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A 90-day Repeated-Dosed Toxicity Study of Euphorbiae kansui radix Extract in Fischer 344/N Rats
Zhong-Ze Han,Hu-Song Zhang,Ki-Hyun Gil,Joo-Young Lee,Kwang-Han Kong,Myoung-Kyu Han,Hyun-Ju Yang,Hak-Soo Kim,Do-Hyung Kim,Tae-Hwan Ahn,Jin-Sook Bae,Hyun-Kyu Ko,Jung-Woon Lee,Moon-Soon Kim,Si-Whan Song 한국실험동물학회 2008 Laboratory Animal Research Vol.24 No.4
This study was performed to evaluate repeated-dose toxicities of Euphorbiae kansui radix extract in F344/N rats. Euphorbiae kansui radix extract was administered orally to rats at dose levels of 0, 37, 111, 333, 1,000 and 2,000 ㎎/㎏/day. Each group consisted of 10 rats of each gender. The Euphorbiae Kansui, Radix extract was given once a day, 5 times a week, for 90 day repeatedly. This study was conducted in accordance with the Protocol of Korea National Toxicology Program (issued by National Institute of Toxicological Research) and The Standards of Toxicity Study for Medicinal Products (issued by Korea Food and Drug Administration). In the present study, there were no dose-related changes in mortality, clinical signs, body weights, ophthalmoscopy, urine analysis, hematological findings, estrus cycle and sperm examination of all animals treated with Euphorbiae kansui radix extract. There were increases of liver weights in 2,000 ㎎/㎏/day groups of males and in 333, 1,000 and 2,000 ㎎/㎏/day groups of females. There were decreases of alkaline phosphatase levels in 1,000 and 2,000 ㎎/㎏/day groups of both sexes. These results suggest that the oral no-observed-adverse-effect level (NOAEL) of the test item, Euphorbiae kansui radix extract, in rats is 2,000 ㎎/㎏/day in both genders; no-observed-effect level (NOEL) is 1,000 ㎎/㎏/day in male and 111 ㎎/㎏/day in female. The target organs were thought to be liver and thymus.
Zhong-Ze Han,Hong-De Xu,Kwang-Ho Kim,Tae-Hwan Ahn,Jin-Sook Bae,Ji-Young Lee,Ki-Hyun Gil,Joo-Young Lee,Su-Jung Woo,Hyun-Jung Yoo,Hyun-Kul Lee,Kap-Ho Kim,Chan-Koo Park,Hu-Song Zhang,Si-Whan Song 한국실험동물학회 2010 Laboratory Animal Research Vol.26 No.2
The purpose of this paper is to provide reference data related to the body weight, food & water consumptions, urinalysis, hematology and serum biochemistry parameters and absolute & relative organ weights obtained from control Sprague-Dawley rats, used in the 4-week and 13-week repeated-dose toxicity studies conducted in our laboratory between 2005 and 2008. The mean, standard deviation, minimum and maximum range values for hematology and serum biochemistry parameters, data of absolute & relative organ weights, and the difference between sexes and study duration of week 4 versus 13 week are presented. The studies were conducted according to “the standards of Toxicity Study for Medicinal Products” (2005) and The KFDA Notification No. 2000-63 ‘Good Laboratory Practice (GLP)’ (2000) issued by KFDA. These data could be used as reference material of Sprague-Dawley rats by conducting the studies to evaluate the toxicological profile of pre-clinical toxicity studies.
SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin
Chen, Jun,Zhong, Ming-Chao,Guo, Huaijian,Davidson, Dominique,Mishel, Sabrin,Lu, Yan,Rhee, Inmoo,Pé,rez-Quintero, Luis-Alberto,Zhang, Shaohua,Cruz-Munoz, Mario-Ernesto,Wu, Ning,Vinh, Donald C.,Si Nature Publishing Group 2017 Nature Vol. No.
<P>Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors(1,2). Phagocytosis by macrophages plays a critical role in cancer control(3-6). Therapeutic blockade of signal regulatory protein (SIRP)-alpha, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo(7-10), suggesting that blockade of the SIRP alpha-CD47 checkpoint could be useful in treating human cancer(11-14). However, the prophagocytic receptor(s) responsible for tumour cell phagocytosis is(are) largely unknown. Here we find that macrophages are much more efficient at phagocytosis of haematopoietic tumour cells, compared with non-haematopoietic tumour cells, in response to SIRP alpha-CD47 blockade. Using a mouse lacking the signalling lymphocytic activation molecule (SLAM) family of homotypic haematopoietic cell-specific receptors, we determined that phagocytosis of haematopoietic tumour cells during SIRP alpha-CD47 blockade was strictly dependent on SLAM family receptors in vitro and in vivo. In both mouse and human cells, this function required a single SLAM family member, SLAMF7 (also known as CRACC, CS1, CD319), expressed on macrophages and tumour cell targets. In contrast to most SLAM receptor functions(15-17), SLAMF7-mediated phagocytosis was independent of signalling lymphocyte activation molecule-associated protein (SAP) adaptors. Instead, it depended on the ability of SLAMF7 to interact with integrin Mac-1 (refs 18-20) and utilize signals involving immunoreceptor tyrosine-based activation motifs(21,22). These findings elucidate the mechanism by which macrophages engulf and destroy haematopoietic tumour cells. They also reveal a novel SAP adaptor-independent function for a SLAM receptor. Lastly, they suggest that patients with tumours expressing SLAMF7 are more likely to respond to SIRP alpha-CD47 blockade therapy.</P>
Ho, Ping-Luen,Yu, Chu-Ping,Zhang, Qiqi,Song, Kyung,Buban, James P.,Choi, Si-Young,Dunin-Borkowski, Rafal E.,Mayer, Joachim,Tai, Nyan-Hwa,Zhu, Jing,Jin, Lei,Zhong, Xiaoyan Elsevier 2018 Ultramicroscopy Vol.193 No.-
<P><B>Abstract</B></P> <P>Superexchange-based magnetic coupling of the two <I>B</I>-site cations in rock-salt-ordered double perovskite oxides is extremely sensitive to the cation ratio and degree of order. However, as a result of the limited spatial resolution of most magnetic characterization techniques, it is challenging to establish a direct relationship between magnetic properties and structure in these materials, including the effects of elemental segregation and cation disorder. Here, we use electron energy-loss magnetic chiral dichroism together with aberration-corrected electron microscopy and spectroscopy to record magnetic circular dichroism (MCD) spectra at the nm scale, in combination with structural and chemical information at the atomic scale from the very same region. We study nanoscale phases in ordered Sr<SUB>2</SUB>[Fe][Re]O<SUB>6</SUB>, ordered Sr<SUB>2</SUB>[Fe][Fe<SUB>1/5</SUB>Re<SUB>4/5</SUB>]O<SUB>6</SUB> and disordered Sr[Fe<SUB>4/5</SUB>Re<SUB>1/5</SUB>]O<SUB>3</SUB> individually, in order to understand the role of cation ratio and order on local magnetic coupling. When compared with ordered Sr<SUB>2</SUB>[Fe][Re]O<SUB>6</SUB>, we find that antiferromagnetic Fe<SUP>3+</SUP>-O<SUP>2−</SUP>-Fe<SUP>3+</SUP>superexchange interactions arising from an excess of Fe suppress the MCD signal from Fe cations in ordered Sr<SUB>2</SUB>[Fe][Fe<SUB>1/5</SUB>Re<SUB>4/5</SUB>]O<SUB>6</SUB>, while dominant Fe<SUP>3+</SUP>-O<SUP>2−</SUP>-Fe<SUP>3+</SUP>antiferromagnetic coupling in disordered Sr[Fe<SUB>4/5</SUB>Re<SUB>1/5</SUB>]O<SUB>3</SUB> leads to a decrease in MCD signal down to the noise level. Our work demonstrates a protocol that can be used to correlate crystallographic, electronic and magnetic information in materials such as Sr<SUB>2</SUB>Fe<SUB>1+</SUB> <I> <SUB>x</SUB> </I>Re<SUB>1-</SUB> <I> <SUB>x</SUB> </I>O<SUB>6</SUB>, in order to provide insight into structure-property relationships in double perovskite oxides at the atomic scale.