1.The Multi-targeted Effect of Fascaplysin on the Proliferation and Dedifferentiation of Schwann Cells Inhibits Peripheral Nerve Degeneration by Blocking CDK4/6 and Androgen Receptor
Hyung-Joo CHUNG ; Ja-Eun KIM ; Youngbuhm HUH ; Jin San LEE ; So-Woon KIM ; Kiyong NA ; Jiwon KIM ; Seung Hyeun LEE ; Hiroyuki KONISHI ; Seung Geun YEO ; Dong Keon YON ; Dokyoung KIM ; Junyang JUNG ; Na Young JEONG
Experimental Neurobiology 2024;33(6):266-281
Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.
2.The Multi-targeted Effect of Fascaplysin on the Proliferation and Dedifferentiation of Schwann Cells Inhibits Peripheral Nerve Degeneration by Blocking CDK4/6 and Androgen Receptor
Hyung-Joo CHUNG ; Ja-Eun KIM ; Youngbuhm HUH ; Jin San LEE ; So-Woon KIM ; Kiyong NA ; Jiwon KIM ; Seung Hyeun LEE ; Hiroyuki KONISHI ; Seung Geun YEO ; Dong Keon YON ; Dokyoung KIM ; Junyang JUNG ; Na Young JEONG
Experimental Neurobiology 2024;33(6):266-281
Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.
3.The Multi-targeted Effect of Fascaplysin on the Proliferation and Dedifferentiation of Schwann Cells Inhibits Peripheral Nerve Degeneration by Blocking CDK4/6 and Androgen Receptor
Hyung-Joo CHUNG ; Ja-Eun KIM ; Youngbuhm HUH ; Jin San LEE ; So-Woon KIM ; Kiyong NA ; Jiwon KIM ; Seung Hyeun LEE ; Hiroyuki KONISHI ; Seung Geun YEO ; Dong Keon YON ; Dokyoung KIM ; Junyang JUNG ; Na Young JEONG
Experimental Neurobiology 2024;33(6):266-281
Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.
4.The Multi-targeted Effect of Fascaplysin on the Proliferation and Dedifferentiation of Schwann Cells Inhibits Peripheral Nerve Degeneration by Blocking CDK4/6 and Androgen Receptor
Hyung-Joo CHUNG ; Ja-Eun KIM ; Youngbuhm HUH ; Jin San LEE ; So-Woon KIM ; Kiyong NA ; Jiwon KIM ; Seung Hyeun LEE ; Hiroyuki KONISHI ; Seung Geun YEO ; Dong Keon YON ; Dokyoung KIM ; Junyang JUNG ; Na Young JEONG
Experimental Neurobiology 2024;33(6):266-281
Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.
5.A Nationwide Study of Surgery in a Newly Diagnosed Spine Metastasis Population
Seil SOHN ; Chun Kee CHUNG ; Kyung Do HAN ; Jin Hyung JUNG ; Joung Ho HYEUN ; Jinhee KIM ; Ung Kyu CHANG ; Moon Jun SOHN ; Sung Hwan KIM
Journal of Korean Neurosurgical Society 2019;62(1):46-52
OBJECTIVE: The aim of this nationwide study was to analyze the current state of patients with newly diagnosed metastatic spine tumors according to surgical methods.METHODS: Data was extracted from the Korean Health Insurance Review and Assessment Service database. Surgery was categorized into three methods : fusion, decompression, and vertebroplasty. Data included patient age, sex, health insurance type, and co-morbidities. Survival rates of metastatic spine tumor patients according to each surgical method were evaluated.RESULTS: Among 1677 patients who had an operation, 823 patients were treated by fusion, 141 patients underwent decompression, and 713 patients were treated by vertebroplasty. The three most prevalent primary tumor sites were the lung, breast, and liver & biliary. On the other hand, the three most prevalent primary tumor sites of patients who underwent surgery were the lung, liver & biliary, and the prostate. The median survival periods for each surgical method in the metastatic spine tumor patients were 228 days for those who underwent surgery, 249 days for decompression, and 154 days for vertebroplasty. Age, sex, and comorbidities significantly affected survival rate.CONCLUSION: For every primary tumor site, decompression was the least common surgical method during the study period. Although the three surgical methods did not significantly affect the survival period, patients with a poor prognosis tended to undergo vertebroplasty.
Breast
;
Comorbidity
;
Decompression
;
Hand
;
Humans
;
Insurance, Health
;
Liver
;
Lung
;
Methods
;
Neoplasm Metastasis
;
Prognosis
;
Prostate
;
Spine
;
Survival Rate
;
Vertebroplasty
6.Clinical Efficacy of Selective Focal Ablation by Navigable Percutaneous Disc Decompression Device in Patients With Cervical Herniated Nucleus Pulposus.
