Immune checkpoint protein V-domain immunoglobulin suppressor of T-cell activation (VISTA) controls antitumor immunity and is a valuable target for cancer immunotherapy. This study identified a role of VISTA in regulating Toll-like receptor (TLR) signaling in myeloid cells and controlling myeloid cell-mediated inflammation and immunosuppression. VISTA modulated the polyubiquitination and protein expression of TRAF6. Consequently, VISTA dampened TLRmediated activation of MAPK/AP-1 and IKK/NF-κB signaling cascades. At cellular levels, VISTA regulated the effector functions of myeloid-derived suppressor cells (MDSCs) and tolerogenic DC subsets. Blocking VISTA augmented their ability to produce proinflammatory mediators and diminished their T cell-suppressive functions. These myeloid cell-dependent effects resulted in a

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Over time, the relative effects of elevated [CO 2 ] on the aboveground photosynthesis, growth and development of rice (Oryza sativa L.) are likely to be changed with increasing duration of CO 2 exposure, but the resultant effects on rice belowground responses remain to be evaluated. To investigate the impacts of elevated [CO 2 ] on seasonal changes in root growth, morphology and physiology of rice, a free-air CO 2 enrichment (FACE) experiment was performed at Wuxi, Jiangsu, China, in 2002-2003. A japonica cultivar with large panicle was exposed to two [CO 2 ] (ambient [CO 2 ], 370 lmol mol À1 ; elevated [CO 2 ], 570 lmol mol À1 ) at three levels of nitrogen (N): low (LN, 15 g N m À2 ), medium (MN, 25 g N m À2 ) and high N (HN, 35 g N m À2 ). Elevated [CO 2 ] increased cumulative root volume, root dry weight, adventitious root length and adventitious root number at all developmental stages by 25-71%, which was mainly associated with increased root growth rate during early growth period (EGP) and lower rate of root senescence during late growth period (LGP), while a slight inhibition of root growth rate occurred during middle growth period (MGP). For individual adventitious roots, elevated [CO 2 ] increased average length, volume, diameter and dry weight early in the season, but the effects gradually disappeared in subsequent stages. Total surface area and active adsorption area per unit root dry weight reached their maxima 10 days earlier in FACE vs. ambient plants, but both of them together with root oxidation ability per unit root dry weight declined with elevated [CO 2 ] during MGP and LGP, the decline being larger during MGP than LGP. The CO 2 -induced decreases in specific root activities during MGP and LGP were associated with a larger amount of root accumulation during EGP and lower N concentration and higher C/N ratio in roots during MGP and LGP in FACE vs. ambient plants. The results suggest that most of the CO 2 -induced increases in shoot growth of rice are similarly associated with increased root growth.

Curcumin was recently discovered to strengthen immune response through multiple mechanisms. Cytotoxic CD8+ T-cells play a critical role in modulating anticancer immune response, but is severely restricted by T-cell exhaustion. Bladder carcinomas express PD-L1 and can abrogate CD8+ T-cell response. Thus, we hypothesized that bisdemethoxycurcumin, a natural dimethoxy derivative of curcumin, may provide a favorable environment for T-cell response against bladder cancer when used in combination with α-PD-L1 antibody. Immunocompetent C56BL/6 mouse models bearing subcutaneous or lung metastasized MB79 bladder cancer were established to validate this conjecture. We found that bisdemethoxycurcumin significantly increased intratumoral CD8+ T-cell infiltration, elevated the level of IFN-γ in the blood, and decreased the number of intratumoral myeloid-derived suppressor cells. Furthermore, α-PD-L1 antibody protected these amplified CD8+ T-cells from exhaustion, and therefore facilitated the secretion of IFN-γ, granzyme B, and perforin through these CD8+ T-cells. As a result, this combination treatment strategy significantly prolonged survival of intraperitoneal metastasized bladder cancer bearing mice, suggesting that bisdemethoxycurcumin in combination with α-PD-L1 antibody may be promising for bladder cancer patients.

BackgroundOur recent studies suggested that the chromodomain helicase DNA binding protein 1-like (CHD1L) gene plays an oncogenic role in human hepatocellular carcinoma. However, the status of CHD1L protein expression in ovarian cancer and its clinical/prognostic significance are obscure.MethodsIn this study, immunohistochemistry (IHC) for CHD1L was performed on a tissue microarray (TMA) containing 102 primary ovarian carcinomas and 44 metastatic lesions (omental metastasis). Receiver-operator curve (ROC) analysis was used to evaluate patients’ survival status.ResultsThere is an augmented tendency of CHD1L expression in ovarian carcinoma metastasis than in primary lesions (P<0.05). A significant association was found between positive expression of CHD1L and tumors histological type (P <0.05). By univariate survival analysis of the ovarian carcinoma cohorts, positive expression of CHD1L was significantly correlated with shortened patient survival (mean 66.7 months versus 97.4 months, P<0.05). Moreover, CHD1L expression was evaluated to be a significant and independent prognostic factor in multivariate analysis (P<0.05).ConclusionsThese findings provide evidence that positive expression of CHD1L protein is significantly correlated with the metastasis proceeding of ovarian carcinoma, and CHD1L protein expression, as examined by IHC, may act as a novel prognostic biomarker for patients with ovarian carcinoma.

Se-enriched lactobacillus can intervene in CCl4-induced liver injury in mice by enhancing macrophage function activity to keep normal and beneficial effects, elevating antioxidant-enzyme activities and reducing lipid peroxidation reaction, inhibiting excessive release of TNF-alpha, preventing the dramatic elevation of [Ca2+]i in hepatocytes.

Here we report a simple all-nucleic-acid enzymefree catalyzed hairpin assembly assisted amplification strategy with quantum dots (QDs) as the nanoscale signal reporter for homogeneous visual and fluorescent detection of A549 lung cancer cells from clinical blood samples. This work was based on the phenomenon that CdTe QDs can selectively recognize Ag + and C-Ag + -C and by using mucin 1 as the circulating tumor cells (CTCs) marker and aptamer as the recognition probe. Under optimized conditions, the limits of detections as low as 0.15 fg/mL of mucin 1 and 3 cells/mL of A549 cells were achieved with fluorescence signals. A 1 fg/mL concentration of mucin 1 and 100 cells/mL of A549 can be distinguished by the naked eye. This method was used to quantitatively analyze CTCs in 51 clinical whole blood samples of patients with lung cancer. The levels of CTCs detected in clinical samples by this method were consistent with those obtained using the folate receptor-polymerase chain reaction clinical test kit and correlated with radiologic and pathological findings.

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