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박수빈 ( Soo Been Park ),문미라 ( Mira Moon ),김현화 ( Hyun Hwa Kim ),박가윤 ( Ga-Yoon Park ),강동윤 ( Dong Yoon Kang ),이주연 ( Ju-yeun Lee ),조윤숙 ( Yoon Sook Cho ),강혜련 ( Hye-ryun Kang ),조상헌 ( Sang-heon Cho ) 대한내과학회 2021 대한내과학회지 Vol.96 No.4
목적: 의약품의 적절한 사용에도 불구하고 약물이상반응(ADR)은 발생할 수 있으며, 이는 환자의 안전과 직접적으로 관련된 문제를 야기할 수 있다. 이 연구의 목적은 단일 3차 의료기관에서 약물이상반응과 중대한 이상사례의 특성을 분석하는 것이다. 방법: 서울대학교병원 약물안전센터에 2010년 1월 1일부터 2019년 12월 31일까지 보고된 약물이상반응 평가자료를 분석하였다. 약물 사용과 이상사례 발생의 인과성은 세계보건기구 웁살라 모니터링센터(World Health Organization-Uppsala Monitoring Centre, WHO-UMC) 인과성 평가 기준을 기반하여 확실함(certain), 가능성 높음(probable), 가능성 있음(possible)으로 평가된 사례들만 분석에 포함하였다. 연령, 성별, 증상 발생 시기, 중증도 및 위중도 그리고 약물이상반응, 중대한 이상사례의 신체기관계 분류가 분석되었다. 결과: 연구 기간 동안 총 49,955건의 약물이상반응 평가지가 가능성 있음, 가능성 높음, 확실함으로 평가되었다. 위장관계 증상(25.9%)은 전체 보고 건수에 비해 중증(2.6%)의 비율이 낮았던 반면, 혈액학적 질환(6.6%)은 중증(39.2%)의 비율이 상대적으로 높았다. 약물이상반응 중 10.2%가 중대한 이상사례로 평가되었으며, 양 극단의 연령대에서 중대한 이상사례의 비율이 높았다. 신체기관계 분류로 분류하였을 때는 전신 질환이 가장 많이 보고되었으며 그 뒤로 피부와 부속기관 장애가 많았다. 항암제와 항생제가 중대한 유해사례의 의심약제로 가장 많이 보고되었다. 아나필락시스 반응이 가장 흔한 중대한 이상사례였다(6.5%). 결론: 중대한 이상사례의 비율은 신체기관계 분류와 약제 별로 다르게 나타났다. 양 극단의 연령대에서 중대한 유해사례의 비율이 높았으므로 어린이와 노인에서는 잠재적인 중대한 유해사례가 발생할 가능성이 있어 세심한 주의가 필요하다. Background/Aims: Despite proper use of pharmaceuticals, adverse drug reactions (ADRs) can lead to problems related to patient safety. We analyzed the characteristics of ADRs, particularly serious adverse events (SAEs), in a single tertiary medical institution. Methods: Spontaneous ADR report data collected from 2010 to 2019 in Seoul National University Hospital were assessed. Causality was evaluated according to the World Health Organization-Uppsala Monitoring Centre criteria. Age, sex, onset, severity, seriousness, and system organ class (SOC) of ADRs and SAEs were analyzed. Results: During the study period, a total of 49,955 individual case safety reports were assessed as possible, probable, or certain. Although the number of gastrointestinal ADR reports was high (25.9%), severe cases were uncommon (2.6%). By contrast, the number of hematologic disorders was low (6.6%) but 39.2% of them were severe. Among ADRs, 10.2% were assessed as SAEs, the proportion of which was high at extreme ages and in males. Body as a whole-general disorders were the most frequently reported SOC for SAEs, followed by skin and appendage disorders. Antineoplastic agents and antibiotics were the most common causative agents of SAEs and ADRs. Anaphylactic reaction was the most frequent SAE (6.5%). Conclusions: The proportion of SAE differs according to SOC and drug. Attention should be paid to SAEs in children and older adults because the rate of SAEs is significantly higher at extreme ages. (Korean J Med 2021;96:341-351)
PSME4 determines mesenchymal stem cell fate towards cardiac commitment through YAP1 degradation
Mira Kim,Yong Sook Kim,Youngkeun Ahn,Gwang Hyeon Eom,Somy Yoon The Korean Society of Pharmacology 2023 The Korean Journal of Physiology & Pharmacology Vol.27 No.4
The regeneration of myocardium following acute circulatory events remains a challenge, despite numerous efforts. Mesenchymal stem cells (MSCs) present a promising cell therapy option, but their differentiation into cardiomyocytes is a time-consuming process. Although it has been demonstrated that PSME4 degrades acetyl-YAP1, the role of PSME4 in the cardiac commitment of MSCs has not been fully elucidated. Here we reported the novel role of PSME4 in MSCs cardiac commitment. It was found that overnight treatment with apicidin in primary-cultured mouse MSCs led to rapid cardiac commitment, while MSCs from PSME4 knock-out mice did not undergo this process. Cardiac commitment was also observed using lentivirus-mediated PSME4 knockdown in immortalized human MSCs. Immunofluorescence and Western blot experiments revealed that YAP1 persisted in the nucleus of PSME4 knockdown cells even after apicidin treatment. To investigate the importance of YAP1 removal, MSCs were treated with shYAP1 and apicidin simultaneously. This combined treatment resulted in rapid YAP1 elimination and accelerated cardiac commitment. However, overexpression of acetylation-resistant YAP1 in apicidin-treated MSCs impeded cardiac commitment. In addition to apicidin, the universal effect of histone deacetylase (HDAC) inhibition on cardiac commitment was confirmed using tubastatin A and HDAC6 siRNA. Collectively, this study demonstrates that PSME4 is crucial for promoting the cardiac commitment of MSCs. HDAC inhibition acetylates YAP1 and facilitates its translocation to the nucleus, where it is removed by PSME4, promoting cardiac commitment. The failure of YAP1 to translocate or be eliminated from the nucleus results in the MSCs' inability to undergo cardiac commitment.
