Macrophages Promote Coal Tar Pitch Extract-induced Tumorigenesis of BEAS-2B Cells and Tumor Metastasis in Nude Mice Mediated by AP-1

Zhang, Peng,Jin, Yue-Fei,Zhang, Qiao,Wu, Yi-Ming,Wu, Wei-Dong,Yao, Wu,Wu, Yong-Jun,Li, Zhi-Tao,Zhao, Yong,Liu, Yu,Feng, Fei-Fei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Background: We sought to evaluate the role of tumor associated macrophages (TAMs) on the promotion of coal tar pitch extract (CTPE)-induced tumorigenesis of human bronchial epithelial cells (BEAS-2B) and tumor metastasis in nude mice, and related mechanisms. Materials and Methods: BEAS-2B cells were first treated with 2.4 mg/mL CTPE for 72 hours. After removal of CTPE, the cells were continuously cultured and passaged using trypsin-EDTA. THP-1 cells were used as macrophage-like cells. BEAS-2B cells under different conditions (n=6/group) were injected into the back necks of nude mice, and alterations of tumor xenograft growth, indicative of tumorigenicity, and tumor metastasis were determined. Pathological changes (tumor nests and microvascular lesions) of HE-stained tumor tissues were also evaluated. The expression of AP-1(c-Jun) in xenografts and metastatic tumors was determined using immunohistochemistry. Results: Tumor size and weight in nude mice transplanted with the mixture of CTPE-induced passage 30 BEAS-2B and THP-1 cells (2:1) were increased compared to those from the CTPE-treated BEAS-2B cells at passage 30 alone at different observation time points. Tumor metastasis to lymph nodes and liver was only detected after transplantation of a mixture the two kinds of cells. The numbers of tumor nests and microvascular lesions, and the expression levels of AP-1 (c-Jun) in tumors from the mixture of two kinds of cells were increased apparently in contrast to those in tumor from the CTPE-treated BEAS-2B cells of passage 30 alone. In addition, there was positive correlation between AP-1 (c-Jun) expression level and the number of microvascular lesions, or between AP-1 (c-Jun) expression level and tumor metastasis in these two groups. Conclusions: TAMs not only facilitate tumorigenesis transformation of CTPE-induced BEAS-2B cells, but also promote tumor growth, angiogenesis and metastasis in nude mice in vivo, which may be mediated by AP-1.

Elevated FBXL6 expression in hepatocytes activates VRK2-transketolase-ROS-mTOR-mediated immune evasion and liver cancer metastasis in mice

Zhang Jie,Lin Xiao-Tong,Yu Hong-Qiang,Fang Lei,Wu Di,Luo Yuan-Deng,Zhang Yu-Jun,Xie Chuan-Ming 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Metastatic hepatocellular carcinoma (HCC) is the most lethal malignancy and lacks effective treatment. FBXL6 is overexpressed in human hepatocellular carcinoma (HCC), but whether this change drives liver tumorigenesis and lung metastasis in vivo remains unknown. In this study, we aimed to identify FBXL6 (F-Box and Leucine Rich Repeat Protein 6) as a key driver of HCC metastasis and to provide a new paradigm for HCC therapy. We found that elevated FBXL6 expression in hepatocytes drove HCC lung metastasis and was a much stronger driver than Kras mutation (KrasG12D/+;Alb-Cre), p53 haploinsufficiency (p53+/-) or Tsc1 loss (Tsc1fl/fl;Alb-Cre). Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation. Activated TKT further increased PD-L1 and VRK2 expression via the ROS-mTOR axis, leading to immune evasion and HCC metastasis. Targeting or knockdown of TKT significantly blocked FBXL6-driven immune evasion and HCC metastasis in vitro and in vivo. Notably, the level of active TKT (p-Thr287 TKT) was increased and was positively correlated with the FBXL6 and VRK2 expression levels in HCC patients. Our work provides novel mechanistic insights into FBXL6-driven HCC metastasis and suggests that targeting the TKT-ROS-mTOR-PD-L1/VRK2 axis is a new paradigm for treating patients with metastatic HCC with high FBXL6 expression.

Protective Effect of Sodium Ferulate on Acetaldehyde-Treated Precision-Cut Rat Liver Slices

Yu Guo,Xiao-Qian Wu,Chun Zhang,Zhang-Xiu Liao,Yong Wu,Hui Wang 한국식품영양과학회 2012 Journal of medicinal food Vol.15 No.6

Activated hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis, and inhibition of HSC activation may prevent liver fibrosis. Acetaldehyde, the most deleterious metabolite of alcohol, triggers HSC activation in alcoholic liver injury. In the present study, we investigated the protective effect of sodium ferulate (SF), a sodium salt of ferulic acid that is rich in fruits and vegetables, on acetaldehyde-stimulated HSC activation using precision-cut liver slices (PCLSs). Rat PCLSs were co-incubated with 700 lM acetaldehyde and different concentrations of SF. Hepatotoxicity was assessed by measuring enzyme leakage and malondialdehyde content in tissue. a-Smooth muscle actin, transforming growth factor-b1, and hydroxyproline were determined to assess the activation of HSCs. In addition, matrix metalloproteinase (MMP)-1 and the tissue inhibitor of metalloproteinase (TIMP-1) were determined to evaluate collagen degradation. SF prominently prevented the enzyme leakage in acetaldehyde-treated slices and also inhibited HSC activation and collagen production stimulated by acetaldehyde. In addition, SF increased MMP-1 expression and decreased TIMP-1 expression. These results showed that SF protected PCLSs from acetaldehyde-stimulated HSC activation and liver injury, which may be associated with the attenuation of oxidative injury and acceleration of collagen degradation

Identification of S-Genotypes in Chinese Pear Cultivars and Analysis of Nucleotide Sequences of New S-Alleles

Yu Yan Zhang,Shao Ling Zhang,Jun Wu 한국원예학회 2006 한국원예학회 기타간행물 Vol.- No.-

Long Noncoding RNA Cytoskeleton Regulator RNA Suppresses Apoptosis in Hepatoma Cells by Modulating the miR-125a-5p/HS1-Associated Protein X-1 Axis to Induce Caspase-9 Inactivation

Wu Zhen-Yu,Wang Yumin,Hu Hao,Ai Xiang-Nan,Zhang Qiang,Qin Yu-Gang 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.6

Background/Aims: The involvement of long noncoding RNAs in the carcinogenesis of hepatocellular carcinoma (HCC) has been well documented by substantial evidence. However, whether cytoskeleton regulator RNA (CYTOR) could affect the progression of HCC remains unclear. Methods: The relative expression of CYTOR, miR-125a-5p and HS1-associated protein X-1 (HAX-1) mRNA in HCC cells were determined via quantitative real-time polymerase chain reaction. The viability of treated HCC cells was measured by Cell Counting Kit-8 assay. Cell apoptosis was estimated by flow cytometry analysis, assessment of caspase-9 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and Western blot of apoptosis-related proteins. The interplay between CYTOR or HAX-1 and miR-125a-5p was validated by dual-luciferase reporter assay. Results: CYTOR was upregulated and miR-125a-5p was downregulated in HCC cells. CYTOR silencing inhibited cell proliferation and promoted cell apoptosis in HepG2 and SMMC-7721 cells. miR-125a-5p was sponged and negatively regulated by CYTOR, and HAX-1 was directly targeted and negatively modulated by miR-125a-5p. Overexpression of miR-125a-5p enhanced the repressive effects of CYTOR knockdown on HCC cells, and knockdown of HAX-1 enhanced the inhibitory effects of miR-125a-5p mimics on HCC cells. Conclusions: CYTOR silencing facilitates HCC cell apoptosis in vitro via the miR-125a-5p/HAX-1 axis.

