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961.
Alexandre Medeiros do Carmo Fabiana Maria Santos Carmen Lucia Ortiz-Agostinho Iêda Nishitokukado Cintia S. Frota Flavia Ubeda Gomes André Zonetti de Arruda Leite Claudio Sérgio Pannuti Lucy Santos Vilas Boas Magaly Gemio Teixeira Aytan Miranda Sipahi 《PloS one》2014,9(11)
Background
Cytomegalovirus is highly prevalent virus and usually occurs in immunocompromised patients. The pathophysiology and treatment of inflammatory bowel disease often induce a state of immunosuppression. Because this, there are still doubts and controversies about the relationship between inflammatory bowel disease and cytomegalovirus.Aim
Evaluate the frequency of cytomegalovirus in patients with inflammatory bowel disease and identify correlations.Methods
Patients with inflammatory bowel disease underwent an interview, review of records and collection of blood and fecal samples. The search for cytomegalovirus was performed by IgG and IgM blood serology, by real-time PCR in the blood and by qualitative PCR in feces. Results were correlated with red blood cell levels, C-reactive protein levels, erythrocyte sedimentation rates and fecal calprotectin levels for each patient.Results
Among the 400 eligible patients, 249 had Crohn''s disease, and 151 had ulcerative colitis. In the group of Crohn''s disease, 67 of the patients had moderate or severe disease, but 126 patients presented with active disease, based on the evaluation of the fecal calprotectin. In patients with ulcerative colitis, only 21 patients had moderate disease, but 76 patients presented with active disease, based on the evaluation of the fecal calprotectin. A large majority of patients had positive CMV IgG. Overall, 10 patients had positive CMV IgM, and 9 patients had a positive qualitative detection of CMV DNA by PCR in the feces. All 400 patients returned negative results after the quantitative detection of CMV DNA in blood by real-time PCR. Analyzing the 19 patients with active infections, we only found that such an association occurred with the use of combined therapy (anti-TNF-alpha + azathioprine)Conclusion
The findings show that latent cytomegalovirus infections are frequent and active cytomegalovirus infection is rare. We did not find any association between an active infection of CMV and inflammatory bowel disease activity. 相似文献962.
Purpose
In addition to excess adiposity, low cardiorespiratory fitness (CRF) and low musculoskeletal fitness (MSF) are important independent risk factors for future cardio-metabolic disease in adolescents, yet global fitness surveillance in adolescents is poor. The objective of this study was to describe and investigate geographical variation in levels of health-related physical fitness, including CRF, MSF, body mass index (BMI), and waist circumference (WC) in Chilean 8th graders.Methods
This cross-sectional study was based on a population-based, representative sample of 19,929 8th graders (median age = 14 years) in the 2011 National Physical Education Survey from Chile. CRF was assessed with the 20-meter shuttle run test, MSF with standing broad jump, and body composition with BMI and WC. Data were classified according to health-related standards. Prevalence of levels of health-related physical fitness was mapped for each of the four variables, and geographical variation was explored at the country level by region and in the Santiago Metropolitan Area by municipality.Results
Girls had significantly higher prevalence of unhealthy CRF, MSF, and BMI than boys (p<0.05). Overall, 26% of boys and 55% of girls had unhealthy CRF, 29% of boys and 35% of girls had unhealthy MSF, 29% of boys and 44% of girls had unhealthy BMI, and 31% of adolescents had unhealthy WC. High prevalence of unhealthy fitness levels concentrates in the northern and middle regions of the country and in the North and Southwest sectors for the Santiago Metropolitan Area.Conclusion
Prevalence of unhealthy CRF, MSF, and BMI is relatively high among Chilean 8th graders, especially in girls, when compared with global estimates. Identification of geographical regions and municipalities with high prevalence of unhealthy physical fitness presents opportunity for targeted intervention. 相似文献963.
