The aim of this study was to evaluate therapeutic potential of edaravone in the murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) and to expand the knowledge of its mechanism of action. Edaravone (6 mg/kg/day) was administered intraperitoneally from the onset of clinical symptoms until the end of the experiment (28 days). Disease progression was assessed daily using severity scores. At the peak of the disease, histological analyses, markers of oxidative stress (OS) and parameters of mitochondrial function in the brains and spinal cords (SC) of mice were determined. Gene expression of inducible nitric oxide synthase (iNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha was determined at the end of the experiment. Edaravone treatment ameliorated EAE severity and attenuated inflammation in the SC of the EAE mice, as verified by histological analysis. Moreover, edaravone treatment decreased OS, increased the gene expression of the Nrf2 and HO-1, increased the activity of the mitochondrial complex II/III, reduced the activity of the mitochondrial complex IV and preserved ATP production in the SC of the EAE mice. In conclusion, findings in this study provide additional evidence of edaravone potential for the treatment of multiple sclerosis and expand our knowledge of the mechanism of action of edaravone in the EAE model.

• MeSH
• edaravon farmakologie   MeSH
• encefalomyelitida autoimunitní experimentální * patologie   MeSH
• encefalomyelitida * MeSH
• exprese genu MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• hemoxygenasa-1 genetika   metabolismus   MeSH
• myši MeSH
• stupeň závažnosti nemoci MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

This work studied a relationship between HO-1/CO system and lipid peroxidation with consequent effects on liver functions and NOS-2. We focused on curcumin pretreatment in rat toxic model of d-galactosamine and lipopolysaccharide. Hepatocyte viability, lipid peroxidation, antioxidant status, ALT and AST were evaluated. HO-1 and NOS-2 expressions and respective enzyme activity were determined. Curcumin caused decreases in ALT and AST levels as well as in lipid peroxidation. Furthermore, curcumin pretreatment increased liver HO-1 (2.4-fold, p=0.001), but reduced NOS-2 (4.1-fold, p=0.01) expressions. In conclusion, the tuning of CO/NO pathways is important in shedding light on curcumin's cytoprotective effects in this model.

• MeSH
• alanintransaminasa krev   MeSH
• antioxidancia farmakologie   terapeutické užití   MeSH
• aspartátaminotransferasy krev   MeSH
• Curcuma chemie   MeSH
• fytoterapie MeSH
• galaktosamin MeSH
• hemoxygenasa-1 metabolismus   MeSH
• játra cytologie   účinky léků   metabolismus   MeSH
• krysa rodu rattus MeSH
• kurkumin farmakologie   terapeutické užití   MeSH
• lékové postižení jater farmakoterapie   metabolismus   MeSH
• lipopolysacharidy MeSH
• modely nemocí na zvířatech MeSH
• oxid uhelnatý metabolismus   MeSH
• peroxidace lipidů účinky léků   MeSH
• potkani Wistar MeSH
• rostlinné extrakty farmakologie   terapeutické užití   MeSH
• signální transdukce MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Preeclampsia (PE) is a major cause of the pregnancy morbidity and mortality over the world. Disorganized placentation caused by trophoblast cell abnormity is one of main risk factors to induce PE. MiR-133a-3p has been shown to contain regulatory effects on oxidative stress in the cardiomyocytes. But the effects of miR-133a-3p on oxidative stress-induced apoptosis in the trophoblast cells remain unknown. In this study, trophoblast HTR-8/SVneo cells were transfected with miR-133a-3p mimics and inhibitor. H2O2 (250 microM) treatment of cells was adopted to induce oxidative stress. A series of typical molecular and cellular experiments was subsequently performed in order to investigate this issue. It was found that miR-133a-3p overexpression attenuated the oxidative stress induced by H2O2 through reduced ROS and MDA levels and enhanced antioxidase activities in the trophoblast cells. Overexpressed miR-133a-3p was shown to relieve the oxidative stress-induced apoptosis of HTR-8/SVneo cells. At molecular levels, a direct binding effect of miR-133a-3p on BACH1 was verified. Moreover, miR-133a-3p overexpression also enhanced BACH1 downstream Nrf2/HO-1 signaling to activate antioxidant genes. It is collectively demonstrated that miR-133a-3p can relieve the oxidative stress-induced apoptosis in the trophoblast cells through the BACH1/Nrf2/HO-1 signaling pathway via targeting BACH1 directly. This regulatory mechanism of miR-133a-3p in the trophoblast cells under oxidative stress may give a new perspective for oxidative stress-induced trophoblast cell abnormality and be useful to study more pathological mechanisms of PE.

