p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid

Liu, Jia,Wu, Ning,Ma, Lei-Na,Zhong, Jia-Teng,Liu, Ge,Zheng, Lan-Hong,Lin, Xiu-Kun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Oleanolic acid (OA) is a nutritional component widely distributed in various vegetables. Although it has been well recognized for decades that OA exerts certain anti-tumor activity by inducing mitochondria-dependent apoptosis, it is still unclear that what molecular signaling is responsible for this effect. In this study, we employed cancer cell lines, A549, BXPC-3, PANC-1 and U2OS to elucidate the molecular mechanisms underlying OA anti-tumor activity. We found that activation of MAPK pathways, including p-38 MAPK, JNK and ERK, was triggered by OA in both a dose and time-dependent fashion in all the tested cancer cells. Activation was accompanied by cleavage of caspases and PARP as well as cytochrome C release. SB203580 (p38 MAPK inhibitor), but not SP600125 (JNK inhibitor) and U0126 (ERK inhibitor), rescued the pro-apoptotic effect of OA on A549 and BXPC-3 cells. OA induced p38 MAPK activation promoted mitochondrial translocation of Bax and Bim, and inhibited Bcl-2 function by enhancing their phosphorylation. OA can induce reactive oxygen species (ROS)-dependent ASK1 activation, and this event was indispensable for p38 MAPK-dependent apoptosis in cancer cells. In vivo, p38 MAPK knockdown A549 tumors proved resistant to the growth-inhibitory effect of OA. Collectively, we elucidated that activation of ROS/ASK1/p38 MAPK pathways is responsible for the apoptosis stimulated by OA in cancer cells. Our finding can contribute to a better understanding of molecular mechanisms underlying the antitumor activity of nutritional components.

Preclinical Study of Cell Therapy for Osteonecrosis of the Femoral Head with Allogenic Peripheral Blood-Derived Mesenchymal Stem Cells

Tao Zhang,Qiang Fu,Ning-Ning Tang,Qian Zhang,Yi Liu,Jia-Chen Peng,Ning Fang,Li-Mei Yu,Jin-Wei Liu 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.4

Purpose: To explore the value of transplanting peripheral blood-derived mesenchymal stem cells from allogenic rabbits (rPBMSCs)to treat osteonecrosis of the femoral head (ONFH). Materials and Methods: rPBMSCs were separated/cultured from peripheral blood after granulocyte colony-stimulating factor mobilization. Afterwards, mobilized rPBMSCs from a second passage labeled with PKH26 were transplanted into rabbit ONFH models, which were established by liquid nitrogen freezing, to observe the effect of rPBMSCs on ONFH repair. Then, the mRNA expressions of BMP-2 and PPAR-γ in the femoral head were assessed by RT-PCR. Results: After mobilization, the cultured rPBMSCs expressed mesenchymal markers of CD90, CD44, CD29, and CD105, but failed to express CD45, CD14, and CD34. The colony forming efficiency of mobilized rPBMSCs ranged from 2.8 to 10.8 per million peripheralmononuclear cells. After local transplantation, survival of the engrafted cells reached at least 8 weeks. Therein, BMP-2 was up-regulated, while PPAR-γ mRNA was down-regulated. Additionally, bone density and bone trabeculae tended to increase gradually. Conclusion: We confirmed that local transplantation of rPBMSCs benefits ONFH treatment and that the beneficial effects are relatedto the up-regulation of BMP-2 expression and the down-regulation of PPAR-γ expression.

Antennal UDP-glycosyltransferase genes in the coffee white stemborer, Xylotrechus quadripes

Ning-Na Yin,Yu-Jie Zhao,Jia-Ying Zhu,Nai-Yong Liu 한국응용곤충학회 2019 Journal of Asia-Pacific Entomology Vol.22 No.4

The antenna of Xylotrechus quadripes is the principle olfactory organ that is subjected to a large number of endogenous and exogenous compounds. The gene families associated with the detoxification of these compounds are essential for the adaptive evolution of insect defensive strategies. However, knowledge on uridine diphosphate (UDP)-glycosyltransferases (UGTs) of X. quadripes is unavailable. Here, we characterized 30 UGT genes identified from an antennal transcriptome of X. quadripes. Among them, 16 UGT genes encoding 508–527 amino acids shared the full-length sequences and signal peptides in N-terminus. Multiple sequence alignment revealed that X. quadripes UGTs had a variable N-terminus and a conserved C-terminus. Phylogenetic analysis showed that X. quadripes UGTs were classified into ten sub-families with the largest UGT one of UGT352 (nine genes) and a strict single copy of UGT50 within coleopteran species. Gene structural analysis indicated that coleopteran UGT50s underwent intron gains or losses. Expression profile revealed that all studied X. quadripes UGTs were transcribed in the antennae of both sexes, some of which exhibited sex-biased expression including UGT2, UGT6, UGT20 and UGT27 in females as well as UGT3, UGT11 and UGT12 in males. In addition, most of UGTs were widely expressed in other tissues, indicating their functional diversities in this beetle. Together, these findings provide valuable information for further functional studies of UGTs in X. quadripes, especially their roles in olfaction.

