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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)***: 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)***: 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 *** 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 ***: 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

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Dietary fat-associated osteoarthritic chondrocytes gain resistance to lipotoxicity through PKCK2/STAMP2/FSP27

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Bone Research 2018年第3期6卷 238-251页

作者： sung Won lee Jee Hyun Rho Sang Yeob lee Won Tae Chung Yoo Jin Oh Jung Ha Kim Seung Hee Yoo Woo Young Kwon Ju Yong Bae Su Young Seo Hokeun sun hye Young Kim Young Hyun Yoo Department of Rheumatology Dong-A University College of Medicine Department of Anatomy and Cell Biology Dong-A University College of Medicine and Mitochondria Hub Regulation Center Department of Microbiology Dong-A University College of Medicine Department of Statistics Pusan National University

Free fatty acids(FFAs), which are elevated with metabolic syndrome, are considered the principal offender exerting lipotoxicity. Few previous studies have reported a causal relationship between FFAs and osteoarthritis pathogenesis. However, the molecular mechanism by which FFAs exert lipotoxicity and induce osteoarthritis remains largely unknown. We here observed that oleate at the usual clinical range does not exert lipotoxicity while oleate at high pathological ranges exerted lipotoxicity through apoptosis in articular chondrocytes. By investigating the differential effect of oleate at toxic and nontoxic concentrations, we revealed that lipid droplet(LD) accumulation confers articular chondrocytes, the resistance to lipotoxicity. Using high fat diet-induced osteoarthritis models and articular chondrocytes treated with oleate alone or oleate plus palmitate, we demonstrated that articular chondrocytes gain resistance to lipotoxicity through protein kinase casein kinase 2(PKCK2)—six-transmembrane protein of prostate 2(STAMP2)—and fat-specific protein 27(FSP27)-mediated LD accumulation. We further observed that the exertion of FFAs-induced lipotoxicity was correlated with the increased concentration of cellular FFAs freed from LDs, whether FFAs are saturated or not. In conclusion, PKCK2/STAMP2/FSP27-mediated sequestration of FFAs in LD rescues osteoarthritic chondrocytes. PKCK2/STAMP2/FSP27 should be considered for interventions against metabolic OA.

关键词： osteoarthritis remains articular chondrocytes

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Enhanced delivery of a low dose of aducanumab via FUS in 5×FAD mice,an AD model

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Translational Neurodegeneration 2022年第1期11卷 31-45页

作者： Chanho Kong Eun-Jeong Yang Jaewoo Shin Junwon Park Si-Hyun Kim Seong-Wook Park Won Seok Chang Chang-Han lee Hyunju Kim hye-sun Kim Jin Woo Chang Department of Neurosurgery Yonsei University College of Medicine50 Yonsei-RoSeodaemun-GuSeoulRepublic of Korea Department of Pharmacology College of MedicineSeoul National University103 DaehakroJongro-GuSeoulRepublic of Korea Neuroscience Research Center College of MedicineSeoul National University103 DaehakroJongro-GuSeoulRepublic of Korea Department of Biomedical Sciences College of MedicineSeoul National University103 DaehakroJongro-GuSeoulRepublic of Korea Bundang Hospital Seoul National University College of MedicineBundang-GuSungnamRepublic of Korea.

Background:Aducanumab(Adu),which is a human IgG1 monoclonal antibody that targets oligomer and fibril forms of beta-amyloid,has been reported to reduce amyloid pathology and improve impaired cognition after administration of a high dose(10 mg/kg)of the drug in Alzheimer’s disease(AD)clinical *** purpose of this study was to investigate the effects of a lower dose of Adu(3 mg/kg)with enhanced delivery via focused ultrasound(FUS)in an AD mouse ***:The FUS with microbubbles opened the blood-brain barrier(BBB)of the hippocampus for the delivery of *** combined therapy of FUS and Adu was performed three times in total and each treatment was performed biweekly.Y-maze test,Brdu labeling,and immunohistochemical experimental methods were employed in this *** addition,RNA sequencing and ingenuity pathway analysis were employed to investigate gene expression profiles in the hippocampi of experimental ***:The FUS-mediated BBB opening markedly increased the delivery of Adu into the brain by approximately 8.1 times in the *** combined treatment induced significantly less cognitive decline and decreased the level of amyloid plaques in the hippocampi of the 5×FAD mice compared with Adu or FUS *** treatment with FUS and Adu activated phagocytic microglia and increased the number of astrocytes associated with amyloid plaques in the hippocampi of 5×FAD ***,RNA sequencing identified that 4 enriched canonical pathways including phagosome formation,neuroinflammation signaling,CREB signaling and reelin signaling were altered in the hippocami of 5×FAD mice receiving the combined ***:In conclusion,the enhanced delivery of a low dose of Adu(3 mg/kg)via FUS decreases amyloid deposits and attenuates cognitive function ***-mediated BBB opening increases adult hippocampal neurogenesis as well as drug *** present an AD treatment strategy through the synergistic effect of the combined therapy of

