The purpose of this study was to explore the mechanism by which human umbilical cord blood mesenchymal stem cells (hUCB-MSCs)-derived exosomes exerted protective effect in hepatic ischemia/reperfusion injury (IRI). hUCB-MSCs-derived exosomes were administrated into hepatic IRI mice or cocultured with naïve CD4 + T cells exposed to hepatic hypoxia/reoxygenation microenvironment. Hepatic function was assessed by determining serum transaminases. Histological changes were observed using hematoxylin and eosin staining. The proportion of T helper 17 (Th17) and regulatory T (Treg) cells were analyzed by flow cytometry. The concentration of inflammatory cytokines was determined by enzyme-linked immunosorbent assay. The interaction between miR-1246 and interleukin 6 (IL-6) signal transducer (also known as gp130) was verified by luciferase activity assay. The miR-1246 expression, Th17/ Treg-related genes, and gp130-signal transducer and activator of transcription 3 (STAT3) pathway were detected by quantitative real-time polymerase chain reaction and western blotting. hUCB-MSCs-derived exosomes ameliorated IRI-induced hepatic dysfunction and decreased Th17/Treg ratio in CD4 + T cells in vitro, whereas treatment of hUCB-MSCs with miR-1246 inhibitor showed opposite effects, which was mediated via the IL-6-gp130-STAT3 pathway. hUCB-MSCs-derived exosomes could alleviate hepatic IRI through modulating the balance between Tregs and Th17 cells via miR-1246-mediated IL-6-gp130-STAT3 axis. K E Y W O R D Sexosomes, gp130, hepatic injury, ischemia/reperfusion, miR-1246

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

The purpose of this study was to explore the associated mechanism by which MSCs-derived exosomes exerted protective effect in hepatic ischemia/reperfusion injury (IRI). Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs)-derived exosomes were administrated into LO2 cells exposed to hypoxia/reoxygenation (H/R) and mice subjected to IRI. Cell viability was assessed by CCK-8 assay. Apoptosis was analyzed by flow cytometry and TUNEL staining. The expression of miR-1246 and Wnt/ β-catenin pathway-related proteins was detected by quantitative real-time PCR (qRT-PCR) and western blotting. The concentration of pro-inflammatory cytokines was determined by ELISA. Luciferase activity assay was performed to confirm the interaction between miR-1246 and glycogen synthase kinase 3β (GSK3β). Hepatic function was assessed by determining serum alanine amino transferase (ALT) and aspartate amino transferase (AST) levels. Histological changes were observed using hematoxylin-eosin (H&E) staining. MiR-1246 was significantly downregulated in H/R-treated LO2 cells. Treatment with exosomes derived from hUCB-MSCs led to miR-1246 upregulation. Furthermore, hUCB-MSCs-derived exosomes induced anti-apoptotic and pro-survival effects in LO2 cells and ameliorated IRI-induced hepatic dysfunction in mice, while treatment of exosomes from miR-1246 inhibitor-transfected hUCB-MSCs showed opposite effect, which was mediated by regulating GSK3β-Wnt/β-catenin pathway. Collectively, hUCB-MSCs-derived exosomes alleviated hepatic IRI by transporting miR-1246 via regulating GSK3β-mediated Wnt/β-catenin pathway.

In this study, thalidomide showed an outstanding effect on β-thalassaemia patients who required frequent red-cell transfusions. Thalidomide increased haemoglobin levels without causing serious adverse reactions, but the long-term curative outcomes and other side effects should be observed continuously.

This study was aimed to establish a standard protocol and to quantitatively assess the reliability of harmonic analysis of the radial pulse wave measured by a harmonic wave analyzer (TD01C system). Both intraobserver and interobserver assessments were conducted to investigate whether the values of harmonics are stable in successive measurements. An intraclass correlation coefficient (ICC) and a Bland–Altman plot were used for this purpose. For the reliability assessments of the intraobserver and the interobserver, 22 subjects (mean age 45 ± 14 years; 14 males and 8 females) were enrolled. The first eleven harmonics of the radial pulse wave presented excellent repeatability (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\text {ICCs}>0.9$ \end{document} and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\text {p}<0.001$ \end{document}) for the intraobserver assessment and high reproducibility (ICCs range from 0.83 to 0.96 and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\text {p}<0.001$ \end{document}) for the interobserver assessment. The Bland–Altman plot indicated that more than 90% of harmonic values fell within two standard deviations of the mean difference. Thus, we concluded that the harmonic analysis of the radial pulse wave using the TD01C system is a feasible and reliable method to assess a hemodynamic characteristic in clinical trial.

Resistive random access memory (RRAM) based on hybrid organic-inorganic halide perovskite (HOIP) has recently gained significant interests due to its low activation energy of ion migration. HOIP RRAM has been...

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