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

Invasive Plants Are a Valuable Alternate Protein Source and Can Contribute to Meeting Climate Change Targets

This work was funded by the Scottish Government through RESAS as part of its strategic research programme. We would like to thank William Rees and Teresa Grohmann for their time in helping with preparation of the manuscript. Jacqueline Wallace (Rowett Institute) and Robin Walker (SRUC) for providing plant samples. Donna Henderson and Jodie Park for technical assistance in NSP measurements. Susan Anderson for technical assistance in amino acid profiling. Gary Duncan and Lorraine Scobbie for technical assistance in phenolic profiling. Lisa Guerrier, Salomé Leveque (IUT- Clermont-Ferrand, France), who assisted and observed procedures as part of their lab-skill training. We would also like to thank Graham Horgan (BIOSS, Rowett Institute) for advise on the statistical analysis. We would like to thank the NHS for its incredible commitment to keeping us safe during these harsh times.Peer reviewedPublisher PD

Non-immortalized human tenocyte cultures as a vehicle for understanding cellular aspects to tendinopathy

The biochemical mechanisms underlying tendinopathy are obscure. We briefly describe preliminary observations of human tenocyte behaviour in culture as a vehicle for determining the role of reactive oxygen in tendon patholog

Gorse (Ulex europeaus) wastes with 5,6-dimethyl benzimidazole supplementation can support growth of vitamin B12 producing commensal gut microbes

Open Access via the PLOS Agreement. Funding: This research was funded by the Scottish Government through Rural and Environmental Science and Analytical Services (RESAS) as part of its strategic funding programme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Toxicity of unsaturated fatty acids to the biohydrogenating ruminal bacterium, Butyrivibrio fibrisolvens

Peer reviewedPublisher PD

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

Folate, genomic stability and colon cancer: the use of single cell gel electrophoresis in assessing the impact of folate in vitro, in vivo and in human biomonitoring.

Intake of folate (vitamin B9) is strongly inversely linked with human cancer risk, particularly colon cancer. In general, people with the highest dietary intake of folate or with high blood folate levels are at a reduced risk (approx. 25%) of developing colon cancer. Folate acts in normal cellular metabolism to maintain genomic stability through the provision of nucleotides for DNA replication and DNA repair and by regulating DNA methylation and gene expression. Folate deficiency can accelerate carcinogenesis by inducing misincorporation of uracil into DNA, by increasing DNA strand breakage, by inhibiting DNA base excision repair capacity and by inducing DNA hypomethylation and consequently aberrant gene and protein expression. Conversely, increasing folate intake may improve genomic stability. This review describes key applications of single cell gel electrophoresis (the comet assay) in assessing genomic instability (misincorporated uracil, DNA single strand breakage and DNA repair capacity) in response to folate status (deficient or supplemented) in human cells in vitro, in rodent models and in human case-control and intervention studies. It highlights an adaptation of the SCGE comet assay for measuring genome-wide and gene-specific DNA methylation in human cells and colon tissue

Caspase-independence and characterization of bisnaphthalimidopropyl spermidine induced cytotoxicity in HL60 cells

The authors wish to thank Viv Buchan of the Rowett Institute Analytical Division for polyamine analysis and gratefully acknowledges the Robert Gordon University (PKTL, LC, CSB, SJD), The Scottish Government (Rural and Environment Science and Analytical Services [RESAS] Division; CSB, SJD, LM) and the Royal Society of Chemistry (PKTL) for financial support.Peer reviewedPostprin

The cost-effectiveness of procalcitonin for guiding antibiotic prescribing in individuals hospitalized with COVID-19: part of the PEACH study

Background Many hospitals introduced procalcitonin (PCT) testing to help diagnose bacterial coinfection in individuals with COVID-19, and guide antibiotic decision-making during the COVID-19 pandemic in the UK. Objectives Evaluating cost-effectiveness of using PCT to guide antibiotic decisions in individuals hospitalized with COVID-19, as part of a wider research programme. Methods Retrospective individual-level data on patients hospitalized with COVID-19 were collected from 11 NHS acute hospital Trusts and Health Boards from England and Wales, which varied in their use of baseline PCT testing during the first COVID-19 pandemic wave. A matched analysis (part of a wider analysis reported elsewhere) created groups of patients whose PCT was/was not tested at baseline. A model was created with combined decision tree/Markov phases, parameterized with quality-of-life/unit cost estimates from the literature, and used to estimate costs and quality-adjusted life years (QALYs). Cost-effectiveness was judged at a £20 000/QALY threshold. Uncertainty was characterized using bootstrapping. Results People who had baseline PCT testing had shorter general ward/ICU stays and spent less time on antibiotics, though with overlap between the groups’ 95% CIs. Those with baseline PCT testing accrued more QALYs (8.76 versus 8.62) and lower costs (£9830 versus £10 700). The point estimate was baseline PCT testing being dominant over no baseline testing, though with uncertainty: the probability of cost-effectiveness was 0.579 with a 1 year horizon and 0.872 with a lifetime horizon. Conclusions Using PCT to guide antibiotic therapy in individuals hospitalized with COVID-19 is more likely to be cost-effective than not, albeit with uncertainty