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Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer

EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013年第1期2013卷 541695-541695页

作者： Chen, Chun-Chieh Sureshbabul, Munisamy Chen, Huei-Wen Lin, Yu-Shuang Lee, Jen-Yi Hong, Qi-Sheng Yang, Ya-Chien Yu, Sung-Liang Natl Taiwan Univ Coll Med Dept Clin Lab Sci & Med Biotechnol Taipei 100 Taiwan Natl Taiwan Univ Ctr Genom Med Taipei 100 Taiwan Natl Taiwan Univ Grad Inst Toxicol Coll Med Taipei 100 Taiwan Natl Taiwan Univ Hosp Dept Lab Med Taipei 100 Taiwan Natl Taiwan Univ Grad Inst Pathol Coll Med Taipei 100 Taiwan Natl Taiwan Univ Coll Med Ctr Optoelect Biomed Taipei 100 Taiwan

Colorectal cancer (CRC) is a serious public health problem that results due to changes of diet and various environmental stress factors in the world. Curcumin is a traditional medicine used for treatment of a wide variety of tumors. However, antimetastasis mechanism of curcumin on CRC has not yet been completely investigated. Here, we explored the underlying molecular mechanisms of curcumin on metastasis of CRC cells in vitro and in vivo. Curcumin significantly inhibits cell migration, invasion, and colony formation in vitro and reduces tumor growth and liver metastasis in vivo. We found that curcumin suppresses Sp-1 transcriptional activity and Sp-1 regulated genes including ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in CRC cells. Curcumin inhibits focal adhesion kinase (FAK) phosphorylation and enhances the expressions of several extracellular matrix components which play a critical role in invasion and metastasis. Curcumin reduces CD24 expression in a dose-dependentmanner in CRC cells. Moreover, E-cadherin expression is upregulated by curcumin and serves as an inhibitor of EMT. These results suggest that curcumin executes its antimetastasis function through downregulation of Sp-1, FAK, and CD24 and by promoting E-cadherin expression in CRC cells.

关键词： CANCER invasiveness PREVENTION METASTASIS DISEASE progression CURCUMIN ANIMAL experimentation CELL lines CELL migration COLON tumors DOSE-response relationship (Biochemistry) EXPERIMENTAL design IMMUNODIAGNOSIS MICE MICROBIOLOGICAL assay POLYMERASE chain reaction RECTUM TUMORS RESEARCH -- Finance WESTERN immunoblotting microarray technology THERAPEUTIC use

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Comparing the Gene Expression Profile of Stromal Cells from Human Cord Blood and Bone Marrow: Lack of the Typical "Bone'' Signature in Cord Blood Cells

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STEM CELLS INTERNATIONAL 2013年第2013期2013卷 631984-631984页

作者： Bosch, Julia Houben, Amelie Pia Hennicke, Tatiana Deenen, Rene Koehrer, Karl Liedtke, Stefanie Koegler, Gesine Univ Dusseldorf Med Ctr Inst Transplantat Diagnost & Cell Therapeut D-40225 Dusseldorf Germany Univ Dusseldorf Biol & Med Res Ctr BMFZ D-40225 Dusseldorf Germany

With regard to the bone-regenerative capacity, bone marrow stromal cells (BMSC) can still be termed the "gold standard." Nevertheless, neonatal stromal cells from cord blood (CB) feature advantages concerning availability, immaturity, and proliferation potential. The detailed gene expression analysis and overexpression of genes expressed differentially provide insight into the inherent capacity of stromal cells. microarray and qRT-PCR analyses revealed closely related gene expression patterns of two stromal cell populations derived from CB. In contrast to the CB-derived cell types, BMSC displayed high expression levels of BSP, OSX, BMP4, OC, and PITX2. Lentiviral overexpression of BSP but not of OSX in CB-cells increased the capacity to form a mineralized matrix. BMP4 induced the secretion of proteoglycans during chondrogenic pellet culture and extended the osteogenic but reduced the adipogenic differentiation potential. BMSC revealed the typical osteogenic gene expression signature. In contrast, the CB-derived cell types exhibited a more immature gene expression profile and no predisposition towards skeletal development. The absence of BSP and BMP4-which were defined as potential key players affecting the differentiation potential-in neonatal stromal cells should be taken into consideration when choosing a cell source for tissue regeneration approaches.

