ATF4, DLX3, FRA1, MSX2, C/EBP-ζ, and C/EBP-α Shape the Molecular Basis of Therapeutic Effects of Zoledronic Acid in Bone Disorders

2020 ◽  
Vol 20 (18) ◽  
pp. 2274-2284
Author(s):  
Faroogh Marofi ◽  
Jalal Choupani ◽  
Saeed Solali ◽  
Ghasem Vahedi ◽  
Ali Hassanzadeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zoledronic Acid ◽  
Mrna Expression ◽  
Promoter Methylation ◽  
Methylation Level ◽  
Target Genes ◽  
Osteoblastic Differentiation ◽  
Therapeutic Effects ◽  
Significant Difference ◽  
Scheduled Time

Objective: Zoledronic Acid (ZA) is one of the common treatment choices used in various boneassociated conditions. Also, many studies have investigated the effect of ZA on Osteoblastic-Differentiation (OSD) of Mesenchymal Stem Cells (MSCs), but its clear molecular mechanism(s) has remained to be understood. It seems that the methylation of the promoter region of key genes might be an important factor involved in the regulation of genes responsible for OSD. The present study aimed to evaluate the changes in the mRNA expression and promoter methylation of central Transcription Factors (TFs) during OSD of MSCs under treatment with ZA. Materials and Methods: MSCs were induced to be differentiated into the osteoblastic cell lineage using routine protocols. MSCs received ZA during OSD and then the methylation and mRNA expression levels of target genes were measured by Methylation Specific-quantitative Polymerase Chain Reaction (MS-qPCR) and real.time PCR, respectively. The osteoblastic differentiation was confirmed by Alizarin Red Staining and the related markers to this stage. Results: Gene expression and promoter methylation level for DLX3, FRA1, ATF4, MSX2, C/EBPζ, and C/EBPa were up or down-regulated in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21. ATF4, DLX3, and FRA1 genes were significantly up-regulated during the OSD processes, while the result for MSX2, C/EBPζ, and C/EBPa was reverse. On the other hand, ATF4 and DLX3 methylation levels gradually reduced in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21, while the pattern was increasing for MSX2 and C/EBPa. The methylation pattern of C/EBPζ was upward in untreated groups while it had a downward pattern in ZA-treated groups at the same scheduled time. The result for FRA1 was not significant in both groups at the same scheduled time (days 0-21). Conclusion: The results indicated that promoter-hypomethylation of ATF4, DLX3, and FRA1 genes might be one of the mechanism(s) controlling their gene expression. Moreover, we found that promoter-hypermethylation led to the down-regulation of MSX2, C/EBP-ζ and C/EBP-α. The results implicate that ATF4, DLX3 and FRA1 may act as inducers of OSD while MSX2, C/EBP-ζ and C/EBP-α could act as the inhibitor ones. We also determined that promoter-methylation is an important process in the regulation of OSD. However, yet there was no significant difference in the promoter-methylation level of selected TFs in ZA-treated and control cells, a methylation- independent pathway might be involved in the regulation of target genes during OSD of MSCs.

scholarly journals D-GPM: A Deep Learning Method for Gene Promoter Methylation Inference

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 807 ◽  
Author(s):  
Pan ◽  
Liu ◽  
Wen ◽  
Liu ◽  
Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Deep Learning ◽  
Promoter Methylation ◽  
Methylation Level ◽  
Target Genes ◽  
Gene Promoter ◽  
Support Vector ◽  
Whole Genome ◽  
Expression Levels ◽  
Gene Expression Levels

