scholarly journals Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations

2021 ◽  
Author(s):  
Alexander Panossian ◽  
Sara Abdelfatah ◽  
Thomas Efferth
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Network Pharmacology ◽  
Pharmacokinetic Studies ◽  
Red Ginseng ◽  
Toxic Concentration ◽  
Wide Range ◽  
Ginsenoside Rg5

Numerous in vitro studies on isolated cells have been conducted to uncover the molecular mechanisms of action of Panax ginseng Meyer root extracts and purified ginsenosides. However, the concentrations of ginsenosides and the extracts used in these studies were much higher than detected in pharmacokinetic studies in humans and animals orally administered with ginseng preparations at therapeutic doses. Our study aimed to assess: (a) the effects of ginsenoside Rg5, the major "rare" ginsenoside of Red Ginseng, on gene expression in the murine neuronal cell line HT22 in a wide range of concentrations, from 10-4 to 10-18 M, and (b) the effects of differentially expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in HT22 cells after treatment with ginsenoside Rg5. Ginsenoside Rg5 exhibits soft-acting effects on gene expression of neuronal cells in a wide range of physiological concentrations and strong reversal impact at high (toxic) concentration: significant up- or downregulation of expression of about 300 genes at concentrations from 10-6 M to 10-18 M, and dramatically increased both the number of differentially expressed target genes (up to 1670) and the extent of their expression (fold changes compared to unexposed cells) at a toxic concentration of 10-4 M. Network pharmacology analyses of genes expression profiles using Ingenuity pathway analysis (IPA) software showed that at low physiological concentrations, ginsenoside Rg5 has the potential to activate the biosynthesis of cholesterol and to exhibit predictable effects in senescence, neuroinflammation, apoptosis, and immune response, suggesting soft-acting, beneficial effects on organismal death, movement disorders, and cancer.

scholarly journals Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations

2021 ◽  
Vol 14 (10) ◽  
pp. 999
Author(s):  
Alexander Panossian ◽  
Sara Abdelfatah ◽  
Thomas Efferth
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Network Pharmacology ◽  
Pharmacokinetic Studies ◽  
Red Ginseng ◽  
Toxic Concentration ◽  
Wide Range ◽  
Ginsenoside Rg5

Numerous in vitro studies on isolated cells have been conducted to uncover the molecular mechanisms of action of Panax ginseng Meyer root extracts and purified ginsenosides. However, the concentrations of ginsenosides and the extracts used in these studies were much higher than those detected in pharmacokinetic studies in humans and animals orally administered with ginseng preparations at therapeutic doses. Our study aimed to assess: (a) the effects of ginsenoside Rg5, the major “rare” ginsenoside of Red Ginseng, on gene expression in the murine neuronal cell line HT22 in a wide range of concentrations, from 10−4 to 10−18 M, and (b) the effects of differentially expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in HT22 cells after treatment with ginsenoside Rg5. Ginsenoside Rg5 exhibits soft-acting effects on gene expression of neuronal cells in a wide range of physiological concentrations and strong reversal impact at high (toxic) concentration: significant up- or downregulation of expression of about 300 genes at concentrations from 10−6 M to 10−18 M, and dramatically increased both the number of differentially expressed target genes (up to 1670) and the extent of their expression (fold changes compared to unexposed cells) at a toxic concentration of 10−4 M. Network pharmacology analyses of genes’ expression profiles using ingenuity pathway analysis (IPA) software showed that at low physiological concentrations, ginsenoside Rg5 has the potential to activate the biosynthesis of cholesterol and to exhibit predictable effects in senescence, neuroinflammation, apoptosis, and immune response, suggesting soft-acting, beneficial effects on organismal death, movement disorders, and cancer.

scholarly journals Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics

2021 ◽  
Author(s):  
Alexander Panossian ◽  
Sara Abdelfatah ◽  
Thomas Efferth
Keyword(s):  
Gene Expression ◽  
Heart Diseases ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Ginseng Root ◽  
Network Pharmacology ◽  
Pharmacokinetic Studies ◽  
Red Ginseng ◽  
Positive Effects ◽  
Wide Range

