1.Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression
Sumin OH ; Yang-Hyun BAEK ; Sungju JUNG ; Sumin YOON ; Byeonggeun KANG ; Su-hyang HAN ; Gaeul PARK ; Je Yeong KO ; Sang-Young HAN ; Jin-Sook JEONG ; Jin-Han CHO ; Young-Hoon ROH ; Sung-Wook LEE ; Gi-Bok CHOI ; Yong Sun LEE ; Won KIM ; Rho Hyun SEONG ; Jong Hoon PARK ; Yeon-Su LEE ; Kyung Hyun YOO
Clinical and Molecular Hepatology 2024;30(2):247-262
Background/Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression.
Methods:
Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD.
Results:
After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort.
Conclusions
We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.
2.Expression of LONP1 Is High in Visceral Adipose Tissue in Obesity, and Is Associated with Glucose and Lipid Metabolism
Ju Hee LEE ; Saet-Byel JUNG ; Seong Eun LEE ; Ji Eun KIM ; Jung Tae KIM ; Yea Eun KANG ; Seul Gi KANG ; Hyon-Seung YI ; Young Bok KO ; Ki Hwan LEE ; Bon Jeong KU ; Minho SHONG ; Hyun Jin KIM
Endocrinology and Metabolism 2021;36(3):661-671
Background:
The nature and role of the mitochondrial stress response in adipose tissue in relation to obesity are not yet known. To determine whether the mitochondrial unfolded protein response (UPRmt) in adipose tissue is associated with obesity in humans and rodents.
Methods:
Visceral adipose tissue (VAT) was obtained from 48 normoglycemic women who underwent surgery. Expression levels of mRNA and proteins were measured for mitochondrial chaperones, intrinsic proteases, and components of electron-transport chains. Furthermore, we systematically analyzed metabolic phenotypes with a large panel of isogenic BXD inbred mouse strains and Genotype-Tissue Expression (GTEx) data.
Results:
In VAT, expression of mitochondrial chaperones and intrinsic proteases localized in inner and outer mitochondrial membranes was not associated with body mass index (BMI), except for the Lon protease homolog, mitochondrial, and the corresponding gene LONP1, which showed high-level expression in the VAT of overweight or obese individuals. Expression of LONP1 in VAT positively correlated with BMI. Analysis of the GTEx database revealed that elevation of LONP1 expression is associated with enhancement of genes involved in glucose and lipid metabolism in VAT. Mice with higher Lonp1 expression in adipose tissue had better systemic glucose metabolism than mice with lower Lonp1 expression.
Conclusion
Expression of mitochondrial LONP1, which is involved in the mitochondrial quality control stress response, was elevated in the VAT of obese individuals. In a bioinformatics analysis, high LONP1 expression in VAT was associated with enhanced glucose and lipid metabolism.
3.Expression of LONP1 Is High in Visceral Adipose Tissue in Obesity, and Is Associated with Glucose and Lipid Metabolism
Ju Hee LEE ; Saet-Byel JUNG ; Seong Eun LEE ; Ji Eun KIM ; Jung Tae KIM ; Yea Eun KANG ; Seul Gi KANG ; Hyon-Seung YI ; Young Bok KO ; Ki Hwan LEE ; Bon Jeong KU ; Minho SHONG ; Hyun Jin KIM
Endocrinology and Metabolism 2021;36(3):661-671
Background:
The nature and role of the mitochondrial stress response in adipose tissue in relation to obesity are not yet known. To determine whether the mitochondrial unfolded protein response (UPRmt) in adipose tissue is associated with obesity in humans and rodents.
Methods:
Visceral adipose tissue (VAT) was obtained from 48 normoglycemic women who underwent surgery. Expression levels of mRNA and proteins were measured for mitochondrial chaperones, intrinsic proteases, and components of electron-transport chains. Furthermore, we systematically analyzed metabolic phenotypes with a large panel of isogenic BXD inbred mouse strains and Genotype-Tissue Expression (GTEx) data.
