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The time-sequential change in immune-related gene expression of the glioblastoma cell line after irradiation was evaluated to speculate the effect of combined immunotherapy with radiotherapy. The U373 MG glioblastoma cell line was irradiated with 6 Gy single dose. Next-generation sequencing (NGS) transcriptome data was generated before irradiation (control), and at 6, 24, and 48 hours post-irradiation. Immune-related pathways were analyzed at each time period. The same analyses were also performed for A549 lung cancer and U87 MG glioblastoma cell lines. Western blotting confirmed the programmed death-ligand 1 (PD-L1) expression levels over time. In the U373 MG cell line, neutrophil-mediated immunity, type I interferon signaling, antigen cross-presentation to T cell, and interferon-γ signals began to increase significantly at 24 hours and were upregulated until 48 hours after irradiation. The results were similar to those of the A549 and U87 MG cell lines. Without T cell infiltration, PD-L1 did not increase even with upregulated interferon-γ signaling in cancer cells. In conclusions, In the glioblastoma cell line, immune-related signals were significantly upregulated at 24 hours after irradiation. Therefore, the time interval between daily radiotherapy might not be enough to expect full immune responses by combined immune checkpoint inhibitors and newly infiltrating immune cells after irradiation.
The time-sequential change in immune-related gene expression of the glioblastoma cell line after irradiation was evaluated to speculate the effect of combined immunotherapy with radiotherapy. The U373 MG glioblastoma cell line was irradiated with 6 Gy single dose. Next-generation sequencing (NGS) transcriptome data was generated before irradiation (control), and at 6, 24, and 48 h post-irradiation. Immune-related pathways were analyzed at each time period. The same analyses were also performed for A549 lung cancer and U87 MG glioblastoma cell lines. Western blotting confirmed the programmed death-ligand 1 (PD-L1) expression levels over time. In the U373 MG cell line, neutrophil-mediated immunity, type I interferon signaling, antigen cross-presentation to T cell, and interferon- γ signals began to increase significantly at 24 h and were upregulated until 48 h after irradiation. The results were similar to those of the A549 and U87 MG cell lines. Without T cell infiltration, PD-L1 did not increase even with upregulated interferon- γ signaling in cancer cells. In conclusions, in the glioblastoma cell line, immune-related signals were significantly upregulated at 24 and 48 h after irradiation. Therefore, the time interval between daily radiotherapy might not be enough to expect full immune responses by combined immune checkpoint inhibitors and newly infiltrating immune cells after irradiation.
ObjectiveImproved molecular testing for common somatic mutations and the identification of mRNA and microRNA expression classifiers are promising approaches for the diagnosis of thyroid nodules. However, there is a need to improve the diagnostic accuracy of such tests for identifying thyroid cancer. Recent findings have revealed a crucial role of long non-coding RNAs (lncRNAs) in gene modulation. Thus, we aimed to evaluate the diagnostic value of selected lncRNAs from The Atlas of Noncoding RNAs in Cancer (TANRIC) thyroid cancer dataset.MethodsLncRNAs in TANRIC thyroid cancer dataset that have significantly increased or decreased expression in papillary thyroid cancer (PTC) tissues were selected as candidates for PTC diagnosis. Surgical specimens from patients who underwent thyroidectomy were used to determine the separation capability of candidate lncRNAs between malignant and benign nodules. Fine needle aspiration samples were obtained and screened for candidate lncRNAs to verify their diagnostic value.ResultsLRRC52-AS1, LINC02471, LINC02082, UNC5B-AS1, LINC02408, MPPED2-AS1, LNCNEF, LOC642484, ATP6V0E2-AS1, and LOC100129129 were selected as the candidate lncRNAs. LRRC52-AS1, LINC02082, UNC5B-AS1, MPPED2-AS1, LNCNEF, and LOC100129129 expression levels were significantly increased or decreased in malignant nodules compared to those in benign nodules and paired normal thyroid tissues. The combination of LRRC52-AS1, LINC02082, and UNC5B-AS1 showed favorable results for the diagnosis of PTC from fine needle aspirates, with 88.9% sensitivity and 100.0% specificity.ConclusionsLncRNA expression analysis is a promising approach for advancing the molecular diagnosis of PTC. Further studies are needed to identify lncRNAs of additional diagnostic value.
