scholarly journals Metabolic Reprogramming of Glioblastoma Cells during HCMV Infection Induces Secretome-Mediated Paracrine Effects in the Microenvironment

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 103
Author(s):  
Mark A. A. Harrison ◽  
Emily M. Hochreiner ◽  
Brooke P. Benjamin ◽  
Sean E. Lawler ◽  
Kevin J. Zwezdaryk
Keyword(s):  
Tumor Progression ◽  
Stromal Cells ◽  
Hcmv Infection ◽  
Underlying Mechanism ◽  
Metabolic Reprogramming ◽  
Paracrine Signaling ◽  
Paracrine Effects ◽  
Reverse Warburg Effect ◽  
The Impact ◽  
The Relationship

Glioblastoma (GBM) is an aggressive primary central nervous system neoplasia with limited therapeutic options and poor prognosis. Following reports of cytomegalovirus (HCMV) in GBM tumors, the anti-viral drug Valganciclovir was administered and found to significantly increase the longevity of GBM patients. While these findings suggest a role for HCMV in GBM, the relationship between them is not clear and remains controversial. Treatment with anti-viral drugs may prove clinically useful; however, their results do not explain the underlying mechanism between HCMV infection and GBM progression. We hypothesized that HCMV infection would metabolically reprogram GBM cells and that these changes would allow for increased tumor progression. We infected LN-18 GBM cells and employed a Seahorse Bioanalyzer to characterize cellular metabolism. Increased mitochondrial respiration and glycolytic rates were observed following infection. These changes were accompanied by elevated production of reactive oxygen species and lactate. Due to lactate’s numerous tumor-promoting effects, we examined the impact of paracrine signaling of HCMV-infected GBM cells on uninfected stromal cells. Our results indicated that, independent of viral transmission, the secretome of HCMV-infected GBM cells was able to alter the expression of key metabolic proteins and epigenetic markers. This suggests a mechanism of action where reprogramming of GBM cells alters the surrounding tumor microenvironment to be permissive to tumor progression in a manner akin to the Reverse-Warburg Effect. Overall, this suggests a potential oncomodulatory role for HCMV in the context of GBM.

Can a replacing sponsor benefit?

2019 ◽  
Vol 53 (12) ◽  
pp. 2481-2500 ◽  
Author(s):  
François Anthony Carrillat ◽  
Reinhard Grohs
Keyword(s):  
Behavioral Intentions ◽  
Underlying Mechanism ◽  
Randomized Experiments ◽  
Altruistic Motive ◽  
Content Type ◽  
Consumer Responses ◽  
Sponsorship Effectiveness ◽  
The Common ◽  
The Impact ◽  
The Relationship

Purpose This paper aims to examine the common situation where the sponsor of an event is replaced and the impact of this situation on consumers’ behavioral intentions toward the new sponsor. Design/methodology/approach An original conceptual framework was developed to account for consumers’ reactions toward a new sponsor in the context of a sponsorship change, depending on whether the former and new sponsors are competitors, the duration of the relationship between the former sponsor and the event (tenure length), and the level of congruence between the new and the former sponsor and the event. This framework, based on consumer motive attributions, was tested by means of three completely randomized experiments. Findings The results of the first experiment show that if the former and new sponsors are competitors, consumers’ behavioral intentions toward the new sponsor are more positive if the former sponsor’s tenure duration was short. When the former and the new sponsors are not competitors, the former sponsor’s tenure duration does not impact behavioral intentions. The second experiment demonstrates that consumers’ altruistic motive attributions are the underlying mechanism that explains these effects. Finally, the third experiment identifies a boundary condition, that is, these effects occur only if the new and the former sponsor are congruent with the sponsored property. Research limitations/implications This research has not considered the situation where the former and new sponsors have different levels of congruence with the event (e.g. when the former sponsor is congruent but the new sponsor is incongruent with the event) and has examined only sponsorship tenure durations of one versus 15 years. Practical implications Sponsorship managers learn that replacing a sponsor that was supporting the event for a short rather than a long period of time is more beneficial, but only if replacing a competitor that is congruent with the sponsored property. The reason is that such a replacement triggers more altruistic motive attributions compared with contexts where the former sponsor is not a competitor or incongruent with the sponsored property. Suggestions of sponsorship activation strategies known to increase perceptions of altruism are provided to enhance sponsorship effectiveness for new sponsors. Originality/value This study is the first to look at how consumer responses to a new sponsor vary depending on the former sponsor’s tenure length, competitor status and event congruency.

