1.Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice
Kyung-Jun BOO ; Edson Luck GONZALES ; Chilly Gay REMONDE ; Jae Young SEONG ; Se Jin JEON ; Yeong-Min PARK ; Byung-Joo HAM ; Chan Young SHIN
Biomolecules & Therapeutics 2023;31(2):161-167
Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses- and target-based treatments. Undesirable side effects and unresponsiveness to current medications fuel the drive to solve this top global health problem. In this study, we focused on neuroinflammatory response-mediated depression which represents a cluster of depression etiology both in animal models and humans. Several meta-analyses reported that proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were increased in major depressive disorder patients. Inflammatory mediators implicated in depression include type-I interferon and inflammasome pathways. To elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression, we introduced hycanthone, an antischistosomal drug, to check whether it can counteract depressive-like behaviors in vivo and normalize the inflammation-induced changes in vitro. Lipopolysaccharide (LPS) treatment increased proinflammatory cytokine expression in the murine microglial cells as well as the stimulation of type I interferon-related pathways that are directly or indirectly regulated by Janus kinase-signal transducer and activator of transcription (JAK-STAT) activation. Hycanthone treatment attenuated those changes possibly by inhibiting the JAK-STAT pathway and inflammasome activation. Hycanthone also ameliorated depressive-like behaviors by LPS. Taken together, we suggest that the inhibitory action of hycanthone against the interferon pathway leading to attenuation of depressive-like behaviors can be a novel therapeutic mechanism for treating depression.
2.Standardized Extract (HemoHIM) Ameliorated High Intensity Exercise Induced Fatigue in Mice
Hyun Jun LEE ; Sang Back KIM ; Kyung Jun BOO ; Darlene Mae ORTIZ ; Leandro Val SAYSON ; Raly James Perez CUSTODIO ; Jae Hoon CHEONG ; Seul Ki KIM ; Mikyung KIM ; Hee Jin KIM
Natural Product Sciences 2022;28(2):68-74
HemoHIM was used as a Korean traditional medicine for anti-inflammatory and antioxidant effects. However, there is no study on the effect of HemoHIM on fatigue. We examined the potential use of HemoHIM to determine whether it can induce anti-fatigue effects. Mice were administered with HemoHIM and VEH for 14 days. On the last day of treatment, mice were subjected to behavioral tests. Subsequently, their plasma and muscle were collected after the treadmill test to measure lactate, lactate dehydrogenase (LDH), ammonia, corticosterone, glycogen, and creatine kinase (CK). We found that HemoHIM moderately increased the running time (s) in the treadmill and mobility duration in the cold swimming tests. In addition, the VEH group showed a significant increase in lactate, LDH, and corticosterone levels in the plasma compared to the group that did not perform the test. However, this was moderately reduced in HemoHIM treatment. Moreover, the HemoHIMtreated group showed significant differences in LDH and glycogen levels, and showed significantly different CK levels in the muscle. HemoHIM is considered to be effective in improving fatigue, given the duration of cold swimming or running time on a treadmill. Also, HemoHIM treatment resulted in reduced concentrations of blood and muscle parameter analysis.
3.Autism-Like Behavioral Phenotypes in Mice Treated with Systemic N-Methyl-D-Aspartate
Keremkleroo JYM ADIL ; Edson Luck GONZALES ; Chilly Gay REMONDE ; Kyung-Jun BOO ; Se Jin JEON ; Chan Young SHIN
Biomolecules & Therapeutics 2022;30(3):232-237
Autism spectrum disorder (ASD) having core characteristics of social interaction problems and repetitive behaviors and interests affects individuals at varying degrees and comorbidities, making it difficult to determine the precise etiology underlying the symptoms. Given its heterogeneity, ASD is difficult to treat and the development of therapeutics is slow due to the scarcity of animal models that are easy to produce and screen with. Based on the theory of excitation/inhibition imbalance in the brain with ASD which involves glutamatergic and/or GABAergic neurotransmission, a pharmacologic agent to modulate these receptors might be a good starting point for modeling. N-methyl-D-aspartic acid (NMDA) is an amino acid derivative acting as a specific agonist at the NMDA receptor and therefore imitates the action of the neurotransmitter glutamate on that receptor. In contrast to glutamate, NMDA selectively binds to and regulates the NMDA receptor, but not other glutamate receptors such as AMPA and kainite receptors. Given this role, we aimed to determine whether NMDA administration could result in autistic-like behavior in adolescent mice. Both male and female mice were treated with saline or NMDA (50 and 75 mg/kg) and were tested on various behavior experiments. Interestingly, acute NMDA-treated mice showed social deficits and repetitive behavior similar to ASD phenotypes. These results support the excitation/inhibition imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model of ASD-like behaviors.
