Article
Biochemistry & Molecular Biology
Zhouyiyuan Xue, Bruce Demple
Summary: Apurinic/apyrimidinic endonuclease 1/redox effector-1 (Ape1/Ref-1) is an important enzyme in mammalian cells that plays a key role in DNA repair and transcription factor activation. Recent studies have shown that APEX1 knockout cell lines are more sensitive to the inhibitors Compound 3 and APX2009, suggesting off-target effects of these inhibitors.
Article
Microbiology
Prerna Dabral, Timsy Uppal, Subhash C. Verma
Summary: In this study, we identified the presence of multiple G-quadruplex sites in the region (oriLyt) of Kaposi's sarcoma-associated herpesvirus (KSHV) DNA, which is essential for DNA replication during the lytic cycle. We demonstrated the roles of these G-quadruplexes through multiple biochemical and biophysical assays in controlling replication and efficient virus production. We demonstrated that KSHV achieves this by recruiting RecQ1 (helicase) at those G-quadruplex sites for efficient viral DNA replication. Analysis of the replicated DNA through nucleoside labeling and immunostaining showed a reduced initiation of DNA replication in cells with a pharmacologic stabilizer of G-quadruplexes. Overall, this study confirmed the role of the G-quadruplex in regulating viral DNA replication, which can be exploited for controlling viral DNA replication.
MICROBIOLOGY SPECTRUM
(2023)
Article
Pharmacology & Pharmacy
Jiayuan Hu, Yan Wang, Yan Yuan
Summary: APE1's redox function is crucial for EBV lytic replication, as shown by the inhibition of APE1 expression or treatment with APE1 redox inhibitors C10 and E3330. Additionally, C10 and E3330 are effective in inhibiting MHV-68 replication and reducing lung damage in mice caused by MHV-68 infection. Overall, APE1 redox function is a potential antiviral target, especially for gamma-herpesvirus infections, and MHV-68 serves as a surrogate for the study of EBV and KSHV infection pathogenesis and therapy in vivo.
ANTIVIRAL RESEARCH
(2021)
Article
Microbiology
Nan Song, Lihong Chen, Zhemin Zhou, Xingmei Ren, Bo Liu, Siyu Zhou, Caihong Wang, Yun Wu, Nicholas R. Waterfield, Jian Yang, Guowei Yang
Summary: This study revealed that Tc toxins are widely present among Gram-negative and positive bacterial genomes, with a database constructed containing numerous Tc loci and putative toxic domains for potential future pest control systems. The study also highlighted the importance of Tc toxins as tools for biotechnological applications and their potential roles in human infectious diseases.
Article
Biochemistry & Molecular Biology
Direnis Erdinc, Bertil Macao, Sebastian Valenzuela, Nicole Lesko, Karin Naess, Bradley Peter, Helene Bruhn, Anna Wedell, Anna Wredenberg, Maria Falkenberg
Summary: Mutations in the catalytic domain of POL? can cause a range of clinical conditions. The p.F907I mutation in POL? leads to a severe clinical phenotype, including developmental arrest and rapid loss of skills. The mutation affects unwinding of parental double-stranded DNA at the replication fork, impairing the ability of POL? to support leading-strand DNA synthesis with the TWINKLE helicase. This study reveals a novel pathogenic mechanism for POL?-related diseases.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Multidisciplinary Sciences
Zack Saud, Matthew D. Hitchings, Tariq M. Butt
Summary: DNA viruses can utilize host cellular epigenetic processes to their advantage, but the epigenome status of most DNA viruses remains unknown. Third generation sequencing technologies enable the identification of modified nucleotides without specialized sample preparation, potentially revealing non-canonical epigenetic modifications that differentiate viral nucleic acid from host DNA.
SCIENTIFIC REPORTS
(2021)
Article
Endocrinology & Metabolism
Tamara Casteels, Yufeng Zhang, Thomas Frogne, Caterina Sturtzel, Charles-Hugues Lardeau, Ilke Sen, Xiaocheng Liu, Shangyu Hong, Florian M. Pauler, Thomas Penz, Marlene Brandstetter, Charlotte Barbieux, Ekaterine Berishvili, Thomas Heuser, Christoph Bock, Christian G. Riedel, Dirk Meyer, Martin Distel, Jacob Hecksher-Sorensen, Jin Li, Stefan Kubicek
Summary: Loss of FoxO1 signaling in response to metabolic stress contributes to type II diabetes by inducing dedifferentiation of pancreatic beta cells. Pharmacological inhibition of FoxO1 can model beta-cell dedifferentiation by downregulating beta-cell-specific transcription factors and aberrantly expressing progenitor genes and alpha-cell markers. Screening identified loperamide as a small molecule that can prevent FoxO inhibitor-induced glucagon expression and enhance insulin secretion by modulating calcium levels, intracellular pH, and FoxO1 localization.
