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2. Brain-restricted mTOR inhibition with binary pharmacology

Author

Zhang, Ziyang, Fan, Qiwen, Luo, Xujun, Lou, Kevin, Weiss, William A, and Shokat, Kevan M

Subjects
Biomedical and Clinical Sciences, Medicinal and Biomolecular Chemistry, Chemical Sciences, Biological Psychology, Psychology, Pharmacology and Pharmaceutical Sciences, Brain Cancer, Cancer, Neurosciences, Rare Diseases, Brain Disorders, Orphan Drug, 5.1 Pharmaceuticals, Generic health relevance, Humans, Brain, Drug Therapy, Combination, Glioblastoma, Ligands, MTOR Inhibitors, Sirolimus, Tacrolimus Binding Protein 1A, TOR Serine-Threonine Kinases, Xenograft Model Antitumor Assays, General Science & Technology
Abstract

On-target-off-tissue drug engagement is an important source of adverse effects that constrains the therapeutic window of drug candidates1,2. In diseases of the central nervous system, drugs with brain-restricted pharmacology are highly desirable. Here we report a strategy to achieve inhibition of mammalian target of rapamycin (mTOR) while sparing mTOR activity elsewhere through the use of the brain-permeable mTOR inhibitor RapaLink-1 and the brain-impermeable FKBP12 ligand RapaBlock. We show that this drug combination mitigates the systemic effects of mTOR inhibitors but retains the efficacy of RapaLink-1 in glioblastoma xenografts. We further present a general method to design cell-permeable, FKBP12-dependent kinase inhibitors from known drug scaffolds. These inhibitors are sensitive to deactivation by RapaBlock, enabling the brain-restricted inhibition of their respective kinase targets.

Published
2022

7. Betacellulin drives therapy resistance in glioblastoma

Author

Fan, Qiwen, An, Zhenyi, Wong, Robyn A, Luo, Xujun, Lu, Edbert D, Baldwin, Albert, Mayekar, Manasi K, Haderk, Franziska, Shokat, Kevan M, Bivona, Trever G, and Weiss, William A

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Orphan Drug, Biotechnology, Brain Cancer, Brain Disorders, Rare Diseases, Neurosciences, 5.1 Pharmaceuticals, Animals, Betacellulin, Cell Line, Tumor, Glioblastoma, Mice, NF-kappa B, Phosphorylation, STAT3 Transcription Factor, glioblastoma, STAT3, BTC, feedback loop, NF-κB, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundThe transcription factor signal transducer and activator of transcription 3 (STAT3) drives progression in glioblastoma (GBM), suggesting STAT3 as a therapeutic target. Surprisingly however, GBM cells generally show primary resistance to STAT3 blockade.MethodsHuman glioblastoma cell lines LN229, U87, SF767, and U373, and patient-derived xenografts (PDXs) GBM8 and GBM43 were used to evaluate epidermal growth factor receptor (EGFR) activation during STAT3 inhibition. Protein and gene expression experiments, protein stability assays, cytokine arrays, phospho-tyrosine arrays and EGFR-ligand protein arrays were performed on STAT3 inhibitor-treated cells. To evaluate antitumor activity, we administered a betacellulin (BTC)-neutralizing antibody alone and in combination with STAT3 inhibition. BTC is an EGFR ligand. We therefore treated mice with orthotopic xenografts using the third-generation EGFR inhibitor osimertinib, with or without STAT3 knockdown.ResultsWe demonstrate that both small-molecule inhibitors and knockdown of STAT3 led to expression and secretion of the EGFR ligand BTC, resulting in activation of EGFR and subsequent downstream phosphorylation of nuclear factor-kappaB (NF-κB). Neutralizing antibody against BTC abrogated activation of both EGFR and NF-κB in response to inhibition of STAT3; with combinatorial blockade of STAT3 and BTC inducing apoptosis in GBM cells. Blocking EGFR and STAT3 together inhibited tumor growth, improving survival in mice bearing orthotopic GBM PDXs in vivo.ConclusionThese data reveal a feedback loop among STAT3, EGFR, and NF-κB that mediates primary resistance to STAT3 blockade and suggest strategies for therapeutic intervention.

Published
2020

9. First result from the Jinping Underground Nuclear Astrophysics experiment JUNA: precise measurement of the 92 keV 25Mg(p, [formula omitted])26Al resonance

Author

Su, Jun, Zhang, Hao, Li, Zhihong, Ventura, Paolo, Li, Yunju, Li, Ertao, Chen, Chen, Shen, Yangping, Lian, Gang, Guo, Bing, Li, Xinyue, Zhang, Liyong, He, Jianjun, Sheng, Yaode, Chen, Yinji, Wang, Luohuan, Zhang, Long, Cao, Fuqiang, Nan, Wei, Nan, Weike, Li, Gexing, Song, Na, Cui, Baoqun, Chen, Lihua, Ma, Ruigang, Zhang, Zhicheng, Jiao, Taoyu, Gao, Bingshui, Tang, Xiaodong, Wu, Qi, Li, Jiaqing, Sun, Liangting, Wang, Shuo, Yan, Shengquan, Liao, Junhui, Wang, Youbao, Zeng, Sheng, Nan, Ding, Fan, Qiwen, Qi, Ningchun, Sun, Wenliang, Guo, Xuyuan, Zhang, Peng, Chen, Yunhua, Zhou, Yong, Zhou, Jifang, He, Jinrong, Shang, Changsong, Li, Mingchuan, Cheng, Jianping, and Liu, Weiping

Published
2022
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13. A Kinase Inhibitor Targeted to mTORC1 Drives Regression in Glioblastoma

Author

Fan, QiWen, Aksoy, Ozlem, Wong, Robyn A, Ilkhanizadeh, Shirin, Novotny, Chris J, Gustafson, William C, Truong, Albert Yi-Que, Cayanan, Geraldine, Simonds, Erin F, Haas-Kogan, Daphne, Phillips, Joanna J, Nicolaides, Theodore, Okaniwa, Masanori, Shokat, Kevan M, and Weiss, William A

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Brain Cancer, Orphan Drug, Rare Diseases, Brain Disorders, Neurosciences, Animals, Brain Neoplasms, Cell Line, Tumor, Female, Glioblastoma, Humans, Mechanistic Target of Rapamycin Complex 1, Mice, Mice, Inbred BALB C, Multiprotein Complexes, Protein Kinase Inhibitors, Sirolimus, TOR Serine-Threonine Kinases, Tacrolimus Binding Protein 1A, FKBP12, FK506 binding protein 12, FRB, FK506 rapamycin binding, GBM, glioblastoma, PI3K, phosphatidylinositol 3' kinase, TORKi, mTOR kinase inhibitor, mTOR mechanistic target of rapamycin, mTORC1, mTOR complex 1, mTORC2, mTOR complex 2, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Although signaling from phosphatidylinositol 3-kinase (PI3K) and AKT to mechanistic target of rapamycin (mTOR) is prominently dysregulated in high-grade glial brain tumors, blockade of PI3K or AKT minimally affects downstream mTOR activity in glioma. Allosteric mTOR inhibitors, such as rapamycin, incompletely block mTORC1 compared with mTOR kinase inhibitors (TORKi). Here, we compared RapaLink-1, a TORKi linked to rapamycin, with earlier-generation mTOR inhibitors. Compared with rapamycin and Rapalink-1, TORKi showed poor durability. RapaLink-1 associated with FKBP12, an abundant mTOR-interacting protein, enabling accumulation of RapaLink-1. RapaLink-1 showed better efficacy than rapamycin or TORKi, potently blocking cancer-derived, activating mutants of mTOR. Our study re-establishes mTOR as a central target in glioma and traces the failure of existing drugs to incomplete/nondurable inhibition of mTORC1.