The Relationship Between Distress and Resource Loss Following Rape

2002 ◽  
Vol 17 (1) ◽  
pp. 85-91 ◽  
Author(s):  
Jeannine Monnier ◽  
Heidi S. Resnick ◽  
Dean G. Kilpatrick ◽  
Brenda Seals
Keyword(s):  
Psychological Distress ◽  
Violent Crime ◽  
Underlying Mechanism ◽  
Zero Order ◽  
Crime Victims ◽  
Hierarchical Regression ◽  
Resource Loss ◽  
Rape Victims ◽  
The Impact ◽  
The Relationship

The present study examined the impact of resource loss on violent crime victims. Participants were 57 women who were recent victims of rape. Zero-order and point-biserial correlations and multiple hierarchical regression results indicated that psychological distress was followed by increased resource loss for rape victims. These results suggest that distress may be an underlying mechanism for resource loss in victims of sexual assault.

scholarly journals The impact of chromatin dynamics on Cas9-mediated genome editing in human cells

2016 ◽  
Author(s):  
René M. Daer ◽  
Josh P. Cutts ◽  
David A. Brafman ◽  
Karmella A. Haynes
Keyword(s):  
Genome Editing ◽  
Mammalian Cells ◽  
Underlying Mechanism ◽  
Genomic Locus ◽  
Chromatin Dynamics ◽  
Transgenic Cell ◽  
The Impact ◽  
The Relationship ◽  
Transgenic Cell Line ◽  
Eukaryotic Genomes

ABSTRACTIn order to efficiently edit eukaryotic genomes, it is critical to test the impact of chromatin dynamics on CRISPR/Cas9 function and develop strategies to adapt the system to eukaryotic contexts. So far, research has extensively characterized the relationship between the CRISPR endonuclease Cas9 and the composition of the RNADNA duplex that mediates the system’s precision. Evidence suggests that chromatin modifications and DNA packaging can block eukaryotic genome editing by custom-built DNA endonucleases like Cas9; however, the underlying mechanism of Cas9 inhibition is unclear. Here, we demonstrate that closed, gene-silencing-associated chromatin is a mechanism for the interference of Cas9-mediated DNA editing. Our assays use a transgenic cell line with a drug-inducible switch to control chromatin states (open and closed) at a single genomic locus. We show that closed chromatin inhibits editing at specific target sites, and that artificial reversal of the silenced state restores editing efficiency. These results provide new insights to improve Cas9-mediated editing in human and other mammalian cells.

scholarly journals How Does House Demolition Affect Family Conspicuous Consumption?

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Yuan ◽  
Shuying Gong ◽  
Jun Gao
Keyword(s):  
Conspicuous Consumption ◽  
Underlying Mechanism ◽  
Household Wealth ◽  
Conservation Of Resources ◽  
Luxury Consumption ◽  
Exploratory Investigation ◽  
House Demolition ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

Family conspicuous consumption behavior is affected by many factors. Existing pieces of literature seldom focus on the impact of house demolition on family conspicuous consumption and its underlying mechanism. Based on the mental accounting theory and conservation of resources theory, this study uses the micro-data of the 2011 China Household Finance Survey to empirically examine the relationship between house demolition and family conspicuous consumption. Robustness results suggest that house demolition positively affects household conspicuous consumption, which is not only reflected in the overall consumption level but also in the level of average consumption. Further analysis finds that household wealth and materialism value have a significant positive moderating effect on the relationship of the main effect. In addition, in order to clarify the relationship between conspicuous consumption and luxury consumption, this study finds that conspicuous consumption and luxury consumption are not completely equivalent through in-depth theoretical analysis and exploratory investigation. There are similarities in both consumption motivation and pattern, but with differences on consumer subject and object. The contribution of this research is to enrich the theory of decision-making in consumer behavior, which also has certain significance in deepening the understanding of the relationship between conspicuous consumption and luxury consumption.

scholarly journals Glycosylation in the Tumor Microenvironment: Implications for Tumor Angiogenesis and Metastasis

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 544 ◽  
Author(s):  
Kevin Brown Chandler ◽  
Catherine E. Costello ◽  
Nader Rahimi
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Stromal Cells ◽  
Tumor Development ◽  
Cancer Therapeutics ◽  
Protein Glycosylation ◽  
Anti Cancer ◽  
Oncogene Activation ◽  
Regulate Protein ◽  
The Impact

Just as oncogene activation and tumor suppressor loss are hallmarks of tumor development, emerging evidence indicates that tumor microenvironment-mediated changes in glycosylation play a crucial functional role in tumor progression and metastasis. Hypoxia and inflammatory events regulate protein glycosylation in tumor cells and associated stromal cells in the tumor microenvironment, which facilitates tumor progression and also modulates a patient’s response to anti-cancer therapeutics. In this review, we highlight the impact of altered glycosylation on angiogenic signaling and endothelial cell adhesion, and the critical consequences of these changes in tumor behavior.

scholarly journals Immunomodulatory Effects of Mesenchymal Stromal Cells Revisited in the Context of Inflammatory Cardiomyopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Kapka Miteva ◽  
Sophie Van Linthout ◽  
Hans-Dieter Volk ◽  
Carsten Tschöpe
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Current Knowledge ◽  
Left Ventricular ◽  
Inflammatory Cardiomyopathy ◽  
Long Term Outcomes ◽  
Paracrine Effects ◽  
Cellular Transplantation ◽  
The Impact

Myocarditis is a common inflammatory cardiomyopathy, associated with cardiomyocyte apoptosis, which can lead to chronic left ventricular dysfunction. Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. Experimental and clinical studies consistently support the application of cellular transplantation as a strategy to improve myocardial function. Mesenchymal stromal cells (MSCs) mediate distinct paracrine effects supporting endogenous regeneration, but most important are their remarkable immunoregulatory properties. In this review, an overview of current knowledge on immunopathology in myocarditis will be given. Furthermore, current research regarding the immunomodulatory properties of MSCs in the context of myocarditis will be discussed. Finally, the impact of MSC priming by the environment on their functionality and the advantages of systemic administration of MSCs under myocarditis are outlined.

The impact of celebrity-following activities on endorsement effectiveness on microblogging platforms

2017 ◽  
Vol 8 (2) ◽  
pp. 158-173 ◽  
Author(s):  
Yue Ding ◽  
Lingyun Qiu
Keyword(s):  
Mass Communication ◽  
Underlying Mechanism ◽  
Parasocial Interaction ◽  
Survey Method ◽  
Celebrity Endorsement ◽  
Marketing Practice ◽  
Content Type ◽  
The Impact ◽  
The Relationship ◽  
Positive Effect

Purpose Celebrity endorsement on microblogging platforms (such as Twitter or Weibo) has become a widely adopted marketing practice. Compared to its counterpart on traditional mass media, celebrity endorsement on microblogging platforms has some unique characteristics. For example, the endorsement information is usually more implicit and the endorsers tend to use different tactics so as to maximize the impact on their followers. However, these new practices have not been thoroughly investigated and the underlying mechanism by which the endorsers influence potential information receivers is not well understood. Anchored on the theory of parasocial interaction borrowed from the mass communication literature, this paper aims to reveal the underlying mechanism of celebrity endorsement on microblogging platforms. More specifically, it examines the relationship between the intensity of microbloggers’ various celebrity-following activities and endorsement effectiveness. Design/methodology/approach The authors designed and conducted a Web-based survey containing scales for all focal constructs and demographic and control variables. Through online and offline campus advertisement, undergraduate and graduates students who have used microblogging for at least three months were recruited. Findings First of all, the survey results show that the intensity of users’ celebrity-following activities on microblogging platforms has a positive effect on the effectiveness of celebrity endorsement. Second, the positive effect of the intensity of microbloggers’ celebrity-following activities on the effectiveness of celebrity endorsement is mediated by the perceived parasocial interaction with the endorsers. Research limitations/implications Firstly, most respondents of the survey are university students. Second, because of the intrinsic disadvantage of the survey method, the causal relationship between constructs cannot be examined directly. Last, parasocial interaction/relationship is a complex theoretical construct whose influence is unveiled partially in this research. Practical implications First, this study found that the effectiveness of celebrity endorsement on microblogging platforms are largely affected by celebrity-followers’ online involvement. Second, this study revealed that celebrity-following activities that help enhance followers’ perceptions of parasocial interactions are particularly beneficial for endorsement effectiveness. Last, the exploratory analysis further revealed that followers’ perceptions of ingenuousness and companionship are two key sub-dimensions of parasocial interaction. Originality/value First, the authors verified the positive relationship between information receiver’s involvement and the effectiveness of celebrity endorsement in the context of microblogging platforms. Second, this study found that parasocial interaction fully mediates the relationship between celebrity-following intensity and endorsement effectiveness. Last, through an exploratory factor analysis, the authors further decomposed the construct of parasocial interaction into three sub-dimensions, namely, ingenuousness, empathy and companionship.

scholarly journals The Macrophage Response Is Driven by Mesenchymal Stem Cell-Mediated Metabolic Reprogramming

2021 ◽  
Vol 12 ◽  
Author(s):  
Noymar Luque-Campos ◽  
Felipe A. Bustamante-Barrientos ◽  
Carolina Pradenas ◽  
Cynthia García ◽  
María Jesús Araya ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Tissue Repair ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Metabolic Reprogramming ◽  
Macrophage Response ◽  
Metabolic Plasticity ◽  
Macrophage Plasticity ◽  
And Function ◽  
The Impact

