At the end point, aortic diameter, elastin content, MMPs’ activity, and cytokines expressed, including interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), TNF-alpha, insulin-like growth factor-1 (IGF-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were quantified.
Results: MSCs suppressed GSK2118436 ic50 MMP-2 with or without MSCs (2.59 vs 3.94, P < .05), MMP-9 (5.83 vs 9.70, P < .05), and TNF-alpha
(2.79 vs 3.38, P < .05) expression in macrophages, and promoted elastin expression in SMCs (19.35 vs 3.23, P < .05) in vitro. MSCs also decreased active MMP-2 activity (0.310 vs 0.0609 U/mu L, P < .05) and preserved elastin content (68.05 vs 40.29 mu g/mg, P < .05) ex vivo. AA development was site-specifically inhibited (0.73 vs 1.04 mm aortic diameter, P < .05) and elastin content was preserved (46.9 vs 25.6 mu g/mg, P < .05) at 4 weeks. Downregulation of MMPs and IL-6, MCP-1, and TNF-alpha, and upregulation
of IGF-1 and TIMP-1 were demonstrated with MSC implantation in vivo.
Conclusions: MSC implantation inhibits Ang II-induced AA development in apoE(-/-) mice through elastin preservation in the aortic wall and is associated with attenuated levels of MMTs and inflammatory cytokines. (J Vase Surg 2011;54:1743-52.)”
“The serotonergic system has been widely implicated in stress related Bucladesine concentration psychiatric disorders such as depression and anxiety. Generation of receptor knockout mice has offered a new approach to study processes underlying anxiety. For instance, knockout mice for both 5-HT1A and 5-HT1B receptors (5-HT1A/1B-/-) display an anxious phenotype, associated with robust physiological Evodiamine and neurochemical
changes related to brain serotonin function. As ventral hippocampus is a key region in the mediation and genesis of anxiety, we explored the transcriptome changes induced by the genetic inactivation of these two receptors in 5-HT1A/1B-/- mice. Dissociation of ventral vs. dorsal hippocampus was confirmed by the over-expression of selective markers in both regions. 723 genes were observed up/down regulated in 5-HT1A/1B-/- mice. Using Ingenuity, biological networks and signal transduction pathway analysis corresponding to the identified gene revealed putative dysregulation of nervous system development and function, especially genes associated with long-term potentiation and adult neurogenesis (including Bdnf,Camk2a,Camk4, and Klf9). Furthermore, immunohistochemistry experiments studying adult hippocampal neurogenesis in adult 5-HT1A/1B-/- mice showed a decreased survival, but not proliferation of newborn cells in our model. (C) 2012 Elsevier Ireland Ltd. All rights reserved.”
“Schizophrenia patients with obsessive-compulsive disorder (OCD) may be a subgroup of schizophrenia, and OCD patients with poor insight may show psychotic-like symptoms.