Norepinephrine inhibits the cytotoxicity of NK92­MI cells via the ß2­adrenoceptor/cAMP/PKA/p­CREB signaling pathway.

Norepinephrine (NE) can regulate natural killer (NK) cell activity, but the mechanism remains unclear. In the present study the roles of adrenergic receptors (ARs) in inhibiting NK92­MI cells­mediated cytotoxicity by NE were investigated. To examine the effect of NE on NK92­MI cytotoxicity, a lactate dehydrogenase­release cytotoxicity assay was used to determine the cytotoxicity of NK92­MI cells against K562 cells. To evaluate the possible function of the α, ß1 and ß2 AR in mediating NE­induced effects, NK92­MI cells were pre­incubated with phenol­amine, CGP20712A and ICI118551 prior to stimulation by NE. To evaluate the role of cyclic adenosine monophosphate (cAMP)­protein kinase A (PKA) signaling pathway in the inhibitory effect on cytotoxicity of NK92­MI cell by NE, NK92­MI cells were pre­incubated with PKA inhibitor Rp­8­Br­cAMP prior to stimulation by NE. It was demonstrated that NE decreased cytotoxicity and downregulated the expression of perforin, granzyme B and interferon (IFN)­Î³ of NK92­MI cells in a dose­dependent manner. Blocking NE functional receptors by ARs antagonists, particularly of ß2 AR antagonist, suppressed the inhibitory effect of NE on cytotoxicity and expression of perforin, granzyme B, IFN­Î³ of NK92­MI cells significantly. Blockade of ß2 AR in NE treated NK92­MI cells resulted in a reduction of the expression of phosphorylated (p)­cAMP­responsive element­binding protein (CREB) and intracellular cAMP concentration. Inhibiting the activity of PKA by Rp­8­Br­cAMP in NE treated NK92­MI cells resulted in increased cytotoxicity. The results of the present study suggest that NE can inhibit cytotoxicity and expression of perforin, granzyme B, IFN­Î³ of NK92­MI cell mainly via the ß2­AR/cAMP/PKA/p­CREB signaling pathway.

A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population.

Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer.

Aqua-[1-(pyrazin-2-yl)ethanone oximato-κ²N,N'][1-(pyrazin-2-yl)ethanone oxime-κ²N,N'](thio-cyanato-κN)nickel(II).

In the title complex, [Ni(C6H6N3O)(NCS)(C6H7N3O)(H2O)] or [Ni(mpko)(SCN)(mpkoH)(H2O)] [where mpkoH = 1-(pyrazin-2-yl)ethanone oxime], the Ni(II) cation is in a slightly distorted octa-hedral geometry, being coordinated in the equatorial plane by four N atoms from two different mpkoH ligands, one of which is deprotonated, and by one N atom from a thio-cyanate anion and one O atom from a water mol-ecule in the axial positions. There is an intra-molecular O-H⋯O hydrogen bond involving the oxime units of the two ligands. In the crystal, a three-dimensional supra-molecular architecture is formed by O-H⋯O and O-H⋯N hydrogen bonds.

[The OmpA-like protein Loa22 from Leptospira interrogans serovar lai induces apoptosis in A549 via Ca2+ signal pathway].

OBJECTIVE: To study the effect of Loa22 mature peptide on the apoptosis of A549 to explore the mechanism of pulmonary impairment in severe forms of leptospirosis. METHODS: Loa22 mature peptide (100 microg/mL) was administered to culture with human lung adenocarcinoma cell line (A549). After 24 hours, the apoptosis, the concentration of calcium of the cells were evaluated. The F-actin cytoskeleton structure was observed and calmdulin (CaM) mRNA expression was also detected. At the same time, after the pretreatment of A549 with PLC specific inhibitor U73122, adding an appropriate amount of mature peptide of Loa22 to act on the cells for a period of time, then detection same index. RESULTS: Loa22 mature peptide could induce the increase of intracellular Ca2+ concentration ([Ca2+]i), CaM expression in mRNA level, the activity of LDH, and cytoskeleton rearrangement of F-actin. But after blocking the signal pathway of PLC, Loa22 mature peptide reduced the increase degree of [Ca2+]i, apoptosis rate, the expression of CaM mRNA, the activity of LDH compared with the unblocked group. CONCLUSION: These data suggest that Loa22 mature peptide involves in the pathological processes of L. interrogans invasion and increase apoptosis in A549 by increase of [Ca2+]i through signaling pathway of PLC.