125 research outputs found
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
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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
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
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
Heterogeneity and Chemical Reactivity of the Remote Troposphere defined by Aircraft Measurements
No full textAuthors: Hao Guo, Clare M. Flynn, Michael J. Prather, Sarah A. Strode, Stephen D. Steenrod, Louisa Emmons, Forrest Lacey, Jean-Francois Lamarque, Arlene M. Fiore, Gus Correa, Lee T. Murray, Glenn M. Wolfe, Jason M. St. Clair, Michelle Kim, John Crounse, Glenn Diskin, Joshua DiGangi, Bruce C. Daube, Roisin Commane, Kathryn McKain, Jeff Peischl, Thomas B. Ryerson, Chelsea Thompson, Thomas F. Hanisco, Donald Blake, Nicola J. Blake, Eric C. Apel, Rebecca S. Hornbrook, James W. Elkins, Eric J. Hintsa, Fred L. Moore, and Steven WofsyThe NASA Atmospheric Tomography (ATom) mission built a photochemical climatology of air parcels based on in situ measurements with the NASA DC-8 aircraft along objectively planned profiling transects through the middle of the Pacific and Atlantic Oceans. ATom measured numerous gases and aerosols, particularly the gaseous species driving the chemical budgets of O₃ and CH₄: i.e., O₃, CH₄, CO, C₂H₆, higher alkanes, alkenes, aromatics, NOₓ, HNO₃, HNO₄, peroxyacetylnitrate, other organic nitrates, H₂O, HCHO, H₂O₂, and CH₃OOH. From the 10 s (2 km) merged observations, a modeling data stream (MDS) based on observations of the core species, consisting of 146,494 distinct air parcels has been constructed from the 4 ATom deployments, providing a continuous data stream for initializing global chemistry models and calculating the 24-hour chemical tendencies. Tendencies derived from 6 chemistry models using the ATom-1 MDS tend to agree and show a highly heterogeneous troposphere where globally 10% of the parcels control as much as 40% of the budget of O₃ and CH₄. Surprisingly, modeled probability distributions (100-km cells) match ATom statistics (2 km parcels), indicating that the majority of the observed heterogeneity can be resolved with current global chemistry models. On the other hand, the models' own chemical climatologies underestimate O₃ production below 4 km in both Pacific and Atlantic basins because they have lower NOₓ levels than observed.The authors are indebted to the entire ATom Science Team including the managers, pilots and crew who made this mission possible. Many other scientists not on the author list enabled the measurements and model results used here. Primary funding of the preparation of this manuscript at UC Irvine was through NASA grant NNX15AG57A.https://acp.copernicus.org/articles/21/13729/2021
Observations of OH and HO&lt;sub&gt;2&lt;/sub&gt; radicals over West Africa
No full textAbstract. The hydroxyl radical (OH) plays a key role in the oxidation of trace gases in the troposphere. However, observations of OH and the closely related hydroperoxy radical (HO2) have been sparse, especially in the tropics. Based on a low-pressure laser-induced fluorescence technique (FAGE – Fluorescence Assay by Gas Expansion), an instrument has been developed to measure OH and HO2 aboard the Facility for Airborne Atmospheric Measurement (FAAM) BAe-146 research aircraft. During the African Monsoon Multidisciplinary Analyses (AMMA) campaign, observations of OH and HO2 (HOx) were made in the boundary layer and free troposphere over West Africa on 13 flights during July and August 2006. Mixing ratios of both OH and HO2 were found to be highly variable, but followed a diurnal cycle: OH varied from 1.3 pptv to below the instrumental limit of detection, with a median mixing ratio of 0.17 pptv. HO2 varied from 42.7 pptv to below the limit of detection, with a median mixing ratio of 8.0 pptv. A median HO2/OH ratio of 95 was observed. Daytime OH observations were compared with the primary production rate of OH from ozone photolysis in the presence of water vapour. Daytime HO2 observations were generally reproduced by a simple steady-state HOx calculation, where HOx was assumed to be formed from the primary production of OH and lost through HO2 self-reaction. Deviations between the observations and this simple model were found to be grouped into a number of specific cases: (a) within cloud, (b) in the presence of high levels of isoprene in the boundary layer and (c) within a biomass burning plume. HO2 was sampled in and around cloud, with significant short-lived reductions of HO2 observed. Up to 9 pptv of HO2 was observed at night, with HO2 above 6 pptv observed at altitudes above 6 km. In the forested boundary layer, HO2 was underestimated by a steady state calculation at altitudes below 500 m but overestimated between 500 m and 2 km. In a biomass burning plume, observed HO2 concentrations were significantly below those calculated.
