scholarly journals Acupuncture May Exert Its Therapeutic Effect through MicroRNA-339/Sirt2/NFκB/FOXO1 Axis

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jia-You Wang ◽  
Hui Li ◽  
Chun-Mei Ma ◽  
Jia-Lu Wang ◽  
Xin-Sheng Lai ◽  
...  
Keyword(s):  
Acupuncture Therapy ◽  
Critical Role ◽  
Luciferase Assay ◽  
Cellular Functions ◽  
Physiological Level ◽  
Forkhead Box ◽  
Bioinformatics Study ◽  
Direct Target ◽  
Future Work

Recently, we have found that a number of microRNAs (miRNAs) and proteins are involved in the response to acupuncture therapy in hypertensive rats. Our bioinformatics study suggests an association between these miRNAs and proteins, which include miR-339 and sirtuin 2 (Sirt2). In this paper, we aimed to investigate whether Sirt2 was a direct target of miR-339 in neurons. In human SH-SY5Y cells, the luciferase assay implied that Sirt2 was likely a target of miRNA-339. Overexpression of miR-339 downregulated Sirt2 expression, while knockdown of miR-339 upregulated Sirt2 expression in human SH-SY5Y cells and rat PC12 cells. In addition, overexpression of miR-399 increased the acetylation of nuclear factor-κB (NF-κB) and forkhead box protein O1 (FOXO1) in SH-SY5Y cells, which are known targets of Sirt2. Our findings demonstrate that miR-339 regulates Sirt2 in human and rat neurons. Since Sirt2 plays a critical role in multiple important cellular functions, our data imply that acupuncture may act through epigenetic changes and subsequent action on their targets, such as miRNA-339/Sirt2/NF-κB/FOXO1 axis. Some physiological level changes of neurons after altering the miR-339 levels are needed to validate the suggested therapeutic role of miR-339/Sirt2/NF-κB/FOXO1 axis in response to acupuncture therapy in the future work.

Exosomal miR-214-5p Released from Glioblastoma Cells Modulates Inflammatory Response of Microglia after Lipopolysaccharide Stimulation through Targeting CXCR5

2019 ◽  
Vol 18 (1) ◽  
pp. 78-87 ◽  
Author(s):  
Jian-kai Yang ◽  
Hong-jiang Liu ◽  
Yuanyu Wang ◽  
Chen Li ◽  
Ji-peng Yang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Prognosis ◽  
Direct Target ◽  
And Migration ◽  
High Level ◽  
Cxcr5 Expression ◽  
Proliferation And Migration

Background and Objective: Exosomes communicate inter-cellularly and miRNAs play critical roles in this scenario. MiR-214-5p was implicated in multiple tumors with diverse functions uncovered. However, whether miR-214-5p is mechanistically involved in glioblastoma, especially via exosomal pathway, is still elusive. Here we sought to comprehensively address the critical role of exosomal miR-214-5p in glioblastoma (GBM) microenvironment.Methods:The relative expression of miR-214-5p was determined by real-time PCR. Cell viability and migration were measured by MTT and transwell chamber assays, respectively. The secretory cytokines were measured with ELISA kits. The regulatory effect of miR-214-5p on CXCR5 expression was interrogated by luciferase reporter assay. Protein level was analyzed by Western blot.Results:We demonstrated that miR-214-5p was aberrantly overexpressed in GBM and associated with poorer clinical prognosis. High level of miR-214-5p significantly contributed to cell proliferation and migration. GBM-derived exosomal miR-214-5p promoted inflammatory response in primary microglia upon lipopolysaccharide challenge. We further identified CXCR5 as the direct target of miR-214- 5p in this setting.Conclusion:Overexpression of miR-214-5p in GBM modulated the inflammatory response in microglia via exosomal transfer.

scholarly journals Chemokine-biased robust self-organizing polarization of migrating cells in vivo

2019 ◽  
Author(s):  
Adan Olguin-Olguin ◽  
Anne Aalto ◽  
Benoît Maugis ◽  
Michal Reichman-Fried ◽  
Erez Raz
Keyword(s):  
Primordial Germ Cells ◽  
Critical Role ◽  
Cell Polarization ◽  
Cellular Functions ◽  
Motile Cells ◽  
Cell Front ◽  
Specific Proteins ◽  
Migrating Cells

