To evaluate the inhibitory effects of trimethoprim and sulfamethoxazole on cytochrome P450 (P450) isoforms, selective marker reactions for CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 were examined in human liver microsomes and recombinant CYP2C8 and CYP2C9. The in vivo drug interactions of trimethoprim and sulfamethoxazole were predicted in vitro using [I]/([I] + K(i)) v...

Wnt5a activates the Wnt/β-catenin-independent pathway and its overexpression is associated with tumor aggressiveness enhancing invasive activity. For this action, Wnt5a-induced receptor endocytosis with clathrin is required. Wnt5a expression was previously believed to be associated with cancer cell motility but not proliferation. Recently, it was reported that Wnt5a is also implicated in cancer...

Sphingosine 1-phosphate (S1P) influences heart rate, coronary artery caliber, endothelial integrity, and lymphocyte recirculation through five related high affinity G-protein-coupled receptors. Inhibition of lymphocyte recirculation by non-selective S1P receptor agonists produces clinical immunosuppression preventing transplant rejection but is associated with transient bradycardia. Understandi...

IntroductIon According to the demographics, the world population over 60 years will double from 605 million to 2 billion people between 2000 and 2050. Aging is a complex process in which the organism and its ability to respond to external stresses become progressive decline. The degenerative aging process is the major underlying cause for aging‐related diseases, including hypertension, diabetes...

miRNAs typically downregulate the expression of target genes by binding to their 3'UTR, and dysregulation of miRNAs may contribute to tumorigenesis. Here, we found that miR-346 and miR-138 competitively bind to a common region in the 3'UTR of hTERT mRNA and have opposite effects on the expression and function of hTERT in human cervical cancer cells. Furthermore, G-rich RNA sequence binding fact...

The Smc5/6 holocomplex executes key functions in genome maintenance that include ensuring the faithful segregation of chromosomes at mitosis and facilitating critical DNA repair pathways. Smc5/6 is essential for viability and therefore, dissecting its chromosome segregation and DNA repair roles has been challenging. We have identified distinct epigenetic and post-translational modifications tha...

Induction of granulocytic differentiation in HL-60 myeloid leukemia cells by retinoids is followed by their death via apoptosis. Retinoids are known to mediate their biological effects through at least two distinct types of nuclear receptors, the retinoic acid receptors and retinoid X receptors. We undertook to characterize the potential role of these receptors in inducing differentiation and a...

The greater incidence of diseases of the ovary during the childbearing period renders their occurrence as complications of pregnancy and labour far from surprising.' Ovarian disease does not afford an effective barrier to conception. Spiegelberg, for example, reports that on two occasions he examined soon after labour cancerous growths of both ovaries in which not a trace of healthy tissue rema...

Blood coagulation in vivo is a spatially nonuniform, multistage process: coagulation factors from plasma bind to tissue factor (TF)-expressing cells, become activated, dissociate, and diffuse into plasma to form enzymatic complexes on the membranes of activated platelets. We studied spatial regulation of coagulation using two approaches: 1), an in vitro experimental model of clot formation in a...

Mutations in the genes ovo or otu can cause abnormal proliferation of XX germ cells, which leads to so-called ovarian tumors, or they can lead to the elimination of XX germ cells, such that adult females possess empty ovaries. Males carrying ovo or otu mutations are unaffected. To find out when this sexual dimorphism affects germ cells, we analyzed the requirement of embryos and larvae for zygo...