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        DJ-1 protects cell death from a mitochondrial oxidative stress due to GBA1 deficiency

        Nam Younwoo,Na Jiyeon,Ma Shi-Xun,Park Ha-Eun,Park Hyeonwoo,Lee Eunmin,Kim Hyerynn,Jang Sang-Min,Ko Han Seok,Kim Sangjune 한국유전학회 2024 Genes & Genomics Vol.46 No.5

        Background GBA1 mutations are the most common genetic risk factor for development of Parkinson’s disease (PD). The loss of catalytic activity in GBA1, as well as the reduction of the GBA1 protein in certain cellular compartment, may increase disease progression. However, the mechanisms underlying cellular dysfunction caused by GBA1 deficiency are still mostly unknown. Objective In this study, we focus on the genetic interaction between GBA1 deficiency and PD-causing genes, such as DJ-1, in mitochondrial dysfunction. Methods GBA1 knockout (KO) SH-SY5Y cells were used to assess DJ-1 functions against oxidative stress in vitro. The levels of cellular reactive oxygen species were monitored with MitoSOX reagent. The expression of the PARK7 gene was analyzed using the quantitative real-time PCR (qRT-PCR). To understand the mechanism underlying DJ-1 upregulation in GBA1 KO cells, we assess ROS levels, antioxidant protein, and cell viability in GBA1 KO cells with treatment of ROS inhibitor N-acetyl-cysteine or miglustat, which is an inhibitor of glucosylceramide synthase. Dopaminergic degeneration was assessed from Gba1 L444P heterozygous mice mated with Park7 knockout mice. Results We find that DJ-1 is significantly upregulated in GBA1 KO cells. Elevated levels of DJ-1 are attributed to the transcriptional expression of PARK7 mRNA, but not the inhibition of DJ-1 protein degradation. Because DJ-1 expression is highly linked to oxidative stress, we observe cellular reactive oxygen species (ROS) in GBA1 KO cells. Moreover, several antioxidant gene expressions and protein levels are increased in GBA1 KO cells. To this end, GBA1 KO cells are more susceptible to H2O2-induced cell death. Importantly, there is a significant reduction in dopaminergic neurons in the midbrain from Gba1 L444P heterozygous mice mated with Park7 knockout mice, followed by mild motor dysfunction. Conclusion Taken together, our results suggest that DJ-1 upregulation due to GBA1 deficiency has a protective role against oxidative stress. It may be supposed that mutations or malfunctions in the DJ-1 protein may have disadvantages in the survival of dopaminergic neurons in the brains of patients harboring GBA1 mutations. Background GBA1 mutations are the most common genetic risk factor for development of Parkinson’s disease (PD). The loss of catalytic activity in GBA1, as well as the reduction of the GBA1 protein in certain cellular compartment, may increase disease progression. However, the mechanisms underlying cellular dysfunction caused by GBA1 deficiency are still mostly unknown. Objective In this study, we focus on the genetic interaction between GBA1 deficiency and PD-causing genes, such as DJ-1, in mitochondrial dysfunction. Methods GBA1 knockout (KO) SH-SY5Y cells were used to assess DJ-1 functions against oxidative stress in vitro. The levels of cellular reactive oxygen species were monitored with MitoSOX reagent. The expression of the PARK7 gene was analyzed using the quantitative real-time PCR (qRT-PCR). To understand the mechanism underlying DJ-1 upregulation in GBA1 KO cells, we assess ROS levels, antioxidant protein, and cell viability in GBA1 KO cells with treatment of ROS inhibitor N-acetyl-cysteine or miglustat, which is an inhibitor of glucosylceramide synthase. Dopaminergic degeneration was assessed from Gba1 L444P heterozygous mice mated with Park7 knockout mice. Results We find that DJ-1 is significantly upregulated in GBA1 KO cells. Elevated levels of DJ-1 are attributed to the transcriptional expression of PARK7 mRNA, but not the inhibition of DJ-1 protein degradation. Because DJ-1 expression is highly linked to oxidative stress, we observe cellular reactive oxygen species (ROS) in GBA1 KO cells. Moreover, several antioxidant gene expressions and protein levels are increased in GBA1 KO cells. To this end, GBA1 KO cells are more susceptible to H2O2-induced cell death. Importantly, there is a significant reduction in dopaminergic neurons in the midbrain from Gba1 L444P heterozygous mice mated with Park7 knockout mice, followed by mild motor dysfunction. Conclusion Taken together, our results suggest that DJ-1 upregulation due to GBA1 deficiency has a protective role against oxidative stress. It may be supposed that mutations or malfunctions in the DJ-1 protein may have disadvantages in the survival of dopaminergic neurons in the brains of patients harboring GBA1 mutations.

