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Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 89-101页

作者： Yunhan Zhang Zhulin Zou Shuang Liu Fangfang Chen Minglu Li Haoyang Zou Haiyan Liu Jianxun Ding key laboratory of pathobiology Ministry of Education Department of AnatomyCollege of Basic Medical SciencesJilin UniversityChangchun 130061China key laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Department of Gastrointestinal Colorectaland Anal SurgeryChina-Japan Union Hospital of Jilin UniversityChangchun 130033China

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

关键词： Poly(amino acid)nanogel Controlled drug delivery Inhibition of ferroptosis Neuroprotection Cerebral ischenia injury therapy

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Mesenchymal stem cells and their derived exosomes for the treatment of COVID-19

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World Journal of Stem Cells 2024年第4期16卷 353-374页

作者： Xiang-Yi Hou La-Mu Danzeng Yi-Lin Wu Qian-Hui Ma Zheng Yu Mei-Ying Li Li-Sha Li The key laboratory of pathobiology Ministry of EducationCollege of Basic Medical SciencesJilin UniversityChangchun 130021Jilin ProvinceChina Department of Pharmacy Jilin UniversityChangchun 130021Jilin ProvinceChina The First Hospital of Jilin University Jilin UniversityChangchun 130021Jilin ProvinceChina

Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,which can progress to severe respiratory distress syndrome and multiple organ failure.In severe cases,these complications may even lead to death.One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response.Therefore,suppressing the overactive immune response may be an effective strategy for treating COVID-19.Mesenchymal stem cells(MSCs)and their derived exosomes(MSCs-Exo)have potent homing abilities,immunomodulatory functions,regenerative repair,and antifibrotic effects,promising an effective tool in treating COVID-19.In this paper,we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19.We also summarize relevant recent clinical trials,including the source of cells,the dosage and the efficacy,and the clinical value and problems in this field,providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.

关键词： COVID-19 Cytokine storm Immunomodulation Mesenchymal stem cell Mesenchymal stem cell-derived exosomes

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Corrigendum to“3Cpro of FMDV inhibits type II interferon-stimulated JAK-STAT signaling pathway by blocking STAT1 nuclear translocation”[Virol Sin 38(2023)387–397]

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Virologica Sinica 2024年第2期39卷 351-354页

作者： Xiangju Wu Lei Chen Chao Sui Yue Hu Dandan Jiang Fan Yang Laura C.Miller Juntong Li Xiaoyan Cong Nataliia Hrabchenko Changhee Lee Yijun Du Jing Qi Shandong key laboratory of Animal Disease Control and Breeding Key Laboratory of Livestock and Poultry Multi-omics of MARAInstitute of Animal Science and Veterinary MedicineInstitute of Crop Germplasm ResourcesShandong Academy of Agricultural SciencesJinan250100China College of Life Science Shandong Normal UniversityJinan250358China State key laboratory of Veterinary Etiological Biology National Foot and Mouth Disease Reference LaboratoryKey Laboratory of Animal Virology of Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou730050China Department of Diagnostic Medicine and pathobiology College of Veterinary MedicineKansas State UniversityManhattanKS66506USA College of Veterinary Medicine and Virus Vaccine Research Center Gyeongsang National UniversityJinju52828Republic of Korea

Due to our negligence,the original version of this article,published online on Mar 14,2023,contained some mistakes in several Figs.In Fig.2D,the positions of the bands for protein 3A and 3B were incorrectly shifted.Th... 详细信息

关键词： STAT1 FMDV bands

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Hologenomic insights into mammalian adaptations to myrmecophagy

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National Science Review 2023年第4期10卷 24-36页

作者： Shao-Chen Cheng Chun-Bing Liu Xue-Qin Yao Jing-Yang Hu Ting-Ting Yin Burton K.Lim Wu Chen Guo-Dong Wang Cheng-Lin Zhang David M.Irwin Zhi-Gang Zhang Ya-Ping Zhang Li Yu State key laboratory for Conservation and Utilization of Bio-Resources in Yunnan School of Life SciencesYunnan University State key laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of Sciences Department of Natural History Royal Ontario Museum Guangzhou Zoo Center for Excellence in Animal Evolution and Genetics Kunming Institute of ZoologyChinese Academy of Sciences Beijing Zoo Department of laboratory Medicine and pathobiology University of Toronto