Karina Alves Toledo Marise Lopes Fermino Camillo del Cistia Andrade Thalita Bachelli Riul Renata Tomé Alves Vanessa Danielle Menjon Muller Raquel Rinaldi Russo Sean R. Stowell Richard D. Cummings Victor Hugo Aquino Marcelo Dias-Baruffi 《PloS one》2014,9(11)
Dengue virus (DENV) is an enveloped RNA virus that is mosquito-transmitted and can infect a variety of immune and non-immune cells. Response to infection ranges from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever. Despite efforts to control the disease, there are no effective treatments or vaccines. In our search for new antiviral compounds to combat infection by dengue virus type 1 (DENV-1), we investigated the role of galectin-1, a widely-expressed mammalian lectin with functions in cell-pathogen interactions and immunoregulatory properties. We found that DENV-1 infection of cells in vitro exhibited caused decreased expression of Gal-1 in several different human cell lines, suggesting that loss of Gal-1 is associated with virus production. In test of this hypothesis we found that exogenous addition of human recombinant Gal-1 (hrGal-1) inhibits the virus production in the three different cell types. This inhibitory effect was dependent on hrGal-1 dimerization and required its carbohydrate recognition domain. Importantly, the inhibition was specific for hrGal-1, since no effect was observed using recombinant human galectin-3. Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at least in part, during the early stages of DENV-1 infection, by inhibiting viral adsorption and its internalization to target cells. To test the in vivo role of Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the expression of endogenous Galectin-1 contributes to resistance of macrophages to in vitro-infection with DENV-1 and it is also important to physiological susceptibility of mice to in vivo infection with DENV-1. These results provide novel insights into the functions of Gal-1 in resistance to DENV infection and suggest that Gal-1 should be explored as a potential antiviral compound. 相似文献
964.
Iryna A. Isakova Calvin Lanclos Julie Bruhn Marcelo J. Kuroda Kate C. Baker Veena Krishnappa Donald G. Phinney 《PloS one》2014,9(1)
The emerging paradigm that MSCs are immune privileged has fostered the use of “off-the-shelf” allogeneic MSC-based therapies in human clinical trials. However, this approach ignores studies in experimental animals wherein transplantation of MSCs across MHC boundaries elicits measurable allo-immune responses. To determine if MSCs are hypo-immunogeneic, we characterized the immune response in rhesus macaques following intracranial administration of allogeneic vs. autologous MSCs. This analysis revealed unambiguous evidence of productive allo-recognition based on expansion of NK, B and T cell subsets in peripheral blood and detection of allo-specific antibodies in animals administered allogeneic but not autologous MSCs. Moreover, the degree of MHC class I and II mismatch between the MSC donor and recipient significantly influenced the magnitude and nature of the allo-immune response. Consistent with these findings, real-time PCR analysis of brain tissue from female recipients administered varying doses of male, allogeneic MSCs revealed a significant inverse correlation between MSC engraftment levels and cell dose. Changes in post-transplant neutrophil and lymphocyte counts also correlated with dose and were predictive of overall MSC engraftment levels. However, secondary antigen challenge failed to elicit a measurable immune response in allogeneic recipients. Finally, extensive behavior testing of animals revealed no main effect of cell dose on motor skills, social development, or temperament. Collectively, these data indicate that allogeneic MSCs are weakly immunogenic when transplanted across MHC boundaries in rhesus macaques and this negatively impacts durable engraftment levels. Therefore the use of unrelated donor MSCs should be carefully evaluated in human patients. 相似文献
965.
