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@#Based on our previous work, the study herein designed and synthesized eight glycoconjugates of natural product harmine (14a-14h)by introducing a cyclohexylmethyloxyl group at its C7 position and coupling a methyl-2-amino-β-D-glucopyranoside to the N9 position through different lengths of alkyl chains.In vitro anti-tumor activity screening and structure-activity relationship studies showed that the antitumor activity of the conjugates increased with the lengthening of the alkyl chain in the linker.Compound 14h exhibited significantly better proliferative inhibitory activity against MDA-MB-231 breast cancer cells than harmine.As compared to harmine, the introduction of the carbohydrate moiety improved the water solubility of compound 14h and enhanced its tumor cell selectivity through the Warburg effect.Mechanism of action studies revealed that compound 14h induced apoptosis and G0/G1 cell cycle arrest in MDA-MB-231 cells, and inhibited tumor cell migration by interfering with epithelial-mesenchymal transition process.This study provides a new approach for the development of antitumor drugs based on harmine.
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@#Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa. The pathogenesis of OLP is still unclear. Immune abnormalities mediated by T cells and related cytokines play a crucial role in the pathogenesis of OLP. In recent years, glycolytic metabolism-related transporters, enzymes and regulators, such as glucose transporter-1 (Glut1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase A (LDHA), mammalian target of rapamycin (mTOR) and hypoxia inducible factor-1α (HIF-1a), have attracted an increasing amount of attention in OLP by regulating the proliferation and differentiation of T cells and the secretion of inflammatory factors. It has been shown that 2-deoxy-D-glucose (2-DG) or rapamycin (RAPA) inhibits the glycolytic metabolism of T cells and then inhibits OLP. This article reviews the research progress of glycolytic metabolism-related transporters, enzymes and regulatory factors in OLP in recent years.
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Objective: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease. Methods: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping. Results: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration. Conclusions: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.
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Objective:To investigate the radiation protection effect of furosemide intervention on 18F-2-deoxy-D-glucose ( 18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging. Methods:A total of 146 patients were randomly divided into two groups, with test group of 74 patients and control group of 72. The test group was administrated orally with furosemide of 40 mg for each one before injection, while the normal control group did not undergo special treatment. 60 and 120 min after 18F-FDG injection, the horizontal measurement of ambient dose equivalent rates was carried out at 0.5 m from the front of both chest and abdomen respectively. Results:For the test group, the ambient dose equivalent rates were measured to be (30.80±8.61) and (41.38±11.06) μSv/h 60 min after injection of 18F-FDG whereas (18.26±4.85) and (24.66±6.50) μSv/h 120 min after injection, respectively, both lower than in the control group and with statistically significant difference between the both ( t =15.36, 13.13, 18.73, 17.29, P<0.05) . No significant difference was found between mediastinal SUV max and liver SUV max in the experimental group and control group ( P>0.05) . Multivariate ANOVA showed that body surface area was a major factor influencing ambient dose equivalent rate regardless of furosemide injection ( t=-13.52, 2.96, P<0.05) , and no obvious effects of age and sex on ambient dose equivalence rate were found. Conclusions:Furosemide intervention can promote urination, effectively reduce the internal radiation exposure of the examinated patietns in the premise of not affecting the image quality, and therefore provide a better radiation protection effect.
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Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies to treat HCC, such as targeted tyrosine kinase inhibitors, immune based therapies and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation and progression is driven by reprogramming of metabolism, in particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal of new nomenclature for non-alcoholic fatty liver disease (NAFLD), indicates growing appreciation of metabolism in the pathogenesis of liver disease, including HCC, thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment. In this review, we introduce directions by highlighting the metabolic targets in glucose, fatty acid, amino acid and glutamine metabolism, which are suitable for HCC pharmaceutical intervention. We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment. Furthermore, opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.
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Coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 is a respiratory tract infection that has already made a huge negative impact in global health situation. Transmission mainly occurs through droplets, and the virus is highly contagious. Mainly symptomatic treatments are given at present with some drugs for serious patients with unproven efficacy and safety. In this context, Institute of Nuclear Medicine and Allied Sciences, a research laboratory of Defence Research and Development Organization in collaboration with Dr. Reddy’s Laboratories, Hyderabad, has introduced a new medicine named 2-Deoxy-d-glucose (2-DG) (which has been previously tried in cancer) for the treatment of seriously ill COVID patients with a target to reduce the oxygen demand. Clinical trials showed evidence that 2-DG effectively reduces oxygen requirement in seriously ill patients, and real-time polymerase chain reaction conversion is also faster. Recently, 2-DG is approved for the use in critically ill patients by the Drug Controller General of India in May 2021. The introduction of 2-DG brings a new hope in reducing the mortality in COVID patients.
