Aspirin, a commonly used anti-inflammatory drug, has been available for more than a century, yet scientists are still uncovering new information about how it works.
Researchers have made important discoveries about aspirin's mechanism of action and its effect on inflammation and the immune response.
The team — led by Prof Subhrangsu Mandal at the University of Texas in Arlington — found that aspirin inhibits the cyclooxygenase enzyme (COX), which plays a critical role in the inflammatory response.
As Prarthana Guha, a graduate student in Prof Mandal's lab, explained: “Aspirin controls transcription factors required for cytokine [signalling molecules that regulate the immune response and inflammation] expression during inflammation while also influencing many other inflammatory proteins and noncoding RNAs that are critically linked to inflammation and immune response.”
Aspirin slows down the breakdown of the amino acid tryptophan into kynurenine [an amino acid metabolite] by inhibiting enzymes called indoleamine dioxygenases (IDOs). This is significant because tryptophan metabolism is central to the inflammation and immune response.
By downregulating IDO1 expression and kynurenine production during inflammation, aspirin may have potential implications for cancer immunotherapies.
“Since aspirin is a COX inhibitor, this suggests potential interplay between COX and IDO1 during inflammation,” Prof Mandal said.
Harmful side effects, such as internal bleeding and organ damage, have been linked to long-term use of aspirin.
Prof Mandal and his team believe that understanding how aspirin works can lead to the development of safer drugs with fewer side effects.
They are currently exploring the potential use of small molecules that modulate the COX-IDO1 axis as anti-inflammatory drugs and immunotherapeutic agents.
These findings could pave the way for safer aspirin alternatives and new therapies for cancer and other diseases.
“This work has required a unique interdisciplinary team with expertise in inflammation signalling biology and organic chemistry,” Prof Mandal said.
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Email sent to Uber team from chief executive Dara Khosrowshahi
From: Dara
To: Team@
Date: March 25, 2019 at 11:45pm PT
Subj: Accelerating in the Middle East
Five years ago, Uber launched in the Middle East. It was the start of an incredible journey, with millions of riders and drivers finding new ways to move and work in a dynamic region that’s become so important to Uber. Now Pakistan is one of our fastest-growing markets in the world, women are driving with Uber across Saudi Arabia, and we chose Cairo to launch our first Uber Bus product late last year.
Today we are taking the next step in this journey—well, it’s more like a leap, and a big one: in a few minutes, we’ll announce that we’ve agreed to acquire Careem. Importantly, we intend to operate Careem independently, under the leadership of co-founder and current CEO Mudassir Sheikha. I’ve gotten to know both co-founders, Mudassir and Magnus Olsson, and what they have built is truly extraordinary. They are first-class entrepreneurs who share our platform vision and, like us, have launched a wide range of products—from digital payments to food delivery—to serve consumers.
I expect many of you will ask how we arrived at this structure, meaning allowing Careem to maintain an independent brand and operate separately. After careful consideration, we decided that this framework has the advantage of letting us build new products and try new ideas across not one, but two, strong brands, with strong operators within each. Over time, by integrating parts of our networks, we can operate more efficiently, achieve even lower wait times, expand new products like high-capacity vehicles and payments, and quicken the already remarkable pace of innovation in the region.
This acquisition is subject to regulatory approval in various countries, which we don’t expect before Q1 2020. Until then, nothing changes. And since both companies will continue to largely operate separately after the acquisition, very little will change in either teams’ day-to-day operations post-close. Today’s news is a testament to the incredible business our team has worked so hard to build.
It’s a great day for the Middle East, for the region’s thriving tech sector, for Careem, and for Uber.
Uber on,
Dara
