Prognostic Gene Expression-Based Signature in Clear-Cell Renal Cell Carcinoma

The inaccuracy of the current prognostic algorithms and the potential changes in the therapeutic management of localized ccRCC demands the development of an improved prognostic model for these patients. To this end, we analyzed whole-transcriptome profiling of 26 tissue samples from progressive and non-progressive ccRCCs using Illumina Hi-seq 4000. Differentially expressed genes (DEG) were intersected with the RNA-sequencing data from the TCGA. The overlapping genes were used for further analysis. A total of 132 genes were found to be prognosis-related genes. LASSO regression enabled the development of the best prognostic six-gene panel. Cox regression analyses were performed to identify independent clinical prognostic parameters to construct a combined nomogram which includes the expression of CERCAM, MIA2, HS6ST2, ONECUT2, SOX12, TMEM132A, pT stage, tumor size and ISUP grade. A risk score generated using this model effectively stratified patients at higher risk of disease progression (HR 10.79; p < 0.001) and cancer-specific death (HR 19.27; p < 0.001). It correlated with the clinicopathological variables, enabling us to discriminate a subset of patients at higher risk of progression within the Stage, Size, Grade and Necrosis score (SSIGN) risk groups, pT and ISUP grade. In summary, a gene expression-based prognostic signature was successfully developed providing a more precise assessment of the individual risk of progression

The brazilian Amaryllidaceae as a source of acetylcholinesterase inhibitory alkaloids

Nine Brazilian Amaryllidaceae species were studied for their alkaloid composition and acetylcholinesterase (AChE) inhibitory activity via GC-MS and a modified Ellman assay, respectively. A total of thirty-six alkaloids were identified in these plants, of which Hippeastrum papilio and H. glau-cescens exhibited the highest galanthamine content and the best IC50 values against AChE. Furthermore, Hippeastrum vittatum and Rhodophiala bifida also showed notable AChE inhibitory effects. X-ray crys-tallographic data for four galanthamine-type com-pounds revealed significant differences in the orientation of theN-methyl group, which are shown to be related to AChE inhibition

Estudi i avaluació del paper dels bacteriòfags en la prevenció d’infeccions en agricultura i en animals de producció

Este art&iacute;culo realiza una breve revisi&oacute;n bibliogr&aacute;fica sobre los bacteri&oacute;fagos, sus caracter&iacute;sticas y sus mecanismos de replicaci&oacute;n. A partir de los estudios revisados, se eval&uacute;a la fagoterapia, como medida profil&aacute;ctica en agricultura y animales de renta. Se comenta la legislaci&oacute;n, y se constata que en la Uni&oacute;n Europea (UE) no est&aacute; incluida la fagoterapia, por lo que, actualmente, no es posible aplicarla. Se aportan y se exponen las ventajas y dificultades derivadas de la aplicaci&oacute;n de bacteri&oacute;fagos como herramienta de prevenci&oacute;n y de control frente a las infecciones de etiolog&iacute;a bacteriana.This paper provides a brief literature review on bacteriophages, their key features and their replication mechanisms. On the basis of the reviewed studies, phage therapy is evaluated as a prophylactic measure in agriculture and for livestock. The relevant legislation is discussed and it is noted that phage therapy is not contemplated in the European Union (EU), which is why it is currently not possible to apply it. The benefits and difficulties involved in the application of bacteriophages as a tool for the prevention and control of infections of bacterial etiology are listed and discussed.Aquest treball fa una breu revisi&oacute; bibliogr&agrave;fica sobre els bacteri&ograve;fags, les seves caracter&iacute;stiques i els seus mecanismes de replicaci&oacute;. A partir dels estudis revisats, s&rsquo;avalua la fagoter&agrave;pia, com a mesura profil&agrave;ctica en l&rsquo;agricultura i els animals de renda. Es comenta la legislaci&oacute; sobre aquesta t&egrave;cnica, i es constata que a la Uni&oacute; Europea (UE) no s&rsquo;inclou la fagoter&agrave;pia com a m&egrave;tode de tractament, ra&oacute; per la qual, actualment, no &eacute;s possible aplicar-la. S&rsquo;aporten i s&rsquo;exposen els avantatges i les dificultats derivades de l&rsquo;aplicaci&oacute; dels bacteri&ograve;fags com a eina de prevenci&oacute; i de control enfront de les infeccions d&rsquo;etiologia bacteriana

Chemical Survey of Three Species of the Genus <i>Rauhia</i> Traub (Amaryllidaceae)

