Inhibitory Effect of MicroRNA-376b-Overexpressing Bone Marrow Mesenchymal Stem Cells (BMSCs) on Malignant Characteristics of Glioma Cells Through Targeting Forkhead Box Protein P2 (FOXP2)

2022 ◽  
Vol 12 (5) ◽  
pp. 971-977
Author(s):  
Ruoyu Zhu ◽  
Zhonglin Wang

This study investigated the impact of microRNA (miR)-376b derived from BMSCs on glioma progression. BMSCs were transfected with miR-376b mimic, miR-376b inhibitor or NC and then cocultured with glioma cells followed by measuring cell behaviors by MTT assay, Transwell assay and flow cytometry, FOXP2 and miR-376b expression by Western blot and RT-qPCR. After confirming the inhibitory and mimicking activity of transfection, we found that overexpression of miR-376b in BMSCs decreased glioma cell invasion, migration and proliferation but promoted cell apoptosis within 24 h and 48 h after transfection along with reduced number of cells in S-phase. Mechanically, miR-376b targeted miR-376b and up-regulation of miR-376b caused down-regulation of FOXP2 (p < 0.05). Overexpression of miR-376b in BMSCs decelerated glioma cell cycle and inhibitedmalignant behaviors of glioma cells by targeting FOXP2 expression. These evidence unveils the potential role of FOXP2 as a biomarker for the treatment of gliomas.

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii30-ii30
Author(s):  
Jingwei Wan ◽  
Alyssa Guo ◽  
Mingli Liu

Abstract Our group found that the inhibitory effect of TRPM7 on proliferation and invasion of human glioma cell is mediated by multiple mechanisms. TRPM7 regulates miR-28-5p expression, which suppresses cell proliferation and invasion in glioma cells by targeting Ras-related protein Rap1b. In particular, our group found that TRPM7 channels regulate glioma stem cell (GSC) growth/proliferation through STAT3 and Notch signaling. However, which Notch component(s) is crucial for its activity regulated by TRPM7, and its relationship with other GSC markers, such as CD133 and ALDH1, remain unclear. In the current project, we elucidate the mechanisms of TRMP7’s regulation of Notch signaling pathway that contribute to the development and progression of glioma and maintenance of self-renewal and tumorigenicity of GSC using multiple glioma cell lines (GC) with different molecular subtypes and GSCs derived from the GC lines. 1) We first analyzed TRPM7 expression using the Oncomine database (https://www.oncomine.org) and found that the TRPM7 mRNA expression is significantly increased in anaplastic astrocytoma, diffuse astrocytoma, and GBM patients compared to that in normal brain tissue controls. 2) TRPM7 is expressed in GBM, and its channel activity is correlated with Notch1 activation. Inhibition of TRPM7 downregulates Notch1 signaling, while upregulation of TRPM7 upregulates Notch1 signaling. 3) GSC markers, CD133 and ALDH1, are correlated with TRPM7 in GBM. 4) Targeting TRPM7 suppresses the growth and proliferation of glioma cells through G1/S arrests and apoptosis of glioma cells. 5) Targeting Notch1 suppresses the TRPM7-induced growth and proliferation of glioma cells, as well as the expression of GSC markers CD133 and ALDH1. In summary, TRPM7 is responsible for sustained Notch signaling activation, enhanced expression of GSC markers, and regulation of glioma stemness, which contribute to malignant glioma cell growth and invasion. Notch1 and ligand DII4 are key components that contribute GSC stemness.


Genome ◽  
2020 ◽  
pp. 1-11
Author(s):  
Bahar Patlar ◽  
Alberto Civetta

It has long been acknowledged that changes in the regulation of gene expression may account for major organismal differences. However, we still do not fully understand how changes in gene expression evolve and how do such changes influence organisms’ differences. We are even less aware of the impact such changes might have in restricting gene flow between species. Here, we focus on studies of gene expression and speciation in the Drosophila model. We review studies that have identified gene interactions in post-mating reproductive isolation and speciation, particularly those that modulate male gene expression. We also address studies that have experimentally manipulated changes in gene expression to test their effect in post-mating reproductive isolation. We highlight the need for a more in-depth analysis of the role of selection causing disrupted gene expression of such candidate genes in sterile/inviable hybrids. Moreover, we discuss the relevance to incorporate more routinely assays that simultaneously evaluate the potential effects of environmental factors and genetic background in modulating plastic responses in male genes and their potential role in speciation.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi206-vi206
Author(s):  
Tomohiro Yamasaki ◽  
Lumin Zhang ◽  
Tyrone Dowdy ◽  
Adrian Lita ◽  
Mark Gilbert ◽  
...  

