Lipid metabolism adaptations are reduced in human compared to murine Schwann cells following injury.

Mammals differ in their regeneration potential after traumatic injury, which might be caused by species-specific regeneration programs. Here, we compared murine and human Schwann cell (SC) response to injury and developed an ex vivo injury model employing surgery-derived human sural nerves. Transcriptomic and lipid metabolism analysis of murine SCs following injury of sural nerves revealed down-regulation of lipogenic genes and regulator of lipid metabolism, including Pparg (peroxisome proliferator-activated receptor gamma) and S1P (sphingosine-1-phosphate). Human SCs failed to induce similar adaptations following ex vivo nerve injury. Pharmacological PPARg and S1P stimulation in mice resulted in up-regulation of lipid gene expression, suggesting a role in SCs switching towards a myelinating state. Altogether, our results suggest that murine SC switching towards a repair state is accompanied by transcriptome and lipidome adaptations, which are reduced in humans.

Autonomous Ultrafast Self-Healing Hydrogels by pH-Responsive Functional Nanofiber Gelators as Cell Matrices.

The synthesis of hybrid hydrogels by pH-controlled structural transition with exceptional rheological properties as cellular matrix is reported. "Depsi" peptide sequences are grafted onto a polypeptide backbone that undergo a pH-induced intramolecular O-N-acyl migration at physiological conditions affording peptide nanofibers (PNFs) as supramolecular gelators. The polypeptide-PNF hydrogels are mechanically remarkably robust. They reveal exciting thixotropic behavior with immediate in situ recovery after exposure to various high strains over long periods and self-repair of defects by instantaneous reassembly. High cytocompatibility, convenient functionalization by coassembly, and controlled enzymatic degradation but stability in 2D and 3D cell culture as demonstrated by the encapsulation of primary human umbilical vein endothelial cells and neuronal cells open many attractive opportunities for 3D tissue engineering and other biomedical applications.

Water-Dispersible Polydopamine-Coated Nanofibers for Stimulation of Neuronal Growth and Adhesion.

Hybrid nanomaterials have shown great potential in regenerative medicine due to the unique opportunities to customize materials properties for effectively controlling cellular growth. The peptide nanofiber-mediated auto-oxidative polymerization of dopamine, resulting in stable aqueous dispersions of polydopamine-coated peptide hybrid nanofibers, is demonstrated. The catechol residues of the polydopamine coating on the hybrid nanofibers are accessible and provide a platform for introducing functionalities in a pH-responsive polymer analogous reaction, which is demonstrated using a boronic acid modified fluorophore. The resulting hybrid nanofibers exhibit attractive properties in their cellular interactions: they enhance neuronal cell adhesion, nerve fiber growth, and growth cone area, thus providing great potential in regenerative medicine. Furthermore, the facile modification by pH-responsive supramolecular polymer analog reactions allows tailoring the functional properties of the hybrid nanofibers in a reversible fashion.

Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury.

Axon injury in the peripheral nervous system (PNS) induces a regeneration-associated gene (RAG) response. Atf3 (activating transcription factor 3) is such a RAG and ATF3's transcriptional activity might induce 'effector' RAGs (e.g. small proline rich protein 1a (Sprr1a), Galanin (Gal), growth-associated protein 43 (Gap43)) facilitating peripheral axon regeneration. We provide a first analysis of Atf3 mouse mutants in peripheral nerve regeneration. In Atf3 mutant mice, facial nerve regeneration and neurite outgrowth of adult ATF3-deficient primary dorsal root ganglia neurons was decreased. Using genome-wide transcriptomics, we identified a neuropeptide-encoding RAG cluster (vasoactive intestinal peptide (Vip), Ngf, Grp, Gal, Pacap) regulated by ATF3. Exogenous administration of neuropeptides enhanced neurite growth of Atf3 mutant mice suggesting that these molecules might be effector RAGs of ATF3's pro-regenerative function. In addition to the induction of growth-promoting molecules, we present data that ATF3 suppresses growth-inhibiting molecules such as chemokine (C-C motif) ligand 2. In summary, we show a pro-regenerative ATF3 function during PNS nerve regeneration involving transcriptional activation of a neuropeptide-encoding RAG cluster. ATF3 is a general injury-inducible factor, therefore ATF3-mediated mechanisms identified herein might apply to other cell and injury types.

Altered immune parameters in chronic alcoholic patients at the onset of infection and of septic shock.

INTRODUCTION: Chronic alcoholic patients have a threefold to fourfold increased risk for developing a severe infection or septic shock after surgery, which might be due to altered immune response. The aim of this outcome matched study was to investigate proinflammatory and anti-inflammatory immune parameters during the course of infection and subsequent septic shock in chronic alcoholic patients, and to compare these parameters with those in nonalcoholic patients. METHODS: Twenty-eight patients from a cohort of fifty-six with either pneumonia or peritonitis and subsequent septic shock were selected. Fourteen patients were chronic alcoholics whereas fourteen were nonalcoholic patients. Chronic alcoholic patients met criteria (Diagnostic and Statistical Manual of Mental Disorders IV, of the American Psychiatric Association) for alcohol abuse or dependence. Measurements were performed during the onset of infection (within 24 hours after the onset of infection), in early septic shock (within 12 hours after onset of septic shock) and in late septic shock (72 hours after the onset). Blood measurements included proinflammatory and anti-inflammatory cytokines. RESULTS: Chronic alcoholic patients exhibited significantly lower plasma levels of IL-8 (P < 0.010) during the onset of infection than did matched nonalcoholic patients. In early septic shock, chronic alcoholic patients had significantly decreased levels of IL-1beta (P < 0.015), IL-6 (P < 0.016) and IL-8 (P < 0.010). The anti-inflammatory parameters IL-10 and tumour necrosis factor receptors I and II did not differ between alcoholic and nonalcoholic patients. CONCLUSION: At the onset of infection and during early septic shock, chronic alcoholic patients had lower levels of proinflammatory immune parameters than did nonalcoholic patients. Therefore, immunomodulatory therapy administered early may be considered in chronic alcoholic patients at the onset of an infection because of their altered proinflammatory immune response.