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Journal of Nuclear Medicine : Official... Dec 2020
Topics: Fluorodeoxyglucose F18; History, 20th Century; History, 21st Century; Multimodal Imaging; Positron-Emission Tomography
PubMed: 33293437
DOI: 10.2967/jnumed.120.252841 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Aug 2022Epilepsy is a syndrome of central nervous system dysfunction caused by many reasons, which is mainly characterized by abnormal discharge of neurons in the brain....
OBJECTIVES
Epilepsy is a syndrome of central nervous system dysfunction caused by many reasons, which is mainly characterized by abnormal discharge of neurons in the brain. Therefore, finding new targets for epilepsy therapy has always been the focus and hotspot in neurological research field. Studies have found that 2-deoxy--glucose (2-DG) exerts anti-epileptic effect by up-regulation of K channel subunit mRNA and protein. By using the database of TargetScan and miRBase to perform complementary pairing analysis on the sequences of miRNA and related target genes, it predicted that miR-194 might be the upstream signaling molecule of K channel. This study aims to explore the mechanism by which 2-DG exerts its anti-epileptic effect by regulating K channel subunits and via miR-194.
METHODS
A magnesium-free epilepsy model was established and randomly divided into a control group, an epilepsy group (EP group), an EP+2-DG group, and miR-194 groups (including EP+miR-194 mimic, EP+miR-194 mimic+2-DG, EP+miR-194 mimic control, EP+miR-194 inhibitor, EP+miR-194 inhibitor+2-DG, and EP+miR-194 inhibitor control groups). The 2-DG was used to intervene miR-194 mimics, patch-clamp method was used to detect the spontaneous recurrent epileptiform discharges, real-time PCR was used to detect neuronal , and expressions, and the protein levels of Kir6.1 and Kir6.2were detected by Western blotting.
RESULTS
Compared with the control group, there was no significant difference in the amplitude of spontaneous discharge potential in the EP group (>0.05), but the frequency of spontaneous discharge was increased (<0.05). Compared with the EP group, the frequency of spontaneous discharge was decreased (<0.05). Compared with the EP+miR-194 mimic control group, the mRNA and protein expressions of and in the EP+miR-194 mimic group were down-regulated (all <0.05). Compared with the EP+miR-194 inhibitor control group, the mRNA and protein expressions of and in the EP+miR-194 inhibitor group were up-regulated (all <0.05). After pretreatment with miR-194 mimics, the mRNA and protein expression levels of K channel subunits and were decreased (all <0.05). Compared with the EP+2-DG group, the mRNA and protein expression levels of and in the EP+miR-194 mimic+2-DG group were down-regulated (all <0.05) and the mRNA and protein expression levels of and in the EP+miR-194 inhibitor+2-DG group were up-regulated (all <0.05).
CONCLUSIONS
The 2-DG might play an anti-epilepsy effect by up-regulating K channel subunits Kir6.1 and Kir6.2via miR-194.
Topics: Adenosine Triphosphate; Anticonvulsants; Deoxyglucose; Epilepsy; Glucose; Humans; MicroRNAs; Potassium Channels, Inwardly Rectifying; RNA, Messenger; Signal Transduction
PubMed: 36097778
DOI: 10.11817/j.issn.1672-7347.2022.220111 -
Epilepsia Open Mar 2022Infantile spasms (IS) is an epileptic encephalopathy with a poor neurodevelopmental prognosis, and limited, often ineffective treatment options. The effectiveness of...
Infantile spasms (IS) is an epileptic encephalopathy with a poor neurodevelopmental prognosis, and limited, often ineffective treatment options. The effectiveness of metabolic approaches to seizure control is being increasingly shown in a wide variety of epilepsies. This study investigates the efficacy of the glycolysis inhibitor 2-deoxyglucose (2-DG) and the ketone body β-hydroxybutyrate (BHB) in the betamethasone-NMDA model of rat IS. Prenatal rats were exposed to betamethasone on gestational day 15 (G15) and NMDA on postnatal day 15 (P15). Video-electroencephalography (v-EEG) was used to monitor spasms. NMDA consistently induced hyperflexion spasms associated with interictal sharp-slow wave EEG activity and ictal flattening of EEG signals, reminiscent of hypsarrhythmia and electrodecrement, respectively. 2-DG (500 mg/kg, i.p), BHB (200 mg/kg, i.p.), or both were administered immediately after occurrence of the first spasm. No experimental treatment altered significantly the number, severity, or progression of spasms compared with saline treatment. These data suggest that metabolic inhibition of glycolysis or ketogenesis does not reduce infantile spasms in the NMDA model. The study further validates the betamethasone-NMDA model in terms of its behavioral and electrographic resemblance to human IS and supports its use for preclinical drug screening.
Topics: 3-Hydroxybutyric Acid; Adrenocorticotropic Hormone; Animals; Animals, Newborn; Betamethasone; Deoxyglucose; Disease Models, Animal; Female; N-Methylaspartate; Pregnancy; Rats; Seizures; Spasm; Spasms, Infantile
PubMed: 34784103
DOI: 10.1002/epi4.12561 -
European Journal of Nuclear Medicine... Jan 2022To assess whether a radiomics and machine learning (ML) model combining quantitative parameters and radiomics features extracted from simultaneous multiparametric F-FDG...
