Germinated brown rice (GBR) reduces the incidence of aberrant crypt foci with the involvement of β-catenin and COX-2 in azoxymethane-induced colon cancer in rats

Chemoprevention has become an important area in cancer research due to the failure of current therapeutic modalities. Epidemiological and preclinical studies have demonstrated that nutrition plays a vital role in the etiology of cancer. This study was conducted to determine the chemopreventive effects of germinated brown rice (GBR) in rats induced with colon cancer. GBR is brown rice that has been claimed to be richer in nutrients compared to the common white rice. The male Sprague Dawley rats (6 weeks of age) were randomly divided into 5 groups: (G1) positive control (with colon cancer, unfed with GBR), (G2) fed with 2.5 g/kg of GBR (GBR (g)/weight of rat (kg)), (G3) fed with 5 g/kg of GBR, (G4) fed with 10 g/kg of GBR and (G5) negative control (without colon cancer, unfed with GBR). GBR was administered orally once daily via gavage after injection of 15 mg/kg of body weight of azoxymethane (AOM) once a week for two weeks, intraperitonially. After 8 weeks of treatment, animals were sacrificed and colons were removed. Colonic aberrant crypt foci (ACF) were evaluated histopathologically. Total number of ACF and AC, and multicrypt of ACF, and the expression of β-catenin and COX-2 reduced significantly (p < 0.05) in all the groups treated with GBR (G2, G3 and G4) compared to the control group (G1). Spearman rank correlation test showed significant positive linear relationship between total β-catenin and COX-2 score (Spearman's rho = 0.616, p = 0.0001). It is demonstrated that GBR inhibits the development of total number of ACF and AC, and multicrypt of ACF, reduces the expression of β-catenin and COX-2, and thus can be a promising dietary supplement in prevention of colon cancer

The antibacterial properties of Malaysian tualang honey against wound and enteric microorganisms in comparison to manuka honey

<p>Abstract</p> <p>Background</p> <p>Antibiotic resistance of bacteria is on the rise, thus the discovery of alternative therapeutic agents is urgently needed. Honey possesses therapeutic potential, including wound healing properties and antimicrobial activity. Although the antimicrobial activity of honey has been effectively established against an extensive spectrum of microorganisms, it differs depending on the type of honey. To date, no extensive studies of the antibacterial properties of tualang (<it>Koompassia excelsa</it>) honey on wound and enteric microorganisms have been conducted. The objectives of this study were to conduct such studies and to compare the antibacterial activity of tualang honey with that of manuka honey.</p> <p>Methods</p> <p>Using a broth dilution method, the antibacterial activity of tualang honey against 13 wound and enteric microorganisms was determined; manuka honey was used as the control. Different concentrations of honey [6.25-25% (w/v)] were tested against each type of microorganism. Briefly, two-fold dilutions of honey solutions were tested to determine the minimum inhibitory concentration (MIC) against each type of microorganism, followed by more assays within a narrower dilution range to obtain more precise MIC values. MICs were determined by both visual inspection and spectrophotometric assay at 620 nm. Minimum bactericidal concentration (MBC) also was determined by culturing on blood agar plates.</p> <p>Results</p> <p>By visual inspection, the MICs of tualang honey ranged from 8.75% to 25% compared to manuka honey (8.75-20%). Spectrophotometric readings of at least 95% inhibition yielded MIC values ranging between 10% and 25% for both types of honey. The lowest MBC for tualang honey was 20%, whereas that for manuka honey was 11.25% for the microorganisms tested. The lowest MIC value (8.75%) for both types of honey was against <it>Stenotrophomonas maltophilia</it>. Tualang honey had a lower MIC (11.25%) against <it>Acinetobacter baumannii </it>compared to manuka honey (12.5%).</p> <p>Conclusion</p> <p>Tualang honey exhibited variable activities against different microorganisms, but they were within the same range as those for manuka honey. This result suggests that tualang honey could potentially be used as an alternative therapeutic agent against certain microorganisms, particularly <it>A. baumannii </it>and <it>S. maltophilia</it>.</p

Airway epithelial barrier, mucins and inflammasome in distinct eosinophilic, neutrophilic and mixed inflammatory phenotypes of asthma

Introduction Asthma is a complex, chronic respiratory disease with marked clinical and pathophysiological heterogeneity. Specific pathways are thought to be involved in the pathomechanisms of different inflammatory phenotypes of asthma, yet direct in vivo comparison has not been performed. In the present study, we aimed to investigate the expression of tight junction molecules, mucins and inflammasome activation in different phenotypes of airway inflammation. Method We developed models of three different phenotypes of airway inflammation in mice, namely · eosinophilic, mixed, and neutrophilic asthma via different methods of house dust mite , sensit isation and challenge. Transcriptome analysis was performed using whole lung tissues, fol lowed by quantitative RT-PCR, western blot analysis and confocal microscopy. Results By unbiased whole genome transcriptomic approach, we found that airway tight junction (TJ) molecules, mucins and inflammasome-related genes are differentially expressed in distinct phenotypes of allergic airway inflammation. Detailed analysis of several molecules from these families revealed that (i) Zo-1 and Cldn18 were downregulated in all phenotypes, while Cldn4 upregulation was characteristic for neutrophilic airway inflammation; (ii) mucins Clcal (GobS) and MucSac were upregulated in eosinophilic and even more in neutrophilic asthma, and (iii) upregulation of inflammasome-related molecules such as Nlrp3, Nlrc4, casp-1 and IL-113 was characteristic for neutrophilic asthma. Finally, we showed that inflammasome/Th· 17 /neutrophilic axis cytokines, namely IL-113 and IL-17, might impair epithelial barrier function and increase mucins expressions in primary hBECs from normal and asthmati< donors. Conclusion Our findings suggest that differential expression of TJs, mucins and inflammasome-relate<: molecules in distinct asthma phenotypes might be mechanistically linked and could further reflect the differences observed in the clinic

Novel biologicals for the treatment of allergic diseases and asthma

PURPOSE OF REVIEW: The development of biological therapies has rapidly progressed during the last few years, and major advances were reported for the treatment of allergic diseases, such as atopic dermatitis, allergic rhinitis, urticaria, food allergy, and asthma. Here, we review biologicals targeting the type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, natural killer T cells, mast cells, basophils, and epithelial cells, such as IL-4, IL-5, IL-13, IL-31, tumor necrosis factor alpha (TNF-α), and thymic stromal lymphopoietin (TSLP). RECENT FINDINGS: The biologicals that have been currently approved for asthma are omalizumab targeting IgE and reslizumab and mepolizumab targeting interleukin (IL)-5. Many other monoclonal antibodies are currently in various phases of clinical development. The new biological therapies for allergic diseases will eventually be tailored to the endotypes of these diseases and the identification of novel biomarkers. Further development of novel biologicals for the treatment of allergic diseases and asthma will be possible upon improved understanding of mechanisms of allergic diseases. Accordingly, further refinement of endotypes of allergen-specific and non-specific type 2 immune response and related inflammatory mediators is needed for optimal treatment of allergic diseases

Fullscreen : a campaign to empower Smart Digital Parents

This report presents Fullscreen, an educational campaign to promote parent-child interaction in the mediation of their child’s digital device usage. The campaign is initiated by four final-year students from the Wee Kim Wee School of Communication and Information, Nanyang Technology University. Fullscreen targets Singaporean parents with children aged 7-12 years old, to address their lack of confidence and knowledge about adopting parental mediation strategies to mediate their child’s digital device usage. Based on primary and secondary research guided by Primary Socialization Theory, Parental Mediation Theory, and the Theory of Planned Behavior, we developed the big idea of Balance, Communicate, and Role Model. Our message advocated to parents a three-pronged approach of restrictive mediation, active mediation, and co- use. We disseminated our message to our target audience through online and on-ground engagement activities conducted from January through March 2018. Our online video series and social media platforms contained educational information to raise parents’ knowledge and skills. We developed Fullscreen Prompts, a card deck distributed at six roving pop-ups held at community events. Based on the outcome evaluation results, parents exposed to the campaign showed an overall increase in (a) awareness of the three-pronged approach, (b) confidence in mediating their child’s digital device usage, (c) attitudes towards the three-pronged approach, and (d) intentions and behaviors to practice the three-pronged approach, as compared to non- exposed parents. A discussion on the campaign and its sustainability are included thereafter. Original documents and relevant data are included in the appendices as references to the main paper.Bachelor of Communication Studie

Inhibitors targeting CDK4/6, PARP and PI3K in breast cancer: a review

Breast cancer is the global leading cause of cancer-related death in women and it represents a major health burden worldwide. One of the promising breast cancer therapeutic avenues is through small molecule inhibitors (SMIs) which have undergone rapid progress with successful clinical trials. Recently, three emerging and vital groups of proteins are targeted by SMIs for breast cancer treatment, namely cyclin-dependent kinase 4 and 6 (CDK4/6), poly (adenosine diphosphate-ribose) polymerase (PARP) and phosphoinositide 3-kinase (PI3K). Several of these inhibitors have been approved for the treatment of breast cancer patients or progressed into late-stage clinical trials. Thus, modeling from these successful clinical trials, as well as their limitations, is pivotal for future development and trials of other inhibitors or therapeutic regimens targeting breast cancer patients. In this review, we discuss eight recently approved or novel SMIs against CDK4/6 (palbociclib, ribociclib and abemaciclib), PARP (olaparib, veliparib and talazoparib), and PI3K (buparlisib and alpelisib). The mechanisms of action, series of clinical trials and limitations are described for each inhibitor

Tight junction, mucin, and inflammasome-related molecules are differentially expressed in eosinophilic, mixed, and neutrophilic experimental asthma in mice

BACKGROUND Asthma is a chronic respiratory disease with marked clinical and pathophysiological heterogeneity. Specific pathways are thought to be involved in the pathomechanisms of different inflammatory phenotypes of asthma; however, direct in vivo comparison has not been performed. METHODS We developed mouse models representing three different phenotypes of allergic airway inflammation-eosinophilic, mixed, and neutrophilic asthma via different methods of house dust mite sensitization and challenge. Transcriptomic analysis of the lungs, followed by the RT-PCR, western blot, and confocal microscopy, was performed. Primary human bronchial epithelial cells cultured in air-liquid interface were used to study the mechanisms revealed in the in vivo models. RESULTS By whole-genome transcriptome profiling of the lung, we found that airway tight junction (TJ), mucin, and inflammasome-related genes are differentially expressed in these distinct phenotypes. Further analysis of proteins from these families revealed that Zo-1 and Cldn18 were downregulated in all phenotypes, while increased Cldn4 expression was characteristic for neutrophilic airway inflammation. Mucins Clca1 (Gob5) and Muc5ac were upregulated in eosinophilic and even more in neutrophilic phenotype. Increased expression of inflammasome-related molecules such as Nlrp3, Nlrc4, Casp-1, and IL-1β was characteristic for neutrophilic asthma. In addition, we showed that inflammasome/Th17/neutrophilic axis cytokine-IL-1β-may transiently impair epithelial barrier function, while IL-1β and IL-17 increase mucin expressions in primary human bronchial epithelial cells. CONCLUSION Our findings suggest that differential expression of TJ, mucin, and inflammasome-related molecules in distinct inflammatory phenotypes of asthma may be linked to pathophysiology and might reflect the differences observed in the clinic

Reduced occludin and claudin-7 expression is associated with urban locations and exposure to second-hand smoke in allergic rhinitis patients

Abstract The breakdown of nasal epithelial barrier occurs in allergic rhinitis (AR) patients. Impairment of cell junction molecules including tight junctions (TJs) and desmosomes plays causative roles in the pathogenesis of AR. In this study, we investigated the transcript expression levels of TJs including occludin (OCLN), claudin-3 and -7 (CLDN3 and CLDN7), desmoglein 3 (DSG3) and thymic stromal lymphopoietin (TSLP) in AR patients (n = 30) and non-allergic controls (n = 30). Nasal epithelial cells of non-allergic controls and AR patients were collected to examine their mRNA expression levels, and to correlate with clinico-demographical and environmental parameters. We demonstrated that the expression of OCLN (p = 0.009), CLDN3 (p = 0.032) or CLDN7 (p = 0.004) transcript was significantly lower in AR patients compared with non-allergic controls. No significant difference was observed in the expression of DSG3 (p = 0.750) or TSLP (p = 0.991) transcript in AR patients compared with non-allergic controls. A significant association between urban locations and lower OCLN expression (p = 0.010), or exposure to second-hand smoke with lower CLDN7 expression (p = 0.042) was found in AR patients. Interestingly, none of the TJs expression was significantly associated with having pets, frequency of changing bedsheet and housekeeping. These results suggest that defective nasal epithelial barrier in AR patients is attributable to reduced expression of OCLN and CLDN7 associated with urban locations and exposure to second-hand smoke, supporting recent findings that air pollution represents one of the causes of AR

Ozone exposure induces respiratory barrier biphasic injury and inflammation controlled by IL-33

Objective We sought to examine the role of the IL-33/ST2 axis in lung inflammation on acute ozone exposure in mice. Methods ST2- and Il33–deficient, IL-33 citrine reporter, and C57BL/6 (wild-type) mice underwent a single ozone exposure (1 ppm for 1 hour) in all studies. Cell recruitment in lung tissue and the bronchoalveolar space, inflammatory parameters, epithelial barrier damage, and airway hyperresponsiveness (AHR) were determined. Results We report that a single ozone exposure causes rapid disruption of the epithelial barrier within 1 hour, followed by a second phase of respiratory barrier injury with increased neutrophil recruitment, reactive oxygen species production, AHR, and IL-33 expression in epithelial and myeloid cells in wild-type mice. In the absence of IL-33 or IL-33 receptor/ST2, epithelial cell injury with protein leak and myeloid cell recruitment and inflammation are further increased, whereas the tight junction proteins E-cadherin and zonula occludens 1 and reactive oxygen species expression in neutrophils and AHR are diminished. ST2 neutralization recapitulated the enhanced ozone-induced neutrophilic inflammation. However, myeloid cell depletion using GR-1 antibody reduced ozone-induced lung inflammation, epithelial cell injury, and protein leak, whereas administration of recombinant mouse IL-33 reduced neutrophil recruitment in Il33–deficient mice. Conclusion Data demonstrate that ozone causes an immediate barrier injury that precedes myeloid cell–mediated inflammatory injury under the control of the IL-33/ST2 axis. Thus IL-33/ST2 signaling is critical for maintenance of intact epithelial barrier and inflammation