Spectroscopic Observation of Na Cations Entrapped in Small Cages of sII Propane Hydrate

Seol, Jiwoong,Shin, Woongchul,Koh, Dong-Yeun,Kang, Hyery,Sung, Boram,Lee, Huen American Chemical Society 2012 JOURNAL OF PHYSICAL CHEMISTRY C - Vol.116 No.1

<P>Although numerous studies have been conducted on various ionic clathrate hydrates, in spite of its potential importance the inclusion of metal cations in continuous water-host frameworks has not yet been clearly identified by direct spectroscopic evidence. Here, a key question arises as to whether the small alkali metals such as Na<SUP>+</SUP> can be entrapped because they are considered to be too small to be stabilized in the hydrate cages. In this study, we first suggested spectroscopic evidence for the enclathration of Na<SUP>+</SUP> in a small cage of sII propane hydrate. First, we checked the overall structure of sII propane hydrate incorporated with NaSO<SUB>3</SUB>CH<SUB>3</SUB> and NaSO<SUB>3</SUB>NH<SUB>2</SUB> with powder XRD and <SUP>13</SUP>C NMR. Next, we revealed the difference of chemical shift of <SUP>23</SUP>Na between Ih and sII hydrate phases with solid-state <SUP>23</SUP>Na MAS NMR as direct evidence of entrapped Na<SUP>+</SUP> in 5<SUP>12</SUP> cages. In addition, we also checked <SUP>13</SUP>C MAS NMR of the CH<SUB>3</SUB>SO<SUB>3</SUB><SUP>–</SUP> anion and found that Na<SUP>+</SUP> cations in a small cage could be stabilized with an enclathrated CH<SUB>3</SUB>SO<SUB>3</SUB><SUP>–</SUP> anion in a large cage. To the best of our knowledge, it is the first discovery of small alkali cations stabilized in a continuous hydrate phase. Finally, we would like to emphasize that clathrate hydrate including small alkali metals can be designed and synthesized for its potential applications to various types of energy devices using its ionic mobility through the hydrate channel.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpccck/2012/jpccck.2012.116.issue-1/jp207450e/production/images/medium/jp-2011-07450e_0005.gif'></P>

Superoxide Ions Entrapped in Water Cages of Ionic Clathrate Hydrates

Cha, Minjun,Shin, Kyuchul,Kwon, Minchul,Koh, Dong-Yeun,Sung, Boram,Lee, Huen American Chemical Society 2010 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.132 No.11

<P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2010/jacsat.2010.132.issue-11/ja1004762/production/images/medium/ja-2010-004762_0005.gif'> <P>In the present work, we first described the stable entrapment of the superoxide ions in γ-irradiated (Me<SUB>4</SUB>NOH + O<SUB>2</SUB>) clathrate hydrate. Owing to peculiar direct guest−guest ionic interaction, the lattice structure of γ-irradiated (Me<SUB>4</SUB>NOH + O<SUB>2</SUB>) clathrate hydrate shows significant change of lattice contraction behavior even at relatively high temperature (120 K). Such findings are expected to provide useful information for a better understanding of unrevealed nature (such as icy nanoreactor concept, ice-based functional material synthesis and lattice tuning by specific ionic guests) of clathrate hydrate fields.</P></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja1004762'>ACS Electronic Supporting Info</A></P>

Proton Beam Radiotherapy versus Radiofrequency Ablation Treatment in Patients with Recurrent Hepatocellular Carcinoma: A Randomized Controlled Phase 3 Non-Inferiority APROH Trial

( Joong-won Park ),( Tae Hyun Kim ),( Young-hwan Koh ),( Bo Hyun Kim ),( Min Ju Kim ),( Ju Hee Lee ),( Boram Park ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Radiofrequency ablation (RFA) is the standard of care for patients (pts) with Barcelona Clinic for Liver Cancer stage 0 and A hepatocellular carcinoma (HCC) not suitable for surgery. The role of external proton beam radiotherapy (PBT) is under investigation and a phase 2 study of PBT showed promising local control and safety. Herein, we conducted an investigator-initiated phase 3 non-inferiority trial to evaluate the clinical outcomes of PBT on recurrent or residual HCC (rHCC). Methods: Patients (pts) with rHCC (size < 3 cm, number ≤2) were randomly assigned (1:1) to receive PBT or RFA according to the Child-Pugh score and tumour stage. If the randomly assigned method was not technically feasible, pts were allowed to enroll in the other treatment. Eligible pts of PBT arm received a total of 66 Gray equivalent in 10 fractions and those of RFA arm received RFA with a monopolar electrode. The primary endpoint was 2-year (y) local progression-free survival (LPFS) rate with a non-inferiority margin of 15%; secondary endpoints included overall survival, progression-free survival, tumor response rate and safety profile (NCT01963429). Results: Between December 2013 and December 2017, 144 pts in PBT arm (n=72) and RFA arm (n=72) comprised the intention-to-treat (ITT) population and the trial was concluded on January 2020. The baseline characteristics of pts were well balanced. In PBT arm, six pts switched to RFA and five pts received another treatment, while in RFA arm, 19 pts switched to PBT and three pts received another treatment. Thus, the per-protocol (PP) population comprised 80 patients receiving PBT and 56 undergoing RFA. In the PP population, the 2-year LPFS rate associated with PBT vs. RFA was 94.8% vs. 83.9% (90% confidence interval [CI], 1.8-20.0%; P<0.001); in the ITT population, the 2-year LPFS rate associated with PBT vs. RFA was 92.8% vs. 83.2% (90% CI, 0.7-18.4%; P<0.001), meeting the criteria for non-inferiority. The 3- and 4-year LPFS rates for PBT were also significantly non-inferior to those for RFA. Efficacy outcomes are shown in the figure. The most common adverse events (AEs) were radiation pneumonitis (32.5%) and decreased leukocyte counts (23.8%) for PBT and increased alanine aminotransferase levels (96.4%) and abdominal pain (30.4%) for RFA. No Grade 4 AEs or mortality were noted. Conclusions: PBT was non-inferior to RFA in terms of LPFS in pts with rHCC, and PBT was tolerable and safe, consistent with the known profile.

Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma

Yu, Jeong Il,Yoo, Gyu Sang,Cho, Sungkoo,Jung, Sang Hoon,Han, Youngyih,Park, Seyjoon,Lee, Boram,Kang, Wonseok,Sinn, Dong Hyun,Paik, Yong-Han,Gwak, Geum-Youn,Choi, Moon Seok,Lee, Joon Hyeok,Koh, Kwang C The Korean Society for Radiation Oncology 2018 Radiation Oncology Journal Vol.36 No.1

Purpose: This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. Materials and Methods: HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of $62-92GyE_{10}$. Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. Conclusion: PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted.

Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma

Jeong Il Yu,Gyu Sang Yoo,Sungkoo Cho,Sang Hoon Jung,Youngyih Han,Seyjoon Park,Boram Lee,Wonseok Kang,Dong Hyun Sinn,Yong-Han Paik,Geum-Youn Gwak,Moon Seok Choi,Joon Hyeok Lee,Kwang Cheol Koh,Seung Woo 대한방사선종양학회 2018 Radiation Oncology Journal Vol.36 No.1

Purpose: This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. Materials and Methods: HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of 62–92 GyE 10 . Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. Conclusion: PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted.

Isocitrate protects <i>DJ-1</i> null dopaminergic cells from oxidative stress through NADP ⁺ -dependent isocitrate dehydrogenase (IDH)

Yang, Jinsung,Kim, Min Ju,Yoon, Woongchang,Kim, Eun Young,Kim, Hyunjin,Lee, Yoonjeong,Min, Boram,Kang, Kyung Shin,Son, Jin H.,Park, Hwan Tae,Chung, Jongkyeong,Koh, Hyongjong Public Library of Science 2017 PLoS genetics Vol.13 No.8

<▼1><P><I>DJ-1</I> is one of the causative genes for early onset familiar Parkinson’s disease (PD) and is also considered to influence the pathogenesis of sporadic PD. DJ-1 has various physiological functions which converge on controlling intracellular reactive oxygen species (ROS) levels. In RNA-sequencing analyses searching for novel anti-oxidant genes downstream of DJ-1, a gene encoding NADP<SUP>+</SUP>-dependent isocitrate dehydrogenase (IDH), which converts isocitrate into α-ketoglutarate, was detected. Loss of <I>IDH</I> induced hyper-sensitivity to oxidative stress accompanying age-dependent mitochondrial defects and dopaminergic (DA) neuron degeneration in <I>Drosophila</I>, indicating its critical roles in maintaining mitochondrial integrity and DA neuron survival. Further genetic analysis suggested that DJ-1 controls IDH gene expression through nuclear factor-E2-related factor2 (Nrf2). Using <I>Drosophila</I> and mammalian DA models, we found that IDH suppresses intracellular and mitochondrial ROS level and subsequent DA neuron loss downstream of DJ-1. Consistently, trimethyl isocitrate (TIC), a cell permeable isocitrate, protected mammalian <I>DJ-1</I> null DA cells from oxidative stress in an IDH-dependent manner. These results suggest that isocitrate and its derivatives are novel treatments for PD associated with <I>DJ-1</I> dysfunction.</P></▼1><▼2><P><B>Author summary</B></P><P>The molecular pathogenesis of Parkinson’s disease (PD) is still elusive even though many causative genes for the disease have been identified. In this study, we demonstrated that isocitrate dehydrogenase (IDH), the enzyme responsible for converting isocitrate into α-ketoglutarate, is critical for the pathogenesis of PD by providing NADPH as a reducing power in the cell. <I>IDH</I> mutant animals showed increased reactive oxygen species (ROS) levels and phenotypes related to PD including dopaminergic (DA) neuron degeneration and locomotor defects. Conversely, elevating IDH function either by overexpression or treating a cell-permeable derivative of isocitrate, trimethyl isocitrate (TIC), made DA cells resist oxidative stress and reduce ROS level, thereby suppressing PD phenotypes induced by <I>DJ-1</I> mutations. These results demonstrate that IDH protects DA neurons from ROS at the downstream of DJ-1 and cell-permeable isocitrates can be novel treatments for PD.</P></▼2>

Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19

Eu Suk Kim,Bum Sik Chin,강창경,Nam Joong Kim,Yu Min Kang,Jae-Phil Choi,Dong Hyun Oh,Jeong-Han Kim,Boram Koh,Seong Eun Kim,Na Ra Yun,Jae Hoon Lee,Jin Yong Kim,Yeonjae Kim,Ji Hwan Bang,송경호,Hong Bin Kim,Ki- 대한의학회 2020 Journal of Korean medical science Vol.35 No.13

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. Methods: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. Results: The median age was 40 years (range, 20–73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5–7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). Conclusion: The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.