Generation of Cell Lines Stably Expressing a dCas9-Fusion or sgRNA to Address Dynamics of Long-Term Effects of Epigenetic Editing.

Epigenetic modifications play a crucial role in regulating gene expression patterns. Through epigenetic editing approaches, the chromatin structure is modified and the activity of the targeted gene can be reprogrammed without altering the DNA sequence. By using the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic repeats) platform with nuclease-deactivated dCas9 proteins to direct epigenetic effector domains (EDs) to genomic regulatory regions, the expression of the targeted gene can be modulated.

Treatment of intestinal and liver features in cystic fibrosis mice by the osmotic laxative polyethylene glycol.

Background: Cystic Fibrosis (CF) is a genetic disease affecting multiple organs, primarily the lungs and digestive system. Improved pulmonary management significantly improved life expectancy of CF patients. As a result, extrapulmonary manifestations, including gastrointestinal and liver-related symptoms, have become more relevant.

The chemotherapeutic drug doxorubicin does not exacerbate p16-positive senescent cell accumulation and cardiometabolic disease development in young adult female LDLR-deficient mice.

Cancer survivors who received chemotherapy, such as the anthracycline doxorubicin (DOX), have an increased risk of developing complications later in life, including the development of chronic metabolic diseases. Although the etiology of this increased risk for late metabolic complications in cancer survivors is poorly understood, a causal role of therapy-induced senescent cells has been suggested. To study the role of cellular senescence in chemotherapy-induced metabolic complications, young adult female low-density lipoprotein receptor-deficient (Ldlr)-p16-3MR mice, in which p16-positive (p16) senescent cells can be genetically eliminated, were treated with four weekly injections of DOX (2.

Pharmacological inhibition of MEK1/2 signaling disrupts bile acid metabolism through loss of Shp and enhanced Cyp7a1 expression.

The RAS-MAPK signaling pathway is one of the most frequently dysregulated pathways in human cancer. Small molecule inhibitors directed against this pathway have clinical activity in patients with various cancer types and can improve patient outcomes. However, the use of these drugs is associated with adverse effects, which can result in dose reduction or treatment interruption.

Defective Lipid Droplet-Lysosome Interaction Causes Fatty Liver Disease as Evidenced by Human Mutations in TMEM199 and CCDC115.

Background & Aims: Recently, novel inborn errors of metabolism were identified because of mutations in V-ATPase assembly factors TMEM199 and CCDC115. Patients are characterized by generalized protein glycosylation defects, hypercholesterolemia, and fatty liver disease. Here, we set out to characterize the lipid and fatty liver phenotype in human plasma, cell models, and a mouse model.

β-Catenin Directs Nuclear Factor-κB p65 Output CREB-Binding Protein/p300 in Human Airway Smooth Muscle.

β-Catenin is a multifunctional protein that apart from its role in proliferative and differentiation events, also acts upon inflammatory processes, mainly interaction with nuclear factor-κB (NF-κB). However, there is still controversy as to whether β-catenin facilitates or represses NF-κB output. Insights into the molecular mechanisms underlying the interaction between β-catenin and NF-κB have highlighted the cofactors CREB-binding protein (CBP) and p300 as important candidates.