Yousef Al-Abed, PhD, and his colleagues at The Feinstein Institute for Medical Research have isolated an immune substance called macrophage migration inhibitory factor (MIF) in semen samples from infertile and reproductively healthy men. MIF is key to helping sperm mature, which is necessary for its union with an egg. The finding could lead to a diagnostic test to determine fertility status.
The study appears in the latest issue of Molecular Medicine. The semen samples were collected from men three to five days after a period of sexual abstinence. The scientists had no idea when analyzing levels of MIF whether the sample came from any of the 68 men who had problems conceiving or from the 27 healthy controls. The findings have a Goldilocks kind of quality: Those with infertility problems had MIF levels that were either too high or too low. Those who had no problems conceiving had levels that were just right.
When the scientists added MIF into lab dishes filled with healthy sperm, it decreased the count and impaired their motility.
If MIF has a role in infertility, Dr. Al-Abed and his colleagues are wondering whether it might just work as a form of male contraception. In the meantime, the scientists have a patent on an assay that can be used to analyze MIF levels to help determine whether a man will have problems conceiving. About 15 percent of couples attempting to get pregnant for the first time have problems conceiving. About 40 percent of infertility problems are due to disorders in the male.
MIF is a key player of the immune system. MIF was identified 40 years ago but it was only recently that scientists discovered its role as a pro-inflammatory substance. MIF has now been linked to many autoimmune and inflammatory diseases - such as diabetes and sepsis - and Al-Abed, an organic chemist by training, has been trying to identify and design small molecules that would block MIF activity.
The Feinstein researchers recently identified a critical area on the MIF protein surface that is crucial for the inflammatory response. Such a substance designed to target this area could be used to treat a variety of conditions, including septic shock, sepsis, rheumatoid arthritis and diabetes. The team designed a specific inhibitor called ISO-1 to fit into this pro-inflammatory site. In an animal model of sepsis, ISO-1 abolishes MIF’s potent inflammatory abilities and the animals respond dramatically. They lived through the once-fatal sepsis.
In patients in the throes of sepsis - an over-reactive and potentially fatal immune response to a bacterial infection - MIF concentrations are 10 to 20 times higher than normal. If MIF goes down, the chance that patients will survive sepsis is increased dramatically. “The idea is to suppress inflammation so that cells stop producing MIF,” said Dr. Al-Abed.
Every year, 215,000 Americans die of sepsis, a systemic inflammatory reaction to infection. Another 500,000 survive the infection, and scientists are still trying to figure out why these patients survive and others don’t. There are no treatments for this massive all-out war on the body. Those who survive often face serious cardiovascular problems. Scientists examining cardiac function during sepsis have identified macrophage migration inhibitory factor (MIF) as a key factor in heart damage. And antibodies targeted to MIF, so-called anti-MIF antibodies, significantly improves cardiac performance during septic shock.
MIF levels are also two times higher in autoimmune diseases like rheumatoid arthritis and diabetes. In the laboratory, Al-Abed and his colleagues found that having MIF on board in high amounts in animals prone to diabetes set the disease process in motion weeks earlier than expected. The team is now trying to design a clinical study to look at MIF levels in type 1, or juvenile, diabetes.
One thing has become clear about the MIF molecule: It needs a network. To act as a pro-inflammatory soldier, it relies on other substances to help. “MIF on its own is not toxic,” Dr. Al-Abed said. They are now trying to figure out what substances MIF partners with to do its dirty work.
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences