CRISPR/Cas9-Based Screening of FDA-Approved Drugs for NRF2 Activation: A Novel Approach to Discover Therapeutics for Non-Alcoholic Fatty Liver Disease
نویسندگان
چکیده
With the rising prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) now affects 20–25% global population. NAFLD, a progressive condition associated with oxidative stress, can result in cirrhosis and cancer 10% 3% patients suffering respectively. Therapeutic options are currently limited, emphasizing need for novel treatments. In this study, we examined potential activating transcription factor NRF2, crucial player combating as an innovative approach to treating NAFLD. Utilizing CRISPR/Cas9-engineered human HEK293T cell line, were able monitor expression heme oxygenase-1 (HMOX1), NRF2 target, using Nanoluc luciferase tag. Our model was validated known activator, after which screened 1200 FDA-approved drugs, unearthing six compounds (Disulfiram, Thiostrepton, Auranofin, Thimerosal, Halofantrine, Vorinostat) that enhanced activity antioxidant response. These demonstrated protective effects against stress induced by hydrogen peroxide lipid droplets accumulation vitro hepatoma HUH-7 cells. study underscores utility CRISPR/Cas9 tagging identifying activators, paving way NAFLD therapeutics.
منابع مشابه
A diagnostic model for cirrhosis in patients with non-alcoholic fatty liver disease: an artificial neural network approach
Background :Timely diagnosis of liver cirrhosis is vital for preventing further liver damage and giving the patient the chance of transplantation. Although biopsy of the liver is the gold standard for cirrhosis assessment, it has some risks and limitations and this has led to the development of new noninvasive methods to determine the stage and prognosis of the patients. We aimed to design an...
متن کاملNon-alcoholic fatty liver disease: a practical approach to treatment
Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population in many developed countries. Between 10% and 30% of patients with NAFLD have non-alcoholic steatohepatitis (NASH) that can progress to cirrhosis. There are metabolic risk factors common to both NAFLD and cardiovascular disease, so patients with NASH have an increased risk of liver-related and cardiovascular death....
متن کاملmore on current evidences on probiotics as a novel treatment for non-alcoholic fatty liver disease
متن کامل
A Nutrigenomic Approach to Non-Alcoholic Fatty Liver Disease
Following the epidemics of obesity due to the consumption of high-calorie diet and sedentary lifestyle, nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in Western countries. NAFLD is epidemiologically associated with metabolic syndrome and insulin resistance, and in susceptible individuals it may progress to cirrhosis and hepatocellular carcinoma. Genetic fact...
متن کاملClinical Manifestations and Diagnosis of Non-Alcoholic Fatty Liver Disease
Background & Objective: Nonalcoholic fatty liver diseases (NAFLD) is the major cause of hepatocellular carcinoma and increases the risk of mortality. Understanding the trends of its clinical and biochemical changes is essential to identify patients with NAFLD that are at the greatest risk of nonalcoholic steatohepatitis (NASH) and cirrhosis in Iran. M...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Antioxidants
سال: 2023
ISSN: ['2076-3921']
DOI: https://doi.org/10.3390/antiox12071363