• Title/Summary/Keyword: miR-194-5p

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circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis

  • Kaiyun Qin;Fenghua Zhang;Hongxia Wang;Na Wang;Hongbing Qiu;Xinzhuan Jia;Shan Gong;Zhengmao Zhang
    • BMB Reports
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    • v.56 no.3
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    • pp.184-189
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    • 2023
  • Ovarian cancer (OC) is the most common gynecological malignancy worldwide, and chemoresistance occurs in most patients, resulting in treatment failure. A better understanding of the molecular processes underlying drug resistance is crucial for development of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucial roles in tumorigenesis and resistance to chemotherapy. However, little is known about the role(s) of circRNAs in regulating ferroptosis in OC. To gain insights into cisplatin resistance in OC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissues that were susceptible or resistant to cisplatin using quantitative real-time PCR. We also conducted in vitro and in vivo assays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cells more sensitive to cisplatin in vitro and in vivo by activating ferroptosis, which was at least partially abolished by downregulation of miR-194-5p. Molecular mechanics studies indicate that circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in OC.

miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone

  • Lee, Su-Yeon;Kang, Youn-Jung;Kwon, Jinie;Nishi, Yoshihiro;Yanase, Toshihiko;Lee, Kyung-Ah;Koong, Mi Kyoung
    • Clinical and Experimental Reproductive Medicine
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    • v.47 no.3
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    • pp.194-206
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    • 2020
  • Objective: The aim of this study was to investigate microRNAs (miRNAs) related to follicle-stimulating hormone (FSH) responsiveness using miRNA microarrays and to identify their target genes to determine the molecular regulatory pathways involved in FSH signaling in KGN cells. Methods: To change the cellular responsiveness to FSH, KGN cells were treated with FSH receptor (FSHR)-specific small interfering RNA (siRNA) followed by FSH. miRNA expression profiles were determined through miRNA microarray analysis. Potential target genes of selected miRNAs were predicted using bioinformatics tools, and their regulatory function was confirmed in KGN cells. Results: We found that six miRNAs (miR-1261, miR-130a-3p, miR-329-3p, miR-185-5p, miR-144-5p and miR-4463) were differentially expressed after FSHR siRNA treatment in KGN cells. Through a bioinformatics analysis, we showed that these miRNAs were predicted to regulate a large number of genes, which we narrowed down to cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and estrogen receptor alpha (ESR1) as the main targets for miR-4463. Functional analysis revealed that miR-4463 is a regulatory factor for aromatase expression and function in KGN cells. Conclusion: In this study, we identified differentially expressed miRNAs related to FSH responsiveness. In particular, upregulation of miR-4463 expression by FSHR deficiency in human granulosa cells impaired 17β-estradiol synthesis by targeting CYP19A1 and ESR1. Therefore, our data might provide novel candidates for molecular biomarkers for use in research into poor responders.

Parenting Stress, Maternal Sensitivity to Infant Cues and Child Rearing Environment of First-time Mothers (초산모의 양육스트레스, 영아신호에 대한 민감성, 양육환경)

  • Kim Hee-Soon;Shin Yeong-Hee;Oh Ka-Sil;Kim Tae-Im;Sim Mi-Kyung
    • Child Health Nursing Research
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    • v.11 no.4
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    • pp.415-426
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    • 2005
  • Purpose: The purpose of this study was to identify relations among the parenting stress, maternal sensitivity to infant cues, parenting environment of first-time mothers. Method: The participants were 194 first-time mothers of babies aged 1-6 months who visited well-baby clinics in 5 hospitals. The data were collected from April 15 to June 15, 2003. Results: The parenting stress level was moderate with a mean score of 2.4(range 1-5). The parent domain and parent-child relationship domain of the parenting stress scale were significantly correlated with maternal sensitivity to infant feeding cues (r=-.178, p<.05; r=-.197, p<.01). Parenting stress was significantly correlated with childrearing environment(r=-2.19, p<.01). Parenting stress and childrearing environment were significantly different according to the educational level of the mothers and their prenatal care. Conclusions: Nursing interventions to reduce parenting stress in first-time mothers are needed to improve maternal sensitivity to infant cues and childrearing environment which foster infant development.

