1,721,010 research outputs found
suppl_table_4 – Supplemental material for Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis
No full textSupplemental material, suppl_table_4 for Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis by Francisco J. Blanco, María Camacho-Encina, Lucía González-Rodríguez, Ignacio Rego-Pérez, Jesús Mateos, Patricia Fernández-Puente, Lucía Lourido, Beatriz Rocha, Florencia Picchi, María T. Silva-Díaz, Marta Herrero, Helena Martínez, Josep Verges, Cristina Ruiz-Romero and Valentina Calamia in Therapeutic Advances in Chronic Disease</p
suppl_table_1 – Supplemental material for Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis
No full textSupplemental material, suppl_table_1 for Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis by Francisco J. Blanco, María Camacho-Encina, Lucía González-Rodríguez, Ignacio Rego-Pérez, Jesús Mateos, Patricia Fernández-Puente, Lucía Lourido, Beatriz Rocha, Florencia Picchi, María T. Silva-Díaz, Marta Herrero, Helena Martínez, Josep Verges, Cristina Ruiz-Romero and Valentina Calamia in Therapeutic Advances in Chronic Disease</p
suppl_table_2 – Supplemental material for Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis
No full textSupplemental material, suppl_table_2 for Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis by Francisco J. Blanco, María Camacho-Encina, Lucía González-Rodríguez, Ignacio Rego-Pérez, Jesús Mateos, Patricia Fernández-Puente, Lucía Lourido, Beatriz Rocha, Florencia Picchi, María T. Silva-Díaz, Marta Herrero, Helena Martínez, Josep Verges, Cristina Ruiz-Romero and Valentina Calamia in Therapeutic Advances in Chronic Disease</p
suppl_table_3 – Supplemental material for Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis
No full textSupplemental material, suppl_table_3 for Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis by Francisco J. Blanco, María Camacho-Encina, Lucía González-Rodríguez, Ignacio Rego-Pérez, Jesús Mateos, Patricia Fernández-Puente, Lucía Lourido, Beatriz Rocha, Florencia Picchi, María T. Silva-Díaz, Marta Herrero, Helena Martínez, Josep Verges, Cristina Ruiz-Romero and Valentina Calamia in Therapeutic Advances in Chronic Disease</p
supplementary_figures – Supplemental material for Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis
No full textSupplemental material, supplementary_figures for Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis by Francisco J. Blanco, María Camacho-Encina, Lucía González-Rodríguez, Ignacio Rego-Pérez, Jesús Mateos, Patricia Fernández-Puente, Lucía Lourido, Beatriz Rocha, Florencia Picchi, María T. Silva-Díaz, Marta Herrero, Helena Martínez, Josep Verges, Cristina Ruiz-Romero and Valentina Calamia in Therapeutic Advances in Chronic Disease</p
Glucosamine affects intracellular signalling through inhibition of mitogen-activated protein kinase phosphorylation in human chondrocytes
Full text linkThe aim of this study was to determine the effects of glucosamine on matrix metalloprotease (MMP) production, on mitogen-activated protein kinase (MAPK) phosphorylation, and on activator protein (AP)-1 transcription factor activation in human chondrocytes. The human immortalized cell line lbpva55 and healthy human chondrocytes (obtained from healthy donors) were subjected to challenge with 10 ng/ml IL-1β after pretreatment with 2.5 or 10 mmol/l glucosamine. MMP mRNA expression levels were evaluated using quantitative real-time PCR, and MMP protein production levels were evaluated in the culture supernatant using ELISA. MAPK phosphorylation was evaluated using Western blotting. AP-1 transcription factor activation was evaluated by measuring AP-1 DNA-binding activity. After IL-1β stimulation, levels of MMP-1, MMP-3 and MMP-13 production were markedly increased. Treatment with 2.5 and 10 mmol/l glucosamine reduced expression of these metalloproteases. MMP expression is regulated by transcription factors such as the AP-1 complex, which is activated by phosphorylated MAPKs. IL-1β stimulated phosphorylation of c jun amino-terminal kinase, p38 MAPK and extracellular signal regulated kinase-1/2. Glucosamine inhibited c-jun amino terminal kinase and p38 phosphorylation, and consequently c jun binding activity. These findings demonstrate, for the first time, that glucosamine inhibits IL-1β-stimulated MMP production in human chondrocytes by affecting MAPK phosphorylation
Comprehensive analysis of a new chemical compound for the treatment of osteoarthritis by proteomic approach on human chondrocytes
Full text linkOsteoarthritis is a widespread and degenerative joint disorder principally characterized by progressive degradation and destruction of articular cartilage, subsequently, all structures of diarthroidal joints (subchondral bone, synovial fluid and synovial membrane) are involved.
