PRPF8 increases the aggressiveness of hepatocellular carcinoma by regulating FAK/AKT pathway via fibronectin 1 splicing

López-Cánovas Juan L.,Hermán-Sánchez Natalia,del Rio-Moreno Mercedes,Fuentes-Fayos Antonio C.,Lara-López Araceli,Sánchez-Frias Marina E.,Amado Víctor,Ciria Rubén,Briceño Javier,de la Mata Manuel,Casta 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Hepatocellular carcinoma (HCC) pathogenesis is associated with alterations in splicing machinery components (spliceosome and splicing factors) and aberrant expression of oncogenic splice variants. We aimed to analyze the expression and potential role of the spliceosome component PRPF8 (pre-mRNA processing factor 8) in HCC. PRPF8 expression (mRNA/protein) was analyzed in a retrospective cohort of HCC patients (n = 172 HCC and nontumor tissues) and validated in two in silico cohorts (TCGA and CPTAC). PRPF8 expression was silenced in liver cancer cell lines and in xenograft tumors to understand the functional and mechanistic consequences. In silico RNAseq and CLIPseq data were also analyzed. Our results indicate that PRPF8 is overexpressed in HCC and associated with increased tumor aggressiveness (patient survival, etc.), expression of HCC-related splice variants, and modulation of critical genes implicated in cancer-related pathways. PRPF8 silencing ameliorated aggressiveness in vitro and decreased tumor growth in vivo. Analysis of in silico CLIPseq data in HepG2 cells demonstrated that PRPF8 binds preferentially to exons of protein-coding genes, and RNAseq analysis showed that PRPF8 silencing alters splicing events in multiple genes. Integrated and in vitro analyses revealed that PRPF8 silencing modulates fibronectin (FN1) splicing, promoting the exclusion of exon 40.2, which is paramount for binding to integrins. Consistent with this finding, PRPF8 silencing reduced FAK/AKT phosphorylation and blunted stress fiber formation. Indeed, HepG2 and Hep3B cells exhibited a lower invasive capacity in membranes treated with conditioned medium from PRPF8-silenced cells compared to medium from scramble-treated cells. This study demonstrates that PRPF8 is overexpressed and associated with aggressiveness in HCC and plays important roles in hepatocarcinogenesis by altering FN1 splicing, FAK/AKT activation and stress fiber formation.

Probing spin and orbital Kondo effects with a mesoscopic interferometer

Ló,pez, Rosa,Sá,nchez, David,Lee, Minchul,Choi, Mahn-Soo,Simon, Pascal,Le Hur, Karyn American Physical Society 2005 Physical review. B, Condensed matter and materials Vol.71 No.11

Analyzing Nursing Leadership at an Academic Historical Event: A Descriptive Study Based On Social Networks

Marqués-Sánchez Pilar,Cummings Greta,Martínez-Fernández María Cristina,Martínez-Gimeno María Lara,López María,Serrano-Fuentes Néstor 한국간호과학회 2020 Asian Nursing Research Vol.14 No.2

Purpose: To analyze the leadership network structure among nursing leaders in Spain identified through the Grupo40Enfermeras y Universidad event. Methods: A descriptive cross-sectional study using social network analysis was used. Study sample consisted of 210 individuals, of whom 119 received nominations as referents. Structural analysis of the network was conducted using centrality and cohesion. Results: A network structure was generated in which different leadership strategies were identified through InDegree, Eigenvector, and Betweenness Centrality. Five leaders were identified as bridges to other individuals using Betweenness. The whole network presented little cohesion although two highly cohesive cores were detected by K-core measurements. Conclusion: A strategy is needed to support nursing leaders with high degree of Betweenness to serve as bridges to connect other nursing leaders

Gallibacterium elongation factor-Tu possesses amyloid-like protein characteristics, participates in cell adhesion, and is present in biofilms

Jaqueline López-Ochoa,J. Fernando Montes-García,Candelario Vázquez,Patricia Sánchez-Alonso,Victor M. Pérez-Márquez,Patrick J. Blackall,Sergio Vaca,Erasmo Negrete-Abascal 한국미생물학회 2017 The journal of microbiology Vol.55 No.9