PURPOSE
To assess whether a radiomics and machine learning (ML) model combining quantitative parameters and radiomics features extracted from simultaneous multiparametric F-FDG PET/MRI can discriminate between benign and malignant breast lesions.
METHODS
A population of 102 patients with 120 breast lesions (101 malignant and 19 benign) detected on ultrasound and/or mammography was prospectively enrolled. All patients underwent hybrid F-FDG PET/MRI for diagnostic purposes. Quantitative parameters were extracted from DCE (MTT, VD, PF), DW (mean ADC of breast lesions and contralateral breast parenchyma), PET (SUVmax, SUVmean, and SUVminimum of breast lesions, as well as SUVmean of the contralateral breast parenchyma), and T2-weighted images. Radiomics features were extracted from DCE, T2-weighted, ADC, and PET images. Different diagnostic models were developed using a fine Gaussian support vector machine algorithm which explored different combinations of quantitative parameters and radiomics features to obtain the highest accuracy in discriminating between benign and malignant breast lesions using fivefold cross-validation. The performance of the best radiomics and ML model was compared with that of expert reader review using McNemar's test.
RESULTS
Eight radiomics models were developed. The integrated model combining MTT and ADC with radiomics features extracted from PET and ADC images obtained the highest accuracy for breast cancer diagnosis (AUC 0.983), although its accuracy was not significantly higher than that of expert reader review (AUC 0.868) (p = 0.508).
CONCLUSION
A radiomics and ML model combining quantitative parameters and radiomics features extracted from simultaneous multiparametric F-FDG PET/MRI images can accurately discriminate between benign and malignant breast lesions.
Topics: Breast Neoplasms; Female; Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Retrospective Studies; Support Vector Machine
PubMed: 34374796
DOI: 10.1007/s00259-021-05492-z -
Cellular and Molecular Life Sciences :... Dec 2021Recent studies have shown the significance of metabolic reprogramming in immune and stromal cell function. Yet, the metabolic reconfiguration of RA macrophages (MΦs) is...
Recent studies have shown the significance of metabolic reprogramming in immune and stromal cell function. Yet, the metabolic reconfiguration of RA macrophages (MΦs) is incompletely understood during active disease and in crosstalk with other cell types in experimental arthritis. This study elucidates a distinct regulation of glycolysis and oxidative phosphorylation in RA MΦs compared to fibroblast (FLS), although PPP (Pentose Phosphate pathway) is similarly reconfigured in both cell types. 2-DG treatment showed a more robust impact on impairing the RA M1 MΦ-mediated inflammatory phenotype than IACS-010759 (IACS, complexli), by reversing ERK, AKT and STAT1 signaling, IRF8/3 transcription and CCL2 or CCL5 secretion. This broader inhibitory effect of 2-DG therapy on RA M1 MΦs was linked to dysregulation of glycolysis (GLUT1, PFKFB3, LDHA, lactate) and oxidative PPP (NADP conversion to NADPH), while both compounds were ineffective on oxidative phosphorylation. Distinctly, in RA FLS, 2-DG and IACS therapies constrained LPS/IFNγ-induced AKT and JNK signaling, IRF5/7 and fibrokine expression. Disruption of RA FLS metabolic rewiring by 2-DG or IACS therapy was accompanied by a reduction of glycolysis (HIF1α, PFKFB3) and suppression of citrate or succinate buildup. We found that 2-DG therapy mitigated CIA pathology by intercepting joint F480iNOSMΦ, Vimentin fibroblast and CD3T cell trafficking along with downregulation of IRFs and glycolytic intermediates. Surprisingly, IACS treatment was inconsequential on CIA swelling, cell infiltration, M1 and Th1/Th17 cytokines (IFN-γ/IL-17) and joint glycolytic mediators. Collectively, our results indicate that blockade of glycolysis is more effective than inhibition of complex 1 in CIA, in part due to its effectiveness on the MΦ inflammatory phenotype.
Topics: Animals; Antimetabolites; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Movement; Cytokines; Deoxyglucose; Fibroblasts; Glycolysis; Humans; Inflammation; Macrophages; Mice; Mice, Inbred DBA; Pentose Phosphate Pathway; Phenotype; Th17 Cells
PubMed: 34705053
DOI: 10.1007/s00018-021-03978-5 -
Seminars in Nuclear Medicine Nov 2020Immune checkpoint blockade has demonstrated the ability to modulate the immune system to produce durable responses in a wide range of cancers and has significantly... (Review)
Review
Immune checkpoint blockade has demonstrated the ability to modulate the immune system to produce durable responses in a wide range of cancers and has significantly impacted the standard of care. However, many cancer patients still do not respond to immune checkpoint blockade or have a limited duration of antitumor responses. Moreover, immune-related adverse events caused by immune checkpoint blockade can be severe and debilitating for some patients, limiting continuation of therapy and resulting in severe autoimmune conditions. Standard-of-care conventional anatomic imaging modalities and tumor response criteria have limitations to adequately assess tumor responses, especially early in the course of therapy, for risk-adapted clinical management to inform care of patients treated with immunotherapy. Molecular imaging with position emission tomography (PET) provides a noninvasive functional biomarker of tumor response, and of immune activation, for patients on immune-based therapies to help address these needs. F-FDG (FDG) PET/CT is readily available clinically and a number of studies have evaluated the use of this agent for assessment of prognosis, treatment response and immune activation for patients treated with immune checkpoint blockade. In this review paper, we discuss the current oncologic applications and imaging needs of cancer immunotherapy, recent studies applying FDG PET/CT for tumor response assessment, and evaluation of immune-related adverse events for improving clinical management. We largely focus on metastatic melanoma; however, we generalize where applicable to immunotherapy in other tumor types. We also briefly discuss PET imaging and quantitation as well as emerging non-FDG PET imaging radiotracers for cancer immunotherapy imaging.
Topics: Fluorodeoxyglucose F18; Humans; Immunotherapy; Neoplasms; Positron Emission Tomography Computed Tomography; Prognosis
PubMed: 33059821
DOI: 10.1053/j.semnuclmed.2020.06.001 -
European Journal of Nuclear Medicine... Sep 2023
Topics: Humans; Muscles; Positron-Emission Tomography; Positron Emission Tomography Computed Tomography; Gallium Radioisotopes; Fluorodeoxyglucose F18; Quinolines; Fibroblasts
PubMed: 37272954
DOI: 10.1007/s00259-023-06263-8 -
PET Clinics Jan 2022Malignant lymphomas are a family of heterogenous disorders caused by clonal proliferation of lymphocytes. F-FDG-PET has proven to provide essential information for... (Review)
Review
Malignant lymphomas are a family of heterogenous disorders caused by clonal proliferation of lymphocytes. F-FDG-PET has proven to provide essential information for accurate quantification of disease burden, treatment response evaluation, and prognostication. However, manual delineation of hypermetabolic lesions is often a time-consuming and impractical task. Applications of artificial intelligence (AI) may provide solutions to overcome this challenge. Beyond segmentation and detection of lesions, AI could enhance tumor characterization and heterogeneity quantification, as well as treatment response prediction and recurrence risk stratification. In this scoping review, we have systematically mapped and discussed the current applications of AI (such as detection, classification, segmentation as well as the prediction and prognostication) in lymphoma PET.
Topics: Artificial Intelligence; Fluorodeoxyglucose F18; Humans; Lymphoma
PubMed: 34809864
DOI: 10.1016/j.cpet.2021.09.006 -
BioMed Research International 2020Our previous research suggests that 3-deoxyglucosone (3DG), formed in the caramelization course and Maillard reactions in food, is an independent factor for the...
Our previous research suggests that 3-deoxyglucosone (3DG), formed in the caramelization course and Maillard reactions in food, is an independent factor for the development of prediabetes. Since the relationship between type 2 diabetes (T2D) and intestinal microbiota is moving from correlation to causality, we investigated the alterations in the composition and function of the intestinal microbiota in 3DG-induced prediabetic rats. Rats were given 50 mg/kg 3DG by intragastric administration for two weeks. Microbial profiling in faeces samples was determined through the 16S rRNA gene sequence. The glucagon-like peptide 2 (GLP-2) and lipopolysaccharide (LPS) levels in plasma and intestinal tissues were measured by ELISA and Limulus test, respectively. 3DG treatment did not significantly change the richness and evenness but affected the composition of intestinal microbiota. At the phylum level, 3DG treatment increased the abundance of nondominant bacteria but did not cause the change of the dominant bacteria. Meanwhile, the abundance of the family and genus and the family and order and its attachment to the class were overrepresented in the 3DG group. The bacteria of genus, genus, and family and its attachment to order were apparently more abundant in the control group. In addition, 45 KEGG pathways were altered after two-week intragastric administration of 3DG. Among these KEGG pathways, 13 KEGG pathways were involved in host metabolic function related to amino acid metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, and metabolism of terpenoids and polyketides. Moreover, the increased LPS levels and the decreased GLP-2 concentration in plasma and intestinal tissues were observed in 3DG-treated rats, together with the impaired fasting glucose and oral glucose tolerance. The alterations in composition and function of the intestinal microbiota were observed in 3DG-treated rats, which provides a possible mechanism linking exogenous 3DG intake to the development of prediabetes.
Topics: Administration, Oral; Animals; Deoxyglucose; Gastrointestinal Microbiome; Glucagon-Like Peptide 2; Glucose Tolerance Test; Lipopolysaccharides; Male; Prediabetic State; RNA, Ribosomal, 16S; Rats, Sprague-Dawley
PubMed: 32908918
DOI: 10.1155/2020/8406846 -
JACC. Cardiovascular Imaging Feb 2022
Topics: Endocarditis; Fluorodeoxyglucose F18; Humans; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Predictive Value of Tests
PubMed: 34656474
DOI: 10.1016/j.jcmg.2021.09.002