These changes in PGC-1a levels served as a causal factor or as a mediator of the corresponding pathophysiologic processes. In addition to alterations of the insulin/glucagon axis, the direct effect of chronic hyperglycemia may affect the Dabrafenib expression level of PGC1a. In our previous study, we were the first to report that high glucose directly inhibits PGC-1a expression in isolated rat islets. Here, we show that PGC-1a mRNA expression is inhibited in blood vessel media in STZ-diabetic rats. Further experiments revealed that high glucose directly, and dose-dependently, inhibits PGC-1a mRNA expression in cultured rat VSMCs. Of the many potential peripheral stress responses, we chose to look specifically at wound healing, as we had previously shown that rats reared in an impoverished environment had substantially worse wound healing and decreased brain activity in a key region of the brain involved in stress response. Furthermore, substantial literature indicates that wound healing is impaired by psychological stress. In humans, female caretakers of Alzheimer patients , women reporting high levels of general life-stress , young adults undergoing an academic exam , couples undergoing marital distress , and patients with pre-existing psychotic illnesses show delayed wound healing. In rodents, restraint stress impairs wound healing and cytokine expression. A few studies have shown that interventions in rodents designed to reduce stress can improve wound healing and abnormal behaviors.. Accurate chromosome segregation during eukaryotic cell division is achieved by a microtubule-based bipolar spindle which generates forces to move the replicated chromosomes toward opposite poles. It has been a long standing question how spindle microtubules generate the poleward forces to segregate chromosomes during cell division. Although the detailed molecular mechanisms are still not completely understood, a proteinaceous structure assembled at the chromosomal centromere region, plays important roles in chromosome segregation. The kinetochore mediates the physical interactions between a replicated chromosome and microtubules to establish a biorientation configuration during metaphase and ensure accurate segregation during anaphase. The kinetochore-connected microtubules, or K-fibers, are thought to apply the poleward forces to the chromosomes and pull chromosomes toward the opposing poles during anaphase. Other studies have shown that physical contact facilitates wound healing. These results indicate that high glucose decreases PGC-1a expression in VSMCs both in vivo and in vitro. However, the precise mechanism through which high glucose regulates PGC-1a expression in VSMC needs further study. HIRA is a histone chaperone capable of nucleosome assembly and deposition outside of S-phase , with a role in deposition of the histone variant H3.3. Furthermore, induced expression of a phosphorylation-site-mutated PSM-RB causes G1 arrest to protect cells from DNA damage-induced apoptosis.