Effects of wheat and oat-based whole grain foods on serum lipoprotein size and distribution in overweight middle aged people : a randomised controlled trial

Peer reviewedPublisher PD

Studies of acute phase proteins and tumour necrosis factor receptors as inflammatory markers in the cat

The measurement of acute phase proteins is used by human clinicians to give valuable infonnation about a patient's inflammatory response, both when monitoring clinical disease and when assessing the effect of therapy. Levels of soluble receptors for the cytokine, tumour necrosis factor, also increase as a result of inflammatory stimuli and are useful prognostic markers over the asymptomatic phase of human immunodeficiency virus infection. The aim of the work presented in this thesis was to detennine whether these markers are of value when investigating feline disease. Reference ranges for two acute phase proteins, aI-acid glycoprotein (AGP) and haptoglobin were detennined by measuring their concentrations in serum samples from healthy cats. Analysis of samples from cats with feline infectious peritonitis (FIP) and from cats suffering from conditions with a similar clinical presentation revealed that measurement of AGP can be a useful adjunct to other laboratory tests when reaching a diagnosis. In contrast, measurement of haptoglobin was not found to be of value. Despite increases in the levels of pro-inflammatory cytokines in samples taken from cats during the asymptomatic phase of feline immunodeficiency virus (FIV) infection, no changes were detected in the levels of AGP and haptoglobin. It was concluded that these acute phase proteins are of no benefit as prognostic markers in FlY. The L929 bioassay was used to investigate anti-TNF-a activity in cell culture fluids from feline splenic cells. Cytotoxic activity was demonstrated in very few of the samples whilst anti-cytotoxic activity was detected in the majority of samples. This anti-cytotoxic activity was attributed to the presence of feline soluble TNF receptor type 1 (sTNFR-I) binding to and inhibiting the effects of TNF-a. This was not confinned because of the lack of specific neutralising antibody. Subsequent work was therefore directed towards the development of immune-based species-specific assays for feline soluble TNF receptors (sTNFRs). The polymerase chain reaction was used to amplify the sequences coding for feline sTNFRs. Most of the extracellular domain of feline TNFR-l and part of the intracellular domain of feline TNFR-2 were cloned and sequenced using this technique. The amplified regions demonstrated 85% and 77% homology at the nucleic acid level and 83% and 67% homology at the amino acid level to the corresponding regions of the human sequences for TNFR-l and 2 respectively. Feline sTNFR-l was expressed as a glutathione-S-transferase fusion protein. After purification, concentration and electrophoresis, the appropriate protein band was excised and used to inoculate a sheep. Antiserum taken from the sheep post-inoculation recognised the expressed protein by western blotting, but results were inconsistent and analysis of the antiserum was hampered by the very small amounts of expressed protein available. Two peptides were synthesised based on regions of antigenicity in feline sTNFR-l and were used to inoculate sheep. Antiserum to peptide A showed a strong reaction against peptide A in an ELISA and gave a positive result when used as the primary antibody to stain healthy feline liver tissue. In conclusion, both antiserum to expressed feline sTNFR-l and anti-peptide antibody based on a region of feline sTNFR-l have been raised in sheep and are available for the development of an assay for this protein. Further expression of feline TNFR-l will be required before these antisera can be analysed fully

Changes in vitamin biomarkers during a 2-year intervention trial involving increased fruit and vegetable consumption by free-living volunteers

Peer reviewedPublisher PD

Ultra-processed foods and human health: an umbrella review and updated meta-analyses of observational evidence.

Ultra-processed food (UPF) intake has increased sharply over the last few decades and has been consistently asserted to be implicated in the development of non-communicable diseases. We aimed to evaluate and update the existing observational evidence for associations between ultra-processed food (UPF) consumption and human health. We searched Medline and Embase from inception to March 2023 to identify and update meta-analyses of observational studies examining the associations between UPF consumption, as defined by the NOVA classification, and a wide spectrum of health outcomes. For each health outcome, we estimated the summary effect size, 95% confidence interval (CI), between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. These metrics were used to evaluate evidence credibility of the identified associations. This umbrella review identified 39 meta-analyses on the associations between UPF consumption and health outcomes. We updated all meta-analyses by including 122 individual articles on 49 unique health outcomes. The majority of the included studies divided UPF consumption into quartiles, with the lowest quartile being the reference group. We identified 25 health outcomes associated with UPF consumption. For observational studies, 2 health outcomes, including renal function decline (OR: 1.25; 95% CI: 1.18, 1.33) and wheezing in children and adolescents (OR: 1.42; 95% CI: 1.34, 1.49), showed convincing evidence (Class I); and five outcomes were reported with highly suggestive evidence (Class II), including diabetes mellitus, overweight, obesity, depression, and common mental disorders. High UPF consumption is associated with an increased risk of a variety of chronic diseases and mental health disorders. At present, not a single study reported an association between UPF intake and a beneficial health outcome. These findings suggest that dietary patterns with low consumption of UPFs may render broad public health benefits

The effect of short-term kaempferol exposure on reactive oxygen levels and integrity of human (HL-60) leukaemic cells

