Medical Bulletin 24/ December/ 2024 - Video

A research team co-led by a physician-scientist at the University of Arizona College of Medicine – Tucson’s Sarver Heart Center found that a subset of artificial heart patients can regenerate heart muscle, which may open the door to new ways to treat and perhaps someday cure heart failure. The results were published in the journal Circulation.

“Skeletal muscle has a significant ability to regenerate after injury. If you’re playing soccer and you tear a muscle, you need to rest it, and it heals,” said Hesham Sadek, MD, PhD, director of the Sarver Heart Center and chief of the Division of Cardiology at the U of A College of Medicine – Tucson’s Department of Medicine. “When a heart muscle is injured, it doesn’t grow back. We have nothing to reverse heart muscle loss.”

The project began with tissue from artificial heart patients provided by colleagues at the University of Utah Health and School of Medicine. Researchers used their own innovative method of carbon dating human heart tissue to track whether these samples contained newly generated cells. The investigators found that patients with artificial hearts regenerated muscle cells at more than six times the rate of healthy hearts.

“This is the strongest evidence we have, so far, that human heart muscle cells can actually regenerate, which really is exciting, because it solidifies the notion that there is an intrinsic capacity of the human heart to regenerate,” Sadek said. “It also strongly supports the hypothesis that the inability of the heart muscle to ‘rest’ is a major driver of the heart’s lost ability to regenerate shortly after birth. It may be possible to target the molecular pathways involved in cell division to enhance the heart’s ability to regenerate.”

Reference: Derks, W., Rode, J., Collin, S., Rost, F., Heinke, P., Hariharan, A., ... & Bergmann, O. (2023). A latent cardiomyocyte regeneration potential in human heart disease. bioRxiv.

Researchers at the Texas A&M University College of Medicine have shed new light on how chronic alcohol use alters brain signaling pathways, specifically focusing on how it impairs cognitive flexibility. Their findings, recently published in Science Advances, demonstrate the significant role of cholinergic interneurons (CINs) in this process.

Researchers demonstrated that alcohol disrupts the brain’s ability to adapt by altering the burst-pause firing patterns of cholinergic interneurons —specialized neurons that release acetylcholine, a key neurotransmitter. cholinergic interneurons are critical gatekeepers in the brain’s striatum, influencing reward-driven learning and motivation by modulating dopamine signaling.

Using advanced tools such as optogenetics, which uses light to control cells, the researchers uncovered that stimulating cholinergic interneurons in animal models of chronic alcohol exposure produced an altered firing pattern compared to models without chronic alcohol exposure. Normally, cholinergic interneurons fire in a “burst-pause” pattern: a quick burst of activity followed by a pause, which is essential for learning new behaviors and adapting to change. However, in alcohol-exposed models, this firing pattern was significantly disrupted, with shorter and weaker pauses, impairing critical learning process such as reversal leaning.

By combining optogenetics—which uses light to control cholinergic interneurons activity—and fiber photometry—which involves genetically engineered biosensors to detect real-time release of acetylcholine while subjects perform tasks—the team discovered distinct roles for different cholinergic interneurons firing phases. The “burst” phase, which increases acetylcholine release from cholinergic interneurons, aids extinction learning—where old behaviors are unlearned. The “pause” phase, on the other hand, which causes a dip in acetylcholine release from the cholinergic interneurons is crucial for reversal learning, where new behaviors replace outdated ones.

Reference: Zhenbo Huang et al., Dynamic responses of striatal cholinergic interneurons control behavioral flexibility.Sci. Adv.10,eadn2446(2024).DOI:10.1126/sciadv.adn2446

Using an AI tool, researchers at Karolinska Institutet have analysed brain images from 70-year-olds and estimated their brains’ biological age. They found that factors detrimental to vascular health, such as inflammation and high glucose levels, are associated with an older-looking brain, while healthy lifestyles were linked to brains with a younger appearance. The results are presented in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

The study involved 739 cognitively healthy 70-year-olds, 389 of whom were female, recruited from Gothenburg’s H70 cohort in Sweden. The researchers took MRI scans of their brains and then estimated the age of the resulting brain images using their own AI-based algorithm.

The brain images were complemented with blood samples for measuring lipids, glucose, and inflammation. The participants also carried out cognitive testing. Data on lifestyle factors such as exercise and medical conditions were also available.

The AI tool estimated the brain age for both sexes to be on average 71 years. The researchers then looked at the “brain age gap” by subtracting the participants' estimated biological brain age from their chronological age.

The researchers found that diabetes, stroke, cerebral small vessel disease, and inflammation were linked to brains with an older appearance, whereas a healthy lifestyle involving regular exercise could be linked to brains of a younger appearance.

The brains of women and men seem to differ in terms of factors linked to older- and younger-looking brains, meaning that women and men may differ in how they build resilience, a phenomenon that the researchers now plan to investigate by looking not only at biological determinants such as hormones but also at sociocultural influences.

Reference: ”Biological brain age and resilience in cognitively unimpaired 70-year-old individuals”, Anna Marseglia, Caroline Dartora, Jessica Samuelsson, Konstantinos Poulakis, Rosaleena Mohanty, Sara Shams, Olof Lindberg, Lina Rydén, Therese Rydberg Sterner, Johan Skoog, Anna Zettergren, Silke Kern, Ingmar Skoog and Eric Westman, Alzheimer's & Dementia, online 20 December 2024. doi: 10.1002/alz.14435.

The research team from the Natural Product Drug Development Center at the Korea Institute of Science and Technology has developed a new therapeutic agent for dry Age-related macular degeneration that can be administered as eye drops. The findings are present in the journal advanced science.

Age-related macular degeneration is the leading cause of vision loss in individuals over 65, characterized by abnormal changes in the macular, resulting in reduced vision and distorted objects. The only FDA-approved treatments for dry Age-related macular degeneration as of 2023 are two injectable drugs, which are limited by concerns over complications from intravitreal injections and modest efficacy in restoring vision.

To address the limitations of injection-based treatments, the research team focused on the inflammatory signaling pathway of Toll-like receptors, which are known to play a critical role in Age-related macular degeneration pathogenesis. By extracting peptide sequences from tens of thousands of proteins with structures similar to natural Toll-like receptors signaling proteins, they established an extensive library of over 190,000 peptide drug candidates. Utilizing advanced technology for rapidly screening peptides that specifically bind to Toll-like receptors signaling proteins, they successfully identified multiple candidate peptides capable of inhibiting interactions between these proteins.

The researchers validated the therapeutic efficacy of the peptides by administering them as eye drops to mice with induced dry Age-related macular degeneration. The treated group exhibited retinal cell protection and significantly reduced retinal degeneration, comparable to normal mice. This demonstrated that peptide-based eye drops could effectively replace existing injectable therapies for dry Age-related macular degeneration.

This new therapeutic agent, delivered in eye drop form, offers enhanced treatment convenience and adherence for patients while reducing complications and costs associated with repetitive invasive treatments. Furthermore, the non-invasive and safe nature of the therapy provides a novel treatment option that improves both efficacy and patient satisfaction.

Reference: Y. Lim, T. K. Kang, M. I. Kim, D. Kim, J. Y. Kim, S. H. Jung, K. Park, W.-B. Lee, M.-H. Seo, Massively Parallel Screening of Toll/Interleukin-1 Receptor (TIR)-Derived Peptides Reveals Multiple Toll-Like Receptors (TLRs)-Targeting Immunomodulatory Peptides. Adv. Sci. 2024, 2406018. https://doi.org/10.1002/advs.202406018