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Ninjurin-1: a biomarker for reflecting the process of neuroinflammation after spinal cord injury

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Neural Regeneration Research 2021年第7期16卷 1331-1335页

作者： Poornima D.E.Weerasinghe-Mudiyanselage Jeongtae Kim Yuna Choi Changjong Moon Taekyun Shin Meejung Ahn Department of veterinary Anatomy College of Veterinary Medicine and Veterinary Medical Research InstituteJeju National UniversityJejuRepublic of Korea Department of veterinary Anatomy College of Veterinary Medicine and BK21 Plus Project TeamChonnam National UniversityGwangjuRepublic of Korea Department of Anatomy Kosin University College of MedicineBusanRepublic of Korea Department of Animal Science College of Life ScienceSangji UniversityWonjuRepublic of Korea

Previous studies have shown that Ninjurin-1 participates in cell trafficking and axonal growth following central and peripheral nervous system neuroinflammation.But its precise roles in these processes and involvement in spinal cord injury pathophysiology remain unclear.Western blot assay revealed that Ninjurin-1 levels in rats with spinal cord injury exhibited an upregulation until day 4 post-injury and slightly decreased thereafter compared with sham controls.Immunohistochemistry analysis revealed that Ninjurin-1 immunoreactivity in rats with spinal cord injury sharply increased on days 1 and 4 post-injury and slightly decreased on days 7 and 21 post-injury compared with sham controls.Ninjurin-1 immunostaining was weak in vascular endothelial cells, ependymal cells, and some glial cells in sham controls while it was relatively strong in macrophages, microglia, and reactive astrocytes.These findings suggest that a variety of cells, including vascular endothelial cells, macrophages, and microglia, secrete Ninjurin-1 and they participate in the pathophysiology of compression-induced spinal cord injury.All experimental procedures were approved by the Care and Use of Laboratory Animals of Jeju National University(approval No.2018-0029) on July 6, 2018.

关键词： astrocytes clip compression injury macrophage microglia neuroinflammation Ninjurin-1 rat spinal cord

Epigenetic mechanisms involved in the neuroprotective effect of scorpion extract in a Parkinson's disease murine model based on multi-omics approach

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Journal of Traditional Chinese medicine 2021年第3期41卷 390-396页

作者： Joong Sun Kim Hye-Sun Lim Byeong Cheol Moon Mary Jasmin Ang Sung-Ho Kim Changjong Moon Boseok Seong Yunji Jang Hyung-Yong Kim Chul Kim Herbal medicine Resources Research Center Korea Institute of Oriental MedicineJeollanamdo 58245Republic of Korea college of veterinary medicine and bk21 plus project team Chonnam National UniversityGwangju 61186Republic of Korea Future medicine Division Korea Institute of Oriental MedicineDaejeon 34054Republic of Korea Research and Development Center Insilicogen Inc.Yonginsi 16954Republic of Korea

OBJECTIVE: To investigate whether scorpion extract elicits a neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated mice models, and the genes associated with the therapeutic effects using RNA sequencing(seq)analysis.METHODS: This study investigated the changes in interaction between messenger ribonucleic acid(m RNA) expression and deoxyribonucleic acid(DNA) methylation related to the protective effects of scorpion extracts, in the substantia nigra(SN)region of a MPTP-induced Parkinson's disease(PD)model.RESULTS: In this model, scorpion extracts attenuated the motor impairment as demonstrated by the rotarod and open field tests. Scorpion extracts consistently attenuated the decrease of tyrosine hydroxylase(TH) positive neural cells in the SN and striatum of mice. We profiled genomewide DNA methylation using Methyl-Seq and measured the transcriptome using RNA-Seq in murine SN in the following groups: vehicle-treated MPTP-induced PD mice and scorpion extracttreated MPTP-induced PD mice. In total, 13 479 differentially expressed genes were identified in association with the anti-PD effect of the scorpion extract, mainly in the promoter and coding regions.Among them, 47 were negatively correlated downregulated genes. Nineteen genes out of 47 downregulated genes were negatively correlated with the expression of the other 28 genes. Among these genes, SGSM1 was related to dopaminergic neurons including dopamine transporters, TH, dihydroxyphenylalanine decarboxylase, and dopamine D2 receptor.CONCLUSION: This study provides insights into the anti-parkinsonian effects of scorpion extract and reveals the epigenetic targets in its therapeutic mechanism.

