Close Functional Coupling Between Ca(2+) Release-Activated Ca(2+) Channels and Reactive Oxygen Species Production in Murine Macrophages

Aim. To investigate the role of Ca(2+) release-activated Ca(2+) (CRAC) channels in the ROS production in macrophages. Methods. The intracellular [Ca(2+)](i) was analyzed by confocal laser microscopy. The production of ROS was assayed by flow cytometry. Results. Both LPS and thapsigargin induced an increase in intracellular [Ca(2+)](i), either in the presence or absence of extracellular Ca(2+) in murine macrophages. The Ca(2+) signal was sustained in the presence of external Ca(2+) and only initiated a mild and transient rise in the absence of external Ca(2+). CRAC channel inhibitor 2-APB completely suppressed the Ca(2+) entry signal evoked by thapsigargin, and suppressed approximately 93% of the Ca(2+) entry signal evoked by LPS. The increase in intracellular [Ca(2+)](i) was associated with increased ROS production, which was completely abolished in the absence of extracellular Ca(2+) or in the presence of CRAC channel inhibitors 2-APB and Gd(3+). The mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxy-phenylhydrazone and the inhibitor of the electron transport chain, antimycin, evoked a marked increase in ROS production and completely inhibited thapsigargin and LPS-evoked responses. Conclusions. These findings indicate that the LPS-induced intracellular [Ca(2+)](i) increase depends on the Ca(2+) entry through CRAC channels, and close functional coupling between CRAC and ROS production in murine macrophages

Polymorphisms of −174G>C and −572G>C in the Interleukin 6 (IL-6) Gene and Coronary Heart Disease Risk: A Meta-Analysis of 27 Research Studies

OBJECTIVE: Elevated serum IL-6 level is a risk factor for coronary heart disease (CHD). The -174 G>C and -572 G>C polymorphisms in the IL-6 gene have previously been shown to modulate IL-6 levels. But the association between the -174 G>C and -572 G>C polymorphisms and the risk of CHD is still unclear. A meta-analysis of all eligible studies was carried out to clarify the role of IL-6 gene polymorphisms in CHD. METHODS AND RESULTS: PubMed, EMBASE, Vip, CNKI and CBM-disc were searched for eligible articles in English and Chinese that were published before October 2010. 27 studies involving 11580 patients with CHD and 17103 controls were included. A meta-analysis was performed for the included articles using the RevMan 5.0 and Stata 10.0 softwares. Overall, the -174 C allele was not significantly associated with CHD risk (ORs = 1.04, 95%CI = 0.98 to 1.10) when compared with the -174 G allele in the additive model, and meta-analysis under other genetic models (dominant, recessive, CC versus GG, and GC versus GG) also did not reveal any significant association. On the contrary, the -572 C allele was associated with a decreased risk of CHD when compared with the -572 G allele (ORs = 0.79, 95%CI = 0.68 to 0.93). Furthermore, analyses under the recessive model (ORs = 0.69, 95% = 0.59 to 0.80) and the allele contrast model (genotype of CC versus GG, ORs = 0.49, 95% = 0.35 to 0.70) yielded similar results. However, statistical significance was not found when the meta-analysis was restricted to studies focusing on European populations, studies with large sample size, and cohort studies by using subgroup analysis. CONCLUSIONS: The -174 G>C polymorphism in the IL-6 gene is not significantly associated with increased risks of CHD. However, The -572 G>C polymorphism may contribute to CHD development. Future investigations with better study design and large number of subjects are needed

Cu(II)-Mediated C–H Amidation and Amination of Arenes: Exceptional Compatibility with Heterocycles

A Cu­(OAc)₂-mediated C–H amidation and amination of arenes and heteroarenes has been developed using a readily removable directing group. A wide range of sulfonamides, amides, and anilines function as amine donors in this reaction. Heterocycles present in both reactants are tolerated, making this a broadly applicable method for the synthesis of a family of inhibitors including 2-benzamidobenzoic acids and <i>N</i>-phenylaminobenzoates

Cu(OAc)₂‑Catalyzed Coupling of Aromatic C–H Bonds with Arylboron Reagents

Cu-catalyzed coupling of aryl C–H bonds with arylboron reagents was accomplished using a readily removable directing group, which provides a useful method for the synthesis of biaryl compounds. The distinct transmetalation step in this Cu-catalyzed C–H coupling with aryl borons provides unique evidence for the formation of an aryl cupperate intermediate

Begg's funnel plot with pseudo 95% confidence limit under the additive genetic model of −572G>C genotype.

<p>The size of the circle is proportional to the weight of the study.</p

ORs and 95% CI for coronary heart disease and the −174G>C, −572 G>C polymorphism in IL-6 gene under various genetic models.

<p>ORs and 95% CI for coronary heart disease and the −174G>C, −572 G>C polymorphism in IL-6 gene under various genetic models.</p

Begg's funnel plot with pseudo 95% confidence limit under the additive genetic model of −174G>C genotype.

<p>The size of the circle is proportional to the weight of the study.</p

Studies of the −174G>C polymorphism in IL-6 gene and risk of coronary heart disease under additive model grouped by study characteristics.

<p>Studies of the −174G>C polymorphism in IL-6 gene and risk of coronary heart disease under additive model grouped by study characteristics.</p