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UV can serve as an effective light spectrum for regulating plant secondary metabolites, while relevant studies on UV-A are much less extensive than those on UV-B. A comprehensive understanding of the selective effects of UV-A on different secondary metabolites and the specific features of primary metabolism that drive these effects is still lacking. To address this knowledge gap, we conducted a study to analyze the dynamic changes in the metabolome and transcriptome of lettuce leaves irradiated with red plus UV-A light (monochromatic red light as control). Generally, UV-A promoted the synthesis of most phenylpropanoids and terpenoids originating from the shikimate and methylerythritol phosphate (MEP) pathway in plastids but sacrificed the synthesis of terpenoids derived from the mevalonate (MVA) pathway, particularly sesquiterpenes. Increased precursors supply for the shikimate and MEP pathway under UV-A was directly supported by the activation of the Calvin-Benson cycle and phosphoenolpyruvate transport. Whereas, along with phosphoenolpyruvate transport, the TCA cycle was restrained, causing deprivation of the MVA pathway precursor. In addition, UV-A also activated the plastidic oxidative branch of the pentose phosphate pathway, photorespiration, and malate shuttle, to ensure a sufficient supply of nitrogen, circulation homeostasis of the Calvin-Benson cycle, and energy balance, thus indirectly supporting UV-A-induced specific secondary metabolic output. This study provides a comprehensive framework for understanding the flexible primary-secondary metabolism interactions that are able to produce specific metabolites favorable for adaptation to environmental stimuli.
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Lactuca , Hojas de la Planta , Metabolismo Secundario , Rayos Ultravioleta , Lactuca/metabolismo , Lactuca/efectos de la radiación , Lactuca/química , Lactuca/genética , Lactuca/crecimiento & desarrollo , Metabolismo Secundario/efectos de la radiación , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de la radiación , Hojas de la Planta/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Metaboloma/efectos de la radiación , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , MultiómicaRESUMEN
Light intensity is a key factor affecting the synthesis of secondary metabolites in plants. However, the response mechanisms of metabolites and genes in Gentiana macrophylla under different light intensities have not been determined. In the present study, G. macrophylla seedlings were treated with LED light intensities of 15 µmol/m2/s (low light, LL), 90 µmol/m2/s (medium light, ML), and 200 µmol/m2/s (high light, HL), and leaves were collected on the 5th day for further investigation. A total of 2162 metabolites were detected, in which, the most abundant metabolites were identified as flavonoids, carbohydrates, terpenoids and amino acids. A total of 3313 and 613 differentially expressed genes (DEGs) were identified in the LL and HL groups compared with the ML group, respectively, mainly enriched in KEGG pathways such as carotenoid biosynthesis, carbon metabolism, glycolysis/gluconeogenesis, amino acids biosynthesis, plant MAPK pathway and plant hormone signaling. Besides, the transcription factors of GmMYB5 and GmbHLH20 were determined to be significantly correlated with loganic acid biosynthesis; the expression of photosystem-related enzyme genes was altered under different light intensities, regulating the expression of enzyme genes involved in the carotenoid, chlorophyll, glycolysis and amino acids pathway, then affecting their metabolic biosynthesis. As a result, low light inhibited photosynthesis, delayed glycolysis, thus, increased certain amino acids and decreased loganic acid production, while high light got an opposite trend. Our research contributed significantly to understand the molecular mechanism of light intensity in controlling metabolic accumulation in G. macrophylla.
