• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.321-326
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• 2015

Background: The aim of this study was to explore the prognostic role of metabolic response to chemotherapy, determined by FDG-PET, in patients with metastatic non-small-cell lung cancer (NSCLC). Materials and Methods: Thirty patients with metastatic NSCLC were analyzed for prognostic factors related to overall survival (OS) and progression free survival (PFS). Disease evaluation was conducted with FDG-PET/CT and contrast-enhanced CT prior to and at the end of first-line chemotherapy. Response evaluation of 19 of 30 patients was also performed after 2-3 cycles of chemotherapy. Morphological and metabolic responses were assessed according to RECIST and PERCIST, respectively. Results: The median OS and PFS were 11 months and 6.2 months, respectively. At the end of first-line chemotherapy, 10 patients achieved metabolic and anatomic responses. Of the 19 patients who had an interim response analysis after 2-3 cycles of chemotherapy, 3 achieved an anatomic response, while 9 achieved a metabolic response. In univariate analyses, favorable prognostic factors for OS were number of cycles of first-line chemotherapy, and achieving a response to chemotherapy at completion of therapy according to the PERCIST and RECIST. The OS of patients with a metabolic response after 2-3 cycles of chemotherapy was also significantly extended. Anatomic response at interim analysis did not predict OS, probably due to few patients with anatomic response. In multivariate analyses, metabolic response after completion of therapy was an independent prognostic factor for OS. Conclusions: Metabolic response is at least as effective as anatomic response in predicting survival. Metabolic response may be an earlier predictive factor for treatment response and OS in NSCLC patients.

• BMB Reports
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• v.57 no.9
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• pp.388-399
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• 2024

Immunotherapy represents a promising treatment strategy for targeting various tumor types. However, the overall response rate is low due to the tumor microenvironment (TME). In the TME, numerous distinct factors actively induce immunosuppression, restricting the efficacy of anticancer immune reactions. Recently, metabolic reprogramming of tumors has been recognized for its role in modulating the tumor microenvironment to enhance immune cell responses in the TME. Furthermore, recent elucidations underscore the critical role of metabolic limitations imposed by the tumor microenvironment on the effectiveness of antitumor immune cells, guiding the development of novel immunotherapeutic approaches. Hence, achieving a comprehensive understanding of the metabolic requirements of both cancer and immune cells within the TME is pivotal. This insight not only aids in acknowledging the current limitations of clinical practices but also significantly shapes the trajectory of future research endeavors in the domain of cancer immunotherapy. In addition, therapeutic interventions targeting metabolic limitations have exhibited promising potential as combinatory treatments across diverse cancer types. In this review, we first discuss the metabolic barriers in the TME. Second, we explore how the immune response is regulated by metabolites. Finally, we will review the current strategy for targeting metabolism to not simply inhibit tumor growth but also enhance antitumor immune responses. Thus, we could suggest potent combination therapy for improving immunotherapy with metabolic inhibitors.

• Biotechnology and Bioprocess Engineering:BBE
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• v.5 no.6
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• pp.422-430
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• 2000

Mechanism of lignin biodegradation caused by basidiomycetes and the history of lignin biodegradation studies were briefly reviewed. The important roles of fungal extracellular ligninolytic enzymes such as lignin and manganese peroxidases (LiP and MnP) were also summarized. These enzymes were unique in their catalytic mechanisms and substrate specificities. Either LiP or MnP system is capable of oxidizing a variety of aromatic substrates via a one-electron oxidation. Extracellular fungal system for aromatic degradation is non-specific, which recently attracts many people working a bioremediation field. On the other hand, an intracellular degradation system for aromatic compounds is rather specific in the fungal cell. Structurally similar compounds were prepared and metabolized, indicating that an intracellular degradation strategy consisted of the cellular systems for substrate recognition and metabolic response. It was assumed that lignin-degrading fungi might be needed to develop multiple metabolic pathways for a variety of aromatic compounds caused by the action of non-specific ligninolytic enzymes on lignin. Our recent results on chemical stress responsible factors analyzed using mRNA differential display techniques were also mentioned.

