1.Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction
Thuy Linh LAI ; So Young PARK ; Giang NGUYEN ; Phuc Thi Minh PHAM ; Seon Mee KANG ; Jeana HONG ; Jae-Ho LEE ; Seung-Soon IM ; Dae-Hee CHOI ; Eun-Hee CHO
Endocrinology and Metabolism 2024;39(6):908-920
Background:
Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction.
Methods:
In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days.
Results:
In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery.
Conclusion
Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.
2.Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction
Thuy Linh LAI ; So Young PARK ; Giang NGUYEN ; Phuc Thi Minh PHAM ; Seon Mee KANG ; Jeana HONG ; Jae-Ho LEE ; Seung-Soon IM ; Dae-Hee CHOI ; Eun-Hee CHO
Endocrinology and Metabolism 2024;39(6):908-920
Background:
Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction.
Methods:
In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days.
Results:
In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery.
Conclusion
Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.
3.Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction
Thuy Linh LAI ; So Young PARK ; Giang NGUYEN ; Phuc Thi Minh PHAM ; Seon Mee KANG ; Jeana HONG ; Jae-Ho LEE ; Seung-Soon IM ; Dae-Hee CHOI ; Eun-Hee CHO
Endocrinology and Metabolism 2024;39(6):908-920
Background:
Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction.
Methods:
In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days.
Results:
In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery.
Conclusion
Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.
4.Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction
Thuy Linh LAI ; So Young PARK ; Giang NGUYEN ; Phuc Thi Minh PHAM ; Seon Mee KANG ; Jeana HONG ; Jae-Ho LEE ; Seung-Soon IM ; Dae-Hee CHOI ; Eun-Hee CHO
Endocrinology and Metabolism 2024;39(6):908-920
Background:
Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction.
Methods:
In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days.
Results:
In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery.
Conclusion
Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.
5.The Current Status of Prolonged Breastfeeding and Its Related Factors in Korean Infants and Their Mothers: A Nationwide Cross-Sectional Study
Jeana HONG ; Ju Young CHANG ; Sohee OH
Journal of Korean Medical Science 2023;38(33):e261-
Background:
International authorities recommend prolonged breastfeeding (PBF) for 12–24 months or more with 6 months of exclusive breastfeeding (EBF). Based on the Korean National Health and Nutrition Examination Survey (KNHANES) data, this study attempted to help encourage and educate breastfeeding (BF) over 1 year by investigating long-term BF trends and related factors in Korean infants and their mothers.
Methods:
This cross-sectional study was based on data on children aged 12–23 months and their mothers from 2010 to 2020. BF rates were compared between KNHANES V (2010– 2012), KNHANES VI (2013–2015), KNHANES VII (2016–2018), and part of KNHANES VIII (2019–2020). In addition, data related to mothers and infants, including demographics, socioeconomic, educational, and health status, were collected, and their association with BF status was analyzed.
Results:
Of the 933 infants included in the study, the proportions achieving full BF at 6 months of age and PBF at 12 and 18 months were 34.8%, 33.7%, and 7.1%, respectively.Over the past 10 years, the trends of all three BF practices have significantly decreased since 2016 (P < 0.001). Of the 849 infants whose maternal data were available, multiple logistic regression analysis showed that EBF for 6 months (defined as full BF at 1, 3, and 6 months of age) positively correlated with maternal and infants’ factors such as unemployed status, past BF experience, no history of drinking, and infants’ birth weight of ≥ 2.5 kg. The mother’s education level, particularly the nutrition label impact, current employment status, and smoking and drinking status, were significantly associated with PBF for ≥ 12 months but were not related to PBF for ≥ 18 months, except for drinking status.
Conclusions
In Korea, the long-term BF rate of ≥ 12 months has declined in the past 10 years, and BF becomes rare after 18 months. Higher maternal interest in nutrition information appears to be driving access to PBF over 12 months than EBF for 6 months or PBF over 18 months. To promote PBF over 12 months in Korea, it may be helpful to strengthen nutrition education that specifically emphasizes the benefits of PBF along with EBF, especially during infant health examinations.
6.Differences in Growth and Dietary and Nutrient Intake Patterns by Breastfeeding Status Over One Year Among Korean Children Aged 24–35Months
Jin A SOHN ; Ju Young CHANG ; Sohee OH ; Jeana HONG
Journal of Korean Medical Science 2023;38(44):e363-
Background:
A previous national study found that Korean children who were breastfed for at least one year had lesser weight gain, lower protein, calcium, and iron intake relative to calories, and different dietary patterns in the second year of life, compared with children weaned before 12 months of age or those who were never breastfed. Therefore, this study aimed to investigate whether growth status, dietary and nutrient intake patterns differed by prolonged breastfeeding (PBF) experience even in the third year of life, when weaning is considered complete.
Methods:
This cross-sectional study was based on the data of children aged 24 to 35 months from the National Health and Nutrition Examination Survey (2010–2020). Data on anthropometry, dietary behavior, food and nutrient intake, maternal education, and household income were extracted to analyze the association between PBF and growth, dietary and nutrient intake patterns.
Results:
In the final analysis, 31.6% of the 931 children with a birth weight of ≥ 2.5 kg continued to breastfeed for at least 12 months of age, and their mean breastfeeding (BF) duration was 15.9 months. Children with PBF had significantly less postnatal weight gain than those without (P = 0.006). Regarding food group intake, PBF was significantly associated with lower legume and soy product intake (β [95% confidence interval], −10.688 [−19.314, −2.062], P = 0.015) and higher fruit intake (32.978 [3.349, 62.608], P = 0.029), after adjusting for sex, age in month, total caloric intake, maternal education and household income. Regarding nutrient intake, after adjusting for these variables, PBF had significantly associated with higher dietary fiber (β [95% CI], 1.607 [0.218, 2.996], P = 0.023), iron (0.848 [0.317, 1.380], P = 0.002) and niacin (0.728 [0.222, 1.235], P = 0.005) intake and was significantly associated with lower saturated fatty acid intake (−1.217 [−2.364, −0.071], P = 0.037) and percentage of energy from fat (−1.351 [−2.666, −0.035], P = 0.044).
Conclusion
Even in the third year of life, children who have been breastfed for over one year continue to have relatively slow growth. However, they do appear to have better intake of some beneficial nutrients, which may be attributed to healthier dietary intake patterns in children with PBF. The results of this study can be used to support the recommendation of long-term BF for Korean infants and toddlers.
7.Growth, Nutritional Status, and Dietary Intake Patterns Associated With Prolonged Breastfeeding in Young Korean Children: A Nationwide Cross-Sectional Study
Jeana HONG ; Ju Young CHANG ; Sohee OH ; Sung Ok KWON
Journal of Korean Medical Science 2023;38(15):e116-
Background:
Although the optimal duration of breastfeeding remains unclear, breastfeeding is generally recommended exclusively for the first 6 months of life, which continues into late infancy. However, the awareness regarding the effects of long-term breastfeeding is relatively low compared with that of breastfeeding in early infancy. We aimed to investigate the growth and nutritional characteristics of the children with prolonged breastfeeding (PBF) over 1 year.
Methods:
This cross-sectional study was based on the data of children aged 12 to 23 months from the National Health and Nutrition Examination Survey (2010–2020) conducted by the Korean Center for Disease Control and Prevention. Data on anthropometric measurements, dietary behavior, and food and nutrient intake were extracted, and the association between PBF and growth, nutritional status, and dietary patterns were analyzed.