Background: Recently, the incidence of nonalcoholic fatty liver disease (NAFLD) has been growing rapidly. Corrected QT (QTc) interval prolongation is known to be associated with the risk of coronary heart disease. In this study, our aim was to establish whether NAFLD diagnosed using ultrasonography is associated with QTc intervals in Korean adult men. Methods: We recruited 1,155 Korean adult men who visited the Gangnam Severance Hospital health promotion center between October 2007 and July 2010. The participants underwent liver ultrasonography according to a standardized protocol, which confirmed the diagnosis of NAFLD. Standard electrocardiography was performed for analysis of the QTc interval. Results: The 1,155 participants had a mean QTc interval of 430.7±21.2 ms. Of them, 366 had a QTc interval ≥440 ms. The values of the QTc interval increased in relation to the severity of NAFLD. After adjustment for confounders, QT interval prolongation was significantly associated with NAFLD in the severe NAFLD group. The odds ratios were 2.102 (95% confidence interval [CI] 1.536-2.877) (model 1), 1.986 (95% CI 1.399-2.819) (model 2), and 1.960 (95% CI 1.347-2.851) (model 3). Conclusion: QTc interval prolongation was significantly associated with NAFLD severity in Korean adult men. Depending on the severity of NAFLD, QTc intervals were prolonged. QTc interval length is easily determined and may contribute to cardiovascular risk stratification in male patients with NAFLD.
Objectives Improved molecular testing for common somatic mutations and identification of mRNA and microRNA expression classifiers have emerged as the most promising approaches for diagnosis of thyroid nodules. However, it is necessary to effectively increase diagnostic accuracy further. Currently, lncRNA research has moved to the forefront of human cancer research, as recent findings have revealed a crucial role of lncRNAs in gene modulation. We evaluated the diagnostic value of the selected lncRNAs from The Atlas of Noncoding RNAs in Cancer (TANRIC) thyroid cancer dataset. Methods Using TANRIC thyroid cancer dataset, we compared 12,727 lncRNAs from the thyroid cancer tissues of 59 thyroid cancer patients with paired normal thyroid tissues. lncRNAs with significantly increased or decreased expression in thyroid cancer tissues were selected as candidates for thyroid cancer diagnosis. The expression levels of candidate lncRNAs were confirmed in patients with thyroid nodules who underwent surgery at the Severance Hospital. Subsequently, the candidate lncRNAs were applied to actual fine needle aspiration to verify their diagnostic value. Results LRRC52-AS1, LINC02471, LINC02082, UNC5B-AS1, LINC02408, MPPED2-AS1, LNCNEF, LOC642484, ATP6V0E2-AS1, and LOC100129129 were selected as candidates for thyroid cancer diagnosis. The expression levels of LRRC52-AS1, LINC02082, UNC5B-AS1, MPPED2-AS1, LNCNEF, and LOC100129129 were significantly increased or decreased in malignant nodules compared to their expression levels in benign nodules or paired normal thyroid tissues in our surgical tissue samples. The combination of LRRC52-AS1, LINC02082, and UNC5B-AS1 showed favorable results, with 89% sensitivity and 100% specificity, for thyroid cancer diagnosis using fine needle aspiration. Conclusions lncRNA expression analysis could be a promising approach for advancing molecular diagnosis of thyroid cancer. Further studies are needed to discover lncRNAs of additional diagnostic value. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
An enzyme mixture (EM) of glucose oxidase, glucosyl transferase, and fructosyl transferase can regulate glucose absorption into the body by converting carbohydrates in food to indigestible oligosaccharides. We evaluated the antidiabetic effects of repeated oral administration of EM in db/db mice. Seven-week-old db/db mice were divided into control, voglibose, and EM groups. Drugs were administered orally mixed with limited feed for one month. Glucose levels were measured every week. A meal tolerance test was conducted after overnight fasting, before the mice were sacrificed. There were no differences in body weight or food intake between the groups. EM treatment reduced blood glucose levels compared with those in the control group. Blood glucose levels during the meal tolerance test were significantly lower in the EM group than those in the control group. A significant decrease in triglyceride level and a tendency for decreased low-density lipoprotein were observed in the EM group compared with in the control group. The Bacteroidetes-to-Firmicutes ratio was higher in the EM group than that in the control group. EM may be useful for people at risk of hyperglycemia or diabetes who need to safely regulate their blood glucose levels. EM may also improve lipid and gut microbiota profiles.
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