Long non-coding RNA signatures in the Ileum and Colon of Crohn’s disease patients and effect of Anti-TNF-α treatment on their modulation

Biological therapies only benefit one-third of patients with Crohn’s disease (CD). For this reason, a deeper understanding of the mechanisms by which biologics elicit their effect on intestinal mucosa is needed. Increasing evidence points toward the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of CD, although their role remains poorly studied. We aimed to characterize lncRNA profiles in the ileum and colon from CD patients and evaluate the effect of anti-TNF-α treatment on their transcription. Terminal ileum and left colon samples from 30 patients (active CD = 10, quiescent CD = 10, and healthy controls (HCs) = 10) were collected for RNA-seq. The patients were classified according to endoscopic activity. Furthermore, biopsies were cultured with infliximab, and their transcriptome was determined by Illumina gene expression array. A total of 678 differentially expressed lncRNAs between the terminal ileum and left colon were identified in HCs, 438 in patients with quiescent CD, and 468 in patients with active CD. Additionally, we identified three new lncRNAs in the ileum associated with CD activity. No differences were observed when comparing the effect of infliximab according to intestinal location, presence of disease (CD vs. HC), and activity (active vs. quiescent). The expression profiles of lncRNAs are associated with the location of intestinal tissue, being very different in the ileum and colon. The presence of CD and disease activity are associated with the differential expression of lncRNAs. No modulatory effect of infliximab has been observed in the lncRNA transcriptom

Envejecimiento de la población

•Actividades básicas de la vida diaria en personas mayores y factores asociados •Asociación entre depresión y posesión de mascotas en personas mayores •Calidad de vida en adultos mayores de Santiago aplicando el instrumento WHOQOL-BREF •Calidad de vida en usuarios con enfermedad de Parkinson, demencia y sus cuidadores, comuna de Vitacura •Caracterización de egresos hospitalarios de adultos mayores en Puerto Natales (2007-2009) •Comportamiento de las patologías incluidas como GES para el adulto mayor atendido en un Cesfam •Contribución de vitaminas y minerales a las ingestas recomendadas diarias en ancianos institucionalizados de Madrid •Estado de salud oral del paciente inscrito en el Programa de Visita Domiciliaria •Evaluación del programa de discapacidad severa en Casablanca con la matriz de marco lógico •Factores asociados a satisfacción vital en una cohorte de adultos mayores de Santiago, Chile •Pauta instrumental para la identificación de riesgos para el adulto mayor autovalente, en su vivienda •Perfil farmacológico del paciente geriátrico institucionalizado y posibles consecuencias en el deterioro cognitivo •Programa de cuidados paliativos y alivio del dolor en Puerto Natales •Rehabilitación mandibular implantoprotésica: efecto en calidad de vida relacionada con salud bucal en adultos mayores •Salud bucodental en adultos mayores autovalentes de la Región de Valparaíso •Transición epidemiológica y el estudio de carga de enfermedad en Brasi

Multi-messenger searches via IceCube’s high-energy neutrinos and gravitational-wave detections of LIGO/Virgo

We summarize initial results for high-energy neutrino counterpart searches coinciding with gravitational-wave events in LIGO/Virgo\u27s GWTC-2 catalog using IceCube\u27s neutrino triggers. We did not find any statistically significant high-energy neutrino counterpart and derived upper limits on the time-integrated neutrino emission on Earth as well as the isotropic equivalent energy emitted in high-energy neutrinos for each event

Differential expression of PMCA2 mRNA isoforms in a cohort of Spanish patients with breast tumor types

© 2018 The Authors. Published by Spandidos Publications. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3892/ol.2018.9540© Romero-Lorca et al. The present study examined the mRNA expression levels of different isoforms of the plasma membrane calcium ATPase 2 (PMCA2) gene generated by alternative splicing at the first intracellular loop (site A) and C-terminal region (site C) in 85 human breast cancer tumor and 69 adjacent non-tumor tissues. Associations were identified between the expression of PMCA2 splice isoforms and the following clinical variables: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, tumor size, staging and histological classification, and lymph node status. Transcripts including splice site A or splice site C were amplified by reverse transcription-quantitative polymerase chain reaction using PMCA2 isoform-specific primers. Tumor and adjacent tissues were determined to express the different PMCA2 splice isoforms 2w, 2x and 2z (site A), and 2b (site C). The mRNA levels for these variants indicated high biological variability, but increased expression was observed in breast tumor tissues, compared with in adjacent tissues. Significantly increased PMCA2x/b expression levels were detected in breast tumor tissues histologically classified as lobulillar, compared with in ductal-types breast tumor tissues (P<0.028). Furthermore, PMCA2z expression was significantly associated with PR status (P<0.024, compared with in PR-negative tumor tissues), and PMCA2w expression was significantly associated with ER status (P<0.048, increased in ER-positive tumor tissues, compared with ER-negative tumor tissues). Finally, PMCA2b was overexpressed in HER2-positive tumor tissues, compared with in HER2-negative tumor tissues (P<0.014). The data demonstrated the differential mRNA expression of a number of splice site A and C variants of PMCA2 in breast tumor and adjacent tissues, depending on tumor hormone receptor status and histological classification. In agreement with previous data, PMCA2b was overexpressed in HER2-positive tumor tissues, indicating that high mRNA levels of this variant could be a marker of poor prognosis.The present study was funded by the Universidad Europea de Madrid (project 2014/UEM005).Published versio

