Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells

Wang, Xu De,Su, Guang Yue,Zhao, Chen,Qu, Fan Zhi,Wang, Peng,Zhao, Yu Qing The Korean Society of Ginseng 2018 Journal of Ginseng Research Vol.42 No.2

Background: AD-2 (20(R)-dammarane-3b, 12b, 20, 25-tetrol; 25-OH-PPD) is a ginsenoside and isolated from Panax ginseng, showing anticancer activity against extensive human cancer cell lines. In this study, effects and mechanisms of 1C ((20R)-3b-O-(L-alanyl)-dammarane-12b, 20, 25-triol), a modified version of AD-2, were evaluated for its development as a novel anticancer drug. Methods: MTT assay was performed to evaluate cell cytotoxic activity. Cell cycle and levels of reactive oxygen species (ROS) were determined using flow cytometry analysis. Western blotting was employed to analyze signaling pathways. Results: 1C concentration-dependently reduces prostate cancer cell viability without affecting normal human gastric epithelial cell line-1 viability. In LNCaP prostate cancer cells, 1C triggered apoptosis via Bcl-2 family-mediated mitochondria pathway, downregulated expression of mouse double minute 2, upregulated expression of p53 and stimulated ROS production. ROS scavenger, N-acetylcysteine, can attenuate 1C-induced apoptosis. 1C also inhibited the proliferation of LNCaP cells through inhibition on $Wnt/{\beta}-catenin$ signaling pathway. Conclusion: 1C shows obvious anticancer activity based on inducing cell apoptosis by Bcl-2 family-mediated mitochondria pathway and ROS production, inhibiting $Wnt/{\beta}-catenin$ signaling pathway. These findings demonstrate that 1C may provide leads as a potential agent for cancer therapy.

Bone Marrow Adiposity, Bone Mineral Density and Wnt/β-catenin Pathway Inhibitors Levels in Hemodialysis Patients

Yue-Pei Wang,Nada Khelifi,Cyrille de Halleux,Roth-Visal Ung,France Samson,Claudia Gagnon,Fabrice Mac-Way 대한골대사학회 2022 대한골대사학회지 Vol.29 No.2

Background: Marrow adipose tissue (MAT) is known to accumulate in patients with chronic kidney disease. This pilot study aimed to evaluate bone mineral density (BMD), MAT, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) using computed tomography (CT) scans and to explore correlations between bone parameters, circulating Wnt/β-catenin pathway inhibitor levels, and adipose tissue parameters. Methods: Single-center cross-sectional pilot study conducted in hemodialysis patients at the Centre Universitaire de Québec, Hôtel-Dieu de Québec hospital, Canada. CT-scan slices were acquired at the levels of the hip, L3 vertebra, and tibia. Volumetric and areal BMD, tibia cortical thickness, VAT and SAT area, and fat marrow index (FMI) were analyzed using the Mindways QCT Pro software. Blood levels of sclerostin, dickkopf-related protein 1 (DKK1), fibroblast growth factor 23, and α-Klotho were assessed. Spearman’s rho test was used to evaluate correlations. Results: Fifteen hemodialysis patients (median age, 75 [66–82] years; 80% male; dialysis vintage, 39.3 [27.4–71.0] months) were included. While inverse correlations were obtained between L3 FMI and BMD, positive correlations were found between proximal tibial FMI and vertebral and tibial BMD, as well as with tibial (proximal and distal) cortical thickness. VAT had a positive correlation with α-Klotho levels, whereas L3 FMI had a negative correlation with DKK1 levels. Conclusions: CT-scan allows simultaneous evaluation of bone and marrow adiposity in dialysis patients. Correlations between MAT and BMD vary depending on the bone site evaluated. DKK1 and α-Klotho levels correlate with adipose tissue accumulation in dialysis patients.

