Research Roundup: Nanotherapy and Islet Transplants for Diabetes and More

For about a century, the way to treat Type 1 diabetes has been via insulin injections. Although research has been conducted on pancreatic islet transplants, it’s a tough nut to crack in terms of organ rejection. There’s been a potential breakthrough in that area involving nanotherapy. For that and more research news, continue reading.

Nanotherapy May Make Islet Transplants Viable to Treat Type 1 Diabetes

Researchers have been working to develop approaches to curing Type 1 diabetes by transplanting healthy islet cells into the pancreas. Type 1 diabetes is caused by the immune system attacking the islet cells, damaging them and preventing them from producing insulin, which is necessary for controlling glucose levels in the blood. Traditional treatment is regular injections of the hormone insulin via syringe, insulin pump or another device. Attempts to transplant islets have had setbacks primarily around immune system rejection of the new islets. Immunosuppressive drugs don’t seem to be effective in protecting the transplanted cells and tissues from the immune system and have other undesirable side effects.

Investigators at Northwestern University have developed a technique to make the immunomodulation effect of immunosuppressive drugs more effective. It utilizes nanocarriers to re-engineer rapamycin, a common immunosuppressant drug. The rapamycin-loaded nanocarriers target specific cells related to the transplant without more broadly dampening the body’s immune response. Rapamycin is usually dosed orally, but because of toxicity, has to be closely monitored. At low doses, it is not effective in islet transplantation. The use of the nanoparticles allowed the team to deliver rapamycin via a subcutaneous injection, which allowed it to be more effective at about half the standard dose. They published their research in Nature Nanotechnology.

The approach in mice with diabetes eradicated the disease for the entire 100-day study with minimal side effects. They also showed that mice treated with the delivery system had a “robust immune response” compared to a cohort of mice receiving standard treatments of rapamycin.

Source: BioSpace

“This approach can be applied to other transplanted tissue and organs, opening up new research areas and options for patients,” said Guillermo Ameer, the Daniel Hale Williams Professor of Biomedical Engineering at Northwestern’s McCormick School of Engineering and director of the Center for Advanced Regenerative Engineering (CARE). “We are now working on taking these very exciting results one step closer to clinical use.”

A Clue to COVID-19 Brain Fog

Researchers at the University of California – San Francisco evaluated 32 adults, 22 with cognitive symptoms and 10 control patients, to investigate “brain fog” in post-COVID-19 patients. They analyzed the cerebrospinal fluid (CSF) of 17 of the participants. All the participants had COVID-19 but did not require hospitalization. They found that 10 of 13 people with cognitive symptoms had abnormalities in their CSF. However, four patients with no cognitive symptoms had normal CSF samples.  Brain fog was identified as problems remembering recent events, remembering names or words, focus issues and problems keeping and manipulating information. They found elevated protein levels in the CSF patients with the abnormalities, suggesting inflammation. They also found the presence of unexpected antibodies in an activated immune system. Some of these were found in the blood as well, which the researchers say suggests a systemic inflammatory response. When it is unique to the CSF, it suggests brain inflammation. They don’t yet know what the targets of the antibodies are, although they speculate they might be attacking the body itself in a sort of auto-immune response. They also found that the participants with cognitive symptoms had an average of 2.5 cognitive risk factors compared to an average of less than one risk factor for participants who did not show brain fog. Those risk factors included diabetes, hypertension, a history of ADHD, anxiety, depression, heavy alcohol or repeated stimulant use, and learning disabilities.

A Gene ID’ed that Acts as a First-Line Response to Viral Infection

Researchers at the University of California – San Diego, working with small worms, Caenorhabditis elegans, to determine how they defended themselves against pathogens, identified a protein called ZIP-1 that act as a centralized site for immune response. ZIP-1is a transcription factor protein that helps transfer DNA information to messenger RNA (mRNA). It appears very early in the immune response and seemed to stimulate defenses to infection. The subset of genes controlled by ZIP-1 is important for immunity. It appeared active against a range of pathogens, including viruses, fungus and heat stress. The responses all went through the same central ZIP-1 hub to switch on a set of immune genes. Future research will focus on how the receptors sense a virus, which is similar to what humans have in their own immune responses.

A New Drug Delivery System?

Investigators at the University of California San Diego School of Medicine and Moores Cancer Center at UC San Diego Health enucleated cells — removed the nucleus — then used the genetically engineered cell to deliver therapeutics precisely to target tissues. They engineered mesenchymal stromal cells (MSCs) to increase their disease-seeking behavior, enucleated them while keeping other organelles that produce energy and proteins. Then, working in mouse models of acute inflammation and of pancreatitis, packed the cells, called “Cargocytes,” with an anti-inflammatory cytokine and administered them systemically to the mice. In the mice, the cells produced bioactive therapeutics at high levels to their targeted locations within days and were effective at treating the disease.

How DNA Gets Packed into the Nucleus

DNA, if stretched out, would be almost six feet long. But in the nucleus of cells, it gets packed into chromosomes about one-millionth its size. All without becoming a tangled mess. Researchers at Pohang University of Science & Technology and Gwangju Institute of Science and Technology used X-rays from a third-generation synchrotron to confirm that chromosomes were formed in a fractal structure instead of the hierarchical structure previously thought. They published their research in the Proceedings of the National Academy of Sciences (PNAS).

Changyong Song, with Pohang University said, “The technique developed in the study not only provides the key to understanding genetics — the essence of all living things — but also to uncover the 3D structures of other materials, such as viruses, whose detailed structure is of significant importance.”

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