Published
2017

14. An expanded universe of cancer targets

Author

Dancik, Vlado, Gill, Shubhroz, Hua, Bruce, Sharifnia, Tanaz, Viswanathan, Vasanthi, Zou, Yilong, Dela Cruz, Filemon, Kung, Andrew, Stockwell, Brent, Boehm, Jesse, Dempster, Josh, Manguso, Robert, Vazquez, Francisca, Cooper, Lee A.D., Du, Yuhong, Ivanov, Andrey, Lonial, Sagar, Moreno, Carlos S., Niu, Qiankun, Owonikoko, Taofeek, Ramalingam, Suresh, Reyna, Matthew, Zhou, Wei, Grandori, Carla, Shmulevich, Ilya, Swisher, Elizabeth, Cai, Jitong, Chan, Issac S., Dunworth, Matthew, Ge, Yuchen, Georgess, Dan, Grasset, Eloïse M., Henriet, Elodie, Knútsdóttir, Hildur, Lerner, Michael G., Padmanaban, Veena, Perrone, Matthew C., Suhail, Yasir, Tsehay, Yohannes, Warrier, Manisha, Morrow, Quin, Nechiporuk, Tamilla, Long, Nicola, Saultz, Jennifer, Kaempf, Andy, Minnier, Jessica, Tognon, Cristina E., Kurtz, Stephen E., Agarwal, Anupriya, Brown, Jordana, Watanabe-Smith, Kevin, Vu, Tania Q., Jacob, Thomas, Yan, Yunqi, Robinson, Bridget, Lind, Evan F., Kosaka, Yoko, Demir, Emek, Estabrook, Joseph, Grzadkowski, Michael, Nikolova, Olga, Chen, Ken, Deneen, Ben, Liang, Han, Bassik, Michael C., Bhattacharya, Asmita, Brennan, Kevin, Curtis, Christina, Gevaert, Olivier, Ji, Hanlee P., Karlsson, Kasper A.J., Karagyozova, Kremena, Lo, Yuan-Hung, Liu, Katherine, Nakano, Michitaka, Sathe, Anuja, Smith, Amber R., Spees, Kaitlyn, Wong, Wing Hing, Yuki, Kanako, Hangauer, Matt, Kaufman, Dan S., Balmain, Allan, Bollam, Saumya R., Chen, Wei-Ching, Fan, QiWen, Kersten, Kelly, Krummel, Matthew, Li, Yun Rose, Menard, Marie, Nasholm, Nicole, Schmidt, Christin, Serwas, Nina K., Yoda, Hiroyuki, Ashworth, Alan, Bandyopadhyay, Sourav, Bivona, Trevor, Eades, Gabriel, Oberlin, Stefan, Tay, Neil, Wang, Yuhao, Weissman, Jonathan, Hahn, William C., Bader, Joel S., Braun, Theodore P., Califano, Andrea, Clemons, Paul A., Druker, Brian J., Ewald, Andrew J., Fu, Haian, Jagu, Subhashini, Kemp, Christopher J., Kim, William, Kuo, Calvin J., McManus, Michael T., B. Mills, Gordon, Mo, Xiulei, Sahni, Nidhi, Schreiber, Stuart L., Talamas, Jessica A., Tamayo, Pablo, Tyner, Jeffrey W., Wagner, Bridget K., Weiss, William A., and Gerhard, Daniela S.

Published
2021
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16. Practice and innovation in the operation and maintenance of HI-13 tandem accelerator for 35 years

Author

LI Kangning, KAN Chaoxin, WANG Xiaofei, HU Yueming, YANG Bingfan, QIN Jiuchang, GUAN Xialing, SU Shengyong, BAO Yiwen, YOU Qubo, WANG Hua, ZHOU Jianming, FAN Qiwen, LIU Dezhong, YANG Tao, HU Renwei, and YANG Baojun

Subjects
hi-13 tandem accelerator, operation and maintenance, key component development, upgrading of subsystems, Nuclear engineering. Atomic power, TK9001-9401
Abstract