Whole-genome bisulfite sequencing generates a comprehensive profiling of the gene methylation levels, but is limited by a high cost. Recent studies have partitioned the genes into landmark genes and target genes and suggested that the landmark gene expression levels capture adequate information to reconstruct the target gene expression levels. This inspired us to propose that the methylation level of the promoters in landmark genes might be adequate to reconstruct the promoter methylation level of target genes, which would eventually reduce the cost of promoter methylation profiling. Here, we propose a deep learning model called Deep-Gene Promoter Methylation (D-GPM) to predict the whole-genome promoter methylation level based on the promoter methylation profile of the landmark genes from The Cancer Genome Atlas (TCGA). D-GPM-15%-7000 × 5, the optimal architecture of D-GPM, acquires the least overall mean absolute error (MAE) and the highest overall Pearson correlation coefficient (PCC), with values of 0.0329 and 0.8186, respectively, when testing data. Additionally, the D-GPM outperforms the regression tree (RT), linear regression (LR), and the support vector machine (SVM) in 95.66%, 92.65%, and 85.49% of the target genes by virtue of its relatively lower MAE and in 98.25%, 91.00%, and 81.56% of the target genes based on its relatively higher PCC, respectively. More importantly, the D-GPM predominates in predicting 79.86% and 78.34% of the target genes according to the model distribution of the least MAE and the highest PCC, respectively.

scholarly journals D-GPM: a deep learning method for gene promoter methylation inference

2018 ◽  
Author(s):  
Xingxin Pan ◽  
Biao Liu ◽  
Xingzhao Wen ◽  
Yulu Liu ◽  
Xiuqing Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Deep Learning ◽  
Promoter Methylation ◽  
Methylation Level ◽  
Target Genes ◽  
Gene Promoter ◽  
Support Vector ◽  
Whole Genome ◽  
Expression Levels ◽  
Gene Expression Levels

AbstractBackgroundGene promoter methylation plays a critical role in a wide range of biological processes, such as transcriptional expression, gene imprinting, X chromosome inactivation,etc. Whole-genome bisulfite sequencing generates a comprehensive profiling of the gene methylation levels but is limited by a high cost. Recent studies have partitioned the genes into landmark genes and target genes and suggested that the landmark gene expression levels capture adequate information to reconstruct the target gene expression levels. Moreover, the methylation level of the promoter is usually negatively correlated with its corresponding gene expression. This result inspired us to propose that the methylation level of the promoters might be adequate to reconstruct the promoter methylation level of target genes, which would eventually reduce the cost of promoter methylation profiling.ResultsHere, we developed a deep learning model (D-GPM) to predict the whole-genome promoter methylation level based on the methylation profile of the landmark genes. We benchmarked D-GPM against three machine learning methods, namely, linear regression (LR), regression tree (RT) and support vector machine (SVM), based on two criteria: the mean absolute deviation (MAE) and the Pearson correlation coefficient (PCC). After profiling the methylation beta value (MBV) dataset from the TCGA, with respect to MAE and PCC, we found that D-GPM outperforms LR by 9.59% and 4.34%, RT by 27.58% and 22.96% and SVM by 6.14% and 3.07% on average, respectively. For the number of better-predicted genes, D-GPM outperforms LR in 92.65% and 91.00%, RT in 95.66% and 98.25% and SVM in 85.49% and 81.56% of the target genes.ConclusionsD-GPM acquires the least overall MAE and the highest overall PCC on MBV-te compared to LR, RT, and SVM. For a genewise comparative analysis, D-GPM outperforms LR, RT, and SVM in an overwhelming majority of the target genes, with respect to the MAE and PCC. Most importantly, D-GPM predominates among the other models in predicting a majority of the target genes according to the model distribution of the least MAE and the highest PCC for the target genes.

scholarly journals The values of AHCY and CBS promoter methylation on the diagnosis of cerebral infarction in Chinese Han population

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiaodong Li ◽  
Shufang Bu ◽  
Ran Ran Pan ◽  
Cong Zhou ◽  
Kun Qu ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Promoter Methylation ◽  
Methylation Level ◽  
Young Group ◽  
Control Group ◽  
Case Group ◽  
Middle Aged ◽  
Aged Group ◽  
Significant Difference ◽  
And Control