Enfermedad boca-mano-pie atípica infantil con rasgos de eczema herpetico y de acrodermatitis.

Hand-foot-mouth disease can present atypically, including forms with more numerous lesions and/or morphologically different from the classic presentation. It may even mimic other viral diseases. We present the case of a 2-year-old child previously diagnosed with atopic dermatitis, who presented with papules and umbilicated vesicles affecting the perioral area and limbs, predominantly in pressure areas, as well as in areas with previous atopic lesions. Although he was clinically diagnosed with herpetic eczema, tests results were negative for herpes virus. However, positive entorovirus polymerase chain reaction results were obtained from the content of a vesicle, a pharyngeal exudate and a stool sample

Abstract 3496: Breast cancer and obesity impact the lipid composition of breast adipose tissue: a preliminary study using shotgun lipidomics

Abstract Obesity, an established risk factor for breast and other cancers, is associated with systemic inflammation and increased visceral adipose tissue. Adipose tissue is a normal constituent of the breast; however, the role of breast adipose tissue in breast cancer development, especially in the context of obesity, has not been addressed before. There is no information on the lipid composition of different fat depots in the body, especially in the context of obesity, and even less among obese tumor hosts. The study of the lipid composition of breast adipose tissue in diet-induced obese (DIO) tumor-bearing and normal mice and its impact in breast cancer progression is novel and has not been previously examined. New profiling methods employing shotgun lipidomics, a technique employed in mass spectrometric analysis using the direct loading of crude lipid extracts into an electrospray ionization source for intrasource separation and identification of numerous lipids, allow for extensive cellular lipid profiles of different tissues being accrued with relative ease. We studied the lipidomic profiles of the breast adipose tissue in lean and DIO normal and tumor bearing mice. Lipidomics analyses were performed using an electrospray triple quadrupole mass spectrometer (TSQ quantum Access Max) and class specific parent-ion or neutral loss scan in positive and negative ion mode with appropriate collision energy. The ratiometic quantification of lipids was done using class specific lipid standards. The phospholipid classes quantified were phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylinositol (PI) and phosphatidylethanolamine (PE). Our results for the PC class reveal an association between the total carbon chain of the lipids and the lipid concentrations based on four conditions: lean control, obese control, lean tumor bearers, and obese tumor bearers. The highest total carbon chain length is associated with the obese tumor condition. The next highest total carbon chain length is associated with lean tumor condition. This demonstrates that both the presence of the tumor as well as obesity play a role in contributing to a higher number of total carbons in the lipid chains. The other lipid classes analyzed express similar patterns from the data gathered when compared to the PC lipid class. Characterizing a particular lipid signature relevant to breast cancer and obesity may allow its targeting with therapeutic purposes. Citation Format: Osvaldo Perez, Michael Margolis, Ana M. Santander, Mitchell Martinez, Sanjoy Bhattacharya, Marta Torroella-Kouri. Breast cancer and obesity impact the lipid composition of breast adipose tissue: a preliminary study using shotgun lipidomics. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3496. doi:10.1158/1538-7445.AM2014-3496</jats:p

Abstract 1086: Paracrine interactions between macrophages, adipocytes and tumor cells in the breast cancer microenvironment of the obese female mouse contribute to tumor progression

