• Journal of Microbiology and Biotechnology
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• v.32 no.10
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• pp.1245-1252
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• 2022

Induced pluripotent stem cells (iPSCs) can be generated from somatic cells using Oct4, Sox2, Klf4, and c-Myc (OSKM). Small molecules can enhance reprogramming. Licochalcone D (LCD), a flavonoid compound present mainly in the roots of Glycyrrhiza inflata, acts on known signaling pathways involved in transcriptional activity and signal transduction, including the PGC1-α and MAPK families. In this study, we demonstrated that LCD improved reprogramming efficiency. LCD-treated iPSCs (LCD-iPSCs) expressed pluripotency-related genes Oct4, Sox2, Nanog, and Prdm14. Moreover, LCD-iPSCs differentiated into all three germ layers in vitro and formed chimeras. The mesenchymal-to-epithelial transition (MET) is critical for somatic cell reprogramming. We found that the expression levels of mesenchymal genes (Snail2 and Twist) decreased and those of epithelial genes (DSP, Cldn3, Crb3, and Ocln) dramatically increased in OR-MEF (OG2^+/+/ROSA26^+/+) cells treated with LCD for 3 days, indicating that MET effectively occurred in LCD-treated OR-MEF cells. Thus, LCD enhanced the generation of iPSCs from somatic cells by promoting MET at the early stages of reprogramming.

• Journal of Life Science
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• v.31 no.9
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• pp.796-805
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• 2021

Hepatic endoplasmic reticulum (ER) stress contributes to the development of steatosis and insulin resistance. The components of unfolded protein response (UPR) regulate lipid metabolism. Recent studies have reported an association between ER stress and aberrant cellular lipid control; moreover, research has confirmed the involvement of sterol regulatory element-binding proteins (SREBPs)-the central regulators of lipid metabolism-in the process. However, the exact role of SREBPs in controlling lipid metabolism during ER stress and its contribution to fatty liver disease remain unknown. Here, we show that SREBP-1c deficiency protects against ER stress-induced hepatic steatosis in mice by regulating UPR, inflammation, and fatty acid oxidation. SREBP-1c directly regulated inositol-requiring kinase 1α (IRE1α) expression and mediated ER stress-induced tumor necrosis factor-α activation, leading to a reduction in expression of peroxisome proliferator-activated receptor γ coactivator 1-α and subsequent impairment of fatty acid oxidation. However, the genetic ablation of SREBP-1c prevented these events, alleviating hepatic inflammation and steatosis. Although the mechanism by which SREBP-1c deficiency prevents ER stress-induced inflammatory signaling remains to be elucidated, alteration of the IRE1α signal in SREBP-1c-depleted Kupffer cells might be involved in the signaling. Overall, the results suggest that SREBP-1c plays a crucial role in the regulation of UPR and inflammation in ER stress-induced hepatic steatosis.

• Animal Bioscience
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• v.35 no.7
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• pp.1010-1020
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• 2022

Objective: The experiment was conducted to evaluate the effects of maternal undernutrition during late pregnancy on the expressions of genes involved in growth and development in ovine fetal perirenal brown adipose tissue (BAT). Methods: Eighteen ewes with singleton fetuses were allocated to three groups at day 90 of pregnancy: restricted group 1 (RG1, 0.33 MJ metabolisable energy [ME]/kg body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.18 MJ ME/kg BW^0.75/d, n = 6), and a control group (CG, ad libitum, 0.67 MJ ME/kg BW^0.75/d, n = 6). The fetuses were removed at day 140 of pregnancy. All data were analyzed by using the analysis of variance procedure. Results: The perirenal fat weight (p = 0.0077) and perirenal fat growth rate (p = 0.0074) were reduced in RG2 compared to CG. In fetal perirenal BAT, the protein level of uncoupling protein 1 (UCP1) (p = 0.0001) was lower in RG1 and RG2 compared with CG and UCP1 mRNA expression (p = 0.0265) was decreased in RG2. The protein level of myogenic factor 5 (Myf5) was also decreased in RG2 (p = 0.0001). In addition, mRNA expressions of CyclinA (p = 0.0109), CyclinB (p = 0.0019), CyclinD (p = 0.0015), cyclin-dependent kinase 1 (CDK1) (p = 0.0001), E2F transcription factor 1 (E2F1) (p = 0.0323), E2F4 (p = 0.0101), and E2F5 (p = 0.0018) were lower in RG1 and RG2. There were decreased protein expression of peroxisome proliferator-activated receptor-γ (PPARγ) (p = 0.0043) and mRNA expression of CCAAT/enhancer-binding protein-α (C/EBPα) (p = 0.0307) in RG2 and decreased PPARγ mRNA expression (p = 0.0008) and C/EBPα protein expression (p = 0.0015) in both RG2 and RG1. Furthermore, mRNA expression of bone morphogenetic protein 4 (BMP4) (p = 0.0083) and BMP7 (p = 0.0330) decreased in RG2 and peroxisome proliferator-activated receptor co-activator-1α (PGC-1α) reduced in RG2 and RG1. Conclusion: Our observations support that repression of regulatory factors promoting differentiation and development results in the inhibition of BAT maturation in fetal perirenal fat during late pregnancy with maternal undernutrition.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.246-256
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• 2022

