48 research outputs found

    Carnosine:can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?

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    The dipeptide carnosine (β-alanyl-L-histidine) has contrasting but beneficial effects on cellular activity. It delays cellular senescence and rejuvenates cultured senescent mammalian cells. However, it also inhibits the growth of cultured tumour cells. Based on studies in several organisms, we speculate that carnosine exerts these apparently opposing actions by affecting energy metabolism and/or protein homeostasis (proteostasis). Specific effects on energy metabolism include the dipeptide's influence on cellular ATP concentrations. Carnosine's ability to reduce the formation of altered proteins (typically adducts of methylglyoxal) and enhance proteolysis of aberrant polypeptides is indicative of its influence on proteostasis. Furthermore these dual actions might provide a rationale for the use of carnosine in the treatment or prevention of diverse age-related conditions where energy metabolism or proteostasis are compromised. These include cancer, Alzheimer's disease, Parkinson's disease and the complications of type-2 diabetes (nephropathy, cataracts, stroke and pain), which might all benefit from knowledge of carnosine's mode of action on human cells. © 2013 Hipkiss et al.; licensee Chemistry Central Ltd

    The ERK and JNK pathways in the regulation of metabolic reprogramming.

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    Most tumor cells reprogram their glucose metabolism as a result of mutations in oncogenes and tumor suppressors, leading to the constitutive activation of signaling pathways involved in cell growth. This metabolic reprogramming, known as aerobic glycolysis or the Warburg effect, allows tumor cells to sustain their fast proliferation and evade apoptosis. Interfering with oncogenic signaling pathways that regulate the Warburg effect in cancer cells has therefore become an attractive anticancer strategy. However, evidence for the occurrence of the Warburg effect in physiological processes has also been documented. As such, close consideration of which signaling pathways are beneficial targets and the effect of their inhibition on physiological processes are essential. The MAPK/ERK and MAPK/JNK pathways, crucial for normal cellular responses to extracellular stimuli, have recently emerged as key regulators of the Warburg effect during tumorigenesis and normal cellular functions. In this review, we summarize our current understanding of the roles of the ERK and JNK pathways in controlling the Warburg effect in cancer and discuss their implication in controlling this metabolic reprogramming in physiological processes and opportunities for targeting their downstream effectors for therapeutic purposes.Brunel Research Initiative & Enterprise Fund, Brunel University of London (to CB), Kay Kendall Leukemia Fund (KKL443) (to CB), 250 Great Minds Fellowship, University of Leeds (to SP), AMMF Cholangiocarcinoma Charity (to SP and PMC), and Bloodwise (17014) (to SP and CB)

    Nationwide survey in greece about knowledge, risk perceptions, and preventive behaviors for covid-19 during the general lockdown in april 2020

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    Background: The aim of this study was to investigate the knowledge, attitudes, and practices of the Greek general population toward coronavirus disease 2019 (COVID-19) during the lockdown period in April 020, to examine factors associated with misperceptions and to determine behavioral patterns that may require interventions. Methods: A cross-sectional study of the general Greek population (N = 1858) was conducted. A geographically stratified cluster sampling was implemented. A questionnaire was composed consisting of 35 questions. Data collection took place from 15 April to 2 May 2020. A random-digit dialing survey was conducted by 29 interviewers. Results: The majority of respondents (62.7%) answered ≥12/17 questions correctly. Participants aged 18–44 years, male gender, specific occupations (freelancer, unemployed, housewife, retiree) and those who sought information about COVID-19 from less than two sources received lower aggregated scores on knowledge questions. Regarding attitudes toward future vaccination, 18.9% declared that were against it, while 81.1% that they may consider or will be vaccinated. About 40% were not using a face mask and only 42% washed their hands appropriately. Conclusion: Adjusting information campaigns targeting especially people below 45 years of age can help to sensitize them and realise their role to control the spread. Further targeted surveys are needed to adjust/design prevention campaigns. © 2020 by the authors. Licensee MDPI, Basel, Switzerland
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