20(S)-Protopanaxadiol enhances angiogenesis via HIF-1α-mediated VEGF secretion by activating p70S6 kinase and benefits wound healing in genetically diabetic mice

Er-Yun Zhang,Bo Gao,Hai-Lian Shi,Ling-Fang Huang,Li Yang,Xiao-Jun Wu,Zheng-Tao Wang 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Impaired angiogenesis is one of the crucial factors that impede the wound healing process in diabetic foot ulcers (DFUs). In this study, we found that 20(S)-protopanaxadiol (PPD), an aglycone of ginsenosides in Panax notoginseng, stimulated angiogenesis and benefited wound healing in genetically diabetic mice. In HUVECs, PPD promoted cell proliferation, tube formation and VEGF secretion accompanied by increased nuclear translocalization of HIF-1α, which led to elevated VEGF mRNA expression. PPD activated both PI3K/Akt/mTOR and Raf/MEK/ERK signaling pathways in HUVECs, which were abrogated by LY294002 and PD98059. Furthermore, these two pathways had crosstalk through p70S6K, as LY294002, PD98059 and p70S6K siRNA abolished the angiogenic responses of PPD. In the excisional wound splinting model established in db/db diabetic mice, PPD (0.6, 6 and 60 mg ml− 1) accelerated wound closure, which was reflected by a significantly reduced wound area and epithelial gaps, as well as elevated VEGF expression and capillary formation. In addition, PPD activated PI3K/Akt/ERK signaling pathways, as well as enhanced p70S6K activity and HIF-1α synthesis in the wounds. Overall, our results revealed that PPD stimulated angiogenesis via HIF-1α-mediated VEGF expression by activating p70S6K through PI3K/Akt/mTOR and Raf/MEK/ERK signaling cascades, which suggests that the compound has potential use in wound healing therapy in patients suffering from DFUs.

Functional RsaI/PstI Polymorphism in Cytochrome P450 2E1 Contributes to Bladder Cancer Susceptibility: Evidence from a Meta-analysis

Deng, Xiao-Dong,Gao, Qin,Zhang, Bo,Zhang, Li-Xia,Zhang, Wei,Er, Zhe-Er Mu,Xie, Ying,Ma, Ying,Liu, Yun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Background: Cytochrome P450 2E1 (CYP2E1) might be involved in the development of bladder cancer. However, previous studies of any association between CYP2E1 RsaI/PstI polymorphism and bladder cancer risk have yielded conflicting results. In this study, we performed a more precise estimation of the relationship by a meta-analysis based on the currently available evidence from the literature. Method: To assess the effect of CYP2E1 RsaI/PstI polymorphism on bladder cancer susceptibility, a meta-analysis of 6 available studies with 1,510 cases and 1,560 controls were performed through Feb 2014. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of association for CYP2E1 RsaI/PstI polymorphism under different genetic models. Results: When available studies were pooled into the meta-analysis, we found that the C1C2 and C2C2 genotypes of CYP2E1 RsaI/PstI polymorphism significantly decreased bladder cancer risk under different genetic models (heterozygote: OR=0.766, 95%CI=0.613-0.957, $P_{OR}$=0.019; homozygote: OR=0.51, 95%CI=0.303-0.858, $P_{OR}$=0.011; dominant: OR=0.733, 95%CI=0.593-0.905, $P_{OR}$=0.004; recessive: OR=0.565, 95%CI=0.337-0.947, $P_{OR}$=0.030). Subgroup analysis indicated that C2C2 genotype was significantly associated with decreased bladder cancer risk under the homozygote genetic model in Caucasians. There was no evidence of heterogeneity or publication bias. Conclusions: The current meta-analysis suggested that the CYP2E1 RsaI/PstI polymorphism might be associated with bladder cancer susceptibility, especially in Caucasians. Further studies are needed to validate the above conclusion.

Human Recombinant Endostatin Combined with Cisplatin Based Doublets in Treating Patients with Advanced NSCLC and Evaluation by CT Perfusion Imaging

Zhang, Feng-Lin,Gao, Er-Yun,Shu, Rong-Bao,Wang, Hui,Zhang, Yan,Sun, Peng,Li, Min,Tang, Wei,Jiang, Bang-Qin,Chen, Shuang-Qi,Cui, Fang-Bo Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Aims: To study the effectiveness of human recombinant endostatin injection (Endostar(R)) combined with cisplatin doublets in treating advanced non-small cell lung cancer (NSCLC), and to evaluate outcome by CT perfusion imaging. Methods: From April 2011 to September 2014, 76 patients with advanced NSCLC who were treated with platinum-based doublets were divided into group A (36 patients) and group B (40 patients). Endostar(R) 15mg/day was administered 4 days before chemotherapy and combined with chemotherapy from day 5 in group A, and combined with chemotherapy from the first day in Group B. Endostar(R) in the two groups was injected intravenously for 14 days. Results: Treatment effectiveness in the two groups differed with statistical significance (p<0.05). Effectiveness evaluated by CT perfusion imaging, BF, BV, MTT and PS also demonstrated significant differences (all p<0.05). Adverse reactions in the two groups did not significantly vary (p> 0.05). Conclusions: The response rate with Endostar(R) administered 4 days before chemotherapy and combined with chemotherapy from day 5 in group A was better than Endostar(R) combined with chemotherapy from the first day, and CT perfusion imaging could be a reasonable method for evaluation of patient outcomes.

