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.Effects of rosiglitazone, an antidiabetic drug, on Kv3.1 channels
Hyang Mi LEE ; Seong Han YOON ; Min-Gul KIM ; Sang June HAHN ; Bok Hee CHOI
The Korean Journal of Physiology and Pharmacology 2023;27(1):95-103
Rosiglitazone is a thiazolidinedione-class antidiabetic drug that reduces blood glucose and glycated hemoglobin levels. We here investigated the interaction of rosiglitazone with Kv3.1 expressed in Chinese hamster ovary cells using the wholecell patch-clamp technique. Rosiglitazone rapidly and reversibly inhibited Kv3.1 currents in a concentration-dependent manner (IC 50 = 29.8 µM) and accelerated the decay of Kv3.1 currents without modifying the activation kinetics. The rosiglitazonemediated inhibition of Kv3.1 channels increased steeply in a sigmoidal pattern over the voltage range of –20 to +30 mV, whereas it was voltage-independent in the voltage range above +30 mV, where the channels were fully activated. The deactivation of Kv3.1 current, measured along with tail currents, was also slowed by the drug. In addition, the steady-state inactivation curve of Kv3.1 by rosiglitazone shifts to a negative potential without significant change in the slope value. All the results with the use dependence of the rosiglitazone-mediated blockade suggest that rosiglitazone acts on Kv3.1 channels as an open channel blocker.
3.Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in management of peritoneal carcinomatosis: Single center experience in Korea
Hee Ju LEE ; HyungJoo BAIK ; Yo Han PARK ; Sang Hyuk SEO ; Kwang Hee KIM ; Ki Beom BAE ; Kwan Hee HONG ; Ki Hyang KIM ; Jung Mi BYUN ; Dae Hoon JEONG ; Kyung Bok LEE ; Min Kyung OH ; Kwang Rae CHO ; Min Sung AN
Korean Journal of Clinical Oncology 2019;15(2):61-67
PURPOSE: Peritoneal carcinomatosis (PC) has been considered a terminal condition and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIEPC) is regarded as an alternative therapeutic option. This study aimed to evaluate the 30-day clinical outcomes of CRS/HIPEC and the feasibility of the surgery by investigating the morbidity and mortality in Inje University Hospital.METHODS: Data were retrospectively collected from 19 patients with PC who underwent CRS/HIPEC at Inje University Hospital in 2018. We evaluated pre-, intra-operative parameters and postoperative clinical outcomes and early complications.RESULTS: The mean operating time was 506.95 minutes and the mean blood loss was 837.11 mL. Six cases (31.58%) had morbidity of grade III or above. A longer operating time (≥560 minutes, P=0.038) and large blood loss (≥700 mL, P=0.060) were positively correlated with grade III or worse postoperative complications.CONCLUSION: Our early experience with CRS/HIPEC resulted in a 31.58% morbidity rate of grade III and above, with risk factors being longer operating time and greater intraoperative blood loss. As the surgical team's skills improve, a shorter operating time with less intraoperative blood loss could result in better short-term outcomes of CRS/HIPEC.
Carcinoma
;
Drug Therapy
;
Humans
;
Korea
;
Mortality
;
Postoperative Complications
;
Retrospective Studies
;
Risk Factors
4.S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial.
Choong kun LEE ; Minkyu JUNG ; Hyo Song KIM ; Inkyung JUNG ; Dong Bok SHIN ; Seok Yun KANG ; Dae Young ZANG ; Ki Hyang KIM ; Moon Hee LEE ; Bong Seog KIM ; Kyung Hee LEE ; Jae Ho CHEONG ; Woo Jin HYUNG ; Sung Hoon NOH ; Hyun Cheol CHUNG ; Sun Young RHA
Cancer Research and Treatment 2019;51(1):1-11
PURPOSE: We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients. MATERIALS AND METHODS: Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2/day on days 1-14 plus docetaxel 35 mg/m2on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2/day on days 1-14 plus cisplatin 60 mg/m2on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate. RESULTS: Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment. CONCLUSION: Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.