4.Behavioral Deficits in Adolescent Mice after Sub-Chronic Administration of NMDA during Early Stage of Postnatal Development
Keremkleroo Jym ADIL ; Chilly Gay REMONDE ; Edson Luck GONZALES ; Kyung-Jun BOO ; Kyong Ja KWON ; Dong Hyun KIM ; Hee Jin KIM ; Jae Hoon CHEONG ; Chan Young SHIN ; Se Jin JEON
Biomolecules & Therapeutics 2022;30(4):320-327
Neurodevelopmental disorders are complex conditions that pose difficulty in the modulation of proper motor, sensory and cognitive function due to dysregulated neuronal development. Previous studies have reported that an imbalance in the excitation/ inhibition (E/I) in the brain regulated by glutamatergic and/or GABAergic neurotransmission can cause neurodevelopmental and neuropsychiatric behavioral deficits such as autism spectrum disorder (ASD). NMDA acts as an agonist at the NMDA receptor and imitates the action of the glutamate on that receptor. NMDA however, unlike glutamate, only binds to and regulates the NMDA receptor subtypes and not the other glutamate receptors. This study seeks to determine whether NMDA administration in mice i.e., over-activation of the NMDA system would result in long-lasting behavioral deficits in the adolescent mice. Both gender mice were treated with NMDA or saline at early postnatal developmental period with significant synaptogenesis and synaptic maturation. On postnatal day 28, various behavioral experiments were conducted to assess and identify behavioral characteristics. NMDAtreated mice show social deficits, and repetitive behavior in both gender mice at adolescent periods. However, only the male mice but not female mice showed increased locomotor activity. This study implies that neonatal exposure to NMDA may illicit behavioral features similar to ASD. This study also confirms the validity of the E/I imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model for ASD. Future studies may explore the mechanism behind the gender difference in locomotor activity as well as the human relevance and therapeutic significance of the present findings.
5.The Relationship between the Causative Allergens of Allergic Diseases and Environments in Korea Over a 8-Year-Period: Based on Skin Prick Test from 2006 to 2015.
Chan Soon PARK ; Boo Young KIM ; Soo Whan KIM ; Joo Hyung LEE ; Soo Kweon KOO ; Kyung Su KIM ; Seon Tae KIM ; Yong Dae KIM ; Jeong Hong KIM ; Jin Kook KIM ; Chang Hoon KIM ; Hyun Jun KIM ; Hyo Yeol KIM ; Ki Sang RHA ; Hwan Jung ROH ; Dong Joon PARK ; Seung Heon SHIN ; Sang Chul LIM ; Jae Hoon LEE ; Heung Man LEE ; Heung Gu LEE ; Young Ha KIM ; Jin Hee CHO
Journal of Rhinology 2018;25(2):91-98
BACKGROUND AND OBJECTIVES: The present study evaluated the results of skin prick test using 55 allergens at 20 centers in the Republic of Korea in 2006, 2010, and 2014–2015. The aim was to assess changes in the positive rate of allergens according to temporal, regional, and environmental factors. MATERIALS AND METHODS: In total, 20 hospitals were selected based on the population distribution in the Republic of Korea. A skin prick test panel comprising 55 aeroallergens was distributed to 18 hospitals for this prospective study. The 2006 and 2010 skin prick test results were collected and analyzed retrospectively from 20 hospitals, while the 2014/2015 skin prick test results (from June 2014 to May 2015) were collected prospectively from 18 hospitals. RESULTS: A total of 14,897 SPT test results were analyzed: 4,319 in 2006, 7,431 in 2010, and 1,852 in 2014/2015. The overall rate of skin prick test positivity to more than two allergens was significantly higher in males than females. The positive rates of alder pollens and birch, oak and ragweed pollen positivity were increased in older patients. Several positive rates were increased according to the temperature in spring. The positive rates for beech pollen, birch pollen, hazel pollen, oak pollen, Tyrophagus putrescentiae, mugwort, cat, Acarus siro, Lepidoglyphus destructor and Tyrophagus putrescentiae were significantly increased, while those of Cult rye pollen and dandelion were significantly decreased over the three test periods. The overall positive rate for allergens in Jeju province varied significantly from Seoul and other cities. CONCLUSION: Change in the positive rate of multiple aeroallergens was evaluated in the Republic of Korea over time. Our findings can be used to recommend aeroallergens suitable for inclusion in skin prick test panels in the Republic of Korea and will facilitate further investigation of changes in the patterns of allergic diseases.