关键词： Aducanumab Alzheimer’s disease Focused ultrasound Transcriptome profiling

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CORM-2-entrapped ultradeformable liposomes ameliorate acute skin inflammation in an ear edema model via effective CO delivery

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Acta Pharmaceutica Sinica B 2020年第12期10卷 2362-2373,2440页

作者： Gwan-Yeong lee Alam Zeb Eun-hye Kim Beomseon Suh Young-Jun Shin Donghyun Kim Kyoung-Won Kim Yeong-Hwan Choe Ho-Ik Choi Cheol-Ho lee Omer Salman Qureshi In-Bo Han sun-Young Chang Ok-Nam Bae Jin-Ki Kim College of Pharmacy Institute of Pharmaceutical Science and TechnologyHanyang UniversityAnsan 15588Republic of Korea Riphah Institute of Pharmaceutical Sciences Riphah International UniversityIslamabad 44000Pakistan Department of Pharmacy Forman Christian CollegeLahore 54600Pakistan Department of Neurosurgery CHA Bundang Medical CenterSchool of MedicineCHA UniversitySeongnam 13496Republic of Korea College of Pharmacy Ajou UniversitySuwon 16499Republic of Korea

The short release half-life of carbon monoxide(CO)is a major obstacle to the effective therapeutic use of carbon monoxide-releasing molecule-2(CORM-2).The potential of CORM-2-entrapped ultradeformable liposomes(CORM-2-UDLs)to enhance the release half-life of CO and alleviate skin inflammation was investigated in the present ***-2-UDLs were prepared by using soy phosphatidylcholine to form lipid bilayers and Tween 80 as an edge *** deformability of CORM-2-UDLs was measured and compared with that of conventional liposomes by passing formulations through a filter device at a constant *** release profile of CO from CORM-2-UDLs was evaluated by myoglobin *** vitro and in vivo anti-inflammatory effects of CORM-2-UDLs were assessed in lipopolysaccharide-stimulated macrophages and TPA-induced ear edema model,*** deformability of the optimized CORM-2-UDLs was 2.3 times higher than conventional ***-2-UDLs significantly prolonged the release half-life of CO from 30 s in a CORM-2 solution to 21.6 ***-2-UDLs demonstrated in vitro anti-inflammatory activity by decreasing nitrite production and pro-inflammatory cytokine ***,CORM-2-UDLs successfully ameliorated skin inflammation by reducing ear edema,pathological scores,neutrophil accumulation,and inflammatory cytokines *** results demonstrate that CORM-2-UDLs could be used as promising therapeutics against acute skin inflammation.

关键词： Carbon monoxide CORM-2 Anti-inflammatory effect Ultradeformable liposomes Skin inflammation Ear edema

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Inhibitory Mechanisms of Water Extract of Oplopanax elatus on Lipopolysaccharide-lnduced Inflammatory Responses in RAW 264.7 Murine Macrophage Cells

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Chinese Journal of Integrative Medicine 2020年第9期26卷 670-676页

作者： Ki sun Kwon Hyun Lim Yong Soo Kwon Myong Jo Kim Ji hye Yoo Nam Ho Yoo Hyun Pyo Kim College of Pharmacy Kangwon National UniversityChuncheon(24341)Republic of Korea Department of Bio-Resource Sciences Kangwon National UniversityChuncheon(24341)Republic of Korea Bioherb Research Institute Kangwon National UniversityChuncheon(24341)Republic of Korea

Objective:To study the anti-inflammatory action and cellular mechanism of Oplopanax ***:A hot water extract of OE(WOE)was prepared and a major constituent,syringin,was successfully *** content in WOE was found to be 214.0 p.g/g dried plant(w/w).Their anti-inflammatory activities were examined using RAW 264.7 macrophages and a mouse model of croton oil-induced ear ***:In lipopolysaccharide(LPS)-treated RAW 264.7 cells,a mouse macrophage cell line,WOE was found to significantly and strongly inhibit cyclooxygenase-2(COX-2)-induced prostaglandin E2(PGE2)production[half maximal inhibitory concentration(IC50)=135.2μg/mL]and inducible nitric oxide synthase(iNOS)-induced NO production(IC50=242.9μg/mL).In the same condition,WOE was revealed to inhibit NO production by downregulating iNOS expression,mainly by interrupting mitogen activated protein kinases(MAPKs)/activator protein-1(AP-1)*** activation of all three major MAPKs,p38 MAPK,extracellular signal-regulated kinase(ERK),and c-Jun N-terminal kinase,was inhibited by WOE(50-300μg/mL).On the other hand,WOE reduced PGE2 production by inhibiting COX-2 enzyme activity,but did not affect COX-2 expression *** addition,WOE inhibited the production of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α.In croton oil-induced ear edema in mice,oral administration of WOE(50-300 mg/kg)dose-dependently inhibited edematic ***:Water extract of OE exhibited multiple anti-inflammatory action mechanisms and may have potential for treating inflammatory disorders.

