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The efficacy of a 2,4-diaminoquinazoline compound as an intranasal vaccine adjuvant to protect against influenza A virus infection in vivo
Kyungseob Noh , Eun Ju Jeong , Timothy An , Jin Soo Shin , Hyejin Kim , Soo Bong Han , Meehyein Kim
J. Microbiol. 2022;60(5):550-559.   Published online April 18, 2022
DOI: https://doi.org/10.1007/s12275-022-1661-7
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AbstractAbstract
Adjuvants are substances added to vaccines to enhance antigen- specific immune responses or to protect antigens from rapid elimination. As pattern recognition receptors, Toll-like receptors 7 (TLR7) and 8 (TLR8) activate the innate immune system by sensing endosomal single-stranded RNA of RNA viruses. Here, we investigated if a 2,4-diaminoquinazolinebased TLR7/8 agonist, (S)-3-((2-amino-8-fluoroquinazolin- 4-yl)amino)hexan-1-ol (named compound 31), could be used as an adjuvant to enhance the serological and mucosal immunity of an inactivated influenza A virus vaccine. The compound induced the production of proinflammatory cytokines in macrophages. In a dose-response analysis, intranasal administration of 1 μg compound 31 together with an inactivated vaccine (0.5 μg) to mice not only enhanced virus-specific IgG and IgA production but also neutralized influenza A virus with statistical significance. Notably, in a virus-challenge model, the combination of the vaccine and compound 31 alleviated viral infection-mediated loss of body weight and increased survival rates by 40% compared with vaccine only-treated mice. We suggest that compound 31 is a promising lead compound for developing mucosal vaccine adjuvants to protect against respiratory RNA viruses such as influenza viruses and potentially coronaviruses.

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  • Efflux-Enhanced Imidazoquinolines To Exploit Chemoresistance
    Muhammad Haroon, Sharmin Sultana, Seyedeh A. Najibi, Emily T. Wang, Abbey Michaelson, Pranto S. M. Al Muied, Amy E. Nielsen, Rock J. Mancini
    ACS Omega.2025;[Epub]     CrossRef
  • Design, Synthesis, and Biological Evaluation of New 2,6,7-Substituted Purine Derivatives as Toll-like Receptor 7 Agonists for Intranasal Vaccine Adjuvants
    Morgan Kim, Kyungseob Noh, Pyeongkeun Kim, Jae Ho Kim, Byeong Wook Choi, Ravi Singh, Jun-Ho Choi, Soo Bong Han, Seong Soon Kim, Eun-Young Lee, Myung Ae Bae, Daeho Shin, Meehyein Kim, Jin Hee Ahn
    Journal of Medicinal Chemistry.2024; 67(11): 9389.     CrossRef
  • Evaluation of Antiviral Activity of Gemcitabine Derivatives against Influenza Virus and Severe Acute Respiratory Syndrome Coronavirus 2
    Hyeon-Min Cha, Uk-Il Kim, Soo Bin Ahn, Myoung Kyu Lee, Haemi Lee, Hyungtae Bang, Yejin Jang, Seong Soon Kim, Myung Ae Bae, Kyungjin Kim, Meehyein Kim
    ACS Infectious Diseases.2023; 9(4): 1033.     CrossRef
  • Identification of broad-spectrum neutralizing antibodies against influenza A virus and evaluation of their prophylactic efficacy in mice
    Sumin Son, Soo Bin Ahn, Geonyeong Kim, Yejin Jang, Chunkyu Ko, Meehyein Kim, Sang Jick Kim
    Antiviral Research.2023; 213: 105591.     CrossRef
  • Inhibition of KIF20A suppresses the replication of influenza A virus by inhibiting viral entry
    Hoyeon Jeon, Younghyun Lim, In-Gu Lee, Dong-In Kim, Keun Pil Kim, So-Hee Hong, Jeongkyu Kim, Youn-Sang Jung, Young-Jin Seo
    Journal of Microbiology.2022; 60(11): 1113.     CrossRef
Antiviral effects of human placenta hydrolysate (Laennec) against SARS-CoV-2 in vitro and in the ferret model
Eun-Ha Kim , Young-il Kim , Seung-Gyu Jang , Minju Im , Kyeongsoo Jeong , Young Ki Choi , Hae-Jung Han
J. Microbiol. 2021;59(11):1056-1062.   Published online October 6, 2021
DOI: https://doi.org/10.1007/s12275-021-1367-2
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AbstractAbstract
