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      • SCIESCOPUSKCI등재

        Dimethyl Cardamonin Exhibits Anti-inflammatory Effects via Interfering with the PI3K-PDK1-PKCα Signaling Pathway

        Yu, Wan-Guo,He, Hao,Yao, Jing-Yun,Zhu, Yi-Xiang,Lu, Yan-Hua The Korean Society of Applied Pharmacology 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.6

        Consumption of herbal tea [flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae)] is associated with health beneficial effects against multiple diseases including diabetes, asthma, and inflammatory bowel disease. Emerging evidences have reported that High mobility group box 1 (HMGB1) is considered as a key "late" proinflammatory factor by its unique secretion pattern in aforementioned diseases. Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone, DMC) is a major ingredient of C. operculatus flower buds. In this study, the anti-inflammatory effects of DMC and its underlying molecular mechanisms were investigated on lipopolysaccharide (LPS)-induced macrophages. DMC notably suppressed the mRNA expressions of TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and HMGB1, and also markedly decreased their productions in a time- and dose-dependent manner. Intriguingly, DMC could notably reduce LPS-stimulated HMGB1 secretion and its nucleo-cytoplasmic translocation. Furthermore, DMC dose-dependently inhibited the activation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), and protein kinase C alpha (PKC${\alpha}$). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKC${\alpha}$ signaling pathway.

      • Impact of Hepatoprotective Medications on the Safety and Efficacy of OBV/PTV/r plus DSV ± Ribavirin in HCV GT1b-infected Asian Patients

        ( Wan-long Chuang ),( Yan Luo ),( Jeong Heo ),( Gui-qing Wang ),( Ming-lung Yu ),( Yoon Jun Kim ),( Qing Xie ),( Cheng-yuan Peng ),( Mingxiang Zhang ),( Yan Huang ),( Wenjing Lu ),( Linda M. Fredrick 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

        Aims: Hepatoprotective medications (HPMs) are commonly used in patients with chronic liver disease, especially across Asia. The phase 3 ONYX-I and ONYX-II studies evaluated the safety and efficacy of the 3-DAA regimen of ombitasvir and paritaprevir/ritonavir (OBV/PTV/r) plus dasabuvir (DSV) ± ribavirin (RBV) in an exclusively HCV GT1b-infected Asian population. This post-hoc analysis evaluated the impact of HPM use in patients treated with OBV/PTV/r + DSV ± RBV in these studies. Methods: ONYX-I and ONYX-II enrolled patients in China, South Korea and Taiwan. SVR12, treatment-emergent adverse events (AEs), and alanine transaminase (ALT) normalization, as well as mean changes in ALT over time were assessed in patients using vs not using HPMs. HPM use defined as all medications administered during any treatment period. Results: Overall, 11% (36/325) of non-cirrhotic and 57% (59/104) of cirrhotic patients were receiving HPMs, with ursodeoxycholic acid being the most commonly used in both non-cirrhotic (5.2% [17/325]) and cirrhotic (14.4% [15/104]) patients. SVR12 rates were high (99.7- 100%) in both non-cirrhotic and cirrhotic patients irrespective of HPM use. The regimen was generally well tolerated, with low rates of SAEs and AEs leading to treatment discontinuation (Table). Of patients with ALT above normal at baseline (BL), 100% vs 95% of non-cirrhotic and 98% vs 89% of cirrhotic patients using or not using HPMs, respectively, had normal ALT values at end of treatment (EOT). Mean ALT levels during treatment declined rapidly and similarly with and without HPM use; mean changes from BL to EOT were -38.8 and -37.0 U/L, respectively, in non-cirrhotic and -54.2 and -66.6 U/L, respectively, in cirrhotic patients. Conclusions: OBV/PTV/r + DSV ± RBV achieved high SVR12 and was generally well tolerated regardless of HPM use. HPM use had no impact on the safety profile of OBV/PTV/r + DSV therapy in Asian HCV infected subjects.