关键词： Oplopanax elatus Chinese medicine stem syringin anti-inflammation RAW 264.7

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Clinical usefulness of ankle brachial index and brachial-ankle pulse wave velocity in patients with ischemic stroke

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The Journal of Biomedical Research 2016年第4期30卷 285-291页

作者： Hyung-Suk lee hye Lim lee Ho-seong Han Minju Yeo Ji Seon Kim sung-Hyun lee Sang-Soo lee Dong-Ick Shin Department of Neurology Yuseong Sun General Hospital Daejeon 34084 Korea Department of Neurology Chungbuk National University College of Medicine Chungbuk National University Hospital Cheongju 28644 Korea

Ankle brachial index （ABI） and brachial-ankle pulse wave velocity （baPWV） are widely used noninvasive modalities to evaluate atherosclerosis. Recently, evidence has increased supporting the use of ABI and baPWV as markers of cerebrovascular disease. This study sought to examine the relationship between ABI and baPWV with ischemic stroke. This study also aimed to determine which pathogenic mechanism, large artery disease （LAD） or small vessel disease （SVD）, is related to ABI or baPWV. Retrospectively, 121 patients with ischemic stroke and 38 subjects with no obvious ischemic stroke history were recruited. First, ABI and baPWV were compared between the groups. Then, within the stroke group, the relevance of ABI and baPWV with regard to SVD and LAD, which were classified by brain magnetic resonance image （MRI） and magnetic resonance angiography （MRA） or computed tomography angiography （CTA） findings, was assessed. The baPWV was higher in the stroke group than non-stroke group （1,944.18±416.6 cm/s vs. 1,749.76±669.6 crn/s, P 〈 0.01）. Regarding LAD, we found that mean ABI value was lower in the group with extracranial large artery stenosis （P 〈 0.01）, and there was an inverse linear correlation between ABI and the grade of extracranial large artery stenosis （P〈 0.01）. For SVD, there was a significant correlation between SVD and baPWV （2,057.6±456.57 cm/s in the SVD （＋） group vs. 1,491±271.62 cm/s in the SVD （-） group; P 〈 0.01）. However, the grade of abnormalities detected in SVD did not correlate linearly with baPWV. These findings show that baPWV is a reliable surrogate marker ofischemic stroke. Furthermore, baPWVand ABI can be used to indicate the presence of small vessel disease and large arterial disease, respectively.

关键词： ABI baPWV small vessel disease intracranial artery stenosis extracranial artery stenosis

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Ex vivo relaxation effect of Cuscuta chinensis extract on rabbit corpus cavernosum

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Asian Journal of Andrology 2013年第1期15卷 134-137页

作者： Kai sun Chen Zhao Xiang-Feng Chen hye-Kyung Kim Bo-Ram Choi Yi-Ran Huang Jong-Kwan Park Department of Urology Renji Hospital Shanghai Jiao Tong University School of Medicine and Shanghai Institute of Andrology Shanghai 200127 China Department of Urology Chonbuk National University and Research Institute of Clinical Medicine and Clinical Trial Center of Medical Device of Chonbuk National University Hospital Jeonju 561-712 South Korea

The effect of Cuscuta chinensis extract on the rabbit penile corpus cavernosum （PCC） was evaluated in the present study. Penises obtained from healthy male New Zealand white rabbits （2.5-3.0 kg） were precontracted with phenylephrine （Phe, 10 pmol I^-1） and then treated with various concentrations of Cuscuta chinensis extract （1, 2, 3, 4 and 5 mg ml^-1）. The change in penile tension was recorded, and cyclic nucleotides in the PCC were measured by radioimmunoassay （RIA）. The interaction between Cuscuta chinensis and sildenafil was also evaluated. The result indicated that the PCC relaxation induced by Cuscuta chinensis extract was concentration-dependent. Pre-treatment with an nitric oxide synthase （NOS） inhibitor （No〉 nitro-L-arginine-methyl ester, L-NAME）, a guanylyl cyclase inhibitor （1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-l-one, ODQ）, or a protein kinase A inhibitor （KT 5720） did not completely inhibit the relaxation. Incubation of penile cavernous tissue with the Cuscuta chinensis extract significantly increased cyclic guanosine monophosphate （cGMP） and cyclic adenosine monophosphate （cAMP） in the PCC. Moreover, the Cuscuta chinensis extract significantly enhanced sildenafil-induced PCC relaxation. In conclusion, the Cuscuta chinensis extract exerts a relaxing effect on penile cavernous tissue in part by activating the NO-cGMP pathway, and it may improve erectile dysfunction （ED）, which does not completely respond to sildenafil citrate.

