2.Novel Histone Deacetylase 6 Inhibitor Confers Anti-inflammatory Effects and Enhances Gut Barrier Function
Jae-Young LEE ; Hyun Woo MA ; Ji Hyung KIM ; I Seul PARK ; Mijeong SON ; Keun Ho RYU ; Jieun SHIN ; Seung Won KIM ; Jae Hee CHEON
Gut and Liver 2023;17(5):766-776
Background/Aims:
The purpose of the current study was to examine the anti-inflammatory effects of CKD-506, a novel histone deacetylase 6 inhibitor, on human peripheral blood mononuclear cells (PBMCs) and CD4+ T cells and to explore the relationship between CKD-506 and gut epithelial barrier function.
Methods:
Lipopolysaccharide-stimulated human PBMCs from inflammatory bowel disease (IBD) patients were treated with CKD-506, and tumor necrosis factor (TNF)-α expression was measured using an enzyme-linked immunosorbent assay. The proliferation of CD4+ T cells from IBD patients was evaluated using flow cytometric analysis. The effects of CKD-506 on gut barrier function in a cell line and colon organoids, based on examinations of mRNA production, goblet cell differentiation, and E-cadherin recovery, were investigated using quantitative reverse transcription polymerase chain reaction, immunofluorescence, and a fluorescein isothiocyanatedextran permeability assay.
Results:
Secretion of TNF-α, a pivotal pro-inflammatory mediator in IBD, by lipopolysaccharidetriggered PBMCs was markedly decreased by CKD-506 treatment in a dose-dependent manner and to a greater extent than by tofacitinib or tubastatin A treatment. E-cadherin mRNA expression and goblet cell differentiation increased significantly and dose-dependently in HT-29 cells in response to CKD-506, and inhibition of E-cadherin loss after TNF-α stimulation was significantly reduced both in HT-29 cells and gut organoids. Caco-2 cells treated with CKD-506 showed a significant reduction in barrier permeability in a dose-dependent manner.
Conclusions
The present study demonstrated that CKD-506 has anti-inflammatory effects on PBMCs and CD4 T cells and improves gut barrier function, suggesting its potential as a smallmolecule therapeutic option for IBD.
3.Succinate-treated macrophages attenuate dextran sodium sulfate colitis in mice
I Seul PARK ; Mijeong SON ; Hyun Woo MA ; Jihyung KIM ; Da Hye KIM ; Seung Won KIM ; Jae Hee CHEON
Intestinal Research 2021;19(3):349-353
The safety and effectiveness of adalimumab was demonstrated in a phase 3 trial in Japanese patients with intestinal Behçet’s disease. The aim of this study was to evaluate the long-term safety and effectiveness of adalimumab in Japanese patients with intestinal Behçet’s disease.
4.Analysis of response of disaster medical assistance teams and public health disaster response teams in incident cases of mass casualty: a comparative analysis of medically underserved area and adequately served area
Jin Sil MA ; Jae-Hyug WOO ; Woo-Sung CHOI ; Hyuk Jun YANG ; Sung Youl HYUN
Journal of the Korean Society of Emergency Medicine 2021;32(2):151-161
Objective:
When mass casualty incidents occur in Korea, disaster medical assistance teams (DMATs) and public health disaster response teams (PHDRTs) treat casualties at the scene. However, the appropriateness of their on-site responses has not been assessed so far. In this study, we evaluated their response and the variations in their response according to the accessibility of medical care.
Methods:
We analyzed mass casualty incidents that were reported to the Disaster Emergency Medical Service Situation Room of the National Emergency Medical Center from July 2014 to December 2018. We divided the accident locations into medically underserved areas (MUAs) and adequately served areas (ASAs) and compared the responses of the two teams in each area.
Results:
Of the 61 incidents, 20 occurred in MUAs, and 41 occurred in ASAs. In MUAs compared to ASAs, time from DMATs' dispatch to arrival was longer (48 [40-58.5] vs. 23 [18-32], P<0.001) but the time taken by the PHDRTs did not vary between two areas (19 [14-35] vs. 15.5 [9-24.5], P=0.263). In MUAs, the time elapsed from the PHDRTs' dispatch to arrival was less than that of the DMATs (48 [40-58.5] vs. 20 [15-35], P<0.001). In MUAs, the distance of the PHDRTs from the scene was lower (31.4 [25-50.95] vs. 13.6 [5.3-19.7], P=0.001) and more members were dispatched to the scene than the DMAT (5 [4-6] vs. 9 [5-10.5], P=0.013).
