Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy.
Aging-related failure of homeostatic mechanisms contribute to articular cartilage degeneration and osteoarthritis (OA), which are disease-modifying treatments are not available. Our goal is to identify the molecule to prevent OA by chondrocytes regulate aging and autophagy.Human chondrocytes with IL-6-induced aging and autophagy suppression and SA-β-gal as the reporter of aging and as a reporter LC3 autophagic flux is used to screen drugs Prestwick Chemical Library approved. Preclinical cellular, tissue and blood from the blood of OA and OA and aging models used to test the effectiveness and relevance of PPARα activating molecules associated with cartilage degeneration.Senotherapeutic with pro-autophagic activity identified.
Fenofibrate (FN), PPARα agonists are used to dyslipidaemias in humans, reducing the number of senescent cells via apoptosis, increase autophagic flux, and protected against cartilage degradation. FN reduced both aging and inflammation and an increase in autophagy in both human aging and OA chondrocytes whereas knockdown PPARα given the opposite effect. In addition, PPARα expression is reduced through both aging and OA in mice and also in the blood and cartilage of the knee OA patients.
Remarkably, in a retrospective study, the treatment of OA fibrates improve the clinical condition in human patients of Osteoarthritis Initiative (OAI) Cohort.These results showed that fibrate drugs approved by the FDA targeting lipid metabolism protect against cartilage degeneration seen with aging and OA. Thus, this drug could have a direct clinical utility for age-related degeneration of cartilage and treatment of OA.
FUNDING: The study was supported by the Instituto de Salud Carlos III Ministerio de Ciencia, Innovación y Universidades, Spain, Plan Estatal 2013-2016 and Fondo Europeo de Desarrollo Regional (FEDER), “Una Manera de hacer Europa”, PI14 / 01324 and PI17 / 02 059, with a platform that Innopharma Pharmacogenomics applied to the validation of targets and the discovery of drug candidates for preclinical phase, Ministerio de Economia y Competitividad, by grants from the National Health Instiutes for PDR (P01 U19 AG043376 and AG056278). We thank FOREUM in Rheumatology Research Foundation for their support.
Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy.
Description: A competitive ELISA for quantitative measurement of Mouse Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Mouse Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Mouse Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rabbit Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rabbit Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rabbit Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Goat Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Goat Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Goat Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Human Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Human Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Human Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Monkey Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Monkey Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Monkey Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Canine Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Canine Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Canine Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Porcine Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Porcine Aspartate Aminotransferase in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Repurposing of Ribavirin as Adjunct Therapy against Invasive Candida Strains in In Vitro Study.
The use of antifungal agents in the clinical setting is limited by the appearance of drug resistance and adverse side effects. There is, therefore, an urgent need to develop new drugs to strengthen the treatment of invasive fungal disease.
The purpose of this study is to describe the potential repurposing ribavirin as adjunctive therapy against Candida spp. primary screening of Prestwick Chemical library to ATCC 90028 and fluconazole-resistant strains of Candida albicans Candida albicans do. Furthermore, we evaluated the responses of 100 Candida sp. strain to ribavirin, antiviral agent, using the broth microdilution method as recommended by CLSI. We examine the involvement of efflux pump activity in the development of resistance to ribavirin. We studied the time-kill curves and test the boxes for the study of the combination of ribavirin-antifungal.
Twenty-one is not standard antifungal compounds were identified, including ribavirin. Ribavirin has in vitro antifungal activity against 63 strains of Candida, including strains of C. albicans, C. parapsilosis, and C. tropicalis, with MICs ranging from 0.37 to 3.02 ug / ml, whereas the MIC for C. krusei, C. glabrata , C. lusitaniae, and some strains of C. albicans remains high (≥24.16 ug / ml).
No association was observed between activity and resistance efflux pump ribavirin. Ribavirin showed fungistatic activity against multidrug-resistant (MDR) of C. albicans and fungicidal activity against strain C parapsilosis ..
Description: Accurate measurement of adenovirus titer is critical for gene delivery. Traditional plaque-forming unit (PFU) assays are long and suffer from high inter-assay variability. The QuickTiter Adenovirus Titer Immunoassay Kit provide a quick, complete system to functionally titer virus infectivity. The assay recognizes all 41 serotypes of adenovirus, and can be used with any adenovirus system that can amplify in HEK 293 cells.
Description: Accurate measurement of adenovirus titer is critical for gene delivery. Traditional plaque-forming unit (PFU) assays are long and suffer from high inter-assay variability. The QuickTiter Adenovirus Titer Immunoassay Kit provide a quick, complete system to functionally titer virus infectivity. The assay recognizes all 41 serotypes of adenovirus, and can be used with any adenovirus system that can amplify in HEK 293 cells.
Description: A rapid test for detection of antibodies (IgG and IgM) for 2019-nCoV, the novel Coronavirus from the Wuhan strain. The test is easy to perform, takes 10 minutes to provide reliable results and is higly specific to the 2019-nCoV Coronavirus.
Description: A rapid test for detection of antibodies (IgG and IgM) for 2019-nCoV, the novel Coronavirus from the Wuhan strain. The test is easy to perform, takes 10 minutes to provide reliable results and is higly specific to the 2019-nCoV Coronavirus.
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