Search

Rationale: Natural variations in the abundance of the stable isotopes of nitrogen (δ15N) and carbon (δ13C) offer valuable insights into metabolic fluxes. In the wake of strong interest in cancer metabolism, recent research has revealed δ15N and δ13C variations in cancerous compared to non‐cancerous tissues and cell lines. However, our understanding of natural isotopic variations in cultured mammalian cells, particularly in relation to metabolism, remains limited. This study aims to start addressing this gap using metabolic modulations in cells cultured under controlled conditions. Methods: Prostate cancer cells (PC3) were cultured in different conditions and their δ15N and δ13C were measured using isotope ratio mass spectrometry. Isotopic variations during successive cell culture passages were assessed and two widely used cell culture media (RPMI and DMEM) were compared. Metabolism was modulated through glutamine deprivation and hypoxia. Results: Successive cell culture passages generally resulted in reproducible δ15N and δ13C values. The impact of culture medium composition on δ15N and δ13C of the cells highlights the importance of maintaining a consistent medium composition across conditions whenever possible. Glutamine deprivation and hypoxia induced a lower δ13C in bulk cell samples, with only the former affecting δ15N. Gaps between theory and experiments were bridged and the lessons learned throughout the process are provided. Conclusions: Exposing cultured cancer cells to hypoxia allowed us to further investigate the relation between metabolic modulations and natural isotopic variations, while mitigating the confounding impact of changing culture medium composition. This study highlights the potential of natural δ13C variations for studying substrate fluxes and nutrient allocation in reproducible culture conditions. Considering cell yield and culture medium composition is pivotal to the success of this approach. [ABSTRACT FROM AUTHOR]

While clinical evidence remains limited, an extensive amount of research suggests a beneficial role of n-3 polyunsaturated fatty acid supplementation in cancer treatment. One potential benefit is an improvement of protein homeostasis, but how protein metabolism depends on proinflammatory cytokines in this context remains unclear. Here, using the natural abundance of the stable isotopes of nitrogen as a marker of changes in protein metabolism during a randomized, double-blind, controlled clinical trial, we show that protein homeostasis is affected way faster than proinflammatory cytokines in metastatic breast cancer patients supplemented with n-3 polyunsaturated fatty acids. We provide some evidence that this response is unrelated to major changes in whole-body substrate oxidation. In addition, we demonstrate that more fatty acids were impacted by metabolic regulations than by differences in their intake levels during the supplementation. This study documents that the percentage of patients that complied with the supplementation decreased with time, making compliance assessment crucial for the kinetic analysis of the metabolic and inflammatory responses. Our results highlight the time-dependent nature of metabolic and inflammatory changes during long-chain n-3 fatty acid supplementation. [ABSTRACT FROM AUTHOR]

Objective: To capture the early effects of the SARS-CoV-2 pandemic on pediatric clinical research.Study Design: Pediatric clinical research networks from 20 countries and 50 of their affiliated research sites completed two surveys over one month from early May to early June 2020. Networks liaised with their affiliated sites and contributed to the interpretation of results through pan-European group discussions. Based on SARS-CoV-2 first detection dates, countries formed one early and one late detecting cluster. We tested the hypothesis that this clustering influenced clinical research.Results: Research sites were first impacted by the pandemic in mid-March 2020 (03/16 ±10 days, the same date as lockdown initiation, P = .99). From first impact up until early June, site initiation and feasibility analysis processes were affected for ˃50% of the sites. Staff were redirected to COVID-19 research for 44% of the sites and 75.5% of sites were involved in pediatric COVID-19 research (only 6.3% reported COVID cases in their other pediatric trials). Mitigations were used, but differently between the early and late detecting country clusters and between countries with and without a pediatric COVID-19 research taskforce. Positive effects include the development of teleworking capacities.Conclusions: Through this collaborative effort from pediatric research networks, we found that pediatric trials were affected and conducted with a range of unequally applied mitigations across countries during the pandemic. The global impact might be greater than captured. In a context where clinical research is increasingly multinational, this report reveals the importance of collaboration between National Networks. [ABSTRACT FROM AUTHOR]

Food choices affect the isotopic composition of the body with each food item leaving its distinct isotopic imprint. The common view is that the natural abundance of the stable isotopes of nitrogen (expressed as δ 15 N) is higher in animals than in plants that constitute our contemporary diets. Higher δ 15 N is thus increasingly viewed as a biomarker for meat and fish intake. Here we show that organic compared to conventional farming increases plant δ 15 N to an extent that can appreciably impact the performance of δ 15 N as a biomarker. The error that can arise when organic plants are consumed was modelled for the entire range of proportions of plant versus animal protein intake, and accounting for various intakes of organic and conventionally grown crops. This mass balance model allows the interpretation of differences in δ 15 N in light of organic food consumption. Our approach shows that the relationship between δ 15 N and meat and fish intake is highly contextual and susceptible to variation at the population, community or group level. We recommend that fertilization practices and organic plant consumption must not be overlooked when using δ 15 N as a biomarker for meat and fish intake or to assess compliance to nutritional interventions.

In cold exposed humans, increasing thermogenic rate is essential to prevent decreases in core temperature. This review describes the metabolic requirements of thermogenic pathways, mainly shivering thermogenesis, the largest contributor of heat. Research has shown that thermogenesis is sustained from a combination of carbohydrates, lipids, and proteins. The mixture of fuels is influenced by shivering intensity and pattern as well as by modifications in energy reserves and nutritional status. To date, there are no indications that differences in the types of fuel being used can alter shivering and overall heat production. We also bring forth the potential contribution of nonshivering thermogenesis in adult humans via the activation of brown adipose tissue (BAT) and explore some means to stimulate the activity of this highly thermogenic tissue. Clearly, the potential role of BAT, especially in young lean adults, can no longer be ignored. However, much work remains to clearly identify the quantitative nature of this tissue's contribution to total thermogenic rate and influence on shivering thermogenesis. Identifying ways to potentiate the effects of BAT via cold acclimation and/or the ingestion of compounds that stimulate the thermogenic process may have important implications in cold endurance and survival.