• Molecules and Cells
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• 제45권5호
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• pp.343-352
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• 2022

The advent of the assay for transposase-accessible chromatin using sequencing (ATAC-seq) has shown great potential as a leading method for analyzing the genome-wide profiling of chromatin accessibility. A comprehensive reference to the ATAC-seq dataset for disease progression is important for understanding the regulatory specificity caused by genetic or epigenetic changes. In this study, we present a genome-wide chromatin accessibility profile of 44 liver samples spanning the full histological spectrum of nonalcoholic fatty liver disease (NAFLD). We analyzed the ATAC-seq signal enrichment, fragment size distribution, and correlation coefficients according to the histological severity of NAFLD (healthy control vs steatosis vs fibrotic nonalcoholic steatohepatitis), demonstrating the high quality of the dataset. Consequently, 112,303 merged regions (genomic regions containing one or multiple overlapping peak regions) were identified. Additionally, we found differentially accessible regions (DARs) and performed transcription factor binding motif enrichment analysis and de novo motif analysis to determine new biomarker candidates. These data revealed the gene-regulatory interactions and noncoding factors that can affect NAFLD progression. In summary, our study provides a valuable resource for the human epigenome by applying an advanced approach to facilitate diagnosis and treatment by understanding the non-coding genome of NAFLD.

• Journal of Genetic Medicine
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• 제19권2호
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• pp.111-114
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• 2022

Many monogenic neurodevelopmental disorders have been newly identified in recent years owing to the rapid development of genetic sequencing technology. These include variants of the epigenetic machinery - up to 300 known epigenetic factors of which about 50 have been linked to specific clinical phenotypes. Chromodomain, helicase, DNA binding 1 (CHD1) is an ATP-dependent chromatin remodeler, known to be the causative gene of the autosomal dominant neurodevelopmental disorder Pilarowski-Bjornsson syndrome. Patients exhibit various degrees of global developmental delay, autism, speech apraxia, seizures, growth retardation, and craniofacial dysmorphism. We report the first case of Pilarowski-Bjornsson syndrome in Korea, due to a de novo missense variant of the CHD1 gene (c.862A>G, p.Thr288Ala) in a previously undiagnosed 17-year-old male. His infantile onset of severe global developmental delay, intellectual disability, speech apraxia, and failure to thrive are compatible with Pilarowski-Bjornsson syndrome. We also noted some features not previously reported in this syndrome such as skeletal dysplasia and ichthyosis. Further studies are needed to discover the specific phenotypes and pathogenic mechanisms behind this rare disorder.

• Journal of Microbiology and Biotechnology
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• 제33권2호
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• pp.242-250
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• 2023

Comparative gene identification-58 (CGI-58) is an activating protein of triacylglycerol (TAG) lipase. It has a variety of catalytic activities whereby it may play different roles in diverse organisms. In this study, a homolog of CGI-58 in Phaeodactylum tricornutum (PtCGI-58) was identified. PtCGI-58 was localized in mitochondria by GFP fusion protein analysis, which is different from the reported subcellular localization of CGI-58 in animals and plants. Respectively, PtCGI-58 overexpression resulted in increased neutral lipid content and TAG accumulation by 42-46% and 21-32%. Likewise, it also increased the relative content of eicosapentaenoic acid (EPA), and in particular, the EPA content in TAGs almost doubled. Transcript levels of genes involved in de novo fatty acid synthesis and mitochondrial β-oxidation were significantly upregulated in PtCGI-58 overexpression strains compared with wild-type cells. Our findings suggest that PtCGI-58 may mediate the breakdown of lipids in mitochondria and the recycling of acyl chains derived from mitochondrial β-oxidation into TAG biosynthesis. Moreover, this study potentially illuminates new functions for CGI-58 in lipid homeostasis and provides a strategy to enrich EPA in algal TAGs.

• 한국발생생물학회지:발생과생식
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• 제27권2호
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• pp.77-89
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• 2023

Metformin is the most widely used anti-diabetic drug that helps maintain normal blood glucose levels primarily by suppressing hepatic gluconeogenesis in type II diabetic patients. We previously found that metformin induces apoptotic death in H4IIE rat hepatocellular carcinoma cells. Despite its anti-diabetic roles, the effect of metformin on hepatic de novo lipogenesis (DNL) remains unclear. We investigated the effect of metformin on hepatic DNL and apoptotic cell death in H4IIE cells. Metformin treatment stimulated glucose consumption, lactate production, intracellular fat accumulation, and the expressions of lipogenic proteins. It also stimulated apoptosis but reduced autophagic responses. These metformin-induced changes were clearly reversed by compound C, an inhibitor of AMP-activated protein kinase (AMPK). Interestingly, metformin massively increased the production of reactive oxygen species (ROS), which was completely blocked by compound C. Metformin also stimulated the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK). Finally, inhibition of p38MAPK mimicked the effects of compound C, and suppressed the metformin-induced fat accumulation and apoptosis. Taken together, metformin stimulates dysregulated glucose metabolism, intracellular fat accumulation, and apoptosis. Our findings suggest that metformin induces excessive glucose-induced DNL, oxidative stress by ROS generation, activation of AMPK and p38MAPK, suppression of autophagy, and ultimately apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2367-2370
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• 2013