MOLECULAR METABOLISM
(2021)
Article
Multidisciplinary Sciences
Scotland E. Farley, Jennifer E. Kyle, Hans C. Leier, Lisa M. Bramer, Jules B. Weinstein, Timothy A. Bates, Joon-Yong Lee, Thomas O. Metz, Carsten Schultz, Fikadu G. Tafesse
Summary: A study using untargeted lipidomics reveals that SARS-CoV-2 infection rewires host lipid metabolism, leading to significant changes in lipid composition to support infection. The study also identifies lipid droplet plasticity as an important feature of infection and demonstrates that small-molecule glycerolipid biosynthesis inhibitors can block viral propagation.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
Xiaojing Chu, Martin Jaeger, Joep Beumer, Olivier B. Bakker, Raul Aguirre-Gamboa, Marije Oosting, Sanne P. Smeekens, Simone Moorlag, Vera P. Mourits, Valerie A. C. M. Koeken, Charlotte de Bree, Trees Jansen, Ian T. Mathews, Khoi Dao, Mahan Najhawan, Jeramie D. Watrous, Irma Joosten, Sonia Sharma, Hans J. P. M. Koenen, Sebo Withoff, Iris H. Jonkers, Romana T. Netea-Maier, Ramnik J. Xavier, Lude Franke, Cheng-Jian Xu, Leo A. B. Joosten, Serena Sanna, Mohit Jain, Vinod Kumar, Hans Clevers, Cisca Wijmenga, Mihai G. Netea, Yang Li
Summary: This study systematically investigated circulating metabolites in healthy subjects, revealing significant impact of major metabolic pathways on cytokine production. Through genome-wide association analysis, genetic regulation of metabolites associated with immune phenotypes was examined, leading to the identification of a locus causally associated with Crohn's disease.
Article
Biochemistry & Molecular Biology
Shane N. Berger, Beatrice Baumberger, Srimal Samaranayake, Melinda Hersey, Sergio Mena, Ian Bain, William Duncan, Michael C. Reed, H. Frederik Nijhout, Janet Best, Parastoo Hashemi
Summary: This study provides an in-depth characterization of real time in vivo histamine dynamics using fast electrochemical tools for the first time. The findings reveal the sensitivity of histamine release to pharmacological manipulation at different levels and highlight the differences in histamine regulation between sexes and the impact of common antihistamine drugs on serotonin levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Mengshi Sun, Siting Wu, Shaozhu Kang, Jiaming Liao, Luhao Zhang, Zhuqing Xu, Hong Chen, Linting Xu, Xin Zhang, Qiwei Qin, Jingguang Wei
Summary: This study found that the infection of red-spotted grouper nervous necrosis virus (RGNNV) induced the formation of stress granules (SGs) in grouper spleen cells. The SGs particles co-located with the classic SG marker protein eIF3 eta, and some SGs depolymerized under treatment with a translation inhibitor. Inhibition of the PERK kinase significantly inhibited the formation of SGs and decreased the phosphorylation of eIF2 alpha. Overexpression of G3BP1 in Epinephelus coioides inhibited the replication of RGNNV by up-regulating the interferon and inflammatory response.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Jiaqi Yin, Na Ding, Jiaxin Yu, Zishan Wang, Limei Fu, Yongsheng Li, Xia Li, Juan Xu
Summary: This study comprehensively investigated the transcriptional control of DNA methylation-mediated dysregulation of transcription factors (TFs) on long non-coding RNAs (lncRNAs) in cancer. The findings revealed that TF regulation of lncRNAs is significantly impacted by DNA methylation. The study also identified DNA methylation-associated TFs and lncRNAs that are closely associated with cancer hallmarks and clinical features. The research provided valuable insights into cancer immunity from the epigenetic and transcriptional regulation perspective.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Rheumatology
Donggeng Guo, Jinhan Lv, Xi Chen, Xiaoxu Yan, Fenglian Ma, Yuanyuan Liu, Xu Chen, Jing Xie, Mingzhu Zhang, Zheyu Jin, Lijun Cai, Xichun Sun, Dongsheng Niu, Dayue D. Duan
Summary: This study characterized serum microRNA and their interactome in active rheumatoid arthritis patients to reveal their roles in RA pathogenesis. The analysis identified several upregulated and downregulated miRs, and highlighted their significant contributions to the infection-inflammation-immune network in RA pathogenesis.
