• Animal Bioscience
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• 제35권6호
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• pp.847-857
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• 2022

Objective: The effects of maternal undernutrition during midgestation on muscle fiber histology, myosin heavy chain (MyHC) expression, methylation modification of myogenic factors, and the mammalian target of rapamycin (mTOR) signaling pathway in the skeletal muscles of prenatal and postnatal goats were examined. Methods: Twenty-four pregnant goats were assigned to a control (100% of the nutrients requirement, n = 12) or a restricted group (60% of the nutrients requirement, n = 12) between 45 and 100 days of gestation. Descendants were harvested at day 100 of gestation and at day 90 after birth to collect the femoris muscle tissue. Results: Maternal undernutrition increased (p<0.05) the fiber area of the vastus muscle in the fetuses and enhanced (p<0.01) the proportions of MyHCI and MyHCIIA fibers in offspring, while the proportion of MyHCIIX fibers was decreased (p<0.01). DNA methylation at the +530 cytosine-guanine dinucleotide (CpG) site of the myogenic factor 5 (MYF5) promoter in restricted fetuses was increased (p<0.05), but the methylation of the MYF5 gene at the +274,280 CpG site and of the myogenic differentiation (MYOD) gene at the +252 CpG site in restricted kids was reduced (p<0.05). mTOR protein signals were down-regulated (p<0.05) in the restricted offspring. Conclusion: Maternal undernutrition altered the muscle fiber type in offspring, but its relationship with methylation in the promoter regions of myogenic genes needs to be elucidated.

• 대한의생명과학회지
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• 제17권3호
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• pp.231-238
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• 2011

During pregnancy, stress induces maternal glucocorticoid secretion, which in turn is known to affect structural malformation, retardation of growth, reduced birth weight of the fetus. As Hox genes are master transcription factors which fulfill critical roles in embryonic development, we aimed to explore the possibility that alterations of the Hox gene expression might be involved in stress-induced malformation. The pregnant mice were injected with dexamethasone at a dose of 1 mg/kg or 10 mg/kg on day 7.5, 8.5 and 9.5 p.c. (post coitum), as well as saline as control. Embryos of E11.5 and E18.5 were obtained by sacrificing pregnant animals. Weight and crown-rump length (CRL) were measured. RT-PCR was performed to examine the Hox gene expression levels. Embryos given dexamethasone at day 7.5~9.5 p.c. had small CRL and weighed less both in E11.5 and E18.5. The percentage of embryos showing abnormalities was high in groups received high dose of dexamethasone. To define the molecular basis for abnormal embryonic development, we analyzed the Hox gene expression pattern and found that many Hox genes display altered expression. Effects of prenatal dexamethasone treatment on embryonic development might be associated with the aberrant Hox gene expression.

• Journal of Microbiology and Biotechnology
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• 제33권9호
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• pp.1213-1227
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• 2023

Fetal growth restriction (FGR) is a prevalent obstetric condition. This study aimed to investigate the role of Toll-like receptor 9 (TLR9) in regulating the inflammatory response and gut microbiota structure in FGR. An FGR animal model was established in rats, and ODN1668 and hydroxychloroquine (HCQ) were administered. Changes in gut microbiota structure were assessed using 16S rRNA sequencing, and fecal microbiota transplantation (FMT) was conducted. HTR-8/Svneo cells were treated with ODN1668 and HCQ to evaluate cell growth. Histopathological analysis was performed, and relative factor levels were measured. The results showed that FGR rats exhibited elevated levels of TLR9 and myeloid differentiating primary response gene 88 (MyD88). In vitro experiments demonstrated that TLR9 inhibited trophoblast cell proliferation and invasion. TLR9 upregulated lipopolysaccharide (LPS), LPS-binding protein (LBP), interleukin (IL)-1β and tumor necrosis factor (TNF)-α while downregulating IL-10. TLR9 activated the TARF3-TBK1-IRF3 signaling pathway. In vivo experiments showed HCQ reduced inflammation in FGR rats, and the relative cytokine expression followed a similar trend to that observed in vitro. TLR9 stimulated neutrophil activation. HCQ in FGR rats resulted in changes in the abundance of Eubacterium_coprostanoligenes_group at the family level and the abundance of Eubacterium_coprostanoligenes_group and Bacteroides at the genus level. TLR9 and associated inflammatory factors were correlated with Bacteroides, Prevotella, Streptococcus, and Prevotellaceae_Ga6A1_group. FMT from FGR rats interfered with the therapeutic effects of HCQ. In conclusion, our findings suggest that TLR9 regulates the inflammatory response and gut microbiota structure in FGR, providing new insights into the pathogenesis of FGR and suggesting potential therapeutic interventions.