Abstract Background The goal of our study is to investigate whether the methylation levels of AHCY and CBS promoters are related to the risk of cerebral infarction by detecting the methylation level of AHCY and CBS genes. Methods We extracted peripheral venous blood from 152 patients with cerebral infarction and 152 gender- and age-matched healthy controls, and determined methylation levels of AHCY and CBS promoters using quantitative methylation-specific polymerase chain reaction. We used the percentage of methylation reference (PMR) to indicate gene methylation level. Results We compared the promoter methylation levels of two genes (AHCY and CBS) in peripheral blood DNA between the cerebral infarction case group and the control group. Our study showed no significant difference in AHCY promoter methylation between case and control. Subgroup analysis by gender showed that the methylation level of AHCY in males in the case group was lower than that in the control group, but the difference was not statistically significant in females. In a subgroup analysis by age, there was no significant difference in the AHCY methylation level between the case and control in the young group (≤44 years old). However, the level of AHCY gene methylation in the middle-aged group (45–59 years old) was significantly higher and the aged group (≥60 years old) was significantly lower than that in the control groups. However, CBS promoter methylation levels were significantly lower in the case group than in the control group (median PMR: 70.20% vs 104.10%, P = 3.71E-10). In addition, the CBS methylation levels of males and females in the case group were significantly lower than those in the control group (male: 64.33% vs 105%, P = 2.667E-08; female: 78.05% vs 102.8%, P = 0.003). We also found that the CBS levels in the young (23–44), middle-aged (45–59), and older (60–90) groups were significantly lower than those in the control group (young group: 69.97% vs 114.71%; P = 0.015; middle-aged group: 56.04% vs 91.71%; P = 6.744E-06; older group: 81.6% vs 119.35%; P = 2.644E-04). Our ROC curve analysis of CBS hypomethylation showed an area under the curve of 0.713, a sensitivity of 67.4%, and a specificity of 74.0%. Conclusion Our study suggests that hypomethylation of the CBS promoter may be closely related to the risk of cerebral infarction and may be used as a non-invasive diagnostic biomarker for cerebral infarction.

THE SEASONAL EFFECTS ON IMF CONTENT OF FAS mRNA EXPRESION IN MUSCLES OF MONGOLIAN SHEEP

2018 ◽  
Vol 21 (02) ◽  
pp. 43-48 ◽  
Author(s):  
Erkigul B ◽  
Gerelt B ◽  
Damdinsuren L
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Expression Level ◽  
Seasonal Effects ◽  
Seasonal Effect ◽  
Triceps Brachii ◽  
Significant Difference ◽  
Fas Mrna ◽  
Mongolian Sheep ◽  
Imf Content

This survey’s aim was to investigate the seasonal effect of Fatty acid synthesis (FAS) expression on intramuscular fat (IMF) content in grazing Mongolian, Ujumqin and grain-fed Ujumqin sheep. Different skeletal muscles of sheep (biceps femoris, longissimus dorsi and triceps brachii) were sampled to measure IMF content and total RNA was extracted to determine FAS mRNA expression levels by real-time PCR. The result revealed that: (1) The difference in IMF content in the muscles of Mongolian sheep grazed in summer was observed to be much higher than sheep grazed in winter (p<0.01). Also there was significant difference in IMF content in the muscles of Ujumqin sheep grazed in summer than winter (p<0.05). The mRNA expression level of FAS in muscles of winter grazing Mongolian sheep was significantly higher than summer (p<0.05). The seasonal effects on IMF content in the muscles and it’s FAS mRNA gene expression was all negative correlated between the sheep breeds. Accordingly, grazing Mongolian sheep’s FAS gene expression level was very high negatively correlated (r=-0.964). This study suggested that grazing Mongolian and Ujumqin sheep able to store large amount of IMF under depends on seasonal effects.

Alteration of ADCC-related genes as a novel predictor of efficacy of cetuximab (cet)-based chemotherapy in patients (pts) with metastatic colorectal cancer (mCRC) (JACCRO CC-05/06 AR).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 589-589
Author(s):  
Yu Sunakawa ◽  
Dongyun Yang ◽  
Shu Cao ◽  
Chris Roberts ◽  
Eva Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nk Cells ◽  
Mrna Expression ◽  
Nk Cell ◽  
Direct Sequencing ◽  
Recursive Partitioning ◽  
Progression Free Survival ◽  
Therapeutic Effects ◽  
Phase Ii Trials ◽  
Functional Polymorphisms