关键词： GENE expression STROMAL cells CORD blood BONE marrow microarray technology

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Elucidation of the role of LMO2 in human erythroid cells

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EXPERIMENTAL HEMATOLOGY 2013年第12期41卷 1062-1076页

作者： Inoue, Ai Fujiwara, Tohru Okitsu, Yoko Katsuoka, Yuna Fukuhara, Noriko Onishi, Yasushi Ishizawa, Kenichi Harigae, Hideo Tohoku Univ Grad Sch Med Dept Hematol & Rheumatol Sendai Miyagi 9808575 Japan Tohoku Univ Grad Sch Med Dept Mol Hematol & Oncol Sendai Miyagi 9808575 Japan Tohoku Univ Hosp Clin Res Innovat & Educ Ctr Sendai Miyagi Japan

LIM-only protein 2 (LMO2) is a non DNA-binding component of a protein complex containing master regulators of hematopoiesis, including GATA-1, SCL/TAL1, and LDB1. However, the role of LMO2 in human erythroid differentiation is unclear. LMO2 knockdown in hemin-treated K562 cells reduced the benzidine-positive cell ratio, suggesting that LMO2 retards hemin-mediated K562 cell differentiation. microarray analysis using K562 cells after siRNA-mediated LMO2 knockdown indicated that 177 and 78 genes were upregulated and downregulated ( > 1.5-fold), respectively. The downregulated gene ensemble contained prototypical erythroid genes (HBB, SLC4A1). Whereas LMO2 knockdown did not affect GATA-1 or SCL/TAL1 expression, it resulted in significantly reduced chromatin occupancy of GATA-1, SCL/TAL1, and LDB1 at the beta-globin locus control region and SLC4A1 locus in both K562 cells and human induced pluripotent stem cell derived erythroid cells. Introduction of GATA-1 mutations, shown to impair direct interaction with LMO2, significantly diminished chromatin occupancy. On the other hand, knockdown of either SCL/TAL1 or LDB1 also resulted in significantly reduced chromatin occupancy of GATA-1 at endogenous loci, suggesting that impaired assembly of these components also affects GATA-1 chromatin occupancy. In an ex vivo model of erythroid differentiation from CD34(+) cells, LMO2 protein level peaked on day 5 and decreased at later stages of differentiation. The LMO2 expression pattern was similar to those of GATA-1 and SCL/TAL1. Furthermore, shRNA-mediated LMO2 knockdown in primary erythroblasts suggested that LMO2 regulates HBB, HBA, and SLC4A1 expression. LMO2 contributes to GATA-1 target gene expression by affecting assembly of the GATA-SCL/TAL1 complex components at endogenous loci. (C) 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

关键词： CYSTEINE ERYTHROCYTE membranes DNA-binding proteins HEMATOPOIESIS -- Regulation CELL differentiation HEMIN microarray technology

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Gene Expression Profiling on the Molecular Action of Danshen-Gegen Formula in a Randomized Placebo-Controlled Trial of Postmenopausal Women with Hypercholesterolemia

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EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013年第1期2013卷 703705-703705页

作者： Koon, Chi-Man Ko, Chun-Hay Sun, Xu-Xu Hoi, SandyWan-Heng Tam, Jacqueline Chor-Wing Cheung, David Wing-Shing Cheng, King-Fai Pang, Suet-Yee Lo, Wing-Man Chook, Ping Lau, Clara Bik-San Chan, Wai-Yee Leung, Ping-Chung Kwok, Timothy Chi-Yui Fung, Kwok-Pui Chinese Univ Hong Kong Inst Chinese Med Shatin Hong Kong Peoples R China Chinese Univ Hong Kong State Key Lab Phytochem & Plant Resources West Ch Shatin Hong Kong Peoples R China Chinese Univ Hong Kong Sch Biomed Sci Shatin Hong Kong Peoples R China Chinese Univ Hong Kong Dept Med & Therapeut Shatin Hong Kong Peoples R China Chinese Univ Hong Kong Zhejiang Univ Joint Lab Na Shatin Hong Kong Peoples R China

