Study on Effects and Active Ingredients of Tibetan Medicine Lamiophlomis rotata against Rheumatoid Arthritis / 中国药房

OBJECTIVE：To study the effects and active ingr edients of Tibetan medicine Lamiophlomis rotata against rheumatoid arthritis （RA）. METHODS ：Fifty-six SD rats were randomly divided into normal control group （0.5％ sodium carboxymethylcellulose），model group （0.5％ sodium carboxymethylcellulose ），methotrexate group （positive control group ，3 mg/kg），L. rotata water extract low-dose ，medium-dose and high-dose groups （0.5，1，2 g/kg，by crude drug ），L. rotata total flavonoid group （200 mg/kg，by flavonoid extat ），with 8 rats in each group. Except for normal control group ，other groups were given Freund ’s complete adjuvant （FCA）on the rat ’s right hind footpad to induce adjuvant-induced arthritis model. The next day after injection of FCA ，rats in all groups were given relevant medicine intragastrically ，once a day （once every 3 days for methotrexate group ）for 30 days. At 15th and 30th day of administration ，the degree of paw swelling of left hind foot was measured，and the arthritis index ，spleen index were calculated. At the end of 30th day of administration ，the levels of TNF-α，IL-1β， IL-6 and IL- 10 in rat serum were determined by ELISA assay ，the thymus index and spleen index were calculated ，the pathological changes of the ankle joints were observed by HE staining. RESULTS ：Compared with normal control group ，degree of paw swelling，arthritis index at 15th and 30th day of administration as well as the spleen index and the levels of TNF-α，IL-1β， msxmX0146） IL-6 in serum at 30th day of administration were significantly com increased in model group （P＜0.01）；while the thymus indexyunbinji- and IL- 10 level at 30th day of administration were ang@swu.edu.cn significantly decreased（P＜0.01）；synovial cell proliferation and infiltration of articular cavity were observed in ankle joint. Compared with model group ，degree of paw swelling ，arthritis index at 15th and 30th day of administration as well as the spleen index and the levels of TNF-α，IL-1β，IL-6 in serum at 30th day of administration were significantly decreased in each medicine group （P＜0.01）；while the thymus index and IL- 10 level at 30th day of administration were significantly increased （P＜0.01）；the pathological changes of arthritis were significantly improved. Compared with L. rotata water extract high-dose group ，there were no significant differences in degree of paw swelling at 15th day of administration as well as the arthritis index ，spleen index ，levels of inflammatory cytokines and pathological changes of ankle joint in L. rotata total flavonoid group （P＞0.05）. CONCLUSIONS ：Tibetan medicine L. rotata shows well anti-RA activity ，and total flavonoids may be the active ingredients of its efficacy.

Bioinformatic analysis of peripheral blood miRNA of breast cancer patients in relation with anthracycline cardiotoxicity.

BACKGROUND: The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. METHODS: Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the Gene Expression Omnibus (GEO) database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the micro RNAs (miRNAs) regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the Gene Ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. RESULT: The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and Target Scan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain seven cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273 g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. The signaling pathway is mainly concentrated in TGF-ß signaling pathway and adhesion signaling pathway. CONCLUSIONS: Changes in expression of hsa-miR-4638-3p and hsa-miR-1273 g-3p may contribute to the detection of anthracyclines induced cardiac toxicity, and their potential function may be related to TGF-ß signaling pathway and adhesion signaling pathway.

Expression of EGFR and hER-2 in colorectal carcinoma and their clinical significance / 临床与实验病理学杂志