Gallibacterium, which is a bacterial pathogen in chickens, can form biofilms. Amyloid proteins present in biofilms bind Congo red dye. The aim of this study was to characterize the cell-surface amyloid-like protein expressed in biofilms formed by Gallibacterium strains and determine the relationship between this protein and curli, which is an amyloid protein that is commonly expressed by members of the Enterobacteriaceae family. The presence of amyloid-like proteins in outer membrane protein samples from three strains of G. anatis and one strain of Gallibacterium genomospecies 2 was evaluated. A protein identified as elongation factor-Tu (EF-Tu) by mass spectrometric analysis and in silico analysis was obtained from the G. anatis strain F149T. This protein bound Congo red dye, cross-reacted with anti-curli polyclonal serum, exhibited polymerizing properties and was present in biofilms. This protein also reacted with pooled serum from chickens that were experimentally infected with G. anatis, indicating the in vivo immunogenicity of this protein. The recombinant EF-Tu purified protein, which was prepared from G. anatis 12656-12, polymerizes under in vitro conditions, forms filaments and interacts with fibronectin and fibrinogen, all of which suggest that this protein functions as an adhesin. In summary, EF-Tu from G. anatis presents amyloid characteristics, is present in biofilms and could be relevant for the pathogenesis of G. anatis.

USO Y DISTRIBUCIÓN DEL TIEMPO EN MUJERES Y HOMBRES OFICIALES DE POLICÍA DE LA CIUDAD DE MÉXICO

Jahel López Guerrero,Abigain Dely García López,Jimena Sánchez Barrenechea Institute of Iberoamerican Studies Pusan Universit 2013 International Journal of Latin American Studies Vol.3 No.1

Abstract. Historically, police workplace has been considered as a male-only-space, with particular characteristics, because it is linked to power and to the legitimate use of it. Therefore, we have decided to investigate whether woman who work in this area are in a process of empowerment. Knowing the existence of diverse factors involved in the process of empowerment, we evaluated time use (classifying time into four categories: paid work time, obligated time, leisure time and unpaid work time) as a tool to analyze gender inequalities and possible changes in status and position in the workplaces and familiar spaces. The aim of this paper is to provide overview data about time use and distribution of women and men who work as police officers in Mexico City Ministry of Public Security, analyzing the distribution of their activities during a working day and during a day off. Even though there was no evidence of gender differences in time use during a working day, we did observe some during a day off, specially attending to unpaid work time and leisure time categories. Palabras clave: tiempo, trabajo, empoderamiento, policías, desigualdades de género. Keywords: time, work, empowerment, police officers, gender inequalities. Resumen. La Policía es un espacio laboral considerado históricamente masculino, que tiene características peculiares al estar ligada al poder y al uso legítimo de la fuerza. Por ello hemos decidido investigar sí las mujeres que laboran en este ámbito están en un proceso de empoderamiento. Sabiendo de antemano que existen diversos factores involucrados en un proceso de empoderamiento, tomamos el tiempo (utilizando las categorías de tiempo de trabajo remunerado, tiempo obligado, tiempo de ocio y tiempo de trabajo no remunerado) como una herramienta para analizar las desigualdades de género y los posibles cambios en la condición y posición de las mujeres, que se pueden estar dando en el ámbito laboral y familiar. El objetivo es presentar los primeros resultados sobre el uso y la distribución del tiempo en mujeres y hombres que realizan trabajo operativo en la Secretaria de Seguridad Pública de la Ciudad de México, analizando las actividades realizadas en un día de trabajo y en un día de descanso. Aunque no se observaron diferencias importantes entre hombres y mujeres en el uso y distribución del tiempo durante un día de trabajo, en el día de descanso sí podemos observar diferencias, sobre todo, en el tiempo dedicado al trabajo no remunerado (doméstico) y ocio.