DEPTOR Expression Negatively Correlates with mTORC1 Activity and Tumor Progression in Colorectal Cancer

Lai, Er-Yong,Chen, Zhen-Guo,Zhou, Xuan,Fan, Xiao-Rong,Wang, Hua,Lai, Ping-Lin,Su, Yong-Chun,Zhang, Bai-Yu,Bai, Xiao-Chun,Li, Yun-Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including colorectal cancer (CRC). DEPTOR is an mTOR inhibitor whose expression is negatively regulated by mTOR. However, the role of DEPTOR in the development of CRC is not known. The aim of this study was to investigate the expression of DEPTOR and mTORC1 activity (P-S6) in a subset of CRC patients and determine their relation to tumor differentiation, invasion, nodal metastasis and disease-free survival. Here, Immunohistochemical expression of P-S6 (S235/236) and DEPTOR were evaluated in 1.5 mm tumor cores from 90 CRC patients and in 90 samples of adjacent normal mucosa by tissue microarray. The expression of P-S6 (S235/236) was upregulated in CRC, with the positive rate of P-S6 (S235/236) in CRC (63.3%) significantly higher than that in control tissues (36.7%, 30%) (p<0.05). P-S6 (S235/236) also correlated with high tumor histologic grade (p=0.002), and positive nodal metastasis (p=0.002). In contrast, the expression level of DEPTOR was correlated with low tumor histological grade (p=0.006), and negative nodal metastasis (p=0.001). Interestingly, P-S6 (S235/236) expression showed a significant negative association with the expression of DEPTOR in CRC (p=0.011, R= -0.279). However, upregulation of P-S6 (S235/236) (p=0.693) and downregulation of DEPTOR (p=0.331) in CRC were not significantly associated with overall survival. Thus, we conclude that expression of DEPTOR negatively correlates with mTORC1 activity and tumor progression in CRC. DEPTOR is a potential marker for prognostic evaluation and a target for the treatment of CRC.

Ultrafast UV Switch Based on ZnO-Ag Heterostructures

XIU-YUN AN,Feng Teng,Zhenxing Zhang,Xiaojun Pan,Jinyuan Zhou,ER-QING XIE 대한금속·재료학회 2014 ELECTRONIC MATERIALS LETTERS Vol.10 No.1

ZnO-silver (Ag) heterostructure nanoparticle films were prepared by spin-coating, followed by annealing at 700°C for 2 h. The films were then used as UV photodetector which show high photoresponse. The heterostructure-film device displayed an ultrafast decay time of 18 ms and a rise time of 50 ms upon ultraviolet irradiation. Additionally, the time-dependent photocurrent upon UV switching reveals a rectangularly shaped profile, rarely reported in previous literature. The highly improved photoresponse properties of ZnO-Ag heterostructure-film device could be attributed to the Schottky barrier height (SBH) and depletion width reduction from the embedded Ag nanoclusters. Compared to a pure ZnO film, both the responsivity (Rλ) and external quantum efficiency (EQE) of the ZnO-Ag heterostructure-film photodetectors were improved more than 13-fold. This research provides a promising strategy for fabricating UV-photodetectors with ultrafast response.

ROOM-TEMPERATURE FERROMAGNETISM IN SnO 2 NANOFIBERS AND NANOTUBES PREPARED BY ELECTROSPINNING

JIAN-GUO ZHAO,WEI-YING ZHANG,ZHAO-JUN LIU,ZHONG-LI LIU,YA-JUAN ZHANG,ER-QING XIE,XIU-YUN AN,YONG-FENG CHEN,CHANG-YOU ZHANG 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2014 NANO Vol.9 No.2

SnO 2 nano¯bers and nanotubes were synthesized by electrospinning method. Magnetizationmeasurement indicates that the SnO 2 nano¯bers and nanotubes annealed in air at 500?C exhibitthe room-temperature ferromagnetism and the ferromagnetism of nanotubes is stronger than thenano¯bers. Selected area electron di®raction, X-ray di®raction and Raman measurements showthat all the samples possess a typical rutile structure and no other impurity phases are observed. The results of the Raman spectra also indicate that there are lots of defects existing in thefabricated samples. The observed room-temperature ferromagnetism in SnO 2 nano¯bers andnanotubes possibly originates from oxygen vacancies. The ¯eld cooled (FC) and zero-¯eld-cooled(ZFC) magnetization curves indicate that the Curie temperature T C is above 300 K.

ISG15 modification of filamin B negatively regulates the type I interferon‐induced JNK signalling pathway

Jeon, Young Joo,Choi, Joon Seok,Lee, Jung Yun,Yu, Kyung Ryun,Kim, Sangman Michael,Ka, Seung Hyeun,Oh, Kyu Hee,Il Kim, Keun,Zhang, Dong‐,Er,Bang, Ok Sun,Ha Chung, Chin EMBO 2009 EMBO reports Vol.10 No.4

<P>Interferon (IFN)-induced signalling pathways have essential functions in innate immune responses. In response to type I IFNs, filamin B tethers RAC1 and a Jun N-terminal kinase (JNK)-specific mitogen-activated protein kinase (MAPK) module--MEKK1, MKK4 and JNK--and thereby promotes the activation of JNK and JNK-mediated apoptosis. Here, we show that type I IFNs induce the conjugation of filamin B by interferon-stimulated gene 15 (ISG15). ISGylation of filamin B led to the release of RAC1, MEKK1 and MKK4 from the scaffold protein and thus to the prevention of sequential activation of the JNK cascade. By contrast, blockade of filamin B ISGylation by substitution of Lys 2467 with arginine or by knockdown of ubiquitin-activating enzyme E1-like (UBEL1) prevented the release of the signalling molecules from filamin B, resulting in persistent promotion of JNK activation and JNK-mediated apoptosis. These results indicate that filamin B ISGylation acts as a negative feedback regulatory gate for the desensitization of type I IFN-induced JNK signalling.</P>