Purpose To exp1ore the expression and c1inica1 significance of epiderma1 growth factor receptor( EGFR)and human epi-derma1 receptor-2(HER-2)in co1orecta1 carcinoma. Methods Immunohistochemistry(IHC)PV-9000 was used to detect the expres-sion of EGFR and HER-2 in 78 cases of co1orecta1 carcinoma. Si1ver in situ hybridization( SISH)was used to detect HER-2 amp1ifica-tion in co1orecta1 carcinoma. Results The positive rates of EGFR in 78 co1orecta1 carcinomas were 69. 23%( 54/78 ). The differ-ences of the expression of EGFR between different depth of invasion group and 1ymph node metastasis group were statistica11y signifi-cant. The differences of the expression of EGFR between different aging group,gender group,tumor size,different histo1ogica1 grading group and Dukes stage were insignificant. The positive rates of HER-2 in 78 cases of co1orecta1 carcinoma were 25. 64%(20/78). The differences of the expression of HER-2 between different depth of invasion group and 1ymph node metastasis group were statistica11y sig-nificant. The differences of the expression of HER-2 between different aging group,gender group,tumor size,histo1ogica1 grading group and Dukes stage were insignificant. The expression of EGFR and HER-2 was positive1y corre1ated. Among the 20 cases of HER-2 protein overexpression,10 cases showed HER-2 gene amp1ification,15 cases showed HER-2 protein overexpression(~)by IHC and 10 cases showed HER-2 gene amp1ification by SISH. The rate of HER-2 gene amp1ification was 66. 67%. 5 cases with 1ow HER-2 protein overexpression( +)and no case showed HER-2 gene amp1ification. Conclusions EGFR and HER-2 are high1y ex-pressed in co1orecta1 carcinoma. EGFR and HER-2 expression is connected to invasion and metastasis process of co1orecta1 carcinoma. The both may be synergy. The corre1ation between HER-2 protein overexpression(~)and HER-2 gene amp1ification is statisti-ca11y significant. Therefore,immunohistochemistry can be regarded as an initia1 screening method for HER-2 gene amp1ification,and then SISH testing shou1d be done as we11 to confirm the resu1t. It is usefu1 for mo1ecu1ar target therapy to detect HER-2 status in co1or-ecta1 carcinoma.

Effects of acrylonitrile on antioxidant status of different brain regions in rats.

While the adverse effects of acrylonitrile (AN) on the central nervous system (CNS) are known to be mediated, at least in part, by the generation of free radicals and oxidative stress, there is a paucity of data on region-specific alterations in biomarkers of oxidative stress in the brain of AN-exposed animals. The present study was designed to examine the effects of AN on biomarkers of oxidative stress in several brain regions of adult Sprague-Dawley rats. Daily intraperitoneal (i.p.) treatment of animals to 0 (control, normal saline solution), 25, 50 or 75mgAN/kg body weight for 7 days resulted in statistically significant (p<0.05) increases in the levels of lipid peroxidation product, malondialdehyde (MDA), in the cortex and cerebellum; a statistically significant (p<0.05) decrease MDA levels were noted in the striatum. Contents of reduced glutathione (GSH) were significantly (p<0.05) decreased in cortex, cerebellum and hippocampus. The activities of the antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were differentially affected by AN and these effects were brain region-specific and AN dose-dependent. Taken together, these data suggest brain region-specific effects of AN on lipid peroxidation, activities of antioxidant enzymes and non-enzymatic antioxidant levels. These effects may provide biochemical evidence for AN-induced neurobehavioral damage and disturbance of monoamine neurotransmitters.

EFFECTS OF VITAMIN E ON MYOCARDIAL ISCHEMIC REPERFUSION INJURY IN DIABETIC RATS / 营养学报

Objective To observe the effects of vitamin E(VE) on the changes of the intercellular adhesion molecule-1(ICAM-1)and free radicals in ischemic-reperfused myocardium(MIR) of diabetic rats Method The diabetic rat model was established by i.p.streptozotocin injection.Four weeks later,MIR models were established,and 30 rats were divided into three groups with each group 10 rats(sham group,MIR group and VE group).The ICAM-1 protein expressions were evaluated by immunocytochemistry.The contents of malonialdehyde(MDA) in serum and myocardial tissues were detected.The activities of superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) in serum and myocardial tissues were measured.The activities of Na+,K+-ATPase,Mg++-ATPase,Ca++-ATPase in myocardial mitochondria were measured.Results Compared with sham group,the activities of Na+,K+-ATPase,Mg++-ATPase,Ca++-ATPase in myocardial mitochondria were decreased,the contents of MDA in serum and myocardium increased,the levels of SOD and GSH-Px in serum and myocardium decreased,and the levels of ICAM-1 in myocardium increased significantly in MIR group.Compared with MIR group,the activities of Na+,K+-ATPase,Mg++-ATPase in myocardial mitochondria were increased,the levels of MDA in serum andmyocardium decreased the activities of SOD and GSH-Px in serum and myocardium increased,and the levels of ICAM-1 in myocardium decreased significantly in VE group.Conclusion VE could relieve myocardial ischemic reperfusion injury and the damage of lipid peroxidation and free radical induced by MIR in diabetic rats,and this effect was mediated by reduction of the expression of ICAM-1 protein.