Panax ginseng C.A.Mey. is an adaptogenic plant traditionally used to enhance mental and physical capacities in cases of weakness, exhaustion, tiredness, loss of concentration, and during recovery. According to ancient records, Red Ginseng root preparations enhance longevity with long-term intake. Recent pharmacokinetic studies of ginsenosides in humans and our in vitro study in neuronal cells suggest that ginsenosides are effective when their level in blood is shallow - at concentrations from 10-6 to 10-18 M. In the present study, we compared the effects of Red Ginseng root preparation HRG80TM(HRG) at concentrations from 0.01 to 10,000 ng/ml with effects of White Ginseng (WG) and purified ginsenosides Rb1, Rg3, Rg5 and Rk1 on gene expression of isolated hippocampal neurons. The aim of this study was to predict the effects of differently expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in murine HT22 cells after treatment with ginseng preparations. Ingenuity pathway downstream/upstream analysis (IPA) was performed with datasets of significantly up-or downregulated genes, and expected effects on cellular function and disease were identified by IPA software. Ginsenosides Rb1, Rg3, Rg5, and Rk1 have substantially various effects on gene expression profiles (signatures) and are different from signatures of HRG and WG. Furthermore, the signature of HRG is changed significantly with dilution from 10000 to 0.01 ng/ml. Network pharmacological analyses of gene expression profiles showed that HRG exhibits predictable positive effects in neuroinflammation, senescence, apoptosis, and immune response, suggesting beneficial soft-acting effects in cancer, gastrointestinal, and endocrine systems diseases and disorders in a wide range of low concentrations in blood.

scholarly journals Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics

2021 ◽  
Vol 14 (10) ◽  
pp. 1010
Author(s):  
Alexander Panossian ◽  
Sara Abdelfatah ◽  
Thomas Efferth
Keyword(s):  
Gene Expression ◽  
Heart Diseases ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Ginseng Root ◽  
Network Pharmacology ◽  
Pharmacokinetic Studies ◽  
Red Ginseng ◽  
Positive Effects ◽  
Wide Range

Panax ginseng C.A.Mey. is an adaptogenic plant traditionally used to enhance mental and physical capacities in cases of weakness, exhaustion, tiredness, or loss of concentration, and during recovery. According to ancient records, red ginseng root preparations enhance longevity with long-term intake. Recent pharmacokinetic studies of ginsenosides in humans and our in vitro study in neuronal cells suggest that ginsenosides are effective when their levels in blood is low—at concentrations from 10−6 to 10−18 M. In the present study, we compared the effects of red ginseng root preparation HRG80TM(HRG) at concentrations from 0.01 to 10,000 ng/mL with effects of white ginseng (WG) and purified ginsenosides Rb1, Rg3, Rg5 and Rk1 on gene expression in isolated hippocampal neurons. The aim of this study was to predict the effects of differently expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in murine HT22 cells after treatment with ginseng preparations. Ingenuity pathway downstream/upstream analysis (IPA) was performed with datasets of significantly up- or downregulated genes, and expected effects on cellular function and disease were identified by IPA software. Ginsenosides Rb1, Rg3, Rg5, and Rk1 have substantially varied effects on gene expression profiles (signatures) and are different from signatures of HRG and WG. Furthermore, the signature of HRG is changed significantly with dilution from 10,000 to 0.01 ng/mL. Network pharmacological analyses of gene expression profiles showed that HRG exhibits predictable positive effects in neuroinflammation, senescence, apoptosis, and immune response, suggesting beneficial soft-acting effects in cancer, gastrointestinal, and endocrine systems diseases and disorders in a wide range of low concentrations in blood.

scholarly journals Insight into Molecular Profile Changes after Skeletal Muscle Contusion Using Microarray and Bioinformatics Analyses

2020 ◽  
Author(s):  
Na Li ◽  
Ru-feng Bai ◽  
Chun Li ◽  
Li-hong Dang ◽  
Qiu-xiang Du ◽  
...  
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Healing Process ◽  
Differentially Expressed ◽  
Molecular Profile ◽  
Wound Age ◽  
Functional Modules

Abstract Background: Muscle trauma frequently occurs in daily life. However, the molecular mechanisms of muscle healing, which partly depend on the extent of the damage, are not well understood. This study aimed to investigate gene expression profiles following mild and severe muscle contusion, and to provide more information about the molecular mechanisms underlying the repair process.Methods: A total of 33 rats were divided randomly into control (n = 3), mild contusion (n = 15), and severe contusion (n = 15) groups; the contusion groups were further divided into five subgroups (1, 3, 24, 48, and 168 h post-injury; n = 3 per subgroup). Then full genome microarray of RNA isolated from muscle tissue was performed to access the gene expression changes during healing process.Results: A total of 2,844 and 2,298 differentially expressed genes were identified in the mild and severe contusion groups, respectively. The analysis of the overlapping differentially expressed genes showed that there are common mechanisms of transcriptomic repair of mild and severe contusion within 48 h post-contusion. This was supported by the results of principal component analysis, hierarchical clustering, and weighted gene co‐expression network analysis of the 1,620 coexpressed genes in mildly and severely contused muscle. From these analyses, we discovered that the gene profiles in functional modules and temporal clusters were similar between the mild and severe contusion groups; moreover, the genes showed time-dependent patterns of expression, which allowed us to identify useful markers of wound age. We then performed an analysis of the functions of genes (including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway annotation, and protein–protein interaction network analysis) in the functional modules and temporal clusters, and the hub genes in each module–cluster pair were identified. Interestingly, we found that genes downregulated within 24−48 h of the healing process were largely associated with metabolic processes, especially oxidative phosphorylation of reduced nicotinamide adenine dinucleotide phosphate, which has been rarely reported. Conclusions: These results improve our understanding of the molecular mechanisms underlying muscle repair, and provide a basis for further studies of wound age estimation.

scholarly journals Characterization of Metabolites and Transcripts Involved in Flower Pigmentation in Primula vulgaris

2020 ◽  
Vol 11 ◽  
Author(s):  
Long Li ◽  
Jing Ye ◽  
Houhua Li ◽  
Qianqian Shi
Keyword(s):  
Gene Expression ◽  
Metabolic Networks ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Flower Color ◽  
Myb Transcription Factor ◽  
High Accumulation ◽  
Primula Vulgaris ◽  
Wide Range

Primula vulgaris exhibits a wide range of flower colors and is a valuable ornamental plant. The combination of flavonols/anthocyanins and carotenoids provides various colorations ranging from yellow to violet-blue. However, the complex metabolic networks and molecular mechanisms underlying the different flower colors of P. vulgaris remain unclear. Based on comprehensive analysis of morphological anatomy, metabolites, and gene expression in different-colored flowers of P. vulgaris, the mechanisms relating color-determining compounds to gene expression profiles were revealed. In the case of P. vulgaris flower color, hirsutin, rosinin, petunidin-, and cyanidin-type anthocyanins and the copigment herbacetin contributed to the blue coloration, whereas peonidin-, cyandin-, and delphinidin-type anthocyanins showed high accumulation levels in pink flowers. The color formation of blue and pink were mainly via the regulation of F3′5′H (c53168), AOMT (c47583, c44905), and 3GT (c50034). Yellow coloration was mainly due to gossypetin and carotenoid, which were regulated by F3H (c43100), F3 1 (c53714), 3GT (c53907) as well as many carotenoid biosynthetic pathway-related genes. Co-expression network and transient expression analysis suggested a potential direct link between flavonoid and carotenoid biosynthetic pathways through MYB transcription factor regulation. This work reveals that transcription changes influence physiological characteristics, and biochemistry characteristics, and subsequently results in flower coloration in P. vulgaris.

scholarly journals Bioinformatics Analysis Reveals the Potential Diagnostic Biomarkers for Abdominal Aortic Aneurysm

2021 ◽  
Vol 8 ◽  
Author(s):  
Xinsheng Xie ◽  
En ci Wang ◽  
Dandan Xu ◽  
Xiaolong Shu ◽  
Yu fei Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Aortic Aneurysms ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Abdominal Aortic

Objectives: Abdominal aortic aneurysms (AAAs) are associated with high mortality rates. The genes and pathways linked with AAA remain poorly understood. This study aimed to identify key differentially expressed genes (DEGs) linked to the progression of AAA using bioinformatics analysis.Methods: Gene expression profiles of the GSE47472 and GSE57691 datasets were acquired from the Gene Expression Omnibus (GEO) database. These datasets were merged and normalized using the “sva” R package, and DEGs were identified using the limma package in R. The functions of these DEGs were assessed using Cytoscape software. We analyzed the DEGs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Protein–protein interaction networks were assembled using Cytoscape, and crucial genes were identified using the Cytoscape plugin, molecular complex detection. Data from GSE15729 and GSE24342 were also extracted to verify our findings.Results: We found that 120 genes were differentially expressed in AAA. Genes associated with inflammatory responses and nuclear-transcribed mRNA catabolic process were clustered in two gene modules in AAA. The hub genes of the two modules were IL6, RPL21, and RPL7A. The expression levels of IL6 correlated positively with RPL7A and negatively with RPL21. The expression of RPL21 and RPL7A was downregulated, whereas that of IL6 was upregulated in AAA.Conclusions: The expression of RPL21 or RPL7A combined with IL6 has a diagnostic value for AAA. The novel DEGs and pathways identified herein might provide new insights into the underlying molecular mechanisms of AAA.

