Curcumin’s Metabolites, Tetrahydrocurcumin and Octahydrocurcumin, Possess Superior Anti-inflammatory Effects in vivo Through Suppression of TAK1-NF-κB Pathway

Curcumin (CUR), a promising naturally occurring dietary compound, is commonly recognized as the potential anti-inflammatory agent. While the application of CUR was hampered by its low stability and poor systemic bioavailability, it has been suggested that the biological activities of CUR are intimately related to its metabolites. In the current investigation, we aimed to comparatively explore the anti-inflammatory effects of tetrahydrocurcumin (THC), octahydrocurcumin (OHC), and CUR, and to elucidate the underlying action mechanisms on experimental mice models of acute inflammation, i.e., xylene-induced ear edema, acetic acid-induced vascular permeability, and carrageenan-induced paw edema. The results showed that THC and OHC exerted significant and dose-dependent inhibitions on the formation of ear edema induced by xylene and paw edema provoked by carrageenan and inhibited the Evans blue dye leakage in peritoneal cavity elicited by acetic acid. Moreover, THC and OHC treatments were more effective than CUR in selectively inhibiting the expression of cyclooxygenase 2 (COX-2) and suppressing nuclear factor-κB (NF-κB) pathways via transforming growth factor β activated kinase-1 (TAK1) inactivation in the carrageenan-induced mouse paw edema model

Influencing factors and health risk assessment of microcystins in the Yongjiang river (China) by Monte Carlo simulation

The Yongjiang river is a large, shallow, hyper-trophic, freshwater river in Guangxi, China. To investigate the presence of microcystin-RR, microcystin-LR, and microcystin-YR (MC-RR, MC-LR, and MC-YR) in the Yongjiang river and describe their correlation with environmental factors, as well as, assess health risk using Monte Carlo simulation, 90 water samples were collected at three sample points from March to December 2017. Results showed that during the monitoring period, total concentrations of MC-RR (TMC-RR), MC-YR (TMC-YR), and MC-LR (TMC-LR) varied from 0.0224 to 0.3783 μg/L, 0.0329 to 0.1433 μg/L, and 0.0341 to 0.2663 μg/L, respectively. Total phosphorus (TP) content appeared to be related to TMC-LR and the total concentrations of microcystins (TMCs), while pH and total nitrogen (TN)/TP ratio appeared to be related to TMC-RR and TMC-YR, respectively. Using the professional health risk assessment software @Risk7.5, the risks of dietary intake of microcystins (MCs), including the carcinogenic risk and non-carcinogenic risk, were evaluated. It was found that the carcinogenic risk of MC-RR from drinking water was higher than MC-LR and MC-YR, and the presence of MCs would lead to high potential health risks, especially in children. The carcinogenic risk of MC-RR to children was >1 × 10−4, the maximum allowance level recommended by the US Environmental Protection Agency; as for adults, it was >5 × 10−5, the maximum allowance level recommended by the International Commission on Radiological Protection. The non-carcinogenic hazard index (HI) of MC-RR, MC-YR, and MC-LR increased successively, indicating that MC-LR was more hazardous to human health than MC-YR and MC-RR, but its HI was <1. This suggests that MCs pose less risk to health. However, it is necessary to strengthen the protection and monitoring of drinking water source for effective control of water pollution and safeguarding of human health

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Synchronous learning best practices: An action research study

Low cost and significant advances in technology now allow instructors to create their own virtual learning environments. Creating social interactions within a virtual space that emulates the physical classroom remains challenging. While students are familiar with virtual worlds and video meetings, they are inexperienced as virtual learners. Over a nine year period we applied iterative cycles of action research through numerous large classes to systematically uncover attributes of success when executing synchronous learning in distributed environments. Findings show technology is not the source of problems; rather, difficulties emerge from human behaviors and their interactions with system features. We conclude with practical takeaway guidelines for video conferencing and immersive virtual environments and a model of nexus of control that elaborates software and classroom management attributes that can lead to successful execution

Clinical effect of selective interventional therapy on sub-acute ST-segment elevation myocardial infarction under the guidance of fractional flow reserve and coronary arteriography

Abstract Objective This study aims to compare the clinical effects of selective interventional therapy (PCI) under the guidance of fractional flow reserve (FFR) and coronary arteriography. Methods Patients with sub-acute ST-segment elevation myocardial infarction (sub-acute STEMI), who were under selective PCI treatment between April 2012 and June 2014, were included into this study. These patients were divided into two groups, based on FFR measurements: FFR-PCI group and radiography-PCI group. Then, differences in clinical symptoms, coronary angiography, intervention, and endpoint events were compared between these two groups. Results A total of 592 patients with sub-acute STEMI were included in this study (207 patients in the FFR-PCI group and 385 patients in the radiography-PCI group). No statistical differences were observed in baseline clinical data and coronary angiography results between these two groups. Mean stent number was greater in the radiography-PCI group (1.22 ± 0.32) than in the FFR-PCI group (1.10 ± 0.29), and the difference was statistically significant (P = 0.019). During the follow-up period, 78 adverse events occurred (21 adverse events in the FFR-PCI group and 57 adverse events in the radiography-PCI group); and no statistical significance was observed between these two groups (log-rank P = 0.112). Conclusion Selective PCI treatment in patients with sub-acute STEMI under FFR acquired similar effects, compared to PCI treatment under the guidance of radiography, which can reduce the mean stent number

Hygroscopic La[B5O8(OH)]NO3·2H 2O: Insight into the evolution of borate fundamental building blocks

Borates have exceptionally diverse fundamental building blocks (FBBs), but factors controlling the formation of borate FBBs are poorly understood. The title compound La[B5O8(OH)]NO3·2H 2O crystallizes in the space group P21/n with a=6.5396(12) A, b=15.550(3) A, c=10.6719(19) A, β=90.44(1) and Z=4 at 173(2) K. Its structure has been refined from single-crystal X-ray diffraction data to R1=0.049 (for 2465) and wR2=0.173 (for 2459 I>2σ(I)). This structure analysis and first-principles calculations show that the change of the FBB from 3Δ2 in the title compound to 2Δ3 in La[B5O8(OH)(H2O)]NO 3·2H2O is accompanied by a rotation of the NO 3 group. FTIR, Rietveld and thermal analysis results show that the hygroscopic title compound is partially changed to La[B5O 8(OH)(H2O)]NO3·2H2O, with the conversion of [BO3] to [BO3(H2O)] by water absorption. ? 2013 Elsevier Inc

Hygroscopic La[B5O8(OH)]NO3 center dot 2H(2)O: Insight into the evolution of borate fundamental building blocks

National Natural Science Foundation of China [40972035, 21233004, 21201144]; Technological Innovation Platform of Fujian Province [2006L2003]; Fundamental Research Funds for the Central Universities [2013121020]; Natural Science and Engineering Research Council of Canada; Canadian Foundation for Innovation; Alberta Innovation and Science; BC Advanced EducationBorates have exceptionally diverse fundamental building blocks (FBBs), but factors controlling the formation of borate FBBs are poorly understood. The title compound La[B5O8(OH)]NO3 center dot 2H(2)O crystallizes in the space group P2(1)/n with a=6.5396(12) angstrom, b=15.550(3) angstrom, c=10.6719(19) angstrom, beta=90A4(1)degrees and Z=4 at 173(2) K. Its structure has been refined from single-crystal X-ray diffraction data to R-1=0.049 (for 2465) and wR(2)=0.173 (for 2459 I > 2 sigma(I)). This structure analysis and first-principles calculations show that the change of the FBB from 3 Delta 2 square in the title compound to 2 Delta 3 square in La[B5O8(OH)(H2O)]NO3 center dot 2H(2)O is accompanied by a rotation of the NO3 group. FTIR, Rietveld and thermal analysis results show that the hygroscopic title compound is partially changed to La[B5O8(OH)(H2O)]NO3 center dot 2H(2)O, with the conversion of [BO3] to [BO3(H2O)] by water absorption. (C) 2013 Elsevier Inc. All rights reserved