Valeria Aguilera Luis Brice?o Hector Contreras Liliana Lamperti Esperanza Sepúlveda Francisca Díaz-Perez Marcelo León Carlos Veas Rafael Maura Jorge Roberto Toledo Paulina Fernández Ambart Covarrubias Felipe Andrés Zu?iga Claudia Radojkovic Carlos Escudero Claudio Aguayo 《PloS one》2014,9(11)
Background
Mesenchymal stem cells have a high capacity for trans-differentiation toward many adult cell types, including endothelial cells. Feto-placental tissue, such as Wharton''s jelly is a potential source of mesenchymal stem cells with low immunogenic capacity; make them an excellent source of progenitor cells with a potential use for tissue repair. We evaluated whether administration of endothelial cells derived from mesenchymal stem cells isolated from Wharton''s jelly (hWMSCs) can accelerate tissue repair in vivo.Methods
Mesenchymal stem cells were isolated from human Wharton''s jelly by digestion with collagenase type I. Endothelial trans-differentiation was induced for 14 (hWMSC-End14d) and 30 (hWMSC-End30d) days. Cell phenotyping was performed using mesenchymal (CD90, CD73, CD105) and endothelial (Tie-2, KDR, eNOS, ICAM-1) markers. Endothelial trans-differentiation was demonstrated by the expression of endothelial markers and their ability to synthesize nitric oxide (NO).Results
hWMSCs can be differentiated into adipocytes, osteocytes, chondrocytes and endothelial cells. Moreover, these cells show high expression of CD73, CD90 and CD105 but low expression of endothelial markers prior to differentiation. hWMSCs-End express high levels of endothelial markers at 14 and 30 days of culture, and also they can synthesize NO. Injection of hWMSC-End30d in a mouse model of skin injury significantly accelerated wound healing compared with animals injected with undifferentiated hWMSC or injected with vehicle alone. These effects were also observed in animals that received conditioned media from hWMSC-End30d cultures.Conclusion
These results demonstrate that mesenchymal stem cells isolated from Wharton''s jelly can be cultured in vitro and trans-differentiated into endothelial cells. Differentiated hWMSC-End may promote neovascularization and tissue repair in vivo through the secretion of soluble pro-angiogenic factors. 相似文献966.
Sabrina Grewe Matteo Ballottari Marcelo Alcocer Cosimo D’Andrea Olga Blifernez-Klassen Ben Hankamer Jan H. Mussgnug Roberto Bassi Olaf Kruse 《The Plant cell》2014,26(4):1598-1611
Photosynthetic organisms developed multiple strategies for balancing light-harvesting versus intracellular energy utilization to survive ever-changing environmental conditions. The light-harvesting complex (LHC) protein family is of paramount importance for this function and can form light-harvesting pigment protein complexes. In this work, we describe detailed analyses of the photosystem II (PSII) LHC protein LHCBM9 of the microalga Chlamydomonas reinhardtii in terms of expression kinetics, localization, and function. In contrast to most LHC members described before, LHCBM9 expression was determined to be very low during standard cell cultivation but strongly increased as a response to specific stress conditions, e.g., when nutrient availability was limited. LHCBM9 was localized as part of PSII supercomplexes but was not found in association with photosystem I complexes. Knockdown cell lines with 50 to 70% reduced amounts of LHCBM9 showed reduced photosynthetic activity upon illumination and severe perturbation of hydrogen production activity. Functional analysis, performed on isolated PSII supercomplexes and recombinant LHCBM9 proteins, demonstrated that presence of LHCBM9 resulted in faster chlorophyll fluorescence decay and reduced production of singlet oxygen, indicating upgraded photoprotection. We conclude that LHCBM9 has a special role within the family of LHCII proteins and serves an important protective function during stress conditions by promoting efficient light energy dissipation and stabilizing PSII supercomplexes. 相似文献
967.
