Rel Family Transcription Factor NFAT5 Upregulates COX2 via HIF-1α Activity in Ishikawa and HEC1a Cells.

Nuclear factor of activated T cells 5 (NFAT5) and cyclooxygenase 2 (COX2; PTGS2) both participate in diverse pathologies including cancer progression. However, the biological role of the NFAT5-COX2 signaling pathway in human endometrial cancer has remained elusive. The present study explored whether NFAT5 is expressed in endometrial tumors and if NFAT5 participates in cancer progression. To gain insights into the underlying mechanisms, NFAT5 protein abundance in endometrial cancer tissue was visualized by immunohistochemistry and endometrial cancer cells (Ishikawa and HEC1a) were transfected with NFAT5 or with an empty plasmid. As a result, NFAT5 expression is more abundant in high-grade than in low-grade endometrial cancer tissue. RNA sequencing analysis of NFAT5 overexpression in Ishikawa cells upregulated 37 genes and downregulated 20 genes. Genes affected included cyclooxygenase 2 and hypoxia inducible factor 1α (HIF1A). NFAT5 transfection and/or treatment with HIF-1α stabilizer exerted a strong stimulating effect on HIF-1α promoter activity as well as COX2 expression level and prostaglandin E2 receptor (PGE2) levels. Our findings suggest that activation of NFAT5-HIF-1α-COX2 axis could promote endometrial cancer progression.

Fucose-Rich Sulfated Polysaccharides from Two Vietnamese Sea Cucumbers Bohadschia argus and Holothuria (Theelothuria) spinifera: Structures and Anticoagulant Activity.

Fucosylated chondroitin sulfates (FCSs) FCS-BA and FCS-HS, as well as fucan sulfates (FSs) FS-BA-AT and FS-HS-AT were isolated from the sea cucumbers Bohadschia argus and Holothuria (Theelothuria) spinifera, respectively. Purification of the polysaccharides was carried out by anion-exchange chromatography on DEAE-Sephacel column. Structural characterization of polysaccharides was performed in terms of monosaccharide and sulfate content, as well as using a series of non-destructive NMR spectroscopic methods. Both FCSs were shown to contain a chondroitin core [→3)-ß-d-GalNAc-(1→4)-ß-d-GlcA-(1→]n bearing sulfated fucosyl branches at O-3 of every GlcA residue in the chain. These fucosyl residues were different in pattern of sulfation: FCS-BA contained Fuc2S4S, Fuc3S4S and Fuc4S at a ratio of 1:8:2, while FCS-HS contained these residues at a ratio of 2:2:1. Polysaccharides differed also in content of GalNAc4S6S and GalNAc4S units, the ratios being 14:1 for FCS-BA and 4:1 for FCS-HS. Both FCSs demonstrated significant anticoagulant activity in clotting time assay and potentiated inhibition of thrombin, but not of factor Xa. FS-BA-AT was shown to be a regular linear polymer of 4-linked α-L-fucopyranose 3-sulfate, the structure being confirmed by NMR spectra of desulfated polysaccharide. In spite of considerable sulfate content, FS-BA-AT was practically devoid of anticoagulant activity. FS-HS-AT cannot be purified completely from contamination of some FCS. Its structure was tentatively represented as a mixture of chains identical with FS-BA-AT and other chains built up of randomly sulfated alternating 4- and 3-linked α-L-fucopyranose residues.

Features and Advantages of Supercritical CO2 Extraction of Sea Cucumber Cucumaria frondosa japonica Semper, 1868.

Extraction process of Cucumaria frondosa japonica Semper, 1868, which are subspecies of Cucumaria frondosa (Gunnerus, 1767), were studied. It was shown that supercritical carbon dioxide extraction of holothuria was more effective than conventional solvent extraction. Step-by-step extraction with carbon dioxide followed by supercritical extraction with the addition of a co-solvent of ethanol can almost double the yields of extracts of triterpene glycosides, styrenes and carotenoids. Moreover, the fraction of triterpene glycosides practically does not contain colored impurities, in contrast to traditional ethanol extraction. The obtained extracts by HPLC in combination with tandem mass spectrometry (HPLC-MS/MS) identified 15 triterpene glycosides, 18 styrene compounds and 14 carotenoids. Supercritical extraction made it possible to obtain extracts with yields superior to conventional hexane and alcohol extracts. Moreover, such an approach with the use of supercritical fluid extraction (SFE) and subsequent profiling of metabolites can help with the study of holothuria species that are not as well studied.

Pectins from the sea grass Enhalus acoroides (L.f.) Royle: Structure, biological activity and ability to form nanoparticles.

Two pectins from the seagrass Enhalus acoroides (L.f.) Royle were isolated for the first time. Their structures and biological activities were investigated. NMR spectroscopy showed one of them to consist exclusively from the repeating →4-α-d-GalpUA→ residue (Ea1), while the other had a much more complex structure that also included 1→3-linked α-d-GalpUA residues, 1→4-linked ß-apiose residues and small amounts of galactose and rhamnose (Ea2). The pectin Ea1 showed noticeable dose-dependent immunostimulatory activity, the Ea2 fraction was less effective. Both pectins were used to create pectin-chitosan nanoparticles for the first time, and the influence of pectin/chitosan mass ratio on their size and zeta potential was investigated. Ea1 particles were slightly smaller than Ea2 particles (77 ± 16 nm vs 101 ± 12 nm) and less negatively charged (-23 mV vs -39 mV). Assessment of their thermodynamic parameters showed that only the second pectin could form nanoparticles at room temperature.

