Fumigaclavine C attenuates adipogenesis in 3T3-L1 adipocytes and ameliorates lipid accumulation in high-fat diet-induced obese mice

Yu, Wan-Guo,He, Yun,Chen, Yun-Fang,Gao, Xiao-Yao,Ning, Wan-E,Liu, Chun-You,Tang, Ting-Fan,Liu, Quan,Huang, Xiao-Cheng The Korean Society of Pharmacology 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.3

Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.

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.

Associations Between TLR9 Polymorphisms and Cancer Risk: Evidence from an Updated Meta-analysis of 25,685 Subjects

Wan, Guo-Xing,Cao, Yu-Wen,Li, Wen-Qin,Li, Yu-Cong,Zhang, Wen-Jie,Li, Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

A meta-analysis incorporating 34 case-control studies from 19 articles involving 12,197 cases and 13,488 controls was conducted to assess the effects of three genetic variants of Toll-like receptor 9 (TLR9): rs187084, rs352140, and rs5743836. Studies on associations between TLR9 polymorphisms and cancer risk were systematically searched in electronic databases. The reported odds ratios (OR) and 95% confidence intervals (CI) were pooled to assess the strength of any associations. The results showed that the rs187084 polymorphism was significantly associated with an increased risk of cancer (CC vs TC+TT: OR=1.14, 95% CI=1.02-1.28), specifically cervical cancer (C vs T: OR=1.19, 95% CI=1.05-1.34; TC vs TT: OR=1.32, 95% CI=1.10-1.58; CC vs TT: OR=1.31, 95% CI=1.03-1.68; CC+TC vs TT: OR=1.32, 95% CI=1.11-1.56), and that this association was significantly positive in Caucasians (CC vs. TC+TT: OR=1.18, 95% CI=1.01-1.38). The rs352140 polymorphism had a protective effect on breast cancer (GA vs GG: OR=0.77, 95% CI=0.66-0.89), whereas the rs5743836 polymorphism was likely protective for digestive system cancers (CC+TC vs TT: OR=0.81, 95% CI=0.66-0.98). In conclusion, our results suggest that the rs187084 polymorphism may be associated with an elevated cancer risk, whereas polymorphisms of rs352140 and rs5743836 may play protective roles in the development of breast and digestive system cancers, respectively. From the results of this meta-analysis further large-scale case-control studies are warranted to verify associations between TLR9 polymorphisms and cancer.

The Catechol-O-Methyltransferase Val158Met Polymorphism Contributes to the Risk of Breast Cancer in the Chinese Population: An Updated Meta- Analysis

Guo-Xing Wan,Yu-Wen Cao,Wen-Qin Li,Yu-Cong Li,Feng Li 한국유방암학회 2014 Journal of breast cancer Vol.17 No.2

Purpose: Catechol-O-methyltransferase (COMT) enzyme plays acentral role in estrogen-induced carcinogenesis. Emerging evidencefrom association studies has revealed that the functionalVal158Met polymorphism (rs4680 G>A) of the Catechol-Omethyltransferasegene (COMT) has been implicated in susceptibilityto breast cancer in the Chinese population, while resultsof individual published studies remain inconclusive and inconsistent. To assess this association in the Chinese population, a meta-analysis was performed. Methods: Eligible studies weresearched on MEDLINE, Embase, Cochrane Library, China NationalKnowledge Infrastructure, and the Chinese BiomedicineDatabase. Odds ratios (ORs) with their corresponding 95% confidenceintervals (CIs) were pooled to assess the association betweenCOMT polymorphisms and the risk of breast cancer usingRevMan 5.2 and Stata 12.0 software. Results: The meta-analysisincluded 14 eligible studies, with a total of 4,626 breast cancercases and 5,637 controls. Overall, the COMT Val158Met polymorphism(rs4680 G>A) was significantly associated with an increasedrisk of breast cancer in several genetic models (A/A vs. G/G: OR, 1.59, 95% CI, 1.12–2.27; A/A vs. G/A+G/G: OR, 1.62,95% CI, 1.14–2.29; A vs. G: OR, 1.15, 95% CI, 1.00–1.32), and asubgroup analysis according to menopausal status showed thatthis association was especially evident among premenopausalChinese women (A/A vs. G/G: OR, 1.87, 95% CI, 0.99–3.54; A/Avs. G/A+G/G: OR, 1.94, 95% CI, 1.03–3.63). Conclusion: The resultsof this meta-analysis indicated that COMT Val158Met variantscontribute to breast cancer susceptibility in the Chinesepopulation, particularly among premenopausal women.

Fumigaclavine C attenuates adipogenesis in 3T3-L1 adipocytes and ameliorates lipid accumulation in high-fat diet-induced obese mice

Wan-Guo Yu,Yun He,Yun-Fang Chen,Xiao-Yao Gao,Wan-E Ning,Chun-You Liu,Ting-Fan Tang,Quan Liu,Xiao-Cheng Huang 대한약리학회 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.3

Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in highfat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin- 7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dosedependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.

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.