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Gentiana , Iridoides , Luz , Metaboloma , Transcriptoma , Gentiana/genética , Gentiana/metabolismo , Iridoides/metabolismo , Metaboloma/efectos de la radiación , Regulación de la Expresión Génica de las Plantas , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/efectos de la radiación , Perfilación de la Expresión GénicaRESUMEN
INTRODUCTION: The world is experiencing exponential growth in communication, especially wireless communication. Wireless connectivity has recently become a part of everyone's daily life. Recent developments in low-cost, low-power, and miniature devices contribute to a significant rise in radiofrequency-electromagnetic field (RF-EM) radiation exposure in our environment, raising concern over its effect on biological systems. The inconsistent and conflicting research results make it difficult to draw definite conclusions about how RF-EM radiation affects living things. OBJECTIVES: This study identified two micro-environments based on their level of exposure to cellular RF-EM radiation, one with significantly less exposure and another with very high exposure to RF-EM radiation. Emphasis is given to studying the metabolites in the urine samples of humans naturally exposed to these two different microenvironments to understand short-term metabolic dysregulations. METHODS: Untargeted 1H NMR spectroscopy was employed for metabolomics analyses to identify dysregulated metabolites. A total of 60 subjects were recruited with 5 ml urine samples each. These subjects were divided into two groups: one highly exposed to RF-EM (n = 30) and the other consisting of low-exposure populations (n = 30). RESULTS: The study found that the twenty-nine metabolites were dysregulated. Among them, 19 were downregulated, and 10 were upregulated. In particular, Glyoxylate and dicarboxylate and the TCA cycle metabolism pathway have been perturbed. The dysregulated metabolites were validated using the ROC curve analysis. CONCLUSION: Untargeted urine metabolomics was conducted to identify dysregulated metabolites linked to RF-EM radiation exposure. Preliminary findings suggest a connection between oxidative stress and gut microbiota imbalance. However, further research is needed to validate these biomarkers and understand the effects of RF-EM radiation on human health. Further research is needed with a diverse population.
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Metaboloma , Metabolómica , Ondas de Radio , Humanos , Masculino , Adulto , Metabolómica/métodos , Femenino , Ondas de Radio/efectos adversos , Metaboloma/efectos de la radiación , Persona de Mediana Edad , Campos Electromagnéticos/efectos adversos , Adulto JovenRESUMEN
BBT-059, a long-acting PEGylated interleukin-11 (IL-11) analog that is believed to have hematopoietic promoting and anti-apoptotic properties, is being developed as a potential radiation medical countermeasure (MCM) for hematopoietic acute radiation syndrome (H-ARS). This agent has been shown to improve survival in lethally irradiated mice. To further evaluate the drug's toxicity and safety profile, 12 naïve nonhuman primates (NHPs, rhesus macaques) were administered one of three doses of BBT-059 subcutaneously and were monitored for the next 21 days. Blood samples were collected throughout the study to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of the drug as well as its effects on complete blood counts, cytokines, vital signs, and to conduct metabolomic studies. No adverse effects were detected in any treatment group during the study. Short-term changes in metabolomic profiles were present in all groups treated with BBT-059 beginning immediately after drug administration and reverting to near normal levels by the end of the study period. Several pathways and metabolites, particularly those related to inflammation and steroid hormone biosynthesis, were activated by BBT-059 administration. Taken together, these observations suggest that BBT-059 has a good safety profile for further development as a radiation MCM for regulatory approval for human use.
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Macaca mulatta , Metabolómica , Polietilenglicoles , Protectores contra Radiación , Animales , Protectores contra Radiación/farmacología , Protectores contra Radiación/farmacocinética , Polietilenglicoles/farmacocinética , Polietilenglicoles/farmacología , Polietilenglicoles/química , Masculino , Interleucina-11 , Femenino , Metaboloma/efectos de los fármacos , Metaboloma/efectos de la radiación , Síndrome de Radiación Aguda/tratamiento farmacológico , Síndrome de Radiación Aguda/prevención & controlRESUMEN
Development of novel biodosimetry assays and medical countermeasures is needed to obtain a level of radiation preparedness in the event of malicious or accidental mass exposures to ionizing radiation (IR). For biodosimetry, metabolic profiling with mass spectrometry (MS) platforms has identified several small molecules in easily accessible biofluids that are promising for dose reconstruction. As our microbiome has profound effects on biofluid metabolite composition, it is of interest how variation in the host microbiome may affect metabolomics based biodosimetry. Here, we 'knocked out' the microbiome of male and female C57BL/6 mice (Abx mice) using antibiotics and then irradiated (0, 3, or 8 Gy) them to determine the role of the host microbiome on biofluid radiation signatures (1 and 3 d urine, 3 d serum). Biofluid metabolite levels were compared to a sham and irradiated group of mice with a normal microbiome (Abx-con mice). To compare post-irradiation effects in urine, we calculated the Spearman's correlation coefficients of metabolite levels with radiation dose. For selected metabolites of interest, we performed more detailed analyses using linear mixed effect models to determine the effects of radiation dose, time, and microbiome depletion. Serum metabolite levels were compared using an ANOVA. Several metabolites were affected after antibiotic administration in the tryptophan and amino acid pathways, sterol hormone, xenobiotic and bile acid pathways (urine) and lipid metabolism (serum), with a post-irradiation attenuative effect observed for Abx mice. In urine, dose×time interactions were supported for a defined radiation metabolite panel (carnitine, hexosamine-valine-isoleucine [Hex-V-I], creatine, citric acid, and Nε,Nε,Nε-trimethyllysine [TML]) and dose for N1-acetylspermidine, which also provided excellent (AUROC ≥ 0.90) to good (AUROC ≥ 0.80) sensitivity and specificity according to the area under the receiver operator characteristic curve (AUROC) analysis. In serum, a panel consisting of carnitine, citric acid, lysophosphatidylcholine (LysoPC) (14:0), LysoPC (20:3), and LysoPC (22:5) also gave excellent to good sensitivity and specificity for identifying post-irradiated individuals at 3 d. Although the microbiome affected the basal levels and/or post-irradiation levels of these metabolites, their utility in dose reconstruction irrespective of microbiome status is encouraging for the use of metabolomics as a novel biodosimetry assay.