scholarly journals Construction and analysis of mRNA, miRNA, lncRNA, and TF regulatory networks reveal the key genes in prostate cancer

2018 ◽  
Author(s):  
Su-Liang Li ◽  
Yun Ye ◽  
Sheng-Yu Wang
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Scale Effects ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Regulation Of Transcription ◽  
Normal Prostate ◽  
Ppi Networks

AbstractPurpose: Prostate cancer (PCa) causes a common male urinary system malignant tumour, and the molecular mechanisms of PCa remain poorly understood. This study aims to investigate the underlying molecular mechanisms of PCa with bioinformatics.Methods: Original gene expression profiles were obtained from the GSE64318 and GSE46602 datasets in the Gene Expression Omnibus (GEO). We conducted differential screens of the expression of genes (DEGs) between two groups using the R software limma package. The interactions between the differentially expressed miRNAs, mRNAs and lncRNAs were predicted and merged with the target genes. Co-expression of the miRNAs, lncRNAs and mRNAs were selected to construct the mRNA-miRNA and-lncRNA interaction networks. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the DEGs. The protein-protein interaction (PPI) networks were constructed, and the transcription factors were annotated. The expression of hub genes in the TCGA datasets was verified to improve the reliability of our analysis.Results: The results demonstrated that 60 miRNAs, 1578 mRNAs and 61 lncRNAs were differentially expressed in PCa. The mRNA-miRNA-lncRNA networks were composed of 5 miRNA nodes, 13 lncRNA nodes, and 45 mRNA nodes. The DEGs were mainly enriched in the nuclei and cytoplasm and were involved in the regulation of transcription, related to sequence-specific DNA binding, and participated in the regulation of the PI3K-Akt signalling pathway. These pathways are related to cancer and focal adhesion signalling pathways. Furthermore, we found that 5 miRNAs, 6 lncRNAs, 6 mRNAs and 2 TFs play important regulatory roles in the interaction network. The expression levels of EGFR, VEGFA, PIK3R1, DLG4, TGFBR1 and KIT were significantly different between PCa and normal prostate tissue.Conclusion: Based on the current study, large-scale effects of interrelated mRNAs, miRNAs, lncRNAs, and TFs were revealed and a model for predicting the mechanism of PCa was provided. This study provides new insight for the exploration of the molecular mechanisms of PCa and valuable clues for further research.

scholarly journals Identification and Verification of Core Genes in Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Houxi Xu ◽  
Yuzhu Ma ◽  
Jinzhi Zhang ◽  
Jialin Gu ◽  
Xinyue Jing ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Malignant Neoplasm ◽  
Gene Expression Profiles ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Core Genes

Colorectal cancer, a malignant neoplasm that occurs in the colorectal mucosa, is one of the most common types of gastrointestinal cancer. Colorectal cancer has been studied extensively, but the molecular mechanisms of this malignancy have not been characterized. This study identified and verified core genes associated with colorectal cancer using integrated bioinformatics analysis. Three gene expression profiles (GSE15781, GSE110223, and GSE110224) were downloaded from the Gene Expression Omnibus (GEO) databases. A total of 87 common differentially expressed genes (DEGs) among GSE15781, GSE110223, and GSE110224 were identified, including 19 upregulated genes and 68 downregulated genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed for common DEGs using clusterProfiler. These common DEGs were significantly involved in cancer-associated functions and signaling pathways. Then, we constructed protein-protein interaction networks of these common DEGs using Cytoscape software, which resulted in the identification of the following 10 core genes: SST, PYY, CXCL1, CXCL8, CXCL3, ZG16, AQP8, CLCA4, MS4A12, and GUCA2A. Analysis using qRT-PCR has shown that SST, CXCL8, and MS4A12 were significant differentially expressed between colorectal cancer tissues and normal colorectal tissues (P<0.05). Gene Expression Profiling Interactive Analysis (GEPIA) overall survival (OS) has shown that low expressions of AQP8, ZG16, CXCL3, and CXCL8 may predict poor survival outcome in colorectal cancer. In conclusion, the core genes identified in this study contributed to the understanding of the molecular mechanisms involved in colorectal cancer development and may be targets for early diagnosis, prevention, and treatment of colorectal cancer.

