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91.
Lima G Furuzawa-Carballeda J Ramos-Bello D Jakez-Ocampo J Pascual-Ramos V Núñez-Alvarez CA Granados J Llorente L 《European cytokine network》2012,23(2):25-28
The aim of this study was to investigate the possible role of the CCR5 59029 A→G promoter point mutation polymorphism in determining the susceptibility to rheumatoid factor-positive and rheumatoid factor-negative rheumatoid arthritis. This polymorphism was assessed in 85 seropositive and 39 seronegative rheumatoid arthritis patients and in 126 healthy individuals of the same geographic and ethnic origin. We found an increase in the genetic frequency of the A allele in the 59029 A→G promoter region of the CCR5 receptor in patients with rheumatoid arthritis compared with healthy controls (p = 0.01; OR = 1.5, 95% CI (1.0-2.2). Likewise, the homozygous state for the A allele was found to be more frequent in rheumatoid arthritis patients, again when compared with healthy controls (p = 0.03; OR = 1.8, 95% CI 1.0-3.0). The increased frequency of the A allele was more evident in the more benign, seronegative rheumatoid arthritis group when compared with controls (p = 0.003; OR 2.4 95% CI 1.3-4.4), and when combining the A homozygous and the AG heterozygous patients compared with healthy subjects. These results suggest that this CCR5 promoter polymorphism seems to play an important role in determining different clinical courses in both forms of rheumatoid arthritis. 相似文献
92.
Candelaria M de la Cruz-Hernandez E Taja-Chayeb L Perez-Cardenas E Trejo-Becerril C Gonzalez-Fierro A Chavez-Blanco A Soto-Reyes E Dominguez G Trujillo JE Diaz-Chavez J Duenas-Gonzalez A 《PloS one》2012,7(3):e29181
Background
Down regulation of genes coding for nucleoside transporters and drug metabolism responsible for uptake and metabolic activation of the nucleoside gemcitabine is related with acquired tumor resistance against this agent. Hydralazine has been shown to reverse doxorubicin resistance in a model of breast cancer. Here we wanted to investigate whether epigenetic mechanisms are responsible for acquiring resistance to gemcitabine and if hydralazine could restore gemcitabine sensitivity in cervical cancer cells.Methodology/Principal Findings
The cervical cancer cell line CaLo cell line was cultured in the presence of increasing concentrations of gemcitabine. Down-regulation of hENT1 & dCK genes was observed in the resistant cells (CaLoGR) which was not associated with promoter methylation. Treatment with hydralazine reversed gemcitabine resistance and led to hENT1 and dCK gene reactivation in a DNA promoter methylation-independent manner. No changes in HDAC total activity nor in H3 and H4 acetylation at these promoters were observed. ChIP analysis showed H3K9m2 at hENT1 and dCK gene promoters which correlated with hyper-expression of G9A histone methyltransferase at RNA and protein level in the resistant cells. Hydralazine inhibited G9A methyltransferase activity in vitro and depletion of the G9A gene by iRNA restored gemcitabine sensitivity.Conclusions/Significance
Our results demonstrate that acquired gemcitabine resistance is associated with DNA promoter methylation-independent hENT1 and dCK gene down-regulation and hyper-expression of G9A methyltransferase. Hydralazine reverts gemcitabine resistance in cervical cancer cells via inhibition of G9A histone methyltransferase. 相似文献93.
V Castro-Leyva A Espejel-Nuñez G Barroso V Zaga-Clavellina A Flores-Pliego I Morales-Mendez S Giono-Cerezo SW Walsh G Estrada-Gutierrez 《PloS one》2012,7(8):e43605
Objective
To compare the inflammatory response preserved ex vivo by decidual cells isolated from women who experienced preterm labor with and without subclinical intrauterine infection.Methods
Fetal membranes were obtained after cesarean section from 35 women who delivered before 37 weeks of gestation following spontaneous preterm labor, with no clinical evidence of intrauterine infection. Decidua was microbiologically tested and cultured. Concentrations of anti-inflammatory cytokines (IL-2, IL-4, IL-10), pro-inflammatory cytokines (IL-6, IL-8, IL-1β and TNF-α), and matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9) were measured in the supernatants using Bio-Plex, and prostaglandin E2 (PGE2) was measured by enzyme immunoassay.Results
Subclinical infection was confirmed in 10 women (28.5%). Microorganisms isolated were Ureaplasma urealyticum (4), group B streptococci (3), Gardnerella vaginalis (1), and Escherichia coli (2). We found a significant increase of pro-inflammatory cytokines and a significant decrease of anti-inflammatory cytokines in supernatants from decidual cells obtained from women with preterm labor and subclinical intrauterine infection compared to women without infection. Secretion of MMP-1, MMP-8, MMP-9 and PGE2 was significantly higher in infected women. Secretion of IL-8 by decidual cells from infected women persisted upon repeated in vitro culture passages.Conclusions
Almost 30% of idiopathic preterm labor cases were associated with subclinical intrauterine infection, and decidual cells isolated from these cases preserved an ex vivo inflammatory status after in vivo bacterial exposure. 相似文献94.
