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.”

Bombshell, Victoria’s Secret’s Bestselling Fragrance, Also Happens to Repel Mosquitoes

Dids, Pexels
Dids, Pexels

People love Bombshell, the best-selling fragrance at Victoria’s Secret, for its summery blend of fruity and floral notes. Not everyone is a huge fan, though: As Quartz reports, the perfume is surprisingly good at warding off mosquitoes. In fact, it’s almost as effective as DEET insect repellent, according to the results of a 2014 experiment by researchers at New Mexico State University.

Researchers took 10 products that are commercially available and tested their ability to repel two different species of mosquitoes: the yellow fever mosquito (Aedes aegypti) and the Asian tiger mosquito (Aedes albopictus), both of which are known to transmit diseases like dengue fever, chikungunya, and yellow fever. In doing so, volunteers subjected their own flesh to the test by placing their hands on either side of a Y-shaped tube containing the blood-sucking critters. One hand was covered in a synthetic rubber glove, while the other hand was sprayed with one of the products but otherwise left bare. Researchers recorded which tunnel the mosquitoes flew to, and how long they avoided the other end.

Three of the products contained DEET, while four products didn’t. In addition, there were two fragrances (including Bombshell) and one vitamin B1 skin patch. The DEET products were the most effective, but Bombshell proved to be nearly as good, keeping mosquitoes at bay for roughly two hours.

“There was some previous literature that said fruity, floral scents attracted mosquitoes, and to not wear those,” Stacy Rodriquez, one of the study’s authors, said in a statement. “It was interesting to see that the mosquitoes weren’t actually attracted to the person that was wearing the Victoria’s Secret perfume—they were repelled by it.”

This isn’t the first time a perfume has had an unintended effect on the natural world. It turns out that tigers are obsessed with Calvin Klein’s Obsession for Men cologne, partly because it contains a synthetic version of civetone, a pheromone that's secreted by glands located near a civet’s anus. This substance was once used to create musky fragrances, but nowadays the scent is mostly reproduced in a lab. Still, the fake stuff must be pretty convincing, because big cats go crazy when they catch a whiff of it.

[h/t Quartz]

Mystery Solved: Scientists Have Figured Out Why Some Squirrels Are Black

Rena-Marie/iStock via Getty Images
Rena-Marie/iStock via Getty Images

It can be something of a surprise to see an animal sporting a fresh coat of paint. Blue lobsters occasionally surface after being caught in traps. A pink dolphin was spotted in Louisiana in 2007 (and several times since). In the Chinese province of Shaanxi, a cute brown and white panda greets zoo visitors.

Another anomalous animal has joined their ranks. Black squirrels have been spotted in both the United States and the UK, and now scientists believe they know why.

Like many animals with unusual color schemes, black squirrels are the result of a genetic detour. Researchers at Anglia Ruskin University, Cambridge University, and the Virginia Museum of Natural History collaborated on a project that tested squirrel DNA. Their findings, which were published in BMC Evolutionary Biology, demonstrated that the black squirrel is the product of interspecies breeding between the common gray squirrel and the fox squirrel. The black squirrel is actually a gray squirrel with a faulty pigment gene carried over from the fox squirrel that turns their fur a darker shade. (Some fox squirrels, which are usually reddish-brown, are also black.)

A black squirrel is pictured
sanches12/iStock via Getty Images

Scientists theorize a black fox squirrel may have joined in on a mating chase involving gray squirrels and got busy with a female. The black fur may offer benefits in colder regions, with squirrels able to absorb and retain more heat, giving them a slight evolutionary edge.

In North America, black squirrels are uncommon, with one estimate putting them at a rate of one in every 10,000 squirrels. In 1961, students at Kent State University in Ohio released 10 black squirrels that had been captured by Canadian wildlife authorities. The squirrels now populate the campus and have become the school’s unofficial mascot. Their coloring might help them hide from predators, which might come in handy at Kent State: The campus is also home to hawks.

[h/t The Guardian]

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