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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.”

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Department Of Classics, University Of Cincinnati
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Stones, Bones, and Wrecks
Ancient Poop Contains First Evidence of Parasites Described by Hippocrates
Department Of Classics, University Of Cincinnati
Department Of Classics, University Of Cincinnati

The long-held mystery of Hippocrates and the parasitic worms has finally been solved, and it’s all thanks to a few samples of ancient poop.

Researchers don’t know much about the parasites that plagued the Greeks thousands of years ago, and what they do know is largely from the Hippocratic Corpus, the medical texts that the father of medicine and his students put together between the 4th and 3rd centuries BCE. Modern historians have spent years trying to figure out which diseases and parasites Hippocrates and his followers were referring to in their writing, relying solely on their descriptions to guess at what ailments the ancient Greeks might have suffered from. Now, they finally have concrete evidence of the existence of some of the intestinal worms Hippocrates mentioned, Helmins strongyle and Ascaris.

As part of a study in the Journal of Archaeological Science: Reports, an international group of researchers analyzed the ancient remains of feces in 25 prehistoric burials on the Greek island of Kea to determine what parasites the people were carrying when they died. Using microscopes, they looked at the soil (formed by the decomposed poop) found on the pelvic bones of skeletons dating back to the Neolithic, Bronze, and Roman periods.

A roundworm egg under the microscope
A roundworm egg
Elsevier

Around 16 percent of the burials they studied contained evidence of parasites. In these ancient fecal samples, they found the eggs of two different parasitic species. In the soil taken from the skeletons dating back to the Neolithic period, they found whipworm eggs, and in the soil taken from the Bronze Age skeletons, roundworm.

With this information, researchers deduced that what Hippocrates called the Helmins strongyle worm was probably what modern doctors would call roundworm. The Ascaris worm probably referred to two different parasites, they conclude, known today as pinworm (which was not found in this analysis) and whipworm (pictured below).

Whipworm under a microscope
A whipworm egg
Elsevier

Though historians already hypothesized that Hippocrates's patients on Kea had roundworm, the Ascaris finding comes as a particular surprise. Previous research based solely on Hippocrates’s writing rather than physical evidence suggested that what he called Ascaris was probably a pinworm, and another worm he mentioned, Helmins plateia, was probably a tapeworm. But the current research didn’t turn up any evidence of either of those two worms. Instead of pinworm eggs, the researchers found whipworm, another worm that’s similarly small and round. (Pinworms may very well have existed in ancient Greece, the researchers caution, since evidence of their fragile eggs could easily have been lost to time.) The soil analysis has already changed what we know about the intestinal woes of the ancient Greeks of Kea.

More importantly, this study provides the earliest evidence of ancient Greece’s parasitic worm population, proving yet again that ancient poop is one of the world’s most important scientific resources.

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Arctic Temperatures are Rising So Fast, They're Confusing the Hell Out of Computers
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This past year was a brutal one for northern Alaska, which saw temperatures that soared above what was normal month after month. But you wouldn't know that by looking at the numbers from the weather station at Utqiaġvik, Alaska. That's because the recent heat was so unusual for the area that computers marked the data as incorrect and failed to report it for the entirety of 2017, leaving a hole in the records of the Climate Monitoring group at the National Centers for Environmental Information (NCEI), according to the Huffington Post.

The weather station in the northernmost tip of Alaska has been measuring temperatures for nearly a century. A computer system there is programed to recognize if the data has been influenced by artificial forces: Perhaps one of the instruments isn't working correctly, or something is making the immediate area unnaturally hot or cold. In these cases, the computer edits out the anomalies so they don't affect the rest of the data.

But climate change has complicated this failsafe. Temperatures have been so abnormally high that the Utqiaġvik station erroneously removed all its data for 2017 and part of 2016. A look at the region's weather history explains why the computers might have sensed a mistake: The average yearly temperature for the era between 2000 and 2017 has gone up by 1.9°F from that of the era between 1979 and 1999. Break it down by month and the numbers are even more alarming: The average temperature increase is 7.8°F for October, 6.9°F for November, and 4.7°F for December.

"In the context of a changing climate, the Arctic is changing more rapidly than the rest of the planet," Deke Arndt, chief of NOAA's Climate Monitoring Branch, wrote for climate.gov. The higher temperatures rise, the faster Arctic sea ice melts. Arctic sea ice acts as a mirror that reflects the Sun's rays back into space, and without that barrier, the sea absorbs more heat from the Sun and speeds up the warming process. “Utqiaġvik, as one of a precious few fairly long-term observing sites in the American Arctic, is often referenced as an embodiment of rapid Arctic change,” Arndt wrote.

As temperatures continue to grow faster than computers are used to, scientists will have to adjust their algorithms in response. The team at NCEI plans to have the Utqiaġvik station ready to record our changing climate once again within the next few months.

[h/t Huffington Post]

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