The Danshen-Gegen formula (DG) is a traditional Chinese herbal formula which has long been used to treat cardiovascular disease. DG was found to be a cardiovascular tonic in our recent research. However, a comprehensive investigation of the molecular mechanism of DG in cardiovascular disease has not been performed. The aim of this study was to clarify the transcriptional profiling of genes modulated by DG on postmenopausal women by using DNAmicroarray technology. We obtained 29 whole blood samples both from DG-treated and placebo-treated subjects. Blood lipid profile and intima-media thickness (IMT) were measured. Affymetrix GeneChip was used to identify differentially expressed genes (DEGs), followed by validation by the real-time PCR method. The results showed that DG-treated group has a significant improvement in IMT and lipid profile as compared to placebo-treated group. For the genomic study, the DG-treated group has a higher number of DEGs identified as compared to the placebo-treated group. Two important biological processes of "regulation of systemic arterial blood pressure by hormone" and "regulation of smooth muscle proliferation" have been identified by GePS in the DG-treated group. No significant biological process and cellular components were identified in the placebo-treated group. This genomic study on the molecular action of DG in postmenopausal women gathered sufficient molecular targets and pathways to reveal that DG could improve neointima thickening and hypertension.

关键词： ANALYSIS of variance DNA GENE expression HERBAL medicine CHINESE medicine POLYMERASE chain reaction RESEARCH -- Finance T-test (Statistics) U-statistics GENOMICS RANDOMIZED controlled trials POSTMENOPAUSE DATA analysis -- Software microarray technology DESCRIPTIVE statistics

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Traditional Chinese Medicine Tang-Luo-Ning Ameliorates Sciatic Nerve Injuries in Streptozotocin-Induced Diabetic Rats

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EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013年第1期2013卷 989670-989670页

作者： Zou, Da-Wei Gao, Yan-Bin Zhu, Zhi-Yao Zhou, Hui Zhang, Tao-Jing Li, Bu-Man Wang, Jin-Yang Li, Min-Zhou Ma, Ming-Fei Zhang, Na Capital Med Univ Sch Tradit Chinese Med Beijing 100069 Peoples R China Beijing Univ Chinese Med Oriental Hosp Dept Endocrinol Beijing Peoples R China Peking Univ Shougang Hosp Tradit Chinese Med Dept Beijing 100871 Peoples R China

Diabetic peripheral neuropathy (DPN) is a common microvascular complication of diabetes associated with high disability rate and low quality of life. Tang-Luo-Ning (TLN) is an effective traditional Chinese medicine for the treatment of DPN. To illustrate the underlying neural protection mechanisms of TLN, the effect of TLN on electrophysiology and sciatic nerve morphology was investigated in a model of streptozotocin-induced DPN, as well as the underlying mechanism. Sciatic motor nerve conduction velocity and digital sensory nerve conduction velocity were reduced in DPN and were significantly improved by TLN or alpha-lipoic acid at 10 and 20weeks after streptozotocin injection. It was demonstrated that TLN intervention for 20weeks significantly alleviated pathological injury as well as increased the phosphorylation of ErbB2, Erk, Bad (Ser112), and the mRNA expression of neuregulin 1 (Nrg1), GRB2-associated binding protein 1 (Gab1), and mammalian target of rapamycin (Mtor) in injured sciatic nerve. These novel therapeutic properties of TLN to promote Schwann cell survival may offer a promising alternative medicine for the patients to delay the progression of DPN. The underlying mechanism may be that TLN exerts neural protection effect after sciatic nerve injury through Nrg1/ErbB2 -> Erk/Bad Schwann cell survival signaling pathway.

