Background-We intended to identify proteins that are differentially expressed in human atherosclerotic plaques. Methods and Results-Comparative 2-dimensional electrophoretic analysis on carotid atherosclerotic endarterectomy specimens (nϭ10) revealed that heat shock protein 27 (Hsp27) expression was significantly increased in the nearby normal-appearing area compared with the plaque core area from the same vessel specimen, which was further confirmed by Western blot analysis. The Hsp27 expression in the adjacent normal-appearing vessel areas was much higher than that in nonatherosclerotic reference arteries. The phosphorylation of Hsp27 showed a gradation in the degree of phosphorylation: greatest in the reference arteries, intermediate in the adjacent normal-appearing area, and lowest in plaque core area. Immunohistochemical analysis showed that the phosphorylation of Hsp27 of smooth muscle cells in the carotid endarterectomy specimens was decreased compared with that in the reference artery specimen. The mean plasma level of Hsp27 was significantly higher in patients with acute coronary syndrome (ACS) (nϭ27; 106.1Ϯ74.1 ng/mL) than in the normal reference subjects (nϭ29; 45.8Ϯ29.5 ng/mL; PϽ0.005). The plasma levels of Hsp27 were significantly correlated with those of heat shock protein 70 (Hsp70) (rϭ0.422, PϽ0.0005), with adjustment for ACS/reference status. Conclusions-In the atherosclerotic lesion, Hsp27 expression is increased in the normal-appearing vessel adjacent to atherosclerotic plaque, whereas levels in the plaque itself are significantly decreased. Both plaque and adjacent artery show decreased Hsp27 phosphorylation compared with reference vessel. In ACS, plasma Hsp27 and Hsp70 are increased, and levels of Hsp27 correlate with Hsp70, C-reactive protein, and CD40L levels.
Poly(γ‐benzyl α, L‐glutamate) fibers with high non‐linear optical activity and thermally stable piezoelectricity are fabricated by simple electrospinning methods that apply directional shear force and electric field causing parallel alignment of helical polymer chains and permanent dipoles.
Persistent organic pollutants such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) are of global concern because of their widespread contamination and adverse health effects. Potential endocrine disruption, especially of thyroid status by PCBs has been repeatedly suggested in both experimental and epidemiological studies. However the associations with PBDEs or OCPs have been arguable especially in human populations. We investigated the associations between major groups of POPs and thyroid hormone balances among pregnant women. One hundred five pregnant women at delivery were recruited from four cities of Korea in 2011 and were investigated. Blood samples were collected within a day before delivery. Serum was then analyzed for 19 PCBs, 19 PBDEs, and 19 OCPs, along with five thyroid hormones (free and total T3 and T4, and TSH). Several PCBs such as PCB28, 52, and 118 showed negative associations with T3 or T4. BDE47 and total PBDEs showed significant associations with T3 or T4. For OCPs, dichlorodiphenyltrichloroethanes (DDTs) and hexachlorobenzene (HCB) were generally associated with reduction of T3 or T4. The thyroid hormone levels of all subjects were within the reference range, however exposure to several target POPs were clearly related with potential for disrupting thyroid hormone balance among pregnant women, at the current level of exposure. Although subtle, the changes in thyroid hormones should be seen with caution because even minor changes within pregnant women may have significant consequences especially on sensitive population like fetus.
Systemic lupus erythematosus (SLE) is a chronic multisystemic autoimmune disease with an unknown etiology. Recently, it has been elucidated that dysregulated histone deacetylase (HDAC) activity is related to the pathogenesis of inflammatory and autoimmune diseases. Broad-spectrum HDAC inhibitors are effective for the treatment of allergy, cancer, and autoimmune diseases, but they have several adverse side effects. Thus, the purpose of this study was to evaluate the effects of a novel HDAC 6-specific inhibitor, CKD-506, in a murine SLE model. CKD-506 significantly improved survival rate and significantly decreased the incidence of severe proteinuria, blood urea nitrogen, kidney inflammation, and glomerular infiltration of IgG and C3. In addition, CKD 506 reduced the proportions of CD138+ plasma cells, CD4−CD8− T cells, and CD25+ cells and the Th1/Th2 ratio in the spleen. CKD-506 significantly reduced inflammatory cytokines such as IL-10, IL-15, IL-17, TNF-α, and IFN-inducible protein (IP-10) and significantly increased TGF-β in serum. CKD-506 also significantly reduced IFN-γ, IL-1β, IL-4, IL-6, IP-10, MCP-1, and CCL4 levels in kidney. CKD-506 decreased the production of various pro-inflammatory cytokines and chemokines in the serum and kidneys, resulting in inhibition of cell migration and suppression of lupus nephritis without adverse effects.
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