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Role of Histone Methyltransferase in Breast Cancer
Published in Meenu Gupta, Rachna Jain, Arun Solanki, Fadi Al-Turjman, Cancer Prediction for Industrial IoT 4.0: A Machine Learning Perspective, 2021
Surekha Manhas, Zaved Ahmed Khan
Further, GFI1 retroviral overexpression in cells of Th2 led to an increase in the rate of cellular survival and proliferation [77]. During the infection or in vitro stimulation with parasites, including Schistosoma mansoni and helminth parasite, T cells that lack of GFI1 failed to generate IL-4 optimally [80]. Mechanistically, GFI1 works to inhibit GATA3 proteasomal degradation by targeting its SNAG domain at the N-terminal position [78]. As cellular differentiation of Th2 cells is getting impaired in the case of G9a-deficient Th2 cells, it may increase the chances of interactions between these three G9a/GFI1/GATA3 critical for transcriptional module establishment, which leads to type 11 cytokine locus activation [15]. As per G9a’s role, the N-terminus of ligand activating receptors present on the nuclear hormone regulate gene expression to act as a scaffold [35]. Based on the above available results, it is very clear that in T cells, G9a N-terminus might aid in GATA3, GFI1, and the various other factors that potentially play a role in optimal Th2-cell development. In the cellular differentiation of Treg cells and Th17 cells, involvement of GFI1 has also been observed [81].
Basics of Allergy
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Rafeul Alam, Dipa K Sheth, Magdalena M Gorska
T cell phenotype: Activated T and B cells in the lymph node downregulate CCR7, begin to express receptors for chemokines that are preferentially expressed in the peripheral tissue and migrate to the site of pathogen entry. CD4 T cells (also called Th0) differentiate into T helper 1 cells (Th1), T helper 2 cells (Th2), and T helper 17 (Th17) cells, whereas CD8 T cells differentiate into cytotoxic T cells (Tables 1.3 and 1.4). Under specific circumstances cytotoxic CD8 T cells can differentiate into Tc1 and Tc2 cells, whose cytokine production profile is similar to that Th1 and Th2 cells. The differentiation of Th1, Th2 and Th17 cells is induced by IL-12, IL-4, and IL6, IL1 (in humans) and TGFb (in mice) respectively (Glimcher 2001). The foregoing cytokines are typically secreted by the antigen-presenting cell and/or other accessory cells. For Th1 differentiation IL-12 signaling via STAT-4 is essential, which activates the master Th1 regulator—T-bet, a transcription factor that induces sustained production of Th1 cytokines and also blocks Th2 differentiation. IL-4 signaling via STAT-6 and other signaling molecules, induces the master Th2 switch—GATA-3. GATA-3 stimulates Th2 cytokine production and inhibits Th1 differentiation (Table 1.4). IL6 stimulated STAT3 in the presence of TGFb induces RORgT, the master regulator of Th17. Th1 cells are primarily induced by and play a critical role in the defense against intracellular pathogens. Th2 cells are induced by extracellular pathogens/antigens. Th17 cells are induced by pathogens but are involved in autoimmunity in addition to defense against pathogens.
