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Macrophages are pivotal effector cells in the innate immune system. When microbial products bind to pathogen recognition receptors, macrophages are activated and release a broad array of mediators, such as cytokines, that orchestrate the inflammatory responses of the host. Phosphatidic acid (PA) has been implicated as an important metabolite of phospholipid biosynthesis and in membrane remodeling and has been further suggested to be a crucial second messenger in various cellular signaling events. Here we show that PA is an essential regulator of inflammatory response. Deleterious effects of PA are associated with the secretion of proinflammatory cytokines, such as tumor necrosis factor-␣, interleukin-1␤, interleukin-6, and the production of nitric oxide, prostaglandin E 2 , which are predominantly released by macrophage Raw264.7 cells. Furthermore, the administration of PA to mice increased the serum cytokine level. Moreover, direct or lipopolysaccharide-induced PA accumulation by macrophages led to the Akt-dependent activation of the mammalian target of rapamycin-p70 S6 kinase 1, a process required for the induction of inflammatory mediators. These findings demonstrate the importance of the role of PA in systemic inflammatory responses, and provide a potential usefulness as specific targets for the development of therapies.

In this study, surface-enhanced Raman spectroscopy (SERS)-encoded magnetic nanoparticles (NPs) are prepared and utilized as a multifunctional tagging material for cancer-cell targeting and separation. First, silver-embedded magnetic NPs are prepared, composed of an 18-nm magnetic core and a 16-nm-thick silica shell with silver NPs formed on the surface. After simple aromatic compounds are adsorbed on the silver-embedded magnetic NPs, they are coated with silica to provide them with chemical and physical stability. The resulting silica-encapsulated magnetic NPs (M-SERS dots) produce strong SERS signals and have magnetic properties. In a model application as a tagging material, the M-SERS dots are successfully utilized for targeting breast-cancer cells (SKBR3) and floating leukemia cells (SP2/O). The targeted cancer cells can be easily separated from the untargeted cells using an external magnetic field. The separated targeted cancer cells exhibit a Raman signal originating from the M-SERS dots. This system proves to be an efficient tool for separating targeted cells. Additionally, the magnetic-field-induced hot spots, which can provide a 1000-times-stronger SERS intensity due to aggregation of the NPs, are studied.

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The induction of inducible NO synthase (iNOS) by group IIA phospholipase A2 (PLA2) involves the stimulation of a novel signaling cascade. In this study, we demonstrate that group IIA PLA2 up-regulates the expression of iNOS through a novel pathway that includes M-type secretory PLA2 receptor (sPLA2R), phosphatidylinositol 3-kinase (PI3K), and Akt. Group IIA PLA2 stimulated iNOS expression and promoted nitrite production in a dose- and time-dependent manner in Raw264.7 cells. Upon treating with group IIA PLA2, Akt is phosphorylated in a PI3K-dependent manner. Pretreatment with LY294002, a PI3K inhibitor, strongly suppressed group IIA PLA2-induced iNOS expression and PI3K/Akt activation. The promoter activity of iNOS was stimulated by group IIA PLA2, and this was suppressed by LY294002. Transfection with Akt cDNA resulted in Akt protein overexpression in Raw264.7 cells and effectively enhanced the group IIA PLA2-induced reporter activity of the iNOS promoter. M-type sPLA2R was highly expressed in Raw264.7 cells. Overexpression of M-type sPLA2R enhanced group IIA PLA2-induced promoter activity and iNOS protein expression, and these effects were abolished by LY294002. However, site-directed mutation in residue responsible for PLA2 catalytic activity markedly reduced their ability to production of nitrites and expression of iNOS. These results suggest that group IIA PLA2 induces nitrite production by involving of M-type sPLA2R, which then mediates signal transduction events that lead to PI3K/Akt activation.

Peptides synthesized on microbeads were encoded by chemically and physically adsorbing surface-enhanced Raman spectroscopic nanoparticles (SERS dots) on the microbead surface during the synthesis, which could be easily and rapidly decoded by Raman spectroscopy.

Expression of estrogen receptors (ER)-α and -β, as well as androgen receptor (AR), in hepatocellular carcinoma (HCC) is thought to be correlated with prognosis, survival, and male prevalence of HCC. These hypotheses are based on investigations of European patients; however the expression patterns of these receptors in Asian patients are largely unknown. In this study, we collected liver carcinoma and peritumor tissues from 32 patients (9 females and 23 males) in South Korea. The expression of ERs and ARs was studied using RT-PCR. Wild-type ER-α and AR were expressed in all of the samples investigated, and their expression was independent of the causal virus or patient sex. Expression of the ER-α variant was independent of sex (100% female vs. 91.3% male) and HCV and HBV status (91.3% vs. 100%). Wild-type ER-β was expressed more often in HCV patients than in HBV patients (95.7% vs. 44.4%; p < 0.05). In conclusion, the stronger ER-α variant expression in HCC tissues implies that this variant has an important role in HCC development. However, at least in Korean patients, expression of the ER-α variant (vER-α) is not related to male HCC prevalence. In addition, the predominant expression of ER-β in HCV patients suggests that it plays an important role in HCV-induced liver disease.

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