The COVID-19 pandemic has caused unprecedented health, social, and economic crises worldwide. However, to date, there is an only a limited effective treatment for this disease. Human placenta hydrolysate (hPH) has previously been shown to be safe and to improve the health condition in patients with hyperferritinemia and COVID-19. In this study, we aimed to determine the antiviral effects of hPH against SARS-CoV-2 in vitro and in vivo models and compared with Remdesivir, an FDA-approved drug for COVID-19 treatment. To assess whether hPH inhibited SARS-CoV-2 replication, we determined the CC50, EC50, and selective index (SI) in Vero cells by infection with a SARS-CoV-2 at an MOI of 0.01. Further, groups of ferrets infected with 105.8 TCID50/ml of SARS-CoV-2 and treated with hPH at 2, 4, 6 dpi, and compared their clinical manifestation and virus titers in respiratory tracts with PBS control-treated group. The mRNA expression of immunerelated cytokines was determined by qRT-PCR. hPH treatment attenuated virus replication in a dose-dependent manner in vitro. In a ferret infection study, treatment with hPH resulted in minimal bodyweight loss and attenuated virus replication in the nasal wash, turbinates, and lungs of infected ferrets. In addition, qRT-PCR results revealed that the hPH treatment remarkably upregulated the gene expression of type I (IFN-α and IFN-β) and II (IFN-γ) IFNs in SARS-CoV-2 infected ferrets. Our data collectively suggest that hPH has antiviral efficacy against SARS-CoV-2 and might be a promising therapeutic agent for the treatment of SARS-CoV-2 infection.

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  • Perinatal Hypoxia and Immune System Activation in Schizophrenia Pathogenesis: Critical Considerations During COVID-19 Pandemic
    I Kawikova, K Hakenova, M Lebedeva, L Kleteckova, L Jakob, V Spicka, L Wen, F Spaniel, K Vales
    Physiological Research.2024; : S615.     CrossRef
  • Human Placenta Extract (HPH) Suppresses Inflammatory Responses in TNF-α/IFN-γ-Stimulated HaCaT Cells and a DNCB Atopic Dermatitis (AD)-Like Mouse Model
    Jung Ok Lee, Youna Jang, A Yeon Park, Jung Min Lee, Kyeongsoo Jeong, So-Hyun Jeon, Hui Jin, Minju Im, Jae-Won Kim, Beom Joon Kim
    Journal of Microbiology and Biotechnology.2024; 34(10): 1969.     CrossRef
  • Systematic analysis of the pharmacology of standardized extracts of human placenta
    T. E. Bogacheva, I. Yu. Torshin, O. A. Gromova
    Pharmacokinetics and Pharmacodynamics.2024; (4): 3.     CrossRef
  • Distinctive Combinations of RBD Mutations Contribute to Antibody Evasion in the Case of the SARS-CoV-2 Beta Variant
    Tae-Hun Kim, Sojung Bae, Sunggeun Goo, Jinjong Myoung
    Journal of Microbiology and Biotechnology.2023; 33(12): 1587.     CrossRef
  • Current state-of-the-art and potential future therapeutic drugs against COVID-19
    Ailong Sha, Yi Liu, Haiyan Hao
    Frontiers in Cell and Developmental Biology.2023;[Epub]     CrossRef
  • SARS-CoV-2 Aerosol and Intranasal Exposure Models in Ferrets
    Elizabeth E. Zumbrun, Samantha E. Zak, Eric D. Lee, Philip A. Bowling, Sara I. Ruiz, Xiankun Zeng, Jeffrey W. Koehler, Korey L. Delp, Russel R. Bakken, Shannon S. Hentschel, Holly A. Bloomfield, Keersten M. Ricks, Tamara L. Clements, April M. Babka, John
    Viruses.2023; 15(12): 2341.     CrossRef
  • Human placenta hydrolysates: from V.P. Filatov to the present day: Review
    Olga A. Gromova, Ivan Yu. Torshin, Alexander G. Chuchalin, Valeriy А. Maximov
    Terapevticheskii arkhiv.2022; 94(3): 434.     CrossRef
Characteristics of the gut microbiota colonization, inflammatory profile, and plasma metabolome in intrauterine growth restricted piglets during the first 12 hours after birth
Shimeng Huang , Na Li , Cong Liu , Tiantian Li , Wei Wang , Lili Jiang , Zhen Li , Dandan Han , Shiyu Tao , Junjun Wang
J. Microbiol. 2019;57(9):748-758.   Published online June 11, 2019
DOI: https://doi.org/10.1007/s12275-019-8690-x
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AbstractAbstract
Intrauterine growth restriction (IUGR) predisposes newborns to inflammatory and metabolic disturbance. Disequilibrium of gut microbiota in early life has been implicated in the incidence of inflammation and metabolic diseases in adulthood. This study aimed to investigate the difference in gut microbiota colonization, cytokines and plasma metabolome between IUGR and normal birth weight (NBW) piglets in early life. At birth, reduced (P < 0.05) body, jejunum, and ileum weights, as well as decreased (P < 0.05) small intestinal villi and increased (P < 0.05) ileal crypt depth were observed in IUGR piglets compared with their NBW counterparts. Imbalanced inflammatory and plasma metabolome profile was observed in IUGR piglets. Furthermore, altered metabolites were mainly involved in fatty acid metabolism and inflammatory response. At 12 h after birth and after suckling colostrum, reduced (P < 0.05) postnatal growth and the small intestinal maturation retardation (P < 0.05) continued in IUGR piglets in comparison with those in NBW littermates. Besides, the gut microbiota structure was significantly altered by IUGR. Importantly, the disruption of the inflammatory profile and metabolic status mainly involved the pro-inflammatory cytokines (IL-1β and IFN-γ) and amino acid metabolism. Moreover, spearman correlation analysis showed that the increased abundance of Escherichia-Shigella and decreased abundance of Clostridium_sensu_stricto_1 in IUGR piglets was closely associated with the alterations of slaughter weight, intestinal morphology, inflammatory cytokines, and plasma metabolites. Collectively, IUGR significantly impairs small intestine structure, modifies gut microbiota colonization, and disturbs inflammatory and metabolic profiles during the first 12 h after birth. The unbalanced gut microbiota mediated by IUGR contributes to the development of inflammation and metabolic diseases.

Citations

Citations to this article as recorded by  
  • Endoplasmic Reticulum Stress Contributes to Intestinal Injury in Intrauterine Growth Restriction Newborn Piglets
    Tingting Fang, Gang Tian, Daiwen Chen, Jun He, Ping Zheng, Xiangbing Mao, Hui Yan, Bing Yu
    Animals.2024; 14(18): 2677.     CrossRef
  • Characterization of the chemical composition of different parts of Dolichos lablab L. and revelation of its anti-ulcerative colitis effects by modulating the gut microbiota and host metabolism
    Yanping Gao, Ruiting Huang, Yongyi Qiu, Yi Liu, Lei Chen
    Journal of Ethnopharmacology.2024; 322: 117629.     CrossRef
  • Plant-Derived Polysaccharides Benefit Weaned Piglets by Regulating Intestinal Microbiota: A Review
    Xiaoyan Huang, Faming Jiang, Xingying Chen, Yuanhua Xian
    Journal of Agricultural and Food Chemistry.2024; 72(51): 28225.     CrossRef
  • Maternal Supplementation with Ornithine Promotes Placental Angiogenesis and Improves Intestinal Development of Suckling Piglets
    Yun Yang, Guanyu Hou, Fengjie Ji, Hanlin Zhou, Renlong Lv, Chengjun Hu
    Animals.2024; 14(5): 689.     CrossRef
  • Dietary supplementation with dihydroartemisinin improves intestinal barrier function in weaned piglets with intrauterine growth retardation by modulating the gut microbiota
    Yu Niu, Ruiqiang Zhang, Caimei Yang, Jintian He, Tian Wang
    Journal of Animal Science.2024;[Epub]     CrossRef
  • Phosphatidylethanolamine Improves Postnatal Growth Retardation by Regulating Mucus Secretion of Intestinal Goblet Cells in Piglets
    Nan Wang, Chengming Wang, Ming Qi, Xingtong Lin, Andong Zha, Bie Tan, Yulong Yin, Jing Wang
    Animals.2024; 14(8): 1193.     CrossRef
  • Microbiota intestinal en recién nacidos prematuros con restricción del crecimiento intrauterino
