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1.
Marta Tejera-Alhambra Armanda Casrouge Clara de Andrés Ansgar Seyfferth Rocío Ramos-Medina Bárbara Alonso Janet Vega Lidia Fernández-Paredes Matthew L. Albert Silvia Sánchez-Ramón 《PloS one》2015,10(6)
Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients. 相似文献
2.
Diana Fiorentini Marta Cipollone Maria Cristina Galli Armanda Pugnaloni Graziella Biagini Laura Landi 《Free radical research》1994,21(5):329-339
The aim of this work was to characterize large unilamellar vesicles (LUVETs) prepared by a hand-driven extrusion device in order to use them for studies of lipid peroxidation and antioxidant activity. Vesicle structure and size were examined by electron microscopy. Lipid and antioxidant content was determined before and after the extrusion procedure. Then LUVETs were subjected to autoxidation initiated by both the lipid-soluble 2,2'-azobis(2,4-dimethylvaleronitrile) and the water-soluble 2,2'-azobis(2-amidinopropane hydrochloride) azocompounds. The results demonstrated that: i) LUVETs prepared with lipid concentrations ranging between 25 and 150 mM were essentially unilamellar and reasonably homogeneous, with an average diameter of 90 nm; ii) the phospholipid, cholesterol and antioxidant amounts retained by filters were about 10-15%; iii) LUVETs were suitable for autoxidation studies initiated by the water-soluble azocompound both in the absence and presence of antioxidants. The lipid-soluble azocompound could be used only at low concentrations and its vesicle content had to be determined since part of the initiator was not incorporated into the lipid bilayer. These data suggest that LUVETs seem to be recommended for studies of lipid peroxidation and antioxidant activity. 相似文献
3.
Renato Sathler-Avelar Danielle Marquete Vitelli-Avelar Armanda Moreira Mattoso-Barbosa Marcelo Perdig?o-de-Oliveira Ronaldo Peres Costa Silvana Maria Elói-Santos Matheus de Souza Gomes Laurence Rodrigues do Amaral Andréa Teixeira-Carvalho Olindo Assis Martins-Filho Edward J. Dick Jr Gene B. Hubbard Jane F. VandeBerg John L. VandeBerg 《PLoS neglected tropical diseases》2016,10(1)
Background
Cynomolgus macaques (Macaca fascicularis) represent a feasible model for research on Chagas disease since natural T. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. However, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species. We have performed a detailed immunophenotypic analysis of circulating leukocytes together with systems biology approaches from 15 cynomolgus macaques naturally infected with T. cruzi (CH) presenting the chronic phase of Chagas disease to identify biomarkers that might be useful for clinical investigations.Methods and Findings
Our data established that CH displayed increased expression of CD32+ and CD56+ in monocytes and enhanced frequency of NK Granzyme A+ cells as compared to non-infected controls (NI). Moreover, higher expression of CD54 and HLA-DR by T-cells, especially within the CD8+ subset, was the hallmark of CH. A high level of expression of Granzyme A and Perforin underscored the enhanced cytotoxicity-linked pattern of CD8+ T-lymphocytes from CH. Increased frequency of B-cells with up-regulated expression of Fc-γRII was also observed in CH. Complex and imbricate biomarker networks demonstrated that CH showed a shift towards cross-talk among cells of the adaptive immune system. Systems biology analysis further established monocytes and NK-cell phenotypes and the T-cell activation status, along with the Granzyme A expression by CD8+ T-cells, as the most reliable biomarkers of potential use for clinical applications.Conclusions
Altogether, these findings demonstrated that the similarities in phenotypic features of circulating leukocytes observed in cynomolgus macaques and humans infected with T. cruzi further supports the use of these monkeys in preclinical toxicology and pharmacology studies applied to development and testing of new drugs for Chagas disease. 相似文献4.
