Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice

Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis. Here, we discovered a molecule (M47) that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The M47 selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and resulted in increasing the circadian period length of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 increased degradation of the CRY1 in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced oxaliplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Systemic repetitive administration of M47 increased the median lifespan of p53−/− mice by ~25%. Collectively our data suggest that M47 is a promising molecule to treat forms of cancer depending on the p53 mutation

Serum and urine TNF-like weak inducer of apoptosis, monocyte chemoattractant protein-1 and neutrophil gelatinase-associated lipocalin as biomarkers of disease activity in patients with systemic lupus erythematosus.

Objective

Prevalence of cervical cytological abnormalities in Turkey

Objective: To evaluate retrospectively the prevalence of cervical cytological abnormalities in patient records obtained from healthcare centers in Turkey. Method: Demographic characteristics and data on cervical cytological abnormalities were evaluated from patients who underwent flap tests in healthcare centers in 2007. Results: Data were collected from 33 healthcare centers totaling 140 334 patients. Overall, the prevalence of cervical cytological abnormalities was 1.8%; the prevalence of ASCUS, ASC-H, LSIL, HSIL, and AGC was 1.07%, 0.07%, 0.3%, 0.17%, and 0.08%, respectively. The prevalence of preinvasive cervical neoplasia was 1.7% and the prevalence of cytologically diagnosed invasive neoplasia was 0.06%. Conclusion: The abnormal cervical cytological prevalence rate in Turkey is lower than in Europe and North America. This might be due to sociocultural differences, lack of population-based screening programs, or a lower HPV prevalence rate in Turkey