Search results for " FIBROSIS"
showing 10 items of 490 documents
Junctional adhesion molecules JAM-B and JAM-C promote autoimmune-mediated liver fibrosis in mice
2018
Fibrosis remains a serious health concern in patients with chronic liver disease. We recently reported that chemically induced chronic murine liver injury triggers increased expression of junctional adhesion molecules (JAMs) JAM-B and JAM-C by endothelial cells and de novo synthesis of JAM-C by hepatic stellate cells (HSCs). Here, we demonstrate that biopsies of patients suffering from primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) or autoimmune hepatitis (AIH) display elevated levels of JAM-C on portal fibroblasts (PFs), HSCs, endothelial cells and cholangiocytes, whereas smooth muscle cells expressed JAM-C constitutively. Therefore, localization and function of JA…
Autophagy Stimulation as a Potential Strategy Against Intestinal Fibrosis
2019
We recently observed reduced autophagy in Crohn’s disease patients and an anti-inflammatory effect of autophagy stimulation in murine colitis, but both anti- and pro-fibrotic effects are associated with autophagy stimulation in different tissues, and fibrosis is a frequent complication of Crohn’s disease. Thus, we analyzed the effects of pharmacological modulation of autophagy in a murine model of intestinal fibrosis and detected that autophagy inhibition aggravates, while autophagy stimulation prevents, fibrosis. These effects are associated with changes in inflammation and in collagen degradation in primary fibroblasts. Thus, pharmacological stimulation of autophagy may be useful against …
Induction of Autophagy by Pterostilbene Contributes to the Prevention of Renal Fibrosis via Attenuating NLRP3 Inflammasome Activation and Epithelial-…
2020
Chronic kidney disease (CKD) is recognized as a global public health problem. NLRP3 inflammasome activation has been characterized to mediate diverse aspect mechanisms of CKD through regulation of proinflammatory cytokines, tubulointerstitial injury, glomerular diseases, renal inflammation, and fibrosis pathways. Autophagy is a characterized negative regulation mechanism in the regulation of the NLRP3 inflammasome, which is now recognized as the key regulator in the pathogenesis of inflammation and fibrosis in CKD. Thus, autophagy is undoubtedly an attractive target for developing new renal protective treatments of kidney disease via its potential effects in regulation of inflammasome. Howe…
Polyphosphate Reverses the Toxicity of the Quasi-Enzyme Bleomycin on Alveolar Endothelial Lung Cells In Vitro
2021
Simple Summary Bleomycin (BLM) is a medication introduced used to treat various types of cancer, including testicular cancer, ovarian cancer, and Hodgkin’s disease. Its most serious side effect is pulmonary fibrosis and impaired lung function. Using A549 human lung cells it is shown that, in parallel to an increased cell toxicity and DNA damage, BLM causes a marked enlargement of the cell nucleus. This effect is abolished by inorganic polyphosphate (polyP), if this physiological polymer is administered together with BLM. The detoxification of BLM is–most likely–caused by the upregulation of the gene encoding the BLM hydrolase which inactivates BLM in vitro and in vivo. This study contribute…
Strategies against nonsense: oxadiazoles as translational readthrough-inducing drugs (TRIDs)
2019
This review focuses on the use of oxadiazoles as translational readthrough-inducing drugs (TRIDs) to rescue the functional full-length protein expression in mendelian genetic diseases caused by nonsense mutations. These mutations in specific genes generate premature termination codons (PTCs) responsible for the translation of truncated proteins. After a brief introduction on nonsense mutations and their pathological effects, the features of various classes of TRIDs will be described discussing differences or similarities in their mechanisms of action. Strategies to correct the PTCs will be presented, particularly focusing on a new class of Ataluren-like oxadiazole derivatives in comparison …
Long-Term Aspartame Administration Leads to Fibrosis, Inflammasome Activation, and Gluconeogenesis Impairment in the Liver of Mice
2021
Background: Aspartame is an artificial sweetener used in foods and beverages worldwide. However, it is linked to oxidative stress, inflammation, and liver damage through mechanisms that are not fully elucidated yet. This work aimed to investigate the effects of long-term administration of aspartame on the oxidative and inflammatory mechanisms associated with liver fibrosis progression in mice. Methods: Mice were divided into two groups with six animals each: control and aspartame. Aspartame (80 mg/kg, via oral) or vehicle was administrated for 12 weeks. Results: Aspartame caused liver damage and elevated serum transaminase levels. Aspartame also generated liver fibrosis, as evidenced by his…
Serial combination of noninvasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with nonalcoholic fatty liver disease
2017
Decreased Fibrogenesis After Treatment with Pirfenidone in a Newly Developed Mouse Model of Intestinal Fibrosis
2016
BACKGROUND Fibrosis as a common problem in patients with Crohn's disease is a result of an imbalance toward excessive tissue repair. At present, there is no specific treatment option. Pirfenidone is approved for the treatment of idiopathic pulmonary fibrosis with both antifibrotic and anti-inflammatory effects. We subsequently investigated the impact of pirfenidone treatment on development of fibrosis in a new mouse model of intestinal fibrosis. METHODS Small bowel resections from donor mice were transplanted subcutaneously into the neck of recipients. Animals received either pirfenidone (100 mg/kg, three times daily, orally) or vehicle. RESULTS After administration of pirfenidone, a signif…
Transient elastography for screening of liver fibrosis: cost-effectiveness analysis from six prospective cohorts in Europe and Asia
2019
Background & Aims: Non-alcoholic fatty liver disease and alcohol-related liver disease pose an important challenge to current clinical healthcare pathways because of the large number of at-risk patients. Therefore, we aimed to explore the cost-effectiveness of transient elastography (TE) as a screening method to detect liver fibrosis in a primary care pathway. Methods: Cost-effectiveness analysis was performed using real-life individual patient data from 6 independent prospective cohorts (5 from Europe and 1 from Asia). A diagnostic algorithm with conditional inference trees was developed to explore the relationships between liver stiffness, socio-demographics, comorbidities, and hepati…
EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update
2021
Summary Non-invasive tests are increasingly being used to improve the diagnosis and prognostication of chronic liver diseases across aetiologies. Herein, we provide the latest update to the EASL Clinical Practice Guidelines on the use of non-invasive tests for the evaluation of liver disease severity and prognosis, focusing on the topics for which relevant evidence has been published in the last 5 years.