589 Background: Cet exerts its therapeutic effects not only through EGFR-signal blockade but also through antibody-dependent cell-mediated cytotoxicity (ADCC), mainly driven by natural killer (NK) cells. NK cells play a key role by releasing granzyme B (GZMB) via perforin (PRF1)-formed pores, leading to tumor cell apoptosis. CD137 (TNFRSF9) is expressed on NK cells, which regulates activation and proliferation of T cells. We hypothesized that genetic alteration in NK cell-mediated ADCC may serve as a predictor of cet in mCRC pts. Methods: Genomic DNA and RNA were isolated from tumor tissues of 77 KRAS exon2 wild-type (wt) pts enrolled in 2 Japanese phase II trials of cet plus oxaliplatin-based chemotherapy as 1st-line therapy, FOLFOX (n= 28/57, UMIN000004197) and SOX (n= 49/67, UMIN000007022). We evaluated associations between functional polymorphisms and gene expression of TNFRSF9, GZMB, and PRF1, and clinical outcome using PCR-based direct sequencing and molecular profiling panel (HTG EdgeSeq Oncology Biomarker Panel) based on next generation sequencing. Recursive partitioning (RP) method was also used to explore the associations. Results: In the population with median age of 63 years and follow-up time of 31.4 months (m), response rate (RR), median progression-free survival (PFS), and overall survival (OS) were 73 %, 10.0 m, and 33.9 m, respectively. TNFRSF9 rs161826 (A > G) was associated with PFS but not RR or OS in both univariate (any G vs A/A: 9.2 m vs 13.8 m, HR 1.75, P= 0.030) and multivariate analyses (P= 0.050). No association of rs161826 with gene expression was observed. PRF1 polymorphisms were not associated with outcome, while high PRF1 mRNA expression had association with shorter PFS (9.7 m vs 18.0 m, HR 2.60, P= 0.028), and it remained significant in multivariate analysis (P= 0.002). In RP analysis, PRF1 mRNA expression also showed significant association with PFS. Conclusions: TNFRSF9 rs161826 and PRF1 gene expression are significantly associated with PFS in pts with KRAS wt mCRC treated with cet-based chemotherapy. Gene expression and variation in NK cell-mediated ADCC may predict efficacy of cet (UMIN000010635). Clinical trial information: UMIN000010635.

scholarly journals High Levels of APOBEC3B Gene Expression Contribute to Poor Prognosis in Multiple Myeloma Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3897-3897
Author(s):  
Valeriy V Lyzogubov ◽  
Pingping Qu ◽  
Cody Ashby ◽  
Adam Rosenthal ◽  
Antje Hoering ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Poor Prognosis ◽  
Target Genes ◽  
Plasma Cells ◽  
Nuclear Fraction ◽  
Advisory Committees ◽  
Significant Difference

