169 research outputs found
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Modelling the role of microbial p-cresol in colorectal genotoxicity
No full textBACKGROUND
A greater understanding of mechanisms explaining the interactions between diet and the gut microbiota in colorectal cancer is desirable. Genotoxic microbial metabolites present in the colon may be implicated in carcinogenesis and potentially influenced by diet.
AIMS
We hypothesised that microbial p-cresol is a colonic genotoxin and set out to model potential exposures in the colon and the effects of these exposures on colonic cells.
METHODS
Batch culture fermentations with human faecal inoculate were used to determine the synthesis of p-cresol and other metabolites in response to various substrates. The fermentation supernatants were evaluated for genotoxicity and the independent effects of p-cresol on colonic cells were studied in vitro.
RESULTS
In batch culture fermentation, supplementary protein increased the synthesis of phenols, indoles and p-cresol, whereas supplementary fructoligosaccharide (FOS) increased the synthesis of short chain fatty acids. The p-cresol was the greatest predictor of genotoxicity against colonocytes in the fermentation supernatants. Spiking fermentation supernatants with exogenous p-cresol further increased DNA damage, and independently p-cresol induced DNA damage in a dose-dependent manner against HT29 and Caco-2 cells and influenced cell cycle kinetics.
CONCLUSIONS
In the colon p-cresol may reach physiologically significant concentrations which contribute to genotoxic exposures in the intestinal lumen, p-cresol production may be attenuated by substrate, and therefore diet, making it a potential modifiable biomarker of genotoxicity in the colon
Metabolic targets of watercress and PEITC in MCF-7 and MCF-10A cells explain differential sensitisation responses to ionising radiation
No full textPurpose: Watercress is a rich source of phytochemicals with anticancer potential, including phenethyl isothiocyanate (PEITC). We examined the potential for watercress extracts and PEITC to increase the DNA damage caused by ionising radiation (IR) in breast cancer cells and to be protective against radiation-induced collateral damage in healthy breast cells. The metabolic events that mediate such responses were explored using metabolic profiling. Methods: 1H nuclear magnetic resonance spectroscopy-based metabolic profiling was coupled with DNA damage-related assays (cell cycle, Comet assay, viability assays) to profile the comparative effects of watercress and PEITC in MCF-7 breast cancer cells and MCF-10A non-tumorigenic breast cells with and without exposure to IR. Results: Both the watercress extract and PEITC-modulated biosynthetic pathways of lipid and protein synthesis and resulted in changes in cellular bioenergetics. Disruptions to the redox balance occurred with both treatments in the two cell lines, characterised by shifts in the abundance of glutathione. PEITC enhanced the sensitivity of the breast cancer cells to IR increasing the effectiveness of the cancer-killing process. In contrast, watercress-protected non-tumorigenic breast cells from radiation-induced damage. These effects were driven by changes in the cellular content of the antioxidant glutathione following exposure to PEITC and other phytochemicals in watercress. Conclusion: These findings support the potential prophylactic impact of watercress during radiotherapy. Extracted compounds from watercress and PEITC differentially modulate cellular metabolism collectively enhancing the therapeutic outcomes of radiotherapy.</p
Telomere length analysis: A new tool for molecular photofitting
No full textThis thesis describes a new assay and analytical protocol to determine the telomere length of an individual, and its potential application in criminal investigations. The most commonly used existing assay is based on real-time qPCR. The Telomeric Multiplication Factor (TMF) assay described here instead uses end-point PCR and densitometry. Because most existing forensic DNA techniques already use end-point PCR, the TMF assay can be more easily integrated into the suite of tests available. Along with the TMF assay, a new procedure to use telomere length to determine age is presented. Previous attempts to do this rely on the calculation of a linear regression, and the interpolation of an age based on telomere length, which is not accurate enough for use in criminal investigations (with a covariance between known and predicted age of 0.2848, P=0.010564). Telomere Length Analysis (TLA) uses a database of known individuals. An unknown individual’s telomere length is compared to all telomere lengths on the database, and used to calculate the unknown individual’s age as a multiple of each age on the database. This increases exponentially the number of comparisons that can be made, and improves the accuracy of age predictions (with a covariance between known and predicted age of 0.4561, P=0.000021). The accuracy increases as the size of the database increases. TLA was developed using buccal epithelial cell samples. However, this thesis demonstrates that TLA also works on hair and blood samples, although to a lesser degree of accuracy. This makes TLA applicable in more forensic scenarios. TLA is intended to operate alongside the recent developments in molecular photofitting, to provide phenotypic and biographical information about an unknown offender to hasten his arrest and conviction, in the event that no matching DNA profile is recorded on investigating authorities’ databases. The new TMF assay and TLA analytical profile are more accurate and more applicable to a forensic scenario than other, previous, attempts to use telomere length to determine age
