Citations

Background: Previous observational studies have demonstrated that outcomes after OHCA can be significantly improved with therapies such as mild therapeutic hypothermia and percutaneous coronary intervention (PCI). However, the optimal candidate and timing for PCI in OHCA remains unknown. This study aimed to assess the impact of emergent PCI on survival and neurological outcome after OHCA. Methods: This is a prospective observational study from a statewide OHCA database in Arizona. Patients included were greater than 18 years old who received CPR and were admitted to one of 34 recognized cardiac receiving centers. Patients who did not achieve ROSC, died within 2 hours of hospital arrival, and DNAR patients were excluded since the likelihood of PCI impacting outcome in these patients is questionable. An in-hospital post-arrest database, including PCI (Y/N), was linked with an Utstein-style OHCA database. Univariate and multivariate logistic regression were utilized to assess the association between PCI and survival to hospital discharge and neurological outcome. Results: During this study period (1-1-2011-12-31-2013), there were a total of 6,543 adult OHCA patients. After exclusions, 782 patients with suspected cardiac etiology OHCA were analyzed. The median age of patients was 64.0 years (Q1:54.0, Q3:73.0) and 70.2% were male. Among them 458 (58.6%) and 238 (30.4%) patients underwent the emergency coronary angiogram (CAG), and Primary PCI, respectively. Among PCI patients, the rate of survival to hospital discharge was 75.2%, vs. 60.4% for those without PCI (p<0.001) and good cerebral outcome (CPC 1-2) was found in 67.6%, vs. 44.3% of those without PCI (p<0.001). After adjusting for age, gender, initial rhythm, bystander CPR, and hypothermia, the Odds Ratio was 1.2 (95% CI:0.8-1.8) for survival and 2.8 (95% CI:1.5-5.1) for good neurologic outcome (CPC 1-2) among PCI patients. Conclusion: This study shows an association with emergent PCI and good neurologic outcome after OHCA. Further study is necessary to determine a potential causal relationship between PCI and outcome.

Human adipose‐derived mesenchymal stromal cells (AMSCs) grown in platelet lysate are promising agents for therapeutic tissue regeneration. Here, we investigated whether manipulation of epigenetic events by the clinically relevant histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) alters differentiation of AMSCs. The multipotency of AMSCs was validated by their ability to differentiate into osteogenic, chondrogenic, and adipogenic lineages. High‐throughput RNA sequencing and RT‐qPCR established that human histone deacetylases (HDAC1 to HDAC11, and SIRT1 to SIRT7) are differentially expressed in AMSCs. SAHA induces hyper‐acetylation of histone H3 and H4, stimulates protein expression of the HDAC‐responsive gene SLC9A3R1/NHERF1 and modulates the AKT/FOXO1 pathway. Biologically, SAHA interferes with osteogenic, chondrogenic and adipogenic lineage commitment of multipotent AMSCs. Mechanistically, SAHA‐induced loss of differentiation potential of uncommitted AMSCs correlates with multiple changes in the expression of principal transcription factors that control mesenchymal or pluripotent states. We propose that SAHA destabilizes the multi‐potent epigenetic state of uncommitted human AMSCs by hyper‐acetylation and perturbation of key transcription factor pathways. Furthermore, AMSCs grown in platelet lysate may provide a useful biological model for screening of new HDAC inhibitors that control the biological fate of human mesenchymal stromal cells. J. Cell. Physiol. 230: 52–62, 2015. © 2014 Wiley Periodicals, Inc.

AbstractRunx2 is the master transcription factor for bone formation. Haploinsufficiency of RUNX2 is the genetic cause of cleidocranial dysplasia (CCD) that is characterized by hypoplastic clavicles and open fontanels. In this study, we found that Pin1, peptidyl prolyl cis–trans isomerase, is a critical regulator of Runx2 in vivo and in vitro. Pin1 mutant mice developed CCD‐like phenotypes with hypoplastic clavicles and open fontanels as found in the Runx2+/− mice. In addition Runx2 protein level was significantly reduced in Pin1 mutant mice. Moreover Pin1 directly interacts with the Runx2 protein in a phosphorylation‐dependent manner and subsequently stabilizes Runx2 protein. In the absence of Pin1, Runx2 is rapidly degraded by the ubiquitin‐dependent protein degradation pathway. However, Pin1 overexpression strongly attenuated uniquitin‐dependent Runx2 degradation. Collectively conformational change of Runx2 by Pin1 is essential for its protein stability and possibly enhances the level of active Runx2 in vivo. J. Cell. Physiol. 228: 2377–2385, 2013. © 2013 Wiley Periodicals, Inc.

Previous linkage analysis of an Asian population proposed possible candidate genes for mandibular prognathism, such as Matrilin-1 (cartilage matrix protein). To investigate the association between the single-nucleotide polymorphisms (SNPs) in Matrilin-1 and mandibular prognathism, we investigated three sequence variants (-158 T>C, 7987 G>A, 8572 C>T) in 164 mandibular prognathism patients and 132 control individuals with a normal occlusion. The results showed that the 8572 TT genotypes in Matrilin-1 showed increased risk of mandibular prognathism (OR = 9.28, 95% Cl = 1.19~197.57, P < 0.05), whereas the 7987 AA genotype showed a protective effect for mandibular prognathism (OR = 0.16, 95% Cl = 0.05~0.47, P < 0.05). Genotyping results showed that the Matrilin-1 polymorphism haplotype TGC (ht4; 158T, 7987G, and 8572C alleles) had a pronounced risk effect for mandibular prognathism compared with controls (OR = 5.16, 95% Cl = 2.03~13.93, P < 0.01). The results suggest that polymorphisms in Matrilin-1 could be used as a marker for genetic susceptibility to mandibular prognathism.