Plos One
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Observational Study
Inflammation-induced acute phase response in skeletal muscle and critical illness myopathy.
Systemic inflammation is a major risk factor for critical-illness myopathy (CIM) but its pathogenic role in muscle is uncertain. We observed that interleukin 6 (IL-6) and serum amyloid A1 (SAA1) expression was upregulated in muscle of critically ill patients. To test the relevance of these responses we assessed inflammation and acute-phase response at early and late time points in muscle of patients at risk for CIM. ⋯ Skeletal muscle contributes to general inflammation and acute-phase response in CIM patients. Muscular SAA1 could be important for CIM pathogenesis.
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Peripheral nerve injury (PNI) is a common disease that often results in axonal degeneration and the loss of neurons, ultimately leading to limited nerve regeneration and severe functional impairment. Currently, there are no effective treatments for PNI. In the present study, we transduced conserved dopamine neurotrophic factor (CDNF) into mesenchymal stem cells (MSCs) in collagen tubes to investigate their regenerative effects on rat peripheral nerves in an in vivo transection model. ⋯ The greater numbers of HRP-labeled neuron cell bodies and increased sciatic nerve index values (SFI) in the CDNF-MSCs group suggest that CDNF exerts neuroprotective effects in vivo. We also observed higher target muscle weights and a significant improvement in muscle atrophism in the CDNF-MSCs group. Collectively, these findings indicate that CDNF gene therapy delivered by MSCs is capable of promoting nerve regeneration and functional recovery, likely because of the significant neuroprotective and neurotrophic effects of CDNF and the superior environment offered by MSCs and collagen tubes.
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The aim of this study is to compare the effect of lactated ringer (LR), vasopressin (Vaso) or terlipressin (Terli) on uncontrolled hemorrhagic shock (UHS) in rats. ⋯ Early optimization of hemodynamics with terlipressin or vasopressin in an animal model of UHS was associated with improved hemodynamics and inflammatory cytokine profile than the LR control. Compared with vasopressin, terlipressin has the advantage of ease of use and sustained effects.
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The endocannabinoid ligand anandamide (AEA) is removed from the extracellular space by a process of cellular uptake followed by metabolism. In many cells, such as the RBL-2H3 cell line, inhibition of FAAH activity reduces the observed uptake, indicating that the enzyme regulates uptake by controlling the intra- : extracellular AEA concentration gradient. However, in other FAAH-expressing cells, no such effect is seen. It is not clear, however, whether these differences are methodological in nature or due to properties of the cells themselves. In consequence, we have reinvestigated the role of FAAH in gating the uptake of AEA. ⋯ When assayed using the same methodology, different FAAH-expressing cells display different sensitivities of uptake to FAAH inhibition.
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Bone marrow mesenchymal stem cells (MSCs) have been found to produce beneficial effects on ischemia-reperfusion injury. However, most of the MSCs died when transplanted into the ischemic tissue, which severely limit their therapeutic potential. ⋯ These findings suggest that sevoflurane preconditioning produces protective effects on survival and migration of MSCs against H/SD, as well as improving the therapeutic potential of MSCs. These beneficial effects might be mediated at least in part by upregulating HIF-1α, HIF-2α, VEGF, and p-Akt/Akt.