      • Slide Session : OS-GAS-04 ; Gastroenterology : Uric Acid Regulates Hepatic Steatosis and Insulin Sig-naling Through the NLRP3 Infl ammasome Dependent Mechanism

        ( Wan Xing Yong ),( Xu Cheng Fu ),( Lu Chao ),( Yu Wei Lai ),( Zhu Hua Tuo ),( Yu Chao Hui ),( Li You Ming ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

        Background: Serum uric acid is strongly associated with nonalcoholic fatty liver disease (NAFLD) and insulin resistance in patients. However, whether this association is causally or coincidentally with NAFLD and insulin resistance remains uncertain, neither the mechanisms behind this association are unclear so far. Methods: We first analyzed the impact of uric acid on development of hepatic steatosis in mice and two cell models (HepG2 and HL7702), and then explored the effect of uric acid on insulin signaling, including phosphorylation of insulin receptor substrate 1 (IRS1) and Akt in HepG2 and HL7702 cells. Further, we studied the role of NLRP3 inflammasome in regulation of hepatic steatosis and insulin signaling. Results: Uric acid directly induced hepatocyte fat accumulation both in vivo and in vitro. Further, uric acid treatment decreased insulin-induced phospho-Akt (ser437) and enhanced the phospho-IRS1(ser307) in HepG2 and HL7702 cells. Then, we found significant increases of NLRP3 inflammasome-related molecules, both mRNA and protein levels, including NLPR3, caspase-1, IL-1ß, and IL-18, in HepG2 and HL7702 cells stimulated with uric acid. We also found that uric acid induced significant elevations of IL-1ß and IL-18 levels in culture supernatants of HepG2 and HL7702 cells. Consistent with in vitro results, mice fed 8 weeks of hyperuricemia-inducing diet resulted in significant up-regulation of hepatic mRNA and protein expressions of NLPR3, caspase-1, IL-1ß and IL-18, and elevation of serum IL-1ß and IL-18 levels. Further experiments indicated that silencing NLRP3 expression significantly alleviated uric acid-induced fat accumulation in vitro. Moreover, inhibition of NLRP3 expression ameliorated uric acid induced insulin signaling impairing, confirmed by increased insulin- induced phospho-Akt (ser437) and reduced the phospho-IRS1(ser307) in vitro. Conclusions: Our results suggest that uric acid contributes to hepatic steatosis and impairs insulin signaling through the NLRP3 inflammasome dependent mechanism.

      • SCIESCOPUSKCI등재

        Dimethyl Cardamonin Exhibits Anti-inflammatory Effects via Interfering with the PI3K-PDK1-PKCα Signaling Pathway

        ( Wan-guo Yu ),( Hao He ),( Jing-yun Yao ),( Yi-xiang Zhu ),( Yan-hua Lu ) 한국응용약물학회 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.6

        Consumption of herbal tea [flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae)] is associated with health beneficial effects against multiple diseases including diabetes, asthma, and inflammatory bowel disease. Emerging evidences have reported that High mobility group box 1 (HMGB1) is considered as a key late proinflammatory factor by its unique secretion pattern in aforementioned diseases. Dimethyl cardamonin (2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone, DMC) is a major ingredient of C. operculatus flower buds. In this study, the anti-inflammatory effects of DMC and its underlying molecular mechanisms were investigated on lipopolysaccharide (LPS)-induced macrophages. DMC notably suppressed the mRNA expressions of TNF-α, IL-1β, IL-6, and HMGB1, and also markedly decreased their productions in a time- and dose-dependent manner. Intriguingly, DMC could notably reduce LPS-stimulated HMGB1 secretion and its nucleo-cytoplasmic translocation. Furthermore, DMC dose-dependently inhibited the activation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), and protein kinase C alpha (PKCα). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-α, IL-1β, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKCα signaling pathway.

      • KCI등재

        Panax ginseng and its ginsenosides: potential candidates for the prevention and treatment of chemotherapy-induced side effects

        Yan Wan,Jing Wang,Jin-feng Xu,Fei Tang,Lu Chen,Yu-zhu Tan,Chao-long Rao,Hui Ao,Cheng Peng 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.6

        Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may causenumerous harmful side effects. Therefore, developing new and effective drugs derived from natural nontoxiccompounds for the treatment of chemotherapy-induced side effects is necessary. Experimentsin vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic andeffective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity,cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on antioxidation,anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, suchas nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun Nterminalkinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signalregulatedkinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin(mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase(PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides onchemotherapy-induced side effects has not yet been published, we provide a comprehensive summarizationwith this aim and shed light on the future research of PG.