The HI-13 tandem accelerator, located at the Beijing Tandem Accelerator National Laboratory, has been in operation for 35 years. To ensure the continued performance of the accelerator, the operation and maintenance team has prioritized focus on various aspects. The operation team conducted research that involved developing key components, cultivating a high-quality operational team, improving the machine time efficiency, and increasing the participation of users outside the China Institute of Atomic Energy (CIAE). The primary emphasis has been on developing key components and upgrading subsystems. These efforts have successfully maintained and improved the accelerator's performance, ensuring its safe and stable operation. Finally, the paper alse discusses the challenges faced by tandem accelerators and presents future development plans.

Published
2023
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18. Neutron spectroscopic factors of 7Li and astrophysical 6Li(n,g)7Li reaction rates

Author

Su, Jun, Li, Zhihong, Guo, Bing, Bai, Xixiang, Li, Zhichang, Liu, Jiancheng, Wang, Youbao, Lian, Gang, Zeng, Sheng, Wang, Baoxiang, Yan, Shengquan, Li, Yunju, Li, Ertao, Fan, Qiwen, and Liu, Weiping

Subjects
Nuclear Experiment
Abstract

Angular distributions of the 7Li(6Li,6Li)7Li elastic scattering and the 7Li(6Li,7Li_{g.s.})6Li, 7Li(6Li,7Li*_{0.48})6Li transfer reactions at Ec.m. = 23.7 MeV were measured with the Q3D magnetic spectrograph. The optical potential of 6Li+7Li was obtained by fitting the elastic scattering differential cross sections. Based on the distorted wave Born approximation (DWBA) analysis, spectroscopic factors of 7Li=6Li+n were determined to be 0.73 +- 0.05 and 0.90 +- 0.09 for the ground and first exited states in 7Li, respectively. Using the spectroscopic factors, the cross sections of the 6Li(n,g)7Li direct neutron capture reactions and the astrophysical 6Li(n,g)7Li reaction rates were derived., Comment: 4 pages, 5 figures

Published
2010
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20. Expression Quantitative Trait Loci and Receptor Pharmacology Implicate Arg1 and the GABA-A Receptor as Therapeutic Targets in Neuroblastoma

Author

Hackett, Christopher S, Quigley, David A, Wong, Robyn A, Chen, Justin, Cheng, Christine, Song, Young K, Wei, Jun S, Pawlikowska, Ludmila, Bao, Yun, Goldenberg, David D, Nguyen, Kim, Gustafson, W Clay, Rallapalli, Sundari K, Cho, Yoon-Jae, Cook, James M, Kozlov, Serguei, Mao, Jian-Hua, Van Dyke, Terry, Kwok, Pui-Yan, Khan, Javed, Balmain, Allan, Fan, QiWen, and Weiss, William A

Subjects
Biological Sciences, Cancer, Pediatric, Neuroblastoma, Neurosciences, Pediatric Cancer, Rare Diseases, 2.1 Biological and endogenous factors, Animals, Apoptosis, Arginase, Brain Neoplasms, Cell Line, Tumor, Cell Survival, Chromosomes, Mammalian, Gene Expression Regulation, Neoplastic, Genetic Association Studies, Genetic Linkage, Genetic Predisposition to Disease, Humans, Mice, Molecular Targeted Therapy, Quantitative Trait Loci, Receptors, GABA-A, Survival Analysis, gamma-Aminobutyric Acid, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

The development of targeted therapeutics for neuroblastoma, the third most common tumor in children, has been limited by a poor understanding of growth signaling mechanisms unique to the peripheral nerve precursors from which tumors arise. In this study, we combined genetics with gene-expression analysis in the peripheral sympathetic nervous system to implicate arginase 1 and GABA signaling in tumor formation in vivo. In human neuroblastoma cells, either blockade of ARG1 or benzodiazepine-mediated activation of GABA-A receptors induced apoptosis and inhibited mitogenic signaling through AKT and MAPK. These results suggest that ARG1 and GABA influence both neural development and neuroblastoma and that benzodiazepines in clinical use may have potential applications for neuroblastoma therapy.