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Ratones Endogámicos C57BL , Animales , Ratones , Femenino , Masculino , Exposición a la Radiación , Microbiota/efectos de la radiación , Metabolómica/métodos , Metaboloma/efectos de la radiación , Radiación IonizanteRESUMEN
A complex cascade of systemic and tissue-specific responses induced by exposure to ionizing radiation can lead to functional impairment over time in the surviving population. Current methods for management of survivors of unintentional radiation exposure episodes rely on monitoring individuals over time for the development of adverse clinical symptoms due to the lack of predictive biomarkers for tissue injury. In this study, we report on changes in metabolomic and lipidomic profiles in multiple tissues of nonhuman primates (NHPs) that received either 4.0 Gy or 5.8 Gy total-body irradiation (TBI) of 60Co gamma rays, and 4.0 or 5.8 Gy partial-body irradiation (PBI) from LINAC-derived photons and were treated with a promising radiation countermeasure, gamma-tocotrienol (GT3). These include small molecule alterations that correlate with radiation effects in the jejunum, lung, kidney, and spleen of animals that either survived or succumbed to radiation toxicities over a 30-day period. Radiation-induced metabolic changes in tissues were observed in animals exposed to both doses and types of radiation, but were partially alleviated in GT3-treated and irradiated animals, with lung and spleen being most responsive. The majority of the pathways protected by GT3 treatment in these tissues were related to glucose metabolism, inflammation, and aldarate metabolism, suggesting GT3 may exert radioprotective effects in part by sparing these pathways from radiation-induced dysregulation. Taken together, the results of our study demonstrate that the prophylactic administration of GT3 results in metabolic and lipidomic shifts that likely provide an overall advantage against radiation injury. This investigation is among the first to highlight the use of a molecular phenotyping approach in a highly translatable NHP model of partial- and total-body irradiation to determine the underlying physiological mechanisms involved in the radioprotective efficacy of GT3.
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Macaca mulatta , Metabolómica , Irradiación Corporal Total , Animales , Irradiación Corporal Total/efectos adversos , Masculino , Metaboloma/efectos de la radiación , Vitamina E/metabolismo , Vitamina E/análogos & derivados , Protectores contra Radiación/farmacología , Rayos gamma/efectos adversos , CromanosRESUMEN
Development of an efficient liquid fermentation method is helpful for food and pharmaceutical applications. This study investigated the effect of ultrasonication on the liquid fermentation of Ganoderma lucidum, a popular edible and medical fungi. Significant changes at both metabolic and transcriptional levels in mycelia were induced by ultrasound treatment. Compared with the control, 857 differential metabolites were identified (578 up- and 279 down-regulated metabolites), with more metabolites biosynthesis after sonication; 569 differentially expressed genes (DEGs) (267 up- and 302 down-) and 932 DEGs (378 up- and 554 down-) were identified in ultrasound-treated samples with recovery time of 0.5 and 3 h, respectively. Furthermore, 334 DEGs were continuously induced within the recovery time of 3 h, indicating the lasting influence of sonication on mycelia. The DEGs and differential metabolites were mainly involved in pathways of carbohydrate, energy metabolism, amino acids, terpenoids biosynthesis and metabolism and membrane transport, suggesting that ultrasound induced multifaceted effects on primary and secondary metabolism. Ultrasonication enhanced the triterpenoids production of G. lucidum (34.96 %) by up-regulating the expression of terpenoids synthase genes. This study shows that the application of ultrasound in liquid fermentation of G. lucidum is an efficient approach to produce more metabolites.
