1.Doxorubicin Attenuates Free Fatty Acid-Induced Lipid Accumulation via Stimulation of p53 in HepG2 Cells
Chawon YUN ; Sou Hyun KIM ; Doyoung KWON ; Mi Ran BYUN ; Ki Wung CHUNG ; Jaewon LEE ; Young-Suk JUNG
Biomolecules & Therapeutics 2024;32(1):94-103
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in the liver, and there is a global increase in its incidence owing to changes in lifestyle and diet. Recent findings suggest that p53 is involved in the development of non-alcoholic fatty liver disease; however, the association between p53 expression and the disease remains unclear. Doxorubicin, an anticancer agent, increases the expression of p53. Therefore, this study aimed to investigate the role of doxorubicin-induced p53 upregulation in free fatty acid (FFA)-induced intracellular lipid accumulation. HepG2 cells were pretreated with 0.5 μg/mL of doxorubicin for 12 h, followed by treatment with FFA (0.5 mM) for 24 h to induce steatosis. Doxorubicin pretreatment upregulated p53 expression and downregulated the expression of endoplasmic reticulum stress- and lipid synthesis-associated genes in the FFA -treated HepG2 cells. Additionally, doxorubicin treatment upregulated the expression of AMP-activated protein kinase, a key modulator of lipid metabolism. Notably, siRNA-targeted p53 knockdown reversed the effects of doxorubicin in HepG2 cells.Moreover, doxorubicin treatment suppressed FFA -induced lipid accumulation in HepG2 spheroids. Conclusively, these results suggest that doxorubicin possesses potential application for the regulation of lipid metabolism by enhance the expression of p53 an in vitro NAFLD model.
2.Molecular Epidemiology of Ciprofloxacin-Resistant Escherichia coli Isolated from Community-Acquired Urinary Tract Infections in Korea
Bongyoung KIM ; Mi-Ran SEO ; Jieun KIM ; Yeonjae KIM ; Seong-Heon WIE ; Moran KI ; Yong Kyun CHO ; Seungkwan LIM ; Jin Seo LEE ; Ki Tae KWON ; Hyuck LEE ; Hee Jin CHEONG ; Dae Won PARK ; Seong Yeol RYU ; Moon-Hyun CHUNG ; Hyunjoo PAI
Infection and Chemotherapy 2020;52(2):194-203
Background:
Escherichia coli is the predominant causative pathogen for community-acquired urinary tract infections (UTIs), and the increase in fluoroquinolone-resistant E. coli is of great concern in Korea. The objectives of this study were to investigate the genotypic characteristics and molecular epidemiology of ciprofloxacin-resistant (CIP-R) E. coli isolated from community-acquired UTIs in Korea.
Materials and Methods:
E. coli samples isolated from the blood or urine were collected from patients with community-acquired acute pyelonephritis aged 15 years and more who were admitted to 12 Korean hospitals from 1st April 2010 to 29th February 2012. Phylogenetic typing, multilocus sequence typing, and molecular characterization of β-lactamase and plasmidmediated quinolone resistance determinants were performed for CIP-R E. coli isolates.
Results:
A total of 569 E. coli isolates were collected, and 122 (21.4%) isolates were CIP-R isolates. The most prevalent sequence type (ST) was ST131 (28.7%, 35/122), followed by ST393 (14.7%, 18/122), ST1193 (13.1%, 16/122), ST38 (9.0%, 11/122), and ST405 (8.2%, 10/122). The antimicrobial resistance rates of ST131 to cefepime (22.9%, 8/35), ST38 to gentamicin (100%, 11/11), and ST405 to cefotaxime (66.7%, 6/9) were significantly higher than the resistance rates of all other STs combined. Notably, 40% (4/10) of ST405 clones produced extendedspectrum β-lactamases and were co-resistant to trimethoprim/sulfamethoxazole. aac(6′)-1b-cr (20%, 7/35) and CTX-M-14 (40%, 4/10) were more frequently observed in ST131 and ST405 compared with other clones, respectively.
