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Reliable electroencephalography (EEG) signatures of transitions between consciousness and unconsciousness under anaesthesia have not yet been identified. Herein we examined network changes using graph theoretical analysis of high-density EEG during patient-titrated propofol-induced sedation. Responsiveness was used as a surrogate for consciousness. We divided the data into five states: baseline, transition into unresponsiveness, unresponsiveness, transition into responsiveness, and recovery. Power spectral analysis showed that delta power increased from responsiveness to unresponsiveness. In unresponsiveness, delta waves propagated from frontal to parietal regions as a traveling wave. Local increases in delta connectivity were evident in parietal but not frontal regions. Graph theory analysis showed that increased local efficiency could differentiate the levels of responsiveness. Interestingly, during transitions of responsive states, increased beta connectivity was noted relative to consciousness and unconsciousness, again with increased local efficiency. Abrupt network changes are evident in the transitions in responsiveness, with increased beta band power/connectivity marking transitions between responsive states, while the delta power/connectivity changes were consistent with the fading of consciousness using its surrogate responsiveness. These results provide novel insights into the neural correlates of these behavioural transitions and EEG signatures for monitoring the levels of consciousness under sedation.

Developing treatments that inhibit skin aging is an important research project. Rejuvenation, which focuses on prevention of skin aging, is one of the major issues. Recent studies suggested that mesenchymal stem cells (MSCs) secrete many cytokines, which are important in wound healing. In this study, we investigated the effect of human umbilical cord blood-derived mesenchymal stem cells conditioned media (USC-CM) in cutaneous wound healing and collagen synthesis. We found that USC-CM has many useful growth factors associated with skin rejuvenation, such as Epithelial Growth Factor (EGF), basic Fibroblast Growth Factor (bFGF), Platelet Derived Growth Factor (PDGF), Hepatocyte Growth Factor (HGF), Collagen type 1, and especially, one of the rejuvenation factors, the growth differentiation factor-11 (GDF-11). Our in vitro results showed that USC-CM stimulate growth and extracellular matrix (ECM) production of Human Dermal Fibroblasts (HDFs) compared to those of other MSCs conditioned media (CM) from different origins. Moreover, we evaluated the roles of GDF-11. The results showed that GDF-11 accelerates growth, migration and ECM production of HDFs. Our In vivo results showed that topical treatment of USC-CM showed anti-wrinkle effect and significantly increased dermal density in women. In conclusion, USC-CM has various useful growth factors including GDF-11 that can stimulate skin rejuvenation by increasing growth and ECM production of HDFs.

Because human mesenchymal stem cells (hMSC) have profound immunomodulatory effects, many attempts have been made to use hMSCs in preclinical and clinical trials. For hMSCs to be used in therapy, a large population of hMSCs must be generated by in vitro expansion. However, the immunomodulatory changes following the in vitro expansion of hMSCs have not been elucidated. In this study, we evaluated the effect of replicative senescence on the immunomodulatory ability of hMSCs in vitro and in vivo. Late-passage hMSCs showed impaired suppressive effect on mitogen-induced mononuclear cell proliferation. Strikingly, late-passage hMSCs had a significantly compromised protective effect against mouse experimental colitis, which was confirmed by gross and histologic examination. Among the anti-inflammatory cytokines, the production of prostaglandin E2 (PGE2) and the expression of its primary enzyme, cyclooxygenase-2 (COX-2), were profoundly increased by pre-stimulation with interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), and this response was significantly decreased with consecutive passages. We demonstrated that the impaired phosphorylation activity of p38 MAP kinase (p38 MAPK) in late-passage hMSCs led to a compromised immunomodulatory ability through the regulation of COX-2. In conclusion, our data indicate that the immunomodulatory ability of hMSCs gradually declines with consecutive passages via a p38-mediated alteration of COX-2 and PGE2 levels.