BreakThrough Digest Medical News |
- Stanford scientists find molecule to starve lung cancer and improve ventilator recovery
- When anxiety won’t go away
- Scientists discover an epigenetic cause of osteoarthritis
| Stanford scientists find molecule to starve lung cancer and improve ventilator recovery Posted: 05 Jul 2012 09:00 PM PDT A new research report published online in the FASEB Journal reveals a connection among sugar, cancer, and dependence on breathing machines–microRNA-320a. In the report, Stanford scientists show that the molecule microRNA-320a is responsible for helping control glycolysis. Glycolysis is the process of converting sugar into energy, which fuels the growth of some cancers, and contributes to the wasting of unused muscles such as the diaphragm when people are using ventilators. Identifying ways to use microRNA-320a to starve tumors and keep unused muscles strong would represent a significant therapeutic leap for numerous diseases and health conditions.
“We hope that this discovery will yield a new avenue of molecular treatment for cancers, particularly lung cancer, which is the number one cause of cancer deaths worldwide,” said Joseph B. Shrager, M.D., a researcher involved in the work who is a Professor of Cardiothoracic Surgery, and Chief of the Division of Thoracic Surgery at Stanford University School of Medicine, and VA Palo Alto Healthcare System in California. “We also hope it can lead to a treatment to be given to intensive care unit patients who require the breathing machine, reducing the length of time they require the machine, and thereby reducing complications and deaths.” To make this discovery, Shrager and colleagues studied lung cancer tissues from patients and tissue from the diaphragm (the primary muscle used for breathing) from patients who had been on a breathing machine for more than a few hours. They found that both types of tissue had increases in glycolysis, as well as reductions in a molecule that controls glycolysis?microRNA-320a. Test tube experiments then showed that microRNA-320a definitely controls how much energy these two very different tissues have available to them. “Just as the discovery of angiogenesis opened new doors to find ways to stop cancers and to help the body heal itself,” said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal, “this discovery, on a smaller scale, does the same by identifying an important molecule that may help starve tumors and help the body recover.” ### Receive monthly highlights from the FASEB Journal by e-mail. Sign up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB) and is among the most cited biology journals worldwide according to the Institute for Scientific Information. In 2010, the journal was recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century. FASEB is composed of 26 societies with more than 100,000 members, making it the largest coalition of biomedical research associations in the United States. Celebrating 100 Years of Advancing the Life Sciences in 2012, FASEB is rededicating its efforts to advance health and well-being by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy. Details; Huibin Tang, Myung Lee, Orr Sharpe, Louis Salamone, Emily J. Noonan, Chuong D. Hoang, Sanford Levine, William H. Robinson, and Joseph B. Shrager. Oxidative stress-responsive microRNA-320 regulates glycolysis in diverse biological systems. FASEB J. doi:10.1096/fj.11-197467 ; http://www.fasebj.org/content/early/2012/07/05/fj.11-197467.abstract Contact: Cody Mooneyhan |
| Posted: 05 Jul 2012 09:00 PM PDT
Feelings of anxiety very effectively prevent people from getting into situations that are too dangerous. Those who have had a terrible experience initially tend to avoid the place of tragedy out of fear. If no other oppressive situation arises, normally the symptoms of fear gradually subside. “The memory of the terrible events is not just erased.” states first author, PD Dr. Andras Bilkei Gorzo, from the Institute for Molecular Psychiatry at the University of Bonn. “Those impacted learn rather via an active learning process that they no longer need to be afraid because the danger has passed.” But following extreme psychical stress resulting from wars, hostage-takings, accidents or catastrophes chronic anxiety disorders can develop which even after months don’t subside.
Body’s own dynorphin weakens fears
Why is it that in some people terrible events are deeply engraved in their memory, while after a while others seem to have completely put aside any anxiety related to the incident? Scientists in the fields of psychiatry, molecular psychiatry and radiology at the University of Bonn are all involved in probing this issue. “We were able to demonstrate by way of a series of experiments that dynorphin plays an important role in weakening anxiety,” says Prof. Dr. Andreas Zimmer, Director of the Institute for Molecular Psychiatry at the University of Bonn. The substance group in question is opiods which also includes, for instance, endorphins. The latter are released by the body of athletes and have an analgesic and euphoric effect. The reverse, however, is true of dynorphins: They are known for putting a damper on emotional moods. Mice with disabled gene exhibit persistent anxiety
The team working with Prof. Zimmer tested the exact impact of dynorphins on the brain using mice whose gene for the formation of this substance had been disabled. After being exposed to a brief and unpleasant electric shock, the animals exhibited persistent anxiety symptoms, even if they hadn’t been confronted with the negative stimulus over a longer time. Mice exhibiting a normal amount of released dynorphin were anxious to begin with as well, but the symptoms quickly subsided. “This behavior is the same in humans: If you burn your hand on the stove once, you don’t forget the incident that quickly,” explains Prof. Zimmer. “Learning vocabulary, on the other hand, typically tends to be more tedious because it’s not tied to emotions.” Results are transferrable to people
Next the researchers showed that these results can be transferred to people. “We took advantage of the fact that people exhibit natural variations of the dynorphin gene that lead to different levels of this substance being released in the brain,” reports Prof. Dr. Dr. Henrik Walter, Director of the Research Area Mind and Brain at the Psychiatric University Clinic at the Charité in Berlin, who also used to perform research in this area at the University Clinic in Bonn. A total of 33 healthy probands were divided into two groups: One with the genetically stronger dynorphin release and the other which exhibits less gene activity. Unpleasant stimulus leads to stress reactions in the probands