关键词： Cuscuta chinensis erectile dysfunction (ED) NO-cGMP pathway penile corpus cavernosum (PCC) sildenafil

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Three-Tesla magnetic resonance elastography for hepatic fibrosis:Comparison with diffusion-weighted imaging and gadoxetic acid-enhanced magnetic resonance imaging

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World Journal of Gastroenterology 2014年第46期20卷 17558-17567页

作者： Hee sun Park Young Jun Kim Mi hye Yu Won hyeok Choe sung Il Jung Hae Jeong Jeon Department of Radiology Konkuk University School of MedicineSeoul 143-729South Korea Digestive Disease Center Konkuk University School of MedicineSeoul 143-729South Korea

AIM: To evaluate the feasibility of 3-Tesla magnetic resonance elastography (MRE) for hepatic fibrosis and to compare that with diffusion-weighted imaging (DWI) and gadoxetic acid-enhanced magnetic resonance (MR) imag... 详细信息

关键词： Magnetic resonance elastography Hepatic fibrosis Diffusion weighted imaging Gadoxetic acid enhanced magnetic resonance imaging Serum markers

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Use of Poly（acrylic acid） and Poly（dimethylsiloxane） Mixture for In-Needle Micrextraction of Volatile Aroma Compounds

Use of Poly（acrylic acid） and Poly（dimethylsiloxane） Mix...

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第六届上海国际分析化学研讨会

作者： hye Lim Jeon sunyoung Bae Dong-sun lee Department of Chemistry Seoul Women's UniversitySeoul 139-774Korea Department of Chemistry Seoul Women’s UniversitySeoul 139-774Korea

＜正＞A prototype stainless steel needle （Hamilton 90022,22 gauge,718 μm O.D.,413 μm I.D.,51 mm length,bevel tip） packed with poly （acrylic acid）（PAA） and poly （dimethylsiloxane）（PDMS） mixture （7:3 ratio） having a micro-bore （290 μm I.D.,10 mm length） tunnel was newly prepared as an in-needle microextraction

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Transcriptome sequencing assisted discovery and computational analysis of novel SNPs associated with flowering in Raphanus sativus in-bred lines for marker-assisted backcross breeding

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Horticulture Research 2019年第1期6卷 248-259页

作者： Jinhee Kim Abinaya Manivannan Do-sun Kim Eun-Su lee hye-Eun lee Vegetable Research Division National Institute of Horticultural and Herbal ScienceRural Development AdministrationJeonju 55365Republic of Korea

The sequencing of radish genome aids in the better understanding and tailoring of traits associated with economic *** order to accelerate the genomics assisted breeding and genetic selection,transcriptomes of 33 radish inbred lines with diverse traits were sequenced for the development of single nucleotide polymorphic(SNP)*** sequence reads ranged from 2,560,543,741 bp to 20,039,688,139 bp with the GC(%)of 47.80–49.34 and phred quality score(Q30)of 96.47–97.54%.A total of 4951 polymorphic SNPs were identified among the accessions after stringent filtering and 298 SNPs with efficient marker assisted backcross breeding(MAB)markers were generated from the polymorphic ***,functional annotations of SNPs revealed the effects and importance of the SNPs identified in the flowering *** SNPs were predominantly associated with the four major flowering related transcription factors such as MYB,MADS box(AG),AP2/EREB,and *** addition,SNPs in the vital flowering integrator gene(FT)and floral repressors(EMBRYONIC FLOWER 1,2,and FRIGIDA)were identified among the radish inbred ***,50 SNPs were randomly selected from 298 SNPs and validated using Kompetitive Allele Specific PCR genotyping system(KASP)in 102 radish inbred *** homozygosity of the inbred lines varied from 56 to 96%and the phylogenetic analysis resulted in the clustering of inbred lines into three *** together,the SNP markers identified in the present study can be utilized for the discrimination,seed purity test,and adjusting parental combinations for breeding in radish.

关键词： breeding Raphanus utilized

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