Mariana P. Fernandes Ana C. R. Leite Flavia F. B. Araújo Sara T. O. Saad M. O. Baratti M. T. S. Correia Luana C. B. B. Coelho Fernanda R. Gadelha Anibal E. Vercesi 《The Journal of eukaryotic microbiology》2014,61(4):381-388
Previous results provided evidence that Cratylia mollis seed lectin (Cramoll 1,4) promotes Trypanosoma cruzi epimastigotes death by necrosis via a mechanism involving plasma membrane permeabilization to Ca2+ and mitochondrial dysfunction due to matrix Ca2+ overload. In order to investigate the mechanism of Ca2+‐induced mitochondrial impairment, experiments were performed analyzing the effects of this lectin on T. cruzi mitochondrial fraction and in isolated rat liver mitochondria (RLM), as a control. Confocal microscopy of T. cruzi whole cell revealed that Cramoll 1,4 binding to the plasma membrane glycoconjugates is followed by its internalization and binding to the mitochondrion. Electrical membrane potential (?Ψm) of T. cruzi mitochondrial fraction suspended in a reaction medium containing 10 μM Ca2+ was significantly decreased by 50 μg/ml Cramoll 1,4 via a mechanism insensitive to cyclosporine A (CsA, membrane permeability transition (MPT) inhibitor), but sensitive to catalase or 125 mM glucose. In RLM suspended in a medium containing 10 μM Ca2+ this lectin, at 50 μg/ml, induced increase in the rate of hydrogen peroxide release, mitochondrial swelling, and ?Ψm disruption. All these mitochondrial alterations were sensitive to CsA, catalase, and EGTA. These results indicate that Cramoll 1, 4 leads to inner mitochondrial membrane permeabilization through Ca2+ dependent mechanisms in both mitochondria. The sensitivity to CsA in RLM characterizes this lectin as a MPT inducer and the lack of CsA effect identifies a CsA‐insensitive MPT in T. cruzi mitochondria. 相似文献
968.
Adriana Farias Silva Erick Leite Bastos Marcelo Der Torossian Torres André Luis Costa‐da‐Silva Rafaella Sayuri Ioshino Margareth Lara Capurro Flávio Lopes Alves Antonio Miranda Renata de Freitas Fischer Vieira Vani Xavier Oliveira Jr. 《Journal of peptide science》2014,20(8):640-648
Angiotensin II (AII) as well as analog peptides shows antimalarial activity against Plasmodium gallinaceum and Plasmodium falciparum, but the exact mechanism of action is still unknown. This work presents the solid‐phase synthesis and characterization of eight peptides corresponding to the alanine scanning series of AII plus the amide‐capped derivative and the evaluation of the antiplasmodial activity of these peptides against mature P. gallinaceum sporozoites. The Ala screening data indicates that the replacement of either the Ile5 or the His6 residues causes minor effects on the in vitro antiplasmodial activity compared with AII, i.e. AII (88%), [Ala6]‐AII (79%), and [Ala5]‐AII (75%). Analogs [Ala3]‐AII, [Ala1]‐AII, and AII‐NH2 showed antiplasmodial activity around 65%, whereas the activity of the [Ala8]‐AII, [Ala7]‐AII, [Ala4]‐AII, and [Ala2]‐AII analogs is lower than 45%. Circular dichroism data suggest that AII and the most active analogs adopt a β‐fold conformation in different solutions. All AII analogs, except [Ala4]‐AII and [Ala8]‐AII, show contractile responses and interact with the AT1 receptor, [Ala5]‐AII and [Ala6]‐AII. In conclusion, this approach is helpful to understand the contribution of each amino acid residue to the bioactivity of AII, opening new perspectives toward the design of new sporozoiticidal compounds. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
969.