Abstract Introduction: Poor prognosis and drug resistance in multiple myeloma (MM) is associated with increased mutational load. APOBEC3B is a major contributor to mutagenesis, especially in myeloma patients with t(14;16) MAF subgroup. It was shown recently that presence of the APOBEC signature at diagnosis is an independent prognostic factor for progression free survival (PFS) and overall survival (OS). We hypothesized that high levels of APOBEC3B gene expression at diagnosis may also have a prognostic impact in myeloma. To consider APOBEC3B as a potential target for therapy more studies are necessary to understand how APOBEC3B expression is regulated and how APOBEC3B generates mutations. Methods: Gene expression profiling (GEP, U133 Plus 2.0) of MM patients was performed. APOBEC3B gene expression levels were investigated in plasma cells of healthy donors (HD; n=34), MGUS (n=154), smoldering myeloma (SMM; n=219), MM low risk (LR; n=739), MM high risk (HR; n=129), relapsed MM (RMM; n=74), and primary plasma cell leukemia (pPCL; n=19) samples. The samples from relapse were taken on or after the progression/relapse date but within 30 days after progression/relapse from Total Therapy trials 3, 4, 5 & 6. GEP70 score was used to separate samples into LR and HR groups. We also investigated APOBEC3B expression in different MM molecular subgroups and used logrank statistics with covariate frequency distribution to determine an optimal cut off APOBEC3B expression value. Gene expression was compared in cases with low expression of APOBEC3B (log2<7.5) and high expression of APOBEC3B (log2>10), and an optimal cut-point in APOBEC3B expression was identified with respect to PFS. To explore the role of MAF and the non-canonical NF-ĸB pathway we performed functional studies using a cellular model of MAF downregulation. TRIPZ lentiviral shRNA MAF knockdown in the RPMI8226 cell lines was used to explore MAF-dependent genes. NF-ĸB proteins, p52 and RelB, were investigated in the nuclear fraction by immunoblot analysis. Results: Expression of APOBEC3B in HD control samples (log2=10.9) was surprisingly higher than in MGUS (log2=9.51), SMM (log2=9.09), and LR (log2=9.40) and was comparable to HR (log2=10.4) and RMM (log2=10.6) groups. Expression levels of APOBEC3B were gradually increased as disease progressed from SMM to pPCL. The high expression of APOBEC3B in HD places plasma cells at risk of APOBEC induced mutagenesis where the regulation of APOBEC3B function is compromised. The correlation between APOBEC3B expression and GEP70 score in MM was 0.37, and there was a significant difference in APOBEC3B expression between GEP70 high and low risk groups (p=0.0003). An optimal cut-point in APOBEC3B expression of log2=10.2 resulted in a significant difference in PFS (median 5.7 yr vs.7.4 yr; p=0.0086) and OS (median 9.1 yr vs. not reached; p<0.0001), between high and low expression. The highest APOBEC3B expression was detected in cases with a t(14;16). We analyzed t(14;16) cases with the APOBEC mutational signature and compared them to t(14;16) cases without the APOBEC signature and found elevated MAF (2-fold) and APOBEC3B (2.7-fold) gene expression in samples with the APOBEC signature. No APOBEC signature was detected in SMM cases, including those with a t(14;16). High APOBEC3B levels in myeloma patients was associated with overexpression of genes related to response to DNA damage and cell cycle control. Significant (p<0.05) increases of NF-κB target genes was seen in high APOBEC3B cases: TNFAIP3 (4.4-fold), NFKB2 (1.7-fold), NFKBIE (1.9-fold), RELB (1.4-fold), NFKBIA (2.0-fold), PLEK (2.5-fold), MALT1 (2.5-fold), WNT10A (2.4-fold). However, in t(14;16) cases there was no significant increase of NF-κB target genes except BIRC3 (2.5-fold) and MALT1 (2.0-fold). MAF downregulation in RPMI8226 cells did not lead to changes in NF-κB target gene expression but MAF-dependent genes were identified, including ETS1, SPP1, RUNX2, HGF, IGFBP2 and IGFBP3. Analysis of nuclear fraction of NF-ĸB proteins did not show significant changes in expression of p52 and RelB in RPMI8226 cells after MAF downregulation. Conclusions: Increased expression of APOBEC3B is a negative prognostic factor in multiple myeloma. MAF is a major factor regulating expression of APOBEC3B in the t(14;16) subgroup. NF-ĸB pathway activation is most likely involved in upregulation of APOBEC3B in non-t(14;16) subgroups. Disclosures Davies: TRM Oncology: Honoraria; MMRF: Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; ASH: Honoraria; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy. Morgan:Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Research Funding; Takeda: Consultancy, Honoraria.

scholarly journals Exploring the Pharmacological Mechanism of the modified Chinese medicine formulas “Shenfu-Linguizhugan decoction” treating Dilated cardiomyopathy Based on Network Pharmacology

2020 ◽  
Author(s):  
Wuxia Quan ◽  
Yandong Miao
Keyword(s):  
Gene Expression ◽  
Chinese Medicine ◽  
Dilated Cardiomyopathy ◽  
Target Genes ◽  
Muscle Disease ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Bioactive Components ◽  
Ppi Network ◽  
Compound Target