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Fermentación , Reishi , Ultrasonido , Fermentación/efectos de la radiación , Metaboloma/efectos de la radiación , Reishi/metabolismo , Transcriptoma/efectos de la radiaciónRESUMEN
Although electric fields (EF) exert beneficial effects on animal wound healing, differentiation, cancers and rheumatoid arthritis, the molecular mechanisms of these effects have remained unclear about a half century. Therefore, we aimed to elucidate the molecular mechanisms underlying EF effects in Drosophila melanogaster as a genetic animal model. Here we show that the sleep quality of wild type (WT) flies was improved by exposure to a 50-Hz (35 kV/m) constant electric field during the day time, but not during the night time. The effect was undetectable in cryptochrome mutant (cryb) flies. Exposure to a 50-Hz electric field under low nutrient conditions elongated the lifespan of male and female WT flies by ~ 18%, but not of several cry mutants and cry RNAi strains. Metabolome analysis indicated that the adenosine triphosphate (ATP) content was higher in intact WT than cry gene mutant strains exposed to an electric field. A putative magnetoreceptor protein and UV-A/blue light photoreceptor, CRYPTOCHROME (CRY) is involved in electric field (EF) receptors in animals. The present findings constitute hitherto unknown genetic evidence of a CRY-based system that is electric field sensitive in animals.
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Criptocromos/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/efectos de la radiación , Terapia por Estimulación Eléctrica , Proteínas del Ojo/metabolismo , Longevidad/efectos de la radiación , Sueño/efectos de la radiación , Adenosina Trifosfato/metabolismo , Animales , Drosophila melanogaster/metabolismo , Femenino , Masculino , Metaboloma/efectos de la radiación , InaniciónRESUMEN
Understanding the global metabolic changes during the senescence of tumor cells can have implications for developing effective anti-cancer treatment strategies. Ionizing radiation (IR) was used to induce senescence in a human colon cancer cell line HCT-116 to examine secretome and metabolome profiles. Control proliferating and senescent cancer cells (SCC) exhibited distinct morphological differences and expression of senescent markers. Enhanced secretion of pro-inflammatory chemokines and IL-1, anti-inflammatory IL-27, and TGF-ß1 was observed in SCC. Significantly reduced levels of VEGF-A indicated anti-angiogenic activities of SCC. Elevated levels of tissue inhibitors of matrix metalloproteinases from SCC support the maintenance of the extracellular matrix. Adenylate and guanylate energy charge levels and redox components NAD and NADP and glutathione were maintained at near optimal levels indicating the viability of SCC. Significant accumulation of pyruvate, lactate, and suppression of the TCA cycle in SCC indicated aerobic glycolysis as the predominant energy source for SCC. Levels of several key amino acids decreased significantly, suggesting augmented utilization for protein synthesis and for use as intermediates for energy metabolism in SCC. These observations may provide a better understanding of cellular senescence basic mechanisms in tumor tissues and provide opportunities to improve cancer treatment.
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Senescencia Celular/genética , Neoplasias del Colon/genética , Redes y Vías Metabólicas/genética , Metaboloma/genética , Senescencia Celular/efectos de la radiación , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Células HCT116 , Humanos , Interleucina-1/genética , Interleucina-27/genética , Redes y Vías Metabólicas/efectos de la radiación , Metaboloma/efectos de la radiación , Radiación Ionizante , Factor de Crecimiento Transformador beta1/genética , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
To date, the United States Food and Drug Administration (FDA) has approved four drugs to mitigate hematopoietic acute radiation syndrome and all four are repurposed radiomitigators. There are several additional drug candidates currently under evaluation that may also be helpful for use during a widespread emergency. One possible candidate is Ex-Rad, also known as ON01210, a chlorobenzyl sulfone derivative (organosulfur compound), which is a novel, small-molecule kinase inhibitor with demonstrated efficacy in the murine model. In this study, we have evaluated the metabolomic and lipidomic profiles in serum samples of nonhuman primates (NHPs) treated with Ex-Rad after exposure to ionizing radiation. Two different dose administration schedules (Ex-Rad I administered 24 and 36 h post-irradiation, and Ex-Rad II administered 48 and 60 h post-irradiation), were used and evaluated using a global molecular profiling approach. We observed alterations in biochemical pathways relating to inflammation and oxidative stress after radiation exposure that were alleviated in animals that received Ex-Rad I or Ex-Rad II. The results from this study lend credence to the possible radiomitigative effects of this drug possibly via a dampening of metabolism-based tissue injury, thus aiding in recovery of vital, radiation-injured organ systems.
