First Per-6-<i>O</i>-tritylation of Cyclodextrins

Because of the large dimension of the trityl group and the truncated conical geometry of cyclodextrin (CD) molecules, it is unclear if there is enough space at the narrower end of CDs to permit a per-6-<i>O</i>-tritylation. This work demonstrates that it is indeed possible to simultaneously install a trityl group at the O6-position of every glucopyranosyl unit in a CD. A novel per-6-substitution method has been developed for CD chemistry

Effect of PM_2.5 exposure on macrophages and neutrophils in bronchoalveolar lavage fluid (BALF).

<p>Flow cytometric analysis of F4/80 (A) or Ly6G (B) in the BALF. N = 6.</p

Primers Used for Real-time PCR.

<p>Primers Used for Real-time PCR.</p

Effect of PM_2.5 exposure on gene expression for macrophage phenotypic changes in visceral adipose tissue.

<p>(A), <i>IL-6</i>, (B) <i>Nos2</i>, (C) <i>TNF-α</i>, (D) <i>Arg-1</i>, (E) <i>IL-10</i>. Open bars represent FA group, and solid bars represent PM_2.5 group. N = 6. *<i>P</i><0.05.</p

Effect of PM_2.5 exposure on chemotactic migration.

<p>Chemotactic migration of macrophages (A) and neutrophils (B). N = 6. ***<i>P</i><0.0001 vs. FA group.</p

Additional file 1: Table S1. of Particulate Air pollution mediated effects on insulin resistance in mice are independent of CCR2

Elemental composition of PM2.5 in OASIS, Columbus, OH. Table S2. 179 inflammation-related genes and 6 internal reference genes for nanoString. (DOCX 32 kb

Effect of PM_2.5 exposure on systemic inflammation in microvasculature measured by intravital microscopy.

<p>Leukocyte adhesion (A) and rolling flux (B) in mesenteric circulation. N = 6. *<i>P</i><0.05, **<i>P</i><0.001.</p

Effect of PM_2.5 exposure on inflammatory cytokines in circulation.

<p>(A) MCP-1, (B) TNF-α, (C) IL-12p70. N = 6. *<i>P</i><0.05.</p

Effect of PM_2.5 exposure on macrophages and neutrophils in the lung and visceral adipose tissue.

<p>Representative images (A) and statistical analysis (B) of the immunohistochemical staining for F4/80⁺ of macrophages in the lung. Statistical analysis of the immunohistochemical staining for neutrophils (NIMP-R14⁺) in the lung (C) and F4/80⁺ of macrophages in the epididymal adipose tissue (D). Arrows point to positive staining. Scale bar, 100 µm. N = 6. WAT, white adipose tissue. *<i>P</i><0.05, **<i>P</i><0.001.</p

Novel Carvedilol Analogues That Suppress Store-Overload-Induced Ca²⁺ Release

Carvedilol is a uniquely effective drug for the treatment of cardiac arrhythmias in patients with heart failure. This activity is in part because of its ability to inhibit store-overload-induced calcium release (SOICR) through the RyR2 channel. We describe the synthesis, characterization, and bioassay of ca. 100 compounds based on the carvedilol motif to identify features that correlate with and optimize SOICR inhibition. A single-cell bioassay was employed on the basis of the RyR2-R4496C mutant HEK-293 cell line in which calcium release from the endoplasmic reticulum through the defective channel was measured. IC₅₀ values for SOICR inhibition were thus obtained. The compounds investigated contained modifications to the three principal subunits of carvedilol, including the carbazole and catechol moieties, as well as the linker chain containing the β-amino alcohol functionality. The SAR results indicate that significant alterations are tolerated in each of the three subunits