Protective association of Klotho rs495392 gene polymorphism against hepatic steatosis in non-alcoholic fatty liver disease patients

Wen-Yue Liu,Xiaofang Zhang,Gang Li,Liang-Jie Tang,Pei-Wu Zhu,Rafael S. Rios,Kenneth I. Zheng,Hong-Lei Ma,Xiao-Dong Wang,Qiuwei Pan,Robert J. de Knegt,Luca Valenti,Mohsen Ghanbari,Ming-Hua Zheng 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.2

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD. Methods: We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392, vitamin D, and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed. Results: Carriage of the rs495392 A allele had a protective effect on steatosis severity (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42–0.89; P=0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR, 0.66; 95% CI, 0.45–0.98; P=0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis. Conclusions: The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.

Study on molten salt oxidation process of simulated Co doped cation exchange resins

Yun Xue,Yue-Lin Wang,Yu Li,Wen-Da Xu,Fu-Qiu Ma,Yang-Hai Zheng,Qing-Guo Zhang,Zhi Zhang,Mi-lin Zhang,Yong-De Yan 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.126 No.-

Cation exchange resins (CERs) are widely applied to purify waste liquids generated during the operationof nuclear reactors. The radioactive nuclides 60Co and 58Co are important corrosion activation products inreactor cooling water. In this study, the simulated Co doped CERs were oxidized with ternary carbonate. According to the thermogravimetric analysis (TG), the decomposition of Co doped CERs includes threeprocesses: 1. Elimination of the osmotic water; 2. Pyrolysis of sulfonic acid group; 3. Destruction of styrene–divinylbenzene copolymer. The X-Ray Diffraction (XRD) patterns indicate that sulfur mainly exists inthe form of sulfate in waste salt. The Co2+ undergoes the path of CoS2 ? Co3O4 with the increase of temperatureand the transition point is 650 C. Combined with Fourier Transform Infrared Spectrometer (FTIR)spectra and X-ray Photoelectron Spectroscopy (XPS) analysis, sulfonic acid groups begin to decomposeat 350 C. During the molten salt oxidation process, most of the sulfur in sulfonic acid groups is entrappedby carbonate as the form of sulfate, and a little of which remains as sulfone group, sulfoxide group andsulfur bridge in residue. When the resins are oxidized at 800 C, the retention rate of Co2+ is 97.3%, indicatingthat the molten salt oxidation can effectively remain Co2+ and convert it into a more stablesubstance.

아드만탄 기반의 새로운 설포네이트 폴리카보네이트 난연제 성능 연구

Jian Wei Guo,Yue Qin Wang,Li Juan Feng,Xing Zhong,Chu Fen Yang,Sa Liu,Ying De Cui 한국고분자학회 2013 폴리머 Vol.37 No.4

A novel sulfonate flame retardant, 1,3,5,7-tetrakis(phenyl-4-sodium sulfonate)adamantane (FR-A), was suc-cessfully synthesized from l-bromoadamantane in sequential four-step reactions involving Fiedel-Crafts phenylation, sul-phonation, hydrolysis, and neutralization. The success of synthesis was confirmed by FTIR spectra, ‘H NMR spectra, elemental analyses and mass spectra. The effect of FR-A on the flame retardacy of polycarbonate (PC) has been studied. Limiting oxygen index (LOI) and thermogravimetric analysis (TGA) showed that this novel sulfonate flame retardant had effective flame retardancy on polycarbonate (PC). With a small amount (0.08 Wt%) of FR-A. the flame retardancy of PC was improved obviously, which got to UL 94 V-0 rating. TGA and DTA curves demonstrated that the additive raised the degradation rate of PC by promoting the quick formation of an insulating carbon layer on the surface, and confirmed that the flame retardant mechanism of PC/FR-A system was similar to potassium diphenylsulfone sulfonate (KSS).

