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Background@#Hepatic stellate cells (HSCs) are the major cells which play a pivotal role in liver fibrosis. During injury, extracellular stimulators can induce HSCs transdifferentiated into active form. Phloretin showed its ability to protect the liver from injury, so in this research we would like to investigate the effect of phloretin on succinate-induced HSCs activation in vitro and liver fibrosis in vivo study. @*Methods@#In in vitro, succinate was used to induce HSCs activation, and then the effect of phloretin on activated HSCs was examined. In in vivo, succinate was used to generated liver fibrosis in mouse and phloretin co-treated to check its protection on the liver. @*Results@#Phloretin can reduce the increase of fibrogenic markers and inhibits the proliferation, migration, and contraction caused by succinate in in vitro experiments. Moreover, an upregulation of proteins associated with aerobic glycolysis occurred during the activation of HSCs, which was attenuated by phloretin treatment. In in vivo experiments, intraperitoneal injection of phloretin decreased expression of fibrotic and glycolytic markers in the livers of mice with sodium succinate diet-induced liver fibrosis. These results suggest that aerobic glycolysis plays critical role in activation of HSCs and succinate can induce liver fibrosis in mice, whereas phloretin has therapeutic potential for treating hepatic fibrosis. @*Conclusion@#Intraperitoneal injection of phloretin attenuated succinate-induced hepatic fibrosis and alleviates the succinate-induced HSCs activation.
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Background@#Dipeptidyl peptidase-4 inhibitors (DPP-4Is) are used clinically as oral antidiabetic agents. Although DPP-4Is are known to ameliorate liver fibrosis, the protective mechanism of DPP-4Is in liver fibrosis remains obscure. In this study, gemigliptin was used to investigate the potential of DPP-4Is to alleviate the progression of liver fibrosis. @*Methods@#To clarify the effects and mechanisms of gemigliptin, we conducted various experiments in LX-2 cells (immortalized human hepatic stellate cells [HSCs], the principal effectors of hepatic fibrogenesis), which were activated by succinate and exhibited elevated expression of α-smooth muscle actin, collagen type 1, and pro-inflammatory cytokines and increased cell proliferation. In vivo, we examined the effects and mechanisms of gemigliptin on a high-fat, high-cholesterol–induced mouse model of nonalcoholic steatohepatitis (NASH). @*Results@#Gemigliptin decreased the expression of fibrogenesis markers and reduced the abnormal proliferation of HSCs. In addition, gemigliptin reduced the succinate-induced production of mitochondrial reactive oxygen species (ROS), intracellular ROS, and mitochondrial fission in HSCs. Furthermore, in the mouse model of NASH-induced liver fibrosis, gemigliptin alleviated both liver fibrosis and mitochondrial dysfunction. @*Conclusion@#Gemigliptin protected against HSC activation and liver fibrosis by alleviating mitochondrial dysfunction and ROS production, indicating its potential as a strategy for preventing the development of liver disease.
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Background@#The incidence of early-onset diabetes is increasing among young adults.However, there are limited data on the characteristics and management of young Korean adults with diabetes. This study assessed the clinical and demographic characteristics, health behaviors, and mental health among young Korean adults with diabetes mellitus. @*Methods@#This cross-sectional study included young Korean adults with diabetes (n = 225) with an onset age of 20–39 years from four university hospitals. Demographic characteristics, management of diabetes, and mental health were assessed using a questionnaire survey. @*Results@#Type 2 diabetes was the most common type (73.3%), and 13.8% of participants were classified as other types or unknown. Approximately, 64.7% of participants had a strong family history of diabetes, and 76% had treatment within three months of diagnosis.Approximately, 11.1% of participants had diabetic complications; 39.1% of participants received insulin injections, including oral anti-diabetic medications. Additionally, 30.4% were smokers, and only 28% had active physical activity; 26.5% of participants had >3 hours of screen time. One third of participants never had breakfast, and 60.5% went out to eat at least three times a week. Half of the participants showed moderate to severe stress perception, and 21.4% of patients had moderate to severe levels of depression based on the Korean version of Beck Depression Inventory score. @*Conclusion@#Early-onset diabetes was associated with a strong family history and early insulin treatment. Young adults with diabetes had poor health behaviors and frequent mental depression. These findings suggest the necessity of health policies for improving health behaviors and mental distress.
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Background@#The incidence of early-onset diabetes is increasing among young adults.However, there are limited data on the characteristics and management of young Korean adults with diabetes. This study assessed the clinical and demographic characteristics, health behaviors, and mental health among young Korean adults with diabetes mellitus. @*Methods@#This cross-sectional study included young Korean adults with diabetes (n = 225) with an onset age of 20–39 years from four university hospitals. Demographic characteristics, management of diabetes, and mental health were assessed using a questionnaire survey. @*Results@#Type 2 diabetes was the most common type (73.3%), and 13.8% of participants were classified as other types or unknown. Approximately, 64.7% of participants had a strong family history of diabetes, and 76% had treatment within three months of diagnosis.Approximately, 11.1% of participants had diabetic complications; 39.1% of participants received insulin injections, including oral anti-diabetic medications. Additionally, 30.4% were smokers, and only 28% had active physical activity; 26.5% of participants had >3 hours of screen time. One third of participants never had breakfast, and 60.5% went out to eat at least three times a week. Half of the participants showed moderate to severe stress perception, and 21.4% of patients had moderate to severe levels of depression based on the Korean version of Beck Depression Inventory score. @*Conclusion@#Early-onset diabetes was associated with a strong family history and early insulin treatment. Young adults with diabetes had poor health behaviors and frequent mental depression. These findings suggest the necessity of health policies for improving health behaviors and mental distress.
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Recently, there has been a controversy over public health remarks to doctors in relation to public health policy. By examining the meaning of public goods and the characteristics of medical service goods for the public implications of doctors, we examine the value contained in the public goods of doctors.
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Background@#Dry sauna treatments improve the quality of life for chronic pain, congestive heart failure, and type 2 diabetes patients. This study aimed to determine whether dry sauna therapy improved the quality of life of obese people. @*Methods@#A total of 38 consecutive participants aged over 20 years with a body mass index of ≥25 kg/m2 were recruited for the study. The participants were treated with a 90°C dry sauna for 15 minutes, twice daily for 4 consecutive days. To assess the quality of life, all participants completed the 5 level EQ-5D questionnaires and the EQ-Visual Analog Scale. Study parameters were measured on the same day prior to commencing the sauna sessions in a fasted state and 2 days after the last sauna session. @*Results@#The average age was 62.3±9.5 years; 84.2% of the participants were female. The mean body mass index was 28.5±2.4 kg/m2. Dry sauna significantly improved the mean 5 level EQ-5D index scores from 0.83±0.12 to 0.89±0.11 and increased the mean EQ-Visual Analog Scale from 79.0±15.2 to 91.1±9.7. However, there were no significant changes in body mass index, blood pressure, heart rate, or body composition before and after the 8-session sauna therapy. @*Conclusion@#Dry sauna improved the health-related quality of life of obese patients without adverse events. Further clinical studies in larger study populations are needed to verify these findings and provide concrete evidence for obesity treatment.
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Background@#Hepatic stellate cells (HSCs) are known to play a fundamental role in the progression of liver fibrosis. Once HSCs are activated, they are involved in proliferation, migration, and contractility which are characteristics of liver fibrogenesis. Recent studies have shown that irisin, a myokine secreted during physical exercise, has a protective effect in various metabolic diseases, especially in renal fibrosis. However, whether irisin is involved in HSC activation and other processes associated with liver fibrosis has not yet been investigated. In this study, we reveal the role of irisin in HSC activation as well as in proliferation, migration, and contractile properties of HSCs in vitro. @*Methods@#LX-2 cells, immortalized human HSCs, were treated with transforming growth factor beta 1 (TGF-β1), a core regulator of HSC fibrosis, with or without irisin, and markers of the aforementioned processes were analyzed. Further, an inflammatory response was stimulated with TGF-β1 and lipopolysaccharide (LPS) in combination with irisin and the expression of cytokines was measured. @*Results@#Recombinant irisin significantly suppressed the expression of TGF-β1-stimulated fibrosis markers including alpha-smooth muscle actin and collagen type 1 alpha 1 and prevented the TGF-β1-induced proliferation, migration, and contractility of LX-2 cells. Additionally, irisin ameliorated the production of interleukin-6 (IL-6) and IL-1β induced by TGF-β1 and LPS treatments. @*Conclusion@#These findings suggested that irisin potently improved the progression of hepatic fibrosis by regulating HSC activation, proliferation, migration, contractility, and HSC-mediated production of inflammatory cytokine.