Conclusion
Because of the low accessibility to the scene in MUAs, DMATs took a long time to initiate medical support . To provide adequate disaster medical support, the PHDRTs must be specialized and trained.
6.Analysis of response of disaster medical assistance teams and public health disaster response teams in incident cases of mass casualty: a comparative analysis of medically underserved area and adequately served area
Jin Sil MA ; Jae-Hyug WOO ; Woo-Sung CHOI ; Hyuk Jun YANG ; Sung Youl HYUN
Journal of the Korean Society of Emergency Medicine 2021;32(2):151-161
Objective:
When mass casualty incidents occur in Korea, disaster medical assistance teams (DMATs) and public health disaster response teams (PHDRTs) treat casualties at the scene. However, the appropriateness of their on-site responses has not been assessed so far. In this study, we evaluated their response and the variations in their response according to the accessibility of medical care.
Methods:
We analyzed mass casualty incidents that were reported to the Disaster Emergency Medical Service Situation Room of the National Emergency Medical Center from July 2014 to December 2018. We divided the accident locations into medically underserved areas (MUAs) and adequately served areas (ASAs) and compared the responses of the two teams in each area.
Results:
Of the 61 incidents, 20 occurred in MUAs, and 41 occurred in ASAs. In MUAs compared to ASAs, time from DMATs' dispatch to arrival was longer (48 [40-58.5] vs. 23 [18-32], P<0.001) but the time taken by the PHDRTs did not vary between two areas (19 [14-35] vs. 15.5 [9-24.5], P=0.263). In MUAs, the time elapsed from the PHDRTs' dispatch to arrival was less than that of the DMATs (48 [40-58.5] vs. 20 [15-35], P<0.001). In MUAs, the distance of the PHDRTs from the scene was lower (31.4 [25-50.95] vs. 13.6 [5.3-19.7], P=0.001) and more members were dispatched to the scene than the DMAT (5 [4-6] vs. 9 [5-10.5], P=0.013).
Conclusion
Because of the low accessibility to the scene in MUAs, DMATs took a long time to initiate medical support . To provide adequate disaster medical support, the PHDRTs must be specialized and trained.
7.Succinate-treated macrophages attenuate dextran sodium sulfate colitis in mice
I Seul PARK ; Mijeong SON ; Hyun Woo MA ; Jihyung KIM ; Da Hye KIM ; Seung Won KIM ; Jae Hee CHEON
Intestinal Research 2021;19(3):349-353
The safety and effectiveness of adalimumab was demonstrated in a phase 3 trial in Japanese patients with intestinal Behçet’s disease. The aim of this study was to evaluate the long-term safety and effectiveness of adalimumab in Japanese patients with intestinal Behçet’s disease.
8.Outcome of cardiopulmonary resuscitation for prehospital traumaticcardiac arrest: focused on Gangwon province
Chang Woo IM ; Taehun LEE ; Taek Geun OHK ; Oh Hyun KIM ; Sang Ku JUNG ; Yunsung KIM ; Bum Sug MA ; Moo Eob AHN ; Jeong Yeol SEO ; Dong Won KIM
Journal of the Korean Society of Emergency Medicine 2020;31(2):135-145
Objective:
This aim examined the outcomes of resuscitation and the clinical characteristics of patients with pre-hospitaltraumatic cardiac arrests (TCA).
Methods:
The charts of patients with pre-hospital TCA who visited the various emergency department (ED) in Gangwondofrom January 2013 to December 2017 were reviewed retrospectively.
Results:
TCA patients comprised 0.3% of patients transferred by 119. A total of 367 patients were enrolled in the study.Traffic accidents were the leading cause of the arrest. The initial field and ED rhythm were mostly asystole (field, 79.6%;ED, 82.3%). It took 11.24±9.95 minutes from the call to the field. From the field to ED, it took 22.87±15.37 minutes. Thetotal CPR time before ED arrival was 21.62±15.29 minutes. The causes of TCA were brain injury (35.7%), hypovolemicshock (29.2%), and severe lung injury (16.3%). Seventy TCA patients experienced at least one return of spontaneous circulation(ROSC). Twenty-six patients (7.14%) were admitted to the ward, and their average injury severity score was38.96. Eight patients expired before 12 hours after transient ROSC. Four more patients expired before 24 hours. Fourpatients were discharged alive among patients who lived for more than 24 hours.
