(Press-News.org) A study published in the online journal Hepatology reports a potential new NADPH oxidase (NOX) inhibitor therapy for liver fibrosis, a scarring process associated with chronic liver disease that can lead to loss of liver function.
"While numerous studies have now demonstrated that advanced liver fibrosis in patients and in experimental rodent models is reversible, there is currently no effective therapy for patients," said principal investigator David A. Brenner, MD, vice chancellor for Health Sciences and dean of the School of Medicine at the University of California, San Diego. "This new study provides important validation of the role of NOX in liver fibrosis, and suggests that a NOX inhibitor could provide an effective treatment for this devastating disease."
Most chronic liver diseases are associated with progressive fibrosis, which is triggered by the loss of liver cells and the activation of inadequate wound healing pathways. In addition, oxidative stress – which results from an inappropriate balance between the production and clearance of highly reactive molecules involved in cell signaling called reactive oxidative species (ROS) – leads to aberrant tissue repair in the liver.
When the liver is injured – for example, through hepatitis or alcohol abuse –HSCs are activated to become myofibroblasts, cells which play a crucial role in wound healing and the body's response to inflammation by recruiting immune cells called macrophages to the injury site. This process, triggered by intracellular signalling pathways involving NOX, can result in an abundance of scarring and eventually result in the loss of organ function.
By inhibiting NOX, the researchers theorized that myofibroblast activation and macrophage recruitment could be interrupted, preventing further fibrosis and potentially allowing regression of established fibrosis.
They assessed the effectiveness of treatment with GKT137831 – a NOX1/4 inhibitor developed by Genkyotex SA of Geneva, Switzerland – in mouse models, and found that treatment with this NOX inhibitor suppressed ROS production, as well as NOX and fibrotic gene expression.
"These data highlight the excellent pharmacological properties of GKT137831 and the broad potential for its use in fibrotic diseases,'' said Patrick Page, chief development officer at Genkyotex and contributor to the study.
According to Brenner, the next steps include a clinical trial with this drug in patients with liver fibrosis.
###
Additional contributors include Tomonori Aoyama, UC San Diego and Juntendo University School of Medicine, Tokyo; Yong-Han Paik, Yonsei University College of Medicine, Seoul, Korea; Sumio Watanabe, Juntendo University; Benoît Laleu, Francesca Gaggini, Laetitia Fioraso-Cartier, Sophie Molangpo, Freddy Heitz, Cédric Merlot and Cédric Szyndralewiez, GenKyoTex SA, Geneva.
The study was funded in part by grants 1 R24 DK090962, 5 P50 AA011999 and 5 R01 GM041804 from the National Institutes of Health and by the American Liver Foundation.
END
PROVIDENCE, R.I. [Brown University] — In a touch-screen display or a solar panel, any conductive overlay had better be clear. Engineers employ transparent thin films of indium tin oxide (ITO) for the job, but a high-tech material's properties are only half its resume. They must also be as cheap and easy to manufacture as possible. In a new study, researchers from Brown University and ATMI Inc. report the best-ever transparency and conductivity performance for an ITO made using a chemical solution, which is potentially the facile, low-cost method manufacturers want.
"Our ...
Diseased trees in forests may be a significant new source of methane that causes climate change, according to researchers at the Yale School of Forestry & Environmental Studies in Geophysical Research Letters.
Sixty trees sampled at Yale Myers Forest in northeastern Connecticut contained concentrations of methane that were as high as 80,000 times ambient levels. Normal air concentrations are less than 2 parts per million, but the Yale researchers found average levels of 15,000 parts per million inside trees.
"These are flammable concentrations," said Kristofer Covey, ...
ST. LOUIS, MO, August 7, 2012— An international research collaboration recently demonstrated progress in protecting cassava against cassava brown streak disease (CBSD), a serious virus disease, in a confined field trial in Uganda using an RNA interference technology. The field trial was planted in November 2010 following approval by the National Biosafety Committee of Uganda. The plants were harvested in November 2011 and results were published in the August 1, 2012 issue of the journal Molecular Plant Pathology . These results point researchers in the right direction ...
New Rochelle, NY, August 7, 2012—The global market value of Alzheimer's disease therapeutics could soar to the $8 billion range once therapeutics are approved that actually change the course of the disease, reports Genetic Engineering & Biotechnology News (GEN). The current therapeutic market is valued at $3 to $4 billion, shared among drugs that temporarily delay disease progression or address the symptoms but do not alter the underlying disease, according to a recent issue of GEN.
"Despite all the research on amyloid plaques and neurofibrillary tangles there is still ...
If you're looking for information on the evolution and function of jaws, University of Notre Dame researcher Matt Ravosa is your man.
His integrative research program investigates major adaptive and morphological transformations in the mammalian musculoskeletal system during development and across higher-level groups. In mammals, the greater diversification and increasingly central role of the chewing complex in food procurement and processing has drawn considerable attention to the biomechanics and evolution of this system. Being among the most highly mineralized, and ...
The 14 years of wildlife studies in and around Madagascar's Ranomafana National Park by Sarah Karpanty, associate professor of wildlife conservation at Virginia Tech's College of Natural Resources and Environment, and her students are summarily part of a paper on biodiversity published July 25 by Nature's Advanced Online Publication and coming out soon in print.
As human activities put increasing pressures on natural systems and wildlife to survive, 200 scientists around the world carved up pieces of the puzzle to present a clearer picture of reality and find ways to mitigate ...
LA JOLLA, CA----It was long thought that methylation, a crucial part of normal organism development, was a static modification of DNA that could not be altered by environmental conditions. New findings by researchers at the Salk Institute for Biological Studies, however, suggest that the DNA of organisms exposed to stress undergo changes in DNA methylation patterns that alter how genes are regulated.
The scientists found that exposure to a pathogenic bacteria caused widespread changes in a plant's epigenetic code, an extra layer of biochemical instructions in DNA that ...
Ann Arbor, Mich. — Significantly more children get health insurance coverage after increases in federal matching funds to states for Medicaid and the Children's Health Insurance Program (CHIP), according to new research from the University of Michigan.
The research, published Monday in the journal Health Affairs, showed that a 10-percentage-point increase in the federal match for Medicaid and CHIP, similar to the increase that occurred with the American Reinvestment and Recovery Act, is associated with an increase of 1.9 percent in the number of children enrolled in ...
Infrared satellite imagery from shows how cold cloud top temperatures are in a tropical cyclone, and recent imagery from NASA's Aqua satellite shows the cloud-top temperatures have been warming in Tropical Storm 13W. Warming cloud top temperatures indicate less strength, and Tropical Storm 13W is weakening.
NASA's Aqua satellite passed over Tropical Storm 13W on August 7 at 0253 UTC. The Atmospheric Infrared Sounder (AIRS) instrument that flies onboard Aqua captured an infrared image of the storm's cloud temperatures that showed very limited strong thunderstorms make ...
Tropical Storm Haikui is headed for landfall in southeastern China, and NASA's Aqua satellite caught a stunning image of its size and its ragged, but wide eye when it was a typhoon earlier today, August 7. As a result of interaction with land, Haikui has weakened to a tropical storm.
When NASA's Aqua satellite passed over Typhoon Haikui on August 6, 2012 at 12:35 a.m. EDT the Moderate Resolution Imaging Spectroradiometer (MODIS) instrument onboard captured an image of the storm as it was approaching China. The MODIS image clearly showed Haikui's ragged and elongated eye ...