Yoon, Jeong-Hyun,Youn, Kumju,Ho, Chi-Tang,Karwe, Mukund V.,Jeong, Woo-Sik,Jun, Mira American Chemical Society 2014 Journal of agricultural and food chemistry Vol.62 No.21
<P>Neuroinflammatory responses induced by amyloid-beta peptide (Aβ) are important causes in the pathogenesis of Alzheimer’s disease (AD). Blockade of Aβ has emerged as a possible therapeutic approach to control the onset of AD. This study investigated the neuroprotective effects and molecular mechanisms of <I>p</I>-coumaric acid (<I>p</I>-CA) and ursolic acid (UA) from <I>Corni fructus</I> against Aβ<SUB>25–35</SUB>-induced toxicity in PC12 cells. <I>p</I>-CA and UA significantly inhibited the expression of iNOS and COX-2 in Aβ<SUB>25–35</SUB>-injured PC12 cells. Blockade of nuclear translocation of the p65 subunit of nuclear factor κB (NF-κB) and phosphorylation of IκB-α was also observed after <I>p</I>-CA and UA treatment. For the upstream kinases, UA exclusively reduced ERK1/2, p-38, and JNK phosphorylation, but <I>p</I>-CA suppressed ERK1/2 and JNK phosphorylation. Both compounds comprehensively inhibited NF-κB activity, but possibly with different upstream pathways. The results provide new insight into the pharmacological modes of <I>p</I>-CA and UA and their potential therapeutic application to AD.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jafcau/2014/jafcau.2014.62.issue-21/jf501314g/production/images/medium/jf-2014-01314g_0005.gif'></P>
Yoon, Junchul David,Hwang, Seon-Ung,Kim, Mirae,Jeon, Yubyeol,Hyun, Sang-Hwan Society for the Study of Reproduction [etc.] 2019 BIOLOGY OF REPRODUCTION Vol.101 No.1
<P> Growth differentiation factor 8 (GDF8), also known as myostatin, is a member of the transforming growth factor-β (TGF-β) family and has been identified as a strong physiological regulator of muscle differentiation. Recently, the functional role of GDF8 in reproductive organs has received increased interest following its detection in the human placenta and uterus. To investigate the effects of GDF8 during porcine oocyte in vitro maturation (IVM), we assessed the quality of matured oocytes. Furthermore, we investigated the specific gene transcription and protein activation levels in oocytes and cumulus cells after IVM and subsequent embryonic development after in vitro fertilization and parthenogenetic activation. Prior to these experiments, the concentration of GDF8 in porcine follicular fluid was determined. During the entire IVM period, 1.3 ng/mL GDF8 and its signaling inhibitor SB431542 (SB) at 5 μM were added as control, SB, SB + GDF8, and GDF8 groups, respectively. Our results demonstrate that supplementation with GDF8 during porcine oocyte IVM enhanced both meiotic and cytoplasmic maturation, with altered transcriptional patterns, via activation of Sma- and Mad-related protein 2/3 (SMAD2/3). Using the pharmacological inhibitor SB431542, we demonstrated that inhibition of GDF8-induced Smad2/3 signaling reduces matured oocyte quality. In conclusion, for the first time, we demonstrated paracrine factor GDF8 in porcine follicular fluid in vivo. Furthermore, we showed that GDF8 supplementation improved mature oocyte quality by regulating p38 mitogen-activated protein kinase phosphorylation and intracellular glutathione and reactive oxygen species levels during porcine IVM. </P>
Mira Choo,JungA Hwang,SangWon Jeon,SoYoung Oh,Hokyoung Yoon,HeonJeong Lee,YongKu Kim 대한신경정신의학회 2015 PSYCHIATRY INVESTIGATION Vol.12 No.4
Objective-We aimed to investigate possible associations between three norepinephrine transporter gene (SLC6A2) single nucleotide polymorphisms (T182C, A3081T, and G1287A) and schizophrenia. Also, we investigated the relationships of those polymorphisms with clinical severity and characteristics of schizophrenia. Methods-Participants were 220 schizophrenia patients in the acute phase and 167 healthy controls. The genotype, allele frequency, and haplotype of each group were analyzed for T182C, A3081T, and G1287A polymorphisms. Of the 220 schizophrenia patients, 163 patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Korean version of the Calgary depression scale for schizophrenia (K-CDSS) at baseline. Results-We found no significant differences between the schizophrenia patient group and the control group in genotype distribution or allele frequency of the three tested polymorphisms. Likewise, we could not find any significant differences in genotype or allele frequency by analyzing according to gender. In the haplotype study, no significant association emerged between specific haplotype combinations and schizophrenia. We also found no association between clinical scales (PANSS and K-CDSS) and the studied polymorphisms. Conclusion-Our results suggest that the investigated polymorphisms of the NET gene are not associated with susceptibility to schizophrenia or its clinical features in a Korean population. However, this study remains significant because it is the first haplotype study to investigate associations between NET gene (SLC6A2) single nucleotide polymorphisms and schizophrenia in a Korean population. Future research with a larger sample size and more genetic markers is needed to replicate our results.