Anti-metastatic mechanism of Tian-Xian Liquid (TXL) and its bioactive fractions in human colorectal cancer cells and xenograft models

Poster Session A: abstract no. 29Colorectal carcinoma is the second most prevalent cancer with an up-rising trend in Hong Kong (Hong Kong Cancer Registry). Traditional Chinese medicine acts as a complementary alternative for tumour therapy with minimal side-effects and traumatic injuries. Tian-Xian Liquid (TXL), one of the well-known natural medicinal herbal formulations, has been commercially used as an anticancer dietary supplement for a decade without known adverse effects. This study aimed to investigate the anti-metastatic property of TXL and its bioactive fractions [butanol fraction (BU), ethyl-acetate fraction (EA) and aqueous fraction (WA)] at molecular level on human colorectal cancer in vitro (HT-29 cancer cells) and in vivo (nude mice xenografts). For the cell model, TXL and its bioactive fractions have similar anti-proliferative effects by MTT assay. At 4-hour-incubation, IC50 values were obtained at 1% (V/V) TXL, 1.25% (V/V) BU, 5% (V/V) EA and 0.3125% (V/V) WA. At IC50, TXL and its bioactive fractions significantly reduced the MMP2 and MMP7 expressions at mRNA level by real-time PCR. At protein level, TXL, BU and EA correspondingly down-regulated MMP2 (active form) and MMP7 protein from 24 to 48 hours; TXL and BU also down-regulated VEGF protein expression; however, no such effect was found in WA-treated cells. Further, only TXL, EA and WA effectively inhibited the cell migration at 48 hours incubation by woundhealing assay. For the xenografts models, MMP2 and MMP7 mRNA expressions were reduced by TXL-, BU- and EA-treated xenografts; however no effects on MMP2 protein expression in all drug-treated xenografts. The VEGF protein expression was significantly down-regulated in TXL- and WA-treated xenografts. Further, TXL, BU and WA effectively inhibited the tumor growth without altering the body weight of the xenografts. In summary, the Chinese medicinal formulation, TXL, demonstrated the most effective anti-metastatic ability on human colorectal cancer in vitro and in vivo.published_or_final_versio

European Paediatric Formulation Initiative (EuPFI)-Formulating Ideas for Better Medicines for Children.

© American Association of Pharmaceutical Scientists 2016, published by Springer US, available online at doi: https://doi.org/10.1208/s12249-016-0584-1The European Paediatric Formulation Initiative (EuPFI), founded in 2007, aims to promote and facilitate the preparation of better and safe medicines for children through linking research and information dissemination. It brings together the capabilities of the industry, academics, hospitals, and regulators within a common platform in order to scope the solid understanding of the major issues, which will underpin the progress towards the future of paediatric medicines we want.The EuPFI was formed in parallel to the adoption of regulations within the EU and USA and has served as a community that drives research and dissemination through publications and the organisation of annual conferences. The membership and reach of this group have grown since its inception in 2007 and continue to develop and evolve to meet the continuing needs and ambitions of research into and development of age appropriate medicines. Five diverse workstreams (age-appropriate medicines, Biopharmaceutics, Administration Devices, Excipients and Taste Assessment & Taste Masking (TATM)) direct specific workpackages on behalf of the EuPFI. Furthermore, EuPFI interacts with multiple diverse professional groups across the globe to ensure efficient working in the area of paediatric medicines. Strong commitment and active involvement of all EuPFI stakeholders have proved to be vital to effectively address knowledge gaps related to paediatric medicines, discuss potential areas for further research and identify issues that need more attention and analysis in the future.Peer reviewedFinal Accepted Versio

Sexual Propagation of Pteris Vittata L. Influenced by pH, Calcium, and Temperature

National High-tech Program (863 Program) of China 2007AA061001;Foundation of the Ministry of Agricultural Key Laboratory of Plant Nutrition and Nutrient CyclingWe aimed to optimize germination and growth conditions of the arsenic hyperaccumulating fern, Pteris vittata L. Pot experiments were carried out to investigate the effects of soil pH, soil calcium (Ca) concentration, and temperature on the sexual propagation of P. vittata. At 25 degrees C, germination was both accelerated and increased by high soil pH and Ca concentration. Spores of P. vittata did not germinate on medium with a pH of 4.6. Amending strongly acid soils with 27.5 or 40 mol/g Ca(OH)2 significantly improved the growth rate during both the germination phase and the gametophyte phase. Amending strongly acid soils with NaOH (55 mol/g) promoted germination, but did not affect subsequent growth. Among the different temperature, germination and growth rates were higher at 25 degrees C than at 20 degrees C or 30 degrees C. The distribution of P. vittata in China might be influenced by its requirement for high pH and high Ca concentration in the soil, and appropriate growth temperature to complete sexual propagation. These results provided important information for improving breeding conditions of P. vitatta and will be helpful for extending the range of areas in which P. vittata can be used for phytoremediation

