18 results on '"Changhan Lee"'
Search Results
2. Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases
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Byung Soo Kong, Changhan Lee, and Young Min Cho
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aging ,diabetes mellitus, type 2 ,intracellular signaling peptides and proteins ,mitochondria ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Mitochondria are complex metabolic organelles with manifold pathophysiological implications in diabetes. Currently published mitochondrial-encoded peptides, which are expressed from the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), 16S rRNA (humanin and short humanin like peptide 1-6 [SHLP1-6]), or small human mitochondrial open reading frame over serine tRNA (SHMOOSE) are associated with regulation of cellular metabolism and insulin action in age-related diseases, such as type 2 diabetes mellitus. This review focuses mainly on recent advances in MOTS-c research with regards to diabetes, including both type 1 and type 2. The emerging understanding of MOTS-c in diabetes may provide insight into the development of new therapies for diabetes and other age or senescence-related diseases.
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- 2023
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3. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
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Joseph C. Reynolds, Rochelle W. Lai, Jonathan S. T. Woodhead, James H. Joly, Cameron J. Mitchell, David Cameron-Smith, Ryan Lu, Pinchas Cohen, Nicholas A. Graham, Bérénice A. Benayoun, Troy L. Merry, and Changhan Lee
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Science - Abstract
Exercise has beneficial effects on metabolism and overall physiologic fitness in aged organisms. Here the authors show that MOTS-c is a mitochondrial-encoded exercise-induced peptide that regulates skeletal muscle metabolism and improves healthspan of older mice.
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- 2021
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4. Optimization of Transposon Mutagenesis Methods in Pseudomonas antarctica
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Sangha Kim and Changhan Lee
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Pseudomonas ,Pseudomonas antarctica ,transposon ,transposon insertion mutant library ,Biology (General) ,QH301-705.5 - Abstract
Pseudomonas is a widespread genus in various host and environmental niches. Pseudomonas exists even in extremely cold environments such as Antarctica. Pseudomonas antarctica is a psychrophilic bacterium isolated from Antarctica. P. antarctica is also known to produce antimicrobial substances. Although P. antarctica can provide insight into how bacteria have adapted to low temperatures and has significant potential for developing novel antimicrobial substances, progress in genetic and molecular studies has not been achieved. Transposon mutagenesis is a useful tool to screen genes of interest in bacteria. Therefore, we attempted for the first time in P. antarctica to generate transposon insertion mutants using the transfer of a conjugational plasmid encoding a transposon. To increase the yield of transposon insertion mutants, we optimized the methods, in terms of temperature for conjugation, the ratio of donor and recipient during conjugation, and the concentration of antibiotics. Here, we describe the optimized methods to successfully generate transposon insertion mutants in P. antarctica.
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- 2023
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5. Protocol for the assessment of human T cell activation by real-time metabolic flux analysis
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Byung Soo Kong, Changhan Lee, and Young Min Cho
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Classification Description: Cell Biology ,Cell isolation ,Cell-based Assays ,Immunology ,Metabolism ,Science (General) ,Q1-390 - Abstract
Summary: The elevation of glycolysis in autoreactive T cells is a key target for the prevention and treatment of T cell-related autoimmune diseases, such as type 1 diabetes (T1D). Here, we describe a simple and efficient protocol for isolating human peripheral blood mononuclear cells (PBMCs) and T cells, and the subsequent assessment of T cell glycolysis using Seahorse analyzer. This protocol is useful to analyze different subsets of T cells and applicable to different autoimmune disease models (i.e., T1D, multiple sclerosis).For complete details on the use and execution of this profile, please refer to Kong et al. (2021).
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- 2022
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6. Remodeling of the H3 nucleosomal landscape during mouse aging
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Yilin Chen, Juan I. Bravo, Jyung Mean Son, Changhan Lee, and Bérénice A. Benayoun
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Aging ,Nucleosome ,Epigenome ,H3 ,Medicine - Abstract
In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and deregulation of gene expression correlates with aging. A key layer in the study of gene regulation mechanisms lies at the level of chromatin: cellular chromatin states (i.e. the ‘epigenome’) can tune transcriptional profiles, and, in line with the prevalence of transcriptional alterations with aging, accumulating evidence suggests that the chromatin landscape is altered with aging across cell types and species. However, although alterations in the chromatin make-up of cells are considered to be a hallmark of aging, little is known of the genomic loci that are specifically affected by age-related chromatin state remodeling and of their biological significance. Here, we report the analysis of genome-wide profiles of core histone H3 occupancy in aging male mouse tissues (i.e. heart, liver, cerebellum and olfactory bulb) and primary cultures of neural stem cells. We find that, although no drastic changes in H3 levels are observed, local changes in H3 occupancy occur with aging across tissues and cells with both regions of increased or decreased occupancy. These changes are compatible with a general increase in chromatin accessibility at pro-inflammatory genes and may thus mechanistically underlie known shift in gene expression programs during aging.
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- 2020
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7. Protein folding while chaperone bound is dependent on weak interactions
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Kevin Wu, Frederick Stull, Changhan Lee, and James C. A. Bardwell
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Science - Abstract
Spy is an ATP independent chaperone that allows folding of its client protein Im7 while continuously bound to Spy. Here the authors employ kinetics measurements to study the folding of another Spy client protein SH3 and find that Spy’s ability to allow a client to fold while bound is inversely related to how strongly it interacts with that client.
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- 2019
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8. Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes
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Byung Soo Kong, Se Hee Min, Changhan Lee, and Young Min Cho
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Biology (General) ,QH301-705.5 - Published
- 2021
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9. Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes
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Byung Soo Kong, Se Hee Min, Changhan Lee, and Young Min Cho
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mitochondria ,MOTS-c ,CD4+ T cell ,mTORC1 ,type 1 diabetes ,Treg ,Biology (General) ,QH301-705.5 - Abstract
Summary: Mitochondria are principal metabolic organelles that are increasingly unveiled as immune regulators. However, it is currently not known whether mitochondrial-encoded peptides modulate T cells to induce changes in phenotype and function. In this study, we found that MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) prevented autoimmune β cell destruction by targeting T cells in non-obese diabetic (NOD) mice. MOTS-c ameliorated the development of hyperglycemia and reduced islet-infiltrating immune cells. Furthermore, adoptive transfer of T cells from MOTS-c-treated NOD mice significantly decreased the incidence of diabetes in NOD-severe combined immunodeficiency (SCID) mice. Metabolic and genomic analyses revealed that MOTS-c modulated T cell phenotype and function by regulating T cell receptor (TCR)/mTOR complex 1 (mTORC1) signaling. Type 1 diabetes (T1D) patients had a lower serum MOTS-c level than did healthy controls. Furthermore, MOTS-c reduced T cell activation by alleviating T cells from the glycolytic stress in T1D patients, suggesting therapeutic potential. Our findings indicate that MOTS-c regulates the T cell phenotype and suppresses autoimmune diabetes.
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- 2021
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10. Stress-Responsive Periplasmic Chaperones in Bacteria
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Hyunhee Kim, Kevin Wu, and Changhan Lee
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periplasmic chaperone ,Spy ,DegP ,HdeA ,HdeB ,UgpB ,Biology (General) ,QH301-705.5 - Abstract
Periplasmic proteins are involved in a wide range of bacterial functions, including motility, biofilm formation, sensing environmental cues, and small-molecule transport. In addition, a wide range of outer membrane proteins and proteins that are secreted into the media must travel through the periplasm to reach their final destinations. Since the porous outer membrane allows for the free diffusion of small molecules, periplasmic proteins and those that travel through this compartment are more vulnerable to external environmental changes, including those that result in protein unfolding, than cytoplasmic proteins are. To enable bacterial survival under various stress conditions, a robust protein quality control system is required in the periplasm. In this review, we focus on several periplasmic chaperones that are stress responsive, including Spy, which responds to envelope-stress, DegP, which responds to temperature to modulate chaperone/protease activity, HdeA and HdeB, which respond to acid stress, and UgpB, which functions as a bile-responsive chaperone.
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- 2021
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11. Investigation on the Printed CNT-Film-Based Electrochemical Sensor for Detection of Liquid Chemicals
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Jaeha Noh, Sangsu An, Changhan Lee, Jiho Chang, Snagtae Lee, Moonjin Lee, and Dongmin Seo
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carbon nanotubes (CNT) ,printed CNT film (PCF) ,electrochemical sensor ,hazardous ,noxious substances (HNS) ,Chemical technology ,TP1-1185 - Abstract
We studied electrochemical sensors using printed carbon nanotubes (CNT) film on a polyethylene telephtalate (PET) substrate. The mechanical stability of the printed CNT film (PCF) was confirmed by using bending and Scotch tape tests. In order to determine the optimum sensor structure, a resistance-type PCF sensor (R-type PCF sensor) and a comb-type PCF sensor (C-type PCF sensor) were fabricated and compared using a diluted NH3 droplet with various concentrations. The magnitude of response, response time, sensitivity, linearity, and limit of detection (LOD) were compared, and it was concluded that C-type PCF sensor has superior performance. In addition, the feasibility of PCF electrochemical sensor was investigated using 12 kinds of hazardous and noxious substances (HNS). The detection mechanism and selectivity of the PCF sensor are discussed.
