China
Africa
Explore chapters and articles related to this topic
Bone Regeneration Effect of Cassia occidentalis Linn. Extract and Its Isolated Compounds
Published in Brijesh Kumar, Vikas Bajpai, Vikaskumar Gond, Subhashis Pal, Naibedya Chattopadhyay, Phytochemistry of Plants of Genus Cassia, 2021
Brijesh Kumar, Vikas Bajpai, Vikaskumar Gond, Subhashis Pal, Naibedya Chattopadhyay
Unlike in rat, where emodin had no effect on preventing the OVX-induced bone loss, in OVX mouse, emodin (100 mg/kg b.i.d. every 3 days) given for 3 months increased osteoblast number with the increase in Runx2 positive cells in the lumbar vertebra and contributed to increases in bone mass and improved microarchitecture. In mouse bone marrow, emodin inhibited the OVX-induced adipocyte number and fat tissue fraction. In cultures of MSCs derived from bone marrow, emodin induced proliferation as well as differentiation. Osteogenic genes including Runx2, osterix, osteocalcin, col1 and BMP-4 were upregulated by emodin. Furthermore, emodin suppressed the differentiation of MSCs to adipocytes with attendant decreases in adipogenic genes including peroxisome proliferator-activated receptor-gamma PPARγ, CCAAT/enhancer-binding protein alpha C/EBPα and adipocyte protein 2 (aP2). Since increased adipogenesis significantly contributes to osteoclastogenic differentiation, emodin’s suppression of adipogenesis is likely to inhibit osteoclastogenesis and ultimately resorption. However, this study did not assess resorption parameters in OVX mice (Yang et al., 2014).
Familial Acute Myeloid Leukemia
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
The CCAAT/enhancer binding protein (C/EBP), alpha gene (CEBPA) is a single exon gene located on chromosome 19q13.1 band. The gene belongs to a family of basic leucine zipper proteins, and encodes for a transcription factor that is crucial for maturation of hematopoietic myeloid cells; no mature granulocytes are observed in CEBPA-mutant mice and the t(8;21) translocation downregulates CEBPA to lead to AML [35–37]. The CEBPA gene has 2 transactivation domains at the N-terminus, and a basic region and leucine zipper region at the C-terminus. Mutations in CEBPA may be present in sporadic AML in 5%–14% cases. Most commonly, mutations in the N-terminus cause a frameshift, leading to premature termination and absence of the normal, full-length 42 kDa protein, but still allowing downstream expression for formation of the smaller 30 kDa protein, a dominant-negative isoform. Mutations in the C-terminus disrupt the leucine zipper region, which prevents dimerization and loss of DNA activity [36].
Mouse Knockout Models of Biliary Epithelial Cell Formation and Disease
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Hepatocytes undergo a transition from a hepatic endodermal epithelum to a nonpolarized cellidar phenotype (hepatoblasts) and then back to a fully differentiated epithelium. By E17, hepatocytes have developed their characteristic cuboidal cell morphology and, are ready to undergo the transition from a hemopoietic support role to primary cells controlling metabolite and serum protein levels. During this perinatal phase, the hepatocytes begin to express many new genes under the control of the transcription factor C/EBPbeta. (CCAAT/enhancer binding protein. They also form the cell junctions that are required to create a polarized epithelium, with the apical cell surface being the site of bile secretion and the basal cell surface opposed to the endothelial cells.
