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1.
Elife ; 122023 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-37219930

RESUMEN

Metabolic scaling, the inverse correlation of metabolic rates to body mass, has been appreciated for more than 80 years. Studies of metabolic scaling have largely been restricted to mathematical modeling of caloric intake and oxygen consumption, and mostly rely on computational modeling. The possibility that other metabolic processes scale with body size has not been comprehensively studied. To address this gap in knowledge, we employed a systems approach including transcriptomics, proteomics, and measurement of in vitro and in vivo metabolic fluxes. Gene expression in livers of five species spanning a 30,000-fold range in mass revealed differential expression according to body mass of genes related to cytosolic and mitochondrial metabolic processes, and to detoxication of oxidative damage. To determine whether flux through key metabolic pathways is ordered inversely to body size, we applied stable isotope tracer methodology to study multiple cellular compartments, tissues, and species. Comparing C57BL/6 J mice with Sprague-Dawley rats, we demonstrate that while ordering of metabolic fluxes is not observed in in vitro cell-autonomous settings, it is present in liver slices and in vivo. Together, these data reveal that metabolic scaling extends beyond oxygen consumption to other aspects of metabolism, and is regulated at the level of gene and protein expression, enzyme activity, and substrate supply.


Asunto(s)
Hígado , Análisis de Flujos Metabólicos , Ratones , Ratas , Animales , Ratones Endogámicos C57BL , Ratas Sprague-Dawley , Consumo de Oxígeno
2.
J Natl Cancer Inst Monogr ; 2023(61): 104-124, 2023 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-37139977

RESUMEN

Cancer cells cannot proliferate without sufficient energy to generate biomass for rapid cell division, as well as to fuel their functions at baseline. For this reason, many recent observational and interventional studies have focused on increasing energy expenditure and/or reducing energy intake during and after cancer treatment. The impact of variance in diet composition and in exercise on cancer outcomes has been detailed extensively elsewhere and is not the primary focus of this review. Instead, in this translational, narrative review we examine studies of how energy balance impacts anticancer immune activation and outcomes in triple-negative breast cancer (TNBC). We discuss preclinical, clinical observational, and the few clinical interventional studies on energy balance in TNBC. We advocate for the implementation of clinical studies to examine how optimizing energy balance-through changes in diet and/or exercise-may optimize the response to immunotherapy in people with TNBC. It is our conviction that by taking a holistic approach that includes energy balance as a key factor to be considered during and after treatment, cancer care may be optimized, and the detrimental effects of cancer treatment and recovery on overall health may be minimized.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Inmunoterapia , Metabolismo Energético
3.
Adv Hematol ; 2022: 4005208, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35103063

RESUMEN

BACKGROUND: The stress of academic life may predispose young adults to poor dietary habits, which could potentially precipitate nutritional deficiencies, such as iron deficiency. This study evaluated factors predictive of optimal iron stores as well as changes in haematological parameters over the course of an academic year in a cohort of tertiary students. MATERIALS AND METHODS: The repeated-measure cohort study recruited 117 undergraduate students from September 2018 to May 2019. Venous blood samples were drawn for full blood count estimation, qualitative glucose-6-phosphate dehydrogenase (G6PD) status, haemoglobin variants, and blood group determination during the first 2 weeks of semester 1. However, anthropometric parameters as well as full blood counts were determined for each participant during the first week and last week of semesters 1 and 2. Additionally, semistructured questionnaires were used to capture sociodemographic data. Also, serum ferritin was estimated for each participant using enzyme-linked immunosorbent assay. RESULTS: Overall, 23.1% and 15.5% of participants inherited G6PD defect (G6PDd) or haemoglobin variants, respectively. However, group O (68/117; 58.1%) was the predominant ABO blood group and an overwhelming 90.6% (106/117) inherited Rh D antigen. The prevalence of anaemia increased from 20% at the beginning of the first semester to 45.1% at the latter part of the second semester. G6PDd participants had significantly higher median serum ferritin than G6PD normal participants (p = 0.003). Also, a significantly higher proportion of females were iron depleted (25% vs. 2.3%) or iron deficient (14.3% vs. 9.3%) compared to males. Moreover, being male, G6PD deficient, or 21-25 years was associated with increased odds of participants having optimal serum ferritin levels. CONCLUSION: The progression of anaemia prevalence from mild to severe public health problem over the course of one academic year should urgently be addressed.

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