Plant homeodomain finger 2 (PHF2) has a role in epigenetic regulation of gene expression by demethylating H3K9-Me2. Several genome-wide studies have demonstrated that the chromosomal region including the PHF2 gene is often deleted in some cancers including colorectal cancer, and this finding encouraged us to investigate the tumor suppressive role of PHF2. As p53 is a critical tumor suppressor in colon cancer, we tested the possibility that PHF2 is an epigenetic regulator of p53. PHF2 was associated with p53, and thereby, promoted p53-driven gene expression in cancer cells under genotoxic stress. PHF2 converted the chromatin that is favorable for transcription by demethylating the repressive H3K9-Me2 mark. In an HCT116 xenograft model, PHF2 was found to be required for the anticancer effects of oxaliplatin and doxorubicin. In PHF2-deficient xenografts, p53 expression was profoundly induced by both drugs, but its downstream product p21 was not, suggesting that p53 cannot be activated in the absence of PHF2. To find clinical evidence about the role of PHF2, we analyzed the expressions of PHF2, p53 and p21 in human colon cancer tissues and adjacent normal tissues from patients. PHF2 was downregulated in cancer tissues and PHF2 correlated with p21 in cancers expressing functional p53. Colon and stomach cancer tissue arrays showed a positive correlation between PHF2 and p21 expressions. Informatics analyses using the Oncomine database also supported our notion that PHF2 is downregulated in colon and stomach cancers. On the basis of these findings, we propose that PHF2 acts as a tumor suppressor in association with p53 in cancer development and ensures p53-mediated cell death in response to chemotherapy.

The preadipocyte-to-adipocyte differentiation (adipogenesis) is a key process in fat mass increase and thus it is regarded as a compelling target for preventing or treating obesity. Of adipogenic hormone receptors, peroxisome proliferator-activated receptor gamma (PPARγ) has crucial roles in adipogenesis and lipid accumulation within adipocytes. Here we demonstrate that the NEDD8 (neuronal precursor cell expressed, developmentally downregulated 8)-based post-translation modification (neddylation) of PPARγ is essential for adipogenesis. During adipogenesis, NEDD8 is robustly induced in preadipocytes and conjugates with PPARγ, leading to PPARγ stabilization. When the neddylation process was blocked by NEDD8-targeting siRNAs (or viral vectors) or an inhibitor MLN4924, adipocyte differentiation and fat tissue development were substantially impaired. We also demonstrate that MLN4924 effectively prevents the high-fat diet-induced obesity and glucose intolerance in mice. This study provides a better understanding of how the PPARγ signaling pathway starts and lasts during adipogenesis and a potential anti-obesity strategy that targets the neddylation of PPARγ.

Symptomatic intracranial atherosclerosis is associated with lower s-adiponectin levels vs other ischemic stroke subtypes.

Fluconazole, which is a drug of the azole family, is safely used in systemic treatment of oral and intravenous injection, but it is difficult to use fluconazole as a topical application because of its large molecular weight and strong hydrophilic property. This study is a multicentre, double-blind, randomised, non-inferiority study to compare the antifungal effect and safety of fluconazole cream 0.5% and 1% with flutrimazole cream 1% in superficial mycosis. A total of 162 subjects selected to participate in this study were equally divided into three groups and assigned to be given fluconazole cream 0.5%, fluconazole cream 1%, and flutrimazole cream 1% in the ratio of 1 : 1. The primary index of drug efficacy was determined by complete mycological cure in which no fungus was detected on KOH smear test 4 weeks after application of fluconazole. The secondary index of efficacy was defined as complete mycological cure 4 weeks after the application of fluconazole, improvement of clinical symptoms and overall effectiveness assessed by the research staff. According to this study, on comparing the efficacy of cure of superficial dermatomycosis after 4 weeks of application, both fluconazole 0.5% and fluconazole 1% cream were found to be equally effective and non-inferior to flutrimazole 1% cream. Given the effectiveness and safety of the drug, both fluconazole 0.5% and 1% cream might be said to be optimal concentration in the treatment of superficial dermatomycosis.

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