• Animal Bioscience
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• 제37권3호
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• pp.451-460
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• 2024

Objective: The objective is to identify genomic regions and candidate genes associated with age to 105 kg (AGE), average daily gain (ADG), backfat thickness (BF), and eye muscle area (EMA) in Yorkshire pig. Methods: This study used a total of 104,380 records and 11,854 single nucleotide polymorphism (SNP) data obtained from Illumina porcine 60K chip. The estimated genomic breeding values (GEBVs) and SNP effects were estimated by single-step genomic best linear unbiased prediction (ssGBLUP). Results: The heritabilities of AGE, ADG, BF, and EMA were 0.50, 0.49, 0.49, and 0.23, respectively. We identified significant SNP markers surpassing the Bonferroni correction threshold (1.68×10^-6), with a total of 9 markers associated with both AGE and ADG, and 4 markers associated with BF and EMA. Genome-wide association study (GWAS) analyses revealed notable chromosomal regions linked to AGE and ADG on Sus scrofa chromosome (SSC) 1, 6, 8, and 16; BF on SSC 2, 5, and 8; and EMA on SSC 1. Additionally, we observed strong linkage disequilibrium on SSC 1. Finally, we performed enrichment analyses using gene ontology and Kyoto encyclopedia of genes and genomes (KEGG), which revealed significant enrichments in eight biological processes, one cellular component, one molecular function, and one KEGG pathway. Conclusion: The identified SNP markers for productive traits are expected to provide valuable information for genetic improvement as an understanding of their expression.

• BMB Reports
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• 제57권5호
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• pp.238-243
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• 2024

Bone marrow-derived mesenchymal stem cells (BM-MSCs) can differentiate into endothelial cells in an inflammatory microenvironment. However, the regulatory mechanisms underlying this process are not entirely understood. Here, we found that TIE2 in BM-MSCs was upregulated at the transcriptional level after stimulation with tumor necrosis factor-alpha (TNFα), a major pro-inflammatory cytokine. Additionally, the STAT-binding sequence within the proximal region of TIE2 was necessary for TNFα-induced TIE2 promoter activation. TIE2 and STAT3 knockdown reduced TNFα-induced endothelial tube formation in BM-MSCs. Among the major TNFα-activated MAP kinases (ERK1/2, JNK1/2, and p38 MAPK) in BM-MSCs, only inhibition of the p38 kinase abrogated TNFα-induced TIE2 upregulation by inhibiting the JAK-STAT signaling pathway. These findings suggest that p38 MAP contributes to the endothelial differentiation of BM-MSCs by activating the JAK-STAT-TIE2 signaling axis in the inflammatory microenvironment.

• Journal of Genetic Medicine
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• 제21권1호
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• pp.14-21
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• 2024

Infantile nystagmus syndrome (INS) refers to congenital forms of nystagmus that are present at birth or during infancy. This syndrome may be caused by afferent visual system disorders or abnormal development of the ocular motor system. INS is a genetically heterogeneous disorder for which there are more than 100 causative genes. Since applying clinical tests for the differential diagnosis of INS can be challenging in early infancy and children, genetic testings such as next-generation sequencing are becoming more important for achieving accurate diagnoses. An improved understanding of the molecular mechanisms of INS may also lead to the development of gene-based therapies for INS. These advantages of genetic testing have the potential to change the diagnostic paradigm of patients with INS. However, the diagnostic pathway based on genetic testing still has several limitations in terms of the therapeutic effect and methodology. This review summarizes genetic and clinical features of INS, and discusses the promise and pitfalls of genetic testing in INS.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.379-387
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• 2023

Dog owners seek treatment when their pets develop cancer. IMMUNIES is traditional herbal medicine-based figment made of 10 natural herbs, designed to maintain host immune function. The major component of IMMUNIES is Dendropanax morbiferus. This clinical pilot study monitored the toxicity and efficacy of IMMUNIES. Four senile dogs with spontaneously occurring mammary and liver cancers were enrolled in this study and treated orally daily for 3 months, and their blood/urine biochemical profiles were examined each month. IMMUNIES was well tolerated during the treatment period. Blood urea nitrogen, creatinine, alanine aminotransferase, alkaline phosphatase, and C-reactive protein levels decreased in all four dogs, whereas red blood cells and hematocrit were within the normal range. IMMUNIES also changed the expression of several molecular targets in the anticancer pathway, such as pro-NAG-1, p53, and cyclin D1. Although the tumors did not completely respond to IMMUNIES, the biochemical profiles and clinical examination showed a stabilized cancer status for 3 months. Thus, IMMUNIES was found to be safe and well-tolerated in the dosage range tested and exhibited cancer antiproliferative activity in canine cancer. Future studies should address other potential benefits of IMMUNIES, including correlative assessments of immune function, quality of life, and owner satisfaction.

• BMB Reports
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• 제57권7호
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• pp.324-329
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• 2024

The aim of the present study is to provide a rational background for silencing the V-set and transmembrane domain containing 2 like (VSTM2L) in consort with recognising soluble VSTM2L against cholangiocarcinoma. A therapeutic target against cholangiocarcinoma was selected using iterative patient partitioning (IPP) calculation, and it was verified by in vitro and in silico analyses. VSTM2L was selected as a potential therapeutic target against cholangiocarcinoma. Silencing the VSTM2L expression significantly attenuated the viability and survival of cholangiocarcinoma cells through blockade of the intracellular signalling pathway. In silico analysis showed that VSTM2L affected the positive regulation of cell growth in cholangiocarcinoma. Liptak's z value revealed that the expression of VSTM2L worsened the prognosis of cholangiocarcinoma patients. In addition, soluble VSTM2L was significantly detected in the whole blood of cholangiocarcinoma patients compared with that of healthy donors. Our report reveals that VSTM2L might be the potential therapeutic target and a soluble prognostic biomarker against cholangiocarcinoma.

• 한국자원식물학회지
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• 제37권3호
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• pp.256-262
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• 2024

Blueberry (BB), fruit of Vacciniumi, has been hailed as an antioxidant superfood. BB is a rich source of vitamins, minerals, flavonoids, phenolic acids and known to have a variety of pharmacological actions. The purpose of this work is to clarify the anti-inflammatory mechanism of BB in lipopolysaccharide (LPS)-activated RAW264.7 macrophage. We explored the effects of BB on the production of inflammatory cytokines, prostaglandin E₂ (PGE₂) and expression of cyclooxygenase (COX)-2 in LPS-activated RAW264.7 macrophage. Moreover, to investigate the molecular mechanisms by BB, we evaluated whether BB modulate nuclear factor-kappa B (NF)-kB pathway and caspase- 1 activation. The findings of this work demonstrated that BB alleviated the LPS-enhanced inflammatory cytokines and PGE₂, as well as COX-2 levels. Additionally, we demonstrated that the anti-inflammatory mechanism of BB occurs due to the attenuation of IκB-α degradation, NF-kB translocation and caspase-1 activation. Conclusively, these findings provide evidence that BB may be useful agents in the treatment of inflammation.

• 한국식품영양과학회지
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• 제39권1호
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• pp.54-63
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• 2010