scholarly journals Gene Expression Profiling of Blood in Ruptured Intracranial Aneurysms: in Search of Biomarkers

2013 ◽  
Vol 33 (7) ◽  
pp. 1025-1031 ◽  
Author(s):  
Joanna Pera ◽  
Michal Korostynski ◽  
Slawomir Golda ◽  
Marcin Piechota ◽  
Jaroslaw Dzbek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intracranial Aneurysms ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Relevant Information ◽  
Specific Pattern ◽  
Differentially Expressed ◽  
Specific Gene ◽  
Ruptured Intracranial Aneurysms

The molecular mechanisms underlying the systemic response to subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms (RAs) are not fully understood. We investigated whether the analysis of gene expression in peripheral blood could provide clinically relevant information regarding the biologic consequences of SAH. Transcriptomics were performed using Illumina HumanHT-12v4 microarrays for 43 RA patients and 18 controls (C). Differentially expressed transcripts were analyzed for overrepresented functional groups and blood cell type-specific gene expression. The set of differentially expressed transcripts was validated using quantitative polymerase chain reaction in an independent group of subjects (15 RA patients and 14 C). There were 135 differentially expressed genes (false discovery rate ≤1%, absolute fold change ≤1.7): the abundant levels of 78 mRNAs increased and 57 mRNAs decreased. Among RA patients, transcripts specific to T lymphocyte subpopulations were downregulated, whereas those related to monocytes and neutrophils were upregulated. Expression profiles of a set of 16 genes and lymphocyte-to-monocyte-and-neutrophil gene expression ratios distinguished RA patients from C. These results indicate that SAH from RAs strongly influences the transcription profiles of blood cells. A specific pattern of these changes suggests suppression in lymphocyte response and enhancements in monocyte and neutrophil activities. This is probably related to the immunodepression observed in SAH.

scholarly journals Identification of Differentially Expressed Genes and Pathways for Abdominal Fat Deposition in Ovariectomized and Sham-Operated Chickens

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 155 ◽  
Author(s):  
Xiaopeng Mu ◽  
Xiaoyan Cui ◽  
Ranran Liu ◽  
Qinghe Li ◽  
Maiqing Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Abdominal Fat ◽  
Fat Deposition ◽  
Differentially Expressed ◽  
Feed Conversion ◽  
Fat Percentage ◽  
Steroid Biosynthesis

Ovariectomy results in improved meat quality (growth rate, tenderness, and flavor) of broilers. However, some negative effects increased (abdominal fat (AF) deposition, low feed conversion, etc.) have also been reported. In this study, the gene expression profiles of AF tissue in ovariectomized and sham-operated chickens were determined to identify differentially expressed genes (DEGs) and pathways to explore the molecular mechanisms underlying AF accumulation. Comparing the ovariectomized group and the sham-operated group, the abdominal fat weight (AFW) and abdominal fat percentage (AFP) were increased significantly (p < 0.05) at 14 and 19 weeks after ovariectomy. According to the gene expression profiling analysis, 108 DEGs of fat metabolism were screened from 1461 DEGs. Among them, ABCA1, ABCACA, LPL, CREB1, PNPLA2, which are involved in glycerolipid—or steroid—associated biological processes, and the hormone receptor genes, ESR1 and PRLR, were down-regulated significantly in the ovariectomized group compared to the sham-operated group (p < 0.05). Conversely, CETP, DGAT2, DHCR24, HSD17B7 and MSMO1, were significantly up-regulated (p < 0.05) after ovariectomy. Based on the DEGs, the glycerolipid metabolism, steroid biosynthesis, and other signaling pathways (MAPK, TGF-β, and adhesion pathways, etc.) were enriched, which may also contribute to the regulation of AF deposition. Our data suggest that AF deposition was significantly increased in ovariectomized chickens by the down-regulation of the decomposition genes of glycerolipid metabolism, which inhibits AF degradation, and the up-regulation of steroid biosynthesis genes, which increases fat accumulation. These findings provide new insights into the molecular mechanisms of fat deposition in the ovariectomized chickens.

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