Butyrate down-regulates CD44 transcription and liver colonisation in a highly metastatic human colon carcinoma cell line

Over-expression of the adhesion molecule CD44 and its splice variants, especially CD44v6, is associated with poor prognosis and metastasis. We aimed at regulating the expression of CD44 in the highly metastatic human colon cancer cell line HM7 and thereby affecting its metastatic ability. HM7 cells show constitutive expression of CD44 standard and variants isoforms, which were significantly down-regulated by treatment with butyrate. Butyrate significantly inhibited transcription of the CD44 gene and abolished epidermal growth factor-mediated up-regulation of the reporter gene luciferase subcloned upstream to the CD44 promoter (−1.1 kb) and transfected to HM7 cells. Nuclear proteins from butyrate-treated cells bound to an epidermal growth factor receptor element motif present in the CD44 promoter. Epidermal growth factor receptor element-site directed mutations eliminated the inducibility of the luciferase reporter gene and did not allowed binding of nuclear proteins harvested from butyrate-treated cells. Butyrate induced CD44 gene repression by specifically interacting with an epidermal growth factor receptor element nuclear transcriptional factor. This interaction affects CD44 transcriptional activity vis-à-vis in vivo metastatic ability of HM7 cells. These results provide additional insight into the anticarcinogenic properties of butyrate

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling

The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice

The Ski and Sno oncoproteins are components of a macromolecular complex containing the co-repressor N-CoR/SMRT, mSin3 and histone deacetylase. This complex has been implicated in the transcriptional repression exerted by a number of repressors including nuclear hormone receptors and Mad. Further more, Ski and Sno negatively regulate transforming growth factor-β (TGF-β) signaling by recruiting this complex to Smads. Here we show that loss of one copy of sno increases susceptibility to tumorigenesis in mice. Mice lacking sno died at an early stage of embryogenesis, and sno was required for blastocyst formation. Heterozygous (sno(+/–)) mice developed spontaneous lymphomas at a low frequency and showed an increased level of tumor formation relative to wild-type mice when challenged with a chemical carcinogen. sno(+/–) embryonic fibroblasts had an increased proliferative capacity and the introduction of activated Ki-ras into these cells resulted in neoplastic transformation. The B cells, T cells and embryonic fibroblasts of sno(+/–) mice had a decreased sensitivity to apoptosis or cell cycle arrest. These findings demonstrate that sno acts as a tumor suppressor at least in some types of cells