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As a member of the class IIa histone deacetylases (HDACs), HDAC9 catalyzes the deacetylation of histones and transcription factors, commonly leading to the suppression of gene transcription. The activity of HDAC9 is regulated transcriptionally and posttranslationally. HDAC9 is known to play an essential role in regulating myocyte and adipocyte differentiation and cardiac muscle development. Also, recent studies have suggested that HDAC9 is involved in the pathogenesis of chronic diseases, including cardiovascular diseases, osteoporosis, autoimmune disease, cancer, obesity, insulin resistance, and liver fibrosis. HDAC9 modulates the expression of genes related to the pathogenesis of chronic diseases by altering chromatin structure in their promotor region or reducing the transcriptional activity of their respective transcription factors. This review summarizes the current knowledge of the regulation of HDAC9 expression and activity. Also, the roles of HDAC9 in the pathogenesis of chronic diseases are discussed, along with potential underlying mechanisms.
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BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) is strongly expressed in the kidney, and soluble levels of this protein are used as a marker in various chronic inflammatory diseases, including diabetes, coronary artery disease, and cancer. This study examined the association between the serum soluble DPP-4 levels and renal function or cardiovascular risk in patients with type 2 diabetes mellitus. METHODS: In this retrospective analysis, soluble DPP-4 levels were measured in preserved sera from 140 patients with type 2 diabetes mellitus who had participated in our previous coronary artery calcium (CAC) score study. RESULTS: The mean±standard deviation soluble DPP-4 levels in our study sample were 645±152 ng/mL. Univariate analyses revealed significant correlations of soluble DPP-4 levels with the total cholesterol (r=0.214, P=0.019) and serum creatinine levels (r=−0.315, P<0.001) and the estimated glomerular filtration rate (eGFR; estimated using the modification of diet in renal disease equation) (r=0.303, P=0.001). The associations of soluble DPP-4 levels with serum creatinine and GFR remained significant after adjusting for age, body mass index, and duration of diabetes. However, no associations were observed between soluble DPP-4 levels and the body mass index, waist circumference, or CAC score. CONCLUSION: These data suggest the potential use of serum soluble DPP-4 levels as a future biomarker of deteriorated renal function in patients with type 2 diabetes mellitus.
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Humans , Body Mass Index , Calcium , Cholesterol , Coronary Artery Disease , Coronary Vessels , Creatinine , Diabetes Mellitus, Type 2 , Diet , Dipeptidyl Peptidase 4 , Glomerular Filtration Rate , Kidney , Retrospective Studies , Waist CircumferenceABSTRACT
BACKGROUND: Dry sauna has been very popular as an alternative therapy for promoting health among people who want to improve their health condition without relying on pharmaceuticals. The aim of this study was to investigate whether dry sauna therapy improved quality of life and reduced pain in participants with low back pain.METHODS: Study participants comprised a total of 37 consecutive patients who were over 20 years of age with low back pain. Dry sauna therapy was performed twice per day for 5 consecutive days over the course of 1 week, thus comprising a total of 10 sessions each of 15 min of exposure to a 90℃ dry sauna.RESULTS: The verbal numerical rating scale (VNRS) and Oswestry disability index (ODI) scores were significantly reduced after dry sauna therapy (P < 0.001 for both). VNRS pain scores had a median (range) of 5 (2–8) before dry sauna therapy and 3 (0–8) after dry sauna therapy. ODI scores had a median (range) of 12 (2–24) before dry sauna therapy and 8 (1–17) after dry sauna therapy. The proportion of participants who reported successful treatment (excellent + good) was 70%. No adverse effects were observed related to dry sauna therapy.CONCLUSIONS: Our results suggest that dry sauna therapy may be useful to improve quality of life and reduce pain in patients with low back pain. Therefore, pain physicians can recommend dry sauna therapy as an alternative and complimentary therapy for patients with low back pain.
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Humans , Low Back Pain , Quality of Life , Steam BathABSTRACT
BACKGROUND: This study aimed to investigate associations between self-reported sleep duration and general and abdominal obesity in Korean adults stratified according to gender and age. METHODS: Data from 41,805 adults, 18–110 years of age, collected by the Korea National Health and Nutrition Examination Survey (KNHANES) in 2007 and 2015, were analyzed. Multivariable logistic regression was used to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for obesity and abdominal obesity by sleep duration after controlling for sociodemographic and lifestyle variables. RESULTS: Among individuals 30–49 years of age, there was an increased AOR for obesity only for sleep duration ≤ 5 hour/day compared with sleep duration 6 to 8 hour/day, both in men (OR, 1.25; 95% CI, 1.02–1.54) and women (OR, 1.56; 95% CI, 1.29–1.90), after controlling for covariates. Regarding women, there was increased AOR for abdominal obesity for sleep duration ≤ 5 hour/day (OR, 1.45; 95% CI, 1.18–1.78) and ≥ 9 hour/day (OR, 1.38; 95% CI, 1.09–1.76) compared with sleep duration 6 to 8 hour/day. However, for elderly individuals (≥ 65 years), there was a negative association between sleep duration ≤ 5 hour/day and obesity, but not with abdominal obesity, in both men and women. CONCLUSION: This study demonstrated a significant association between sleep duration and obesity, which varied according to gender and age.