Eugenia Negredo Anna Bonjoch Moisés Gómez-Mateu Carla Estany Jordi Puig Nuria Perez-Alvarez Joaquin Rosales Silvana di Gregorio Luis del Rio Guadalupe Gómez Bonaventura Clotet 《PloS one》2012,7(10)
Background
Algorithms for bone mineral density (BMD) management in HIV-infected patients are lacking. Our objective was to assess how often a dual-energy x-ray absorptiometry (DXA) scan should be performed by assessing time of progression to osteopenia/osteoporosis.Methods
All DXA scans performed between 2000 and 2009 from HIV-infected patients with at least two DXA were included. Time to an event (osteopenia and osteoporosis) was assessed using the Kaplan–Meier method. Strata (tertiles) were defined using baseline minimum T scores. Differences between strata in time to an event were compared with the log-rank test.Results
Of 391 patients (1,639 DXAs), 49.6% had osteopenia and 21.7% osteoporosis at their first DXA scan. Of the 112 (28.6%) with normal BMD, 35.7% progressed to osteopenia; median progression time was 6.7 years. These patients were stratified: “low-risk" (baseline minimum T score >−0.2 SD), “middle-risk" (between −0.2 and −0.6 SD), and “high-risk" (from −0.6 to −1 SD); median progression time to osteopenia was 8.7, >7.2, and 1.7 years, respectively (p<0.0001). Of patients with osteopenia, 23.7% progressed to osteoporosis; median progression time was >8.5 years. Progression time was >8.2 years in “low-risk" tertile (T score between −1.1 and −1.6 SD), >8.5 years in “middle-risk" (between −1.6 and −2), and 3.2 years in “high-risk" (from −2 to −2.4) (p<0.0001).Conclusions
Our results may help to define the BMD testing interval. The lowest T score tertiles would suggest recommending a subsequent DXA in 1–2 years; in the highest tertiles, ≥6 years. Early intervention in patients with bone demineralization could reduce fracture–related morbidity/mortality. 相似文献95.
96.
Serotonin 1A (5-HT(1A)) receptors are found in high densities in prefrontal cortex. However, their distribution within cortical cell populations is unknown in both humans and primates. We used double in situ hybridization histochemistry to quantify the percentage of glutamatergic and GABAergic neurons expressing 5-HT(1A) receptors in human and monkey prefrontal cortex. Moreover, in the case of the monkey, we also quantified the parvalbumin and calbindin GABAergic subpopulations expressing this receptor. 5-HT(1A) receptor mRNAs were expressed in about 80% of glutamatergic neurons in external layers II and upper III, and in around 50% in layer VI; they were also present in approximately 20% of GABAergic neurons in both species. Although they were found in up to 43% of the calbindin cell subpopulation they were rarely present in parvalbumin cells in monkey prefrontal cortex. The knowledge of the phenotype of the prefrontal cortex (PFC) cells expressing 5-HT(1A) will help understanding serotonin actions in PFC. 相似文献
97.