Strain energy-based fatigue life prediction under variable amplitude loadings

Shun-Peng Zhu,Peng Yue,José Correia,Sergio Blasón,Abílio De Jesus,Qingyuan Wang 국제구조공학회 2018 Structural Engineering and Mechanics, An Int'l Jou Vol.66 No.2

With the aim to evaluate the fatigue damage accumulation and predict the residual life of engineering components under variable amplitude loadings, this paper proposed a new strain energy-based damage accumulation model by considering both effects of mean stress and load interaction on fatigue life in a low cycle fatigue (LCF) regime. Moreover, an integrated procedure is elaborated for facilitating its application based on S-N curve and loading conditions. Eight experimental datasets of aluminum alloys and steels are utilized for model validation and comparison. Through comparing experimental results with model predictions by the proposed, Miner’s rule, damaged stress model (DSM) and damaged energy model (DEM), results show that the proposed one provides more accurate predictions than others, which can be extended for further application under multi-level stress loadings.

Strain energy-based fatigue life prediction under variable amplitude loadings

Zhu, Shun-Peng,Yue, Peng,Correia, Jose,Blason, Sergio,De Jesus, Abilio,Wang, Qingyuan Techno-Press 2018 Structural Engineering and Mechanics, An Int'l Jou Vol.66 No.2

With the aim to evaluate the fatigue damage accumulation and predict the residual life of engineering components under variable amplitude loadings, this paper proposed a new strain energy-based damage accumulation model by considering both effects of mean stress and load interaction on fatigue life in a low cycle fatigue (LCF) regime. Moreover, an integrated procedure is elaborated for facilitating its application based on S-N curve and loading conditions. Eight experimental datasets of aluminum alloys and steels are utilized for model validation and comparison. Through comparing experimental results with model predictions by the proposed, Miner's rule, damaged stress model (DSM) and damaged energy model (DEM), results show that the proposed one provides more accurate predictions than others, which can be extended for further application under multi-level stress loadings.

IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1−/−Mice Mediated by miR-33

Chen-Yi Tang,Xiao-Fei Man,Yue Guo,Hao-Neng Tang,Jun Tang,Ci-La Zhou,Shu-Wen Tan,Min Wang,Hou-De Zhou 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.2

Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse (Irs-1−/−) with growth retardation and subcutaneous adipocyte atrophy. Irs-1−/− mice exhibited mild insulin resistance, as demonstrat-ed by the insulin tolerance test. Phosphatidylino-sitol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcu-taneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of Irs-1−/− mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What’s more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of Irs-1−/− mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1^-/- Mice Mediated by miR-33

Tang, Chen-Yi,Man, Xiao-Fei,Guo, Yue,Tang, Hao-Neng,Tang, Jun,Zhou, Ci-La,Tan, Shu-Wen,Wang, Min,Zhou, Hou-De Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.2

Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse ($Irs-1^{-/-}$) with growth retardation and subcutaneous adipocyte atrophy. $Irs-1^{-/-}$ mice exhibited mild insulin resistance, as demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of $Irs-1^{-/-}$ mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What's more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of $Irs-1^{-/-}$ mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

Versicolols A and B, two new prenylated isocoumarins from endophytic fungus Aspergillus versicolor and their cytotoxic activity

Min Zhou,Jie Lou,Yin-Ke Li,Yue-De Wang,Kun Zhou,Bing-Kun Ji,Wei Dong,Xue-Mei Gao,Gang Du,Qiu-Fen Hu 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.1

Versicolols A and B (1 and 2), two rareprenylated isocoumarin derivatives, along with five knownisocoumarins (3–7) were isolated from the fermentationproducts of an endophytic fungus Aspergillus versicolor. Their structures were elucidated on the basis of extensivespectroscopic analysis, including 1D- and 2D-NMR techniques. Compounds 1 and 2 were evaluated for their cytotoxicityagainst five human tumor cell lines. The resultsshowed that compounds 1 exhibited weak cytotoxicityagainst A549 and MCF7 cells with IC50 values of 9.4 and8.8 lm, and compound 2 exhibited weak cytotoxicityagainst SHSY5Y and MCF7 cells with IC50 values of 8.2and 6.8 lm, respectively.