Evaluation of a specialist weight management service for patients with severe obesity in Liverpool
No full textObjective: To evaluate a specialist weight management treatment for patients with severe obesity and follow up at 3 months, monitoring changes in weight, BMI and clinical outcome variables. Changes in food intake, self esteem and health related quality of life (HRQL) were also compared to pre- and post- intervention. Design: Step by step is a new obesity servive which specifically targets obese patients at greater risk of further ill health. Only patients who are referred by their G.P. or health professional have been included in the evaluation. After an assessment appointment all patients choose one of two treatment options: group programme, individual dietetic care or both. The group programme offered weekly contact over twelve weeks and monthly follow up thereafter in a community setting. One-to-one care offered monthly appointments with the Dietician over a three month period. Subjects: A total of 50 patients with a BMI>30kg/m2, mean age 59 years, mean weight for males 113.5kg, BMI 39,3kg/m2 and females 92.7kg, BMI 36.5kg/m2. Main outcome measures: weight, BMI, total cholesterol, LDL, TG, HDL, FBG, HbA1C, blood pressure, food intake, self esteem and quality of life were measured pre and post intervention. Results: Patients who attended the group programme showed significant weight loss 1.99kg (P<0.05) and BMI 0.66kg/m2 at three months. Male patients lost more weight (3.9kg) during the three month period compared to females (1.4kg). Data was not available for individual dietetic care. Patients significantly reduced intake of negative marker foods (P<0.00). No changes were observed between self esteem pre and post programme however quality of life score increased considerably, 44.83 (S.D. 34.26) to 70.37 (S.D. 15.86) P<0.001. Conclusion: Patients attending a twelve week weight management programme run by community dietians and foodworkers achieve clinically worth while reducations in weight and BMI, improvements in food choice and choice and improved HRQL
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MYOD-1 in normal colonic mucosa : role as a putative biomarker?
No full textBackground
DNA methylation of promoter-associated CpG islands of certain genes may play a role in the development of colorectal cancer. The MYOD-1 gene which is a muscle differentiation gene has been showed to be significantly methylated in colorectal cancer which, is an age related event. However the role of this gene in the colonic mucosa is not understood and whether methylation occurs in subjects without colon cancer. In this study, we have determined the frequency of methylation of the MYOD-1 gene in normal colonic mucosa and investigated to see if this is associated with established colorectal cancer risk factors primarily ageing.
Results
We analysed colonic mucosal biopsies in 218 normal individuals and demonstrated that in most individuals promoter hypermethylation was not quantified for MYOD-1. However, promoter hypermethylation increased significantly with age (p < 0.001 using regression analysis) and this was gender independent. We also showed that gene promoter methylation increased positively with an increase in waist to hip (WHR) ratio – the latter is also a known risk factor for colon cancer development.
Conclusions
Our study suggests that promoter gene hypermethylation of the MYOD-1 gene increases significantly with age in normal individuals and thus may offer potential as a putative biomarker for colorectal cancer
The effects of the Wigan Borough Healthy Business Award on the dietary attitudes and behaviours of awardees
No full textAim: The study aims to investigate whether the Wigan Borough Healthy Business Award (HBA) influences the dietary attitudes and behaviours of awardees. Objectives are to: investigate the dietary attitudes of awardees prior to the HBA intervention; investigate the dietary behaviours of awardees prior to the HBA intervention; investigate the dietary attitudes of awardees post intervention; investigate the dietary behaviours of awardees post intervention; assess whether the HBA intervention has influenced attitudes and/or behaviours - positively, negatively or no change; gain a basic overview of the links between dietary attitudes and behaviours; form a set of recommendations based on the findings from the above objectives to inform best practice. Methodology: Case - control study, using purposive sampling of businesses undertaking the HBA, conducted using a pre and post intervention questionnaire and short supplementary post intervention semi structured interview, which seeks to assess whether the HBA affects the dietary attitudes and behaviours of awardees. Main findings: 6 staff from HBA businesses were compared with 7 staff from none HBA businesses. From the interview data, most participants demonstrated positive dietary attitudes and behaviours though not always directly linked with the HBA. Key themes included appreciation of learning and support, enablement to promote healthier options, benefits to the business and customers, other influences on dietary attitudes and behaviours, such as weight, family, health, individual responsibility, practical barriers such as time and society and upbringing. Where participants indicated the HBA had no direct impact on them as individuals, they still showed positive attitudes towards the receipt and recognition of the award, wanted to promote healthier options for customers and were positive about the award. Statistical analysis of the baseline and follow up questionnaire data showed the results were not significant, however due to the small sample size the relevance of this analysis for making generalisations, and identification of trends is limited. Overall conclusions: Participants involved in the HBA demonstrated positive dietary attitudes and behaviours manifesting from a range of influencing factors. The factors that linked with the HBA highlighted some key insights into the impact of the HBA and the complex interrelationship between dietary attitudes and behaviours. Whether the HBA positively influenced individuals dietary attitudes and behaviours or not, overall participants found the intervention to be worthwhile