Allergens*
;
Alnus
;
Ambrosia
;
Animals
;
Artemisia
;
Betula
;
Cats
;
Demography
;
Fagus
;
Female
;
Humans
;
Korea*
;
Male
;
Mites
;
Pollen
;
Prospective Studies
;
Republic of Korea
;
Retrospective Studies
;
Secale
;
Seoul
;
Skin*
;
Taraxacum
6.A Case of Management for Early Recurrence after Hepatic Resection for the Treatment of Small Hepatocellular Carcinoma.
Kyung Woo PARK ; Young Seok KIM ; Sang Gyune KIM ; Soung Won JEONG ; Jae Young JANG ; Hong Soo KIM ; Sae Hwan LEE ; Boo Sung KIM ; Jun Cheol JEONG ; Min Hee LEE ; Jae Myeong LEE ; Hee Kyung KIM
Journal of Liver Cancer 2015;15(2):122-125
For a small hepatocellular carcinoma (HCC), liver resection shows most favorable outcome in case which liver transplantation is not available, although it has also substantial recurrence rate. Here, we report a case of recurred HCC with multiple intrahepatic metastasis at 5 months after surgical resection for small HCC was done. A 55-year-old man with chronic HBV infection received subsegmentectomy for HCC less than 2 cm. A follow-up computed tomography (CT) at 5 months from operation revealed that there were multiple enhancing nodules in entire remnant liver. Intra-arterial injections of adriamycin mixed lipiodol and gelfoam particles were instituted through hepatic artery. We assume that poorly differentiated cellular feature would be attributable to this kind of very early and aggressive recurrence of HCC.
Carcinoma, Hepatocellular*
;
Doxorubicin
;
Ethiodized Oil
;
Follow-Up Studies
;
Gelatin Sponge, Absorbable
;
Hepatic Artery
;
Humans
;
Injections, Intra-Arterial
;
Liver
;
Liver Transplantation
;
Middle Aged
;
Neoplasm Metastasis
;
Recurrence*
7.Multicenter Study on the Clinician's Diagnostic and Therapeutic Approaches for Benign Paroxysmal Positional Vertigo in Korea
Eun Ju JEON ; Won Ho CHUNG ; Jeong Hwan CHOI ; Eui Cheol NAM ; Hong Ju PARK ; Jong Dae LEE ; Won Sang LEE ; Kyu Sung KIM ; Eui Kyung GOH ; Ja Won KOO ; Min Bum KIM ; Min Beom KIM ; Se Hyung KIM ; Young Jin KIM ; Chang Hee KIM ; Sung Il NAM ; Seog Kyun MUN ; Ga Young PARK ; Sang Yoo PARK ; Shi Nae PARK ; Chang Hoon BAE ; Sung Hyun BOO ; Myung Whan SUH ; Jae Hyun SEO ; Eun Jin SON ; Jae Jun SONG ; Jae Jin SONG ; Joong Wook SHIN ; Dae Bo SHIM ; Seong Ki AHN ; Hye Youn YOUM ; Shin Young YOO ; Dong Hee LEE ; Seung Hwan LEE ; Chang Ho LEE ; Hyun Seok LEE ; Hwan Ho LEE ; Hyo Jeong LEE ; Yun Hoon CHOUNG ; Seung Hyo CHOI ; Jee Sun CHOI ; Seok Min HONG ; Sung Kwang HONG
Journal of the Korean Balance Society 2013;12(3):79-92
BACKGROUND AND OBJECTIVES: It is necessary to establish the most efficient diagnostic and therapeutic method for benign paroxysmal positional vertigo (BPPV), which is appropriate for Korean healthcare system. We aimed to evaluate current state of Korean clinician's diagnostic and therapeutic approaches for BPPV. MATERIALS AND METHODS: A 16-item survey was emailed to the members of dizziness department of Otology Research Interest Group in the Korean Otologic Society (n=68). 