Background: In recent years, due to modern lifestyles and exposure to chemical carcinogens, cancer cases are steadily increasing. From this standpoint, azoxymethane (AOM), a chemical carcinogen which causes de novo liver damage, and resveratrol, which is an antioxidant found in foods and protects against oxidative stress damage, are of interest. We here aimed to evaluate whether resveratrol could protect the liver tissues from the effects of AOM. Materials and Methods: The study was conducted in 4 groups, each consisting of seven rats, the first receiving only AOM (2 times per week, 5 mg/kg), group 2 AOM and resveratrol (2 times a week, 20 mg/kg), group 3 assessed only as a control and group 4 administered only resveratrol. At the end of the seventh week, the rats were sacrificed. Rat liver MDA, NO, GSH levels were analyzed biochemically, as well as the tissues being evaluated histopathologically. Results: MDA and NO increased in AOM group as signs of increased oxidative stress. The group concomitantly administered resveratrol was been found to be significantly decreased in MDA and NO levels and increased in GSH activity. However, there were no significant findings on histopathological evaluation. Conclusions: In the light of these results, resveratrol appears to exert protective effect on oxidative s tress in the liver tissue due to deleterious effects of chemical carcinogens.

• 혜화의학회지
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• 제28권2호
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• pp.41-47
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• 2019

Objectives : Atopic dermatitis is an irritable skin disease accompanying rash and itching leading to impaired skin barrier. ATO-ALL is an ethanol extract of natural products comprising 12 herbs and effective on atopic dermatitis. In this study, we aimed to propose that the effect of ATO-ALL on skin regeneration in human keratinocyte cell line, HaCaT cells. Methods : To evaluate the skin regenerating effects of ATO-ALL, scratch wound healing assay, bromodeoxyuridine (BrdU) assay, and propidum iodide (PI) assay were performed using cultured HaCaT cell line. Result : Scratch wound healing assay showed that ATO-ALL was able to enhance the gap filling activity more than 2-fold at 7 ppm concentration compared with control group. BrdU assay demonstrated that ATO-ALL treatment increased the de novo cell proliferation in a dose-dependent manner. Finally, PI assay indicated that the cell cycle of HaCaT cells was modulated by ATO-ALL treatment. Conclusions : These results suggested that ATO-ALL may have skin regenerating effects by increasing cell proliferation via cell cycle regulation. Taken together, ATO-ALL is supposed to have a potential on regeneration of damaged skin or functional disease including atopic dermatitis.

• Asian Pacific Journal of Cancer Prevention
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• 제17권10호
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• pp.4699-4711
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• 2016

Background: In the last decade, it has become clear that change of gene expression may alter the hematopoietic cell quiescent state and consequently play a major role in leukemogenesis. WT1 is known to be a player in acute myeloid leukemia (AML) and FOXP3 has a crucial role in regulating the immune response. Objectives: To evaluate the impact of overexpression of WT1and FOXP3 genes on clinical course in adult and pediatric AML patients in Egypt. Patients and methods: Bone marrow and peripheral blood samples were obtained from 97 de novo non M3 AML patients (63 adult and 34 pediatric). Real-time quantitative PCR was used to detect overexpression WT1 and FOXP3 genes. Patient follow up ranged from 0.2 to 39.0 months with a median of 5 months. Results: In the pediatric group; WT1 was significantly expressed with a high total leukocyte count median 50X109/L (p=0.018). In the adult group, WT1 had an adverse impact on complete remission induction, disease-free survival and overall survival (p=0.02, p=0.035, p=0.019 respectively). FOXP3 overexpression was associated with FAB subtypes AML M0 +M1 vs. M2, M4+M5 (p =0.039) and the presence of hepatomegaly (p=0.005). Conclusions: WT1 and FOXP3 overexpression has an adverse impact on clinical presentation, treatment response and survival of pediatric and adult Egyptian AML patients.

