Induction of the mesenchymal to epithelial transition by demethylation-activated microRNA-125b is involved in the anti-migration/invasion effects of arsenic trioxide on human chondrosarcoma

Background: In addition to treating acute promyelocytic leukemia, arsenic trioxide (ATO) suppresses other solid tumors, including chondrosarcoma. However, the effects of ATO on metastasis in chondrosarcoma cells, and the underlying molecular mechanisms remain unclear. Methods: The effects of ATO on the migratory and invasive capacities of chondrosarcoma cells were investigated by Wound healing, Transwell and EMT assays. The expression of miR-125b in human chondrosarcoma tissues and cell lines was detected by real-time PCR analysis. Bisulfite sequencing analysis (BSP) was used to detect the effects of ATO on the expression of miR-125b. The gain-of-function and loss-of-function experiments were performed on chondrosarcoma cell lines to investigate the effects of miR-125b on chondrosarcoma invasion, and to determine whether signal transducer and activator of transcription 3(Stat3) mediates these effects. Dual-luciferase reporter assay was used to identify whether Stat3 is a direct target of miR-125b. Results: MiR-125b was significantly downregulated in human metastatic chondrosarcoma tissues and cell lines but not in non-metastatic chondrosarcoma tissues. ATO up-regulates the expression of miR-125b by the demethylation of DNA. ATO induces MET and attenuates the invasive capacities of chondrosarcoma cells through miR-125b. Stat3 was verified as a direct target of miR-125b, which is involved in ATO regulating EMT-associated traits. Conclusions: These findings, for the first time, provides evidence that the miR-125b-mediated inhibition of Stat3 is involved in the ATO-induced attenuation of metastasis in chondrosarcoma cells.National Natural Science Foundation of China [81572633]; Research Fund for the Doctoral Program of Higher Education of China [20130001110076]SCI(E)[email protected]

HMGB1 cytoplasmic translocation in patients with acute liver failure

<p>Abstract</p> <p>Background</p> <p>High-mobility group box 1 (HMGB1) is a late mediator of lethal systemic inflammation. Acute liver failure (ALF) has been shown to trigger systemic inflammation in clinical and animal studies. To evaluate the possibility of HMGB1 cytoplasmic translocation in ALF, we determined whether HMGB1 is released in hepatocytes and end organ in patients with liver failure/injury.</p> <p>Methods</p> <p>HepG2 cell were stimulated with LPS or TNF-α, the increase of HMGB1 extracellularly in the culture medium and intracellularly in various cellular fractions were determined by western blot or immunocytochemistry. To observe sub-cellular location of HMGB1 in hepatocytes, liver specimens were obtained from 6 patients with ALF caused by HBV infection, 10 patients with chronic viral hepatitis B, 6 healthy controls, as well as animals model of ALF by intraperitoneal administration of D-GalN (600 mg/kg) and LPS (0.5 mg/kg).</p> <p>Results</p> <p>In HepG2 cell culture, LPS or TNF actively induced HMGB1 cytoplasmic translocation and release in a time- and dose-dependent fashion. In animal model of ALF, cytoplasmic HMGB1 translocation was observed in hepatocyts as early as 3 hours post onset of ALF. In patients with ALF caused by HBV infection, cytoplasmic HMGB1 translocation was similarly observed in some hepatocytes of the liver specimen.</p> <p>Conclusions</p> <p>Cytoplasmic HMGB1 translocation may occur during ALF, which may potentially contribute to the pathogenesis of liver inflammatory diseases.</p

Plasma Interleukin-37 is elevated in patients with rheumatoid arthritis: Its correlation with disease activity and Th1/Th2/Th17-related cytokines