      • Effect of Korean Herbal Medicine Combined with a Probiotic Mixture on Diarrhea-Dominant Irritable Bowel Syndrome: A Double-Blind, Randomized, Placebo-Controlled Trial

        Ko, Seok-Jae,Han, Gajin,Kim, Seul-Ki,Seo, Jae-Gu,Chung, Won-Seok,Ryu, Bongha,Kim, Jinsung,Yeo, Inkwon,Lee, Beom-Joon,Lee, Jin-Moo,Park, Jae-Woo Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

        <P><I>Introduction</I>. Although combination therapy with herbal medicine and probiotics is gaining popularity for controlling diarrhea-dominant irritable bowel syndrome (D-IBS) symptoms, few studies have investigated its clinical effects. <I>Materials and Methods</I>. Fifty-three patients with D-IBS were randomly allocated into 1 of the following 4 groups: herbal medicine (<I>Gwakhyangjeonggisan</I>; GJS) plus probiotics (Duolac7S; DUO), GJS plus placebo DUO, placebo GJS plus DUO, and placebo GJS plus placebo DUO. The study period consisted of a 2-week run-in, 8 weeks of administration, and 2 weeks of follow-up. The primary outcomes were weekly adequate relief (AR) of overall IBS symptoms and the proportion of responders (PR) during the administration period. The secondary outcomes included individual IBS symptoms, stool assessment, and quality of life. Changes of intestinal microbiota and intestinal permeability were also analyzed. <I>Results and Discussion</I>. Weekly AR was not different among the 4 groups throughout the treatment period. However, the 3 treatment groups exhibited significant improvements in PR compared to the findings in the placebo group. In the intestinal microbiota assessment, herbal medicine and probiotics synergistically increased beneficial bacteria counts. <I>Conclusion</I>. Combination therapy with herbal medicine and probiotics appears to relieve overall IBS symptoms by synergistically increasing beneficial intestinal microbe counts.</P>

      • Effect of Underlayer, CoFeB Composition and Annealing Temperature on Perpendicular Magnetic Anisotropy of CoFeB

        Han Seok Ko,Taehyun Kim,Jiyoung Lee,Young Keun Kim 한국자기학회 2021 한국자기학회 학술연구발표회 논문개요집 Vol.31 No.1

        Recently, magnetic random access memory (MRAM) is getting attention as a next-generation memory device due to its high speed performance, low power consumption and long life span. Among several elements that consist of MRAM, magnetic tunnel junction (MTJ) structure is the most essential part as it directly governs writing and reading mechanism of MRAM. As MTJ with perpendicular magnetic anisotropy (PMA) have advantage of small switching current density over in-plane magnetic anisotropy MTJ, magnetic materials exhibiting perpendicular magnetic anisotropy (PMA) have attracted a lot of research interest [1]. Although previous studies presented several ferromagnetic material systems exhibiting PMA characteristics, including rare-earth transition-metal alloys, the MTJs with these alloys loss PMA after post-annealing process above 200℃ [2]. Among the potential candidates, CoFeB/MgO is one of the most promising candidates with strong PMA even after 300oC post-deposition annealing process [3]. Here, we investigate the magnitude of PMA in underlayer/Co<sub>x</sub>Fe<sub>1-x</sub>B/MgO structure by varying the materials of underlayer, composition of Co and Fe of CoFeB alloy and annealing temperature. Two different underlayers of W and Ta, which are known for their large spin-orbit coupling are used in this experiment [4]. Co<sub>40</sub>Fe<sub>40</sub>B<sub>20</sub> and Co<sub>20</sub>Fe<sub>60</sub>B<sub>20</sub> are used to compare their PMA characteristics. Co<sub>40</sub>Fe<sub>40</sub>B<sub>20</sub> is known to be advantageous over Co<sub>20</sub>Fe<sub>60</sub>B<sub>20</sub>as it requires small switching current density due to its small saturation magnetization (M<sub>s</sub>) [5] and Co<sub>20</sub>Fe<sub>60</sub>B<sub>20</sub> is well known for its strong PMA [6]. Furthermore, 300℃ and 400℃ annealing temperatures were selected to examine each sample’s thermal annealing stability since the temperature is maintained at 300℃-400℃ during the back-end-of-line process. Microstructures of Ta and W were evaluated using X-ray diffraction (XRD). In the case of W underlayer, Co<sub>40</sub>Fe<sub>40</sub>B<sub>20</sub> exhibited PMA at 300℃ and 400℃, while Co<sub>20</sub>Fe<sub>60</sub>B<sub>20</sub> exhibited PMA only at 400℃. In the case of Ta underlayer, Co<sub>40</sub>Fe<sub>40</sub>B<sub>20</sub> exhibited PMA at 300oC but it vanished at 400℃. The PMA characteristics of Co<sub>20</sub>Fe<sub>60</sub>B<sub>20</sub> with Ta underlayer was strong 300℃ and weakened at 400℃. In addition, to investigate the effect of the annealing condition, 400℃ annealing process was divided into three methods, direct 400℃annealing process, 300℃ annealing followed by 400oC heat annealing, and 200℃ annealing followed by 300℃ annealing and then 400℃ annealing. However, all these three processes showed the same result. From the experimental results, we have shown a rough guideline for selecting material combinations at different annealing temperatures with PMA.

      • KCI등재

        감염된 인공 고관절의 치료

        고한석 ( Han Seok Ko ),배우한 ( Woo Han Bae ) 대한고관절학회 2010 Hip and Pelvis Vol.22 No.2

        인공 고관절 치환술 후 발생하는 심부 감염은 술 후 발생하는 합병증 중에서 가장 심각한 것이다. 인공 고관절의 감염이 있는 경우 항생제의 치료에 반응하지 않아 염증에 대한 치료가 어려운 경우가 많다. 인공 고관절 전치환술 후에 발생하는 감염은 예방적 항생제 투여 및 수술기구 및 수술실 환경의 소독, 그리고 적절한 환자 선택 및 수술 방법의 발달로 인해 감소하고 있다. 그러나 아직도 1차 수술 이후 및 재수술 이후에 1~2%의 감염률을 보이고 있다. 따라서 본 연구에서는 고관절 전치환술을 시행하는데 있어 감염을 일으키는 원인 및 환경 그리고 감염의 진단 및 치료에 대하여 여러 문헌을 통하여 알아보고자 하였다. Deep infection after total hip arthroplasty is one of the most serious post operative complications. Treatment of infection of the hip joint can be made very difficult by poor response to antibiotic therapy. Infection rates of total hip arthroplasty have decreased due to prophylactic antibiotics, sterilization of surgical instruments, cleaner operation environments, Improvement of surgical methods and proper patient selection. Recently, post operative infection rates of primary or revision arthroplasties were reported to still be as high as 1% to 2%. Therefore, the aim of this article is to review the recent literature and to evaluate the cause, environment diagnosis and treatment of infection after total hip arthroplasty.

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