Anemia
;
Capecitabine
;
Chemotherapy, Adjuvant*
;
Cisplatin
;
Disease-Free Survival
;
Follow-Up Studies
;
Gastrectomy
;
Hand-Foot Syndrome
;
Humans
;
Korea
;
Lymph Node Excision
;
Mucositis
;
Neutropenia
;
Stomach Neoplasms*
5.Investigation of bovine tuberculosis outbreaks by using a trace-back system and molecular typing in Korean Hanwoo beef cattle
Bok Kyung KU ; Bo Young JEON ; Jae Myung KIM ; Young Boo JANG ; Hyeyoung LEE ; Jae Young CHOI ; Suk Chan JUNG ; Hyang Mi NAM ; Hun PARK ; Sang Nae CHO
Journal of Veterinary Science 2018;19(1):45-50
Bovine tuberculosis is a chronic contagious disease responsible for major agricultural economic losses. Abattoir monitoring and trace-back systems are an appropriate method to control bovine tuberculosis, particularly in beef cattle. In the present study, a trace-back system was applied to bovine tuberculosis cases in Korean native Hanwoo beef cattle. Bovine tuberculosis was detected in three index beef cattle during abattoir monitoring in Jeonbuk Province, Korea, and the original herds were traced back from each index cow. All cattle in each original herd were subjected to tuberculin skin test. The positive rates in the tuberculin skin test were 64.6% (62 of 96), 4.8% (2 of 42), and 8.1% (3 of 37) at farms A, B, and C, respectively. On post-mortem examination of 56 tuberculin-positive cattle, 62% had granulomatous lesions, and Mycobacterium bovis was cultured from 40 (71.4%) of the cattle. Molecular typing by spoligotyping and the mycobacterial interspersed repetitive unit-variable-number tandem repeat assay revealed the genotype of the M. bovis strains from the index cattle were same as the M. bovis genotype in each original herd. The results suggest that tracing back from index cattle to the original herd is an effective method to control bovine tuberculosis in beef cattle.
Abattoirs
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Agriculture
;
Animals
;
Autopsy
;
Cattle
;
Disease Outbreaks
;
Genotype
;
Jeollabuk-do
;
Korea
;
Methods
;
Molecular Typing
;
Mycobacterium bovis
;
Red Meat
;
Skin Tests
;
Tandem Repeat Sequences
;
Tuberculin
;
Tuberculosis, Bovine
6.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*
7.Effects of Horticultural Therapy for the Korean Elderly : A Systematic Literature Review.
Joo Hyun KIM ; Sung Bok KWON ; Hyeon Ju KIM ; Gyeong Hye CHOI ; Hyang Mi LEE
Journal of Korean Biological Nursing Science 2016;18(3):153-159
PURPOSE: This study was conducted to ascertain the effectiveness of horticultural therapy by analyzing researches on horticultural therapy applied to elderly Koreans. METHODS: We evaluated 401 research papers including dissertations on horticultural therapy applied to elderly Koreans from Jan. 2000 to Feb. 2016. We reviewed the appropriate 12 papers among them for the final analysis. RESULTS: Horticultural therapy had physiological and psychosocial effects. First of all, it showed the physiological effects of reducing stress hormones. Outdoor horticultural therapy improved the gross motor movements of the body. Indoor horticulture therapy improved delicate cognitive & operating functions. Second, horticultural therapy showed the psychosocial effects of reducing depression and improving cognitive functions, language abilities, comprehension, daily activity, life satisfaction and sociality. But the effects appeared differently dependent on the implementation protocol & period of horticultural therapy, as well as the professionalism of the therapists. Therefore, if horticultural therapy were to be administered through nursing, it should be based on its key principle, in other words, the principle of action-interaction-response of horticultural therapy. CONCLUSION: The results of this study will be useful for developing therapeutic interventions through nursing. Also they will be helpful in applying horticultural therapy programs in nursing practice.
Aged*
;
Cognition
;
Comprehension
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Depression
;
Horticultural Therapy*
;
Humans
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Language
;
Nursing
;
Professionalism
8.Kojic Acid Peptide: A New Compound with Anti-Tyrosinase Potential.
Birendra Kumar SINGH ; Seok Hoon PARK ; Hyang Bok LEE ; Young Aae GOO ; Hyoung Shik KIM ; Seung Hee CHO ; Jeong Hun LEE ; Ghe Whan AHN ; Jin Pyo KIM ; Su Myoung KANG ; Eun Ki KIM
Annals of Dermatology 2016;28(5):555-561
BACKGROUND: Kojic acid was used for decades in the cosmetic industry as an antimelanogenic agent. However, there are two major drawbacks of Kojic acid, one is cytotoxicity and second are instability on storage. These limitations led the scientist to synthesize the active Kojic acid peptides. OBJECTIVE: In the present study, we synthesize and investigate the effect of five Kojic acid peptides to overcome the limitation of Kojic acid. METHODS: The peptide was analyzed and purified by high-performance liquid chromatography and matrix-assisted laser desorption ionization time of flight mass spectroscopy. Further, the tyrosinase activities of the Kojic acid and Kojic acid peptides were compared. The toxicity was measured and the melanin content is recorded in B16F10 mouse melanoma cells. RESULTS: Maximum tyrosinase activity was measured by Kojic acid peptides. Therefore, Kojic acid peptides were subjected to melanin assay and cytotoxicity assay and finally the stability of the Kojic acid peptide was measured. CONCLUSION: It was observed that this newly synthesized Kojic acid peptide is stable and potent to inhibit the tyrosinase activity and melanin content of B16F10 mouse melanoma cells without exhibiting cell toxicity. Together, these preliminary results suggest that a further exploration is being needed to establish Kojic acid peptide as antimelanogenic agent.