Article
Multidisciplinary Sciences
Yung-Che Chen, Ying-Huang Tsai, Chin-Chou Wang, Shih-Feng Liu, Ting-Wen Chen, Wen-Feng Fang, Chiu-Ping Lee, Po-Yuan Hsu, Tung-Ying Chao, Chao-Chien Wu, Yu-Feng Wei, Huang-Chih Chang, Chia-Cheng Tsen, Yu-Ping Chang, Meng-Chih Lin
Summary: This study suggests that ACO patients have specific DNA methylation patterns compared to pure COPD patients or healthy individuals. Hypermethylation or hypomethylation of certain genes may be associated with clinical features such as lung function decline and exacerbation frequency.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Rommel J. Gestuveo, Jamie Royle, Claire L. Donald, Douglas J. Lamont, Edward C. Hutchinson, Andres Merits, Alain Kohl, Margus Varjak
Summary: The authors developed mosquito cell lines expressing Zika virus (ZIKV) capsid and conducted proteomics experiments, identifying 157 protein interactors, with 8 shown to act as pro-viral factors, demonstrating the transitional endoplasmic reticulum 94 (TER94) and its human ortholog VCP target ZIKV capsid to proteasomal degradation to facilitate infection.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yu-ting Zhang, Chen Hu, Song-xuan Zhang, Hui-hao Zhou, Jun Xu, Jian-da Ma, Lie Dai, Qiong Gu
Summary: Euphoesulatin A (Eup A) is a newly discovered compound that inhibits osteoclastogenesis through modulation of multiple signaling pathways, showing potential as a candidate for the development of anti-osteoporosis agents. It has been shown to significantly prevent bone loss in ovariectomized mice, highlighting its therapeutic potential in osteoporosis treatment.
BIOORGANIC CHEMISTRY
(2022)
Article
Geriatrics & Gerontology
Mengjiao Hao, Zhikang Zhang, Yijun Guo, Huihao Zhou, Qiong Gu, Jun Xu
Summary: In this study, the antiaging effect of rubidium chloride (RbCl) in Caenorhabditis elegans was reported. It was found that RbCl can increase lifespan and enhance stress resistance in the worms without affecting their fecundity. The mechanism involves the induction of superoxide dismutase expression and the activation of the AMPK/FOXO pathway, mediated by AAK-2 and DAF-16.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Plant Sciences
Xing Peng, Qingyun Tan, Leiming Wu, Deyin Wu, Jun Xu, Huihao Zhou, Qiong Gu
Summary: This study isolated two new abietane diterpenoids containing 3,4-epoxy groups from Ajuga decumbens, and elucidated their structures through spectroscopic analysis and experiments. One of the compounds exhibited strong antioxidation activity and a significant inhibition against ferroptosis.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Plant Sciences
Yanfang Cheng, Qian Wang, Zhikang Zhang, Chao Zhao, Huihao Zhou, Jun Xu, Qiong Gu
Summary: This study demonstrates that saucerneol (SN) inhibits the growth and metastasis of nasopharyngeal carcinoma (NPC) cells by targeting Grp94 and blocking the PI3K/AKT/mTOR/HIF-1 alpha signaling pathway. SN has been identified as a selective Grp94 inhibitor and a potential candidate for NPC treatment.
Article
Chemistry, Medicinal
Yuting Zhang, Xing Peng, Zhejun Sun, Chen Hu, Huihao Zhou, Jun Xu, Qiong Gu
Summary: A phytochemical investigation of Atractylodes chinensis led to the discovery of polyacetylenes and meroterpenoids. Some of the polyacetylenes showed inhibitory activity against osteoclastogenesis.