Abstract BACKGROUND Increased de novo lipogenesis is a hallmark of cancer metabolism. In this study, we interrogated the role of de novo lipogenesis in IDH1 mutated glioma’s growth and identified the key enzyme, Stearoyl-CoA desaturase 1 (SCD1) that provides this growth advantage. MATERIALS ANDMETHODS We prepared genetically engineered glioma cell lines (U251 wild-type: U251WT and U251 IDHR132H mutant: U251RH) and normal human astrocytes (empty vector induced-NHA: NHAEV and IDHR132H mutant: NHARH). Lipid metabolic analysis was conducted by using LC-MS and Raman imaging microscopy. SCD1 expression was investigated by The Cancer Genome Atlas (TCGA) data analysis and Western-blotting method. Knock-out of SCD1 was conducted by using CRISPR/Cas9 and shRNA. RESULTS Previously, we showed that IDH1 mut glioma cells have increased monounsaturated fatty acids (MUFAs). TCGA data revealed IDH mut glioma shows significantly higher SCD1 mRNA expression than wild-type glioma. Our model systems of IDH1 mut (U251RH, NHARH) showed increased expression of this enzyme compared with their wild-type counterpart. Moreover, addition of D-2HG to U251WT increased SCD1 expression. Herein, we showed that inhibition of SCD1 with CAY10566 decreased relative cell number and sphere forming capacity in a dose-dependent manner. Furthermore, addition of MUFAs were able to rescue the SCD1 inhibitor induced-cell death and sphere forming capacity. Knock out of SCD1 revealed decreased cell proliferation and sphere forming ability. Decreasing lipid content from the media did not alter the growth of these cells, suggesting that glioma cells rely on de novo lipid synthesis rather than scavenging them from the microenvironment. CONCLUSION Overexpression of IDH mutant gene altered lipid composition in U251 cells to enrich MUFA levels and we confirmed that D-2HG caused SCD1 upregulation in U251WT. We demonstrated the glioma cell growth requires SCD1 expression and the results of the present study may provide novel insights into the role of SCD1 in IDH mut gliomas growth.


Dementia ◽  
2017 ◽  
Vol 18 (7-8) ◽  
pp. 3161-3164 ◽  
Author(s):  
Rudi Coetzer

The paper explores the important role of relatives in designing assistive technologies in collaboration with practitioners. A brief case study reports the collaborative design of a 24-hour clock to reduce the impact of visual–spatial impairment on a family member's ability to read time and prevent temporal disorientation.


Hepatology ◽  
2014 ◽  
Vol 60 (3) ◽  
pp. 1110-1111 ◽  
Author(s):  
Emeric Limagne ◽  
Vanessa Cottet ◽  
Alexia Karen Cotte ◽  
Samia Hamza ◽  
Patrick Hillon ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2034
Author(s):  
Zubair Ahmed Ratan ◽  
Fazla Rabbi Mashrur ◽  
Anisha Parsub Chhoan ◽  
Sadi Md. Shahriar ◽  
Mohammad Faisal Haidere ◽  
...  

Since the early 1990s, nanotechnology has led to new horizons in nanomedicine, which encompasses all spheres of science including chemistry, material science, biology, and biotechnology. Emerging viral infections are creating severe hazards to public health worldwide, recently, COVID-19 has caused mass human casualties with significant economic impacts. Interestingly, silver nanoparticles (AgNPs) exhibited the potential to destroy viruses, bacteria, and fungi using various methods. However, developing safe and effective antiviral drugs is challenging, as viruses use host cells for replication. Designing drugs that do not harm host cells while targeting viruses is complicated. In recent years, the impact of AgNPs on viruses has been evaluated. Here, we discuss the potential role of silver nanoparticles as antiviral agents. In this review, we focus on the properties of AgNPs such as their characterization methods, antiviral activity, mechanisms, applications, and toxicity.