Effect of the Polymorphisms of Keratin Associated Protein 8.2 Gene on Fibre Traits in Inner Mongolia Cashmere Goats

Liu, Haiying,Li, Ning,Jia, Cunling,Zhu, Xiaoping,Jia, Zhihai Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.6

The aim of the experiment was to detect polymorphisms in the keratin-associated protein 8.2 (KAP8.2) gene to determine associations between the genotype and fibre traits in Chinese Inner Mongolia cashmere goats. The fibre traits data investigated were cashmere fibre diameter, combed cashmere weight, cashmere fibre length and guard hair length. Five hundred and forty-two animals were used to detect polymorphisms in the complete coding sequence of the hircine KAP8.2 gene by means of PCR-SSCP. The results identified six genotypes, AA, BB, DD, AB, AD and BD, coded for by three different alleles A, B and D. Two SNPs in the coding region were confirmed by sequencing, which were A214G and T218C respectively. The relationships between the genotypes and cashmere fibre diameter, combed cashmere weight, cashmere fibre length and guard hair length were analyzed. There were significant differences (p<0.01) between the associations of the different genotypes with cashmere fibre diameter, cashmere weight and hair length. Cashmere length was the only trait that was not associated with the genotypes. The genotype AA (0.73) was found to be predominant in Inner Mongolia cashmere goats and the animals with this genotype had the thinnest cashmere fibre diameter compared with the other genotypes. These results suggested that polymorphisms in the hircine KAP8.2 gene may be a potential molecular marker for cashmere fibre diameter in cashmere goats.

Comparison of Liver Transplantation and Liver Resection for Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus Type I and Type II

Jia-Yu Lv,Ning-Ning Zhang,Ya-Wei Du,Ying Wu,Tian-Qiang Song,Ya-Min Zhang,Yan Qu,Yu-Xin Liu,Jie Gu,Ze-Yu Wang,Yi-Bo Qiu,Bing Yang,Da-Zhi Tian,Qing-Jun Guo,Li Zhang,Ji-San Sun,Yan Xie,Zheng-Lu Wang,Xin 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.1

Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellularcarcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involvedand divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were comparedbefore and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR(p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longermedian RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335,respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase(AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion: LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels>200 ng/mL.

Isolation of Eight DM domains of Dmrt genes in Rana Livida (Amphibia: Anura)

Rui Jia,Liu Wang Nie,Jing Jing Wang,Ning Wang 한국유전학회 2008 Genes & Genomics Vol.30 No.6

The Dmrt gene family encodes putative transcription factors, sharing a highly conserved DNA-binding domain-the DM domain, related to the sexual regulators Doublesex from Drosophila melanogaster and MAB-3 from Caenorhabditis elegans. Besides sex determination or differentiation, this gene family has evolved to adopt functions in other developmental pathways. In this paper, eight distinct DM related transcription factor (Dmrt) genes from both male and female and detected using PCR and the SSCP technique. No sexual differences were observed. These fragments (named RlDmrt1a, RlDmrt1b, RlDmrt2a, RlDmrt2b, RlDmrt2c, RlDmrt3, RlDmrt4, RlDmrt5) exhibited 98%, 98%, 95%, 95%, 95%, 99%, 92% and 83% similarity respectively to the corresponding homologous human Dmrt genes. Phylogenetic analysis based on DM domain amino acid sequence similarities suggested that vertebrate and invertebrate Dmrt genes can be grouped into seven distinct subfamilies. Interestingly, sequence analysis further illustrates that the gene Dmrt1 and 2 found in R. livida are duplicated. The DM domains of R. livida genes contained two conserved zinc-chelating sites (CCHC and HCCC). Identification of these genes is a potential step in understanding development regulations including sex determination in green cascade frog.

Mechanical simulation for the bending process of the AMOLED panel pad

Wu Di,Jia Yongzhen,Liao Dunming,Zhang Bo,Liu Chen,Wang Ning,Peng Wenjing,Huang Liting 한국정보디스플레이학회 2023 Journal of information display Vol.24 No.2

Panel pad bending is a critical process to improve the screen-to-body ratio of an active-matrix organic light-emitting diode (AMOLED) panel. The failure analysis of the metal wirings is the key to ensure the reliability of signal transmission when the pad be bent to the back of the panel. In the present work, the sub-modeling technique combined with the periodic boundary condition was used to simulate the stress distribution of the bending area of the pad. The progressive failure of bent metal wirings was investigated by the extended finite element method. It is proved to be rational to prevent the wirings damage if the interlayer dielectric is replaced by an organic layer. In order to reduce stress of metal wirings, it is a measure to replace the original ultraviolet (UV) curable adhesive with a higher-modulus UV adhesive. The simulated results also show that rectangular perforations can avoid the stress concentration caused by the holes compared with circular perforations. For better stress distribution of metal wirings, it is necessary to increase the lengths of the rectangular holes and decrease the widths of that to a certain extent, which is helpful for restraining crack propagation by means of low-stress zones and holes.