关键词： scorpions 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine Parkinson disease DNA methylation

Intravenous morphine self-administration alters accumbal microRNA profiles in the mouse brain

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Neural Regeneration Research 2018年第1期13卷 77-85页

作者： Juhwan Kim Heh-In Im Changjong Moon Department of veterinary Anatomy and Animal Behavior College of Veterinary Medicine and BK21 Plus Project Team Chonnam National University Gwangju South Korea Center for Neuroscience Korea Institute of Science and Technology (KIST) Seoul South Korea Convergence Research Center for Diagnosis Treatment and Care System of Dementia Korea Institute of Science and Technology (KIST) Seoul South Korea Division of Biomedical Science & Technology KIST School Korea University of Science and Technology Seoul South Korea

A significant amount of evidence indicates that microRNAs （miRNAs） play an important role in drug addiction. The nucleus accumbens （NAc） is a critical part of the brain’s reward circuit and is involved in a variety of psychiatric disorders, including depression, anxiety, and drug addiction. However, few studies have examined the expression of miRNAs and their functional roles in the NAc under conditions of morphine addiction. In this study, mice were intravenously infused with morphine （0.01, 0.03, 0.3, 1 and 3 mg/kg/infusion） and showed inverted U-shaped response. After morphine self-administration, NAc was used to analyze the functional networks of altered miRNAs and their putative target mRNAs in the NAc following intravenous self-administration of morphine. We utilized several bioinformatics tools, including Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway mapping and CyTargetLinker. We found that 62 miRNAs were altered and exhibited differential expression patterns. The putative targets were related to diverse regulatory functions, such as neurogenesis, neurodegeneration, and synaptic plasticity, as well as the pharmacological effects of morphine （receptor internalization/endocytosis）. The present findings provide novel insights into the regulatory mechanisms of accumbal molecules under conditions of morphine addiction and identify several novel biomarkers associated with morphine addiction.

关键词： nerve regeneration nucleus accumbens microRNA morphine self-administration bioinformatics neural regeneration

Prevalence of coronavirus from diarrheic calves in the Republic of Korea

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Asian Pacific Journal of Tropical Biomedicine 2018年第1期8卷 1-6页

作者： Jinho Park Du-Gyeong Han Su Hee Kim Jeong-Byoung Chae Joon-Seok Chae Do-Hyeon Yu Kyoung-Seong Choi college of veterinary medicine Chonbuk National University Department of Animal Science and Biotechnology College of Ecology and Environmental Science Kyungpook National University Animal Disease & Biosecurity team National Institute of Animal Science Rural Development Administration Laboratory of veterinary Internal medicine BK21 PLUS Program for Creative Veterinary Science Research Research Institute for Veterinary Science and College of Veterinary Medicine Seoul National University college of veterinary medicine Gyeongsang National University

Objective: To investigate the prevalence of bovine coronavirus(BCo V), bovine rotavirus, and bovine viral diarrhea virus in the feces of normal and diarrheic Korean native calves aged 1-81 days between April and October of 2016 in the Republic of Korea. Methods: Samples were obtained from 50 normal and 93 diarrheic(56 semi-formed, 28 loose, and 9 watery feces) calves in six different regions of northern and southern Korea. These fecal samples were tested for BCo V, bovine rotavirus, and bovine viral diarrhea virus by RT-PCR. Results: Among the three pathogens examined, infection with BCo V was especially prominent in relation to diarrhea among calves aged 1-21 days [odds ratio(OR)=9.3, 95% confidence interval(CI): 1.1-78.9; P=0.02). Infection with BCo V alone(OR=2.9; 95% CI: 1.1-7.6; P=0.03) or coinfection of BCo V with bovine viral diarrhea virus(OR=3.6; 95% CI: 1.0-12.4; P=0.04) was significantly associated with the development of loose feces. Grazing and colostrum intake strongly reduced the occurrence of diarrhea as compared to housed calves(OR=0.2; 95% CI: 0.1-0.4; P=0.00) and calves that had not been fed colostrum(OR=0.2; 95% CI: 0.1-0.7; P=0.02), respectively. Conclusions: The present study suggests that BCo V is involved in calf diarrhea in the Republic of Korea. Therefore, grazing and colostrum intake is recommended for preventing and controlling calf diarrhea caused by BCoV.