Complete analysis of the B-cell response to a protein antigen, from in vivo germinal centre formation to 3-D modelling of affinity maturation

Somatic hypermutation of immunoglobulin variable region genes occurs within germinal centres (GCs) and is the process responsible for affinity maturation of antibodies during an immune response. Previous studies have focused almost exclusively on the immune response to haptens, which may be unrepresentative of epitopes on protein antigens. In this study, we have exploited a model system that uses transgenic B and CD4<sup>+</sup> T cells specific for hen egg lysozyme (HEL) and a chicken ovalbumin peptide, respectively, to investigate a tightly synchronized immune response to protein antigens of widely differing affinities, thus allowing us to track many facets of the development of an antibody response at the antigen-specific B cell level in an integrated system <i>in</i> <i>vivo</i>. Somatic hypermutation of immunoglobulin variable genes was analysed in clones of transgenic B cells proliferating in individual GCs in response to HEL or the cross-reactive low-affinity antigen, duck egg lysozyme (DEL). Molecular modelling of the antibody–antigen interface demonstrates that recurring mutations in the antigen-binding site, selected in GCs, enhance interactions of the antibody with DEL. The effects of these mutations on affinity maturation are demonstrated by a shift of transgenic serum antibodies towards higher affinity for DEL in DEL-cOVA immunized mice. The results show that B cells with high affinity antigen receptors can revise their specificity by somatic hypermutation and antigen selection in response to a low-affinity, cross-reactive antigen. These observations shed further light on the nature of the immune response to pathogens and autoimmunity and demonstrate the utility of this novel model for studies of the mechanisms of somatic hypermutation

Supernatants from lymphocytes stimulated with Bacillus Calmette-Guerin can modify the antigenicity of tumours and stimulate allogeneic T-cell responses

BACKGROUND: Reduced expression of class 1 human leucocyte antigens (HLA1) is often a mechanism by which tumours evade surveillance by the host immune system. This is often associated with an immune function that is unable to mount appropriate responses against disease, which can result in a state that favours carcinogenesis. METHODS: In the current study, we have explored the effects of Bacillus Calmette-Guerin (BCG) on the cytokine output of leucocytes, which is a key determinant in generating antitumour action, and have also assessed the effect of these cytokine cocktails on HLA1 expression in solid tumour cell lines. RESULTS: BCG potently activated a broad range of leucocytes, and also enhanced the production of cytokines that were Th(1)-predominant. Supernatants from BCG-treated leucocytes significantly increased the expression of HLA1 on the surface of cancer cell lines, which correlated with increased cytolytic T-cell activity. We also showed that the increased HLA1 expression was associated with activation of intracellular signalling pathways, which was triggered by the increases in the Th(1)-cytokines interferon-γ and tumour necrosis factor-α, as counteracting their effects negated the enhancement. CONCLUSION: These studies reaffirm the role of BCG as a putative immunotherapy through their cytokine-modifying effects on leucocytes and their capacity to enhance tumour visibility

Airborne measurements of western U.S. wildfire emissions: Comparison with prescribed burning and air quality implications

Wildfires emit significant amounts of pollutants that degrade air quality. Plumes from three wildfires in the western U.S. were measured from aircraft during the Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) and the Biomass Burning Observation Project (BBOP), both in summer 2013. This study reports an extensive set of emission factors (EFs) for over 80 gases and 5 components of submicron particulate matter (PM1) from these temperate wildfires. These include rarely, or never before, measured oxygenated volatile organic compounds and multifunctional organic nitrates. The observed EFs are compared with previous measurements of temperate wildfires, boreal forest fires, and temperate prescribed fires. The wildfires emitted high amounts of PM1 (with organic aerosol (OA) dominating the mass) with an average EF that is more than 2 times the EFs for prescribed fires. The measured EFs were used to estimate the annual wildfire emissions of carbon monoxide, nitrogen oxides, total nonmethane organic compounds, and PM1 from 11 western U.S. states. The estimated gas emissions are generally comparable with the 2011 National Emissions Inventory (NEI). However, our PM1 emission estimate (1530 ± 570 Gg yr-1) is over 3 times that of the NEI PM2.5 estimate and is also higher thanthe PM2.5 emitted from all other sources in these states in the NEI. This study indicates that the source of OA from biomass burning in the western states is significantly underestimated. In addition, our results indicate that prescribed burning may be an effective method to reduce fine particle emissions

Improving Hurricane Power Outage Prediction Models Through the Inclusion of Local Environmental Factors

