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Improved Management of Autism Spectrum Disorder (ASD) by Micronutrients
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
In the lymphoblast cell lines from monozygotic twins with ASD, the expression of two microRNAs has-miR-29b and has-miR-219-5p that target inhibitor of DNA binding protein 3 (ID3) and polio-like kinase2 (PLK2), respectively, were altered.46
Immunological causes of recurrent implantation failure
Published in Efstratios M. Kolibianakis, Christos A. Venetis, Recurrent Implantation Failure, 2019
Ari Kim, Wael Saab, Nayoung Sung, Joanne Kwak-Kim
Local immune effectors and factors in endometrium may play a role in RIF. Inhibitor of DNA-binding protein 3 (Id3) is required for angiogenesis and proliferation of Treg cells.30 T lymphocyte-associated molecule-4 (CTLA-4) is expressed on the surface of Treg and conventional T cells and acts as a brake to shut down the activation of effector T cells.31 Id3+ and CTLA-4+ cells, but not forehead box P3 (FOXP3)+ cells, were significantly increased in the endometrium of women with RIF and RPL as compared with those in controls. There was neither coordinated expression of Id3+ cells and CD34+ vessels nor colocalization of Id3+ and FOXP3+ cells in the endometrium. Aberrant expressions of Id3 and CTLA-4 in peri-implantation endometrium may suggest a population of women with RIF may have chronic inflammatory microenvironments in endometrium during the embryo implantation period.30 Several endometrial biomarkers for the endometrial immune inflammatory status have been reported. Ratios of the IL-15/fibroblast growth factor-inducible 14 (Fn-14) mRNA expression in endometrium, together with the uNK cell count, were reported to reflect uNK cell activation and maturation status. Ratios of the IL-18/TNF-like weak inducer of apoptosis (TWEAK) mRNA expression in endometrium were reported to be a biomarker of both angiogenesis and the Th1/Th2 balance. In 81.7% of the RIF patients, at least one of these parameters (CD56+ NK cell numbers in the endometrium, the ratios of IL-15/Fn-14 mRNA, and IL-18/TWEAK mRNA) was reported to be dysregulated.32 Based on these data, women with RIF may have dysregulated immunotropism and angiogenesis at the implantation site, and further studies are needed to advance current knowledge and understanding of immune responses during implantation and early pregnancy.
Bone morphogenetic protein (BMP)9 in cancer development: mechanistic, diagnostic, and therapeutic approaches?
Published in Journal of Drug Targeting, 2023
Ali G. Alkhathami, Mustafa Ryadh Abdullah, Muhjaha Ahmed, Hanan Hassan Ahmed, Sarab W. Alwash, Zahra Muhammed Mahdi, Fahad Alsaikhan, Ayed A. Dera
The initial phase in tumour metastasis is the acquirement of invasive phenotypes such as the expression of adhesion molecules in tumour cells, leading to the interaction with ECM to invade distant organs. For instance, the expression of EpCAM in HCC cells endows a migratory and invasive phenotype to these cells so that EpCAM blockade inhibits HCC progression and metastasis [68]. To delineate BMP9 effects on HCC invasiveness from the perspective of EpCAM, it has been shown that BMP9 expression positively correlated to EpCAM expression in HCC cells. Mechanistically, it was speculated that BMP9 increases EpCAM expression through activating both SMAD1/5 and Wnt/β-catenin signalling and subsequently enhancing transcription factor inhibitor of DNA-binding protein 1 (ID1). Therefore, BMP9 via upregulating EpCAM in HCC cells promotes tumour invasiveness [69].
Deciphering the vascular labyrinth: role of microRNAs and candidate gene SNPs in brain AVM development – literature review
Published in Neurological Research, 2020
Ioan Alexandru Florian, Teodora Larisa Timiș, Gheorghe Ungureanu, Ioan Stefan Florian, Adrian Bălașa, Ioana Berindan-neagoe
The brain endothelial cells of AVMs (AVM-BECs) are believed to be highly active, possess a more rapid proliferation and migration, and display anomalous functions as well as altered expression of certain growth factors that promote angiogenesis [11,14,19]. Such an example would be the low levels of thrombospondin-1 (TSP-1), a Vascular Endothelial Growth Factor A (VEGF-A) antagonist found within these cells, due to the high levels of ‘inhibitor of DNA-binding protein A’ (Id-1), which suppresses the transcription of TSP-1 [11,12,20]. In order to downregulate this inhibitor, the increase of microRNA-18a (miR-18a), belonging to the miR-17 to miR-92 cluster, seems like an encouraging option that may impede the anarchic and unfettered growth of AVMs, even after partial surgical removal or embolization. Although miR-17, miR-18a, miR-19a and miR-20a possess antiangiogenic activity, at least when assessed independently, they have also been linked to tumor angiogenesis [9]. As shown by Ferreira et al., the clearest effects of miR-18a appeared on cells exposed to different arterial shear flow conditions, its signaling considerably diminishing the discharge of VEGF-A and VEGF-D from AVM-BECs subjected to this specific condition [11]. Their study was also the first to indicate that the internalization of miR-18a can be achieved without a transfection reagent (naked miRNA) in untransformed cells, specifically endothelial cells, while also remaining functionally significant.