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101.
102.
Mahesh Mohan Deepak Kaushal Pyone P. Aye Xavier Alvarez Ronald S. Veazey Andrew A. Lackner 《PloS one》2013,8(4)
The Gastrointestinal (GI) tract plays a pivotal role in AIDS pathogenesis as it is the primary site for viral transmission, replication and CD4+ T cell destruction. Accordingly, GI disease (enteropathy) has become a well-known complication and a driver of AIDS progression. To better understand the molecular mechanisms underlying GI disease we analyzed global gene expression profiles sequentially in the intestinal epithelium of the same animals before SIV infection and at 21 and 90 days post infection (DPI). More importantly we obtained sequential excisional intestinal biopsies and examined distinct mucosal components (epithelium. intraepithelial lymphocytes, lamina propria lymphocytes, fibrovascular stroma) separately. Here we report data pertaining to the epithelium. Overall genes associated with epithelial cell renewal/proliferation/differentiation, permeability and adhesion were significantly down regulated (<1.5–7 fold) at 21 and 90DPI. Genes regulating focal adhesions (n = 6), gap junctions (n = 3), ErbB (n = 3) and Wnt signaling (n = 4) were markedly down at 21DPI and the number of genes in each of these groups that were down regulated doubled between 21 and 90DPI. Notable genes included FAK, ITGA6, PDGF, TGFβ3, Ezrin, FZD6, WNT10A, and TCF7L2. In addition, at 90DPI genes regulating ECM-receptor interactions (laminins and ITGB1), epithelial cell gene expression (PDX1, KLF6), polarity/tight junction formation (PARD3B&6B) and histone demethylase (JMJD3) were also down regulated. In contrast, expression of NOTCH3, notch target genes (HES4, HES7) and EZH2 (histone methyltransferase) were significantly increased at 90DPI. The altered expression of genes linked to Wnt signaling together with decreased expression of PDX1, PARD3B, PARD6B and SDK1 suggests marked perturbations in intestinal epithelial function and homeostasis leading to breakdown of the mucosal barrier. More importantly, the divergent expression patterns of EZH2 and JMJD3 suggests that an epigenetic mechanism involving histone modifications may contribute to the massive decrease in gene expression at 90DPI leading to defects in enterocyte maturation and differentiation. 相似文献
103.
Leonardo M. Fonseca Adriana B. Alvarez Rachel C. Rodrigues Diego H. F. Santos Anibal G. Lopes Marcia A. M. Capella 《PloS one》2013,8(6)
Aims
Glutathione (GSH) plays an important role in protecting cells against oxidative damage. ABCC1 protein transports GSH. Although this protein is largely studied in cancer, due to multidrug resistance phenotype, its role in the tubular cells of the kidney is unknown. The goal of this study was to find out whether ABCC1 has a role in protecting cells from the distal nephron against the stress caused by high medullar osmolality.Main Methods
MA104 cells were treated with high concentrations of sodium chloride, urea, or both to raise the osmolality of the culture medium. Cell viability was accessed by MTT and trypan blue assays. ABCC1 expression and extrusion of carboxi-fluorescein (CF), a fluorescent ABCC1 substrate, were measured by flow cytometry.Key Findings
Incubation of MA104 cells in a high sodium concentration medium resulted in changes in cell granularity and altered expression and activity of ABCC1. Urea did not alter ABCC1 expression or activity, but reversed the observed NaCl effects. High sodium concentrations also had a negative effect on cell viability and urea also protected cells against this effect.Significance
Our findings demonstrate that ABCC1 plays a significant role in the protection of kidney epithelial cells against the stress caused by high sodium environment present in renal medulla. 相似文献104.
Victor M. Victor Susana Rovira-Llopis Celia Ba?uls Noelia Diaz-Morales Arantxa Martinez de Mara?on Cesar Rios-Navarro Angeles Alvarez Marcelino Gomez Milagros Rocha Antonio Hernández-Mijares 《PloS one》2016,11(3)
Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IR<2.5) and PCOS IR (HOMA-IR>2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (ROS) production, MPO levels, interactions between human umbilical vein endothelial cells and leukocytes, adhesion molecules (E-selectin, ICAM-1 and VCAM-1) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated. Oxidative stress was observed in PCOS patients, in whom there was an increase in total and mitochondrial ROS production and MPO levels. Enhanced rolling flux and adhesion, and a decrease in polymorphonuclear cell rolling velocity were also detected in PCOS subjects. Increases in IL-6 and TNF-α and adhesion molecules (E-selectin, ICAM-1 and VCAM-1) were also observed, particularly in the PCOS IR group, providing evidence that inflammation and oxidative stress are related in PCOS patients. HOMA-IR was positively correlated with hsCRP (p<0.001, r = 0.304), ROS production (p<0.01, r = 0.593), leukocyte rolling flux (p<0.05, r = 0.446), E-selectin (p<0.01, r = 0.436) and IL-6 (p<0.001, r = 0.443). The results show an increase in the rate of ROS and MPO levels in PCOS patients in general, and particularly in those with IR. Inflammation in PCOS induces leukocyte-endothelium interactions and a simultaneous increase in IL-6, TNF-α, E-selectin, ICAM-1 and VCAM-1. These conditions are aggravated by the presence of IR. 相似文献
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106.
