Fabrication of Gelatin/PCL Electrospun Fiber Mat with Bone Powder and the Study of Its Biocompatibility

Fabricating ideal scaffolds for bone tissue engineering is a great challenge to researchers. To better mimic the mineral component and the microstructure of natural bone, several kinds of materials were adopted in our study, namely gelatin, polycaprolactone (PCL), nanohydroxyapatite (nHA), and bone powder. Three types of scaffolds were fabricated using electrospinning; gelatin/PCL, gelatin/PCL/nHA, and gelatin/PCL/bone powder. Scaffolds were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations. Then, Adipose-derived Stem Cells (ADSCs) were seeded on these scaffolds to study cell morphology, cell viability, and proliferation. Through this study, we found that nHA and bone powder can be successfully united in gelatin/PCL fibers. When compared with gelatin/PCL and gelatin/PCL/nHA, the gelatin/PCL/bone powder scaffolds could provide a better environment to increase ADSCs’ growth, adhesion, and proliferation. Thus, we think that gelatin/PCL/bone powder has good biocompatibility, and, when compared with nHA, bone powder may be more effective in bone tissue engineering due to the bioactive factors contained in it

YAGG:Ce transparent ceramics with high luminous efficiency for solid-state lighting application

YAGG:Ce transparent ceramics with high luminous efficiency for solid-state lighting applicatio

Whole-Genome Expression Analysis and Signal Pathway Screening of Synovium-Derived Mesenchymal Stromal Cells in Rheumatoid Arthritis

Synovium-derived mesenchymal stromal cells (SMSCs) may play an important role in the pathogenesis of rheumatoid arthritis (RA) and show promise for therapeutic applications in RA. In this study, a whole-genome microarray analysis was used to detect differential gene expression in SMSCs from RA patients and healthy donors (HDs). Our results showed that there were 4828 differentially expressed genes in the RA group compared to the HD group; 3117 genes were upregulated, and 1711 genes were downregulated. A Gene Ontology analysis showed significantly enriched terms of differentially expressed genes in the biological process, cellular component, and molecular function domains. A Kyoto Encyclopedia of Genes and Genomes analysis showed that the MAPK signaling and rheumatoid arthritis pathways were upregulated and that the p53 signaling pathway was downregulated in RA SMSCs. Quantitative real-time polymerase chain reaction was applied to verify the expression variations of the partial genes mentioned above, and a western blot analysis was used to determine the expression levels of p53, p-JNK, p-ERK, and p-p38. Our study found that differentially expressed genes in the MAPK signaling, rheumatoid arthritis, and p53 signaling pathways may help to explain the pathogenic mechanism of RA and lead to therapeutic RA SMSC applications

TNF-α Induced the Enhanced Apoptosis of Mesenchymal Stem Cells in Ankylosing Spondylitis by Overexpressing TRAIL-R2

Ankylosing spondylitis (AS) is an autoimmune disease with unknown etiology. Dysregulated mesenchymal stem cells (MSCs) apoptosis may contribute to the pathogenesis of autoimmune diseases. However, apoptosis of MSCs from patients with AS (ASMSCs) has not been investigated yet. The present study aims to assess the apoptosis of bone marrow-derived ASMSCs and to investigate the underlying mechanisms of altered ASMSCs apoptosis. We successfully induced the apoptosis of ASMSCs and MSCs from healthy donors (HDMSCs) using the combination of tumor necrosis factor alpha (TNF-α) and cycloheximide (CHX). We found that ASMSCs treated with TNF-α and CHX showed higher apoptosis levels compared to HDMSCs. During apoptosis, ASMSCs expressed significantly more TRAIL-R2, which activated both the death receptor pathway and mitochondria pathway by increasing the expression of FADD, cleaved caspase-8, cytosolic cytochrome C, and cleaved caspase-3. Inhibiting TRAIL-R2 expression using shRNA eliminated the apoptosis differences between HDMSCs and ASMSCs by partially reducing ASMSCs apoptosis but minimally affecting that of HDMSCs. Furthermore, the expression of FADD, cleaved caspase-8, cytosolic cytochrome C, and cleaved caspase-3 were comparable between HDMSCs and ASMSCs after TRAIL-R2 inhibition. These results indicated that increased TRAIL-R2 expression results in enhanced ASMSCs apoptosis and may contribute to AS pathogenesis

Drug Repurposing of Histone Deacetylase Inhibitors That Alleviate Neutrophilic Inflammation in Acute Lung Injury and Idiopathic Pulmonary Fibrosis via Inhibiting Leukotriene A4 Hydrolase and Blocking LTB4 Biosynthesis

Acute lung injury (ALI) and idiopathic pulmonary fibrosis (IPF) are both serious public health problems with high incidence and mortality rate in adults, and with few drugs available for the efficient treatment in clinic. In this study, we identified that two known histone deacetylase (HDAC) inhibitors, suberanilohydroxamic acid (SAHA, <b>1</b>) and its analogue 4-(dimethylamino)-<i>N</i>-[7-(hydroxyamino)-7-oxoheptyl]­benzamide (<b>2</b>), are effective inhibitors of Leukotriene A4 hydrolase (LTA4H), a key enzyme in the biosynthesis of leukotriene B4 (LTB4), across a panel of 18 HDAC inhibitors, using enzymatic assay, thermofluor assay, and X-ray crystallographic investigation. Importantly, both <b>1</b> and <b>2</b> markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose. Detailed mechanisms of down-regulation of proinflammatory cytokines by <b>1</b> or <b>2</b> were determined <i>in vivo</i>. Collectively, <b>1</b> and <b>2</b> would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis