3-Chloro-4-hydroxy­furan-2(5H)-one

In the title compound, C4H3ClO3, mol­ecules are linked via O—H⋯O hydrogen bonds into an infinite chain with graph-set motif C(6) along the c axis

High serum levels of procalcitonin and soluble TREM-1 correlated with poor prognosis in pulmonary tuberculosis

SummaryObjectivesComparisons of procalcitonin (PCT), C-reactive protein (CRP), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) would expand our knowledge of which biomarker is the best predictor for outcomes of patients with pulmonary tuberculosis (PTB).MethodsWe prospectively enrolled 243 PTB patients, in whom PCT, CRP, and sTREM-1 measurement were performed to evaluate their prognostic value for 6-month mortality.ResultsSerum PCT, CRP, and sTREM-1 levels on diagnosis of PTB were significantly higher in nonsurvivors (2.22 ± 6.22 vs. 0.13 ± 0.31 ng/mL, P = 0.043; 42.1 ± 59.4 vs. 12.5 ± 29.1 mg/L, P = 0.004; 332 ± 362 vs. 128 ± 98 pg/mL, P = 0.001, respectively) as compared with 6-month survivors. In multivariate Cox regression analysis, PCT ≧0.5 ng/mL (hazard ratio 4.13, 95% CI, 1.99–8.58) and sTREM-1 ≧129 pg/mL (hazard ratio 3.39, 95% CI, 1.52–7.58) remained independent mortality predictors. Serum PCT and sTREM-1 levels above the cutoffs were also associated with the presence of disseminated tuberculosis.ConclusionsAmong PTB patients, higher PCT, CRP, and sTREM-1 levels are observed in nonsurvivors than in 6-month survivors. Serum levels of PCT and sTREM-1 over the cutoffs are independently associated with a poor outcome. In addition, higher PCT and sTREM-1 levels would raise the clinical suspicion of disseminated tuberculosis

Depletion of OLFM4 gene inhibits cell growth and increases sensitization to hydrogen peroxide and tumor necrosis factor-alpha induced-apoptosis in gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Human olfactomedin 4 (OLFM4) gene is a secreted glycoprotein more commonly known as the anti-apoptotic molecule GW112. OLFM4 is found to be frequently up-regulated in many types of human tumors including gastric cancer and it was believed to play significant role in the progression of gastric cancer. Although the function of OLFM4 has been indicated in many studies, recent evidence strongly suggests a cell or tissue type-dependent role of OLFM4 in cell growth and apoptosis. The aim of this study is to examine the role of gastric cancer-specific expression of OLFM4 in cell growth and apoptosis resistance.</p> <p>Methods</p> <p>OLFM4 expression was eliminated by RNA interference in SGC-7901 and MKN45 cells. Cell proliferation, anchorage-independent growth, cell cycle and apoptosis were characterized in vitro. Tumorigenicity was analyzed in vivo. The apoptosis and caspase-3 activation in response to hydrogen peroxide (H₂O₂) or tumor necrosis factor-alpha (TNF α) were assessed in the presence or absence of caspase inhibitor Z-VAD-fmk.</p> <p>Results</p> <p>The elimination of OLFM4 protein by RNA interference in SGC-7901 and MKN45 cells significantly inhibits tumorigenicity both in vitro and in vivo by induction of cell G1 arrest (all P < 0.01). OLFM4 knockdown did not trigger obvious cell apoptosis but increased H₂O₂or TNF α-induced apoptosis and caspase-3 activity (all P < 0.01). Treatment of Z-VAD-fmk attenuated caspase-3 activity and significantly reversed the H₂O₂or TNF α-induced apoptosis in OLFM4 knockdown cells (all P < 0.01).</p> <p>Conclusion</p> <p>Our study suggests that depletion of OLFM4 significantly inhibits tumorigenicity of the gastric cancer SGC-7901 and MKN45 cells. Blocking OLFM4 expression can sensitize gastric cancer cells to H₂O₂or TNF α treatment by increasing caspase-3 dependent apoptosis. A combination strategy based on OLFM4 inhibition and anticancer drugs treatment may provide therapeutic potential in gastric cancer intervention.</p

Comprehensive study of the blazars from Fermi-LAT LCR: The log-normal flux distribution and linear RMS-Flux relation

Fermi-LAT LCR provide continuous and regularly-sampled gamma-ray light curves, spanning about 14 years, for a large sample of blazars. The log-normal flux distribution and linear RMS-Flux relation of the light curves for a few of Fermi blazar have been examined in previous studies. However, the probability that blazars exhibit log-normal flux distribution and linear RMS-Flux relation in their gamma-ray light curves has not been systematically explored. In this study, we comprehensively research on the distribution of gamma-ray flux and the statistical characteristics on a large sample of 1414 variable blazars from the Fermi-LAT LCR catalog, including 572 FSRQs, 477 BL Lacs, and 365 BCUs, and statistically compare their flux distributions with normal and log-normal distributions. The results indicate that the probability of not reject log-normal is 42.05% for the large sample, and there is still 2.05% probability of not reject normality, based on the joint of Kolmogorov-Smirnov, Shapiro-Wilk and Normality tests. We further find that the probability that BL Lacs conforms to the log-normal distribution is higher than that of FSRQs. Besides, after removing sources with less than 200 data points from this large sample, a sample of 549 blazars, which is still a large sample comparing to the previous studies, was obtained. Basing on dividing the light curves into segments every 20 points (or 40 points, or one year), we fitted the linear RMS-Flux relation of this three different sets, and found that the Pearson correlation coefficients are all close to 1 of the most blazars. This result indicates a strong linear correlation between the RMS and the flux of this 549 blazars. The log-normal distribution and linear RMS-Flux relation indicate that the variability of gamma-ray flux for most blazars is non-linear and multiplicative process.Comment: 13pages, 5figures, Accepted for publication in RA

Identification of polyunsaturated fatty acids as potential biomarkers of osteoarthritis after sodium hyaluronate and mesenchymal stem cell treatment through metabolomics

Introduction: Osteoarthritis (OA) is a prevalent joint disorder worldwide. Sodium hyaluronate (SH) and mesenchymal stem cells (MSCs) are promising therapeutic strategies for OA. Previous studies showed they could improve knee function and clinical symptoms of OA. However, the mechanism of the therapeutic effects on the improvement of OA has not been clearly explained.Methods: In our study, we used a technique called 5-(diisopropylamino)amylamine derivatization liquid chromatography coupled with mass spectrometry to find the metabolites in OA synovial fluid under different treatments.Results and Discussion: After looking into the metabolomics, we discovered that SH and MSC treatment led to the downregulation of ω-6 polyunsaturated fatty acids (PUFAs) and the upregulation of ω-3 PUFAs. Significantly, the contents of 5(S)-HETE, PGA2, PGB2, and PGJ2 were lower in the MSC group than in the SH group after quantification using 5-(diisopropylamino)amylamine derivatization–UHPLC–QQQ-MS. This is the first report on the relationship of 11(S)-HETE, PGA2, PGB2, PGF2β, 11β-PGF2α, and DK-PGE2 with OA. Moreover, the correlation analysis of metabolites and inflammation factors showed the positive association of ω-6 PUFAs with pro-inflammation cytokines, and of ω-3 PUFAs with anti-inflammation cytokines. Our results indicated the therapeutic effect of SH and MSCs in patients with OA. In addition, this reliable metabolic approach could uncover novel biomarkers to treat OA

HPtaa database-potential target genes for clinical diagnosis and immunotherapy of human carcinoma

Tumor-associated antigens (TAAs) have been the most actively employed targets in the clinical diagnosis and treatment of human carcinoma, such as PSA in the diagnosis of prostate cancer and NY-ESO-1 in the immunotherapy of melanoma and other cancers. However, identification of TAAs has often been hampered by the complicated and laborsome laboratory procedures. In order to accelerate the process of tumor antigen discovery, and thereby improve diagnosis and treatment of human carcinoma, we have made an effort to establish a publicly available Human Potential Tumor Associated Antigen database (HPtaa) with potential TAAs identified by in silico computing (). Tumor specificity was chosen as the core of tumor antigen evaluation, together with other relevant clues. Various platforms of gene expression, including microarray, expressed sequence tag and SAGE data, were processed and integrated by several penalty algorithms. A total of 3518 potential TAAs have been included in the database, which is freely available to academic users. As far as we know, this database is the first one addressing human potential TAAs, and the first one integrating various kinds of expression platforms for one purpose

Huperzine A attenuates nonalcoholic fatty liver disease by regulating hepatocyte senescence and apoptosis: an in vitro study

Objective This study was undertaken to detect if free fatty acids (FFA) induce hepatocyte senescence in L-02 cells and if huperzine A has an anti-aging effect in fatty liver cells. Methods L-02 cells were treated with a FFA mixture (oleate/palmitate, at 3:0, 2:1, 1:1, 1:2 and 0:3 ratios) at different concentrations. Cell viability and fat accumulation rate were assessed by a Cell Counting Kit 8 and Nile Red staining, respectively. The mixture with the highest cell viability and fat accumulation rate was selected to continue with the following experiment. The L-02 cells were divided into five groups, including the control group, FFA group, FFA + 0.1 μmol/L huperzine A (LH) group, FFA + 1.0 μmol/L huperzine A (MH) group and FFA + 10 μmol/L huperzine A (HH) group, and were cultured for 24 h. The expression of senescence-associated β-galactosidase (SA-β-gal) was detected by an SA-β-gal staining kit. The expression levels of aging genes were measured by qRT-PCR. The expression levels of apoptosis proteins were detected by a Western blot. ELISA kits were used to detect inflammatory factors and oxidative stress products. The expression of nuclear factor (NF-κB) and IκBα were detected by immunofluorescence. Results The FFA mixture (oleate/palmitate, at a 2:1 ratio) of 0.5 mmol/L had the highest cell viability and fat accumulation rate, which was preferable for establishing an in vitro fatty liver model. The expression of inflammatory factors (TNF-α and IL-6) and oxidants Malonaldehyde (MDA), 4-hydroxynonenal (HNE) and reactive oxygen species (ROS) also increased in the L-02 fatty liver cells. The expression levels of aging markers and aging genes, such as SA-β-gal, p16, p21, p53 and pRb, increased more in the L-02 fatty liver cells than in the L-02 cells. The total levels of the apoptosis-associated proteins Bcl2, Bax, Bax/Bcl-2, CyCt and cleaved caspase 9 were also upregulated in the L-02 fatty liver cells. All of the above genes and proteins were downregulated in the huperzine A and FFA co-treatment group. In the L-02 fatty liver cells, the expression of IκBα decreased, while the expression of NF-κB increased. After the huperzine A and FFA co-treatment, the expression of IκBα increased, while the expression of NF-κB decreased. Conclusion Fatty liver cells showed an obvious senescence and apoptosis phenomenon. Huperzine A suppressed hepatocyte senescence, and it might exert its anti-aging effect via the NF-κB pathway