      • SCIESCOPUSKCI등재

        Profiles of Bacillus spp. Isolated from the Rhizosphere of Suaeda glauca and Their Potential to Promote Plant Growth and Suppress Fungal Phytopathogens

        ( Ping Lu ),( Ke Jiang ),( Ya-qiao Hao ),( Wan-ying Chu ),( Yu-dong Xu ),( Jia-yao Yang ),( Jia-le Chen ),( Guo-hong Zeng ),( Zhou-hang Gu ),( Hong-xin Zhao ) 한국미생물 · 생명공학회 2021 Journal of microbiology and biotechnology Vol.31 No.9

        Members of the genus Bacillus are known to play an important role in promoting plant growth and protecting plants against phytopathogenic microorganisms. In this study, 21 isolates of Bacillus spp. were obtained from the root micro-ecosystem of Suaeda glauca. Analysis of the 16S rRNA genes indicated that the isolates belong to the species Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus subtilis, Bacillus pumilus, Bacillus aryabhattai and Brevibacterium frigoritolerans. One of the interesting findings of this study is that the four strains B1, B5, B16 and B21 are dominant in rhizosphere soil. Based on gyrA, gyrB, and rpoB gene analyses, B1, B5, and B21 were identified as B. amyloliquefaciens and B16 was identified as B. velezensis. Estimation of antifungal activity showed that the isolate B1 had a significant inhibitory effect on Fusarium verticillioides, B5 and B16 on Colletotrichum capsici (syd.) Butl, and B21 on Rhizoctonia cerealis van der Hoeven. The four strains grew well in medium with 1-10% NaCl, a pH value of 5-8, and promoted the growth of Arabidopsis thaliana. Our results indicate that these strains may be promising agents for the biocontrol and promotion of plant growth and further study of the relevant bacteria will provide a useful reference for the development of microbial resources.

      • KCI등재

        Opportunities for 2-[18F] Fluoro-2-Deoxy-D-Glucose PET/CT in Cervical-Vaginal Neuroendocrine Carcinoma: Case Series and Literature Review

        Yin Lin,Wan Y. Lin,Ji A. Liang,Yu Y. Lu,Hsin Y. Wang,Shih C. Tsai,Chia H. Kao 대한영상의학회 2012 Korean Journal of Radiology Vol.13 No.6

        Objective: Neuroendocrine cervical carcinoma is a rare subtype of cervical cancer. These tumors exhibit an aggressive behavior with early regional lymph node and distant metastases. The purpose of our study was to describe five cases of neuroendocrine cervical-vaginal carcinoma and to discuss the potential of the 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan for the detection of this rare malignancy. Materials and Methods: Five cases of cervical-vaginal neuroendocrine tumor were retrospectively collected, during a two year (from September 2009 to August 2011) period in our hospital. The clinical staging distributions were International Federation of Gynecology and Obstetrics (FIGO) stage IB2 (1 of 5), stage IIA (3 of 5) and stage IVA (1 of 5). Results: Two cases (cases 1 and 4) were restaged after 18F-FDG PET/CT scan in the initial staging process. Post-treatment 18F-FDG PET/CT scans, in three patients, revealed positive findings for tumor recurrence or lymph node metastases. Two patients (cases 2 and 3) died of tumor within two years. Conclusion: 18F-FDG PET/CT scan is a useful tool in cervical-vaginal neuroendocrine tumor. In its initial staging, the 18F-FDG PET/CT scan may help assess the possible nodal involvement or early hematogeneous spreading. We can also use the 18F-FDG PET/CT to detect local recurrence and to evaluate the treatment response after clinical manipulation. Objective: Neuroendocrine cervical carcinoma is a rare subtype of cervical cancer. These tumors exhibit an aggressive behavior with early regional lymph node and distant metastases. The purpose of our study was to describe five cases of neuroendocrine cervical-vaginal carcinoma and to discuss the potential of the 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan for the detection of this rare malignancy. Materials and Methods: Five cases of cervical-vaginal neuroendocrine tumor were retrospectively collected, during a two year (from September 2009 to August 2011) period in our hospital. The clinical staging distributions were International Federation of Gynecology and Obstetrics (FIGO) stage IB2 (1 of 5), stage IIA (3 of 5) and stage IVA (1 of 5). Results: Two cases (cases 1 and 4) were restaged after 18F-FDG PET/CT scan in the initial staging process. Post-treatment 18F-FDG PET/CT scans, in three patients, revealed positive findings for tumor recurrence or lymph node metastases. Two patients (cases 2 and 3) died of tumor within two years. Conclusion: 18F-FDG PET/CT scan is a useful tool in cervical-vaginal neuroendocrine tumor. In its initial staging, the 18F-FDG PET/CT scan may help assess the possible nodal involvement or early hematogeneous spreading. We can also use the 18F-FDG PET/CT to detect local recurrence and to evaluate the treatment response after clinical manipulation.

      • SCIESCOPUSKCI등재

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