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.”

14 Retro Gifts for Millennials

Ravi Palwe, Unsplash
Ravi Palwe, Unsplash

Millennials were born between 1981 and 1996, which means the pop culture they grew up with is officially retro. No matter what generation you belong to, consider these gifts when shopping for the Millennials in your life this holiday season.

1. Reptar Funko Pop!; $29

Amazon

This vinyl Reptar figurine from Funko is as cool as anything you’d find in the rugrats’ toy box. The monster dinosaur has been redesigned in classic Pop! style, making it a perfect desk or shelf accessory for the grown-up Nickelodeon fan. It also glows in the dark, which should appeal to anyone’s inner child.

Buy it: Amazon

2. Dragon Ball Z Slippers; $20

Hot Topic

You don’t need to change out of your pajamas to feel like a Super Saiyan. These slippers are emblazoned with the same kanji Goku wears on his gi in Dragon Ball Z: one for training under King Kai and one for training with Master Roshi. And with a soft sherpa lining, the footwear feels as good as it looks.

Buy it: Hot Topic

3. The Pokémon Cookbook; $15

Hop Topic

What do you eat after a long day of training and catching Pokémon? Any dish in The Pokémon Cookbook is a great option. This book features more than 35 recipes inspired by creatures from the Pokémon franchise, including Poké Ball sushi rolls and mashed Meowth potatoes.

Buy it: Hot Topic

4. Lisa Frank Activity Book; $5

Urban Outfitters

Millennials will never be too old for Lisa Frank, especially when the artist’s playful designs come in a relaxing activity book. Watercolor brings the rainbow characters in this collection to life. Just gather some painting supplies and put on a podcast for a relaxing, nostalgia-fueled afternoon.

Buy it: Urban Outfitters

5. Shoebox Tape Recorder with USB; $28

Amazon

The days of recording mix tapes don’t have to be over. This device looks and functions just like tape recorders from the pre-smartphone era. And with a USB port as well as a line-in jack and built-in mic, users can easily import their digital music collection onto retro cassette tapes.

Buy it: Amazon

6. Days of the Week Scrunchie Set; $12

Urban Outfitters

Millennials can be upset that a trend from their youth is old enough to be cool again, or they can embrace it. This scrunchie set is for anyone happy to see the return of the hair accessory. The soft knit ponytail holders come in a set of five—one for each day of the school (or work) week.

Buy it: Urban Outfitters

7. D&D Graphic T-shirt; $38-$48

80s Tees

The perfect gift for the Dungeon Master in your life, this graphic tee is modeled after the cover of the classic Dungeons & Dragons rule book. It’s available in sizes small through 3XL.

Buy it: 80s Tees

8. Chuck E. Cheese T-shirt; $36-$58

80s Tees

Few Millennials survived childhood without experiencing at least one birthday party at Chuck E. Cheese. This retro T-shirt sports the brand’s original name: Chuck E. Cheese’s Pizza Time Theatre. It may be the next-best gift for a Chuck E. Cheese fan behind a decommissioned animatronic.

Buy it: 80s Tees

9. The Nightmare Before Christmas Picnic Blanket Bag; $40

Shop Disney

Fans of Tim Burton’s The Nightmare Before Christmas will recognize the iconic scene on the front of this messenger bag. Unfold it and the bag becomes a blanket fit for a moonlit picnic among the pumpkins. The bottom side is waterproof and the top layer is made of soft fleece.

Buy it: Shop Disney

10. Toy Story Alien Socks; $15

Shop Disney

You don’t need to be skilled at the claw machine to take home a pair of these socks. Decorated with the aliens from Toy Story, they’re made from soft-knit fabric and are big enough to fit adult feet.

Buy it: Shop Disney

11. Goosebumps Board Game; $24

Amazon

Fans that read every book in R.L. Stine’s series growing up can now play the Goosebumps board game. In this game, based on the Goosebumps movie, players take on the role of their favorite monster from the series and race to the typewriter at the end of the trail of manuscripts.

Buy it: Amazon

12. Tamagotchi Mini; $19

Amazon

If you know someone who killed their Tamagotchi in the '90s, give them another chance to show off their digital pet-care skills. This Tamagotchi is a smaller, simplified version of the original game. It doubles as a keychain, so owners have no excuse to forget to feed their pet.

Buy it: Amazon

13. SNES Classic; $275

Amazon

The SNES Classic is much easier to find now than when it first came out, and it's still just as entertaining for retro video game fans. This mini console comes preloaded with 21 Nintendo games, including Super Mario Kart and Street Fighter II.

Buy it: Amazon

14. Planters Cheez Balls; $24

Amazon

Planters revived its Cheez Balls in 2018 after pulling them from shelves nearly a decade earlier. To Millennials unaware of that fact, this gift could be their dream come true. The throwback snack even comes in the classic canister fans remember.

Buy it: Amazon

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Late MythBusters Star Grant Imahara Honored With New STEAM Foundation

Grant Imahara attends San Diego Comic-Con
Grant Imahara attends San Diego Comic-Con
Genevieve via Flickr // CC BY 2.0

Fans of MythBusters and White Rabbit Project host Grant Imahara were saddened to hear of his passing due to a brain aneurysm in July 2020 at the age of 49. Imahara, a graduate of the University of Southern California, used the television medium to share his love of science and engineering. Now, his passion for education will continue via an educational foundation developed in his name.

The Grant Imahara STEAM Foundation was announced Thursday, October 23, 2020 by family and friends on what would have been Imahara’s 50th birthday. The Foundation will provide mentorships, grants, and scholarships that will allow students from diverse backgrounds access to STEAM education, which places an emphasis on science, technology, engineering, arts, and math. (Formerly referred to as STEM, the “A” for art was added more recently.)

Imahara had a history of aiding students. While working at Industrial Light and Magic in the early 2000s, he mentored the robotics team at Richmond High School to prepare for the international FIRST Robotics Competition. Whether he was working on television or behind-the-scenes on movies like the Star Wars prequels and The Matrix sequels, Imahara always found time to promote and encourage young engineering talent.

The Grant Imahara STEAM Foundation’s founding board members include Imahara’s mother, Carolyn Imahara, and close friends Don Bies, Anna Bies, Edward Chin, Fon H. Davis, Coya Elliott, and Ioanna Stergiades.

“There are many students, like my son Grant, who need the balance of the technical and the creative, and this is what STEAM is all about,” Carolyn Imahara said in a statement. “I’m so proud of my son’s career, but I’m equally proud of the work he did mentoring students. He would be thrilled that we plan to continue this, plus much more, through The Grant Imahara STEAM Foundation.”

Imahara friend Wade Bick is also launching an effort in concert with the USC Viterbi School of Engineering to name a study lounge after Imahara. Donations can be made here.

You can find out more about the foundation, and make a donation, on its website.