Development and relative validation of a food frequency questionnaire for French-Canadian adolescent and young adult survivors of acute lymphoblastic leukemia.

BACKGROUND: Survivors of childhood acute lymphoblastic leukemia (cALL) experience cardiometabolic and bone complications after treatments. This study aimed at developing and validating an interview-administrated food frequency questionnaire (FFQ) that will serve to estimate the impact of nutrition in the development of long-term sequalea of French-Canadian cALL survivors. METHODS: The FFQ was developed to assess habitual diet, Mediterranean diet score, nutrients promoting bone health and antioxidants. It was validated using a 3-day food record (3-DFR) in 80 cALL survivors (50% male) aged between 11.4 and 40.1 years (median of 18.0 years). Reproducibility was evaluated by comparing FFQs from visit 1 and 2 in 29 cALL survivors. RESULTS: When compared to 3-DFR, the mean values for macro- and micronutrient intake were overestimated by our FFQ with the exception of lipid-related nutrients. Correlations between nutrient intakes derived from the FFQs and the 3-DFRs showed moderate to very good correlations (0.46-0.74). Intraclass correlation coefficients assessing FFQ reproducibility ranged from 0.62 to 0.92, indicating moderate to good reliability. Furthermore, classification into quartiles showed more than 75% of macro- and micronutrients derived from FFQs 1 and 2 classified into the same or adjacent quartile. CONCLUSIONS: Overall, our results support the reproducibility and accuracy of the developed FFQ to appropriately classify individuals according to their dietary intake. This validated tool will be valuable for future studies analyzing the impact of nutrition on cardiometabolic and bone complications in French-speaking populations.

Lipid and lipoprotein abnormalities in acute lymphoblastic leukemia survivors.

Survivors of acute lymphoblastic leukemia (ALL), the most common cancer in children, are at increased risk of developing late cardiometabolic conditions. However, the mechanisms are not fully understood. This study aimed to characterize the plasma lipid profile, Apo distribution, and lipoprotein composition of 80 childhood ALL survivors compared with 22 healthy controls. Our results show that, despite their young age, 50% of the ALL survivors displayed dyslipidemia, characterized by increased plasma triglyceride (TG) and LDL-cholesterol, as well as decreased HDL-cholesterol. ALL survivors exhibited lower plasma Apo A-I and higher Apo B-100 and C-II levels, along with elevated Apo C-II/C-III and B-100/A-I ratios. VLDL fractions of dyslipidemic ALL survivors contained more TG, free cholesterol, and phospholipid moieties, but less protein. Differences in Apo content were found between ALL survivors and controls for all lipoprotein fractions except HDL3 HDL2, especially, showed reduced Apo A-I and raised Apo A-II, leading to a depressed Apo A-I/A-II ratio. Analysis of VLDL-Apo Cs disclosed a trend for higher Apo C-III1 content in dyslipidemic ALL survivors. In conclusion, this thorough investigation demonstrates a high prevalence of dyslipidemia in ALL survivors, while highlighting significant abnormalities in their plasma lipid profile and lipoprotein composition. Special attention must, therefore, be paid to these subjects given the atherosclerotic potency of lipid and lipoprotein disorders.

Insight from mitochondrial functions and proteomics to understand cardiometabolic disorders in survivors of acute lymphoblastic leukemia.

BACKGROUND: Childhood acute lymphoblastic leukemia (cALL) is the most prevalent form of cancer in children. Due to advances in treatment and therapy, young cALL subjects now achieve a 90% survival rate. However, this tremendous advance does not come without consequence since ~2/3 of cALL survivors are affected by long-term and late, severe complications. Although the metabolic syndrome is a very serious sequel of cALL, the mechanisms remain undefined. It is also surprising to note that the mitochondrion, a central organelle in metabolic functions and the main cellular energy generator, have not yet been explored. OBJECTIVES: To determine whether cALL survivors exhibit impairments in their mitochondrial functions and proteomic profiling in relationship with metabolic disorders in cALL survivors compared to healthy controls. METHODS AND RESULTS: Anthropometric measures, metabolic characteristics and lipid profiles were assessed, mitochondria isolated from peripheral blood mononuclear cells, and proteomic analyzed. Our data demonstrated that metabolically. Unhealthy survivors exhibited several metabolic syndrome components (e.g. overweight, insulin resistance, dyslipidemia, inflammation) whereas Healthy cALL survivors resemble the Controls. In line with these abnormalities, functional experiments in these subjects revealed a significant decrease in the protein expression of mitochondrial antioxidant superoxide dismutase, PGC1-α transcription factor (a key modulator of mitochondrion biogenesis), and an increase in pro-apoptotic cytochrome c. Proteomic analysis of mitochondria by mass spectrometry revealed changes in the regulation of proteins related to inflammation, apoptosis, energy production, redox and antioxidant activity, fatty acid ß-oxidation, protein transport and metabolism, and signalling pathways between groups. CONCLUSIONS: Through the use of proteomic analysis, our work demonstrated a number of significant alterations in protein expression in mitochondria of cALL survivors, especially the metabolically Unhealthy survivor group. Further investigation of these proteins may help delineate the mechanisms by which mitochondrial dysfunctions exert cardiometabolic derangements in cALL survivors.

Apple peel polyphenols reduce mitochondrial dysfunction in mice with DSS-induced ulcerative colitis.

Inflammatory bowel diseases (IBDs) are multifaceted and relapsing immune disorders, which necessitate long-term dependence on powerful drugs. As the use of natural product-based therapies has emerged as a promising intervention, the present study aimed to further characterize dried apple peel powder (DAPP) mechanisms of action and evaluate the preventive and curative effects of DAPP on mitochondrial functions in a murine model. Induction of intestinal inflammation in mice is performed by oral administration of the dextran sodium sulfate (DSS) at 2.5% for 10 days. Doses of DAPP (200 or 400 mg/kg/day) were administered by gavage for 10 days pre- and 1 day after colitis induction simultaneously with DSS treatment for a period of 10 days. The preventive (200 mg/kg/day) and therapeutic (400 mg/kg/day) doses of DAPP limited DSS-induced histological lesions, improved macroscopic parameters and attenuated clinical signs. DAPP at the same conditions reduced massive infiltration of inflammatory cells and concomitantly displayed a robust potential of counteracting inflammation and oxidative stress in DSS mice. Moreover, DAPP partially restored mitochondrial abnormalities related to size, density, redox homeostasis, fatty acid ß-oxidation, ATP synthesis, apoptosis and regulatory mitochondrial transcription factors. Our findings demonstrate the preventive and therapeutic impact of DAPP on experimental colitis while underlying the role of mitochondria. They also suggest that this natural DAPP product may represent an interesting candidate for further studies on the prevention/treatment of IBD.