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Kim, Yejin,Chang, Yoosoo,Cho, Yong Kyun,Ahn, Jiin,Shin, Hocheol,Ryu, Seungho Elsevier 2019 Clinical gastroenterology and hepatology Vol.17 No.3
<P><B>Background & Aims</B></P> <P>The effects of weight change on the progression of liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) in the general population are unclear. We evaluated the association of weight change and baseline body mass index (BMI) with fibrosis progression, determined by non-invasive measurement of a marker, in young and middle-aged adults with NAFLD.</P> <P><B>Methods</B></P> <P>We performed a prospective cohort study of 40,700 adults with NAFLD in Korea who received regular health screening examinations and were followed for a median 6.0 years. Weight change was defined as the difference between weights measured at baseline and at a subsequent follow-up visit. The progression from a low to an intermediate or high probability of advanced fibrosis was assessed using the aspartate aminotransferase to platelet ratio index (APRI).</P> <P><B>Results</B></P> <P>During 275,421.5 person-years of follow-up, 5454 subjects with a low APRI progressed to an intermediate or high APRI. Multivariable-adjusted hazard ratios for APRI progression, determined by comparing the first and second weight change quintiles (the weight-loss group) and the fourth and fifth quintiles (weight-gain group) with the third quintile (weight-stable group, reference), were 0.68 (95% CI, 0.62–0.74), 0.86 (95% CI, 0.78–0.94), 1.17 (95% CI, 1.07–1.28), and 1.71 (95% CI, 1.58–1.85), respectively. The multivariable-adjusted hazard ratios for APRI progression were determined by comparing subjects with BMIs of 23–24.9, 25–29.9, and ≥30 with subjects with BMIs of 18.5–22.9 kg/m<SUP>2</SUP> (reference); these ratios were 1.13 (95% CI, 1.02–1.26), 1.41 (95% CI, 1.28–1.55), and 2.09 (95% CI, 1.86–2.36), respectively.</P> <P><B>Conclusions</B></P> <P>In a prospective cohort study of 40,700 adults with NAFLD, we found obesity and weight gain to be independently associated with increased risk of fibrosis progression, based on APRI. Maintaining a normal healthy weight and preventing weight gain may help reduce fibrosis progression in individuals with NAFLD.</P>
Alcoholic and Nonalcoholic Fatty Liver Disease and Liver-Related Mortality : A Cohort Study
Chang, Yoosoo,Cho, Yong Kyun,Cho, Juhee,Jung, Hyun-Suk,Yun, Kyung Eun,Ahn, Jiin,Sohn, Chong Il,Shin, Hocheol,Ryu, Seungho American College of Gastroenterology 2019 The American journal of gastroenterology Vol.114 No.4
Chang, Yoosoo,Cho, Juhee,Cho, Yong Kyun,Cho, Ara,Hong, Yun Soo,Zhao, Di,Ahn, Jiin,Sohn, Chong Il,Shin, Hocheol,Guallar, Eliseo,Ryu, Seungho Elsevier 2020 Clinical gastroenterology and hepatology Vol.18 No.1
<P><B>Background & Aims</B></P> <P>We compared the associations of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated fatty liver disease (AFLD) with risk of incident hospitalization for liver and cardiovascular diseases.</P> <P><B>Methods</B></P> <P>We collected data from the Kangbuk Samsung Health Study on 218,030 men and women in Korea who underwent a health examination from 2011 through 2016. Fatty liver disease (FLD) was detected by ultrasound during the initial examination. The Fibrosis-4 index was used to identify individuals with liver fibrosis. Participants were followed up for as long as 5.9 years and data on hospitalizations for liver and cardiovascular diseases were collected.</P> <P><B>Results</B></P> <P>The prevalence of NAFLD was 22.0% and the prevalence of AFLD was 6.4%. Over a median follow-up period of 4.2 years, we observed 51 and 1097 incident cases of liver disease– or cardiovascular disease–related hospitalizations, respectively. After adjustment for potential confounders, the multivariable-adjusted hazard ratios for liver disease–related hospitalization, comparing NAFLD and AFLD with the reference category (no excessive alcohol intake and no FLD), were 1.73 (95% CI, 0.76–3.96) and 5.00 (95% CI, 2.12–11.83), respectively. The corresponding hazard ratios for cardiovascular disease hospitalization were 1.20 (95% CI, 1.02–1.40) and 1.08 (95% CI, 0.86–1.34), respectively. Among participants with FLD, the risk of liver disease–related hospitalization increased with high Fibrosis-4 index scores, whereas the risk of incident cardiovascular disease did not.</P> <P><B>Conclusions</B></P> <P>In a large cohort study, we found an increased risk of liver disease–related hospitalizations for patients with NAFLD or AFLD, especially among those with Fibrosis-4 index scores. An increased risk of cardiovascular disease–associated hospitalization was observed in patients with NAFLD but not AFLD.</P>
Chang, Yoosoo,Ryu, Seungho,Sung, Ki-Chul,Cho, Yong Kyun,Sung, Eunju,Kim, Han-Na,Jung, Hyun-Suk,Yun, Kyung Eun,Ahn, Jiin,Shin, Hocheol,Wild, Sarah Helen,Byrne, Christopher D BMJ Publishing Group Ltd 2019 Gut: journal of the British Society of Gastroenter Vol.68 No.9
<P><B>Objective</B></P><P>Recent evidence suggests that alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) may differentially affect risk of cardiovascular mortality. To investigate whether early liver disease due to AFLD or NAFLD have similar or dissimilar effects on risk of early coronary artery atherosclerosis, we have investigated the associations between AFLD and NAFLD and coronary artery calcium (CAC).</P><P><B>Design</B></P><P>A cross-sectional study was performed in 105 328 Korean adults who attended a health check-up programme. CAC score was assessed using CT, daily alcohol intake was recorded as grams/day and liver fat by ultrasound. Logistic regression model was used to calculate ORs with 95% CIs for prevalent CAC.</P><P><B>Results</B></P><P>Both NAFLD and AFLD were positively associated with CAC score. After adjusting for potential confounders, multivariable-adjusted OR (95% CIs) for CAC >0 comparing NAFLD and AFLD to the reference (absence of both excessive alcohol use and fatty liver disease) were 1.10 (95% CI 1.05 to 1.16) and 1.20 (95% CI 1.11 to 1.30), respectively. In post hoc analysis, OR (95% CI) for detectable CAC comparing AFLD to NAFLD was 1.09 (95% CI 1.01 to 1.17). Associations of NAFLD and AFLD with CAC scores were similar in both non-obese and obese individuals without significant interaction by obesity (p for interaction=0.088). After adjusting for homeostasis model assessment of insulin resistance and high-sensitivity C reactive protein, the associations between fatty liver disease and CAC scores remained statistically significant.</P><P><B>Conclusion</B></P><P>In this large sample of young and middle-aged individuals, early liver disease due to NAFLD and AFLD were both significantly associated with the presence of coronary artery calcification.</P>
Yang, Yoosoo,Shin, Jae Yoon,Oh, Jung-Mi,Jung, Chang Hwa,Hwang, Yunha,Kim, Sehyun,Kim, Jun-Seob,Yoon, Kee-Jung,Ryu, Ji-Young,Shin, Jaeil,Hwang, Jae Sung,Yoon, Tae-Young,Shin, Yeon-Kyun,Kweon, Dae-Hyuk National Academy of Sciences 2010 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.107 No.51
<P>Neuronal SNARE proteins mediate neurotransmitter release at the synapse by facilitating the fusion of vesicles to the presynaptic plasma membrane. Cognate v-SNAREs and t-SNAREs from the vesicle and the plasma membrane, respectively, zip up and bring about the apposition of two membranes attached at the C-terminal ends. Here, we demonstrate that SNARE zippering can be modulated in the midways by wedging with small hydrophobic molecules. Myricetin, which intercalated into the hydrophobic inner core near the middle of the SNARE complex, stopped SNARE zippering in motion and accumulated the trans-complex, where the N-terminal region of v-SNARE VAMP2 is in the coiled coil with the frayed C-terminal region. Delphinidin and cyanidin inhibited N-terminal nucleation of SNARE zippering. Neuronal SNARE complex in PC12 cells showed the same pattern of vulnerability to small hydrophobic molecules. We propose that the half-zipped trans-SNARE complex is a crucial intermediate waiting for a calcium trigger that leads to fusion pore opening.</P>