Tropical cyclones can significantly damage the electrical power system, so an accurate spatiotemporal forecast of outages prior to landfall can help utilities to optimize the power restoration process. The purpose of this article is to enhance the predictive accuracy of the Spatially Generalized Hurricane Outage Prediction Model (SGHOPM) developed by Guikema et al. (2014). In this version of the SGHOPM, we introduce a new two‐step prediction procedure and increase the number of predictor variables. The first model step predicts whether or not outages will occur in each location and the second step predicts the number of outages. The SGHOPM environmental variables of Guikema et al. (2014) were limited to the wind characteristics (speed and duration of strong winds) of the tropical cyclones. This version of the model adds elevation, land cover, soil, precipitation, and vegetation characteristics in each location. Our results demonstrate that the use of a new two‐step outage prediction model and the inclusion of these additional environmental variables increase the overall accuracy of the SGHOPM by approximately 17%.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147200/1/risa12728_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147200/2/risa12728.pd

The Anti-Inflammatory properties of interleukin 18 binding protein in rheumatoid arthritis

Objectives: Interleukin-18 binding protein (IL-18BP) is functioning as a natural anti-inflammatory and immunosuppressive molecule by neutralizing the effects of IL-18 during inflammation. This study aimed to identify the role of IL-18BPa in the regulation of immune responses associated with the pathogenesis of RA.Materials and Methods: 65 RA patients, 22 OA patients, and 40 sex and age matched healthy donors were enrolled in this study. Synovial specimens were obtained through synovectomy or arthroscopic procedures. SFMC and PBMC were prepared by using Ficoll-Hypaque separationprocedure. Superarray analysis was used to measure the expression profile of immune-related genes in normal PBMC treated with recombinant human IL-18BPa.The mRNA levels of Th1 and Th2 cytokines were measured by Real-time PCR, and the protein levels of IFN-ã, IL-4 were detected by ELISA.Results: SuperArray analysis of immune related gene expression profile in normal PBMC treated with IL-18BPa indicated decreases in the gene expression of IFN-ã and its regulatory molecules STAT-1 and STAT-2. This study pointed out that IL-18BPa has additional anti-inflammatory property through downregulating the expression of IFN-ã and IL-12, at the same time, upregulating the expression of IL-4 and IL-10. Both IFN-ã and IL-12 could upregulated the mRNA and protein levels of IL-18BPa in both the normal and RA subjects. Conclusion: Our results demonstrated the importance of IL-18BPa as an immune regulatory molecule and as a promising therapy for treating RA.Key words: IL-18BPa, Inflammation, Rheumatoid Arthritis, Osteoarthriti

Ameliorating effect of Erxian decoction combined with Fructus Schisandrae chinensis (Wu Wei Zi) on menopausal sweating and serum hormone profiles in a rat model.

Background Modified Erxian decoction (MEXD), i.e., Erxian decoction (EXD) with Fructus Schisandrae chinensis (Wu Wei Zi) added, has been used to alleviate menopausal symptoms. This study aimed to investigate the effects of MEXD on menopausal sweating and serum hormone levels in a rat model of menopause after oral administration of MEXD. Methods Quality control of MEXD was conducted by employing a reversed-phase high performance liquid chromatography column. The three treatment groups received oral administration of MEXD in 0.5% sodium carboxylmethyl cellulose (CMC-Na) at three different doses (5.5, 11, and 22 g/kg body weight) once-daily for 6 consecutive weeks, with 10 animals per group. Huangqijing oral liquor (5 mL/kg) prepared from the roots of Huang qi (Astragalus membranaceus) with an antiperspirant effect was used as a positive control. The negative control group received the same volume of vehicle (0.5% CMC-Na). Ten 3-month-old Sprague–Dawley rats were used as a young group for comparison with the treatment groups (12–14 months old rats). Blood was collected from all animals after 3–6 weeks of treatment. At the end of the treatment, the uterine weight, ovarian weight, and body weight were recorded. Serum malondialdehyde contents and superoxide dismutase activities were determined by thiobarbituric acid colorimetric assays and chemoluminescence assays, respectively. Serum levels of estradiol, follicle-stimulating hormone, and luteinizing hormone were measured by radioimmunoassays. Rat foot pad assays were used to determine the antiperspirant activity of MEXD and histological examinations were conducted on plantar sweat glands. Results Treatment with MEXD (11 g/kg) significantly inhibited sweat excretion in the menopause model rats after treatment for 3 (P = 0.0026) and 6 (P < 0.0001) weeks. The decoction markedly decreased the number of secretory cells in plantar sweat glands. In addition, MEXD (11 g/kg) significantly increased the serum estradiol levels (P < 0.001) and superoxide dismutase activities (P = 0.0405). Furthermore, MEXD (11 g/kg) markedly decreased the serum levels of follicle-stimulating hormone (P = 0.001), luteinizing hormone (P = 0.0213), and malondialdehyde (P = 0.01). Conclusion Modified Erxian decoction significantly inhibited sweat excretion, regulated serum levels of pituitary gonadotropins and estradiol, and exhibited antioxidative effects in a rat model of menopause.published_or_final_versio