Published
2014

23. Cross section measurement for the 14N(n,α0,1)11B reactions in the 4.5–11.5 MeV neutron energy region.

Author

Hu, Yiwei, Gledenov, Yu. M., Cui, Zengqi, Liu, Jie, Bai, Haofan, Xia, Cong, Chen, Zhenpeng, Wu, Zepeng, Ren, Wenkai, Cao, Wentian, Fan, Tieshuan, Zhang, Guohui, Sansarbayar, E., Khuukhenkhuu, G., Krupa, L., Chuprakov, I., Fan, Qiwen, Ruan, Xichao, Huang, Hanxiong, and Ren, Jie

Subjects
NEUTRON temperature, NUCLEAR energy, ACCELERATOR mass spectrometry, NEUTRON capture
Abstract

With more accurate measurement method for gas samples, cross sections of the 14N(n,α0,1)11B reactions were measured at 24 energy points in the 4.5–11.5 MeV neutron energy region based on the 4.5 MV Van de Graaff accelerator at Peking University and the HI-13 tandem accelerator of China Institute of Atomic Energy (CIAE). The average neutron fluence (Φ) through the gas sample was obtained through the combination of a highly enriched 238U3O8 sample and the simulation based on SuperMC. The cross sections of the 14N(n,α0)11B reaction measured using the gas sample and the solid samples are in agreement with each other. R-matrix analysis was carried out for the n + 14N system using code RAC in the neutron energy region below 30 MeV. A possible valley structure in both the excitation functions of the 14N(n,α0,1)11B reactions in the 10–11 MeV neutron energy region was found for the first time. [ABSTRACT FROM AUTHOR]

Published
2024
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26. 63Cu(n, α)60Co cross sections in the MeV region

Author

Liu, Jie, primary, Cui, Zengqi, additional, Hu, Yiwei, additional, Bai, Haofan, additional, Yang, Yi, additional, Ruan, Xichao, additional, Xia, Cong, additional, Chen, Jinxiang, additional, Zhang, Guohui, additional, Gledenov, Yu M, additional, Sansarbayar, E, additional, Khuukhenkhuu, G, additional, Krupa, L, additional, Chuprakov, I, additional, Huang, Hanxiong, additional, Ren, Jie, additional, Fan, Qiwen, additional, Gao, Yuan, additional, and Yang, Xiangjun, additional

Published
2023
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27. New Determination of the 12C(α, γ)16O Reaction Rate and Its Impact on the Black-hole Mass Gap

Author

Shen, Yangping, primary, Guo, Bing, additional, deBoer, Richard J., additional, Li, Ertao, additional, Li, Zhihong, additional, Li, Yunju, additional, Tang, Xiaodong, additional, Pang, Danyang, additional, Adhikari, Sucheta, additional, Basu, Chinmay, additional, Su, Jun, additional, Yan, Shengquan, additional, Fan, Qiwen, additional, Liu, Jiancheng, additional, Chen, Chen, additional, Han, Zhiyu, additional, Li, Xinyue, additional, Lian, Gang, additional, Ma, Tianli, additional, Nan, Wei, additional, Nan, Weike, additional, Wang, Youbao, additional, Zeng, Sheng, additional, Zhang, Hao, additional, and Liu, Weiping, additional

Published
2023
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30. Photonuclear reaction study with the (p, γ) resonance γ-source

Author

He Chuangye, Dang Yongle, Liu Fulong, Fu Guangyong, Wu Di, Shen Yangping, Han Zhiyu, Fan Qiwen, Guo Bing, and Wang Naiyan

Subjects
Physics, QC1-999
Abstract

The (p, γ) resonance is a good way to produce monoenergetic γ rays. It becomes an important tool for studying photonuclear reactions. In this work, 13C(p, γ)14N resonance is studied to produce 9.17 MeV γ ray using the 2 × 1.7 MV tandem accelerator at CIAE. The flux of 9.17 MeV γ was determined to be 2.3 × 105/s. 197Au photoneutron cross section was measured to be 45.4 ± 6.9 mb under the irradiation of 13C(p, γ)14N resonance γ -source. The value is close to the previous results. It certificates that we have developed an experimental method for photonuclear reaction study.

