1.mTOR Plays an Important Role in the Stemness of Human Fetal Cartilage Progenitor Cells (hFCPCs)
Him-Cha SHIN ; Jiyoung KIM ; So Ra PARK ; Byung Hyune CHOI
Tissue Engineering and Regenerative Medicine 2024;21(2):309-318
BACKGROUND:
Mammalian target of rapamycin (mTOR) is known to regulate self-renewal ability and potency of embryonic stem cells (ESCs) and adult stem cells in opposite manners. However, its effects vary even among adult stem cells and are not reported in fetal stem/progenitor cells. This study investigated the role of mTOR in the function of human fetal cartilage-derived progenitor cells (hFCPCs).
METHODS:
mTOR activity in hFCPCs was first examined via the level of phosphor-mTOR until passage 19, together with doubling time of cells and senescence-associated b-galactosidase (SA-bGal). Then, the effect of 100 nM rapamycin, the inhibitor of mTOR, was investigated on self-renewal ability, proliferation rate and osteogenic/adipogenic potential of hFCPCs in vitro. Expression of stemness genes (Oct-4, Sox2 and Nanog) and cell cycle regulators (CDK4 and Cyclin D1) was measured at mRNA or protein levels.
RESULTS:
mTOR activity was maintained constantly at high levels in hFCPCs until passage 19, while their proliferation rate was decreasing from 48 h at passage 13 to 70 h at passage 9 and senescent cells were observed at passage 18 (8.3 ± 1.2%) and 19 (15.6 ± 1.9%). Inhibition of mTOR in hFCPCs impaired their colony forming frequency (CFU-F) by 4 folds, while showing no change in their doubling time and expression of CDK4 and Cyclin D1. Upon mTOR inhibition, Oct4 expression decreased by 2 folds and 4 folds at the mRNA and protein levels, respectively, while that of Sox2 and Nanog did not change significantly. Finally, mTOR inhibition reduced osteogenic and adipogenic differentiation of hFCPCs in vitro.
CONCLUSION
This study has shown that mTOR plays an important role in the self-renewal ability of hFCPCS but not in their proliferation, The effect of mTOR appears to be associated with Oct-4 expression and important in the osteogenic and adipogenic differentiation ability of hFCPCs.
2.Morning Spot Urine Glucose-to-Creatinine Ratios Predict Overnight Urinary Glucose Excretion in Patients With Type 2 Diabetes.
So Ra KIM ; Yong Ho LEE ; Sang Guk LEE ; Sun Hee LEE ; Eun Seok KANG ; Bong Soo CHA ; Hyun Chul LEE ; Jeong Ho KIM ; Byung Wan LEE
Annals of Laboratory Medicine 2017;37(1):9-17
BACKGROUND: With the advent of sodium glucose co-transporter 2 inhibitors to control glucose and treat diabetes, laboratory data aided by either timed or spot glucose levels in the urine could be used as an alternative marker of drug response. The aim of this study was to assess the agreement between overnight urinary glucose excretion (UGE) and morning spot urinary glucose-to-creatinine ratio (UGCR). METHODS: In this prospective cross-sectional study, we enrolled a total of 215 participants with either normal glucose tolerance (NGT), pre-diabetes, or type 2 diabetes mellitus (T2DM). To exclude external factors such as food intake and physical activity, urine samples collected overnight at an 8-hr interval and the first-voided morning spot urine were collected and compared. RESULTS: The median values of overnight 8-hr UGE in participants with NGT (N=14), pre-diabetes (N=41), and T2DM (N=160) were 35.0 mg, 35.6 mg, and 653.4 mg, respectively. In participants with T2DM, the median values of overnight 8-hr UGCR and first-voided morning spot UGCR (M-UGCR) were 1.37 mg/mg and 0.16 mg/mg, respectively. Quantitative analyses using an intraclass correlation coefficient (ICC) demonstrated a good reliability of measurement of the overnight 8-hr UGCR and M-UGCR (ICC=0.943, P<0.001). The M-UGCR was also significantly related to the overnight 8-hr UGE (r=0.828, P<0.001). CONCLUSIONS: M-UGCR and overnight 8-hr UGCR showed good agreement, suggesting that M-UGCR be used as a simple index for estimating overnight amounts of UGE in patients with T2DM.
Adult
;
Aged
;
Blood Glucose/analysis
;
Creatinine/*urine
;
Cross-Sectional Studies
;
Diabetes Mellitus, Type 2/*pathology
;
Female
;
Glucose/*analysis/metabolism
;
Humans
;
Linear Models
;
Male
;
Middle Aged
;
Prospective Studies
;
Urinalysis
3.Drainage of an acute spinal epidural hematoma that developed without risk factors in the thoracic spine using epidural needle: A case report.
Young Deog CHA ; Gi Won KIM ; Chun Woo YANG ; So Ra OH ; Seung Won RYOO ; Byung Gun KIM
Anesthesia and Pain Medicine 2017;12(3):266-270
Epidural hematoma after epidural block is a rare complication in healthy patients without risk factor. However, this rare disease can lead to neurological symptoms or paralysis. It is usually treated with surgical drainage. Herein we report a case of acute thoracic epidural hematoma associated with neurologic symptoms after epidural block in a healthy male without risk factors. We performed drainage of the epidural hematoma using 18-gauge Tuohy needle without surgical intervention. The patient's neurological symptoms and pain were relieved. He was discharged without sequelae.
Drainage*
;
Hematoma
;
Hematoma, Epidural, Spinal*
;
Humans
;
Male
;
Needles*
;
Neurologic Manifestations
;
Paralysis
;
Rare Diseases
;
Risk Factors*
;
Spine*
4.Erratum to: Characteristics and Cardiomyogenic Potential of RatFetal Cardiac Progenitor Cells at Different Developmental Stage.
Tung Nguyen THANH ; Him Cha SHIN ; Hwal Ran KIM ; So Ra PARK ; Jiyoung KIM ; Byung Hyune CHOI
Tissue Engineering and Regenerative Medicine 2017;14(4):477-477
There are some errors in the published article. The authors would like to make corrections in the original version of the article
5.Characteristics and Cardiomyogenic Potential of Rat Fetal Cardiac Progenitor Cells at Different Developmental Stage.
Tung Nguyen THANH ; Him Cha SHIN ; Hwal Ran KIM ; So Ra PARK ; Jiyoung KIM ; Byung Hyune CHOI
Tissue Engineering and Regenerative Medicine 2017;14(3):253-265
In recent years, several kinds of cardiac progenitor cells have been identified and isolated from heart tissue. These cells showed differentiation potential into cardiomyocytes, smooth muscle cells, and endothelial cells in vitro and in vivo. Morphogenetic events are tightly regulated during development to determine cell destiny and reshape the embryonic lineage. In this study, we directly compared the characteristics of rat fetal cardiac progenitor cells (rFCPCs) isolated from the chamber formation stage at embryonic day 12 (E12) and at the septation stage of E15. Both kinds of rFCPCs expressed mesenchymal stem cell markers (CD105, CD73, and CD29) but not CD34 and CD45. The E12 rFCPCs expressed a high level of Oct4 compared to E15 until passage 5 and showed a steep decline of Nkx2.5 expression at passage 5. However, Nkx2.5 expression at E15 was maintained until passage 5 and Oct4 expression slightly increased at passage 5. We also detected an intense staining for Oct4 antibody in E12 heart tissue sections. The average doubling time of the E12 rFCPCs from passage 3 to passage 15 was about 5 hours longer than E15. These cells could also be induced into cardiomyocytes expressing α-MHC, cTnT, cTnC, and Cx43 under cardiomyogenic culture conditions and rFCPCs at E15 showed more intense staining of α-MHC than cells at E12 by immunocytochemistry. Taken together, our results show that developmental differences between E12 and E15 may influence their properties and differentiation. Furthermore those differences should be considered when deciding on the optimal cell source for cell replacement therapy in cardiovascular regeneration.
Animals
;
Connexin 43
;
Endothelial Cells
;
Heart
;
Immunohistochemistry
;
In Vitro Techniques
;
Mesenchymal Stromal Cells
;
Myocytes, Cardiac
;
Myocytes, Smooth Muscle
;
Rats*
;
Regeneration
;
Stem Cells*
6.Fasting Glucose is a Useful Indicator for Cerebrovascular Risk in Non-Diabetic Koreans: Association With Oxidative Stress and Inflammation.
Jae Hyang LEE ; So Ra YOON ; Ga Yoon NA ; Mira JUN ; Mok Ryeon AHN ; Jae Kwan CHA ; Oh Yoen KIM
Clinical Nutrition Research 2016;5(1):33-42
Diabetes and impaired fasting glucose are associated with incidence of cerebro-/cardio-vascular diseases. This study hypothesized that fasting glycemic status may reflect cerebrovascular risk in non-diabetic Koreans. Fasting glycemic status, lipid profiles, oxidative stress, and inflammation markers were measured in non-diabetic subjects (healthy controls, n = 112 and stroke n = 41). Systolic blood pressure, fasting glucose, glycated hemoglobin (HbA1C), triglycerides, high sensitivity C-reactive protein (hs-CPR), interleukin-6, and tumor necrosis factor-alpha were higher, and high density lipoprotein (HDL)-cholesterols were lower in patients with stroke than healthy controls. Fasting glucose positively correlated with hs-CRP, interleukin-6, tumor necrosis factor-alpha, oxidized low density lipoprotein (LDL) and malondialdehyde. The significances continued or at least turned to a trend after adjustments for confounding factors. Multiple regression analyses revealed that fasting glucose was mainly associated with cerebrovascular risk (beta'-coefficient = 0.284, p < 0.0001) together with age, systolic blood pressure, total cholesterol, hs-CRP, body mass index, dietary poly unsaturated fatty acid/saturated fatty acid (PUFA/SFA), and HbA1C (r2 = 0.634, p = 0.044). The subjects were subdivided by their fasting glucose levels [normal fasting glucose: 70-99 mg/dL, n = 91 [NFG-control] and n = 27 [NFG-stroke]; higher fasting glucose: 100-125 mg/dL, n = 21 [HFG-control] and n = 14 [HFG-stroke]). In both controls and stroke patients, HFG groups show higher triglyceride, total- and LDL-cholesterol and lower HDL-cholesterol than NFG groups. Control-HFG group showed significantly higher levels of oxidative stress and inflammation than control-NFG group. Stroke-HFG group also showed significantly higher inflammatory levels than stroke-NFG group, moreover the highest among the groups. Additionally, stroke-NFG group consumed higher PUFA/SFA than stroke-HFG group. Fasting glucose may be a useful indicator for cerebrovascular risk in non-diabetic individuals which may be mediated by oxidative stress and inflammation status.
Blood Pressure
;
Body Mass Index
;
C-Reactive Protein
;
Cholesterol
;
Fasting*
;
Glucose*
;
Hemoglobin A, Glycosylated
;
Humans
;
Incidence
;
Inflammation*
;
Interleukin-6
;
Lipoproteins
;
Malondialdehyde
;
Oxidative Stress*
;
Stroke
;
Triglycerides
;
Tumor Necrosis Factor-alpha
7.The usefulness of end-tidal carbon dioxide monitoring during apnea test in brain-dead patients.
Ha Yeon KIM ; Gaab Soo KIM ; Young Hee SHIN ; So Ra CHA
Korean Journal of Anesthesiology 2014;67(3):186-192
BACKGROUND: The apnea test (AT) is essential to confirming the diagnosis of brain death, but critical complications can occur if the AT is maintained over a long period. To minimize the AT period, we used end-tidal carbon dioxide (ETCO2) monitoring because ETCO2 is closely correlated with partial pressure of arterial carbon dioxide (PaCO2). The aim of the present study is to evaluate the usefulness of ETCO2 monitoring during apnea testing. METHODS: We reviewed 61 patients who were pronounced brain dead at our hospital from July 2009 to December 2012. The subjects were divided into two groups: the N-group, in which capnography was not used, and the C-group, in which capnography was used to monitor ETCO2. In the C-group, whenever arterial blood was sampled, the PaCO2 - ETCO2 gradients were calculated and the ventilator setting adjusted to maintain normocapnia prior to apnea testing. RESULTS: Twenty-eight subjects in the N-group and twenty-nine subjects in the C-group were included. The gender ratio, age, and cause of brain death were not different between the two groups. Prior to the AT, the normocapnia ratio was higher in the C-group than in the N-group. During the AT, the total test period was shorter in the C-group. Moreover, systolic blood pressure increased in the C-group and decreased in the N-group during apnea testing. CONCLUSIONS: ETCO2 monitoring during AT allows the PaCO2 level to be predicted, which reduces the duration of the test and stabilizes systolic blood pressure. Thus, with ETCO2 monitoring, the AT can be fast and safe.
Apnea*
;
Blood Gas Analysis
;
Blood Pressure
;
Brain Death
;
Capnography
;
Carbon Dioxide*
;
Diagnosis
;
Humans
;
Partial Pressure
;
Ventilators, Mechanical
8.Three cases of glycogenic hepatopathy mimicking acute and relapsing hepatitis in type I diabetes mellitus.
Jae Hwang CHA ; Sang Ho RA ; Yu Mi PARK ; Yong Kwan JI ; Ji Hyun LEE ; So Yeon PARK ; Soon Koo BAIK ; Sang Ok KWON ; Mee Yon CHO ; Moon Young KIM
Clinical and Molecular Hepatology 2013;19(4):421-425
Glycogenic hepatopathy (GH) is an uncommon cause of serum transaminase elevation in type I diabetes mellitus (DM). The clinical signs and symptoms of GH are nonspecific, and include abdominal discomfort, mild hepatomegaly, and transaminase elevation. In this report we describe three cases of patients presenting serum transaminase elevation and hepatomegaly with a history of poorly controlled type I DM. All of the cases showed sudden elevation of transaminase to more than 30 times the upper normal range (like in acute hepatitis) followed by sustained fluctuation (like in relapsing hepatitis). However, the patients did not show any symptom or sign of acute hepatitis. We therefore performed a liver biopsy to confirm the cause of liver enzyme elevation, which revealed GH. Clinicians should be aware of GH so as to prevent diagnostic delay and misdiagnosis, and have sufficient insight into GH; this will be aided by the present report of three cases along with a literature review.
Acute Disease
;
Adult
;
Alanine Transaminase/blood
;
Aspartate Aminotransferases/blood
;
Delayed Diagnosis
;
Diabetes Mellitus, Type 1/complications/*pathology
;
Diagnostic Errors
;
Female
;
Glycogen Storage Disease/complications/*diagnosis/ultrasonography
;
Hepatitis/diagnosis
;
Hepatomegaly/complications/*diagnosis/ultrasonography
;
Humans
;
Liver/pathology
;
Recurrence
;
Young Adult
9.Biomechanical considerations for the screw of implant prosthesis: A literature review.
So Min IM ; Dae Gon KIM ; Chan Jin PARK ; Min Sang CHA ; Lee Ra CHO
The Journal of Korean Academy of Prosthodontics 2010;48(1):61-68
PURPOSE: This article attempted to determine the factors affecting the preload and screw loosening. METHODS: Available clinical studies from 1981 to 2008 from the PUBMED that presented screw loosening data and review articles regarding screw joint stability were evaluated. Eleven studies dealing the biomechanical principles of the screw mechanics were reviewed. Moreover, the results of our data were included. RESULTS: The frequency of screw loosening was consequently reduced due to the advancement in torque tightening with torque wrench, screw material, coating technique for reducing the frictional force, and thread design, etc. If preload in the screw falls below a critical level, joint stability may be compromised, and the screw joint may fail clinically. The types of fatigue failure of screw were divided to adhesive wear, plastic deformation, and screw fracture. CONCLUSION: An optimum preload is essential to the success of the implant-abutment complex. To maintain optimum preload, using a torque wrench and re-tightening at recall time were needed.
Adhesives
;
Fatigue
;
Friction
;
Joints
;
Mechanics
;
Plastics
;
Torque
10.Successful Pregnancy after Paclitaxel-Cisplatin Chemotherapy in Invasive Squamous Cell Carcinoma of Cervix During Pregnancy: A Case Report and Review of the Literature.
Seung Youn YU ; So Ra RYU ; Seung Hee CHA ; Jung Yeol HAN ; Jin Hoon JUNG
Korean Journal of Obstetrics and Gynecology 2004;47(7):1385-1388
Paclitaxel-Cisplatin based chemotherapy in invasive squamous cell carcinoma of cervix during pregnancy has not been reported previously. A woman was diagnosed with stage II b invasive squamous cell carcinoma of cervix during pregnancy at 27 weeks gestational age. She was treated with two cycles of paclitaxel and cisplatin during pregnancy. At 36 weeks, she underwent a classical cesarean section and bilateral paraaortic lymphadenectomy. One additional cycles of chemotherapy and radiotherapy were given. She developed a recurrence within 6 months of surgery. The infant has normal growth and development at 4.3 months of age. This is the first reported case of paclitaxel-cisplatin use in cervical cancer during pregnancy.
Carcinoma, Squamous Cell*
;
Cervix Uteri*
;
Cesarean Section
;
Cisplatin
;
Drug Therapy*
;
Female
;
Gestational Age
;
Growth and Development
;
Humans
;
Infant
;
Lymph Node Excision
;
Paclitaxel
;
Pregnancy*
;
Radiotherapy
;
Recurrence
;
Uterine Cervical Neoplasms

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