关键词： Calf diarrhea Bovine coronavirus Bovine viral diarrhea virus Loose feces Grazing

Effects of Gastrodiae rhizoma on proliferation and differentiation of human embryonic neural stem cells

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Asian Pacific Journal of Tropical medicine 2015年第10期8卷 776-781页

作者： Samrat Baral Ramesh Pariyar Chi-Su Yoon Dong-Cheol Kim Jong-Min Yun Seok O Jang Sung Yeon Kim Hyuncheol Oh Youn-Chul Kim Jungwon Seo From the bk21 plus team Institute of Pharmaceutical Research and Development College of PharmacyWonkwang University Professional Graduate School of Oriental medicine Wonkwang University Hanbang Body-Fluid Research Center Wonkwang University Standardized Material Bank for New Botanical Drugs College of PharmacyWonkwang University Department of Internal medicine College of Korean MedicineWonkwang University

Objective:To investigate the effects of Gastrodiae rhizoma,a dried root of Gastrodia elata Blume,on proliferation and differentiation of human NSCs derived from embryonic stem cells.Methods:A 70%ethanol extract of Gastrodiae rhizoma(EEGR) was estimated with4-hydroxybenzyl alcohol as a representative constituent by HPLC.Results:MTT assay showed that the treatment with EEGR increased the viability of NSCs in growth media.Compared to contro1,EEGR increased the number of dendrites and denritic spines extended from a differentiated NSC.Whereas EEGR decreased the mRNA expression of Nestin,it increased that of Tuj1 and MAP2 in NSCs grown in differentiation media.Immunocytochemical analysis using confocal microscopy also revealed the increased expression of MAP2 in dendrites of EEGR-treated NSCs.Furthermore,EEGR decreased mRNA expression of Sox2 in NSCs grown even in growth media.Conclusions:In conclusion,our study demonstrates for the first time that EEGR induced proliferation and neuronal differentiation of NSCs,suggesting its potential benefits on NSC-based therapies and neuroregeneration in various neurodegenerative diseases and brain Injuries.

关键词： Gastrodiac rhizoma Neural stem cells Neuronal diff

Regenerative potential of mouse embryonic stem cell-derived PDGFRα+ cardiac lineage committed cells in infarcted myocardium

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World Journal of Stem Cells 2019年第1期11卷 44-54页

作者： Seon Pyo Hong Sukhyun Song Seungjoo Lee Hyeonju Jo Hyoung Kyu Kim Jin Han Jae-Hyeong Park Sung Woo Cho Center for Vascular Research Institute of Basic Science (IBS)Daejeon Department of Neurosurgery Asan Medical Center University of Ulsan College of Medicine Cardiovascular and Metabolic Disease Center Department of Physiology Department of Health Sciences and Technology BK21 plus Project Team Inje University College of Medicine Department of Cardiology in Internal medicine School of MedicineChungnam National University Hospital Chungnam National University Division of Cardiology Department of Internal Medicine Inje University College of Medicine Seoul Paik Hospital Cardiovascular and Metabolic Disease Center Inje University College of Medicine