Flavonoid 계열의 한 종류인 baicalin은 항염증, 항암, 항바이러스, 항세균 등의 효능을 가진다. 본 연구진은 선행연구를 통한 이전의 보고에서 baiclain이 adipogenesis pathway(지방세포 형성 경로)의 anti-adipogenic(지방세포 형성억제)과 pro-adipogenic(지방세포 형성 유도) factor들을 조절함으로써 비만 및 adipogenesis를 억제함을 밝혔다. 본 연구에서는, microarray 기술을 이용하여 3T3-L1 세포에서 baiclain이 유도하는 지방세포 형성 억제 효과에 대한 분자적 기작을 보다 상세하게 연구하고자 하였다. 지방세포의 분화 시간(0일, 2일, 4일 및 7일)과 분화 시 baicalin의 처리 유무에 따라 유전자 발현 양상을 분석하기 위해 해당 시료들을 microarray에 적용하였다. Microarray 결과로부터 2배이상의 변화가 있는 3972개의 유전자를 확보하였다. 그 유전자들의 발현 양상을 좀 더 자세히 살펴보기 위해 hierarchical clustering 분석을 진행하였고 그 결과로 20개의 cluster를 분류할 수 있었다. 그들 중 4개의 cluster는 분화의 전반적인 기간에서 baicalin의 첨가에 의해 뚜렷하게 상승(cluster 8과 cluster 10)하거나 반대로 뚜렷하게 감소(cluster 12와 cluster 14)하는 양상을 보였다. Cluster 8과 cluster 10에는 CHOP(CCAAT/enhancer-binding protein homologous protein), INSIG1(insulin induced gene 1), WISP2(WNT1 inducible signaling pathway protein 2), ADM(adrenomedullin), CCND2(cyclin D2), GRN(granulin) 및 TGFB3(transforming growth factor, beta 3)과 같은 세포 증식과 지방세포 형성 억제를 상승시키는 유전자들이 다수 포함되었다. 반대로 cluster 12와 cluster 14에는 세포 증식 억제, 세포 주기 억제 및 세포 성장 억제와 연관되거나 지방세포를 유도하는 유전자인 LTA(lympotoxin A), ACADSB(acyl-Coenzyme A dehydrogenase, short/branched chain), HMGCS2(3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2), IGFBP7(insulin-like growth factor binding protein 7), MERTK(c-merproto-oncogene tyrosine kinase), RASSF2(ras association(RalGDS/AF-6) domain family 2), RHOU(ras homolog gene family, member U) 및 SESN1(sestrin1) 등이 포함되었다. 결론적으로 baicalin은 세포 증식 및 지방세포 형성과 연관된 유전자들을 조절함으로써 지방세포의 분화를 억제하는 것으로 사료된다. 이러한 결과는 baicalin이 유도하는 지방세포 형성 억제 및 비만 억제 효과의 분자적 기작에 대한 중요한 정보를 제시한다.

• Journal of Plant Biotechnology
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• 제42권3호
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• pp.245-256
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• 2015

농업에서의 LED는 단지 광을 보충해주는 역할로만 이용되는 것뿐 아니라, 시설 재배 시스템에 있어 매우 중요한 주광원이다. 인공광을 이용한 시설재배에서 주광인 형광등에 다양한 파장의 광질을 혼합하여 식물의 생육 및 대사를 증진시키는 시도가 있어 왔다. 주광인 형광등에 청색광을 혼합한 조건과 청색 단독광 조건을 배추 유묘에 조사한 후 마이크로어레이 분석을 수행한 결과 배추 속 작물의 기능성 물질로 주목을 받고 있는 글루코시놀레이트 합성에 관여하는 일부 유전자들 중 청색 혼합광 조건에서 3.6-4.6배는 증가 하는 유전자 3개를 찾을 수 있었다. 글루코시놀레이트 합성 유전자를 배추 데이터베이스에서 더 선발하여 적, 녹, 청색광을 형광등에 각각 혼합한 조건에 반응하여 발현이 변하하는지 관찰하였는데 청색광 혼합 조건뿐아니라 적색광 혼합 조건에서도 발현이 증가하는 유전자들이 있었다. 각각 애기장대 CYP79F1, ST5a, FMOGS-OX1와 이종상동 유전자인 Bra026058, Bra015379와 Bra021429는 청색광 조건에서 발현량이 증가하였으나 MAM1, AOP3, UGT74B1, BCAT4의 이종상동유전자인 Bra029355, Bra034180, Bra024634, Bra022448은 청색광 보다 적색 혼합광 조건에서 발현이 증가하였다. 혼합광 처리에 의한 글루코시놀레이트 합성의 효과는 배추 품종에 따라 차이를 보였으나 몇가지 글루코시놀레이트가 청색광을 혼합한 조건에서 합성이 증가하였다. 이러한 결과는 유묘의 생육 시설에서 기능적으로 우수한 작물을 생산하는 인공광 조건을 조성하는데 유용한 기초 자료가 될 것으로 사료된다.

