1.Adipose Tissue-Derived Mesenchymal Stem Cell Inhibits Osteoclast Differentiation through Tumor Necrosis Factor Stimulated Gene-6
Kwanghoon LEE ; Eunhee KO ; Yongbeom PARK
Tissue Engineering and Regenerative Medicine 2024;21(4):587-594
BACKGROUND:
Mesenchymal stem cells (MSCs) have been highlighted as a potent therapeutic option for conditions with excessive osteoclast activity such as systemic and local bone loss in rheumatic disease. In addition to their immunomodulatory functions, MSCs also directly suppress osteoclast differentiation and activation by secreting osteoprotegerin (OPG) and IL-10 but the underlying mechanisms are still to be clarified. Tumor necrosis factor-stimulated gene-6 (TSG-6) is a potent anti-inflammatory molecule that inhibits osteoclast activation and has been shown to mediate MSC’s immunomodulatory functions. In this study, we aimed to determine whether adipose tissue-derived MSC (ADMSC) inhibits the differentiation from osteoclast precursors to mature osteoclasts through TSG-6.
METHODS:
Human ADMSCs were co-cultured with bone marrow-derived monocyte/macrophage (BMMs) from DBA/ 1J or B6 mouse in the presence of osteoclastogenic condition (M-CSF 10 ng/mL and RANKL 10 ng/mL). In some coculture groups, ADMSCs were transfected with siRNA targeting TSG-6 or OPG to determine their role in osteoclastogenesis. Tartrate-resistant acid phosphatase (TRAP) activity in culture supernatant and mRNA expression of osteoclast markers were investigated. TRAP+ multinucleated cells and F-actin ring formation were counted.
RESULTS:
ADMSCs significantly inhibited osteoclast differentiation under osteoclastogenic conditions. Suppression of TSG-6 significantly reversed the inhibition of osteoclast differentiation in a degree similar to that of OPG based on TRAP activity, mRNA expression of osteoclast markers, and numbers of TRAP+ multinucleated cell and F-actin ring formation.
CONCLUSION
This study demonstrated that ADMSCs inhibit osteoclast differentiation through TSG-6 under osteoclastogenic conditions.
2.Brain Tumor Classification by Methylation Profile
Jin Woo PARK ; Kwanghoon LEE ; Eric Eunshik KIM ; Seong-Ik KIM ; Sung-Hye PARK
Journal of Korean Medical Science 2023;38(43):e356-
The goal of the methylation classifier in brain tumor classification is to accurately classify tumors based on their methylation profiles. Accurate brain tumor diagnosis is the first step for healthcare professionals to predict tumor prognosis and establish personalized treatment plans for patients. The methylation classifier can be used to perform classification on tumor samples with diagnostic difficulties due to ambiguous histology or mismatch between histopathology and molecular signatures, i.e., not otherwise specified (NOS) cases or not elsewhere classified (NEC) cases, aiding in pathological decision-making. Here, the authors elucidate upon the application of a methylation classifier as a tool to mitigate the inherent complexities associated with the pathological evaluation of brain tumors, even when pathologists are experts in histopathological diagnosis and have access to enough molecular genetic information. Also, it should be emphasized that methylome cannot classify all types of brain tumors, and it often produces erroneous matches even with high matching scores, so, excessive trust is prohibited. The primary issue is the considerable difficulty in obtaining reference data regarding the methylation profile of each type of brain tumor. This challenge is further amplified when dealing with recently identified novel types or subtypes of brain tumors, as such data are not readily accessible through open databases or authors of publications. An additional obstacle arises from the fact that methylation classifiers are primarily research-based, leading to the unavailability of charging patients. It is important to note that the application of methylation classifiers may require specialized laboratory techniques and expertise in DNA methylation analysis.
3.Development of a smartphone application for providing disinfectant information on livestock industry
Hansung CHUNG ; Su kwon KIM ; Kwanghoon CHOI ; Ji Heon PARK ; Swe Lynn HTET ; Nonghoon CHOE
Korean Journal of Veterinary Research 2019;59(2):97-100
It is important to select the correct disinfectants and to use them appropriately in order to prevent the initial spread of highly infectious livestock disease, such as foot-and-mouth disease or highly pathogenic avian influenza. This study describes a smartphone application developed to enable livestock workers to observe information related to disinfectants for the prevention of livestock disease in the domestic market, regardless of time and location, through a Linux-based Android mobile platform. This application (Konkuk-Disinfectant Information Database) provides information on disinfectant names, components, license and use; it was designed to enable the user to share disinfectant information through social media.
4.Development of a smartphone application for providing disinfectant information on livestock industry
Hansung CHUNG ; Su kwon KIM ; Kwanghoon CHOI ; Ji Heon PARK ; Swe Lynn HTET ; Nonghoon CHOE
Korean Journal of Veterinary Research 2019;59(2):97-100
It is important to select the correct disinfectants and to use them appropriately in order to prevent the initial spread of highly infectious livestock disease, such as foot-and-mouth disease or highly pathogenic avian influenza. This study describes a smartphone application developed to enable livestock workers to observe information related to disinfectants for the prevention of livestock disease in the domestic market, regardless of time and location, through a Linux-based Android mobile platform. This application (Konkuk-Disinfectant Information Database) provides information on disinfectant names, components, license and use; it was designed to enable the user to share disinfectant information through social media.