43 were returned and analyzed. RESULTS: All respondents (100%) used Dix-Hallpike test as a diagnostic tool for vertical canal-BPPV. Supine roll test was used for diagnosing lateral canal BPPV in nearly all the respondents (97.7%). Epley maneuver was chosen as otolith repositioning maneuver (ORM) for posterior canal BPPV in all respondents and barbecue rotation (BBQ) was used for treating lateral canal BPPV with geotropic nystagmus in 95.3% of respondents. Extreme variation was noted for therapeutic approach of lateral canal BPPV with ageotropic nystagmus BBQ, with 4 kinds of ORM and adjunctive measures to liberate otolith from cupula, while BBQ was again the most commonly used ORM (76.7%). CONCLUSION: The development of practical and efficient ORM for lateral canal BPPV with ageotropic nystagmus is necessary.
Surveys and Questionnaires
;
Delivery of Health Care
;
Dizziness
;
Electronic Mail
;
Korea
;
Otolaryngology
;
Otolithic Membrane
;
Public Opinion
;
Vertigo
8.An Analysis of Metamorphopsia Using Preferential Hyperacuity Perimeter Following Macular-off RRD Surgical Repair.
Hyun Jun PARK ; Seung Wook LEE ; Kyung Ho KIM ; Jung Hyun LEE ; Ji Eun LEE ; Boo Sup OUM
Journal of the Korean Ophthalmological Society 2010;51(4):552-557
PURPOSE: To determine the efficacy of using the preferential hyperacuity perimeter (PHP) for the analysis of metamorphopsia following macular-off rhegmatogenous retinal detachment (RRD) surgical repair. METHODS: PHP examination was performed in those who complained of metamorphopsia after successful surgical reattachment of RRD. The subjective symptoms were evaluated based on a scale, ranging from 0 to 10, and were compared with the results of PHP examination. Patients age, duration of retinal detachment, pre and post-operative visual acuity, postoperative presence of subretinal fluid (SRF), surgical methods, presence of epiretinal membrane, and time from operation to PHP test were analyzed to find the correlation with the PHP results. RESULTS: Of the 19 eyes included in this study, nine eyes were found to have a hyperacuity defect upon PHP examination. In this group, the subjective level of metamorphopsia was significantly worse (p<0.01), the age was significantly higher (p=0.02), and SRF persisted in the macula more frequently at two months postoperatively (p=0.04), as compared to those without the defect. There were no significant differences in the other factors. CONCLUSIONS: Subjectively severe metamorphopsia after surgery for RRD could be confirmed objectively using PHP. In the case of older patients and persistent submacular fluid, metamorphopsia would develop more frequently due to displacement of the photoreceptors in the process of reattachment.
Displacement (Psychology)
;
Epiretinal Membrane
;
Eye
;
Humans
;
Retinal Detachment
;
Subretinal Fluid
;
Vision Disorders
;
Visual Acuity
9.Intramedullary Kirschner Wire Fixation for Forearm Fractures in Children.