Results:
In VAT, expression of mitochondrial chaperones and intrinsic proteases localized in inner and outer mitochondrial membranes was not associated with body mass index (BMI), except for the Lon protease homolog, mitochondrial, and the corresponding gene LONP1, which showed high-level expression in the VAT of overweight or obese individuals. Expression of LONP1 in VAT positively correlated with BMI. Analysis of the GTEx database revealed that elevation of LONP1 expression is associated with enhancement of genes involved in glucose and lipid metabolism in VAT. Mice with higher Lonp1 expression in adipose tissue had better systemic glucose metabolism than mice with lower Lonp1 expression.
Conclusion
Expression of mitochondrial LONP1, which is involved in the mitochondrial quality control stress response, was elevated in the VAT of obese individuals. In a bioinformatics analysis, high LONP1 expression in VAT was associated with enhanced glucose and lipid metabolism.
4.Chronic Hepatitis B Infection Is Significantly Associated with Chronic Kidney Disease: a Population-based, Matched Case-control Study.
Sung Eun KIM ; Eun Sun JANG ; Moran KI ; Geum Youn GWAK ; Kyung Ah KIM ; Gi Ae KIM ; Do Young KIM ; Dong Joon KIM ; Man Woo KIM ; Yun Soo KIM ; Young Seok KIM ; In Hee KIM ; Chang Wook KIM ; Ho Dong KIM ; Hyung Joon KIM ; Neung Hwa PARK ; Soon Koo BAIK ; Jeong Ill SUH ; Byung Cheol SONG ; Il Han SONG ; Jong Eun YEON ; Byung Seok LEE ; Youn Jae LEE ; Young Kul JUNG ; Woo Jin CHUNG ; Sung Bum CHO ; Eun Young CHO ; Hyun Chin CHO ; Gab Jin CHEON ; Hee Bok CHAE ; DaeHee CHOI ; Sung Kyu CHOI ; Hwa Young CHOI ; Won Young TAK ; Jeong HEO ; Sook Hyang JEONG
Journal of Korean Medical Science 2018;33(42):e264-
BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m² or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m² (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m² along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m². CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m² and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.
Anemia
;
Antigens, Surface
;
Bilirubin
;
Case-Control Studies*
;
Female
;
Glomerular Filtration Rate
;
Hepatitis B Surface Antigens
;
Hepatitis B virus
;
Hepatitis B, Chronic*
;
Hepatitis, Chronic*
;
Humans
;
Male
;
Multivariate Analysis
;
Prevalence
;
Proteinuria
;
Renal Insufficiency, Chronic*
5.Obesity in Korean Men: Results from the Fourth through Sixth Korean National Health and Nutrition Examination Surveys (2007~2014).
Yeon Won PARK ; Kwi Bok CHOI ; Soon Ki KIM ; Dong Gi LEE ; Jun Ho LEE
The World Journal of Men's Health 2016;34(2):129-136
PURPOSE: Obesity is related to many diseases, including urological conditions. We investigated the prevalence, risk factors, and treatment of male obesity. MATERIALS AND METHODS: This study included 17,485 men older than 20 years of age who participated in the fourth, fifth, and sixth administrations of the Korean National Health and Nutrition Examination Survey. Two main cutoff points for obesity were defined: a body mass index (BMI) ≥25 kg/m2 and a BMI≥30 kg/m2. Additionally, we defined obesity requiring pharmacotherapy as the presence of a BMI≥30 kg/m2 or a BMI≥27 kg/m2 co-occurring with at least one associated comorbid medical condition, such as hypertension, dyslipidemia, or diabetes. RESULTS: The prevalence rates of a BMI≥25 kg/m2, a BMI≥30 kg/m2, and obesity requiring pharmacotherapy were 35.7%, 3.4%, and 10.5%, respectively. The prevalence of obesity increased over time for all definitions of obesity. The prevalence of obesity requiring pharmacotherapy was highest in Jeju (12.5%) and lowest in Gangwon-do (7.7%). Having a higher income, being a non-manual worker, and having completed a high level of education were significantly related to obesity requiring pharmacotherapy. More than 70% of patients with obesity requiring pharmacotherapy reported taking diet pills, eating functional foods, or consuming a one-food diet for weight reduction, but only 13.9% reported exercising for this purpose. CONCLUSIONS: Male obesity is a common condition, the prevalence of which is expected to continue to increase over time. A better strategy is required to manage male obesity in Korea.
