Li, Xiao-Jiang Li
Summary: Research indicates that the kinase form of PINK1 is selectively expressed in human and monkey brains, causing neurodegeneration when deficient, without affecting mitochondrial protein expression and morphology. Mutations in PINK1 reduce protein phosphorylation crucial for neuronal survival, suggesting that its kinase activity is essential for primate brain function, potentially implicating kinase dysfunction in the pathogenesis of Parkinson's disease.
Article
Multidisciplinary Sciences
Carlos Moreno-Yruela, Di Zhang, Wei Wei, Michael Baek, Wenchao Liu, Jinjun Gao, Daniela Dankova, Alexander L. Nielsen, Julie E. Bolding, Lu Yang, Samuel T. Jameson, Jiemin Wong, Christian A. Olsen, Yingming Zhao
Summary: Lysine L-lactylation is a newly discovered histone modification that is stimulated under conditions of high glycolysis. Through systematic evaluation of histone deacetylases (HDACs), HDAC1-3 and SIRT1-3 were identified as delactylases for this modification. This study provides important insights into the regulatory mechanisms of histone lactylation.
Article
Biochemistry & Molecular Biology
Bin Jiang, Jia Zhang, Guohui Zhao, Mengjue Liu, Jielu Hu, Furong Lin, Jinyang Wang, Wentao Zhao, Huanhuan Ma, Cixiong Zhang, Caiming Wu, Luming Yao, Qingfeng Liu, Xin Chen, Yating Cao, Yi Zheng, Chensong Zhang, Aidong Han, Donghai Lin, Qinxi Li
Summary: GLS1 promotes cell proliferation when glutamine is abundant, but facilitates apoptosis when glutamine is deprived. Under glutamine deprivation, GLS1 forms filamentous polymers with enhanced catalytic activity, depleting intracellular glutamine.
Article
Biochemistry & Molecular Biology
Haibin Zhang, Qiuyang Zheng, Tiantian Guo, Shijun Zhang, Shuang Zheng, Ruimin Wang, Qingfang Deng, Guowei Yang, Shuo Zhang, Linxin Tang, Qiuping Qi, Lin Zhu, Xiu-Fang Zhang, Hong Luo, Xian Zhang, Hao Sun, Yue Gao, Hongfeng Zhang, Ying Zhou, Aidong Han, Chen-Song Zhang, Huaxi Xu, Xin Wang
Summary: This study reveals the role of astrocytic metabolic dysregulation in neuronal dysfunction in intellectual disability and suggests a strategy for treating intellectual disability by restoring astrocytic metabolic function.
MOLECULAR PSYCHIATRY
(2022)
Article
Biology
Chen-Song Zhang, Bingchang Zhang, Mengqi Li, Xiaoyan Wei, Kai Gong, Zhiyong Li, Xiangyang Yao, Jianfeng Wu, Cixiong Zhang, Mingxia Zhu, Lei Zhang, Xiufeng Sun, Yi-Hong Zhan, Zhengye Jiang, Wenpeng Zhao, Wei Zhong, Xinguo Zhuang, Dawang Zhou, Hai-Long Piao, Sheng-Cai Lin, Zhanxiang Wang
Summary: By analyzing the serum metabolome and lipidome in COVID-19 patients at different stages, we identified significant alterations in 611 metabolites. Among them, agmatine and putrescine were prominently elevated, while 2-quinolinecarboxylate showed a biphasic change. These metabolites were found to activate the NF-kappa B pathway and induce strong proinflammatory cytokine production. Interestingly, they had limited effects on interferon production. These findings may provide insights for the development of drugs to alleviate inflammation in COVID-19 patients.
SCIENCE CHINA-LIFE SCIENCES
(2022)
Article
Cell Biology
Tian Xia, Di Chen, Xiaolong Liu, Huan Qi, Wen Wang, Huan Chen, Ting Ling, Wuxiyar Otkur, Chen-Song Zhang, Jongchan Kim, Sheng-Cai Lin, Hai-long Piao
Summary: In this study, it was found that intracellular MDK interacts with LKB1 and STRAD, leading to the disruption of the LKB1-STRAD-Mo25 complex. As a result, the activity of LKB1 is decreased, dampening the activation of AMPK. Additionally, MDK expression is significantly upregulated in liver, kidney, and breast cancers, and is inversely correlated with phosphorylated AMPK levels.
