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Is Lactate an Oncometabolite? Evidence Supporting a Role for Lactate in the Regulation of Transcriptional Activity of Cancer-Related Genes in MCF7 Breast Cancer Cells.
Lactate is a ubiquitous molecule in cancer. In this exploratory study, our aim was to test the hypothesis that lactate could function as an oncometabolite by evaluating whether lactate exposure modifies the expression of oncogenes, or genes encoding transcription factors, cell division, and cell proliferation in MCF7 cells, a human breast cancer cell line. Gene transcription was compared between MCF7 cells incubated in (a) glucose/glutamine-free media (control), (b) glucose-containing media to stimulate endogenous lactate production (replicating some of the original Warburg studies), and (c) glucose-containing media supplemented with L-lactate (10 and 20 mM). We found that both endogenous, glucose-derived lactate and exogenous, lactate supplementation significantly affected the transcription of key oncogenes (MYC, RAS, and PI3KCA), transcription factors (HIF1A and E2F1), tumor suppressors (BRCA1, BRCA2) as well as cell cycle and proliferation genes involved in breast cancer (AKT1, ATM, CCND1, CDK4, CDKN1A, CDK2B) (0.001 < p < 0.05 for all genes). Our findings support the hypothesis that lactate acts as an oncometabolite in MCF7 cells. Further research is necessary on other cell lines and biopsy cultures to show generality of the findings and reveal the mechanisms by which dysregulated lactate metabolism could act as an oncometabolite in carcinogenesis
Indirect Assessment of Skeletal Muscle Glycogen Content in Professional Soccer Players before and after a Match through a Non-Invasive Ultrasound Technology
Skeletal muscle glycogen (SMG) stores in highly glycolytic activities regulate muscle contraction by controlling calcium release and uptake from sarcoplasmic reticulum, which could affect muscle contraction. Historically, the assessment of SMG was performed through invasive and non-practical muscle biopsies. In this study we have utilized a novel methodology to assess SMG through a non-invasive high-frequency ultrasound. Nine MLS professional soccer players (180.4 ± 5.9 cm; 72.4 ± 9.3 kg; 10.4% ± 0.7% body fat) participated. All followed the nutritional protocol 24 h before the official match as well as performing the same practice program the entire week leading to the match. The SMG decreased from 80 ± 8.6 to 63.9 ± 10.2; p = 0.005 on MuscleSound® score (0–100) representing a 20% ± 10.4% decrease in muscle glycogen after match. Inter-individual differences in both starting glycogen content (65–90) and in percentage decrease in glycogen after the match (between 6.2% and 44.5%). Some players may not start the match with adequate SMG while others’ SMG decreased significantly throughout the game. Adequate pre-match SMG should be achieved during half-time and game-play in order to mitigate the decrease in glycogen. Further and more ample studies are needed before the application of this technology
Reply to Comment On: “Indirect Assessment of Skeletal Muscle Glycogen Content in Professional Soccer Players before and after a Match through a Non-Invasive Ultrasound Technology Nutrients 2020, 12(4), 971”
We would like to thank Professor Niels Ørtenblad et al [...
Catálogo de monumentos megalíticos en Navarra. Homenaje a Francisco Ondarra (1925-2005)
Este trabajo pretende llenar el vacío que existe actualmente en relación con el megalitismo
de esta región. Se da a conocer un catálogo actualizado, de más de 1500 megalitos, resultado de una prospección
y revisión de datos intensa llevada a cabo por los firmantes del mismo durante años. El listado que aquí se
incluye es paso previo a la publicación individualizada de las fichas de todos estos monumentos, como contribución
a la Carta Arqueológica de Navarra
Insights into the Late Mesolithic toolkit: use-wear analysis of the notched blades. Case-studies from the Iberian Peninsula
During the last decades we have gained a considerable amount of data about the Mesolithic lithic toolkit in the Western Mediterranean. A large set of instruments probably existed for a variety of pur-poses: foraging practices (both hunting and fishing), food processing, crafting activities, etc. Dispos-able tools, scarcely elaborated, coexisted with formal and more complex instruments, often com-posed of multiple parts and realized on a variety of raw-materials (e.g. stone, shell or bone inserts; bone or wood hafts, etc.). In this paper we will consider one particular type of tool that appears in the Western Mediterranean starting from the Seventh-Sixth millennia BC: the notched and denticulated blades. We will consider and interpret from a functional viewpoint materials from five different Late Mesolithic contexts: the Cocina Cave and Vallmayor IX in the NE of the Peninsula, Artusia rock-shel-ters in Navarre and Atxoste and Mendandia rock-shelters in the Basque country
The Key Role of Mitochondrial Function in Health and Disease
The role of mitochondrial function in health and disease has become increasingly recognized, particularly in the last two decades. Mitochondrial dysfunction as well as disruptions of cellular bioenergetics have been shown to be ubiquitous in some of the most prevalent diseases in our society, such as type 2 diabetes, cardiovascular disease, metabolic syndrome, cancer, and Alzheimer’s disease. However, the etiology and pathogenesis of mitochondrial dysfunction in multiple diseases have yet to be elucidated, making it one of the most significant medical challenges in our history. However, the rapid advances in our knowledge of cellular metabolism coupled with the novel understanding at the molecular and genetic levels show tremendous promise to one day elucidate the mysteries of this ancient organelle in order to treat it therapeutically when needed. Mitochondrial DNA mutations, infections, aging, and a lack of physical activity have been identified to be major players in mitochondrial dysfunction in multiple diseases. This review examines the complexities of mitochondrial function, whose ancient incorporation into eukaryotic cells for energy purposes was key for the survival and creation of new species. Among these complexities, the tightly intertwined bioenergetics derived from the combustion of alimentary substrates and oxygen are necessary for cellular homeostasis, including the production of reactive oxygen species. This review discusses different etiological mechanisms by which mitochondria could become dysregulated, determining the fate of multiple tissues and organs and being a protagonist in the pathogenesis of many non–communicable diseases. Finally, physical activity is a canonical evolutionary characteristic of humans that remains embedded in our genes. The normalization of a lack of physical activity in our modern society has led to the perception that exercise is an “intervention”. However, physical activity remains the modus vivendi engrained in our genes and being sedentary has been the real intervention and collateral effect of modern societies. It is well known that a lack of physical activity leads to mitochondrial dysfunction and, hence, it probably becomes a major etiological factor of many non–communicable diseases affecting modern societies. Since physical activity remains the only stimulus we know that can improve and maintain mitochondrial function, a significant emphasis on exercise promotion should be imperative in order to prevent multiple diseases. Finally, in populations with chronic diseases where mitochondrial dysfunction is involved, an individualized exercise prescription should be crucial for the “metabolic rehabilitation” of many patients. From lessons learned from elite athletes (the perfect human machines), it is possible to translate and apply multiple concepts to the betterment of populations with chronic diseases