Equipped with computer glasses the probands observed blue and green squares which appeared and then disappeared again in a magnetic resonance tomograph (MRT). When the green square was visible the scientists repeatedly gave probands an unpleasant stimulus on the hand using a laser. Scientists were able to prove that these negative stimuli actually led to a stress reaction given the increased sweat on the skin. At the same time, researchers recorded the activities of various brain areas with the tomograph. After this conditioning stage came part two of the experiment: The researchers showed the colored squares without any unpleasant stimuli and recorded how long the stress reaction acquired earlier lasted. The next day the experiment was continued without the laser stimulus in an effort to monitor the longer-term development. New paths in the treatment of trauma patients
It became apparent that, as in mice human, probands with lower gene activity for dynorphin exhibited stress reactions lasting considerably longer than those probands who released considerably more. Moreover, in brain scans it could be observed that the amygdala ? a brain structure in the temporal lobes that processes emotional contents – was also active even if in later testing rounds a green square was shown without the subsequent laser stimulus. “After the negative laser stimulus stopped this amygdala activity gradually became weaker. This means that the acquired anxiety reaction to the stimulus was forgotten,” reports Prof. Walter. This effect was not as pronounced in the group with less dynorphin activity and prolonged anxiety. “But the ‘forgetting’ of acquired anxiety reactions isn’t a fading, but, rather, an active process which involves the ventromedial prefrontal cortex,” emphasizes Prof. Walter. To corroborate this, researchers found that in the group with less dynorphin activity there was reduced coupling between the prefrontal cortex and the amygdala. “In all likelihood dynorphins affect fear forgetting in a crucial way through this structure,” says Prof. Walter. The scientists now hope that by using the results they will be able to develop long-term approaches for new strategies when it comes to the treatment of trauma patients. ### Publication: Dynorphins Regulate Fear Memory: From Mice to Men, The Journal of Neuroscience, DOI: 10.1523/JNEUROSCI.1034-12.2012; www.jneurosci.org/content/32/27/9335.full You can view photos for this press release at: http://www3.uni-bonn.de/Pressemitteilungen/180-2012 Contact: PD Dr. rer. nat. Andras Bilkei Gorzo Prof. Dr. Andreas Zimmer Prof. Dr. Dr. Henrik Walter Contact: Dr. Andras Bilkei Gorzo |
| Scientists discover an epigenetic cause of osteoarthritis Posted: 05 Jul 2012 09:00 PM PDT
In what could be a breakthrough in the practical application of epigenetic science, U.K. scientists used human tissue samples to discover that those with osteoarthritis have a signature epigenetic change (DNA methylation) responsible for switching on and off a gene that produces a destructive enzyme called MMP13. This enzyme is known to play a role in the destruction of joint cartilage, making MMP13 and the epigenetic changes that lead to its increased levels, prime targets for osteoarthritis drug development. In addition to offering a new epigenetic path toward a cure for osteoarthritis, this research also helps show how epigenetic changes play a role in diseases outside of cancer. This finding was recently published online in the FASEB Journal.
“As the population gets older, osteoarthritis presents increasing social and economic problems,” said David A. Young, Ph.D., a researcher involved in the work from the Musculoskeletal Research Group at the Institute of Cellular Medicine at Newcastle University in Newcastle upon Tyne in the United Kingdom. “Our work provides a better understanding of the events that cause cartilage damage during osteoarthritis and provides hope that tailored drug development to prevent the progress of disease will improve the quality of life and mobility of many arthritis sufferers.” To make the discovery, Young and colleagues compared the extent to which DNA methylation was different in cartilage from patients suffering from osteoarthritis and healthy people of similar age. They found that at one small position, the gene for MMP13 had less DNA methylation in diseased patients. Then they confirmed that reduced methylation of this gene increases levels of the destructive enzyme MMP13. “We’ve already seen how epigenetics has advanced our approach to cancer. Now we’re seeing it with other diseases and even exercise.” said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. “This study not only lays the groundwork for a new understanding of osteoarthritis, but also shows that the old ‘either/or’ nature v. nurture argument is outdated: epigenetics teaches us that nature (the daily wear and tear of joints) regulates nurture (the genes in our cartilage) to cause arthritis.” ### Receive monthly highlights from the FASEB Journal by e-mail. Sign up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB) and is the most cited biology journal worldwide according to the Institute for Scientific Information. In 2010, the journal was recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century. FASEB is composed of 26 societies with more than 100,000 members, making it the largest coalition of biomedical research associations in the United States. Celebrating 100 Years of Advancing the Life Sciences in 2012, FASEB is rededicating its efforts to advance health and well-being by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy. Details: Catherine Bui, Matt J. Barter, Jenny L. Scott, Yaobo Xu, Martin Galler, Louise N. Reynard, Andrew D. Rowan, and David A. Young. cAMP response element-binding (CREB) recruitment following a specific CpG demethylation leads to the elevated expression of the matrix metalloproteinase 13 in human articular chondrocytes and osteoarthritis. FASEB J July 2012 26:3000-3011; doi:10.1096/fj.12-206367 ; http://www.fasebj.org/content/26/7/3000.abstract Contact: Cody Mooneyhan |
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