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.Treatment and Prognostic Factors for Traumatic Liver Injury.
Jung Min BAE ; Nak Hi KIM ; Hyun Kyu LEE ; Kyu Ha JEON ; Bong Choon JEON ; Jong Dae BAE ; Ho Keun JUNG ; Ki Hoon JUNG ; Byung Wook JUNG ; Sung Han BAE
Journal of the Korean Surgical Society 2004;66(6):490-495
PURPOSE: Due to its size and locatin, the liver is frequently injured in abdominal trauma. Recently, nonoperative management for liver injuries has been extended due to the development CT imaging, intensive care units, and their equipment and techniques. Herein, patients with traumatic liver injury were analyzed to evaluate its treatment and prognostic factors. METHODS: From 2001, January to 2003, July, 65 patients at our facility were confirmed to have traumatic liver injury. The operative or nonoperative managements were decided on the basis of the systolic blood pressure if no peritoneal irritation sign was noted. If the systolic blood pressure was stable, or recovered to within the normal range following hydration and transfusion at the emergency room, patients were managed nonoperatively. Hemodynamically unstable patients were managed operatively. The data were analysed using the SPSS program (Chi-squared tests and logistic regression analyses). RESULTS: 48 patients were treated nonoperatively, with 3 mortalities. The overall mortality rate was 15.8%, but only 6.4% in the nonoperative management group, compared to 67% in operative management group. In a Multivariate analysis the systolic blood pressure was found to be a reliable factor in traumatic liver injury and the mentality and ISS (injury severity score) reliable in finding complications in the nonoperative management group. The mentality was found statistically reliable for determining mortality in the operative management group, with the exception for the systolic blood pressure. CONCLUSION: The systolic blood pressure was an important indicator when considering the treatment plan in traumatic liver injury. An extensive study will be required that incorporates both nonoperative and operative management groups.
Blood Pressure
;
Emergency Service, Hospital
;
Humans
;
Intensive Care Units
;
Liver*
;
Logistic Models
;
Mortality
;
Multivariate Analysis
;
Reference Values
8.Plantar Pressure Reducing Effect of Diabetic Shoes with Different Rigid Rockers.
Young Kwon CHOI ; Ji Hye HWANG ; Hi Dae LEE ; Young Tae WOO ; Young Kil KIM ; Dong Youp KIM
Journal of the Korean Academy of Rehabilitation Medicine 2004;28(2):169-174
OBJECTIVE: To determine the most effective type of rigid rocker bottom for prevention of diabetic foot complications according to the different rocker angles and axes of diabetic shoes. METHOD: Thirteen healthy volunteers participated in this study and the plantar peak pressure and pressure time integrals were measured by insole plantar pressure system for subjects either barefoot and wearing rigid rocker shoes with 12 kinds of different rocking angles and rocking points (15, 20, 25, 30degrees and 60, 65, 70% of shoe length). Evaluation was analyzed at M1 (hindfoot), M2 (midfoot), M3 (medial forefoot area), M4 (central forefoot area), M5 (lateral forefoot area), M6 (1st toe area), M7 (lesser toes area) zones respectively. RESULTS: Reduced pressure was observed in all kinds of rockers at central-metatarsal area (p<0.05). But pressure was not significantly changed at lateral metatarsal area in almost all types of rocker. With rocking point at 65 and 70%, pressure was increased at first and lesser toe area in all rocking angles. With rocking point at 60 and 70%, pressure was increased at midfoot area. CONCLUSION: Most effectively reduced pressure was observed with shoe of rocking point at 65% and rocking angle 30degress.
Diabetic Foot
;
Healthy Volunteers
;
Metatarsal Bones
;
Shoes*
;
Toes
9.A Case of Eosinophilic Colitis in a 11-year-old Boy.
Joo Hee NAH ; Young Shil PARK ; Sun Mi KIM ; Jung Hyun LEE ; Dae Chul JEONG ; Jin Tack KIM ; Seung Yun CHUNG ; An Hi LEE ; Jin Han KANG ; Joon Sung LEE
Korean Journal of Pediatric Gastroenterology and Nutrition 2002;5(1):91-95
Eosinophilic gastroenteritis, which shows characteristic eosinophilic inflammation, involves any part of the intestine from esophagus to colon. The immunopathogenesis is expected to be associated with IgE-mediated or non-IgE-mediated reaction, but the precise mechanism is not revealed yet. The clinical manifestation is variably dependent on the extent of eosinophilic infiltration. Usually the symptoms, such as abdominal pain, diarrhea, vomiting, wax and wane for a few months result in failure to thrive, which implicates the importance of early detection. Although the diagnosis is made through clinical and histopathologic evidences, we should suspect the illness in a case of anemia, hypoalbuminemia, and peripheral eosinophilia. Recently, we experienced a case of non- IgE-mediated eosinophilic colitis in a 11-year-old male who complained of diarrhea, right lower abdominal pain, body weight loss, was diagnosed with peculiar histopathologic finding of sigmoid colon specimens obtained by sigmoidoscopy.
Abdominal Pain
;
Anemia
;
Body Weight
;
Child*
;
Colitis*
;
Colon
;
Colon, Sigmoid
;
Diagnosis
;
Diarrhea
;
Eosinophilia
;
Eosinophils*
;
Esophagus
;
Failure to Thrive
;
Gastroenteritis
;
Humans
;
Hypoalbuminemia
;
Inflammation
;
Intestines
;
Male*
;
Sigmoidoscopy
;
Vomiting
10.A Case of Waldenstrom's Macroglobulinemia Treated with 2-Chlorodeoxyadenosine (Cladribine).
Ho Sung PARK ; Hyeon Seok EOM ; Yu Mi SOU ; Jae Wook KIM ; Dae Hyung JUN ; Chi Wha HAN ; Je Hoon LEE ; An Hi LEE
Korean Journal of Hematology 2002;37(3):227-230
Waldenstrom's macroglobulinemia is a low- grade lymphoproliferative disorder with monoclonal IgM protein. It is characterized by normocytic, normochromic anemia and lymphoplasmacytic marrow infiltration. Chemotherapy with alkylating agents and steroids has been the standard therapy for patients with symptomatic macroglobulinemia. The purine nucleoside analogues, either alone or in combination with other chemotherapeutic agents are increasingly used, and approximately 40% of patients who have received prior therapy with alkylating agents responded. We experienced a case of Waldenstrom's macroglobulinemia suc-cessfully treated with three courses of cladribine, who had previously received unsuccessful therapy using an alkylating agent, steroid and plasmapheresis. Treatment was well tolerated except for frequent upper respiratory infections with severe pancytopenia. A marked and sustained bone marrow suppression occurred in this patient but resolved in three months without any severe infection.
Alkylating Agents
;
Anemia
;
Bone Marrow
;
Cladribine*
;
Drug Therapy
;
Humans
;
Immunoglobulin M
;
Lymphoproliferative Disorders
;
Pancytopenia
;
Plasmapheresis
;
Respiratory Tract Infections
;
Steroids
;
Waldenstrom Macroglobulinemia*

Result Analysis
Print
Save
E-mail