Published
2020
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31. Effects of diets with various levels of forage rape ( <scp> Brassi </scp> <scp> ca napus </scp> ) on growth performance, carcass traits, meat quality and rumen microbiota of <scp>Hu</scp> lambs

Author

Na Zhao, Chen Fang, Jintao Wei, Guo Wanzheng, Du Encun, Tingdong Fu, Fan Qiwen, Zhang Wei, Huang Shaowen, and Guangsheng Zhou

Subjects
chemistry.chemical_classification, Nutrition and Dietetics, biology, Lachnospiraceae, Brassica, food and beverages, Fatty acid, Forage, Total mixed ration, biology.organism_classification, Feed conversion ratio, Crop, Rumen, Animal science, chemistry, Agronomy and Crop Science, Food Science, Biotechnology
Abstract

Background Apart from being an oil crop, forage rape (Brassica napus) can be used to feed ruminants. The objective of this study was to investigate the effects of pelleted total mixed ration (TMR) diets with various levels of forage rape on growth performance, carcass traits, meat quality, meat nutritional value and rumen microbiota of Hu lambs, which was important for the efficient utilization of forage rape and alleviating the shortage of high-quality forage in China. Results Lambs fed on diets with 200-400 g kg-1 forage rape had greater average daily gain (ADG) and lower feed conversion ratio (FCR) than those fed on diets with 0-100 g kg-1 of forage rape (P 0.05). However, the inclusion of forage rape increased the relative abundance of cellulolytic bacteria and short-chain fatty acid producers, including Succiniclasticum, Fibrobacter and members of the Lachnospiraceae. Besides, Succiniclasticum was found to be positively correlated with the final body weight of lambs. Conclusion TMR diets that included 200-400 g kg-1 forage rape could improve the growth performance of lambs, and elevated the content of intramuscular α-linolenic acid and a variety of amino acids in the muscle, accompanied by increased abundance of cellulolytic bacteria in the rumen.

Published
2021
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32. Supplemental magnolol or honokiol attenuates adverse effects in broilers infected with Salmonella pullorum by modulating mucosal gene expression and the gut microbiota

Author

Na Zhao, Guo Wanzheng, Hao Zhang, Du Encun, Huang Shaowen, Fan Qiwen, Feng Jin, Zhang Wei, Chen Fang, and Jintao Wei

Subjects
Honokiol, Globulin, Veterinary medicine, Ileum, Gut microbiota, Salmonella pullorum, Gut flora, Pharmacology, Biochemistry, SF1-1100, chemistry.chemical_compound, Lactobacillus, SF600-1100, medicine, biology, Chemistry, Research, Broiler, biology.organism_classification, Magnolol, Animal culture, Immune, Magnolia officinalis, medicine.anatomical_structure, biology.protein, Animal Science and Zoology, Food Science, Biotechnology
Abstract

Background Salmonella pullorum is one of the most harmful pathogens to avian species. Magnolol and honokiol, natural compounds extracted from Magnolia officinalis, exerts anti-inflammatory, anti-oxidant and antibacterial activities. This study was conducted to evaluate the effects of dietary supplemental magnolol and honokiol in broilers infected with S. pullorum. A total of 360 one-day-old broilers were selected and randomly divided into four groups with six replicates: the negative control group (CTL), S. pullorum-infected group (SP), and the S. pullorum-infected group supplemented with 300 mg/kg honokiol (SPH) or magnolol (SPM). Results The results showed that challenging with S. pullorum impaired growth performance in broilers, as indicated by the observed decreases in body weight (P P P P P P Lactobacillus (P Cyanobacteria (P Conclusions Supplemental magnolol and honokiol alleviated S. pullorum-induced impairments in growth performance, and the effect of magnolol was better than that of honokiol, which could be partially due to magnolol’s ability to improve the intestinal microbial and mucosal barrier.

