Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Medulloblastoma is the most common brain tumor in children, and its prognosis is worse than for many other common pediatric cancers. Survivors undergoing treatment suffer from serious therapy-related side effects. Thus, it is imperative to identify safer, effective treatments for medulloblastoma. In this study we evaluated the anti-cancer potential of curcumin in medulloblastoma by testing its ability to induce apoptosis and inhibit tumor growth <it>in vitro </it>and <it>in vivo </it>using established medulloblastoma models.</p> <p>Methods</p> <p>Using cultured medulloblastoma cells, tumor xenografts, and the Smo/Smo transgenic medulloblastoma mouse model, the antitumor effects of curcumin were tested <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>Curcumin induced apoptosis and cell cycle arrest at the G2/M phase in medulloblastoma cells. These effects were accompanied by reduced histone deacetylase (HDAC) 4 expression and activity and increased tubulin acetylation, ultimately leading to mitotic catastrophe. In <it>in vivo </it>medulloblastoma xenografts, curcumin reduced tumor growth and significantly increased survival in the Smo/Smo transgenic medulloblastoma mouse model.</p> <p>Conclusions</p> <p>The <it>in vitro </it>and <it>in vivo </it>data suggest that curcumin has the potential to be developed as a therapeutic agent for medulloblastoma.</p

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

In-situ photoluminescence measurements during MOVPE of GaN and InGaN in a CCS reactor

Gallium Nitride (GaN) and Indium Gallium Nitride (InGaN) have become important semiconductor materials for the LED lighting industry. Recently, a photoluminescence (PL) technique for direct in-situ characterization of GaN and InGaN layers during epitaxial growth in a planetary metalorganic vapor phase epitaxy (MOVPE) reactor was reported. The PL signals reveal – at the earliest possible stage – information about current layer thickness, temperature, composition, surface roughness, and self-absorption. Thus, the PL data is valuable for both controlling and optimizing the growth parameters, thereby promising both better devices and a better yield for the LED industry. This technical report describes an extension of this PL technique to close coupled showerhead (CCS) reactors with narrow optical viewports. In contrast to the wide aperture optics in previous investigations, a compact and all-fiber optical probe without voluminous lens optics, filter elements or beam splitters was used.Gallium Nitrid (GaN) und Indium Gallium Nitrid (InGaN) sind mittlerweile wichtige Halbleitermaterialien für die LED-Beleuchtungstechnik. Über eine Photolumineszenz (PL)-Technik für eine direkte In-situ Charakterisierung von GaN- und InGaN-Schichten während des epitaktischen Wachstums innerhalb eines Metal Organic Vapor Phase Epitaxy (MOVPE) Planeten-Reaktors wurde kürzlich berichtet. Die PL-Signale liefern – zum frühestmöglichen Zeitpunkt – Informationen über die aktuelle Schichtdicke, Temperatur, Komposition, Oberflächenrauheit und Selbst-Absorption. Somit sind die PL-Daten sowohl nützlich zur Kontrolle als auch zur Optimierung der Wachstumsparameter und damit vielversprechend für bessere Produkte und eine bessere Ausbeute in der LED-Industrie. Dieser technische Bericht beschreibt eine Erweiterung dieser PL-Technik auf Close Coupled Showerhead (CCS) Reaktoren mit eingeschränkten optischen Zugängen. Im Gegensatz zu verwendeten Optiken mit weiter Apertur in vorherigen Untersuchungen wird hier eine kompakte, komplett-faserbasierte optische Sonde ohne voluminöse optische Linsen, Filterelemente oder Strahlteiler verwendet

Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis

The development and severity of inflammatory bowel diseases and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria. However, the mechanisms that integrate these diverse cues remain undefined. Here we demonstrate that mice with an intestinal epithelial cell (IEC)-specific deletion of the epigenome-modifying enzyme histone deacetylase 3 (HDAC3(ΔIEC) mice) exhibited extensive dysregulation of IEC-intrinsic gene expression, including decreased basal expression of genes associated with antimicrobial defence. Critically, conventionally housed HDAC3(ΔIEC) mice demonstrated loss of Paneth cells, impaired IEC function and alterations in the composition of intestinal commensal bacteria. In addition, HDAC3(ΔIEC) mice showed significantly increased susceptibility to intestinal damage and inflammation, indicating that epithelial expression of HDAC3 has a central role in maintaining intestinal homeostasis. Re-derivation of HDAC3(ΔIEC) mice into germ-free conditions revealed that dysregulated IEC gene expression, Paneth cell homeostasis and intestinal barrier function were largely restored in the absence of commensal bacteria. Although the specific mechanisms through which IEC-intrinsic HDAC3 expression regulates these complex phenotypes remain to be determined, these data indicate that HDAC3 is a critical factor that integrates commensal-bacteria-derived signals to calibrate epithelial cell responses required to establish normal host-commensal relationships and maintain intestinal homeostasis