• KSBB Journal
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• 제20권5호
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• pp.363-370
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• 2005

중추신경계의 신경간세포가 파킨슨병과 뇌졸중과 같은 퇴행성 뇌 질환의 치료뿐만이 아니라 신경세포 발생과정에서의 중요성 때문에 최근에 커다란 관심의 대상이 되고 있다. 중추신경계의 발생과정 동안에, 중뇌의 도파민 신경세포의 형성은 두 가지의 분자생물학적인 기작에 의해서 결정된다. 첫째로, FGF-8, sonic hedgehog 그리고 전사조절인자 인 Nurr1이 도파민 신경세포의 형질을 결정짓는다. 또 다른 기작으로는, 전사조절인자 인 $Lm{\times}lb$와 $Pt{\times}3$가 중요하게 관련되어있다. 특히 Nurr1이 결핍된 생쥐에서, 타이로신수산화효소 (Tyrosine bydroxylase, TH) 면역양성 세포들이 중뇌흑색질에서 발견되지 않으므로 Nurr1이 도파민 신경세포의 발생에 필수적임을 알 수 있다. 본 연구에서는 도파민 신경세포의 형질을 유도하는데 있어서 Nurr1이 매개하는 기작을 연구하기 위해서 레트로 바이러스를 이용하여 Nurr1을 도입한 무한증식 신경간세포를 사용하였다. Nurr1 유전자의 과발현 만으로는 신경간세포에서 도파민 신경세포의 형질을 유도하지는 못하지만, 레티노이드 (retinoid, RA)와 폴스콜린 (forskolin, FK)을 처리하여 TH와 방향성 L-아미노산 탈카르복시화효소 (aromatic L-amino acid decarboxylase, AADC) mRNA의 발현을 유도하였다. 또한, Nurr1 과발현 신경간세포를 사람 별아교세포와 공동배양 하여 TH 발현량을 많이 증가시켰다. 이러한 공동배양실험에서, RA와 FK를 처리하면 TH의 발현수준이 더욱 더 증가함을 발견하였다. 이러한 결과들은 Nurr1 유전자를 도입한 사람 신경간세포가 파킨슨병 환자들에게 세포이식을 통한 유전자 치료의 유용성을 시사하고 있다.

• BMB Reports
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• 제40권5호
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• pp.715-722
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• 2007

A new full-length cDNA encoding hyoscyamine $6\beta$-hydroxylase (designated as aah6h, GenBank Accession No. EF187826), which catalyzes the last committed step in the scopolamine biosynthetic pathway, was isolated from young roots of Anisodus acutangulus by rapid amplification of cDNA ends (RACE) for the first time. The full-length cDNA of aah6h was 1380 bp and contained a 1035 bp open reading frame (ORF) encoding a deduced protein of 344 amino acid residues. The deduced protein had an isoelectric point (pI) of 5.09 and a calculated molecular mass of about 38.7 kDa. Sequence analyses showed that AaH6H had high homology with other H6Hs isolated from some scopolamine-producing plants such as Hyoscyamus niger, Datura metel and Atropa belladonna etc. Bioinformatics analyses results indicated AaH6H belongs to 2-oxoglutarate-dependent dioxygenase superfamily. Phylogenetic tree analysis showed that AaH6H had closest relationship with H6H from A. tanguticus. Southern hybridization analysis of the genomic DNA revealed that aah6h belonged to a multi-copy gene family. Tissue expression pattern analysis firstly founded that aah6h expressed in all the tested tissues including roots, stems and leaves and indicated that aah6h was a constitutive-expression gene, which was the first reported tissue-independent h6h gene compared to other known h6h genes.