    Lizbeth Miranda-García, Francisco Josué Fernández-Becerra, Paulina Briseño-Sahagun
    Revista Mexicana de Pediatría.2024; 91(2): 72.     CrossRef
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    Yu Pi, Yujun Wu, Xiangyu Zhang, Dongdong Lu, Dandan Han, Jiangchao Zhao, Xiaojiao Zheng, Shiyi Zhang, Hao Ye, Shuai Lian, Yu Bai, Zhenyu Wang, Shiyu Tao, Dongjiao Ni, Xinhua Zou, Wei Jia, Guolong Zhang, Defa Li, Junjun Wang
    Microbiome.2023;[Epub]     CrossRef
  • Oil source regulates intestinal health of hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatu): Structure, inflammation and microorganisms homeostasis
    Xiaobo Yan, Hao Liu, Simiao Pan, Beiping Tan, Shuang Zhang, Hongyu Liu, Shuyan Chi, Qihui Yang, Yuanzhi Yang, Xiaohui Dong
    Aquaculture.2023; 565: 739121.     CrossRef
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    Hongjian Dai, Jian Gao, Yi Zhang, Haoze Wu, Yuqi Li, Zhanying Sun, Donghai Lv, Weiyun Zhu, Yanfen Cheng
    Animal Feed Science and Technology.2023; 305: 115786.     CrossRef
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    Naser A. Alsharairi, Li Li
    Life.2023; 13(12): 2239.     CrossRef
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    Lijuan Fan, Yaoyao Xia, Youxia Wang, Dandan Han, Yanli Liu, Jiahuan Li, Jie Fu, Leli Wang, Zhending Gan, Bingnan Liu, Jian Fu, Congrui Zhu, Zhenhua Wu, Jinbiao Zhao, Hui Han, Hao Wu, Yiwen He, Yulong Tang, Qingzhuo Zhang, Yibin Wang, Fan Zhang, Xin Zong,
    Science China Life Sciences.2023; 66(11): 2466.     CrossRef
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    Yang Liu, Md. Abul Kalam Azad, Sujuan Ding, Qian Zhu, Francois Blachier, Zugong Yu, Haijun Gao, Xiangfeng Kong
    Journal of Animal Science and Biotechnology.2023;[Epub]     CrossRef
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    Melanie R. White, Dustin T. Yates
    Frontiers in Physiology.2023;[Epub]     CrossRef
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    Yan Li, Qingshan Ma, Guiqin Liu, Zhenwei Zhang, Yandong Zhan, Mingxia Zhu, Changfa Wang
    Frontiers in Microbiology.2022;[Epub]     CrossRef
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    Tingting Zhang, Beizhen Xie, Hong Liu
    Food Research International.2022; 154: 110989.     CrossRef
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    Metabolites.2022; 12(9): 860.     CrossRef
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    Oxidative Medicine and Cellular Longevity.2022; 2022: 1.     CrossRef
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    Frontiers in Veterinary Science.2022;[Epub]     CrossRef
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    Translational Animal Science.2022;[Epub]     CrossRef
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    BMC Pregnancy and Childbirth.2022;[Epub]     CrossRef
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    Riley D Messman, Zully E Contreras-Correa, Henry A Paz, Caleb O Lemley
    Journal of Animal Science.2021;[Epub]     CrossRef
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    Kevin Van Tichelen, Sara Prims, Miriam Ayuso, Céline Van Kerschaver, Mario Vandaele, Jeroen Degroote, Steven Van Cruchten, Joris Michiels, Chris Van Ginneken
    Animals.2021; 12(1): 55.     CrossRef
  • Dietary dihydroartemisinin supplementation alleviates intestinal inflammatory injury through TLR4/NOD/NF-κB signaling pathway in weaned piglets with intrauterine growth retardation
    Yu Niu, Yongwei Zhao, Jintian He, Yang Yun, Mingming Shen, Zhending Gan, Lili Zhang, Tian Wang
    Animal Nutrition.2021; 7(3): 667.     CrossRef
  • Effects of Bacillus subtilis on jejunal integrity, redox status, and microbial composition of intrauterine growth restriction suckling piglets
    Yang Yun, Shuli Ji, Ge Yu, Peilu Jia, Yu Niu, Hao Zhang, Xin Zhang, Tian Wang, Lili Zhang
