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.Therapeutic Outcomes and Electrophysiological Biomarkers in Anti-Myelin-Associated Glycoprotein Neuropathy:A Multicenter Cohort Study in South Korea
Young Gi MIN ; Hee-Jo HAN ; Ha Young SHIN ; Jong-Gyu BAEK ; Jun-Soon KIM ; Kyung-Seok PARK ; Seol-Hee BAEK ; Ilhan YOO ; So-Young HUH ; Young Nam KWON ; Seok-Jin CHOI ; Sung-Min KIM ; Yoon-Ho HONG ; Jung-Joon SUNG
Journal of Clinical Neurology 2024;20(1):50-58
Background:
and Purpose Unlike other immune-mediated neuropathies, anti-myelin-associated glycoprotein (MAG) neuropathy is often refractory to immunotherapy. It is necessary to compare the relative efficacies of various immunotherapies and develop objective biomarkers in order to optimize its clinical management.
Methods:
This study recruited 91 patients with high anti-MAG antibody titers from 7 tertiary hospitals in South Korea. We analyzed the baseline characteristics, therapeutic outcomes, and nerve conduction study (NCS) findings of 68 patients and excluded 23 false positive cases.
Results:
The rate of positive responses to treatment was highest using zanubrutinib (50%) and rituximab (36.4%), followed by corticosteroids (16.7%), immunosuppressants (9.5%), intravenous immunoglobulin (5%), and plasma exchange (0%). Disability and weakness were significantly associated with multiple NCS parameters at the time of diagnosis, especially distal compound muscle action potential (CMAP) amplitudes. Moreover, the longitudinal trajectory of the average CMAP amplitudes paralleled the clinical courses, with a 16.2 percentile decrease as an optimal cutoff for predicting a clinical exacerbation (area under the receiver operating characteristic curve=0.792).
Conclusions
Our study supports the use of NCS as an objective marker for estimating disease burden and tracking clinical changes in patients with anti-MAG neuropathy. We have described the beneficial effects of rituximab and a new drug, zanubrutinib, compared with conventional immunotherapies.
6.Clinical performance of implant-assisted removable partial dentures using implant surveyed crowns: a systematic review and meta-analysis
So-Yeun KIM ; Young-Eun CHO ; Seoung-Jin HONG ; Jung-Bo HUH ; Se-Wook PYO ; Yuseung YI ; Soo-Yeon YOO
The Journal of Advanced Prosthodontics 2024;16(4):255-266
PURPOSE:
This study aimed to evaluate the clinical performance of implant-assisted removable partial dentures (IARPD) with surveyed crowns, also known as implant-crown-retained removable partial dentures (ICRPDs).
MATERIALS AND METHODS:
Electronic searches of MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials, the Web of Science, and the Korea Citation Index were performed according to the established search terms for ICRPD. A literature search was conducted for studies published in English or Korean until September 2023, using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines.
RESULTS:
A total of 216 journals were searched, and 31 eligible studies were selected based on the inclusion and exclusion criteria. One systematic review included five case reports of ICRPD. Nine retrospective studies evaluated implant survival/success rate, implant failure cases, marginal bone loss, periodontal status, clinical complications, and patient satisfaction. Twenty-one case reports published in Korea showed good prognoses.
CONCLUSION
According to the findings of this systematic review, ICRPD has a reasonable survival/success rate, minimal bone loss, and high patient satisfaction.
7.Zirconia removable prosthesis using a milled bar in patient with mandible anterior edentulous area with severe alveolar bone resorption: a case report
Jin-Young PARK ; Chang-Mo JEONG ; Mi-Jung YUN ; Jung-Bo HUH ; So-Hyoun LEE ; Dae-Sung KIM
The Journal of Korean Academy of Prosthodontics 2024;62(3):193-200
In patients with severe alveolar bone resorption on mandibular anterior edentulous areas, it can be difficult to place implants in the location for crowns, and to create the fixed prosthesis having an adequate emergence profile or embrasure, which makes maintenance difficult. Fabricating a removable zirconia prosthesis with a milled bar on poorly positioned implants can be a good option because of easy maintenance. In this case, the patient had severe bone resorption on mandibular anterior region, and large vertical space. We report on the aesthetical and easy-to-maintain results by placing two implants and fabricating a zirconia prosthesis using milled bar.