CELL DEATH & DISEASE
(2022)
Article
Plant Sciences
Cheng Song, Yunpeng Zhang, Rui Chen, Fucheng Zhu, Peipei Wei, Haoyu Pan, Cunwu Chen, Jun Dai
Summary: This study identified differentially expressed proteins in Dendrobium huoshanense, revealing the enrichment of proteins involved in vitamin B6 metabolism, photosynthesis, spliceosome, arginine biosynthesis, oxidative phosphorylation, and MAPK signaling. Peroxidases and antioxidant enzymes were also identified.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Juanjuan Feng, Zhengke Lian, Xinting Xia, Yue Lu, Kewen Hu, Yunpeng Zhang, Yanan Liu, Longmiao Hu, Kun Yuan, Zhenliang Sun, Xiufeng Pang
Summary: It is found that KRAS-mutant non-small cell lung cancer (NSCLC) is resistant to MEK inhibitors due to the activation of mitochondrial oxidative phosphorylation (OX-PHOS), and the co-administration of trametinib and IACS-010759 can effectively inhibit tumor growth and prolong mouse survival.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Biochemistry & Molecular Biology
Qian Zhang, Shengduo Liu, Chen-Song Zhang, Qirou Wu, Xinyuan Yu, Ruyuan Zhou, Fansen Meng, Ailian Wang, Fei Zhang, Shasha Chen, Xiaojian Wang, Lei Li, Jun Huang, Yao-Wei Huang, Jian Zou, Jun Qin, Tingbo Liang, Xin-Hua Feng, Sheng-Cai Lin, Pinglong Xu
Summary: This study found that viral infection leads to a rapid decrease in blood glucose levels, resulting in the activation of AMPK. The activated AMPK directly phosphorylates TBK1, triggering the recruitment of IRF3 and the assembly of MAVS or STING signalosomes. However, depletion or inhibition of AMPK and increased glucose levels impair nucleic acid sensing, while enhancing the AMPK-TBK1 cascade significantly improves antiviral immunity.
Article
Biochemistry & Molecular Biology
Li Kang, Yujie Liu, Jianzhong He, Yaling Wang, Mengyang Xue, Xin Wu, Zhen Wang, Yunpeng Zhang, Manyu Chu, Jialun Li, Wei Wei, Jiwen Li, Enmin Li, Lujian Liao, Jianru Xiao, Rong Zhang, Liyan Xu, Jiemin Wong
Summary: By screening a small-molecule kinase inhibitor library, GSK3 ss was identified as a critical kinase for promoting the overexpression of SOX2 in ESCC. Inhibition of GSK3 ss selectively impaired the proliferation and stemness of SOX2-positive ESCC cells. Clinical studies also showed a positive correlation between GSK3 ss and SOX2 protein levels in esophageal tumors, indicating the potential of targeting GSK3 ss for the treatment of ESCC.
Article
Multidisciplinary Sciences
Yanan Liu, Longmiao Hu, Zhengzhen Wu, Kun Yuan, Guangliang Hong, Zhengke Lian, Juanjuan Feng, Na Li, Dali Li, Jiemin Wong, Jiekai Chen, Mingyao Liu, Jiangping He, Xiufeng Pang
Summary: Immunotherapy has become a major treatment modality for various solid tumors, including colorectal cancer. The study identifies PHF8 as an essential mediator of immune escape in colorectal cancer, and targeting PHF8 induces a viral mimicry response to enhance anti-tumor immunity.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Yu-Qing Wu, Chen-Song Zhang, Jinye Xiong, Dong-Qi Cai, Chen-Zhe Wang, Yu Wang, Yan-Hui Liu, Yu Wang, Yiming Li, Jian Wu, Jianfeng Wu, Bin Lan, Xuefeng Wang, Siwei Chen, Xianglei Cao, Xiaoyan Wei, Hui-Hui Hu, Huiling Guo, Yaxin Yu, Abdul Ghafoor, Changchuan Xie, Yaying Wu, Zheni Xu, Cixiong Zhang, Mingxia Zhu, Xi Huang, Xiufeng Sun, Shu-Yong Lin, Hai-Long Piao, Jianyin Zhou, Sheng-Cai Lin
Summary: This study uncovers a mechanism by which low levels of glycolytic metabolite 3-PGA can switch PHGDH from serine synthesis to pro-apoptotic activation of p53. The interaction between PHGDH and AXIN in complex with HIPK2 leads to the formation of a multivalent p53-binding complex, allowing HIPK2 to phosphorylate p53-Ser46 and promote apoptosis. Mutants of PHGDH that are unable to bind 3-PGA either abolish p53 activation or cause constitutive activation and apoptosis in HCC cells. Caloric restriction can impede HCC growth dependent on PHGDH by lowering whole-body glucose levels.
Article
Endocrinology & Metabolism
Chen-Song Zhang, Mengqi Li, Yu Wang, Xiaoyang Li, Yue Zong, Shating Long, Mingliang Zhang, Jin-Wei Feng, Xiaoyan Wei, Yan-Hui Liu, Baoding Zhang, Jianfeng Wu, Cixiong Zhang, Wenhua Lian, Teng Ma, Xiao Tian, Qi Qu, Yaxin Yu, Jinye Xiong, Dong-Tai Liu, Zhenhua Wu, Mingxia Zhu, Changchuan Xie, Yaying Wu, Zheni Xu, Chunyan Yang, Junjie Chen, Guohong Huang, Qingxia He, Xi Huang, Lei Zhang, Xiufeng Sun, Qingfeng Liu, Abdul Ghafoor, Fu Gui, Kaili Zheng, Wen Wang, Zhi-Chao Wang, Yong Yu, Qingliang Zhao, Shu-Yong Lin, Zhi-Xin Wang, Hai-Long Piao, Xianming Deng, Sheng-Cai Lin
Summary: A small-molecule aldolase inhibitor, aldometanib, is reported to selectively activate the lysosomal pool of AMPK, leading to glucose-lowering effects. This compound mimics the cellular state of glucose starvation and shows potential as a therapeutic for metabolic disorders in humans.