BRCA1 Gene Exon 11 Mutations in Uighur and Han Women with Early-onset Sporadic Breast Cancer in the Northwest Region of China

Cao, Yu-Wen,Fu, Xin-Ge,Wan, Guo-Xing,Yu, Shi-Ying,Cui, Xiao-Bin,Li, Li,Jiang, Jin-Fang,Zheng, Yu-Qin,Zhang, Wen-Jie,Li, Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

The prevalence of BRCA1 gene mutations in breast cancer differs between diverse ethnic groups. Relatively little information is known about patterns of BRCA1 mutations in early-onset breast cancer in women of Uighur or Han descent, the major ethnic populations of the Xinjiang region in China. The aim of this study was to identify BRCA1 mutations in Uighur and Han patients with early-onset (age <35 years), and sporadic breast cancer for genetic predisposition to breast cancer. For detection of BRCA1 mutations, we used a polymerase chain reaction single-stranded conformation polymorphism approach, followed by direct DNA sequencing in 22 Uighur and 13 Han women with early-onset sporadic breast cancer, and 32 women with benign breast diseases. The prevalence of BRCA1 mutations in this population was 22.9% (8/35) among early-onset sporadic breast cancer cases. Of these, 31.8% (7/22) of Uighur patients and 7.69% (1/13) of Han patients were found to have BRCA1 mutations. In 7 Uighur patients with BRCA1 mutations, there were 11 unique sequence alterations in the BRCA1 gene, including 4 clearly disease-associated mutations on exon 11 and 3 variants of uncertain clinical significance on exon 11, meanwhile 4 neutral variants on intron 20 or 2. None of the 11 BRCA1 mutations identified have been previously reported in the Breast Cancer Information Core database. These findings reflect the prevalence of BRCA1 mutations in Uighur women with early-onset and sporadic breast cancer, which will allow for provision of appropriate genetic counseling and treatment for Uighur patients in the Xinjiang region.

Fix-frequency robust power model predictive control method for three-phase PWM rectifiers under unbalanced grid conditions

Guo, Xin,Xiao, Min,Gao, Yu-er,Wang, Qingyu,Wan, Yihao The Korean Institute of Power Electronics 2020 JOURNAL OF POWER ELECTRONICS Vol.20 No.5

Under unbalanced grid conditions, the controller design of a three-phase pulse width modulation (PWM) rectifier is based on an instantaneous power model. By calculating the current references of the converter according to the instantaneous power model, traditional voltage-oriented control (VOC) methods realize the positive-sequence and negative-sequence active and reactive current control of the converter separately using the proportional-integral (PI) controller. However, due to the inner current loop control structure of the traditional VOC method, it is impossible to realize the regulation of all six power components in a common instantaneous power model under an unbalanced grid. Meanwhile, the control performance of the traditional VOC method with a PI controller is degraded under the circuit parameters uncertainty condition. In this paper, a fixed switching frequency robust power model predictive control method (FRP-MPC) is proposed for three-phase PWM rectifiers under the unbalanced grid condition. The proposed control strategy has a number of advantages. An improved instantaneous power model is used for the fixed switching frequency model predictive controller design under the unbalanced grid condition, which has less power variables than the common instantaneous power model. The robustness of the MPC controller is improved by adding a robust item into the predictive model under circuit parameters uncertainty. Simulation and experiment results verify the effectiveness of the proposed control method.

Research on total resistance of ice-going ship for different floe ice distributions based on virtual mass method

Guo, Wei,Zhao, Qiao-sheng,Tian, Yu-kui,Zhang, Wan-chao The Society of Naval Architects of Korea 2020 International Journal of Naval Architecture and Oc Vol.12 No.-

This paper presents the virtual mass method to implement the prediction of total resistance for ice-going ship in floe ice region based on the combined method of CFD and DEM. Two ways of floe ice distribution are adopted for the analysis and comparison. The synthetic ice model test has been conducted to determine the optimal virtual mass coefficients for the two different floe ice distributions. Moreover, the further verification and prediction are developed in different ice conditions. The results show that, the fixed and random distributions in numerical method can simulate the interaction of ship and ice vividly, the trend of total resistance varying with the speed and ice concentration obtained by the numerical simulation is consistent with the model test. The random distribution of floe ice has higher similarity and better accuracy than fixed distribution.

Prognostic Value of Serum Epstein–Barr Virus Antibodies and Their Correlation with TNM Classification in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma

Wan-Ru Zhang,Yu-Yun Du,Chun-Yan Guo,Han-Xing Zhou,Jie-Yi Lin,Xiao-Han Meng,Hao-Yuan Mo,Dong-Hua Luo 대한암학회 2021 Cancer Research and Treatment Vol.53 No.4

Purpose This study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients. Materials and Methods Serum EBV antibody levels were measured by enzyme-linked immunosorbent assay in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS). Results Rta-IgG and Zta-IgA levels were positively correlated with the N category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by PFS (77% vs. 89.8%, p=0.004), distant metastasis–free survival (DMFS) (88.3% vs. 95.8%, p=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤ 1,500 copies/mL), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p < 0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T category (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS, and LRFS (both p < 0.05). Conclusion Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T category or low EBV DNA level.