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Craniofacial Surgery
Published in John C Watkinson, Raymond W Clarke, Christopher P Aldren, Doris-Eva Bamiou, Raymond W Clarke, Richard M Irving, Haytham Kubba, Shakeel R Saeed, Paediatrics, The Ear, Skull Base, 2018
Benjamin Robertson, Sujata De, Astrid Webber, Ajay Sinha
OAVS is usually a sporadic condition. Multiple theories have been put forward to try to explain the aetiology but it is likely to be a multifactorial condition due to varying combinations of genetic and environmental (including teratogenic) factors. Rare cases (fewer than 1%) may be due to a mutation in the recently identified MYT1 gene.67
Phytochemistry of Harmal
Published in Ephraim Shmaya Lansky, Shifra Lansky, Helena Maaria Paavilainen, Harmal, 2017
Ephraim Shmaya Lansky, Shifra Lansky, Helena Maaria Paavilainen
Yet, in spite of the advances in synthetic harmine analogs and novel delivery aggregates, simple harmine (or harmine hydrochloride) continues to provoke interest as an anticancer drug. Harmine caused mitochondrial apoptosis in human gastric carcinoma and hepatocellular cancer cells, but not in LO-2 immortalized liver cells via upregulated expression of p21, activation of Myt1, inhibition of cdc2 by phospho-cdc2, and triggering G2 phase arrest, in both MGC-803 human gastric cancer cells and SMMC-7721 human hepatocellular carcinoma cells. Harmine caused as well mitochondria-related cell apoptosis via caspase-8/Bid, inhibiting the ERK/Bad pathway (Zhang et al. 2016).
In vivo reprogramming
Published in Christine Hauskeller, Arne Manzeschke, Anja Pichl, The Matrix of Stem Cell Research, 2019
Neuronal loss is a common hallmark of many neurodegenerative diseases which can lead to functional impairments (Guo et al., 2014). Recently, the reprogramming of somatic cells to neurons has been introduced as a novel strategy in the enhancement of endogenous repair. The earliest report, by Vierbuchen et al., demonstrated that both embryonic and postnatal fibroblasts can be efficiently converted to neurons using the overexpression of neural lineage-specific transcription factors such as Ascl1, Brn2, and Myt1 (ABM). These induced neurons expressed a specific neuronal marker and had the ability for action potential firing (Vierbuchen et al., 2010). Further study by this group also showed that human fibroblasts converted to functional neurons by the introduction of ABM and NeuroD1 transcription factors into a culture medium (Pang et al., 2011). Interestingly, the Ascl1-induced neurons were mostly excitatory – revealing the generation of certain subtypes of neuron through this approach. In addition to the ectopic expression of transcription factors, neuronal induction can be achieved using certain microRNAs and small molecules (Chen et al., 2016). However, though the overexpression of neuronal-specific microRNAs such as miR-9/9* and miR-124 could convert human fibroblasts to neurons, the efficiency of this process was low and the overexpression of transcription factors was required to obtain functional neurons (Yoo et al., 2011). Delivery of transcription factors and microRNAs through viral injection has been noticed as the main problem for using this approach in patients (Li and Chen, 2016). An alternative method is the direct conversion of cells by the specific combinations of small molecules. Interestingly, Li et al. could convert 90% of fibroblasts to neurons using a combination of four small molecules (Li et al., 2015). Additionally, astrocytes have also been converted to neurons by a combination of small molecules (Zhang et al., 2015). Furthermore, induced neurons can be derived from the human fibroblasts of Alzheimer’s disease (AD) patients using small molecules (Hu et al., 2015). Despite the beneficial effects of chemical reprogramming, there is no possibility for the application of small molecules in vivo – and the induced cells have to be transplanted into an adult brain which still faces the hurdle of immunorejection (Li and Chen, 2016).
PARP inhibitors as single agents and in combination therapy: the most promising treatment strategies in clinical trials for BRCA-mutant ovarian and triple-negative breast cancers
Published in Expert Opinion on Investigational Drugs, 2022
Another kinase in the same class as WEE1 kinase is the MYT1 kinase, which also inhibits CDK1 by phosphorylation, contributing to checkpoint recovery in a WEE1-independent manner [93]. Specifically, cyclin B-CDK1 complexes are inactivated before mitosis through phosphorylation of Thr14 and Tyr15 by WEE1 and MYT1. WEE1 specifically phosphorylates Tyr15 on both CDK1 and CDK2 [87], while MYT1 preferentially phosphorylates Thr14 on CDK1 [94,95]. A previous study suggested that upregulation of MYT1 promotes acquired resistance of cancer cells to WEE1 inhibition while downregulating MYT1 enhances ectopic CDK1 activity and restores sensitivity to the WEE1 inhibitor (adavosertib) [96]. These data suggest MYT1 could be a potential predictive biomarker of acquired resistance to adavosertib. Currently, there is only one recent phase-I clinical trial of MYT1 inhibitor (RP-6306) as monotherapy in treating advanced solid tumors, which was initiated in late 2021, and no results are yet available (NCT04855656).
Dysregulation of Myt1 expression acts as a potential peripheral biomarker for major depressive disorder and bipolar disorder
Published in Journal of Neurogenetics, 2021
Maryam Ghanbarirad, Mehrdad Hashemi, Seyed Mehdi Saberi, Ahmad Majd
Myelin transcription factor 1 (known as Myt1, Nzf2, and Mtf1) is a conserved transcription factor and a nonclassical neural zinc finger protein (NZF), involved in neurogenesis and differentiating neuronal precursors (Manukyan, Kowalczyk, Melhuish, Lemiesz, & Wotton, 2018; Vasconcelos et al., 2016). In addition, Myt1 binds to the promoter of proteolipid (PLP) gene, which is considered as the myelin gene of central nervous system. Myt1 transcription factor is located in the nucleus of immature oligodendrocytes and decreases after maturation and final differentiation of the cell. Eventually, its expression decreases after myelin production (Vana, Lucchinetti, Le, & Armstrong, 2007).
A novel gene signature to predict immune infiltration and outcome in patients with prostate cancer
Published in OncoImmunology, 2020
Ning Shao, Hong Tang, Yuanyuan Mi, Yao Zhu, Fangning Wan, Dingwei Ye
Further, Ye J found that TROAP regulates prostate cancer progression via the WNT3/survivin signaling pathway.21 Leyten GH indicated that PPFIA2 is a promising biomarker in urine for the detection of prostate cancer.22 Visconti R suggested that inhibition of MYT1 expression may improve the efficacy of antimicrotubule drugs and reduce the acquisition of drug resistance by tumor cells.23 These studies, therefore, provide a functional rationale to explain the significant associations of the expression of TROAP, PPFIA2, and MYT1 with the risk of BCR after patients with PCa undergo RP.