AbstractFlavonoids may be a principal contributor to the cancer preventative activity of fruit- and vegetable-rich diets and there is interest in their use as dietary supplements. However, there is potential conflict between the cytoprotective and cytotoxic activities of flavonoids, and their efficacy as anti-cancer agents is unresolved. Here, the integrity and survival of HL-60 promyelocytic leukaemia cells following short-term (90 min) exposure to the dietary abundant flavonoid kaempferol (1–100 μM) is reported. Supplementation initially decreased reactive oxygen levels but, paradoxically, a dose-dependent increase in single-strand DNA breakage occurred. However, there was no increase in oxidised DNA purines or membrane damage. Following a 24-h recovery period in non-kaempferol supplemented media, DNA single-strand breakage had declined and kaempferol exposed and control cultures possessed similar reactive oxygen levels. A reduction in 3H-thymidine incorporation occurred with ≥10 μM kaempferol. One hundred micromolar kaempefrol increased the proportion of cells in G2-M phase, the proportion of cells with a sub-G1 DNA content and enhanced ‘active’ caspase-3 expression but only induced a loss of mitochondrial membrane potential within a minority of cells. The relevance of induced DNA damage within a non-overtly oxidatively stressed environment to the disease preventative and therapeutic use of kaempferol is discussed

Healthy snacks in hospitals : testing the potential effects of changes in availability

Acknowledgements: The authors would like to thank the food retail staff and managers in each location and the food retailers who provided access to their sales data. Funding: Study 1 was funded by the Scottish Government Chief Scientist Office [CGA/16/17]. Study 2 was conducted while JA was a Royal Society of Edinburgh Sabbatical Grant Holder. Open access via Sage agreementPeer reviewedPostprin

Consumption of a Recommended Serving of Wheat Bran Cereals Significantly Increases Human Faecal Butyrate Levels in Healthy Volunteers and Reduces Markers of Inflammation

Funding We acknowledge financial support from Kellogg Europe and The Scottish Government’s Rural and Environment Science and Analytical Services (RESAS) division. Acknowledgments The authors are grateful to all the volunteers for their participance in this human study. The authors also are thankful for the assistance from Karen Taylor and Jean Bryce for the preparation of the study diets and Sylvia Stephen, David Bremner and Lorna Hermitage for their support in the Human Nutrition Unit.Peer reviewedPublisher PD

Oral human papillomavirus infection in England and associated risk factors: a case control study.

Objectives - This study was conducted to determine the prevalence of and associated risk factors for infection with oral high-risk human papillomavirus (HR-HPV) in adult participants within England, and to explore any association with oral mucosal buccal epithelial cell and whole blood folate concentration. Design - This was an observational study to determine oral HR-HPV prevalence in the study population. A case-control study was performed to explore the association between infection and folate status. Setting - This study was conducted in Sheffield, United Kingdom between April 2013 and August 2014. Participants - Seven hundred participants, aged 18-60 yr, were recruited from university students (n=179), university and hospital staff (n=163), dental hospital patients (n=13), Sexual Health Sheffield patients (n=122) and the general public (n=223). Interventions - Participants completed a lifestyle and sexual behaviour questionnaire, provided an oral rinse and gargle sample for the detection of oral HR-HPV and an oral mucosal buccal epithelial cell sample for the measurement of oral mucosal buccal epithelial cell folate. A blood sample was collected for measurement of whole blood folate concentration. Outcome measures - The prevalence of oral HR-HPV infection in the study population was the primary outcome measure. Secondary outcome measures included associations between risk factors, folate status and infection. Results - The prevalence of oral HR-HPV infection in this cohort was 2.2% (15/680) with 0.7% (5/680) positive for HPV16 or HPV18. Twenty samples were excluded due to insufficient material for HPV detection. Participants with oral HR-HPV infection were more likely to be a former smoker, and have a greater number of sexual and oral sexual partners. Folate status was not linked to likelihood of HPV infection. Conclusions - The prevalence of oral infection with HR-HPV in adult men and women in Sheffield in the north of England was low. Smoking and sexual behaviour were associated with HR-HPV positivity

Effect of increasing fruit and vegetable intake by dietary intervention on nutritional biomarkers and attitudes to dietary change : a randomised trial

This work was funded by The Scottish Government Rural and Environmental Science and Analytical Sciences Division (RESAS) and supported by the Rank Prize Funds.Peer reviewedPublisher PD

Differential effects of nutritional folic acid deficiency and moderate hyperhomocysteinemia on aortic plaque formation and genome-wide DNA methylation in vascular tissue from ApoE-/- mice

Low folate intake is associated with vascular disease. Causality has been attributed to hyperhomocysteinemia. However, human intervention trials have failed to show the benefit of homocysteine-lowering therapies. Alternatively, low folate may promote vascular disease by deregulating DNA methylation. We investigated whether folate could alter DNA methylation and atherosclerosis in ApoE null mice. Mice were fed one of six diets (n = 20 per group) for 16 weeks. Basal diets were either control (C; 4% lard) or high fat (HF; 21% lard and cholesterol, 0.15%) with different B-vitamin compositions: (1) folic acid and B-vitamin replete, (2) folic acid deficient (−F), (3) folic acid, B6 and B12 deficient (−F−B). −F diets decreased plasma (up to 85%; P < 0.05), whole blood (up to 70%; P < 0.05), and liver folate (up to 65%; P < 0.05) and hepatic SAM/SAH (up to 80%; P < 0.05). −F−B diets reduced plasma (up to 76%; P < 0.05), whole blood (up to 72%; P < 0.05), and liver B12 (up to 39%; P < 0.05) and hepatic SAM/SAH (up to 90%; P < 0.05). −F increased homocysteine 2-fold, while −F−B increased homocysteine 3.6- and 6.8-fold in the C and HF groups (P < 0.05). Plaque formation was increased 2-fold (P < 0.0001) in mice fed a HF diet. Feeding a HF–F diet increased lesion formation by 17% (P < 0.05). There was no change in 5-methyldeoxycytidine in liver or vascular tissue (aorta, periadventitial tissue and heart). These data suggest that atherogenesis is not associated with genome-wide epigenetic changes in this animal model