关键词： SCIATIC nerve WOUNDS & injuries ANALYSIS of variance ANIMAL experimentation APOPTOSIS CELL physiology DIABETIC neuropathies ELECTROPHYSIOLOGY GENE expression HERBAL medicine CHINESE medicine NEURAL conduction RATS RESEARCH -- Finance T-test (Statistics) WESTERN immunoblotting DISEASE progression DATA analysis -- Software microarray technology THERAPEUTICS

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Characteristic Analysis from Excessive to Deficient Syndromes in Hepatocarcinoma Underlying miRNA Array Data

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EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013年第1期2013卷 1-8页

作者： Chen, Qi-Long Lu, Yi-Yu Zhang, Gui-Biao Song, Ya-Nan Zhou, Qian-Mei Zhang, Hui Zhang, Wei Tang, Xin-sheng Su, Shi-Bing Shanghai Univ TCM Res Ctr TCM Complex Syst Shanghai 201203 Peoples R China Huangshan Univ Coll Life & Environm Sci Huangshan 245021 Peoples R China Shanghai Univ TCM Shanghai Longhua Hosp Shanghai 200126 Peoples R China

Traditional Chinese medicine (TCM) treatment is regarded as a safe and effective method for many diseases. In this study, the characteristics among excessive, excessive-deficient, and deficient syndromes of Hepatocellular carcinoma (HCC) were studied using miRNA array data. We first calculated the differentially expressed miRNAs based on random module t-test and classified three TCM syndromes of HCC using SVM method. Then, the weighted miRNA-target networks were constructed for different TCM syndromes using predicted miRNA targets. Subsequently, the prioritized target genes of upexpression network of TCM syndromes were analyzed using DAVID online analysis. The results showed that there are distinctly different hierarchical cluster and network structure of TCM syndromes in HCC, but the excessive-deficient combination syndrome is extrinsically close to deficient syndrome. GO and pathway analysis revealed that the molecular mechanisms of excessive-deficient and deficient syndromes of HCC are more complex than excessive syndrome. Furthermore, although excessive-deficient and deficient syndromes have similar complex mechanisms, excessive-deficient syndrome is more involved than deficient syndrome in development of cancer process. This study suggested that miRNAs might be important mediators involved in the changing process from excessive to deficient syndromes and could be potential molecular markers for the diagnosis of TCM syndromes in HCC.

关键词： HEPATOMA DIAGNOSIS RNA -- Analysis ALTERNATIVE medicine COMPARATIVE studies CHINESE medicine RESEARCH -- Finance SYNDROMES T-test (Statistics) microarray technology DESCRIPTIVE statistics

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Systemic Revealing Pharmacological Signalling Pathway Networks in the Hippocampus of Ischaemia-Reperfusion Mice Treated with Baicalin

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EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013年第1期2013卷 1-11页

作者： Li, Haixia Zhang, Yingying Yu, Yanan Li, Bing Chen, YinYing Wu, Hongli Wang, Jingtao Li, Jun Xiong, Xingjiang He, Qiongyong Tian, Jinzhou Wang, Zhong Wang, Jie China Acad Chinese Med Sci Guanganmen Hosp Dept Cardiol Beijing 100053 Peoples R China China Acad Chinese Med Sci Inst Basic Res Clin Med Beijing 100700 Peoples R China Beijing Univ Chinese Med Dongzhimen Hosp Geriatr Dept Beijing 100007 Peoples R China

Background. Baicalin (BA) exhibits ill understood neuroprotective, anti-inflammatory, and antioxidative effects in brain injury. Objective. To identify the differential network pathways associated with BA-related biological effects. Methods. MCAO-induced mice received BA 5mg/Kg (BA group). Controls received vehicle only. Following ischaemia-reperfusion, ArrayTrack analysed the whole genome microarray of hippocampal genes, and MetaCore analysed differentially expressed genes. Results. Four reversing pathways were common to BA and controls, but only 6 were in the top 10 for BA. Three of the top 5 signalling pathways in controls were not observed in BA. BA treatment made absent 3 pathways of the top 5 signalling pathways from the top 5 in controls. There were 2 reversing pathways between controls and BA that showed altered gene expression. Controls had 6 networks associated with cerebral ischaemia. After BA treatment, 9 networks were associated with cerebral ischaemia. Enrichment analysis identified 10 significant biological processes in BA and controls. Of the 10 most significant molecular functions, 7 were common to BA and controls, and only 3 occurred in BA. BA and controls had 7 significant cellular components. Conclusions. This study showed that the clinical effectiveness of BA was based on the complementary effects of multiple pathways and networks.

