scholarly journals Clinical and Genetic Characteristics of Thymoma Patients With Autoimmune Hepatitis and Myocarditis

2022 ◽  
Vol 11 ◽  
Author(s):  
Xin-tao Yu ◽  
Lei Yu ◽  
Xin Du ◽  
Zhen Yu ◽  
Xing-guo Yang ◽  
...  

BackgroundOur study investigated a special series of thymoma with autoimmune hepatitis and myocarditis and tried to reveal the gene expression profiles of this series of thymoma.MethodsFrom 2011 to 2019, a total of 13 special thymoma patients presented with autoimmune hepatitis and myocarditis, accounting for about 1.26% of thymoma patients undergoing surgery in Beijing TongRen Hospital. Clinical data were retrospectively collected. All samples were harvested during surgical procedures, and analyzed to identify changes in gene expression using the CapitalBio mRNA microarray analysis, the Whole exome sequencing analysis (WES), qPCR and immunohistochemistry (IHC) tools.ResultsAfter surgery, patient symptoms were relieved gradually. Levels of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate transaminase (AST), and alanine amiotransferase (ALT) increased to some extent within 1 to 3 months after surgery, and fluctuated, and then, gradually decreased close to normal within 6 months after surgery. Enrichment analysis of Kyoto Genome and Genome Encyclopedia (KEGG) pathway was performed and enrichment results were visualized. It indicated that gene expression of 5 signaling pathways, including cell cycle and p53 signaling pathway, were generally abnormal. P53 expression was up-regulated in all tumor tissues. However, IHC and qPCR analysis showed that there was no significant difference in p21 expression between normal and tumor tissue. Results of WES showed that only one driver gene-MDM4 amplified 4 fold in 53.2% thymoma cells. Further qPCR and IHC analysis confirmed the up-regulation of the expression of p53 and mdm4 in 13 thymoma patients with autoimmune hepatitis and myocarditis.ConclusionOur study reveals the clinical and genetic characteristics of thymoma patients with autoimmune hepatitis and myocarditis. For this special category of thymoma, the up-regulation of p53 and mdm4 plays an important role in the occurrence of thymoma and autoimmune hepatitis/myocarditis.

2020 ◽  
Author(s):  
Kwan-Sik Min ◽  
Jong-Ju Park ◽  
So-Yun Lee ◽  
Munkhzaya Byambaragchaa ◽  
Myung-Hwa Kang

Abstract Background: Equine chorionic gonadotropin (eCG) induces super-ovulation in laboratory animals. Notwithstanding its extensive usage, limited information is available regarding the differences between the in vivo effects of natural eCG (N-eCG) and recombinant eCG (R-eCG). This study aimed to investigate the gene expression profiles of mouse ovaries upon stimulation with N-eCG and R-eCG produced from CHO-suspension (CHO-S) cells. R-eCG gene was constructed and transfected into CHO-S cells and quantified. Subsequently, we determined the metabolic clearance rate (MCR) of N-eCG and R-eCG up to 24 h after intravenous administration through the mice tail vein and identified differentially expressed genes in both ovarian tissues, via quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC).Results: R-eCG was markedly expressed initially after transfection and maintained until recovery on day 9. Glycan chains were substantially modified in R-eCG protein produced from CHO-S cells and eliminated through PNGase F treatment. The MCR was higher for R-eCG than for N-eCG, and no significant difference was observed after 60 min. Notwithstanding their low concentrations, R-eCG and N-eCG were detected in the blood at 24h post-injection. Microarray analysis of ovarian tissue revealed that 20 of 12,816 genes assessed therein were significantly up-regulated and 43 genes were down-regulated by >2-fold in the group that received R-eCG (63 [0.49%] differentially regulated genes in total). The microarray results were concurrent with and hence validated by those of RT-PCR, qRT-PCR, and IHC analyses.Conclusions: The present results indicate that R-eCG can be adequately produced through a cell-based expression system through post-translational modification of eCG and can induce ovulation in vivo. These results provide novel insights into the molecular mechanisms underlying the up- or down-regulation of specific ovarian genes and the production of R-eCG with enhanced biological activity in vivo.


2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Wang ◽  
Quanwei Lu ◽  
Hui Song ◽  
Nan Hu ◽  
Yangyang Wei ◽  
...  