Plant biodiversity is an important source of compounds with medicinal properties. The alkaloid galanthamine, first isolated from Galanthus woronowii (Amaryllidaceae), is approved by the FDA for the palliative treatment of mild to moderate Alzheimer’s disease due to its acetylcholinesterase (AChE) inhibitory activity. Obtaining this active pharmaceutical ingredient, still sourced on an industrial scale from the Amaryllidaceae species, is a challenge for pharmaceutical companies due to its low natural yield and the high cost of its synthesis. The aim of this work was to determine the alkaloid profile of three different Rauhia (Amaryllidaceae) species collected in Peru, and to assess the potential application of their extracts for the treatment of Alzheimer’s disease. The alkaloids were identified by gas chromatography coupled to mass spectrometry (GC-MS), and the AChE inhibitory activity of the extracts was analyzed. Thirty compounds were quantified from the Rauhia species, the R. multiflora extract being the most interesting due to its high diversity of galanthamine-type structures. The R. multiflora extract was also the most active against AChE, with the half maximal inhibitory concentration (IC50) values of 0.17 ± 0.02 μg·mL−1 in comparison with the IC50 values of 0.53 ± 0.12 μg·mL−1 for galanthamine, used as a reference. Computational experiments were carried out on the activity of the galanthamine-type alkaloids identified in R. multiflora toward five different human AChE structures. The simulation of the molecules 3-O-acetylgalanthamine, 3-O-acetylsanguinine, narwedine, and lycoraminone on the 4EY6 crystal structure theoretically showed a higher inhibition of hAChE and different interactions with the active site compared to galanthamine. In conclusion, the results of this first alkaloid profiling of the Rauhia species indicate that R. multiflora is an important natural source of galanthamine-type structures and could be used as a model for the development of biotechnological tools necessary to advance the sustainable production of galanthamine

Alkaloid Profile in Wild Autumn-Flowering Daffodils and Their Acetylcholinesterase Inhibitory Activity

Amaryllidaceae alkaloids are secondary metabolites with interesting medicinal properties. Almost every Narcissus species can synthesize them and constitute an excellent source for their isolation and study. Several Amaryllidaceae alkaloids have shown acetylcholinesterase inhibitory activities and are a promising tool for treating cholinergic disorders such as Alzheimer&rsquo;s disease (AD). Indeed, three of the four palliative treatments approved for AD are acetylcholinesterase (AChE) inhibitors and one of them, galanthamine, is an Amaryllidaceae alkaloid itself. This molecule is currently isolated from natural sources. However, its production is insufficient to supply the increasing demand for the active principle. Our main aim is to discover tools to improve galanthamine production and to prospect for potential new and more efficient drugs for AD treatment. Furthermore, we seek to broaden the knowledge of plants of the genus Narcissus from a chemotaxonomic perspective. Hence, in this study, we evaluate the alkaloid content through GC&ndash;MS and the AChE inhibitory activity of ten autumn-flowering Narcissus, which have been less studied than their spring-flowering counterparts. A total of thirty Amaryllidaceae alkaloids have been found, twenty-eight properly identified. Two Narcissus contained galanthamine, and seven were able to inhibit AChE

Alkaloid Profile in Wild Autumn-Flowering Daffodils and Their Acetylcholinesterase Inhibitory Activity

Amaryllidaceae alkaloids are secondary metabolites with interesting medicinal properties. Almost every Narcissus species can synthesize them and constitute an excellent source for their isolation and study. Several Amaryllidaceae alkaloids have shown acetylcholinesterase inhibitory activities and are a promising tool for treating cholinergic disorders such as Alzheimer’s disease (AD). Indeed, three of the four palliative treatments approved for AD are acetylcholinesterase (AChE) inhibitors and one of them, galanthamine, is an Amaryllidaceae alkaloid itself. This molecule is currently isolated from natural sources. However, its production is insufficient to supply the increasing demand for the active principle. Our main aim is to discover tools to improve galanthamine production and to prospect for potential new and more efficient drugs for AD treatment. Furthermore, we seek to broaden the knowledge of plants of the genus Narcissus from a chemotaxonomic perspective. Hence, in this study, we evaluate the alkaloid content through GC–MS and the AChE inhibitory activity of ten autumn-flowering Narcissus, which have been less studied than their spring-flowering counterparts. A total of thirty Amaryllidaceae alkaloids have been found, twenty-eight properly identified. Two Narcissus contained galanthamine, and seven were able to inhibit AChE

Sleep Duration is Inversely Associated with Serum Uric Acid Concentrations and Uric Acid to Creatinine Ratio in an Elderly Mediterranean Population at High Cardiovascular Risk

The aim of the study was to evaluate sleep duration and sleep variability in relation to serum uric acid (SUA) concentrations and SUA to creatinine ratio. This is a cross-sectional analysis of baseline data from 1842 elderly participants with overweight/obesity and metabolic syndromein the (Prevención con Dieta Mediterránea) PREDIMED-Plus trial. Accelerometry-derived sleep duration and sleep variability were measured. Linear regression models were fitted to examine the aforementioned associations. A 1 hour/night increment in sleep duration was inversely associated with SUA concentrations (β = 0.07, p = 0.047). Further adjustment for leukocytes attenuated this association (p = 0.050). Each 1-hour increment in sleep duration was inversely associated with SUA to creatinine ratio (β = 0.15, p = 0.001). The findings of this study suggest that longer sleep duration is associated with lower SUA concentrations and lower SUA to creatinine ratio