关键词： ANIMAL experimentation APOPTOSIS CEREBRAL ischemia FISHER exact test FLAVONOIDS HIPPOCAMPUS (Brain) INJECTIONS MICE REPERFUSION injury RESEARCH -- Finance DATA analysis -- Software microarray technology

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Integration of Different "-omics" Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells

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EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013年第1期2013卷 1-11页

作者： Wiench, Benjamin Chen, Yet-Ran Paulsen, Malte Hamm, Rebecca Schroeder, Sven Yang, Ning-Sun Efferth, Thomas Johannes Gutenberg Univ Mainz Dept Pharmaceut Biol Inst Pharm & Biochem D-55128 Mainz Germany Acad Sinica Agr Biotechnol Res Ctr Taipei 115 Taiwan Inst Mol Biol Cytometry Core Facil D-55128 Mainz Germany Univ Med Ctr Eppendorf HanseMerkur Ctr Tradit Chinese Med D-20246 Hamburg Germany

Hematological malignancies frequently have a poor prognosis and often remain incurable. Drug resistance, severe side effects, and relapse are major problems of currently used drugs, and new candidate compounds are required for improvement of therapy success. The naphthoquinone shikonin derived from the Chinese medicinal herb, Lithospermum erythrorhizon, is a promising candidate for the next generation of chemotherapy. The basal cellular mechanism of shikonin is the direct targeting of mitochondria. Cytotoxicity screenings showed that the compound is particularly effective against leukemia cells suggesting an additional cellular mechanism. mRNA and miRNA microarrays were used to analyze changes in gene expression in leukemia cells after shikonin treatment and combined with stable-isotope dimethyl labeling for quantitative proteomics. The integration of bioinformatics and the three "-omics" assays showed that the PI3K-Akt-mTOR pathway was affected by shikonin. Deregulations of this pathway are frequently associated with cancerogenesis, especially in a wide range of hematological malignancies. The effect on the PI3K-Akt-mTOR axis was validated by demonstrating a decreased phosphorylation of Akt and a direct inhibition of the IGF1R kinase activity after shikonin treatment. Our results indicate that inhibiting the IGF1R-Akt-mTOR signaling cascade is a new cellular mechanism of shikonin strengthening its potential for the treatment of hematological malignancies.

关键词： BIOLOGICAL assay CELL lines HERBAL medicine LEUKEMIA MEDICINAL plants CHINESE medicine MOLECULAR structure POLYMERASE chain reaction RESEARCH -- Finance TOXICITY testing BIOINFORMATICS microarray technology IN vitro studies

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Ten Years' Research on a Cardiovascular Tonic: A Comprehensive Approach-From Quality Control and Mechanisms of Action to Clinical Trial

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EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013年第1期2013卷 1-6页

作者： Leung, Ping-Chung Koon, Chi-Man Lau, Clara Bik-San Chook, Ping Cheng, William King-Fai Fung, Kwok-Pui Kwok, Timothy Chi-Yui Woo, Kam-Sang Chinese Univ Hong Kong Inst Chinese Med Hong Kong Hong Kong Peoples R China Chinese Univ Hong Kong State Key Lab Phytochem & Plant Resources West Ch Hong Kong Hong Kong Peoples R China Chinese Univ Hong Kong Sch Med Sci Hong Kong Hong Kong Peoples R China Chinese Univ Hong Kong Fac Med Dept Med & Therapeut Hong Kong Hong Kong Peoples R China Chinese Univ Hong Kong Sch Life Sci Hong Kong Hong Kong Peoples R China Chinese Univ Hong Kong Biochem Programme Sch Life Sci Hong Kong Hong Kong Peoples R China