Published
2021

33. Cross sections of the Ca40(n,α0)37Ar and Ca40(n,α)37Ar reactions in the 8.50–9.50 MeV neutron energy range

Author

Liu, Jie, primary, jiang, Haoyu, additional, Cui, Zengqi, additional, Hu, Yiwei, additional, Bai, Haofan, additional, Chen, Jinxiang, additional, Zhang, Guohui, additional, Gledenov, Yu. M., additional, Sansarbayar, E., additional, Khuukhenkhuu, G., additional, Battsooj, N., additional, Krupa, L., additional, Chuprakov, I., additional, Ruan, Xichao, additional, Huang, Hanxiong, additional, Ren, Jie, additional, and Fan, Qiwen, additional

Published
2022
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38. Effects of magnolol on egg production, egg quality, antioxidant capacity, and intestinal health of laying hens in the late phase of the laying cycle

Author

Du Encun, Feng Jin, Chen Fang, Guo Wanzheng, Jintao Wei, Fan Qiwen, Chao Zheng, Huang Shaowen, Na Zhao, Hao Zhang, and Zhang Wei

Subjects
Eggs, Oviposition, egg quality, Ileum, antioxidant capacity, Feed conversion ratio, hen, Antioxidants, Lignans, Nitric oxide, Metabolism and Nutrition, Jejunum, 03 medical and health sciences, chemistry.chemical_compound, Animal science, medicine, Animals, Haugh unit, lcsh:SF1-1100, 030304 developmental biology, Ovum, 0303 health sciences, biology, Chemistry, Biphenyl Compounds, 0402 animal and dairy science, 04 agricultural and veterinary sciences, General Medicine, Metabolism, Lipid Metabolism, 040201 dairy & animal science, magnolol, Animal Feed, Magnolol, Diet, Nitric oxide synthase, Intestines, medicine.anatomical_structure, Liver, Dietary Supplements, biology.protein, Animal Science and Zoology, intestinal health, Female, lcsh:Animal culture, Chickens
Abstract

Magnolol is a multifunctional plant polyphenol. To evaluate the effects of magnolol on laying hens in the late laying period, 360 (50-week-old) laying hens were randomly assigned to 4 dietary treatments: a non-supplemented control diet (C), and control diets supplemented with 100, 200, and 300 mg/kg of magnolol (M100, M200, and M300), respectively. Each treatment had 6 replicates with 15 hens per replicate. Results showed that dietary supplementation of 200 and 300 mg/kg of magnolol increased the laying rate and the M200 group had a lower feed conversion ratio (P

Published
2020

40. Cross-section measurements for the 58,60,61Ni(n, α)55,57,58Fe reactions at 8.50, 9.50 and 10.50 MeV neutron energies *

Author

Jiang, Haoyu, primary, Cui, Zengqi, additional, Hu, Yiwei, additional, Liu, Jie, additional, Bai, Haofan, additional, Chen, Jinxiang, additional, Zhang, Guohui, additional, Gledenov, Yu. M., additional, Sansarbayar, E., additional, Khuukhenkhuu, G., additional, Krupa, L., additional, Chuprakov, I., additional, Ruan, Xichao, additional, Huang, Hanxiong, additional, Ren, Jie, additional, and Fan, Qiwen, additional

Published
2022
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41. First result from the Jinping Underground Nuclear Astrophysics experiment JUNA: precise measurement of the 92 keV 25Mg(p, γ)26Al resonance