Grain filling is a crucial process for crop yield and quality. Certain studies already gained insight into the molecular mechanism of grain filling. However, it is unclear whether epigenetic modifications are associated with grain filling in foxtail millet. Global DNA methylation and transcriptome analysis were conducted in foxtail millet spikelets during different stages to interpret the epigenetic effects of the grain filling process. The study employed the whole-genome bisulfite deep sequencing and advanced bioinformatics to sequence and identify all DNA methylation during foxtail millet grain filling; the DNA methylation-mediated gene expression profiles and their involved gene network and biological pathway were systematically studied. One context of DNA methylation, namely, CHH methylation, was accounted for the largest percentage, and it was gradually increased during grain filling. Among all developmental stages, the methylation levels were lowest at T2, followed by T4, which mainly occurred in CHG. The distribution of differentially methylated regions (DMR) was varied in the different genetic regions for three contexts. In addition, gene expression was negatively associated with DNA methylation. Evaluation of the interconnection of the DNA methylome and transcriptome identified some stage-specific differentially expressed genes associated with the DMR at different stages compared with the T1 developmental stage, indicating the potential function of epigenetics on the expression regulation of genes related to the specific pathway at different stages of grain development. The results demonstrated that the dynamic change of DNA methylation plays a crucial function in gene regulation, revealing the potential function of epigenetics in grain development in foxtail millet.


2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Shuin Park ◽  
Sara Ranjbarvaziri ◽  
Fides Lay ◽  
Peng Zhao ◽  
Aldons J Lusis ◽  
...  

Fibroblasts are a heterogeneous population of cells that function within the injury response mechanisms across various tissues. Despite their importance in pathophysiology, the effects of different genetic backgrounds on fibroblast contribution to the development of disease has yet to be addressed. It has previously been shown that mice in the Hybrid Mouse Diversity Panel, which consists of 110 inbred mouse strains, display a spectrum in severity of cardiac fibrosis in response to chronic treatment of isoproterenol (ISO). Here, we characterized cardiac fibroblasts (CFbs) from three different mouse strains (C57BL/6J, C3H/HeJ, and KK/HIJ) which exhibited varying degrees of fibrosis after ISO treatment. The select strains of mice underwent sham or ISO treatment via intraperitoneally-implanted osmotic pumps for 21 days. Masson’s Trichrome staining showed significant differences in fibrosis in response to ISO, with KK/HIJ mice demonstrating the highest levels, C3H/HeJ exhibiting milder levels, and C57BL/6J demonstrating little to no fibrosis. When CFbs were isolated and cultured from each strain, the cells demonstrated similar traits at the basal level but responded to ISO stimuli in a strain-specific manner. Likewise, CFbs demonstrated differential behavior and gene expression in vivo in response to ISO. ISO treatment caused CFbs to proliferate similarly across all strains, however, immunofluorescence staining showed differential levels of CFb activation. Additionally, RNA-sequencing analysis revealed unique gene expression profiles of all three strains upon ISO treatment. Our study depicts the phenotypic heterogeneity of CFbs across different strains of mice and our results suggest that ISO-induced cardiac fibrosis is a complex process that is independent of fibroblast proliferation and is mainly driven by the activation/inhibition of genes involved in pro-fibrotic pathways.


2021 ◽  
pp. 1-14
Author(s):  
Danbi Seo ◽  
Jungwook Roh ◽  
Yeonsoo Chae ◽  
Wanyeon Kim

Lung cancer accounts for a large proportion of cancer-related deaths worldwide. Personalized therapeutic medicine based on the genetic characteristics of non-small cell lung cancer (NSCLC) is a promising field, and discovering clinically applicable biomarkers of NSCLC is required. LINC00472 is a long non-coding RNA and has been recently suggested to be a biomarker of NSCLC, but little is known of its mechanism in NSCLC. Thus, the current study was performed to document changes in gene expression after LINC00472 overexpression in NSCLC cells. As a result of cell viability and migration assay, LINC00472 downregulated cell survival, proliferation, and motility. Transcriptome sequencing analysis showed 3,782 genes expression were changed in LINC00472 overexpressing cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed most genes were associated with intracellular metabolism. The PPP1R12B, RGS5, RBM5, RBL2, LDLR and PTPRM genes were upregulated by LINC00472 overexpression and these genes functioned as tumor suppressors in several cancers. In contrast, SPSB1, PCNA, CD24, CDK5, CDC25A, and EIF4EBP1 were downregulated by LINC00472, and they functioned as oncogenes in various cancers. Consequently, the function of LINC00472 in tumorigenesis might be related to changes in the expressions of other oncogenes and tumor suppressors.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Laurent-Emmanuel Monfoulet ◽  
Caroline Buffiere ◽  
Geoffrey Istas ◽  
Claire Dufour ◽  
Carine le Bourvelec ◽  
...  