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Objective: To explore the effect of the protease inhibitor from Agaricus bisporus (J.E. Lange) Imbach (AbPI) on glucose uptake and oxidative stress in 3T3-L1 adipocytes. Methods: Adipocytes were differentiated and stained with Oil-Red-O staining to confirm adipogenesis. The toxic/protective effect of AbPI on the adipocytes was determined by MTT assay, intracellular reactive oxygen species generation through flow cytometry, and morphologically through confocal microscopy using propidium iodide, 4,6-diamino-2-phenylindol dihydrochloride, and 2',7'-dichlorofluorescein diacetate dyes. The uptake of fluorescent glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose by adipocytes was also studied through confocal microscopy. Results: MTT assay showed that the cell survival rate was (28.00±3.00)%, (92.33±2.60)%, and (71.34±2.10)% in the presence of 2 mM H
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Objective: To explore the effect of the protease inhibitor from Agaricus bisporus (J.E. Lange) Imbach (AbPI) on glucose uptake and oxidative stress in 3T3-L1 adipocytes. Methods: Adipocytes were differentiated and stained with Oil-Red-O staining to confirm adipogenesis. The toxic/protective effect of AbPI on the adipocytes was determined by MTT assay, intracellular reactive oxygen species generation through flow cytometry, and morphologically through confocal microscopy using propidium iodide, 4,6-diamino-2-phenylindol dihydrochloride, and 2',7'-dichlorofluorescein diacetate dyes. The uptake of fluorescent glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose by adipocytes was also studied through confocal microscopy. Results: MTT assay showed that the cell survival rate was (28.00±3.00)%, (92.33±2.60)%, and (71.34±2.10)% in the presence of 2 mM H2O2, AbPI alone, and AbPI and H2O2 both, respectively, in comparison to the control. Oil-Red-O staining indicated that AbPI enhanced adipogenesis. AbPI stimulated the glucose uptake by adipocytes similar to the drug rosiglitazone, and showed insulin-sensitizing effect in the presence of insulin, but failed to stimulate the uptake in the absence of insulin. Intracellular reactive oxygen species generation was reduced in differentiating adipocytes upon AbPI treatment. Confocal microscopy showed that the damaged cell population rose to 3.50%, 117.84%, and 261.50% in the presence of AbPI alone, AbPI with H2O2, and H2O2 alone, respectively. Conclusions: The protease inhibitor enhances glucose uptake by adipocytes and exhibits a cytoprotective effect on them.
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2-[ F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ( F-FDG PET/CT) combining positron emission tomography with computed tomography is used to evaluate the body's glucose metabolic changes under different conditions. In addition to its established role in oncological imaging, F-FDG PET/CT has clinical utility in suspected inflammation and infection. The technique can identify the source of infection in a timely fashion ahead of morphological changes, map the extent and severity of inflammation, guide the site for tissue biopsy and assess therapy response. This article reviewed the use of F-FDG PET/CT in infection and inflammation, such as fever of unknown origin, sarcoidosis, vessel vasculitis, osteomyelitis, joint prosthesis or implant-related complications, human immunodeficiency virus-related infections, and other indications, such as inflammatory bowel disease, so as to provide reference for clinicians to select F-FDG PET/CT to help them in the diagnosis and treatment of inflammatory diseases.
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Humanos , Fluorodesoxiglucosa F18 , Inflamación , Tomografía Computarizada por Tomografía de Emisión de Positrones , RadiofármacosRESUMEN
Abstract Expression of pectinolytic genes is regulated by catabolic repression limiting the production of pectin lyase (PL) if the natural inducer, pectin, is missing from the growth medium. Here, we report the isolation of Penicillium griseoroseum mutants resistant to 2-deoxy-d-glucose (DG) that show resistance to catabolite repression and overproduce PL. Three spontaneous and nine UV-induced mutants were obtained. Some mutants produced sectors (segments morphologically different) that were also studied. The mutants were analyzed for pectinases production on pectinase-agar plates and five mutants and two sectors showing larger clearing zones than the wild type were selected for quantitative assay. Although PL production higher than the wild type has been found, phenotype instability was observed for most of the mutants and, after transfers to nonselective medium, the DG resistance was no longer present. Only mutants M03 and M04 were stable maintaining the DG-resistance phenotype. When growing for 120 h in liquid medium containing glucose with or without pectin, both mutants showed higher PL production. In the presence of glucose as sole carbon source, the mutant M03 produced 7.8-fold more PL than the wild type. Due its phenotypic stability and PL overproduction, the mutant M03 presents potential for industrial applications.