• Clinical and Experimental Pediatrics
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• 제59권sup1호
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• pp.41-44
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• 2016

We report here a case of maternal 3-methylcrotonyl-coenzyme A carboxylase (3-MCC) deficiency in a Korean woman. Her 2 infants had elevated 3-hydroxyisovalerylcarnitine (C5-OH) on a neonatal screening test by liquid chromatography-tandem mass spectrometry (LC-MS/MS), but normal results were found on urine organic acid analysis. The patient was subjected to serial testing and we confirmed a maternal 3-MCC deficiency by blood spot and breast milk spot test by LC-MS/MS, serum amino acid analysis, urine organic acid and molecular genetic analysis that found c.838G>T (p.Asp280Tyr) homozygous mutation within exon 9 of the MCCB gene. Especially, we confirmed marked higher levels of C5-OH on breast milk spot by LC-MS/MS, in the case of maternal 3-MCC deficiency vs. controls.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5375-5379
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• 2012

Introduction: Published studies on the association between Nijmegen breakage syndrome 1(NBS1) gene polymorphisms and breast cancer risk have been inconclusive, and a meta-analysis was therefore performed for clarification. Methods: Eligible articles were identified by a search of MEDLINE and EMBASE bibliographic databases for the period up to March 2012. The presence of between-study heterogeneity was investigated using the chi-square-based Cochran's Q statistic test. When there was statistical heterogeneity, the random effects model was chosen; otherwise, fixed effects estimates were reported as an alternative approach. Results: A total of 11 eligible articles (14 case-control studies) were identified, nine case-control studies were for the 657del5 mutation (7,534 breast cancer cases, 14,034 controls) and five case-control studies were for the I171V mutation (3,273 breast cancer cases, 4,004 controls). Our analysis results indicated that the 657del5 mutation was associated with breast cancer risk (carriers vs. non-carriers: pooled OR =2.63, 95% CI: 1.76-3.93), whereas the I171V mutation was not (carriers vs. non-carriers: pooled OR =1.52, 95% CI: 0.70-3.28). Conclusion: The present meta-analysis suggests that the 657del5 gene mutation in the NBS1 gene plays a role in breast cancer risk, while the I171V mutation does not exert a significant influence.

• Asian-Australasian Journal of Animal Sciences
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• 제27권12호
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• pp.1695-1704
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• 2014

Maternal malnutrition during pregnancy may give rise to female offspring with disrupted ovary functions in adult age. Neonatal ovary development predisposes adult ovary function, yet the effect of maternal nutrition on the neonatal ovary has not been described. Therefore, here we show the impact of maternal protein restriction on the expression of folliculogenic and steroidogenic genes, their regulatory microRNAs and promoter DNA methylation in the ovary of neonatal piglets. Sows were fed either standard-protein (SP, 15% crude protein) or low-protein (LP, 7.5% crude protein) diets throughout gestation. Female piglets born to LP sows showed significantly decreased ovary weight relative to body weight (p<0.05) at birth, which was accompanied with an increased serum estradiol level (p<0.05). The LP piglets demonstrated higher ratio of bcl-2 associated X protein/B cell lymphoma/leukemia-2 mRNA (p<0.01), which was associated with up-regulated mRNA expression of bone morphogenic protein 4 (BMP4) (p<0.05) and proliferating cell nuclear antigen (PCNA) (p<0.05). The steroidogenic gene, cytochrome P450 aromatase (CYP19A1) was significantly down-regulated (p<0.05) in LP piglets. The alterations in ovarian gene expression were associated with a significant down-regulation of follicle-stimulating hormone receptor mRNA expression (p<0.05) in LP piglets. Moreover, three microRNAs, including miR-423-5p targeting both CYP19A1 and PCNA, miR-378 targeting CYP19A1 and miR-210 targeting BMP4, were significantly down-regulated (p<0.05) in the ovary of LP piglets. These results suggest that microRNAs are involved in mediating the effect of maternal protein restriction on ovarian function through regulating the expression of folliculogenic and steroidogenic genes in newborn piglets.

• Clinical and Experimental Pediatrics
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• 제59권sup1호
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• pp.49-52
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• 2016

X-linked agammaglobulinemia (XLA) is a hereditary humoral immunodeficiency that results from Bruton's tyrosine kinase (BTK ) gene mutations. These mutations cause defects in B-cell development, resulting in the virtual absence of these lymphocytes from the peripheral circulation. Consequently, this absence leads to a profound deficiency of lg all isotypes, and an increased susceptibility to encapsulated bacterial infections. A 15-month-old Korean boy presented with recurrent sinusitis and otitis media after 6 months of age, and had a family history of 2 maternal uncles with XLA. Laboratory tests revealed a profound deficiency of Ig isotypes, and a decreased count of $CD19^+$ B cells in the peripheral circulation. Based on his family history and our laboratory test results, he was diagnosed with XLA. We performed BTK gene analysis of peripheral blood samples obtained from family members to confirm the diagnosis. Mutational analysis revealed a novel hemizygous frameshift mutation (c.82delC, p.Arg28Alafs*5), in the BTK gene. His mother and maternal grandmother were heterozygous carriers of this mutation and his two maternal uncles were hemizygous at the same position. After XLA diagnosis, intravenous immunoglobulin (400 mg/kg, monthly) treatment was initiated; recurrent sinusitis and otitis media were subsequently brought under control. To our knowledge, this is the first reported case of a Korean pedigree with a novel mutation in the BTK gene.

• Neonatal Medicine
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• 제16권2호
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• pp.137-145
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• 2009

목 적: 본 연구의 목적은 한국 미숙아에서의 IL-10 유전자형의 빈도와 신생아 호흡 곤란증의 발생 빈도와의 연관성을 조사하고자 하였다. 방 법: 이대목동병원에서 2003년도 11월부터 2008년도 7월에 태어난 214명의 미숙아를 대상으로 하였다. 제대혈과 모체혈에서 IL-10 유전자(IL-10 -1082A/G, -819T/C, -592A/C) 의 다형성을 조사하였고, 임상적인 자료는 의무기록조사를 통해서 분석하였다. 결 과: 미숙아를 분만한 한국 엄마들의 유전자형 빈도는 기존의 보고된 바와 달랐다. IL-10-1082GG homozygote는 발견되지 않았고, 다변량 회귀분석에서 호흡곤란증은 IL-10-592AC/CC 유전형에서 AA 유전자형보다 적게 발현되었다(P=0.033). 호흡곤란증의 위험도가 모체가 IL-10-819TC/CC 유전자형인 경우 TT 유전자형보다 적게 발견되었다(P-0.030). 하지만 제대혈에서는 이러한 차이가 없었다. 각각의 유전자형에서 분석해보면 IL-10 A-1082G/T-819C/A-592C 중, ACC haplotype인 경우, 호흡곤란증에서 보호되는 효과가 있었다(P=0.07). 결 론: 모체의 IL-10-592A/C 과 IL-10-819T/C 유전자 다형성이 미숙아에서 호흡곤란증의 발생에 관여한다고 생각된다.

• 생물정신의학
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• 제13권2호
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• pp.110-116
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• 2006

Objectives : Alteration of hippocampus was demonstrated in the maternal social separation(MSS) pups, separated from dams on postnatal day(pnd) 14 and placed alone. Therefore, to understand the molecular events involved in the MSS, we have initiated a search for gene profiles that are up or down-regulated in the hippocampus of MSS pups. Methods : Analysis of cDNA microarray was performed by using total RNA extracted from the hippocampus of control and MSS pups on pnd 17. Also, passive-avoidance test was demonstrated on pnd 35. Results : Up-regulation of Nedd4a was observed in the hippocampus of MSS pups. Also, MSS rats showed less elongation of latency in passive avoidance test. Conclusion : We suggest that environmental effects of MSS may be altered the neural and/or glial differentiation and synapse formation-related genes which may lead cognitive alterations in MSS rats.

• 한국수정란이식학회지
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• 제28권4호
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• pp.343-348
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• 2013

Cell-free fetal RNA has been highlighted as useful tools for the fetal sex determination or other genetic inherent disorder. However, there is no knowledge about the sex determination using cell free fetal RNA in bovine field. Thus, the present study aimed to evaluate the presence of transcripts of DDX3Y, USP9Y and ZRSR2Y genes in maternal plasma of pregnant cows to determine the sex of the fetus using real-time quantitative polymerase chain reaction assay, and verify its accuracy, sensitivity and specificity compared with the molecular testing and the calf sex at birth. Transcripts of USP9Y and DDX3Y genes were expressed in the all plasma of males and females both the control group and the experimental group. However, ZRSR2Y gene was matched up with the molecular testing and the true sex in control group and has an overall accuracy of 82.6%, a sensitivity of 75%, and a specificity of 100% in experimental group. Therefore, these results indicated that real time PCR technique, as a noninvasive and cost-efficient method, is possible to determination fetal sex in the bovine species using circulating cell free RNA in maternal plasma and especially ZRSR2Y gene could be a good candidate for the RNA based sex determination work.