    Journal of Animal Science.2021;[Epub]     CrossRef
  • Management and Feeding Strategies in Early Life to Increase Piglet Performance and Welfare around Weaning: A Review
    Laia Blavi, David Solà-Oriol, Pol Llonch, Sergi López-Vergé, Susana María Martín-Orúe, José Francisco Pérez
    Animals.2021; 11(2): 302.     CrossRef
  • Malnutrition, poor post-natal growth, intestinal dysbiosis and the developing lung
    Mark A. Underwood, Satyan Lakshminrusimha, Robin H. Steinhorn, Stephen Wedgwood
    Journal of Perinatology.2021; 41(8): 1797.     CrossRef
  • The Effect of Dietary Protein Imbalance during Pregnancy on the Growth, Metabolism and Circulatory Metabolome of Neonatal and Weaned Juvenile Porcine Offspring
    Quentin L. Sciascia, Cornelia Prehn, Jerzy Adamski, Gürbüz Daş, Iris S. Lang, Winfried Otten, Solvig Görs, Cornelia C. Metges
    Nutrients.2021; 13(9): 3286.     CrossRef
  • Differences in Intestinal Barrier Development between Intrauterine Growth Restricted and Normal Birth Weight Piglets
    Jarosław Olszewski, Romuald Zabielski, Tomasz Skrzypek, Piotr Matyba, Małgorzata Wierzbicka, Antoni Adamski, Elżbieta Grzesiuk, Maria Sady, Zdzisław Gajewski, Karolina Ferenc
    Animals.2021; 11(4): 990.     CrossRef
  • Changes in Faecal Microbiota Profiles Associated With Performance and Birthweight of Piglets
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    Frontiers in Microbiology.2020;[Epub]     CrossRef
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    Jonah Bardos, Desiree Fiorentino, Ryan E. Longman, Michael Paidas
    Frontiers in Immunology.2020;[Epub]     CrossRef
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    Animals.2020; 10(6): 1073.     CrossRef
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    Flaminia Bardanzellu, Vassilios Fanos
    Italian Journal of Pediatrics.2020;[Epub]     CrossRef
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    Shi-Meng Huang, Zhen-Hua Wu, Tian-Tian Li, Cong Liu, Dan-Dan Han, Shi-Yu Tao, Yu Pi, Na Li, Jun-Jun Wang
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  • Intrauterine Growth Restriction: New Insight from the Metabolomic Approach
    Elena Priante, Giovanna Verlato, Giuseppe Giordano, Matteo Stocchero, Silvia Visentin, Veronica Mardegan, Eugenio Baraldi
    Metabolites.2019; 9(11): 267.     CrossRef
NMR-based metabolomics reveals the metabolite profiles of Vibrio parahaemolyticus under ferric iron stimulation
Jun Zhou , Chenyang Lu , Dijun Zhang , Chennv Ma , Xiurong Su
J. Microbiol. 2017;55(8):628-634.   Published online July 28, 2017
DOI: https://doi.org/10.1007/s12275-017-6551-z
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AbstractAbstract
Vibrio parahaemolyticus is a halophilic bacterium endemic to coastal areas, and its pathogenicity has caused widespread seafood poisoning. In our previous research, the protein expression of V. parahaemolyticus in Fe3+ medium was determined using isobaric tags for relative and absolute quantitation (iTRAQ). Here, nuclear magnetic resonance (NMR) was used to detect changes in the V. parahaemolyticus metabolome. NMR spectra were obtained using methanol-water extracts of intracellular metabolites from V. parahaemolyticus under various culture conditions, and 62 metabolites were identified, including serine, arginine, alanine, ornithine, tryptophan, glutamine, malate, NAD+, NADP+, oxypurinol, xanthosine, dCTP, uracil, thymine, hypoxanthine, and betaine. Among these, 21 metabolites were up-regulated after the stimulation of the cells by ferric iron, and 9 metabolites were down-regulated. These metabolites are involved in amino acid and protein synthesis, energy metabolism, DNA and RNA synthesis and osmolality. Based on these results, we conclude that Fe3+ influences the metabolite profiles of V. parahaemolyticus.

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