The structure of fucoidan from Sargassum oligocystum and radiosensitizing activity of galactofucans from some algae of genus Sargassum.

The aim of this study was to establish the fine structure of fucoidan from Sargassum oligocystum and to study the radiosensitizing effect of fucoidans from three algae of genus Sargassum (S. oligocystum, S. duplicatum, and S. feldmannii) with different structures. The fucoidan SoF2 from S. oligocystum was sulfated (32%) galactofucan (Fuc:Gal = 2:1), with a Mw of 183 kDa (Mw/Mn = 2.0). Its supposed structure was found to be predominantly 1,3-linked fucose as the main chain, with branching points at C2 and C4. The branches could be single galactose and/or fucose short chains with terminal galactose residues. Sulfate groups were found at positions C3, C2, and/or C4 of fucose residues and at C2 and/or C4 of galactose residues. The radiosensitizing effect of galactofucans from S. oligocystum, S. duplicatum, and S. feldmannii against human melanoma SK-MEL-28, colon HT-29, and breast MDA-MB-231 cancer cells was investigated. The influence of all investigated polysaccharides treatments with/without X-ray radiation on colony formation of human melanoma cells SK-MEL-28 was weak. Fucoidan from S. feldmannii has been shown to be the most promising radiosensitizing compound against human colon HT-29 and breast MDA-MB-231 cancer cells.

Genetic epidemiology and risk factors for brain tumors / 中南大学学报(医学版)

This report summarized current knowledge and findings relevant to environmental and genetic risk factors in brain tumors,with a particular focus on glioma.To date,the established risk factors for brain tumors are family history and ionizing radiation exposure;whereas there is an inverse association between tumors and other factors such as history of allergies,atopic conditions,chickenpox,and varicella zoster virus infection.To identify inherited genetic variants impacting susceptibility of brain tumors,large scale familial linkage-scan pedigree analysis,populationbased candidate genes,and genome-wide association study were performed.More recently;next generation exome and whole genome sequencing studies were also conducted.

Investigation of the effects induced by 1 400 W on nasopharyngeal carcinoma cell and the mechanism / 中国医师杂志

Objective To investigate the effect induced by specific inducible nitric oxide synthase (iNOS) inhibitor 1 400 W on nasopharyngeal carcinoma CNE-2 cells lines and its mechanism.Methods CNE-2 cells were treated by different concentrations of 1 400 W,diamminedichloroplatinum (DDP),and both chemicals.Cell counting kit-8 (CCK-8) was used to examine the viability of cells.Quantitative realtime polymerase chain reaction (qRT-PCR) was applied to detect the iNOS mRNA expression.Results The expression of iNOS mRNA was down-regulated by 1400W and was positively correlated with inhibitionrate of cell proliferation.1 400 W inhibits proliferation of CNE-2 cell in a concentration-dependent manner.The proliferation inhibition rate of CNE-2 cells treated by 1 400 W combined with DDP was not enhanced.Conclusions Specific inducible nitric oxide synthase inhibitor 1 400 W can exerts anti-tumor effect though inhibiting the expression of iNOS mRNA;The mechanism of chemosensitization induced by iNOS inhibitor on CNE-2 cells may be closely related level of down-regulation of iNOS expression.

Time of salvage treatment on sudden sensorineural hearing loss / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the best time of intratympanic dexamethasone injection to treat sudden sensorineural hearing loss (SSNHL) as salvage therapy so that to improve the curative efficacy on sudden deafness at the utmost.@*METHOD@#A total of 192 patients with SSNHL were included in this study, among whom 63 cases received the systemic steroid therapy throughout the study, while the other ones were treated with systemic steroid as initial treatment and were given intratympanic steroid administration as salvage treatment starting at different time point. The salvage treatment started on the 3rd day after the beginning of the initial treatment for 29 cases, on the 7th day for 38 cases, on the 14th day for 43 cases, and 1 month later for 19 cases. All the patients were followed up for 2 months.@*RESULT@#The recovery rates and total effective rates showed no statistically significant difference between the patients received only systemic steroid therapy and the ones received intratympanic steroid administration on the 3rd, 7th day and 1 month later after the initial treatment. The recovery rate and total effective rate exhibited statistically significant difference between the patients received intratympanic steroid administration since the 14th day after the initial treatment and the ones received only systemic steroid therapy, with the numerical value of P 0. 037 and 0. 034, respectively.@*CONCLUSION@#(1) As an initial management plan, the curative effects. between the intratympanic steroid administration and the systemic steroid therapy were not significantly different. (2) As a salvage treatment, intratympanic steroid was a better choice for patients who have not completely recover from ISSNHL after failure of initial management with systemic steroid only. (3) The best time point of salvage treatment with intratympanic steroid was about 2 weeks after initial management with systemic steroid.