2014 ◽  
Vol 9 (3) ◽  
pp. 400-423 ◽  
Author(s):  
Tendai Chikweche ◽  
Richard Fletcher

Purpose – The purpose of this paper is to expand knowledge about how middle class consumers in Sub-Saharan African markets behave, focusing on the potential role of social networks and the subsequent interactions that take place between these consumers and firms. Design/methodology/approach – A qualitative research method approach comprising personal interviews and observations targeted at consumers and business executives was used covering all four countries. Findings – Key findings include identification of middle of the pyramid (MOP) social networks, their impact on consumer behaviour and nature of consumer and firm interactions that take place as a result of the impact of social networks. Research limitations/implications – The sample size was restricted to 80 consumers in each of the four countries. This might limit generalisability. Practical implications – The study provides managers with insights on the potential role of social networks on marketing to the MOP in Africa. Social implications – The study provides managers with insights on the potential opportunities for corporate social responsibility solutions at the MOP. Originality/value – Research into the middle class in markets other than western advanced economies is a relatively new area of study. The majority of studies on the middle class have focused on North America and Europe ignoring the merging middle class in Africa. Hence, this research expands knowledge by providing basis for exploring new insights on the emerging marketing opportunity within the middle class in Africa.


2020 ◽  
Vol 8 (3) ◽  
pp. 206-214
Author(s):  
Xiaoli Zhang ◽  
Zui Pan

Abstract Gastric and esophageal cancers are multifactorial and multistage-involved malignancy. While the impact of gut microbiota on overall human health and diseases has been well documented, the influence of gastric and esophageal microbiota on gastric and esophageal cancers remains unclear. This review will discuss the reported alteration in the composition of gastric and esophageal microbiota in normal and disease conditions, and the potential role of dysbiosis in carcinogenesis and tumorigenesis. This review will also discuss how dysbiosis stimulates local and systemic immunity, which may impact on the immunotherapy for cancer.


2020 ◽  
Author(s):  
Stephen McLoughlin

Abstract This article examines the impact that three political leaders—Seretse Khama, Kenneth Kaunda and Julius Nyerere—had on navigating the long-term risk associated with mass atrocities. While the scholarship on comparative genocide studies has acknowledged the crucial dimension of leadership in the perpetration of such violence, very little is known about the preventive influence of leaders in cases where risk is present. This influence works both ways: the ideas, decisions and policies of political leaders are often the most instrumental factor in effective processes of risk mitigation. Yet to date, there has been no systematic study of the role of leadership in managing and ameliorating risk associated with mass atrocities. Indeed, the more general question of why mass atrocities do not occur is also largely neglected. I argue that these leaders were cognisant of the disruptive potential of tribal, ethnic and religious division; they advocated for inclusive national identities and developed policies that fostered social cohesion; and were effective in creating social and political environments that had an inhibitory effect on structural risk factors associated with atrocity crimes.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Fakai Wang ◽  
Huanjun Zhang ◽  
Bing Liu ◽  
Wei Liu ◽  
Zengchao Zhang

Accumulating studies have suggested the dysregulated microRNAs (miRNAs) play important roles in brain tumors, including glioma. miR-6869-5p has been documented to be aberrantly expressed in diverse cancers. However, the precise role of miR-6869-5p in glioma remains poorly understood. This study is aimed at evaluating its modifying effects on glioma. Significantly decreased expression of miR-6869-5p was found in glioma tissues and cells. Negative association was documented between miR-6869-5p and PGK1 in glioma cells, and PGK1 was demonstrated to be a targeted gene of this miRNA by luciferase reporter assay. miR-6869-5p regulated glioma cell proliferation and invasion via targeting PGK1. In addition, the survival analysis had suggested that low miR-6869-5p expression predicted poor prognosis of glioma patients. This study has suggested that miR-6869-5p is a useful tumor suppressor and prognostic marker in glioma.


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