Entamoeba histolytica is an extracellular tissue parasite causing colitis and occasional liver abscess in humans. E. histolytica-derived secretory products (SPs) contain large amounts of cysteine proteases (CPs), one of the important amoebic virulence factors. Although tissue-residing mast cells play an important role in the mucosal inflammatory response to this pathogen, it is not known whether the SPs induce mast cell activation. In this study, when human mast cells (HMC-1 cells) were stimulated with SPs collected from pathogenic wild-type amoebae, interleukin IL-8 mRNA expression and production were significantly increased compared with cells incubated with medium alone. Inhibition of CP activity in the SPs with heat or the CP inhibitor E64 resulted in significant reduction of IL-8 production. Moreover, SPs obtained from inhibitors of cysteine protease (ICP)-overexpressing amoebae with low CP activity showed weaker stimulatory effects on IL-8 production than the wild-type control. Preincubation of HMC-1 cells with antibodies to human protease-activated receptor 2 (PAR2) did not affect the SP-induced IL-8 production. These results suggest that cysteine proteases in E. histolytica-derived secretory products stimulate mast cells to produce IL-8 via a PAR2-independent mechanism, which contributes to IL-8-mediated tissue inflammatory responses during the early phase of human amoebiasis.

In this study, the anti-inflammatory and antisepticemic activities of a water extract of aged black garlic (AGE), which is not pungent, were compared with those of raw garlic extract (RGE). The methyl thiazolyl tetrazolium (MTT) assay showed that AGE was not toxic up to 1000 μg/mL and was at least four times less cytotoxic than RGE. AGE significantly suppressed the production of nitric oxide (NO), tumor-necrosis factor-α (TNF-α), and prostaglandin (PG)-E2 in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Furthermore, the inhibitory effect of AGE on LPS-induced inflammation was confirmed by downregulation of inducible NO synthase and TNF-α mRNA expression, as well as cyclooxygenase-2 protein expression. The anti-inflammatory activities of AGE were similar to those of RGE at nontoxic concentrations up to 250 μg/mL. Signal transduction pathway studies further indicated that both garlic extracts inhibited activation of mitogen-activated protein kinase and nuclear factor-κB induced by LPS stimulation. Treatment with both AGE and RGE in an in vivo experiment of LPS-induced endotoxemia significantly reduced the level of TNF-α and interleukin-6 in serum and completely protected against LPS-induced lethal shock in C57BL/6 mice. The results suggest that AGE is a more promising nutraceutical or medicinal agent to prevent or cure inflammation-related diseases for safety aspects compared with RGE.

Study Objectives To assess, using fractional anisotropy (FA) analysis, alterations of brain network connectivity in adults with obstructive sleep apnea (OSA). Abnormal networks could mediate clinical functional deficits and reflect brain tissue injury. Methods Structural brain networks were constructed using diffusion tensor imaging (DTI) from 165 healthy (age 57.99 ± 6.02 years, male 27.9%) and 135 OSA participants (age 59.01 ± 5.91 years, male 28.9%) and global network properties (strength, global efficiency, and local efficiency) and regional efficiency were compared between groups. We examined MRI biomarkers of brain tissue injury using FA analysis and its effect on the network properties. Results Differences between groups of interest were noted in global network properties (p-value < 0.05, corrected), and regional efficiency (p-value < 0.05, corrected) in the left middle cingulate and paracingulate gyri, right posterior cingulate gyrus, and amygdala. In FA analysis, OSA participants showed lower FA values in white matter (WM) of the right transverse temporal, anterior cingulate and paracingulate gyri, and left postcentral, middle frontal and medial frontal gyri, and the putamen. After culling fiber tracts through WM which showed significant differences in FA, we observed no group difference in network properties. Conclusions Changes in WM integrity and structural connectivity are present in OSA participants. We found that the integrity of WM affected brain network properties. Brain network analysis may improve understanding of neurocognitive deficits in OSA, enable longitudinal tracking, and provides explanations for specific symptoms and recovery kinetics.

Our results suggest that LTB(4) receptors BLT1 and BLT2 are involved in IL-8 production in neutrophils induced by T. vaginalis.

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