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Functional Significance of Cytochrome P450 1A2 Allelic Variants, P450 1A2*8, *15, and *16 (R456H, P42R, and R377Q)

  • Lim, Young-Ran;Kim, In-Hyeok;Han, Songhee;Park, Hyoung-Goo;Ko, Mi-Jung;Chun, Young-Jin;Yun, Chul-Ho;Kim, Donghak
    • Biomolecules & Therapeutics
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    • v.23 no.2
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    • pp.189-194
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    • 2015
  • P450 1A2 is responsible for the metabolism of clinically important drugs and the metabolic activation of environmental chemicals. Genetic variations of P450 1A2 can influence its ability to perform these functions, and thus, this study aimed to characterize the functional significance of three P450 1A2 allelic variants containing nonsynonymous single nucleotide polymorphisms (P450 $1A2^*8$, R456H; $^*15$, P42R; $^*16$, R377Q). Variants containing these SNPs were constructed and the recombinant enzymes were expressed and purified in Escherichia coli. Only the P42R variant displayed the typical CO-binding spectrum indicating a P450 holoenzyme with an expression level of ~ 170 nmol per liter culture, but no P450 spectra were observed for the two other variants. Western blot analysis revealed that the level of expression for the P42R variant was lower than that of the wild type, however the expression of variants R456H and R377Q was not detected. Enzyme kinetic analyses indicated that the P42R mutation in P450 1A2 resulted in significant changes in catalytic activities. The P42R variant displayed an increased catalytic turnover numbers ($k_{cat}$) in both of methoxyresorufin O-demethylation and phenacetin O-deethylation. In the case of phenacetin O-deethylation analysis, the overall catalytic efficiency ($k_{cat}/K_m$) increased up to 2.5 fold with a slight increase of its $K_m$ value. This study indicated that the substitution P42R in the N-terminal proline-rich region of P450 contributed to the improvement of catalytic activity albeit the reduction of P450 structural stability or the decrease of substrate affinity. Characterization of these polymorphisms should be carefully examined in terms of the metabolism of many clinical drugs and environmental chemicals.

Anti-obesity Effect of Sargassum confusum Ethanol Extract in Obese Rats (알쏭이모자반 주정추출물의 항비만 효과)

  • Jang, Yu-Jung;Kwon, Sang-Oh;Yeo, Kyung-Mok;Hong, Mi-Jung;Kim, Bok-Nam;Han, Dae-Seok
    • Korean Journal of Food Science and Technology
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    • v.43 no.2
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    • pp.189-194
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    • 2011
  • Effect of Sargassum confusum extract on the reduction of body weight gain and lipid contents in obese rats were evaluated to find natural materials with anti-obesity benefits. After inducing obesity by feeding 42.5% high-fat diet for 5 weeks, each 10 Sprague-Dawley rats were randomly assigned to high-fat diet control (HFD) group and high-fat diet group containing 3% Sargassum confusum extract (HFDSC). Weight gain of HFD group ($2.96{\pm}0.31g/day$) was significantly (p<0.05) higher as compared to that of normal diet (ND) group ($2.19{\pm}0.17g/day$). Weights of adipose tissues of HFD group were higher than those of ND group. Body weight gain of HFDSC group, however, was $2.36{\pm}0.24g/day$, which was significantly (p<0.05) lower by 21% than that of HFD group. In addition, weights of epididymal and perirenal adipose tissues were lower by 15% and 16%, respectively, as compared to those of HFD group. Biochemical analyses showed that concentration of triglyceride, total cholesterol, and fatty acids were significantly (p<0.05) lower in HFDSC group. These results suggest that Sargassum confusum extract has a high potential as an anti-obesity material by reducing weight gain and obesity-related factors in serum.

Relationship between Perception of Patient Safety Culture and Performance for Safety Care Activity in Rehabilitation Hospital Nurse (재활전문병원 간호사의 환자안전문화에 대한 인식과 안전간호활동 수행의 관계)

  • Kang, Jung Mi;Park, Jung Suk
    • The Korean Journal of Rehabilitation Nursing
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    • v.19 no.1
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    • pp.12-19
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    • 2016
  • Purpose: This study was to examine the relationships between nurse's perception of patient safety culture and performance for safety nursing activities at rehabilitation hospitals. Methods: This study applied a descriptive research design. Participants were 194 nurses who have provided nursing services for more than 6 months at 4 rehabilitation hospitals located in B metropolitan city. Data were analyzed using descriptive statistics, t-test, ANOVA, $Scheff{\acute{e}}$ test, Pearson's correlation coefficients and multiple regression. Results: There was a positive correlation between the awareness of patient safety culture and safety nursing activity. Multivariate analysis showed that hospital work environment, experience of education, hospital climate, frequency of reported events, and marital status were significantly associated with the safety nursing activity. Overall, approximately 23.1% of total variability in the safety nursing activity could be explained by the 5 variables ($R^2=0.231$, p<.005). Conclusion: Nurses at rehabilitation hospitals are relatively positive about patient safety culture. Therefore, we need to develop safety education programs at the level of organization in order to improve patient safety through performing effective safety nursing activities in addition to increase awareness of patient safety culture among nurses. Furthermore, we need hospital's strategies at the system level for open communication and outcome reports regarding patient safety.