BACKGROUND Pluripotent stem cell-derived cardiomyocytes(CMs) have become one of the most attractive cellular resources for cell-based therapy to rescue damaged cardiac tissue.AIM We investigated the regenerative potential of mouse embryonic stem cell(ESC)-derived platelet-derived growth factor receptor-α(PDGFRα)+ cardiac lineagecommitted cells(CLCs), which have a proliferative capacity but are in a morphologically and functionally immature state compared with differentiated CMs.METHODSWe induced mouse ESCs into PDGFRα+ CLCs and αMHC+ CMs using a combination of the small molecule cyclosporin A, the rho-associated coiled-coil kinase inhibitor Y27632, the antioxidant Trolox, and the ALK5 inhibitor EW7197.We implanted PDGFRα+ CLCs and differentiated αMHC+ CMs into a myocardial infarction(MI) murine model and performed functional analysis using transthoracic echocardiography(TTE) and histologic analysis.RESULTS Compared with the untreated MI hearts, the anterior and septal regional wall motion and systolic functional parameters were notably and similarly improved in the MI hearts implanted with PDGFRα+ CLCs and αMHC+ CMs based on TTE.In histologic analysis, the untreated MI hearts contained a thinner ventricular wall than did the controls, while the ventricular walls of MI hearts implanted with PDGFRα+ CLCs and αMHC+ CMs were similarly thicker compared with that of the untreated MI hearts. Furthermore, implanted PDGFRα+ CLCs aligned and integrated with host CMs and were mostly differentiated into α-actinin+ CMs,and they did not convert into CD31+ endothelial cells or αSMA+ mural cells.CONCLUSION PDGFRα+ CLCs from mouse ESCs exhibiting proliferative capacity showed a regenerative effect in infarcted myocardium. Therefore, mouse ESC-derived PDGFRα+ CLCs may represent a potential cellular resource for cardiac regeneration.

关键词： Pluripotent stem cell Embryonic stem cell Cardiomyocyte Myocardial infarction Regeneration

Potentiating activity of luteolin on membrane permeabilizing agent and ATPase inhibitor against methicillin-resistant Staphylococcus aureus

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Asian Pacific Journal of Tropical medicine 2016年第1期9卷 16-19页

作者： Dae-Ki Joung Young-Seob Lee Sin-Hee Han Sang-Won Lee Seon-Woo Cha Su-Hyun Mun Ryong Kong Ok-Hwa Kang Ho-Jun Song Dong-Won Shin Dong-Yeul Kwon Department of Oriental Pharmacy College of Pharmacy and Wonkwang-Oriental Medicines Research Institute.Wonkwang University Department of Herbal Crop Research National Institute of Horticultural & Herbal ScienceRDA bk21 plus team Professional Graduate School of Oriental MedicineWonkwang University Department of Oriental medicine Resources Sunchon National University

Objective:To investigate the mechanism of antibacterial activity of luteoiin(LUT) against methicillin-resistant Staphylococcus aureus(MRSA).Methods:The mechanism of anti-MRSA activity of LUT was analyzed by the viability assay in membrane permeabilizing agent ATPase inhibitors,and peptidoglycan(PGN) derived from Staphylococcus aureus(S.aureus).Also,transmission electron microscopy was used to monitor survival characteristics and changes in S.aureus morphology.Results:Compared to the LUT alone,the optical density of suspensions treated with the combination of 125 μg/mL Tris and 230 μg/mL DCCD were reduced to 60%and 46%,respectively.PGN(15.6 μg/mL) gradually impeded the activity of LUT,and PGN(62.5 μg/mL) completely blocked the activity of LUT on S.aureus.Conclusions:Increased susceptibility to LUT with me Tris and DCCD combinations is evident in all tested MRSA isolates.The results indicate LUT synergy in increasing cytoplasmic membrane permeability and inhibiting ATPase.S.aureus PGN directly blocks the antibacterial activity of LUT,suggesting the direct binding of LUT with PGN.These findings may be validated for the development of antibacterial agent for low MRSA resistance.