Ocellatin‐PT antimicrobial peptides: High‐resolution microscopy studies in antileishmania models and interactions with mimetic membrane systems
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Mayara Oliveira Ana Georgina Gomes‐Alves Carla Sousa Mariela Mirta Marani Alexandra Plácido Nuno Vale Cristina Delerue‐Matos Paula Gameiro Selma A. S. Kückelhaus Ana M. Tomas José Roberto S. A. Leite Peter Eaton 《Biopolymers》2016,105(12):873-886
Although the mechanism of action of antimicrobial peptides (AMPs) is not clear, they can interact electrostatically with the cell membranes of microorganisms. New ocellatin‐PT peptides were recently isolated from the skin secretion of Leptodactylus pustulatus. The secondary structure of these AMPs and their effect on Leishmania infantum cells, and on different lipid surface models was characterized in this work. The results showed that all ocellatin‐PT peptides have an α‐helix structure and five of them (PT3, PT4, PT6 to PT8) have leishmanicidal activity; PT1 and PT2 affected the cellular morphology of the parasites and showed greater affinity for leishmania and bacteria‐mimicking lipid membranes than for those of mammals. The results show selectivity of ocellatin‐PTs to the membranes of microorganisms and the applicability of biophysical methods to clarify the interaction of AMPs with cell membranes. 相似文献
5.
Lúcia Mara J. dos Anjos Pollyanna A. Salvador lvaro C. de Souza Adenilson de Souza da Fonseca Flvia de Paoli Jacy Gameiro 《Journal of biophotonics》2019,12(2)
As low‐level laser therapy immune cells responses are not always clarified, this study aimed to evaluate cytokines and immune cells profile after low‐level laser therapy (LLLT) on arthritis‐induced model. Arthritis was induced in C57BL/6 mice divided into five groups: euthanized 5 hours after inflammation induction; untreated; dexamethasone treated; LLLT at 3 Jcm?2; LLLT at 30 Jcm?2. Cytokine measurements by enzyme‐linked immunosorbent assay and mRNA cytokine relative levels by real‐time quantitative polymerase chain reaction were performed with arthritic ankle (IL‐1β, IL‐6, TNF‐α, IL‐10 and TGF‐β). Macrophages, dendritic cells, natural killer cells, lymphocytes CD4+, CD8+, Treg and costimulatory proteins were quantified in proximal lymph node by flow cytometry. Data showed decrease in all cytokine levels after LLLT and alteration in mRNA relative levels, depending on the energy density used. LLLT was able to increase of immune cell populations analyzed in the lymph node as well as costimulatory proteins expression on macrophages and dendritic cells. Treg TCD4+ and TCD8+ population enrichment were observed in LLLT at 3 and 30 Jcm?2 groups, respectively. Furthermore, Treg TCD8+ cells expressing higher levels of CD25 were observed at LLLT at 30 Jcm?2 group. Our results indicate that LLLT could change the inflammatory course of arthritis, tending to accelerate its resolution through immune cells photobiostimulation. 相似文献
6.
Marques MP Girão T Pedroso De Lima MC Gameiro A Pereira E Garcia P 《Biochimica et biophysica acta》2002,1589(1):63-70
Cytotoxicity and cell growth inhibition studies were performed for three distinct polynuclear platinum(II) complexes of spermidine, which showed to have significant cytotoxic and antiproliferative properties on the HeLa cancer cell line. The chemical environment of the metal centres in the drugs, as well as the coordination pattern of the ligand, were found to be strongly determinant of their cytotoxic ability. In the light of the results gathered, the most effective anticancer compound among the ones tested (IC50=5 microM) was found to be the one displaying three difunctional (PtCl2N2) moieties ((PtCl2)3(spd)2). Both the cytotoxic activity and the antiproliferative properties of the complexes studied showed to be irreversible for all the concentrations tested. 相似文献
7.
Battino M Bompadre S Leone L Pugnaloni A Rubini C Ferreiro MS Gallardo I Bullon P 《BioFactors (Oxford, England)》2003,18(1-4):271-275
Cyclosporine A (CsA) plays a pivotal role in controlling Ca2+ movement in the cell modulating also the mitochondrial permeability transition pore. We investigated if chronic administration of CsA may have some effects on the lipophilic and hydrophilic antioxidant pattern of rat liver mitochondria and on their morphological structure. It seems that CsA administration does not statistically affect the redox status of the antioxidants investigated and their amounts (vitamin E, CoQ9, CoQ10, glutathione, uric acid and ascorbic acid) despite the variety of effects that this treatment produces at physiological and morphological levels. However, some kind of derangement could occur in the liver biochemical machinery since CsA treatment induces a markedly increased variability in antioxidant contents. 相似文献
8.