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Rayos gamma/efectos adversos , Metaboloma , Traumatismos Experimentales por Radiación , Sulfonamidas/farmacología , Animales , Macaca mulatta , Masculino , Metaboloma/efectos de los fármacos , Metaboloma/efectos de la radiación , Traumatismos Experimentales por Radiación/sangre , Traumatismos Experimentales por Radiación/tratamiento farmacológicoRESUMEN
Future space missions will include a return to the Moon and long duration deep space roundtrip missions to Mars. Leaving the protection that Low Earth Orbit provides will unavoidably expose astronauts to higher cumulative doses of space radiation, in addition to other stressors, e.g., microgravity. Immune regulation is known to be impacted by both radiation and spaceflight and it remains to be seen whether prolonged effects that will be encountered in deep space can have an adverse impact on health. In this study, we investigated the effects in the overall metabolism of three different low dose radiation exposures (γ-rays, 16O, and 56Fe) in spleens from male C57BL/6 mice at 1, 2, and 4 months after exposure. Forty metabolites were identified with significant enrichment in purine metabolism, tricarboxylic acid cycle, fatty acids, acylcarnitines, and amino acids. Early perturbations were more prominent in the γ irradiated samples, while later responses shifted towards more prominent responses in groups with high energy particle irradiations. Regression analysis showed a positive correlation of the abundance of identified fatty acids with time and a negative association with γ-rays, while the degradation pathway of purines was positively associated with time. Taken together, there is a strong suggestion of mitochondrial implication and the possibility of long-term effects on DNA repair and nucleotide pools following radiation exposure.
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Radiación Cósmica , Metaboloma/efectos de la radiación , Exposición a la Radiación , Bazo/metabolismo , Bazo/efectos de la radiación , Animales , Ciclo del Ácido Cítrico/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Modelos Lineales , Masculino , Ratones Endogámicos C57BL , Análisis Multivariante , Purinas/metabolismoRESUMEN
Ultraviolet A (UV-A) radiation is a significant environmental factor that causes photoreceptor damage, apoptosis, and oxidative stress in insects. Ostrinia furnacalis is an important pest of corn. To understand the adaptation mechanisms of insect response to UV-A exposure, this study revealed differentially expressed genes (DEGs) and differently expressed metabolites (DEMs) in O. furnacalis under UV-A exposure. Three complementary DNA libraries were constructed from O. furnacalis adult females (CK, UV1h, and UV2h), and 50,106 expressed genes were obtained through Illumina sequencing. Of these, 157 and 637 DEGs were detected in UV1h and UV2h after UV-A exposure for 1 and 2 h, respectively, compared to CK, with 103 and 444 upregulated and 54 and 193 downregulated genes, respectively. Forty four DEGs were detected in UV2h compared to UV1h. Comparative transcriptome analysis between UV-treated and control groups revealed signal transduction, detoxification and stress response, immune defense, and antioxidative system involvement. Metabolomics analysis showed that 181 (UV1h vs. CK), 111 (UV2h vs. CK), and 34 (UV2h vs. UV1h) DEMs were obtained in positive ion mode, while 135 (UV1h vs. CK), 93 (UV2h vs. CK), and 36 (UV2h vs. UV1h) DEMs were obtained in negative ion mode. Moreover, UV-A exposure disturbed amino acid, sugar, and lipid metabolism. These findings provide insight for further studies on how insects protect themselves under UV-A stress.