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 µM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7r-NLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

• Molecules and Cells
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• v.39 no.7
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• pp.543-549
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• 2016

MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neuro-degenerative diseases, Parkinson's disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, ${\beta}$-amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes involved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$(PGC-$1{\alpha}$), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process.

• Korean Journal of Breeding Science
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• v.41 no.3
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• pp.236-243
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• 2009

This study was conducted to develop a japonica-type rice cultivar with brown planthopper (BPH) resistance using DNA markers. A doubled haploid (DH) population consisting of 120 pure-lines was established by anther culture of $F_1$ hybrids between 'Samgang', a Tongil type BPH resistance cultivar, and 'Nagdong', a japonica cultivar. To determine the map position of genes responsible for BPH resistance in rice, a genetic map was constructed based on 120 DH lines. A total of 162 molecular markers were classified into 12 linkage groups, covering 1,884 Kosami centimorgan (cM) with an average of 11.6 cM. Five QTLs (qBPR3, qBPR6, qBPR7, qBPR8, and qBPR12) associated with BPH resistance were identified and mapped on chromosomes 3, 6, 7, 8, and 12, respectively, using the genetic map constructed in this study. To analyze the relationship between BPH resistance and agronomic traits, a total of eight QTLs related to the agronomic traits were detected on 12 rice chromosomes. In an analysis of relationships, three QTLs (qBPR3, qBPR7, and qBPR8) showed a linkage with tested agronomic traits. A QTL (qBPR3) located on chromosome 3 (RM282-3023) was closely linked to culm length (qCL3). The QTL (qBPR8) for BPH resistance on the short arm of chromosome 8 also overlapped the region detected in culm length (qCL8).

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.7
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• pp.1012-1020
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• 2013

The objective of this study was to investigate the effect of dietary supplementation with thiazolidinedione (TZD) on growth performance and meat quality of finishing pigs. In Experiment 1, 80 castrated finishing pigs (Large White${\times}$Landrace, BW = 54.34 kg) were randomly assigned to 2 treatments with 5 replicates of 8 pigs each. The experimental pigs in the 2 groups were respectively fed with a diet with or without a TZD supplementation (15 mg/kg). In Experiment 2, 80 castrated finishing pigs (Large White${\times}$Landrace, BW = 71.46 kg) were divided into 2 treatments as designed in Experiment 1, moreover, carcass evaluations were performed. The results from Experiment 1 showed that TZD supplementation could significantly decreased the average daily feed intake (ADFI) (p<0.05) during 0 to 28 d, without impairing the average daily gain (ADG) (p>0.05). In Experiment 2, the ADG was significantly increased by TZD supplementation during 14 to 28 d and 0 to 28 d (p<0.05) and the feed:gain ratio (F:G) was significantly decreased by TZD supplementation during 0 to 28 d (p<0.05). Compared with the control group, TZD group had significantly higher serum triglyceride (TG) concentration at 28h and serum high-density lipoprotein (HDL) levels at 14 d (p<0.05). Moreover, there was an apparent improvement in the marbling score (p<0.10) and intramuscular fat (IMF) content (p<0.10) of the longissimus dorsi muscle in pigs treated by TZD supplementation. Real-time RT-PCR analyses demonstrated that pigs of TZD group had higher mRNA abundance of $PPAR{\gamma}$ coactivator 1 (PGC-1) (p<0.05) and fatty acid-binding protein 3 (FABP3) (p<0.05) than pigs of control group. Taken together, these results suggested that dietary TZD supplementation could improve growth performance and increase the IMF content of finishing pigs through regulating the serum parameters and genes mRNA abundance involved in fat metabolism.

