Objective To determine whether aquaporin-4 (AQP4) regulates acute lesions, delayed lesions, and the associated microglial activation after cryoinjury to the brain. Methods Brain cryoinjury was applied to AQP4 knockout (KO) and wild-type mice. At 24 h and on days 7 and 14 after cryoinjury, lesion volume, neuronal loss, and densities of microglia and astrocytes were determined, and their changes were compared between AQP4 KO and wild-type mice. Results Lesion volume and neuronal loss in AQP4 KO mice were milder at 24 h following cryoinjury, but worsened on days 7 and 14, compared to those in wild-type mice. Besides, microglial density increased more, and astrocyte proliferation and glial scar formation were attenuated on days 7 and 14 in AQP4 KO mice. Conclusion AQP4 deficiency ameliorates acute lesions, but worsens delayed lesions, perhaps due to the microgliosis in the late phase.

G protein-coupled receptor 17 (GPR17), the new P2Y-like receptor, is phylogenetically related to the P2Y and cysteinyl leukotriene receptors, and responds to both uracil nucleotides and cysteinyl leukotrienes. GPR17 has been proposed to be a damage sensor in ischemic stroke; however, its role in brain inflammation needs further detailed investigation. Here, we extended previous studies on the spatiotemporal profiles of GPR17 expression and localization, and their implications for brain injury after focal cerebral ischemia. We found that in the ischemic core, GPR17 mRNA and protein levels were upregulated at both 12-24 h and 7-14 days, but in the boundary zone the levels increased 7-14 days after reperfusion. The spatiotemporal pattern of GPR17 expression well matched the acute and late (subacute/chronic) responses in the ischemic brain. According to previous findings, in the acute phase, after ischemia (24 h), upregulated GPR17 was localized in injured neurons in the ischemic core and in a few microglia in the ischemic core and boundary zone. In the late phase (14 days), it was localized in microglia, especially in activated (ED1-positive) microglia in the ischemic core, but weakly in most microglia in the boundary zone. No GPR17 was detectable in astrocytes. GPR17 knockdown by a small interfering RNA attenuated the neurological dysfunction, infarction, and neuron loss at 24 h, and brain atrophy, neuron loss, and microglial activation at 14 days after reperfusion. Thus, GPR17 might mediate acute neuronal injury and late microgliosis after focal cerebral ischemia.

Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme in the salvaging pathway for the synthesis of nicotinamide adenine dinucleotide (NAD) that is involved in cell metabolism and proliferation. NAMPT is normally absent in astrocyte but highly expressed in glioblastoma, suggesting that it may promote cell survival through synthesizing more NAD. In this report, we evaluated the effect of APO866, a potent inhibitor of NAMPT against C6 glioblastoma. We found that APO866 inhibited the growth of C6 glioblastoma cells with IC(50) in nano-molar range. APO866 depleted intracellular NAD, caused marked inhibition of ERK activation and induced G2/M cell-cycle arrest. The effects by APO866 were abrogated by nicotinamide mononucleotide (NMN), the direct product of NAMPT. Administration of U0126, an ERK1/2 inhibitor, inhibited cell growth but displayed no synergistic effect with APO866. Taken together, our results indicated that APO866 is a potent growth inhibitor against glioblastoma through targeting NAMPT.

ABSTRACT: Many athletes need to participate in multiple events in a single day. The efficient post-exercise glycogen recovery may be critical for the performance in subsequent exercise. This study examined whether post-exercise carbohydrate supplementation could restore the performance in the subsequent simulated wrestling match. The effect of branched-chain amino acids and arginine on glucose disposal and performance was also investigated. Nine well-trained male wrestlers participated in 3 trials in a random order. Each trial contained 3 matches with a 1-hr rest between match 1 and 2, and a 2-hr rest between match 2 and 3. Each match contained 3 exercise periods interspersed with 1-min rests. The subjects alternated 10-s all-out sprints and 20-s rests in each exercise period. At the end of match 2, 3 different supplementations were consumed: 1.2 g/kg glucose (CHO trial), 1 g/kg glucose + 0.1 g/kg Arg + 0.1 g/kg BCAA (CHO+AA trial), or water (placebo trial). The peak and average power in the 3 matches was similar in the 3 trials. After the supplementation, CHO and CHO+AA trial showed significantly higher glucose and insulin, and lower glycerol and non-esterified fatty acid concentrations than the placebo trial. There was no significant difference in these biochemical parameters between the CHO and CHO+AA trials. Supplementation of carbohydrate with or without BCAA and arginine during the post-match period had no effect on the performance in the following simulated match in wrestlers. In addition, BCAA and arginine did not provide additional insulinemic effect.

The purpose of this study was to investigate the factors affecting the unplanned peripheral intravenous reinsertion in pediatric inpatients at a teaching hospital in Taiwan. Researchers recruited 206 pediatric inpatients and their caretakers for the study and used multivariate regression in calculating their results. The results showed the following: whether pediatric patients received drugs (P <.001), whether the appropriate height of the drops was adhered to (P =.053), and whether the adjustment of the drip rate was done by the clients or caretakers themselves (P =.046) were significant determinants of unplanned peripheral intravenous reinsertions. It may be worthwhile to incorporate the findings regarding factors affecting the unplanned peripheral intravenous reinsertion into pediatric nurses' educational programs.