Preparation of nano-sized Mg-doped copper silicate materials using coal gangue as the raw material and its characterization for CO2 adsorption

Yu Wu,Zhaojun Wu,Kai Liu,Fu Li,Yujie Pang,Jianbin Zhang,Huayan Si 한국화학공학회 2020 Korean Journal of Chemical Engineering Vol.37 No.10

This work presents a simple method for the preparation of the Mg-doped nanocomposite copper silicates (Mgx-Cu1x-SiO3) (x=0.25, 0.5, 0.75 and 0.9) using coal gangue waste as the silicon source for CO2 capture at low temperature. The as-prepared Mgx-Cu1x-SiO3 was systemically characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller surface area analysis (BET). The results suggest that all Mgx-Cu1x-SiO3 possess large surface areas, micropores and mesoporous structures composed of the agglomerates of small nanoparticles. They exhibit high CO2 adsorption capacity at 298.15 K under 1 bar, and that of Mg0.9-Cu0.1-SiO3 was the highest with the value of 16.73 cm3/g. The Freundlich isotherm model fits the CO2 adsorption isotherm well. Thermodynamic analysis indicates that the CO2 adsorption on Mg0.9-Cu0.1-SiO3 is exothermic (Ho<0), chaotic (So<0), and spontaneous (Go<0). This work highlights the low-temperature adsorption behavior of silicate materials on CO2, which can provide some research basis for the utilization of silica in coal gangue.

Fotemustine, Teniposide and Dexamethasone in Treating Patients with CNS Lymphoma

Wu, Jing-Jing,Wang, Xin-Hua,Li, Ling,Li, Xin,Zhang, Lei,Sun, Zhen-Chang,Fu, Xiao-Rui,Ma, Wang,Chang, Yu,Zhang, Xu-Dong,Han, Li-Juan,Zhang, Ming-Zhi Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Purpose: We developed and evaluated a regimen including fotemustine, teniposide and dexamethasone (FTD) for treating patients with central nervous system (CNS) lymphoma based on pharmacokinetic properties of individual agents and in combination. Patients and Methods: In a comparison study, 8 patients with primary CNS lymphoma (PCNSL) and 8 with secondary CNS lymphoma (SCNSL) were treated with FTD (comprising fotemustine 100 mg/m2, 1h infusion, day 1; teniposide 60 mg/m2, >0.5 h infusion, on day 2, 3, 4; dexamethasone 40 mg, 1h infusion, on day 1, 2, 3, 4 and 5; and methotrexate 12 mg, cytosine arabinoside 50 mg plus dexamethasone 5 mg intrathecally, on day 2 and 7). Cycles were repeated every 3 weeks. After response assessment, patients received whole brain radiotherapy. Results: Of the 8 PCNSL patients, 4 (50%) achieved CR and 3 (38%) PR, an overall response rate of 88%. Four patients (50%) were in continuing remission at the end of this study after a median follow-up of 30 months (range 10 to 56 months). Of the 8 SCNSL patients the overall response rate was 63% (CR+PR: 38%+25%). All responses were achievable with predictable toxicity mainly reflecting reversible myelosuppression. Conclusion: This study suggests that FTD could be an effective treatment for CNS lymphoma, and is worthy of further evaluation.

Identification of novel rheumatoid arthritis-associated MiRNA-204-5p from plasma exosomes

Wu Long-Fei,Zhang Qin,Mo Xing-Bo,Lin Jun,Wu Yang-Lin,Lu Xin,He Pei,Wu Jian,Guo Yu-Fan,Wang Ming-Jun,Ren Wen-Yan,Deng Hong-Wen,Lei Shu-Feng,Deng Fei-Yan 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of immune cells in the synovium. However, the crosstalk of immune cells and synovial fibroblasts is still largely unknown. Here, global miRNA screening in plasma exosomes was carried out with a custom microarray (RA patients vs. healthy controls = 9:9). A total of 14 exosomal miRNAs were abnormally expressed in the RA patients. Then, downregulated expression of exosomal miR-204-5p was confirmed in both the replication (RA patients vs. healthy controls = 30:30) and validation groups (RA patients vs. healthy controls = 56:60). Similar to the findings obtained in humans, a decreased abundance of exosomal miR-204-5p was observed in mice with collagen-induced arthritis (CIA). Furthermore, Spearman correlation analysis indicated that plasma exosomal miR-204-5p expression was inversely correlated with disease parameters of RA patients, such as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. In vitro, our data showed that human T lymphocytes released exosomes containing large amounts of miR-204-5p, which can be transferred into synovial fibroblasts, inhibiting cell proliferation. Overexpression of miR-204-5p in synovial fibroblasts suppressed synovial fibroblast activation by targeting genes related to cell proliferation and invasion. In vivo assays found that administration of lentiviruses expressing miR-204-5p markedly alleviated the disease progression of the mice with CIA. Collectively, this study identified a novel RA-associated plasma exosomal miRNA-204-5p that mediates the communication between immune cells and synovial fibroblasts and can be used as a potential biomarker for RA diagnosis and treatment.