Jung, Chang-Hwa,Choi, Jin-Kyu,Yang, Yoosoo,Koh, Hyun-Ju,Heo, Paul,Yoon, Kee-Jung,Kim, Sehyun,Park, Won-Seok,Shing, Hong-Ju,Kweon, Dae-Hyuk Informa Healthcare 2012 PHARMACEUTICAL BIOLOGY Vol.50 No.9
<P><I>Context: Botulinum</I> neurotoxins (BoNTs) are popularly used to treat various diseases and for cosmetic purposes. They act by blocking neurotransmission through specific cleavage of soluble <I>N</I>-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Recently, several polyphenols were shown to interfere with SNARE complex formation by wedging into the hydrophobic core interface, thereby leading to reduced neuroexocytosis.</P><P><I>Objective</I>: In order to find industrially-viable plant extract that functions like BoNT, 71 methanol extracts of flowers were screened and BoNT-like activity of selected extract was evaluated.</P><P><I>Materials and methods</I>: After evaluating the inhibitory effect of 71 flower methanol extracts on SNARE complex formation, seven candidates were selected and they were subjected to SNARE-driven membrane fusion assay. Neurotransmitter release from neuronal PC12 cells and SNARE complex formation inside the cell was also evaluated. Finally, the effect of one selected extract on muscle contraction and digit abduction score was determined.</P><P><I>Results</I>: The extract of <I>Potentilla chinensis</I> Ser. (Rosaceae)(Chinese cinquefoil) flower inhibited neurotransmitter release from neuronal PC12 cells by approximately 90% at a concentration of 10 μg/mL. The extract inhibited neuroexocytosis by interfering with SNARE complex formation inside cells. It reduced muscle contraction of phrenic nerve-hemidiaphragm by approximately 70% in 60 min, which is comparable to the action of the Ca<SUP>2+</SUP>-channel blocker verapamil and BoNT type A.</P><P><I>Discussion and conclusion</I>: While BoNT blocks neuroexocytosis by cleaving SNARE proteins, the <I>Potentilla chinensis</I> extract exhibited the same activity by inhibiting SNARE complex formation. The extract paralyzed muscle as efficiently as BoNT, suggesting the potential versatility in cosmetics and therapeutics.</P>
Yim, Gyeyoon,Ahn, Younjhin,Chang, Yoosoo,Ryu, Seungho,Lim, Joong-Yeon,Kang, Danbee,Choi, Eun-Kyung,Ahn, Jiin,Choi, Yuni,Cho, Juhee,Park, Hyun-Young by The North American Menopause Society. 2015 Menopause Vol.22 No.10
OBJECTIVE:: The present study investigated the prevalence and severity of menopause symptoms experienced by Korean women aged 44 to 56 years and their associated factors. METHODS:: A cross-sectional study was performed on 2,201 women aged 44 to 56 years in health checkup centers between November 2012 and March 2013. The 29-item Menopause-Specific Quality of Life Questionnaire was used to assess vasomotor, psychosocial, physical, and sexual symptoms related to menopause. The guidelines for the classification of reproductive aging stages proposed at the Stages of Reproductive Aging Workshop were used. Multivariable linear regression analyses were performed to identify factors associated with severity of menopause symptoms. RESULTS:: Among participants, 42.6% were premenopausal, 36.7% were perimenopausal, and 20.7% were postmenopausal. Although physical symptoms were the most severe menopause symptoms experienced by premenopausal and perimenopausal women, postmenopausal women reported sexual symptoms as the most bothersome. The mean scores for each domain increased from the premenopausal period through the postmenopausal period (P for trend < 0.001). The regression model revealed that age (for vasomotor and sexual symptoms) and obesity (for vasomotor and physical symptoms) were significantly associated with severity of menopause symptoms (P < 0.05). Physically active women had fewer severe physical symptoms related to menopause than inactive women. CONCLUSIONS:: Postmenopausal women experience the most severe symptoms. Obesity and physical activity are the main modifiable factors associated with symptom severity. Further studies are needed to examine the effects of physical activity promotion and weight control interventions on preventing menopause symptoms in Korean women.