GUAR: Seed, Plant and Population Studies

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Role of Interleukin 17 in arthritis chronicity through survival of synoviocytes via regulation of synoviolin expression

Background: The use of TNF inhibitors has been a major progress in the treatment of chronic inflammation. However, not all patients respond. In addition, response will be often lost when treatment is stopped. These clinical aspects indicate that other cytokines might be involved and we focus here on the role of IL-17. In addition, the chronic nature of joint inflammation may contribute to reduced response and enhanced chronicity. Therefore we studied the capacity of IL-17 to regulate synoviolin, an E3 ubiquitin ligase implicated in synovial hyperplasia in human rheumatoid arthritis (RA) FLS and in chronic reactivated streptococcal cell wall (SCW)-induced arthritis.<p></p> Methodology/Principal Findings: Chronic reactivated SCW-induced arthritis was examined in IL-17R deficient and wild-type mice. Synoviolin expression was analysed by real-time RT-PCR, Western Blot or immunostaining in RA FLS and tissue, and p53 assessed by Western Blot. Apoptosis was detected by annexin V/propidium iodide staining, SS DNA apoptosis ELISA kit or TUNEL staining and proliferation by PCNA staining. IL-17 receptor A (IL-17RA), IL-17 receptor C (IL-17-RC) or synoviolin inhibition were achieved by small interfering RNA (siRNA) or neutralizing antibodies. IL-17 induced sustained synoviolin expression in RA FLS. Sodium nitroprusside (SNP)-induced RA FLS apoptosis was associated with reduced synoviolin expression and was rescued by IL-17 treatment with a corresponding increase in synoviolin expression. IL-17RC or IL-17RA RNA interference increased SNP-induced apoptosis, and decreased IL-17-induced synoviolin. IL-17 rescued RA FLS from apoptosis induced by synoviolin knockdown. IL-17 and TNF had additive effects on synoviolin expression and protection against apoptosis induced by synoviolin knowndown. In IL-17R deficient mice, a decrease in arthritis severity was characterized by increased synovial apoptosis, reduced proliferation and a marked reduction in synoviolin expression. A distinct absence of synoviolin expressing germinal centres in IL-17R deficient mice contrasted with synoviolin positive B cells and Th17 cells in synovial germinal centre-like structures.<p></p> Conclusion/Significance: IL-17 induction of synoviolin may contribute at least in part to RA chronicity by prolonging the survival of RA FLS and immune cells in germinal centre reactions. These results extend the role of IL-17 to synovial hyperplasia.<p></p&gt

Feasibility of offering nicotine replacement therapy as a relapse prevention treatment in routine smoking cessation services

Background: National Health Service stop smoking services (NHS SSS) in the UK offer cost- effective smoking cessation services. Despite high abstinence rates after acute cessation treatment, the majority of clients have relapsed by one year. Several interventions have been identified, from trial data, as effective in preventing relapse to smoking. This study investigated uptake, feasibility and acceptability of offering nicotine replacement therapy (NRT) as a relapse prevention intervention (RPI) in NHS SSS. Methods: Eligible smokers who had successfully completed acute cessation treatment using NRT at Nottingham City NHS SSS between April 2010 and January 2011 were offered the RPI and the rate of uptake was monitored. Consenting individuals completed a baseline questionnaire, providing demographic and smoking behaviour data. The RPI consisted of using NRT for a further 12 weeks after initial cessation-orientated treatment had ended. At a six-month review, self-reported smoking status was assessed via telephone. Anonymised demographic data on NHS SSS users who did not agree to participate in the study were retrieved from NHS SSS records and used to determine the presence of any socio-demographic differences between individuals who agreed to participate in the study and those who did not. Semi-structured telephone interviews were conducted with a selection of participants; these were audio-recorded, transcribed and analysed to identify participants’ views on the RPI. Results: Of 493 stop smoking service clients who were assessed, 260 were eligible for and offered the RPI and 115 (44%, CI 38%- 50%) accepted. Individuals who accepted NRT were significantly more likely to be older (p < 0.001) and to pay for their prescriptions (p < 0.001). Quitters who had never worked or were unemployed were significantly less likely to accept the offer of relapse prevention compared to those in routine and manual occupations (55% reduction in odds, p = 0.026). Interview findings revealed that clients who accepted extended NRT felt the longer duration of pharmacological and psychological support were both valuable in helping them to remain abstinent. Conclusion: In routine smoking cessation service care, it is feasible to offer clients extended courses of NRT as a RPI. The RPI was acceptable to them as almost half of the eligible clients offered this treatment accepted it. Keywords: Smoking relapse prevention, Nicotine replacement therapy, Feasibility study, Smoking cessation servic

Possible Novel Therapy for Malignant Gliomas with Secretable Trimeric TRAIL

Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and many novel therapeutic approaches, average survival for the patients with malignant gliomas is only about 1 year. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancers, but concerns over delivery and toxicity have limited progress. We have developed a secretable trimeric TRAIL (stTRAIL) and here evaluated the therapeutic potential of this stTRAIL-based gene therapy in brain tumors. An adenovirus (Ad-stTRAIL) delivering stTRAIL was injected into intra-cranial human glioma tumors established in nude mice and tumor growth monitored using the magnetic resonance imaging (MRI). Ad-stTRAIL gene therapy showed potent tumor suppressor activity with no toxic side effects at therapeutically effective doses. When compared with 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a conventional therapy for malignant gliomas, Ad-stTRAIL suppressed tumor growth more potently. The combination of Ad-stTRAIL and BCNU significantly increased survival compared to the control mice or mice receiving Ad-stTRAIL alone. Our data indicate that Ad-stTRAIL, either alone or combined with BCNU, has promise as a novel therapy for malignant gliomas

Cigarette smokers' intention to quit smoking in Dire Dawa town Ethiopia: an assessment using the Transtheoretical Model

<p>Abstract</p> <p>Background</p> <p>Cessation of smoking reduces morbidity and mortality related to tobacco smoking. It is essential to explore the intention of individuals to quit smoking to design effective interventions. The objective of this study was to assess cigarette smokers' intention to quit smoking in Dire Dawa town using the Transtheoretical model.</p> <p>Methods</p> <p>From February 15 to 19, 2009, we conducted a community based cross-sectional study among 384 current cigarette smokers in Dire Dawa town east Ethiopia. Data was collected by trained personnel using a pretested structured questionnaire. The data was analyzed using SPSS version 16.0.</p> <p>Results</p> <p>Two hundred and nineteen (57%) smokers in the study area had the intention to quit cigarette smoking within the next six months and all the process of change had an increasing trend across the stages. Based on the Fragestrom test of nicotine dependence of cigarette, 35 (9.1%), 69 (18%) and 48(12.5%) were very high, high and medium dependent on nicotine respectively. For the majority 247(64.3%) of the respondents, the mean score of cons of smoking outweighs the pros score (negative decisional balance). Only 66(17.2%) had high self efficacy not to smoke in places and situations that can aggravate smoking.</p> <p>Conclusions</p> <p>Majority of the smokers had the intention to quit smoking. All the process of change had an increasing trend across the stages. Those who had no intention to quit smoking had high level of dependence on nicotine and low self efficacy. The pros of smoking were decreasing while the cons were increasing across the stages. Stage based interventions should be done to move the smokers from their current stage to an advanced stages of quitting cigarette smoking.</p

Non-specific psychological distress, smoking status and smoking cessation: United States National Health Interview Survey 2005

<p>Abstract</p> <p>Background</p> <p>It is well established that smoking rates in people with common mental disorders such as anxiety or depressive disorders are much higher than in people without mental disorders. It is less clear whether people with these mental disorders want to quit smoking, attempt to quit smoking or successfully quit smoking at the same rate as people without such disorders.</p> <p>Methods</p> <p>We used data from the 2005 Cancer Control Supplement to the United States National Health Interview Survey to explore the relationship between psychological distress as measured using the K6 scale and smoking cessation, by comparing current smokers who had tried unsuccessfully to quit in the previous 12 months to people able to quit for at least 7 to 24 months prior to the survey. We also used data from the 2007 Australian National Survey of Mental Health and Wellbeing to examine the relationship between psychological distress (K6) scores and duration of mental illness.</p> <p>Results</p> <p>The majority of people with high K6 psychological distress scores also meet diagnostic criteria for mental disorders, and over 90% of these people had first onset of mental disorder more than 2 years prior to the survey. We found that people with high levels of non-specific psychological distress were more likely to be current smokers. They were as likely as people with low levels of psychological distress to report wanting to quit smoking, trying to quit smoking, and to have used smoking cessation aids. However, they were significantly less likely to have quit smoking.</p> <p>Conclusions</p> <p>The strong association between K6 psychological distress scores and mental disorders of long duration suggests that the K6 measure is a useful proxy for ongoing mental health problems. As people with anxiety and depressive disorders make up a large proportion of adult smokers in the US, attention to the role of these disorders in smoking behaviours may be a useful area of further investigation for tobacco control.</p

Use and perceived helpfulness of smoking cessation methods: results from a population survey of recent quitters

<p>Abstract</p> <p>Background</p> <p>Increasing rates of smoking cessation is one of the most effective measures available to improve population health. To advance the goal of increasing successful cessation at the population level, it is imperative that we understand more about smokers' use of cessation methods, as well as the helpfulness of those methods in real-world experiences of quitting. In this survey of recent quitters, we simultaneously examined rates of use and perceived helpfulness of various cessation methods.</p> <p>Methods</p> <p>Recent quitters (within 12 months; n = 1097) completed a telephone survey including questions relating to 13 cessation methods. Indices of use and perceived helpfulness for each method were plotted in a quadrant analysis. Socio-demographic differences were explored using bivariate and multivariate analyses.</p> <p>Results</p> <p>From the quadrant analysis, cold turkey, NRT and gradual reduction before quitting had high use and helpfulness; GP advice had high use and lower helpfulness. Prescribed medication and online programs had low use but high helpfulness. Remaining methods had low use and helpfulness. Younger quitters were more likely to use unassisted methods such as cold turkey; older or less educated quitters were more likely to use assisted methods such as prescribed medication or advice from a general practitioner.</p> <p>Conclusions</p> <p>The majority of recent quitters quit cold turkey or cut down before quitting, and reported that these methods were helpful. Efforts to influence population smoking prevalence should attempt to provide support and motivation for smokers choosing these methods, in addition to assessing the effectiveness and accessibility of other methods for smokers who need or choose them.</p

A Protective Role by Interleukin-17F in Colon Tumorigenesis

Interleukin-17F (IL-17F), produced by Th17 cells and other immune cells, is a member of IL-17 cytokine family with highest homology to IL-17A. IL-17F has been shown to have multiple functions in inflammatory responses. While IL-17A plays important roles in cancer development, the function of IL-17F in tumorigenesis has not yet been elucidated. In the current study, we found that IL-17F is expressed in normal human colonic epithelial cells, but this expression is greatly decreased in colon cancer tissues. To examine the roles of IL-17F in colon cancer, we have used IL-17F over-expressing colon cancer cell lines and IL-17F-deficient mice. Our data showed decreased tumor growth of IL-17F-transfected HCT116 cells comparing to mock transfectants when transplanted in nude mice. Conversely, there were increased colonic tumor numbers and tumor areas in Il-17f−/− mice than those from wild-type controls after colon cancer induction. These results indicate that IL-17F plays an inhibitory role in colon tumorigenesis in vivo. In IL-17F over-expressing tumors, there was no significant change in leukocyte infiltration; instead, we found decreased VEGF levels and CD31+ cells. While the VEGF levels were increased in the colon tissues of Il-17f−/− mice with colon cancer. Together, our findings demonstrate a protective role for IL-17F in colon cancer development, possibly via inhibiting tumor angiogenesis

SSR and AFLP based genetic diversity of soybean germplasm differing in photoperiod sensitivity

Forty-four soybean genotypes with different photoperiod response were selected after screening of 1000 soybean accessions under artificial condition and were profiled using 40 SSR and 5 AFLP primer pairs. The average polymorphism information content (PIC) for SSR and AFLP marker systems was 0.507 and 0.120, respectively. Clustering of genotypes was done using UPGMA method for SSR and AFLP and correlation was 0.337 and 0.504, respectively. Mantel's correlation coefficients between Jaccard's similarity coefficient and the cophenetic values were fairly high in both the marker systems (SSR = 0.924; AFLP = 0.958) indicating very good fit for the clustering pattern. UPGMA based cluster analysis classified soybean genotypes into four major groups with fairly moderate bootstrap support. These major clusters corresponded with the photoperiod response and place of origin. The results indicate that the photoperiod insensitive genotypes, 11/2/1939 (EC 325097) and MACS 330 would be better choice for broadening the genetic base of soybean for this trait

The protocol for the Be Our Ally Beat Smoking (BOABS) study, a randomised controlled trial of an intensive smoking cessation intervention in a remote Aboriginal Australian health care setting

Background: Australian Aboriginal peoples and Torres Strait Islanders (Indigenous Australians) smoke at much higher rates than non-Indigenous people and smoking is an important contributor to increased disease, hospital admissions and deaths in Indigenous Australian populations. Smoking cessation programs in Australia have not had the same impact on Indigenous smokers as on non-Indigenous smokers. This paper describes the protocol for a study that aims to test the efficacy of a locally-tailored, intensive, multidimensional smoking cessation program.\ud \ud Methods/Design: This study is a parallel, randomised, controlled trial. Participants are Aboriginal and Torres Strait Islander smokers aged 16 years and over, who are randomly allocated to a 'control' or 'intervention' group in a 2:1 ratio. Those assigned to the 'intervention' group receive smoking cessation counselling at face-to-face visits, weekly for the first four weeks, monthly to six months and two monthly to 12 months. They are also encouraged to attend a monthly smoking cessation support group. The 'control' group receive 'usual care' (i.e. they do not receive the smoking cessation program). Aboriginal researchers deliver the intervention, the goal of which is to help Aboriginal peoples and Torres Strait Islanders quit smoking. Data collection occurs at baseline (when they enrol) and at six and 12 months after enrolling. The primary outcome is self-reported smoking cessation with urinary cotinine confirmation at 12 months.\ud \ud Discussion: Stopping smoking has been described as the single most important individual change Aboriginal and Torres Strait Islander smokers could make to improve their health. Smoking cessation programs are a major priority in Aboriginal and Torres Strait Islander health and evidence for effective approaches is essential for policy development and resourcing. A range of strategies have been used to encourage Aboriginal peoples and Torres Strait Islanders to quit smoking however there have been few good quality studies that show what approaches work best. More evidence of strategies that could work more widely in Indigenous primary health care settings is needed if effective policy is to be developed and implemented. Our project will make an important contribution in this area.\ud \ud Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN12608000604303