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Garcinia indica (Kokum) and Ilex aquifolium (European Holly)
Published in Azamal Husen, Herbs, Shrubs, and Trees of Potential Medicinal Benefits, 2022
Dicson Sheeja Malar, Mani Iyer Prasanth, Tewin Tencomnao, James Michael Brimson, Anchalee Prasansuklab
The ethyl acetate extract of I. aquifolium leaves exhibits anticancer activity against colon carcinoma cells and glioblastoma cells (Frédérich et al., 2009). UA, the bioactive component of I. aquifolium exhibits potential anticancer effects. It inhibits angiogenesis, invasion, and migration of NSCLC cells by attenuating programmed death ligand-1 (PD-L1) expression, that mediates metastasis through the EGFR/JAK2/STAT3 pathway (Kang et al., 2021). Invasion of lung cancer cells was inhibited by the diminution of epithelial–mesenchymal transition by downregulating the expression of astrocyte-elevated gene-1 (AEG-1) by targeting NFκB pathway (Liu et al., 2013). Further, UA attenuated the expression of DNMT1 and EZH2, which are involved in tumor progression through SAP/JNK pathway (Wu et al., 2015). In NSCLC cells with EGFR T790M mutations, UA suppressed the expression of the proto-oncogene CT45A2 gene, which is involved in tumorigenesis through β‐catenin/TCF4 signaling pathway (Yang et al., 2019). Moreover, UA increased the sensitivity of chemoresistant NSCLC cells by inhibiting miR-149-5p/MyD88 signaling (Chen et al., 2020a). UA specifically binds and inhibits activity of vaccinia-related kinase 1 (VRK1) kinase domain and induces DNA damage in lung cancer cells (Kim et al., 2015).
Corneal Disorders
Published in Ching-Yu Cheng, Tien Yin Wong, Ophthalmic Epidemiology, 2022
Darren S. J. Ting, Rashmi Deshmukh, Daniel S. W. Ting, Marcus Ang
Amongst all, keratoconus and FECD are two of the most commonly investigated corneal diseases. This is primarily attributed to the high disease prevalence and the need for corneal transplantation for the severe form of these diseases, which places substantial burden on the limited pool of donor corneas.95 Over the years, GWLS have successfully identified a number of genetic mutations implicated in keratoconus, including COL8A1, CAST, LOX, TCEB1, and TGFBI genes, amongst others.124 GWAS has increasingly been used to identify genetic susceptibility regions in keratoconus and FECD.124,125 For instance, McComish et al.115 recently identified a novel genetic locus in PNPLA2 at chromosome 11 for keratoconus based on over 6 million genetic variants. Several novel genetic loci for FECD, including TCF4, KANK4 rs79742895, LAMC1 rs3768617, and LINC00970/ATP1B1 rs1200114, have also been discovered through GWAS.119 Next-generation sequencing (NGS), which represents the most comprehensive tool in identifying genomic variants,126 has recently been utilized to unravel novel mutations associated with other types of corneal dystrophy.127
Pathogenesis: Molecular mechanisms of osteoporosis
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
Anastasia E. Markatseli, Theodora E. Markatseli, Alexandros A. Drosos
Lef/Tcf transcription factors: Various isoforms of Lef/Tcf transcription factors have been described in the literature. The main isoforms expressed in osteoblasts are Tcf1 and Tcf4 (17,23). In the absence of Wnt signaling, Lef/Tcf factors are bound to transcriptional co-repressors (266–268). The activation of the canonical Wnt signaling pathway leads to the replacement of co-repressors by β-catenin and its binding to Lef/Tcf factors. Of note, several studies indicate that the activity of Lef/Tcf transcription factors is increased in areas of the skeleton that undergo bone remodeling (248,269–272).
The Association of RGS2 and Slug in the Androgen-induced Acquisition of Mesenchymal Features of Breast MDA-MB-453 Cancer Cells
Published in Endocrine Research, 2022
Dana B. Alsafadi, Mohammad S. Abdullah, Randa Bawadi, Mamoun Ahram
It is interesting to note that inhibition of Slug expression does not reduce the DHT-induced migration of these cells. The separation of morphological-altering pathways from cell migration is not unprecedented and has previously been reported.41 This strongly suggests the involvement of divergent pathways once AR is activated. A potential pathway may proceed through Wnt/β-catenin/TCF4. The connection between AR signaling and the latter pathway is well established in prostate and breast cancers.42 In bladder cancer, activation of AR by DHT results in stimulation of the Wnt/β-catenin pathway marked by the nuclear translocation of β-catenin, which stimulates the expression of slug.27 However, the mesenchymal transformation of MDA-MB-453 cells is associated with the down-regulation of expression of β-catenin, N-cadherin, TCF4, and fibronectin and the lack of change in the expression of E-cadherin, vimentin, and ZEB1 and ZEB2 in DHT-treated MDA-MB-453 cells.12 Another possible mechanism is the suppression of the expression of desmocollin 2, which is essential for cell-cell adhesion and whose down-regulation induces MDA-MB-453 cells to assume a mesenchymal shape in association with a slight, but insignificant, increase in cell migration.43 The β-catenin pathway is still involved in regulating the function of desmocollin 2.
Role and molecular mechanism of stem cells in colorectal cancer initiation
Published in Journal of Drug Targeting, 2020
Meng-Yan Wang, Yu-Han Qiu, Mei-Lian Cai, Cong-Hui Zhang, Xiao-Wei Wang, Hong Liu, Yi- Chen, Wu-Li Zhao, Jing-Bo Liu, Rong-Guang Shao
The traditional Wnt activation pathway is initiated when the receptor binds to the ligand to increase the downstream activation of β-catenin transport into the nucleus. Then, β-catenin and TCF4/LEF form a complex that binds to the target gene promoter to initiate transcription. TRIB3 binds to TCF4/LEF complexes to increase the transcriptional activity of β-catenin/TCF4/LEF, enhancing Wnt target gene expression to promote stem maintenance. Additionally, activated Wnt signalling induces TRIB3 upregulation, which acts as part of a positive feedback loop. Conversely, β-catenin can stabilise TRIB3 by inhibiting the ubiquitin ligase SIAH1. The activation of the Wnt pathway together with TRIB3 maintains the phenotype of colon CSCs and promotes tumour proliferation [61]. This positive feedback between the TRIB3 and Wnt pathways is a key factor in the poor prognosis of colorectal cancer patients, but it also gives researchers a possible new target for targeting cancer cells.
Association of transcription factor 7-like 2 (rs7903146) gene polymorphism with diabetic retinopathy
Published in Ophthalmic Genetics, 2020
Hadeel Ahmed Shawki, Ekbal M.Abo-Hashem, Magdy M. Youssef, Maha Shahin, Rasha Elzehery
Transcription factor 7-like 2 “TCF7L2” also known as transcription factor 4 “Tcf4” is a member of the T-cell factor “Tcf” -Lymphoid enhancer factor “Lef” transcription factor family. TCF7L2 is an effector in the Wnt signaling pathway (11). TCF7L2 gene located on chromosome 10q25.3 with 17 exons and regulates insulin biosynthesis, secretion, and processing. TCF7L2 gene plays a significant role in maintaining blood-glucose homeostasis and β -cell function (12). In addition, it has an important role in the formation of mature insulin by coordinating the expression of proinsulin (13). TCF7L2 has at least four polymorphic markers which are: C-to-T (genomic position: 114748339) substitution at SNP rs7903146 of the intron 3 (IVS3 C > T), T-to-C (genomic position: 114744078) substitution at SNP rs7901695 of the intron3 (IVS3 T > C), G-to-T (genomic position: 14798892) substitution at SNP rs12255372 of theintron4 (IVS4 G > T), and G-to-C (genomic position: 114797037) substitution at SNP rs11196205 of the intron4 (IVS4 G > C) (14). TCF7L2 gene polymorphisms are associated with type 2 diabetes and cardiovascular disease (15,16). Beside, TCF7L2 (rs7903146) had major roles in gestational diabetes mellitus in Indian pregnant women (17), and TCF7L2 rs7903146 polymorphisms are associated with Post-transplant diabetes mellitus in the Asian Indian population (18). The role of the genetic variation in the development of DR may not only reveal novel molecular mechanisms but also help to discover biomarkers and ultimately novel therapies to prevent and treat the disease (19). Therefore, the present study aimed to investigate the association between TCF7L2 (rs7903146) gene polymorphism and the risk of diabetic retinopathy in a group of Egyptian diabetic patients (both type1 and type 2 DM).