WNT pathway alteration is related to dysplastic cortical tissue and not to adjacent tissue of patients with FCD and refractory epilepsy

Abstract Background Focal cortical dysplasia (FCD) is a malformation of the cortical development that cause medical refractory seizures and the only treatment may be surgical resection of the affected area of the brain. People affected by FCD may present seizures of variable severity since childhood. The physiopathology of the disease is not yet understood, however it is known that several genes alterations may play their role. The WNT/β-catenin pathway is associated with cell transformation and migration and for this reason may be crucial for understanding FCD’s aetiology. The aim of this study was to explore genes related to the WNT/β-catenin pathway in patients with FCD type II. Methods Dysplastic tissue and tissue adjacent to the primary dysplastic lesion of patients with FCD type II were obtained from two patients who underwent surgical treatment. The analysis of the relative expression of genes was performed by a qRT-PCR array containing 84 genes related to the WNT pathway. Results In patient 1, the analysis showed a difference in the expression of seven genes, demonstrating an increase in AXIN2, FRAT2, FZD9, KREMENI and PP2R1A genes and a reduction in CSNK1G3 and PPP2CA genes in dysplastic tissue. In patient 2, the analysis showed increased expression of CSNK1A1, FZD4 and PPP2CA genes, as well as reduced of CTNNBIP1 gene in dysplastic tissue. Conclusion Dysregulation in the expression of genes that control the receptors of the WNT pathway keeps it in an inactivated state. Therefore, a eventual manipulation of this pathway focusing on its activation may influence molecular manifestations underlying the epileptogenic status in injured brain tissue, which could act as a therapeutic alternative to FCD type II. The WNT/ β-catenin signaling pathway is crucial for the control of embryonic development, which takes place through the regulation of cell differentiation, migration and proliferation, and apoptosis process.

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Effects of Silver Nanoparticles on Proliferation and Apoptosis in Granulosa Cells of Chicken Preovulatory Follicles: An In Vitro Study

Animals ◽

10.3390/ani11061652 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1652

Author(s):

Dorota Katarzyńska-Banasik ◽

Anna Kozubek ◽

Małgorzata Grzesiak ◽

Andrzej Sechman

Keyword(s):

Silver Nanoparticles ◽

Granulosa Cells ◽

Caspase 3 ◽

In Vitro Study ◽

Poultry Production ◽

Cell Death Pathways ◽

Preovulatory Follicles ◽

Proliferation And Apoptosis ◽

Apoptosis Process

The continuous development of poultry production related to the growing demand for eggs and chicken meat makes it necessary to use modern technologies. An answer to this demand may be the use of nanotechnology in poultry farming. One of the promising nanomaterials in this field are silver nanoparticles (AgNPs), which are used as disinfectants, reducing microbial pollution and the amounts of greenhouse gases released. This study aimed to evaluate the effect of AgNPs on the proliferation and apoptosis process in the granulosa cells of chicken preovulatory follicles. The in vitro culture experiment revealed that both 13 nm and 50 nm AgNPs inhibited the proliferation of the granulosa cells. However, a faster action was observed in 50 nm AgNPs than in 13 nm ones. A size-dependent effect of AgNP was also demonstrated for the caspase-3 activity. AgNPs 13 nm in size increased the caspase-3 activity in granulosa cells, while 50 nm AgNPs did not exert an effect, which may indicate the induction of distinct cell death pathways by AgNPs. In conclusion, our study reveals that AgNPs in vitro inhibit granulosa cell proliferation and stimulate their apoptosis. These results suggest that AgNPs may disrupt the final stage of preovulatory follicle maturation and ovulation.

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LINC01234 aggravates cell growth and migration of triple‐negative breast cancer by activating the Wnt pathway

Environmental Toxicology ◽

10.1002/tox.23318 ◽

2021 ◽

Author(s):

Feng Xiao ◽

Hongyao Jia ◽

Di Wu ◽

Zhiru Zhang ◽

Sijie Li ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Triple Negative Breast Cancer ◽

Wnt Pathway ◽

Triple Negative ◽

Cell Growth And Migration ◽

And Migration

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Transcriptomic profiling of high- and low-spiking regions reveals novel epileptogenic mechanisms in focal cortical dysplasia type II patients

Molecular Brain ◽

10.1186/s13041-021-00832-4 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Arpna Srivastava ◽

Krishan Kumar ◽

Jyotirmoy Banerjee ◽

Manjari Tripathi ◽

Vivek Dubey ◽

...