AbstractFood matrix is known to interact with some dietary constituents and microconstituents during digestion. These interactions may potentially affect the metabolism and bioavailability of some compounds, and as a consequence modulate their biological effects. In this context, the aim of this study was to determine the effect of apple food matrix on the bioavailability of flavan-3-ols and on the ability of these compounds to modulate the nutrigenomic response to a high fat challenge in minipigs.Adult male Yucatan minipigs (n = 5) were assigned to a random treatment sequence of high-fat meals non supplemented or supplemented with 250 g of raw apple, 250 g of apple puree or 1.4 g of apple polyphenols extract, with a 7-days washout period between each treatment. Each supplementation provided 155 mg flavan-3-ol monomers. At each treatment period, fasting- and 1h-, 2h-, 3h-postprandial blood samples were collected, and the concentration in flavan-3-ol monomers was measured on hydrolyzed serum, using UPLC-Q-TOF MS. The ability of apple-derived products to modulate the postprandial gene expression profile was assessed and compared in circulating PBMCs collected at 3 h after consumption of the four tested meals using a microarray analysis.Results show that the apple matrix did not affect the kinetic of the postprandial absorption of flavan-3-ol monomers. The total flavan-3-ols concentrations measured at peak were significantly higher in the extract (x1.75), suggesting an impact of the apple matrix on flavan-3-ols absorption. However, no significant difference in total flavanols was observed between raw apple and apple puree.Principal Component Analysis of the microarray data from PBMCs identified three distinct clusters of gene expression patterns: one corresponding to gene expression profiles after the high-fat meal, one for meal supplemented with raw apples or apple puree, and a third cluster for meal supplemented with polyphenol extract. A set of 309 genes was identified as differentially expressed by apple-derived products compared to high-fat meal alone, including 93 modulated with the three apple products. The variations in gene expression were similar for only 75% of the 93 genes, suggesting that the apple matrix affects the nutrigenomic response to flavan-3-ols. A bioinformatics analysis revealed that genes affected by apple-derived products are involved in inflammation and leukocyte transendothelial migration, suggesting a beneficial impact of apple-derived products.In conclusion, these results raise awareness for considering the impact of food matrix on the biological responsiveness of polyphenols in future nutritional studies.


2020 ◽  
Author(s):  
Kwan-Sik Min ◽  
Jong-Ju Park ◽  
So-Yun Lee ◽  
Munkhzaya Byambaragchaa ◽  
Myung-Hwa Kang

Abstract Background: Equine chorionic gonadotropin (eCG) induces super-ovulation in laboratory animals. Notwithstanding its extensive usage, limited information is available regarding the differences between the in vivo effects of native eCG and recombinant eCG (rec-eCG). This study aimed to investigate the gene expression profiles of mouse ovaries upon stimulation with native eCG and rec-eCG produced from CHO-suspension (CHO-S) cells. eCG and rec-eCG were cloned and transfected into CHO-S cells and quantified. Thereafter, we determined the metabolic clearance rate (MCR) of native eCG and rec-eCG up to 24 h after intravenous administration through the tail vein and identified differentially expressed genes in both ovarian tissues, via quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC).Results: Rec-eCG was markedly up-regulated initially after transfection and maintained until recovery on day 9. Oligosaccharide chains were substantially modified in rec-eCG protein produced from CHO-S cells and eliminated through PNGase F treatment. The MCR was slightly lower for rec-eCG than for eCG, and no significant difference was observed after 60 min. Notwithstanding their low concentration, rec-eCG and native eCG were detected in the blood at 24h post-injection. Microarray analysis of ovarian tissue revealed that 20 of 12,816 genes assessed therein were significantly up-regulated and 43 genes were down-regulated by >2-fold in the group receiving rec-eCG (63 [0.49%] differentially regulated genes in total). The microarray results were concurrent with and hence validated by those of RT-PCR, qRT-PCR, and IHC analyses.Conclusions: The present results indicate that rec-eCG can be adequately produced through a cell-based expression system through post-translational modification of eCG and can induce ovulation in vivo. These results provide novel insights into the molecular mechanisms underlying the up- or down-regulation of specific ovarian genes and the production of rec-eCG with enhanced biological activity in vivo.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Kwan-Sik Min ◽  
Jong-Ju Park ◽  
So-Yun Lee ◽  
Munkhzaya Byambaragchaa ◽  
Myung-Hwa Kang

Abstract Background Equine chorionic gonadotropin (eCG) induces super-ovulation in laboratory animals. Notwithstanding its extensive usage, limited information is available regarding the differences between the in vivo effects of natural eCG (N-eCG) and recombinant eCG (R-eCG). This study aimed to investigate the gene expression profiles of mouse ovaries upon stimulation with N-eCG and R-eCG produced from CHO-suspension (CHO-S) cells. R-eCG gene was constructed and transfected into CHO-S cells and quantified. Subsequently, we determined the metabolic clearance rate (MCR) of N-eCG and R-eCG up to 24 h after intravenous administration through the mice tail vein and identified differentially expressed genes in both ovarian tissues, via quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Results R-eCG was markedly expressed initially after transfection and maintained until recovery on day 9. Glycan chains were substantially modified in R-eCG protein produced from CHO-S cells and eliminated through PNGase F treatment. The MCR was higher for R-eCG than for N-eCG, and no significant difference was observed after 60 min. Notwithstanding their low concentrations, R-eCG and N-eCG were detected in the blood at 24 h post-injection. Microarray analysis of ovarian tissue revealed that 20 of 12,816 genes assessed therein were significantly up-regulated and 43 genes were down-regulated by > 2-fold in the group that received R-eCG (63 [0.49%] differentially regulated genes in total). The microarray results were concurrent with and hence validated by those of RT-PCR, qRT-PCR, and IHC analyses. Conclusions The present results indicate that R-eCG can be adequately produced through a cell-based expression system through post-translational modification of eCG and can induce ovulation in vivo. These results provide novel insights into the molecular mechanisms underlying the up- or down-regulation of specific ovarian genes and the production of R-eCG with enhanced biological activity in vivo.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15587-e15587
Author(s):  
Sharon Wilks ◽  
Kristi McIntyre ◽  
Linda K. Han ◽  
Michelina Marie Cairo ◽  
Julie Barone ◽  
...  

e15587 Background: Interval breast cancers (BC) are detected between routine screening mammograms and are associated with worse prognosis, requiring more aggressive treatment compared to screen-detected BC identified during scheduled mammograms. Identifying molecular differences between interval BC and screen detected BC may lay the foundation for developing novel therapies. In this study, we compared gene expression profiles of interval BC to screen-detected BC. Methods: This analysis included a subset of 2260 patients enrolled in the FLEX Registry (NCT03053193), an ongoing, prospective study evaluating primary tumor samples from stage I-III BC patients who receive 70-gene risk of recurrence testing (70GS), 80-gene molecular subtyping (80GS), and consent to collection of clinically annotated full genome data. Interval BC were diagnosed < 12 months following a normal screening mammogram. Breast tumors were classified by 70GS as having a Low Risk (LR) or High Risk (HR) of distant metastases. Tumors were classified as Luminal, HER2, or Basal type by 80GS. Differential gene expression analysis was performed with limma and subsequent pathway analysis with DAVID and GSEA. Differences in the proportion of 70GS or 80GS results, 70GS index, and Ki67 were assessed by Chi-squared test or t-test. Results: In this study, 81% (1834/2260) of patients had screen-detected BC and 19% (426) had interval BC. A higher proportion of interval BC (51%) were HR compared to screen-detected BC (44%; p = 0.01). Most LR tumors were invasive ductal carcinoma (78% interval and 73% screen-detected) and over 99% were Luminal type. Between the two LR groups, 70GS indices were similar and there was no significant difference in transcriptional profiles. Basal and HER2 subtypes were more frequent among HR interval BC compared to screen-detected BC (p = 0.03). HR interval BC had 70GS indices of higher risk compared to HR screen-detected BC (p = 0.02). Differentially expressed genes in HR interval BC compared to HR screen-detected BC were associated with MYC signaling and mitosis, which was concordant with higher Ki67 by IHC (p = 0.007). Conclusions: This real-world data analysis shows interval BC are not all biologically High Risk and can be further stratified by the 70GS, aiding in treatment decisions. Preliminary results suggest that following 70GS LR classification, there is no biological difference between interval BC and screen-detected BC. In contrast, there are distinct biological processes associated with HR interval BC, which may have implications in the management of these cancers. Clinical trial information: NCT03053193.


