Outcomes with lower 25D levels across a range that is also associated with Vorinostat 149647-78-9 significant but small reductions in bone mineral density. In our model dietary vitamin D deficiency induced relative changes in bone mineral density by 12 weeks greater than those associated with variation in vitamin D levels in community populations. This suggests that the degree of vitamin D deficiency attained by our intervention approach was sufficiently severe to be physiologically relevant. Consequently, cardiovascular pathology induced in more severe models of vitamin D deficiency may not relate to clinical observations, though there may of course be species differences in tissue-specific susceptibility to vitamin D deficiency. Our model suggests that increased diffuse atherosclerotic calcification is an earlier sequel of vitamin D-deficiency than adverse metabolic profile, hypertension and lower nitric oxide levels. The relevance of this increase to the association of lower vitamin D levels with cardiovascular outcomes is unclear. Further work is needed to determine the underlying mechanism and consequences of this phenomenon. Importantly, cardiovascular benefits of vitamin D supplementation are currently being investigated in a large clinical trial. Cervical cancer is a major contributor to cancer-related death in females worldwide and accounts for 250,000 deaths each year. Although infection with high-risk human papillomaviruses is intimately related to the development of cervical carcinoma, progressing from an HPV-positive premalignant lesion to invasive carcinoma is a rare event. Several reports have suggested that the aggressive nature of human cervical carcinoma is related to a number of molecular abnormalities, including inactivation of various tumor suppressor genes and activation of various oncogenes. The development of novel targeted therapies for cervical cancer has been hindered by the lack of sufficient genetic and epigenetic data concerning its pathogenesis and the paucity of targets. The KLF4 gene, a critical transcription regulator of cell growth and differentiation, has been reported to be dysregulated in several human cancers. The KLF4 gene was found to be frequently downregulated in gastric cancers, pancreatic ductal carcinoma, lung cancer, and medulloblastoma. Moreover, forced overexpression of KLF4 inhibits cell proliferation and growth of colon, bladder, and esophageal cancers. However, KLF4 expression was shown to be increased in breast cancer and head and neck squamous cell carcinomas. The KLF4 gene was shown to be genetically and epigenetically inactivated in human pancreatic cancer and gastric cancer, as well as in medulloblastoma, and to be mutated in colon cancer. In our pervious study, the KLF4 gene was found to be inactivated and to function as a tumor suppressor in cervical carcinogenesis. However, it remains unknown how KLF4 is silenced in cervical carcinomas.