Conclusion
In this study, 1.5% of patients were discharged alive. The possibility of ROSC was higher as the time to ED,and the cardiopulmonary resuscitation time of 119 was shorter. Pulseless electrical activity rather than asystole tends topromote ROSC. The survival rate increased when ROSC occurred before arriving at the ED.
9.Acer tegmentosum Maxim Prevents Bone Loss by Inhibiting Osteoclastogenesis and Promoting Osteoblast Mineralization in Ovariectomized Mice
Tae Woo OH ; Kwang-Il PARK ; Hyun Ju DO ; Kyungho KIM ; Hye Jin YANG ; Won Kyung CHO ; Jin Yeul MA
Natural Product Sciences 2020;26(1):83-89
Osteoporosis is a worldwide disease leading to significant economic and societal burdens globally. Osteoporosis is caused by unbalanced bone remodeling between the rate of osteoclast bone resorption and osteoblast bone formation. Acer tegmentosum Maxim (AT) is a traditional herbal medicine containing multiple biological activities such as anti-oxidant and anti-inflammatory purposes. However, its role in osteoporosis has not been fully studied. Therefore, we investigated whether AT has a potent inhibitory effect on osteoporosis and its mechanism through a systemic evaluation in ovariectomized (OVX) mice. OVX mice were orally administrated with the AT at doses of 50, 100, and 200 mg/kg for 10 weeks. Histological images and histomorphometry analyses were performed by H&E and Toluidine blue satin, and the expression levels of receptor activator for nuclear factor-kB ligand (RANKL), nuclear factor of activated T cells cytoplasm 1 (NFATc1), c-Fos, and matrix metalloproteinase 9 (MMP9) related to the osteoclast differentiation were investigated using immunohistochemical analysis. Administration of AT prevented bone loss and the alternations of osteoporotic bone parameters at the distinct regions of the distal femur and spongiosa region in OVX mice. Further, administration of AT increased periosteal bone formation in a dose-dependent manner. Meanwhile, AT inhibited not only the expression of NFATc1 and c-Fos, which are two major regulators of osteoclastogenesis but also reduced bone resorbed encoding expression of MMP9 and RANKL. Our results indicated that administration of AT prevented bone loss and the alternations of osteoporotic bone parameters at the distinct regions of the distal femur and spongiosa region in OVX mice. Also AT has the bone protective effect through the suppression of osteoclast and promotion of osteoblast, suggesting that it could be a preventive and therapeutic candidate for anti-osteoporosis.
10.Cognitive Dysfunction in Drug-induced Parkinsonism Caused by Prokinetics and Antiemetics.
Hyun Jung AHN ; Woo Kyoung YOO ; Jaeseol PARK ; Hyeo Il MA ; Yun Joong KIM
Journal of Korean Medical Science 2015;30(9):1328-1333
The use of prokinetics/antiemetics is one of the leading causes of drug-induced parkinsonism (DIP) observed in neurology clinics. Cognitive dysfunction in DIP has recently been recognized, but pathologies related with cognitive dysfunction is unknown. Among our retrospective cohort of 385 consecutive parkinsonian patients enrolled in our parkinsonism registry, 14 patients were identified who satisfied our inclusion criteria: parkinsonism caused by prokinetics/antiemetics, existing T1-weighted 3D volumetric MR images, and normal [18F]-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane PET scan images. For the comparison of volumetric MR data, 30 age- and sex-matched healthy individuals were included in this study. Among 14 patients with DIP, 4 patients were diagnosed with dementia, and all other patients had mild cognitive impairment (MCI). Comparisons of MR volumetric data between DIP patients with MCI and controls show that cortical gray matter volumes are reduced bilaterally in DIP (P=0.041) without changes in either total white matter volume or total intracranial volume. Among subcortical structures, the volume of the right hippocampus is reduced in DIP patients compared with controls (P=0.011, uncorrected). In DIP, cortical thickness is reduced in the bilateral lingual (P=0.002), right fusiform (P=0.032) and part of the left lateral occipital gyri (P=0.007). Our results suggests that cognitive dysfunction in DIP caused by prokinetics/antiemetics is common. Structural changes in the brain by 3D MRI may be associated with cognitive decline in DIP.
Aged
;
Aged, 80 and over
;
Antiemetics/*adverse effects
;
Brain/drug effects/pathology
;
Cognition Disorders/*chemically induced/*pathology
;
Female
;
Gastrointestinal Agents/*adverse effects
;
Humans
;
Male
;
Parkinson Disease, Secondary/*chemically induced/*pathology
;
Republic of Korea
;
Retrospective Studies
;
Risk Assessment
;
Treatment Outcome

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