Body Mass Index
;
Diet
;
Drug Therapy
;
Dyslipidemias
;
Eating
;
Education
;
Functional Food
;
Gangwon-do
;
Humans
;
Hypertension
;
Korea
;
Male
;
Nutrition Surveys
;
Obesity*
;
Prevalence
;
Risk Factors
;
Weight Loss
6.A Telephone Method for Helping Lay Rescuers Perform High Quality Cardiopulmonary Resuscitation.
Sung Gon LEE ; Gu Hyun KANG ; Yong Soo JANG ; Taek Geun OHK ; Gi Hun CHOI ; Jung Hwan AHN ; Bok Ja LEE ; Min Gook SUNG ; Woo Jun KIM
Journal of the Korean Society of Emergency Medicine 2013;24(6):644-649
PURPOSE: Dispatcher-assisted telephone instruction during cardiopulmonary resuscitation (CPR) improves the quality of CPR performed by laypersons. However, in Korea, CPR instruction guidelines for bystanders have not made. We therefore studied the effects of verbal instruction on the quality of chest compression. METHODS: Data from two randomized, double-blinded, controlled trials using identical methodology were combined to obtain 175 records for analysis. Subjects were randomized into either a "push as hard as you can and fast" (n=87) or "push down 5~6 cm, 100~120 rate/min" (n=88), verbal instructions in the 2011 Korea Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC). Data were recorded via a Resusci(R) Anne SkillReporter(TM), Laerdal Medical mannequin. Primary outcome measures included chest compression depth and chest compression rate per minute. RESULTS: The average compression depth and speed of chest compressions did not significantly differ between the two verbal instructions. CONCLUSION: The verbal istructions provided by telephone based on the 2011 Korean Guidelines for CPR and ECC are not effective. The instructions for high quality CPR of layperson should therefore be studied.
Cardiopulmonary Resuscitation*
;
Emergencies
;
Heart Massage
;
Korea
;
Manikins
;
Methods
;
Outcome Assessment (Health Care)
;
Telephone*
;
Thorax
;
Verbal Learning
7.Bilateral Multiple Intracerebral Hemorrhagic Infarction after Cranioplasty in a Patient with Cerebral Infarction: Case Report.
Byung Sub KIM ; Do Sung YOO ; Pil Woo HUH ; Kyoung Suok CHO ; Sang Bok LEE
Korean Journal of Cerebrovascular Surgery 2010;12(3):136-140
Bilateral multiple intracranial hemorrhagic infarction after cranioplasty is an extremely rare complication. We present a case of a bilateral multiple intracranial hemorrhagic infarction following cranioplasty with an autologous bone graft. A 63-year-old woman had a previous decompressive craniectomy after a right middle cerebral artery infarction. The possible pathogenesis of the complication is discussed.
Decompressive Craniectomy
;
Female
;
Humans
;
Infarction
;
Infarction, Middle Cerebral Artery
;
Middle Aged
;
Reperfusion Injury
;
Transplants
8.Intramedullary Kirschner Wire Fixation for Forearm Fractures in Children.
Boo Kyung KWON ; Hong Gi PARK ; Deuk Soo JUN ; Jang Seok CHOI ; Dong Hwan KIM ; Sang Bok LEE ; Jong Ryoon BAEK
Journal of the Korean Society for Surgery of the Hand 2010;15(3):122-127
PURPOSE: To evaluate the clinical and radiological results of intramedullary fixation using Kirschner wires (K-wires) for the treatment of unstable forearm fractures in children. MATERIALS AND METHODS: Forty-three children who underwent intramedullary fixation using K-wires for the treatment of a forearm bone fracture were evaluated. The rodiological results were based on the time to union and angular deformity at last follow-up. The clinical results were analyzed according to Price criteria. RESULTS: Average union time was 6.9 weeks. Preoperatively, average angular deformity of radius is 11.4 degrees in anteroposterior (AP) view and 15.3 degrees in lateral view. In case of the ulna, arerage angular deformity was 8.3 degrees in AP view and 12.7 degrees in lateral view. At last follow up, average angular deformity of radius was 1.5 degrees in AP view and 1.6 degrees in lateral view. In case of the ulna, arerage angular deformity was 1.3 degrees in AP view and 2.5 degrees in lateral view. According to the criteria of Price et al., 42 patients (97%) were excellent and one patient (3%) was good. No specific complication was observed. CONCLUSION: An intramedullary fixation using K-wires is an attractive treatment option for unstable forearm fractures in children in terms of safety, excellent cosmesis, short hospitalization, easy hardware removal, and providing excellent radiological and clinical results.