Interleukin- (IL-) 37 is a novel anti-inflammatory cytokine that suppresses immune response and inflammation. This study was performed to determine whether IL-37 was elevated in patients with rheumatoid arthritis (RA) and investigate the correlation between IL-37 level and disease activity and the concentration of Th1/Th2/Th17-related cytokines. Clinical parameters of disease activity, including the 28-joint disease activity score (DAS28) and C-reactive protein (CRP), were collected in 34 RA patients and 34 age- and sex-matched healthy controls. Plasma IL-37 was measured by ELISA. Plasma levels of TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, IFN-γ, MCP-1, and MIP-1β were analyzed using the Bio-Plex suspension array system. It was found that IL-37 levels were elevated markedly in RA patients and almost undetectable in healthy controls. In addition, IL-37 levels in patients with active RA were significantly enhanced as compared with those in patients of remission. More importantly, IL-37 showed a significant correlation with disease activity (DAS28) and IL-4, IL-7, IL-10, IL-12, and IL-13 concentrations in RA patients. These findings suggest that IL-37 plays an important role in the pathogenesis of RA and may prove to be a potential biomarker of active RA

Genetic Diversity in Echinococcus multilocularis From the Plateau Vole and Plateau Pika in Jiuzhi County, Qinghai Province, China

The Qinghai-Tibet Plateau is a highly endemic area of alveolar echinococcosis where a series of intermediate hosts, especially voles and pikas, are infected with Echinococcus multilocularis. The metacestodes of E. multilocularis are fluid-filled, asexually proliferating cysts, and they are mainly found in the host's liver in the form of tumor-like growths. In this study, we investigated the genetic variations of E. multilocularis in four mitochondrial (mt) genes, namely, NADH dehydrogenase subunit 5 (nad5), adenosine triphosphate subunit 6 (atp6), cytochrome c oxidase subunit 1 (cox1), and NADH dehydrogenase subunit 1 (nad1). The complete nad5, atp6, cox1, and nad1 genes were amplified separately from each hydatid cyst isolate using polymerase chain reaction (PCR) and then sequenced. Phylogenetic trees were then generated based on the combined mt genes using MrBayes 3.1.2 and PAUP version 4.0b10. The results showed that thirty of 102 voles and two of 49 pikas were infected with E. multilocularis. The genetic variation distances among all E. multilocularis samples were 0.1–0.4%, 0.2–0.4%, 0.1–0.6%, and 0.1–0.4% for nad5, atp6, nad1, and cox1, respectively. Compared to previous studies of the genetic diversity of E. multilocularis based on the cox1 gene, the genetic distances within the same group were 1.3–1.7% (Mongolia strain), 0.6–0.8% (North American strain), 0.3–0.6% (European strain), and 0.1–0.4% (Asian strain). Based on concatenated sequences of the nad5, atp6, cox1, and nad1 genes all haplotypes were divided into two clusters. In conclusion, the genetic diversity of E. multilocularis based on mt genes on a small local area is at low level but between different regions with long distance and different ecological environment each other, the genetic diversity is at relatively high level; genetic variation is higher in the nad1 gene than that in the other three mt genes. The results on a local scale provide basic information for further study of the molecular epidemiology, genetic differences and control of E. multilocularis in Qinghai Province, China

Revealing histological and morphological features of female reproductive system in tree shrew (Tupaia belangeri)

The tree shrew has been used as a primate animal model in neuroscience studies but it has only rarely been employed in the study of reproductive systems. This is mainly because we know very little about the histological features of reproductive organs of the tree shrew. In this study, we have systematically analyzed the histology of reproductive organs of tree shrew, in comparison with human organs. The uterus of female tree shrew is uterus biomes unicolis, which is connected with an enveloped ovary through a thin fallopian tube. Histologically, the fallopian tube consists of folded mucosa, muscularis and serosa. Like other mammalian animals, the different developmental stages (primordial, primary, secondary and Graafian follicles) of ovarian follicles including inner oocyte and outer granulosa cells are embedded in the cortex. The luminal endometrium, middle muscular myometrium and serosa constitute the wall of uterus of tree shrew. The uterine endometrium contains simple columnar ciliated cells and goblet cells, and there are rich uterine glands in underlying stroma. Furthermore, these glands of tree shrew are round and smaller during anestrus, and become much longer when they are in estrus. The uterine endometrium in younger animals was less developed when compared to a mature tree shrew. Compared to human uterine endometrium, the histological features of tree shrew are very similar, indicating that it could potentially be good primate animal model for studying the diseases in reproductive system