Phloretin Ameliorates Succinate-Induced Liver Fibrosis by Regulating Hepatic Stellate Cells

Cong Thuc Le,Giang Nguyen,박소영,Hanh Nguyen Dong,조윤경,이재호,임승순,최대호,조은희 대한내분비학회 2023 Endocrinology and metabolism Vol.38 No.4

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.

Succinate induces hepatic fibrogenesis by promoting activation, proliferation, and migration, and inhibiting apoptosis of hepatic stellate cells

Park, So Young,Le, Cong Thuc,Sung, Kun Yong,Choi, Dae Hee,Cho, Eun-Hee Academic Press 2018 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>Liver fibrosis is a progressive pathological process that accompanies wound healing; however, therapeutics for reversing hepatic fibrosis are unavailable. Activation of hepatic stellate cells (HSCs) play a critical role in liver fibrosis. Recent reports showed that succinate and its receptor, G-protein coupled receptor 91 (GPR91), act as signaling molecules during the activation of HSCs. However, the role of succinate in proliferation, apoptosis, and migration of HSCs has not been studied. In this study, we determined whether succinate regulates proliferation, apoptosis, and migration of HSCs and induces liver fibrosis in a mouse model.</P> <P>Succinate treatment not only induced activation of HSCs, but also increased the proliferation and migration of LX-2 HSCs and inhibited apoptosis. To investigate whether succinate causes hepatic fibrosis, 100 mg/kg succinate or control PBS was administered by intraperitoneal injection to mice once a day for four weeks. There were significant molecular changes such as increased α-SMA and collagen type 1 production and increased production of inflammatory cytokines such as IL-6 and TNF-α, but not TGF-β, in the succinate-treated group compared to the control group. However, no morphological changes were observed in Masson's trichrome staining. In conclusion, the present study demonstrated that succinate induces activation, proliferation, and migration of HSCs and attenuates apoptosis in LX-2 HSCs. Therefore, inhibition of succinate accumulation may be an effective method for reversing liver fibrosis by controlling HSC survival and growth.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Succinate induces proliferation and migration of hepatic stellate cells. </LI> <LI> Succinate inhibits apoptosis of hepatic stellate cells. </LI> <LI> Succinate intraperitoneal injection induces production of α.-smooth muscle actin in mice. </LI> </UL> </P>

Irisin Regulates the Functions of Hepatic Stellate Cells

Hanh Nguyen Dong,박소영,Cong Thuc Le,최대희,조은희 대한내분비학회 2020 Endocrinology and metabolism Vol.35 No.3

Background: Hepatic stellate cells (HSCs) are known to play a fundamental role in the progression of liver fibrosis. Once HSCs areactivated, 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 hasnot 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 ofHSC fibrosis, with or without irisin, and markers of the aforementioned processes were analyzed. Further, an inflammatory responsewas 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-smoothmuscle 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.

Metformin ameliorates activation of hepatic stellate cells and hepatic fibrosis by succinate and GPR91 inhibition