Animals
;
Disinfectants
;
Foot-and-Mouth Disease
;
Influenza in Birds
;
Licensure
;
Livestock
;
Methyltestosterone
;
Smartphone
;
Social Media
5.Echinostoma miyagawai Ishii, 1932 (Echinostomatidae) from Ducks in Aceh Province, Indonesia with Special Reference to Its Synonymy with Echinostoma robustum Yamaguti, 1935
Jong-Yil CHAI ; Bong-Kwang JUNG ; Taehee CHANG ; Hyejoo SHIN ; Jaeeun CHO ; Jin-Youp RYU ; Hyun-Seung KIM ; Kwanghoon PARK ; Mun-Hyoo JEONG ; Eui-Hyug HOANG ; Marzuki Bin Muhammad ABDULLAH
The Korean Journal of Parasitology 2021;59(1):35-45
Adult echinostomes having 37 collar spines collected from the intestine of Pitalah ducks in Aceh Province, Indonesia in 2018 were morphologically and molecularly determined to be Echinostoma miyagawai Ishii, 1932 (Digenea: Echinostomatidae). Among 20 ducks examined, 7 (35.0%) were found to be infected with this echinostome, and the number of flukes collected was 48 in total with average 6.9 (1-17) worms per duck. The adult flukes were 7.2 (6.1-8.5) mm in length and 1.2 (1.0-1.4) mm in width (pre-ovarian or testicular level) and characterized by having a head collar armed with 37 collar spines (dorsal spines arranged in 2 alternating rows), including 5 end group spines, and variable morphology of the testes, irregularly or deeply lobed (3-5 lobes) at times with horizontal extension. The eggs within the worm uterus were 93 (79-105) µm long and 62 (56-70) µm wide. These morphological features were consistent with both E. miyagawai and Echinostoma robustum, for which synonymy to each other has been raised. Sequencing of 2 mitochondrial genes, cox1 and nad1, revealed high homology with E. miyagawai (98.6-100% for cox1 and 99.0-99.8% for nad1) and also with E. robustum (99.3-99.8% for nad1) deposited in GenBank. We accepted the synonymy between the 2 species and diagnosed our flukes as E. miyagawai (syn. E. robustum) with redescription of its morphology. Further studies are required to determine the biological characteristics of E. miyagawai in Aceh Province, Indonesia, including the intermediate host and larval stage information.
6.Methylation-based Subclassifications of Embryonal Tumor with Multilayered Rosettes in Not Just Pediatric Brains
Eric Eunshik KIM ; Kwanghoon LEE ; Ji-Hoon PHI ; Min-Sung KIM ; Hyoung Jin KANG ; Hongseok YUN ; Sung-Hye PARK
Experimental Neurobiology 2023;32(5):354-361
The aim of this study is to investigate the genetic profiles and methylation-based classifications of Embryonal tumor with multilayered rosettes (ETMR), with a specific focus on differentiating between C19MC amplified and C19MC-not amplified groups, including cases with DICER1 mutations. To achieve this, next-generation sequencing using a targeted gene panel for brain tumors and methylation class studies using the Epic850K microarray were performed to identify tumor subclasses and their clinicopathological characteristics. The study cohort consisted of four patients, including 3 children (a 4-months/F, a 9-months/M, and a 2 y/F), and one adult (a 30 y/Male). All three tumors in the pediatric patients originated in the posterior fossa and exhibited TTYH1:C19MC fusion and C19MC amplification. The fourth case in the adult patient involved the cerebellopontine angle with biallelic DICER1 mutation. Histopathological examination revealed typical embryonal features characterized by multilayered rosettes and abundant neuropils in all cases, while the DICER1-mutant ETMR also displayed cartilage islands in addition to the classic ETMR pathology. All four tumors showed positive staining for LIN28A. The t-SNE clustering analysis demonstrated that the first three cases clustered with known subtypes of ETMR, specifically C19MC amplified, while the fourth case clustered separately to non-C19MC amplified subclass. During the follow-up period of 6~12 months, leptomeningeal dissemination of the tumor occurred in all patients. Considering the older age of onset in DICER1-mutant ETMR, genetic counseling should be recommended due to the association of DICER1 mutations with germline and second-hit somatic mutations in cancer.
7.An Autopsy-proven Case-based Review of Autoimmune Encephalitis
Yu-Mi SHIM ; Seong-Ik KIM ; So Dug LIM ; Kwanghoon LEE ; Eric Eunshik KIM ; Jae Kyung WON ; Sung-Hye PARK
Experimental Neurobiology 2024;33(1):1-17
Autoimmune encephalitis (AIE) is a type of immunoreactive encephalitic disorder and is recognized as the most prevalent noninfectious encephalitis. Nevertheless, the rarity of definitive AIE diagnosis through biopsy or autopsy represents a significant hurdle to understanding and managing the disease. In this article, we present the pathological findings of AIE and review the literature based on a distinct case of AIE presenting as CD8+ T-lymphocyte predominant encephalitis. We describe the clinical progression, diagnostic imaging, laboratory data, and autopsy findings of an 80-year-old deceased male patient. The patient was diagnosed with pulmonary tuberculosis 6 months before death and received appropriate medications. A week before admission to the hospital, the patient manifested symptoms such as a tendency to sleep, decreased appetite, and confusion.Although the patient temporally improved with medication including correction of hyponatremia, the patient progressed rapidly and died in 6 weeks. The brain tissue revealed lymphocytic infiltration in the gray and white matter, leptomeninges, and perivascular infiltration with a predominance of CD8+ T lymphocytes, suggesting a case of AIE. There was no detectable evidence of viral infection or underlying neoplasm. The autopsy revealed that this patient also had Alzheimer’s disease, atherosclerosis, arteriolosclerosis, and aging-related tau astrogliopathy. This report emphasizes the pivotal role of pathological examination in the diagnosis of AIE, especially when serological autoantibody testing is not available or when a patient is suspected of having multiple diseases.