Sung Hoon KIM ; Sang Heon LEE ; Nack Hwan KIM ; Min Hyun KIM ; Hyeun Jun PARK ; Yong Jin JUNG ; Hyun Joon YOO ; Won Jun MENG ; Victoria KIM
Annals of Rehabilitation Medicine 2017;41(1):80-89
OBJECTIVE: To evaluate the clinical efficacy and safety following percutaneous disc decompression, using navigable disc decompression device for cervical herniated nucleus pulposus (HNP). METHODS: Twenty subjects diagnosed with cervical HNP and refractory to conservative management were enrolled for the study. The herniated discs were decompressed under fluoroscopic guidance, using radiofrequency ablation device with navigable wand. The sagittal and axial plain magnetic resonance images of the clinically significant herniated disc, decided the space between the herniated base and outline as the target area for ablation. Clinical outcome was determined by Numeric Rating Scale (NRS), Neck Disability Index (NDI), and Bodily Pain scale of Short Form-36 (SF-36 BP), assessed after 48 weeks. After the procedure, we structurally matched the magnetic resonance imaging (MRI) and C-arm images through bony markers. The wand position was defined as being ‘correct’ if the tip was placed within the target area of both AP and lateral views; if not, the position was stated as ‘incorrect’. RESULTS: The average NRS fell from 7 to 1 at 48 weeks post procedure (p<0.05). In addition, statistically significant improvement was noted in the NDI and SF-36BP (p<0.05). The location of the wand tip resulted in 16 correct and 4 incorrect placements. Post-48 weeks, 3 of the incorrect tip cases and 1 correct tip case showed unsuccessful outcomes. CONCLUSION: The study demonstrated the promising results and safety of the procedure. Thus, focal plasma ablation of cervical HNP with navigable wand can be another effective treatment option.
Catheter Ablation
;
Decompression*
;
Humans
;
Intervertebral Disc Displacement
;
Magnetic Resonance Imaging
;
Neck
;
Neck Pain
;
Plasma
;
Treatment Outcome*
7.Association between Alcohol Drinking and the Ratio of Aspartate Aminotransferase to Alanine Aminotransferase in Korean Adult Male.
Young Hee CHO ; Jong Sung KIM ; Sung Soo KIM ; Jin Kyu JUNG ; Seok Joon YOON ; Hyeun Young KIM ; Yoon Kyung BAE
Korean Journal of Health Promotion 2017;17(2):64-70
BACKGROUND: The aspartate transaminase (AST)/alanine transferase (ALT) ratio increases with alcohol consumption. This study investigated AST/ALT ratio according to alcohol drinking and predictive power of AST/ALT ratio for heavy drinking in Korean men. METHODS: In 2015, 830 men with no history of disease or medication affecting liver function values were selected. Using 14 g of alcohol as the standard glass, odd ratios (ORs) of AST/ALT ratio over 1 among the drinking group were compared with the non-drinking group by multiple logistic analyses. Screening of heavy drinkers was conducted according to both NIAAA and Korean guidelines. Using AST/ALT ratio >1, sensitivity, specificity, positive predictive values, negative predictive values, positive likelihood ratios, negative likelihood ratios and odds ratios were investigated. RESULTS: After correcting for age, body mass index, exercising, and smoking history, ORs (95% confidence interval) of AST/ALT >1 were 1.607 (1.048-2.464) in <8 glasses group, 2.172 (1.160-4.065) in the 14 glasses group, and 3.670 (2.218-6.053) in the >14 glasses group. When AST/ALT >1 in the drinking group, sensitivity, specificity, positive predictive values, negative predictive values, likelihood ratios (LR)+, LR- and OR according to NIAAA guidelines, were 57.2%, 52.7%, 23.2%, 76.8%, 1.21 (1.04-1.41), 0.81 (0.67-0.98), and 1.49 (1.05-2.01), respectively. By Korean guidelines, these values were 55.2%, 55.3%, 33.7%, 66.3%, 1.24 (1.03-1.36), 0.84 (0.72-0.98), and 1.40 (1.04-1.89), respectively. CONCLUSIONS: Healthy male adults showed a positive correlation between risk of AST/ALT >1 and drinking amount compared to the non-drinking group. Use of the AST/ALT >1 in combination with other blood markers to predict excessive drinking is advisable.
Adult*
;
Alanine Transaminase*
;
Alanine*
;
Alcohol Drinking*
;
Aspartate Aminotransferases*
;
Aspartic Acid*
;
Body Mass Index
;
Drinking
;
Eyeglasses
;
Glass
;
Humans
;
Liver
;
Male*
;
Mass Screening
;
National Institute on Alcohol Abuse and Alcoholism (U.S.)
;
Odds Ratio
;
Sensitivity and Specificity
;
Smoke
;
Smoking
;
Transferases
8.Effects of SLA surface treated with NaOH on surface characteristics and response of osteoblast-like cell.
Jin Chul PARK ; Joo Hyeun KIM ; Eun Sook KANG ; Jae Jun RYU ; Jung Bo HUH
The Journal of Korean Academy of Prosthodontics 2014;52(3):211-221
PURPOSE: The purpose of this study was to evaluate the surface characteristics and response of osteoblast-like cell at SLA surface treated with NaOH. MATERIALS AND METHODS: Three kinds of specimens were fabricated for the experiment groups. Control group was a machined surface, SLA group was a conventionally SLA treated surface, and SLA/NaOH gorup was SLA surface treated with NaOH. To evaluate the surface characteristics, the surface elemental composition (XPS), surface roughness and surface contact angle were evaluated in each group. And the cytotoxicity, cell adhesion, cell proliferation and ATP activity of osteoblast-like cells (MG-63 cells) were compared in each group for evaluatation of the cell responses. Statistical comparisons between groups were carried out via one-way ANOVA using the SPSS software (SPSS Inc., Chicago, USA), and then performed multiple comparisons. The differences were considered statistically significant at P<.05. RESULTS: SLA surface treated with NaOH (SLA / NaOH group) was changed to hydrophilic surface. All groups did not show the cytotoxicity to the MG-63. In cell adhesion studies, SLA / NaOH group showed the higher degree of adhesion than anothers (P<.05), Up to 7 days of incubation, the proliferation was showed the increasing tendency in all groups but SLA / NaOH group showed the highest cell proliferation between the three groups (P<.05). At 7 days of incubation, there was no difference in ALP activities between the three groups, but at 14 days, SLA / NaOH group showed significant increase in ALP activities (P<.05). CONCLUSION: In this study, SLA surface treated with NaOH promoted cell adhesion, proliferation and differentiation. It means that SLA/NaOH group is possible to promote osseointegration of implants.
Adenosine Triphosphate
;
Cell Adhesion
;
Cell Culture Techniques
;
Cell Proliferation
;
Osseointegration
9.Newly Identified TLR9 Stimulant, M6-395 Is a Potent Polyclonal Activator for Murine B Cells.
Mi Hee PARK ; Yu Jin JUNG ; Pyeung Hyeun KIM
Immune Network 2012;12(1):27-32
BACKGROUND: Toll-like receptors (TLRs) have been extensively studied in recent years. However, functions of these molecules in murine B cell biology are largely unknown. A TLR4 stimulant, LPS is well known as a powerful polyclonal activator for murine B cells. METHODS: In this study, we explored the effect of a murine TLR9 stimulant, M6-395 (a synthetic CpG ODNs) on B cell proliferation and Ig production. RESULTS: First, M6-395 was much more potent than LPS in augmenting B cell proliferation. As for Ig expression, M6-395 facilitated the expression of both TGF-beta1-induced germ line transcript alpha (GLTalpha) and IL-4-induced GLTgamma1 as levels as those by LPS and Pam3CSK4 (TLR1/2 agonist) : a certain Ig GLT expression is regarded as an indicative of the corresponding isotype switching recombination. However, IgA and IgG1 secretion patterns were quite different--these Ig isotype secretions by M6-395 were much less than those by LPS and Pam3CSK4. Moreover, the increase of IgA and IgG1 production by LPS and Pam3CSK4 was virtually abrogated by M6-395. The same was true for the secretion of IgG3. We found that this unexpected phenomena provoked by M6-395 is attributed, at least in part, to its excessive mitogenic nature. CONCLUSION: Taken together, these results suggest that M6-395 can act as a murine polyclonal activator but its strong mitogenic activity is unfavorable to Ig isotype switching.
B-Lymphocytes
;
Cell Proliferation
;
Germ Cells
;
Immunoglobulin A
;
Immunoglobulin Class Switching
;
Immunoglobulin G
;
Oligodeoxyribonucleotides
;
Recombination, Genetic
;
Toll-Like Receptors
10.Emergent Endovascular Embolization for Iatrogenic Vertebral Artery Injury during Cervical Discectomy and Fusion.
Hyeun Jin JUNG ; Dong Min KIM ; Seok Won KIM ; Sung Myung LEE
Journal of Korean Neurosurgical Society 2011;50(6):520-522
Injury to the vertebral artery during anterior cervical discectomy is rare but potentially fatal. We report a case of cerebellar infarction after endovascular embolization for iatrogenic vertebral artery injury at C5-C6 during an anterior cervical discectomy and fusion. A 61-year-old man had an intraoperative injury of the right vertebral artery that occurred during anterior cervical discectomy and fusion at C5-C6. Hemorrhage was not controlled successfully by packing with surgical hemostatic agents. While the patient was still intubated, an emergency angiogram was performed. The patient underwent endovascular occlusion of the right V2 segment with coils. After the procedure, his course was uneventful and he did not show any neurologic deficits. Brain computed tomographic scans taken 3 days after the operation revealed a right cerebellar infarction. Anti-coagulation medication was administered, and at 3-month follow-up examination, he had no neurologic sequelae in spite of the cerebellar infarction.
Brain
;
Diskectomy
;
Emergencies
;
Follow-Up Studies
;
Hemorrhage
;
Humans
;
Infarction
;
Middle Aged
;
Neurologic Manifestations
;
Vertebral Artery

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