Preparation of Hybrid Devices Containing Nylon/M(II)Pc-TTF (M=Cu, Zn) Films with Potential Optical and Electrical Applications

María Elena Sánchez-Vergara,Diana Monserrat López-Romero,Pablo Vidal-García,Christian Jiménez-Jarquín,Aline Hernandez-García,Omar Jiménez-Sandoval 대한금속·재료학회 2017 ELECTRONIC MATERIALS LETTERS Vol.13 No.3

Hybrid devices consisting of metallophthalocyanines, MPcs(M=Zn, Cu), doped with a Tetrathiafulvalene (TTF) derivativeand dispersed in nylon 11 have been prepared by using a thermalevaporation technique. The effects of thermal relaxation on thestructure and morphology of the samples were studied by FT-IRspectroscopy, SEM and X-ray diffraction. The thermalrelaxation in nylon 11 produced a crystalline arrangement in theα- and β-form MPc molecules. Changes in conductivity of thedevices suggest the formation of alternative paths for carrierconduction. It was found that the temperature-dependent electriccurrent in Zn devices showed a semiconductor behavior. Finally,the optical direct and indirect band gap of these hybrid deviceswas evaluated from optical absorption measurements. The bandgap values were found to decrease from 3.7 to 1.38 eV (for theZnPc device), and from 1.9 to 1.1 eV (for the CuPc device), withthe addition of TTF in the polymeric matrix.

The fibrogenic process and the unleashing of acute-on-chronic liver failure

Guillermo Nahúm López-Sánchez,Mayra Dóminguez-Pérez,Misael Uribe,Natalia Nuño-Lámbarri 대한간학회 2020 Clinical and Molecular Hepatology(대한간학회지) Vol.26 No.1

Acute-on-chronic liver failure (ACLF) is a life-threatening condition characterized by a rapid deterioration of previously well-compensated chronic liver diseases. One of the main obstacles in ACLF is the lack of knowledge of the pathogenesis and specific broad-spectrum treatments. An excessive systemic inflammatory response has been proposed to explain the pathogenesis of ACLF; this hypothesis involves stellate cells, which are implicated in many liver homeostatic functions that include vitamin A storage, regulation of sinusoidal blood flow, local inflammation, maintenance of the hepatocyte phenotype and extracellular matrix remodeling. However, when there is damage to the liver, these cells are the main target of the inflammatory stimulus, as a result, the secretion of the extracellular matrix is altered. Activated hepatic stellate cells raise the survival of neutrophils by the stimulation of granulocytes colonies and macrophages, which exacerbates liver inflammation and promotes damage to hepatocytes. Elevation of pathogen-associated molecular patterns is related to liver damage by different pathophysiological mechanisms of decompensation, showing ballooning degeneration and cell death with a predominance of cholestatic infection. Moreover, patients with ACLF present a marked elevation of C-reactive protein together with an elevation of the leukocyte count. Chronic liver disease is a complex pathological state with a heterogeneous pathophysiology in which genetic factors of the host and external triggers interact and culminate in hepatic insufficiency. The better understanding of such interactions should lead to a better comprehension of the disease and to the discovery of new treatment targets that will make acute decompensations preventable and even decrease mortality.

Curcumin promotes oxidative stress, apoptosis and autophagy in H9c2 rat cardiomyoblasts

Iván Zepeda‑Quiróz,Helen Sánchez‑Barrera,Zaira Colín‑Val,Diana Xochiquetzal Robledo‑Cadena,Sara Rodríguez‑Enríquez,Rebeca López‑Marure 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.4

Background Curcumin, a polyphenol derived from Curcuma longa, has some adverse efects on heart; however, its toxic efects on cardiac cells are poorly understood. Objective To evaluate the toxicity of curcumin on H9c2 rat cardiomyoblasts. To this, H9c2 cells were exposed to diferent concentrations of curcumin and proliferation, viability, cell cycle, oxidative stress, mitochondrial membrane potential (ΔΨm), death and autophagy were evaluated. Results Curcumin caused concentration-dependent inhibition of H9c2 cells proliferation and viability. A higher sub-G1 population was observed in cells treated with curcumin, which was related with phosphatidylserine translocation and increase of activated caspase-9, indicating apoptotic death. Curcumin induced oxidative stress and decreased ΔΨm causing mitochondrial dysfunction. Additionally, it promoted autophagy, revealed by higher LC3B and beclin-1 protein expression and mitophagy. Conclusion Curcumin exhibited toxic efects in cardiac cells and further studies are required to validate its therapeutic potential and use as anti-infammatory and anti-oxidant agent in the cardiovascular system.