Results:
Of the 872 children with a birth weight of ≥ 2.5 kg in the final analysis, 34.2% continued breastfeeding over 12 months of age, and their median breastfeeding duration was 14.2 months. Children with PBF were more likely to have lower current body weight (P < 0.001) and weight gain (P < 0.001), lower daily protein (P = 0.012), calcium (P < 0.001), and iron (P < 0.001) intake per calorie compared with children weaned by 12 months of age or those who were never breastfed. Furthermore, they were started on complementary food at 6 months or later rather than 4–5 months (P < 0.001), consumed cow’s milk earlier (P = 0.012), and consumed probiotics as dietary supplements (P < 0.001) significantly less commonly. When comparing the intake of food groups, children with PBF had a significantly higher intake of cereals and grains (P = 0.023) and fruits (P = 0.020) and a significantly lower intake of bean products (P = 0.020) and milk and dairy products (P = 0.003).
Conclusion
Korean children who continued breastfeeding over 12 months of age showed distinct characteristics in terms of growth, nutritional status, and dietary patterns in the second year of life compared to children who did not. Long-term additional research on their growth and nutritional status may be needed; however, these findings are significant as important fundamental data for nutritional counseling to establish healthy PBF.
8.A Report on a Nationwide Surveillance System for Pediatric Acute Hepatitis of Unknown Etiology in Korea
Kyung Jae LEE ; Jae Sung KO ; Kie Young PARK ; Ki Soo KANG ; Kunsong LEE ; Jeana HONG ; Soon Chul KIM ; Yoon LEE ; Ben KANG ; Yu Bin KIM ; Hyun Jin KIM ; Byung Wook EUN ; Hye-Kyung CHO ; Yae-Jean KIM ; Mi Jin KIM ; Jin LEE ; Taek-Jin LEE ; Seak Hee OH ; Sowon PARK ; Eun Ha HWANG ; Sangjun SOHN ; Jin Gyu LIM ; YooJin KIM ; Yeoun Joo LEE
Journal of Korean Medical Science 2023;38(47):e401-
Background:
Several cases of pediatric acute hepatitis of unknown etiology related to adenoviral infections have been reported in Europe since January 2022. The aim of this study was to compare the incidence, severity, possible etiology, and prognosis of the disease with those in the past in Korea.
Methods:
The surveillance group collected data between May and November 2022 using a surveillance system. Acute hepatitis of unknown etiology was defined in patients aged < 16 years with a serum transaminase level > 500 IU/L, not due to hepatitis A-E or other underlying causes. For comparison, data from 18 university hospitals were retrospectively collected as a control group between January 2021 and April 2022.
Results:
We enrolled 270 patients (mean age, 5 years). The most common symptom was fever. However, the incidence was similar between 2021 and 2022. Liver function test results, number of patients with acute liver failure (ALF), liver transplantation (LT), death, and adenovirus detection rates did not differ between the two groups. None of the adenoviruspositive patients in either group experienced ALF, LT, or death. In the surveillance group, adenovirus-associated virus-2 was detected in four patients, one of whom underwent LT. Patients with an unknown etiology showed significantly higher bilirubin levels, a lower platelet count, and a higher LT rate than patients with a possible etiology.
Conclusion
The incidence of pediatric acute hepatitis of unknown etiology and adenovirus detection rate have not increased in Korea.
9.Epidemiological Trends of Pediatric Inflammatory Bowel Disease in Korea: A Multicenter Study of the Last 3 Years Including the COVID-19 Era
So Yoon CHOI ; Sujin CHOI ; Ben KANG ; Byung-Ho CHOE ; Yeoun Joo LEE ; Jae Hong PARK ; Yu Bin KIM ; Jae Young KIM ; Kunsong LEE ; Kyung Jae LEE ; Ki Soo KANG ; Yoo Min LEE ; Hyun Jin KIM ; Yunkoo KANG ; Hyo-Jeong JANG ; Dae Yong YI ; Suk Jin HONG ; You Jin CHOI ; Jeana HONG ; Soon Chul KIM
Journal of Korean Medical Science 2022;37(37):e279-
Background:
Studies on how the coronavirus pandemic has affected pediatric inflammatory bowel disease (PIBD) are lacking. We aimed to investigate the trends in epidemiology, characteristics, initial management, and short-term outcomes of PIBD in South Korea over the recent three years including the era of coronavirus disease 2019 (COVID-19).