• 한국발생생물학회지:발생과생식
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• 제20권3호
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• pp.197-205
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• 2016

Adipose tissue is one of the major endocrine gland. More recently, local production of steroids in adipocytes differentiated from mouse 3T3-L1 cell-line was reported. We hypothesized that rat adipocytes have steroidogenic machinery and the expression patterns of the components might be differentially regulated, depending on the distribution and sex. To verify this hypothesis, we collected the adipose tissues depot-and sex-specifically at postnatal day (PND) 30, and performed quantitative RT-PCRs. In overall aspects, the abundances of the transcripts were lower in the brown adipose of both sexes. $3{\beta}-HSD$ transcript levels in female abdominal and reproductive adipose, CYP17 transcript levels in female reproductive adipose, $17{\beta}-HSD$ transcript levels in female abdominal and reproductive adipose, and CYP19 transcript levels in female abdominal adipose were significantly lower than those of male counterparts. Similar to steroidogenic factors, the abundance of the $ER-{\alpha}$ transcripts were generally lower in the brown adipose of both sexes. $ER-{\beta}$ transcripts were more abundant in male white adipose depots than their female counterparts. The levels of LHR transcripts in female reproductive adipose were significantly higher than those of male counterpart. In conclusion, our study demonstrated that the expressions of steroidogenesis-related genes were depot- and sex-specifically occurred in the immature male and female rat adipose tissues. Our study suggested that the adipose tissues are not only targets but de novo synthesizing sites of sex steroid(s), though the synthesizing activities could be much less than in gonads. Further researches in this field will be helpful for understanding the adipose physiology and for medical application such as sex-specific steroid supplement therapies for older populations.

• Journal of Microbiology and Biotechnology
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• 제27권4호
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• pp.660-667
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• 2017

PineXol, extracted from Korean red pine bark, has beneficial effects, such as antioxidant, antiinflammatory, and antilipogenic activities in vitro. We tested the hypothesis that PineXol supplementation could have anti-obesity effects on mice fed a high-fat diet (HFD). Four-week-old male C57BL/6 mice were fed normal chow (18% kcal from fat) or a HFD (60% kcal from fat). HFD-fed animals were also subjected to PineXol treatment at a dose of 10 or 50 mg/kg body weight (BW) (PX10 or PX50, respectively) body weight. The body weight and body fat mass in the PX50 group were statistically lower than those in the HFD group (p < 0.05 and p < 0.001, respectively). The concentration of hepatic triglycerides, total cholesterol, and low-density lipoprotein cholesterol were reduced in the PX50 group compared with the HFD group (p < 0.01). Acetyl CoA carboxylase (p < 0.01), elongase of very long chain fatty acids 6 (p < 0.01), stearoyl CoA desaturase 1 (p < 0.05), microsomal triglyceride transfer protein (p < 0.01), and sterol regulatory element-binding protein 1 (p < 0.05) were significantly decreased in the PX50 group compared with that in the HFD group. In white adipose tissue, CCAAT-enhancer-binding protein alpha (p < 0.05), peroxisome proliferator-activated receptor gamma (p < 0.001), and perilipin (p < 0.01) were decreased in the PX50 group compared with those in the HFD group. Therefore, the current study implies the potential of PineXol for the prevention and/or amelioration of obesity, in part by inhibition of both hepatic lipid synthesis and adipogenesis in white adipose tissue.

• 생물정신의학
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• 제12권2호
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• pp.151-158
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• 2005

Background:Clozapine is a unique atypical antipsychotic medication. It is considered to be superior, even amongst the newer agents, in treatment-resistant schizophrenia. However, de novo emergence or exacerbation of obsessive-compulsive(OC) symptoms during treatment with clozapine has been reported. We prospectively evaluated 19 cases which newly developed OC symptoms during clozapine treatment and discussed the treatment of OC symptoms induced by it. Methods:We recruited 19 patients(8 males, 11 females) with a DSM-IV diagnosis of schizophrenia and schizoaffective disorder who had developed OC symptoms during clozapine treatment. OC symptoms were assessed using the Padua-ICMA and YBOCS on a monthly basis over three months. Results:Eleven female and eight male patients were enrolled and the average age of patients was 32.8 years. At baseline, no patients showed OC symptoms. Moderate to severe OC symptoms appeared with mean daily dose of 298.68 mg of clozapine. There were no significant differences in improving OC symptoms between the clozapine dose reduction group and the OC treatment group. Conclusion:We noticed the possibility that the appearance of OC symptoms is connected with the effect of clozapine. The clozapine-induced OC symptoms were improved both by reducing clozapine daily doses, and by adding OC treatment drugs. With other atypical antipsychotics now available, to know and treat the side effects of clozapine would be of considerable value, offering clinical guidance in making a decision on treatment-resistant schizophrenia.