Search

La presente tesis doctoral, Edición crítica y estudio del «Examen de la composición teriacal de Andrómaco», del licenciado Liaño, médico de Burgos, tiene como propósito recuperar y poner a disposición de la comunidad científica un valioso testimonio de nuestro acervo históricoliterario e histórico-médico del siglo XVI: un diálogo de tema médico-farmacológico en castellano sobre el medicamento denominado triaca magna o triaca de Andrómaco, obra de un muy poco conocido médico de nombre Juan de Liaño. Hasta la fecha, y a excepción de la bibliografía material y repertorial, las diferentes disciplinas potencialmente interesadas en el estudio del Examen de la composición teriacal de Andrómaco habían ignorado su existencia. Tampoco se disponía de ninguna edición posterior a la única conocida, impresa en Burgos, en casa de Martín Muñoz y Tomé Rico, en 1546. Por ello, el objetivo fundamental de esta tesis doctoral ha sido la edición crítica y la anotación del diálogo. Asimismo, esta edición se acompaña de un estudio introductorio en el que se analizan las cuestiones más relevantes para situar e interpretar esta obra en el contexto histórico, científico y literario de su época...

La presente tesis doctoral, Edición crítica y estudio del «Examen de la composición teriacal de Andrómaco», del licenciado Liaño, médico de Burgos, tiene como propósito recuperar y poner a disposición de la comunidad científica un valioso testimonio de nuestro acervo históricoliterario e histórico-médico del siglo XVI: un diálogo de tema médico-farmacológico en castellano sobre el medicamento denominado triaca magna o triaca de Andrómaco, obra de un muy poco conocido médico de nombre Juan de Liaño. Hasta la fecha, y a excepción de la bibliografía material y repertorial, las diferentes disciplinas potencialmente interesadas en el estudio del Examen de la composición teriacal de Andrómaco habían ignorado su existencia. Tampoco se disponía de ninguna edición posterior a la única conocida, impresa en Burgos, en casa de Martín Muñoz y Tomé Rico, en 1546. Por ello, el objetivo fundamental de esta tesis doctoral ha sido la edición crítica y la anotación del diálogo. Asimismo, esta edición se acompaña de un estudio introductorio en el que se analizan las cuestiones más relevantes para situar e interpretar esta obra en el contexto histórico, científico y literario de su época..., The purpose of this PhD thesis, Critical edition and study of the «Exam of Andromachus’s theriacal composition», by Licensed Liaño, physician of Burgos, is to recover and to make available to the scientific community a significant testimony of our 16th century historical-literary and historical-medical heritage: a medical and pharmacological dialogue in Spanish on the medication known as the theriaca magna or theriaca Andromachi, written by a very little-known physician named Juan de Liaño. To this date, Exam of Andromachus’s theriacal composition had gone unnoticed to the specialists in the different disciplines potentially interested in its study, with the exemption of the material and repertorial bibliography, which had indeed given an account of its existence. Nor was there any edition available to the only one that was known, printed in Burgos, in the house of Martín Muñoz and Tomé Rico, in 1546. Thus, the main objective of this PhD thesis has been the critical edition as well as the annotation of the dialogue. Furthermore, this edition is accompanied by an introductory study that analyses the most relevant issues to situate and interpret this work in the historical, scientific and literary context of its time. Our critical edition relies on the study of the printed transmission of the work and, more specifically, in the material analysis of the only known copy, the one from Burgos in 1546, as well as in the collating of 5 out of the 6 copies localized. Such methodology assures the possibility of reaching a reliable and refined version of the printed texts; hence it is the one that has been used in this work...

Consumers’ perception of meat products has changed in recent years, which has led to an increased interest in healthier meat products. In response to this demand, academia and industry have made efforts to reformulate meat products, especially dry fermented meat products, which are known for their high fat contents, mainly saturated fat. The use of plant or marine oils stabilized in emulsion gels (EGs) or oil-bulking agents (OBAs) as animal fat replacers has been one of the most advantageous strategies to reformulate dry fermented meat products with a healthier lipid content (quality and quantity), but an increase in their polyunsaturated fatty acid content can trigger a significant increase in lipid oxidation, negatively affecting sensory and nutritional quality. The use of antioxidants is the main strategy to delay this deteriorative reaction, but the controversy around the safety and toxicity of synthetic antioxidants has driven consumers and industry toward the use of plant antioxidants, such as phenolic compounds, carotenoids, and some vitamins and minerals. This review provides information about the use of plant antioxidants to control lipid oxidation of dry fermented meat products with healthier lipids.