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Novel Techniques for the Characterisation of Exopolysaccharides Secreted by Lactic Acid Bacteria
No full textThis project investigated the structures and physical characteristics of exopolysaccharides
(EPSs) secreted by lactic acid bacteria.
The structure of a novel exopolysaccharide (EPS) produced by Lactobacillus acidophilus 5e2 has been characterised. Analysis of the anomeric region of the H-NMR showed that the repeating oligosaccharide contained seven monosaccharides. GC-MS showed the structure to consist of D-glucose, D-galactose and D-N-acetyl-glucosamine in a molar ratio of 3:3:1. The linkage analysis showed that there were two terminal, three di-linked and two tri-linked monosaccharides, and in collaboration with data generated from a series of D-NMR experiments, an overall structure was determined.
The weight-average molecular weight (Mw) of the EPS secreted by Lactobacillus acidophilus 5e2 when grown in skimmed milk was monitored during extended fermentation times. During the exponential growth phase, the increase in Mw closely followed the increase in yield of EPS. Under the fermentation conditions applied in this study, few if any new polysaccharide chains were formed during this growth phase despite a twenty five-fold increase in the cell count; almost the entire increase in yield can be accounted for by an increase in chain length.
These results suggested that synthesis of new EPS chains is switched off during the exponential and stationary phase of fermentation. The increase in
yield observed in this period is a consequence of the bacteria's ability to extend existing chains right up to the mid-stationary phase. These results raise questions about the factors that control EPS production and chain length.
Depolymerisation techniques have been shown to reduce the Mw of the polysaccharide in a controlled manner. The H-NMR results have shown that the physical methods, constant pressure and ultrasonic disruption break the EPS randomly through the repeating oligosaccharide unit; polydispersity data suggests that the breakages were occurring midchain.
A change to the peaks in the anomeric region of the H-NMR spectrum showed that depolymerisation, by acid hydrolysis, was chemically modifying the EPS structure. The approximate intrinsic viscosities of the EPS produced by Lactobacillus acidophilus 5e2 were determined to range between 0.6–2.0 dL g-1 for the Mw range of 1.59x105 – 4.78x105 g mol-1.
A capillary zone electrophoresis method was developed to determine the monosaccharide
composition of two EPS samples. The method successfully determined D-glucose and Dgalactose,
but a peak for D-N-acetyl-glucosamine was not seen. The method was sensitive compared to current techniques, but not as low as using a HP-AEC-PAD.
A novel method using LC-MS was developed for the linkage analysis of EPSs. Methylation, hydrolysis and reductive amination were used to derivatise the polysaccharide, and the fragmentation patterns were examined to determine the different linkage positions. Due to undesirable further fragmentation the method could not unequivocally differentiate between the different linkage positions, but the method was capable of resolving the monosaccharides residues with different linkage positions, at approximately the correct relative ratio
Mitochondrial DNA (MTDNA) mutations in human colonic crypts: A novel biomarker of colorectal cancer.
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Nutritional factors and gender influence age-related DNA methylation in the human rectal mucosa
No full textAberrant methylation of CpG islands (CGI) occurs in many genes expressed in colonic epithelial cells, and may contribute to the dysregulation of signalling pathways associated with carcinogenesis. This cross-sectional study assessed the relative importance of age, nutritional exposures and other environmental factors in the development of CGI methylation. Rectal biopsies were obtained from 185 individuals (84 male, 101 female) shown to be free of colorectal disease, and for whom measurements of age, body size, nutritional status and blood cell counts were available. We used quantitative DNA methylation analysis combined with multivariate modelling to investigate the relationships between nutritional, anthropometric and metabolic factors and the CGI methylation of 11 genes, together with LINE-1 as an index of global DNA methylation. Age was a consistent predictor of CGI methylation for 9/11 genes but significant positive associations with folate status and negative associations with vitamin D and selenium status were also identified for several genes. There was evidence for positive associations with blood monocyte levels and anthropometric factors for some genes. In general, CGI methylation was higher in males than in females and differential effects of age and other factors on methylation in males and females were identified. In conclusion, levels of age-related CGI methylation in the healthy human rectal mucosa are influenced by gender, the availability of folate, vitamin D and selenium, and perhaps by factors related to systemic inflammatio
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