Molecular map of chronic lymphocytic leukemia and its impact on outcome

Recent advances in cancer characterization have consistently revealed marked heterogeneity, impeding the completion of integrated molecular and clinical maps for each malignancy. Here, we focus on chronic lymphocytic leukemia (CLL), a B cell neoplasm with variable natural history that is conventionally categorized into two subtypes distinguished by extent of somatic mutations in the heavy-chain variable region of immunoglobulin genes (IGHV). To build the ‘CLL map,’ we integrated genomic, transcriptomic and epigenomic data from 1,148 patients. We identified 202 candidate genetic drivers of CLL (109 new) and refined the characterization of IGHV subtypes, which revealed distinct genomic landscapes and leukemogenic trajectories. Discovery of new gene expression subtypes further subcategorized this neoplasm and proved to be independent prognostic factors. Clinical outcomes were associated with a combination of genetic, epigenetic and gene expression features, further advancing our prognostic paradigm. Overall, this work reveals fresh insights into CLL oncogenesis and prognostication

Lipid Alterations in Experimental Murine Colitis: Role of Ceramide and Imipramine for Matrix Metalloproteinase-1 Expression

BACKGROUND:Dietary lipids or pharmacologic modulation of lipid metabolism are potential therapeutic strategies in inflammatory bowel disease (IBD). Therefore, we analysed alterations of bioactive lipids in experimental models of colitis and examined the functional consequence of the second messenger ceramide in inflammatory pathways leading to tissue destruction. METHODOLOGY/PRINCIPAL FINDINGS:Chronic colitis was induced by dextran-sulphate-sodium (DSS) or transfer of CD4(+)CD62L(+) cells into RAG1(-/-)-mice. Lipid content of isolated murine intestinal epithelial cells (IEC) was analysed by tandem mass spectrometry. Concentrations of MMP-1 in supernatants of Caco-2-IEC and human intestinal fibroblasts from patients with ulcerative colitis were determined by ELISA. Imipramine was used for pharmacologic inhibition of acid sphingomyelinase (ASM). Ceramide increased by 71% in chronic DSS-induced colitis and by 159% in the transfer model of colitis. Lysophosphatidylcholine (LPC) decreased by 22% in both models. No changes were detected for phosphatidylcholine. Generation of ceramide by exogenous SMase increased MMP-1-protein production of Caco-2-IEC up to 7-fold. Inhibition of ASM completely abolished the induction of MMP-1 by TNF or IL-1beta in Caco-2-IEC and human intestinal fibroblasts. CONCLUSIONS/SIGNIFICANCE:Mucosal inflammation leads to accumulation of ceramide and decrease of LPC in the intestinal epithelium. One aspect of ceramide generation is an increase of MMP-1. Induction of MMP-1 by TNF or IL-1beta is completely blocked by inhibition of ASM with imipramine. Therefore, inhibition of ASM may offer a treatment strategy to reduce MMP-1 expression and tissue destruction in inflammatory conditions

Estudio de la difusividad térmica de peloides termales en aplicaciones terapéuticas

International audienc

Hydrobiome of Thermal Waters: Potential Use in Dermocosmetics

Over the course of the last 20 years, numerous studies have identified the benefits of thermal waters on different skin conditions. Consequently, several investigations have been carried out on their effects on the skin, which are linked to their chemical composition, and, recently, scientists have turned their attention to the role of the thermal spring’s microbiota, named “hydrobiome”, regarding these therapeutic effects. At the same time, the development of cosmetics based on pre, pro, and postbiotics has reached great relevance and research is increasing every day. This review gathers information on the biological diversity of thermal spring waters and their potential use in obtaining biological compounds, metabolites, or bacterial extracts for use in dermocosmetics as active ingredients. These bioactive compounds are able to improve dermatological diseases such as atopic dermatitis or rosacea and ameliorate pruritus and xerosis; moreover, they can increase protection against UV exposure, strengthen barrier function, maintain good homeostasis of skin defenses, repair damaged skin, promote wound healing, improve skin condition, reduce uneven skin pigmentation, and prevent skin aging. From a future perspective, fruitful cooperation among researchers, hydrologists, thermal spa centers, and cosmetic industries will drive this sector toward a better understanding of the role of the hydrobiome of thermal spring waters on healthy skin and dermatological diseases and consider the inclusion of derivatives of this hydrobiome (in the form of fermenters, lysates, extracts, etc.) in dermocosmetic formulations. Therefore, and being aware of the potential of the hydrobiome in dermatological and skin care applications, the future prospects for the use of bioactive substances derived from it in dermocosmetic formulations are promising

EVOLVING OPTIMAL MULTI-OBJECTIVE HARDWARE USING STRENGTH PARETO EVOLUTIONARY ALGORITHMS

In this paper, we focus on engineering Pareto-optimal digital circuits given the expected input/output behaviour with a minimal design effort. The design objectives to be minimised are: hardware area, response time and power consumption. We do so using the Strength Pareto Evolutionary Algorithms. This is novel application of multi-objective optimisation to circuit design. The performance and quality of the circuits evolved for some benchmarks are presented then compared to those of single objective genetic algorithms as well as to the circuits obtained by human designers. We show that the evolutionary hardware is far better with respect to all objectives than those designed using traditional methods. Keywords: Evolvable hardware, Multi-objective optimisation, Digital circuits, SPEA. 1

Cosmeceuticals and Thalassotherapy: Recovering the Skin and Well-Being after Cancer Therapies

Cancer treatments have undergone significant advances in recent years, although they are not exempt from side effects, including skin toxicity. Different studies show that skin care for cancer patients can be effective in reducing sequelae such as inflammation, xerosis, skin rash, and radiodermatitis, among others. This is the reason why research is being carried out on the ingredients of cosmeceuticals for those indicated for oncological skin care. On the other hand, it is necessary to implement measures that improve the patient’s well-being and, therefore, thalassotherapy techniques and the marine environment could be an effective resource to achieve this goal. This article reviews the publications related to skin care after cancer treatment, including thalassotherapy techniques that can also contribute to well-being

The Potential Use of Marine Microalgae and Cyanobacteria in Cosmetics and Thalassotherapy

The use of microalgae and cyanobacteria for nutritional purposes dates back thousands of years; during the last few decades, microalgae culture has improved to become one of the modern biotechnologies. This has allowed high amounts of algal biomass to be obtained for use in different applications. Currently, the global production of microalgae and cyanobacteria is predominately aimed at applications with high added value given that algal biomass contains pigments, proteins, essential fatty acids, polysaccharides, vitamins, and minerals, all of which are of great interest in the preparation of natural products, both as food and in cosmetics. Hence, the bioactive components from microalgae can be incorporated in cosmetic and cosmeceutical formulations, and can help achieve benefits including the maintenance of skin structure and function. Thalassotherapy involves using seawater and all related marine elements, including macroalgae, however, there has been limited use of microalgae. Microalgae and cyanobacteria could be incorporated into health and wellness treatments applied in thalassotherapy centers due to their high concentration of biologically active substances that are of interest in skin care. This paper briefly reviews the current and potential cosmetic and cosmeceutical applications of marine microalgae and cyanobacteria compounds and also recommends its use in thalassotherapy well-being treatments