Keyword(s):

Rna Sequencing ◽

Focal Cortical Dysplasia ◽

Phospholipid Metabolism ◽

Cortical Dysplasia ◽

Type Ii ◽

Tissue Samples ◽

Significant Enrichment ◽

Gene Expression Studies ◽

Oligodendrocyte Development ◽

High Throughput Gene Expression

AbstractFocal cortical dysplasia (FCD) is a malformation of the cerebral cortex with poorly-defined epileptogenic zones (EZs), and poor surgical outcome in FCD is associated with inaccurate localization of the EZ. Hence, identifying novel epileptogenic markers to aid in the localization of EZ in patients with FCD is very much needed. High-throughput gene expression studies of FCD samples have the potential to uncover molecular changes underlying the epileptogenic process and identify novel markers for delineating the EZ. For this purpose, we, for the first time performed RNA sequencing of surgically resected paired tissue samples obtained from electrocorticographically graded high (MAX) and low spiking (MIN) regions of FCD type II patients and autopsy controls. We identified significant changes in the MAX samples of the FCD type II patients when compared to non-epileptic controls, but not in the case of MIN samples. We found significant enrichment for myelination, oligodendrocyte development and differentiation, neuronal and axon ensheathment, phospholipid metabolism, cell adhesion and cytoskeleton, semaphorins, and ion channels in the MAX region. Through the integration of both MAX vs non-epileptic control and MAX vs MIN RNA sequencing (RNA Seq) data, PLP1, PLLP, UGT8, KLK6, SOX10, MOG, MAG, MOBP, ANLN, ERMN, SPP1, CLDN11, TNC, GPR37, SLC12A2, ABCA2, ABCA8, ASPA, P2RX7, CERS2, MAP4K4, TF, CTGF, Semaphorins, Opalin, FGFs, CALB2, and TNC were identified as potential key regulators of multiple pathways related to FCD type II pathology. We have identified novel epileptogenic marker elements that may contribute to epileptogenicity in patients with FCD and could be possible markers for the localization of EZ.

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LGK974 suppresses lipopolysaccharide-induced endotoxemia in mice by modulating the crosstalk between the Wnt/β-catenin and NF-κB pathways

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00577-z ◽

2021 ◽

Vol 53 (3) ◽

pp. 407-421

Author(s):

Jaewoong Jang ◽

Jaewon Song ◽

Hyunji Lee ◽

Inae Sim ◽

Young V. Kwon ◽

...

Keyword(s):

Animal Model ◽

Survival Rate ◽

Wnt Pathway ◽

Cytokine Production ◽

Cytokine Storm ◽

Plasma Cytokine ◽

Gram Negative ◽

Multiple Organs ◽

Expression Of Genes ◽

Cytokine Levels

AbstractEndotoxemia, a type of sepsis caused by gram-negative bacterial endotoxin [i.e., lipopolysaccharide (LPS)], is associated with manifestations such as cytokine storm; failure of multiple organs, including the liver; and a high mortality rate. We investigated the effect and mechanism of action of LGK974, a Wnt signaling inhibitor, in mice with LPS-induced endotoxemia, an animal model of sepsis. LGK974 significantly and dose-dependently increased the survival rate and reduced plasma cytokine levels in mice with LPS-induced endotoxemia. Transcriptome analysis of liver tissues revealed significant changes in the expression of genes associated with the Wnt pathway as well as cytokine and NF-κB signaling during endotoxemia. LGK974 treatment suppressed the activation of NF-κB signaling and cytokine expression as well as the Wnt/β-catenin pathway in the livers of endotoxemic mice. Coimmunoprecipitation of phospho-IκB and β-transducin repeat-containing protein (β-TrCP) was increased in the livers of endotoxemic mice but was reduced by LGK974 treatment. Moreover, LGK974 treatment decreased the coimmunoprecipitation and colocalization of β-catenin and NF-κB, which were elevated in the livers of endotoxemic mice. Our results reveal crosstalk between the Wnt/β-catenin and NF-κB pathways via interactions between β-TrCP and phospho-IκB and between β-catenin and NF-κB during endotoxemia. The results of this study strongly suggest that the crosstalk between the Wnt/β-catenin and NF-κB pathways contributes to the mutual activation of these two pathways during endotoxemia, which results in amplified cytokine production, liver damage and death, and that LGK974 suppresses this vicious amplification cycle by reducing the crosstalk between these two pathways.

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Genome-wide DNA Methylation and RNAseq Analyses Identify Aberrant Signalling Pathways in Focal Cortical Dysplasia (FCD) Type II

Scientific Reports ◽

10.1038/s41598-018-35892-5 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 7

Author(s):

Aparna Banerjee Dixit ◽

Devina Sharma ◽

Manjari Tripathi ◽

Arpna Srivastava ◽

Debasmita Paul ◽

...

Keyword(s):

Dna Methylation ◽

Focal Cortical Dysplasia ◽

Cortical Dysplasia ◽

Signalling Pathways ◽

Type Ii ◽

Genome Wide

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MMP1 regulated by NEAT1/miR-361-5p axis facilitates the proliferation and migration of cutaneous squamous cell carcinoma via the activation of Wnt pathway

Cancer Biology & Therapy ◽

10.1080/15384047.2021.1941583 ◽

2021 ◽

pp. 1-11

Author(s):

Shiqiu Jiang ◽

Hairong Liu ◽

Jie Zhang ◽

Fang Zhang ◽

Jiawei Fan ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Wnt Pathway ◽

Cutaneous Squamous Cell Carcinoma ◽

And Migration ◽

Proliferation And Migration

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Preconditioning by Hydrogen Peroxide Enhances Multiple Properties of HumanDecidua BasalisMesenchymal Stem/Multipotent Stromal Cells

Stem Cells International ◽

10.1155/2018/6480793 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 8

Author(s):

T. Khatlani ◽

D. Algudiri ◽

R. Alenzi ◽

A. M. Al Subayyil ◽

F. M. Abomaray ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Stem Cell ◽

Cellular Functions ◽

Beneficial Effects ◽

Decidua Basalis ◽

Expression Of Genes ◽

Toxic Environment ◽

Stress Environment ◽

And Migration ◽

Hostile Environments

Stem cell-based therapies rely on stem cell ability to repair in an oxidative stress environment. Preconditioning of mesenchymal stem cells (MSCs) to a stress environment has beneficial effects on their ability to repair injured tissues. We previously reported that MSCs from thedecidua basalis(DBMSCs) of human placenta have many important cellular functions that make them potentially useful for cell-based therapies. Here, we studied the effect of DBMSC preconditioning to a stress environment. DBMSCs were exposed to various concentrations of hydrogen peroxide (H2O2), and their functions were then assessed. DBMSC expression of immune molecules after preconditioning was also determined. DBMSC preconditioning with H2O2enhanced their proliferation, colonogenicity, adhesion, and migration. In addition, DBMSCs regardless of H2O2treatment displayed antiangiogenic activity. H2O2preconditioning also increased DBMSC expression of genes that promote cellular functions and decreased the expression of genes, which have opposite effect on their functions. Preconditioning also reduced DBMSC expression of IL-1β, but had no effects on the expression of other immune molecules that promote proliferation, adhesion, and migration. These data show that DBMSCs resist a toxic environment, which adds to their potential as a candidate stem cell type for treating various diseases in hostile environments.

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Scalp High Frequency Oscillations Associated with Rhythmic Spikes Activity in Focal Cortical Dysplasia Type II

Journal of the Japan Epilepsy Society ◽

10.3805/jjes.33.672 ◽

2016 ◽

Vol 33 (3) ◽

pp. 672-682

Author(s):

Azusa Tabata ◽

Keiko Hara ◽

Motoki Inaji ◽

Natsumi Tamada ◽

Reina Kawanami ◽

...

Keyword(s):

High Frequency ◽

Focal Cortical Dysplasia ◽

Cortical Dysplasia ◽

Type Ii ◽

High Frequency Oscillations

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Is resistant starch protective against colorectal cancer via modulation of the WNT signalling pathway?

Proceedings of The Nutrition Society ◽

10.1017/s002966511500004x ◽

2015 ◽

Vol 74 (3) ◽

pp. 282-291 ◽

Cited By ~ 11

Author(s):

Fiona C. Malcomson ◽

Naomi D. Willis ◽

John C. Mathers

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Resistant Starch ◽

Wnt Pathway ◽

Wnt Signalling ◽

Signalling Pathway ◽

Wnt Signalling Pathway ◽

Crypt Cell Proliferation ◽

And Migration ◽

Epigenetic Modulation

Epidemiological and experimental evidence suggests that non-digestible carbohydrates (NDC) including resistant starch are protective against colorectal cancer. These anti-neoplastic effects are presumed to result from the production of the SCFA, butyrate, by colonic fermentation, which binds to the G-protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes. The WNT pathway is central to the maintenance of homeostasis within the large bowel through regulation of processes such as cell proliferation and migration and is frequently aberrantly hyperactivated in colorectal cancers. Abnormal WNT signalling can lead to irregular crypt cell proliferation that favours a hyperproliferative state. Butyrate has been shown to modulate the WNT pathway positively, affecting functional outcomes such as apoptosis and proliferation. Butyrate's ability to regulate gene expression results from epigenetic mechanisms, including its role as a histone deacetylase inhibitor and through modulating DNA methylation and the expression of microRNA. We conclude that genetic and epigenetic modulation of the WNT signalling pathway may be an important mechanism through which butyrate from fermentation of resistant starch and other NDC exert their chemoprotective effects.

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