Angelica sinensis polysaccharides alleviate the oxidative burden on hematopoietic cells by restoring 5-fluorouracil-induced oxidative damage in perivascular mesenchymal progenitor cells.

CONTEXT: 5-Fluorouracil (5-FU)-injured stromal cells may cause chronic bone marrow suppression; however, the underlying mechanism remains unclear. Angelica sinensis polysaccharide (ASP), the main biologically active ingredient of the Chinese herb, Angelica sinensis (Oliv.) Diels (Apiaceae), may enrich the blood and promote antioxidation. OBJECTIVE: This study investigated the protective antioxidative effects of ASP on perivascular mesenchymal progenitors (PMPs) and their interactions with hematopoietic cells. MATERIALS AND METHODS: PMPs were dissociated from C57BL/6 mouse femur and tibia and were subsequently divided into the control, ASP (0.1 g/L), 5-FU (0.025 g/L), and 5-FU + ASP (pre-treatment with 0.1 g/L ASP for 6 h, together with 0.025 g/L 5-FU) then cultured for 48 h. Hematopoietic cells were co-cultured on these feeder layers for 24 h. Cell proliferation, senescence, apoptosis, and oxidative indices were detected, along with stromal osteogenic and adipogenic differentiation potentials. Intercellular and intracellular signaling was analyzed by real-time quantitative reverse transcription polymerase chain reaction and Western blotting. RESULTS: ASP ameliorated the reactive oxygen species production/scavenge balance in PMPs; improved osteogenic differentiation; increased SCF, CXCL12, VLA-4/VCAM-1, ICAM-1/LFA1, and TPO/MPL, Ang-1/Tie-2 gene expression. Further, the ASP-treated feeder layer alleviated hematopoietic cells senescence (from 21.9 ± 1.47 to 12.1 ± 1.13); decreased P53, P21, p-GSK-3ß, ß-catenin and cyclin-D1 protein expression, and increased glycogen synthase kinase (GSK)-3ß protein expression in co-cultured hematopoietic cells. DISCUSSION AND CONCLUSIONS: ASP delayed oxidative stress-induced premature senescence of 5-FU-treated feeder co-cultured hematopoietic cells via down-regulation of overactivated Wnt/ß-catenin signaling. These findings provide a new strategy for alleviating myelosuppressive stress.

Space-Confined Nucleation of Semimetal-Oxo Clusters within a [H7P8W48O184]33- Macrocycle: Synthesis, Structure, and Enhanced Proton Conductivity.

Spatially confined assembly of semimetallic oxyanions (AsO33- and SbO33-) within a [H7P8W48O184]33- (P8W48) macrocycle has afforded three nanoscale polyanions, [{AsIII5O4(OH)3}2(P8W48O184)]32- (As10), [(SbIIIOH)4(P8W48O184)]32- (Sb4), and [(SbIIIOH)8(P8W48O184)]24- (Sb8), which were crystallized as the hydrated mixed-cation salts (Me2NH2)13K7Na2Li10[{AsIII5O4(OH)3}2(P8W48O184)]·32H2O (DMA-KNaLi-As10), K20Li12[(SbIIIOH)4(P8W48O184)]·52H2O (KLi-Sb4), and (Me2NH2)8K6Na5Li5[(SbIIIOH)8(P8W48O184)]·65H2O (DMA-KNaLi-Sb8), respectively. A multitude of solid- and solution-state physicochemical techniques were employed to systematically characterize the structure and composition of the as-made compounds. The polyanion of As10 represents the first example of a semimetal-oxo cluster-substituted P8W48 and accommodates the largest AsIII-oxo cluster in polyoxometalates (POMs) reported to date. The number of incorporated SbO33- groups in Sb4 and Sb8 could be customized by a simple variation of SbIII-containing precursors. Encapsulation of semimetallic oxyanions inside P8W48 sets out a valid strategy not only for the development of host-guest assemblies in POM chemistry but also for their function expansion in emerging applications such as proton-conducting materials, for which DMA-KNaLi-As10 showcases an outstanding conductivity of 1.2 × 10-2 S cm-1 at 85 °C and 70% RH.

