1.FoxO6-Mediated TXNIP Induces Lipid Accumulation in the Liver through NLRP3 Inflammasome Activation
Mi Eun KIM ; Jun Sik LEE ; Tae Won KIM ; Min Hi PARK ; Dae Hyun KIM
Endocrinology and Metabolism 2024;39(1):127-139
Background:
Hepatic steatosis, which involves the excessive accumulation of lipid droplets in hepatocytes, presents a significant global health concern due to its association with obesity and metabolic disorders. Inflammation plays a crucial role in the progression of hepatic steatosis; however, the precise molecular mechanisms responsible for this process remain unknown.
Methods:
This study investigated the involvement of the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome and the forkhead box O6 (FoxO6) transcription factor in the pathogenesis of hepatic steatosis. We monitored the NLRP3 inflammasome and lipogenesis in mice overexpressing the constitutively active (CA)-FoxO6 allele and FoxO6-null mice. In an in vitro study, we administered palmitate to liver cells overexpressing CA-FoxO6 and measured changes in lipid metabolism.
Results:
We administered palmitate treatment to clarify the mechanisms through which FoxO6 activates cytokine interleukin (IL)-1β through the NLRP3 inflammasome. The initial experiments revealed that dephosphorylation led to palmitate-induced FoxO6 transcriptional activity. Further palmitate experiments showed increased expression of IL-1β and the hepatic NLRP3 inflammasome complex, including adaptor protein apoptotic speck protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Furthermore, thioredoxin-interacting protein (TXNIP), a key regulator of cellular redox conditions upstream of the NLRP3 inflammasome, was induced by FoxO6 in the liver and HepG2 cells.
Conclusion
The findings of this study shed light on the molecular mechanisms underpinning the FoxO6-NLRP3 inflammasome axis in promoting inflammation and lipid accumulation in the liver.
2.Characterization of hidden rules linking symptoms and selection of acupoint using an artificial neural network model.
Won-Mo JUNG ; In-Soo PARK ; Ye-Seul LEE ; Chang-Eop KIM ; Hyangsook LEE ; Dae-Hyun HAHM ; Hi-Joon PARK ; Bo-Hyoung JANG ; Younbyoung CHAE
Frontiers of Medicine 2019;13(1):112-120
Comprehension of the medical diagnoses of doctors and treatment of diseases is important to understand the underlying principle in selecting appropriate acupoints. The pattern recognition process that pertains to symptoms and diseases and informs acupuncture treatment in a clinical setting was explored. A total of 232 clinical records were collected using a Charting Language program. The relationship between symptom information and selected acupoints was trained using an artificial neural network (ANN). A total of 11 hidden nodes with the highest average precision score were selected through a tenfold cross-validation. Our ANN model could predict the selected acupoints based on symptom and disease information with an average precision score of 0.865 (precision, 0.911; recall, 0.811). This model is a useful tool for diagnostic classification or pattern recognition and for the prediction and modeling of acupuncture treatment based on clinical data obtained in a real-world setting. The relationship between symptoms and selected acupoints could be systematically characterized through knowledge discovery processes, such as pattern identification.
Acupuncture Points
;
Acupuncture Therapy
;
Humans
;
Neural Networks (Computer)
;
Republic of Korea
;
Syndrome
3.Changes in small intestinal motility and related hormones by acupuncture stimulation at Zusanli (ST 36) in mice.
Jung-Hee JANG ; Deuk-Joo LEE ; Chang-Hwan BAE ; Ki-Tae HA ; Sunoh KWON ; Hi-Joon PARK ; Dae-Hyun HAHM ; Hyejung LEE ; Seungtae KIM
Chinese journal of integrative medicine 2017;23(3):215-220
OBJECTIVESTo clarify the effects of acupuncture stimulation at Zusanli (ST 36) on the hormonal changes.
METHODSEight-week-old male C57BL/6 mice received acupuncture stimulation at acupoint ST 36 or Quchi (LI 11) once a day for 3 or 5 days in the acupuncture-stimulated groups, but not received in the normal group (n=6 in each group). On day 3 or 5, animals were given 0.1 mL of charcoal orally with a bulbed steel needle, 30 min after the last acupuncture stimulation. Ten minutes later, mice were anesthetized, and the intestinal transit and the concentrations of vasoactive intestinal peptide (VIP), motilin, ghrelin and gastrin in the serum were measured.
RESULTSCompared to no acupuncture stimulation, acupuncture stimulation at ST 36 for 5 days increased the intestinal transit and down-regulated the concentration of VIP and up-regulated the concentrations of motilin, ghrelin and gastrin (P<0.05 or 0.01), whereas acupuncture stimulation at LI 11 did not change them signifificantly (P>0.05).
CONCLUSIONAcupuncture stimulation at ST 36 for 5 days enhances the small intestinal motility and regulates the secretion of hormones related to small intestinal motility.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Gastrointestinal Motility ; physiology ; Hormones ; blood ; Intestine, Small ; physiology ; Male ; Mice, Inbred C57BL
4.Thyroid Autoantibody Positive Anti-N-Methyl-D-Aspartate Receptor Encephalitis.
Yoori JUNG ; Soonwon PARK ; Hwan Jun SON ; Dae Soo JUNG ; Eun Hi SA ; Sun Tae LEE ; Eun Soo KIM ; Na Yeon JUNG ; Eun Joo KIM
Dementia and Neurocognitive Disorders 2016;15(1):24-27
BACKGROUND: Hashimoto's encephalopathy (HE) and anti N-methyl-D-aspartate receptor (NMDAR) encephalitis have clinical overlaps. CASE REPORT: A 70-year-old woman presented with acutely developed confusion, disorientations and psychosis. HE was suspected based on goiter, markedly elevated anti-thyroglobulin and anti-thyroid peroxidase antibody. She was placed on high dose steroid and intravenous immunoglobulins administration, which did not ameliorate her symptoms. After the antibodies to the NMDAR were identified, weekly 500 mg of rituximab with 4 cycles were started. The current followed up indicated a complete recovery. CONCLUSIONS: The possible associations between NMDAR antibody and autoimmune thyroid antibodies in anti-NMDAR encephalitis with positive thyroid autoantibodies remain unclear. However, a trend toward a higher incidence of NMDAR antibody in patients with autoimmune thyroid antibodies than without has been observed. Cases of encephalitis with only NMDAR antibody (pure anti-NMDAR encephalitis) also occur. Therefore, it is important for clinicians to know the clinical and pathogenic differences between anti-NMDAR encephalitis with positive thyroid autoantibody and pure anti-NMDAR encephalitis for relevant treatment, predicting prognosis, and future follow-up.
Aged
;
Anti-N-Methyl-D-Aspartate Receptor Encephalitis*
;
Antibodies
;
Autoantibodies
;
Encephalitis
;
Female
;
Follow-Up Studies
;
Goiter
;
Humans
;
Immunoglobulins, Intravenous
;
Incidence
;
N-Methylaspartate
;
Peroxidase
;
Prognosis
;
Psychotic Disorders
;
Thyroid Gland*
;
Rituximab
5.Human bone marrow-derived mesenchymal stem cell gene expression patterns vary with culture conditions.
Myoung Woo LEE ; Dae Seong KIM ; Keon Hee YOO ; Hye Ryung KIM ; In Keun JANG ; Ji Hyang LEE ; So Yeon KIM ; Meong Hi SON ; Soo Hyun LEE ; Hye Lim JUNG ; Ki Woong SUNG ; Hong Hoe KOO
Blood Research 2013;48(2):107-114
BACKGROUND: Because of the heterogeneity of human mesenchymal stem cells (MSCs), methods for cell expansion in culture and the effects on gene expression are critical factors that need to be standardized for preparing MSCs. We investigated gene expression patterns of MSCs with different seeding densities and culture times. METHODS: Bone marrow-derived MSCs were plated at densities from 200 cells/cm2 to 5,000 cells/cm2, and the gene expression patterns were evaluated over time using a reverse-transcription polymerase chain reaction assay. RESULTS: The mRNA levels of factors that play a critical role in cell migration and tissue regeneration, such as podocalyxin-like protein (PODXL), alpha4-integrin, alpha6-integrin, and leukemia inhibitory factor (LIF), were higher in MSCs plated at 200 cells/cm2 than in MSCs plated at 5,000 cells/cm2. The mRNA levels of these factors gradually increased for 10 days and then decreased by day 15 in culture. MSCs seeded at 200 cells/cm2 that were cultured for 10 days expressed high levels of Oct-4 and Nanog. Indoleamine 2,3-dioxygenase, cyclooxygenase-1, and hepatocyte growth factor expression were upregulated in the presence of the proinflammatory cytokine interferon-gamma in these cells. CONCLUSION: We found differences in the gene expression patterns of MSCs under different culture conditions. MSCs from 10-day cultures seeded at a low density were efficiently expanded, expressed PODXL, alpha6-integrin, alpha4-integrin, and LIF, and maintained properties like stemness and immunomodulation. Therefore, ex vivo expansion of MSCs maintained for an adequate culture time after plating at low cell density can provide an effective regenerative medicinal strategy for cell therapies using MSCs.
Cell Count
;
Cell Movement
;
Cyclooxygenase 1
;
Gene Expression
;
Hepatocyte Growth Factor
;
Humans
;
Immunomodulation
;
Indoleamine-Pyrrole 2,3,-Dioxygenase
;
Interferon-gamma
;
Leukemia Inhibitory Factor
;
Mesenchymal Stromal Cells
;
Polymerase Chain Reaction
;
Population Characteristics
;
Regeneration
;
RNA, Messenger
;
Seeds
;
Tissue Therapy
6.Hematologic Recovery after Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Children with High-Risk Solid Tumors.
Meong Hi SON ; Dong Hwan KIM ; Soo Hyun LEE ; Keon Hee YOO ; Ki Woong SUNG ; Hong Hoe KOO ; Ju Youn KIM ; Eun Joo CHO ; Eun Suk KANG ; Dae Won KIM
Journal of Korean Medical Science 2013;28(2):220-226
Although the number of studies using tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) for the treatment of high-risk pediatric solid tumors has been increasing, documentation of hematologic recovery after tandem HDCT/autoSCT is very limited. For this reason, we retrospectively analyzed the hematologic recovery of 236 children with high-risk solid tumors who underwent tandem HDCT/autoSCT. The median numbers of CD34+ cells transplanted during the first and second HDCT/autoSCT were 4.3 x 10(6)/kg (range 0.6-220.2) and 4.1 x 10(6)/kg (range 0.9-157.6), respectively (P = 0.664). While there was no difference in neutrophil recovery between the first and second HDCT/autoSCT, platelet and RBC recoveries were significantly delayed in the second HDCT/autoSCT (P < 0.001 and P < 0.001, respectively). Delayed recovery in the second HDCT/autoSCT was more prominent when the number of transplanted CD34+ cells was lower, especially if it was < 2 x 10(6)/kg. A lower CD34+ cell count was also associated with increased RBC transfusion requirements and a higher serum ferritin level after tandem HDCT/autoSCT. More CD34+ cells need to be transplanted during the second HDCT/autoSCT in order to achieve the same hematologic recovery as the first HDCT/autoSCT.
Adolescent
;
Antigens, CD34/metabolism
;
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
;
Blood Cell Count
;
Blood Platelets/cytology
;
Child
;
Child, Preschool
;
Combined Modality Therapy
;
Erythrocytes/cytology
;
Female
;
Ferritins/blood
;
Humans
;
Infant
;
Male
;
Neoplasms/*drug therapy
;
Neutrophils/cytology
;
Retrospective Studies
;
*Stem Cell Transplantation
;
Stem Cells/cytology/metabolism
;
Transplantation, Autologous
;
Young Adult
7.The Fate of Butterfly Fragments in Extremity Shaft Comminuted Fractures Treated with Closed Interlocking Intramedullary Nailing.
Ki Chan AN ; Yoon Jun KIM ; Jang Suk CHOI ; Seung Suk SEO ; Hi Chul GWAK ; Dae Won JUNG ; Dong Woo JEONG
Journal of the Korean Fracture Society 2012;25(1):46-51
PURPOSE: For conservative treatment of shaft fractures, the butterfly fragments that were somewhat larger in the closed intra-medullary (IM) nailing. The results of treatment were monitored using radiography separately for the weight-bearing femur and non-weight-bearing humerus. MATERIALS AND METHODS: 27 from Group I and 31 from Group II. In the two groups, the displacement and angulation changes in the fragments, and the degree of improvement of these two factors, were compared using follow-up radiography. RESULTS: The mean angulation of fragments in Groups I and II were 9.2degrees and 9.6degrees, and the mean degree of displacement of the fragments in Groups I and II were 16.7 mm and 21.2 mm, respectively. Follow-up radiography showed that the above factors improved in both groups. The degree of displacement was significantly lower in the normal cases than in the complicated cases (p=0.001). CONCLUSION: Displacement and angulation gradually improved in both groups. It was found that the degree of displacement after the initial reduction is more important than the influence of anatomical position or weight bearing. This indicates that care should be taken when inserting IM nails to prevent displacement or angulation.
Butterflies
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Displacement (Psychology)
;
Extremities
;
Femur
;
Follow-Up Studies
;
Fracture Fixation, Intramedullary
;
Fractures, Comminuted
;
Nails
;
Weight-Bearing
8.Predictive factors for invasive intraductal papillary mucinous neoplasm of the pancreas.