Animals
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Chromatography, Liquid
;
Mass Spectrometry
;
Melanins
;
Melanoma
;
Mice
;
Monophenol Monooxygenase
;
Peptides
9.Current Status of Management in Type 2 Diabetes Mellitus at General Hospitals in South Korea.
Jin Hee JUNG ; Jung Hwa LEE ; Jin Won NOH ; Jeong Eun PARK ; Hee Sook KIM ; Joo Wha YOO ; Bok Rye SONG ; Jeong rim LEE ; Myeong Hee HONG ; Hyang Mi JANG ; Young NA ; Hyun Joo LEE ; Jeong Mi LEE ; Yang Gyo KANG ; Sun Young KIM ; Kang Hee SIM
Diabetes & Metabolism Journal 2015;39(4):307-315
BACKGROUND: In Korea, the prevalence, complications, and mortality rate of diabetes are rapidly increasing. However, investigations on the actual condition of diabetes management are very limited due to lack of nation-wide research or multicenter study. Hence, we have minutely inquired the current status of diabetes management and achievement of glucose target goal in general hospital offering education program. That way, we are able to furnish data for policy making of diabetes education and draw up guideline which may allow us to reduce the morbidity and mortality of diabetes. METHODS: The subjects consisted of 2,610 patients with type 2 diabetes who visited the 13 general hospital in Seoul or Gyeonggi region from March 19 to May 29, 2013. General characteristics, associated diseases, complications, and management status were investigated. RESULTS: The mean age was 61.0+/-11.6 years, body mass index was 25.0+/-3.3 kg/m2, and family history of diabetes was 50.5%. The mean duration of diabetes was 10.7+/-7.9 years and 53% received education about diabetes. The prevalence of hypertension and dyslipidemia were 59.2% and 65.5%, respectively, and 18.3% of the subjects were accompanied by liver disease. Diabetic retinopathy appeared in 31.6%, nephropathy in 28.1%, and neuropathy in 19.9% of the subjects. The mean glycosylated hemoglobin (HbA1c) level was 7.3%+/-1.3% and the achieving rate based on Korean Diabetes Association guideline (HbA1c <6.5%) was 24.8%, blood pressure (130/80 mm Hg or less) was 49.4%, and low density lipoprotein cholesterol (<100 mg/dL) was 63.6%. The reaching rate to the target level in four parameters (blood glucose, blood pressure, lipids, and body weight) was 7.8%. CONCLUSION: The blood glucose control rate was lower than other parameters, and the implementation rate of diabetes education was only 53%. Thus more appropriate glucose control and systematic diabetes education are imperative.
Blood Glucose
;
Blood Pressure
;
Body Mass Index
;
Cholesterol, LDL
;
Diabetes Mellitus, Type 2*
;
Diabetic Retinopathy
;
Dyslipidemias
;
Education
;
Glucose
;
Gyeonggi-do
;
Hemoglobin A, Glycosylated
;
Hospitals, General*
;
Humans
;
Hypertension
;
Korea*
;
Liver Diseases
;
Mortality
;
Policy Making
;
Prevalence
;
Seoul
10.Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease.
Young Seok KIM ; Eun Sun JUNG ; Wonhee HUR ; Si Hyun BAE ; Jong Young CHOI ; Myeong Jun SONG ; Chang Wook KIM ; Se Hyun JO ; Chang Don LEE ; Young Sok LEE ; Sang Wook CHOI ; Jin Mo YANG ; Jeong Won JANG ; Sang Gyune KIM ; Seung Won JUNG ; Hee Kyung KIM ; Hee Bok CHAE ; Seung Kew YOON
Clinical and Molecular Hepatology 2013;19(2):120-130
BACKGROUND/AIMS: The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH. METHODS: One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8+/-13.5 years, mean+/-SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea. RESULTS: According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis > or =2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH. CONCLUSIONS: Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.
Adult
;
Aged
;
Aged, 80 and over
;
Alanine Transaminase/blood
;
Asian Continental Ancestry Group
;
Aspartate Aminotransferases/blood
;
Biological Markers/blood
;
Fatty Liver/classification/metabolism/*pathology
;
Female
;
Ferritins/blood
;
Fibrosis/complications
;
Humans
;
Keratin-18/analysis
;
Male
;
Middle Aged
;
Predictive Value of Tests
;
Prospective Studies
;
Republic of Korea
;
Severity of Illness Index
;
Young Adult

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