Scientists Make Progress Toward a New Potential Treatment for Asthma

Some 24.6 million American adults and children have asthma, which can range from mild to life threatening. A chronic pulmonary disorder, asthma is characterized by inflammation of the lungs, narrowing of the airways, and excessive mucus production—essentially, causing difficulty breathing.

Researchers looking for new drugs to treat this condition at Cincinnati Children’s Hospital Medical Center (CCHMC) have made a recent breakthrough by identifying long-sought transcription factors, proteins responsible for turning genes on or off in the nucleus of cells. These transcription factors are buried deep inside the nucleus of cells where it’s challenging to access or study them.

But the CCHMC researchers managed to identify a small molecule which blocks a key inflammatory transcription factor, FOXM1. FOXM1 stimulates excessive mucus production and inflammation, leading to respiratory distress, and is often found in severe asthma and other pulmonary diseases. Their results were published in the journal Science Signaling.

Asthma is usually triggered by an outside stimulus, ranging from mold to animal fur to pollen. “In response to [a] particular insult from outside, our lungs start to be inflamed, so the cells from the blood come into the lung and start populating our alveoli, which we need to keep clear to breathe,” lead author Vladimir Kalinichenko tells Mental Floss. Kalinichenko is the director for the Center for Lung Regenerative Medicine and a member of the Division of Pulmonary Biology at CCHMC. He explains that in response to an allergen, epithelial (lung) cells start differentiation, or metaplasia, and produce a lot of the goblet cells that secrete the mucus that narrows airways and makes breathing difficult.

Kalinichenko found that inside the lungs, FOXM1 is an important transcription factor responsible for cells becoming mucus-producing goblet cells—a key step in what makes it hard to breathe. His research team’s aim was to find a compound that would specifically target FOXM1, and by blocking its activation, keep the whole process of pro-inflammatory molecules stimulating goblet cells into over-producing mucus from launching.

To do this, the CCHMC researchers screened a database of 50,000 small molecule compounds that have been created in previous scientific research to see if they could find one that inhibited FOXM1. After narrowing it down to 20, they settled on a molecule called RCM-1, which exhibited the inhibiting function they sought.

They first tested RCM-1 on dish-cultured human epithelial cells, with good results; it prevented the transcription factor, FOXM1, from going to the nucleus, says Kalinichenko.

Next they exposed mice that were genetically modified to express high amounts of the FOXM1 transcription factor to dust mites, a common allergen in humans, over the course of two weeks. With repeated exposure to the allergen, the mice began to exhibit asthma symptoms. When they gave the mice just two injections of RCM-1, Kalinichenko says, “The mice would not develop mucus overproduction in the airways and their breathing would be much clearer.”

Then Kalinichenko’s team evoked asthma symptoms in another group of mice, by injecting an inflammatory molecule called interleukin-13—which is normally produced by T-cell lymphocytes as a response to an allergen. Just giving the interleukin-13 to mice (even without the presence of an allergen) causes asthma-like symptoms of lung inflammation, narrowing airways, and difficulty breathing. When the mice were given RCM-1, these symptoms abated, essentially demonstrating a kind of “downstream inflammatory effect” of the immune system.

The team was pleased not to observe any symptoms of toxicity in the mice, which bodes well for human applications, though Kalinichenko cautions that human clinical trials are still far off. First, they’ll have to test the molecule in other animal models, such as non-human primates, assess toxicity levels in different concentrations of the compound, and work on perfecting the compound itself.

“We are just in discovery mode. We have proven in two mouse models of asthma that [RCM-1] works," he notes. "That is a long way to human use.”

Still, Kalinichenko thinks RCM-1 is promising. It could be especially helpful in treating the progressive nature of asthma, which damages the lungs over time from repeat acute attacks. “With every new asthmatic attack, the lungs become much worse. This drug, with others, could be used to prevent these attacks and treat patients in earlier stages, before the lungs get bad,” he says.

However, Kalinichenko says its real value could be in treating serious diseases such as chronic obstructive pulmonary disease, cystic fibrosis, and even lung cancer. “Those diseases are associated with excess mucus production and clogging airways. For those diseases where FOXM1 is expressed in high levels, this drug could be highly beneficial—and even life-saving.”

5 Signs Humans Are Still Evolving

Lealisa Westerhoff, AFP/Getty Images
Lealisa Westerhoff, AFP/Getty Images

When we think of human evolution, our minds wander back to the millions of years it took natural selection to produce modern-day man. Recent research suggests that, despite modern technology and industrialization, humans continue to evolve. "It is a common misunderstanding that evolution took place a long time ago, and that to understand ourselves we must look back to the hunter-gatherer days of humans," Dr. Virpi Lummaa, a professor at the University of Turku, told Gizmodo.

But not only are we still evolving, we're doing so even faster than before. In the last 10,000 years, the pace of our evolution has sped up, creating more mutations in our genes, and more natural selections from those mutations. Here are some clues that show humans are continuing to evolve.

1. Humans drink milk.

Historically, the gene that regulated humans' ability to digest lactose shut down as we were weaned off our mothers' breast milk. But when we began domesticating cows, sheep, and goats, being able to drink milk became a nutritionally advantageous quality, and people with the genetic mutation that allowed them to digest lactose were better able to propagate their genes.