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Proteínas Fúngicas/metabolismo , Penicillium/enzimología , Polisacárido Liasas/metabolismo , Represión Catabólica , Medios de Cultivo/química , Medios de Cultivo/metabolismo , Proteínas Fúngicas/genética , Mutación , Pectinas/metabolismo , Penicillium/genética , Penicillium/metabolismoRESUMEN
Objective To investigate the combined effect and mechanism of metformin (Met) and 2-deoxy-D-glucose (2DG) on cell proliferation and apoptosis in liver cancer cells HepG2 and Hep3B.Methods Wst-1 reagent was used to determine the anti-proliferation effects after treatments with Met and 2DG alone or combined in HepG2 and Hep3B cells.Microscopy was used to observe cell morphological changes after treatments with Met and 2DG alone or combined in HepG2 and Hep3B cells.Cell apoptosis was observed by flow cytometry after treatment of different kinds of drugs.Western blotting was used to analyze the protein expressions of Caspase-3,PARP,Mcl-1 of HepG2.Results The survival rate of HepG2 cells in the combination group was (22.48 ± 0.51)%,and compared with the control group (100.00 ± 5.05)%,Met group (80.68 ±5.10)% and 2DG group (72.56 ±4.34)%,the differences were statistically significant (P < 0.001;P < 0.001;P =0.001).The survival rate of Hep3B cells in the combination group was (29.16 ± 1.34) %,and compared with the control group (100.00 ± 1.23) %,Met group (59.58 ± 1.92) % and 2DG group (33.87 ± 1.95) %,the differences were statistically significant (P < 0.001;P < 0.001;P =0.001).Microscopy observation showed that combined treatment of Met and 2DG caused less viable adherent cells of HepG2,but more floating dead cells.While the combination group also caused a decrease in the density of Hep3B cells,but did not significantly increase the shedding of cells.The apoptosis of HepG2 cells in the combination group was (39.63 ± 0.21) %,and compared with the control group (7.12 ± 0.14) %,Met group (12.56 ± 0.35) % and 2DG group (15.16 ± 1.93) %,the differences were statistically significant (P <0.001;P < 0.001;P =0.001).The apoptosis of Hep3B cells in the combination group was (12.58 ± 1.03) %,and compared with the control group (2.82 ± 0.51) % and Met group (8.98 ± 0.86) %,the differences were statistically significant (P < 0.001;P =0.007),but compared with the 2DG group (12.40 ± 1.78) %,the difference was not statistically significant (P =1.000).Furthermore,Western blotting demonstrated that the combined treatment induced evident Caspase-3 activation and poly ADP-ribose polymerase (PARP) cleavages,and decreased expression of Mcl-1.Conclusion The combination of Met and 2DG can effectively inhibit cell proliferation of HepG2 and Hep3B,and induce apoptosis of HepG2 cells.The mechanism may be involved with Caspase-3 activation,cutting PARP substrate and decreasing Mcl-1 protein.
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Aim To investigate the effect of 2-deoxy-D-glucose(2-DG)on the sensitivity of leukemia multi-drug resistant K562/ADMcells to adriamycin by inhib-iting glycolytic pathway as well as its molecular mecha-nisms.Methods The leukemia drug-resistant K562/ADM cells and parental K562 cells were used as the target cell models.The cell proliferating activity was assessed with an MTT colorimetric assay,and the gly-colysis including glucose consumption,lactate export, and hexokinase activity was determined by glucose, lactic acid and hexokinase (HK)testing kits.The ex-pression and phosphorylation of mammalian target of rapamycin(mTOR)and glucose transporter-4 (GLUT-4)expression were analyzed by western blot.Results K562/ADM drug-resistant cells possessed higher HK activity,GLUT-4 expression level and aerobic glycolic ability than K562 sensitive cells. 2-DG treatment markedly inhibited HK activity,glucose consumption, and lactate export both in K562 cells and K562/ADM cells,and suppressed the proliferation of the two cells in a time-and concentration-dependent manner.Low concentration of 2-DG or adriamycin could increase the expression and phosphorylation of mTOR.However, the co-administration of 2-DG and adriamycin markedly counteracted adriamycin-mediated enhancement of mTOR expression and phosphorylation and down-regu-lated GLUT-4 expression in K562/ADM cells,and 2-DG dramatically improved the sensitivity of K562/ADM cells to cytotoxicity.Conclusion 2-DG inhibits the proliferation of drug-resistant K562/ADM cells and en-hances the sensitivity to adriamycin by blocking aerobic glycolysis pathway through inhibiting hexokinase activi-ty,counteracting adriamycin-stimulated increased ex-pression and phosphorylation of mTOR and downregu-lating GLUT-4 expression.
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Aim To explore the role of endoplasmic reticulum stress(ERS) in Astragaloside Ⅳ-induced cardioprotection in H9c2 cardiac cells, and to explore the potential mitochondrial mechanism.Methods Conventional culture was performed of rat heart tissue-derived H9c2 cells.Experiment was randomly divided into the control group, the ERS inducer 2-Deoxy-D-Glucose(2-DG) group, Astragaloside Ⅳ and 2-DG combination group, Astragaloside Ⅳ group.Confocal microscopy was used to observe the changes of TMRE fluorescence intensity so as to confirm the influence of ERS on the mitochondrial potential, and further speculate on the opening of the mitochondrial permeability transition pore(mPTP).Western blot analysis was applied to detect the expressions of ERS proteins GRP 78, GRP 94 and IRE1.Transmission electron microscopy was used to observe the ultrastructure of the cells.Results Different doses of 2-DG could mimic the mPTP opener atractyloside to induce the mPTP opening with the peak at 100 μmol·L-1;Astragaloside Ⅳ significantly reduced 2-DG-induced mPTP opening, the expression of GPR 78, GRP 94 and IRE1 and reduced injury of mitochondria and endoplasmic reticulum.Conclusions Endoplasmic reticulum stress could be induced by 2-DG.Astragaloside ⅳ-induced mitochondrial cardioprotection involves inhibition of the ERS through GRP 78, GRP 94 and IRE1 by prevention of the mPTP opening.
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BACKGROUND: Cognitive therapy may have therapeutic benefit in patients with early Alzheimer's disease (AD). CASE REPORT: This was a 12-week, single-blind pilot study of 4 patients with AD. The cognitive therapy included exercises for orientation to time and place; memory training, including face-name association, object recall training, and spaced retrieval; visuo-motor organization using software; similarity and ruled based categorization; and behavior modification and sequencing (e.g., making change, paying bills). The regional cerebral metabolic abnormalities and the effects of treatment on cortical metabolic responses were evaluated using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (PET). After 12 weeks, the participants showed slight improvement in some neuropsychological measures, and three of them showed increased regional cortical metabolism on brain PET studies. CONCLUSIONS: Cognitive therapy may stabilize or improve cognitive and functional performance of patients with early AD and increase regional cortical metabolism of the patients' brain.
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Humanos , Enfermedad de Alzheimer , Terapia Conductista , Encéfalo , Terapia Cognitivo-Conductual , Ejercicio Físico , Aprendizaje , Metabolismo , Proyectos Piloto , Tomografía de Emisión de PositronesRESUMEN
Frogs have been used as an alternative model to study pain mechanisms because the simplicity of their nervous tissue and the phylogenetic aspect of this question. One of these models is the sciatic nerve transection (SNT), which mimics the clinical symptoms of “phantom limb”, a condition that arises in humans after amputation or transverse spinal lesions. In mammals, the SNT increases glucose metabolism in the central nervous system, and the lactate generated appears to serve as an energy source for nerve cells. An answerable question is whether there is elevated glucose uptake in the dorsal root ganglia (DRG) after peripheral axotomy. As glucose is the major energy substrate for frog nervous tissue, and these animals accumulate lactic acid under some conditions, bullfrogs Lithobates catesbeianus were used to demonstrate the effect of SNT on DRG and spinal cord 1-[14C] 2-deoxy-D-glucose (14C-2-DG) uptake in the presence and absence of lactate. We also investigated the effect of this condition on the formation of 14CO2 from 14C-glucose and 14C-L-lactate, and plasmatic glucose and lactate levels. The 3-O-[14C] methyl-D-glucose (14C-3-OMG) uptake was used to demonstrate the steady-state tissue/medium glucose distribution ratio under these conditions. Three days after SNT, 14C-2-DG uptake increased, but 14C-3-OMG uptake remained steady. The increase in 14C-2-DG uptake was lower when lactate was added to the incubation medium. No change was found in glucose and lactate oxidation after SNT, but lactate and glucose levels in the blood were reduced. Thus, our results showed that SNT increased the glucose metabolism in the frog DRG and spinal cord. The effect of lactate on this uptake suggests that glucose is used in glycolytic pathways after SNT.
As rãs são usadas como modelos experimentais alternativos no estudo da nocicepção, tanto pela simplicidade do seu tecido nervoso como por permitirem uma abordagem filogenética sobre o tema. Um desses modelos é a secção do nervo isquiático (SNI), o qual simula os sintomas clínicos do “membro fantasma”, uma condição que ocorre nos humanos após amputação ou secção completa da medula espinal. Em mamíferos, a SNI aumenta o metabolismo da glicose no sistema nervoso central, e o lactato é uma fonte energética para as células nervosas. Porém é desconhecido se essa é a situação em gânglio da raiz dorsal (GRD). Como a glicose é o principal substrato energético para o tecido nervoso de rãs, e a concentração plasmática de lactato está aumentada nesses animais em distintas situações, a rã-touro Lithobates catesbeianus foi usada para demonstrar os efeitos da SNI sobre a captação de 1-[14C] 2-deoxi-D-glicose (14C-2-DG), na presença e ausência de lactato, em GRD e medula espinal. Foram demonstrados ainda os efeitos dessa condição experimental sobre a formação de 14CO2 a partir de 14C-glicose e 14C-L-lactato, e a concentração plasmática de glicose e lactato. A captação de 3-O-[14C] metil-D-glicose (14C-3-OMG) foi usada para demonstrar a relação tecido/meio estável da glicose nessas condições. A captação de 14C-2-DG aumentou três dias após a SNI, sem qualquer alteração na captação de 14C-3-OMG. O aumento foi reduzido quando o lactato foi acrescentado ao meio de incubação. A taxa de oxidação da glicose e do lactato não modificou após SNI, mas houve redução na concentração plasmática de glicose e lactato. Assim, a SNI aumenta o metabolismo da glicose no GRD e medula espinal de rãs. Os efeitos do lactato sobre essa captação sugerem o uso da glicose na via glicolítica após a SNI.
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Animales , Masculino , Anuros/sangre , Ganglios Espinales/metabolismo , Glucosa/metabolismo , Ácido Láctico/metabolismo , Nervio Ciático/cirugía , Médula Espinal/metabolismo , Anuros/cirugía , Glucosa/análisis , Ácido Láctico/sangreRESUMEN
Frogs have been used as an alternative model to study pain mechanisms because the simplicity of their nervous tissue and the phylogenetic aspect of this question. One of these models is the sciatic nerve transection (SNT), which mimics the clinical symptoms of phantom limb, a condition that arises in humans after amputation or transverse spinal lesions. In mammals, the SNT increases glucose metabolism in the central nervous system, and the lactate generated appears to serve as an energy source for nerve cells. An answerable question is whether there is elevated glucose uptake in the dorsal root ganglia (DRG) after peripheral axotomy. As glucose is the major energy substrate for frog nervous tissue, and these animals accumulate lactic acid under some conditions, bullfrogs Lithobates catesbeianus were used to demonstrate the effect of SNT on DRG and spinal cord 1-[14C] 2-deoxy-D-glucose (14C-2-DG) uptake in the presence and absence of lactate. We also investigated the effect of this condition on the formation of 14CO2 from 14C-glucose and 14C-L-lactate, and plasmatic glucose and lactate levels. The 3-O-[14C] methyl-D-glucose (14C-3-OMG) uptake was used to demonstrate the steady-state tissue/medium glucose distribution ratio under these conditions. Three days after SNT, 14C-2-DG uptake increased, but 14C-3-OMG uptake remained steady. The increase in 14C-2-DG uptake was lower when lactate was added to the incubation medium. No change was found in glucose and lactate oxidation after SNT, but lactate and glucose levels in the blood were reduced. Thus, our results showed that SNT increased the glucose metabolism in the frog DRG and spinal cord. The effect of lactate on this uptake suggests that glucose is used in glycolytic pathways after SNT.
As rãs são usadas como modelos experimentais alternativos no estudo da nocicepção, tanto pela simplicidade do seu tecido nervoso como por permitirem uma abordagem filogenética sobre o tema. Um desses modelos é a secção do nervo isquiático (SNI), o qual simula os sintomas clínicos do membro fantasma, uma condição que ocorre nos humanos após amputação ou secção completa da medula espinal. Em mamíferos, a SNI aumenta o metabolismo da glicose no sistema nervoso central, e o lactato é uma fonte energética para as células nervosas. Porém é desconhecido se essa é a situação em gânglio da raiz dorsal (GRD). Como a glicose é o principal substrato energético para o tecido nervoso de rãs, e a concentração plasmática de lactato está aumentada nesses animais em distintas situações, a rã-touro Lithobates catesbeianus foi usada para demonstrar os efeitos da SNI sobre a captação de 1-[14C] 2-deoxi-D-glicose (14C-2-DG), na presença e ausência de lactato, em GRD e medula espinal. Foram demonstrados ainda os efeitos dessa condição experimental sobre a formação de 14CO2 a partir de 14C-glicose e 14C-L-lactato, e a concentração plasmática de glicose e lactato. A captação de 3-O-[14C] metil-D-glicose (14C-3-OMG) foi usada para demonstrar a relação tecido/meio estável da glicose nessas condições. A captação de 14C-2-DG aumentou três dias após a SNI, sem qualquer alteração na captação de 14C-3-OMG. O aumento foi reduzido quando o lactato foi acrescentado ao meio de incubação. A taxa de oxidação da glicose e do lactato não modificou após SNI, mas houve redução na concentração plasmática de glicose e lactato. Assim, a SNI aumenta o metabolismo da glicose no GRD e medula espinal de rãs. Os efeitos do lactato sobre essa captação sugerem o uso da glicose na via glicolítica após a SNI.
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Objective To explore the neuronal apoptosis,endoplasmic reticulum stress(ERS)-related factors glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein-homologous protein (CHOP) expressions in hippocampus and possible mechanism of brain protection by 2-deoxy-D-glucose(2-DG) on their expressions in epileptic brain damage rats induced by pentetrazole.Methods Rats aged 21 d (n =120) were randomly divided into 3 groups:control group,status epilepticus (SE) group and SE + DG group,with 40 rats in each group.On a SE rat model,the neuronal apoptosis in the hippocampus was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling method.And the expression of GRP78 and CHOP were detected by Western blot and Real-time PCR.Results Apoptotic cells in the hippocampus were increased remarkably at 12 h,24 h,and 48 h after the seizures,as compared with those of control rats.In SE group,chromatin condensation and breakdown of the nucleus in neurons in hippocampus were also easily observed by Hoechst staining.Meanwhile,the ERS was induced by SE,as witness by up-regulating GRP78 expression at both protein and mRNA level.The expression of GRP78 protein in the hippocampus was elevated at 3 h,6 h and 12 h,with the maximum elevation noted at 6 h after SE.The GRP78 transcript expression was increased at 3 h,6 h,and 12 h after SE.DG treatment enhanced the changes of GRP78 protein and transcript at 3 h,and abrogated the increase of GRP78 at 6 h and 12 h,as compared with those in SE group.CHOP activation occurred at 12 h,24 h and 48 h in SE group.And the CHOP-mRNA expression was the same as the CHOP protein expression.The expression of CHOP protein and mRNA was decreased at 12 h,24 h,and 48 h after using DG.Conclusion The endoplasmic reticulum stress response mediated by CHOP seems to be involved in the neuronal apoptosis caused by status epilepticus.
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OBJECTIVE: Angiomyolipoma is the most common benign kidney tumor. However, literature describing FDG PET findings on renal angiomyolipoma (AML) is limited. This study reports the FDG PET and PET/CT findings of 21 cases of renal AML. MATERIALS AND METHODS: The study reviews FDG PET and PET/CT images of 21 patients diagnosed with renal AML. The diagnosis is based on the classical appearance of an AML on CT scan with active surveillance for 6 months. The study is focused on the observation of clinical and radiographic features. RESULTS: Six men and 15 women were included in our study. The mean age of the patients was 57.14 +/- 9.67 years old. The mean diameter of 21 renal AML on CT scans was 1.76 +/- 1.00 cm (Min: 0.6 cm; Max: 4.4 cm). CT scans illustrated renal masses typical of AMLs, and the corresponding FDG PET scans showed minimal FDG activities in the area of the tumors. None of the 21 AMLs showed a maximum standardized uptake value (SUVmax) greater than 1.98. No statistically significant correlation was present between SUVmax and tumor size. CONCLUSION: Renal AMLs demonstrate very low to low uptake on FDG PET and PET/CT imaging in this study. When a fat-containing tumor in the kidney is found on a CT scan, it is critical to differentiate an AML from a malignant tumor including an RCC, liposarcoma, and Wilms tumor. This study suggests that FDG PET or PET/CT imaging is useful for differentiating a renal AML from a fat-containing malignant tumor.
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Femenino , Humanos , Masculino , Persona de Mediana Edad , Angiomiolipoma/diagnóstico por imagen , Medios de Contraste , Síndrome de Ehlers-Danlos , Fluorodesoxiglucosa F18 , Neoplasias Renales/diagnóstico por imagen , Tomografía de Emisión de Positrones , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Estudios RetrospectivosRESUMEN
Breast cancer is the most common malignancy, and it is also the major cause of cancer-related deaths of women worldwide. Breast cancer treatment involves surgery, chemotherapy, radiation therapy, or combination therapy, and novel strategies are needed to boost the oncologic outcome. The non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG) which inhibits glucose synthesis and adenosine triphosphate production, is one of the important discoveries involving the disturbances that can be caused to the process of the metabolism. The glucose analogue, 2-DG, is known as a tumor sensitizer to irradiation (IR) and chemotherapy, which help improve the treatment rates. It enhances the cytotoxicity via oxidative stress, which is more redundant in tumor cells than in normal ones. This article provides a brief summary on studies related to 2-DG chemo-/radio-sensitization effects by combination therapy of 2-DG/IR or 2-DG/doxorubicin.
Asunto(s)
Femenino , Humanos , Adenosina Trifosfato , Mama , Neoplasias de la Mama , Línea Celular Tumoral , Terapia Combinada , Desoxiglucosa , Glucosa , Estrés Oxidativo , Polifosfatos , Tolerancia a RadiaciónRESUMEN
PURPOSE: To investigate the effects of 2-deoxy-D-glucose (2-DG) and quercetin (QCT) on gene expression of bone sialoprotein (BSP) and osteocalcin (OC) during the differentiation in irradiated MC3T3-E1 osteoblastic cells. MATERIALS AND METHODS: When MC3T3-E1 osteoblastic cells had reached 70-80% confluence, cultures were transferred to a differentiating medium supplemented with 5 mM 2-DG or 10 micrometer QCT, and then irradiated with 2, 4, 6, and 8 Gy. At various times after irradiation, the cells were analyzed for the synthesis of type I collagen, and expression of BSP and OC. RESULTS: The synthesis of type I collagen in cells exposed to 2 Gy of radiation in the presence of 2-DG or QCT showed no significant difference compared with the control group within 15 days post-irradiation. When the cells were irradiated with 8 Gy, 2-DG facilitated the irradiation mediated decrease of type I collagen synthesis, whereas such decrease was inhibited by treating with QCT. During MC3T3-E1 osteoblastic cell differentiation, the mRNA expression of BSP and OC showed the peak value at 14 days and 21 days, respectively. 2-DG or QCT treatment alone decreased the level of BSP mRNA, but increased the OC mRNA level only at early time of differentiation (day 7). In the cells irradiated with 2, 4, 8 Gy, the mRNA expression of BSP and OC decreased at 7 days after the irradiation. The cells were treated with various dose of radiation in the presence of 2-DG or QCT, the mRNA level of both BSP and OC increased although this increase was observed at low dose of radiation (2 Gy) and at the early stage of differentiation. However, when the cells were exposed to 4, 6, or 8 Gy, the increase of BSP and OC mRNAs was detected only in cells co-incubated with QCT. CONCLUSION: This study demonstrates that 2-DG and QCT affect differently the expression of bone formation related factors, type I collagen, BSP, and OC in the irradiated MC3T3-E1 osteoblasic cells, according to the dose of radiation and the times of differentiation. Overall, the present findings suggest that 2-DG and QCT could have the regulatory roles as radiation-sensitizer and -protector, respectively.