Article
Multidisciplinary Sciences
Dane Huang, Chao Zhao, Ruyue Li, Bingyi Chen, Yuting Zhang, Zhejun Sun, Junkang Wei, Huihao Zhou, Qiong Gu, Jun Xu
Summary: This study reports an approach to identify selective and druggable binding sites on protein surfaces for designing anti-osteoporotic drugs. A specific binding site was discovered that allows disruption of a particular protein interaction without interfering with other related interactions. The developed inhibitor demonstrates specificity and anti-osteoporotic effects through in vitro and in vivo studies.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Yuying Fang, Qingyun Tan, Huihao Zhou, Jun Xu, Qiong Gu
Summary: This study discovered a new ferroptosis inducer, FA-S, through phenotypic screenings. Further research showed that FA16, an analog of FA-S, induced ferroptosis by inhibiting system X(-)c. FA16 exhibited better metabolic stability than the classic system X(-)c inhibitor erastin and effectively inhibited tumor growth in vivo.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Bao Cheng, Zhengjun Cai, Ziqing Luo, Siting Luo, Zhiteng Luo, Yanfang Cheng, Ying Yu, Junsong Guo, Yingchen Ju, Qiong Gu, Jun Xu, Xianxing Jiang, Geng Li, Huihao Zhou
Summary: Aminoacyl-tRNA synthetases are a promising antimicrobial target and this study found that halofuginone, derived from herbs, moderately inhibits prolyl-tRNA synthetases from various pathogenic bacteria. The researchers were able to determine the structure of the enzyme and design new analogs. Compound 3 showed potent inhibition and antibacterial activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Hao Chen, Pei Hua, Dane Huang, Yuting Zhang, Huihao Zhou, Jun Xu, Qiong Gu
Summary: Osteoclasts have a higher demand for cholesterol, and the LXR# agonist can regulate cholesterol balance to inhibit osteoclast differentiation. By introducing privileged fragments from anti-osteoporosis agents, we synthesized a novel LXR# agonist. This agonist effectively inhibited osteoclast production and demonstrated potential for treating osteoporosis.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Zhong-Hui Huang, Xiao Liang, Qiong Gu, Xuan Ma, Shu-Hua Qi
Summary: Seven undescribed polyhydroxylated mycoecdysteroids, punicesterones A-G, and two known analogues were isolated from a deep-sea-derived fungal strain. The structures and absolute configurations of these compounds were determined through NMR spectroscopic analysis, HRESIMS data, and single-crystal X-ray diffraction experiments. Punicesterone A was found to have a nicotinoyl unit at C-22 of the typical ecdysteroid skeleton. The isolated compounds were evaluated for their anti-inflammatory, lipid-lowering, and antibacterial activities, with punicesterones B and C showing promising results.
Article
Biochemistry & Molecular Biology
Xiufen Jiang, Xifeng Teng, Huiwen Shi, Liudan Cao, Lin He, Qiong Gu
Summary: Ferroptosis is a new type of cell death correlated with various human diseases, and discovering ferroptosis inhibitors has become a novel strategy for the treatment of related diseases. Through screening the FDA-approved drug library, olanzapine was found to have potent ferroptosis inhibitory activity. Structural optimization and SARs analysis resulted in the synthesis of 41 new derivatives and one known compound. Derivative 36 showed significantly improved ferroptosis inhibition compared to olanzapine and low cytotoxicity. Mechanistic studies revealed its specific inhibition of ferroptosis through antioxidative ability. Olanzapine and its derivative 36 hold promise for drugs targeting ferroptosis-related neurological diseases.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Huiwen Shi, Xiufen Jiang, Liudan Cao, Xing Peng, Qingyun Tan, Xifeng Teng, Qiong Gu, Lin He
Summary: Six new neoclerodane diterpenoids and ten known compounds were isolated from Ajuga forrestii. Their structures were determined by various analytical techniques. The structure of a known compound was revised based on NMR empirical rules. The compounds were evaluated for their inhibitory effect on RSL3-induced ferroptosis, and compounds 8, 9, and 12 showed significant inhibitory activity.
Article
Multidisciplinary Sciences
Lu Han, Zhiteng Luo, Yingchen Ju, Bingyi Chen, Taotao Zou, Junjian Wang, Jun Xu, Qiong Gu, Xiang-Lei Yang, Paul Schimmel, Huihao Zhou
Summary: Aminoacyl-transfer RNA (tRNA) synthetases (aaRSs) are essential enzymes in protein translation, categorized into two classes with distinct active site architectures. The orphan GlyRS in bacteria has a unique X-shaped structure. A cocrystal structure elucidates how this orphan GlyRS specifically recognizes its substrate tRNA. The X shape of orphan GlyRS suggests potential nonactive site targets for aaRS-directed antibiotics.
Article
Plant Sciences
Xing Peng, Qingyun Tan, Zhikang Zhang, Deyin Wu, Jun Xu, Huihao Zhou, Qiong Gu
Summary: Twelve new neo-clerodane diterpenoids, eight undescribed methoxy/ethoxy acetal analogues, and one new nor-iridane monoterpenoid were isolated from Ajuga campylantha. Their structures were determined using various methods. This study provides valuable information on the structural features, synthesis, and biological activities of A. campylantha compounds.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Pharmacology & Pharmacy
Shijie Huang, Huifang Li, Jun Xu, Huihao Zhou, Navindra P. P. Seeram, Hang Ma, Qiong Gu
Summary: The chemical constituents of hemp roots were investigated, and the anti-inflammatory activities of phytochemicals isolated from the roots were evaluated. A total of 32 compounds were identified, including cannabinoids, phytosterols, triterpenoids, lignans, and other compounds. Both cannabinoids and non-cannabinoids showed promising anti-inflammatory effects.
JOURNAL OF CANNABIS RESEARCH
(2023)