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RESULTS Endothelial integrity (measured in a scale from 1-worst to 5-best) was significantly better after cardioplegic solution storage (2.83 ± 0.15 and 3.10 ± 0.13 in cold and room temperature, respectively) compared with storage in conventional solutions (2.23 ± 0.16 and 2.0 ± 0.15 in cold and room temperature, respectively). A significant effect of cardioplegic storage solution, as well as of cold temperature and cardioplegic solution interaction on endothelial preservation was reported, whereas storage temperature did not prove a significant factor by its own. CONCLUSIONS Cardioplegic storage solutions result in significantly better endothelial preservation compared with conventional heparin-enriched blood solutions. The association with superior clinical outcomes remains to be proved. © 2020 Wiley Periodicals, Inc.The O-linked β-N-acetylglucosamine (O-GlcNAc) modification, termed O-GlcNAcylation, is an essential and dynamic post-translational modification in cells. O-GlcNAc transferase (OGT) installs this modification on serine and threonine residues while O-GlcNAcase (OGA) hydrolyzes it. O-GlcNAc modifications are found on thousands of intracellular proteins involved in diverse biological processes. Dysregulation of O-GlcNAcylation and O-GlcNAc cycling enzymes has been detected in many diseases including cancer, diabetes, cardiovascular and neurodegenerative diseases. In this minireview, we will discuss recent advances in the development of molecular tools to investigate OGT and OGA functions and substrate recognition. We will also cover new chemical approaches to study O-GlcNAc dynamics and its potential roles in the immune system. We hope this minireview will encourage more research in these areas to advance understanding of O-GlcNAc in biology and diseases. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Assessment of reproductive toxicity is one of the important safety considerations in drug development. Thus, in the present research, the naïve Bayes (NB)-classifier method was applied to develop binary classification models. Six important molecular descriptors for reproductive toxicity were selected by the genetic algorithm. Then, 110 classification models were developed using six molecular descriptors and10 types of fingerprints with 11 different maximum diameters. Among these established models, the model based on six molecular descriptors and the SciTegic extended-connectivity fingerprints with 20 maximum diameters (LCFC_20) displayed the best prediction performance for reproductive toxicity (NB-1), which gave a 0.884 receiver operating characteristic (ROC) score and 91.8% overall prediction accuracy for the Training Set, and produced a 0.888 ROC score and 83.0% overall accuracy for the external Test Set I. In addition, for the external rat multi-generation reproductive toxicity dataset (Test Set II), the NB-1 model generated a 0.806 ROC score and 85.1% concordance. The generated prediction results indicated that the NB-1 model could give robust and reliable predictions for a reproductive toxicity potential of chemicals. Thus, the established model could be applied to filter early-stage molecules for potential reproductive adverse effects. In addition, six important molecular descriptors and new structural alerts for reproductive toxicity were identified, which could help medicinal chemists rationally guide the optimization of lead compounds and select chemicals with the best prospects of being safe and effective. © 2020 John Wiley & Sons, Ltd.Bexarotene is useful for both early and advanced cutaneous T-cell lymphoma (CTCL), and is sometimes applied to ultraviolet-tolerant early CTCL patients as one of the first-line therapies in the real world. However, continuous administration of bexarotene is sometimes difficult because of its adverse events (AE). Development of an appropriate protocol for bexarotene that can induce a consistent response for CTCL without severe AE (SAE) is needed. We retrospectively investigated 29 Japanese cases of CTCL and evaluated the efficacy of treatment and incident ratios of all AE and SAE. Objective response rate (ORR) for the overall cohort was 65.5%. ORR of the 300 mg/m2 cohort (conventional dose) was 76.2%, while that of the 150-300 mg/body (low dose) with narrowband ultraviolet B light (NBUVB) cohort was 37.5%. https://www.selleckchem.com/products/17-AAG(Geldanamycin).html Mean event-free survival was 10.0 months for all patients, 6.7 months for the bexarotene conventional-dose cohort and 19.1 months for the low-dose with NBUVB cohort. The incident ratio of total SAE for all patients was 20.7%. The incident ratio of total SAE was 23.8% for the conventional-dose cohort and 12.5% for the low-dose with NBUVB cohort. Our present study suggests that low-dose bexarotene plus NBUVB therapy is well-tolerated and could be one of the optimal therapies for advanced CTCL. © 2020 Japanese Dermatological Association.Superparamagnetic iron oxide nanoparticles (SPIONs) are extensively applied in biomedical fields, such as magnetic resonance imaging and as nanocarriers. However, the biosafety of SPIONs is not completely established, especially their effect on the immune system and inflammatory responses. Toll-like receptor (TLR) signaling is essential for many acute and chronic human inflammatory diseases. Regulation of TLR responses with drugs is helpful for these inflammatory conditions. In this study, we investigated the effects of 10 and 30 nm SPIONs on macrophages in the presence or absence of the TLR4 agonist lipopolysaccharide (LPS). We found that SPIONs inhibited the release of inflammatory cytokines induced by LPS both in murine and human macrophages in a concentration-dependent manner. Meanwhile, SPIONs suppressed inducible nitric oxide synthase expression activated by SPIONs in RAW264.7 macrophages. Additionally, TLR4 mRNA transcription and expression were attenuated with SPIONs treatment, which positively correlated with the release of inflammatory cytokines. In summary, our study demonstrates that SPIONs can suppress inflammatory responses, and the underlying mechanism may be regulated by TLR4 expression. Our present work contributes to clarifying the biosafety of SPIONs and provides a potential approach to alleviate human inflammatory diseases. © 2020 John Wiley & Sons, Ltd.
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