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- 2021
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12. Two FtsH Proteases Contribute to Fitness and Adaptation of Pseudomonas aeruginosa Clone C Strains
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Shady Mansour Kamal, Morten Levin Rybtke, Manfred Nimtz, Stefanie Sperlein, Christian Giske, Janja Trček, Julien Deschamps, Romain Briandet, Luciana Dini, Lothar Jänsch, Tim Tolker-Nielsen, Changhan Lee, and Ute Römling
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Pseudomonas aeruginosa ,clone C strains ,FtsH protease ,heat shock factor RpoH ,phenazine ,secondary metabolite ,Microbiology ,QR1-502 - Abstract
Pseudomonas aeruginosa is an environmental bacterium and a nosocomial pathogen with clone C one of the most prevalent clonal groups. The P. aeruginosa clone C specific genomic island PACGI-1 harbors a xenolog of ftsH encoding a functionally diverse membrane-spanning ATP-dependent metalloprotease on the core genome. In the aquatic isolate P. aeruginosa SG17M, the core genome copy ftsH1 significantly affects growth and dominantly mediates a broad range of phenotypes, such as secretion of secondary metabolites, swimming and twitching motility and resistance to aminoglycosides, while the PACGI-1 xenolog ftsH2 backs up the phenotypes in the ftsH1 mutant background. The two proteins, with conserved motifs for disaggregase and protease activity present in FtsH1 and FtsH2, have the ability to form homo- and hetero-oligomers with ftsH2 distinctively expressed in the late stationary phase of growth. However, mainly FtsH1 degrades a major substrate, the heat shock transcription factor RpoH. Pull-down experiments with substrate trap-variants inactive in proteolytic activity indicate both FtsH1 and FtsH2 to interact with the inhibitory protein HflC, while the phenazine biosynthesis protein PhzC was identified as a substrate of FtsH1. In summary, as an exception in P. aeruginosa, clone C harbors two copies of the ftsH metallo-protease, which cumulatively are required for the expression of a diversity of phenotypes.
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- 2019
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13. Nuclear transcriptional regulation by mitochondrial-encoded MOTS-c
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Changhan Lee
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mitochondria ,mitonuclear communication ,mitochondrial-derived peptides ,mdps ,mots-c ,nuclear translocation ,adaptive gene expression ,stress response ,stress resistance ,homeostasis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Cellular stress response is coordinated through the communication between mitochondria and the nucleus. However, whereas mitochondria are regulated by nuclear-encoded proteins, the nucleus was considered ungoverned by mitochondrial-encoded factors. We recently reported that a mitochondrial-encoded peptide directly regulates the nuclear genome upon cellular stress, indicating an integrated bi-genomic cross-communication mechanism.
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- 2019
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14. Correction: Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy.
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Stefano Di Biase, Hong Seok Shim, Kyung Hwa Kim, Manlio Vinciguerra, Francesca Rappa, Min Wei, Sebastian Brandhorst, Francesco Cappello, Hamed Mirzaei, Changhan Lee, and Valter D Longo
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Biology (General) ,QH301-705.5 - Abstract
[This corrects the article DOI: 10.1371/journal.pbio.2001951.].
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- 2017
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15. Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy.
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Stefano Di Biase, Hong Seok Shim, Kyung Hwa Kim, Manlio Vinciguerra, Francesca Rappa, Min Wei, Sebastian Brandhorst, Francesco Cappello, Hamed Mirzaei, Changhan Lee, and Valter D Longo
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Fasting reduces glucose levels and protects mice against chemotoxicity, yet drugs that promote hyperglycemia are widely used in cancer treatment. Here, we show that dexamethasone (Dexa) and rapamycin (Rapa), commonly administered to cancer patients, elevate glucose and sensitize cardiomyocytes and mice to the cancer drug doxorubicin (DXR). Such toxicity can be reversed by reducing circulating glucose levels by fasting or insulin. Furthermore, glucose injections alone reversed the fasting-dependent protection against DXR in mice, indicating that elevated glucose mediates, at least in part, the sensitizing effects of rapamycin and dexamethasone. In yeast, glucose activates protein kinase A (PKA) to accelerate aging by inhibiting transcription factors Msn2/4. Here, we show that fasting or glucose restriction (GR) regulate PKA and AMP-activated protein kinase (AMPK) to protect against DXR in part by activating the mammalian Msn2/4 ortholog early growth response protein 1 (EGR1). Increased expression of the EGR1-regulated cardioprotective peptides atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in heart tissue may also contribute to DXR resistance. Our findings suggest the existence of a glucose-PKA pathway that inactivates conserved zinc finger stress-resistance transcription factors to sensitize cells to toxins conserved from yeast to mammals. Our findings also describe a toxic role for drugs widely used in cancer treatment that promote hyperglycemia and identify dietary interventions that reverse these effects.