Gadolinium- and lead-containing functional terpolymers for low energy X-ray protection

Yu-Juan Zhang,Xin-Tao Guo,Chun-Hong Wang,Xiang An Lu,De-Feng Wu,Ming Zhang 한국원자력학회 2021 Nuclear Engineering and Technology Vol.53 No.12

By polymerization of gadolinium methacrylate (Gd (MAA)3), lead methacrylate (Pb(MAA)2) and methylmethacrylate (MMA), Gd and Pb were chemically bonded into polymers. The X-ray shielding performance was evaluated by Monte Carlo simulation method, and the results showed that the more metalfunctional organic monomer, the better the shielding performance of terpolymers. When the X-rayenergy is 65 keV, Gd (MAA)3-containing polymers have better shielding performance than Pb(MAA)2-containing polymers. Gd could compensate for the weak absorption region of Pb. Therefore, polymerscontaining both Gd and Pb enhanced shielding efficiency against X-ray in various low-energy ranges. Forobtaining terpolymers with uniform monomer compositions, the relationship between the monomercomposition of the terpolymers and the conversion level was optimized by calculating the reactivityratios. The value of reactivity ratios of r (Gd (MAA)3/Pb(MAA)2), r (Pb(MAA)2/Gd (MAA)3), r (Gd (MAA)3/MMA), r (MMA/Gd (MAA)3), r (Pb(MAA)2/MMA) and r (MMA/Pb(MAA)2) was 0.483, 0.004, 0.338, 2.508,0.255, 0.029. The terpolymers with uniform monomer composition could be obtained by controlling themonomer compositions or conversion levels. The results can provide new radiation protection materialsand contribute to the improvement in nuclear safety.

Reference gene selection for transcriptional profiling by RT-qPCR in the 28-spotted larger potato ladybird

Zhang Yu-Xing,Tan Qiao,Shen Chen-Hui,Wu Jian-Jian,Wu Yi-Kuan,Li Wen-Ze,Jin Lin,Li Guo-Qing 한국응용곤충학회 2022 Journal of Asia-Pacific Entomology Vol.25 No.2

Henosepilachna vigintioctomaculata is one of the most serious defoliates attacking potatoes. However, studies on functional genes have greatly been limited due to the insufficiency of effective and stable endogenous references to normalize RT-qPCR data. In this report, nine housekeeping genes (RPL4, RPL6, RPL13, RPL32, RPS18, ACT, EF1α, GAPDH and α-TUB) involved in different biological processes were selected. Their expression levels under diverse experimental conditions including developmental stages, tissues, temperatures and host plants were determined using RT-qPCR technology. The tested candidate genes were comprehensively ranked based on five alternative stability analysis methods (Ct value, geNorm, NormFinder, BestKeeper and ReFinder). The results revealed that the optimal internal reference genes varied under different experimental conditions. Any gene pair among the five candidates (RPL4, RPL13, RPL32, RPS18 and EF1α) was a suitable reference gene set under different temperatures and on different host plants. A combination of RPL6 and RPL13 was recommended as the best reference gene set across different developmental stages. A pair of RPS18 and EF1α was ranked as the optimal reference gene combination within different tissues. The most suitable reference genes were RPS18 and RPL13 under four different experimental conditions. Our findings not only establish an accurate and reliable normalization of RT-qPCR data, but also lay a solid foundation for further functional gene researches in H. vigintioctomaculata