Fumarate drives EMT in renal cancer

Medical Research Counci

Isoflavones and other compounds from the roots of Iris marsica I. Ricci E Colas. Collected from Majella National Park, Italy

In this study, a phytochemical analysis was performed, for the first time, on Iris marsica I. Ricci e Colas. In particular, the attention was focused on the constituents of the roots. Twenty-one compounds were isolated by column chromatography and were analyzed/identified by NMR spectroscopy and mass spectrometry. They all own chemotaxonomic, ethno-pharmacological and nutraceutical relevance which allowed us to provide a phytochemical rationale, for the correct botanical classification of this species, for the employment of its roots in folk medicine like for all the other species belonging to the Iris genus and, lastly, for their further uses as food with important healthy benefits. All of these parts were broadly discussed about within the text

Mitochondrial metabolites: Undercover signalling molecules

Mitochondria are one of most characterized metabolic hubs of the cell. Here, crucial biochemical reactions occur and most of the cellular adenosine triphosphate (ATP) is produced. In addition, mitochondria act as signalling platforms and communicate with the rest of the cell by modulating calcium fluxes, by producing free radicals, and by releasing bioactive proteins. It is emerging that mitochondrial metabolites can also act as second messengers and can elicit profound (epi)genetic changes. This review describes the many signalling functions of mitochondrial metabolites under normal and stress conditions, focusing on metabolites of the tricarboxylic acid cycle. We provide a new framework for understanding the role of mitochondrial metabolism in cellular pathophysiology.C.F. is funded by the MRC Core Fund to the MRC Cancer Unit

Fumarate drives EMT in renal cancer

Medical Research Counci

Metabolic reprogramming and epithelial-to-mesenchymal transition in cancer

Several lines of evidence indicate that during transformation epithelial cancer cells can acquire mesenchymal features via a process called epithelial-to-mesenchymal transition (EMT). This process endows cancer cells with increased invasive and migratory capacity, enabling tumour dissemination and metastasis. EMT is associated with a complex metabolic reprogramming, orchestrated by EMT transcription factors, which support the energy requirements of increased motility and growth in harsh environmental conditions. The discovery that mutations in metabolic genes such as FH, SDH and IDH activate EMT provided further evidence that EMT and metabolism are intertwined. In this review, we discuss the role of EMT in cancer and the underpinning metabolic reprogramming. We also put forward the hypothesis that, by altering chromatin structure and function, metabolic pathways engaged by EMT are necessary for its full activation.MS and CF are funded by an MRC Core Funding to the MRC Cancer Unit

Finite-Size and Illumination Conditions Effects in All-Dielectric Metasurfaces

Dielectric metasurfaces have emerged as a promising alternative to their plasmonic counterparts due to lower ohmic losses, which hinder sensing applications and nonlinear frequency conversion, and their larger flexibility to shape the emission pattern in the visible regime. To date, the computational cost of full-wave numerical simulations has forced the exploitation of the Floquet theorem, which implies infinitely periodic structures, in designing such devices. In this work, we show the potential pitfalls of this approach when considering finite-size metasurfaces and beam-like illumination conditions, in contrast to the typical infinite plane-wave illumination compatible with the Floquet theorem

Essential oil composition and polar fraction analysis of Tanacetum macrophyllum (Waldst. et Kit.) Schultz Bip.

Tanacetum macrophyllum (Waldst. et Kit.) Schultz Bip, also known as Tansy, is a perennial herbaceous plant belonging to the Asteraceae family. This species is typical of the Balcan area but is punctually spread in other European countries as a rare species [1]. In Italy, it is found mainly within forests [1, 2]. This species is often erroneously confused with Achillea grandifolia Friv. [1, 2]. In this work, a comprehensive phytochemical analysis on the volatile components and polar fraction of T. macrophyllum growing in central Italy was carried out. Flowers and leaves were separately analyzed for the essential oil composition and were characterized by oxygenated monoterpenes (39.4%) and oxygenated sesquiterpenes (28.0%) and sesquiterpene hydrocarbons (39.3%) and oxygenated monoterpenes (25.4%), respectively. The phytochemical analysis conducted on the ethanolic extract of the total aerial parts evidenced the presence of twelve compounds: apigenin, cirsimaritin, apigenin-7-O-glucoside, apigenin-7-O-glucuronide, kaempferol-7-O-glucoside, kaempferol-7-O-glucuronide, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, chlorogenic acid, shikimic acid, quinic acid and 4-O-β-D-glucopyranosyl-vanillic acid. Most of these compounds were reported for the first time in the species while three of them are new phytochemicals for the Tanacetum genus. The presence of all these compounds provides a phytochemical rationale for the botanical classification of this species and encourages further ethno-pharmacological studies just like for T. parthenium [3]

Evolution of human IgH3 ' EC duplicated structures: both enhancers HS1,2 are polymorphic with variation of transcription factor's consensus sites

The enhancer complex regulatory region at the 3' of the immunoglobulin heavy cluster (IgH3'EC) is duplicated in apes along with four constant genes and the region is highly conserved throughout humans. Both human IgH3'ECs consist of three loci high sensitive (HS) to DNAse I with enhancer activity. It is thus possible that the presence of structural divergences between the two IgH3'ECs and of relative polymorphisms correspond to functional regulatory changes. To analyse the polymorphisms of these almost identical regions, it resulted mandatory to identify the presence of divergent sequences, in order to select distinctive primers for specific PCR genomic amplifications. To this aim, we first compared the two entire IgH3'ECs in silicio, utilising the updated GenBank (GB) contigs, then we analysed the two IgH3'ECs by cloning and sequencing amplicons from independent genomes. In silicio analysis showed that several inversions, deletions and short insertions had occurred after the duplication. We analysed in detail, by sequencing specific regions, the polymorphisms occurring in enhancer HS1,2-A (which lies in IgH3'EC-1, 3' to the C alpha-1 gene) and in enhancer HS1,2-B (which lies in IgH3'EC-2, 3' to C alpha-2). Polymorphisms are due to the repetition (occurring one to four times) of a 38-bp sequence present at the 3' of the core of enhancers HS1,2. The structure of both human HS1,2 enhancers has revealed not yet described polymorphic features due to the presence of variable spacer elements separating the 38-bp repetitions and to variable external elements bordering the repetition cluster. We found that one of the external elements gave rise to a divergent allele 3 in the two clusters. The frequency of the different alleles of the two loci varies in the Italian population and allele 3 of both loci are very rare. The analysis of the Callicebus moloch, Gorilla gorilla and Pan troglodytes HS1,2 enhancers showed the transformation from the ancestral structure with the 31- to the 17-by external element in hominids. The relevance of the polymorphisms in the HS1,2 enhancers is due to the variable number of binding sites for the transcription factors: NF-kappa B, CMYB, BSAP1/2, AP1/4, E47, MyoD and mu E5 and thus to the possible influence of these variations on switch, production of Ig and on maturation of B cells. (c) 2004 Elsevier B.V. All rights reserved