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Local measurements of magnetic circular dichroism, atomic arrangement, cation order, chemical state and elemental distribution from the very same region provide an improved understanding of structure-property relationships at the nm scale in double perovskites with different structural complexities. </LI> <LI> Antiferromagnetic Fe<SUP>3+</SUP>-O<SUP>2−</SUP>-Fe<SUP>3+</SUP>superexchange interactions arising from an excess of Fe suppress the magnetic circular dichroism signal from Fe cations in ordered Sr<SUB>2</SUB>[Fe][Fe<SUB>1/5</SUB>Re<SUB>4/5</SUB>]O<SUB>6</SUB>, when compared with ordered Sr<SUB>2</SUB>[Fe][Re]O<SUB>6</SUB>. </LI> <LI> Dominant Fe<SUP>3+</SUP>-O<SUP>2−</SUP>-Fe<SUP>3+</SUP>antiferromagnetic coupling in disordered Sr[Fe<SUB>4/5</SUB>Re<SUB>1/5</SUB>]O<SUB>3</SUB> leads to a decrease in magnetic circular dichroism signal down to the noise level. </LI> </UL> </P>
Promoter demethylation mediates the expression of ZNF645, a novel cancer/testis gene
( Gang Bai ),( Yun Qiang Liu ),( Hao Zhang ),( Dan Su ),( Da Chang Tao ),( Yuan Yang ),( Yong Xin Ma ),( Si Zhong Zhang ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2010 BMB Reports Vol.43 No.6
Cancer/testis (CT) antigens exhibit highly tissue-restricted expression and are considered promising targets for cancer vaccines. Here we identified a novel CT gene ZNF645 which restrictively expresses in normal human testes and lung cancer patients (68.3%). To investigate the promoter methylation status of ZNF645, we carried out bisulfite genomic sequencing and found that the CpG island in its promoter was heavily methylated in normal lung tissues without the expression of ZNF645, whereas there was high demethylation in normal human testes and lung carcinoma tissues with its expression. Also ZNF645 could be remarkably activated in A549 and HEK293T cells treated by DNA demethylation agent 5`-aza-2`-deoxycytidine. And the dual luciferase assay revealed that the promoter activity of the ZNF645 was inhibited by methylation of the CpG island region. Therefore, we proposed that ZNF645 is a CT gene and activated in human testis and lung cancers by demethylation of its promoter region. [BMB reports 2010; 43(6): 400-406]
Fan, Fang-Tian,Shen, Cun-Si,Tao, Li,Tian, Chao,Liu, Zhao-Guo,Zhu, Zhi-Jie,Liu, Yu-Ping,Pei, Chang-Song,Wu, Hong-Yan,Zhang, Lei,Wang, Ai-Yun,Zheng, Shi-Zhong,Huang, Shi-Le,Lu, Yin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5
Pyruvate kinase isozyme type M2 (PKM2) was first found in hepatocellular carcinoma (HCC), and its expression has been thought to correlate with prognosis. A large number of studies have demonstrated that epithelial-mesenchymal transition (EMT) is a crucial event in hepatocellular carcinoma (HCC) and associated metastasis, resulting in enhanced malignancy of HCC. However, the roles of PKM2 in HCC EMT and metastasis remain largely unknown. The present study aimed to determine the effects of PKM2 in EGF-induced HCC EMT and elucidate the molecular mechanisms in vitro. Our results showed that EGF promoted EMT in HCC cell lines as evidenced by altered morphology, expression of EMT-associated markers, and enhanced invasion capacity. Furthermore, the present study also revealed that nuclear translocation of PKM2, which is regulated by the ERK pathway, regulated ${\beta}$-catenin-TCF/LEF-1 transcriptional activity and associated EMT in HCC cell lines. These discoveries provide evidence of novel roles of PKM2 in the progression of HCC and potential therapeutic target for advanced cases.