Methods:
This multicenter study retrospectively investigated temporal trends in the epidemiology of PIBD in Korea. Annual occurrences, disease phenotypes, and initial management at diagnosis were analyzed from January 2018 to June 2021.
Results:
A total of 486 patients from 17 institutions were included in this epidemiological evaluation. Analysis of the occurrence trend confirmed a significant increase in PIBD, regardless of the COVID-19 pandemic. In Crohn’s disease, patients with post-coronavirus outbreaks had significantly higher fecal calprotectin levels than those with previous onset 1,339.4 ± 717.04 vs. 1,595.5 ± 703.94, P = 0.001). Patients with post-coronavirus-onset ulcerative colitis had significantly higher Pediatric Ulcerative Colitis Activity Index scores than those with previous outbreaks (48 ± 17 vs. 36 ± 15, P = 0.004). In the initial treatment of Crohn’s disease, the use of 5-aminosalicylic acid (5-ASA) and steroids significantly decreased (P = 0.006 and 0.001, respectively), and enteral nutrition and the use of infliximab increased significantly (P = 0.045 and 0.009, respectively). There was a significant increase in azathioprine use during the initial treatment of ulcerative colitis (P = 0.020).
Conclusion
Regardless of the COVID-19 pandemic, the number of patients with PIBD is increasing significantly annually in Korea. The initial management trends for PIBD have also changed. More research is needed to establish appropriate treatment guidelines considering the epidemiological and clinical characteristics of Korean PIBD.
10.Nationwide “Pediatric Nutrition Day” survey on the nutritional status of hospitalized children in South Korea
Yoo Min LEE ; Eell RYOO ; Jeana HONG ; Ben KANG ; Byung-Ho CHOE ; Ji-Hyun SEO ; Ji Sook PARK ; Hyo-Jeong JANG ; Yoon LEE ; Eun Jae CHANG ; Ju Young CHANG ; Hae Jeong LEE ; Ju Young KIM ; Eun Hye LEE ; Hyun Jin KIM ; Ju-Young CHUNG ; You Jin CHOI ; So Yoon CHOI ; Soon Chul KIM ; Ki-Soo KANG ; Dae Yong YI ; Kyung Rye MOON ; Ji Hyuk LEE ; Yong Joo KIM ; Hye Ran YANG
Nutrition Research and Practice 2021;15(2):213-224
BACKGROUND/OBJECTIVES:
To evaluate the nutritional status and prevalence of malnutrition in hospitalized children at admission and during hospitalization in South Korea.
SUBJECTS/METHODS:
This first cross-sectional nationwide “Pediatric Nutrition Day (pNday)” survey was conducted among 872 hospitalized children (504 boys, 368 girls; 686 medical, 186 surgical) from 23 hospitals in South Korea. Malnutrition risk was screened using the Pediatric Yorkhill Malnutrition Score (PYMS) and the Screening Tool Risk on Nutritional status and Growth. Nutritional status was assessed by z-scores of weight-for-age for underweight, weight-for-height for wasting, and height-for-age for stunting as well as laboratory tests.
RESULTS:
At admission, of the 872 hospitalized children, 17.2% were underweight, and the prevalence of wasting and stunting was 20.2% and 17.3%, respectively. During hospitalization till pNday, 10.8% and 19.6% experienced weight loss and decreased oral intake, respectively.During the aforementioned period, fasting was more prevalent in surgical patients (7.5%) than in medical patients (1.6%) (P < 0.001). According to the PYMS, 34.3% and 30% of the children at admission and on pNday, respectively, had a high-risk of malnutrition, requiring consultation with the nutritional support team (NST). However, only 4% were actually referred to the NST during hospitalization.
CONCLUSIONS
Malnutrition was prevalent at admission and during hospitalization in pediatric patients, with many children experiencing weight loss and poor oral intake. To improve the nutritional status of hospitalized children, it is important to screen and identify all children at risk of malnutrition and refer malnourished patients to the multidisciplinary NST for proper nutritional interventions.

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