• Journal of the Korean Applied Science and Technology
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• v.37 no.4
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• pp.744-754
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• 2020

We investigated the whether endurance exercise and MitoQ intake mediated neuroprotection are associated with mitochondrial function in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine(MPTP) -induced mice model of Parkinson's disease. C57BL/6 male mice were randomly assigned to five groups: Normal Conrol(NC, n=10), MPTP Control(MC, n=10), MPTP +MitoQ(MQ, n=10), MPTP + Exercise(ME, n=10) and MPTP + MitoQ + Exercise(MQE, n=10). Exercise intervention groups performed the treadmill exercise for 5days/week for 5 weeks with gradual increase of intensity. MitoQ intake groups consumed the MitoQ at a concentration of 250μmol by dissolving with water during experiment period. Our data demonstrated that ME and MQE group restored MPTP-induced motor dysfunction. In addition, treatment groups(MQ, ME and MQE) increased tyrosine hydroxylase levels, and suppressed the accumulation of α-synuclein levels. Futhermore, treatment groups modulated the mitochondrial function such as upregulated mitochondrial biogenesis, increased antioxidant enzyme, enhanced a anti-apoptotic protein(e.g., BCL2), and reduced a pro-apoptotic protein(e.g., BAX). Taken together, these results suggested that endurance exercise and MitoQ intake-mediated increase in mitochondrial function contributes to improvement of aggravated dopaminergic neuronal, resulting in attenuation of motor function of Parkinson's disease.

• Journal of Korean Clinical Health Science
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• v.2 no.1
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• pp.35-45
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• 2014

Purpose: This study analyzes occupational therapy interventions to improve activities of daily living (ADL) in dementia patients and the instruments used to verify their effects through a systematic review and attempts to use the results as preliminary data in selecting further interventions and instruments. Method: The databases searched included NDSL, DBpia, RISS, KISS and National Assembly Library with search words including 'Alzheimer's disease', 'Alzheimer', 'daily living' and 'ADL.' The subjects of analysis were a total of 7 studies, and a frequency analysis was used for the usage count of the interventions used in each study. In order to provide evidence, PICO Method was used for sorting. Result: As a result of this study, there were 7 occupational therapy interventions applied to improve ADL in dementia patients, which were used 7 times total. As for the instruments used to validate the effects of the interventions for the ADL, it turned out that '3 studies used AMPS (42.9%),' which was the most, followed by 'Allen Cognitive Level Screen' (ACLS) and Functional Independence Measure' (FIM), respectively used in 2 studies (28.6%); and 'Modified Barthel Index' (MBI) and 'Philadelphia Geriatric Center IADL' (PGC IADL), respectively used in 1 study. Regarding the qualitative level of evidence, it turned out that 4 studies were Level III (57.1%), followed by 2 studies at Level IV (28.6%) and 1 study at Level I (14.3%). Conclusion: This study suggested the kinds and frequencies of usage of the interventions and instruments of occupational therapy for the improvement of ADL in dementia patients, and the studies of evidence were presented by the PICO Method. It is judged that the results of this study can be used as preliminary data in selecting interventions and instruments to improve the ADL in dementia patients. In the future, studies should be carried out on the ADL in other areas related to dementia.

• Journal of the Korean Chemical Society
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• v.10 no.4
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• pp.166-174
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• 1966

The multistep mechanism of photosensitized curing reaction cinnamoylated photosensitive polymer is proposed from the energy level diagram of cinnamic acid and sensitizer, and from the fact that excess of sensitizer brings the sensitivity to a limiting value etc. Various factors which have effects on the ability of sensitizer are also discussed. The mechanism involves following steps: activation to the first excited singlet states of cinnamoyl group(C) and sensitizer(S) by their absorption of photon, their intersystem crossing to the lowest triplet state, bimolecular internal quenching by formation of excimer of sensitizer, triplet excitation energy transfer and intermolecular addition between cinnamoyl group in ground state and that in triplet state. The rate equation derived from this mechanism is $-\frac{d[C]}{dt} = \frac{K_1[C]}{K_2 + [C]}[\frac{I^c_{abs}}{K_3 + [S]} + \frac{K_4[C]}{(K_5 + [C])(K_6 + [S])}(I^s_{abs} + \frac{K_7I^c_{abs}[S]}{K_8 + [S]})]$ where $I^c_{abs}\;and\;I^s_{abs}$: the rates of absorption of photon by cinnamoyl group and sensitizer $K_n$: Constants. It is proved with the cinnamate of poly(glyceryl phthalate)(PGC) in the absence of sensitizer using the infrared analytical method and successfully applied for the experimental data reported on the effects of the degree of cinnamoyl esterification and the concentration of sensitizer upon the sensitivity.