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- 2017
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16. Dietary restriction with and without caloric restriction for healthy aging [version 1; referees: 3 approved]
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Changhan Lee and Valter Longo
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Aging ,Animal Genetics ,Control of Gene Expression ,Developmental Molecular Mechanisms ,Endocrinology ,Integrative Physiology ,Medical Genetics ,Neurobiology of Disease & Regeneration ,Medicine ,Science - Abstract
Caloric restriction is the most effective and reproducible dietary intervention known to regulate aging and increase the healthy lifespan in various model organisms, ranging from the unicellular yeast to worms, flies, rodents, and primates. However, caloric restriction, which in most cases entails a 20–40% reduction of food consumption relative to normal intake, is a severe intervention that results in both beneficial and detrimental effects. Specific types of chronic, intermittent, or periodic dietary restrictions without chronic caloric restriction have instead the potential to provide a significant healthspan increase while minimizing adverse effects. Improved periodic or targeted dietary restriction regimens that uncouple the challenge of food deprivation from the beneficial effects will allow a safe intervention feasible for a major portion of the population. Here we focus on healthspan interventions that are not chronic or do not require calorie restriction.
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- 2016
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17. Bacterial Responses to Glyoxal and Methylglyoxal: Reactive Electrophilic Species
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Changhan Lee and Chankyu Park
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glyoxal ,reactive electrophilic species (RES) ,glyoxalase ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Glyoxal (GO) and methylglyoxal (MG), belonging to α-oxoaldehydes, are produced by organisms from bacteria to humans by glucose oxidation, lipid peroxidation, and DNA oxidation. Since glyoxals contain two adjacent reactive carbonyl groups, they are referred to as reactive electrophilic species (RES), and are damaging to proteins and nucleotides. Therefore, glyoxals cause various diseases in humans, such as diabetes and neurodegenerative diseases, from which all living organisms need to be protected. Although the glyoxalase system has been known for some time, details on how glyoxals are sensed and detoxified in the cell have not been fully elucidated, and are only beginning to be uncovered. In this review, we will summarize the current knowledge on bacterial responses to glyoxal, and specifically focus on the glyoxal-associated regulators YqhC and NemR, as well as their detoxification mediated by glutathione (GSH)-dependent/independent glyoxalases and NAD(P)H-dependent reductases. Furthermore, we will address questions and future directions.
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- 2017
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18. Fasting enhances the response of glioma to chemo- and radiotherapy.
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Fernando Safdie, Sebastian Brandhorst, Min Wei, Weijun Wang, Changhan Lee, Saewon Hwang, Peter S Conti, Thomas C Chen, and Valter D Longo
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Medicine ,Science - Abstract
Glioma, including anaplastic astrocytoma and glioblastoma multiforme (GBM) are among the most commonly diagnosed malignant adult brain tumors. GBM is a highly invasive and angiogenic tumor, resulting in a 12 to 15 months median survival. The treatment of GBM is multimodal and includes surgical resection, followed by adjuvant radio-and chemotherapy. We have previously reported that short-term starvation (STS) enhances the therapeutic index of chemo-treatments by differentially protecting normal cells against and/or sensitizing tumor cells to chemotoxicity.To test the effect of starvation on glioma cells in vitro, we treated primary mouse glia, murine GL26, rat C6 and human U251, LN229 and A172 glioma cells with Temozolomide in ad lib and STS mimicking conditions. In vivo, mice with subcutaneous or intracranial models of GL26 glioma were starved for 48 hours prior to radio- or chemotherapy and the effects on tumor progression and survival were measured. Starvation-mimicking conditions sensitized murine, rat and human glioma cells, but not primary mixed glia, to chemotherapy. In vivo, starvation for 48 hours, which causes a significant reduction in blood glucose and circulating insulin-like growth factor 1 (IGF-1) levels, sensitized both subcutaneous and intracranial glioma models to radio-and chemotherapy.Starvation-induced cancer sensitization to radio- or chemotherapy leads to extended survival in the in vivo glioma models tested. These results indicate that fasting and fasting-mimicking interventions could enhance the efficacy of existing cancer treatments against aggressive glioma in patients.
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- 2012
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