Selective cyclooxigenase (COX)-2 inhibitors were developed to prevent the gastro-intestinal adverse effects related to tNSAIDs, generally used for the treatment of OA. VA692, a new hydroxyetyl selective COX-2 inhibitor, showed anti-inflammatory, anti-nociceptive and chondroprotective properties. Proteomics is classified as a identification and characterization of the global protein content of a tissue or a particular cell type; it is a research tool for large-scale studies of structure, function and interaction of proteins. Proteomics is being applied for the study of drug mechanism of action or toxicity to identify new drugs targets. The aim of this project was to evaluate the anti-inflammatory effect of VA692, in comparison with celecoxib (already known). In addition, we would establish if the new compound present any advantages over other COX-2 inhibitors already available in therapeutic use. By iTRAQ methodology, we quantitatively analyzed the different expressed profiles in T/C-28a2 treated with the studied drugs and IL-1β.
Human T/C-28a2 chondrocytes cell line were generated by Goldring group. Human articular cartilage was achieved from femoral heads of five III grade OA patients. Following an enzymatic digestion of articular cartilage, the obtained cells were incubated with VA692 and celecoxib (1μM, 0.5μM and 0.2μM) in presence of Interleukin (IL)-1β (5ng/ml) for 48 hours. The expression of inflammatory cytokines and anti-oxidant enzymes was evaluated by quantitative qRT-PCR, PGE2 release by ELISA, and apoptosis and ROS production by flow cytometry. T/C-28a2 cell line was also processed to carry out western blot analysis and employed the iTRAQ methodology. Statistical analysis was carried out by using ANOVA and Bonferroni multiple comparison tests.
IL-1β-stimulated chondrocytes showed a significant increase (p<0.001) of COX-2, IL-1β, IL-6, IL-8, superoxide dismutase (SOD)-2 and catalase (CAT) gene expression, as well as of PGE2 levels in both analyzed cells type. The tested drugs significantly counteracted the effect of IL-1β, with a better modulation by VA692 1μM in T/C-28a2 cell line (p<0.01 for COX-2, IL-1β, IL-8, CAT; p<0.001 for IL-6, SOD-2 and PGE2). Regarding apoptosis and superoxide anion production, the new drug was able to significantly reduce (p<0.05) their increase induced by IL-1β (p<0.05) in T/C-28a2 cell line. Proteomic analysis identified 797 proteins in T/C-28a2 cell line, 123 of which were significantly modulated by VA692 in
presence of IL-1β (p<0.001) and 34 modulated by IL-1β alone (p<0.05). 22 proteins were commonly modulated by the two groups, indicating that 101 proteins were regulated by the only effect of VA692. Among the proteins down-regulated by VA692, some with structural function were detected, responsible for cytoskeleton reorganization, as well as chaperones (heat shock proteins) and glycolitic enzymes. Proteins involved in calcium metabolism and in ribosome biogenesis resulted up-regulated instead, as well as Cu-Zn SOD, another member of SOD family, as confirmed by western blot analysis on SOD-2.
Our data underlined the anti-inflammatory effect of VA692, suggesting also its anti-apoptotic and anti-oxidant role. The proteomic profile demonstrated that VA692 induced not only an anti-inflammatory regulation in chondrocytes but, interestingly, seemed to regulate their anabolic response. On the basis of our results, we can affirm that VA692 has more beneficial effect in comparison to celecoxib in particular regarding the modulation of oxidant/anti-oxidant system and of the proteome profile. So, we hypothesize that VA692 could present any advantages over other COX-2 inhibitors already available for therapeutic use. However, further in vitro and in vivo experiments are necessary to elucidate and confirm the importance of this pharmacological compound before to in therapeutic approach of joint diseases
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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