Conclusions
Among the CIP-R uropathogenic E. coli isolates in this study, ST131, ST38, and ST405 were specifically associated with antimicrobial resistance.
3.Flow Cytometry for the Diagnosis of Primary Immunodeficiency Diseases: A Single Center Experience
Won Kyung KWON ; SooIn CHOI ; Hee jin KIM ; Hee Jae HUH ; Ji Man KANG ; Yae Jean KIM ; Keon Hee YOO ; Kangmo AHN ; Hye Kyung CHO ; Kyong Ran PECK ; Ja Hyun JANG ; Chang Seok KI ; Eun Suk KANG
Allergy, Asthma & Immunology Research 2020;12(2):292-305
PURPOSE: While there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute.METHODS: Between January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing.RESULTS: Of 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring.CONCLUSIONS: The initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome.
Agammaglobulinemia
;
Diagnosis
;
Exome
;
Flow Cytometry
;
Genetic Testing
;
Granulomatous Disease, Chronic
;
Humans
;
Immunophenotyping
;
Korea
;
Leukocytes
;
Lymphocyte Subsets
;
Lymphohistiocytosis, Hemophagocytic
;
Phenotype
;
Retrospective Studies
;
Seoul
;
Severe Combined Immunodeficiency
;
Tertiary Healthcare
4.Usefulness of Blood Cultures and Radiologic Imaging Studies in the Management of Patients with Community-Acquired Acute Pyelonephritis.
Yeonjae KIM ; Mi Ran SEO ; Seong Jong KIM ; Jieun KIM ; Seong Heon WIE ; Yong Kyun CHO ; Seung Kwan LIM ; Jin Seo LEE ; Ki Tae KWON ; Hyuck LEE ; Hee Jin CHEONG ; Dae Won PARK ; Seong Yeol RYU ; Moon Hyun CHUNG ; Hyunjoo PAI
Infection and Chemotherapy 2017;49(1):22-30
BACKGROUND: The objective of this study was to examine the usefulness of blood cultures and radiologic imaging studies for developing therapeutic strategies in community-acquired acute pyelonephritis (CA-APN) patients. MATERIALS AND METHODS: We prospectively collected the clinical data of CA-APN patients who visited 11 hospitals from March 2010 to February 2011. RESULTS: Positive urine and blood cultures were obtained in 69.3% (568/820) and 42.7% (277/648), respectively, of a total of 827 CA-APN patients. Blood culture identified the urinary pathogen in 60 of 645 (9.3%) patients for whom both urine and blood cultures were performed; the organisms isolated from urine were inconsistent with those from blood in 11 and only blood cultures were positive in 49 patients. Final clinical failure was more common in the bacteremic patients than the non-bacteremic ones (8.0% vs. 2.7%, P = 0.003), as was hospital mortality (3.6% vs. 0.3%, P = 0.003). Likewise, durations of hospitalization and fever were significantly longer. Bacteremia was independent risk factor for mortality (OR 9.290, 1.145-75.392, P = 0.037). With regard to radiologic studies, the detection rate of APN was 84.4% (445/527) by abdominal computed tomography and 40% (72/180) by abdominal ultrasonography. Eighty-one of 683 patients (11.9%) were found to have renal abscess, perinephric abscess, urolithiasis, hydronephorosis/hydroureter or emphysematous cystitis, which could potentially impact on clinical management. Patients with Pitt score ≥ 1, flank pain or azotemia were significantly more likely to have such structural abnormalities. CONCLUSION: Blood cultures are clinically useful for diagnosis of CA-APN, and bacteremia is predictive factor for hospital mortality. Early radiologic imaging studies should be considered for CA-APN patients with Pitt scores ≥1, flank pain or azotemia.
Abscess
;
Azotemia
;
Bacteremia
;
Cystitis
;
Diagnosis
;
Diagnostic Imaging
;
Fever
;
Flank Pain
;
Hospital Mortality
;
Hospitalization
;
Humans
;
Mortality
;
Prospective Studies
;
Pyelonephritis*
;
Risk Factors
;
Ultrasonography
;
Urolithiasis
5.A Multicenter Retrospective Case Study of Anaphylaxis Triggers by Age in Korean Children.
So Yeon LEE ; Kangmo AHN ; Jihyun KIM ; Gwang Cheon JANG ; Taek Ki MIN ; Hyeon Jong YANG ; Bok Yang PYUN ; Ji Won KWON ; Myung Hyun SOHN ; Kyung Won KIM ; Kyu Earn KIM ; Jinho YU ; Soo Jong HONG ; Jung Hyun KWON ; Sung Won KIM ; Tae Won SONG ; Woo Kyung KIM ; Hyung Young KIM ; You Hoon JEON ; Yong Ju LEE ; Hae Ran LEE ; Hye Young KIM ; Youngmin AHN ; Hye Yung YUM ; Dong In SUH ; Hyun Hee KIM ; Jin Tack KIM ; Jeong Hee KIM ; Yong Mean PARK ; Sooyoung LEE
Allergy, Asthma & Immunology Research 2016;8(6):535-540
PURPOSE: Although anaphylaxis is recognized as an important, life-threatening condition, data are limited regarding its triggers in different age groups. We aimed to identify anaphylaxis triggers by age in Korean children. METHODS: We performed a retrospective review of medical records for children diagnosed with anaphylaxis between 2009 and 2013 in 23 secondary or tertiary hospitals in South Korea. RESULTS: A total of 991 cases (mean age=5.89±5.24) were reported, with 63.9% involving patients younger than 6 years of age and 66% involving male children. Food was the most common anaphylaxis trigger (74.7%), followed by drugs and radiocontrast media (10.7%), idiopathic factors (9.2%), and exercise (3.6%). The most common food allergen was milk (28.4%), followed by egg white (13.6%), walnut (8.0%), wheat (7.2%), buckwheat (6.5%), and peanut (6.2%). Milk and seafood were the most common anaphylaxis triggers in young and older children, respectively. Drug-triggered anaphylaxis was observed more frequently with increasing age, with antibiotics (34.9%) and nonsteroidal anti-inflammatory drugs (17.9%) being the most common causes. CONCLUSIONS: The most common anaphylaxis trigger in Korean children was food. Data on these triggers show that their relative frequency may vary by age.
Anaphylaxis*
;
Anti-Bacterial Agents
;
Arachis
;
Child*
;
Contrast Media
;
Egg White
;
Epidemiology
;
Fagopyrum
;
Humans
;
Juglans
;
Korea
;
Male
;
Medical Records
;
Milk
;
Retrospective Studies*
;
Seafood
;
Tertiary Care Centers
;
Triticum
6.Risky Behavior Subtypes and Suicide Attempts in Adolescents with Depression.
Ran KIM ; Hoin KWON ; Young Ho LEE ; Ki Hwan YOOK ; Jeongun SONG ; Min A SONG ; Hyun Ju HONG
Journal of the Korean Academy of Child and Adolescent Psychiatry 2015;26(3):149-158
OBJECTIVES: The objective of this study was to identify the risky behavior subtypes in adolescents with depression, and the relationship between those subtypes and suicide attempt. METHODS: Ninety adolescents who met the Diagnostic and Statistical Manual of Mental Disorders-4th edition criteria for major depressive disorder, dysthymia, or depressive disorder not otherwise specified participated in the study. Participants were interviewed about suicidal attempts, non-suicidal self-injuries. Smoking, drinking behaviors, and searching for the word "suicide" on the internet, negative life events including bulling-bullied experiences, and history of abuse were also included with questionnaires. RESULTS: The results of cluster analysis showed that four risky behaviors were divided into three clusters : non-risky type, characterized by few risky behaviors ; delinquency type, which was characterized by smoking and drinking ; non-suicidal self-injury type. In non-suicidal self-injury type, percentage of girls was higher and clinical symptoms were more severe than delinquency type. In addition, delinquency type members could be a bully, while non-suicidal self-injury type members could be abused by a family member. Logistic regression analysis showed that both risky behavior subtypes were significant predictors of suicide attempt. CONCLUSION: These results suggest that two types of risky behaviors of depressed adolescents have an effect on the suicide attempts independently. Then, the implications and limitations of the study were discussed and directions for future studies were suggested.
Adolescent*
;
Depression*
;
Depressive Disorder
;
Depressive Disorder, Major
;
Drinking
;
Drinking Behavior
;
Female
;
Humans
;
Internet
;
Logistic Models
;
Smoke
;
Smoking
;
Suicide*
7.Postsurgical Wound Infection Caused by Mycobacterium conceptionense Identified by Sequencing of 16S rRNA, hsp65, and rpoB Genes in an Immunocompetent Patient.
Ja Young LEE ; Si Hyun KIM ; Jeong Hwan SHIN ; Hyun Kyung LEE ; Young Min LEE ; Sae Am SONG ; Il Kwon BAE ; Chang Ki KIM ; Kyung Ran JUN ; Hye Ran KIM ; Jeong Nyeo LEE ; Chulhun L CHANG
Annals of Clinical Microbiology 2014;17(1):23-27
Rapidly growing mycobacteria are ubiquitous in the environment and are increasingly being recognized as opportunistic pathogens. Recently, a new species, Mycobacteium conceptionense, has been validated from the Mycobacterium fortuitum third biovariant complex by molecular analysis. However, there are few reports, and postsurgical wound infection by this species is rare. We report a case of postsurgical wound infection caused by M. conceptionense in an immunocompetent patient that was identified by a sequencing analysis of 16S rRNA, hps65, and rpoB genes.
Humans
;
Mycobacterium fortuitum
;
Mycobacterium*
;
Wound Infection*
;
Wounds and Injuries*
8.Susceptibility of Escherichia coli from Community-Acquired Urinary Tract Infection to Fosfomycin, Nitrofurantoin, and Temocillin in Korea.
Mi Ran SEO ; Seong Jong KIM ; Yeonjae KIM ; Jieun KIM ; Tae Yeal CHOI ; Jung Oak KANG ; Seong Heon WIE ; Moran KI ; Young Kyun CHO ; Seung Kwan LIM ; Jin Seo LEE ; Ki Tae KWON ; Hyuck LEE ; Hee Jin CHEONG ; Dae Won PARK ; Seong Yeol RYU ; Moon Hyun CHUNG ; Hyunjoo PAI
Journal of Korean Medical Science 2014;29(8):1178-1181
With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.
Anti-Bacterial Agents/*administration & dosage
;
Cell Survival/*drug effects
;
Cephalosporins/administration & dosage
;
Ciprofloxacin/administration & dosage
;
Community-Acquired Infections/drug therapy/*microbiology
;
Dose-Response Relationship, Drug
;
Drug Combinations
;
Drug Resistance, Bacterial/drug effects
;
Escherichia coli/*drug effects
;
Escherichia coli Infections/drug therapy/*microbiology
;
Fosfomycin/administration & dosage
;
Humans
;
Nitrofurantoin/administration & dosage
;
Penicillins/administration & dosage
;
Republic of Korea
;
Sulfadoxine/administration & dosage
;
Treatment Outcome
;
Trimethoprim/administration & dosage
;
Urinary Tract Infections/diagnosis/*microbiology
9.Susceptibility of Escherichia coli from Community-Acquired Urinary Tract Infection to Fosfomycin, Nitrofurantoin, and Temocillin in Korea.
Mi Ran SEO ; Seong Jong KIM ; Yeonjae KIM ; Jieun KIM ; Tae Yeal CHOI ; Jung Oak KANG ; Seong Heon WIE ; Moran KI ; Young Kyun CHO ; Seung Kwan LIM ; Jin Seo LEE ; Ki Tae KWON ; Hyuck LEE ; Hee Jin CHEONG ; Dae Won PARK ; Seong Yeol RYU ; Moon Hyun CHUNG ; Hyunjoo PAI
Journal of Korean Medical Science 2014;29(8):1178-1181
With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.
Anti-Bacterial Agents/*administration & dosage
;
Cell Survival/*drug effects
;
Cephalosporins/administration & dosage
;
Ciprofloxacin/administration & dosage
;
Community-Acquired Infections/drug therapy/*microbiology
;
Dose-Response Relationship, Drug
;
Drug Combinations
;
Drug Resistance, Bacterial/drug effects
;
Escherichia coli/*drug effects
;
Escherichia coli Infections/drug therapy/*microbiology
;
Fosfomycin/administration & dosage
;
Humans
;
Nitrofurantoin/administration & dosage
;
Penicillins/administration & dosage
;
Republic of Korea
;
Sulfadoxine/administration & dosage
;
Treatment Outcome
;
Trimethoprim/administration & dosage
;
Urinary Tract Infections/diagnosis/*microbiology
10.Mortality of Community-Acquired Pneumonia in Korea: Assessed with the Pneumonia Severity Index and the CURB-65 Score.
Hye In KIM ; Shin Woo KIM ; Hyun Ha CHANG ; Seung Ick CHA ; Jae Hee LEE ; Hyun Kyun KI ; Hae Suk CHEONG ; Kwang Ha YOO ; Seong Yeol RYU ; Ki Tae KWON ; Byung Kee LEE ; Eun Ju CHOO ; Do Jin KIM ; Cheol In KANG ; Doo Ryeon CHUNG ; Kyong Ran PECK ; Jae Hoon SONG ; Gee Young SUH ; Tae Sun SHIM ; Young Keun KIM ; Hyo Youl KIM ; Chi Sook MOON ; Hyun Kyung LEE ; Seong Yeon PARK ; Jin Young OH ; Sook In JUNG ; Kyung Hwa PARK ; Na Ra YUN ; Sung Ho YOON ; Kyung Mok SOHN ; Yeon Sook KIM ; Ki Suck JUNG
Journal of Korean Medical Science 2013;28(9):1276-1282
The pneumonia severity index (PSI) and CURB-65 are widely used tools for the prediction of community-acquired pneumonia (CAP). This study was conducted to evaluate validation of severity scoring system including the PSI and CURB-65 scores of Korean CAP patients. In the prospective CAP cohort (participated in by 14 hospitals in Korea from January 2009 to September 2011), 883 patients aged over 18 yr were studied. The 30-day mortalities of all patients were calculated with their PSI index classes and CURB scores. The overall mortality rate was 4.5% (40/883). The mortality rates per CURB-65 score were as follows: score 0, 2.3% (6/260); score 1, 4.0% (12/300); score 2, 6.0% (13/216); score 3, 5.7% (5/88); score 4, 23.5% (4/17); and score 5, 0% (0/2). Mortality rate with PSI risk class were as follows: I, 2.3% (4/174); II, 2.7% (5/182); III, 2.3% (5/213); IV, 4.5% (11/245); and V, 21.7% (15/69). The subgroup mortality rate of Korean CAP patients varies based on the severity scores and CURB-65 is more valid for the lower scores, and PSI, for the higher scores. Thus, these variations must be considered when using PSI and CURB-65 for CAP in Korean patients.
Adolescent
;
Adult
;
Aged
;
Aged, 80 and over
;
Asian Continental Ancestry Group
;
Cohort Studies
;
Community-Acquired Infections/*mortality
;
Female
;
Humans
;
Intensive Care Units
;
Male
;
Middle Aged
;
Pneumonia/*mortality
;
Prospective Studies
;
Republic of Korea
;
*Severity of Illness Index
;
Young Adult

Result Analysis
Print
Save
E-mail