A computationally simplistic poly-phasic approach to explore microbial communities from the Yucatan aquifer as a potential sources of novel natural products

Marfil-Santana Miguel David,O’Connor-Sánchez Aileen,Ramírez-Prado Jorge Humberto,De los Santos-Briones Cesar,López-Aguiar,Lluvia Korynthia,Rojas-Herrera Rafael,Lago-Lestón Asunción,Prieto-Davó Alejand 한국미생물학회 2016 The journal of microbiology Vol.54 No.11

The need for new antibiotics has sparked a search for the microbes that might potentially produce them. Current sequencing technologies allow us to explore the biotechnological potential of microbial communities in diverse environments without the need for cultivation, benefitting natural product discovery in diverse ways. A relatively recent method to search for the possible production of novel compounds includes studying the diverse genes belonging to polyketide synthase pathways (PKS), as these complex enzymes are an important source of novel therapeutics. In order to explore the biotechnological potential of the microbial community from the largest underground aquifer in the world located in the Yucatan, we used a polyphasic approach in which a simple, non-computationally intensive method was coupled with direct amplification of environmental DNA to assess the diversity and novelty of PKS type I ketosynthase (KS) domains. Our results suggest that the bioinformatic method proposed can indeed be used to assess the novelty of KS enzymes; nevertheless, this in silico study did not identify some of the KS diversity due to primer bias and stringency criteria outlined by the metagenomics pipeline. Therefore, additionally implementing a method involving the direct cloning of KS domains enhanced our results. Compared to other freshwater environments, the aquifer was characterized by considerably less diversity in relation to known ketosynthase domains; however, the metagenome included a family of KS type I domains phylogenetically related, but not identical, to those found in the curamycin pathway, as well as an outstanding number of thiolases. Over all, this first look into the microbial community found in this large Yucatan aquifer and other fresh water free living microbial communities highlights the potential of these previously overlooked environments as a source of novel natural products.

In Vitro and In Vivo Nematicide Effect of Extract Fractions of Pleurotus djamor Against Haemonchus contortus

Manases González-Cortázar,José E Sánchez,Magaly Huicochea-Medina,Victor M Hernández-Velázquez,Pedro Mendoza-de-Gives,Alejandro Zamilpa,Ma Eugenia López-Arellano,Jesús Antonio Pineda-Alegría,Liliana Ag 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.3

Sheep haemonchosis is a disease that causes anemia, diarrhea, weight loss, low production, and even death of young animals. This represents a negative economic impact on the livestock sector. For decades, chemicals have been used to control this parasitic disease; however, cases of anthelmintic resistance have increased around the world. For this reason, the search for control alternatives is necessary. Several studies have shown that edible mushrooms of Pleurotus genus have different medicinal properties, including nematicidal activity. In this study, the chromatographic fractionation of the hydroalcoholic extract of fruiting bodies Pleurotus djamor was carried out to identify and isolate the metabolites responsible for nematicidal activity. From the fractionation of the extract, the fraction PdR2 and the subfraction PdB were obtained, which were evaluated against Haemonchus contortus under in vitro conditions. The nematicidal effect of the fraction PdB in gerbils infected artificially with H. contortus was evaluated. Finally, the analysis of the PdB fraction by gas chromatography-mass spectrometry and nuclear magnetic resonance was carried out. The results showed that the PdB had 100% of egg hatching inhibition from 5 mg/mL. Regarding larvicidal activity, it presented >97.2% from 24 h to 20 mg/mL. The in vivo evaluation of the PdB fraction showed a reduction of H. contortus larvae of 92.56%. The compounds present in this fraction were the mixture of allitol and an unidentified terpene in a ratio of 9:1. The PdB fraction is a potential alternative for the control of H. contortus, where allitol and a terpene could be responsible for nematicidal activity.