Mesenchymal stem cell (MSC)-mediated periodontal tissue regeneration is considered a promising method for periodontitis treatment. The molecular mechanism underlying directed differentiation and anti-inflammatory actions remains unclear, thus limiting potential MSC application. We previously found that insulin-like growth factor binding protein 5 (IGFBP5) is highly expressed in dental tissue-derived MSCs compared with in non-dental tissue-derived MSCs. IGFBP5 is mainly involved in regulating biological activity of insulin-like growth factors, and its functions in human MSCs and tissue regeneration are unclear. In this study, we performed gainand loss-of-function assays to test whether IGFBP5 could regulate the osteogenic differentiation and anti-inflammatory potential in MSCs. We found that IGFBP5 expression was upregulated upon osteogenic induction, and that IGFBP5 enhanced osteogenic differentiation in MSCs. We further showed that IGFBP5 prompted the anti-inflammation effect of MSCs via negative regulation of NFjB signaling. Depletion of the histone demethylase lysine (K)-specific demethylase 6B (KDM6B) downregulated IGFBP5 expression by increasing histone K27 methylation in the IGFBP5 promoter. Moreover, IGFBP5 expression in periodontal tissues was downregulated in individuals with periodontitis compared with in healthy people, and IGFBP5 enhanced MSC-mediated periodontal tissue regeneration and alleviated local inflammation in a swine model of periodontitis. In conclusion, our present results reveal a new function for IGFBP5, provide insight into the mechanism underlying the directed differentiation and anti-inflammation capacities of MSCs, and identify a potential target mediator for improving tissue regeneration. STEM CELLS 2015;33:2523-2536
At
present, the complex pathogenesis, the difficult-to-overcome
blood–brain barrier (BBB), the development of the disease course
which cannot be prevented, and other problems are serious challenges
in the treatment of Alzheimer’s disease (AD). In order to enhance
the therapeutic effect of drugs through BBB, we synthesized simple
and easy-to-obtain selenium quantum dots (SeQDs), with a multitarget
therapeutic effect. This new type of SeQDs has an ultrasmall size
and can quickly penetrate the BBB. According to the fluorescence characteristics
of SeQDs, we can diagnose and track AD. The experimental results show
that SeQDs have strong free-radical scavenging activity, protect cells
from oxidative stress induced by different stimuli, and show broad-spectrum
antioxidant activity. The SeQDs can not only effectively inhibit Aβ
aggregation and significantly reduce Aβ-mediated cytotoxicity,
thus preventing AD cascade reaction, but also effectively reduce tau
protein phosphorylation by down-regulating PHF1 and CP13 and further
reduce oxidative stress, restore mitochondrial functions, and maintain
nerve cell stability and protect nerve cells from oxidative stress.
In vivo studies demonstrate that SeQDs can continuously accumulate
in the brain after rapid passage of BBB and can quickly alleviate
AD, significantly improve the memory impairment of AD mice, and improve
their learning and memory ability. Therefore, the use of SeQDs in
the treatment of AD has great advantages compared with traditional
single-target drugs and provides a new direction for the combination
of prevention and treatment of neurodegenerative diseases.
Objectives: To evaluate the efficacy of a short-term intravenous infusion of levosimendan in patients with heart failure due to acute myocardial infarction (AMI). Methods: This was a randomized, single-center, single-blind study that included 160 patients. Patients were randomly divided into 2 groups: 1 received levosimendan (n = 80) and the other received placebo (n = 80). The study included multiple primary end points (death, myocardial ischemia or worsening heart at the 6 month follow-up) and used a composite outcome. Results: The primary end point rate in the levosimendan group was lower than that in placebo group (43.7 vs. 62.5%, HR 0.636, 95% CI 0.413-0.981, p = 0.041). Moreover, the mortality rate at 6 months was similar between the 2 groups (17.5 vs. 22.5%, HR 0.786, 95% CI 0.382-1.543, p = 0.458). There was a higher incidence of myocardial ischemia in the levosimendan group at 14 days than in the placebo group (11.2 vs. 7.5%, HR 1.510, p = 0.435), but between 15 and 180 days, it was significantly lower in the levosimendan group than in the placebo group (3.8 vs. 13.8%, HR 0.261, p = 0.036). Conclusion: Short-term intravenous infusion of levosimendan appears to be more effective than placebo for treating patients with heart failure complicated by AMI.
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