Highly specialized myrmecophagy(ant-and termite-eating) has independently evolved multiple times in species of various mammalian orders and represents a textbook example of phenotypic evolutionary convergence. We explored the mechanisms involved in this unique dietary adaptation and convergence through multi-omic analyses, including analyses of host genomes and transcriptomes, as well as gut metagenomes, in combination with validating assays of key enzymes’ activities, in the species of three mammalian orders(anteaters, echidnas and pangolins of the orders Xenarthra, Monotremata and Pholidota, respectively) and their relatives. We demonstrate the complex and diverse interactions between hosts and their symbiotic microbiota that have provided adaptive solutions for nutritional and detoxification challenges associated with high levels of protein and lipid metabolisms, trehalose degradation, and toxic substance detoxification. Interestingly, we also reveal their spatially complementary cooperation involved in degradation of ants’ and termites’ chitin exoskeletons. This study contributes new insights into the dietary evolution of mammals and the mechanisms involved in the coordination of physiological functions by animal hosts and their gut commensals.

关键词： myrmecophagy adaptive evolution hologenome genomics metagenomics convergent evolution

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Towards an actionable One Health approach

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贫困所致传染病(英文) 2024年第2期13卷 1-6页

作者： Zhang Xiao-Xi Lederman Zohar Han Le-Fei Schurer Janna M. Xiao Li-Hua Zhang Zhi-Bing Chen Qiu-Lan Pfeiffer Dirk Ward Michael P. Sripa Banchob Gabri?l Sarah Dhama Kuldeep Acharya Krishna Prasad Robertson Lucy J. Deem Sharon L. Aenishaenslin Cécile Dantas-Torres Filipe Otranto Domenico Grace Delia Wang Yang Li Peng Fu Chao Poeta Patrícia Rahman Md. Tanvir Kassegne Kokouvi Zhu Yong-Zhang Yin Kun Liu Jiming Wang Zhao-Jun Guo Xiao-Kui Gong Wen-Feng Schwartl?nder Bernhard Ren Ming-Hui Zhou Xiao-Nong Sydney School of Veterinary Science The University of Sydney Camden Australia Tropical Disease Research Center Department of Tropical Medicine Faculty of Medicine Khon Kaen University Khon Kaen Thailand laboratory of foodborne parasitic zoonoses Department of translational physiology infectiology and public health Chair Faculty Committee on Internationalisation Faculty of Veterinary Medicine Ghent University Merelbeke Belgium Division of Pathology ICAR-Indian Veterinary Research Institute (IVRI) Bareilly Uttar Pradesh India Department of Livestock Services Animal Quarantine Office-Kathmandu Budhanilkantha Kathmandu Nepal Parasitology Department of Paraclinical Sciences Faculty of Veterinary Medicine Norwegian University of Life Sciences ?s Norway One Government Drive Saint Louis Zoo Institute for Conservation Medicine St. Louis USA Groupe de Recherche en épidémiologie des Zoonoses et Santé Publique (GREZOSP) Faculté de médecine vétérinaire Université de Montréal Saint-Hyacinthe Québec Canada Centre de recherche en santé publique de l Université de Montréal et du CIUSSS du Centre-Sud-de-l’?le-de-Montréal Montréal Québec Canada Department of Immunology Aggeu Magalh?es Institute Oswaldo Cruz Foundation (Fiocruz) Recife Brazil School of Global Health Chinese Center for Tropical Diseases Research Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of China Department of Veterinary Medicine University of Bari Valenzano Italy Department of pathobiology Faculty of Veterinary Science Bu-Ali Sina University Hamedan Iran Natural Resources Institute University of Greenwich Chatham Maritime UK International Livestock Research Institute Nairobi Kenya Director of key laboratory of Animal Antimicrobial Resistance Surveillance Ministry of Agriculture and Rural Affairs Beijing People’s Republic of China Institute of Animal Science Chinese Academy of Agricultural Sciences Beijing People’s Republic of China key laboratory of Ecosystem Network O

Background Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact.Main text This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation.Conclusions By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

关键词： One Health Global Health One Health Action Commission Research agenda

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Pangolin HKU4-related coronaviruses found in greater bamboo bats from southern China

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Virologica Sinica 2023年第6期38卷 868-876页

作者： Min Guo Kai Zhao Xingwen Peng Xiangyang He Jin Deng Bo Wang Xinglou Yang Libiao Zhang Guangdong key laboratory of Animal Conservation and Resource Utilization Guangdong Public Laboratory of Wild Animal Conservation and UtilizationInstitute of ZoologyGuangdong Academy of SciencesGuangzhou510260China Yunnan key laboratory of Biodiversity Information Kunming Institute of ZoologyChinese Academy of SciencesKunming650023China Department of Biomedical Sciences and pathobiology Virginia Polytechnic Institute and State UniversityBlacksburgVA24060USA Hubei Jiangxia Lab Wuhan430071China

Coronavirus(CoV)spillover originating from game animals,particularly pangolins,is currently a significant concern.Meanwhile,vigilance is urgently needed for coronaviruses carried by bats,which are known as natural reservoirs of many coronaviruses.In this study,we collected 729 anal swabs of 20 different bat species from nine locations in Yunnan and Guangdong provinces,southern China,in 2016 and 2017,and described the molecular characteristics and genetic diversity of alphacoronaviruses(αCoVs)and betacoronaviruses(βCoVs)found in these bats.Using RT-PCR,we identified 58(8.0%)bat CoVs in nine bat species from six locations.Furthermore,using the Illumina platform,we obtained two representative full-length genomes of the bat CoVs,namely TyRo-CoV-162275 and TyRo-CoV-162269.Sequence analysis showed that TyRo-CoV-162275 shared the highest identity with Malayan pangolin(Manis javanica)HKU4-related coronaviruses(MjHKU4r-CoVs)from Guangxi Province,whereas TyRo-CoV-162269 was closely related to HKU33-CoV discovered in a greater bamboo bat(Tylonycteris robustula)from Guizhou Province.Notably,TyRo-CoV-162275 has a putative furin protease cleavage site in its S protein and is likely to utilize human dipeptidyl peptidase-4(hDPP4)as a cell-entry receptor,similar to MERSCoV.To the best of our knowledge,this is the first report of a bat HKU4r-CoV strain containing a furin protease cleavage site.These findings expand our understanding of coronavirus geographic and host distributions.

关键词： Coronavirus Pangolin HKU4r-CoV Bat HKU4r-CoV Tylonycteris robustula Spillover risk

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Sperm Mitochondria in Reproduction:Good or Bad and Where Do They Go?

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Journal of Genetics and Genomics 2013年第11期40卷 549-556页

作者： Shi-Ming Luo Heide Schatten Qing-Yuan Sun key laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong Qingdao Agricultural University Department of Veterinary pathobiology University of MissouriColumbia State key laboratory of Reproductive Biology Institute of ZoologyChinese Academy of Sciences

The mitochondrion is the major energy provider to power sperm motility. In mammals, aside from the nuclear genome, mitochondrial DNA （mtDNA） also contributes to oxidative phosphorylation to impact production of ATP by coding 13 polypeptides. However, the role of sperm mitochondria in fertilization and its final fate after fertilization are still controversial. The viewpoints that sperm bearing more mtDNA will have a better fertilizing capability and that sperm mtDNA is actively eliminated during early embryogenesis are widely accepted. However, this may be not true for several mammalian species, including mice and humans. Here, we review the sperm mitochondria and their mtDNA in sperm functions, and the mechanisms of maternal mitochondrial inheritance in mammals.

关键词： Mitochondrial DNA Maternal inheritance Paternal inheritance Autophagy Oxidative phosphorylation Ubiquitination

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MicroRNA-370-5p inhibits pigmentation and cell proliferation by downregulating mitogen-activated protein kinase kinase kinase 8 expression in sheep melanocytes

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Journal of Integrative Agriculture 2023年第4期22卷 1131-1141页

作者： JI Kai-yuan WEN Ru-jun WANG Zheng-zhou TIAN Qian-qian ZHANG Wei ZHANG Yun-hai Anhui Province key laboratory of Veterinary pathobiology and Disease Control College of Animal Science and TechnologyAnhui Agricultural UniversityHefei 230036P.R.China Anhui Province key laboratory of Local Livestock and Poultry Genetic Resources Conservation and Bio-Breeding College of Animal Science and TechnologyAnhui Agricultural UniversityHefei 230036P.R.China Linquan Comprehensive Experimental Station Anhui Agricultural UniversityLinquan 236400P.R.China