Silvana L. Della Penna Gabriel Cao Nicolás M. Kouyoumdzian Lorena Sarati Andrea Fellet Ana M. Balaszczuk Marcelo R. Choi Elsa Zotta Susana Gorzalczany Marcela Pandolfo Jorge E. Toblli María I. Rosón Belisario E. Fernández 《Journal of physiology and biochemistry》2014,70(2):465-478
The aim of this study was to assess whether endogenous Ang II and oxidative stress produced by acute hypertonic sodium overload may regulate the expression of aquaporin-1 (AQP-1) and aquaporin-2 (AQP-2) in the kidney. Groups of anesthetized male Sprague–Dawley rats were infused with isotonic saline solution (control) or with hypertonic saline solution (Na group, 1 M NaCl), either alone or with losartan (10 mg kg?1) or tempol (0.5 mg min?1 kg?1) during 2 h. Renal function parameters were measured. Groups of unanesthetized animals were injected intraperitoneally with hypertonic saline solution, with or without free access to water intake, Na+W, and Na?W, respectively. The expression of AQP-1, AQP-2, Ang II, eNOS, and NF-kB were evaluated in the kidney by Western blot and immunohistochemistry. AQP-2 distribution was assessed by immunofluorescence. Na group showed increased natriuresis and diuresis, and Ang II and NF-kB expression, but decreased eNOS expression. Losartan or tempol enhanced further the diuresis, and AQP-2 and eNOS expression, as well as decreased Ang II and NF-kB expression. Confocal immunofluorescence imaging revealed labeling of AQP-2 in the apical plasma membrane with less labeling in the intracellular vesicles than the apical membrane in kidney medullary collecting duct principal cells both in C and Na groups. Importantly, our data also show that losartan and tempol induces a predominantly accumulation of AQP-2 in intracellular vesicles. In unanesthetized rats, Na+W group presented increased diuresis, natriuresis, and AQP-2 expression (112?±?25 vs 64?±?16; *p?<?0.05). Water deprivation increased plasma sodium and diuresis but decreased AQP-2 (46?±?22 vs 112?±?25; §p?<?0.05) and eNOS expression in the kidney. This study is a novel demonstration that renal endogenous Ang II–oxidative stress, induced in vivo in hypernatremic rats by an acute sodium overload, regulates AQP-2 expression. 相似文献
970.
Alejandra Martinez Gonzalo Peluffo Ariel A. Petruk Martín Hugo Dolores Pi?eyro Verónica Demicheli Diego M. Moreno Analía Lima Carlos Batthyány Rosario Durán Carlos Robello Marcelo A. Martí Nicole Larrieux Alejandro Buschiazzo Madia Trujillo Rafael Radi Lucía Piacenza 《The Journal of biological chemistry》2014,289(18):12760-12778
Trypanosoma cruzi, the causative agent of Chagas disease, contains exclusively iron-dependent superoxide dismutases (Fe-SODs) located in different subcellular compartments. Peroxynitrite, a key cytotoxic and oxidizing effector biomolecule, reacted with T. cruzi mitochondrial (Fe-SODA) and cytosolic (Fe-SODB) SODs with second order rate constants of 4.6 ± 0.2 × 104
m−1 s−1 and 4.3 ± 0.4 × 104
m−1 s−1 at pH 7.4 and 37 °C, respectively. Both isoforms are dose-dependently nitrated and inactivated by peroxynitrite. Susceptibility of T. cruzi Fe-SODA toward peroxynitrite was similar to that reported previously for Escherichia coli Mn- and Fe-SODs and mammalian Mn-SOD, whereas Fe-SODB was exceptionally resistant to oxidant-mediated inactivation. We report mass spectrometry analysis indicating that peroxynitrite-mediated inactivation of T. cruzi Fe-SODs is due to the site-specific nitration of the critical and universally conserved Tyr35. Searching for structural differences, the crystal structure of Fe-SODA was solved at 2.2 Å resolution. Structural analysis comparing both Fe-SOD isoforms reveals differences in key cysteines and tryptophan residues. Thiol alkylation of Fe-SODB cysteines made the enzyme more susceptible to peroxynitrite. In particular, Cys83 mutation (C83S, absent in Fe-SODA) increased the Fe-SODB sensitivity toward peroxynitrite. Molecular dynamics, electron paramagnetic resonance, and immunospin trapping analysis revealed that Cys83 present in Fe-SODB acts as an electron donor that repairs Tyr35 radical via intramolecular electron transfer, preventing peroxynitrite-dependent nitration and consequent inactivation of Fe-SODB. Parasites exposed to exogenous or endogenous sources of peroxynitrite resulted in nitration and inactivation of Fe-SODA but not Fe-SODB, suggesting that these enzymes play distinctive biological roles during parasite infection of mammalian cells. 相似文献