Author

Su, Jun, primary, Zhang, Hao, additional, Li, Zhihong, additional, Ventura, Paolo, additional, Li, Yunju, additional, Li, Ertao, additional, Chen, Chen, additional, Shen, Yangping, additional, Lian, Gang, additional, Guo, Bing, additional, Li, Xinyue, additional, Zhang, Liyong, additional, He, Jianjun, additional, Sheng, Yaode, additional, Chen, Yinji, additional, Wang, Luohuan, additional, Zhang, Long, additional, Cao, Fuqiang, additional, Nan, Wei, additional, Nan, Weike, additional, Li, Gexing, additional, Song, Na, additional, Cui, Baoqun, additional, Chen, Lihua, additional, Ma, Ruigang, additional, Zhang, Zhicheng, additional, Jiao, Taoyu, additional, Gao, Bingshui, additional, Tang, Xiaodong, additional, Wu, Qi, additional, Li, Jiaqing, additional, Sun, Liangting, additional, Wang, Shuo, additional, Yan, Shengquan, additional, Liao, Junhui, additional, Wang, Youbao, additional, Zeng, Sheng, additional, Nan, Ding, additional, Fan, Qiwen, additional, Qi, Ningchun, additional, Sun, Wenliang, additional, Guo, Xuyuan, additional, Zhang, Peng, additional, Chen, Yunhua, additional, Zhou, Yong, additional, Zhou, Jifang, additional, He, Jinrong, additional, Shang, Changsong, additional, Li, Mingchuan, additional, Cheng, Jianping, additional, and Liu, Weiping, additional

Published
2022
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44. Maternal magnolol supplementation alters placental morphology, promotes placental angiogenesis during mid-gestation and improves offspring growth in a pregnant mouse model

Author

Huang Shaowen, Xianghua Yan, Du Encun, Na Zhao, Guo Wanzheng, Mingxin Chen, Zhang Wei, Chen Fang, Jintao Wei, and Fan Qiwen

Subjects
Offspring, Placenta, Drug Evaluation, Preclinical, Neovascularization, Physiologic, Biology, Lignans, Andrology, Fetal Development, chemistry.chemical_compound, Mice, Endocrinology, Pregnancy, medicine, CXCL10, Animals, Fetus, Plant Extracts, Decidua, Biphenyl Compounds, medicine.disease, Magnolol, Vascular endothelial growth factor, medicine.anatomical_structure, chemistry, Gene Expression Regulation, Magnolia, Dietary Supplements, Cytokines, Animal Science and Zoology, Female, Developmental Biology, Phytotherapy
Abstract

The placenta is the organ that determines the growth of the fetus and the outcome of pregnancy. Magnolol is a multifunctional polyphenol with antioxidant, anti-inflammatory, anticancer and neuroprotective functions. However, there is less knowledge of the effects or complications in the placenta and the mechanism underlying the effect of magnolol when used during pregnancy. The aim of this study was to explore the effects of maternal magnolol supplementation on pregnancy outcomes and placental alterations in a pregnant mouse model. A total of 128 pregnant mice were randomly divided into 4 groups supplemented with 0, 40, 80 and 160 μM magnolol from gestational day 0 (GD0) to delivery. Our results revealed that the number of large-for-gestation-age fetuses on GD13 and the weaning weight of offspring were increased in the magnolol treatment groups. Moreover, maternal magnolol supplementation increased superoxide dismutase (SOD), decreased malondialdehyde (MDA) in maternal serum, and promoted the expression of heme oxygenase-1 (HO-1) in the placenta. Furthermore, magnolol significantly increased the area of the junctional zone and decidua in the placentas and increased the expression of interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), chemokine (CC Motif) Ligand 3 (CCL3), chemokine (CXC motif) ligand 10 (CXCL10), insulin-like growth factor-1 (IGF-1) and T-box transcription factor 21 (T-bet) in the placenta during GD13 in pregnant mice, while suppressor of cytokine signaling 1 (SOCS1) was reduced. Moreover, the ratio of blood space in the labyrinth area, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were all increased in the magnolol treatment groups on GD13. Taken together, these results indicate that magnolol can improve the growth of offspring, which might be due to the alteration of placental morphology and the promotion of placental angiogenesis during mid-gestation.

Published
2021

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