In mammals,microRNAs(miRNAs)play key roles in multiple biological processes by regulating the expression of target genes.Studies have found that the levels of miR-370-5p expression differ significantly in the skins of sheep with different hair colors;however,its function remains unclear.In this study,we investigated the roles of miR-370-5p in sheep melanocytes and found that the overexpression of miR-370-5p significantly inhibited cell proliferation(P<0.01),tyrosinase activity(P=0.001)and significantly reduced(P<0.001)melanin production.Functional prediction revealed that the 3′-untranslated region(UTR)of MAP3K8 has a putative miR-370-5p binding site,and the interaction between these two molecules was confirmed using luciferase reporter assays.In situ hybridization assays revealed that MAP3K8 is expressed in the cytoplasm of melanocytes.The results of quantitative RT-PCR and Western blotting analyses revealed that overexpression of miR-370-5p in melanocytes significantly inhibits(P<0.01)MAP3K8 expression via direct targeting of its 3′UTR.Inhibition of MAP3K8 expression by siRNA-MAP3K8 transfection induced a significant inhibition(P<0.01)of melanocyte proliferation and significant reduction(P<0.001)in melanin production,which is consistent with our observations for miR-370-5p.Target gene rescue experiments indicated that the expression of MAP3K8 in melanocytes co-transfected with miR-370-5p and MAP3K8-cDNA(containing sites for the targeted binding to miR-370-5p)was significantly rescued(P≤0.001),which subsequently promoted significant increases in cell proliferation(P<0.001)and melanin production(P<0.01).Collectively,these findings indicate that miR-370-5p plays a functional role in inhibiting sheep melanocyte proliferation and melanogenesis by downregulating the expression of MAP3K8.

关键词： microRNA mitogen-activated protein kinase kinase kinase 8 melanogenesis sheep melanocytes cell proliferation

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3C^(pro)of FMDV inhibits type II interferon-stimulated JAK-STAT signaling pathway by blocking STAT1 nuclear translocation

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Virologica Sinica 2023年第3期38卷 387-397页

作者： Xiangju Wu Lei Chen Chao Sui Yue Hu Dandan Jiang Fan Yang Laura C.Miller Juntong Li Xiaoyan Cong Nataliia Hrabchenko Changhee Lee Yijun Du Jing Qi Shandong key laboratory of Animal Disease Control and Breeding/key laboratory of Livestock and Poultry Multi-omics of MARA Institute of Animal Science and Veterinary MedicineInstitute of Crop Germplasm ResourcesShandong Academy of Agricultural SciencesJinan250100China College of Life Science Shandong Normal UniversityJinan250358China State key laboratory of Veterinary Etiological Biology/National Foot and Mouth Disease Reference laboratory/key laboratory of Animal Virology of Ministry of Agriculture Lanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou730050China Department of Diagnostic Medicine and pathobiology College of Veterinary MedicineKansas State UniversityManhattanKS66506USA College of Veterinary Medicine and Virus Vaccine Research Center Gyeongsang National UniversityJinju52828Republic of Korea

Foot-and-mouth disease virus(FMDV)has developed various strategies to antagonize the host innate immunity.FMDV Lpro and 3Cpro interfere with type I IFNs through different mechanisms.The structural protein VP3 of FMDV degrades Janus kinase 1 to suppress IFN-γsignaling transduction.Whether non-structural proteins of FMDV are involved in restraining type II IFN signaling pathways is unknown.In this study,it was shown that FMDV replication was resistant to IFN-γtreatment after the infection was established and FMDV inhibited type II IFN induced expression of IFN-γ-stimulated genes(ISGs).We also showed for the first time that FMDV non-structural protein 3C antagonized IFN-γ-stimulated JAK-STAT signaling pathway by blocking STAT1 nuclear translocation.3C^(pro)expression significantly reduced the ISGs transcript levels and palindromic gamma-activated sequences(GAS)promoter activity,without affecting the protein level,tyrosine phosphorylation,and homodimerization of STAT1.Finally,we provided evidence that 3C protease activity played an essential role in degrading KPNA1 and thus inhibited ISGs mRNA and GAS promoter activities.Our results reveal a novel mechanism by which an FMDV non-structural protein antagonizes host type II IFN signaling.

关键词： Foot-and-mouth disease virus(FMDV) 3C IFN-γ JAK-STAT signaling pathway STAT1 KPNA1

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Poultry gut health and beyond

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Animal Nutrition 2023年第2期13卷 240-248页

作者： Richard Ducatelle Evy Goossens Venessa Eeckhaut Filip Van Immerseel Livestock Gut Health Team Department of PathobiologyPharmacology and Zoological MedicineFaculty of Veterinary MedicineGhent UniversityBelgium

Intestinal health is critically important for the digestion and absorption of nutrients and thus is a key factor in determining performance.Intestinal health issues are very common in high performing poultry lines due to the high feed intake,which puts pressure on the physiology of the digestive system.Excess nutrients which are not digested and absorbed in the small intestine may trigger dysbiosis,i.e.a shift in the microbiota composition in the intestinal tract.Dysbiosis as well as other stressors elicit an inflammatory response and loss of integrity of the tight junctions between the epithelial cells,leading to gut leakage.In this paper,key factors determining intestinal health and the most important nutritional tools which are available to support intestinal health are reviewed.

关键词： Poultry Intestinal health Inflammation Gut leakage Microbiota Feed additive

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