Castro MM Geraldes CF Gameiro P Pereira E Castro B Rangel M 《Journal of inorganic biochemistry》2000,80(1-2):177-179
The interaction of vanadate with the ligand 1,2-dimethyl-3-hydroxy-4-pyridinone (Hdmpp) was studied in aqueous solution using a combination of multinuclear NMR and EPR spectroscopies, as well as potentiometry and cyclic voltammetry. The different species in solution were identified and characterized, and their pKa values and stability constants determined. The vanadium complexes formed in solution are strongly dependent on media composition (ionic strength, presence of buffer), pH and metal-to-ligand ratio (M:L). Two major species--V(V)/dmpp and V(V)/(dmpp)2--are formed in a 140 mM NaCl solution within the pH range 4.5 to 9.0, when M:L = 1:2. In the presence of excess ligand (M:L < or = 1:5), only the 1:2 complex is present, and at pH < 4 paramagnetic species are detected by EPR in solution, thus indicating a reducing capacity of the ligand. Cyclic voltammetry shows that redox processes in solution are not just electron transfer, but are accompanied by chemical reactions. The pK, values and stability constants were determined both by 51V NMR spectroscopy and potentiometry. The present results have a particular interest in the understanding of the aqueous solution chemistry in aerobic conditions of bis(1,2-dimethyl-3-hydroxy-4-pyridinonato) oxovanadium(IV) complex, VO(dmpp)2, a vanadium compound with potential insulin-mimetic properties. 相似文献
9.
Gabriel Costa Serr?o de Araújo Natália Teixeira Mour?o Igor Natário Pinheiro Analúcia Rampazzo Xavier Vinicius Schott Gameiro 《PloS one》2015,10(10)
Background
Gunshot wounds require surgeons to decide whether to remove or leave bullet fragments in the body. Surgeons also decide how to follow up with patients who have lead fragments retained in their body. Current literature recommends to remove only intra-articular fragments without the need for a follow-up for patients with the metal retained. Therefore, this study investigates chronic lead toxicity for gunshot wounds.Methods
The study was performed in the metropolitan area of Rio de Janeiro/Brazil, between 2013 and 2015. It was a case-control study that included 45 victims of gunshot lesions with metallic fragments retained for more than 6 months. The 45 controls were matched for gender, age, and race. We compared the lead blood levels and frequency of symptoms.Results
The control group had average blood lead levels of 2.17 μg/dL (95% Confidence Interval [CI]; 1.71–2.63) and median 2.1 μg/dL. The case group had average values of 9.01 μg/dL (CI; 6.07–11.96) and median values of 6.5 μg/dL with p-values < = 0.001. The case group reported the following more frequently: irritancy, bad mood, headache, memory losses, daylight drowsiness, myalgia, weakness, abdominal pain, joint pain, trembling, tingling limbs. There was statistical significance for the differences of symptoms frequencies and for odds ratio between groups.Conclusions
Although the mean lead levels found were lower than the current laboratory references, low levels have been associated with both rising morbidity and mortality. The WHO stated: “There is no known level of lead exposure that is considered safe”. In conclusion, this work showed that bullets retained in the body are not innocuous. There are impacts in the blood lead levels and symptoms related to it, even with few fragments, extra-articular located or existing with low blood lead levels. 相似文献10.
Alexandre Hinzpeter Abdel Aissat Elvira Sondo Catherine Costa Nicole Arous Christine Gameiro Natacha Martin Agathe Tarze Laurence Weiss Alix de Becdelièvre Bruno Costes Michel Goossens Luis J. Galietta Emmanuelle Girodon Pascale Fanen 《PLoS genetics》2010,6(10)
Approximately 30% of alleles causing genetic disorders generate premature termination codons (PTCs), which are usually associated with severe phenotypes. However, bypassing the deleterious stop codon can lead to a mild disease outcome. Splicing at NAGNAG tandem splice sites has been reported to result in insertion or deletion (indel) of three nucleotides. We identified such a mechanism as the origin of the mild to asymptomatic phenotype observed in cystic fibrosis patients homozygous for the E831X mutation (2623G>T) in the CFTR gene. Analyses performed on nasal epithelial cell mRNA detected three distinct isoforms, a considerably more complex situation than expected for a single nucleotide substitution. Structure-function studies and in silico analyses provided the first experimental evidence of an indel of a stop codon by alternative splicing at a NAGNAG acceptor site. In addition to contributing to proteome plasticity, alternative splicing at a NAGNAG tandem site can thus remove a disease-causing UAG stop codon. This molecular study reveals a naturally occurring mechanism where the effect of either modifier genes or epigenetic factors could be suspected. This finding is of importance for genetic counseling as well as for deciding appropriate therapeutic strategies. 相似文献