Plos One
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Maresins are a new family of anti-inflammatory and pro-resolving lipid mediators biosynthesized from docosahexaenoic acid (DHA) by macrophages. Here we identified a novel pro-resolving product, 13R,14S-dihydroxy-docosahexaenoic acid (13R,14S-diHDHA), produced by human macrophages. PCR mapping of 12-lipoxygenase (12-LOX) mRNA sequence in human macrophages and platelet showed that they are identical. ⋯ However, MaR1 proved more potent than the 13R,14S-diHDHA at enhancing efferocytosis with human macrophages. Taken together, the present findings demonstrate that macrophages produced a novel bioactive product identified in the maresin metabolome as 13R,14S-dihydroxy-docosahexaenoic acid, from DHA via conversion by human 12-LOX followed by sEH. Given its potent bioactions, we coined 13R,14S-diHDHA maresin 2 (MaR2).
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Chemokine (C-C motif) receptor 8 (CCR8), the chemokine receptor for chemokine (C-C motif) ligand 1 (CCL1), is expressed in T-helper type-2 lymphocytes and peritoneal macrophages (PMφ) and is involved in various pathological conditions, including peritoneal adhesions. However, the role of CCR8 in inflammatory responses is not fully elucidated. To investigate the function of CCR8 in macrophages, we compared cytokine secretion from mouse PMφ or bone marrow-derived macrophages (BMMφ) stimulated with various Toll-like receptor (TLR) ligands in CCR8 deficient (CCR8-/-) and wild-type (WT) mice. ⋯ R243 also prevented hapten-induced colitis. These results are indicative of cross talk between signaling pathways downstream of CCR8 and TLR-4 that induces cytokine production by PMφ. Through use of CCR8-/- mice and the new CCR8 inhibitor, R243, we identified a novel macrophage innate immune response pathway that involves a chemokine receptor.
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Remifentanil with appropriate pharmacological properties seems to be an ideal alternative to epidural analgesia during labour. A retrospective cohort study was undertaken to assess the efficacy and safety of remifentanil intravenous patient-controlled analgesia (IVPCA) compared with epidural analgesia. Medical records of 370 primiparas who received remifentanil IVPCA or epidural analgesia were reviewed. ⋯ Neonatal outcomes such as Apgar scores and umbilical-cord blood gas analysis were within the normal range, but umbilical pH and base excess of neonatus in the remifentanil group were significantly lower. Remifentanil IVPCA provides poorer efficacy on labor analgesia than epidural analgesia, with more sedation on parturients and a trend of newborn acidosis. Despite these adverse effects, remifentanil IVPCA can still be an alternative option for labor analgesia under the condition of one-to-one bedside care, continuous monitoring, oxygen supply and preparation for neonatal resuscitation.
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Epidural anesthesia is a common anesthesia method yet up to 10% of procedures fail to provide adequate analgesia. This is usually due to misinterpreting the tactile information derived from the advancing needle through the complex tissue planes. Incorrect placement also can cause dural puncture and neural injury. ⋯ Our system was tested in a porcine model and identified the epidural space in the lumbar, low and high thoracic regions of the spine. The new technology identified the epidural space in all but 1 of 46 attempts. Experimental results from our fabricated integrated circuit and animal study show the new tool has future clinical potential.
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Dicer is required for the maturation of microRNA, and loss of Dicer and miRNA processing has been found to alter numerous biological events during embryogenesis, including the development of mammalian skin and hair. We have previously examined the role of miRNA biogenesis in mouse embryonic fibroblasts and found that deletion of Dicer induces cell senescence regulated, in part, by the p53 tumor suppressor. Although Dicer and miRNA molecules are thought to have either oncogenic or tumor suppressing roles in various types of cancer, a role for Dicer and miRNAs in skin carcinogenesis has not been established. ⋯ Co-ablation of Dicer and p53 did not alter the timing or extent of fur loss, but greatly reduced survival of Dicer-skin ablated mice, as these mice developed multiple and highly aggressive skin carcinomas. Our results describe a new mouse model for spontaneous basal and squamous cell tumorigenesis. Furthermore, our findings reveal that loss of Dicer in the epidermis induces extensive DNA damage, activation of the DNA damage response and p53-dependent apoptosis, and that Dicer and p53 cooperate to suppress mammalian skin carcinogenesis.