Gómez-Baena G López-Lozano A Gil-Martínez J Lucena JM Diez J Candau P García-Fernández JM 《PloS one》2008,3(10):e3416
The marine cyanobacteria Prochlorococcus have been considered photoautotrophic microorganisms, although the utilization of exogenous sugars has never been specifically addressed in them. We studied glucose uptake in different high irradiance- and low irradiance-adapted Prochlorococcus strains, as well as the effect of glucose addition on the expression of several glucose-related genes. Glucose uptake was measured by adding radiolabelled glucose to Prochlorococcus cultures, followed by flow cytometry coupled with cell sorting in order to separate Prochlorococcus cells from bacterial contaminants. Sorted cells were recovered by filtration and their radioactivity measured. The expression, after glucose addition, of several genes (involved in glucose metabolism, and in nitrogen assimilation and its regulation) was determined in the low irradiance-adapted Prochlorococcus SS120 strain by semi-quantitative real time RT-PCR, using the rnpB gene as internal control. Our results demonstrate for the first time that the Prochlorococcus strains studied in this work take up glucose at significant rates even at concentrations close to those found in the oceans, and also exclude the possibility of this uptake being carried out by eventual bacterial contaminants, since only Prochlorococcus cells were used for radioactivity measurements. Besides, we show that the expression of a number of genes involved in glucose utilization (namely zwf, gnd and dld, encoding glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and lactate dehydrogenase, respectively) is strongly increased upon glucose addition to cultures of the SS120 strain. This fact, taken together with the magnitude of the glucose uptake, clearly indicates the physiological importance of the phenomenon. Given the significant contribution of Prochlorococcus to the global primary production, these findings have strong implications for the understanding of the phytoplankton role in the carbon cycle in nature. Besides, the ability of assimilating carbon molecules could provide additional hints to comprehend the ecological success of Prochlorococcus. 相似文献
98.
Kaba NK Schultz J Law FY Lefort CT Martel-Gallegos G Kim M Waugh RE Arreola J Knauf PA 《American journal of physiology. Cell physiology》2008,295(5):C1454-C1463
Ischemia-reperfusion injury is a common pathological occurrence causing tissue damage in heart attack and stroke. Entrapment of neutrophils in the vasculature during ischemic events has been implicated in this process. In this study, we examine the effects that lactacidosis and consequent reductions in intracellular pH (pH(i)) have on surface expression of adhesion molecules on neutrophils. When human neutrophils were exposed to pH 6 lactate, there was a marked decrease in surface L-selectin (CD62L) levels, and the decrease was significantly enhanced by inclusion of Na(+)/H(+) exchanger (NHE) inhibitor 5-(N,N-hexamethylene)amiloride (HMA). Similar effects were observed when pH(i) was reduced while maintaining normal extracellular pH, by using an NH(4)Cl prepulse followed by washes and incubation in pH 7.4 buffer containing NHE inhibitors [HMA, cariporide, or 5-(N,N-dimethyl)amiloride (DMA)]. The amount of L-selectin shedding induced by different concentrations of NH(4)Cl in the prepulse correlated with the level of intracellular acidification with an apparent pK of 6.3. In contrast, beta(2)-integrin (CD11b and CD18) was only slightly upregulated in the low-pH(i) condition and was enhanced by NHE inhibition to a much lesser extent. L-selectin shedding was prevented by treating human neutrophils with inhibitors of extracellular metalloproteases (RO-31-9790 and KD-IX-73-4) or with inhibitors of intracellular signaling via p38 MAP kinase (SB-203580 and SB-239063), implying a transmembrane effect of pH(i). Taken together, these data suggest that the ability of NHE inhibitors such as HMA to reduce ischemia-reperfusion injury may be related to the nearly complete removal of L-selectin from the neutrophil surface. 相似文献
99.
100.
Teresa Pérez Antoni Gómez Raimon Sanmarti Odette Vi?as Guadalupe Ercilla Isabel Haro 《Letters in Peptide Science》2002,9(6):291-300
Antifilaggrin autoantibodies (AFA) have described to be the most specific markers of rheumatoid arthritis (RA) and epitopes containing citrulline within the sequence of filaggrin identified as major antigenic sites recognised by AFA. In this paper we confirm that citrulline is an essential constituent of filaggrin related antigenic determinants recognised by RA specific autoantibodies, thus having an important role for the development of filaggrin peptides based serological tests. Moreover, we describe our findings on the comparative conformational analysis of filaggrin (306–324) peptide sequence and an analogue in which two arginines were simultaneously substituted by citrulline carried out by Circular Dichroism (CD) and Fourier-Transform Infrared Spectroscopy (FTIR). Results might contribute to the understanding of the structural features that may be important to explain the enhanced binding characteristics of citrullinated peptides to the autoantibodies in rheumatoid arthritis. 相似文献