Dae Young JUN ; Hyung Jun KWON ; Sang Geol KIM ; Sung Hi KIM ; Jae Min CHUN ; Young Bong KWON ; Kyung Jin YOON ; Yoon Jin HWANG ; Young Kook YUN
Korean Journal of Hepato-Biliary-Pancreatic Surgery 2011;15(4):237-242
BACKGROUNDS/AIMS: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has malignant potential. Predicting invasive IPMN has proven difficult and controversial. We tried to identify predictive factors for invasive IPMN. METHODS: Thirty six patients underwent resection for IPMN from February 2001 to July 2011. Clinicopathological features including demographic, imaging, microscopic, and serological findings were retrospectively reviewed. Receiver operating characteristic (ROC) curve analysis was used to analyze sensitivity and specificity of all possible cut-off values for the diameter of the main pancreatic duct and mass size predicting invasive IPMN. Student t-test, chi-square test, and logistic regression were used for univariate and multivariate analysis. RESULTS: The mean age was 63.5+/-8.4 years. Males were more commonly affected (58.3% vs 41.7%). Pancreaticoduodenectomy was performed in 55.6% of patients, distal pancreatectomy in 36.1%, and central pancreatic resection in 8.3%. Non-invasive IPMNs were present in 80.6% (n=29), whereas invasive IPMNs were present in 19.4% (n=7). In univariate analysis, tumor location (p=0.036), Kuroda classification (p=0.048), mural nodule (p=0.016), and main duct dilatation (> or =8 mm) (p=0.006) were statistically significant variables. ROC curve analysis showed that a value of 8 mm for the main duct dilatation and a value of 35 mm for the size of the mass lesion have 80% sensitivity and 75% specificity and 100% sensitivity and 82.6% specificity, respectively. However, in multivariate analysis, main ductal dilatation (> or =8 mm) was identified to be the only independent factor for invasive IPMN (p=0.049). CONCLUSIONS: Main duct dilatation appears to be a useful indicator for predicting invasive IPMN.
Dilatation
;
Humans
;
Logistic Models
;
Male
;
Mucins
;
Multivariate Analysis
;
Pancreas
;
Pancreatectomy
;
Pancreatic Ducts
;
Pancreaticoduodenectomy
;
Retrospective Studies
;
ROC Curve
;
Sensitivity and Specificity
9.Ileal Stenosis Occurred 3 Months after Blunt Abdominal Trauma.
Gun Hi KANG ; Tae Joo JEON ; Dong Dae SEO ; Tae Hoon OH ; Soohyun KIM ; Hyun Sun CHO ; Byung Noe BAE ; Jung Yeon KIM
The Korean Journal of Gastroenterology 2011;57(6):370-373
We present a case of ileal stenosis with delayed presentation 3 months after car accident. Ileal stenosis after blunt abdominal trauma is a rare clinical entity. We present CT and small bowel series 3 months after trauma. Image showed segmental thickening of intestinal wall and proximal bowel dilation. At surgery, a stenotic bowel loop was adjacent to a fibrotic mesentery. Histological examination showed ulcers, inflammatory cells and fibroblasts infiltrated to the muscularis mucosae, submucosa, and mesentery. The most likely cause, supported by most authors, implicates an injury to the mesentery. Post-traumatic ischemic bowel stenosis may result from even small tears and contusions of mesentery. Posttraumatic intestinal stenosis should be included in the differential diagnosis in a patient with a history of blunt abdominal trauma and signs of intestinal obstruction.
10.The Relationship between Aortic Calcification Volume and Obstructive Coronary Artery Disease: Comparison with Coronary Calcification Volume.
Dae Seok KIM ; Jeong Ho KIM ; Chul Hi PARK ; Seon Young PARK ; Soo Jin CHOE ; Hee Young HWANG ; Hyung Sik KIM
Journal of the Korean Radiological Society 2007;57(6):511-518
PURPOSE: We compared the diagnostic performance of aortic calcification volume with that of coronary artery calcification volume at CT in diagnosing obstructive coronary artery disease (OCAD). MATERIALS AND METHODS: A total of 308 patients (M: F=141:167) underwent coronary CT angiography using a 64-slice MDCT. We measured the calcification volume (mm3) of coronary artery (CAC), thoracic aorta (TAC), abdominal aorta (AAC), and whole aorta (AC) at unenhanced CT. OCAD was defined as the significant stenosis (>=50%) in any coronary artery at CT angiography. The diagnostic performance for OCAD was evaluated by calculating the area under the receiver operating characteristic (ROC) curve. RESULTS: Among the 308 patients studied, 45 patients were diagnosed with OCAD. The mean volumes of TAC, AAC, AC, and CAC were 518.8 mm3, 551.5 mm3, 1069.9 mm3, 57.6 mm3, respectively. The areas under the ROC curve of TAC, AAC, AC, and CAC for OCAD were 0.766 (0.694<95% confidence interval <0.838), 0.837 (0.784<95% confidence interval <0.892), 0.814 (0.755<95% confidence interval <0.873), 0.871 (0.812<95% confidence interval<0.930), respectively. CONCLUSION: The volume of aortic calcification as well as coronary artery calcification is associated with obstructive coronary artery disease.
Angiography
;
Aorta
;
Aorta, Abdominal
;
Aorta, Thoracic
;
Calcinosis
;
Constriction, Pathologic
;
Coronary Artery Disease*
;
Coronary Disease
;
Coronary Vessels*
;
Humans
;
ROC Curve
;
Tomography, X-Ray Computed

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