Nguyen, Giang,Park, So Young,Le, Cong Thuc,Park, Won Sun,Choi, Dae Hee,Cho, Eun-Hee Academic Press 2018 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Chronic liver disease is becoming a major cause of morbidity and mortality worldwide. During liver injury, hepatic stellate cells (HSCs) trans-differentiate into activated myofibroblasts, which produce extracellular matrix.</P> <P>Succinate and succinate receptor (G-protein coupled receptor91, GPR91) signaling pathway has now emerged as a regulator of metabolic signaling. A previous study showed that succinate and its specific receptor, GPR91, are involved in the activation of HSCs and the overexpression of α-smooth muscle actin (α-SMA).</P> <P>Metformin, a well-known anti-diabetic drug, inhibits hepatic gluconeogenesis in the liver. Many studies have shown that metformin not only prevented, but also reversed, steatosis and inflammation in a nonalcoholic steatohepatitis (NASH) animal model. However, the role of metformin in HSC activation and succinate-GPR91 signaling has not been clarified.</P> <P><B>Methods</B></P> <P>The immortalized human HSCs, LX-2 cells, were used for the in vitro study. For the <I>in vivo</I> study, male C57BL/J6 mice were randomly divided into 3 groups and were fed with a methionine-choline-deficient diet (MCD diet group) as a nonalcoholic steatohepatitis (NASH) mouse model with or without 0.1% metformin for 12 weeks, or were fed a control methionine-choline-sufficient diet (MCS diet group).</P> <P><B>Results</B></P> <P>In our study, metformin and 5-aminoimidazole-4-carboxamide 1-β-<SMALL>D</SMALL>-ribofuranoside (AICAR), which is an analog of adenosine monophosphate, were shown to suppress α-SMA expression via enhanced phosphorylation of AMP-activated protein kinase (AMPK) and inhibition of succinate-GPR91 signaling in activated LX-2 cells induced by palmitate- or succinate. Metformin and AICAR also reduced succinate concentration in the cell lysates when LX-2 cells were treated with palmitate. Moreover, metformin and AICAR reduced interleukin-6 and, transforming growth factor-β1 production in succinate-treated LX-2 cells. Both metformin and AICAR inhibited succinate-stimulated HSC proliferation and cell migration.</P> <P>Mice fed a MCD diet demonstrated increased steatohepatitis and liver fibrosis compared to that of mice fed control diet. Metformin ameliorated steatohepatitis, liver fibrosis, inflammatory cytokine production and decreased α -SMA and GPR91expression in the livers of the MCD diet-fed mice.</P> <P><B>Conclusion</B></P> <P>This study shows that metformin can attenuate activation of HSCs by activating the AMPK pathway and inhibiting the succinate-GPR91 pathway. Metformin has therapeutic potential for treating steatohepatitis and liver fibrosis.</P>

Repeated Dry Sauna Therapy Improves Quality of Life in Obese Korean People

최훈성,Hyuki Kwon,Keun-Hyok Cho,Le Cong Thuc,So Young Park,김남훈,Wae-Jung Kim,Yun-Ki Kim,Woo-Seok Jeon,Ju-Ah Lee,Hyoung-Chun Kim,조은희 대한가정의학회 2020 Korean Journal of Family Medicine Vol.41 No.5

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.

Aluminum in rocks: Optimized microwave-assisted acid digestion and UV-Vis spectrophotometric measurement

Nguyen Thanh-Nho,Thai Huynh-Thuc,Le-Thi Anh-Dao,Do Minh-Huy,Le-Thi Huynh-Mai,Le Quang-Huy,Nguyen-Thi Kim-Sinh,Nguyen Cong-Hau 한국분석과학회 2023 분석과학 Vol.36 No.5

Aluminium (Al) is one of the major elements in rocks and its concentration can be varied, depending on different rock types as well as sources. The present study aimed to propose an analytical method based on the UV-Vis as a cheap, simple, and common instrument equipped in most laboratories for Al quantification in rocks after the microwave assisted acid digestion. The aluminone and 8-hydroxyquinoline were investigated for the colorimetric assay. The results show that the 8-hydroxyquinoline reagent was more favorable in terms of the minimized affects of the potential interferences present in the digested solutions, i.e., Fe3+, Si4+ and F–. The calibration curve was constructed from 0.10 mg/L to 3.00 mg/L with the goodness of linearity (R2 = 0.9996). The limits of detection and quantification (LOD and LOQ) were estimated, i.e., 0.029 mg/L and 0.087 mg/L, respectively. The 8-hydroxyquinoline was applied to real rock samples, demonstrating favorable precision (RSD = 0.34 %-1.8 %) and no remarkable differences were found compared to the inductively coupled plasma-mass spectrometry (ICP-MS) as a reference measurement approach.

Synthesis of Green Chitosan - Silver Nanoparticle Composite Material: Parameter Optimization and Physicochemical Characterization

Tran Thi Y Nhi,Do Truong Thien,Trinh Duc Cong,Lai Thi Thuy,Le Thi Thanh Ha,Nguyen Thi Thuc,Ngo Trinh Tung 한국고분자학회 2022 한국고분자학회 학술대회 연구논문 초록집 Vol.47 No.1