The gene was first identified in 2002 in a population of northern Europeans that lived between 6000 and 5000 years ago. The genetic mutation for digesting milk is now carried by more than 95 percent of northern European descendants. In addition, a 2006 study suggests this tolerance for lactose developed again, independently of the European population, 3000 years ago in East Africa.

2. We're losing our wisdom teeth.

Our ancestors had much bigger jaws than we do, which helped them chew a tough diet of roots, nuts, and leaves. And what meat they ate they tore apart with their teeth, all of which led to worn-down chompers that needed replacing. Enter the wisdom teeth: A third set of molars is believed to be the evolutionary answer to accommodate our ancestors' eating habits.

Today, we have utensils to cut our food. Our meals are softer and easier to chew, and our jaws are much smaller, which is why wisdom teeth are often impacted when they come in — there just isn't room for them. Unlike the appendix, wisdom teeth have become vestigial organs. One estimate says 35 percent of the population is born without wisdom teeth, and some say they may disappear altogether.

3. We're resisting infectious diseases.

In 2007, a group of researchers looking for signs of recent evolution identified 1800 genes that have only become prevalent in humans in the last 40,000 years, many of which are devoted to fighting infectious diseases like malaria. More than a dozen new genetic variants for fighting malaria are spreading rapidly among Africans. Another study found that natural selection has favored city-dwellers. Living in cities has produced a genetic variant that allows us to be more resistant to diseases like tuberculosis and leprosy. "This seems to be an elegant example of evolution in action," says Dr. Ian Barnes, an evolutionary biologist at London's Natural History Museum, said in 2010 statement. "It flags up the importance of a very recent aspect of our evolution as a species, the development of cities as a selective force."

4. Our brains are shrinking.

While we may like to believe our big brains make us smarter than the rest of the animal world, our brains have actually been shrinking over the last 30,000 years. The average volume of the human brain has decreased from 1500 cubic centimeters to 1350 cubic centimeters, which is an amount equivalent to the size of a tennis ball.

There are several different conclusions as to why this is: One group of researchers suspects our shrinking brains mean we are in fact getting dumber. Historically, brain size decreased as societies became larger and more complex, suggesting that the safety net of modern society negated the correlation between intelligence and survival. But another, more encouraging theory says our brains are shrinking not because we're getting dumber, but because smaller brains are more efficient. This theory suggests that, as they shrink, our brains are being rewired to work faster but take up less room. There's also a theory that smaller brains are an evolutionary advantage because they make us less aggressive beings, allowing us to work together to solve problems, rather than tear each other to shreds.

5. Some of us have blue eyes.

Originally, we all had brown eyes. But about 10,000 years ago, someone who lived near the Black Sea developed a genetic mutation that turned brown eyes blue. While the reason blue eyes have persisted remains a bit of a mystery, one theory is that they act as a sort of paternity test. “There is strong evolutionary pressure for a man not to invest his paternal resources in another man’s child,” Bruno Laeng, lead author of a 2006 study on the development of blue eyes, told The New York Times. Because it is virtually impossible for two blue-eyed mates to create a brown-eyed baby, our blue-eyed male ancestors may have sought out blue-eyed mates as a way of ensuring fidelity. This would partially explain why, in a recent study, blue-eyed men rated blue-eyed women as more attractive compared to brown-eyed women, whereas females and brown-eyed men expressed no preference.

Now Ear This: A New App Can Detect a Child's Ear Infection

iStock.com/Techin24
iStock.com/Techin24

Generally speaking, using an internet connection to diagnose a medical condition is rarely recommended. But technology is getting better at outpacing skepticism over handheld devices guiding decisions and suggesting treatment relating to health care. The most recent example is an app that promises to identify one of the key symptoms of ear infections in kids.

The Associated Press reports that researchers at the University of Washington are close to finalizing an app that would allow a parent to assess whether or not their child has an ear infection using their phone, some paper, and some soft noises. A small piece of paper is folded into a funnel shape and inserted into the ear canal to focus the app's sounds (which resemble bird chirps) toward the child’s ear. The app measures sound waves bouncing off the eardrum. If pus or fluid is present, the sound waves will be altered, indicating a possible infection. The parent would then receive a text from the app notifying them of the presence of buildup in the middle ear.

The University of Washington tested the efficacy of the app by evaluating roughly 50 patients scheduled to undergo ear surgery at Seattle Children’s Hospital. The app was able to identify fluid in patients' ears about 85 percent of the time. That’s roughly as well as traditional exams, which involve visual identification as well as specialized acoustic devices.

While the system looks promising, not all cases of fluid in the ear are the result of infections or require medical attention. Parents would need to evaluate other symptoms, such as fever, if they intend to use the app to decide whether or not to seek medical attention. It may prove most beneficial in children with persistent fluid accumulation, a condition that needs to be monitored over the course of months when deciding whether a drain tube needs to be placed. Checking for fluid at home would save both time and money compared to repeated visits to a physician.

The app does not yet have Food and Drug Administration (FDA) approval and there is no timetable for when it might be commercially available. If it passes muster, it would join a number of FDA-approved “smart” medical diagnostic tools, including the AliveKor CardiaBand for the Apple Watch, which conducts EKG monitoring for heart irregularities.

[h/t WGRZ]

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