Maria I. Alvarez‐Mora Petar Podlesniy Ellen Gelpi Renate Hukema Irene Madrigal Javier Pagonabarraga Ramon Trullas Montserrat Mila Laia Rodriguez‐Revenga 《Genes, Brain & Behavior》2019,18(5)
Fragile X‐associated tremor/ataxia syndrome (FXTAS) is a late‐onset neurodegenerative disorder that appears in at least one‐third of adult carriers of a premutation (55‐200 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene. Several studies have shown that mitochondrial dysfunction may play a central role in aging and also in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease as well as in FXTAS. It has been recently proposed that mtDNA copy number, measured by the number of mitochondrial genomes per nuclear genome (diploid), could be a useful biomarker of mitochondrial dysfunction. In order to elucidate the role of mtDNA variation in the pathogenesis of FXTAS, mtDNA copy number was quantified by digital droplet Polymerase chain reaction. In human brain samples, mtDNA levels were measured in the cerebellar vermis, dentate nucleus, parietal and temporal cortex, thalamus, caudate nucleus and hippocampus from a female FXTAS patient, a FMR1 premutation male carrier without FXTAS and from three male controls. The mtDNA copy number was further analyzed using this technology in dermal fibroblasts primary cultures derived from three FXTAS patients and three controls as well as in cortex and cerebellum of a CGG knock in FXTAS mice model. Finally, qPCR was carried out in human blood samples. Results indicate reduced mtDNA copy number in the specific brain region associated with disease progression in FXTAS patients, providing new insights into the role of mitochondrial dysfunction in the pathogenesis of FXTAS. 相似文献
107.
Sabrina Viau Anaïs Lagrange Lucie Chabrand Judith Lorant Marine Charrier Karl Rouger Ignacio Alvarez Sandy Eap Bruno Delorme 《Cytotherapy》2019,21(7):738-754
BackgroundHuman platelet lysate (hPL) represents a powerful alternative to fetal bovine serum (FBS) for human mesenchymal stromal cell (hMSC) expansion. However, the large variability in hPL sources and production protocols gives rise to discrepancies in product quality, characterization and poor batch-to-batch standardization.MethodshPL prepared with more than 200 donors (200+DhPL) or with five donors (5DhPL) were compared in terms of growth factor (GF) contents and biochemical analysis. A multiple protein assay and proteomic analysis were performed to further characterize 200+DhPL batches. We also compared the phenotypic and functional characteristics of bone marrow (BM)-hMSCs grown in 200+DhPL versus FBS+basic fibroblast growth factor (bFGF).ResultsBy contrast to 5DhPL, industrial 200+DhPL displayed a strong standardization of GF contents and biochemical characteristics. We identified specific plasmatic components and platelet-released factors as the most relevant markers for the evaluation of the standardization of hPL batches. We used a multiplex assay and proteomic analysis of 200+DhPL to establish a proteomic signature and demonstrated the robust standardization of batches. 200+DhPL was shown to improve and standardize BM-hMSC expansion compared with FBS+bFGF. The levels of expression of BM-hMSC membrane markers were found to be much more homogeneous between batches when cells were cultured in 200+DhPL. BM-hMSCs cultured in parallel under both conditions displayed similar adipogenic and osteogenic differentiation potential and immunosuppressive properties.ConclusionsWe report a standardization of hPL and the importance of such standardization for the efficient amplification of more homogeneous and reproducible cell therapy products. 相似文献
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110.
Sara Martinez Maria del Mar Delgado Ruben Martinez Marin Sergio Alvarez 《Journal of Industrial Ecology》2019,23(4):879-892
The implementation of global sustainability has gained worldwide attention in recent years. The Organization Environmental Footprint, which encompasses 14 impact categories, is a multicriteria measure of the environmental performance of goods and services provided by an organization from a life cycle perspective. In this article, the focus is on quantifying the Organization Environmental Footprint of a construction company in Spain. By applying an environmentally extended input‐output approach, its total footprint and impacts along the supply chain from two consecutive years were calculated. The results show that the environmental impacts from the second year of implementation were significantly higher than those from the first year. The impact category climate change was found to have experienced the greatest increase from one year to the other, with a 31% increase. This work provides an overview of 14 environmental impact categories of the company assessed, as well as recommendations for the implementation of this indicator in companies and public procurement. This approach could pave the way to shape organizations’ action plans and meet the European environmental challenges. 相似文献