The incidence of early-onset colorectal cancer (EOCRC; age younger than 50 years) has been progressively increasing over the last decades globally, with causes unexplained. A distinct molecular feature of EOCRC is that compared with cases of late-onset colorectal cancer, in EOCRC cases, there is a higher incidence of Nodal Modulator 1 (NOMO1) somatic deletions. However, the mechanisms of NOMO1 in early-onset colorectal carcinogenesis are currently unknown. In this study, we show that in 30% of EOCRCs with heterozygous deletion of NOMO1, there were pathogenic mutations in this gene, suggesting that NOMO1 can be inactivated by deletion or mutation in EOCRC. To study the role of NOMO1 in EOCRC, CRISPR/cas9 technology was employed to generate NOMO1 knockout HCT-116 (EOCRC) and HS-5 (bone marrow) cell lines. NOMO1 loss in these cell lines did not perturb Nodal pathway signaling nor cell proliferation. Expression microarrays, RNA sequencing, and protein expression analysis by LC–IMS/MS showed that NOMO1 inactivation deregulates other signaling pathways independent of the Nodal pathway, such as epithelial–mesenchymal transition and cell migration. Significantly, NOMO1 loss increased the migration capacity of CRC cells. Additionally, a gut-specific conditional NOMO1 KO mouse model revealed no subsequent tumor development in mice. Overall, these findings suggest that NOMO1 could play a secondary role in early-onset colorectal carcinogenesis because its loss increases the migration capacity of CRC cells. Therefore, further study is warranted to explore other signalling pathways deregulated by NOMO1 loss that may play a significant role in the pathogenesis of the disease.

Metastatic melanoma is a highly immunogenic tumor with very poor survival rates due to immune system escape-mechanisms. Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and the programmed death-1 (PD1) receptors, are being used to impede immune evasion. This immunotherapy entails an increment in the overall survival rates. However, melanoma cells respond with evasive molecular mechanisms. ERK cascade inhibitors are also used in metastatic melanoma treatment, with the RAF activity blockade being the main therapeutic approach for such purpose, and in combination with MEK inhibitors improves many parameters of clinical efficacy. Despite their efficacy in inhibiting ERK signaling, the rewiring of the melanoma cell-signaling results in disease relapse, constituting the reinstatement of ERK activation, which is a common cause of some resistance mechanisms. Recent studies revealed that the combination of RAS–ERK pathway inhibitors and ICI therapy present promising advantages for metastatic melanoma treatment. Here, we present a recompilation of the combined therapies clinically evaluated in patients.

The effects of gelled emulsions (GE) used as animal fat replacers in terms of the nutritional, technological, and sensory properties of Bologna sausages during 60 days of chilled storage have been studied. Samples with GE added exhibited a fat reduction of 31%. Sausages with GE had higher values of L* and lower values of a* compared to the control. Harder sausages were obtained by the addition of GE. Higher lipid oxidation rates were found with increasing amounts of GE in the reformulated products. In addition, the relaxation time was not affected by the reformulation. All samples were deemed acceptable by consumer tests. However, CATA (Check-all-that-apply) tests showed that Bolognas formulated with partial or total pork fat replaced with GE were described as rubbery, not very spicy and firm, appeared to be dry and opaque, and had an aftertaste. Chilled storage significantly affected the Thiobarbituric Acid Reactive Substances (TBARS) values and slightly affected the pH values, texture, color, and NMR data. An important result is that the panelists did not detect the oxidation results in relation to the TBARS values, and the addition of a GE with inulin as dietary fiber may be a good strategy to make Bologna sausage healthier.

In addition to central functions in cell adhesion signalling, integrin-associated proteins have wider roles at sites distal to adhesion receptors. In experimentally defined adhesomes, we noticed that there is clear enrichment of proteins that localise to the nucleus, and conversely, we now report that nuclear proteomes contain a class of adhesome components that localise to the nucleus. We here define a nucleo-adhesome, providing experimental evidence for a remarkable scale of nuclear localisation of adhesion proteins, establishing a framework for interrogating nuclear adhesion protein functions. Adding to nuclear FAK’s known roles in regulating transcription, we now show that nuclear FAK regulates expression of many adhesion-related proteins that localise to the nucleus and that nuclear FAK binds to the adhesome component and nuclear protein Hic-5. FAK and Hic-5 work together in the nucleus, co-regulating a subset of genes transcriptionally. We demonstrate the principle that there are subcomplexes of nuclear adhesion proteins that cooperate to control transcription.

[Background]: IRE1 is an unfolded protein response (UPR) sensor with kinase and endonuclease activity. It plays a central role in the endoplasmic reticulum (ER) stress response through unconventional splicing of XBP1 mRNA and regulated IRE1-dependent decay (RIDD). Multiple myeloma (MM) cells are known to exhibit an elevated level of baseline ER stress due to immunoglobulin production, however RIDD activity has not been well studied in this disease. In this study, we aimed to investigate the potential of RNA-sequencing in the identification of novel RIDD targets in MM cells and to analyze the role of these targets in MM cells., [Methods]: In vitro IRE1-cleavage assay was combined with RNA sequencing. The expression level of RIDD targets in MM cell lines was measured by real-time RT-PCR and Western blot., [Results]: Bioinformatic analysis revealed hundreds of putative IRE1 substrates in the in vitro assay, 32 of which were chosen for further validation. Looking into the secondary structure of IRE1 substrates, we found that the consensus sequences of IRF4, PRDM1, IKZF1, KLF13, NOTCH1, ATR, DICER, RICTOR, CDK12, FAM168B, and CENPF mRNAs were accompanied by a stem-loop structure essential for IRE1-mediated cleavage. In fact, we show that mRNA and protein levels corresponding to these targets were attenuated in an IRE1-dependent manner by treatment with ER-stress-inducing agents. In addition, a synergistic effect between IMiDs and ER-stress inducers was found., [Conclusion]: This study, using RNA sequencing, shows that IRE1 RNase has a broad range of mRNA substrates in myeloma cells and demonstrates for the first time that IRE1 is a key regulator of several proteins of importance in MM survival and proliferation.