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

Evolutive emergence and divergence of an Ig regulatory node: An environmental sensor getting cues from the aryl hydrocarbon receptor?

One gene, the immunoglobulin heavy chain (IgH) gene, is responsible for the expression of all the different antibody isotypes. Transcriptional regulation of the IgH gene is complex and involves several regulatory elements including a large element at the 3’ end of the IgH gene locus (3’RR). Animal models have demonstrated an essential role of the 3’RR in the ability of B cells to express high affinity antibodies and to express different antibody classes. Additionally, environmental chemicals such as aryl hydrocarbon receptor (AhR) ligands modulate mouse 3’RR activity that mirrors the effects of these chemicals on antibody production and immunocompetence in mouse models. Although first discovered as a mediator of the toxicity induced by the high affinity ligand 2,3,7,8-tetracholordibenzo-p-dioxin (dioxin), understanding of the AhR has expanded to a physiological role in preserving homeostasis and maintaining immunocompetence. We posit that the AhR also plays a role in human antibody production and that the 3’RR is not only an IgH regulatory node but also an environmental sensor receiving signals through intrinsic and extrinsic pathways, including the AhR. This review will 1) highlight the emerging role of the AhR as a key transducer between environmental signals and altered immune function; 2) examine the current state of knowledge regarding IgH gene regulation and the role of the AhR in modulation of Ig production; 3) describe the evolution of the IgH gene that resulted in species and population differences; and 4) explore the evidence supporting the environmental sensing capacity of the 3’RR and the AhR as a transducer of these cues. This review will also underscore the need for studies focused on human models due to the premise that understanding genetic differences in the human population and the signaling pathways that converge at the 3’RR will provide valuable insight into individual sensitivities to environmental factors and antibody-mediated disease conditions, including emerging infections such as SARS-CoV-2

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]