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281.
282.
Masterjohn C Mah E Guo Y Koo SI Bruno RS 《The Journal of nutritional biochemistry》2012,23(3):292-298
Postprandial hyperglycemia contributes to the risk of cardiovascular disease in part by increasing concentrations of the reactive dicarbonyl methylglyoxal (MGO), a byproduct of glucose metabolism. Oxidative stress increases MGO formation from glucose in vitro and decreases its glutathione-dependent detoxification to lactate. We hypothesized that the antioxidant γ-tocopherol, a form of vitamin E, would decrease hyperglycemia-mediated postprandial increases in plasma MGO in healthy, normoglycemic, college-aged men. Participants (n=12 men; 22.3±1.0 years; 29.3±2.4 kg/m(2)) received an oral dose of glucose (75 g) in the fasted state prior to and following 5-day ingestion of a vitamin E supplement enriched in γ-tocopherol (500 mg/day). γ-Tocopherol supplementation increased (P<.0001) plasma γ-tocopherol from 2.22±0.32 to 7.06±0.71 μmol/l. Baseline MGO concentrations and postprandial hyperglycemic responses were unaffected by γ-tocopherol supplementation (P>.05). Postprandial MGO concentrations increased in the absence of supplemental γ-tocopherol (P<.05), but not following γ-tocopherol supplementation (P>.05). Area under the curve for plasma MGO was significantly (P<.05) smaller with the supplementation of γ-tocopherol than without (area under the curve (0-180 min), -778±1010 vs. 2277±705). Plasma concentrations of γ-carboxyethyl-hydroxychroman, reduced glutathione and markers of total antioxidant capacity increased after supplementation, and these markers and plasma γ-tocopherol were inversely correlated with plasma MGO (r=-0.48 to -0.67, P<.05). These data suggest that short-term supplementation of γ-tocopherol abolishes the oral glucose-mediated increases in postprandial MGO through its direct and indirect antioxidant properties and may reduce hyperglycemia-mediated cardiovascular disease risk. 相似文献
283.
Shkreli M Sarin KY Pech MF Papeta N Chang W Brockman SA Cheung P Lee E Kuhnert F Olson JL Kuo CJ Gharavi AG D'Agati VD Artandi SE 《Nature medicine》2012,18(1):111-119
Mechanisms of epithelial cell renewal remain poorly understood in the mammalian kidney, particularly in the glomerulus, a site of cellular damage in chronic kidney disease. Within the glomerulus, podocytes--differentiated epithelial cells crucial for filtration--are thought to lack substantial capacity for regeneration. Here we show that podocytes rapidly lose differentiation markers and enter the cell cycle in adult mice in which the telomerase protein component TERT is conditionally expressed. Transgenic TERT expression in mice induces marked upregulation of Wnt signaling and disrupts glomerular structure, resulting in a collapsing glomerulopathy resembling those in human disease, including HIV-associated nephropathy (HIVAN). Human and mouse HIVAN kidneys show increased expression of TERT and activation of Wnt signaling, indicating that these are general features of collapsing glomerulopathies. Silencing transgenic TERT expression or inhibiting Wnt signaling through systemic expression of the Wnt inhibitor Dkk1 in either TERT transgenic mice or in a mouse model of HIVAN results in marked normalization of podocytes, including rapid cell-cycle exit, re-expression of differentiation markers and improved filtration barrier function. These data reveal an unexpected capacity of podocytes to reversibly enter the cell cycle, suggest that podocyte renewal may contribute to glomerular homeostasis and implicate the telomerase and Wnt-β-catenin pathways in podocyte proliferation and disease. 相似文献
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287.
Wen-Chi Yin Thevagi Satkunendran Rong Mo Sorana Morrissy Xiaoyun Zhang Eunice Shiao Huang Liis Uusküla-Reimand Huayun Hou Joe Eun Son Weifan Liu Yulu C. Liu Jianing Zhang Jessica Parker Xin Wang Hamza Farooq Hayden Selvadurai Xin Chen Elly Sau-Wai Ngan Chi-chung Hui 《Developmental cell》2019,48(2):167-183.e5
288.