• MeSH
• apoptóza účinky léků   MeSH
• buněčné linie MeSH
• faktor 2 související s NF-E2 metabolismus   MeSH
• hemoxygenasa-1 metabolismus   MeSH
• lidé MeSH
• mikro RNA aplikace a dávkování   genetika   MeSH
• oxidační stres účinky léků   MeSH
• preeklampsie metabolismus   patologie   prevence a kontrola   MeSH
• signální transdukce MeSH
• těhotenství MeSH
• transkripční faktory bZIP metabolismus   MeSH
• trofoblasty účinky léků   metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

Projekt si klade za cíl: 1/ Ověřit a dále studovat efekty HA na replikaci a reaktivaci HIV-1 pozorované in vitro na tkáňových kulturách v primárních periferních lymfocytech (PBMC): a/ ověřit inhibiční efekt HA na akutní infekci PBMC zdravých dárců virem HIV-1. b/ studovat efekt HA na reaktivaci latentní infekce HIV-1 v PBMC HIV+ pacientů. 2/ Charakterizovat redoxní stav a metabolismus hemu u HIV+ pacientů, zejména hladiny GSH, nitrátů a hBVR, aktivitu HO-1 a známky anémie. Korelovat tyto charakteristiky s výší viremie ev. s progresí HIV/AIDS. 3/ Na podkladě získaných výsledků vypracovat žádost pro SÚKL o povolení aplikace Normosangu omezenému počtu vybraných HIV+ pacientů. Budou použity tyto metody: průtoková cytometrie - intracelulární hladiny p24 Ag, HO-1, produkce volných radikálů a GSH; ELISA - hladiny p24 Ag v supernatantu; western blot analýza jednotlivých proteinů; PCR a real-time RT-PCR - reversní transkripce a reaktivace HIV-1; spektrofoto(fluori)metrie - HO-1 aktivita, hladiny GSH, nitrátů.; Goals of the project: 1/ To verify and further study effects of HA on HIV-1 replication and reactivation observed in cell lines also in primary PBMC's: a/ To verify HA effect on acute infection of PBMC's of healthy donors with HIV-1 b/ To study HA effect on reactivation of HIV-1 latent infection in PBMC's of HIV+ patients 2/ To characterize redox state and heme metabolism in HIV+ patients, namely GSH, nitrate and hBVR levels , HO-1 activity and anemia. To correlate these characteristics with virus load (HIV RNA) and with progression of HIV/AIDS. 3/ Based on the results, to submit application to the State Institute of Drug Control for administration of Normosang to selected HIV+ patients. Methods: flow cytometry - intracellular levels of p24 Ag, HO-1, production of free radicals, GSH; ELISA - p24 Ag levels in supernatnats; western blotting of individual proteins; PCR and real-time RT-PCR - reverse transcription and reactivation of HIV-1; spectrophoto(fluori)metry - HO-1 activity, GSH and nitrate levels

• MeSH
• AIDS MeSH
• arginin MeSH
• biliverdin MeSH
• ELISA MeSH
• hem MeSH
• hemoxygenasa-1 MeSH
• HIV infekce MeSH
• HIV-1 MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• průtoková cytometrie MeSH
• reverzní transkripce MeSH
• spektrofotometrie MeSH
• western blotting MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biochemie
• infekční lékařství
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

• Publikační typ
• abstrakty MeSH
• kongresy MeSH

• MeSH
• lidé MeSH
• podpůrné srdeční systémy * MeSH
• srdeční selhání * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• práce podpořená grantem MeSH

Background Extracorporeal membrane oxygenation (ECMO) has been increasingly used for postcardiotomy cardiogenic shock, but without a concomitant reduction in observed in-hospital mortality. Long-term outcomes are unknown. This study describes patients' characteristics, in-hospital outcome, and 10-year survival after postcardiotomy ECMO. Variables associated with in-hospital and postdischarge mortality are investigated and reported. Methods and Results The retrospective international multicenter observational PELS-1 (Postcardiotomy Extracorporeal Life Support) study includes data on adults requiring ECMO for postcardiotomy cardiogenic shock between 2000 and 2020 from 34 centers. Variables associated with mortality were estimated preoperatively, intraoperatively, during ECMO, and after the occurrence of any complications, and then analyzed at different time points during a patient's clinical course, through mixed Cox proportional hazards models containing fixed and random effects. Follow-up was established by institutional chart review or contacting patients. This analysis included 2058 patients (59% were men; median [interquartile range] age, 65.0 [55.0-72.0] years). In-hospital mortality was 60.5%. Independent variables associated with in-hospital mortality were age (hazard ratio [HR], 1.02 [95% CI, 1.01-1.02]) and preoperative cardiac arrest (HR, 1.41 [95% CI, 1.15-1.73]). In the subgroup of hospital survivors, the overall 1-, 2-, 5-, and 10-year survival rates were 89.5% (95% CI, 87.0%-92.0%), 85.4% (95% CI, 82.5%-88.3%), 76.4% (95% CI, 72.5%-80.5%), and 65.9% (95% CI, 60.3%-72.0%), respectively. Variables associated with postdischarge mortality included older age, atrial fibrillation, emergency surgery, type of surgery, postoperative acute kidney injury, and postoperative septic shock. Conclusions In adults, in-hospital mortality after postcardiotomy ECMO remains high; however, two-thirds of those who are discharged from hospital survive up to 10 years. Patient selection, intraoperative decisions, and ECMO management remain key variables associated with survival in this cohort. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03857217.

• MeSH
• dospělí MeSH
• kardiochirurgické výkony * škodlivé účinky   MeSH
• kardiogenní šok etiologie   terapie   MeSH
• lidé MeSH
• mimotělní membránová oxygenace * škodlivé účinky   MeSH
• mortalita v nemocnicích MeSH
• následná péče MeSH
• pooperační komplikace etiologie   MeSH
• propuštění pacienta MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH