Thermal Analysis and Crystal Structure of Poly(Acrylonitrile-Co-Itaconic Acid) Copolymers Synthesized in Water.

The composition and structure of polyacrylonitrile (PAN) precursors play an important role during thermal stabilization, which influences the properties of the resulting carbon fibers. In this paper, PAN homopolymer and PAN-itaconic (IA) copolymers with different IA contents were synthesized by aqueous phase precipitation polymerization. The effects of IA content on the structure and thermal properties were studied using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The morphology of PAN polymers showed that the average size of the PAN particles increased with the increase of IA content in the feed. The content of the IA comonomer on the copolymers was quantitatively characterized by the relative absorbance intensity (A1735/A2243) in FTIR spectrum. With the increase of IA content in the feed, PAN-IA copolymers exhibited lower degree of crystallinity and crystal size than the control PAN homopolymer. The results from DSC curves indicated that PAN-IA1.0 copolymers had lower initial exothermic temperature (192.4 °C) and velocity of evolving heat (6.33 J g-1 °C-1) in comparison with PAN homopolymer (Ti = 238.1 °C and ΔH/ΔT = 34.6 J g-1 °C-1) in an air atmosphere. TGA results suggested that PAN-IA1.0 copolymers had higher thermal stability than PAN homopolymer, which can form a ladder structure easier during thermal processing. Therefore, PAN-IA1.0 copolymers would be a suitable candidate for preparing high performance PAN based carbon fibers.

The Structure and Properties of Polyacrylonitrile Nascent Composite Fibers with Grafted Multi Walled Carbon Nanotubes Prepared by Wet Spinning Method.

Polyacrylonitrile (PAN) grafted amino-functionalized multi walled carbon nanotubes (amino-MWCNTs) were synthesized by in situ polymerization under aqueous solvent. The grafted MWCNT/PAN nascent composite fibers were prepared by the wet spinning method. Fourier transform infrared spectroscopy and Raman spectroscopy indicated that the amino-MWCNTs and PAN macromolecular chains had interfacial interactions and formed chemical bonds. The grafting content of the PAN polymer on the amino-MWCNTs was up to 73.2% by thermo gravimetric analysis. The incorporation of the grafted MWCNTs improved the degree of crystallization and crystal size of PAN nascent fibers, and changed the thermal properties during exothermic processing in an air atmosphere. Morphology analysis and testing of mechanical properties showed that the grafted MWCNT/PAN nascent composite fibers with a more uniform diameter distribution and larger diameter had higher tensile strength and tensile modulus than the control PAN nascent fibers.

Orexin A prevents degradation of the articular matrixes in human primary chondrocyte culture.

Excessive production of pro-inflammatory cytokines such as interleukin-1ß (IL-1ß) plays a key role in the pathophysiological development of osteoarthritis (OA). Orexin A is an important peptide of hypothalamic origin, which has displayed its multiple biological functions in several chronic diseases via activation of its specific G-protein coupled receptors, orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R). In this study, we aimed to characterize the protective effects of orexin A against IL-1ß-induced degradation of articular cartilage matrixes in human chondrocytes. Our results indicate that OX1R but not OX2R was expressed in human chondrocytes. We also found that the expression of OX1R was significantly lower in chondrocytes from OA patients, and that treatment with IL-1ß decreased the expression of OX1R in a dose-dependent manner. The presence of orexin A ameliorated IL-1ß-induced degradation of type II collagen and aggrecan, the two major components of articular cartilage matrixes. Our results also show that orexin A prevented IL-1ß-induced expression of catabolic enzymes such as MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5. Mechanistically, orexin A treatment abolished activation of the transcriptional factor NF-κB via inhibition of KKα/IκB-α phosphorylation and IκB-α degradation. These findings suggest that orexin A might act as an effective therapeutic agent for the treatment of OA.

Rheological Behavior of Amino-Functionalized Multi-Walled Carbon Nanotube/Polyacrylonitrile Concentrated Solutions and Crystal Structure of Composite Fibers.

The rheological behavior of amino-functionalized multi-walled carbon nanotubes (amino-CNTs)/polyacrylonitrile (PAN) concentrated solutions in the dimethyl sulphoxide solvent and the effects of the amino-CNTs on the PAN precursor fibers by wet-spinning method were investigated. The amino-CNT/PAN concentrated solutions prepared by in situ solution polymerization with homogeneous dispersion of amino-CNTs have higher complex viscosity, storage modulus and loss modulus as compared to the control PAN concentrated solutions containing 22% PAN polymer by mass. The composite fibers with amino-CNTs of 1 wt % have lower degree of crystallization, crystal size and crystal region orientation compared to the control PAN precursor fibers. However, the amino-CNT/PAN composite fibers with diameter of about 10.5 µm exhibit higher mechanical properties than the control PAN precursor fibers with diameter of about 8.0 µm. Differential scanning calorimetry analysis demonstrated that the cyclization reaction in composite fibers have broad exothermic temperature range and low exothermic rate. These results indicate that the addition of amino-CNTs into PAN precursor fibers is beneficial to controlling the process of thermal stabilization and obtaining the higher performance of composite fibers.

A novel interplay between HOTAIR and DNA methylation in osteosarcoma cells indicates a new therapeutic strategy.

PURPOSE: Osteosarcoma (OS) is one of the most prevalent primary malignant bone tumors in adolescent. HOTAIR is highly expressed and associated with the epigenetic modifications, especially DNA methylation, in cancer. However, the regulation mechanism between HOTAIR and DNA methylation and the biological effects of them in the pathogenesis of osteosarcoma remains elusive. METHOD: Through RNA-sequencing and computational analysis, followed by a variety of experimental validations, we report a novel interplay between HOTAIR, miR-126, and DNA methylation in OS. RESULTS: We found that HOTAIR is highly expressed in OS cells and the knockdown of HOTAIR leads to the down-regulation of DNMT1, as well as the decrease of global DNA methylation level. RNA-sequencing analysis of HOTAIR-regulated gene shows that CDKN2A is significantly repressed by HOTAIR. A series of experiments show that HOTAIR represses the expression of CDKN2A through inhibiting the promoter activity of CDKN2A by DNA hypermethylation. Further evidence shows that HOTAIR activates the expression of DNMT1 through repressing miR-126, which is the negative regulator of DNMT1. Functionally, HOTAIR depletion increases the sensibility of OS cells to DNMT1 inhibitor through regulating the viability and apoptosis of OS cells via HOTAIR-miR126-DNMT1-CDKN2A axis. CONCLUSION: These results not only enrich our understanding of the regulation relationship between non-coding RNA, DNA methylation, and gene expression, however, also provide a novel direction in developing more sophisticated therapeutic strategies for OS patients.

MicroRNA-184 Modulates Doxorubicin Resistance in Osteosarcoma Cells by Targeting BCL2L1.

BACKGROUND Early metastasis of osteosarcoma (OS) is highly lethal and responds poorly to drug and radiation therapies. MicroRNAs (miRNAs) are a class of small noncoding RNAs that modulate gene expression at the post-transcriptional level. However, the detailed functions of specific miRNAs are not entirely understood. The aim of the present study was to investigate the role of miR-184 as a mediator of drug resistance in human osteosarcoma. MATERIAL AND METHODS qRT-PCR was used to analyze the expression level of miR-184 in OS cell line U-2 OS and MG-63 treated with doxorubicin. MiR-184 agomir or miR-184 antagomir was transferred into cells to regulated miR-184. The target of miR-184 was predicted by TargetScan and confirmed by luciferase reporter assay. Bcl-2-like protein 1 (BCL2L1) expression was detected by Western blot. Cell apoptosis was determined by Annexin V staining and analysis by flow cytometry. RESULTS Doxorubicin induced time-dependent expression of miR-184 in OS cell line U-2 OS and MG-63. Luciferase reporter assay identified BCL2L1 as the direct target gene of miR-184. Furthermore, doxorubicin reduced BCL2L1 expression, which was reversed by miR-184 overexpression and further decreased by miR-184 inhibition in OS cells. In addition, miR-184 agomir reduced doxorubicin-induced cell apoptosis, whereas miR-184 antagomir enhanced apoptosis in OS cells, suggesting that up-regulation of miR-184 contributes to chemoresistance of the OS cell line. CONCLUSIONS Our data show that miR-184 was up-regulated in OS patients treated with doxorubicin therapy and leads to poor response to drug therapy by targeting BCL2L1.

siRNA targeting TCTP suppresses osteosarcoma cell growth and induces apoptosis in vitro and in vivo.