Abstract Background: Dilated cardiomyopathy (DCM) is a non-ischaemic cardiac muscle disease with structural and functional myocardial aberration can lead to extensive morbidity and mortality due to complications in particular heart failure and arrhythmia. Two classic Chinese medicine formulas, Shenfu decoction and Linguizhugan decoction, were both shown to exert therapeutic effects on heart disease. Thus, modified Shenfu and Linguizhugan decoction (SFLGZGD) is recommended for treatment DCM. However, its chemical and pharmacological characteristics remain to be elucidated. In the current study, a network pharmacology approach was applied to characterize the action mechanism and target genes of SFLGZGD on DCM.Methods: The gene expression of DCM was obtained from the Gene Expression Omnibus (GEO). All compounds were obtained from the correlative databases, and active mixture were selected according to their oral bioavailability (OB) and drug-likeness (DL) index. The potential targets of SFLGZGD were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database. The compound-target and target-pathway networks were constructed. The protein-protein interactive (PPI) network generated by R software was visualized by Cytoscape, and the topology scores, functional regions, and gene annotations were analyzed using plugins of Bisogenet and CytoNCA. The potential pathways related to target genes were determined by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.Results: A total of 963 differentially expressed genes (DEGs), including 538 upregulated genes and 425 downregulated, were obtained from GSE19303. A total of 636 ingredients in SFLGZGD were obtained, among which, 93 were chosen as bioactive components. The compound-target network included 10 bioactive components and 18 potential targets and a total of 1939 genes obtained in the PPI network, among them, a total of 16 genes were screened out. Moreover,129 terms on the GO analysis and six pathways obtained. Among these potential targets, EGFR, CDKN1A, MMP1, COL1A1, COL3A1, MMP3, ICAM1, and HSPB1 were identified as relatively high-degree targets.Conclusions: The network pharmacology-based approach in the current study has shown promising potential in identifying major therapeutic targets from TCM formulations. Besides, our study suggested that network pharmacology prediction may provide a useful tool for describing the molecular mechanism of SFLGZGD on DCM.

scholarly journals Correlation between miRNA-targeted-gene promoter methylation and miRNA regulation of target genes

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 21 ◽  
Author(s):  
Y-h Taguchi
Keyword(s):  
Gene Expression ◽  
Promoter Methylation ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Gene Promoter ◽  
Gene Expression Omnibus ◽  
Seed Region ◽  
Mirna Regulation ◽  
Regulate Gene Expression ◽  
Mirna Targeting

Background miRNA regulation of target genes and promoter methylation are known to be the primary mechanisms underlying the epigenetic regulation of gene expression. However, how these two processes cooperatively regulate gene expression has not been extensively studied.Methods Gene expression and promoter methylation profiles of 270 distinct human cell lines were obtained from Gene Expression Omnibus. P-values that describe both miRNA-targeted-gene promoter methylation and miRNA regulation of target genes were computed using the MiRaGE method proposed recently by the author.Results Significant changes in promoter methylation were associated with miRNA targeting. It was also found that miRNA-targeted-gene promoter hypomethylation was related to differential target gene expression; the genes with miRNA-targeted-gene promoter hypomethylation were downregulated during cell senescence and upregulated during cellular differentiation. Promoter hypomethylation was especially enhanced for genes targeted by miR-548 miRNAs, which are non-conserved, primate-specific miRNAs that are typically expressed at lower levels than the frequently investigated conserved miRNAs. miRNA-targeted-gene promoter methylation may also be related to the seed region features of miRNA.Conclusions It was found that promoter methylation was correlated to miRNA targeting. Furthermore, miRNA-targeted-gene promoter hypomethylation was especially enhanced in promoters of genes targeted by miRNAs that are not strongly expressed (e.g., miR-548 miRNAs) and was suggested to be highly related to some seed region features of miRNAs.