Bone Wires
;
Child
;
Congenital Abnormalities
;
Follow-Up Studies
;
Forearm
;
Fractures, Bone
;
Hospitalization
;
Humans
;
Radius
;
Ulna
9.Anthropological Study on Ancient Human Skull and Teeth Discovered from Urn Coffin of Proto-Three Kingdoms Period in Korea.
Myeung Ju KIM ; Yi Suk KIM ; Chang Seok OH ; Sang Jun LEE ; Gi Dae BOK ; Yang Su YI ; Suk In YOUN ; Na Li LEE ; Dong Hoon SHIN
Korean Journal of Physical Anthropology 2010;23(4):169-175
Increase in agricultural production or steel manufacturing during Proto-Three Kingdoms Period enabled ancient people to establish well-organized ancient kingdoms in Korean peninsula. A pottery in which human skeletons were buried, the urn coffin, has been regarded as one of the frequently used burial system in ancient Korean society. Among them, the small-sized urn coffin was thought to be used for reburial of adult skeleton or burial for infants and children. In this report, we showed that the human adult bones were buried in a very unique pattern. Based on anthropological study, the dead person buried in the urn coffin died in his/her 30s; and every bone fragment belonged to human skull without exception. The dead person might be a warrior killed in action because there have been reports on exclusive burial of skull in a small-sized, ancient urn coffin in Japan, that was commonly interpreted as the burial of ancient warrior's heads decapitated during ancient battle, and were reburied in the burial ground. Nevertheless, considering that the cervical bones were not found along with the skull bone fragments, the tell tale sign of decapitation, more future studies are needed to confirm the hypothesis. However, even so, it could not be easily denied that very unique funeral customs: burial of human adult skull in a small-sized urn coffin, prevailed in the ancient Korean societies in certain regions.
Adult
;
Burial
;
Child
;
Decapitation
;
Head
;
Humans
;
Infant
;
Japan
;
Korea
;
Skeleton
;
Skull
;
Steel
;
Tooth
10.Cholestatic Hepatitis and Thrombocytosis in a Secondary Syphilis Patient.
Gi Hyun KIM ; Byeong Uk KIM ; Ju Hee LEE ; Yong Heok CHOI ; Hee Bok CHAE ; Seon Mee PARK ; Sei Jin YOUN ; Ji Yeoun LEE ; Tae Young YOON ; Rohyun SUNG
Journal of Korean Medical Science 2010;25(11):1661-1664
The incidence of acute hepatitis in syphilis patient is rare. First of all, our patient presented with hepatitis comorbid with thrombocytosis. To our knowledge, this is only the second report of syphilitic hepatitis with thrombocytosis. The 42-yr-old male complained of flulike symptoms and skin eruptions on his palms and soles. Laboratory findings suggested an acute hepatitis and thrombocytosis. Serologic test results were positive for VDRL. He recovered from his symptoms and elevated liver related enzymes with treatment. Because syphilitic hepatitis can present without any typical signs of accompanying syphilis, syphilis should be considered as a possible cause in acute hepatitis patients.
Acute Disease
;
Adult
;
Alkaline Phosphatase/blood
;
Bilirubin/blood
;
Epidermis/pathology
;
Hepatitis/*diagnosis/etiology/pathology
;
Humans
;
Jaundice
;
Male
;
Penicillin G Benzathine/therapeutic use
;
Syphilis/*complications
;
Syphilis Serodiagnosis
;
Thrombocytosis/*etiology
;
Tomography, X-Ray Computed

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