Non-Hodgkin Lymphoma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Piers Blombery, David C. Linch
PTCL-NOS—PTCL-NOS accounts for around half of the cases of PTCL in Western countries.84,85,106 It is a heterogeneous group of diseases with a predominantly nodal presentation. Genomic characterization of this broad biological group has identified three major subgroups within PTCL-NOS: (i) PTCL-GATA3 which overexpresses GATA3 and has an inferior prognosis, (ii) PTCL-TBX21 which overexpresses TBX21, and (iii) PTCL-TFH which is a nodal PTCL-NOS that expresses a TFH phenotype (CD4+, PD1+, CD10+, BCL6+ CXCL13, and/or ICOS).96 The overall prognosis is variable reflecting the biological heterogeneity of the underlying disorder, ranging from a 5-year OS under 20% in the highest-risk patients to approximately 60% in patients without adverse risk factors.83 Although optimal frontline therapy is unclear, CHOP-type chemotherapy is usually used (with the addition of etoposide possibly adding benefit).90 In addition, there have been attempts to add targeted therapy to CHOP regimens analogous to the addition of rituximab to CHOP in the treatment of B-lineage NHL. CHOP-alemtuzumab,107 CHOP-bortezomib,108 and CHOP-denileukin diftitox109 have all been trialed with varying success. One potential option for CD30-expressing PTCL-NOS is BV-CHP.91
Chao Nang Qing prescription promotes granulosa cell apoptosis and autophagy by targeting GATA3
Published in Gynecological Endocrinology, 2023
Lan Luo, Yan Shen, Donghong Ning, Mi Tang, Licen Xie, Qiuman Zheng, Ziting Ouyang
GATA3 is a transcriptional activator that can promote downstream gene expression by recognizing and binding to the promoter of target genes. The JASPAR database (https://jaspar.genereg.net/) showed there are two binding sites for GATA3 in the MYCT1 promoter (Figure 3D), and the binding motif is AGATAAGA (Figure 3E). We performed ChIP experiments to detect the binding of GATA3 and the MYCT1 promoter. As shown in Figure 3F, compared to IgG, GATA3 strongly bound with MYCT1 (p < .01). To observe the effect of GATA3 on MYCT1 promoter activity, we selectively constructed two luciferase reporter vectors containing MYCT1 promoter fragments (Figure 3G). GATA3 knockdown reduced the luminescence of the MYCT1 promoter reporter vectors in KGN cells (Figure 3H, p < .01). Altogether, GATA3 activates MYCT1 transcription by binding to the MYCT1 promoter.
The Promising Therapeutic Potential of Oligonucleotides for Pulmonary Fibrotic Diseases
Published in Expert Opinion on Drug Discovery, 2023
Divyani Paul, Madelyn H Miller, Josh Born, Shayak Samaddar, Huanzhen Ni, Hugo Avila, Venkata R. Krishnamurthy, Kannan Thirunavukkarasu
DNAzymes are single-stranded DNA molecules that bind to target mRNA by Watson–Crick base pairing and cause catalytic cleavage of target mRNA strands in the presence of metal ions (such as Na+, Mg2+, Ca2+, Pb2+ etc.). A typical DNAzyme contains an active size for catalytic cleavage surrounded by two binding arms responsible for mRNA recognition. SB-010 is an inhalable DNAzyme formulation that is being developed by Sterna Biologicals for the treatment of asthma and COPD. The ASO is administered in phosphate-buffered saline solution via an inhalation device at a dose of 5.0 mg/ml [50]. GATA-3 is the master transcription factor in regulating the Th2 response. SB-010 prevents translation of GATA-3 by binding and cleaving the mRNA precursor of the protein. SB-010 was evaluated in Phase IIa clinical trials for asthma and COPD patients. Orally inhaled SB-010 improved lung function in both early and late-phase asthma patients. SB-010 utilized for the treatment of moderate-to-severe COPD patients showed that it was efficacious by reducing the relative sputum eosinophil count by 58.8% as compared to 11% in the placebo group and patients who received the standard therapy of inhaled corticosteroids. In both the studies, SB-010 was demonstrated to be safe, well tolerated with no serious adverse effects [51].
Immunohistochemical Panels to Evaluate Important Immunophenotypes of Human Mesonephros
Published in Fetal and Pediatric Pathology, 2023
Ping L. Zhang, Jacqueline K. Macknis
The main goals of our current study were to determine whether glomerular and tubular structures of mesonephros express similar protein markers to those in early metanephros. We selected the following key markers, known to be related to the development of metanephros, for evaluating the mesonephros in this study. PAX8 is involved in intermediate mesoderm transition and pronephric duct formation and is positive in parietal epithelial cells and at all levels of renal tubules [20,21]. GATA3 is another marker mainly involving in the development of the ureteric bud and its differentiation, and is also expressed in mesangial cells from the metanephric stromal progenitor cells [22,23]. AMACR was selected to confirm proximal tubules of mesonephros, as this marker is commonly used for identifying lesions associated with the proximal tubules [24]. In addition to routine hematoxylin and eosin staining, conventional PAS was utilized to detect the brush borders of proximal tubules and glomerular basement membranes (GBM) in mesonephros.