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.”

Justin Tallis, AFP/Getty Images
Stones, Bones, and Wrecks
8 Cemeteries Unearthed at Construction Sites
Justin Tallis, AFP/Getty Images
Justin Tallis, AFP/Getty Images

The people who lived before us are often just beneath our feet, even if their tombs are sometimes forgotten. Lost under urban development, they are rediscovered when a subway, building, or other structure claims the ground for progress. Here are eight burial sites that came to light in this unconventional manner.


The construction of Rome's subway has unearthed everything from a 2nd-century home decorated with mosaics and frescos to a 2300-year-old aqueduct. The San Giovanni station, slated to open in 2018, will feature displays of artifacts found during its excavation, such as Renaissance ceramics and the remains of a 1st-century agricultural fountain.

Back in 2016, extension work on Line C ran into a 2nd-century military barracks with 39 rooms, likely used by Emperor Hadrian's army, as well as a mass grave of 13 skeletons. The dead may have been members of the elite Praetorian Guard, protectors of the Roman emperor. Investigations are ongoing, although officials have planned for the barracks to be incorporated into the station architecture. Its opening date remains in limbo as archaeological finds continue to slow its construction.


In 1991, construction of a federal office building revealed a colonial-era burial ground in Lower Manhattan. The graves, dating back to the 1690s, had been lost due to landfill and development, yet were identified as part of the African burial grounds that in the 17th century were located outside the old city.

Banned from interment in white cemeteries, free and enslaved Africans and African Americans had established a place to give respect to their dead, with an estimated 10,000 to 20,000 burials. Thanks to grassroots activism, including protests against continued construction, the site is now commemorated with the African Burial Ground National Monument, which opened in 2006.

It's not the sole black cemetery to be buried under development in New York: The Second African Burial Ground, dating from the 18th and 19th centuries, is located below today's Sarah D. Roosevelt Park on the Lower East Side; and in East Harlem, a 17th-century slave burial ground, discovered by construction workers at a bus depot, awaits a planned memorial.


Burrowing deep under London, the ongoing Crossrail commuter rail project has exposed obscure layers of the city's past—and a treasure trove of history. Along with medieval ice skates and a Tudor bowling ball, archaeologists have identified two mass graves. One has 13 skeletons of people who probably died in the 14th century of Black Death (with DNA on their teeth still holding the plague bacterium Yersinia pestis); a larger site has 42 skeletons of victims of the Great Plague of 1665. The study of the Great Plague skeletons, excavated in 2015 by Museum of London Archaeology, similarly showed traces of the disease in their old teeth. (Luckily the bacteria is no longer active, so no need to dust off your plague doctor beak mask.)

While such "plague pits" have long been rumored—some urban legends say the London Underground had to curve to avoid messy heaps of bodies—study of the sites indicated that there was in fact great care taken with the deceased. The bodies were placed in individual coffins, giving them some dignity even in this hasty mass burial.


Sometimes, to borrow a line from Poltergeist, people only move the headstones when relocating a cemetery, and stray bones and coffins are left behind (digging up the dead is generally unpleasant work). That seemed to be the case with a graveyard unearthed at a construction site on Arch Street in Philadelphia in March 2017. The dozens of coffins that were discovered are believed to be part of the First Baptist Church Burial Ground, established in 1707 and supposedly moved to Mount Moriah Cemetery in 1859. The Mütter Institute spearheaded a crowdfunding campaign for analysis and reinterment of the bones, and volunteer archaeologists convened at the site, racing against time to map the grounds and remove the burials of more than 100 people. Their remains were carefully analyzed.

Archaeologists subsequently found the remains of more than 400 people at the site as construction went on in other areas. Building at the site continues, as does the grassroots-funded research on the bones (you can follow the team's progress at the Arch Street Bones Project website).


In 2013, construction on a subway in Thessaloniki, Greece, turned up the grave of a woman buried around 2300 years ago. The Early Hellenistic lady was interred with a gold olive branch wreath.

Surprisingly, this wasn't the first such skeleton found during subway construction to be so regally crowned. In 2008, another Hellenistic woman was discovered with four gold wreaths and gold earrings in the shape of dogs' heads, all indicators of wealth and respectability—something marred a bit by the sewage pipe that had wrecked part of her grave.


While digging a trench in 2013 for a gas pipeline in Saskatchewan, Canada, a contractor noticed bone fragments in the soil that turned out to be 1000-year-old human remains.

Construction was halted so First Nations elders and archaeologists could examine the area. Ultimately, the pipeline company opted to tunnel deeper to avoid disturbing the ancient burials.

It was only one of many instances of massive infrastructure projects coming in contact with pre-colonial burial grounds. In 2017, for example, road construction in Duluth, Minnesota desecrated graves when the state's department of transportation failed to evaluate the area for artifacts prior to breaking ground.


Near Weymouth in Dorset, England, a mass grave of more than 50 young men was discovered in 2009 by archaeologists doing a survey before road construction began. All the victims had been killed brutally, at once, with multiple blows from a sharp weapon visible on their bones, and their heads had been severed. In 2010, researchers identified them as Vikings by radio-carbon dating the bones to 910 to 1030 CE, when the English clashed with Viking invaders. Analysis of the isotopes in the teeth indicated Scandinavian origins. Due to their lack of clothing and their similar manner of death, they were likely executed as captives. They're now part of the Dorset County Museum.


Among the roughly 38,000 people interred beneath a neighborhood on Chicago's Far Northwest Side are the impoverished inmates of the Cook County almshouse and patients from the county insane asylum. The area was known as Dunning, and its squalid institutions were so well known that a judge in 1889 declared them a "tomb for the living." The 20 acres of the site also included a potter's field for the indigent and unclaimed, and the burials of more than 100 unidentified dead from the Great Chicago Fire of 1871.

The potter's field was revealed in 1989 during construction on luxury homes. Sewer workers who were laying pipes also turned up a corpse that was so well-preserved his handlebar mustache was still visible. Bodies were relocated to a site now called Read-Dunning Memorial Park, giving these dead some recognition in the city for the first time.

Just Two Cans of Soda a Day May Double Your Risk of Death From Heart Disease

If you've been stocking your refrigerator full of carbonated corn syrup in anticipation of warmer weather, the American Heart Association has some bad news. The advocacy group on Wednesday released results of research that demonstrate a link between consumption of sugary drinks—including soda, fruit juices, and other sweetened beverages—and an increased risk of dying from heart disease.

Study participants who reported consuming 24 ounces or more of sugary drinks per day had twice the risk of death from coronary artery disease of those who averaged less than 1 ounce daily. There was also an increased risk of death overall, including from other cardiovascular conditions.

The study, led by Emory University professor Jean Welsh, examined data taken from a longitudinal study of 17,930 adults over the age of 45 with no previous history of heart disease, stroke, or diabetes. Researchers followed participants for six years, and examined death records to determine causes. They observed a greater risk of death associated with sugary drinks even when they controlled for other factors, including race, income, education, smoking habits, and physical activity. The study does not show cause and effect, the researchers said, but does illuminate a trend.

The study also noted that while it showed an increased risk of death from heart disease, consumption of sugary foods was not shown to carry similar risk. One possible explanation is that the body metabolizes the sugars differently: Solid foods carry other nutrients, like fat and protein, that slow metabolism, while sugary drinks provide an undiluted influx of carbohydrates that the body must process.

The news will likely prove troublesome for the beverage industry, which has long contended with concerns that sugary drinks contribute to type 2 diabetes and tooth decay. Some cities, including Seattle, have introduced controversial "soda tax" plans that raise the sales tax on the drinks in an effort to discourage consumption.


More from mental floss studios