Cilostazol is a phosphodiesterase-3 inhibitor that functions as a platelet aggregation inhibitor and is used for treating peripheral artery diseases and ischemic stroke. Dendritic cells (DCs) play an active role in the immunological processes related to atherosclerosis. Cilostazol has anti-atherogenic and anti-inflammatory effects, but the effects of cilostazol on DC maturation remain unknown. The purpose of this study was to determine the effects of cilostazol on lipopolysaccharide (LPS)-induced maturation of DCs. DC2.4 cells were treated with cilostazol for 12 h and subsequently stimulated with LPS to induce maturation. Cilostazol reduced the expression of maturation-associated markers induced by LPS, such as CD40, CD86, and MHCII, improved the endocytotic function, and decreased production of the tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) of these cells. To further elucidate the mechanisms responsible for the inhibition of DC2.4 maturation by cilostazol, we investigated the effect of cilostazol on LPS-stimulated nuclear factor-kappa B (NF-κB) activation. Our results indicated that cilostazol treatment decreased IκBα degradation and inhibited NF-κB p65 translocation, and the inhibitory effects of cilostazol were cAMP-independent. Therefore, inhibition of NF-κB by cilostazol might result in the suppression of DC maturation. In conclusion, cilostazol suppressed LPS-stimulated DC maturation, which might contribute to its anti-atherosclerosis effect.

• MeSH
• antigeny CD40 imunologie   MeSH
• antigeny CD86 imunologie   MeSH
• ateroskleróza imunologie   patofyziologie   MeSH
• buněčná imunita imunologie   účinky léků   MeSH
• dendritické buňky * chemie   imunologie   účinky léků   MeSH
• fibrinolytika MeSH
• inhibitory agregace trombocytů MeSH
• inhibitory fosfodiesterasy 3 MeSH
• interleukin-6 imunologie   MeSH
• lipopolysacharidy terapeutické užití   MeSH
• MHC antigeny II. třídy imunologie   MeSH
• NF-kappa B * genetika   imunologie   účinky léků   MeSH
• polymerázová řetězová reakce MeSH
• průtoková cytometrie MeSH
• techniky in vitro MeSH
• tetrazoly * farmakologie   imunologie   MeSH
• TNF-alfa imunologie   MeSH
• vazodilatancia MeSH
• western blotting MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: Tetracentron sinense is an endemic and endangered deciduous tree. It belongs to the Trochodendrales, one of four early diverging lineages of eudicots known for having vesselless secondary wood. Sequencing and resequencing of the T. sinense genome will help us understand eudicot evolution, the genetic basis of tracheary element development, and the genetic diversity of this relict species. RESULTS: Here, we report a chromosome-scale assembly of the T. sinense genome. We assemble the 1.07 Gb genome sequence into 24 chromosomes and annotate 32,690 protein-coding genes. Phylogenomic analyses verify that the Trochodendrales and core eudicots are sister lineages and showed that two whole-genome duplications occurred in the Trochodendrales approximately 82 and 59 million years ago. Synteny analyses suggest that the γ event, resulting in paleohexaploidy, may have only happened in core eudicots. Interestingly, we find that vessel elements are present in T. sinense, which has two orthologs of AtVND7, the master regulator of vessel formation. T. sinense also has several key genes regulated by or regulating TsVND7.2 and their regulatory relationship resembles that in Arabidopsis thaliana. Resequencing and population genomics reveals high levels of genetic diversity of T. sinense and identifies four refugia in China. CONCLUSIONS: The T. sinense genome provides a unique reference for inferring the early evolution of eudicots and the mechanisms underlying vessel element formation. Population genomics analysis of T. sinense reveals its genetic diversity and geographic structure with implications for conservation.

• MeSH
• Arabidopsis genetika   MeSH
• fylogeneze MeSH
• genetická variace MeSH
• genom rostlinný * MeSH
• genom * MeSH
• Magnoliopsida genetika   MeSH
• molekulární evoluce * MeSH
• rostlinné proteiny genetika   MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza MeSH
• syntenie MeSH
• transkripční faktory genetika   MeSH
• xylém MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Čína MeSH

There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients' care.

• MeSH
• akutní nemoc MeSH
• hospitalizace MeSH
• kohortové studie MeSH
• lidé MeSH
• pankreatitida * terapie   MeSH
• propuštění pacienta * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH