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Association of Bone Metabolic Markers With Diabetic Retinopathy and Diabetic Macular Edema in Elderly Chinese Individuals With Type 2 Diabetes Mellitus.
Zhang, X, Yang, J, Zhong, Y, Xu, L, Wang, O, Huang, P, Li, C, Qu, B, Wang, J, Zheng, C, et al
The American journal of the medical sciences. 2017;(4):355-361
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Abstract
BACKGROUND Diabetic retinopathy (DR) is a common and specific microvascular complication of diabetes. The association of bone metabolic markers with the risk of DR and diabetic macular edema (DME) is unclear. MATERIALS AND METHODS We investigated the association between bone turnover markers commonly examined in a clinical setting and DR and DME risk in elderly Chinese patients with type 2 diabetes mellitus (T2DM). A total of 408 patients aged 55-70 years with T2DM were included. We first performed univariable logistic regression followed by multivariable logistic regression that included variables selected using purposeful selection. RESULTS Fasting blood glucose (P = 0.007) and duration of diabetes (P < 0.0001) were significantly associated with DME in multivariable logistic regression; however, the association of beta C-terminal telopeptide of collagen type I (β-CTx) with DME risk was not statistically significant (P = 0.053). Sex-stratified analysis showed that β-CTx was significantly associated with DME only in female subjects (P = 0.011). CONCLUSIONS β-CTx had no significant association with DR. It was significantly associated with DME in female patients with T2DM, but not in male patients with T2DM. More prospective studies with larger sample sizes are warranted to validate our findings.
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Exenatide exerts direct protective effects on endothelial cells through the AMPK/Akt/eNOS pathway in a GLP-1 receptor-dependent manner.
Wei, R, Ma, S, Wang, C, Ke, J, Yang, J, Li, W, Liu, Y, Hou, W, Feng, X, Wang, G, et al
American journal of physiology. Endocrinology and metabolism. 2016;(11):E947-57
Abstract
Glucagon-like peptide-1 (GLP-1) may have direct favorable effects on cardiovascular system. The aim of this study was to investigate the effects of the GLP-1 analog exenatide on improving coronary endothelial function in patients with type 2 diabetes and to investigate the underlying mechanisms. The newly diagnosed type 2 diabetic subjects were enrolled and given either lifestyle intervention or lifestyle intervention plus exenatide treatment. After 12-wk treatment, coronary flow velocity reserve (CFVR), an important indicator of coronary endothelial function, was improved significantly, and serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were remarkably decreased in the exenatide treatment group compared with the baseline and the control group. Notably, CFVR was correlated inversely with hemoglobin A1c (Hb A1c) and positively with high-density lipoprotein cholesterol (HDL-C). In human umbilical vein endothelial cells, exendin-4 (a form of exenatide) significantly increased NO production, endothelial NO synthase (eNOS) phosphorylation, and GTP cyclohydrolase 1 (GTPCH1) level in a dose-dependent manner. The GLP-1 receptor (GLP-1R) antagonist exendin (9-39) or GLP-1R siRNA, adenylyl cyclase inhibitor SQ-22536, AMPK inhibitor compound C, and PI3K inhibitor LY-294002 abolished the effects of exendin-4. Furthermore, exendin-4 reversed homocysteine-induced endothelial dysfunction by decreasing sICAM-1 and reactive oxygen species (ROS) levels and upregulating NO production and eNOS phosphorylation. Likewise, exendin (9-39) diminished the protective effects of exendin-4 on the homocysteine-induced endothelial dysfunction. In conclusion, exenatide significantly improves coronary endothelial function in patients with newly diagnosed type 2 diabetes. The effect may be mediated through activation of AMPK/PI3K-Akt/eNOS pathway via a GLP-1R/cAMP-dependent mechanism.
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Proteogenomic Analysis of Trichophyton rubrum Aided by RNA Sequencing.
Xu, X, Liu, T, Ren, X, Liu, B, Yang, J, Chen, L, Wei, C, Zheng, J, Dong, J, Sun, L, et al
Journal of proteome research. 2015;(5):2207-18
Abstract
Infections caused by dermatophytes, Trichophyton rubrum in particular, are among the most common diseases in humans. In this study, we present a proteogenomic analysis of T. rubrum based on whole-genome proteomics and RNA-Seq studies. We confirmed 4291 expressed proteins in T. rubrum and validated their annotated gene structures based on 35 874 supporting peptides. In addition, we identified 323 novel peptides (not present in the current annotated protein database of T. rubrum) that can be used to enhance current T. rubrum annotations. A total of 104 predicted genes supported by novel peptides were identified, and 127 gene models suggested by the novel peptides that conflicted with existing annotations were manually assigned based on transcriptomic evidence. RNA-Seq confirmed the validity of 95% of the total peptides. Our study provides evidence that confirms and improves the genome annotation of T. rubrum and represents the first survey of T. rubrum genome annotations based on experimental evidence. Additionally, our integrated proteomics and multisourced transcriptomics approach provides stronger evidence for annotation refinement than proteomic data alone, which helps to address the dilemma of one-hit wonders (uncertainties supported by only one peptide).
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Novel decapeptides that bind avidly and deliver radioisotope to colon cancer cells.
Abraham, JM, Sato, F, Cheng, Y, Paun, B, Kan, T, Olaru, A, Jin, Z, Yang, J, Agarwal, R, David, S, et al
PloS one. 2007;(10):e964
Abstract
BACKGROUND The rapidly growing field of targeted tumor therapy often utilizes an antibody, sometimes tagged with a tumor-ablating material such as radioisotope, directed against a specific molecule. METHODOLOGY/PRINCIPAL FINDINGS This report describes the discovery of nine novel decapeptides which can be radioactively labeled, bind to, and deliver (32)P to colon cancer cells. The decapeptides vary from one another by one to three amino acids and demonstrate vastly different binding abilities. The most avidly binding decapeptide can permanently deliver very high levels of radioisotope to the adenocarcinoma cancer cell lines at an efficiency 35 to 150 times greater than to a variety of other cell types, including cell lines derived from other types of cancer or from normal tissue. CONCLUSIONS/SIGNIFICANCE This experimental approach represents a new example of a strategy, termed peptide binding therapy, for the potential treatment of colorectal and other adenocarcinomas.