The medication restored normal NAD+ levels and fully reversed cognitive function in advanced Alzheimer’s models.
Category: biotech/medical – Page 14
Controlled colonization of the human gut with a genetically engineered microbial therapeutic
Great paper highlighting key challenges for genetically engineered bacterial therapies in the human gut. It is respectable that this paper was published in Science despite some “negative” results. Although the genetically engineered bacteria were all supposed to die after removal of porphyrin from the diet, they sometimes rebounded. Even with an improved porphyrin pathway which was supposed to resist mutational rebound, the bacteria still persisted in a mouse model, apparently by mysterious non-mutational means. Maybe the microbiomes of the mice somehow supplied porphyrin to the bacteria without the knowledge of the researchers. Furthermore, therapeutic application of the genetically engineered bacteria in humans only resulted in modest (and not statistically significant) decreases in urine oxalate. This was partly due to horizontal gene transfer which replaced the engineered oxalate degradation pathway and partly due to the general fitness burden of the engineered oxalate degradation pathway. As such, this paper revealed a lot of important obstacles which will need to be worked on for bacterial therapies to move forward in the future.
(https://www.science.org/doi/10.1126/science.adu8000)
Precision microbiome programming for therapeutic applications is limited by challenges in achieving reproducible colonic colonization. Previously, we created an exclusive niche that we used to engraft engineered bacteria into diverse microbiota in mice by using a porphyran prebiotic. Building on this approach, we have now engineered conditional attenuation into a porphyran-utilizing strain of Phocaeicola vulgatus by replacing native essential gene regulation with a porphyran-inducible promoter to allow reversible engraftment. Engineering a five-gene oxalate degradation pathway into the reversibly engrafting strain resulted in a therapeutic candidate that reduced hyperoxaluria, a cause of kidney stones, in preclinical models.
Scientists Think We Could ‘Recharge’ Our Cells—And Rewind the Aging Clock
Think of cells as the biological answer to battery-powered electronics. Mitochondria are the batteries that supply them with enough energy to keep going. Unfortunately, just like the two standard AAs in your remote control, they eventually run out of power and die—but (much like actual batteries) they can also be recharged and replaced.
Breakdown of mitochondria causes cells to glitch. Wear and tear can happen with age, usually from years of exposure to free radicals that cause oxidative stress and inflammation, but can also be caused by injury from degenerative diseases or mitochondrial toxicity from certain drugs and other harmful substances. When there is damage to the cell, mitochondria begin to lose their capacity to generate energy. Losing mitochondria is detrimental to cell function. This is why biomedical engineer Akhilesh Gaharwar and his research team at Texas A&M University have come up with a way to regenerate them.
Breast cancer drug boosts leukemia treatment: Unexpected duo shows promise in overcoming resistance
A research team at Oregon Health & Science University has discovered a promising new drug combination that may help people with acute myeloid leukemia overcome resistance to one of the most common frontline therapies.
In a study published in Cell Reports Medicine, researchers analyzed more than 300 acute myeloid leukemia, or AML, patient samples and found that pairing venetoclax, a standard AML drug, with palbociclib, a cell-cycle inhibitor currently approved for breast cancer, produced significantly stronger and more durable anti-leukemia activity than venetoclax alone. The findings were confirmed in human tissue samples, as well as in mouse models carrying human leukemia cells.
“Of the 25 drug combinations tested, venetoclax plus palbociclib was the most effective. That really motivated us to dig deeper into why it works so well—and why it appears to overcome resistance seen with current therapy,” said Melissa Stewart, Ph.D., research assistant professor at OHSU and lead author of the study.
The Robot Revolution Is Closer Than You Think
A robot revolution, driven by advancements in robotics and AI, is imminent and will drastically transform the economy, labor, and society, leading to a post-labor, post-scarcity system with abundant energy and labor ##
## Questions to inspire discussion.
Investment & National Strategy.
🚀 Q: Why should governments prioritize humanoid robot investment now? A: Governments must treat humanoid robots as a national priority for transforming productivity and defense, with enormous investments justified because there’s no time to lose as both the US and China have already recognized this imperative.
💰 Q: What economic growth rates become possible with early humanoid robot adoption? A: Spinning up the humanoid robot flywheel early enables exponential economic growth rates of 20–100% per year, unlocking unprecedented prosperity and catapulting societies up the curve over the next 15 years.
⚡ Q: Which countries or entities will likely lead the humanoid robot transformation? A: Outsiders rather than incumbents or centers of power will lead the transformation to a new economic paradigm, as history shows leadership typically comes from the edge rather than the status quo.
Lessons learned in linking PROTACs from discovery to the clinic
Proteolysis targeting chimeras (PROTACs) are an emerging platform in drug discovery with the potential to unlock novel pharmacology and tackle undruggable targets. This Review highlights learnings from the first cohort of clinical-stage PROTACs, which use short, ring-rich linkers, often complemented with one basic centre, to achieve good bioavailability and metabolic stability.
Endothelial IL-36 receptor activation promotes vascular stability to limit pathological microvessel permeability in the CNS
Only a small number of barrier-enhancing factors have been discovered to specifically increase barrier integrity, enhance vessel stability, and make vessels resistant to fluid leakage. Here, Fahey et al. present DEVDIL-36β as a cytokine promoter of vascular integrity in the CNS, with barrier-enhancing properties through upregulation of junctional components.