Longterm effects of preoperative carbohydrate loading for colorectal surgery
No full textRecent changes in preoperative fasting guidelines have resulted in the development of preoperative carbohydrate drinks. Almost all research to date has examined the immediate/early postoperative metabolic and physiological effects, concluding beneficial clinical outcomes post surgery. The aim of this study was to test the hypothesis that preoperative carbohydrate loading results in longer term improvements in wellbeing, sustained return of postoperative physical function and better retention of muscle mass and nutritional status at a later (and potentially more clinically relevant) stage in the postoperative recovery period. This double-blinded placebo controlled randomised control trial took place at Salford Royal NHS Foundation Trust between 1st April 2008 and 31st January 2010. 10 males and 4 females, with a median age of 65.5 years, were included in the study and these were all listed for potentially curative colorectal cancer surgery. Each participant was assessed preoperatively, daily throughout their hospital admission and then at 30 days post surgery. Assessments included anthropometric measurements, analysis of dietary intake, physical activity and an evaluation of pain and well-being. The results showed that carbohydrate loading had no significant effects on anthropometric, dietary, physical or well-being parameters. However it was seen that pain scores in those patients who received carbohydrate loading were significantly lower (p=0.017) 30 days post surgery than those who received the placebo drinks. The trial was a pilot study and has shown that further research is needed to determine whether carbohydrate loading may have long-term clinical benefits
Data for: Intercomparison of commercial analyzers for atmospheric ethane and methane observations
No full textMethane (CH4) is a strong greenhouse gas that has become the focus of climate mitigation policies in recent years. Ethane / methane ratios can be used to identify and partition the different sources of methane, especially in areas with natural gas mixed with biogenic methane emissions, such as cities. We assessed the precision, accuracy, and selectivity of three commercially available laser-based analyzers that have been marketed as measuring instantaneous dry mole fractions of methane and ethane in ambient air. The Aerodyne SuperDUAL instrument performed best of the three instruments but it requires expertise to operate and space for the large footprint. The Aeris Mira Ultra LDS analyzer also performed well for the price point and small footprint but required characterization of the water vapor dependence of reported concentrations and careful setup for use. The Picarro G2210-i precisely measured methane but it did not detect the 10 ppbv increases in ambient ethane detected by the other two instruments when sampling a plume of incompletely combusted natural gas. For long-term tower deployments or those with large mobile laboratories, the Aerodyne SuperDUAL provides the best precision for methane and ethane. For smaller mobile platforms, the Aeris MIRA is a more compact analyzer, and with careful use, can quantify thermogenic methane sources to sufficient precision for short term deployments in urban or oil and gas areas. We weighed the advantages of each instrument, including size, power requirement, ease of use on mobile platforms, and expertise needed to operate the instrument, and we recommend the Aerodyne SuperDUAL or the Aeris MIRA Ultra LDS depending on the situation.The raw data are in RData format. An R script is included to open the file and process it to the final data in csv format.
Funding provided by: Climate Program OfficeCrossref Funder Registry ID: http://dx.doi.org/10.13039/100007298Award Number: NA20OAR4310306Funding provided by: New York State Energy Research and Development AuthorityCrossref Funder Registry ID: http://dx.doi.org/10.13039/100004862Award Number: 160536Funding provided by: New York State Energy Research and Development AuthorityCrossref Funder Registry ID: http://dx.doi.org/10.13039/100004862Award Number: 100413Funding provided by: New York State Energy Research and Development AuthorityCrossref Funder Registry ID: http://dx.doi.org/10.13039/100004862Award Number: 137484Funding provided by: New York State Energy Research and Development AuthorityCrossref Funder Registry ID: http://dx.doi.org/10.13039/100004862Award Number: 183865We collected data and assessed the precision, accuracy, and selectivity of three commercially available laser-based analyzers that have been marketed as measuring instantaneous dry-mole fractions of methane and ethane in ambient air. The instruments were calibrated against NOAA standards and the humidity correction was characterized and applied. We took the data reported by each analyzer and merged them into one file (EthaneIntercomp_Feb_merged_v20220802.RData). We also conducted stability tests by sampling compressed air and sampled ambient air outside. We analyzed the data in R using the script Commane_EthaneIntercomp_analysis_archive.R. The merged data file is output as merged_data.csv and contains raw, humidity corrected and final calibrated dry mole fractions of various trace gases. The readme guide is a text/R Markdown file
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