Mesenchymal stem cells (MSCs) are multipotent adult stromal cells widely studied for their regenerative and immunomodulatory properties. They are capable of modulating macrophage plasticity depending on various microenvironmental signals. Current studies have shown that metabolic changes can also affect macrophage fate and function. Indeed, changes in the environment prompt phenotype change. Therefore, in this review, we will discuss how MSCs orchestrate macrophage’s metabolic plasticity and the impact on their function. An improved understanding of the crosstalk between macrophages and MSCs will improve our knowledge of MSC’s therapeutic potential in the context of inflammatory diseases, cancer, and tissue repair processes in which macrophages are pivotal.

scholarly journals Nuclear Receptor-Mediated Metabolic Reprogramming and the Impact on HR+ Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4808
Author(s):  
Shaimaa Hussein ◽  
Pooja Khanna ◽  
Neha Yunus ◽  
Michael L. Gatza
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Hormone Receptor ◽  
Metabolic Reprogramming ◽  
Metabolic Energy ◽  
Biological Macromolecules ◽  
Breast Cancers ◽  
Metabolic Processes ◽  
Therapeutic Implications ◽  
The Impact

Metabolic reprogramming enables cancer cells to adapt to the changing microenvironment in order to maintain metabolic energy and to provide the necessary biological macromolecules required for cell growth and tumor progression. While changes in tumor metabolism have been long recognized as a hallmark of cancer, recent advances have begun to delineate the mechanisms that modulate metabolic pathways and the consequence of altered signaling on tumorigenesis. This is particularly evident in hormone receptor positive (HR+) breast cancers which account for approximately 70% of breast cancer cases. Emerging evidence indicates that HR+ breast tumors are dependent on multiple metabolic processes for tumor progression, metastasis, and therapeutic resistance and that changes in metabolic programs are driven, in part, by a number of key nuclear receptors including hormone-dependent signaling. In this review, we discuss the mechanisms and impact of hormone receptor mediated metabolic reprogramming on HR+ breast cancer genesis and progression as well as the therapeutic implications of these metabolic processes in this disease.

Multiomics Study of Key Differentially Expressed Methylation Genes in HCC Based on Epigenome and Transcriptome Analyses

2021 ◽  
Author(s):  
Yu Wang ◽  
Fei Qi ◽  
Xun Wang ◽  
Shi Jin ◽  
Hui He
Keyword(s):  
Tumor Progression ◽  
Differentially Expressed Genes ◽  
Drug Sensitivity ◽  
Differentially Expressed ◽  
Immune Infiltration ◽  
Chemotherapy Drugs ◽  
Key Genes ◽  
The Impact ◽  
The Relationship ◽  
Core Genes

Abstract Objective: To screen out key differentially expressed methylation genes in hepatocellular carcinoma (HCC) by extracting data from the NCBI-GEO and TCGA databases, discuss the interaction of key genes in HCC and explore the influence of these genes on tumor progression.Methods: The clinical information and sequence data of HCC patients and healthy controls were extracted from the NCBI-GEO and TCGA databases. The module that presented the highest correlation with the tumor phenotypes was selected by the WGCNA network and TOM analysis. GO and KEGG analyses were used for signaling pathway analysis. Key differentially expressed genes were screened out from the module. KM plot analysis was performed to determine the impact of key genes on patient survival. The relationship between core genes and tumor immune infiltration was also discussed. Drug sensitivity analysis was performed to observe the sensitivity of key genes methylated by chemotherapeutic drugs and thus determine the associated effects on patient prognosis. Finally, the molecular mechanisms of the genes involved in tumor progression were analyzed by GSVA, and the interactions between key genes were revealed using Gene MANIA analysis.Results: A total of 373 differentially expressed genes were screened, including 88 upregulated genes and 285 downregulated genes. Three of these genes, CHST4, CRHBP, and IGFBP3, were found to be abnormally methylated in HCC patients and significantly associated with expected survival. The relationship between these key genes and tumor immune invasion was confirmed, and these genes play a protumor or antitumor role through immune cell mediation. In addition, we found that CHST4 and IGFBP3 expression can significantly reduce the sensitivity of several commonly used chemotherapy drugs to tumor cells, while CRHBP expression plays a synergistic role with chemotherapy drugs to enhance mutual effects. The participation of these genes in specific signaling pathways involved in liver metabolism and tumor progression has also been identified. Finally, complex interactions between the three core genes and other related genes were presented.Conclusion: The CHST4, CRHBP and IGFBP3 genes present significant methylation and differential expression in HCC, are involved in tumor immune infiltration, and affect chemotherapy drug sensitivity. As potential biomarkers and therapeutic targets, they may be beneficial to the diagnosis and prognosis of HCC patients in the future.

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