Electro-acupuncture on Nei Guan and Bai Hui: How Does It Affect GRP78 and Caspase-12 Gene Expression in Rats with Ischemia-Reperfusion Injury

2015 ◽  
Vol 3 (1) ◽  
pp. 65-69
Author(s):  
Jing Shen ◽  
Xiao-Ming Lei ◽  
Yang Song ◽  
Xing Tan ◽  
Qin Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reperfusion Injury ◽  
Mrna Expression ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Statistical Significance ◽  
Tunel Staining ◽  
Caspase 12 ◽  
Significant Difference ◽  
Operation Group

Abstract Objective: To observe the effects of electro-acupuncture (EA) on GRP78 and Caspase-12 gene expression in rats with ischemia- reperfusion injury (IRI) by stimulation on Nei Guan (PC6) and Bai Hui (GV20) points, so that to understand whether or not the protective effects of acupuncture is related to endocytoplasmic reticulum (ER) stressapoptosis passage. Methods: 50 rats were randomly assigned to five groups (10 in each group): normal control(A), pseudo-operation(B), operation(C), Edaravone(D) and EA(E). The ischemia/reperfusion model of middle cerebral artery occlusion (MCAO) was established by suture embolic method. TUNEL staining method was employed to measure the apoptosis index of nerve cells in rats. Real-time polymerase chain reaction (RT-PCR) was employed to measure the mRNA expression of GRP78 and Caspase-12. Results: Compared with normal group and pseudo-operation group, the apoptosis indexes and mRNA expression of GRP78 and Caspase-12 in operation group, Edaravone group and EA group were increased, with statistical significance（P＜0.05 or P＜0.01）; compared with operation group, the apoptosis indexes and Caspase-12 mRNA expression in Edaravone group and EA group were decreased（P＜0.05 or P＜0.01）, but GRP78 mRNA expression were increased（P＜0.01）; there were no significant difference between Edaravone group and EA group on the above indexes（P＞0.05). Conclusion: Acupuncture on Nei Guan and Bai Hui points could effectively suppress the nerve cell apoptosis in cerebral ischemia. The underlying mechanism might be related to upregulation of the ERS-protective GRP78 expression and downregulation of apoptosis-promotion Caspase-12 expression.

scholarly journals mRNA Expression of CYP2E1, CYP2A19, CYP1A2, HSD3B, SULT1A1 and SULT2A1 genes in surgically castrated, immunologically castrated, entire male and female pigs and correlation with androstenone, skatole, indole and Improvac-specific antibody levels

2019 ◽  
Vol 64 (No. 2) ◽  
pp. 89-97
Author(s):  
A. Kubešová ◽  
K. Šťastný ◽  
M. Faldyna ◽  
Z. Sládek ◽  
I. Steinhauserová ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Mrna Level ◽  
Boar Taint ◽  
Control Group ◽  
Mrna Levels ◽  
Large White ◽  
Specific Antibodies ◽  
Significant Difference ◽  
Entire Male

This study aimed to obtain a comprehensive look at the influence of castration on mRNA expression of the genes CYP2E1, CYP1A2, CYP2A19, HSD3B, SULT2A1 and SULT1A1 and their correlation with boar taint compounds (androstenone, skatole and indole) and Improvac-specific antibodies in a Czech commercial hybrid (Large White × Landrace (sow) × Duroc (boar)). Pigs were divided into groups of entire male pigs (NC), pigs castrated surgically (SC), pigs immunologically castrated and slaughtered 8 weeks (IM8) or 15 weeks (IM15) after the second dose of Improvac, and gilts (GI). Hepatic mRNA expression, measured by quantitative real-time polymerase chain reaction, differed significantly between the control group (entire male pigs) and all groups of interest for CYP2E1, CYP1A2 and CYP2A19. The mRNA level of the HSD3B gene differed significantly between the control group and the IM8, IM15 and GI groups. SULT1A1 gene expression was significantly different between the control group and the SC, IM8 and GI. In the case of SULT2A1, a significant difference was observed only between the control group and IM8 pigs. For all genes and treatment groups described above, expression was increased relative to the control. Significant differences for Improvac-specific antibodies between IM8 and IM15 groups were observed, indicating decrease of antibodies over time. Moreover, negative correlations between androstenone and mRNA levels of CYP2A19, CYP2E1 and SULT1A1 suggest that gene expression is suppressed.

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