The aim of this study was to investigate the cumulative effects of intensive resistance training on salivary immunoglobulin A (SIgA) and cortisol responses in elite male weightlifters. Eleven elite male Taiwanese weightlifters trained through three training stages before a national weightlifting competition and followed by a two-week recovery stage. Resting saliva samples were collected once in each of the four stages. Salivary concentrations of total protein (TP), SIgA, lactoferrin and cortisol were measured. Results showed (a) salivary TP concentrations were not significantly affected;(b) resting levels of SIgA, SIgA/TP, cortisol, and cortisol/TP were significantly higher in training stages than in recovery stage;(c) a positive correlation was revealed between the ratios of SIgA/TP and cortisol/TP; and (d) the resting salivary lactoferrin concentrations and the ratio of lactoferrin/TP were significantly lower in stage I than in recovery stage. The findings in this study suggest that prolonged, intensive resistance training exerts cumulative effects on SIgA and cortisol responses in elite weightlifters.

Intragastric growth of Helicobacter pylori and non-Helicobacter microorganisms is thought to be associated with elevated levels of pro-inflammatory cytokines and the production of NO these effects can lead to chronic inflammation. Microorganisms can activate the expression of iNOS and the production of NO by macrophages through stimulation with bacterial LPS. Helicobacter pylori can evade these vigorous immune responses, but the underlying mechanism remains unknown. In this study, we used a murine model of macrophage infection to demonstrate that H. pylori inhibits LPS-induced expression of iNOS and production of NO by macrophages. Suppression of LPS-induced NO production by macrophages led to elevated survival of H. pylori in a trans-well system. This effect was abrogated in macrophages from iNOS(-/-) mice. Analysis of iNOS mRNA and protein levels revealed that H. pylori inhibits iNOS expression at both transcriptional and post-transcriptional levels, and that these effects occurred with live bacteria. Furthermore, the effect of H. pylori involved down-regulation of the mitogen-activated protein kinase pathway and the translocation of active NF-κB into the nucleus. Taken together, our results reveal a new mechanism by which H. pylori modulates the innate immune responses of the host and maintains a persistent infection within the stomach.

Cysteinyl leukotrienes (CysLTs), potent inflammatory mediators, are released from ischemic brain, and may regulate ischemic injury through activating CysLT(1) and CysLT(2) receptors. The CysLT(1) receptor is closely associated with ischemic injury and post-ischemic repair; however, the CysLT(2) receptor-mediated responses remain unknown. Here, we investigated the spatiotemporal profiles and implications of CysLT(2) receptor expression and localization in rat brain after focal cerebral ischemia. CysLT(2) receptors were normally localized in astrocytes in the cortex and around the ventricles. After focal cerebral ischemia, CysLT(2) receptor expression was up-regulated in concert with neuronal and glial responses. In the acute phase (6-24 h), up-regulated CysLT(2) receptors were restricted to injured neurons in the ischemic core; while in the late phase (3-28 days), the up-regulation was restricted to hypertrophic microglia (ischemic core) and mainly localized in hypertrophic astrocytes (boundary zone). Thus, the spatiotemporal profiles of CysLT(2) receptor expression suggest that it plays regulatory roles in acute neuron injury, and astrocytosis and microgliosis in the late phase.

Honokiol (HNK) is a phenolic compound isolated from the bark of houpu (Magnolia officinalis), a plant widely used in traditional Chinese and Japanese medicine. While substantial evidence indicates that HNK possesses anti-inflammatory activity, its effect on dendritic cells (DCs) during the inflammatory reaction remains unclear. The present study investigates how HNK affects lipopolysaccharide (LPS)-stimulated human monocyte-derived DCs. Our experimental results show that HNK inhibits the inflammatory response of LPS-induced DCs by (1) suppressing the expression of CD11c, CD40, CD80, CD83, CD86, and MHC-II on LPS-activated DCs,(2) reducing the production of TNF-α, IL-1β, IL-6, and IL-12p70 but increasing the production of IL-10 and TGF-β1 by LPS-activated DCs,(3) inhibiting the LPS-induced DC-elicited allogeneic T-cell proliferation, and (4) shifting the LPS-induced DC-driven Th1 response toward a Th2 response. Further, our results show that HNK inhibits the phosphorylation levels of ERK1/2, p38, JNK1/2, IKKα, and IκBα in LPS-activated DCs. Collectively, the findings show that the anti-inflammatory actions of HNK on LPS-induced DCs are associated with the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways.

BACKGROUND Beneficial effects of probiotics have been reported for patients with allergic diseases and intestinal disorders. There is increasing interest in studying the role of different strains or combined probiotic administration on immunoregulation. In this study, we investigated whether probiotics modulate the immune response through regulating T cell proliferation and differentiation. METHODS We examined the effect of probiotic I (a combination of Lactobacillus acidophilus and Bifidobacterium bifidus) and probiotic II (a combination of L. acidophilus and B. infantis) on cell survival and proliferation, the progression of the cell cycle, and the production of Th1/Th2 cytokines by mitogen-stimulated murine spleen cells and human peripheral blood mononuclear cells (PBMCs). RESULTS Our experimental results showed that high concentrations (≥ 1 × 10(6) CFU/ml) of probiotic I or II inhibited mitogen-induced cell proliferation and arrested the cell cycle at the G0/G1 stage in both mitogen-stimulated spleen cells and PBMCs. In the results of low concentrations (<1 × 10(6) CFU/ml), probiotic I or II enhanced the production of IFN-γ but inhibited the production of IL-4. Our results indicated that high concentrations of probiotic I or II treatment could attenuate mitogen-induced overactive immune responses. On the other hand, low concentrations of probiotic I or II treatment could promote a shift in the Th1/Th2 balance toward Th1-skewed immunity. CONCLUSION Dose selection is an important issue for probiotic studies. Our results indicated that probiotics have beneficial effects on regulating T cell-mediated immune responses by attenuating mitogen-induced overactive immune responses and promoting Th1 immune responses.