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Adult , Aged , Female , Humans , Male , Korea , Life Style , Logistic Models , Nutrition Surveys , Obesity , Obesity, Abdominal , Odds RatioABSTRACT
No abstract available.
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BACKGROUND: Despite the beneficial effect of fibroblast growth factor 21 (FGF21) on metabolic disease, there are concerns about adverse effects on bone metabolism, supported by animal studies. However, a recent human study showed the positive association between serum FGF21 level and bone mineral density (BMD) in healthy premenopausal women. We undertook this study to examine the association between FGF21 level and BMD in healthy postmenopausal Korean women who are susceptible to osteoporosis. METHODS: We used data of 115 participants from a cohort of healthy postmenopausal women (>50 years old) to examine the association between serum FGF21 level and BMD. The clinical characteristics were obtained from the participants, and blood testing and serum FGF21 testing were undertaken. BMD of the lumbar spine, femoral neck and total hip area, and bone markers were used in the analyses. RESULTS: The mean age of the participants was 60.2±7.2 years. Serum FGF21 levels showed negative correlation with BMD and T-scores in all three areas, but there were no statistically significant differences. Multivariate analyses with adjustment for age and body mass index also did not show significant association between serum FGF21 level and BMD. In addition, serum FGF21 level also showed no correlation with osteocalcin and C-telopeptide levels. CONCLUSION: In our study, serum FGF21 level showed no significant correlation with BMD and T-scores.
Subject(s)
Animals , Female , Humans , Body Mass Index , Bone Density , Cohort Studies , Femur Neck , Fibroblast Growth Factors , Fibroblasts , Hematologic Tests , Hip , Metabolic Diseases , Metabolism , Multivariate Analysis , Osteocalcin , Osteoporosis , SpineABSTRACT
BACKGROUND: The purpose of this study was to determine the impact of an educational intervention that includes information sharing about absolute fracture risk on the knowledge of osteoporosis and modifiable risk factors among Korean patients with osteoporosis. METHODS: Adults aged >50 years who visited the outpatient clinic for osteoporosis were recruited. Subjects with trauma-related fractures or pathological fractures were excluded. The anthropometric data and clinical risk factors for fracture were collected at baseline. The participants completed the survey questionnaire that measured their knowledge regarding osteoporosis at baseline and then received information about the risk of fracture and individual education. Fracture risk was classified into five groups according to degree. The post-survey was conducted 3 months later. The pretest results were compared with the posttest results. RESULTS: In this study, 179 subjects (15 men and 164 women) were enrolled. After the educational intervention, the mean osteoporosis knowledge score significantly increased from 10.6±5.7 at pre-education (baseline) to 11.7±6.3 at post-education (P < 0.001). When comparing the pre- and post-education Korean fracture risk scores, a negligible difference was found between the “very low risk” and “low risk” groups. However, the scores in the “very high risk” and “high risk” groups decreased from 77.6% to 76.0%. We found a difference over time only in physical activity. CONCLUSIONS: Simple educational intervention is effective in increasing osteoporosis knowledge among Korean patients with osteoporosis. It may confer some benefit by providing information about osteoporotic fracture risks to improve knowledge and awareness regarding osteoporosis.
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Adult , Humans , Male , Ambulatory Care Facilities , Education , Fractures, Spontaneous , Information Dissemination , Motor Activity , Osteoporosis , Osteoporotic Fractures , Risk Assessment , Risk FactorsABSTRACT
Glucokinase maturity-onset diabetes of the young (GCK-MODY) represents a distinct subgroup of MODY that does not require hyperglycemia-lowering treatment and has very few diabetes-related complications. Three patients from two families who presented with clinical signs of GCK-MODY were evaluated. Whole-exome sequencing was performed and the effects of the identified mutations were assessed using bioinformatics tools, such as PolyPhen-2, SIFT, and in silico modeling. We identified two mutations: p.Leu30Pro and p.Ser383Leu. In silico analyses predicted that these mutations result in structural conformational changes, protein destabilization, and thermal instability. Our findings may inform future GCK-MODY diagnosis; furthermore, the two mutations detected in two Korean families with GCK-MODY improve our understanding of the genetic basis of the disease.
Subject(s)
Humans , Computational Biology , Computer Simulation , Diabetes Complications , Diabetes Mellitus, Type 2 , Diagnosis , GlucokinaseABSTRACT
BACKGROUND: The aim of this study was to evaluate the longitudinal changes of trabecular bone score (TBS) during and after bisphosphonate (BP) treatment in postmenopausal Korean women with osteoporosis. METHODS: We analyzed 191 patients who took BP and underwent bone mineral density (BMD) test for the period from January 2010 to December 2015. The mean follow up period during treatment and after treatment was 22.8 months and 18 months, respectively. The TBS and BMD values were evaluated by the percent changes relative to the baseline. RESULTS: In 191 patients, who treated with BPs, L-spine BMD increased 3.65±0.5% and TBS increased 0.26±0.4% from baseline during first 1 year. At 2 to 4 years, the changes of BMD and TBS from baseline gradually increased up to 9.3±3.25% and 2.69±0.98% and both results showed statistically significant correlation. In 86 patients who stopped BPs, L-spine BMD decreased -0.54±1.07% and TBS increased 0.33±1.96% from baseline during 3 years follow up period. CONCLUSIONS: Lumbar spine TBS increase over time with BPs treatment although the changes were less than that of BMD. Also, it preserve for years after stopping treatment, as the changes of lumbar spine BMD. The results of BMD and TBS showed significant correlation during treatment but not during drug withdrawal.
Subject(s)
Female , Humans , Bone Density , Follow-Up Studies , Osteoporosis , Spine , Withholding TreatmentABSTRACT
BACKGROUND: Multipotent mesenchymal stem cells can differentiate into adipocytes or osteoblasts through closely regulated lineage-control processes. However, adipocyte precursor cells release preadipocyte factor 1 (Pref-1), which inhibits the differentiation of mesenchymal stem cells into mature adipocytes and osteoblasts. Previous studies have also reported an inverse association between Pref-1 levels and bone mineral density (BMD) among patients with anorexia nervosa. METHODS: In this retrospective study, we examined the correlations between Pref-1 levels and BMD among 124 healthy postmenopausal women (>50 years old). The patients had provided information regarding their clinical characteristics, and underwent blood testing and serum Pref-1 testing. RESULTS: The subjects' mean age was 59.9±7.1 years and the median time since menopause onset was 9.1 years. A history of osteoporotic fracture was identified in 23 subjects (19%). Serum Pref-1 levels were not significantly correlated with BMD values at the lumbar spine (R²=0.038, P=0.109), femur neck (R²=0.017, P=0.869), and total hip (R²=0.041, P=0.09), and multivariate analyses with adjustment for age and body mass index also did not detect any significant correlations. Subgroup analyses according to a history of fracture also did not detect significant associations between Pref-1 levels and BMD values. CONCLUSION: In our study population, it does not appear that serum Pref-1 levels are significantly associated with BMD values and osteoporosis.
Subject(s)
Female , Humans , Adipocytes , Anorexia Nervosa , Body Mass Index , Bone Density , Femur Neck , Hematologic Tests , Hip , Menopause , Mesenchymal Stem Cells , Multivariate Analysis , Osteoblasts , Osteoporosis , Osteoporotic Fractures , Retrospective Studies , SpineABSTRACT
The rapid increases in childhood obesity and physical inactivity are linked to the incidence of diabetes among young individuals. However, few studies have evaluated the prevalence of diabetes among this population. Therefore, we used Korea National Health and Nutrition Examination Survey (KNHANES) data to evaluate the prevalence and management of diabetes and pre-diabetes among young Koreans. We evaluated KNHANES data (2005–2014) from 10–29-year-old individuals. Individuals were considered eligible if they had completed the health examination and the health interview survey, and we excluded individuals with missing data regarding fasting glucose or glycated haemoglobin levels. Among the 100,101 potentially eligible individuals who participated in KNHANES (2005–2014), we included 83,577 (37,677 male and 45,900 female) individuals. The overall prevalences of diabetes and pre-diabetes among 10–19-year-old individuals were 0.2% and 11.9%, respectively. Among 20–29-year-old individuals, the prevalences of diabetes and pre-diabetes were 0.9% and 9.6%, respectively. The overall rates of diabetes awareness during the study period were 36.6% for 10–19-year-old individuals and 50.8% for 20–29-year-old individuals. However, the prevalence of diabetes and pre-diabetes had noticeably increased at the 2013–2014 KNHANES: 0.6% and 25.9% among 10–19-year-old individuals, and 0.8% and 19.2% among 20–29-year-old individuals. The prevalence of diabetes and pre-diabetes is rapidly increasing among Korean teenagers and young adults. Pre-emptive interventions to diagnose and treat diabetes and pre-diabetes are needed to improve glycaemic control among this population.