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Metaboloma/efectos de la radiación , Mariposas Nocturnas/metabolismo , Transcriptoma/efectos de la radiación , Rayos Ultravioleta , Animales , Regulación hacia Abajo/efectos de la radiación , Femenino , Biblioteca de Genes , Mariposas Nocturnas/genética , Mariposas Nocturnas/efectos de la radiación , Estrés Oxidativo/genética , Análisis de Componente Principal , Transducción de Señal/genética , Factores de Tiempo , Regulación hacia Arriba/efectos de la radiación , Zea mays/parasitologíaRESUMEN
In the present study, the effects of elevated UV-B (eUVB; ambient ± 7.2 kJ m-2 day-1) were evaluated on the biochemical and metabolic profile of Adhatoda vasica Nees. (an indigenous medicinal plant) at different growth stages. The results showed reduction in superoxide radical production rate, whereas increase in the content of hydrogen peroxide which was also substantiated by the histochemical localization. Malondialdehyde content, which is a measure of oxidative stress, did not show significant changes at any of the growth stages however photosynthetic rate and chlorophyll content showed reduction at all growth stages under eUV-B exposure. Increased activities of the enzymatic and non-enzymatic antioxidants were noticed except ascorbic acid, which was reduced under eUV-B exposure. The metabolic profile of A. vasica revealed 43 major compounds (assigned under different classes) at different growth stages. Triterpenes, phytosterols, unsaturated fatty acids, diterpenes, tocopherols, and alkaloids showed increment, whereas reduction in saturated fatty acids and sesquiterpenes were observed under eUV-B treatment. Vasicinone and vasicoline, the two important alkaloids of A. vasica, showed significant induction under eUV-B exposure as compared to control. Treatment of eUV-B leads to the synthesis of some new compounds, such as oridonin oxide (diterpene) and α-Bisabolol oxide-B (sesquiterpene), which possess potent anti-inflammatory and anticancerous activities. The study displayed that differential crosstalk between antioxidants and secondary metabolites at different growth stages, were responsible for providing protection to A. vasica against eUV-B induced oxidative stress and enhancing its medicinal properties.
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Antioxidantes/metabolismo , Género Justicia/metabolismo , Metaboloma/efectos de la radiación , Extractos Vegetales/metabolismo , Plantas Medicinales/metabolismo , Antioxidantes/efectos de la radiación , Ácido Ascórbico/metabolismo , Clorofila/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Peróxido de Hidrógeno/metabolismo , Género Justicia/efectos de la radiación , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de la radiación , Fitosteroles/metabolismo , Plantas Medicinales/efectos de la radiación , Metabolismo Secundario/efectos de la radiación , Factores de Tiempo , Tocoferoles/metabolismo , Triterpenos/metabolismo , Rayos UltravioletaRESUMEN
UV-B-driven modulation of secondary metabolism in peach fruit by enhancing the biosynthesis of specific phenolic subclasses, is attracting interest among consumers. However, current literature explored the UV-B-induced metabolic changes only in peach skin subjected to direct UV-B irradiation. Accordingly, this study aimed to understand whether UV-B radiation penetrates the fruit skin and is able to induce metabolic changes also within the inner flesh. Peaches were UV-B-irradiated either 10 or 60 min, and the flesh was sampled after 24 and 36 h. Non-targeted metabolomics revealed that UV-B has a strong impact on peach flesh metabolome, determining an initial decrease after 24 h, followed by an overall increase after 36 h, particularly for terpenoids, phenylpropanoids, phytoalexins and fatty acids in the 60 min UV-B-treated samples (+150.02, +99.14, +43.79 and +25.44 log2FC, respectively). Transmittance analysis indicated that UV-B radiation does not penetrate below the skin, suggesting a possible signalling pathway between tissues.
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Frutas/metabolismo , Frutas/efectos de la radiación , Metaboloma/efectos de la radiación , Epidermis de la Planta/efectos de la radiación , Prunus persica/metabolismo , Prunus persica/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Prunus persica/crecimiento & desarrolloRESUMEN
We aimed to evaluate whether resveratrol affects radiation-induced changes in metabolite profiles of the mouse heart. Hearts were irradiated in vivo with a single 2 Gy dose during the resveratrol administration and metabolite profiles of heart tissue were analyzed by the untargeted HR-MAS NMR approach twenty weeks after irradiation. The administration of resveratrol mitigated the radiation-induced decline in the content of choline-containing compounds and unsaturated lipids, which might reflect the stabilization of cell membrane structure against radiation-related damage. Results obtained with this mouse model suggest that the resveratrol supplementation may prevent metabolic changes related to radiation-induced damage in the heart.
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Cardiotónicos/farmacología , Corazón/efectos de la radiación , Metaboloma/efectos de los fármacos , Fosfatidilcolinas/metabolismo , Traumatismos Experimentales por Radiación/prevención & control , Resveratrol/farmacología , Administración Oral , Animales , Femenino , Glicina/metabolismo , Ácido Láctico/metabolismo , Metaboloma/efectos de la radiación , Ratones , Ratones Endogámicos C57BL , Fotones/efectos adversos , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/patología , Radiación Ionizante , Taurina/análogos & derivados , Taurina/metabolismoRESUMEN
Several photorespiratory bypasses have been introduced into plants and shown to improve photosynthesis by increasing chloroplastic CO2 concentrations or optimizing energy balance. We recently reported that an engineered GOC bypass could increase photosynthesis and productivity in rice. However, the grain yield of GOC plants was unstable, fluctuating in different cultivation seasons because of varying seed setting rates. In this study, we designed a synthetic photorespiratory shortcut (the GCGT bypass) consisting of genes encoding Oryza sativa glycolate oxidase and Escherichia coli catalase, glyoxylate carboligase, and tartronic semialdehyde reductase. The GCGT bypass was guided by an optimized chloroplast transit peptide that targeted rice chloroplasts and redirected 75% of carbon from glycolate metabolism to the Calvin cycle, identical to the native photorespiration pathway. GCGT transgenic plants exhibited significantly increased biomass production and grain yield, which were mainly attributed to enhanced photosynthesis due to increased chloroplastic CO2 concentrations. Despite the increases in biomass production and grain yield, GCGT transgenic plants showed a reduced seed setting rate, a phenotype previously reported for the GOC plants. Integrative transcriptomic, physiological, and biochemical assays revealed that photosynthetic carbohydrates were not transported to grains in an efficient manner, thereby reducing the seed setting rate. Taken together, our results demonstrate that the GCGT photorespiratory shortcut confers higher yield by promoting photosynthesis in rice, mainly through increasing chloroplastic CO2 concentrations.
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Biomasa , Luz , Oryza/crecimiento & desarrollo , Oryza/efectos de la radiación , Fotosíntesis/efectos de la radiación , Semillas/crecimiento & desarrollo , Transporte Biológico/efectos de la radiación , Metabolismo de los Hidratos de Carbono/efectos de la radiación , Dióxido de Carbono/metabolismo , Respiración de la Célula/efectos de la radiación , Cloroplastos/metabolismo , Cloroplastos/efectos de la radiación , Cloroplastos/ultraestructura , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Metaboloma/efectos de la radiación , Oryza/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de la radiación , Hojas de la Planta/ultraestructura , Plantas Modificadas Genéticamente , Semillas/efectos de la radiación , Transcriptoma/genéticaRESUMEN
Radiotherapy (RT) is applied in 45-60% of all cancer patients either alone or in multimodal therapy concepts comprising surgery, RT and chemotherapy. However, despite technical innovations approximately only 50% are cured, highlight a high medical need for innovation in RT practice. RT is a multidisciplinary treatment involving medicine and physics, but has always been successful in integrating emerging novel concepts from cancer and radiation biology for improving therapy outcome. Currently, substantial improvements are expected from integration of precision medicine approaches into RT concepts.Altered metabolism is an important feature of cancer cells and a driving force for malignant progression. Proper metabolic processes are essential to maintain and drive all energy-demanding cellular processes, e.g. repair of DNA double-strand breaks (DSBs). Consequently, metabolic bottlenecks might allow therapeutic intervention in cancer patients.Increasing evidence now indicates that oncogenic activation of metabolic enzymes, oncogenic activities of mutated metabolic enzymes, or adverse conditions in the tumor microenvironment can result in abnormal production of metabolites promoting cancer progression, e.g. 2-hyroxyglutarate (2-HG), succinate and fumarate, respectively. Interestingly, these so-called "oncometabolites" not only modulate cell signaling but also impact the response of cancer cells to chemotherapy and RT, presumably by epigenetic modulation of DNA repair.Here we aimed to introduce the biological basis of oncometabolite production and of their actions on epigenetic regulation of DNA repair. Furthermore, the review will highlight innovative therapeutic opportunities arising from the interaction of oncometabolites with DNA repair regulation for specifically enhancing the therapeutic effects of genotoxic treatments including RT in cancer patients.
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Epigénesis Genética , Metaboloma/efectos de la radiación , Neoplasias/metabolismo , Radioterapia/métodos , Animales , Humanos , Neoplasias/patología , Neoplasias/radioterapia , Transducción de SeñalRESUMEN
The liver is the pivotal metabolic organ primarily responsible for metabolic activities, detoxification and regulation of carbohydrate, protein, amino acid, and lipid metabolism. However, very little is known about the complicated pathophysiologic mechanisms of liver injury result from ionizing radiation exposure. Therefore, a pseudotargeted metabolomics approach based on gas chromatography-tandem mass spectrometry with selected reaction monitoring (GC-MS-SRM) was developed to study metabolic alterations of liver tissues in radiation-induced hepatic injury. The pseudotargeted GC-MS-SRM method was validated with satisfactory analytical characteristics in terms of precision, linearity, sensitivity and recovery. Compared to the SIM-based approach, the SRM scanning method had mildly better precision, higher sensitivity, and wider linear ranges. A total of 37 differential metabolites associated with radiation-induced hepatic injury were identified using the GC-MS-SRM metabolomics method. Global metabolic clustering analysis showed that amino acids, carbohydrates, unsaturated fatty acids, organic acids, metabolites associated with pyrimidine metabolism, ubiquinone biosynthesis and oxidative phosphorylation appeared significantly declined after high dose irradiation exposure, whereas metabolites related to lysine catabolism, glycerolipid metabolism and glutathione metabolism presented the opposite behavior. These changes indicate energy deficiency, antioxidant defense damage, accumulation of ammonia and lipid oxidation of liver tissues in response to radiation exposure. It is shown that the developed pseudotargeted method based on GC-MS-SRM is a useful tool for metabolomics study.
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Cromatografía de Gases y Espectrometría de Masas/métodos , Hepatopatías/metabolismo , Metaboloma/efectos de la radiación , Metabolómica/métodos , Traumatismos Experimentales por Radiación/metabolismo , Animales , Modelos Lineales , Hígado/química , Hígado/metabolismo , Hígado/efectos de la radiación , Masculino , Ratas , Ratas Wistar , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: In this exploratory study, the impact of local irradiation on systemic changes in stress and immune parameters was investigated in eight patients treated with intensity-modulated radiation therapy (IMRT) or stereotactic ablative body radiotherapy (SABR) for prostate adenocarcinoma to gain deeper insights into how radiotherapy (RT) modulates the immune system. PATIENTS AND METHODS: RT-qPCR, flow cytometry, metabolomics, and antibody arrays were used to monitor a panel of stress- and immune-related parameters before RT, after the first fraction (SABR) or the first week of treatment (IMRT), after the last fraction, and 3 weeks later in the blood of IMRT (Nâ¯= 4) or SABR (Nâ¯= 4) patients. Effect size analysis was used for comparison of results at different timepoints. RESULTS: Several parameters were found to be differentially modulated in IMRT and SABR patients: the expression of TGFB1, IL1B, and CCL3 genes; the expression of HLA-DR on circulating monocytes; the abundance and ratio of phosphatidylcholine and lysophosphatidylcholine metabolites in plasma. More immune modulators in plasma were modulated during IMRT than SABR, with only two common proteins, namely GDF-15 and Tim3. CONCLUSION: Locally delivered RT induces systemic modulation of the immune system in prostate adenocarcinoma patients. IMRT and SABR appear to specifically affect distinct immune components.
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Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Sistema Inmunológico/efectos de la radiación , Metaboloma/efectos de la radiación , Proteínas de Neoplasias/sangre , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Proteoma/efectos de la radiación , Radiocirugia/métodos , Radioterapia de Intensidad Modulada/métodos , Estrés Fisiológico/efectos de la radiación , Adenocarcinoma/inmunología , Adenocarcinoma/fisiopatología , Anciano , Anciano de 80 o más Años , Biomarcadores , Citocinas/sangre , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Antígenos HLA/sangre , Humanos , Mediadores de Inflamación/sangre , Lisofosfatidilcolinas/sangre , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Fosfatidilcolinas/sangre , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/fisiopatologíaRESUMEN
Establishing the metabolism pathway of the drug undergoing the hepatic biotransformation pathway is one of the most important aspects in the preclinical discovery process since the presence of toxic or reactive metabolites may result in drug withdrawal from the market. In this study, we present the structural elucidation of six, not described yet, metabolites of an antipsychotic molecule: molindone. The elucidation of metabolites was supported with a novel photocatalytical approach with the use of WO3 and WS2 assisted photochemical reactions. An UHPLC-ESI-Q-TOF combined system was used for the registration of all obtained metabolite profiles as well as to record the high resolution fragmentation spectra of the observed transformation products. As a reference in the in vitro metabolism simulation method, the incubation with human liver microsomes was used. Chemometric comparison of the obtained profiles pointed out the use of the WO3 approach as being more convenient in the field of drug metabolism studies. Moreover, the photocatalysis was used in the direction of the main drug metabolite synthesis in order to further isolation and characterization.