Comprehensive analysis of miRNAs, lncRNAs and mRNAs profiles in backfat tissue between Daweizi and Yorkshire pigs

  • Chen Chen;Yitong Chang;Yuan Deng;Qingming Cui;Yingying Liu;Huali Li;Huibo Ren;Ji Zhu;Qi Liu;Yinglin Peng
    • Animal Bioscience
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    • v.36 no.3
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    • pp.404-416
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    • 2023
  • Objective: Daweizi (DWZ) is a famous indigenous pig breed in China and characterized by tender meat and high fat percentage. However, the expression profiles and functions of transcripts in DWZ pigs is still in infancy. The object of this study was to depict the transcript profiles in DWZ pigs and screen the potential pathway influence adipogenesis and fat deposition, Methods: Histological analysis of backfat tissue was firstly performed between DWZ and lean-type Yorkshire pigs, and then RNA sequencing technology was utilized to explore miRNAs, lncRNAs and mRNAs profiles in backfat tissue. 18 differentially expressed (DE) transcripts were randomly selected for quantitative real-time polymerase chain reaction (QPCR) to validate the reliability of the sequencing results. Finally, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were conducted to investigate the potential pathways influence adipocyte differentiation, adipogenesis and lipid metabolism, and a schematic model was further proposed. Results: A total of 1,625 differentially expressed transcripts were identified in DWZ pigs, including 27 upregulated and 45 downregulated miRNAs, 64 upregulated and 119 down-regulated lncRNA, 814 upregulated and 556 downregulated mRNAs. QPCR analysis exhibited strong consistency with the sequencing data. GO and KEGG analysis elucidated that the differentially expressed transcripts were mainly associated with cell growth and death, signal transduction, peroxisome proliferator-activated receptors (PPAR), AMP-activated protein kinase (AMPK), PI3K-Akt, adipocytokine and foxo signaling pathways, all of which are strongly involved in cell development, lipid metabolism and adipogenesis. Further analysis indicated that the BGIR9823_87926/miR-194a-5p/AQP7 network may be effective in the process of adipocyte differentiation or adipogenesis. Conclusion: Our study provides comprehensive insights into the regulatory network of backfat deposition and lipid metabolism in pigs from the point of view of miRNAs, lncRNAs and mRNAs.

Effect of Cultivars and Cooking Methods on the Trypsin Inhibitor Activities of Potatoes

  • Kim, Mi-Yeon;Son, Chan-Wok;Shim, Hyun-Jung;Lee, Jeung-Hee;Lee, Kun-Jong;Sok, Dai-Eun;Kim, Hyoung-Chin;Yoon, Won-Kee;Kim, Hwan-Mook;Kim, Mee-Ree
    • Food Science and Biotechnology
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    • v.17 no.1
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    • pp.161-165
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    • 2008
  • The trypsin inhibitor activities (TIA) of various potato cultivars were evaluated by measuring the inhibition of trypsin inhibitor activity using N-benzoyl-DL-arginine-p-nitroanilide (BAPNA) as substrate. The TIA values of 5 potato cultivars (1.99 to 2.88 mg/g) were significantly different among cultivars (p<0.05). When the TIA values of commercially processed potatoes were determined, no TIA was detected. During cooking, the $IT_{50}$ (time required to reach 50% inhibition of TIA) values were decreased as heating temperature and time increased. The ITso of moist heating was estimated to be 0.34 min at $100^{\circ}C$, whereas for deep-fat frying the $IT_{50}$ was 0.13 min at $180^{\circ}C$ and 5.28 min for oven baking at $100^{\circ}C$. The $IT_{50}$ value of microwave cooking was 0.194 min at medium heat, and which was similar to that of pressure cooking at $120^{\circ}C$ (0.185 min). Moreover, there was a negative relationship between temperature (${\geq}80^{\circ}C$) and $IT_{50}$ values ($R^2=0.99$, p<0.01). The TIA of potato was completely inactivated by moist heating at $100^{\circ}C$ within 5 min, whereas the pressure cooking at $120^{\circ}C$ and deep-fat frying at $180^{\circ}C$ within 60 and 30 sec, respectively. Based on our results, deep-fat frying is the most effective cooking method to reduce TIA in potatoes.