Age Hardening Characteristics of Cu-Ag-Zr Alloy

S. G. Jia,X. M. Ning,M. S. Zheng,G. S. Zhou,P. Liu 대한금속·재료학회 2009 METALS AND MATERIALS International Vol.15 No.4

Cu-Ag-Zr alloy is a newly developed copper alloy material which has an excellent combination of high mechanical strength and high electrical conductivity. By means of vacuum induction melting, Cu-Ag-Zr alloy was produced. The effects of aging processes on the microhardness and electrical conductivity characteristics of Cu-Ag-Zr alloy were studied. After aging at 450 °C for 4h, the alloy showed an excellent combination of microhardness and electrical conductivity: the microhardness and electrical conductivity reach 126 HV and 84%IACS, respectively. The precipitates responsible for the age-hardening effect are the fine and dispersed Cu5Zr, which has a face center cubic structure. Cu5Zr precipitates are fully coherent with the Cu matrix and give the Cu- Ag-Zr alloy higher microhardness and higher electrical conductivity. Cu-Ag-Zr alloy is a newly developed copper alloy material which has an excellent combination of high mechanical strength and high electrical conductivity. By means of vacuum induction melting, Cu-Ag-Zr alloy was produced. The effects of aging processes on the microhardness and electrical conductivity characteristics of Cu-Ag-Zr alloy were studied. After aging at 450 °C for 4h, the alloy showed an excellent combination of microhardness and electrical conductivity: the microhardness and electrical conductivity reach 126 HV and 84%IACS, respectively. The precipitates responsible for the age-hardening effect are the fine and dispersed Cu5Zr, which has a face center cubic structure. Cu5Zr precipitates are fully coherent with the Cu matrix and give the Cu- Ag-Zr alloy higher microhardness and higher electrical conductivity.

Effects of moderate pressure on premeability and viability of Saccharomyces cerevisiae cells

Shi-Ru Jia,Na-Chen,Yu-Jie Dai,Chang-Sheng Qiao,Jian-Dong Cui,Bo-Ning Liu 한국화학공학회 2009 Korean Journal of Chemical Engineering Vol.26 No.3

With CO2 and N2 as the pressure media, the effects of the moderate pressure (0.1-1.0MPa) and the holding time on the conductivities of the cell suspension of Saccharomyces cerevisiae CICC1447 and Saccharomyces cerevisiae CICC1339, as well as the absorbances of the supernatant (after centrifuged) at 280 nm (A280) and 260 nm (A260) were determined. The membrane permeability of Saccharomyces cerevisiae CICC1447 increased significantly and the cell leakage was aggravated with the pressure increase. For Saccharomyces cerevisiae CICC1339, the conductivity of the cell suspension, A280 and A260 of the supernatant fluctuated with the pressure increase; as a whole, they increased with pressure. Different from high pressure, a moderate pressure not only remarkably improved the permeability of the yeast cell membrane, but also kept yeast cell viability; moreover, the integrity of the yeast cell membrane could be maintained.

Isomangiferin, a Novel Potent Vascular Endothelial Growth Factor Receptor 2 Kinase Inhibitor, Suppresses Breast Cancer Growth, Metastasis and Angiogenesis

Banghua Wang,Jia Shen,Zexia Wang,Jian-Xia Liu,Zhifeng Ning,Meichun Hu 한국유방암학회 2018 Journal of breast cancer Vol.21 No.1

Purpose: Vascular endothelial growth factor (VEGF) signal transduction mainly depends on its binding to VEGF receptor 2 (VEGFR-2). VEGF downstream signaling proteins mediate several of its effects in cancer progression, including those on tumor growth, metastasis, and blood vessel formation. The activation of VEGFR-2 signaling is a hallmark of and is considered a therapeutic target for breast cancer. Here, we report a study of the regulation of the VEGFR-2 signaling pathway by a small molecule, isomangiferin. Methods: A human breast cancer xenograft mouse model was used to investigate the efficacy of isomangiferin in vivo. The inhibitory effect of isomangiferin on breast cancer cells and the underlying mechanism were examined in vitro. Results: Isomangiferin suppressed tumor growth in xenografts. In vitro, isomangiferin treatment inhibited cancer cell proliferation, migration, invasion, and adhesion. The effect of isomangiferin on breast cancer growth was well coordinated with its suppression of angiogenesis. A rat aortic ring assay revealed that isomangiferin significantly inhibited blood vessel formation during VEGF-induced microvessel sprouting. Furthermore, isomangiferin treatment inhibited VEGF-induced proliferation of human umbilical vein endothelial cells and the formation of capillary-like structures. Mechanistically, isomangiferin induced caspase-dependent apoptosis of breast cancer cells. Furthermore, VEGFinduced activation of the VEGFR-2 kinase pathway was downregulated by isomangiferin. Conclusion: Our findings demonstrate that isomangiferin exerts anti-breast cancer effects via the functional inhibition of VEGFR-2. Pharmaceutically targeting VEGFR-2 by isomangiferin could be an effective therapeutic strategy for breast cancer.