关键词： Iuteolin Methicillin-resistant Staphylococcus aureus Membrane permeabilizing agent ATPase inhibitor Peptidoglycan

Quantitative changes of nitrergic neurons during postnatal development of chicken myenteric plexus

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2013年第10期14卷 886-895页

作者： Ping YANG Jameel Ahmed GANDAHI Qian ZHANG Lin-li ZHANG Xun-guang BIAN Li WU Yi LIU Qiu-sheng CHEN Key Laboratory of Animal Physiology and Biochemistry College of Veterinary MedicineNanjing Agricultural University Department of Anatomy and Histology Sindh Agriculture University

Objective: Information regarding the development of the enteric nervous system(ENS) is important for understanding the functional abnormalities of the gut.Because fertilized chicken eggs provide easy access to embryos,chicken models have been widely used to study embryonic development of myenteric plexus;however,no study has been focused on the postnatal period.The aim of this study was to perform a qualitative and quantitative analysis of the nitrergic neurons in the myenteric plexus of developing chickens in the postnatal period.Methods: Whole-mount preparations of the myenteric plexus were made in 7-d,15-d,and 40-d old(adult) chickens of either sex(n=15).The myenteric plexus was studied after nicotinamide adenine dinucleotide phosphate diaphorase(NADPH-d) histochemistry using light microscopy,digital photography,and Image-Pro plus 6.0 software.The numbers of positively stained neurons and ganglia were counted in the duodenum,jejunum,ileum,caecum,and colon in the different age groups.Data were expressed as mean±standard deviation(SD),and statistical analysis was performed using a one-way analysis of variance(ANOVA) test.Results: The positively stained neurons showed various morphologies and staining intensities,and formed bead-shaped and U-shaped arrangements in the myenteric plexus.The densities of neurons and ganglia increased with age.However,the number of positive neurons per ganglion increased.The number of NADPH-d-positive neurons was highest in the colon,followed by the ileum,the jejunum,the duodenum,and the caeca in all age groups.Conclusions: Developmental changes in the myenteric plexus of chickens continue in the postnatal period,indicating that the maturation process of the gastrointestinal function is gradual.In addition,no significant difference is happening among different intestinal segments during postnatal development,suggesting that the function of different intestinal segments had been determined after birth.

关键词： NADPH-d histochemistry Enteric nervous system(ENS) Development Myenteric plexus Chicken

COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm

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Signal Transduction and Targeted Therapy 2020年第1期5卷 910-920页

作者： Wonhwa Lee June Hong Ahn Hee Ho Park Hong Nam Kim Hyelim Kim Youngbum Yoo Hyosoo Shin Kyung Soo Hong Jong Geol Jang Chun Gwon Park Eun Young Choi Jong-Sup Bae Young-Kyo Seo Aging Research Center Korea Research Institute of Bioscience and BiotechnologyDaejeon 34141Republic of Korea Division of Pulmonology and Allergy Department of Internal MedicineCollege of MedicineYeungnam University and Regional Center for Respiratory DiseasesYeungnam University Medical CenterDaegu 42415Republic of Korea Department of Biotechnology and Bioengineering Kangwon National UniversityChuncheonGangwon-do 24341Republic of Korea Center for BioMicrosystems Brain Science InstituteKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea Division of Bio-Medical Science and Technology KIST SchoolKorea University of Science and TechnologySeoul 02792Republic of Korea college of Pharmacy Chungnam National UniversityDaejeon 34134Republic of Korea Department of Biomedical Engineering SKKU Institute for ConvergenceSungkyunkwan University(SKKU)SuwonRepublic of Korea Biomedical Institute for Convergence at SKKU(BICS) Sungkyunkwan University2066 Seobu-roJangan-guSuwon 16419Republic of Korea college of Pharmacy CMRIResearch Institute of Pharmaceutical SciencesBK21 Plus KNU Multi-Omics based Creative Drug Research TeamKyungpook National UniversityDaegu 41566Republic of Korea

Sterol regulatory element binding protein-2(SREBP-2)is activated by cytokines or pathogen,such as virus or bacteria,but its association with diminished cholesterol levels in COVID-19 patients is unknown.Here,we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in COVID-19.Intriguingly,we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients’blood and propose SREBP-2 C-terminal fragment as an indicator for determining severity.We confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression,while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU patients.Using an infectious disease mouse model,inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary damages.These results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.

关键词： cytokine diagnosis damage