Melatonin promotes hair regeneration by modulating the Wnt/ß-catenin signalling pathway.

Melatonin (MLT) is a circadian hormone that reportedly influences the development and cyclic growth of secondary hair follicles; however, the mechanism of regulation remains unknown. Here, we systematically investigated the role of MLT in hair regeneration using a hair depilation mouse model. We found that MLT supplementation significantly promoted hair regeneration in the hair depilation mouse model, whereas supplementation of MLT receptor antagonist luzindole significantly suppressed hair regeneration. By analysing gene expression dynamics between the MLT group and luzindole-treated groups, we revealed that MLT supplementation significantly up-regulated Wnt/ß-catenin signalling pathway-related genes. In-depth analysis of the expression of key molecules in the Wnt/ß-catenin signalling pathway revealed that MLT up-regulated the Wnt/ß-catenin signalling pathway in dermal papillae (DP), whereas these effects were facilitated through mediating Wnt ligand expression levels in the hair follicle stem cells (HFSCs). Using a DP-HFSCs co-culture system, we verified that MLT activated Wnt/ß-catenin signalling in DPs when co-cultured with HFSCs, whereas supplementation of DP cells with MLT alone failed to activate Wnt/ß-catenin signalling. In summary, our work identified a critical role for MLT in promoting hair regeneration and will have potential implications for future hair loss treatment in humans.

In vitro oogenesis from murine premeiotic germ cells using a new three-dimensional culture system.

A faithful reconstitution of the complete process of oogenesis in vitro is helpful for understanding the molecular mechanisms, genetics, and epigenetic changes related to gametogenesis; it can also be useful for clinical drug screening, disease research, and regenerative medicine. To this end, given the consensus that murine female germ cells initiate meiosis at E13.5, substantial works have reported the successful generation of fertile oocytes using E12.5 female gonads as starting materials. Nevertheless, our data demonstrated that murine germ cells at E12.5 have heterogeneously initiated a meiotic transcriptional program based on a measurement of pre-mRNAs (unspliced) and mature mRNAs (spliced) at a single-cell level. Therefore, to establish a platform that faithfully recapitulates the entire process in vitro (from premeiotic murine germ cells to fully developed oocytes), we here report a novel three-dimensional organoid culture (3-DOC) system, which successfully induced fully developed oocytes from E11.5 premeiotic female germ cells (oogonia). Compared with 2D culture and other 3D culture methods, this new culture system is more cost-effective and can create high-quality oocytes similar to in vivo oocytes. In summary, our new culture platform provides an experimental model for future research in regenerative medicine and reproductive biology.

ISLES 2016 and 2017-Benchmarking Ischemic Stroke Lesion Outcome Prediction Based on Multispectral MRI.

Performance of models highly depend not only on the used algorithm but also the data set it was applied to. This makes the comparison of newly developed tools to previously published approaches difficult. Either researchers need to implement others' algorithms first, to establish an adequate benchmark on their data, or a direct comparison of new and old techniques is infeasible. The Ischemic Stroke Lesion Segmentation (ISLES) challenge, which has ran now consecutively for 3 years, aims to address this problem of comparability. ISLES 2016 and 2017 focused on lesion outcome prediction after ischemic stroke: By providing a uniformly pre-processed data set, researchers from all over the world could apply their algorithm directly. A total of nine teams participated in ISLES 2015, and 15 teams participated in ISLES 2016. Their performance was evaluated in a fair and transparent way to identify the state-of-the-art among all submissions. Top ranked teams almost always employed deep learning tools, which were predominately convolutional neural networks (CNNs). Despite the great efforts, lesion outcome prediction persists challenging. The annotated data set remains publicly available and new approaches can be compared directly via the online evaluation system, serving as a continuing benchmark (www.isles-challenge.org).