The mechanisms facilitating the establishment of front-rear polarity in migrating cells are not fully understood, in particular in the context of bleb-driven directional migration. To gain further insight into this issue we utilized the migration of zebrafish primordial germ cells (PGCs) as an in vivo model. We followed the molecular and morphological cascade that converts apolar cells into polarized bleb-forming motile cells and analyzed the cross dependency among the different cellular functions we identified. Our results underline the critical role of antagonistic interactions between the front and the rear, in particular the role of biophysical processes including formation of barriers and transport of specific proteins to the back of the cell. These interactions direct the formation of blebs to a specific part of the cell that is specified as the cell front. In this way, spontaneous cell polarization facilitates non-directional cell motility and when biased by chemokine signals leads to migration towards specific locations.

scholarly journals MicroRNA-1271-5p inhibits the tumorigenesis of ovarian cancer through targeting E2F5 and negatively regulates the mTOR signaling pathway

2020 ◽  
Author(s):  
Qin Li ◽  
Junyu Shi ◽  
Xiaoli Xu
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Poor Prognosis ◽  
Mtor Signaling ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Direct Target ◽  
The Relationship

Abstract Background: MicroRNA-1271-5p (miR-1271-5p) has been reported to participate in the progression of many human cancers. However, the role of miR-1271-5p still remains unclear in ovarian cancer (OC). Therefore, we explored the effect of miR-1271-5p on the development of OC in present study. Methods: We measured the miR-1271-5p expression via the qRT-PCR assay. Then the function of miR-1271-5p was analyzed through MTT and Transwell assays. The relationship among miR-1271-5p and E2F5 was verified by dual luciferase assay. The protein expression levels were examined through western blot.Results: MiR-1271-5p was downregulated in OC tissues which predicted poor prognosis of OC patients. Moreover, E2F5 was a direct target of miR-1271-5p in OC. And miR-1271-5p suppressed cell proliferation, migration and invasion in OC through targeting E2F5. Furthermore, E2F5 was upregulated in OC tissues which predicted poor prognosis of OC patients. Besides that, miR-1271-5p suppressed EMT and mTOR pathway in OC. Conclusion: MiR-1271-5p inhibited the tumorigenesis of OC through targeting E2F5 and negatively regulated the mTOR signaling pathway.

PtdIns5P: a little phosphoinositide with big functions?

2007 ◽  
Vol 74 ◽  
pp. 117-128 ◽  
Author(s):  
Sophie Coronas ◽  
Damien Ramel ◽  
Caroline Pendaries ◽  
Frédérique Gaits-Iacovoni ◽  
Hélène Tronchère ◽  
...  
Keyword(s):  
Potential Role ◽  
Current Knowledge ◽  
Critical Role ◽  
Cell Regulation ◽  
Cellular Functions ◽  
Minor Constituents ◽  
Signalling Molecules ◽  
Phosphoinositide 3 Kinase ◽  
Synthesis And Degradation

Phosphoinositides are minor constituents of cell membranes playing a critical role in the regulation of many cellular functions. Recent discoveries indicate that mutations in several phosphoinositide kinases and phosphatases generate imbalances in the levels of phosphoinositides, thereby leading to the development of human diseases. Although the roles of phosphoinositide 3-kinase products and PtdIns(4,5)P2 were largely studied these last years, the potential role of phosphatidylinositol monophosphates as direct signalling molecules is just emerging. PtdIns5P, the least characterized phosphoinositide, appears to be a new player in cell regulation. This review will summarize the current knowledge on the mechanisms of synthesis and degradation of PtdIns5P as well as its potential roles.

scholarly journals miR-145 Contributes to the Progression of Cervical Carcinoma by Directly Regulating FSCN1

2019 ◽  
Vol 28 (9-10) ◽  
pp. 1299-1305 ◽  
Author(s):  
Li Ma ◽  
Ling-Ling Li
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cervical Carcinoma ◽  
Hela Cells ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
Cancer Cell Proliferation ◽  
Expression Levels ◽  
Direct Target

The purpose of our study was to investigate the underlying mechanism and functional role of microRNA-145 (miR-145) in cervical cancer. In this study, quantitative real-time PCR (qRT-PCR) was used to detect miR-145 and FSCN1 expression levels in tissues and HeLa cells. Western blotting was performed to determine the protein level of FSCN1. The luciferase assay was used to verify the direct target of miR-145. The CCK-8 assay and 2D colony formation assays were performed to determine the effects of miR-145 mimics or FSCN1 silencing on cell proliferation. miR-145 expression levels were significantly down-regulated, while FSCN1 expression levels were significantly up-regulated in the cervical carcinoma tissues compared with their matched non-cancerous tissues. In addition, FSCN1 expression levels were negatively correlated to miR-145 in tissues. Next, FSCN1 was verified as the direct target of miR-145 in HeLa cells. Moreover, overexpression of miR-145 dramatically inhibited the proliferation of HeLa cells. The silencing of FSCN1 exhibited the similar patterns on cell proliferation as miR-145 overexpression. The miR-145/ FSCN1 axis contributes to the progression of cervical cancer by inhibition of cervical cancer cell proliferation.