Abstract Most studies linking obesity and cancer focus on the systemic effects of adiposity in tumorigenesis. The mammary gland has white adipose tissue required for normal gland development, yet the plausible role that this local breast fat may play in breast cancer, especially in obese females, has been overlooked. Whether obesity also promotes breast cancer through its effect in local adipose tissue inflammation and innate immune signaling in the breast, where cancer occurs, has not been thoroughly investigated. Adipocytes and tumor cells in the breast may recruit macrophages to the tumor microenvironment contributing to tumor progression, particularly in obese females. We examined the interplay between these three cell types and its effects on macrophage chemotaxis in an in vitro setting, using co-cultures of mouse peritoneal macrophages, E0771 murine mammary tumor cells and in vitro differentiated or ex vivo isolated adipocytes from murine obese fat tissue. We also exposed macrophages in vitro to the individual or mixed paracrine factors leptin, lauric acid, estrogen and CCL2 produced by fat and mammary tumor cells to study macrophage chemotaxis, cellular differentiation and M1/M2 activation profiles. Specific signaling inhibitors of these paracrine factors were used to analyze reversion of these actions and proteomics analyses was undertaken to identify novel molecules secreted by adipocytes and mammary tumor cells with actions on macrophages or on the tumor microenvironment. We centered on the adipokine leptin, which has a main role in breast cancer progression, and we showed that leptin decreases pro-inflammatory IL-12, nitric oxide and VEGF production in macrophages but does not alter IL-10 production. A novel leptin-signaling inhibitor peptide was also used in in vivo experiments with diet-induced obese female C57BL6 mice bearing the syngeneic E0771 mammary tumor cells to analyze reduction of tumor progression, tumor-associated macrophage recruitment, crown-like structures in the breast adipose tissue and tumor angiogenesis. Our results underscore the relevance of the interactions between macrophages, adipocytes and tumor cells in the breast cancer microenvironment for tumor progression and demonstrate that the synergistic actions of various paracrine factors from these different cell types play the most crucial role in macrophage recruitment and tumor progression. Citation Format: Ana M. Santander, Tulay Koru-Sengul, Olivia Casas, Lidia Sanchez, Osvaldo Perez, Marta Torroella-Kouri. Paracrine interactions between macrophages, adipocytes and tumor cells in the breast cancer microenvironment of the obese female mouse contribute to tumor progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1086. doi:10.1158/1538-7445.AM2014-1086</jats:p

Abstract 1300: Breast cancer-associated macrophages undergo proliferation at different rates across ethnicities: results of a pilot study

Abstract The tumor microenvironment is a complex biosystem composed of diverse cells, including tumor, immune and non-immune stromal cells. It has become increasingly clear that stromal cells have critical roles in tumor progression. Among the immune stromal cells, tumor-associated macrophages (TAM) are found in abundance, playing critical roles in tumor progression and are signs of poor prognosis. Whereas in chronic inflammation of a tissue M1 pro-inflammatory macrophages may play a role in tumor initiation, in advanced tumors, TAMs promote anti-inflammatory functions including suppression of immunity, tumor invasion, angiogenesis, metastasis, and resemble the behavior of M2 anti-inflammatory macrophages. CD163 is considered a human pan macrophage marker and has been extensively used in TAMs recognition in human tumors. Until recently, macrophages were considered end-differentiated cells without mitotic activity. However, more recently proliferative activity of macrophages has been identified in several settings, but not in tumors. In a recent study, we demonstrated that breast cancers from different ethnicities exhibit diverse degree of TAMs colonization. African American (AA) and Latina (LA) patients present with more aggressive tumors and lower survival rates than Caucasian (CA) women. We recently demonstrated that AA breast cancer patients exhibit tumors with very high numbers of macrophages, followed by LA, with CA showing the lowest numbers of TAMs. Consequently, in the present study we sought to examine whether the high numbers of TAMs detected in these cancer health disparity groups were associated with macrophage capacity to proliferate. To assess TAM mitotic potential, the Ki-67 nuclear marker was used. To examine this question, we carried out a pilot study with a small number of cases where the co-expression levels of Ki-67 and CD163 were determined by immunofluorescence (IF) in sections of human breast cancers from a retrospective breast cancer tumor bank encompassing these three ethnicities. Our results reveal that tumors from AA patients contain the highest numbers of CD163+/Ki-67+ cells among the three ethnic groups, followed by LA, with CA exhibiting the lowest numbers, thus paralleling our results with TAM numbers in these same ethnicities. As far as we know, this is the first report of macrophage proliferation in a tumor microenvironment, and particularly in association with ethnicity cancer disparity groups. Citation Format: Lidia G. Sanchez, Jorge E. Torrez-Munoz, Ana M. Santander, Tan A. Ince, Marta Torroella-Kouri. Breast cancer-associated macrophages undergo proliferation at different rates across ethnicities: results of a pilot study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1300. doi:10.1158/1538-7445.AM2015-1300</jats:p