Osteosarcoma (OS) remains the most frequent primary malignant bone tumor in adolescents. However, the molecular cause of the disease is poorly elucidated. In the present study, we primarily found that translationally controlled tumor protein (TCTP) was overexpressed in human OS tissues and cell lines. To investigate the function of TCTP in OS cell growth, an RNA interference lentivirus system was employed to deplete TCTP expression in Saos-2 and U2OS cell lines. Specific knockdown of TCTP significantly impaired cell proliferation and colony-formation capacity in both OS cell lines. Moreover, depletion of TCTP caused a significant accumulation of OS cells in the S phase and eventually induced cell apoptosis. Expression levels of the G2/M phase regulators cyclin B1 and Cdc25A were decreased, and apoptotic markers Bad and caspase-3 were increased in both OS cell lines after depletion of TCTP. Furthermore, depletion of TCTP potently inhibited the growth of xenografts in nude mice. Our results indicate that inhibition of TCTP expression exerts potential antitumor activity and may be a novel therapeutic approach in human OS.

The effect of CTLA-4 A49G polymorphism on rheumatoid arthritis risk: a meta-analysis.

BACKGROUND: Recently, a number of studies have been performed to explore the association between CTLA-4 A49G polymorphism and rheumatoid arthritis (RA). However, the results of previous works are still controversial and ambiguous. METHODS: In this work, we attempted to perform an updated meta-analysis of available case-control study in order to assess the association between CTLA-4 A49G polymorphism and RA risk. We searched the various citation databases without limits on languages. Article searching was performed by screening the references of retrieved studies manually. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the strength of the association. RESULTS: We totally compiled 27 studies in 24 articles (9805 RA patients and 10691 control subjects) into our meta-analysis work. We found significant association between CTL-A4 A49G polymorphism and RA risk (GG vs. AA: OR = 1.13, 95% CI = 1.03-1.23; GA vs. AA: OR = 1.19, 95% CI = 1.07-1.33; GA + GG vs. AA: OR = 1.18, 95% CI = 1.07-1.29). In the subgroup analysis by ethnicity, evidences of significantly increased risk was also found in both Asian (GG vs. AA: OR = 1.34, 95% CI = 1.15-1.55; GA + GG vs. AA: OR = 1.24, 95% CI = 1.08-1.41) and Caucasian population (GA vs. AA: OR = 1.19, 95% CI = 1.03-1.37; GA + GG vs. AA: OR = 1.14, 95% CI = 1.01-1.29). No evidence of publication bias was found in this work. CONCLUSIONS: Our meta-analysis suggests that CTLA-4 A49G polymorphism was associated with RA risk. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_157.

Inhibition of EGFR-induced glucose metabolism sensitizes chondrosarcoma cells to cisplatin.

Chondrosarcomas are malignant cartilage-forming tumors which are resistant to conventional chemotherapy and radiotherapy. By searching in Oncomine which is a cancer microarray database and web-based data mining platform, we found Glut1 and LDHA were upregulated in human chondrosarcoma patient samples. In this study, we reported total epidermal growth factor receptor (EGFR) expression and phosphorylated EGFR were highly activated in human chondrosarcoma cell lines. In addition, overexpression of EGFR contributed to cisplatin resistance. EGFR promoted glucose metabolism of chondrosarcoma cells through the upregulation of glycolysis key enzymes. Interestingly, cisplatin-resistant chondrosarcoma cells showed upregulated glucose metabolism and EGFR signaling pathway. Finally, we demonstrated that the combination of either EGFR inhibitor or anaerobic glycolysis inhibitor with cisplatin showed synergistically inhibitory effects on cisplatin-resistant chondrosarcoma cells through the inducements of apoptosis and cell cycle arrest. Our project proposed a novel function of EGFR in the regulation of glucose metabolism in chondrosarcoma cells and contributed to the development of therapeutic strategies for the clinical treatment of chondrosarcoma patient.