2020 ◽  
Vol 19 ◽  
pp. 117693511989991
Author(s):  
Po-Ming Chen ◽  
Jian-Rong Li ◽  
Chun-Chi Liu ◽  
Feng-Yao Tang ◽  
En-Pei Isabel Chiang

RNA-Sequencing (RNA-Seq), the most commonly used sequencing application tool, is not only a method for measuring gene expression but also an excellent media to detect important structural variants such as single nucleotide variants (SNVs), insertion/deletion (Indels), or fusion transcripts. The Cancer Genome Atlas (TCGA) contains genomic data from a variety of cancer types and also provides the raw data generated by TCGA consortium. p53 is among the top 10 somatic mutations associated with hepatocellular carcinoma (HCC). The aim of the present study was to analyze concordant different gene profiles and the priori defined set of genes based on p53 mutation status in HCC using RNA-Seq data. In the study, expression profile of 11 799 genes on 42 paired tumor and adjacent normal tissues was collected, processed, and further stratified by the mutated versus normal p53 expression. Furthermore, we used a knowledge-based approach Gene Set Enrichment Analysis (GSEA) to compare between normal and p53 mutation gene expression profiles. The statistical significance (nominal P value) of the enrichment score (ES) genes was calculated. The ranked gene list that reflects differential expression between p53 wild-type and mutant genotypes was then mapped to metabolic process by KEGG, an encyclopedia of genes and genomes to assign functional meanings. These approaches enable us to identify pathways and potential target gene/pathways that are highly expressed in p53 mutated HCC. Our analysis revealed 2 genes, the hexokinase 2 ( HK2) and Enolase 1 ( ENO1), were conspicuous of red pixel in the heatmap. To further explore the role of these genes in HCC, the overall survival plots by Kaplan-Meier method were performed for HK2 and ENO1 that revealed high HK2 and ENO1 expression in patients with HCC have poor prognosis. These results suggested that these glycolysis genes are associated with mutated-p53 in HCC that may contribute to poor prognosis. In this proof-of-concept study, we proposed an approach for identifying novel potential therapeutic targets in human HCC with mutated p53. These approaches can take advantage of the massive next-generation sequencing (NGS) data generated worldwide and make more out of it by exploring new potential therapeutic targets.


Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 998 ◽  
Author(s):  
Xiufang Dong ◽  
Hang Qi ◽  
Baoyu He ◽  
Di Jiang ◽  
Beiwei Zhu

Sea cucumber (Apostichopus japonicus) is an economically significant species in China having great commercial value. It is challenging to maintain the textural properties during thermal processing due to the distinctive physiochemical structure of the A. japonicus body wall (AJBW). In this study, the gene expression profiles associated with tenderization in AJBW were determined at 0 h (CON), 1 h (T_1h), and 3 h (T_3h) after treatment at 37 °C using Illumina HiSeq™ 4000 platform. Seven-hundred-and-twenty-one and 806 differentially expressed genes (DEGs) were identified in comparisons of T_1h vs. CON and T_3h vs. CON, respectively. Among these DEGs, we found that two endogenous proteases—72 kDa type IV collagenase and matrix metalloproteinase 16 precursor—were significantly upregulated that could directly affect the tenderness of AJBW. In addition, 92 genes controlled four types of physiological and biochemical processes such as oxidative stress response (3), immune system process (55), apoptosis (4), and reorganization of the cytoskeleton and extracellular matrix (30). Further, the RT-qPCR results confirmed the accuracy of RNA-sequencing analysis. Our results showed the dynamic changes in global gene expression during tenderization and provided a series of candidate genes that contributed to tenderization in AJBW. This can help further studies on the genetics/molecular mechanisms associated with tenderization.


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