• Journal of the Korean Magnetic Resonance Society
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• v.21 no.1
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• pp.31-43
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• 2017

Together with radiotherapy, chemotherapy using cytotoxic agents is one of the most common therapies in cancer. Metabolic changes in cancer cells are drawing much attention recently, but the metabolic alterations by anticancer agents have not been much studied. Here, we investigated the effects of commonly used cytotoxic agents on lung normal cell MRC5 and lung cancer cell A549. We employed cis-plastin, doxorubicin, and 5-Fluorouracil and compared their effects on the viability and metabolism of the normal and cancer cell lines. We first established the concentration of the cytotoxic reagents that give differences in the viabilities of normal and cancer cell lines. In those conditions, the viability of A549 decreased significantly, whereas that of MRC5 remained unchanged. To study the metabolic alterations implicated in the viability differences, we obtained the metabolic profiles using $^1H$-NMR spectrometry. The $^1H$-NMR data showed that the metabolic changes of A549 cells are more remarkable than that of MRC5 cells and the effect of 5-FU on the A549 cells is the most distinct compared to other treatments. Heat map analysis showed that metabolic alterations under treatment of cytotoxic agents are totally different between normal and cancer cells. Multivariate analysis and weighted correlation network analysis (WGCNA) revealed a distinctive metabolite signature and hub metabolites. Two different analysis tools revealed that the changes of cell metabolism in response to cytotoxic agents were highly correlated with the Warburg effect and Reductive lipogenesis, two pathways having important effects on the cell survival. Taken together, our study addressed the correlation between the viability and metabolic profiles of MRC5 and A549 cells upon the treatment of cytotoxic anticancer agents.

• Korean Journal of Agricultural Science
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• v.45 no.2
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• pp.154-168
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• 2018

Salinity is a major abiotic stress that adversely affects crop productivity and quality. In this study, the metabolic profile and nutritional composition of rice in response to NaCl were analyzed. The plants were exposed to stressed or unstressed conditions, and their metabolic changes were examined in the shoots, roots, and grains collected at different growth stages. The levels of nutrients and anti-nutrients, including proximates, amino acids, fatty acids, minerals, vitamins, and phytic acid, were also determined for the grains. Application of NaCl significantly decreased the shoot and root growth and induced metabolic alterations at the tillering stage. During the heading stage, only the root metabolites were influenced by NaCl, and no metabolic variations related to salinity were found in the shoot, roots, and grains at the ripening stage. Nutritional analysis of the grain samples revealed that the amounts of linolenic acid and tricosanoic acid were significantly reduced while those of copper, sodium, and phytic acid were enhanced in response to stress. However, except for sodium, those differences were not great. Our results suggest that although NaCl-salinity influences the phenotypic and metabolic profiles of rice shoots and roots at the tillering stage, this impact becomes negligible as tissue development proceeds. This is especially true for the grains. Compositional analysis of the grains indicated that salinity induces some changes in fatty acids, minerals, and anti-nutrients.

• Korean Journal of Radiology
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• v.22 no.12
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• pp.2034-2051
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• 2021

Metabolic encephalopathy is a critical condition that can be challenging to diagnose. Imaging provides early clues to confirm clinical suspicions and plays an important role in the diagnosis, assessment of the response to therapy, and prognosis prediction. Diffusion-weighted imaging is a sensitive technique used to evaluate metabolic encephalopathy at an early stage. Metabolic encephalopathies often involve the deep regions of the gray matter because they have high energy requirements and are susceptible to metabolic disturbances. Understanding the imaging patterns of various metabolic encephalopathies can help narrow the differential diagnosis and improve the prognosis of patients by initiating proper treatment regimen early.

• IMMUNE NETWORK
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• v.20 no.6
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• pp.46.1-46.13
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• 2020

Neutrophils are innate immune cells that constitute the first line of defense against invading pathogens. Due to this characteristic, they are exposed to diverse immunological environments wherein sources for nutrients are often limited. Recent advances in the field of immunometabolism revealed that neutrophils utilize diverse metabolic pathways in response to immunological challenges. In particular, neutrophils adopt specific metabolic pathways for modulating their effector functions in contrast to other immune cells, which undergo metabolic reprogramming to ensure differentiation into distinct cell subtypes. Therefore, neutrophils utilize different metabolic pathways not only to fulfill their energy requirements, but also to support specialized effector functions, such as neutrophil extracellular trap formation, ROS generation, chemotaxis, and degranulation. In this review, we discuss the basic metabolic pathways used by neutrophils and how these metabolic alterations play a critical role in their effector functions.

• Animal cells and systems
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• v.2 no.1
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• pp.49-53
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• 1998

The winter-resident Korean bats, Murina leucogaster ognevi, show a circadian cycle of thermoregulation and locomotion in summer, as do other bat species in temperate regions. They are most active between dusk and dawn with body temperature (Tb) of 35-4OC, and are usually torpid in their roost sites for the rest of day with their Tb close to ambient temperature (Ta) of around 15C. The present study was conducted to determine thermogenic and thermolabile properties of the heterothermic bats that would influence their daily feeding activities and ultimately, their energy conservation strategy. Testing on active male Murina, resting metabolic rate (RMR, gauged by oxygen consumption rate) at the lower limit of thermoneutral zone (31C) was 2.0 L kq-1 h-1. The regression slope of RMR below the thermoneutral zone (an index of metabolic thermal sensitivity) was -0.38 L $kg^{-l} h^{-1} C^{-1}$. The metabolic rate at the roost Ta (15C) was 4.5 times the lowest RMR in the active state but becomes nearly zero in the torpid state. This implies that by being torpid during daytime (between dawn and dusk), the individual bats would save about 4.7 kcal each day in mid-summer. Interspecific comparisons of thermal metabolic response over a mass scale suggest that the smaller bats show a relatively higher metabolic rate in thermoneutral zone and a greater thermal sensitivity of metabolism, which follows the general principle seen in homeothermic metabolism. Thermolabile features in metabolic responses seem to be fairly common for these bats in conditions other than a fully active state. Types of thermolabile responses and their energetic significance are discussed.

• Journal of Nutrition and Health
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• v.55 no.1
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• pp.70-84
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• 2022

Purpose: Skeletal muscles display significant heterogeneity in metabolic responses, owing to the composition of metabolically distinct fiber types. Recently, numerous studies have reported that in skeletal muscles, suppression of genes related to fatty acid channeling alters the triacylglycerol (TAG) synthesis and switches the energy substrates. However, such responses may differ, depending on the type of muscle fiber. Hence, we conducted in vitro and animal studies to compare the metabolic responses of different types of skeletal muscle fibers to the deficiency of fatty acyl-CoA synthetase (Acsl)6, one of the main fatty acid-activating enzymes. Methods: Differentiated skeletal myotubes were transfected with selected Acsl6 short interfering RNA (siRNA), and C57BL/6J mice were subjected to siRNA to induce Acsl6 deficiency. TAG accumulation and expression levels of insulin signaling proteins in response to acute glucose supplementation were measured in immortalized cell-based skeletal myotubes, oxidative muscles (OM), and glycolytic muscles (GM) derived from the animals. Results: Under conditions of high glucose supplementation, suppression of the Acsl6 gene resulted in decreased TAG and glycogen synthesis in the C2C12 skeletal myotubes. The expression of Glut4, a glucose transporter, was similarly downregulated. In the animal study, the level of TAG accumulation in OM was higher than levels determined in GM. However, a similar decrease in TAG accumulation was obtained in the two muscle types in response to Acsl6 suppression. Moreover, Acsl6 suppression enhanced the phosphorylation of insulin signaling proteins (Foxo-1, mTORc-1) only in GM, while no such changes were observed in OM. In addition, the induction ratio of phosphorylated proteins in response to glucose or Acsl6 suppression was significantly higher in GM than in OM. Conclusion: The results of this study demonstrate that Acsl6 differentially regulates the energy metabolism of skeletal muscles in response to glucose supplementation, thereby indicating that the fiber type or fiber composition of mixed muscles may skew the results of metabolic studies.

• Journal of Nutrition and Health
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• v.55 no.4
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• pp.450-461
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• 2022

Purpose: DNA damage and repair responses are induced by metabolic diseases and environmental stress. The balance of DNA repair response and the antioxidant system play a role in modulating the entire body's health. This study uses a high-fat and high-calorie (HFC) drink to examine the new roles of a plant-based multivitamin/mineral supplement with phytonutrients (PMP) for regulating the antioxidant system and cellular DNA repair signaling in the body resulting from metabolic stress. Methods: In a double-blind, randomized, parallel-arm, and placebo-controlled trial, healthy adults received a capsule containing either a PMP supplement (n = 12) or a placebo control (n = 12) for 8 weeks. Fasting blood samples were collected at 0, 1, and 3 hours after consuming a HFC drink (900 kcal). The blood samples were analyzed for the following oxidative stress makers: areas under the curve reactive oxygen species (ROS) levels, plasma malondialdehyde (MDA), erythrocytes MDA, urinary MDA, oxidized low-density lipoprotein, and the glutathione:oxidized glutathione ratio at the time points. We further examined the related protein levels of DNA repair signaling (pCHK1 (Serine 345), p-P53 (Serine 15), and 𝛄H2AX expression) in the plasma of subjects to evaluate the time-dependent effects of a HFC drink. Results: In a previous study, we showed that PMP supplementation for eight weeks reduces the ROS and endogenous DNA damage in human blood plasma. Results of the current study further show that PMP supplementation is significantly correlated with antioxidant defense. Compared to the placebo samples, the blood plasma obtained after PMP supplementation showed enhanced DNA damage response genes such as pCHK1(Serine 345) (a transducer of DNA response) and 𝛄H2AX (a hallmark of DNA damage) during the 8 weeks trial on metabolic challenges. Conclusion: Our results indicate that PMP supplementation for 8 weeks enhances the antioxidant system against oxidative stress and prevents DNA damage signaling in humans.