Co-treatment with interferon-γ and 1-methyl tryptophan ameliorates cardiac fibrosis through cardiac myofibroblasts apoptosis

Molecular and Cellular Biochemistry - Electron transfer occurs through heme-Fe across the cytochrome c protein. The current models of long range electron transfer pathways in proteins include...     

p53 negatively regulates Pin1 expression under ER stress

Accumulating evidence suggests that endoplasmic reticulum (ER) stress plays a major role in the development of many diseases. A previous study indicated that the apoptotic regulator p53 is significantly increased in response to ER stress and participates in ER stress-induced apoptosis. However, the regulators of p53 expression during ER stress are still not fully understood. Here, we investigated whether p53 contributes to the impairment of Pin1 signaling under ER stress. We found that treatment with thapsigargin, a stimulator of p53 expression and an inducer of ER stress, decreased Pin1 expression in HCT116 cells. Also, we identified functional p53 response elements (p53REs) in the Pin1 promoter. Overexpression of p53 significantly decreased Pin1 expression in HCT116 cells while abolition of p53 gene expression induced Pin1 expression. Pin1 expression was significantly increased by treatment with the p53 inhibitor pifithrin-α or down-regulation of p53 expression. Taken together, ER stress decreased Pin1 expression through p53 activation, and this mechanism may be associated with ER stress-induced cell death. These data reported here support the importance of Pin1 as a potential target molecule mediating tumor development.     

Therapeutic granulocyte transfusions for the treatment of febrile neutropenia in patients with hematologic diseases: a 10-year experience at a single institute

Background aimsThis single-center 10-year retrospective study assessed clinical efficacies and adverse events and determined prognostic factors in patients with hematologic disease and febrile neutropenia treated with granulocyte transfusions (GT) from unrelated healthy donors stimulated with recombinant human granulocyte–colony-stimulating factor (rhG-CSF) and dexamethasone.MethodsBetween September 1999 and June 2009, 1027 therapeutic GT were performed for the treatment of 170 episodes of febrile neutropenia in 157 patients. Efficacy analysis included 979 GT for 138 episodes in 128 patients who received at least three GT per episode. Adverse event analysis included all patients who received at least one GT.ResultsThe median granulocyte dose was 0.96 × 10⁹/kg/transfusion (range 0.47–1.80 × 10⁹/kg/transfusion). Infection was controlled in 73 episodes (52.9%). The 28-day infection-related survival rate was 64.7 ± 4.1%. The dose of granulocytes transfused did not correlate with clinical outcome. Multivariate analysis revealed that septic shock and pneumonia/multiple primary infection sites were related to infection control failure. Furthermore, refractory underlying disease and septic shock were associated with shorter infection-related survival. Massive hemoptysis (3.5%) and respiratory failure (5.9%) occurred in a few patients. Prior pneumonic infiltration, azotemia and a larger volume of daily GT were associated with serious respiratory complications.ConclusionsGT therapy is a viable adjunctive treatment option for febrile neutropenia as a bridge to autologous hematopoietic recovery in patients with hematologic disease with tolerable toxicity. GT therapy requires close monitoring in patients with prior pneumonic infiltration and azotemia. It is recommended that transfusion with higher volumes is avoided.