8.Loss of Neutralizing Activity of Tixagevimab/Cilgavimab (Evusheld™) Against Omicron BN.1, a Dominant Circulating Strain Following BA.5During the Seventh Domestic Outbreak in Korea in Early 2023
Jinyoung YANG ; Seokhwan HYEON ; Jin Yang BAEK ; Min Seo KANG ; Keon Young LEE ; Young Ho LEE ; Kyungmin HUH ; Sun Young CHO ; Cheol-In KANG ; Doo Ryeon CHUNG ; Kyong Ran PECK ; Gunho WON ; Hye Won LEE ; Kwangwook KIM ; Insu HWANG ; So Yeon LEE ; Byung Chul KIM ; Yoo-kyoung LEE ; Jae-Hoon KO
Journal of Korean Medical Science 2023;38(27):e205-
Tixagevimab/cilgavimab is a monoclonal antibody used to prevent coronavirus disease 2019 among immunocompromised hosts and maintained neutralizing activity against early omicron variants. Omicron BN.1 became a dominant circulating strain in Korea early 2023, but its susceptibility to tixagevimab/cilgavimab is unclear. We conducted plaque reduction neutralization test (PRNT) against BN.1 in a prospective cohort (14 patients and 30 specimens). BN.1 PRNT was conducted for one- and three-months after tixagevimab/ cilgavimab administration and the average PRNT ND 50 of each point was lower than the positive cut-off value of 20 (12.9 ± 4.5 and 13.2 ± 4.2, respectively, P = 0.825). In the paired analyses, tixagevimab/cilgavimab-administered sera could not actively neutralize BN.1 (PRNT ND 50 11.5 ± 2.9, P = 0.001), compared with the reserved activity against BA.5 (ND 50 310.5 ± 180.4). Unlike virus-like particle assay, tixagevimab/cilgavimab was not active against BN.1 in neutralizing assay, and would not be effective in the present predominance of BA.2.75 sublineages.
9.Safety and Temporal Pattern of the Lymphocyte Count During Fingolimod Therapy in Patients With Multiple Sclerosis: Real-World Korean Experience
So-Young HUH ; Su-Hyun KIM ; Ki Hoon KIM ; Young Nam KWON ; Sung-Min KIM ; Seung Woo KIM ; Ha Young SHIN ; Yeon Hak CHUNG ; Ju-Hong MIN ; Jungmin SO ; Young-Min LIM ; Kwang-Kuk KIM ; Nam-Hee KIM ; Tai-Seung NAM ; Sa-Yoon KANG ; Jeeyoung OH ; Seong-il OH ; Eunhee SOHN ; Ho Jin KIM
Journal of Clinical Neurology 2022;18(6):663-670
Background:
and Purpose Fingolimod (FTY) inhibits lymphocyte egress from lymphoid organs to cause lymphopenia, but the clinical implications of FTY-induced lymphopenia are not fully understood. We aimed to determine the frequency and severity of lymphopenia during FTY treatment among Korean patients with multiple sclerosis (MS), and its association with infections.
Methods:
We retrospectively reviewed the medical records of patients with MS treated using FTY from 12 referral centers in South Korea between March 2013 and June 2021. Patients were classified according to their nadir absolute lymphocyte count (ALC) during treatment:grade 1, 800–999/μL; grade 2, 500–799/μL; grade 3, 200–499/μL; and grade 4, <200/μL.
Results:
FTY treatment was administered to 69 patients with a median duration of 18 months (range=1–169 months), with 11 patients being treated for ≥7 years. During FTY treatment, mean ALCs were reduced after the first month (653.0±268.9/μL, mean±standard deviation) (p<0.0001) and remained low during treatment lasting up to 84 months. During follow-up, 41 (59.4%) and 7 (10.1%) patients developed grade-3 and grade-4 lymphopenia, respectively.No significant difference was found in age at FTY initiation, sex, baseline ALC, body mass index, or prior disease-modifying treatment between patients with and without grade-4 lymphopenia. Infections were observed in 11 (15.9%) patients, and the frequencies of patients with and without grade-4 lymphopenia were similar.
Conclusions
FTY treatment induced grade-4 lymphopenia in 10% of South Korean patients with MS, but did not appear to be associated with an increased infection risk.
10.A Case with Multiple Fungal Coinfections in a Patient who Presented with Pancoast Syndrome
Hyungsuk JIN ; Dongsub KIM ; Joon-sik CHOI ; Hee Jae HUH ; Nam Yong LEE ; Joungho HAN ; Hee Won CHO ; Youngeun MA ; Tae Yeon JEON ; So-Young YOO ; Keon Hee YOO ; Hong Hoe KOO ; Yae-Jean KIM
Pediatric Infection & Vaccine 2021;28(1):42-48
Invasive fungal infection (IFI) is a serious threat to pediatric patients with cancer given high morbidity and mortality. We present an 18-year-old male with precursor T-cell lymphoblastic leukemia who developed Pancoast syndrome, presented with paresthesia and numbness in the right shoulder and arm during a neutropenic fever period. He was diagnosed with pneumonia in the right upper lung field. He was later found to have an invasive pulmonary fungal infection caused by multiple fungi species, including Rhizomucor, confirmed by histology and polymerase chain reaction (PCR) (proven infection), Penicillium decumbens diagnosed by PCR, and Aspergillus suspected from galactomannan assay (probable infection). Unfortunately, the patient's condition further worsened owing to the aggravation of leukemia, chemotherapy-induced neutropenia, and bacterial coinfection, leading to multiorgan failure and death. Here, we report a case of IFI caused by multiple fungal species that presented as Pancoast syndrome.

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