Objective. Mortality arising from cardiovascular pathologies remains one of the highest. Maintenance of cardiovascular health therefore remains a universal concern. Interventional therapies and medications have made impressive advances, but preventive measures would be of the same importance. Method. Ten years' search for a simple herbal formula has resulted in a two-herb combination, consisting of Salviae Miltiorrhizae Radix et Rhizoma and Puerariae Lobatae Radix. The formula has been studied extensively on cardiovascular biological platforms and then put on three clinical trials. Results. In the laboratory, the formula was found to have the biological effects of anti-inflammation, anti-oxidation, anti-foam cell formation on vascular endothelium, and vasodilation. Clinical trials using ultrasonic carotid intima thickness as a surrogate marker showed very significant benefits. No significant adverse effects were encountered. Conclusion. It is therefore recommended that the herbal formula could be used as an adjuvant therapy in cardiac patients under treatment or as a preventive agent among the susceptible.

关键词： ATHEROSCLEROSIS -- Prevention BLOOD-vessels -- Physiology CARDIOVASCULAR diseases -- Prevention ENDOTHELIUM -- Physiology HYPERTENSION -- Prevention PROTEIN metabolism PLANT extracts BRACHIAL artery PHYSIOLOGY DOSAGE forms of drugs METHODOLOGY ALTERNATIVE medicine ANIMAL experimentation ANTI-inflammatory agents ANTIOXIDANTS BIOLOGICAL assay BIOLOGICAL models BIOPHYSICS VASODILATION CLINICAL trials CYTOKINES DRUGS -- Toxicology ENZYME-linked immunosorbent assay GENES HEART beat HYPERCHOLESTEREMIA LONGITUDINAL method MACROPHAGES DRUG-herb interactions RESEARCH -- Methodology BOTANIC medicine MICE MYOCARDIUM NITRIC oxide POLYMERASE chain reaction QUALITY assurance RATS RESEARCH -- Finance SAMPLING (Statistics) WESTERN immunoblotting DRUG development RANDOMIZED controlled trials BLIND experiment POSTMENOPAUSE REVERSE transcriptase polymerase chain reaction microarray technology DESCRIPTIVE statistics IN vitro studies CAROTID intima-media thickness THERAPEUTIC use

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Expression of SET Protein in the Ovaries of Patients with Polycystic Ovary Syndrome

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INTERNATIONAL JOURNAL OF ENDOCRINOLOGY 2013年第unknown期2013卷 367956-367956页

作者： Xu Boqun Dai Xiaonan Cui YuGui Gao Lingling Dai Xue Chao Gao Diao Feiyang Liu Jiayin Li Gao Mei Li Yuan Zhang Xiang Ma Nanjing Med Univ Affiliated Hosp 1 Clin Ctr Reprod Med State Lab Reprod Med Nanjing 210029 Jiangsu Peoples R China Nanjing Med Univ Affiliated Hosp 2 Dept Obstet & Gynecol Nanjing 210011 Jiangsu Peoples R China Nanjing Med Univ Affiliated Hosp 1 Nanjing Peoples R China

Background. We previously found that expression of SET gene was up-regulated in polycystic ovaries by using microarray. It suggested that SET may be an attractive candidate regulator involved in the pathophysiology of polycystic ovary syndrome (PCOS). In this study, expression and cellular localization of SET protein were investigated in human polycystic and normal ovaries. Method. Ovarian tissues, six normal ovaries and six polycystic ovaries, were collected during transsexual operation and surgical treatment with the signed consent form. The cellular localization of SET protein was observed by immunohistochemistry. The expression levels of SET protein were analyzed by Western Blot. Result. SET protein was expressed predominantly in the theca cells and oocytes of human ovarian follicles in both PCOS ovarian tissues and normal ovarian tissues. The level of SET protein expression in polycystic ovaries was triple higher than that in normal ovaries (P < 0.05). Conclusion. SET was overexpressed in polycystic ovaries more than that in normal ovaries. Combined with its localization in theca cells, SET may participate in regulating ovarian androgen biosynthesis and the pathophysiology of hyperandrogenism in PCOS.

关键词： PROTEIN expression POLYCYSTIC ovary syndrome PATIENTS microarray technology PATHOLOGICAL physiology HYPERANDROGENISM IMMUNOHISTOCHEMISTRY

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