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81.
Anand P Kunnumakkara AB Harikumar KB Ahn KS Badmaev V Aggarwal BB 《Cancer research》2008,68(21):8861-8870
Picroliv, an iridoid glycoside derived from the plant Picrorhiza kurroa, is used traditionally to treat fever, asthma, hepatitis, and other inflammatory conditions. However, the exact mechanism of its therapeutic action is still unknown. Because nuclear factor-kappaB (NF-kappaB) activation plays a major role in inflammation and carcinogenesis, we postulated that picroliv must interfere with this pathway by inhibiting the activation of NF-kappaB-mediated signal cascade. Electrophoretic mobility shift assay showed that pretreatment with picroliv abrogated tumor necrosis factor (TNF)-induced activation of NF-kappaB. The glycoside also inhibited NF-kappaB activated by carcinogenic and inflammatory agents, such as cigarette smoke condensate, phorbol 12-myristate 13-acetate, okadaic acid, hydrogen peroxide, lipopolysaccharide, and epidermal growth factor. When examined for the mechanism of action, we found that picroliv inhibited activation of IkappaBalpha kinase, leading to inhibition of phosphorylation and degradation of IkappaBalpha. It also inhibited phosphorylation and nuclear translocation of p65. Further studies revealed that picroliv directly inhibits the binding of p65 to DNA, which was reversed by the treatment with reducing agents, suggesting a role for a cysteine residue in interaction with picroliv. Mutation of Cys(38) in p65 to serine abolished this effect of picroliv. NF-kappaB inhibition by picroliv leads to suppression of NF-kappaB-regulated proteins, including those linked with cell survival (inhibitor of apoptosis protein 1, Bcl-2, Bcl-xL, survivin, and TNF receptor-associated factor 2), proliferation (cyclin D1 and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (intercellular adhesion molecule-1 and matrix metalloproteinase-9). Suppression of these proteins enhanced apoptosis induced by TNF. Overall, our results show that picroliv inhibits the NF-kappaB activation pathway, which may explain its anti-inflammatory and anticarcinogenic effects. 相似文献
82.
Rajaraman P Bhatti P Doody MM Simon SL Weinstock RM Linet MS Rosenstein M Stovall M Alexander BH Preston DL Sigurdson AJ 《International journal of cancer. Journal international du cancer》2008,123(11):2713-2716
Exposure to ionizing radiation has been consistently associated with increased risk of female breast cancer. Although the majority of DNA damage caused by ionizing radiation is corrected by the base-excision repair pathway, certain types of multiple-base damage can only be repaired through the nucleotide excision repair pathway. In a nested case-control study of breast cancer in US radiologic technologists exposed to low levels of ionizing radiation (858 cases, 1,083 controls), we examined whether risk of breast cancer conferred by radiation was modified by nucleotide excision gene polymorphisms ERCC2 (XPD) rs13181, ERCC4 (XPF) rs1800067 and rs1800124, ERCC5 (XPG) rs1047769 and rs17655; and ERCC6 rs2228526. Of the 6 ERCC variants examined, only ERCC5 rs17655 showed a borderline main effect association with breast cancer risk (OR(GC) = 1.1, OR(CC) = 1.3; p-trend = 0.08), with some indication that individuals carrying the C allele variant were more susceptible to the effects of occupational radiation (EOR/Gy(GG) = 1.0, 95% CI = <0, 6.0; EOR/Gy(GC/CC) = 5.9, 95% CI = 0.9, 14.4; p(het) = 0.10). ERCC2 rs13181, although not associated with breast cancer risk overall, statistically significantly modified the effect of occupational radiation dose on risk of breast cancer (EOR/Gy(AA) = 9.1, 95% CI = 2.1-21.3; EOR/Gy(AC/CC) = 0.6, 95% CI = <0, 4.6; p(het) = 0.01). These results suggest that common variants in nucleotide excision repair genes may modify the association between occupational radiation exposure and breast cancer risk. 相似文献
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Suresh Rao Kemundel Genny Preetha Elangovan Nandkishore Kapadia Balakrishnan Komarakshi Rajagopalan 《Indian Journal of Thoracic and Cardiovascular Surgery》2013,29(1):22-25
A case of Posterior Reversible Encephalopathy Syndrome is reported in a child following surgery under cardio pulmonary bypass. This syndrome is described as a neurotoxic state with a unique imaging appearance which involves the posterior regions of the brain but resolves completely leaving no residual symptoms. Relevant literature is briefly reviewed. The pathogenesis of the syndrome with cardiopulmonary bypass as a potential risk factor for this condition is described. 相似文献
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Shui-Hua Wang Preetha Phillips Yuxiu Sui Bin Liu Ming Yang Hong Cheng 《Journal of medical systems》2018,42(5):85
Alzheimer’s disease (AD) is a progressive brain disease. The goal of this study is to provide a new computer-vision based technique to detect it in an efficient way. The brain-imaging data of 98 AD patients and 98 healthy controls was collected using data augmentation method. Then, convolutional neural network (CNN) was used, CNN is the most successful tool in deep learning. An 8-layer CNN was created with optimal structure obtained by experiences. Three activation functions (AFs): sigmoid, rectified linear unit (ReLU), and leaky ReLU. The three pooling-functions were also tested: average pooling, max pooling, and stochastic pooling. The numerical experiments demonstrated that leaky ReLU and max pooling gave the greatest result in terms of performance. It achieved a sensitivity of 97.96%, a specificity of 97.35%, and an accuracy of 97.65%, respectively. In addition, the proposed approach was compared with eight state-of-the-art approaches. The method increased the classification accuracy by approximately 5% compared to state-of-the-art methods. 相似文献
88.
Sandrine Major CEGEP Anas El Fathi MScA Emilie Palisaitis MEng Robert Kearney PhD Julia E. Von Oettingen MD Preetha Krishnamoorthy MD Laurent Legault MD Ahmad Haidar PhD 《Diabetes, obesity & metabolism》2020,22(8):1474-1477
Conventional bolus calculators apply negative prandial corrections when premeal glucose levels are low. However, no study has evaluated the need for this negative correction with closed-loop systems. We analysed data retrospectively from a cohort study evaluating a closed-loop artificial pancreas system conducted in a diabetes camp over a period of 11 days. Meal boluses with negative correction (n = 98) of 47 participants aged 8 to 22 years were examined. If there was no insulin-on-board from previous boluses at mealtime, the postprandial hyperglycaemia rate increased with increased duration of insulin suspension (P = .03), with odds ratios being exaggerated by 17% per 10 minutes of suspension. However, if there was insulin-on-board from previous boluses, the hyperglycaemia rate did not change with increased duration of insulin suspension (P = .24). When there was no insulin-on-board, the rate of hyperglycaemia after meals preceded by no suspension was 21% (3/14), compared with 52% (12/23) and 64% (9/14) after meals preceded by suspensions of ≥50 and ≥70 minutes, respectively. Meal size did not influence these results. We conclude that, in the absence of insulin-on-board, negative prandial corrections may not be necessary following long insulin suspensions. 相似文献
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