Attenuation of obesity related inflammation in RAW 264.7 macrophages and 3T3-L1 adipocytes by varanadi kashayam and identification of potential bioactive molecules by UHPLC-Q-Orbitrap HRMS
Published in Archives of Physiology and Biochemistry, 2023
J. U. Chinchu, Mohind C. Mohan, B. Prakash Kumar
Obesity is a major health problem characterised by excessive body fat accumulation through an imbalance between energy intake and consumption and is responsible for developing type 2 diabetes, coronary heart disease and certain cancers (Guyenet and Schwartz 2012). Obesity is mainly associated with an increase in white adipose tissue mass through activation of adipogenesis and increased deposition of cytoplasmic triglycerides (Frigolet et al. 2008). Adipogenesis is a highly regulated process in which undifferentiated fibroblasts (preadipocytes) become mature adipocytes and is regulated by an elaborate network of transcription factors including CCAAT/enhancer-binding protein (C/EBP) and peroxisome proliferator-activated receptor-γ (PPAR-γ) (Yu et al. 2014). C/EBP-α and PPAR-γ work cooperatively in inducing the adipocyte differentiation process and promote the expression of fatty acid synthase (FAS) to trigger the synthesis and accumulation of triglyceride (TG) in mature adipocyte (Farmer 2006). Therefore, adipogenesis inhibition by downregulating adipogenic transcriptional factor expressions is critical for achieving an anti-obesity effect.
CEBPA mutants down-regulate AML cell susceptibility to NK-mediated lysis by disruption of the expression of NKG2D ligands, which can be restored by LSD1 inhibition
Published in OncoImmunology, 2022
Meng Liu, Mengbao Du, Jian Yu, Zijun Qian, Yang Gao, Wenjue Pan, Xiujie Zhao, Mowang Wang, Huimin Li, Jiaqi Zheng, Qianshuo Huang, Li-Mengmeng Wang, Haowen Xiao
CCAAT/enhancer-binding protein α (C/EBPα) is one of the most studied lineage-specific transcription factors (TFs) in hematopoiesis, which is mainly involved in cell fate decisions, including a key role in governing myeloid differentiation.1 In line with the critical role of C/EBPα in granulocytic differentiation, the CEBPA gene was found to be mutated in approximately 7% of all patients with acute myeloid leukemia (AML), and the incidence increased to 10–15% in AML patients with normal karyotype.2 Full-length C/EBPα is a 42-kDa protein (C/EBPα-p42) that contains two transactivation domains (TAD, TAD1 and TAD2) in the amino terminus and a basic leucine zipper domain (bZIP) at its carboxy terminus for DNA binding. Two major categories of collaborating CEBPA mutations have been described in human AML: (1) frameshift (FS) insertions or deletions affecting the N-terminal region resulting in a loss of the 42-kDa protein and overexpression of a shorter 30-kDa isoform (C/EBPα-p30), proposed to exhibit a dominant negative activity, and (2) in-frame mutations in the C-terminal region that alter the basic leucine zipper domain, leading to impaired DNA binding and disrupted protein–protein interactions.3 Furthermore, it has been shown that nearly 10% of AMLs with biallelic mutations in CEBPA also harbor a germline CEBPA mutation.4 These germline mutations are commonly additional C-terminal CEBPA mutations.5,6 So CEBPA mutations may be clustered to germline mutations, N-terminal frameshift mutations and C-terminal mutations.
Frequency and clinical impact of WT1 mutations in the context of CEBPA-mutated acute myeloid leukemia
Published in Hematology, 2022
Ting Wang, Haiying Hua, Zheng Wang, Biao Wang, Liujun Cao, Wei Qin, Pin Wu, Xiaohui Cai, Hongying Chao, XuZhang Lu
CCAAT/enhancer binding protein a (CEBPA) plays a crucial role in the repression of self-renewal, cell cycle arrest, and myeloid differentiation of mature neutrophils during normal hematopoiesis[1, 2]. Mutations in the CEBPA gene can occur across the whole coding region and have been described in approximately 6-24% of all acute myeloid leukemia (AML) patients[3–5]. CEBPA-mutated (CEBPAmut) patients can be subdivided into two different subgroups: (1) AML carrying one mutation on one allele (single-mutated CEBPA, CEBPAsm) and (2) AML with two CEBPA mutations (double-mutated CEBPA, CEBPAdm), typically showing an N-terminal mutation and a basic leucine zipper gene mutation. However, only patients who harbor CEBPA double mutations are associated with favorable outcomes[6, 7]. In the 2016 World Health Organization (WHO) classification of leukemia, AML with CEBPAdm was included as a distinctive disease entity due to its unique biological and clinical profiles[8].