Downregulation of miR-633 activated AKT/mTOR pathway by targeting AKT1 in lupus CD4+ T cells

Lupus ◽  
2019 ◽  
Vol 28 (4) ◽  
pp. 510-519 ◽  
Author(s):  
S Chen ◽  
Y Wang ◽  
H Qin ◽  
J Lin ◽  
L Xie ◽  
...  
Keyword(s):  
T Cells ◽  
Western Blot ◽  
Lupus Erythematosus ◽  
Quantitative Polymerase Chain Reaction ◽  
Mtor Pathway ◽  
Jurkat Cells ◽  
Luciferase Assay ◽  
Mtor Inhibition ◽  
Direct Target

Background Accumulating evidence suggests that the AKT/mTOR pathway plays an important role in the pathogenesis of systemic lupus erythematosus (SLE) through activating T cells, and there are few studies looking into the role of microRNA (miRNAs) in the mechanism. We first found that miR-633 expression in CD4+T cells of SLE patients was significantly reduced. Objective To investigate the role of miR-633 in the AKT/mTOR pathway in lupus CD4+T cells. Methods Samples of 17 SLE cases and 16 healthy controls were collected to detect the expression of miR-633, AKT1, mTOR mRNA and proteins by quantitative polymerase chain reaction (qPCR) and Western-blot, respectively. To determine whether AKT1 is a direct target of miR-633, a luciferase assay was performed. In vitro, AKT1 siRNA, miR-633 mimics/inhibitors or negative controls were transfected to Jurkat cells, human primary CD4+T cells and lupus CD4+T cells. RNA and proteins were extracted after 48 h, and levels of AKT/mTOR pathway markers and downstream multiple cytokines were detected by qPCR or Western-blot. Results In SLE patients, the miR-633 levels in CD4+T cells were significantly decreased and negatively correlated with SLEDAI. AKT1, mTOR mRNA and proteins were all up-regulated. The degree of downregulation of miR-633 was correlated negatively with AKT1 mRNA. The luciferase assay proved that AKT1 is a direct target of miR-633. In Jurkat and lupus CD4+T cells, overexpression of miR-633 could result in lower levels of AKT1 and mTOR. Inhibition of miR-633 expression in primary CD4+T cells caused reverse effects, and protein levels of p-AKT, p-mTOR, and p-S6RP increased. Moreover, among various cytokines, the expression of IL-4, IL-17, and IFN-γ mRNA was raised. Conclusion Our study suggests that miR-633 deletion can activate the AKT/mTOR pathway by targeting AKT1 to participate in the pathogenesis of SLE.

scholarly journals The Microtubule Severing Protein Katanin Regulates Proliferation of Neuronal Progenitors in Embryonic and Adult Neurogenesis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Franco L. Lombino ◽  
Mary Muhia ◽  
Jeffrey Lopez-Rojas ◽  
Monika S. Brill ◽  
Edda Thies ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Critical Role ◽  
Mammalian Brain ◽  
Cellular Functions ◽  
Microtubule Severing ◽  
Neuronal Progenitor ◽  
Neuronal Progenitors ◽  
Adult Hippocampus

Abstract Microtubule severing regulates cytoskeletal rearrangement underlying various cellular functions. Katanin, a heterodimer, consisting of catalytic (p60) and regulatory (p80) subunits severs dynamic microtubules to modulate several stages of cell division. The role of p60 katanin in the mammalian brain with respect to embryonic and adult neurogenesis is poorly understood. Here, we generated a Katna1 knockout mouse and found that consistent with a critical role of katanin in mitosis, constitutive homozygous Katna1 depletion is lethal. Katanin p60 haploinsufficiency induced an accumulation of neuronal progenitors in the subventricular zone during corticogenesis, and impaired their proliferation in the adult hippocampus dentate gyrus (DG) subgranular zone. This did not compromise DG plasticity or spatial and contextual learning and memory tasks employed in our study, consistent with the interpretation that adult neurogenesis may be associated with selective forms of hippocampal-dependent cognitive processes. Our data identify a critical role for the microtubule-severing protein katanin p60 in regulating neuronal progenitor proliferation in vivo during embryonic development and adult neurogenesis.