Amit Priyadarshi Yasar Saleem Key-Sun Kim Eunice EunKyeong Kim Kwang Yeon Hwang 《Biochemical and biophysical research communications》2009,380(4):797-751
MenD (2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexadiene-1-carboxylate) synthase belongs to the superfamily of thiamin diphosphate-dependent decarboxylases, which converts isochorismate and 2-oxoglutarate to SHCHC, pyruvate, and carbon dioxide. Here, we report the first crystal structure of apo-MenD from Escherichia coli determined in tetragonal crystal form. The subunit displays the typical three-domain structure observed for ThDP-dependent enzymes. Analytical gel filtration shows that EcMenD behaves as a dimer as well as a tetramer. Circular dichroism and isothermal calorimetry results confirm EcMenD dependency on ThDP, which concomitantly helps to stabilize with better configuration. 相似文献
289.
Drake AS Brady MT Wang XH Sait SJ Earp JC Ghoshal Gupta S Ferrone S Wang ES Wetzler M 《Cancer immunology, immunotherapy : CII》2009,58(3):415-427
Background Acute leukemia with 11q23 aberrations is associated with a poor outcome with therapy. The lack of efficacy of conventional
therapy has stimulated interest in developing novel strategies. Recent studies have shown that 11q23-positive acute leukemia
cells express the high molecular weight-melanoma associated antigen (HMW-MAA). This tumor antigen represents a useful target
to control growth of human melanoma tumors in patients and in severe combined immunodeficient (SCID) mice, utilizing antibody-based
immunotherapy. This effect appears to be mediated by inhibition of the HMW-MAA function such as triggering of the focal adhesion
kinase/proline-rich tyrosine kinase 2 (Pyk2) pathways. Therefore, in this study we tested whether HMW-MAA-specific monoclonal
antibodies (mAb) could inhibit growth of 11q23-positive leukemia cells in SCID mice.
Methods HMW-MAA-specific mAb were tested for their ability to inhibit the in vitro proliferation of an 11q23-positive acute myeloid
leukemia (AML) cell line and blasts from four patients with 11q23 aberrations and their in vivo growth in subcutaneous and
disseminated xenograft models.
Results The HMW-MAA-specific mAb did not affect in vitro proliferation although they down-regulated phosphorylated (P) Pyk2 expression.
Furthermore, the mAb enhanced the in vitro anti-proliferative effect of cytarabine. In vivo the mAb inhibited the growth of
leukemic cells in a dose-dependent fashion. However, the difference did not reach statistical significance. No effect was
detected on P-Pyk2 expression. Furthermore, HMW-MAA-specific mAb in combination with cytarabine did not improve tumor inhibition.
Lastly, the combination of two mAb which recognize distinct HMW-MAA determinants had no detectable effect on survival in a
disseminated xenograft model.
Conclusions HMW-MAA-specific mAb down-regulated P-Pyk2 expression and enhanced the anti-proliferative effect of cytarabine in vitro, but
had no detectable effect on survival or growth of leukemia cells in vivo. Whether the HMW-MAA-specific mAb can be used as
carriers of toxins or chemotherapeutic agents against 11q23-acute leukemia remains to be determined. 相似文献
290.
This review focuses on the recent developments in nanoplasmonic gene regulations. Types of nanoplasmonic carriers and DNA/RNA cargo are described. Strategies to liberate cargo from their carriers using NIR and enable on-demand silencing of endogenous intracellular genes are reviewed. In addition to inhibitory effects, exogenous foreign genes are also introduced and expressed on-demand using nanoplasmonic optical switches. The magnitude and timing of genetic activities can therefore be systematically controlled on-demand remotely. Equipped with new nanoplasmonic optics to directly probe the intracellular space, quantitative approaches should capture many dynamic activities within living systems that were otherwise previously impossible to control using conventional methods. 相似文献