Boo Kyung KWON ; Hong Gi PARK ; Deuk Soo JUN ; Jang Seok CHOI ; Dong Hwan KIM ; Sang Bok LEE ; Jong Ryoon BAEK
Journal of the Korean Society for Surgery of the Hand 2010;15(3):122-127
PURPOSE: To evaluate the clinical and radiological results of intramedullary fixation using Kirschner wires (K-wires) for the treatment of unstable forearm fractures in children. MATERIALS AND METHODS: Forty-three children who underwent intramedullary fixation using K-wires for the treatment of a forearm bone fracture were evaluated. The rodiological results were based on the time to union and angular deformity at last follow-up. The clinical results were analyzed according to Price criteria. RESULTS: Average union time was 6.9 weeks. Preoperatively, average angular deformity of radius is 11.4 degrees in anteroposterior (AP) view and 15.3 degrees in lateral view. In case of the ulna, arerage angular deformity was 8.3 degrees in AP view and 12.7 degrees in lateral view. At last follow up, average angular deformity of radius was 1.5 degrees in AP view and 1.6 degrees in lateral view. In case of the ulna, arerage angular deformity was 1.3 degrees in AP view and 2.5 degrees in lateral view. According to the criteria of Price et al., 42 patients (97%) were excellent and one patient (3%) was good. No specific complication was observed. CONCLUSION: An intramedullary fixation using K-wires is an attractive treatment option for unstable forearm fractures in children in terms of safety, excellent cosmesis, short hospitalization, easy hardware removal, and providing excellent radiological and clinical results.
Bone Wires
;
Child
;
Congenital Abnormalities
;
Follow-Up Studies
;
Forearm
;
Fractures, Bone
;
Hospitalization
;
Humans
;
Radius
;
Ulna
10.Effects of ezetimibe on lipid profiles and hemostatic markers in end-stage renal disease.
Kyung Sun PARK ; Young Sun YEO ; Mi Hyun YOO ; Jun Seok CHOI ; Ji Woong JANG ; Sun Jin BOO ; Dong Jun YOO ; Soon Bae KIM
Korean Journal of Medicine 2009;77(4):461-471
BACKGROUND/AIMS: Dyslipidemia is one of the major causes of cardiovascular disease in end-stage renal disease (ESRD) patients. Most of them are dyslipidemic despite the use of lipid-lowering agents. Ezetimibe is a novel chemical entity that inhibits the intestinal absorption of dietary and biliary cholesterol. This study evaluated the effects of ezetimibe on the lipid profile, inflammation markers, endothelial injury, and thrombogenesis in ESRD patients. METHODS: Sixty-five patients with serum low-density lipoprotein (LDL)-cholesterol levels > or =100 mg/d were recruited: 33 patients were on hemodialysis and 32 patients were on peritoneal dialysis. They were assigned randomly to the ezetimibe (10 mg) monotherapy group and the ezetimibe (10 mg) plus simvastatin (10 mg) combination therapy group. Both drugs were administered for 8 weeks. RESULTS: There were no significant differences in the baseline demographic and laboratory characteristics between the two groups. In the monotherapy group, the total and LDL-cholesterol levels were reduced by 14.7 and 21.9%, respectively. There were no changes in the high-density lipoprotein (HDL)-cholesterol or triglyceride levels. Fibrinogen increased significantly (p=0.04). In the combination therapy group, the total and LDL-cholesterol levels were reduced by 29.8 and 42.4%, respectively. There was an additional 15.1% reduction in total cholesterol and an additional 20.5% reduction in LDL cholesterol compared with monotherapy. Several patients complained of minor adverse effects and only one patient in the ezetimibe monotherapy group discontinued medication, because of diarrhea. CONCLUSIONS: In ESRD patients, ezetimibe used as combination therapy with a statin is more effective than ezetimibe monotherapy in ESRD patients.
Azetidines
;
Cardiovascular Diseases
;
Cholesterol
;
Cholesterol, LDL
;
Dyslipidemias
;
Fibrinogen
;
Humans
;
Hydroxymethylglutaryl-CoA Reductase Inhibitors
;
Inflammation
;
Intestinal Absorption
;
Kidney Failure, Chronic
;
Lipoproteins
;
Peritoneal Dialysis
;
Renal Dialysis
;
Simvastatin
;
Ezetimibe

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