Leadership in Counseling Psychology: Introduction to the Special Issue

2017 ◽  
Vol 45 (6) ◽  
pp. 742-751 ◽  
Author(s):  
Ruth E. Fassinger ◽  
Lydia P. Buki ◽  
Sandra L. Shullman
Keyword(s):  
Counseling Psychology ◽  
Critical Role ◽  
Current Status ◽  
Special Issue ◽  
Research Education ◽  
Future Work ◽  
And Training ◽  
Scholarly Inquiry ◽  
Training Practice

In this article, we introduce a special two-part issue of The Counseling Psychologist focused on leadership in counseling psychology. Despite the critical role of leadership in the field’s development, current status, and future possibilities, the topic has received little attention as a focus of scholarly inquiry within counseling psychology. We first present a context and rationale for the creation of this special issue, noting the timeliness of this topic within psychology and in society more broadly. Next, we introduce the articles that comprise this two-part special issue as well as two closely related articles contained in the August issue. A brief concluding article at the end this two-part special issue will (a) review the scholarship presented, (b) discuss its relevance, and (c) consider implications and directions for future work in the areas of research, education and training, practice, advocacy, and social justice.

scholarly journals SP1 governs primordial folliculogenesis by regulating pregranulosa cell development in mice

2019 ◽  
Vol 12 (3) ◽  
pp. 230-244 ◽  
Author(s):  
Han Cai ◽  
Bingying Liu ◽  
Huarong Wang ◽  
Guanghong Sun ◽  
Lizhao Feng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Level ◽  
Critical Role ◽  
Somatic Cells ◽  
Primordial Follicle ◽  
Cell Development ◽  
Reporter Mouse ◽  
Forkhead Box

Abstract Establishment of the primordial follicle (PF) pool is pivotal for the female reproductive lifespan; however, the mechanism of primordial folliculogenesis is poorly understood. Here, the transcription factor SP1 was shown to be essential for PF formation in mice. Our results showed that SP1 is present in both oocytes and somatic cells during PF formation in the ovary. Knockdown of Sp1 expression, especially in pregranulosa cells, significantly suppressed nest breakdown, oocyte apoptosis, and PF formation, suggesting that SP1 expressed by somatic cells functions in the process of primordial folliculogenesis. We further demonstrated that SP1 governs the recruitment and maintenance of Forkhead box L2-positive (FOXL2+) pregranulosa cells using an Lgr5-EGFP-IRES-CreERT2 (Lgr5-KI) reporter mouse model and a FOXL2+ cell-specific knockdown model. At the molecular level, SP1 functioned mainly through manipulation of NOTCH2 expression by binding directly to the promoter of the Notch2 gene. Finally, consistent with the critical role of granulosa cells in follicle survival in vitro, massive loss of oocytes in Sp1 knockdown ovaries was evidenced before puberty after the ovaries were transplanted under the renal capsules. Conclusively, our results reveal that SP1 controls the establishment of the ovarian reserve by regulating pregranulosa cell development in the mammalian ovary.

scholarly journals Models of communication and control for brain networks: distinctions, convergence, and future outlook

2020 ◽  
Vol 4 (4) ◽  
pp. 1122-1159 ◽  
Author(s):  
Pragya Srivastava ◽  
Erfan Nozari ◽  
Jason Z. Kim ◽  
Harang Ju ◽  
Dale Zhou ◽  
...  
Keyword(s):  
White Matter ◽  
Human Brain ◽  
Computational Models ◽  
Critical Role ◽  
Brain Networks ◽  
Signal Propagation ◽  
Network Control ◽  
And Control ◽  
Future Work

Recent advances in computational models of signal propagation and routing in the human brain have underscored the critical role of white-matter structure. A complementary approach has utilized the framework of network control theory to better understand how white matter constrains the manner in which a region or set of regions can direct or control the activity of other regions. Despite the potential for both of these approaches to enhance our understanding of the role of network structure in brain function, little work has sought to understand the relations between them. Here, we seek to explicitly bridge computational models of communication and principles of network control in a conceptual review of the current literature. By drawing comparisons between communication and control models in terms of the level of abstraction, the dynamical complexity, the dependence on network attributes, and the interplay of multiple spatiotemporal scales, we highlight the convergence of and distinctions between the two frameworks. Based on the understanding of the intertwined nature of communication and control in human brain networks, this work provides an integrative perspective for the field and outlines exciting directions for future work.

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